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  1. Whole blood transcriptional profiling reveals significant down-regulation of human leukocyte antigen class I and II genes in essential thrombocythemia, polycythemia vera and myelofibrosis

    DEFF Research Database (Denmark)

    Skov, Vibe; Riley, Caroline Hasselbalch; Thomassen, Mads

    2013-01-01

    Gene expression profiling studies in the Philadelphia-negative chronic myeloproliferative neoplasms have revealed significant deregulation of several immune and inflammation genes that might be of importance for clonal evolution due to defective tumor immune surveillance. Other mechanisms might b...

  2. Dynamic metabolome profiling reveals significant metabolic changes during grain development of bread wheat (Triticum aestivum L.).

    Science.gov (United States)

    Zhen, Shoumin; Dong, Kun; Deng, Xiong; Zhou, Jiaxing; Xu, Xuexin; Han, Caixia; Zhang, Wenying; Xu, Yanhao; Wang, Zhimin; Yan, Yueming

    2016-08-01

    Metabolites in wheat grains greatly influence nutritional values. Wheat provides proteins, minerals, B-group vitamins and dietary fiber to humans. These metabolites are important to human health. However, the metabolome of the grain during the development of bread wheat has not been studied so far. In this work the first dynamic metabolome of the developing grain of the elite Chinese bread wheat cultivar Zhongmai 175 was analyzed, using non-targeted gas chromatography/mass spectrometry (GC/MS) for metabolite profiling. In total, 74 metabolites were identified over the grain developmental stages. Metabolite-metabolite correlation analysis revealed that the metabolism of amino acids, carbohydrates, organic acids, amines and lipids was interrelated. An integrated metabolic map revealed a distinct regulatory profile. The results provide information that can be used by metabolic engineers and molecular breeders to improve wheat grain quality. The present metabolome approach identified dynamic changes in metabolite levels, and correlations among such levels, in developing seeds. The comprehensive metabolic map may be useful when breeding programs seek to improve grain quality. The work highlights the utility of GC/MS-based metabolomics, in conjunction with univariate and multivariate data analysis, when it is sought to understand metabolic changes in developing seeds. © 2015 Society of Chemical Industry. © 2015 Society of Chemical Industry.

  3. Genome Wide Expression Profiling of Cancer Cell Lines Cultured in Microgravity Reveals Significant Dysregulation of Cell Cycle and MicroRNA Gene Networks.

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    Prasanna Vidyasekar

    Full Text Available Zero gravity causes several changes in metabolic and functional aspects of the human body and experiments in space flight have demonstrated alterations in cancer growth and progression. This study reports the genome wide expression profiling of a colorectal cancer cell line-DLD-1, and a lymphoblast leukemic cell line-MOLT-4, under simulated microgravity in an effort to understand central processes and cellular functions that are dysregulated among both cell lines. Altered cell morphology, reduced cell viability and an aberrant cell cycle profile in comparison to their static controls were observed in both cell lines under microgravity. The process of cell cycle in DLD-1 cells was markedly affected with reduced viability, reduced colony forming ability, an apoptotic population and dysregulation of cell cycle genes, oncogenes, and cancer progression and prognostic markers. DNA microarray analysis revealed 1801 (upregulated and 2542 (downregulated genes (>2 fold in DLD-1 cultures under microgravity while MOLT-4 cultures differentially expressed 349 (upregulated and 444 (downregulated genes (>2 fold under microgravity. The loss in cell proliferative capacity was corroborated with the downregulation of the cell cycle process as demonstrated by functional clustering of DNA microarray data using gene ontology terms. The genome wide expression profile also showed significant dysregulation of post transcriptional gene silencing machinery and multiple microRNA host genes that are potential tumor suppressors and proto-oncogenes including MIR22HG, MIR17HG and MIR21HG. The MIR22HG, a tumor-suppressor gene was one of the highest upregulated genes in the microarray data showing a 4.4 log fold upregulation under microgravity. Real time PCR validated the dysregulation in the host gene by demonstrating a 4.18 log fold upregulation of the miR-22 microRNA. Microarray data also showed dysregulation of direct targets of miR-22, SP1, CDK6 and CCNA2.

  4. DNA entropy reveals a significant difference in complexity between housekeeping and tissue specific gene promoters.

    Science.gov (United States)

    Thomas, David; Finan, Chris; Newport, Melanie J; Jones, Susan

    2015-10-01

    The complexity of DNA can be quantified using estimates of entropy. Variation in DNA complexity is expected between the promoters of genes with different transcriptional mechanisms; namely housekeeping (HK) and tissue specific (TS). The former are transcribed constitutively to maintain general cellular functions, and the latter are transcribed in restricted tissue and cells types for specific molecular events. It is known that promoter features in the human genome are related to tissue specificity, but this has been difficult to quantify on a genomic scale. If entropy effectively quantifies DNA complexity, calculating the entropies of HK and TS gene promoters as profiles may reveal significant differences. Entropy profiles were calculated for a total dataset of 12,003 human gene promoters and for 501 housekeeping (HK) and 587 tissue specific (TS) human gene promoters. The mean profiles show the TS promoters have a significantly lower entropy (pentropy distributions for the 3 datasets show that promoter entropies could be used to identify novel HK genes. Functional features comprise DNA sequence patterns that are non-random and hence they have lower entropies. The lower entropy of TS gene promoters can be explained by a higher density of positive and negative regulatory elements, required for genes with complex spatial and temporary expression. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Polyomic profiling reveals significant hepatic metabolic alterations in glucagon-receptor (GCGR knockout mice: implications on anti-glucagon therapies for diabetes

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    Molloy Mark P

    2011-06-01

    Full Text Available Abstract Background Glucagon is an important hormone in the regulation of glucose homeostasis, particularly in the maintenance of euglycemia and prevention of hypoglycemia. In type 2 Diabetes Mellitus (T2DM, glucagon levels are elevated in both the fasted and postprandial states, which contributes to inappropriate hyperglycemia through excessive hepatic glucose production. Efforts to discover and evaluate glucagon receptor antagonists for the treatment of T2DM have been ongoing for approximately two decades, with the challenge being to identify an agent with appropriate pharmaceutical properties and efficacy relative to potential side effects. We sought to determine the hepatic & systemic consequence of full glucagon receptor antagonism through the study of the glucagon receptor knock-out mouse (Gcgr-/- compared to wild-type littermates. Results Liver transcriptomics was performed using Affymetric expression array profiling, and liver proteomics was performed by iTRAQ global protein analysis. To complement the transcriptomic and proteomic analyses, we also conducted metabolite profiling (~200 analytes using mass spectrometry in plasma. Overall, there was excellent concordance (R = 0.88 for changes associated with receptor knock-out between the transcript and protein analysis. Pathway analysis tools were used to map the metabolic processes in liver altered by glucagon receptor ablation, the most notable being significant down-regulation of gluconeogenesis, amino acid catabolism, and fatty acid oxidation processes, with significant up-regulation of glycolysis, fatty acid synthesis, and cholesterol biosynthetic processes. These changes at the level of the liver were manifested through an altered plasma metabolite profile in the receptor knock-out mice, e.g. decreased glucose and glucose-derived metabolites, and increased amino acids, cholesterol, and bile acid levels. Conclusions In sum, the results of this study suggest that the complete ablation

  6. Core microbial functional activities in ocean environments revealed by global metagenomic profiling analyses.

    KAUST Repository

    Ferreira, Ari J S

    2014-06-12

    Metagenomics-based functional profiling analysis is an effective means of gaining deeper insight into the composition of marine microbial populations and developing a better understanding of the interplay between the functional genome content of microbial communities and abiotic factors. Here we present a comprehensive analysis of 24 datasets covering surface and depth-related environments at 11 sites around the world\\'s oceans. The complete datasets comprises approximately 12 million sequences, totaling 5,358 Mb. Based on profiling patterns of Clusters of Orthologous Groups (COGs) of proteins, a core set of reference photic and aphotic depth-related COGs, and a collection of COGs that are associated with extreme oxygen limitation were defined. Their inferred functions were utilized as indicators to characterize the distribution of light- and oxygen-related biological activities in marine environments. The results reveal that, while light level in the water column is a major determinant of phenotypic adaptation in marine microorganisms, oxygen concentration in the aphotic zone has a significant impact only in extremely hypoxic waters. Phylogenetic profiling of the reference photic/aphotic gene sets revealed a greater variety of source organisms in the aphotic zone, although the majority of individual photic and aphotic depth-related COGs are assigned to the same taxa across the different sites. This increase in phylogenetic and functional diversity of the core aphotic related COGs most probably reflects selection for the utilization of a broad range of alternate energy sources in the absence of light.

  7. Core microbial functional activities in ocean environments revealed by global metagenomic profiling analyses.

    KAUST Repository

    Ferreira, Ari J S; Siam, Rania; Setubal, Joã o C; Moustafa, Ahmed; Sayed, Ahmed; Chambergo, Felipe S; Dawe, Adam S; Ghazy, Mohamed A; Sharaf, Hazem; Ouf, Amged; Alam, Intikhab; Abdel-Haleem, Alyaa M; Lehvä slaiho, Heikki; Ramadan, Eman; Antunes, André ; Stingl, Ulrich; Archer, John A.C.; Jankovic, Boris R; Sogin, Mitchell; Bajic, Vladimir B.; El-Dorry, Hamza

    2014-01-01

    Metagenomics-based functional profiling analysis is an effective means of gaining deeper insight into the composition of marine microbial populations and developing a better understanding of the interplay between the functional genome content of microbial communities and abiotic factors. Here we present a comprehensive analysis of 24 datasets covering surface and depth-related environments at 11 sites around the world's oceans. The complete datasets comprises approximately 12 million sequences, totaling 5,358 Mb. Based on profiling patterns of Clusters of Orthologous Groups (COGs) of proteins, a core set of reference photic and aphotic depth-related COGs, and a collection of COGs that are associated with extreme oxygen limitation were defined. Their inferred functions were utilized as indicators to characterize the distribution of light- and oxygen-related biological activities in marine environments. The results reveal that, while light level in the water column is a major determinant of phenotypic adaptation in marine microorganisms, oxygen concentration in the aphotic zone has a significant impact only in extremely hypoxic waters. Phylogenetic profiling of the reference photic/aphotic gene sets revealed a greater variety of source organisms in the aphotic zone, although the majority of individual photic and aphotic depth-related COGs are assigned to the same taxa across the different sites. This increase in phylogenetic and functional diversity of the core aphotic related COGs most probably reflects selection for the utilization of a broad range of alternate energy sources in the absence of light.

  8. Core microbial functional activities in ocean environments revealed by global metagenomic profiling analyses.

    Directory of Open Access Journals (Sweden)

    Ari J S Ferreira

    Full Text Available Metagenomics-based functional profiling analysis is an effective means of gaining deeper insight into the composition of marine microbial populations and developing a better understanding of the interplay between the functional genome content of microbial communities and abiotic factors. Here we present a comprehensive analysis of 24 datasets covering surface and depth-related environments at 11 sites around the world's oceans. The complete datasets comprises approximately 12 million sequences, totaling 5,358 Mb. Based on profiling patterns of Clusters of Orthologous Groups (COGs of proteins, a core set of reference photic and aphotic depth-related COGs, and a collection of COGs that are associated with extreme oxygen limitation were defined. Their inferred functions were utilized as indicators to characterize the distribution of light- and oxygen-related biological activities in marine environments. The results reveal that, while light level in the water column is a major determinant of phenotypic adaptation in marine microorganisms, oxygen concentration in the aphotic zone has a significant impact only in extremely hypoxic waters. Phylogenetic profiling of the reference photic/aphotic gene sets revealed a greater variety of source organisms in the aphotic zone, although the majority of individual photic and aphotic depth-related COGs are assigned to the same taxa across the different sites. This increase in phylogenetic and functional diversity of the core aphotic related COGs most probably reflects selection for the utilization of a broad range of alternate energy sources in the absence of light.

  9. Extensive translational regulation during seed germination revealed by polysomal profiling

    NARCIS (Netherlands)

    Bai, Bing; Peviani, Alessia; Horst, van der Sjors; Gamm, Magdalena; Snel, Berend; Bentsink, Leónie; Hanson, Johannes

    2017-01-01

    This work investigates the extent of translational regulation during seed germination. The polysome occupancy of each gene is determined by genome-wide profiling of total mRNA and polysome-associated mRNA. This reveals extensive translational regulation during Arabidopsis thaliana seed

  10. The distinctive gastric fluid proteome in gastric cancer reveals a multi-biomarker diagnostic profile

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    Eng Alvin KH

    2008-10-01

    Full Text Available Abstract Background Overall gastric cancer survival remains poor mainly because there are no reliable methods for identifying highly curable early stage disease. Multi-protein profiling of gastric fluids, obtained from the anatomic site of pathology, could reveal diagnostic proteomic fingerprints. Methods Protein profiles were generated from gastric fluid samples of 19 gastric cancer and 36 benign gastritides patients undergoing elective, clinically-indicated gastroscopy using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry on multiple ProteinChip arrays. Proteomic features were compared by significance analysis of microarray algorithm and two-way hierarchical clustering. A second blinded sample set (24 gastric cancers and 29 clinically benign gastritides was used for validation. Results By significance analysyis of microarray, 60 proteomic features were up-regulated and 46 were down-regulated in gastric cancer samples (p Conclusion This simple and reproducible multimarker proteomic assay could supplement clinical gastroscopic evaluation of symptomatic patients to enhance diagnostic accuracy for gastric cancer and pre-malignant lesions.

  11. Proteomic profiling in multiple sclerosis clinical courses reveals potential biomarkers of neurodegeneration.

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    Maria Liguori

    Full Text Available The aim of our project was to perform an exploratory analysis of the cerebrospinal fluid (CSF proteomic profiles of Multiple Sclerosis (MS patients, collected in different phases of their clinical course, in order to investigate the existence of peculiar profiles characterizing the different MS phenotypes. The study was carried out on 24 Clinically Isolated Syndrome (CIS, 16 Relapsing Remitting (RR MS, 11 Progressive (Pr MS patients. The CSF samples were analysed using the Matrix Assisted Laser Desorption Ionisation Time Of Flight (MALDI-TOF mass spectrometer in linear mode geometry and in delayed extraction mode (m/z range: 1000-25000 Da. Peak lists were imported for normalization and statistical analysis. CSF data were correlated with demographic, clinical and MRI parameters. The evaluation of MALDI-TOF spectra revealed 348 peak signals with relative intensity ≥ 1% in the study range. The peak intensity of the signals corresponding to Secretogranin II and Protein 7B2 were significantly upregulated in RRMS patients compared to PrMS (p<0.05, whereas the signals of Fibrinogen and Fibrinopeptide A were significantly downregulated in CIS compared to PrMS patients (p<0.04. Additionally, the intensity of the Tymosin β4 peak was the only signal to be significantly discriminated between the CIS and RRMS patients (p = 0.013. Although with caution due to the relatively small size of the study populations, and considering that not all the findings remained significant after adjustment for multiple comparisons, in our opinion this mass spectrometry evaluation confirms that this technique may provide useful and important information to improve our understanding of the complex pathogenesis of MS.

  12. Comprehensive Genomic Profiling of Esthesioneuroblastoma Reveals Additional Treatment Options.

    Science.gov (United States)

    Gay, Laurie M; Kim, Sungeun; Fedorchak, Kyle; Kundranda, Madappa; Odia, Yazmin; Nangia, Chaitali; Battiste, James; Colon-Otero, Gerardo; Powell, Steven; Russell, Jeffery; Elvin, Julia A; Vergilio, Jo-Anne; Suh, James; Ali, Siraj M; Stephens, Philip J; Miller, Vincent A; Ross, Jeffrey S

    2017-07-01

    Esthesioneuroblastoma (ENB), also known as olfactory neuroblastoma, is a rare malignant neoplasm of the olfactory mucosa. Despite surgical resection combined with radiotherapy and adjuvant chemotherapy, ENB often relapses with rapid progression. Current multimodality, nontargeted therapy for relapsed ENB is of limited clinical benefit. We queried whether comprehensive genomic profiling (CGP) of relapsed or refractory ENB can uncover genomic alterations (GA) that could identify potential targeted therapies for these patients. CGP was performed on formalin-fixed, paraffin-embedded sections from 41 consecutive clinical cases of ENBs using a hybrid-capture, adaptor ligation based next-generation sequencing assay to a mean coverage depth of 593X. The results were analyzed for base substitutions, insertions and deletions, select rearrangements, and copy number changes (amplifications and homozygous deletions). Clinically relevant GA (CRGA) were defined as GA linked to drugs on the market or under evaluation in clinical trials. A total of 28 ENBs harbored GA, with a mean of 1.5 GA per sample. Approximately half of the ENBs (21, 51%) featured at least one CRGA, with an average of 1 CRGA per sample. The most commonly altered gene was TP53 (17%), with GA in PIK3CA , NF1 , CDKN2A , and CDKN2C occurring in 7% of samples. We report comprehensive genomic profiles for 41 ENB tumors. CGP revealed potential new therapeutic targets, including targetable GA in the mTOR, CDK and growth factor signaling pathways, highlighting the clinical value of genomic profiling in ENB. Comprehensive genomic profiling of 41 relapsed or refractory ENBs reveals recurrent alterations or classes of mutation, including amplification of tyrosine kinases encoded on chromosome 5q and mutations affecting genes in the mTOR/PI3K pathway. Approximately half of the ENBs (21, 51%) featured at least one clinically relevant genomic alteration (CRGA), with an average of 1 CRGA per sample. The most commonly altered

  13. Prevalence of conventional risk factors and lipid profiles in patients with acute coronary syndrome and significant coronary disease

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    González-Pacheco H

    2014-10-01

    Full Text Available Héctor González-Pacheco,1 Jesús Vargas-Barrón,2 Maite Vallejo,2 Yigal Piña-Reyna,3 Alfredo Altamirano-Castillo,1 Pedro Sánchez-Tapia,1 Carlos Martínez-Sánchez1 1Coronary Care Unit, National Institute of Cardiology in Mexico City, Mexico City, Mexico; 2Department of Clinical Research, National Institute of Cardiology in Mexico City, Mexico City, Mexico; 3Catheterization Laboratory, National Institute of Cardiology in Mexico City, Mexico City, Mexico Background: Among patients with coronary artery disease (CAD, 80%–90% present at least one conventional risk factor. On the other hand, lipid profile modification after a cardiovascular event related to acute coronary syndrome (ACS has been recognized. The prevalence of conventional risk factors and the lipid profile at the time of admission in patients with ACS and significant CAD (stenosis ≥50% determined through coronary angiography is not well described. Methods: We studied 3,447 patients with a diagnosis of ACS and significant CAD with stenosis ≥50%, as shown on angiography. We recorded the presence of conventional risk factors, including smoking, hypertension, dyslipidemia, and diabetes. In addition, we analyzed the lipid profiles within the first 24 hours of admission. We analyzed the studied population and compared findings according to sex.Results: Most patients (81.7% were male. ST-elevation myocardial infarction was present in 51.3% of patients, and non-ST-elevation acute coronary syndrome was present in 48.7%. The most frequent risk factor was smoking, which was present in 68% of patients, followed by hypertension (57.8%, dyslipidemia (47.5%, and diabetes (37.7%. In women, the most frequent risk factors were hypertension, diabetes, and dyslipidemia, whereas in men, smoking was the most frequent. We identified at least one risk factor in 95.7% of all patients, two or three risk factors in 62%, and four risk factors in 8.6% of patients. The lipid profile analysis revealed that

  14. 1H NMR-based metabolic profiling reveals inherent biological variation in yeast and nematode model systems

    International Nuclear Information System (INIS)

    Szeto, Samuel S. W.; Reinke, Stacey N.; Lemire, Bernard D.

    2011-01-01

    The application of metabolomics to human and animal model systems is poised to provide great insight into our understanding of disease etiology and the metabolic changes that are associated with these conditions. However, metabolomic studies have also revealed that there is significant, inherent biological variation in human samples and even in samples from animal model systems where the animals are housed under carefully controlled conditions. This inherent biological variability is an important consideration for all metabolomics analyses. In this study, we examined the biological variation in 1 H NMR-based metabolic profiling of two model systems, the yeast Saccharomyces cerevisiae and the nematode Caenorhabditis elegans. Using relative standard deviations (RSD) as a measure of variability, our results reveal that both model systems have significant amounts of biological variation. The C. elegans metabolome possesses greater metabolic variance with average RSD values of 29 and 39%, depending on the food source that was used. The S. cerevisiae exometabolome RSD values ranged from 8% to 12% for the four strains examined. We also determined whether biological variation occurs between pairs of phenotypically identical yeast strains. Multivariate statistical analysis allowed us to discriminate between pair members based on their metabolic phenotypes. Our results highlight the variability of the metabolome that exists even for less complex model systems cultured under defined conditions. We also highlight the efficacy of metabolic profiling for defining these subtle metabolic alterations.

  15. Global transcription profiling reveals comprehensive insights into hypoxic response in Arabidopsis.

    Science.gov (United States)

    Liu, Fenglong; Vantoai, Tara; Moy, Linda P; Bock, Geoffrey; Linford, Lara D; Quackenbush, John

    2005-03-01

    Plants have evolved adaptation mechanisms to sense oxygen deficiency in their environments and make coordinated physiological and structural adjustments to enhance their hypoxic tolerance. To gain insight into how plants respond to low-oxygen stress, gene expression profiling using whole-genome DNA amplicon microarrays was carried out at seven time points over 24 h, in wild-type and transgenic P(SAG12):ipt Arabidopsis (Arabidopsis thaliana) plants under normoxic and hypoxic conditions. Transcript levels of genes involved in glycolysis and fermentation pathways, ethylene synthesis and perception, calcium signaling, nitrogen utilization, trehalose metabolism, and alkaloid synthesis were significantly altered in response to oxygen limitation. Analysis based on gene ontology assignments suggested a significant down-regulation of genes whose functions are associated with cell walls, nucleosome structures, water channels, and ion transporters and a significant up-regulation of genes involved in transcriptional regulation, protein kinase activity, and auxin responses under conditions of oxygen shortage. Promoter analysis on a cluster of up-regulated genes revealed a significant overrepresentation of the AtMYB2-binding motif (GT motif), a sugar response element-like motif, and a G-box-related sequence, and also identified several putative anaerobic response elements. Finally, quantitative real-time polymerase chain reactions using 29 selected genes independently verified the microarray results. This study represents one of the most comprehensive analyses conducted to date investigating hypoxia-responsive transcriptional networks in plants.

  16. {sup 1}H NMR-based metabolic profiling reveals inherent biological variation in yeast and nematode model systems

    Energy Technology Data Exchange (ETDEWEB)

    Szeto, Samuel S. W.; Reinke, Stacey N.; Lemire, Bernard D., E-mail: bernard.lemire@ualberta.ca [University of Alberta, Department of Biochemistry, School of Molecular and Systems Medicine (Canada)

    2011-04-15

    The application of metabolomics to human and animal model systems is poised to provide great insight into our understanding of disease etiology and the metabolic changes that are associated with these conditions. However, metabolomic studies have also revealed that there is significant, inherent biological variation in human samples and even in samples from animal model systems where the animals are housed under carefully controlled conditions. This inherent biological variability is an important consideration for all metabolomics analyses. In this study, we examined the biological variation in {sup 1}H NMR-based metabolic profiling of two model systems, the yeast Saccharomyces cerevisiae and the nematode Caenorhabditis elegans. Using relative standard deviations (RSD) as a measure of variability, our results reveal that both model systems have significant amounts of biological variation. The C. elegans metabolome possesses greater metabolic variance with average RSD values of 29 and 39%, depending on the food source that was used. The S. cerevisiae exometabolome RSD values ranged from 8% to 12% for the four strains examined. We also determined whether biological variation occurs between pairs of phenotypically identical yeast strains. Multivariate statistical analysis allowed us to discriminate between pair members based on their metabolic phenotypes. Our results highlight the variability of the metabolome that exists even for less complex model systems cultured under defined conditions. We also highlight the efficacy of metabolic profiling for defining these subtle metabolic alterations.

  17. Metabolomic Profiling of Plasma from Melioidosis Patients Using UHPLC-QTOF MS Reveals Novel Biomarkers for Diagnosis

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    Susanna K. P. Lau

    2016-02-01

    Full Text Available To identify potential biomarkers for improving diagnosis of melioidosis, we compared plasma metabolome profiles of melioidosis patients compared to patients with other bacteremia and controls without active infection, using ultra-high-performance liquid chromatography-electrospray ionization-quadruple time-of-flight mass spectrometry. Principal component analysis (PCA showed that the metabolomic profiles of melioidosis patients are distinguishable from bacteremia patients and controls. Using multivariate and univariate analysis, 12 significant metabolites from four lipid classes, acylcarnitine (n = 6, lysophosphatidylethanolamine (LysoPE (n = 3, sphingomyelins (SM (n = 2 and phosphatidylcholine (PC (n = 1, with significantly higher levels in melioidosis patients than bacteremia patients and controls, were identified. Ten of the 12 metabolites showed area-under-receiver operating characteristic curve (AUC >0.80 when compared both between melioidosis and bacteremia patients, and between melioidosis patients and controls. SM(d18:2/16:0 possessed the largest AUC when compared, both between melioidosis and bacteremia patients (AUC 0.998, sensitivity 100% and specificity 91.7%, and between melioidosis patients and controls (AUC 1.000, sensitivity 96.7% and specificity 100%. Our results indicate that metabolome profiling might serve as a promising approach for diagnosis of melioidosis using patient plasma, with SM(d18:2/16:0 representing a potential biomarker. Since the 12 metabolites were related to various pathways for energy and lipid metabolism, further studies may reveal their possible role in the pathogenesis and host response in melioidosis.

  18. Metabolomic Profiling of Plasma from Melioidosis Patients Using UHPLC-QTOF MS Reveals Novel Biomarkers for Diagnosis.

    Science.gov (United States)

    Lau, Susanna K P; Lee, Kim-Chung; Lo, George C S; Ding, Vanessa S Y; Chow, Wang-Ngai; Ke, Tony Y H; Curreem, Shirly O T; To, Kelvin K W; Ho, Deborah T Y; Sridhar, Siddharth; Wong, Sally C Y; Chan, Jasper F W; Hung, Ivan F N; Sze, Kong-Hung; Lam, Ching-Wan; Yuen, Kwok-Yung; Woo, Patrick C Y

    2016-02-27

    To identify potential biomarkers for improving diagnosis of melioidosis, we compared plasma metabolome profiles of melioidosis patients compared to patients with other bacteremia and controls without active infection, using ultra-high-performance liquid chromatography-electrospray ionization-quadruple time-of-flight mass spectrometry. Principal component analysis (PCA) showed that the metabolomic profiles of melioidosis patients are distinguishable from bacteremia patients and controls. Using multivariate and univariate analysis, 12 significant metabolites from four lipid classes, acylcarnitine (n = 6), lysophosphatidylethanolamine (LysoPE) (n = 3), sphingomyelins (SM) (n = 2) and phosphatidylcholine (PC) (n = 1), with significantly higher levels in melioidosis patients than bacteremia patients and controls, were identified. Ten of the 12 metabolites showed area-under-receiver operating characteristic curve (AUC) >0.80 when compared both between melioidosis and bacteremia patients, and between melioidosis patients and controls. SM(d18:2/16:0) possessed the largest AUC when compared, both between melioidosis and bacteremia patients (AUC 0.998, sensitivity 100% and specificity 91.7%), and between melioidosis patients and controls (AUC 1.000, sensitivity 96.7% and specificity 100%). Our results indicate that metabolome profiling might serve as a promising approach for diagnosis of melioidosis using patient plasma, with SM(d18:2/16:0) representing a potential biomarker. Since the 12 metabolites were related to various pathways for energy and lipid metabolism, further studies may reveal their possible role in the pathogenesis and host response in melioidosis.

  19. Transcriptional profiling at whole population and single cell levels reveals somatosensory neuron molecular diversity

    Science.gov (United States)

    Chiu, Isaac M; Barrett, Lee B; Williams, Erika K; Strochlic, David E; Lee, Seungkyu; Weyer, Andy D; Lou, Shan; Bryman, Gregory S; Roberson, David P; Ghasemlou, Nader; Piccoli, Cara; Ahat, Ezgi; Wang, Victor; Cobos, Enrique J; Stucky, Cheryl L; Ma, Qiufu; Liberles, Stephen D; Woolf, Clifford J

    2014-01-01

    The somatosensory nervous system is critical for the organism's ability to respond to mechanical, thermal, and nociceptive stimuli. Somatosensory neurons are functionally and anatomically diverse but their molecular profiles are not well-defined. Here, we used transcriptional profiling to analyze the detailed molecular signatures of dorsal root ganglion (DRG) sensory neurons. We used two mouse reporter lines and surface IB4 labeling to purify three major non-overlapping classes of neurons: 1) IB4+SNS-Cre/TdTomato+, 2) IB4−SNS-Cre/TdTomato+, and 3) Parv-Cre/TdTomato+ cells, encompassing the majority of nociceptive, pruriceptive, and proprioceptive neurons. These neurons displayed distinct expression patterns of ion channels, transcription factors, and GPCRs. Highly parallel qRT-PCR analysis of 334 single neurons selected by membership of the three populations demonstrated further diversity, with unbiased clustering analysis identifying six distinct subgroups. These data significantly increase our knowledge of the molecular identities of known DRG populations and uncover potentially novel subsets, revealing the complexity and diversity of those neurons underlying somatosensation. DOI: http://dx.doi.org/10.7554/eLife.04660.001 PMID:25525749

  20. Gastric microbial community profiling reveals a dysbiotic cancer-associated microbiota

    Science.gov (United States)

    Pereira-Marques, Joana; Pinto-Ribeiro, Ines; Costa, Jose L; Carneiro, Fatima; Machado, Jose C

    2018-01-01

    Objective Gastric carcinoma development is triggered by Helicobacter pylori. Chronic H. pylori infection leads to reduced acid secretion, which may allow the growth of a different gastric bacterial community. This change in the microbiome may increase aggression to the gastric mucosa and contribute to malignancy. Our aim was to evaluate the composition of the gastric microbiota in chronic gastritis and in gastric carcinoma. Design The gastric microbiota was retrospectively investigated in 54 patients with gastric carcinoma and 81 patients with chronic gastritis by 16S rRNA gene profiling, using next-generation sequencing. Differences in microbial composition of the two patient groups were assessed using linear discriminant analysis effect size. Associations between the most relevant taxa and clinical diagnosis were validated by real-time quantitative PCR. Predictive functional profiling of microbial communities was obtained with PICRUSt. Results The gastric carcinoma microbiota was characterised by reduced microbial diversity, by decreased abundance of Helicobacter and by the enrichment of other bacterial genera, mostly represented by intestinal commensals. The combination of these taxa into a microbial dysbiosis index revealed that dysbiosis has excellent capacity to discriminate between gastritis and gastric carcinoma. Analysis of the functional features of the microbiota was compatible with the presence of a nitrosating microbial community in carcinoma. The major observations were confirmed in validation cohorts from different geographic origins. Conclusions Detailed analysis of the gastric microbiota revealed for the first time that patients with gastric carcinoma exhibit a dysbiotic microbial community with genotoxic potential, which is distinct from that of patients with chronic gastritis. PMID:29102920

  1. Metabolite Profiling of Peppers of Various Colors Reveals Relationships Between Tocopherol, Carotenoid, and Phytosterol Content.

    Science.gov (United States)

    Kim, Tae Jin; Choi, Jaehyuk; Kim, Kil Won; Ahn, Soon Kil; Ha, Sun-Hwa; Choi, Yongsoo; Park, Nam Il; Kim, Jae Kwang

    2017-12-01

    Peppers are widely consumed in Korea; the varietal development of peppers with increased content of beneficial plant metabolites is, therefore, of considerable interest. This requires a comprehensive understanding of the metabolic profile of pepper plants and the factors affecting this profile. To this end, we determined the content of various metabolites, such as hydrophilic and lipophilic compounds, phenolic acids, carotenoids, and capsaicinoids in peppers of various colors (green, red, pale green, and violet peppers) and in a high-pungency (green) pepper. We also performed principal component analysis (PCA), Pearson's correlation analysis, and hierarchical clustering analysis (HCA) to determine the relationships among these metabolites in peppers. PCA results indicated no significant variances among the 3 sample replicates. The HCA showed correlations between the metabolites resulting from common or closely linked biosynthesis pathways. Our results showed that carotenoids correlated positively with tocopherols and negatively with phytosterols; our findings also indicated a close relationship between the methylerythritol 4-phosphate and mevalonic acid biosynthesis pathways, providing evidence in favor of an earlier hypothesis regarding crosstalk across the chloroplast membrane. We, thus, demonstrate that metabolic profiling combined with multivariate analysis is a useful tool for analyzing metabolic networks. A total of 71 metabolites were measured in 5 peppers of different colors. The metabolic profiling with multivariate analysis revealed that tocopherol content had a positive correlation with the carotenoid content and a negative correlation with the phytosterol content. The results of this study may help in breeding programs to produce new germplasm with enhanced nutritional quality. © 2017 Institute of Food Technologists®.

  2. Bovine teat microbiome analysis revealed reduced alpha diversity and significant changes in taxonomic profiles in quarters with a history of mastitis

    Directory of Open Access Journals (Sweden)

    Helene eFalentin

    2016-04-01

    Full Text Available Mastitis is a mammary gland inflammatory disease often due to bacterial infections. Like many other infections, it used to be considered as a host-pathogen interaction driven by host and bacterial determinants. Until now, the involvement of the bovine mammary gland microbiota in the host-pathogen interaction has been poorly investigated, and mainly during the infectious episode. In this study, the bovine teat microbiome was investigated in 31 quarters corresponding to 27 animals, which were all free of inflammation at sampling time but which had different histories regarding mastitis: from no episode of mastitis on all the previous lactations (Healthy quarter, Hq to one or several clinical mastitis events (Mastitic quarter, Mq. Several quarters whose status was unclear (possible history of subclinical mastitis were classified as NDq. Total bacterial DNA was extracted from foremilk samples and swab samples of the teat canal. Taxonomic profiles were determined by pyrosequencing on 16s amplicons of the V3-4 region. Hq quarters showed a higher diversity compared to Mq ones (Shannon index: ~8 and 6, respectively. Clustering of the quarters based on their bacterial composition made it possible to separate Mq and Hq quarters into two separate clusters (C1 and C2, respectively. Discriminant analysis of taxonomic profiles between these clusters revealed several differences and allowed the identification of taxonomic markers in relation to mastitis history. C2 quarters were associated with a higher proportion of the Clostridia class (including genera such as Ruminococcus, Oscillospira, Roseburia, Dorea, etc., the Bacteroidetes phylum (Prevotella, Bacteroides, Paludibacter, etc., and the Bifidobacteriales order (Bifidobacterium, whereas C1 quarters showed a higher proportion of the Bacilli class (Staphylococcus and Chlamydiia class. These results indicate that microbiota is altered in udders which have already developed mastitis, even far from the

  3. Phenolic profiling of caffeic acid O-methyltransferase-deficient poplar reveals novel benzodioxane oligolignols.

    Science.gov (United States)

    Morreel, Kris; Ralph, John; Lu, Fachuang; Goeminne, Geert; Busson, Roger; Herdewijn, Piet; Goeman, Jan L; Van der Eycken, Johan; Boerjan, Wout; Messens, Eric

    2004-12-01

    Caffeic acid O-methyltransferase (COMT) catalyzes preferentially the methylation of 5-hydroxyconiferaldehyde to sinapaldehyde in monolignol biosynthesis. Here, we have compared HPLC profiles of the methanol-soluble phenolics fraction of xylem tissue from COMT-deficient and control poplars (Populus spp.), using statistical analysis of the peak heights. COMT down-regulation results in significant concentration differences for 25 of the 91 analyzed peaks. Eight peaks were exclusively detected in COMT-deficient poplar, of which four could be purified for further identification using mass spectrometry/mass spectrometry, nuclear magnetic resonance, and spiking of synthesized reference compounds. These new compounds were derived from 5-hydroxyconiferyl alcohol or 5-hydroxyconiferaldehyde and were characterized by benzodioxane moieties, a structural type that is also increased in the lignins of COMT-deficient plants. One of these four benzodioxanes amounted to the most abundant oligolignol in the HPLC profile. Furthermore, all of the differentially accumulating oligolignols involving sinapyl units were either reduced in abundance or undetectable. The concentration levels of all identified oligolignols were in agreement with the relative supply of monolignols and with their chemical coupling propensities, which supports the random coupling hypothesis. Chiral HPLC analysis of the most abundant benzodioxane dimer revealed the presence of both enantiomers in equal amounts, indicating that they were formed by radical coupling reactions under simple chemical control rather than guided by dirigent proteins.

  4. Global Transcription Profiling Reveals Comprehensive Insights into Hypoxic Response in Arabidopsis1[w

    Science.gov (United States)

    Liu, Fenglong; VanToai, Tara; Moy, Linda P.; Bock, Geoffrey; Linford, Lara D.; Quackenbush, John

    2005-01-01

    Plants have evolved adaptation mechanisms to sense oxygen deficiency in their environments and make coordinated physiological and structural adjustments to enhance their hypoxic tolerance. To gain insight into how plants respond to low-oxygen stress, gene expression profiling using whole-genome DNA amplicon microarrays was carried out at seven time points over 24 h, in wild-type and transgenic PSAG12:ipt Arabidopsis (Arabidopsis thaliana) plants under normoxic and hypoxic conditions. Transcript levels of genes involved in glycolysis and fermentation pathways, ethylene synthesis and perception, calcium signaling, nitrogen utilization, trehalose metabolism, and alkaloid synthesis were significantly altered in response to oxygen limitation. Analysis based on gene ontology assignments suggested a significant down-regulation of genes whose functions are associated with cell walls, nucleosome structures, water channels, and ion transporters and a significant up-regulation of genes involved in transcriptional regulation, protein kinase activity, and auxin responses under conditions of oxygen shortage. Promoter analysis on a cluster of up-regulated genes revealed a significant overrepresentation of the AtMYB2-binding motif (GT motif), a sugar response element-like motif, and a G-box-related sequence, and also identified several putative anaerobic response elements. Finally, quantitative real-time polymerase chain reactions using 29 selected genes independently verified the microarray results. This study represents one of the most comprehensive analyses conducted to date investigating hypoxia-responsive transcriptional networks in plants. PMID:15734912

  5. Metabolomic profiling reveals deep chemical divergence between two morphotypes of the zoanthid Parazoanthus axinellae

    Science.gov (United States)

    Cachet, Nadja; Genta-Jouve, Grégory; Ivanisevic, Julijana; Chevaldonné, Pierre; Sinniger, Frédéric; Culioli, Gérald; Pérez, Thierry; Thomas, Olivier P.

    2015-01-01

    Metabolomics has recently proven its usefulness as complementary tool to traditional morphological and genetic analyses for the classification of marine invertebrates. Among the metabolite-rich cnidarian order Zoantharia, Parazoanthus is a polyphyletic genus whose systematics and phylogeny remain controversial. Within this genus, one of the most studied species, Parazoanthus axinellae is prominent in rocky shallow waters of the Mediterranean Sea and the NE Atlantic Ocean. Although different morphotypes can easily be distinguished, only one species is recognized to date. Here, a metabolomic profiling approach has been used to assess the chemical diversity of two main Mediterranean morphotypes, the “slender” and “stocky” forms of P. axinellae. Targeted profiling of their major secondary metabolites revealed a significant chemical divergence between the morphotypes. While zoanthoxanthin alkaloids and ecdysteroids are abundant in both morphs, the “slender” morphotype is characterized by the presence of additional and bioactive 3,5-disubstituted hydantoin derivatives named parazoanthines. The absence of these specific compounds in the “stocky” morphotype was confirmed by spatial and temporal monitoring over an annual cycle. Moreover, specimens of the “slender” morphotype are also the only ones found as epibionts of several sponge species, particularly Cymbaxinella damicornis thus suggesting a putative ecological link. PMID:25655432

  6. Comparative genomic analysis of Lactobacillus plantarum ZJ316 reveals its genetic adaptation and potential probiotic profiles.

    Science.gov (United States)

    Li, Ping; Li, Xuan; Gu, Qing; Lou, Xiu-Yu; Zhang, Xiao-Mei; Song, Da-Feng; Zhang, Chen

    2016-08-01

    In previous studies, Lactobacillus plantarum ZJ316 showed probiotic properties, such as antimicrobial activity against various pathogens and the capacity to significantly improve pig growth and pork quality. The purpose of this study was to reveal the genes potentially related to its genetic adaptation and probiotic profiles based on comparative genomic analysis. The genome sequence of L. plantarum ZJ316 was compared with those of eight L. plantarum strains deposited in GenBank. BLASTN, Mauve, and MUMmer programs were used for genome alignment and comparison. CRISPRFinder was applied for searching the clustered regularly interspaced short palindromic repeats (CRISPRs). We identified genes that encode proteins related to genetic adaptation and probiotic profiles, including carbohydrate transport and metabolism, proteolytic enzyme systems and amino acid biosynthesis, CRISPR adaptive immunity, stress responses, bile salt resistance, ability to adhere to the host intestinal wall, exopolysaccharide (EPS) biosynthesis, and bacteriocin biosynthesis. Comparative characterization of the L. plantarum ZJ316 genome provided the genetic basis for further elucidating the functional mechanisms of its probiotic properties. ZJ316 could be considered a potential probiotic candidate.

  7. Comparative genomic analysis of Lactobacillus plantarum ZJ316 reveals its genetic adaptation and potential probiotic profiles* #

    Science.gov (United States)

    Li, Ping; Li, Xuan; Gu, Qing; Lou, Xiu-yu; Zhang, Xiao-mei; Song, Da-feng; Zhang, Chen

    2016-01-01

    Objective: In previous studies, Lactobacillus plantarum ZJ316 showed probiotic properties, such as antimicrobial activity against various pathogens and the capacity to significantly improve pig growth and pork quality. The purpose of this study was to reveal the genes potentially related to its genetic adaptation and probiotic profiles based on comparative genomic analysis. Methods: The genome sequence of L. plantarum ZJ316 was compared with those of eight L. plantarum strains deposited in GenBank. BLASTN, Mauve, and MUMmer programs were used for genome alignment and comparison. CRISPRFinder was applied for searching the clustered regularly interspaced short palindromic repeats (CRISPRs). Results: We identified genes that encode proteins related to genetic adaptation and probiotic profiles, including carbohydrate transport and metabolism, proteolytic enzyme systems and amino acid biosynthesis, CRISPR adaptive immunity, stress responses, bile salt resistance, ability to adhere to the host intestinal wall, exopolysaccharide (EPS) biosynthesis, and bacteriocin biosynthesis. Conclusions: Comparative characterization of the L. plantarum ZJ316 genome provided the genetic basis for further elucidating the functional mechanisms of its probiotic properties. ZJ316 could be considered a potential probiotic candidate. PMID:27487802

  8. Genetic networks of liver metabolism revealed by integration of metabolic and transcriptional profiling.

    Directory of Open Access Journals (Sweden)

    Christine T Ferrara

    2008-03-01

    Full Text Available Although numerous quantitative trait loci (QTL influencing disease-related phenotypes have been detected through gene mapping and positional cloning, identification of the individual gene(s and molecular pathways leading to those phenotypes is often elusive. One way to improve understanding of genetic architecture is to classify phenotypes in greater depth by including transcriptional and metabolic profiling. In the current study, we have generated and analyzed mRNA expression and metabolic profiles in liver samples obtained in an F2 intercross between the diabetes-resistant C57BL/6 leptin(ob/ob and the diabetes-susceptible BTBR leptin(ob/ob mouse strains. This cross, which segregates for genotype and physiological traits, was previously used to identify several diabetes-related QTL. Our current investigation includes microarray analysis of over 40,000 probe sets, plus quantitative mass spectrometry-based measurements of sixty-seven intermediary metabolites in three different classes (amino acids, organic acids, and acyl-carnitines. We show that liver metabolites map to distinct genetic regions, thereby indicating that tissue metabolites are heritable. We also demonstrate that genomic analysis can be integrated with liver mRNA expression and metabolite profiling data to construct causal networks for control of specific metabolic processes in liver. As a proof of principle of the practical significance of this integrative approach, we illustrate the construction of a specific causal network that links gene expression and metabolic changes in the context of glutamate metabolism, and demonstrate its validity by showing that genes in the network respond to changes in glutamine and glutamate availability. Thus, the methods described here have the potential to reveal regulatory networks that contribute to chronic, complex, and highly prevalent diseases and conditions such as obesity and diabetes.

  9. Signalling pathways involved in adult heart formation revealed by gene expression profiling in Drosophila.

    Directory of Open Access Journals (Sweden)

    Bruno Zeitouni

    2007-10-01

    Full Text Available Drosophila provides a powerful system for defining the complex genetic programs that drive organogenesis. Under control of the steroid hormone ecdysone, the adult heart in Drosophila forms during metamorphosis by a remodelling of the larval cardiac organ. Here, we evaluated the extent to which transcriptional signatures revealed by genomic approaches can provide new insights into the molecular pathways that underlie heart organogenesis. Whole-genome expression profiling at eight successive time-points covering adult heart formation revealed a highly dynamic temporal map of gene expression through 13 transcript clusters with distinct expression kinetics. A functional atlas of the transcriptome profile strikingly points to the genomic transcriptional response of the ecdysone cascade, and a sharp regulation of key components belonging to a few evolutionarily conserved signalling pathways. A reverse genetic analysis provided evidence that these specific signalling pathways are involved in discrete steps of adult heart formation. In particular, the Wnt signalling pathway is shown to participate in inflow tract and cardiomyocyte differentiation, while activation of the PDGF-VEGF pathway is required for cardiac valve formation. Thus, a detailed temporal map of gene expression can reveal signalling pathways responsible for specific developmental programs and provides here substantial grasp into heart formation.

  10. Paralytic toxin profile of the marine dinoflagellate Gymnodinium catenatum Graham from the Mexican Pacific as revealed by LC-MS/MS.

    Science.gov (United States)

    Bustillos-Guzmán, José J; Band-Schmidt, Christine J; Durán-Riveroll, Lorena M; Hernández-Sandoval, Francisco E; López-Cortés, David J; Núñez-Vázquez, Erick J; Cembella, Allan; Krock, Bernd

    2015-01-01

    The paralytic shellfish toxin (PST) profiles of Gymnodinium catenatum Graham have been reported for several strains from the Pacific coast of Mexico cultured under different laboratory conditions, as well as from natural populations. Up to 15 saxitoxin analogues occurred and the quantity of each toxin depended on the growth phase and culture conditions. Previous analysis of toxin profiles of G. catenatum isolated from Mexico have been based on post-column oxidation liquid chromatography with fluorescence detection (LC-FLD), a method prone to artefacts and non-specificity, leading to misinterpretation of toxin composition. We describe, for the first time, the complete toxin profile for several G. catenatum strains from diverse locations of the Pacific coast of Mexico. The new results confirmed previous reports on the dominance of the less potent sulfocarbamoyl toxins (C1/2); significant differences, however, in the composition (e.g., absence of saxitoxin, gonyautoxin 2/3 and neosaxitoxin) were revealed in our confirmatory analysis. The LC-MS/MS analyses also indicated at least seven putative benzoyl toxin analogues and provided support for their existence. This new toxin profile shows a high similarity (> 80%) to the profiles reported from several regions around the world, suggesting low genetic variability among global populations.

  11. In vivo transcriptional profile analysis reveals RNA splicing and chromatin remodeling as prominent processes for adult neurogenesis.

    Science.gov (United States)

    Lim, Daniel A; Suárez-Fariñas, Mayte; Naef, Felix; Hacker, Coleen R; Menn, Benedicte; Takebayashi, Hirohide; Magnasco, Marcelo; Patil, Nila; Alvarez-Buylla, Arturo

    2006-01-01

    Neural stem cells and neurogenesis persist in the adult mammalian brain subventricular zone (SVZ). Cells born in the rodent SVZ migrate to the olfactory bulb (Ob) where they differentiate into interneurons. To determine the gene expression and functional profile of SVZ neurogenesis, we performed three complementary sets of transcriptional analysis experiments using Affymetrix GeneChips: (1) comparison of adult mouse SVZ and Ob gene expression profiles with those of the striatum, cerebral cortex, and hippocampus; (2) profiling of SVZ stem cells and ependyma isolated by fluorescent-activated cell sorting (FACS); and (3) analysis of gene expression changes during in vivo SVZ regeneration after anti-mitotic treatment. Gene Ontology (GO) analysis of data from these three separate approaches showed that in adult SVZ neurogenesis, RNA splicing and chromatin remodeling are biological processes as statistically significant as cell proliferation, transcription, and neurogenesis. In non-neurogenic brain regions, RNA splicing and chromatin remodeling were not prominent processes. Fourteen mRNA splicing factors including Sf3b1, Sfrs2, Lsm4, and Khdrbs1/Sam68 were detected along with 9 chromatin remodeling genes including Mll, Bmi1, Smarcad1, Baf53a, and Hat1. We validated the transcriptional profile data with Northern blot analysis and in situ hybridization. The data greatly expand the catalogue of cell cycle components, transcription factors, and migration genes for adult SVZ neurogenesis and reveal RNA splicing and chromatin remodeling as prominent biological processes for these germinal cells.

  12. Coral transcriptome and bacterial community profiles reveal distinct Yellow Band Disease states in Orbicella faveolata

    KAUST Repository

    Closek, Collin J.

    2014-06-20

    Coral diseases impact reefs globally. Although we continue to describe diseases, little is known about the etiology or progression of even the most common cases. To examine a spectrum of coral health and determine factors of disease progression we examined Orbicella faveolata exhibiting signs of Yellow Band Disease (YBD), a widespread condition in the Caribbean. We used a novel combined approach to assess three members of the coral holobiont: the coral-host, associated Symbiodinium algae, and bacteria. We profiled three conditions: (1) healthy-appearing colonies (HH), (2) healthy-appearing tissue on diseased colonies (HD), and (3) diseased lesion (DD). Restriction fragment length polymorphism analysis revealed health state-specific diversity in Symbiodinium clade associations. 16S ribosomal RNA gene microarrays (PhyloChips) and O. faveolata complimentary DNA microarrays revealed the bacterial community structure and host transcriptional response, respectively. A distinct bacterial community structure marked each health state. Diseased samples were associated with two to three times more bacterial diversity. HD samples had the highest bacterial richness, which included components associated with HH and DD, as well as additional unique families. The host transcriptome under YBD revealed a reduced cellular expression of defense- and metabolism-related processes, while the neighboring HD condition exhibited an intermediate expression profile. Although HD tissue appeared visibly healthy, the microbial communities and gene expression profiles were distinct. HD should be regarded as an additional (intermediate) state of disease, which is important for understanding the progression of YBD. © 2014 International Society for Microbial Ecology. All rights reserved.

  13. Multitaxon activity profiling reveals differential microbial response to reduced seawater pH and oil pollution.

    Science.gov (United States)

    Coelho, Francisco J R C; Cleary, Daniel F R; Costa, Rodrigo; Ferreira, Marina; Polónia, Ana R M; Silva, Artur M S; Simões, Mário M Q; Oliveira, Vanessa; Gomes, Newton C M

    2016-09-01

    There is growing concern that predicted changes to global ocean chemistry will interact with anthropogenic pollution to significantly alter marine microbial composition and function. However, knowledge of the compounding effects of climate change stressors and anthropogenic pollution is limited. Here, we used 16S and 18S rRNA (cDNA)-based activity profiling to investigate the differential responses of selected microbial taxa to ocean acidification and oil hydrocarbon contamination under controlled laboratory conditions. Our results revealed that a lower relative abundance of sulphate-reducing bacteria (Desulfosarcina/Desulfococcus clade) due to an adverse effect of seawater acidification and oil hydrocarbon contamination (reduced pH-oil treatment) may be coupled to changes in sediment archaeal communities. In particular, we observed a pronounced compositional shift and marked reduction in the prevalence of otherwise abundant operational taxonomic units (OTUs) belonging to the archaeal Marine Benthic Group B and Marine Hydrothermal Vent Group (MHVG) in the reduced pH-oil treatment. Conversely, the abundance of several putative hydrocarbonoclastic fungal OTUs was higher in the reduced pH-oil treatment. Sediment hydrocarbon profiling, furthermore, revealed higher concentrations of several alkanes in the reduced pH-oil treatment, corroborating the functional implications of the structural changes to microbial community composition. Collectively, our results advance the understanding of the response of a complex microbial community to the interaction between reduced pH and anthropogenic pollution. In future acidified marine environments, oil hydrocarbon contamination may alter the typical mixotrophic and k-/r-strategist composition of surface sediment microbiomes towards a more heterotrophic state with lower doubling rates, thereby impairing the ability of the ecosystem to recover from acute oil contamination events. © 2016 John Wiley & Sons Ltd.

  14. Melodic multi-feature paradigm reveals auditory profiles in music-sound encoding

    Directory of Open Access Journals (Sweden)

    Mari eTervaniemi

    2014-07-01

    Full Text Available Musical expertise modulates preattentive neural sound discrimination. However, this evidence up to great extent originates from paradigms using very simple stimulation. Here we use a novel melody paradigm (revealing the auditory profile for six sound parameters in parallel to compare memory-related MMN and attention-related P3a responses recorded from non-musicians and Finnish Folk musicians. MMN emerged in both groups of participants for all sound changes (except for rhythmic changes in non-musicians. In Folk musicians, the MMN was enlarged for mistuned sounds when compared with non-musicians. This is taken to reflect their familiarity with pitch information which is in key position in Finnish folk music when compared with e.g., rhythmic information. The MMN was followed by P3a after timbre changes, rhythm changes, and melody transposition. The MMN and P3a topographies differentiated the groups for all sound changes. Thus, the melody paradigm offers a fast and cost-effective means for determining the auditory profile for music-sound encoding and also, importantly, for probing the effects of musical expertise on it.

  15. Melodic multi-feature paradigm reveals auditory profiles in music-sound encoding.

    Science.gov (United States)

    Tervaniemi, Mari; Huotilainen, Minna; Brattico, Elvira

    2014-01-01

    Musical expertise modulates preattentive neural sound discrimination. However, this evidence up to great extent originates from paradigms using very simple stimulation. Here we use a novel melody paradigm (revealing the auditory profile for six sound parameters in parallel) to compare memory-related mismatch negativity (MMN) and attention-related P3a responses recorded from non-musicians and Finnish Folk musicians. MMN emerged in both groups of participants for all sound changes (except for rhythmic changes in non-musicians). In Folk musicians, the MMN was enlarged for mistuned sounds when compared with non-musicians. This is taken to reflect their familiarity with pitch information which is in key position in Finnish folk music when compared with e.g., rhythmic information. The MMN was followed by P3a after timbre changes, rhythm changes, and melody transposition. The MMN and P3a topographies differentiated the groups for all sound changes. Thus, the melody paradigm offers a fast and cost-effective means for determining the auditory profile for music-sound encoding and also, importantly, for probing the effects of musical expertise on it.

  16. Phenolic Profiling of Caffeic Acid O-Methyltransferase-Deficient Poplar Reveals Novel Benzodioxane Oligolignols1

    Science.gov (United States)

    Morreel, Kris; Ralph, John; Lu, Fachuang; Goeminne, Geert; Busson, Roger; Herdewijn, Piet; Goeman, Jan L.; Van der Eycken, Johan; Boerjan, Wout; Messens, Eric

    2004-01-01

    Caffeic acid O-methyltransferase (COMT) catalyzes preferentially the methylation of 5-hydroxyconiferaldehyde to sinapaldehyde in monolignol biosynthesis. Here, we have compared HPLC profiles of the methanol-soluble phenolics fraction of xylem tissue from COMT-deficient and control poplars (Populus spp.), using statistical analysis of the peak heights. COMT down-regulation results in significant concentration differences for 25 of the 91 analyzed peaks. Eight peaks were exclusively detected in COMT-deficient poplar, of which four could be purified for further identification using mass spectrometry/mass spectrometry, nuclear magnetic resonance, and spiking of synthesized reference compounds. These new compounds were derived from 5-hydroxyconiferyl alcohol or 5-hydroxyconiferaldehyde and were characterized by benzodioxane moieties, a structural type that is also increased in the lignins of COMT-deficient plants. One of these four benzodioxanes amounted to the most abundant oligolignol in the HPLC profile. Furthermore, all of the differentially accumulating oligolignols involving sinapyl units were either reduced in abundance or undetectable. The concentration levels of all identified oligolignols were in agreement with the relative supply of monolignols and with their chemical coupling propensities, which supports the random coupling hypothesis. Chiral HPLC analysis of the most abundant benzodioxane dimer revealed the presence of both enantiomers in equal amounts, indicating that they were formed by radical coupling reactions under simple chemical control rather than guided by dirigent proteins. PMID:15563622

  17. What Do Women's Advertised Mate Preferences Reveal? An Analysis of Video Dating Profiles

    Directory of Open Access Journals (Sweden)

    Cari D. Goetz

    2013-04-01

    Full Text Available This study examined women's video dating profiles to determine what their advertised mate preferences revealed about their mate value and relationship interests. Women created a one-minute long video dating profile for a hypothetical dating website. The videos were content analyzed into four categories of stated mate preferences: 1 “good genes” indicators 2 good resource investment potential indicators 3 good parenting indicators and 4 good partner indicators. Long-term mating interest was positively correlated with describing good partner indicators and self-perceived mate value was positively correlated with describing good genes indicators. Short-term mating interest was negatively correlated with describing any mate preferences while attractiveness was positively correlated with doing so. Results suggest that women's advertised mate preferences provide clues to their underlying relationship interests and mate value.

  18. Gene expression profiling reveals new potential players of gonad differentiation in the chicken embryo.

    Directory of Open Access Journals (Sweden)

    Gwenn-Aël Carré

    Full Text Available BACKGROUND: In birds as in mammals, a genetic switch determines whether the undifferentiated gonad develops into an ovary or a testis. However, understanding of the molecular pathway(s involved in gonad differentiation is still incomplete. METHODOLOGY/PRINCIPAL FINDINGS: With the aim of improving characterization of the molecular pathway(s involved in gonad differentiation in the chicken embryo, we developed a large scale real time reverse transcription polymerase chain reaction approach on 110 selected genes for evaluation of their expression profiles during chicken gonad differentiation between days 5.5 and 19 of incubation. Hierarchical clustering analysis of the resulting datasets discriminated gene clusters expressed preferentially in the ovary or the testis, and/or at early or later periods of embryonic gonad development. Fitting a linear model and testing the comparisons of interest allowed the identification of new potential actors of gonad differentiation, such as Z-linked ADAMTS12, LOC427192 (corresponding to NIM1 protein and CFC1, that are upregulated in the developing testis, and BMP3 and Z-linked ADAMTSL1, that are preferentially expressed in the developing ovary. Interestingly, the expression patterns of several members of the transforming growth factor β family were sexually dimorphic, with inhibin subunits upregulated in the testis, and bone morphogenetic protein subfamily members including BMP2, BMP3, BMP4 and BMP7, upregulated in the ovary. This study also highlighted several genes displaying asymmetric expression profiles such as GREM1 and BMP3 that are potentially involved in different aspects of gonad left-right asymmetry. CONCLUSION/SIGNIFICANCE: This study supports the overall conservation of vertebrate sex differentiation pathways but also reveals some particular feature of gene expression patterns during gonad development in the chicken. In particular, our study revealed new candidate genes which may be potential actors

  19. Gene Expression Profiling Reveals New Potential Players of Gonad Differentiation in the Chicken Embryo

    Science.gov (United States)

    Carré, Gwenn-Aël; Couty, Isabelle; Hennequet-Antier, Christelle; Govoroun, Marina S.

    2011-01-01

    Background In birds as in mammals, a genetic switch determines whether the undifferentiated gonad develops into an ovary or a testis. However, understanding of the molecular pathway(s) involved in gonad differentiation is still incomplete. Methodology/Principal Findings With the aim of improving characterization of the molecular pathway(s) involved in gonad differentiation in the chicken embryo, we developed a large scale real time reverse transcription polymerase chain reaction approach on 110 selected genes for evaluation of their expression profiles during chicken gonad differentiation between days 5.5 and 19 of incubation. Hierarchical clustering analysis of the resulting datasets discriminated gene clusters expressed preferentially in the ovary or the testis, and/or at early or later periods of embryonic gonad development. Fitting a linear model and testing the comparisons of interest allowed the identification of new potential actors of gonad differentiation, such as Z-linked ADAMTS12, LOC427192 (corresponding to NIM1 protein) and CFC1, that are upregulated in the developing testis, and BMP3 and Z-linked ADAMTSL1, that are preferentially expressed in the developing ovary. Interestingly, the expression patterns of several members of the transforming growth factor β family were sexually dimorphic, with inhibin subunits upregulated in the testis, and bone morphogenetic protein subfamily members including BMP2, BMP3, BMP4 and BMP7, upregulated in the ovary. This study also highlighted several genes displaying asymmetric expression profiles such as GREM1 and BMP3 that are potentially involved in different aspects of gonad left-right asymmetry. Conclusion/Significance This study supports the overall conservation of vertebrate sex differentiation pathways but also reveals some particular feature of gene expression patterns during gonad development in the chicken. In particular, our study revealed new candidate genes which may be potential actors of chicken gonad

  20. Comprehensive Lipidome-Wide Profiling Reveals Dynamic Changes of Tea Lipids during Manufacturing Process of Black Tea.

    Science.gov (United States)

    Li, Jia; Hua, Jinjie; Zhou, Qinghua; Dong, Chunwang; Wang, Jinjin; Deng, Yuliang; Yuan, Haibo; Jiang, Yongwen

    2017-11-22

    As important biomolecules in Camellia sinensis L., lipids undergo substantial changes during black tea manufacture, which is considered to contribute to tea sensory quality. However, limited by analytical capacity, detailed lipid composition and its dynamic changes during black tea manufacture remain unclear. Herein, we performed tea lipidome profiling using high resolution liquid chromatography coupled to mass spectrometry (LC-MS), which allows simultaneous and robust analysis of 192 individual lipid species in black tea, covering 17 (sub)classes. Furthermore, dynamic changes of tea lipids during black tea manufacture were investigated. Significant alterations of lipid pattern were revealed, involved with chlorophyll degradation, metabolic pathways of glycoglycerolipids, and other extraplastidial membrane lipids. To our knowledge, this report presented most comprehensive coverage of lipid species in black tea. This study provides a global and in-depth metabolic map of tea lipidome during black tea manufacture.

  1. Embryonic stem cell-like features of testicular carcinoma in situ revealed by genome-wide gene expression profiling

    DEFF Research Database (Denmark)

    Almstrup, Kristian; Hoei-Hansen, Christina E; Wirkner, Ute

    2004-01-01

    in their stoichiometry on progression into embryonic carcinoma. We compared the CIS expression profile with patterns reported in embryonic stem cells (ESCs), which revealed a substantial overlap that may be as high as 50%. We also demonstrated an over-representation of expressed genes in regions of 17q and 12, reported......Carcinoma in situ (CIS) is the common precursor of histologically heterogeneous testicular germ cell tumors (TGCTs), which in recent decades have markedly increased and now are the most common malignancy of young men. Using genome-wide gene expression profiling, we identified >200 genes highly...

  2. The Genetic Relationship between Leishmania aethiopica and Leishmania tropica Revealed by Comparing Microsatellite Profiles.

    Science.gov (United States)

    Krayter, Lena; Schnur, Lionel F; Schönian, Gabriele

    2015-01-01

    Leishmania (Leishmania) aethiopica and L. (L.) tropica cause cutaneous leishmaniases and appear to be related. L. aethiopica is geographically restricted to Ethiopia and Kenya; L. tropica is widely dispersed from the Eastern Mediterranean, through the Middle East into eastern India and in north, east and south Africa. Their phylogenetic inter-relationship is only partially revealed. Some studies indicate a close relationship. Here, eight strains of L. aethiopica were characterized genetically and compared with 156 strains of L. tropica from most of the latter species' geographical range to discern the closeness. Twelve unlinked microsatellite markers previously used to genotype strains of L. tropica were successfully applied to the eight strains of L. aethiopica and their microsatellite profiles were compared to those of 156 strains of L. tropica from various geographical locations that were isolated from human cases of cutaneous and visceral leishmaniasis, hyraxes and sand fly vectors. All the microsatellite profiles were subjected to various analytical algorithms: Bayesian statistics, distance-based and factorial correspondence analysis, revealing: (i) the species L. aethiopica, though geographically restricted, is genetically very heterogeneous; (ii) the strains of L. aethiopica formed a distinct genetic cluster; and (iii) strains of L. aethiopica are closely related to strains of L. tropica and more so to the African ones, although, by factorial correspondence analysis, clearly separate from them. The successful application of the 12 microsatellite markers, originally considered species-specific for the species L. tropica, to strains of L. aethiopica confirmed the close relationship between these two species. The Bayesian and distance-based methods clustered the strains of L. aethiopica among African strains of L. tropica, while the factorial correspondence analysis indicated a clear separation between the two species. There was no correlation between

  3. Dietary Inulin Supplementation Modifies Significantly the Liver Transcriptomic Profile of Broiler Chickens

    Science.gov (United States)

    Sevane, Natalia; Bialade, Federica; Velasco, Susana; Rebolé, Almudena; Rodríguez, Maria Luisa; Ortiz, Luís T.; Cañón, Javier; Dunner, Susana

    2014-01-01

    Inclusion of prebiotics in the diet is known to be advantageous, with positive influences both on health and growth. The current study investigated the differences in the hepatic transcriptome profiles between chickens supplemented with inulin (a storage carbohydrate found in many plants) and controls. Liver is a major metabolic organ and has been previously reported to be involved in the modification of the lipid metabolism in chickens fed with inulin. A nutrigenomic approach through the analysis of liver RNA hybridized to the Affymetrix GeneChip Chicken Genome Array identified 148 differentially expressed genes among both groups: 104 up-regulated (≥1.4-fold) and 44 down-regulated (≤0.6-fold). Quantitative real-time PCR analysis validated the microarray expression results for five out of seven genes tested. The functional annotation analyses revealed a number of genes, processes and pathways with putative involvement in chicken growth and performance, while reinforcing the immune status of animals, and fostering the production of long chain fatty acids in broilers supplemented with 5 g of inulin kg−1 diet. As far as we are aware, this is the first report of a microarray based gene expression study on the effect of dietary inulin supplementation, supporting further research on the use of this prebiotic on chicken diets as a useful alternative to antibiotics for improving performance and general immunity in poultry farming, along with a healthier meat lipid profile. PMID:24915441

  4. Glycoprotein profiles of macrophages at different stages of activation as revealed by lectin binding after electrophoretic separation.

    Science.gov (United States)

    Irimura, T; North, S M; Nicolson, G L

    1987-01-01

    Glycoprotein profiles of rat macrophages (M phi) at different stages of activation were studied by examining the reactivity of various lectins to the glycoproteins separated by polyacrylamide gel electrophoresis. Ricinus communis agglutinin 1 (RCA1) revealed several components including glycoproteins of Mr 160 kDa and 65 kDa prominent in resident M phi. A pokeweed mitogen (PWM) isolectin, Pa-4, recognizes branched poly(N-acetyllactosamine)-type carbohydrate chains, and revealed a significant increase in glycoproteins of Mr ranging from 70 kDa to 150 kDa on thioglycolate-elicited M phi. Increased reactivity of PWM to thioglycolate-elicited M phi was observed by direct binding of 125I-labeled Pa-4 to intact or glutaraldehyde-fixed M phi. Histochemical staining of formaldehyde-fixed M phi in vitro with biotinylated Pa-4 was consistent with the gel analysis, that is, resident M phi had no reactivity while thioglycolate-elicited M phi showed slight reactivity. Alveolar and intratumoral M phi bound more Pa-4 than resident or thioglycolate-elicited M phi. The PWM isolectin may therefore serve as a marker for an early stage of M phi activation.

  5. SIGNIFICANCE OF THYROID PROFILE (Serum T3, T4 & TSH IN INFERTILE WOMEN

    Directory of Open Access Journals (Sweden)

    Bindu Sharma

    2012-06-01

    Full Text Available Objective: To evaluate the relation of female infertility to thyroid dysfunction. Material & Methods: The present study was carried out in the department of Biochemistry in collaboration with the Gynae & Obst deptt., Subharti Medical College & Hospital Meerut. Serum T3, T4 and TSH estimation was done by Enzyme Linked Fluorescent Assay. Results: Serum T3 level in control group was 1.8 ± 0.64 nmol/L while it was 10.5 ± 0.5 nmol/L in hyperthyroid (p value 0.05, i.e., not significant. Serum TSH in control group was 3.5 ± 1.71 mIU/L, while it was 0.14 ± 0.01 mIU/L (p value <0.001, i.e., highly significant in hyperthyroidism, 8.4 ± 1.06 mIU/L in hypothyroidism (p value <0.001, i.e., highly significant. Out of 65 patients of study group thyroid dysfunction was associated with 25 (38.5% infertile women. 23 (35.4% women had hypothyroidism, 2 (3.1% women had hyperthyroidism and 40 women (61.5% were with euthyroid state, while in control group all the 25 women had euthyroid profile. Conclusions: Every infertile woman with ovulatory dysfunction should also investigated thyroid profile along with other investigations, to open better prospects of conception for such desperate infertile women.

  6. Mutational Profiling of Malignant Mesothelioma Revealed Potential Therapeutic Targets in EGFR and NRAS

    Directory of Open Access Journals (Sweden)

    Jeong Eun Kim

    2018-04-01

    Full Text Available Pemetrexed and platinum (PP combination chemotherapy is the current standard first-line therapy for treatment of malignant mesothelioma (MM. However, a useful predictive biomarker for PP therapy is yet to be found. Here, we performed targeted exome sequencing to profile somatic mutations and copy number variations in 12 MM patients treated with PP therapy. We identified 187 somatic mutations in 12 patients (65 synonymous, 102 missense, 2 nonsense, 5 splice site, and 13 small coding insertions/deletions. We identified somatic mutations in 23 genes including BAP1, TP53, NRAS, and EGFR. Interestingly, rare NRAS p.Q61K and EGFR exon 19 deletions were observed in 2 patients. We also found somatic chromosomal copy number deletions in CDKN2A and CDKN2B genes. Genetic alteration related to response after PP therapy was not found. Somatic mutation profiling in MM patients receiving PP therapy revealed genetic alterations in potential therapeutic targets such as NRAS and EGFR. No alterations in genes with potential predictive role for PP therapy were found.

  7. Mutational Profiling of Malignant Mesothelioma Revealed Potential Therapeutic Targets in EGFR and NRAS.

    Science.gov (United States)

    Kim, Jeong Eun; Kim, Deokhoon; Hong, Yong Sang; Kim, Kyu-Pyo; Yoon, Young Kwang; Lee, Dae Ho; Kim, Sang-We; Chun, Sung-Min; Jang, Se Jin; Kim, Tae Won

    2018-04-01

    Pemetrexed and platinum (PP) combination chemotherapy is the current standard first-line therapy for treatment of malignant mesothelioma (MM). However, a useful predictive biomarker for PP therapy is yet to be found. Here, we performed targeted exome sequencing to profile somatic mutations and copy number variations in 12 MM patients treated with PP therapy. We identified 187 somatic mutations in 12 patients (65 synonymous, 102 missense, 2 nonsense, 5 splice site, and 13 small coding insertions/deletions). We identified somatic mutations in 23 genes including BAP1, TP53, NRAS, and EGFR. Interestingly, rare NRAS p.Q61K and EGFR exon 19 deletions were observed in 2 patients. We also found somatic chromosomal copy number deletions in CDKN2A and CDKN2B genes. Genetic alteration related to response after PP therapy was not found. Somatic mutation profiling in MM patients receiving PP therapy revealed genetic alterations in potential therapeutic targets such as NRAS and EGFR. No alterations in genes with potential predictive role for PP therapy were found. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  8. Multi-Omics Analysis Reveals a Correlation between the Host Phylogeny, Gut Microbiota and Metabolite Profiles in Cyprinid Fishes

    Science.gov (United States)

    Li, Tongtong; Long, Meng; Li, Huan; Gatesoupe, François-Joël; Zhang, Xujie; Zhang, Qianqian; Feng, Dongyue; Li, Aihua

    2017-01-01

    Gut microbiota play key roles in host nutrition and metabolism. However, little is known about the relationship between host genetics, gut microbiota and metabolic profiles. Here, we used high-throughput sequencing and gas chromatography/mass spectrometry approaches to characterize the microbiota composition and the metabolite profiles in the gut of five cyprinid fish species with three different feeding habits raised under identical husbandry conditions. Our results showed that host species and feeding habits significantly affect not only gut microbiota composition but also metabolite profiles (ANOSIM, p ≤ 0.05). Mantel test demonstrated that host phylogeny, gut microbiota, and metabolite profiles were significantly related to each other (p ≤ 0.05). Additionally, the carps with the same feeding habits had more similarity in gut microbiota composition and metabolite profiles. Various metabolites were correlated positively with bacterial taxa involved in food degradation. Our results shed new light on the microbiome and metabolite profiles in the gut content of cyprinid fishes, and highlighted the correlations between host genotype, fish gut microbiome and putative functions, and gut metabolite profiles. PMID:28367147

  9. Melodic multi-feature paradigm reveals auditory profiles in music-sound encoding

    DEFF Research Database (Denmark)

    Tervaniemi, Mari; Huotilainen, Minna; Brattico, Elvira

    2014-01-01

    Musical expertise modulates preattentive neural sound discrimination. However, this evidence up to great extent originates from paradigms using very simple stimulation. Here we use a novel melody paradigm (revealing the auditory profile for six sound parameters in parallel) to compare memory......-related mismatch negativity (MMN) and attention-related P3a responses recorded from non-musicians and Finnish Folk musicians. MMN emerged in both groups of participants for all sound changes (except for rhythmic changes in non-musicians). In Folk musicians, the MMN was enlarged for mistuned sounds when compared...... with non-musicians. This is taken to reflect their familiarity with pitch information which is in key position in Finnish folk music when compared with e.g., rhythmic information. The MMN was followed by P3a after timbre changes, rhythm changes, and melody transposition. The MMN and P3a topographies...

  10. Melatonin Distribution Reveals Clues to Its Biological Significance in Basal Metazoans

    Science.gov (United States)

    Roopin, Modi; Levy, Oren

    2012-01-01

    Although nearly ubiquitous in nature, the precise biological significance of endogenous melatonin is poorly understood in phylogenetically basal taxa. In the present work, we describe insights into the functional role of melatonin at the most “basal” level of metazoan evolution. Hitherto unknown morphological determinants of melatonin distribution were evaluated in Nematostella vectensis by detecting melatonin immunoreactivity and examining the spatial gene expression patterns of putative melatonin biosynthetic and receptor elements that are located at opposing ends of the melatonin signaling pathway. Immuno-melatonin profiling indicated an elaborate interaction with reproductive tissues, reinforcing previous conjectures of a melatonin-responsive component in anthozoan reproduction. In situ hybridization (ISH) to putative melatonin receptor elements highlighted the possibility that the bioregulatory effects of melatonin in anthozoan reproduction may be mediated by interactions with membrane receptors, as in higher vertebrates. Another intriguing finding of the present study pertains to the prevalence of melatonin in centralized nervous structures. This pattern may be of great significance given that it 1) identifies an ancestral association between melatonin and key neuronal components and 2) potentially implies that certain effects of melatonin in basal species may be spread widely by regionalized nerve centers. PMID:23300630

  11. Differential lysine acetylation profiles of Erwinia amylovora strains revealed by proteomics

    Science.gov (United States)

    Wu, Xia; Vellaichamy, Adaikkalam; Wang, Dongping; Zamdborg, Leonid; Kelleher, Neil L.; Huber, Steven C.; Zhao, Youfu

    2015-01-01

    Protein lysine acetylation (LysAc) has recently been demonstrated to be widespread in E. coli and Salmonella, and to broadly regulate bacterial physiology and metabolism. However, LysAc in plant pathogenic bacteria is largely unknown. Here we first report the lysine acetylome of Erwinia amylovora, an enterobacterium causing serious fire blight disease of apples and pears. Immunoblots using generic anti-lysine acetylation antibodies demonstrated that growth conditions strongly affected the LysAc profiles in E. amylovora. Differential LysAc profiles were also observed for two E. amylovora strains, known to have differential virulence in plants, indicating translational modification of proteins may be important in determining virulence of bacterial strains. Proteomic analysis of LysAc in two E. amylovora strains identified 141 LysAc sites in 96 proteins that function in a wide range of biological pathways. Consistent with previous reports, 44% of the proteins are involved in metabolic processes, including central metabolism, lipopolysaccharide, nucleotide and amino acid metabolism. Interestingly, for the first time, several proteins involved in E. amylovora virulence, including exopolysaccharide amylovoran biosynthesis- and type III secretion-associated proteins, were found to be lysine acetylated, suggesting that LysAc may play a major role in bacterial virulence. Comparative analysis of LysAc sites in E. amylovora and E. coli further revealed the sequence and structural commonality for LysAc in the two organisms. Collectively, these results reinforce the notion that LysAc of proteins is widespread in bacterial metabolism and virulence. PMID:23234799

  12. The distribution of organic carbon fractions in a typical loess-paleosol profile and its paleoenvironmental significance

    Directory of Open Access Journals (Sweden)

    Qingqing Zhang

    2018-04-01

    Full Text Available Background The loess-paleosol sequence on the Loess Plateau has been considered an important paleoclimatic archive to study global climatic and environmental changes in the Quaternary. So far, little attention has been paid to the characteristics of soil organic carbon fractions in loess-paleosol sequences, which may provide valuable information for exploring the evolution of climate and environment in the Quaternary on the Loess Plateau. Methods In order to explore the significance of mineral-associated organic carbon to total organic carbon (MOC/TOC ratios in the loess-paleosol sequence for reconstructing paleoenvironmental and paleoclimatic evolution in the Quaternary on the Loess Plateau, we selected a typical loess-paleosol profile in Chunhua county, Xianyang city, Shaanxi province, as the research object. The content of total organic carbon (TOC and MOC/TOC ratio in each loess and paleosol layers of the Chunhua loess-paleosol profile were analyzed, together with the paleoclimatic proxies, such as soil grain size, CaCO3 content and their correlations with organic carbon parameters. Results The main results were as follows: (1 the total content of soil organic carbon and MOC/TOC ratios were generally higher in paleosol layers than in the underlying loess layers of the Chunhua loess-paleosol profile. Compared to total organic carbon content, MOC/TOC ratios changed more obviously in soil layers below a paleosol layer S8; (2 soil clay content and median grain size (Md (ϕ were higher in paleosol than in the underlying loess, while CaCO3 content showed an opposite tendency. In the Chunhua profile, the distribution characteristics of the three paleoclimatic proxies showed good indications of paleoclimate changes in the Quaternary; (3 in the Chunhua loess-paleosol profile, MOC/TOC ratios were positively correlated with clay content and median grain size (ϕ, while negatively correlated with CaCO3 content, and the correlations were more significant

  13. The distribution of organic carbon fractions in a typical loess-paleosol profile and its paleoenvironmental significance

    Science.gov (United States)

    Hu, Feinan; Huo, Na; Shang, Yingni; Chang, Wenqian

    2018-01-01

    Background The loess-paleosol sequence on the Loess Plateau has been considered an important paleoclimatic archive to study global climatic and environmental changes in the Quaternary. So far, little attention has been paid to the characteristics of soil organic carbon fractions in loess-paleosol sequences, which may provide valuable information for exploring the evolution of climate and environment in the Quaternary on the Loess Plateau. Methods In order to explore the significance of mineral-associated organic carbon to total organic carbon (MOC/TOC) ratios in the loess-paleosol sequence for reconstructing paleoenvironmental and paleoclimatic evolution in the Quaternary on the Loess Plateau, we selected a typical loess-paleosol profile in Chunhua county, Xianyang city, Shaanxi province, as the research object. The content of total organic carbon (TOC) and MOC/TOC ratio in each loess and paleosol layers of the Chunhua loess-paleosol profile were analyzed, together with the paleoclimatic proxies, such as soil grain size, CaCO3 content and their correlations with organic carbon parameters. Results The main results were as follows: (1) the total content of soil organic carbon and MOC/TOC ratios were generally higher in paleosol layers than in the underlying loess layers of the Chunhua loess-paleosol profile. Compared to total organic carbon content, MOC/TOC ratios changed more obviously in soil layers below a paleosol layer S8; (2) soil clay content and median grain size (Md (ϕ)) were higher in paleosol than in the underlying loess, while CaCO3 content showed an opposite tendency. In the Chunhua profile, the distribution characteristics of the three paleoclimatic proxies showed good indications of paleoclimate changes in the Quaternary; (3) in the Chunhua loess-paleosol profile, MOC/TOC ratios were positively correlated with clay content and median grain size (ϕ), while negatively correlated with CaCO3 content, and the correlations were more significant in soil

  14. Gene Expression Profiling Reveals a Massive, Aneuploidy-Dependent Transcriptional Deregulation and Distinct Differences between Lymph Node–Negative and Lymph Node–Positive Colon Carcinomas

    Science.gov (United States)

    Grade, Marian; Hörmann, Patrick; Becker, Sandra; Hummon, Amanda B.; Wangsa, Danny; Varma, Sudhir; Simon, Richard; Liersch, Torsten; Becker, Heinz; Difilippantonio, Michael J.; Ghadimi, B. Michael; Ried, Thomas

    2016-01-01

    To characterize patterns of global transcriptional deregulation in primary colon carcinomas, we did gene expression profiling of 73 tumors [Unio Internationale Contra Cancrum stage II (n = 33) and stage III (n = 40)] using oligonucleotide microarrays. For 30 of the tumors, expression profiles were compared with those from matched normal mucosa samples. We identified a set of 1,950 genes with highly significant deregulation between tumors and mucosa samples (P 5-fold average expression difference between normal colon mucosa and carcinomas, including up-regulation of MYC and of HMGA1, a putative oncogene. Furthermore, we identified 68 genes that were significantly differentially expressed between lymph node–negative and lymph node–positive tumors (P deregulated genes were validated using quantitative real-time reverse transcription-PCR in >40 tumor and normal mucosa samples with good concordance between the techniques. Finally, we established a relationship between specific genomic imbalances, which were mapped for 32 of the analyzed colon tumors by comparative genomic hybridization, and alterations of global transcriptional activity. Previously, we had conducted a similar analysis of primary rectal carcinomas. The systematic comparison of colon and rectal carcinomas revealed a significant overlap of genomic imbalances and transcriptional deregulation, including activation of the Wnt/β-catenin signaling cascade, suggesting similar pathogenic pathways. PMID:17210682

  15. Protein profiling in serum after traumatic brain injury in rats reveals potential injury markers.

    Science.gov (United States)

    Thelin, Eric Peter; Just, David; Frostell, Arvid; Häggmark-Månberg, Anna; Risling, Mårten; Svensson, Mikael; Nilsson, Peter; Bellander, Bo-Michael

    2018-03-15

    The serum proteome following traumatic brain injury (TBI) could provide information for outcome prediction and injury monitoring. The aim with this affinity proteomic study was to identify serum proteins over time and between normoxic and hypoxic conditions in focal TBI. Sprague Dawley rats (n=73) received a 3mm deep controlled cortical impact ("severe injury"). Following injury, the rats inhaled either a normoxic (22% O 2 ) or hypoxic (11% O 2 ) air mixture for 30min before resuscitation. The rats were sacrificed at day 1, 3, 7, 14 and 28 after trauma. A total of 204 antibodies targeting 143 unique proteins of interest in TBI research, were selected. The sample proteome was analyzed in a suspension bead array set-up. Comparative statistics and factor analysis were used to detect differences as well as variance in the data. We found that complement factor 9 (C9), complement factor B (CFB) and aldolase c (ALDOC) were detected at higher levels the first days after trauma. In contrast, hypoxia inducing factor (HIF)1α, amyloid precursor protein (APP) and WBSCR17 increased over the subsequent weeks. S100A9 levels were higher in hypoxic-compared to normoxic rats, together with a majority of the analyzed proteins, albeit few reached statistical significance. The principal component analysis revealed a variance in the data, highlighting clusters of proteins. Protein profiling of serum following TBI using an antibody based microarray revealed temporal changes of several proteins over an extended period of up to four weeks. Further studies are warranted to confirm our findings. Copyright © 2016 The Author(s). Published by Elsevier B.V. All rights reserved.

  16. Clinical significance of determination of plasma NPY levels and serum lipid profile in patients with cerebral hemorrhage and cerebral infarction

    International Nuclear Information System (INIS)

    Huang Fujuan; Shen Airong; Yang Yongqing

    2010-01-01

    Objective: To study the clinical significance of changes of plasma NPY levels and serum lipid profile in patients with cerebral hemorrhage and cerebral infarction. Methods: Plasma NPY levels (with RIA) and serum lipid profile (with biochemistry) were determined in (1) 48 patients with acute cerebral hemorrhage (2) 46 patients with acute cerebral infarction and (3) controls.Results Plasma NPY levels in both patients with cerebral hemorrhage and patients with cerebral infarction were significantly higher than those in controls (P 0.05). Conclusion: NPY played important roles in the development and pathogenesis of cerebral vascular accidents. Lipid profile changes was the basic etiological factor. (authors)

  17. Significant Differences Characterise the Correlation Coefficients between Biocide and Antibiotic Susceptibility Profiles in Staphylococcus aureus.

    Science.gov (United States)

    Oggioni, Marco R; Coelho, Joana Rosado; Furi, Leonardo; Knight, Daniel R; Viti, Carlo; Orefici, Graziella; Martinez, Jose-Luis; Freitas, Ana Teresa; Coque, Teresa M; Morrissey, Ian

    2015-01-01

    There is a growing concern by regulatory authorities for the selection of antibiotic resistance caused by the use of biocidal products. We aimed to complete the detailed information on large surveys by investigating the relationship between biocide and antibiotic susceptibility profiles of a large number of Staphylococcus aureus isolates using four biocides and antibiotics commonly used in clinical practice. The minimal inhibitory concentration (MIC) for most clinically-relevant antibiotics was determined according to the standardized methodology for over 1600 clinical S. aureus isolates and compared to susceptibility profiles of benzalkonium chloride, chlorhexidine, triclosan, and sodium hypochlorite. The relationship between antibiotic and biocide susceptibility profiles was evaluated using non-linear correlations. The main outcome evidenced was an absence of any strong or moderate statistically significant correlation when susceptibilities of either triclosan or sodium hypochlorite were compared for any of the tested antibiotics. On the other hand, correlation coefficients for MICs of benzalkonium chloride and chlorhexidine were calculated above 0.4 for susceptibility to quinolones, beta-lactams, and also macrolides. Our data do not support any selective pressure for association between biocides and antibiotics resistance and furthermore do not allow for a defined risk evaluation for some of the compounds. Importantly, our data clearly indicate that there does not involve any risk of selection for antibiotic resistance for the compounds triclosan and sodium hypochlorite. These data hence infer that biocide selection for antibiotic resistance has had so far a less significant impact than feared.

  18. Kinome-wide transcriptional profiling of uveal melanoma reveals new vulnerabilities to targeted therapeutics.

    Science.gov (United States)

    Bailey, Fiona P; Clarke, Kim; Kalirai, Helen; Kenyani, Jenna; Shahidipour, Haleh; Falciani, Francesco; Coulson, Judy M; Sacco, Joseph J; Coupland, Sarah E; Eyers, Patrick A

    2018-03-01

    Metastatic uveal melanoma (UM) is invariably fatal, usually within a year of diagnosis. There are currently no effective therapies, and clinical studies employing kinase inhibitors have so far demonstrated limited success. This is despite common activating mutations in GNAQ/11 genes, which trigger signalling pathways that might predispose tumours to a variety of targeted drugs. In this study, we have profiled kinome expression network dynamics in various human ocular melanomas. We uncovered a shared transcriptional profile in human primary UM samples and across a variety of experimental cell-based models. The poor overall response of UM cells to FDA-approved kinase inhibitors contrasted with much higher sensitivity to the bromodomain inhibitor JQ1, a broad transcriptional repressor. Mechanistically, we identified a repressed FOXM1-dependent kinase subnetwork in JQ1-exposed cells that contained multiple cell cycle-regulated protein kinases. Consistently, we demonstrated vulnerability of UM cells to inhibitors of mitotic protein kinases within this network, including the investigational PLK1 inhibitor BI6727. We conclude that analysis of kinome-wide signalling network dynamics has the potential to reveal actionable drug targets and inhibitors of potential therapeutic benefit for UM patients. © 2017 The Authors. Pigment Cell & Melanoma Research Published by John Wiley & Sons.

  19. Integrated microRNA and gene expression profiling reveals the crucial miRNAs in curcumin anti-lung cancer cell invasion.

    Science.gov (United States)

    Zhan, Jian-Wei; Jiao, De-Min; Wang, Yi; Song, Jia; Wu, Jin-Hong; Wu, Li-Jun; Chen, Qing-Yong; Ma, Sheng-Lin

    2017-09-01

    Curcumin (diferuloylmethane) has chemopreventive and therapeutic properties against many types of tumors, both in vitro and in vivo. Previous reports have shown that curcumin exhibits anti-invasive activities, but the mechanisms remain largely unclear. In this study, both microRNA (miRNA) and messenger RNA (mRNA) expression profiles were used to characterize the anti-metastasis mechanisms of curcumin in human non-small cell lung cancer A549 cell line. Microarray analysis revealed that 36 miRNAs were differentially expressed between the curcumin-treated and control groups. miR-330-5p exhibited maximum upregulation, while miR-25-5p exhibited maximum downregulation in the curcumin treatment group. mRNA expression profiles and functional analysis indicated that 226 differentially expressed mRNAs belonged to different functional categories. Significant pathway analysis showed that mitogen-activated protein kinase, transforming growth factor-β, and Wnt signaling pathways were significantly downregulated. At the same time, axon guidance, glioma, and ErbB tyrosine kinase receptor signaling pathways were significantly upregulated. We constructed a miRNA gene network that contributed to the curcumin inhibition of metastasis in lung cancer cells. let-7a-3p, miR-1262, miR-499a-5p, miR-1276, miR-331-5p, and miR-330-5p were identified as key microRNA regulators in the network. Finally, using miR-330-5p as an example, we confirmed the role of miR-330-5p in mediating the anti-migration effect of curcumin, suggesting the importance of miRNAs in the regulation of curcumin biological activity. Our findings provide new insights into the anti-metastasis mechanism of curcumin in lung cancer. © 2017 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

  20. Embryonic stem cell-like features of testicular carcinoma in situ revealed by genome-wide gene expression profiling.

    Science.gov (United States)

    Almstrup, Kristian; Hoei-Hansen, Christina E; Wirkner, Ute; Blake, Jonathon; Schwager, Christian; Ansorge, Wilhelm; Nielsen, John E; Skakkebaek, Niels E; Rajpert-De Meyts, Ewa; Leffers, Henrik

    2004-07-15

    Carcinoma in situ (CIS) is the common precursor of histologically heterogeneous testicular germ cell tumors (TGCTs), which in recent decades have markedly increased and now are the most common malignancy of young men. Using genome-wide gene expression profiling, we identified >200 genes highly expressed in testicular CIS, including many never reported in testicular neoplasms. Expression was further verified by semiquantitative reverse transcription-PCR and in situ hybridization. Among the highest expressed genes were NANOG and POU5F1, and reverse transcription-PCR revealed possible changes in their stoichiometry on progression into embryonic carcinoma. We compared the CIS expression profile with patterns reported in embryonic stem cells (ESCs), which revealed a substantial overlap that may be as high as 50%. We also demonstrated an over-representation of expressed genes in regions of 17q and 12, reported as unstable in cultured ESCs. The close similarity between CIS and ESCs explains the pluripotency of CIS. Moreover, the findings are consistent with an early prenatal origin of TGCTs and thus suggest that etiologic factors operating in utero are of primary importance for the incidence trends of TGCTs. Finally, some of the highly expressed genes identified in this study are promising candidates for new diagnostic markers for CIS and/or TGCTs.

  1. Significant profile differences among male and female adventure tourists in Pretoria, South Africa

    Directory of Open Access Journals (Sweden)

    Melissa Jeanette Lötter

    2014-01-01

    Full Text Available Different adventure activities/experiences evolve because individuals, their motives, behaviours, and experiences differ and change over time. This notion illustrates the broad nature of adventure tourism and its links with other forms of tourism. In turn, adventure tourism companies are compelled to promote/sell an array of activities/experiences to a diverse range of markets as novel and exclusive experiences to facilitate the growth of adventure holidays (Swarbrooke et al., 2003. To assist adventure tourism companies in achieving effective marketing strategies, the study’s objective is to identify significant sociopsychological profile differences among male and female adventure tourists in Pretoria, South Africa. Furthermore, to facilitate the comparison of adventure tourists’ profiles, an equal number of respondents were male (117 and female (117, which provided a 93.6% response rate. In comparison to female respondents, male respondents prefer winter as a season to participate in hard/high-risk adventure activities when they are with or without their family, and they participate in adventure activities for travelling and socialising purposes. Whereas, female respondents predominantly regard scuba-diving, abseiling, and helicopter flights as a hard/high-risk adventure activity, although these activities are generally regarded by the overall sample as being soft/low-risk adventure activities. Furthermore, even though females’ participation in adventure activities is sponsored, they did not participate or only participated in adventure activities once over the past year due to fear/risk and/or lack of skill. This study established that there is a need to further research adventure tourists’ profiles before it could be equally accepted and interpreted.

  2. Transcriptome sequencing revealed significant alteration of cortical promoter usage and splicing in schizophrenia.

    Directory of Open Access Journals (Sweden)

    Jing Qin Wu

    Full Text Available While hybridization based analysis of the cortical transcriptome has provided important insight into the neuropathology of schizophrenia, it represents a restricted view of disease-associated gene activity based on predetermined probes. By contrast, sequencing technology can provide un-biased analysis of transcription at nucleotide resolution. Here we use this approach to investigate schizophrenia-associated cortical gene expression.The data was generated from 76 bp reads of RNA-Seq, aligned to the reference genome and assembled into transcripts for quantification of exons, splice variants and alternative promoters in postmortem superior temporal gyrus (STG/BA22 from 9 male subjects with schizophrenia and 9 matched non-psychiatric controls. Differentially expressed genes were then subjected to further sequence and functional group analysis. The output, amounting to more than 38 Gb of sequence, revealed significant alteration of gene expression including many previously shown to be associated with schizophrenia. Gene ontology enrichment analysis followed by functional map construction identified three functional clusters highly relevant to schizophrenia including neurotransmission related functions, synaptic vesicle trafficking, and neural development. Significantly, more than 2000 genes displayed schizophrenia-associated alternative promoter usage and more than 1000 genes showed differential splicing (FDR<0.05. Both types of transcriptional isoforms were exemplified by reads aligned to the neurodevelopmentally significant doublecortin-like kinase 1 (DCLK1 gene.This study provided the first deep and un-biased analysis of schizophrenia-associated transcriptional diversity within the STG, and revealed variants with important implications for the complex pathophysiology of schizophrenia.

  3. African-American esophageal squamous cell carcinoma expression profile reveals dysregulation of stress response and detox networks.

    Science.gov (United States)

    Erkizan, Hayriye Verda; Johnson, Kory; Ghimbovschi, Svetlana; Karkera, Deepa; Trachiotis, Gregory; Adib, Houtan; Hoffman, Eric P; Wadleigh, Robert G

    2017-06-19

    Esophageal carcinoma is the third most common gastrointestinal malignancy worldwide and is largely unresponsive to therapy. African-Americans have an increased risk for esophageal squamous cell carcinoma (ESCC), the subtype that shows marked variation in geographic frequency. The molecular architecture of African-American ESCC is still poorly understood. It is unclear why African-American ESCC is more aggressive and the survival rate in these patients is worse than those of other ethnic groups. To begin to define genetic alterations that occur in African-American ESCC we conducted microarray expression profiling in pairs of esophageal squamous cell tumors and matched control tissues. We found significant dysregulation of genes encoding drug-metabolizing enzymes and stress response components of the NRF2- mediated oxidative damage pathway, potentially representing key genes in African-American esophageal squamous carcinogenesis. Loss of activity of drug metabolizing enzymes would confer increased sensitivity of esophageal cells to xenobiotics, such as alcohol and tobacco smoke, and may account for the high incidence and aggressiveness of ESCC in this ethnic group. To determine whether certain genes are uniquely altered in African-American ESCC we performed a meta-analysis of ESCC expression profiles in our African-American samples and those of several Asian samples. Down-regulation of TP53 pathway components represented the most common feature in ESCC of all ethnic groups. Importantly, this analysis revealed a potential distinctive molecular underpinning of African-American ESCC, that is, a widespread and prominent involvement of the NRF2 pathway. Taken together, these findings highlight the remarkable interplay of genetic and environmental factors in the pathogenesis of African-American ESCC.

  4. Global Metabolomics of the Placenta Reveals Distinct Metabolic Profiles between Maternal and Fetal Placental Tissues Following Delivery in Non-Labored Women

    Directory of Open Access Journals (Sweden)

    Jacquelyn M. Walejko

    2018-01-01

    Full Text Available We evaluated the metabolic alterations in maternal and fetal placental tissues from non-labored women undergoing cesarean section using samples collected from 5 min to 24 h following delivery. Using 1H-NMR, we identified 14 metabolites that significantly differed between maternal and fetal placental tissues (FDR-corrected p-value < 0.05, with 12 metabolites elevated in the maternal tissue, reflecting the flux of these metabolites from mother to fetus. In the maternal tissue, 4 metabolites were significantly altered at 15 min, 10 metabolites at 30 min, and 16 metabolites at 1 h postdelivery, while 11 metabolites remained stable over 24 h. In contrast, in the fetal placenta tissue, 1 metabolite was significantly altered at 15 min, 2 metabolites at 30 min, and 4 metabolites at 1 h postdelivery, while 22 metabolites remained stable over 24 h. Our study provides information on the metabolic profiles of maternal and fetal placental tissues delivered by cesarean section and reveals that there are different metabolic alterations in the maternal and fetal tissues of the placenta following delivery.

  5. Phylogeographic analysis reveals significant spatial genetic structure of Incarvillea sinensis as a product of mountain building

    Directory of Open Access Journals (Sweden)

    Chen Shaotian

    2012-04-01

    Full Text Available Abstract Background Incarvillea sinensis is widely distributed from Southwest China to Northeast China and in the Russian Far East. The distribution of this species was thought to be influenced by the uplift of the Qinghai-Tibet Plateau and Quaternary glaciation. To reveal the imprints of geological events on the spatial genetic structure of Incarvillea sinensis, we examined two cpDNA segments ( trnH- psbA and trnS- trnfM in 705 individuals from 47 localities. Results A total of 16 haplotypes was identified, and significant genetic differentiation was revealed (GST =0.843, NST = 0.975, P  Conclusions The results revealed that the uplift of the Qinghai-Tibet Plateau likely resulted in the significant divergence between the lineage in the eastern Qinghai-Tibet Plateau and the other one outside this area. The diverse niches in the eastern Qinghai-Tibet Plateau created a wide spectrum of habitats to accumulate and accommodate new mutations. The features of genetic diversity of populations outside the eastern Qinghai-Tibet Plateau seemed to reveal the imprints of extinction during the Glacial and the interglacial and postglacial recolonization. Our study is a typical case of the significance of the uplift of the Qinghai-Tibet Plateau and the Quaternary Glacial in spatial genetic structure of eastern Asian plants, and sheds new light on the evolution of biodiversity in the Qinghai-Tibet Plateau at the intraspecies level.

  6. Gene array analysis of PD-1H overexpressing monocytes reveals a pro-inflammatory profile

    Directory of Open Access Journals (Sweden)

    Preeti Bharaj

    2018-02-01

    Full Text Available We have previously reported that overexpression of Programmed Death -1 Homolog (PD-1H in human monocytes leads to activation and spontaneous secretion of multiple pro inflammatory cytokines. Here we evaluate changes in monocytes gene expression after enforced PD-1H expression by gene array. The results show that there are significant alterations in 51 potential candidate genes that relate to immune response, cell adhesion and metabolism. Genes corresponding to pro-inflammatory cytokines showed the highest upregulation, 7, 3.2, 3.0, 5.8, 4.4 and 3.1 fold upregulation of TNF-α, IL-1 β, IFN-α, γ, λ and IL-27 relative to vector control. The data are in agreement with cytometric bead array analysis showing induction of proinflammatory cytokines, IL-6, IL-1β and TNF-α by PD-1H. Other genes related to inflammation, include transglutaminase 2 (TG2, NF-κB (p65 and p50 and toll like receptors (TLR 3 and 4 were upregulated 5, 4.5 and 2.5 fold, respectively. Gene set enrichment analysis (GSEA also revealed that signaling pathways related to inflammatory response, such as NFκB, AT1R, PYK2, MAPK, RELA, TNFR1, MTOR and proteasomal degradation, were significantly upregulated in response to PD-1H overexpression. We validated the results utilizing a standard inflammatory sepsis model in humanized BLT mice, finding that PD-1H expression was highly correlated with proinflammatory cytokine production. We therefore conclude that PD-1H functions to enhance monocyte activation and the induction of a pro-inflammatory gene expression profile.

  7. Transcriptome Sequencing Revealed Significant Alteration of Cortical Promoter Usage and Splicing in Schizophrenia

    Science.gov (United States)

    Wu, Jing Qin; Wang, Xi; Beveridge, Natalie J.; Tooney, Paul A.; Scott, Rodney J.; Carr, Vaughan J.; Cairns, Murray J.

    2012-01-01

    Background While hybridization based analysis of the cortical transcriptome has provided important insight into the neuropathology of schizophrenia, it represents a restricted view of disease-associated gene activity based on predetermined probes. By contrast, sequencing technology can provide un-biased analysis of transcription at nucleotide resolution. Here we use this approach to investigate schizophrenia-associated cortical gene expression. Methodology/Principal Findings The data was generated from 76 bp reads of RNA-Seq, aligned to the reference genome and assembled into transcripts for quantification of exons, splice variants and alternative promoters in postmortem superior temporal gyrus (STG/BA22) from 9 male subjects with schizophrenia and 9 matched non-psychiatric controls. Differentially expressed genes were then subjected to further sequence and functional group analysis. The output, amounting to more than 38 Gb of sequence, revealed significant alteration of gene expression including many previously shown to be associated with schizophrenia. Gene ontology enrichment analysis followed by functional map construction identified three functional clusters highly relevant to schizophrenia including neurotransmission related functions, synaptic vesicle trafficking, and neural development. Significantly, more than 2000 genes displayed schizophrenia-associated alternative promoter usage and more than 1000 genes showed differential splicing (FDRschizophrenia-associated transcriptional diversity within the STG, and revealed variants with important implications for the complex pathophysiology of schizophrenia. PMID:22558445

  8. MicroRNA profiling in Muc2 knockout mice of colitis-associated cancer model reveals epigenetic alterations during chronic colitis malignant transformation.

    Directory of Open Access Journals (Sweden)

    Yonghua Bao

    Full Text Available Our previous studies have demonstrated that genetic deletion of the Muc2 gene causes colorectal cancers in mice. The current study further showed that at the early stage (3 months the mice exhibited colorectal cancer, including a unique phenotype of rectal prolapsed (rectal severe inflammation and adenocarcinoma. Thus, the age of 3 months might be the key point of the transition from chronic inflammation to cancer. To determine the mechanisms of the malignant transformation, we conducted miRNA array on the colonic epithelial cells from the 3-month Muc2-/- and +/+ mice. MicroRNA profiling showed differential expression of miRNAs (i.e. lower or higher expression enrichments in Muc2-/- mice. 15 of them were validated by quantitative PCR. Based on relevance to cytokine and cancer, 4 miRNAs (miR-138, miR-145, miR-146a, and miR-150 were validate and were found significantly downregulated in human colitis and colorectal cancer tissues. The network of the targets of these miRNAs was characterized, and interestedly, miRNA-associated cytokines were significantly increased in Muc2-/-mice. This is the first to reveal the importance of aberrant expression of miRNAs in dynamically transformation from chronic colitis to colitis-associated cancer. These findings shed light on revealing the mechanisms of chronic colitis malignant transformation.

  9. Transcriptional profiling reveals gland-specific differential expression in the three major salivary glands of the adult mouse.

    Science.gov (United States)

    Gao, Xin; Oei, Maria S; Ovitt, Catherine E; Sincan, Murat; Melvin, James E

    2018-04-01

    RNA-Seq was used to better understand the molecular nature of the biological differences among the three major exocrine salivary glands in mammals. Transcriptional profiling found that the adult murine parotid, submandibular, and sublingual salivary glands express greater than 14,300 protein-coding genes, and nearly 2,000 of these genes were differentially expressed. Principle component analysis of the differentially expressed genes revealed three distinct clusters according to gland type. The three salivary gland transcriptomes were dominated by a relatively few number of highly expressed genes (6.3%) that accounted for more than 90% of transcriptional output. Of the 912 transcription factors expressed in the major salivary glands, greater than 90% of them were detected in all three glands, while expression for ~2% of them was enriched in an individual gland. Expression of these unique transcription factors correlated with sublingual and parotid specific subsets of both highly expressed and differentially expressed genes. Gene ontology analyses revealed that the highly expressed genes common to all glands were associated with global functions, while many of the genes expressed in a single gland play a major role in the function of that gland. In summary, transcriptional profiling of the three murine major salivary glands identified a limited number of highly expressed genes, differentially expressed genes, and unique transcription factors that represent the transcriptional signatures underlying gland-specific biological properties.

  10. Prospective Genomic Profiling of Prostate Cancer Across Disease States Reveals Germline and Somatic Alterations That May Affect Clinical Decision Making.

    Science.gov (United States)

    Abida, Wassim; Armenia, Joshua; Gopalan, Anuradha; Brennan, Ryan; Walsh, Michael; Barron, David; Danila, Daniel; Rathkopf, Dana; Morris, Michael; Slovin, Susan; McLaughlin, Brigit; Curtis, Kristen; Hyman, David M; Durack, Jeremy C; Solomon, Stephen B; Arcila, Maria E; Zehir, Ahmet; Syed, Aijazuddin; Gao, Jianjiong; Chakravarty, Debyani; Vargas, Hebert Alberto; Robson, Mark E; Joseph, Vijai; Offit, Kenneth; Donoghue, Mark T A; Abeshouse, Adam A; Kundra, Ritika; Heins, Zachary J; Penson, Alexander V; Harris, Christopher; Taylor, Barry S; Ladanyi, Marc; Mandelker, Diana; Zhang, Liying; Reuter, Victor E; Kantoff, Philip W; Solit, David B; Berger, Michael F; Sawyers, Charles L; Schultz, Nikolaus; Scher, Howard I

    2017-07-01

    A long natural history and a predominant osseous pattern of metastatic spread are impediments to the adoption of precision medicine in patients with prostate cancer. To establish the feasibility of clinical genomic profiling in the disease, we performed targeted deep sequencing of tumor and normal DNA from patients with locoregional, metastatic non-castrate, and metastatic castration-resistant prostate cancer (CRPC). Patients consented to genomic analysis of their tumor and germline DNA. A hybridization capture-based clinical assay was employed to identify single nucleotide variations, small insertions and deletions, copy number alterations and structural rearrangements in over 300 cancer-related genes in tumors and matched normal blood. We successfully sequenced 504 tumors from 451 patients with prostate cancer. Potentially actionable alterations were identified in DNA damage repair (DDR), PI3K, and MAP kinase pathways. 27% of patients harbored a germline or a somatic alteration in a DDR gene that may predict for response to PARP inhibition. Profiling of matched tumors from individual patients revealed that somatic TP53 and BRCA2 alterations arose early in tumors from patients who eventually developed metastatic disease. In contrast, comparative analysis across disease states revealed that APC alterations were enriched in metastatic tumors, while ATM alterations were specifically enriched in CRPC. Through genomic profiling of prostate tumors representing the disease clinical spectrum, we identified a high frequency of potentially actionable alterations and possible drivers of disease initiation, metastasis and castration-resistance. Our findings support the routine use of tumor and germline DNA profiling for patients with advanced prostate cancer, for the purpose of guiding enrollment in targeted clinical trials and counseling families at increased risk of malignancy.

  11. Quantitative Analysis of Serum Lipid Profile in Gallstone Patients and Controls

    International Nuclear Information System (INIS)

    Channa, N.A.; Ghanghro, A.B.; Soomro, A.M.

    2010-01-01

    The present study was undertaken to explore the possible role of serum lipid profile in gallstone formation. For this serum lipid profile such as total, free and bound cholesterol, LDL cholesterol, HDL cholesterol, triacylglycerols and total lipids were determined in 109 gallstone patients and 100 controls (matched for age, sex and with negative personal or family history of gallstones) treated at Liaquat University Hospital, Jamshoro, Pakistan. Comparison for serum lipid profile between different groups of gallstone patients and controls revealed no significant variation except for the triacylglycerols and total lipids, which were differed significantly between females of up to 45 and above 45 years age. Comparison for serum lipid profile between pure cholesterol and mixed composition gallstone formers showed no significant difference (p>0.05) between the two groups. The serum lipid profile significantly varied between gallstone patients and controls except bound cholesterol level. Comparison of total cholesterol, free cholesterol, LDL cholesterol, HDL cholesterol, triacylglycerols and total lipids between gallstone patients and controls revealed that there was a significant difference between gallstone patients and controls for (a) females with or without gallstones, (b) females of up to 45 years age and (c) females having more than 3 children. HDL cholesterol is significantly decreased in all the groups of gallstone patients as compared to controls, whereas, bound cholesterol remained non significant in all the groups of gallstone patients when compared with controls. In conclusion, elevated serum total cholesterol, free cholesterol, LDL cholesterol, triacylglycerols and decreased levels of HDL cholesterol seem to play major contributing role in the pathogenesis of gallstones in females of up to 45 years age with more than three children. (author)

  12. Lipidomic profiling reveals distinct differences in plasma lipid composition in healthy, prediabetic, and type 2 diabetic individuals

    Science.gov (United States)

    Zhong, Huanzi; Fang, Chao; Fan, Yanqun; Lu, Yan; Wen, Bo; Ren, Huahui; Hou, Guixue; Yang, Fangming; Xie, Hailiang; Jie, Zhuye; Peng, Ye; Ye, Zhiqiang; Wu, Jiegen; Zi, Jin; Zhao, Guoqing; Chen, Jiayu; Bao, Xiao; Hu, Yihe; Gao, Yan; Zhang, Jun; Yang, Huanming; Wang, Jian; Madsen, Lise; Kristiansen, Karsten

    2017-01-01

    Abstract The relationship between dyslipidemia and type 2 diabetes mellitus (T2D) has been extensively reported, but the global lipid profiles, especially in the East Asia population, associated with the development of T2D remain to be characterized. Liquid chromatography coupled to tandem mass spectrometry was applied to detect the global lipidome in the fasting plasma of 293 Chinese individuals, including 114 T2D patients, 81 prediabetic subjects, and 98 individuals with normal glucose tolerance (NGT). Both qualitative and quantitative analyses revealed a gradual change in plasma lipid features with T2D patients exhibiting characteristics close to those of prediabetic individuals, whereas they differed significantly from individuals with NGT. We constructed and validated a random forest classifier with 28 lipidomic features that effectively discriminated T2D from NGT or prediabetes. Most of the selected features significantly correlated with diabetic clinical indices. Hydroxybutyrylcarnitine was positively correlated with fasting plasma glucose, 2-hour postprandial glucose, glycated hemoglobin, and insulin resistance index (HOMA-IR). Lysophosphatidylcholines such as lysophosphatidylcholine (18:0), lysophosphatidylcholine (18:1), and lysophosphatidylcholine (18:2) were all negatively correlated with HOMA-IR. The altered plasma lipidome in Chinese T2D and prediabetic subjects suggests that lipid features may play a role in the pathogenesis of T2D and that such features may provide a basis for evaluating risk and monitoring disease development. PMID:28505362

  13. Discrepancy between WISC-III and WISC-IV Cognitive Profile in Autism Spectrum: What Does It Reveal about Autistic Cognition?

    Science.gov (United States)

    Nader, Anne-Marie; Jelenic, Patricia; Soulières, Isabelle

    2015-01-01

    The cognitive profile and measured intellectual level vary according to assessment tools in children on the autism spectrum, much more so than in typically developing children. The recent inclusion of intellectual functioning in the diagnostic process for autism spectrum disorders leads to the crucial question on how to assess intelligence in autism, especially as some tests and subtests seem more sensitive to certain neurodevelopmental conditions. Our first aim was to examine the cognitive profile on the current version of the most widely used test, the Wechsler Intelligence Scales for Children (WISC-IV), for a homogenous subgroup of children on the autism spectrum, i.e. corresponding to DSM-IV diagnosis of “autism”. The second aim was to compare cognitive profiles obtained on the third edition versus 4th edition of WISC, in order to verify whether the WISC-IV yields a more distinctive cognitive profile in autistic children. The third aim was to examine the impact of the WISC-IV on the cognitive profile of another subgroup, children with Asperger’s Syndrome. 51 autistic, 15 Asperger and 42 typically developing children completed the WISC-IV and were individually matched to children who completed the WISC-III. Divergent WISC-IV profiles were observed despite no significant intelligence quotient difference between groups. Autistic children scored significantly higher on the Perceptual Reasoning Index than on the Verbal Comprehension Index, a discrepancy that nearly tripled in comparison to WISC-III results. Asperger children scored higher on the VCI than on other indexes, with the lowest score found on the Processing Speed Index. WISC-IV cognitive profiles were consistent with, but more pronounced than WISC-III profiles. Cognitive profiles are a valuable diagnostic tool for differential diagnosis, keeping in mind that children on the autism spectrum might be more sensitive to the choice of subtests used to assess intelligence. PMID:26673881

  14. Discrepancy between WISC-III and WISC-IV Cognitive Profile in Autism Spectrum: What Does It Reveal about Autistic Cognition?

    Science.gov (United States)

    Nader, Anne-Marie; Jelenic, Patricia; Soulières, Isabelle

    2015-01-01

    The cognitive profile and measured intellectual level vary according to assessment tools in children on the autism spectrum, much more so than in typically developing children. The recent inclusion of intellectual functioning in the diagnostic process for autism spectrum disorders leads to the crucial question on how to assess intelligence in autism, especially as some tests and subtests seem more sensitive to certain neurodevelopmental conditions. Our first aim was to examine the cognitive profile on the current version of the most widely used test, the Wechsler Intelligence Scales for Children (WISC-IV), for a homogenous subgroup of children on the autism spectrum, i.e. corresponding to DSM-IV diagnosis of "autism". The second aim was to compare cognitive profiles obtained on the third edition versus 4th edition of WISC, in order to verify whether the WISC-IV yields a more distinctive cognitive profile in autistic children. The third aim was to examine the impact of the WISC-IV on the cognitive profile of another subgroup, children with Asperger's Syndrome. 51 autistic, 15 Asperger and 42 typically developing children completed the WISC-IV and were individually matched to children who completed the WISC-III. Divergent WISC-IV profiles were observed despite no significant intelligence quotient difference between groups. Autistic children scored significantly higher on the Perceptual Reasoning Index than on the Verbal Comprehension Index, a discrepancy that nearly tripled in comparison to WISC-III results. Asperger children scored higher on the VCI than on other indexes, with the lowest score found on the Processing Speed Index. WISC-IV cognitive profiles were consistent with, but more pronounced than WISC-III profiles. Cognitive profiles are a valuable diagnostic tool for differential diagnosis, keeping in mind that children on the autism spectrum might be more sensitive to the choice of subtests used to assess intelligence.

  15. Discrepancy between WISC-III and WISC-IV Cognitive Profile in Autism Spectrum: What Does It Reveal about Autistic Cognition?

    Directory of Open Access Journals (Sweden)

    Anne-Marie Nader

    Full Text Available The cognitive profile and measured intellectual level vary according to assessment tools in children on the autism spectrum, much more so than in typically developing children. The recent inclusion of intellectual functioning in the diagnostic process for autism spectrum disorders leads to the crucial question on how to assess intelligence in autism, especially as some tests and subtests seem more sensitive to certain neurodevelopmental conditions. Our first aim was to examine the cognitive profile on the current version of the most widely used test, the Wechsler Intelligence Scales for Children (WISC-IV, for a homogenous subgroup of children on the autism spectrum, i.e. corresponding to DSM-IV diagnosis of "autism". The second aim was to compare cognitive profiles obtained on the third edition versus 4th edition of WISC, in order to verify whether the WISC-IV yields a more distinctive cognitive profile in autistic children. The third aim was to examine the impact of the WISC-IV on the cognitive profile of another subgroup, children with Asperger's Syndrome. 51 autistic, 15 Asperger and 42 typically developing children completed the WISC-IV and were individually matched to children who completed the WISC-III. Divergent WISC-IV profiles were observed despite no significant intelligence quotient difference between groups. Autistic children scored significantly higher on the Perceptual Reasoning Index than on the Verbal Comprehension Index, a discrepancy that nearly tripled in comparison to WISC-III results. Asperger children scored higher on the VCI than on other indexes, with the lowest score found on the Processing Speed Index. WISC-IV cognitive profiles were consistent with, but more pronounced than WISC-III profiles. Cognitive profiles are a valuable diagnostic tool for differential diagnosis, keeping in mind that children on the autism spectrum might be more sensitive to the choice of subtests used to assess intelligence.

  16. Simultaneous profiling of seed-associated bacteria and fungi reveals antagonistic interactions between microorganisms within a shared epiphytic microbiome on Triticum and Brassica seeds

    Science.gov (United States)

    Links, Matthew G; Demeke, Tigst; Gräfenhan, Tom; Hill, Janet E; Hemmingsen, Sean M; Dumonceaux, Tim J

    2014-01-01

    In order to address the hypothesis that seeds from ecologically and geographically diverse plants harbor characteristic epiphytic microbiota, we characterized the bacterial and fungal microbiota associated with Triticum and Brassica seed surfaces. The total microbial complement was determined by amplification and sequencing of a fragment of chaperonin 60 (cpn60). Specific microorganisms were quantified by qPCR. Bacteria and fungi corresponding to operational taxonomic units (OTU) that were identified in the sequencing study were isolated and their interactions examined. A total of 5477 OTU were observed from seed washes. Neither total epiphytic bacterial load nor community richness/evenness was significantly different between the seed types; 578 OTU were shared among all samples at a variety of abundances. Hierarchical clustering revealed that 203 were significantly different in abundance on Triticum seeds compared with Brassica. Microorganisms isolated from seeds showed 99–100% identity between the cpn60 sequences of the isolates and the OTU sequences from this shared microbiome. Bacterial strains identified as Pantoea agglomerans had antagonistic properties toward one of the fungal isolates (Alternaria sp.), providing a possible explanation for their reciprocal abundances on both Triticum and Brassica seeds. cpn60 enabled the simultaneous profiling of bacterial and fungal microbiota and revealed a core seed-associated microbiota shared between diverse plant genera. PMID:24444052

  17. Physicochemical state of the nanotopographic surface of commercially pure titanium following anodization-hydrothermal treatment reveals significantly improved hydrophilicity and surface energy profiles.

    Science.gov (United States)

    Takebe, Jun; Ito, Shigeki; Miura, Shingo; Miyata, Kyohei; Ishibashi, Kanji

    2012-01-01

    A method of coating commercially pure titanium (cpTi) implants with a highly crystalline, thin hydroxyapatite (HA) layer using discharge anodic oxidation followed by hydrothermal treatment (Spark discharged Anodic oxidation treatment ; SA-treated cpTi) has been reported for use in clinical dentistry. We hypothesized that a thin HA layer with high crystallinity and nanostructured anodic titanium oxide film on such SA-treated cpTi implant surfaces might be a crucial function of their surface-specific potential energy. To test this, we analyzed anodic oxide (AO) cpTi and SA-treated cpTi disks by SEM and AFM. Contact angles and surface free energy of each disk surface was measured using FAMAS software. High-magnification SEM and AFM revealed the nanotopographic structure of the anodic titanium oxide film on SA-treated cpTi; however, this was not observed on the AO cpTi surface. The contact angle and surface free energy measurements were also significantly different between AO cpTi and SA-treated cpTi surfaces (Tukey's, P<0.05). These data indicated that the change of physicochemical properties of an anodic titanium oxide film with HA crystals on an SA-treated cpTi surface may play a key role in the phenomenon of osteoconduction during the process of osseointegration. Copyright © 2011 Elsevier B.V. All rights reserved.

  18. Glacio-tectonic thrust and deformation structures in the Vejle Fjord, Denmark revealed by high-resolution subbottom-profile data

    DEFF Research Database (Denmark)

    Andresen, Katrine Juul; Boldreel, Lars Ole; Wahlgreen, Katrine Bak

    Surface geomorphological features and partial cliff exposures up till now represent the predominant source of information of glaciation related deformation in Denmark. In this study we apply high-resolution marine reflection seismic data from the Vejle Fjord area, supported by gravity and Rumohr...... coring, to document intense glacio-tectonic deformation in the shallow subsurface of Denmark. The subbottom profiler seismic data have a peak frequency around 13 kHz and a vertical resolution in the order of 10-20 cm. The data reveal several variations of glacio-tectonic deformation structures, primarily...... movements from outcrops and shallow cores. The subbottom profiler data provides larger (longer and deeper) sectional views on for instance deformation and deposition complexes related to ice progressions and retreats and thus represents a very good supplement and valuable input to field mapping and outcrops...

  19. Comparative expression profiling reveals gene functions in female meiosis and gametophyte development in Arabidopsis.

    Science.gov (United States)

    Zhao, Lihua; He, Jiangman; Cai, Hanyang; Lin, Haiyan; Li, Yanqiang; Liu, Renyi; Yang, Zhenbiao; Qin, Yuan

    2014-11-01

    Megasporogenesis is essential for female fertility, and requires the accomplishment of meiosis and the formation of functional megaspores. The inaccessibility and low abundance of female meiocytes make it particularly difficult to elucidate the molecular basis underlying megasporogenesis. We used high-throughput tag-sequencing analysis to identify genes expressed in female meiocytes (FMs) by comparing gene expression profiles from wild-type ovules undergoing megasporogenesis with those from the spl mutant ovules, which lack megasporogenesis. A total of 862 genes were identified as FMs, with levels that are consistently reduced in spl ovules in two biological replicates. Fluorescence-assisted cell sorting followed by RNA-seq analysis of DMC1:GFP-labeled female meiocytes confirmed that 90% of the FMs are indeed detected in the female meiocyte protoplast profiling. We performed reverse genetic analysis of 120 candidate genes and identified four FM genes with a function in female meiosis progression in Arabidopsis. We further revealed that KLU, a putative cytochrome P450 monooxygenase, is involved in chromosome pairing during female meiosis, most likely by affecting the normal expression pattern of DMC1 in ovules during female meiosis. Our studies provide valuable information for functional genomic analyses of plant germline development as well as insights into meiosis. © 2014 The Authors The Plant Journal © 2014 John Wiley & Sons Ltd.

  20. A Shotgun Proteomic Approach Reveals That Fe Deficiency Causes Marked Changes in the Protein Profiles of Plasma Membrane and Detergent-Resistant Microdomain Preparations from Beta vulgaris Roots.

    Science.gov (United States)

    Gutierrez-Carbonell, Elain; Takahashi, Daisuke; Lüthje, Sabine; González-Reyes, José Antonio; Mongrand, Sébastien; Contreras-Moreira, Bruno; Abadía, Anunciación; Uemura, Matsuo; Abadía, Javier; López-Millán, Ana Flor

    2016-08-05

    In the present study we have used label-free shotgun proteomic analysis to examine the effects of Fe deficiency on the protein profiles of highly pure sugar beet root plasma membrane (PM) preparations and detergent-resistant membranes (DRMs), the latter as an approach to study microdomains. Altogether, 545 proteins were detected, with 52 and 68 of them changing significantly with Fe deficiency in PM and DRM, respectively. Functional categorization of these proteins showed that signaling and general and vesicle-related transport accounted for approximately 50% of the differences in both PM and DRM, indicating that from a qualitative point of view changes induced by Fe deficiency are similar in both preparations. Results indicate that Fe deficiency has an impact in phosphorylation processes at the PM level and highlight the involvement of signaling proteins, especially those from the 14-3-3 family. Lipid profiling revealed Fe-deficiency-induced decreases in phosphatidic acid derivatives, which may impair vesicle formation, in agreement with the decreases measured in proteins related to intracellular trafficking and secretion. The modifications induced by Fe deficiency in the relative enrichment of proteins in DRMs revealed the existence of a group of cytoplasmic proteins that appears to be more attached to the PM in conditions of Fe deficiency.

  1. Quantitative PCR Profiling of Escherichia coli in Livestock Feces Reveals Increased Population Resilience Relative to Culturable Counts under Temperature Extremes.

    Science.gov (United States)

    Oliver, David M; Bird, Clare; Burd, Emmy; Wyman, Michael

    2016-09-06

    The relationship between culturable counts (CFU) and quantitative PCR (qPCR) cell equivalent counts of Escherichia coli in dairy feces exposed to different environmental conditions and temperature extremes was investigated. Fecal samples were collected in summer and winter from dairy cowpats held under two treatments: field-exposed versus polytunnel-protected. A significant correlation in quantified E. coli was recorded between the qPCR and culture-based methods (r = 0.82). Evaluation of the persistence profiles of E. coli over time revealed no significant difference in the E. coli numbers determined as either CFU or gene copies during the summer for the field-exposed cowpats, whereas significantly higher counts were observed by qPCR for the polytunnel-protected cowpats, which were exposed to higher ambient temperatures. In winter, the qPCR returned significantly higher counts of E. coli for the field-exposed cowpats, thus representing a reversal of the findings from the summer sampling campaign. Results from this study suggest that with increasing time post-defecation and with the onset of challenging environmental conditions, such as extremes in temperature, culture-based counts begin to underestimate the true resilience of viable E. coli populations in livestock feces. This is important not only in the long term as the Earth changes in response to climate-change drivers but also in the short term during spells of extremely cold or hot weather.

  2. Metabolic profiling of presymptomatic Huntington’s disease sheep reveals novel biomarkers

    Science.gov (United States)

    Skene, Debra J.; Middleton, Benita; Fraser, Cara K.; Pennings, Jeroen L. A.; Kuchel, Timothy R.; Rudiger, Skye R.; Bawden, C. Simon; Morton, A. Jennifer

    2017-01-01

    The pronounced cachexia (unexplained wasting) seen in Huntington’s disease (HD) patients suggests that metabolic dysregulation plays a role in HD pathogenesis, although evidence of metabolic abnormalities in HD patients is inconsistent. We performed metabolic profiling of plasma from presymptomatic HD transgenic and control sheep. Metabolites were quantified in sequential plasma samples taken over a 25 h period using a targeted LC/MS metabolomics approach. Significant changes with respect to genotype were observed in 89/130 identified metabolites, including sphingolipids, biogenic amines, amino acids and urea. Citrulline and arginine increased significantly in HD compared to control sheep. Ten other amino acids decreased in presymptomatic HD sheep, including branched chain amino acids (isoleucine, leucine and valine) that have been identified previously as potential biomarkers of HD. Significant increases in urea, arginine, citrulline, asymmetric and symmetric dimethylarginine, alongside decreases in sphingolipids, indicate that both the urea cycle and nitric oxide pathways are dysregulated at early stages in HD. Logistic prediction modelling identified a set of 8 biomarkers that can identify 80% of the presymptomatic HD sheep as transgenic, with 90% confidence. This level of sensitivity, using minimally invasive methods, offers novel opportunities for monitoring disease progression in HD patients. PMID:28223686

  3. Secretome profiling of oral squamous cell carcinoma-associated fibroblasts reveals organization and disassembly of extracellular matrix and collagen metabolic process signatures.

    Science.gov (United States)

    Bagordakis, Elizabete; Sawazaki-Calone, Iris; Macedo, Carolina Carneiro Soares; Carnielli, Carolina M; de Oliveira, Carine Ervolino; Rodrigues, Priscila Campioni; Rangel, Ana Lucia C A; Dos Santos, Jean Nunes; Risteli, Juha; Graner, Edgard; Salo, Tuula; Paes Leme, Adriana Franco; Coletta, Ricardo D

    2016-07-01

    An important role has been attributed to cancer-associated fibroblasts (CAFs) in the tumorigenesis of oral squamous cell carcinoma (OSCC), the most common tumor of the oral cavity. Previous studies demonstrated that CAF-secreted molecules promote the proliferation and invasion of OSCC cells, inducing a more aggressive phenotype. In this study, we searched for differences in the secretome of CAFs and normal oral fibroblasts (NOF) using mass spectrometry-based proteomics and biological network analysis. Comparison of the secretome profiles revealed that upregulated proteins involved mainly in extracellular matrix organization and disassembly and collagen metabolism. Among the upregulated proteins were fibronectin type III domain-containing 1 (FNDC1), serpin peptidase inhibitor type 1 (SERPINE1), and stanniocalcin 2 (STC2), the upregulation of which was validated by quantitative PCR and ELISA in an independent set of CAF cell lines. The transition of transforming growth factor beta 1 (TGF-β1)-mediating NOFs into CAFs was accompanied by significant upregulation of FNDC1, SERPINE1, and STC2, confirming the participation of these proteins in the CAF-derived secretome. Type I collagen, the main constituent of the connective tissue, was also associated with several upregulated biological processes. The immunoexpression of type I collagen N-terminal propeptide (PINP) was significantly correlated in vivo with CAFs in the tumor front and was associated with significantly shortened survival of OSCC patients. Presence of CAFs in the tumor stroma was also an independent prognostic factor for OSCC disease-free survival. These results demonstrate the value of secretome profiling for evaluating the role of CAFs in the tumor microenvironment and identify potential novel therapeutic targets such as FNDC1, SERPINE1, and STC2. Furthermore, type I collagen expression by CAFs, represented by PINP levels, may be a prognostic marker of OSCC outcome.

  4. In-Depth Two-Year Study of Phenolic Profile Variability among Olive Oils from Autochthonous and Mediterranean Varieties in Morocco, as Revealed by a LC-MS Chemometric Profiling Approach

    Directory of Open Access Journals (Sweden)

    Aadil Bajoub

    2016-12-01

    Full Text Available Olive oil phenolic fraction considerably contributes to the sensory quality and nutritional value of this foodstuff. Herein, the phenolic fraction of 203 olive oil samples extracted from fruits of four autochthonous Moroccan cultivars (“Picholine Marocaine”, “Dahbia”, “Haouzia” and “Menara”, and nine Mediterranean varieties recently introduced in Morocco (“Arbequina”, “Arbosana”, “Cornicabra”, “Frantoio”, “Hojiblanca”, “Koroneiki”, “Manzanilla”, “Picholine de Languedoc” and “Picual”, were explored over two consecutive crop seasons (2012/2013 and 2013/2014 by using liquid chromatography-mass spectrometry. A total of 32 phenolic compounds (and quinic acid, belonging to five chemical classes (secoiridoids, simple phenols, flavonoids, lignans and phenolic acids were identified and quantified. Phenolic profiling revealed that the determined phenolic compounds showed variety-dependent levels, being, at the same time, significantly affected by the crop season. Moreover, based on the obtained phenolic composition and chemometric linear discriminant analysis, statistical models were obtained allowing a very satisfactory classification and prediction of the varietal origin of the studied oils.

  5. Circadian profile of QT interval and QT interval variability in 172 healthy volunteers

    DEFF Research Database (Denmark)

    Bonnemeier, Hendrik; Wiegand, Uwe K H; Braasch, Wiebke

    2003-01-01

    of sleep. QT and R-R intervals revealed a characteristic day-night-pattern. Diurnal profiles of QT interval variability exhibited a significant increase in the morning hours (6-9 AM; P ... lower at day- and nighttime. Aging was associated with an increase of QT interval mainly at daytime and a significant shift of the T wave apex towards the end of the T wave. The circadian profile of ventricular repolarization is strongly related to the mean R-R interval, however, there are significant...

  6. Proteomic Characterization of Armillaria mellea Reveals Oxidative Stress Response Mechanisms and Altered Secondary Metabolism Profiles

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    Cassandra Collins

    2017-09-01

    Full Text Available Armillaria mellea is a major plant pathogen. Yet, the strategies the organism uses to infect susceptible species, degrade lignocellulose and other plant material and protect itself against plant defences and its own glycodegradative arsenal are largely unknown. Here, we use a combination of gel and MS-based proteomics to profile A. mellea under conditions of oxidative stress and changes in growth matrix. 2-DE and LC-MS/MS were used to investigate the response of A. mellea to H2O2 and menadione/FeCl3 exposure, respectively. Several proteins were detected with altered abundance in response to H2O2, but not menadione/FeCl3 (i.e., valosin-containing protein, indicating distinct responses to these different forms of oxidative stress. One protein, cobalamin-independent methionine synthase, demonstrated a common response in both conditions, which may be a marker for a more general stress response mechanism. Further changes to the A. mellea proteome were investigated using MS-based proteomics, which identified changes to putative secondary metabolism (SM enzymes upon growth in agar compared to liquid cultures. Metabolomic analyses revealed distinct profiles, highlighting the effect of growth matrix on SM production. This establishes robust methods by which to utilize comparative proteomics to characterize this important phytopathogen.

  7. Gene expression profiling reveals multiple toxicity endpoints induced by hepatotoxicants

    Energy Technology Data Exchange (ETDEWEB)

    Huang Qihong; Jin Xidong; Gaillard, Elias T.; Knight, Brian L.; Pack, Franklin D.; Stoltz, James H.; Jayadev, Supriya; Blanchard, Kerry T

    2004-05-18

    Microarray technology continues to gain increased acceptance in the drug development process, particularly at the stage of toxicology and safety assessment. In the current study, microarrays were used to investigate gene expression changes associated with hepatotoxicity, the most commonly reported clinical liability with pharmaceutical agents. Acetaminophen, methotrexate, methapyrilene, furan and phenytoin were used as benchmark compounds capable of inducing specific but different types of hepatotoxicity. The goal of the work was to define gene expression profiles capable of distinguishing the different subtypes of hepatotoxicity. Sprague-Dawley rats were orally dosed with acetaminophen (single dose, 4500 mg/kg for 6, 24 and 72 h), methotrexate (1 mg/kg per day for 1, 7 and 14 days), methapyrilene (100 mg/kg per day for 3 and 7 days), furan (40 mg/kg per day for 1, 3, 7 and 14 days) or phenytoin (300 mg/kg per day for 14 days). Hepatic gene expression was assessed using toxicology-specific gene arrays containing 684 target genes or expressed sequence tags (ESTs). Principal component analysis (PCA) of gene expression data was able to provide a clear distinction of each compound, suggesting that gene expression data can be used to discern different hepatotoxic agents and toxicity endpoints. Gene expression data were applied to the multiplicity-adjusted permutation test and significantly changed genes were categorized and correlated to hepatotoxic endpoints. Repression of enzymes involved in lipid oxidation (acyl-CoA dehydrogenase, medium chain, enoyl CoA hydratase, very long-chain acyl-CoA synthetase) were associated with microvesicular lipidosis. Likewise, subsets of genes associated with hepatotocellular necrosis, inflammation, hepatitis, bile duct hyperplasia and fibrosis have been identified. The current study illustrates that expression profiling can be used to: (1) distinguish different hepatotoxic endpoints; (2) predict the development of toxic endpoints; and

  8. Comparative mRNA and microRNA expression profiling of three genitourinary cancers reveals common hallmarks and cancer-specific molecular events.

    Directory of Open Access Journals (Sweden)

    Xianxin Li

    Full Text Available Genome-wide gene expression profile using deep sequencing technologies can drive the discovery of cancer biomarkers and therapeutic targets. Such efforts are often limited to profiling the expression signature of either mRNA or microRNA (miRNA in a single type of cancer.Here we provided an integrated analysis of the genome-wide mRNA and miRNA expression profiles of three different genitourinary cancers: carcinomas of the bladder, kidney and testis.Our results highlight the general or cancer-specific roles of several genes and miRNAs that may serve as candidate oncogenes or suppressors of tumor development. Further comparative analyses at the systems level revealed that significant aberrations of the cell adhesion process, p53 signaling, calcium signaling, the ECM-receptor and cell cycle pathways, the DNA repair and replication processes and the immune and inflammatory response processes were the common hallmarks of human cancers. Gene sets showing testicular cancer-specific deregulation patterns were mainly implicated in processes related to male reproductive function, and general disruptions of multiple metabolic pathways and processes related to cell migration were the characteristic molecular events for renal and bladder cancer, respectively. Furthermore, we also demonstrated that tumors with the same histological origins and genes with similar functions tended to group together in a clustering analysis. By assessing the correlation between the expression of each miRNA and its targets, we determined that deregulation of 'key' miRNAs may result in the global aberration of one or more pathways or processes as a whole.This systematic analysis deciphered the molecular phenotypes of three genitourinary cancers and investigated their variations at the miRNA level simultaneously. Our results provided a valuable source for future studies and highlighted some promising genes, miRNAs, pathways and processes that may be useful for diagnostic or

  9. Peptide profiling of bovine kefir reveals 236 unique peptides released from caseins during its production by starter culture or kefir grains.

    Science.gov (United States)

    Ebner, Jennifer; Aşçı Arslan, Ayşe; Fedorova, Maria; Hoffmann, Ralf; Küçükçetin, Ahmet; Pischetsrieder, Monika

    2015-03-18

    Kefir has a long tradition in human nutrition due to its presupposed health promoting effects. To investigate the potential contribution of bioactive peptides to the physiological effects of kefir, comprehensive analysis of the peptide profile was performed by nano-ESI-LTQ-Orbitrap MS coupled to nano-ultrahigh-performance liquid chromatography. Thus, 257 peptides were identified, mainly released from β-casein, followed by αS1-, κ-, and αS2-casein. Most (236) peptides were uniquely detected in kefir, but not in raw milk indicating that the fermentation step does not only increase the proteolytic activity 1.7- to 2.4-fold compared to unfermented milk, but also alters the composition of the peptide fraction. The influence of the microflora was determined by analyzing kefir produced from traditional kefir grains or commercial starter culture. Kefir from starter culture featured 230 peptide sequences and showed a significantly, 1.4-fold higher proteolytic activity than kefir from kefir grains with 127 peptides. A match of 97 peptides in both varieties indicates the presence of a typical kefir peptide profile that is not influenced by the individual composition of the microflora. Sixteen of the newly identified peptides were previously described as bioactive, including angiotensin-converting enzyme (ACE)-inhibitory, antimicrobial, immunomodulating, opioid, mineral binding, antioxidant, and antithrombotic effects. The present study describes a comprehensive peptide profile of kefir comprising 257 sequences. The peptide list was used to identify 16 bioactive peptides with ACE-inhibitory, antioxidant, antithrombotic, mineral binding, antimicrobial, immunomodulating and opioid activity in kefir. Furthermore, it was shown that a majority of the kefir peptides were not endogenously present in the raw material milk, but were released from milk caseins by proteases of the microbiota and are therefore specific for the product. Consequently, the proteolytic activity and the

  10. Parent Prevention Communication Profiles and Adolescent Substance Use: A Latent Profile Analysis and Growth Curve Model

    Science.gov (United States)

    Choi, Hye Jeong; Miller-Day, Michelle; Shin, YoungJu; Hecht, Michael L.; Pettigrew, Jonathan; Krieger, Janice L.; Lee, JeongKyu; Graham, John W.

    2017-01-01

    This current study identifies distinct parent prevention communication profiles and examines whether youth with different parental communication profiles have varying substance use trajectories over time. Eleven schools in two rural school districts in the Midwestern United States were selected, and 784 students were surveyed at three time points from the beginning of 7th grade to the end of 8th grade. A series of latent profile analyses were performed to identify discrete profiles/subgroups of substance-specific prevention communication (SSPC). The results revealed a 4-profile model of SSPC: Active-Open, Passive-Open, Active-Silent, and Passive-Silent. A growth curve model revealed different rates of lifetime substance use depending on the youth’s SSPC profile. These findings have implications for parenting interventions and tailoring messages for parents to fit specific SSPC profiles. PMID:29056872

  11. EG-09EPIGENETIC PROFILING REVEALS A CpG HYPERMETHYLATION PHENOTYPE (CIMP) ASSOCIATED WITH WORSE PROGRESSION-FREE SURVIVAL IN MENINGIOMA

    Science.gov (United States)

    Olar, Adriana; Wani, Khalida; Mansouri, Alireza; Zadeh, Gelareh; Wilson, Charmaine; DeMonte, Franco; Fuller, Gregory; Jones, David; Pfister, Stefan; von Deimling, Andreas; Sulman, Erik; Aldape, Kenneth

    2014-01-01

    BACKGROUND: Methylation profiling of solid tumors has revealed biologic subtypes, often with clinical implications. Methylation profiles of meningioma and their clinical implications are not well understood. METHODS: Ninety-two meningioma samples (n = 44 test set and n = 48 validation set) were profiled using the Illumina HumanMethylation450 BeadChip. Unsupervised clustering and analyses for recurrence-free survival (RFS) were performed. RESULTS: Unsupervised clustering of the test set using approximately 900 highly variable markers identified two clearly defined methylation subgroups. One of the groups (n = 19) showed global hypermethylation of a set of markers, analogous to CpG island methylator phenotype (CIMP). These findings were reproducible in the validation set, with 18/48 samples showing the CIMP-positive phenotype. Importantly, of 347 highly variable markers common to both the test and validation set analyses, 107 defined CIMP in the test set and 94 defined CIMP in the validation set, with an overlap of 83 markers between the two datasets. This number is much greater than expected by chance indicating reproducibly of the hypermethylated markers that define CIMP in meningioma. With respect to clinical correlation, the 37 CIMP-positive cases displayed significantly shorter RFS compared to the 55 non-CIMP cases (hazard ratio 2.9, p = 0.013). In an effort to develop a preliminary outcome predictor, a 155-marker subset correlated with RFS was identified in the test dataset. When interrogated in the validation dataset, this 155-marker subset showed a statistical trend (p < 0.1) towards distinguishing survival groups. CONCLUSIONS: This study defines the existence of a CIMP phenotype in meningioma, which involves a substantial proportion (37/92, 40%) of samples with clinical implications. Ongoing work will expand this cohort and examine identification of additional biologic differences (mutational and DNA copy number analysis) to further characterize the aberrant

  12. Deep RNA-Seq profile reveals biodiversity, plant-microbe interactions and a large family of NBS-LRR resistance genes in walnut (Juglans regia) tissues.

    Science.gov (United States)

    Chakraborty, Sandeep; Britton, Monica; Martínez-García, P J; Dandekar, Abhaya M

    2016-03-01

    Deep RNA-Seq profiling, a revolutionary method used for quantifying transcriptional levels, often includes non-specific transcripts from other co-existing organisms in spite of stringent protocols. Using the recently published walnut genome sequence as a filter, we present a broad analysis of the RNA-Seq derived transcriptome profiles obtained from twenty different tissues to extract the biodiversity and possible plant-microbe interactions in the walnut ecosystem in California. Since the residual nature of the transcripts being analyzed does not provide sufficient information to identify the exact strain, inferences made are constrained to the genus level. The presence of the pathogenic oomycete Phytophthora was detected in the root through the presence of a glyceraldehyde-3-phosphate dehydrogenase. Cryptococcus, the causal agent of cryptococcosis, was found in the catkins and vegetative buds, corroborating previous work indicating that the plant surface supported the sexual cycle of this human pathogen. The RNA-Seq profile revealed several species of the endophytic nitrogen fixing Actinobacteria. Another bacterial species implicated in aerobic biodegradation of methyl tert-butyl ether (Methylibium petroleiphilum) is also found in the root. RNA encoding proteins from the pea aphid were found in the leaves and vegetative buds, while a serine protease from mosquito with significant homology to a female reproductive tract protease from Drosophila mojavensis in the vegetative bud suggests egg-laying activities. The comprehensive analysis of RNA-seq data present also unraveled detailed, tissue-specific information of ~400 transcripts encoded by the largest family of resistance (R) genes (NBS-LRR), which possibly rationalizes the resistance of the specific walnut plant to the pathogens detected. Thus, we elucidate the biodiversity and possible plant-microbe interactions in several walnut (Juglans regia) tissues in California using deep RNA-Seq profiling.

  13. MicroRNA Profiling Reveals Marker of Motor Neuron Disease in ALS Models.

    Science.gov (United States)

    Hoye, Mariah L; Koval, Erica D; Wegener, Amy J; Hyman, Theodore S; Yang, Chengran; O'Brien, David R; Miller, Rebecca L; Cole, Tracy; Schoch, Kathleen M; Shen, Tao; Kunikata, Tomonori; Richard, Jean-Philippe; Gutmann, David H; Maragakis, Nicholas J; Kordasiewicz, Holly B; Dougherty, Joseph D; Miller, Timothy M

    2017-05-31

    Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder marked by the loss of motor neurons (MNs) in the brain and spinal cord, leading to fatally debilitating weakness. Because this disease predominantly affects MNs, we aimed to characterize the distinct expression profile of that cell type to elucidate underlying disease mechanisms and to identify novel targets that inform on MN health during ALS disease time course. microRNAs (miRNAs) are short, noncoding RNAs that can shape the expression profile of a cell and thus often exhibit cell-type-enriched expression. To determine MN-enriched miRNA expression, we used Cre recombinase-dependent miRNA tagging and affinity purification in mice. By defining the in vivo miRNA expression of MNs, all neurons, astrocytes, and microglia, we then focused on MN-enriched miRNAs via a comparative analysis and found that they may functionally distinguish MNs postnatally from other spinal neurons. Characterizing the levels of the MN-enriched miRNAs in CSF harvested from ALS models of MN disease demonstrated that one miRNA (miR-218) tracked with MN loss and was responsive to an ALS therapy in rodent models. Therefore, we have used cellular expression profiling tools to define the distinct miRNA expression of MNs, which is likely to enrich future studies of MN disease. This approach enabled the development of a novel, drug-responsive marker of MN disease in ALS rodents. SIGNIFICANCE STATEMENT Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease in which motor neurons (MNs) in the brain and spinal cord are selectively lost. To develop tools to aid in our understanding of the distinct expression profiles of MNs and, ultimately, to monitor MN disease progression, we identified small regulatory microRNAs (miRNAs) that were highly enriched or exclusive in MNs. The signal for one of these MN-enriched miRNAs is detectable in spinal tap biofluid from an ALS rat model, where its levels change as disease

  14. Metabolite profiling reveals a role for atypical cinnamyl alcohol dehydrogenase CAD1 in the synthesis of coniferyl alcohol in tobacco xylem.

    Science.gov (United States)

    Damiani, Isabelle; Morreel, Kris; Danoun, Saïda; Goeminne, Geert; Yahiaoui, Nabila; Marque, Christiane; Kopka, Joachim; Messens, Eric; Goffner, Deborah; Boerjan, Wout; Boudet, Alain-Michel; Rochange, Soizic

    2005-11-01

    In angiosperms, lignin is built from two main monomers, coniferyl and sinapyl alcohol, which are incorporated respectively as G and S units in the polymer. The last step of their synthesis has so far been considered to be performed by a family of dimeric cinnamyl alcohol dehydrogenases (CAD2). However, previous studies on Eucalyptus gunnii xylem showed the presence of an additional, structurally unrelated, monomeric CAD form named CAD1. This form reduces coniferaldehyde to coniferyl alcohol, but is inactive on sinapaldehyde. In this paper, we report the functional characterization of CAD1 in tobacco (Nicotiana tabacum L.). Transgenic tobacco plants with reduced CAD1 expression were obtained through an RNAi strategy. These plants displayed normal growth and development, and detailed biochemical studies were needed to reveal a role for CAD1. Lignin analyses showed that CAD1 down-regulation does not affect Klason lignin content, and has a moderate impact on G unit content of the non-condensed lignin fraction. However, comparative metabolic profiling of the methanol-soluble phenolic fraction from basal xylem revealed significant differences between CAD1 down-regulated and wild-type plants. Eight compounds were less abundant in CAD1 down-regulated lines, five of which were identified as dimers or trimers of monolignols, each containing at least one moiety derived from coniferyl alcohol. In addition, 3-trans-caffeoyl quinic acid accumulated in the transgenic plants. Together, our results support a significant contribution of CAD1 to the synthesis of coniferyl alcohol in planta, along with the previously characterized CAD2 enzymes.

  15. Beneficial Phytochemicals with Anti-Tumor Potential Revealed through Metabolic Profiling of New Red Pigmented Lettuces (Lactuca sativa L.

    Directory of Open Access Journals (Sweden)

    Xiao-Xiao Qin

    2018-04-01

    Full Text Available The present study aimed to compare polyphenols among red lettuce cultivars and identify suitable cultivars for the development and utilization of healthy vegetables. Polyphenols, mineral elements, and antioxidant activity were analyzed in the leaves of six red pigmented lettuce (Lactuca sativa L. cultivars; thereafter, we assessed the anti-tumor effects of cultivar B-2, which displayed the highest antioxidant activity. Quadrupole–Orbitrap mass spectrometry analysis revealed four classes of polyphenols in these cultivars. The composition and contents of these metabolites varied significantly among cultivars and primarily depended on leaf color. The B-2 cultivar had the highest antioxidant potential than others because it contained the highest levels of polyphenols, especially anthocyanin, flavone, and phenolic acid; furthermore, this cultivar displayed anti-tumor effects against the human lung adenocarcinoma cell line A549, human hepatoma cell line Bel7402, human cancer colorectal adenoma cell line HCT-8, and HT-29 human colon cancer cell line. Hence, the new red-leaf lettuce cultivar B-2 has a distinct metabolite profile, with high potential for development and utilization of natural phytochemical and mineral resources in lettuces and can be used as a nutrient-dense food product.

  16. Beneficial Phytochemicals with Anti-Tumor Potential Revealed through Metabolic Profiling of New Red Pigmented Lettuces (Lactuca sativa L.).

    Science.gov (United States)

    Qin, Xiao-Xiao; Zhang, Ming-Yue; Han, Ying-Yan; Hao, Jing-Hong; Liu, Chao-Jie; Fan, Shuang-Xi

    2018-04-11

    The present study aimed to compare polyphenols among red lettuce cultivars and identify suitable cultivars for the development and utilization of healthy vegetables. Polyphenols, mineral elements, and antioxidant activity were analyzed in the leaves of six red pigmented lettuce ( Lactuca sativa L.) cultivars; thereafter, we assessed the anti-tumor effects of cultivar B-2, which displayed the highest antioxidant activity. Quadrupole-Orbitrap mass spectrometry analysis revealed four classes of polyphenols in these cultivars. The composition and contents of these metabolites varied significantly among cultivars and primarily depended on leaf color. The B-2 cultivar had the highest antioxidant potential than others because it contained the highest levels of polyphenols, especially anthocyanin, flavone, and phenolic acid; furthermore, this cultivar displayed anti-tumor effects against the human lung adenocarcinoma cell line A549, human hepatoma cell line Bel7402, human cancer colorectal adenoma cell line HCT-8, and HT-29 human colon cancer cell line. Hence, the new red-leaf lettuce cultivar B-2 has a distinct metabolite profile, with high potential for development and utilization of natural phytochemical and mineral resources in lettuces and can be used as a nutrient-dense food product.

  17. Dual Transcriptome Profiling of Leishmania-Infected Human Macrophages Reveals Distinct Reprogramming Signatures.

    Science.gov (United States)

    Fernandes, Maria Cecilia; Dillon, Laura A L; Belew, Ashton Trey; Bravo, Hector Corrada; Mosser, David M; El-Sayed, Najib M

    2016-05-10

    Macrophages are mononuclear phagocytes that constitute a first line of defense against pathogens. While lethal to many microbes, they are the primary host cells of Leishmania spp. parasites, the obligate intracellular pathogens that cause leishmaniasis. We conducted transcriptomic profiling of two Leishmania species and the human macrophage over the course of intracellular infection by using high-throughput RNA sequencing to characterize the global gene expression changes and reprogramming events that underlie the interactions between the pathogen and its host. A systematic exclusion of the generic effects of large-particle phagocytosis revealed a vigorous, parasite-specific response of the human macrophage early in the infection that was greatly tempered at later time points. An analogous temporal expression pattern was observed with the parasite, suggesting that much of the reprogramming that occurs as parasites transform into intracellular forms generally stabilizes shortly after entry. Following that, the parasite establishes an intracellular niche within macrophages, with minimal communication between the parasite and the host cell later during the infection. No significant difference was observed between parasite species transcriptomes or in the transcriptional response of macrophages infected with each species. Our comparative analysis of gene expression changes that occur as mouse and human macrophages are infected by Leishmania spp. points toward a general signature of the Leishmania-macrophage infectome. Little is known about the transcriptional changes that occur within mammalian cells harboring intracellular pathogens. This study characterizes the gene expression signatures of Leishmania spp. parasites and the coordinated response of infected human macrophages as the pathogen enters and persists within them. After accounting for the generic effects of large-particle phagocytosis, we observed a parasite-specific response of the human macrophages early in

  18. CRISPR/Cas9 cleavages in budding yeast reveal templated insertions and strand-specific insertion/deletion profiles.

    Science.gov (United States)

    Lemos, Brenda R; Kaplan, Adam C; Bae, Ji Eun; Ferrazzoli, Alexander E; Kuo, James; Anand, Ranjith P; Waterman, David P; Haber, James E

    2018-02-27

    Harnessing CRISPR-Cas9 technology provides an unprecedented ability to modify genomic loci via DNA double-strand break (DSB) induction and repair. We analyzed nonhomologous end-joining (NHEJ) repair induced by Cas9 in budding yeast and found that the orientation of binding of Cas9 and its guide RNA (gRNA) profoundly influences the pattern of insertion/deletions (indels) at the site of cleavage. A common indel created by Cas9 is a 1-bp (+1) insertion that appears to result from Cas9 creating a 1-nt 5' overhang that is filled in by a DNA polymerase and ligated. The origin of +1 insertions was investigated by using two gRNAs with PAM sequences located on opposite DNA strands but designed to cleave the same sequence. These templated +1 insertions are dependent on the X-family DNA polymerase, Pol4. Deleting Pol4 also eliminated +2 and +3 insertions, which are biased toward homonucleotide insertions. Using inverted PAM sequences, we also found significant differences in overall NHEJ efficiency and repair profiles, suggesting that the binding of the Cas9:gRNA complex influences subsequent NHEJ processing. As with events induced by the site-specific HO endonuclease, CRISPR-Cas9-mediated NHEJ repair depends on the Ku heterodimer and DNA ligase 4. Cas9 events are highly dependent on the Mre11-Rad50-Xrs2 complex, independent of Mre11's nuclease activity. Inspection of the outcomes of a large number of Cas9 cleavage events in mammalian cells reveals a similar templated origin of +1 insertions in human cells, but also a significant frequency of similarly templated +2 insertions.

  19. Urine Proteomics Revealed a Significant Correlation Between Urine-Fibronectin Abundance and Estimated-GFR Decline in Patients with Bardet-Biedl Syndrome

    Directory of Open Access Journals (Sweden)

    Marianna Caterino

    2018-03-01

    Full Text Available Background:/Aims: Renal disease is a common cause of morbidity in patients with Bardet-Biedl syndrome (BBS, however the severity of kidney dysfunction is highly variable. To date, there is little information on the pathogenesis, the risk and predictor factors for poor renal outcome in this setting. The present study aims to analyze the spectrum of urinary proteins in BBS patients, in order to potentially identify 1 disease-specific proteomic profiles that may differentiate the patients from normal subjects; 2 urinary markers of renal dysfunction. Methods: Fourteen individuals (7 males and 7 females with a clinical diagnosis of BBS have been selected in this study. A pool of 10 aged-matched males and 10 aged-matched females have been used as controls for proteomic analysis. The glomerular filtration rate (eGFR has been estimated using the CKD-EPI formula. Variability of eGFR has been retrospectively assessed calculating average annual eGFR decline (ΔeGFR in a mean follow-up period of 4 years (3-7. Results: 42 proteins were significantly over- or under-represented in BBS patients compared with controls; the majority of these proteins are involved in fibrosis, cell adhesion and extracellular matrix organization. Statistic studies revealed a significant correlation between urine fibronectin (u-FN (r2=0.28; p<0.05, CD44 antigen (r2 =0.35; p<0.03 and lysosomal alfa glucosidase ( r20.27; p<0.05 abundance with the eGFR. In addition, u-FN (r2 =0.2389; p<0.05 was significantly correlated with ΔeGFR. Conclusion: The present study demonstrates that urine proteome of BBS patients differs from that of normal subjects; in addition, kidney dysfunction correlated with urine abundance of known markers of renal fibrosis.

  20. Lipidomics profiling reveals the role of glycerophospholipid metabolism in psoriasis.

    Science.gov (United States)

    Zeng, Chunwei; Wen, Bo; Hou, Guixue; Lei, Li; Mei, Zhanlong; Jia, Xuekun; Chen, Xiaomin; Zhu, Wu; Li, Jie; Kuang, Yehong; Zeng, Weiqi; Su, Juan; Liu, Siqi; Peng, Cong; Chen, Xiang

    2017-10-01

    Psoriasis is a common and chronic inflammatory skin disease that is complicated by gene-environment interactions. Although genomic, transcriptomic, and proteomic analyses have been performed to investigate the pathogenesis of psoriasis, the role of metabolites in psoriasis, particularly of lipids, remains unclear. Lipids not only comprise the bulk of the cellular membrane bilayers but also regulate a variety of biological processes such as cell proliferation, apoptosis, immunity, angiogenesis, and inflammation. In this study, an untargeted lipidomics approach was used to study the lipid profiles in psoriasis and to identify lipid metabolite signatures for psoriasis through ultra-performance liquid chromatography-tandem quadrupole mass spectrometry. Plasma samples from 90 participants (45 healthy and 45 psoriasis patients) were collected and analyzed. Statistical analysis was applied to find different metabolites between the disease and healthy groups. In addition, enzyme-linked immunosorbent assay was performed to validate differentially expressed lipids in psoriatic patient plasma. Finally, we identified differential expression of several lipids including lysophosphatidic acid (LPA), lysophosphatidylcholine (LysoPC), phosphatidylinositol (PI), phosphatidylcholine (PC), and phosphatidic acid (PA); among these metabolites, LPA, LysoPC, and PA were significantly increased, while PC and PI were down-regulated in psoriasis patients. We found that elements of glycerophospholipid metabolism such as LPA, LysoPC, PA, PI, and PC were significantly altered in the plasma of psoriatic patients; this study characterizes the circulating lipids in psoriatic patients and provides novel insight into the role of lipids in psoriasis. © The Author 2017. Published by Oxford University Press.

  1. Effects of Ramadan Fasting on Lipid Profile: A Narrative Review

    OpenAIRE

    Mohsen Mazidi; Peyman Rezaie; Ehsan Karimi; Mohsen Nematy

    2014-01-01

    Ramadan Fasting during the month of Ramadan is a religious obligation, practiced by millions of people around the world. Ramadan fasting is essentially a fundamental change in lifestyle for one lunar month. This type of fasting may have significant effects on lipid profile. Although there is no scientific consensus about the effects of fasting on cardiovascular risks such as changes in lipid profile, some studies have revealed the positive effects of Ramadan fasting (and similar religious fas...

  2. Metabolic profiling reveals potential metabolic markers associated with Hypoxia Inducible Factor-mediated signalling in hypoxic cancer cells.

    Science.gov (United States)

    Armitage, Emily G; Kotze, Helen L; Allwood, J William; Dunn, Warwick B; Goodacre, Royston; Williams, Kaye J

    2015-10-28

    Hypoxia inducible factors (HIFs) plays an important role in oxygen compromised environments and therefore in tumour survival. In this research, metabolomics has been applied to study HIFs metabolic function in two cell models: mouse hepatocellular carcinoma and human colon carcinoma, whereby the metabolism has been profiled for a range of oxygen potentials. Wild type cells have been compared to cells deficient in HIF signalling to reveal its effect on cellular metabolism under normal oxygen conditions as well as low oxygen, hypoxic and anoxic environments. Characteristic responses to hypoxia that were conserved across both cell models involved the anti-correlation between 2-hydroxyglutarate, 2-oxoglutarate, fructose, hexadecanoic acid, hypotaurine, pyruvate and octadecenoic acid with 4-hydroxyproline, aspartate, cysteine, glutamine, lysine, malate and pyroglutamate. Further to this, network-based correlation analysis revealed HIF specific pathway responses to each oxygen condition that were also conserved between cell models. From this, 4-hydroxyproline was revealed as a regulating hub in low oxygen survival of WT cells while fructose appeared to be in HIF deficient cells. Pathways surrounding these hubs were built from the direct connections of correlated metabolites that look beyond traditional pathways in order to understand the mechanism of HIF response to low oxygen environments.

  3. Proanthocyanidin profile of cowpea (Vigna unguiculata) reveals catechin-O-glucoside as the dominant compound.

    Science.gov (United States)

    Ojwang, Leonnard O; Yang, Liyi; Dykes, Linda; Awika, Joseph

    2013-08-15

    Proanthocyanidin (PA) profile and content can have important nutritional and health implications on plant foods. Six diverse cowpea phenotypes (black, red, green, white, light-brown and golden-brown) were investigated for PA composition using normal-phase HPLC and reversed-phase UPLC-TQD-MS. Catechin and (epi)afzelechin were the major flavan-3-ol units. Unusual composition was observed in all cowpea phenotypes with significant degrees of glycosylation in the monomers and dimers. The PA content of cowpea (dry basis) ranged between 2.2 and 6.3 mg/g. Monomeric flavan-3-ols were the largest group of PA (36-69%) in cowpea, with catechin-7-O-glucoside accounting for most (about 88%) of the monomers. The oligomers with degree of polymerization (DP) 2-4 ranged from 0.41 to 1.3 mg/g (15-20%), whereas DP>10 polymers accounted for only 13.5% of PA. Future studies that highlight the impact of the unusual cowpea PA profile on nutritional and bioactive properties of this important legume are warranted. Copyright © 2013 Elsevier Ltd. All rights reserved.

  4. Recent aquatic ecosystem response to environmental events revealed from 210Pb sediment profiles

    International Nuclear Information System (INIS)

    Mulsow, S.; Piovano, E.; Cordoba, F.

    2009-01-01

    The 210 Pb dating method was first introduced by , and since then has been applied to study sediment from lakes, estuaries and coastal marine environments. Hundreds of studies around the world have used 210 Pb as a geochronological tool in aquatic ecosystems. However little attention has been paid to the potential of this naturally occurring isotope as an environmental tracer of ecological events. Here we report three instances in which 210 Pb profiles measured on undisturbed sediment cores from lakes, rivers and fjords show us the potential of 210 Pb profile as a tracer of natural and anthropogenic processes. The methodology used here is a suite of techniques combining biogeochemistry (micro-electrodes), paleomagnetism (susceptibility), sediment characteristics (LOI) and visualization (SPI and X-ray) applied to the interpretation of 210 Pb profiles. We measured 210 Pb profiles on sediments from a river, Cruces River (Chile), which recorded a clear shift in the water chemistry caused by a pulp mill effluent to the river. Here metal mobilization and remobilization of the tracer may be the cause of the observed profile. We also measured 210 Pb profiles in sediment from two fjords of Southern Chile (Pillan and Renihue), the sudden deposition change of fresh 210 Pb with depth observed could very well be the result of bioturbation but it occurred in a seafloor area deprived of bioturbators. In this case, 210 Pb recorded the onset of aquaculture activities (fish farming) that took place two decades ago. Finally, 210 Pb profiles measured in two lakes in the 'pampa Argentina': Epecuen and Venado showed a particular shape with depth. These profiles apparently registered a sudden depositional event with recent 210 Pb material, probably related to strong shifts in precipitation and drought cycles in that part of the world. These three examples show that 210 Pb profiles provide valuable information not only on geochronology, but also related to natural and anthropogenic short

  5. Antifungal susceptibility profiles of 1698 yeast reference strains revealing potential emerging human pathogens.

    Directory of Open Access Journals (Sweden)

    Marie Desnos-Ollivier

    Full Text Available New molecular identification techniques and the increased number of patients with various immune defects or underlying conditions lead to the emergence and/or the description of novel species of human and animal fungal opportunistic pathogens. Antifungal susceptibility provides important information for ecological, epidemiological and therapeutic issues. The aim of this study was to assess the potential risk of the various species based on their antifungal drug resistance, keeping in mind the methodological limitations. Antifungal susceptibility profiles to the five classes of antifungal drugs (polyens, azoles, echinocandins, allylamines and antimetabolites were determined for 1698 yeast reference strains belonging to 992 species (634 Ascomycetes and 358 Basidiomycetes. Interestingly, geometric mean minimum inhibitory concentrations (MICs of all antifungal drugs tested were significantly higher for Basidiomycetes compared to Ascomycetes (p<0.001. Twenty four strains belonging to 23 species of which 19 were Basidiomycetes seem to be intrinsically "resistant" to all drugs. Comparison of the antifungal susceptibility profiles of the 4240 clinical isolates and the 315 reference strains belonging to 53 shared species showed similar results. Even in the absence of demonstrated in vitro/in vivo correlation, knowing the in vitro susceptibility to systemic antifungal agents and the putative intrinsic resistance of yeast species present in the environment is important because they could become opportunistic pathogens.

  6. Active Tectonics Revealed by River Profiles along the Puqu Fault

    Directory of Open Access Journals (Sweden)

    Ping Lu

    2015-04-01

    Full Text Available The Puqu Fault is situated in Southern Tibet. It is influenced by the eastward extrusion of Northern Tibet and carries the clockwise rotation followed by the southward extrusion. Thus, the Puqu Fault is bounded by the principal dynamic zones and the tectonic evolution remains active alongside. This study intends to understand the tectonic activity in the Puqu Fault Region from the river profiles obtained from the remotely sensed satellite imagery. A medium resolution Digital Elevation Model (DEM, 20 m was generated from an Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER stereo pair of images and the stream network in this region was extracted from this DEM. The indices of slope and drainage area were subsequently calculated from this ASTER DEM. Based on the stream power law, the area-slope plots of the streams were delineated to derive the indices of channel concavity and steepness, which are closely related to tectonic activity. The results show the active tectonics varying significantly along the Puqu Fault, although the potential influence of glaciations may exist. These results are expected to be useful for a better understanding of tectonic evolution in Southeastern Tibet.

  7. Metabolic profiling of hypoxic cells revealed a catabolic signature required for cell survival.

    Directory of Open Access Journals (Sweden)

    Christian Frezza

    Full Text Available Hypoxia is one of the features of poorly vascularised areas of solid tumours but cancer cells can survive in these areas despite the low oxygen tension. The adaptation to hypoxia requires both biochemical and genetic responses that culminate in a metabolic rearrangement to counter-balance the decrease in energy supply from mitochondrial respiration. The understanding of metabolic adaptations under hypoxia could reveal novel pathways that, if targeted, would lead to specific death of hypoxic regions. In this study, we developed biochemical and metabolomic analyses to assess the effects of hypoxia on cellular metabolism of HCT116 cancer cell line. We utilized an oxygen fluorescent probe in anaerobic cuvettes to study oxygen consumption rates under hypoxic conditions without the need to re-oxygenate the cells and demonstrated that hypoxic cells can maintain active, though diminished, oxidative phosphorylation even at 1% oxygen. These results were further supported by in situ microscopy analysis of mitochondrial NADH oxidation under hypoxia. We then used metabolomic methodologies, utilizing liquid chromatography-mass spectrometry (LC-MS, to determine the metabolic profile of hypoxic cells. This approach revealed the importance of synchronized and regulated catabolism as a mechanism of adaptation to bioenergetic stress. We then confirmed the presence of autophagy under hypoxic conditions and demonstrated that the inhibition of this catabolic process dramatically reduced the ATP levels in hypoxic cells and stimulated hypoxia-induced cell death. These results suggest that under hypoxia, autophagy is required to support ATP production, in addition to glycolysis, and that the inhibition of autophagy might be used to selectively target hypoxic regions of tumours, the most notoriously resistant areas of solid tumours.

  8. Diverse Brain Myeloid Expression Profiles Reveal Distinct Microglial Activation States and Aspects of Alzheimer’s Disease Not Evident in Mouse Models

    Directory of Open Access Journals (Sweden)

    Brad A. Friedman

    2018-01-01

    Full Text Available Microglia, the CNS-resident immune cells, play important roles in disease, but the spectrum of their possible activation states is not well understood. We derived co-regulated gene modules from transcriptional profiles of CNS myeloid cells of diverse mouse models, including new tauopathy model datasets. Using these modules to interpret single-cell data from an Alzheimer’s disease (AD model, we identified microglial subsets—distinct from previously reported “disease-associated microglia”—expressing interferon-related or proliferation modules. We then analyzed whole-tissue RNA profiles from human neurodegenerative diseases, including a new AD dataset. Correcting for altered cellular composition of AD tissue, we observed elevated expression of the neurodegeneration-related modules, but also modules not implicated using expression profiles from mouse models alone. We provide a searchable, interactive database for exploring gene expression in all these datasets (http://research-pub.gene.com/BrainMyeloidLandscape. Understanding the dimensions of CNS myeloid cell activation in human disease may reveal opportunities for therapeutic intervention.

  9. Gene expression profiling during asexual development of the late blight pathogen Phytophthora infestans reveals a highly dynamic transcriptome.

    Science.gov (United States)

    Judelson, Howard S; Ah-Fong, Audrey M V; Aux, George; Avrova, Anna O; Bruce, Catherine; Cakir, Cahid; da Cunha, Luis; Grenville-Briggs, Laura; Latijnhouwers, Maita; Ligterink, Wilco; Meijer, Harold J G; Roberts, Samuel; Thurber, Carrie S; Whisson, Stephen C; Birch, Paul R J; Govers, Francine; Kamoun, Sophien; van West, Pieter; Windass, John

    2008-04-01

    Much of the pathogenic success of Phytophthora infestans, the potato and tomato late blight agent, relies on its ability to generate from mycelia large amounts of sporangia, which release zoospores that encyst and form infection structures. To better understand these stages, Affymetrix GeneChips based on 15,650 unigenes were designed and used to profile the life cycle. Approximately half of P. infestans genes were found to exhibit significant differential expression between developmental transitions, with approximately (1)/(10) being stage-specific and most changes occurring during zoosporogenesis. Quantitative reverse-transcription polymerase chain reaction assays confirmed the robustness of the array results and showed that similar patterns of differential expression were obtained regardless of whether hyphae were from laboratory media or infected tomato. Differentially expressed genes encode potential cellular regulators, especially protein kinases; metabolic enzymes such as those involved in glycolysis, gluconeogenesis, or the biosynthesis of amino acids or lipids; regulators of DNA synthesis; structural proteins, including predicted flagellar proteins; and pathogenicity factors, including cell-wall-degrading enzymes, RXLR effector proteins, and enzymes protecting against plant defense responses. Curiously, some stage-specific transcripts do not appear to encode functional proteins. These findings reveal many new aspects of oomycete biology, as well as potential targets for crop protection chemicals.

  10. Seed metabolomic study reveals significant metabolite variations and correlations among different soybean cultivars.

    Science.gov (United States)

    Lin, Hong; Rao, Jun; Shi, Jianxin; Hu, Chaoyang; Cheng, Fang; Wilson, Zoe A; Zhang, Dabing; Quan, Sheng

    2014-09-01

    Soybean [Glycine max (L.) Merr.] is one of the world's major crops, and soybean seeds are a rich and important resource for proteins and oils. While "omics" studies, such as genomics, transcriptomics, and proteomics, have been widely applied in soybean molecular research, fewer metabolomic studies have been conducted for large-scale detection of low molecular weight metabolites, especially in soybean seeds. In this study, we investigated the seed metabolomes of 29 common soybean cultivars through combined gas chromatography-mass spectrometry and ultra-performance liquid chromatography-tandem mass spectrometry. One hundred sixty-nine named metabolites were identified and subsequently used to construct a metabolic network of mature soybean seed. Among the 169 detected metabolites, 104 were found to be significantly variable in their levels across tested cultivars. Metabolite markers that could be used to distinguish genetically related soybean cultivars were also identified, and metabolite-metabolite correlation analysis revealed some significant associations within the same or among different metabolite groups. Findings from this work may potentially provide the basis for further studies on both soybean seed metabolism and metabolic engineering to improve soybean seed quality and yield. © 2014 Institute of Botany, Chinese Academy of Sciences.

  11. Seed metabolomic study reveals significant metabolite variations and correlations among different soybean cultivars

    Institute of Scientific and Technical Information of China (English)

    Hong Lin; Jun Rao; Jianxin Shi; Chaoyang Hu; Fang Cheng; Zoe AWilson; Dabing Zhang; Sheng Quan

    2014-01-01

    Soybean [Glycine max (L.) Merr.] is one of the world’s major crops, and soybean seeds are a rich and important resource for proteins and oils. While “omics”studies, such as genomics, transcriptomics, and proteomics, have been widely applied in soybean molecular research, fewer metabolomic studies have been conducted for large-scale detection of low molecular weight metabolites, especial y in soybean seeds. In this study, we investigated the seed metabolomes of 29 common soybean cultivars through combined gas chromatography-mass spectrometry and ultra-performance liquid chromatography-tandem mass spectrometry. One hundred sixty-nine named metabolites were identified and subsequently used to construct a metabolic network of mature soybean seed. Among the 169 detected metabolites, 104 were found to be significantly variable in their levels across tested cultivars. Metabolite markers that could be used to distinguish genetical y related soybean cultivars were also identified, and metabolite-metabolite correlation analysis revealed some significant associations within the same or among different metabolite groups. Findings from this work may potentially provide the basis for further studies on both soybean seed metabolism and metabolic engineering to improve soybean seed quality and yield.

  12. High-Throughput Data of Circular RNA Profiles in Human Temporal Cortex Tissue Reveals Novel Insights into Temporal Lobe Epilepsy.

    Science.gov (United States)

    Li, Jiaxin; Lin, Haijun; Sun, Zhenrong; Kong, Guanyi; Yan, Xu; Wang, Yujiao; Wang, Xiaoxuan; Wen, Yanhua; Liu, Xiang; Zheng, Hongkun; Jia, Mei; Shi, Zhongfang; Xu, Rong; Yang, Shaohua; Yuan, Fang

    2018-01-01

    Circular RNAs (circRNAs) are a class of long noncoding RNAs with a closed loop structure that regulate gene expression as microRNA sponges. CircRNAs are more enriched in brain tissue, but knowledge of the role of circRNAs in temporal lobe epilepsy (TLE) has remained limited. This study is the first to identify the global expression profiles and characteristics of circRNAs in human temporal cortex tissue from TLE patients. Temporal cortices were collected from 17 TLE patients and 17 non-TLE patients. Total RNA was isolated, and high-throughput sequencing was used to profile the transcriptome of dysregulated circRNAs. Quantitative PCR was performed for the validation of changed circRNAs. In total, 78983 circRNAs, including 15.29% known and 84.71% novel circRNAs, were detected in this study. Intriguingly, 442 circRNAs were differentially expressed between the TLE and non-TLE groups (fold change≥2.0 and FDR≤0.05). Of these circRNAs, 188 were up-regulated, and 254 were down-regulated in the TLE patient group. Eight circRNAs were validated by real-time PCR. Remarkably, circ-EFCAB2 was intensely up-regulated, while circ-DROSHA expression was significantly lower in the TLE group than in the non-TLE group (P<0.05). Bioinformatic analysis revealed that circ-EFCAB2 binds to miR-485-5p to increase the expression level of the ion channel CLCN6, while circ-DROSHA interacts with miR-1252-5p to decrease the expression level of ATP1A2. The dysregulations of circRNAs may reflect the pathogenesis of TLE and circ-EFCAB2 and circ-DROSHA might be potential therapeutic targets and biomarkers in TLE patients. © 2018 The Author(s). Published by S. Karger AG, Basel.

  13. The Transcriptome and Terpene Profile of Eucalyptus grandis Reveals Mechanisms of Defense Against the Insect Pest, Leptocybe invasa.

    Science.gov (United States)

    Oates, Caryn N; Külheim, Carsten; Myburg, Alexander A; Slippers, Bernard; Naidoo, Sanushka

    2015-07-01

    Plants have evolved complex defenses that allow them to protect themselves against pests and pathogens. However, there is relatively little information regarding the Eucalyptus defensome. Leptocybe invasa is one of the most damaging pests in global Eucalyptus forestry, and essentially nothing is known regarding the molecular mechanisms governing the interaction between the pest and host. The aim of the study was to investigate changes in the transcriptional landscape and terpene profile of a resistant and susceptible Eucalyptus genotype in an effort to improve our understanding of this interaction. We used RNA-seqencing to investigate transcriptional changes following L. invasa oviposition. Expression levels were validated using real-time quantitative PCR. Terpene profiles were investigated using gas chromatography coupled to mass spectometry on uninfested and oviposited leaves. We found 698 and 1,115 significantly differentially expressed genes from the resistant and susceptible interactions, respectively. Gene Ontology enrichment and Mapman analyses identified putative defense mechanisms including cell wall reinforcement, protease inhibitors, cell cycle suppression and regulatory hormone signaling pathways. There were significant differences in the mono- and sesquiterpene profiles between genotypes and between control and infested material. A model of the interaction between Eucalyptus and L. invasa was proposed from the transcriptomic and chemical data. © The Author 2015. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  14. Computational dissection of human episodic memory reveals mental process-specific genetic profiles.

    Science.gov (United States)

    Luksys, Gediminas; Fastenrath, Matthias; Coynel, David; Freytag, Virginie; Gschwind, Leo; Heck, Angela; Jessen, Frank; Maier, Wolfgang; Milnik, Annette; Riedel-Heller, Steffi G; Scherer, Martin; Spalek, Klara; Vogler, Christian; Wagner, Michael; Wolfsgruber, Steffen; Papassotiropoulos, Andreas; de Quervain, Dominique J-F

    2015-09-01

    Episodic memory performance is the result of distinct mental processes, such as learning, memory maintenance, and emotional modulation of memory strength. Such processes can be effectively dissociated using computational models. Here we performed gene set enrichment analyses of model parameters estimated from the episodic memory performance of 1,765 healthy young adults. We report robust and replicated associations of the amine compound SLC (solute-carrier) transporters gene set with the learning rate, of the collagen formation and transmembrane receptor protein tyrosine kinase activity gene sets with the modulation of memory strength by negative emotional arousal, and of the L1 cell adhesion molecule (L1CAM) interactions gene set with the repetition-based memory improvement. Furthermore, in a large functional MRI sample of 795 subjects we found that the association between L1CAM interactions and memory maintenance revealed large clusters of differences in brain activity in frontal cortical areas. Our findings provide converging evidence that distinct genetic profiles underlie specific mental processes of human episodic memory. They also provide empirical support to previous theoretical and neurobiological studies linking specific neuromodulators to the learning rate and linking neural cell adhesion molecules to memory maintenance. Furthermore, our study suggests additional memory-related genetic pathways, which may contribute to a better understanding of the neurobiology of human memory.

  15. Computational dissection of human episodic memory reveals mental process-specific genetic profiles

    Science.gov (United States)

    Luksys, Gediminas; Fastenrath, Matthias; Coynel, David; Freytag, Virginie; Gschwind, Leo; Heck, Angela; Jessen, Frank; Maier, Wolfgang; Milnik, Annette; Riedel-Heller, Steffi G.; Scherer, Martin; Spalek, Klara; Vogler, Christian; Wagner, Michael; Wolfsgruber, Steffen; Papassotiropoulos, Andreas; de Quervain, Dominique J.-F.

    2015-01-01

    Episodic memory performance is the result of distinct mental processes, such as learning, memory maintenance, and emotional modulation of memory strength. Such processes can be effectively dissociated using computational models. Here we performed gene set enrichment analyses of model parameters estimated from the episodic memory performance of 1,765 healthy young adults. We report robust and replicated associations of the amine compound SLC (solute-carrier) transporters gene set with the learning rate, of the collagen formation and transmembrane receptor protein tyrosine kinase activity gene sets with the modulation of memory strength by negative emotional arousal, and of the L1 cell adhesion molecule (L1CAM) interactions gene set with the repetition-based memory improvement. Furthermore, in a large functional MRI sample of 795 subjects we found that the association between L1CAM interactions and memory maintenance revealed large clusters of differences in brain activity in frontal cortical areas. Our findings provide converging evidence that distinct genetic profiles underlie specific mental processes of human episodic memory. They also provide empirical support to previous theoretical and neurobiological studies linking specific neuromodulators to the learning rate and linking neural cell adhesion molecules to memory maintenance. Furthermore, our study suggests additional memory-related genetic pathways, which may contribute to a better understanding of the neurobiology of human memory. PMID:26261317

  16. Offset-electrode profile acquisition strategy for electrical resistivity tomography

    Science.gov (United States)

    Robbins, Austin R.; Plattner, Alain

    2018-04-01

    We present an electrode layout strategy that allows electrical resistivity profiles to image the third dimension close to the profile plane. This "offset-electrode profile" approach involves laterally displacing electrodes away from the profile line in an alternating fashion and then inverting the resulting data using three-dimensional electrical resistivity tomography software. In our synthetic and field surveys, the offset-electrode method succeeds in revealing three-dimensional structures in the vicinity of the profile plane, which we could not achieve using three-dimensional inversions of linear profiles. We confirm and explain the limits of linear electrode profiles through a discussion of the three-dimensional sensitivity patterns: For a homogeneous starting model together with a linear electrode layout, all sensitivities remain symmetric with respect to the profile plane through each inversion step. This limitation can be overcome with offset-electrode layouts by breaking the symmetry pattern among the sensitivities. Thanks to freely available powerful three-dimensional resistivity tomography software and cheap modern computing power, the requirement for full three-dimensional calculations does not create a significant burden and renders the offset-electrode approach a cost-effective method. By offsetting the electrodes in an alternating pattern, as opposed to laying the profile out in a U-shape, we minimize shortening the profile length.

  17. Antioxidant profiling of native Andean potato tubers (Solanum tuberosum L.) reveals cultivars with high levels of beta-carotene, alpha-tocopherol, chlorogenic acid, and petanin.

    Science.gov (United States)

    Andre, Christelle M; Oufir, Mouhssin; Guignard, Cédric; Hoffmann, Lucien; Hausman, Jean-François; Evers, Danièle; Larondelle, Yvan

    2007-12-26

    The antioxidant profile of 23 native Andean potato cultivars has been investigated from a human nutrition perspective. The main carotenoid and tocopherol compounds were studied using high-performance liquid chromatography coupled with a diode array detector (HPLC-DAD) and a fluorescence detector, respectively, whereas polyphenols (including anthocyanins in colored tubers) were identified by means of both HPLC-mass spectrometry and HPLC-DAD. Antioxidant profiling revealed significant genotypic variations as well as cultivars of particular interest from a nutritional point of view. Concentrations of the health-promoting carotenoids, lutein and zeaxanthin, ranged from 1.12 to 17.69 microg g(-1) of dry weight (DW) and from 0 to 17.7 microg g(-1) of DW, with cultivars 704353 and 702472 showing the highest levels in lutein and zeaxanthin, respectively. Whereas beta-carotene is rarely reported in potato tubers, remarkable levels of this dietary provitamin A carotenoid were detected in 16 native varieties, ranging from 0.42 to 2.19 microg g(-1) of DW. The amounts of alpha-tocopherol found in Andean potato tubers, extending from 2.73 to 20.80 microg g(-1) of DW, were clearly above the quantities generally reported for commercial varieties. Chlorogenic acid and its isomers dominated the polyphenolic profile of each cultivar. Dark purple-fleshed tubers from the cultivar 704429 contained exceptionally high levels of total anthocyanins (16.33 mg g(-1) of DW). The main anthocyanin was identified as petanin (petunidin-3-p-coumaroyl-rutinoside-5-glucoside). The results suggest that Andean potato cultivars should be exploited in screening and breeding programs for the development of potato varieties with enhanced health and nutritional benefits.

  18. Systematic profiling of alternative splicing signature reveals prognostic predictor for ovarian cancer.

    Science.gov (United States)

    Zhu, Junyong; Chen, Zuhua; Yong, Lei

    2018-02-01

    The majority of genes are alternatively spliced and growing evidence suggests that alternative splicing is modified in cancer and is associated with cancer progression. Systematic analysis of alternative splicing signature in ovarian cancer is lacking and greatly needed. We profiled genome-wide alternative splicing events in 408 ovarian serous cystadenocarcinoma (OV) patients in TCGA. Seven types of alternative splicing events were curated and prognostic analyses were performed with predictive models and splicing network built for OV patients. Among 48,049 mRNA splicing events in 10,582 genes, we detected 2,611 alternative splicing events in 2,036 genes which were significant associated with overall survival of OV patients. Exon skip events were the most powerful prognostic factors among the seven types. The area under the curve of the receiver-operator characteristic curve for prognostic predictor, which was built with top significant alternative splicing events, was 0.937 at 2,000 days of overall survival, indicating powerful efficiency in distinguishing patient outcome. Interestingly, splicing correlation network suggested obvious trends in the role of splicing factors in OV. In summary, we built powerful prognostic predictors for OV patients and uncovered interesting splicing networks which could be underlying mechanisms. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. MOTIVATIONAL PROFILES IN PHYSICAL EDUCATION AND THEIR RELATION TO THE THEORY OF PLANNED BEHAVIOR

    Directory of Open Access Journals (Sweden)

    Juan Antonio Moreno-Murcia

    2013-09-01

    Full Text Available The aim of this study was to establish motivational profiles for doing physical activity according to the variables from the theory of planned action in a sample of 698 students aged 14 to 16. The instruments used were the Questionnaire of Behavioral Regulation in Sport (BRQ-R and the Questionnaire of the Theory of Planned Behavior (TCP. Cluster analysis revealed two motivational profiles: a "self-determined" profile with high scores in intrinsic motivation and low scores in extrinsic motivation and amotivation, and a "non self- determined" profile with low scores in intrinsic motivation and high scores in extrinsic motivation and amotivation. Positive significant differences in attitudes, norms, and intent to control were found for the self-determined profile related to "non self-determined" profile

  20. Expression profiling of a genetic animal model of depression reveals novel molecular pathways underlying depressive-like behaviours.

    Directory of Open Access Journals (Sweden)

    Ekaterini Blaveri

    2010-09-01

    Full Text Available The Flinders model is a validated genetic rat model of depression that exhibits a number of behavioural, neurochemical and pharmacological features consistent with those observed in human depression.In this study we have used genome-wide microarray expression profiling of the hippocampus and prefrontal/frontal cortex of Flinders Depression Sensitive (FSL and control Flinders Depression Resistant (FRL lines to understand molecular basis for the differences between the two lines. We profiled two independent cohorts of Flinders animals derived from the same colony six months apart, each cohort statistically powered to allow independent as well as combined analysis. Using this approach, we were able to validate using real-time-PCR a core set of gene expression differences that showed statistical significance in each of the temporally distinct cohorts, representing consistently maintained features of the model. Small but statistically significant increases were confirmed for cholinergic (chrm2, chrna7 and serotonergic receptors (Htr1a, Htr2a in FSL rats consistent with known neurochemical changes in the model. Much larger gene changes were validated in a number of novel genes as exemplified by TMEM176A, which showed 35-fold enrichment in the cortex and 30-fold enrichment in hippocampus of FRL animals relative to FSL.These data provide significant insights into the molecular differences underlying the Flinders model, and have potential relevance to broader depression research.

  1. Comprehensive profiling of DNA methylation in colorectal cancer reveals subgroups with distinct clinicopathological and molecular features

    International Nuclear Information System (INIS)

    Ang, Pei Woon; Soong, Richie; Loh, Marie; Liem, Natalia; Lim, Pei Li; Grieu, Fabienne; Vaithilingam, Aparna; Platell, Cameron; Yong, Wei Peng; Iacopetta, Barry

    2010-01-01

    Most previous studies of the CpG island methylator phenotype (CIMP) in colorectal cancer (CRC) have been conducted on a relatively small numbers of CpG sites. In the present study we performed comprehensive DNA methylation profiling of CRC with the aim of characterizing CIMP subgroups. DNA methylation at 1,505 CpG sites in 807 cancer-related genes was evaluated using the Illumina GoldenGate ® methylation array in 28 normal colonic mucosa and 91 consecutive CRC samples. Methylation data was analyzed using unsupervised hierarchical clustering. CIMP subgroups were compared for various clinicopathological and molecular features including patient age, tumor site, microsatellite instability (MSI), methylation at a consensus panel of CpG islands and mutations in BRAF and KRAS. A total of 202 CpG sites were differentially methylated between tumor and normal tissue. Unsupervised hierarchical clustering of methylation data from these sites revealed the existence of three CRC subgroups referred to as CIMP-low (CIMP-L, 21% of cases), CIMP-mid (CIMP-M, 14%) and CIMP-high (CIMP-H, 65%). In comparison to CIMP-L tumors, CIMP-H tumors were more often located in the proximal colon and showed more frequent mutation of KRAS and BRAF (P < 0.001). Comprehensive DNA methylation profiling identified three CRC subgroups with distinctive clinicopathological and molecular features. This study suggests that both KRAS and BRAF mutations are involved with the CIMP-H pathway of CRC rather than with distinct CIMP subgroups

  2. Comprehensive profiling of DNA methylation in colorectal cancer reveals subgroups with distinct clinicopathological and molecular features

    Directory of Open Access Journals (Sweden)

    Vaithilingam Aparna

    2010-05-01

    Full Text Available Abstract Background Most previous studies of the CpG island methylator phenotype (CIMP in colorectal cancer (CRC have been conducted on a relatively small numbers of CpG sites. In the present study we performed comprehensive DNA methylation profiling of CRC with the aim of characterizing CIMP subgroups. Methods DNA methylation at 1,505 CpG sites in 807 cancer-related genes was evaluated using the Illumina GoldenGate® methylation array in 28 normal colonic mucosa and 91 consecutive CRC samples. Methylation data was analyzed using unsupervised hierarchical clustering. CIMP subgroups were compared for various clinicopathological and molecular features including patient age, tumor site, microsatellite instability (MSI, methylation at a consensus panel of CpG islands and mutations in BRAF and KRAS. Results A total of 202 CpG sites were differentially methylated between tumor and normal tissue. Unsupervised hierarchical clustering of methylation data from these sites revealed the existence of three CRC subgroups referred to as CIMP-low (CIMP-L, 21% of cases, CIMP-mid (CIMP-M, 14% and CIMP-high (CIMP-H, 65%. In comparison to CIMP-L tumors, CIMP-H tumors were more often located in the proximal colon and showed more frequent mutation of KRAS and BRAF (P Conclusions Comprehensive DNA methylation profiling identified three CRC subgroups with distinctive clinicopathological and molecular features. This study suggests that both KRAS and BRAF mutations are involved with the CIMP-H pathway of CRC rather than with distinct CIMP subgroups.

  3. Metabolic profiling reveals ethylene mediated metabolic changes and a coordinated adaptive mechanism of 'Jonagold' apple to low oxygen stress.

    Science.gov (United States)

    Bekele, Elias A; Beshir, Wasiye F; Hertog, Maarten L A T M; Nicolai, Bart M; Geeraerd, Annemie H

    2015-11-01

    Apples are predominantly stored in controlled atmosphere (CA) storage to delay ripening and prolong their storage life. Profiling the dynamics of metabolic changes during ripening and CA storage is vital for understanding the governing molecular mechanism. In this study, the dynamics of the primary metabolism of 'Jonagold' apples during ripening in regular air (RA) storage and initiation of CA storage was profiled. 1-Methylcyclopropene (1-MCP) was exploited to block ethylene receptors and to get insight into ethylene mediated metabolic changes during ripening of the fruit and in response to hypoxic stress. Metabolic changes were quantified in glycolysis, the tricarboxylic acid (TCA) cycle, the Yang cycle and synthesis of the main amino acids branching from these metabolic pathways. Partial least square discriminant analysis of the metabolic profiles of 1-MCP treated and control apples revealed a metabolic divergence in ethylene, organic acid, sugar and amino acid metabolism. During RA storage at 18°C, most amino acids were higher in 1-MCP treated apples, whereas 1-aminocyclopropane-1-carboxylic acid (ACC) was higher in the control apples. The initial response of the fruit to CA initiation was accompanied by an increase of alanine, succinate and glutamate, but a decline in aspartate. Furthermore, alanine and succinate accumulated to higher levels in control apples than 1-MCP treated apples. The observed metabolic changes in these interlinked metabolites may indicate a coordinated adaptive strategy to maximize energy production. © 2015 Scandinavian Plant Physiology Society.

  4. GOAL PROFILES, MENTAL TOUGHNESS AND ITS INFLUENCE ON PERFORMANCE OUTCOMES AMONG WUSHU ATHLETES

    Directory of Open Access Journals (Sweden)

    Garry Kuan

    2007-10-01

    Full Text Available This study examined the association between goal orientations and mental toughness and its influence on performance outcomes in competition. Wushu athletes (n = 40 competing in Intervarsity championships in Malaysia completed Task and Ego Orientations in Sport Questionnaire (TEOSQ and Psychological Performance Inventory (PPI. Using cluster analysis techniques including hierarchical methods and the non-hierarchical method (k-means cluster to examine goal profiles, a three cluster solution emerged viz. cluster 1 - high task and moderate ego (HT/ME, cluster 2 - moderate task and low ego (MT/LE and, cluster 3 - moderate task and moderate ego (MT/ME. Analysis of the fundamental areas of mental toughness based on goal profiles revealed that athletes in cluster 1 scored significantly higher on negative energy control than athletes in cluster 2. Further, athletes in cluster 1 also scored significantly higher on positive energy control than athletes in cluster 3. Chi-square (χ2 test revealed no significant differences among athletes with different goal profiles on performance outcomes in the competition. However, significant differences were observed between athletes (medallist and non medallist in self- confidence (p = 0.001 and negative energy control (p = 0.042. Medallist's scored significantly higher on self-confidence (mean = 21.82 ± 2.72 and negative energy control (mean = 19.59 ± 2.32 than the non-medallists (self confidence-mean = 18.76 ± 2.49; negative energy control mean = 18.14 ± 1.91.

  5. Analysis of biostimulated microbial communities from two field experiments reveals temporal and spatial differences in proteome profiles

    Energy Technology Data Exchange (ETDEWEB)

    Callister, S.J.; Wilkins, M.J.; Nicora, C.D.; Williams, K.H.; Banfield, J.F.; VerBerkmoes, N.C.; Hettich, R.L.; NGuessan, A.L.; Mouser, P.J.; Elifantz, H.; Smith, R.D.; Lovley, D.R.; Lipton, M.S.; Long, P.E.

    2010-07-15

    Stimulated by an acetate-amendment field experiment conducted in 2007, anaerobic microbial populations in the aquifer at the Rifle Integrated Field Research Challenge site in Colorado reduced mobile U(VI) to insoluble U(IV). During this experiment, planktonic biomass was sampled at various time points to quantitatively evaluate proteomes. In 2008, an acetate-amended field experiment was again conducted in a similar manner to the 2007 experiment. As there was no comprehensive metagenome sequence available for use in proteomics analysis, we systematically evaluated 12 different organism genome sequences to generate sets of aggregate genomes, or “pseudo-metagenomes”, for supplying relative quantitative peptide and protein identifications. Proteomics results support previous observations of the dominance of Geobacteraceae during biostimulation using acetate as sole electron donor, and revealed a shift from an early stage of iron reduction to a late stage of iron reduction. Additionally, a shift from iron reduction to sulfate reduction was indicated by changes in the contribution of proteome information contributed by different organism genome sequences within the aggregate set. In addition, the comparison of proteome measurements made between the 2007 field experiment and 2008 field experiment revealed differences in proteome profiles. These differences may be the result of alterations in abundance and population structure within the planktonic biomass samples collected for analysis.

  6. Application of xCELLigence RTCA Biosensor Technology for Revealing the Profile and Window of Drug Responsiveness in Real Time

    Directory of Open Access Journals (Sweden)

    Dan Kho

    2015-04-01

    Full Text Available The xCELLigence technology is a real-time cellular biosensor, which measures the net adhesion of cells to high-density gold electrode arrays printed on custom-designed E-plates. The strength of cellular adhesion is influenced by a myriad of factors that include cell type, cell viability, growth, migration, spreading and proliferation. We therefore hypothesised that xCELLigence biosensor technology would provide a valuable platform for the measurement of drug responses in a multitude of different experimental, clinical or pharmacological contexts. In this manuscript, we demonstrate how xCELLigence technology has been invaluable in the identification of (1 not only if cells respond to a particular drug, but (2 the window of drug responsiveness. The latter aspect is often left to educated guess work in classical end-point assays, whereas biosensor technology reveals the temporal profile of the response in real time, which enables both acute responses and longer term responses to be profiled within the same assay. In our experience, the xCELLigence biosensor technology is suitable for highly targeted drug assessment and also low to medium throughput drug screening, which produces high content temporal data in real time.

  7. Arabian Sea GEOSECS stations revisited: Tracer-depth profiles reveal temporal variations?

    International Nuclear Information System (INIS)

    Mulsow, S.; Povinec, P.P.; Somayajulu, B.L.K.

    2002-01-01

    In March-April 1998, the Physical Research Laboratory and the Regional Research Laboratory (Ahmedabad, India) together with the IAEA Marine Environment Laboratory, Monaco, participated in the research mission to visit GEOSECS (Geochemical Ocean Sections Study) stations in the Arabian Sea. The main objective was to reoccupy these stations which were sampled in the early seventies to observe possible time variations in trace behaviour in this region. It is generally accepted that both natural (climate variations) and anthropogenic (greenhouse effect) changes can cause modifications of the oceanic characteristics and properties of deep waters on yearly and decadal scales. For long time-scales (100 to 1000 years) one needs to look at the sediments where these changes are subtly recorded. Tracers such as 14 C and 3 H (deep waters) and 228 Ra surface waters are useful markers of water circulation patterns and changes. Also man-made radiotracers such as 90 Sr, 137 Cs, 99 Tc, 238 Pu, 239 , 240 Pu and 241 Am, can give information on air-sea exchange as well as penetration (vertical change) rates in the open ocean [2]. We visited GEOSECS stations 415 to 419. In each station, CTD profiles, 3 H, 14 C, 90 Sr, 137 Cs, Pu and Am profiles, nutrients, Be, TOC and oxygen were determined from surface to bottom. Also uranium and trace elements were sampled in function of the oxygen minimum zone. In this paper we report the findings on the physical properties as well as the variations in water circulation patterns and also vertical exchange rates in the Arabian Sea. PSU profiles collected in this mission compared with those PSU profiles measured in 1974 (GEOSECS) showed marked differences in those stations located in the southeast part of the Arabian Sea. In contrast, those located more towards the north (415-416) showed little temporal variation. We think these changes may be real given that the PSU values at depth are comparable and reflect the presence of deep Antarctic bottom

  8. Placental gene-expression profiles of intrahepatic cholestasis of pregnancy reveal involvement of multiple molecular pathways in blood vessel formation and inflammation.

    Science.gov (United States)

    Du, QiaoLing; Pan, YouDong; Zhang, YouHua; Zhang, HaiLong; Zheng, YaJuan; Lu, Ling; Wang, JunLei; Duan, Tao; Chen, JianFeng

    2014-07-07

    Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-associated liver disease with potentially deleterious consequences for the fetus, particularly when maternal serum bile-acid concentration >40 μM. However, the etiology and pathogenesis of ICP remain elusive. To reveal the underlying molecular mechanisms for the association of maternal serum bile-acid level and fetal outcome in ICP patients, DNA microarray was applied to characterize the whole-genome expression profiles of placentas from healthy women and women diagnosed with ICP. Thirty pregnant women recruited in this study were categorized evenly into three groups: healthy group; mild ICP, with serum bile-acid concentration ranging from 10-40 μM; and severe ICP, with bile-acid concentration >40 μM. Gene Ontology analysis in combination with construction of gene-interaction and gene co-expression networks were applied to identify the core regulatory genes associated with ICP pathogenesis, which were further validated by quantitative real-time PCR and histological staining. The core regulatory genes were mainly involved in immune response, VEGF signaling pathway and G-protein-coupled receptor signaling, implying essential roles of immune response, vasculogenesis and angiogenesis in ICP pathogenesis. This implication was supported by the observed aggregated immune-cell infiltration and deficient blood vessel formation in ICP placentas. Our study provides a system-level insight into the placental gene-expression profiles of women with mild or severe ICP, and reveals multiple molecular pathways in immune response and blood vessel formation that might contribute to ICP pathogenesis.

  9. Gene expression profiles of prostate cancer reveal involvement of multiple molecular pathways in the metastatic process

    International Nuclear Information System (INIS)

    Chandran, Uma R; Ma, Changqing; Dhir, Rajiv; Bisceglia, Michelle; Lyons-Weiler, Maureen; Liang, Wenjing; Michalopoulos, George; Becich, Michael; Monzon, Federico A

    2007-01-01

    Prostate cancer is characterized by heterogeneity in the clinical course that often does not correlate with morphologic features of the tumor. Metastasis reflects the most adverse outcome of prostate cancer, and to date there are no reliable morphologic features or serum biomarkers that can reliably predict which patients are at higher risk of developing metastatic disease. Understanding the differences in the biology of metastatic and organ confined primary tumors is essential for developing new prognostic markers and therapeutic targets. Using Affymetrix oligonucleotide arrays, we analyzed gene expression profiles of 24 androgen-ablation resistant metastatic samples obtained from 4 patients and a previously published dataset of 64 primary prostate tumor samples. Differential gene expression was analyzed after removing potentially uninformative stromal genes, addressing the differences in cellular content between primary and metastatic tumors. The metastatic samples are highly heterogenous in expression; however, differential expression analysis shows that 415 genes are upregulated and 364 genes are downregulated at least 2 fold in every patient with metastasis. The expression profile of metastatic samples reveals changes in expression of a unique set of genes representing both the androgen ablation related pathways and other metastasis related gene networks such as cell adhesion, bone remodelling and cell cycle. The differentially expressed genes include metabolic enzymes, transcription factors such as Forkhead Box M1 (FoxM1) and cell adhesion molecules such as Osteopontin (SPP1). We hypothesize that these genes have a role in the biology of metastatic disease and that they represent potential therapeutic targets for prostate cancer

  10. Liver protein profiles in insulin receptor-knockout mice reveal novel molecules involved in the diabetes pathophysiology.

    Science.gov (United States)

    Capuani, Barbara; Della-Morte, David; Donadel, Giulia; Caratelli, Sara; Bova, Luca; Pastore, Donatella; De Canio, Michele; D'Aguanno, Simona; Coppola, Andrea; Pacifici, Francesca; Arriga, Roberto; Bellia, Alfonso; Ferrelli, Francesca; Tesauro, Manfredi; Federici, Massimo; Neri, Anna; Bernardini, Sergio; Sbraccia, Paolo; Di Daniele, Nicola; Sconocchia, Giuseppe; Orlandi, Augusto; Urbani, Andrea; Lauro, Davide

    2015-05-01

    Liver has a principal role in glucose regulation and lipids homeostasis. It is under a complex control by substrates such as hormones, nutrients, and neuronal impulses. Insulin promotes glycogen synthesis, lipogenesis, and lipoprotein synthesis and inhibits gluconeogenesis, glycogenolysis, and VLDL secretion by modifying the expression and enzymatic activity of specific molecules. To understand the pathophysiological mechanisms leading to metabolic liver disease, we analyzed liver protein patterns expressed in a mouse model of diabetes by proteomic approaches. We used insulin receptor-knockout (IR(-/-)) and heterozygous (IR(+/-)) mice as a murine model of liver metabolic dysfunction associated with diabetic ketoacidosis and insulin resistance. We evaluated liver fatty acid levels by microscopic examination and protein expression profiles by orthogonal experimental strategies using protein 2-DE MALDI-TOF/TOF and peptic nLC-MS/MS shotgun profiling. Identified proteins were then loaded into Ingenuity Pathways Analysis to find possible molecular networks. Twenty-eight proteins identified by 2-DE analysis and 24 identified by nLC-MS/MS shotgun were differentially expressed among the three genotypes. Bioinformatic analysis revealed a central role of high-mobility group box 1/2 and huntigtin never reported before in association with metabolic and related liver disease. A different modulation of these proteins in both blood and hepatic tissue further suggests their role in these processes. These results provide new insight into pathophysiology of insulin resistance and hepatic steatosis and could be useful in identifying novel biomarkers to predict risk for diabetes and its complications. Copyright © 2015 the American Physiological Society.

  11. Transcriptome profiling in engrailed-2 mutant mice reveals common molecular pathways associated with autism spectrum disorders.

    Science.gov (United States)

    Sgadò, Paola; Provenzano, Giovanni; Dassi, Erik; Adami, Valentina; Zunino, Giulia; Genovesi, Sacha; Casarosa, Simona; Bozzi, Yuri

    2013-12-19

    Transcriptome analysis has been used in autism spectrum disorder (ASD) to unravel common pathogenic pathways based on the assumption that distinct rare genetic variants or epigenetic modifications affect common biological pathways. To unravel recurrent ASD-related neuropathological mechanisms, we took advantage of the En2-/- mouse model and performed transcriptome profiling on cerebellar and hippocampal adult tissues. Cerebellar and hippocampal tissue samples from three En2-/- and wild type (WT) littermate mice were assessed for differential gene expression using microarray hybridization followed by RankProd analysis. To identify functional categories overrepresented in the differentially expressed genes, we used integrated gene-network analysis, gene ontology enrichment and mouse phenotype ontology analysis. Furthermore, we performed direct enrichment analysis of ASD-associated genes from the SFARI repository in our differentially expressed genes. Given the limited number of animals used in the study, we used permissive criteria and identified 842 differentially expressed genes in En2-/- cerebellum and 862 in the En2-/- hippocampus. Our functional analysis revealed that the molecular signature of En2-/- cerebellum and hippocampus shares convergent pathological pathways with ASD, including abnormal synaptic transmission, altered developmental processes and increased immune response. Furthermore, when directly compared to the repository of the SFARI database, our differentially expressed genes in the hippocampus showed enrichment of ASD-associated genes significantly higher than previously reported. qPCR was performed for representative genes to confirm relative transcript levels compared to those detected in microarrays. Despite the limited number of animals used in the study, our bioinformatic analysis indicates the En2-/- mouse is a valuable tool for investigating molecular alterations related to ASD.

  12. Diurnal and circadian expression profiles of glycerolipid biosynthetic genes in Arabidopsis.

    Science.gov (United States)

    Nakamura, Yuki; Andrés, Fernando; Kanehara, Kazue; Liu, Yu-chi; Coupland, George; Dörmann, Peter

    2014-01-01

    Glycerolipid composition in plant membranes oscillates in response to diurnal change. However, its functional significance remained unclear. A recent discovery that Arabidopsis florigen FT binds diurnally oscillating phosphatidylcholine molecules to promote flowering suggests that diurnal oscillation of glycerolipid composition is an important input in flowering time control. Taking advantage of public microarray data, we globally analyzed the expression pattern of glycerolipid biosynthetic genes in Arabidopsis under long-day, short-day, and continuous light conditions. The results revealed that 12 genes associated with glycerolipid metabolism showed significant oscillatory profiles. Interestingly, expression of most of these genes followed circadian profiles, suggesting that glycerolipid biosynthesis is partially under clock regulation. The oscillating expression profile of one representative gene, PECT1, was analyzed in detail. Expression of PECT1 showed a circadian pattern highly correlated with that of the clock-regulated gene GIGANTEA. Thus, our study suggests that a considerable number of glycerolipid biosynthetic genes are under circadian control.

  13. Proteomic Profiles Reveal the Function of Different Vegetative Tissues of Moringa oleifera.

    Science.gov (United States)

    Wang, Lei; Zou, Qiong; Wang, Jinxing; Zhang, Junjie; Liu, Zeping; Chen, Xiaoyang

    2016-12-01

    Moringa oleifera is a rich source of bioactive compounds and is widely used in traditional medicine and food for its nutritional value; however, the protein and peptide components of different tissues are rarely discussed. Here, we describe the first investigation of M. oleifera proteomes using mass spectrometry and bioinformatics methods. We aimed to elucidate the protein profiles of M. oleifera leaves, stem, bark, and root. Totally 202 proteins were identified from four vegetative organs. We identified 101 proteins from leaves, 51 from stem, 94 from bark and 67 from root, finding that only five proteins existed in both four vegetative parts. The calculated pI of most of the proteins is distributed in 5-10 and the molecular weight distributed below 100 kDa. Functional classification analysis revealed that proteins which are involved in catalytic activities are the most abundant both in leaves, stem, bark and root. Identification of several heat shock proteins in four vegetative tissues might be adaptive for resistance to high temperature environmental stresses of tropical or subtropical areas. Some enzymes involved in antioxidant processes were also identified in M. oleifera leaves, stem, bark and root. Among the four tissues studies here, leaves protein content and molecular diversity were the highest. The identification of the flocculating protein MO2.1 and MO2.2 in the bark and root provides clue to clarify the antimicrobial molecular mechanisms of root and bark. This study provides information on the protein compositions of M. oleifera vegetative tissues that will be beneficial for potential drug and food supplement development and plant physiology research.

  14. Proteome Profiling Outperforms Transcriptome Profiling for Coexpression Based Gene Function Prediction

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Jing; Ma, Zihao; Carr, Steven A.; Mertins, Philipp; Zhang, Hui; Zhang, Zhen; Chan, Daniel W.; Ellis, Matthew J. C.; Townsend, R. Reid; Smith, Richard D.; McDermott, Jason E.; Chen, Xian; Paulovich, Amanda G.; Boja, Emily S.; Mesri, Mehdi; Kinsinger, Christopher R.; Rodriguez, Henry; Rodland, Karin D.; Liebler, Daniel C.; Zhang, Bing

    2016-11-11

    Coexpression of mRNAs under multiple conditions is commonly used to infer cofunctionality of their gene products despite well-known limitations of this “guilt-by-association” (GBA) approach. Recent advancements in mass spectrometry-based proteomic technologies have enabled global expression profiling at the protein level; however, whether proteome profiling data can outperform transcriptome profiling data for coexpression based gene function prediction has not been systematically investigated. Here, we address this question by constructing and analyzing mRNA and protein coexpression networks for three cancer types with matched mRNA and protein profiling data from The Cancer Genome Atlas (TCGA) and the Clinical Proteomic Tumor Analysis Consortium (CPTAC). Our analyses revealed a marked difference in wiring between the mRNA and protein coexpression networks. Whereas protein coexpression was driven primarily by functional similarity between coexpressed genes, mRNA coexpression was driven by both cofunction and chromosomal colocalization of the genes. Functionally coherent mRNA modules were more likely to have their edges preserved in corresponding protein networks than functionally incoherent mRNA modules. Proteomic data strengthened the link between gene expression and function for at least 75% of Gene Ontology (GO) biological processes and 90% of KEGG pathways. A web application Gene2Net (http://cptac.gene2net.org) developed based on the three protein coexpression networks revealed novel gene-function relationships, such as linking ERBB2 (HER2) to lipid biosynthetic process in breast cancer, identifying PLG as a new gene involved in complement activation, and identifying AEBP1 as a new epithelial-mesenchymal transition (EMT) marker. Our results demonstrate that proteome profiling outperforms transcriptome profiling for coexpression based gene function prediction. Proteomics should be integrated if not preferred in gene function and human disease studies

  15. MicroRNA profiling in intraocular medulloepitheliomas.

    Directory of Open Access Journals (Sweden)

    Deepak P Edward

    Full Text Available To study the differential expression of microRNA (miRNA profiles between intraocular medulloepithelioma (ME and normal control tissue (CT.Total RNA was extracted from formalin fixed paraffin embedded (FFPE intraocular ME (n=7 and from age matched ciliary body controls (n=8. The clinical history and phenotype was recorded. MiRNA profiles were determined using the Affymetrix GeneChip miRNA Arrays analyzed using expression console 1.3 software. Validation of significantly dysregulated miRNA was confirmed by quantitative real-time PCR. The web-based DNA Intelligent Analysis (DIANA-miRPath v2.0 was used to perform enrichment analysis of differentially expressed (DE miRNA gene targets in Kyoto Encyclopedia of Genes and Genomes (KEGG pathway.The pathologic evaluation revealed one benign (benign non-teratoid, n=1 and six malignant tumors (malignant teratoid, n=2; malignant non-teratoid, n = 4. A total of 88 miRNAs were upregulated and 43 miRNAs were downregulated significantly (P<0.05 in the tumor specimens. Many of these significantly dysregulated miRNAs were known to play various roles in carcinogenesis and tumor behavior. RT-PCR validated three significantly upregulated miRNAs and three significantly downregulated miRNAs namely miR-217, miR-216a, miR-216b, miR-146a, miR-509-3p and miR-211. Many DE miRNAs that were significant in ME tumors showed dysregulation in retinoblastoma, glioblastoma, and precursor, normal and reactive human cartilage. Enriched pathway analysis suggested a significant association of upregulated miRNAs with 15 pathways involved in prion disease and several types of cancer. The pathways involving significantly downregulated miRNAs included the toll-like receptor (TLR (p<4.36E-16 and Nuclear Factor kappa B (NF-κB signaling pathways (p<9.00E-06.We report significantly dysregulated miRNAs in intraocular ME tumors, which exhibited abnormal profiles in other cancers as well such as retinoblastoma and glioblastoma. Pathway analysis

  16. Prenatal exposure to TCDD triggers significant modulation of microRNA expression profile in the thymus that affects consequent gene expression.

    Directory of Open Access Journals (Sweden)

    Narendra P Singh

    Full Text Available MicroRNAs (miRs are a class of small RNAs that regulate gene expression. There are over 700 miRs encoded in the mouse genome and modulate most of the cellular pathways and functions by controlling gene expression. However, there is not much known about the pathophysiological role of miRs. TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin, an environmental contaminant is well known to induce severe toxicity (acute and chronic with long-term effects. Also, in utero exposure of fetus to TCDD has been shown to cause thymic atrophy and alterations in T cell differentiation. It is also relevant to understand "the fetal basis of adult disease" hypothesis, which proposes that prenatal exposure to certain forms of nutritional and environmental stress can cause increased susceptibility to clinical disorders later in life. In the current study, therefore, we investigated the effects of prenatal exposure to TCDD on miR profile in fetal thymocytes and searched for their possible role in causing thymic atrophy and alterations in the expression of apoptotic genes.miR arrays of fetal thymocytes post exposure to TCDD and vehicle were performed. Of the 608 mouse miRs screened, 78 miRs were altered more than 1.5 fold and 28 miRs were changed more than 2 fold in fetal thymocytes post-TCDD exposure when compared to vehicle controls. We validated the expression of several of the miRs using RT-PCR. Furthermore, several of the miRs that were downregulated contained highly complementary sequence to the 3'-UTR region of AhR, CYP1A1, Fas and FasL. Also, the Ingenuity Pathway Analysis software and database was used to analyze the 78 miRs that exhibited significant expression changes and revealed that as many as 15 pathways may be affected.These studies revealed that TCDD-mediated alterations in miR expression may be involved in the regulation of its toxicity including cancer, hepatic injury, apoptosis, and cellular development.

  17. Haemato-biochemical and endocrine profiling of north western Himalayan Gaddi sheep during various physiological/reproductive phases

    Directory of Open Access Journals (Sweden)

    A. Sharma

    2015-08-01

    Full Text Available The study was aimed to provide baseline data regarding haemato-biochemical and endocrine profiling of Gaddi sheep found in north western Himalayan region of Himachal Pradesh, India. Each random sample was collected from 45 Gaddi sheep reared in government sheep breeding farm Tal, Hamirpur, India, during various reproductive phases viz. anestrus, breeding season and post partum period. Haematology revealed significantly higher (P<0.05 RBC as well as haematocrit values in pregnant animals (n=23 during breeding season than during other reproductive phases. The number of platelets were significantly lower (P<0.05 and MCH, MCHC values were statistically higher (P<0.05 during postpartum period than during other reproductive phases. Blood biochemistry revealed significantly higher (P<0.05 concentrations of plasma cholesterol (83.98±3.68 mg/dl, plasma calcium (71.06±1.52 mg/l, magnesium (18.21±0.53 mg/l, potassium (5.10±0.13 mEq/l and significantly lower (P<0.05 concentrations of plasma total protein (5.75±0.31 gm/dl, globulin (3.04±0.29 gm/dl and sodium (138.83±1.83 mEq/l during postpartum period in comparison to other reproductive phases. Endocrine profile revealed significantly higher (P<0.05 serum estrogen (60.97±1.24 pg/ml and T4 (6.0±0.27 μg/ml concentrations during postpartum phase. Similarly, significantly higher (P<0.05 serum progesterone (5.16±0.76 ng/ml as well as TSH (0.70±0.14 μg/ml concentration were recorded during pregnancy. From the study it can be concluded that physiological status significantly affects the blood metabolic and endocrine profile in Gaddi sheep.

  18. Profiling mRNAs of two Cuscuta species reveals possible candidate transcripts shared by parasitic plants.

    Directory of Open Access Journals (Sweden)

    Linjian Jiang

    Full Text Available Dodders are among the most important parasitic plants that cause serious yield losses in crop plants. In this report, we sought to unveil the genetic basis of dodder parasitism by profiling the trancriptomes of Cuscuta pentagona and C. suaveolens, two of the most common dodder species using a next-generation RNA sequencing platform. De novo assembly of the sequence reads resulted in more than 46,000 isotigs and contigs (collectively referred to as expressed sequence tags or ESTs for each species, with more than half of them predicted to encode proteins that share significant sequence similarities with known proteins of non-parasitic plants. Comparing our datasets with transcriptomes of 12 other fully sequenced plant species confirmed a close evolutionary relationship between dodder and tomato. Using a rigorous set of filtering parameters, we were able to identify seven pairs of ESTs that appear to be shared exclusively by parasitic plants, thus providing targets for tailored management approaches. In addition, we also discovered ESTs with sequences similarities to known plant viruses, including cryptic viruses, in the dodder sequence assemblies. Together this study represents the first comprehensive transcriptome profiling of parasitic plants in the Cuscuta genus, and is expected to contribute to our understanding of the molecular mechanisms of parasitic plant-host plant interactions.

  19. Profiling mRNAs of two Cuscuta species reveals possible candidate transcripts shared by parasitic plants.

    Science.gov (United States)

    Jiang, Linjian; Wijeratne, Asela J; Wijeratne, Saranga; Fraga, Martina; Meulia, Tea; Doohan, Doug; Li, Zhaohu; Qu, Feng

    2013-01-01

    Dodders are among the most important parasitic plants that cause serious yield losses in crop plants. In this report, we sought to unveil the genetic basis of dodder parasitism by profiling the trancriptomes of Cuscuta pentagona and C. suaveolens, two of the most common dodder species using a next-generation RNA sequencing platform. De novo assembly of the sequence reads resulted in more than 46,000 isotigs and contigs (collectively referred to as expressed sequence tags or ESTs) for each species, with more than half of them predicted to encode proteins that share significant sequence similarities with known proteins of non-parasitic plants. Comparing our datasets with transcriptomes of 12 other fully sequenced plant species confirmed a close evolutionary relationship between dodder and tomato. Using a rigorous set of filtering parameters, we were able to identify seven pairs of ESTs that appear to be shared exclusively by parasitic plants, thus providing targets for tailored management approaches. In addition, we also discovered ESTs with sequences similarities to known plant viruses, including cryptic viruses, in the dodder sequence assemblies. Together this study represents the first comprehensive transcriptome profiling of parasitic plants in the Cuscuta genus, and is expected to contribute to our understanding of the molecular mechanisms of parasitic plant-host plant interactions.

  20. Transcriptome Comparative Profiling of Barley eibi1 Mutant Reveals Pleiotropic Effects of HvABCG31 Gene on Cuticle Biogenesis and Stress Responsive Pathways

    Directory of Open Access Journals (Sweden)

    Eviatar Nevo

    2013-10-01

    Full Text Available Wild barley eibi1 mutant with HvABCG31 gene mutation has low capacity to retain leaf water, a phenotype associated with reduced cutin deposition and a thin cuticle. To better understand how such a mutant plant survives, we performed a genome-wide gene expression analysis. The leaf transcriptomes between the near-isogenic lines eibi1 and the wild type were compared using the 22-k Barley1 Affymetrix microarray. We found that the pleiotropic effect of the single gene HvABCG31 mutation was linked to the co-regulation of metabolic processes and stress-related system. The cuticle development involved cytochrome P450 family members and fatty acid metabolism pathways were significantly up-regulated by the HvABCG31 mutation, which might be anticipated to reduce the levels of cutin monomers or wax and display conspicuous cuticle defects. The candidate genes for responses to stress were induced by eibi1 mutant through activating the jasmonate pathway. The down-regulation of co-expressed enzyme genes responsible for DNA methylation and histone deacetylation also suggested that HvABCG31 mutation may affect the epigenetic regulation for barley development. Comparison of transcriptomic profiling of barley under biotic and abiotic stresses revealed that the functions of HvABCG31 gene to high-water loss rate might be different from other osmotic stresses of gene mutations in barley. The transcriptional profiling of the HvABCG31 mutation provided candidate genes for further investigation of the physiological and developmental changes caused by the mutant.

  1. YOUNG ATHLETES' MOTIVATIONAL PROFILES

    Directory of Open Access Journals (Sweden)

    Juan Antonio Moreno Murcia

    2007-06-01

    Full Text Available The aim of this study was to examine the relationship between motivational characteristics and dispositional flow. In order to accomplish this goal, motivational profiles emerging from key constructs within Achievement Goal Theory and Self-Determination Theory were related to the dispositional flow measures. A sample of 413 young athletes (Age range 12 to 16 years completed the PMCSQ-2, POSQ, SMS and DFS measures. Cluster analysis results revealed three profiles: a "self-determined profile" characterised by higher scores on the task-involving climate perception and on the task orientation; a "non-self-determined profile", characterised by higher scores on ego-involving climate perception and ego orientation; and a "low self-determined and low non-self-determined profile" which had the lowest dispositional flow. No meaningful differences were found between the "self-determined profile" and the "non-self-determined profile" in dispositional flow. The "self-determined profile" was more commonly associated with females, athletes practising individual sports and those training more than three days a week. The "non-self-determined profile" was more customary of males and athletes practising team sports as well as those training just two or three days a week

  2. miR-155, identified as anti-metastatic by global miRNA profiling of a metastasis model, inhibits cancer cell extravasation and colonization in vivo and causes significant signaling alterations

    DEFF Research Database (Denmark)

    Gravgaard, Karina Hedelund; Terp, Mikkel G; Lund, Rikke R

    2015-01-01

    To gain insight into miRNA regulation in metastasis formation, we used a metastasis cell line model that allows investigation of extravasation and colonization of circulating cancer cells to lungs in mice. Using global miRNA profiling, 28 miRNAs were found to exhibit significantly altered...... proliferation or apoptosis in established lung tumors. To identify proteins regulated by miR-155 and thus delineate its function in our cell model, we compared the proteome of xenograft tumors derived from miR-155-overexpressing CL16 cells and CL16 control cells using mass spectrometry-based proteomics. >4......,000 proteins were identified, of which 92 were consistently differentially expressed. Network analysis revealed that the altered proteins were associated with cellular functions such as movement, growth and survival as well as cell-to-cell signaling and interaction. Downregulation of the three metastasis...

  3. Deep sequencing-based transcriptome profiling analysis of bacteria-challenged Lateolabrax japonicus reveals insight into the immune-relevant genes in marine fish

    Directory of Open Access Journals (Sweden)

    Xiang Li-xin

    2010-08-01

    Full Text Available Abstract Background Systematic research on fish immunogenetics is indispensable in understanding the origin and evolution of immune systems. This has long been a challenging task because of the limited number of deep sequencing technologies and genome backgrounds of non-model fish available. The newly developed Solexa/Illumina RNA-seq and Digital gene expression (DGE are high-throughput sequencing approaches and are powerful tools for genomic studies at the transcriptome level. This study reports the transcriptome profiling analysis of bacteria-challenged Lateolabrax japonicus using RNA-seq and DGE in an attempt to gain insights into the immunogenetics of marine fish. Results RNA-seq analysis generated 169,950 non-redundant consensus sequences, among which 48,987 functional transcripts with complete or various length encoding regions were identified. More than 52% of these transcripts are possibly involved in approximately 219 known metabolic or signalling pathways, while 2,673 transcripts were associated with immune-relevant genes. In addition, approximately 8% of the transcripts appeared to be fish-specific genes that have never been described before. DGE analysis revealed that the host transcriptome profile of Vibrio harveyi-challenged L. japonicus is considerably altered, as indicated by the significant up- or down-regulation of 1,224 strong infection-responsive transcripts. Results indicated an overall conservation of the components and transcriptome alterations underlying innate and adaptive immunity in fish and other vertebrate models. Analysis suggested the acquisition of numerous fish-specific immune system components during early vertebrate evolution. Conclusion This study provided a global survey of host defence gene activities against bacterial challenge in a non-model marine fish. Results can contribute to the in-depth study of candidate genes in marine fish immunity, and help improve current understanding of host

  4. Global methylation profiling of lymphoblastoid cell lines reveals epigenetic contributions to autism spectrum disorders and a novel autism candidate gene, RORA, whose protein product is reduced in autistic brain

    Science.gov (United States)

    Nguyen, AnhThu; Rauch, Tibor A.; Pfeifer, Gerd P.; Hu, Valerie W.

    2010-01-01

    Autism is currently considered a multigene disorder with epigenetic influences. To investigate the contribution of DNA methylation to autism spectrum disorders, we have recently completed large-scale methylation profiling by CpG island microarray analysis of lymphoblastoid cell lines derived from monozygotic twins discordant for diagnosis of autism and their nonautistic siblings. Methylation profiling revealed many candidate genes differentially methylated between discordant MZ twins as well as between both twins and nonautistic siblings. Bioinformatics analysis of the differentially methylated genes demonstrated enrichment for high-level functions including gene transcription, nervous system development, cell death/survival, and other biological processes implicated in autism. The methylation status of 2 of these candidate genes, BCL-2 and retinoic acid-related orphan receptor alpha (RORA), was further confirmed by bisulfite sequencing and methylation-specific PCR, respectively. Immunohistochemical analyses of tissue arrays containing slices of the cerebellum and frontal cortex of autistic and age- and sex-matched control subjects revealed decreased expression of RORA and BCL-2 proteins in the autistic brain. Our data thus confirm the role of epigenetic regulation of gene expression via differential DNA methylation in idiopathic autism, and furthermore link molecular changes in a peripheral cell model with brain pathobiology in autism.—Nguyen, A., Rauch, T. A., Pfeifer, G. P., Hu, V. W. Global methylation profiling of lymphoblastoid cell lines reveals epigenetic contributions to autism spectrum disorders and a novel autism candidate gene, RORA, whose protein product is reduced in autistic brain. PMID:20375269

  5. Functional profiles reveal unique ecological roles of various biological soil crust organisms

    Science.gov (United States)

    Bowker, M.A.; Mau, R.L.; Maestre, F.T.; Escolar, C.; Castillo-Monroy, A. P.

    2011-01-01

    1. At the heart of the body of research on biodiversity effects on ecosystem function is the debate over whether different species tend to be functionally singular or redundant. When we consider ecosystem multi-function, the provision of multiple ecosystem functions simultaneously, we may find that seemingly redundant species may in fact play unique roles in ecosystems. 2. Over the last few decades, the significance of biological soil crusts (BSCs) as ecological boundaries and ecosystem engineers, and their multi-functional nature, has become increasingly well documented. We compiled 'functional profiles' of the organisms in this understudied community, to determine whether functional singularity emerges when multiple ecosystem functions are considered. 3. In two data sets, one representing multiple sites around the semi-arid regions of Spain (regional scale), and another from a single site in central Spain (local scale), we examined correlations between the abundance or frequency of BSC species in a community, and multiple surrogates of ecosystem functioning. There was a wide array of apparent effects of species on specific functions. 4. Notably, in gypsiferous soils and at regional scale, we found that indicators of carbon (C) and phosphorus cycling were apparently suppressed and promoted by the lichens Diploschistes diacapsis and Squamarina lentigera, respectively. The moss Pleurochaete squarrosa appears to promote C cycling in calcareous soils at this spatial scale. At the local scale in gypsiferous soils, D. diacapsis positively correlated with carbon cycling, but negatively with nitrogen cycling, whereas numerous lichens exhibited the opposite profile. 5. We found a high degree of functional singularity, i.e. that species were highly individualistic in their effects on multiple functions. Many functional attributes were not easily predictable from existing functional grouping systems based primarily on morphology. 6. Our results suggest that maintaining

  6. Analyses in zebrafish embryos reveal that nanotoxicity profiles are dependent on surface-functionalization controlled penetrance of biological membranes.

    Science.gov (United States)

    Paatero, Ilkka; Casals, Eudald; Niemi, Rasmus; Özliseli, Ezgi; Rosenholm, Jessica M; Sahlgren, Cecilia

    2017-08-21

    Mesoporous silica nanoparticles (MSNs) are extensively explored as drug delivery systems, but in depth understanding of design-toxicity relationships is still scarce. We used zebrafish (Danio rerio) embryos to study toxicity profiles of differently surface functionalized MSNs. Embryos with the chorion membrane intact, or dechoroniated embryos, were incubated or microinjected with amino (NH 2 -MSNs), polyethyleneimine (PEI-MSNs), succinic acid (SUCC-MSNs) or polyethyleneglycol (PEG-MSNs) functionalized MSNs. Toxicity was assessed by viability and cardiovascular function. NH 2 -MSNs, SUCC-MSNs and PEG-MSNs were well tolerated, 50 µg/ml PEI-MSNs induced 100% lethality 48 hours post fertilization (hpf). Dechoroniated embryos were more sensitive and 10 µg/ml PEI-MSNs reduced viability to 5% at 96hpf. Sensitivity to PEG- and SUCC-, but not NH 2 -MSNs, was also enhanced. Typically cardiovascular toxicity was evident prior to lethality. Confocal microscopy revealed that PEI-MSNs penetrated into the embryos whereas PEG-, NH2- and SUCC-MSNs remained aggregated on the skin surface. Direct exposure of inner organs by microinjecting NH 2 -MSNs and PEI-MSNs demonstrated that the particles displayed similar toxicity indicating that functionalization affects the toxicity profile by influencing penetrance through biological barriers. The data emphasize the need for careful analyses of toxicity mechanisms in relevant models and constitute an important knowledge step towards the development of safer and sustainable nanotherapies.

  7. Transcription Profiles Reveal Sugar and Hormone Signaling Pathways Mediating Flower Induction in Apple (Malus domestica Borkh.).

    Science.gov (United States)

    Xing, Li-Bo; Zhang, Dong; Li, You-Mei; Shen, Ya-Wen; Zhao, Cai-Ping; Ma, Juan-Juan; An, Na; Han, Ming-Yu

    2015-10-01

    Flower induction in apple (Malus domestica Borkh.) is regulated by complex gene networks that involve multiple signal pathways to ensure flower bud formation in the next year, but the molecular determinants of apple flower induction are still unknown. In this research, transcriptomic profiles from differentiating buds allowed us to identify genes potentially involved in signaling pathways that mediate the regulatory mechanisms of flower induction. A hypothetical model for this regulatory mechanism was obtained by analysis of the available transcriptomic data, suggesting that sugar-, hormone- and flowering-related genes, as well as those involved in cell-cycle induction, participated in the apple flower induction process. Sugar levels and metabolism-related gene expression profiles revealed that sucrose is the initiation signal in flower induction. Complex hormone regulatory networks involved in cytokinin (CK), abscisic acid (ABA) and gibberellic acid pathways also induce apple flower formation. CK plays a key role in the regulation of cell formation and differentiation, and in affecting flowering-related gene expression levels during these processes. Meanwhile, ABA levels and ABA-related gene expression levels gradually increased, as did those of sugar metabolism-related genes, in developing buds, indicating that ABA signals regulate apple flower induction by participating in the sugar-mediated flowering pathway. Furthermore, changes in sugar and starch deposition levels in buds can be affected by ABA content and the expression of the genes involved in the ABA signaling pathway. Thus, multiple pathways, which are mainly mediated by crosstalk between sugar and hormone signals, regulate the molecular network involved in bud growth and flower induction in apple trees. © The Author 2015. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists.

  8. Approximate Stokes Drift Profiles in Deep Water

    Science.gov (United States)

    Breivik, Øyvind; Janssen, Peter A. E. M.; Bidlot, Jean-Raymond

    2014-09-01

    A deep-water approximation to the Stokes drift velocity profile is explored as an alternative to the monochromatic profile. The alternative profile investigated relies on the same two quantities required for the monochromatic profile, viz the Stokes transport and the surface Stokes drift velocity. Comparisons with parametric spectra and profiles under wave spectra from the ERA-Interim reanalysis and buoy observations reveal much better agreement than the monochromatic profile even for complex sea states. That the profile gives a closer match and a more correct shear has implications for ocean circulation models since the Coriolis-Stokes force depends on the magnitude and direction of the Stokes drift profile and Langmuir turbulence parameterizations depend sensitively on the shear of the profile. The alternative profile comes at no added numerical cost compared to the monochromatic profile.

  9. Gene expression profiling in equine polysaccharide storage myopathy revealed inflammation, glycogenesis inhibition, hypoxia and mitochondrial dysfunctions

    Directory of Open Access Journals (Sweden)

    Benech Philippe

    2009-08-01

    Full Text Available Abstract Background Several cases of myopathies have been observed in the horse Norman Cob breed. Muscle histology examinations revealed that some families suffer from a polysaccharide storage myopathy (PSSM. It is assumed that a gene expression signature related to PSSM should be observed at the transcriptional level because the glycogen storage disease could also be linked to other dysfunctions in gene regulation. Thus, the functional genomic approach could be conducted in order to provide new knowledge about the metabolic disorders related to PSSM. We propose exploring the PSSM muscle fiber metabolic disorders by measuring gene expression in relationship with the histological phenotype. Results Genotypying analysis of GYS1 mutation revealed 2 homozygous (AA and 5 heterozygous (GA PSSM horses. In the PSSM muscles, histological data revealed PAS positive amylase resistant abnormal polysaccharides, inflammation, necrosis, and lipomatosis and active regeneration of fibers. Ultrastructural evaluation revealed a decrease of mitochondrial number and structural disorders. Extensive accumulation of an abnormal polysaccharide displaced and partially replaced mitochondria and myofibrils. The severity of the disease was higher in the two homozygous PSSM horses. Gene expression analysis revealed 129 genes significantly modulated (p Conclusion The main disorders observed in PSSM muscles could be related to mitochondrial dysfunctions, glycogenesis inhibition and the chronic hypoxia of the PSSM muscles.

  10. Transcriptomic profiling of bovine IVF embryos revealed candidate genes and pathways involved in early embryonic development

    Directory of Open Access Journals (Sweden)

    Yandell Brian S

    2010-01-01

    Full Text Available Abstract Background Early embryonic loss is a large contributor to infertility in cattle. Although genetic factors are known to affect early embryonic development, the discovery of such factors has been a serious challenge. The objective of this study was to identify genes differentially expressed between blastocysts and degenerative embryos at early stages of development. Results Using microarrays, genome-wide RNA expression was profiled and compared for in vitro fertilization (IVF - derived blastocysts and embryos undergoing degenerative development up to the same time point. Surprisingly similar transcriptomic profiles were found in degenerative embryos and blastocysts. Nonetheless, we identified 67 transcripts that significantly differed between these two groups of embryos at a 15% false discovery rate, including 33 transcripts showing at least a two-fold difference. Several signaling and metabolic pathways were found to be associated with the developmental status of embryos, among which were previously known important steroid biosynthesis and cell communication pathways in early embryonic development. Conclusions This study presents the first direct and comprehensive comparison of transcriptomes between IVF blastocysts and degenerative embryos, providing important information for potential genes and pathways associated with early embryonic development.

  11. Metabolomic profiling reveals mitochondrial-derived lipid biomarkers that drive obesity-associated inflammation.

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    Brante P Sampey

    Full Text Available Obesity has reached epidemic proportions worldwide. Several animal models of obesity exist, but studies are lacking that compare traditional lard-based high fat diets (HFD to "Cafeteria diets" (CAF consisting of nutrient poor human junk food. Our previous work demonstrated the rapid and severe obesogenic and inflammatory consequences of CAF compared to HFD including rapid weight gain, markers of Metabolic Syndrome, multi-tissue lipid accumulation, and dramatic inflammation. To identify potential mediators of CAF-induced obesity and Metabolic Syndrome, we used metabolomic analysis to profile serum, muscle, and white adipose from rats fed CAF, HFD, or standard control diets. Principle component analysis identified elevations in clusters of fatty acids and acylcarnitines. These increases in metabolites were associated with systemic mitochondrial dysfunction that paralleled weight gain, physiologic measures of Metabolic Syndrome, and tissue inflammation in CAF-fed rats. Spearman pairwise correlations between metabolites, physiologic, and histologic findings revealed strong correlations between elevated markers of inflammation in CAF-fed animals, measured as crown like structures in adipose, and specifically the pro-inflammatory saturated fatty acids and oxidation intermediates laurate and lauroyl carnitine. Treatment of bone marrow-derived macrophages with lauroyl carnitine polarized macrophages towards the M1 pro-inflammatory phenotype through downregulation of AMPK and secretion of pro-inflammatory cytokines. Results presented herein demonstrate that compared to a traditional HFD model, the CAF diet provides a robust model for diet-induced human obesity, which models Metabolic Syndrome-related mitochondrial dysfunction in serum, muscle, and adipose, along with pro-inflammatory metabolite alterations. These data also suggest that modifying the availability or metabolism of saturated fatty acids may limit the inflammation associated with obesity

  12. Lipid profile in cerebrovascular accidents.

    Science.gov (United States)

    Togha, Mansoureh; Gheini, Mohamad Reza; Ahmadi, Babak; Khashaiar, Patricia; Razeghi, Soodeh

    2011-01-01

    Changes in the lipid profile have been suggested as a risk factor for developing ischemic stroke. Their role in intra-cerebral hemorrhage, however, is not clear. The present study was designed to evaluate the lipid profile levels of patients who had experienced an acute stroke during the first 24-hour and to compare these levels in different patients suffering from the stroke, either hemorrhagic or ischemic, and healthy individuals. In this cross-sectional study, 258 consecutive patients with acute stroke admitted to the neurology department of our center during September 2006 and September 2007 were studied. As for the control group, 187 apparently healthy subjects living in the same community and matched for age and sex were selected. Lipid profile was measured and compared between the three groups. In the patients' group, 65 suffered from hemorrhagic stroke (group 1) and the other 193 had ischemic stroke (group 2). Except for TG values, there was no significant difference among the ischemic and hemorrhagic lipid profile. Age, cholesterol, and LDL influenced the risk of developing an ischemic stroke; TG was not reported as a risk factor or a protective one. While the comparison of data retrieved from patients suffering from hemorrhagic strokes with the controls, revealed LDL as the risk factor contributing to the development of ICH whereas TG was reported as a protective factor. It could be concluded that LDL level can be considered as a risk factor for both ischemic and hemorrhagic cerebral events.

  13. Psychological profiles and emotional regulation characteristics of women engaged in risk-taking sports.

    Science.gov (United States)

    Cazenave, Nicolas; Le Scanff, Christine; Woodman, Tim

    2007-12-01

    We investigated the psychological profiles and emotional regulation characteristics of women involved in risk-taking sports. The research sample (N=180) consisted of three groups of women engaged in: (1) non-risk sports (N=90); (2) risk-taking sports for leisure purposes (N=53); or (3) risk-taking sports as professionals (N=37). Each participant completed five questionnaires, the Sensation Seeking Scale, the Bem Sex Role Inventory, the Barratt Impulsiveness Scale, Risk & Excitement Inventory, and the Toronto Alexithymia Scale. The results revealed significant differences between the groups' profiles. Of particular interest are the differences that exist between the profiles of Group 2 (escape profile, masculine gender identity, and high scores on sensation seeking, impulsivity, alexithymia) and Group 3 (compensation profile, androgynous gender identity, average score on sensation seeking, and low scores on impulsivity, alexithymia). We propose that the professional woman might be considered a model for preventing destructive risk-taking behaviors.

  14. Multivariable Regression Analysis in Schistosoma mansoni-Infected Individuals in the Sudan Reveals Unique Immunoepidemiological Profiles in Uninfected, egg+ and Non-egg+ Infected Individuals.

    Science.gov (United States)

    Elfaki, Tayseer Elamin Mohamed; Arndts, Kathrin; Wiszniewsky, Anna; Ritter, Manuel; Goreish, Ibtisam A; Atti El Mekki, Misk El Yemen A; Arriens, Sandra; Pfarr, Kenneth; Fimmers, Rolf; Doenhoff, Mike; Hoerauf, Achim; Layland, Laura E

    2016-05-01

    In the Sudan, Schistosoma mansoni infections are a major cause of morbidity in school-aged children and infection rates are associated with available clean water sources. During infection, immune responses pass through a Th1 followed by Th2 and Treg phases and patterns can relate to different stages of infection or immunity. This retrospective study evaluated immunoepidemiological aspects in 234 individuals (range 4-85 years old) from Kassala and Khartoum states in 2011. Systemic immune profiles (cytokines and immunoglobulins) and epidemiological parameters were surveyed in n = 110 persons presenting patent S. mansoni infections (egg+), n = 63 individuals positive for S. mansoni via PCR in sera but egg negative (SmPCR+) and n = 61 people who were infection-free (Sm uninf). Immunoepidemiological findings were further investigated using two binary multivariable regression analysis. Nearly all egg+ individuals had no access to latrines and over 90% obtained water via the canal stemming from the Atbara River. With regards to age, infection and an egg+ status was linked to young and adolescent groups. In terms of immunology, S. mansoni infection per se was strongly associated with increased SEA-specific IgG4 but not IgE levels. IL-6, IL-13 and IL-10 were significantly elevated in patently-infected individuals and positively correlated with egg load. In contrast, IL-2 and IL-1β were significantly lower in SmPCR+ individuals when compared to Sm uninf and egg+ groups which was further confirmed during multivariate regression analysis. Schistosomiasis remains an important public health problem in the Sudan with a high number of patent individuals. In addition, SmPCR diagnostics revealed another cohort of infected individuals with a unique immunological profile and provides an avenue for future studies on non-patent infection states. Future studies should investigate the downstream signalling pathways/mechanisms of IL-2 and IL-1β as potential diagnostic markers in order to

  15. Multivariable Regression Analysis in Schistosoma mansoni-Infected Individuals in the Sudan Reveals Unique Immunoepidemiological Profiles in Uninfected, egg+ and Non-egg+ Infected Individuals.

    Directory of Open Access Journals (Sweden)

    Tayseer Elamin Mohamed Elfaki

    2016-05-01

    Full Text Available In the Sudan, Schistosoma mansoni infections are a major cause of morbidity in school-aged children and infection rates are associated with available clean water sources. During infection, immune responses pass through a Th1 followed by Th2 and Treg phases and patterns can relate to different stages of infection or immunity.This retrospective study evaluated immunoepidemiological aspects in 234 individuals (range 4-85 years old from Kassala and Khartoum states in 2011. Systemic immune profiles (cytokines and immunoglobulins and epidemiological parameters were surveyed in n = 110 persons presenting patent S. mansoni infections (egg+, n = 63 individuals positive for S. mansoni via PCR in sera but egg negative (SmPCR+ and n = 61 people who were infection-free (Sm uninf. Immunoepidemiological findings were further investigated using two binary multivariable regression analysis.Nearly all egg+ individuals had no access to latrines and over 90% obtained water via the canal stemming from the Atbara River. With regards to age, infection and an egg+ status was linked to young and adolescent groups. In terms of immunology, S. mansoni infection per se was strongly associated with increased SEA-specific IgG4 but not IgE levels. IL-6, IL-13 and IL-10 were significantly elevated in patently-infected individuals and positively correlated with egg load. In contrast, IL-2 and IL-1β were significantly lower in SmPCR+ individuals when compared to Sm uninf and egg+ groups which was further confirmed during multivariate regression analysis.Schistosomiasis remains an important public health problem in the Sudan with a high number of patent individuals. In addition, SmPCR diagnostics revealed another cohort of infected individuals with a unique immunological profile and provides an avenue for future studies on non-patent infection states. Future studies should investigate the downstream signalling pathways/mechanisms of IL-2 and IL-1β as potential diagnostic markers

  16. Investigating a multigene prognostic assay based on significant pathways for Luminal A breast cancer through gene expression profile analysis.

    Science.gov (United States)

    Gao, Haiyan; Yang, Mei; Zhang, Xiaolan

    2018-04-01

    The present study aimed to investigate potential recurrence-risk biomarkers based on significant pathways for Luminal A breast cancer through gene expression profile analysis. Initially, the gene expression profiles of Luminal A breast cancer patients were downloaded from The Cancer Genome Atlas database. The differentially expressed genes (DEGs) were identified using a Limma package and the hierarchical clustering analysis was conducted for the DEGs. In addition, the functional pathways were screened using Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses and rank ratio calculation. The multigene prognostic assay was exploited based on the statistically significant pathways and its prognostic function was tested using train set and verified using the gene expression data and survival data of Luminal A breast cancer patients downloaded from the Gene Expression Omnibus. A total of 300 DEGs were identified between good and poor outcome groups, including 176 upregulated genes and 124 downregulated genes. The DEGs may be used to effectively distinguish Luminal A samples with different prognoses verified by hierarchical clustering analysis. There were 9 pathways screened as significant pathways and a total of 18 DEGs involved in these 9 pathways were identified as prognostic biomarkers. According to the survival analysis and receiver operating characteristic curve, the obtained 18-gene prognostic assay exhibited good prognostic function with high sensitivity and specificity to both the train and test samples. In conclusion the 18-gene prognostic assay including the key genes, transcription factor 7-like 2, anterior parietal cortex and lymphocyte enhancer factor-1 may provide a new method for predicting outcomes and may be conducive to the promotion of precision medicine for Luminal A breast cancer.

  17. Analysis of temporal transcription expression profiles reveal links between protein function and developmental stages of Drosophila melanogaster.

    Science.gov (United States)

    Wan, Cen; Lees, Jonathan G; Minneci, Federico; Orengo, Christine A; Jones, David T

    2017-10-01

    Accurate gene or protein function prediction is a key challenge in the post-genome era. Most current methods perform well on molecular function prediction, but struggle to provide useful annotations relating to biological process functions due to the limited power of sequence-based features in that functional domain. In this work, we systematically evaluate the predictive power of temporal transcription expression profiles for protein function prediction in Drosophila melanogaster. Our results show significantly better performance on predicting protein function when transcription expression profile-based features are integrated with sequence-derived features, compared with the sequence-derived features alone. We also observe that the combination of expression-based and sequence-based features leads to further improvement of accuracy on predicting all three domains of gene function. Based on the optimal feature combinations, we then propose a novel multi-classifier-based function prediction method for Drosophila melanogaster proteins, FFPred-fly+. Interpreting our machine learning models also allows us to identify some of the underlying links between biological processes and developmental stages of Drosophila melanogaster.

  18. Analysis of temporal transcription expression profiles reveal links between protein function and developmental stages of Drosophila melanogaster.

    Directory of Open Access Journals (Sweden)

    Cen Wan

    2017-10-01

    Full Text Available Accurate gene or protein function prediction is a key challenge in the post-genome era. Most current methods perform well on molecular function prediction, but struggle to provide useful annotations relating to biological process functions due to the limited power of sequence-based features in that functional domain. In this work, we systematically evaluate the predictive power of temporal transcription expression profiles for protein function prediction in Drosophila melanogaster. Our results show significantly better performance on predicting protein function when transcription expression profile-based features are integrated with sequence-derived features, compared with the sequence-derived features alone. We also observe that the combination of expression-based and sequence-based features leads to further improvement of accuracy on predicting all three domains of gene function. Based on the optimal feature combinations, we then propose a novel multi-classifier-based function prediction method for Drosophila melanogaster proteins, FFPred-fly+. Interpreting our machine learning models also allows us to identify some of the underlying links between biological processes and developmental stages of Drosophila melanogaster.

  19. Profiling trait anxiety: transcriptome analysis reveals cathepsin B (Ctsb as a novel candidate gene for emotionality in mice.

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    Ludwig Czibere

    Full Text Available Behavioral endophenotypes are determined by a multitude of counteracting but precisely balanced molecular and physiological mechanisms. In this study, we aim to identify potential novel molecular targets that contribute to the multigenic trait "anxiety". We used microarrays to investigate the gene expression profiles of different brain regions within the limbic system of mice which were selectively bred for either high (HAB or low (LAB anxiety-related behavior, and also show signs of comorbid depression-like behavior. We identified and confirmed sex-independent differences in the basal expression of 13 candidate genes, using tissue from the entire brain, including coronin 7 (Coro7, cathepsin B (Ctsb, muscleblind-like 1 (Mbnl1, metallothionein 1 (Mt1, solute carrier family 25 member 17 (Slc25a17, tribbles homolog 2 (Trib2, zinc finger protein 672 (Zfp672, syntaxin 3 (Stx3, ATP-binding cassette, sub-family A member 2 (Abca2, ectonucleotide pyrophosphatase/phosphodiesterase 5 (Enpp5, high mobility group nucleosomal binding domain 3 (Hmgn3 and pyruvate dehydrogenase beta (Pdhb. Additionally, we confirmed brain region-specific differences in the expression of synaptotagmin 4 (Syt4.Our identification of about 90 polymorphisms in Ctsb suggested that this gene might play a critical role in shaping our mouse model's behavioral endophenotypes. Indeed, the assessment of anxiety-related and depression-like behaviors of Ctsb knock-out mice revealed an increase in depression-like behavior in females. Altogether, our results suggest that Ctsb has significant effects on emotionality, irrespective of the tested mouse strain, making it a promising target for future pharmacotherapy.

  20. Global phosphoproteome profiling reveals unanticipated networks responsive to cisplatin treatment of embryonic stem cells

    DEFF Research Database (Denmark)

    Pines, Alex; Kelstrup, Christian D; Vrouwe, Mischa G

    2011-01-01

    (stable isotope labeling by amino acids in cell culture)-labeled murine embryonic stem cells with the anticancer drug cisplatin. Network and pathway analyses indicated that processes related to the DNA damage response and cytoskeleton organization were significantly affected. Although the ATM (ataxia...... rearrangements. Integration of transcriptomic and proteomic data revealed a poor correlation between changes in the relative levels of transcripts and their corresponding proteins, but a large overlap in affected pathways at the levels of mRNA, protein, and phosphoprotein. This study provides an integrated view...

  1. Transcriptome analysis of paired primary colorectal carcinoma and liver metastases reveals fusion transcripts and similar gene expression profiles in primary carcinoma and liver metastases

    International Nuclear Information System (INIS)

    Lee, Ja-Rang; Kwon, Chae Hwa; Choi, Yuri; Park, Hye Ji; Kim, Hyun Sung; Jo, Hong-Jae; Oh, Nahmgun; Park, Do Youn

    2016-01-01

    Despite the clinical significance of liver metastases, the difference between molecular and cellular changes in primary colorectal cancers (CRC) and matched liver metastases is poorly understood. In order to compare gene expression patterns and identify fusion genes in these two types of tumors, we performed high-throughput transcriptome sequencing of five sets of quadruple-matched tissues (primary CRC, liver metastases, normal colon, and liver). The gene expression patterns in normal colon and liver were successfully distinguished from those in CRCs; however, RNA sequencing revealed that the gene expression between primary CRCs and their matched liver metastases is highly similar. We identified 1895 genes that were differentially expressed in the primary carcinoma and liver metastases, than that in the normal colon tissues. A major proportion of the transcripts, identified by gene expression profiling as significantly enriched in the primary carcinoma and metastases, belonged to gene ontology categories involved in the cell cycle, mitosis, and cell division. Furthermore, we identified gene fusion events in primary carcinoma and metastases, and the fusion transcripts were experimentally confirmed. Among these, a chimeric transcript resulting from the fusion of RNF43 and SUPT4H1 was found to occur frequently in primary colorectal carcinoma. In addition, knockdown of the expression of this RNF43-SUPT4H1 chimeric transcript was found to have a growth-inhibitory effect in colorectal cancer cells. The present study reports a high concordance of gene expression in the primary carcinoma and liver metastases, and reveals potential new targets, such as fusion genes, against primary and metastatic colorectal carcinoma. The online version of this article (doi:10.1186/s12885-016-2596-3) contains supplementary material, which is available to authorized users

  2. Proteomic profiling of human keratinocytes undergoing UVB-induced alternative differentiation reveals TRIpartite Motif Protein 29 as a survival factor.

    Directory of Open Access Journals (Sweden)

    Véronique Bertrand-Vallery

    Full Text Available BACKGROUND: Repeated exposures to UVB of human keratinocytes lacking functional p16(INK-4a and able to differentiate induce an alternative state of differentiation rather than stress-induced premature senescence. METHODOLOGY/PRINCIPAL FINDINGS: A 2D-DIGE proteomic profiling of this alternative state of differentiation was performed herein at various times after the exposures to UVB. Sixty-nine differentially abundant protein species were identified by mass spectrometry, many of which are involved in keratinocyte differentiation and survival. Among these protein species was TRIpartite Motif Protein 29 (TRIM29. Increased abundance of TRIM29 following UVB exposures was validated by Western blot using specific antibody and was also further analysed by immunochemistry and by RT-PCR. TRIM29 was found very abundant in keratinocytes and reconstructed epidermis. Knocking down the expression of TRIM29 by short-hairpin RNA interference decreased the viability of keratinocytes after UVB exposure. The abundance of involucrin mRNA, a marker of late differentiation, increased concomitantly. In TRIM29-knocked down reconstructed epidermis, the presence of picnotic cells revealed cell injury. Increased abundance of TRIM29 was also observed upon exposure to DNA damaging agents and PKC activation. The UVB-induced increase of TRIM29 abundance was dependent on a PKC signaling pathway, likely PKCdelta. CONCLUSIONS/SIGNIFICANCE: These findings suggest that TRIM29 allows keratinocytes to enter a protective alternative differentiation process rather than die massively after stress.

  3. ROLE OF FCA WELDING PROCESS PARAMETERS ON BEAD PROFILE, ANGULAR AND BOWING DISTORTION OF FERRITIC STAINLESS STEEL SHEETS

    Directory of Open Access Journals (Sweden)

    VENKATESAN M. V.

    2014-02-01

    Full Text Available This paper discusses the influence of flux cored arc welding (FCAW process parameters such as welding current, travel speed, voltage and CO2 shielding gas flow rate on bead profile, bowing distortion and angular distortion of 409 M ferritic stainless steel sheets of 2 mm thickness. The bowing and angular distortions of the welded plates were measured using a simple device called profile tracer and Vernier bevel protractor respectively. The study revealed that the FCAW process parameters have significant effect on bead profile, and distortion. The relationship between bead profile and distortions were analyzed. Most favorable process parameters that give uniform bead profile and minimum distortion for the weld are recommended for fabrication.

  4. Gene expression profiles reveal key pathways and genes associated with neuropathic pain in patients with spinal cord injury.

    Science.gov (United States)

    He, Xijing; Fan, Liying; Wu, Zhongheng; He, Jiaxuan; Cheng, Bin

    2017-04-01

    Previous gene expression profiling studies of neuropathic pain (NP) following spinal cord injury (SCI) have predominantly been performed in animal models. The present study aimed to investigate gene alterations in patients with spinal cord injury and to further examine the mechanisms underlying NP following SCI. The GSE69901 gene expression profile was downloaded from the public Gene Expression Omnibus database. Samples of peripheral blood mononuclear cells (PBMCs) derived from 12 patients with intractable NP and 13 control patients without pain were analyzed to identify the differentially expressed genes (DEGs), followed by functional enrichment analysis and protein‑protein interaction (PPI) network construction. In addition, a transcriptional regulation network was constructed and functional gene clustering was performed. A total of 70 upregulated and 61 downregulated DEGs were identified in the PBMC samples from patients with NP. The upregulated and downregulated genes were significantly involved in different Gene Ontology terms and pathways, including focal adhesion, T cell receptor signaling pathway and mitochondrial function. Glycogen synthase kinase 3 β (GSK3B) was identified as a hub protein in the PPI network. In addition, ornithine decarboxylase 1 (ODC1) and ornithine aminotransferase (OAT) were regulated by additional transcription factors in the regulation network. GSK3B, OAT and ODC1 were significantly enriched in two functional gene clusters, the function of mitochondrial membrane and DNA binding. Focal adhesion and the T cell receptor signaling pathway may be significantly linked with NP, and GSK3B, OAT and ODC1 may be potential targets for the treatment of NP.

  5. Profiling extracellular vesicle release by the filarial nematode Brugia malayi reveals sex-specific differences in cargo and a sensitivity to ivermectin.

    Directory of Open Access Journals (Sweden)

    Hiruni Harischandra

    2018-04-01

    Full Text Available The filarial nematode Brugia malayi is an etiological agent of Lymphatic Filariasis. The capability of B. malayi and other parasitic nematodes to modulate host biology is recognized but the mechanisms by which such manipulation occurs are obscure. An emerging paradigm is the release of parasite-derived extracellular vesicles (EV containing bioactive proteins and small RNA species that allow secretion of parasite effector molecules and their potential trafficking to host tissues. We have previously described EV release from the infectious L3 stage B. malayi and here we profile vesicle release across all intra-mammalian life cycle stages (microfilariae, L3, L4, adult male and female worms. Nanoparticle Tracking Analysis was used to quantify and size EVs revealing discrete vesicle populations and indicating a secretory process that is conserved across the life cycle. Brugia EVs are internalized by murine macrophages with no preference for life stage suggesting a uniform mechanism for effector molecule trafficking. Further, the use of chemical uptake inhibitors suggests all life stage EVs are internalized by phagocytosis. Proteomic profiling of adult male and female EVs using nano-scale LC-MS/MS described quantitative and qualitative differences in the adult EV proteome, helping define the biogenesis of Brugia EVs and revealing sexual dimorphic characteristics in immunomodulatory cargo. Finally, ivermectin was found to rapidly inhibit EV release by all Brugia life stages. Further this drug effect was also observed in the related filarial nematode, the canine heartworm Dirofilaria immitis but not in an ivermectin-unresponsive field isolate of that parasite, highlighting a potential mechanism of action for this drug and suggesting new screening platforms for anti-filarial drug development.

  6. Phenotypically anchored transcriptome profiling of developmental exposure to the antimicrobial agent, triclosan, reveals hepatotoxicity in embryonic zebrafish

    International Nuclear Information System (INIS)

    Haggard, Derik E.; Noyes, Pamela D.; Waters, Katrina M.; Tanguay, Robert L.

    2016-01-01

    Triclosan (TCS) is an antimicrobial agent commonly found in a variety of personal care products and cosmetics. TCS readily enters the environment through wastewater and is detected in human plasma, urine, and breast milk due to its widespread use. Studies have implicated TCS as a disruptor of thyroid and estrogen signaling; therefore, research examining the developmental effects of TCS is warranted. In this study, we used embryonic zebrafish to investigate the developmental toxicity and potential mechanism of action of TCS. Embryos were exposed to graded concentrations of TCS from 6 to 120 hours post-fertilization (hpf) and the concentration where 80% of the animals had mortality or morbidity at 120 hpf (EC 80 ) was calculated. Transcriptomic profiling was conducted on embryos exposed to the EC 80 (7.37 μM). We identified a total of 922 significant differentially expressed transcripts (FDR adjusted P-value ≤ 0.05; fold change ≥ 2). Pathway and gene ontology enrichment analyses identified biological networks and transcriptional hubs involving normal liver functioning, suggesting TCS may be hepatotoxic in zebrafish. Tissue-specific gene enrichment analysis further supported the role of the liver as a target organ for TCS toxicity. We also examined the in vitro bioactivity profile of TCS reported by the ToxCast screening program. TCS had a diverse bioactivity profile and was a hit in 217 of the 385 assay endpoints we identified. We observed similarities in gene expression and hepatic steatosis assays; however, hit data for TCS were more concordant with the hypothesized CAR/PXR activity of TCS from rodent and human in vitro studies. - Highlights: • Triclosan is a common antimicrobial agent with widespread human exposure. • Exposure to the triclosan EC 80 causes robust gene expression changes in zebrafish. • The liver may be a target organ of triclosan toxicity in embryonic zebrafish. • Triclosan disrupts normal liver functioning and development in

  7. Phenotypically anchored transcriptome profiling of developmental exposure to the antimicrobial agent, triclosan, reveals hepatotoxicity in embryonic zebrafish

    Energy Technology Data Exchange (ETDEWEB)

    Haggard, Derik E. [Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR (United States); Noyes, Pamela D. [Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR (United States); Office of Science Coordination and Policy (OSCP), Office of Chemical Safety and Pollution Prevention, U.S. Environmental Protection Agency, Washington, DC (United States); Waters, Katrina M. [Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA (United States); Tanguay, Robert L., E-mail: Robert.Tanguay@oregonstate.edu [Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR (United States)

    2016-10-01

    Triclosan (TCS) is an antimicrobial agent commonly found in a variety of personal care products and cosmetics. TCS readily enters the environment through wastewater and is detected in human plasma, urine, and breast milk due to its widespread use. Studies have implicated TCS as a disruptor of thyroid and estrogen signaling; therefore, research examining the developmental effects of TCS is warranted. In this study, we used embryonic zebrafish to investigate the developmental toxicity and potential mechanism of action of TCS. Embryos were exposed to graded concentrations of TCS from 6 to 120 hours post-fertilization (hpf) and the concentration where 80% of the animals had mortality or morbidity at 120 hpf (EC{sub 80}) was calculated. Transcriptomic profiling was conducted on embryos exposed to the EC{sub 80} (7.37 μM). We identified a total of 922 significant differentially expressed transcripts (FDR adjusted P-value ≤ 0.05; fold change ≥ 2). Pathway and gene ontology enrichment analyses identified biological networks and transcriptional hubs involving normal liver functioning, suggesting TCS may be hepatotoxic in zebrafish. Tissue-specific gene enrichment analysis further supported the role of the liver as a target organ for TCS toxicity. We also examined the in vitro bioactivity profile of TCS reported by the ToxCast screening program. TCS had a diverse bioactivity profile and was a hit in 217 of the 385 assay endpoints we identified. We observed similarities in gene expression and hepatic steatosis assays; however, hit data for TCS were more concordant with the hypothesized CAR/PXR activity of TCS from rodent and human in vitro studies. - Highlights: • Triclosan is a common antimicrobial agent with widespread human exposure. • Exposure to the triclosan EC{sub 80} causes robust gene expression changes in zebrafish. • The liver may be a target organ of triclosan toxicity in embryonic zebrafish. • Triclosan disrupts normal liver functioning and

  8. Transcriptome analysis reveals key differentially expressed genes involved in wheat grain development

    Directory of Open Access Journals (Sweden)

    Yonglong Yu

    2016-04-01

    Full Text Available Wheat seed development is an important physiological process of seed maturation and directly affects wheat yield and quality. In this study, we performed dynamic transcriptome microarray analysis of an elite Chinese bread wheat cultivar (Jimai 20 during grain development using the GeneChip Wheat Genome Array. Grain morphology and scanning electron microscope observations showed that the period of 11–15 days post-anthesis (DPA was a key stage for the synthesis and accumulation of seed starch. Genome-wide transcriptional profiling and significance analysis of microarrays revealed that the period from 11 to 15 DPA was more important than the 15–20 DPA stage for the synthesis and accumulation of nutritive reserves. Series test of cluster analysis of differential genes revealed five statistically significant gene expression profiles. Gene ontology annotation and enrichment analysis gave further information about differentially expressed genes, and MapMan analysis revealed expression changes within functional groups during seed development. Metabolic pathway network analysis showed that major and minor metabolic pathways regulate one another to ensure regular seed development and nutritive reserve accumulation. We performed gene co-expression network analysis to identify genes that play vital roles in seed development and identified several key genes involved in important metabolic pathways. The transcriptional expression of eight key genes involved in starch and protein synthesis and stress defense was further validated by qRT-PCR. Our results provide new insight into the molecular mechanisms of wheat seed development and the determinants of yield and quality.

  9. In-Depth Temporal Transcriptome Profiling Reveals a Crucial Developmental Switch with Roles for RNA Processing and Organelle Metabolism That Are Essential for Germination in Arabidopsis1[W][OA

    Science.gov (United States)

    Narsai, Reena; Law, Simon R.; Carrie, Chris; Xu, Lin; Whelan, James

    2011-01-01

    Germination represents a rapid transition from dormancy to a high level of metabolic activity. In-depth transcriptomic profiling at 10 time points in Arabidopsis (Arabidopsis thaliana), including fresh seed, ripened seed, during stratification, germination, and postgermination per se, revealed specific temporal expression patterns that to our knowledge have not previously been identified. Over 10,000 transcripts were differentially expressed during cold stratification, with subequal numbers up-regulated as down-regulated, revealing an active period in preparing seeds for germination, where transcription and RNA degradation both play important roles in regulating the molecular sequence of events. A previously unidentified transient expression pattern was observed for a group of genes, whereby a significant rise in expression was observed at the end of stratification and significantly lower expression was observed 6 h later. These genes were further defined as germination specific, as they were most highly expressed at this time in germination, in comparison with all developmental tissues in the AtGenExpress data set. Functional analysis of these genes using genetic inactivation revealed that they displayed a significant enrichment for embryo-defective or -arrested phenotype. This group was enriched in genes encoding mitochondrial and nuclear RNA-processing proteins, including more than 45% of all pentatricopeptide domain-containing proteins expressed during germination. The presence of mitochondrial DNA replication factors and RNA-processing functions in this germination-specific subset represents the earliest events in organelle biogenesis, preceding any changes associated with energy metabolism. Green fluorescent protein analysis also confirmed organellar localization for 65 proteins, largely showing germination-specific expression. These results suggest that mitochondrial biogenesis involves a two-step process to produce energetically active organelles: an

  10. Work-to-Family Enrichment and Conflict Profiles: Job Characteristics and Employees' Well-Being.

    Science.gov (United States)

    Carvalho, Vânia Sofia; Chambel, Maria José

    2016-10-03

    This article aims to analyze work-to-family conflict (WFC) and enrichment (WFE) profiles related to job characteristics and well-being at work and general well-being. A cross-sectional survey data of 1885 employees was analyzed. The Latent Profile Analysis revealed that the five-profile solution exhibited strong statistical significance (p > .001). ANCOVAs were performed to analyze the relationship of the identified profiles with job characteristics and well-being. Employees in the Beneficial profile had the best perception of job characteristics (lowest demands and the highest control and support) and the highest well-being, and those in the Harmful profile had the lowest job characteristics perceptions and the lowest well-being. Through a comparison of the Moderate Active profile and the Moderate Harmful profile, WFE was found to buffer the effects of the WFC on well-being at work (burnout; engagement) and on general well-being (i.e., health perceptions). The promotion of WFE through higher job autonomy, job support, and fewer demands is a crucial aspect to consider. This study helps to consolidate the work-family balance typology and its effects on employees' well-being, and broadens this framework to consider job characteristics.

  11. A latent profile analysis of childhood trauma in women with bulimia nervosa: Associations with borderline personality disorder psychopathology.

    Science.gov (United States)

    Utzinger, Linsey M; Haukebo, Justine E; Simonich, Heather; Wonderlich, Stephen A; Cao, Li; Lavender, Jason M; Mitchell, James E; Engel, Scott G; Crosby, Ross D

    2016-07-01

    The aim of this study was to empirically examine naturally occurring groups of individuals with bulimia nervosa (BN) based on their childhood trauma (CT) histories and to compare these groups on a clinically relevant external validator, borderline personality disorder (BPD) psychopathology. This study examined the relationship between CT and BPD psychopathology among 133 women with BN using latent profile analysis (LPA) to classify participants based on histories of CT. Participants completed the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I/P), the Diagnostic Interview for Borderlines-Revised (DIB-R), and the Childhood Trauma Questionnaire (CTQ). The LPA revealed four trauma profiles: low/no trauma, emotional trauma, sexual trauma, and polytrauma. Results indicated that the sexual and polytrauma profiles displayed significantly elevated scores on the DIB-R and that the low/no and emotional trauma profiles did not differ significantly on the DIB-R. Secondary analyses revealed elevated levels of a composite CT score among those with both BN and BPD psychopathology compared to those with BN only. These findings suggest that both childhood sexual abuse and the additive effects of childhood polytrauma may be linked to BPD psychopathology in BN. © 2016 Wiley Periodicals, Inc. (Int J Eat Disord 2016; 49:689-694). © 2016 Wiley Periodicals, Inc.

  12. Probing Genomic Aspects of the Multi-Host Pathogen Clostridium perfringens Reveals Significant Pangenome Diversity, and a Diverse Array of Virulence Factors.

    Science.gov (United States)

    Kiu, Raymond; Caim, Shabhonam; Alexander, Sarah; Pachori, Purnima; Hall, Lindsay J

    2017-01-01

    Clostridium perfringens is an important cause of animal and human infections, however information about the genetic makeup of this pathogenic bacterium is currently limited. In this study, we sought to understand and characterise the genomic variation, pangenomic diversity, and key virulence traits of 56 C. perfringens strains which included 51 public, and 5 newly sequenced and annotated genomes using Whole Genome Sequencing. Our investigation revealed that C. perfringens has an "open" pangenome comprising 11667 genes and 12.6% of core genes, identified as the most divergent single-species Gram-positive bacterial pangenome currently reported. Our computational analyses also defined C. perfringens phylogeny (16S rRNA gene) in relation to some 25 Clostridium species, with C. baratii and C. sardiniense determined to be the closest relatives. Profiling virulence-associated factors confirmed presence of well-characterised C. perfringens -associated exotoxins genes including α-toxin ( plc ), enterotoxin ( cpe ), and Perfringolysin O ( pfo or pfoA ), although interestingly there did not appear to be a close correlation with encoded toxin type and disease phenotype. Furthermore, genomic analysis indicated significant horizontal gene transfer events as defined by presence of prophage genomes, and notably absence of CRISPR defence systems in >70% (40/56) of the strains. In relation to antimicrobial resistance mechanisms, tetracycline resistance genes ( tet ) and anti-defensins genes ( mprF ) were consistently detected in silico ( tet : 75%; mprF : 100%). However, pre-antibiotic era strain genomes did not encode for tet , thus implying antimicrobial selective pressures in C. perfringens evolutionary history over the past 80 years. This study provides new genomic understanding of this genetically divergent multi-host bacterium, and further expands our knowledge on this medically and veterinary important pathogen.

  13. Proteomic profiling reveals candidate markers for arsenic-induced skin keratosis.

    Science.gov (United States)

    Guo, Zhiling; Hu, Qin; Tian, Jijing; Yan, Li; Jing, Chuanyong; Xie, Heidi Qunhui; Bao, Wenjun; Rice, Robert H; Zhao, Bin; Jiang, Guibin

    2016-11-01

    Proteomics technology is an attractive biomarker candidate discovery tool that can be applied to study large sets of biological molecules. To identify novel biomarkers and molecular targets in arsenic-induced skin lesions, we have determined the protein profile of arsenic-affected human epidermal stratum corneum by shotgun proteomics. Samples of palm and foot sole from healthy subjects were analyzed, demonstrating similar protein patterns in palm and sole. Samples were collected from the palms of subjects with arsenic keratosis (lesional and adjacent non-lesional samples) and arsenic-exposed subjects without lesions (normal). Samples from non-exposed healthy individuals served as controls. We found that three proteins in arsenic-exposed lesional epidermis were consistently distinguishably expressed from the unaffected epidermis. One of these proteins, the cadherin-like transmembrane glycoprotein, desmoglein 1 (DSG1) was suppressed. Down-regulation of DSG1 may lead to reduced cell-cell adhesion, resulting in abnormal epidermal differentiation. The expression of keratin 6c (KRT6C) and fatty acid binding protein 5 (FABP5) were significantly increased. FABP5 is an intracellular lipid chaperone that plays an essential role in fatty acid metabolism in human skin. This raises a possibility that overexpression of FABP5 may affect the proliferation or differentiation of keratinocytes by altering lipid metabolism. KRT6C is a constituent of the cytoskeleton that maintains epidermal integrity and cohesion. Abnormal expression of KRT6C may affect its structural role in the epidermis. Our findings suggest an important approach for future studies of arsenic-mediated toxicity and skin cancer, where certain proteins may represent useful biomarkers of early diagnoses in high-risk populations and hopefully new treatment targets. Further studies are required to understand the biological role of these markers in skin pathogenesis from arsenic exposure. Copyright © 2016 Elsevier Ltd

  14. MicroRNA profiling reveals distinct signatures in B cell chronic lymphocytic leukemias

    Science.gov (United States)

    Calin, George Adrian; Liu, Chang-Gong; Sevignani, Cinzia; Ferracin, Manuela; Felli, Nadia; Dumitru, Calin Dan; Shimizu, Masayoshi; Cimmino, Amelia; Zupo, Simona; Dono, Mariella; Dell'Aquila, Marie L.; Alder, Hansjuerg; Rassenti, Laura; Kipps, Thomas J.; Bullrich, Florencia; Negrini, Massimo; Croce, Carlo M.

    2004-01-01

    Little is known about the expression levels or function of micro-RNAs (miRNAs) in normal and neoplastic cells, although it is becoming clear that miRNAs play important roles in the regulation of gene expression during development [Ambros, V. (2003) Cell 113, 673–676; McManus, M. T. (2003) Semin. Cancer Biol. 13, 253–258]. We now report the genomewide expression profiling of miRNAs in human B cell chronic lymphocytic leukemia (CLL) by using a microarray containing hundreds of human precursor and mature miRNA oligonucleotide probes. This approach allowed us to identify significant differences in miRNome expression between CLL samples and normal CD5+ B cells; data were confirmed by Northern blot analyses and real-time RT-PCR. At least two distinct clusters of CLL samples can be identified that were associated with the presence or absence of Zap-70 expression, a predictor of early disease progression. Two miRNA signatures were associated with the presence or absence of mutations in the expressed Ig variableregion genes or with deletions at 13q14, respectively. These data suggest that miRNA expression patterns have relevance to the biological and clinical behavior of this leukemia. PMID:15284443

  15. Gene expression profiling reveals different molecular patterns in G-protein coupled receptor signaling pathways between early- and late-onset preeclampsia.

    Science.gov (United States)

    Liang, Mengmeng; Niu, Jianmin; Zhang, Liang; Deng, Hua; Ma, Jian; Zhou, Weiping; Duan, Dongmei; Zhou, Yuheng; Xu, Huikun; Chen, Longding

    2016-04-01

    Early-onset preeclampsia and late-onset preeclampsia have been regarded as two different phenotypes with heterogeneous manifestations; To gain insights into the pathogenesis of the two traits, we analyzed the gene expression profiles in preeclamptic placentas. A whole genome-wide microarray was used to determine the gene expression profiles in placental tissues from patients with early-onset (n = 7; 36 weeks) preeclampsia and their controls who delivered preterm (n = 5; 36 weeks). Genes were termed differentially expressed if they showed a fold-change ≥ 2 and q-value preeclampsia (177 genes were up-regulated and 450 were down-regulated). Gene ontology analysis identified significant alterations in several biological processes; the top two were immune response and cell surface receptor linked signal transduction. Among the cell surface receptor linked signal transduction-related, differentially expressed genes, those involved in the G-protein coupled receptor protein signaling pathway were significantly enriched. G-protein coupled receptor signaling pathway related genes, such as GPR124 and MRGPRF, were both found to be down-regulated in early-onset preeclampsia. The results were consistent with those of western blotting that the abundance of GPR124 was lower in early-onset compared with late-onset preeclampsia. The different gene expression profiles reflect the different levels of transcription regulation between the two conditions and supported the hypothesis that they are separate disease entities. Moreover, the G-protein coupled receptor signaling pathway related genes may contribute to the mechanism underlying early- and late-onset preeclampsia. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Quantitative proteomics reveals protein profiles underlying major transitions in aspen wood development.

    Science.gov (United States)

    Obudulu, Ogonna; Bygdell, Joakim; Sundberg, Björn; Moritz, Thomas; Hvidsten, Torgeir R; Trygg, Johan; Wingsle, Gunnar

    2016-02-18

    Wood development is of outstanding interest both to basic research and industry due to the associated cellulose and lignin biomass production. Efforts to elucidate wood formation (which is essential for numerous aspects of both pure and applied plant science) have been made using transcriptomic analyses and/or low-resolution sampling. However, transcriptomic data do not correlate perfectly with levels of expressed proteins due to effects of post-translational modifications and variations in turnover rates. In addition, high-resolution analysis is needed to characterize key transitions. In order to identify protein profiles across the developmental region of wood formation, an in-depth and tissue specific sampling was performed. We examined protein profiles, using an ultra-performance liquid chromatography/quadrupole time of flight mass spectrometry system, in high-resolution tangential sections spanning all wood development zones in Populus tremula from undifferentiated cambium to mature phloem and xylem, including cell expansion and cell death zones. In total, we analyzed 482 sections, 20-160 μm thick, from four 47-year-old trees growing wild in Sweden. We obtained high quality expression profiles for 3,082 proteins exhibiting consistency across the replicates, considering that the trees were growing in an uncontrolled environment. A combination of Principal Component Analysis (PCA), Orthogonal Projections to Latent Structures (OPLS) modeling and an enhanced stepwise linear modeling approach identified several major transitions in global protein expression profiles, pinpointing (for example) locations of the cambial division leading to phloem and xylem cells, and secondary cell wall formation zones. We also identified key proteins and associated pathways underlying these developmental landmarks. For example, many of the lignocellulosic related proteins were upregulated in the expansion to the early developmental xylem zone, and for laccases with a rapid decrease

  17. Dynamic genome wide expression profiling of Drosophila head development reveals a novel role of Hunchback in retinal glia cell development and blood-brain barrier integrity.

    Directory of Open Access Journals (Sweden)

    Montserrat Torres-Oliva

    2018-01-01

    Full Text Available Drosophila melanogaster head development represents a valuable process to study the developmental control of various organs, such as the antennae, the dorsal ocelli and the compound eyes from a common precursor, the eye-antennal imaginal disc. While the gene regulatory network underlying compound eye development has been extensively studied, the key transcription factors regulating the formation of other head structures from the same imaginal disc are largely unknown. We obtained the developmental transcriptome of the eye-antennal discs covering late patterning processes at the late 2nd larval instar stage to the onset and progression of differentiation at the end of larval development. We revealed the expression profiles of all genes expressed during eye-antennal disc development and we determined temporally co-expressed genes by hierarchical clustering. Since co-expressed genes may be regulated by common transcriptional regulators, we combined our transcriptome dataset with publicly available ChIP-seq data to identify central transcription factors that co-regulate genes during head development. Besides the identification of already known and well-described transcription factors, we show that the transcription factor Hunchback (Hb regulates a significant number of genes that are expressed during late differentiation stages. We confirm that hb is expressed in two polyploid subperineurial glia cells (carpet cells and a thorough functional analysis shows that loss of Hb function results in a loss of carpet cells in the eye-antennal disc. Additionally, we provide for the first time functional data indicating that carpet cells are an integral part of the blood-brain barrier. Eventually, we combined our expression data with a de novo Hb motif search to reveal stage specific putative target genes of which we find a significant number indeed expressed in carpet cells.

  18. Dynamic genome wide expression profiling of Drosophila head development reveals a novel role of Hunchback in retinal glia cell development and blood-brain barrier integrity

    Science.gov (United States)

    Torres-Oliva, Montserrat; Schneider, Julia; Wiegleb, Gordon

    2018-01-01

    Drosophila melanogaster head development represents a valuable process to study the developmental control of various organs, such as the antennae, the dorsal ocelli and the compound eyes from a common precursor, the eye-antennal imaginal disc. While the gene regulatory network underlying compound eye development has been extensively studied, the key transcription factors regulating the formation of other head structures from the same imaginal disc are largely unknown. We obtained the developmental transcriptome of the eye-antennal discs covering late patterning processes at the late 2nd larval instar stage to the onset and progression of differentiation at the end of larval development. We revealed the expression profiles of all genes expressed during eye-antennal disc development and we determined temporally co-expressed genes by hierarchical clustering. Since co-expressed genes may be regulated by common transcriptional regulators, we combined our transcriptome dataset with publicly available ChIP-seq data to identify central transcription factors that co-regulate genes during head development. Besides the identification of already known and well-described transcription factors, we show that the transcription factor Hunchback (Hb) regulates a significant number of genes that are expressed during late differentiation stages. We confirm that hb is expressed in two polyploid subperineurial glia cells (carpet cells) and a thorough functional analysis shows that loss of Hb function results in a loss of carpet cells in the eye-antennal disc. Additionally, we provide for the first time functional data indicating that carpet cells are an integral part of the blood-brain barrier. Eventually, we combined our expression data with a de novo Hb motif search to reveal stage specific putative target genes of which we find a significant number indeed expressed in carpet cells. PMID:29360820

  19. Female choice for male cuticular hydrocarbon profile in decorated crickets is not based on similarity to their own profile.

    Science.gov (United States)

    Steiger, S; Capodeanu-Nägler, A; Gershman, S N; Weddle, C B; Rapkin, J; Sakaluk, S K; Hunt, J

    2015-12-01

    Indirect genetic benefits derived from female mate choice comprise additive (good genes) and nonadditive genetic benefits (genetic compatibility). Although good genes can be revealed by condition-dependent display traits, the mechanism by which compatibility alleles are detected is unclear because evaluation of the genetic similarity of a prospective mate requires the female to assess the genotype of the male and compare it to her own. Cuticular hydrocarbons (CHCs), lipids coating the exoskeleton of most insects, influence female mate choice in a number of species and offer a way for females to assess genetic similarity of prospective mates. Here, we determine whether female mate choice in decorated crickets is based on male CHCs and whether it is influenced by females' own CHC profiles. We used multivariate selection analysis to estimate the strength and form of selection acting on male CHCs through female mate choice, and employed different measures of multivariate dissimilarity to determine whether a female's preference for male CHCs is based on similarity to her own CHC profile. Female mating preferences were significantly influenced by CHC profiles of males. Male CHC attractiveness was not, however, contingent on the CHC profile of the choosing female, as certain male CHC phenotypes were equally attractive to most females, evidenced by significant linear and stabilizing selection gradients. These results suggest that additive genetic benefits, rather than nonadditive genetic benefits, accrue to female mate choice, in support of earlier work showing that CHC expression of males, but not females, is condition dependent. © 2015 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2015 European Society For Evolutionary Biology.

  20. Gene Expression Profiles in Paired Gingival Biopsies from Periodontitis-Affected and Healthy Tissues Revealed by Massively Parallel Sequencing

    Science.gov (United States)

    Båge, Tove; Lagervall, Maria; Jansson, Leif; Lundeberg, Joakim; Yucel-Lindberg, Tülay

    2012-01-01

    Periodontitis is a chronic inflammatory disease affecting the soft tissue and bone that surrounds the teeth. Despite extensive research, distinctive genes responsible for the disease have not been identified. The objective of this study was to elucidate transcriptome changes in periodontitis, by investigating gene expression profiles in gingival tissue obtained from periodontitis-affected and healthy gingiva from the same patient, using RNA-sequencing. Gingival biopsies were obtained from a disease-affected and a healthy site from each of 10 individuals diagnosed with periodontitis. Enrichment analysis performed among uniquely expressed genes for the periodontitis-affected and healthy tissues revealed several regulated pathways indicative of inflammation for the periodontitis-affected condition. Hierarchical clustering of the sequenced biopsies demonstrated clustering according to the degree of inflammation, as observed histologically in the biopsies, rather than clustering at the individual level. Among the top 50 upregulated genes in periodontitis-affected tissues, we investigated two genes which have not previously been demonstrated to be involved in periodontitis. These included interferon regulatory factor 4 and chemokine (C-C motif) ligand 18, which were also expressed at the protein level in gingival biopsies from patients with periodontitis. In conclusion, this study provides a first step towards a quantitative comprehensive insight into the transcriptome changes in periodontitis. We demonstrate for the first time site-specific local variation in gene expression profiles of periodontitis-affected and healthy tissues obtained from patients with periodontitis, using RNA-seq. Further, we have identified novel genes expressed in periodontitis tissues, which may constitute potential therapeutic targets for future treatment strategies of periodontitis. PMID:23029519

  1. Use of Google Scholar public profiles in orthopedics.

    Science.gov (United States)

    Tetsworth, Kevin; Fraser, Dave; Glatt, Vaida; Hohmann, Erik

    2017-01-01

    The purpose of this study was to survey the growth of Google Scholar public profiles in orthopedics over a 12-month period and to investigate global patterns. Data was prospectively acquired from June 2013 to June 2014. Google Scholar queries specific to orthopedic surgery were performed at 90-day intervals. Demographic aspects of each user were also compiled, including gender, current location, and primary interests. To determine differences between the growth of Google Scholar public profile registrations and citation counts, as well as differences in growth in different regions, repeated measures of analysis of variance (RMANOVA) were used. RMANOVA revealed statistically significant differences ( p = 0.0001) for regional growth. The largest growth was observed in the United Kingdom ( p = 0.009, 289%), followed by the Asia-Pacific region ( p = 0.004, 177%) and "Other" ( p = 0.006, 172%). The mean growth per 90-day interval is 19.9% ( p = 0.003) and the mean 12-month growth is 107% ( p = 0.05). Statistically significant differences between gender (male vs. female) and basic and clinical sciences ( χ 2 = 22.4, p = 0.0001) were observed. This study suggests an exponential growth in the number of authors in the field of orthopedic surgery creating a Google Scholar public profile, and at the current rate participation doubles every 10.6 months.

  2. Distillery effluent induced alterations in the haematological profile of fingerlings of Colisa fasciatus.

    Science.gov (United States)

    Shukla, Anuradha; Shukla, J P

    2013-09-01

    Present study deals with the impact of Gorakhpur distillery effluent at various concentration levels (5, 10 and 20%) on the blood profile of fingerling of, Colisa fosciotus after 30 days of exposure. Observations revealed that 5% of effluent concentration produced no significant alterations in various haematological parameters except for clotting time and immature erythrocytes. However, 10% of effluent concentration brought significant alterations in hematocrit as well as clotting time and 20% of effluent concentration produced highly significant (P<0.001) alteration in most of the haematological parameters except for hemoglobin percentage.

  3. MOTIVATIONAL CLUSTER PROFILES OF ADOLESCENT ATHLETES: AN EXAMINATION OF DIFFERENCES IN PHYSICAL-SELF PERCEPTION

    Directory of Open Access Journals (Sweden)

    Emine Çağlar

    2010-06-01

    Full Text Available The primary purpose of the present study was to identify motivational profiles of adolescent athletes using cluster analysis in non-Western culture. A second purpose was to examine relationships between physical self-perception differences of adolescent athletes and motivational profiles. One hundred and thirty six male (Mage = 17.46, SD = 1.25 years and 80 female adolescent athletes (Mage = 17.61, SD = 1.19 years from a variety of team sports including basketball, soccer, volleyball, and handball volunteered to participate in this study. The Sport Motivation Scale (SMS and Physical Self-Perception Profile (PSPP were administered to all participants. Hierarchical cluster analysis revealed a four-cluster solution for this sample: amotivated, low motivated, moderate motivated, and highly motivated. A 4 x 5 (Cluster x PSPP Subscales MANOVA revealed no significant main effect of motivational clusters on physical self-perception levels (p > 0.05. As a result, findings of the present study showed that motivational types of the adolescent athletes constituted four different motivational clusters. Highly and moderate motivated athletes consistently scored higher than amotivated athletes on the perceived sport competence, physical condition, and physical self-worth subscales of PSPP. This study identified motivational profiles of competitive youth-sport participants

  4. Transcriptome profiling of the Plutella xylostella (Lepidoptera: Plutellidae) ovary reveals genes involved in oogenesis.

    Science.gov (United States)

    Peng, Lu; Wang, Lei; Yang, Yi-Fan; Zou, Ming-Min; He, Wei-Yi; Wang, Yue; Wang, Qing; Vasseur, Liette; You, Min-Sheng

    2017-12-30

    As a specialized organ, the insect ovary performs valuable functions by ensuring fecundity and population survival. Oogenesis is the complex physiological process resulting in the production of mature eggs, which are involved in epigenetic programming, germ cell behavior, cell cycle regulation, etc. Identification of the genes involved in ovary development and oogenesis is critical to better understand the reproductive biology and screening for the potential molecular targets in Plutella xylostella, a worldwide destructive pest of economically major crops. Based on transcriptome sequencing, a total of 7.88Gb clean nucleotides was obtained, with 19,934 genes and 1861 new transcripts being identified. Expression profiling indicated that 61.7% of the genes were expressed (FPKM≥1) in the P. xylostella ovary. GO annotation showed that the pathways of multicellular organism reproduction and multicellular organism reproduction process, as well as gamete generation and chorion were significantly enriched. Processes that were most likely relevant to reproduction included the spliceosome, ubiquitin mediated proteolysis, endocytosis, PI3K-Akt signaling pathway, insulin signaling pathway, cAMP signaling pathway, and focal adhesion were identified in the top 20 'highly represented' KEGG pathways. Functional genes involved in oogenesis were further analyzed and validated by qRT-PCR to show their potential predominant roles in P. xylostella reproduction. Our newly developed P. xylostella ovary transcriptome provides an overview of the gene expression profiling in this specialized tissue and the functional gene network closely related to the ovary development and oogenesis. This is the first genome-wide transcriptome dataset of P. xylostella ovary that includes a subset of functionally activated genes. This global approach will be the basis for further studies on molecular mechanisms of P. xylostella reproduction aimed at screening potential molecular targets for integrated pest

  5. Pure versus combined Merkel cell carcinomas: immunohistochemical evaluation of cellular proteins (p53, Bcl-2, and c-kit) reveals significant overexpression of p53 in combined tumors.

    Science.gov (United States)

    Lai, Jonathan H; Fleming, Kirsten E; Ly, Thai Yen; Pasternak, Sylvia; Godlewski, Marek; Doucette, Steve; Walsh, Noreen M

    2015-09-01

    Merkel cell polyomavirus is of oncogenic significance in approximately 80% of Merkel cell carcinomas. Morphological subcategories of the tumor differ in regard to viral status, the rare combined type being uniformly virus negative and the predominant pure type being mainly virus positive. Indications that different biological subsets of the tumor exist led us to explore this diversity. In an Eastern Canadian cohort of cases (75 patients; mean age, 76 years [range, 43-91]; male/female ratio, 43:32; 51 [68%] pure and 24 [34%] combined tumors), we semiquantitatively compared the immunohistochemical expression of 3 cellular proteins (p53, Bcl-2, and c-kit) in pure versus combined groups. Viral status was known in a subset of cases. The significant overexpression of p53 in the combined group (mean [SD], 153.8 [117.8] versus 121.6 [77.9]; P = .01) and the increased epidermal expression of this protein (p53 patches) in the same group lend credence to a primary etiologic role for sun damage in these cases. Expression of Bcl-2 and c-kit did not differ significantly between the 2 morphological groups. A relative increase in c-kit expression was significantly associated with a virus-negative status (median [interquartile range], 100 [60-115] versus 70 [0-100]; P = .03). Emerging data reveal divergent biological pathways in Merkel cell carcinoma, each with a characteristic immunohistochemical profile. Virus-positive tumors (all pure) exhibit high retinoblastoma protein and low p53 expression, whereas virus-negative cases (few pure and all combined) show high p53 and relatively high c-kit expression. The potential biological implications of this dichotomy call for consistent stratification of these tumors in future studies. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Urinary proteomic profiling reveals diclofenac-induced renal injury and hepatic regeneration in mice

    Energy Technology Data Exchange (ETDEWEB)

    Swelm, Rachel P.L. van [Department of Pharmacology and Toxicology, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB Nijmegen (Netherlands); Laarakkers, Coby M.M. [Department of Laboratory Medicine, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB Nijmegen (Netherlands); Pertijs, Jeanne C.L.M.; Verweij, Vivienne; Masereeuw, Rosalinde [Department of Pharmacology and Toxicology, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB Nijmegen (Netherlands); Russel, Frans G.M., E-mail: F.Russel@pharmtox.umcn.nl [Department of Pharmacology and Toxicology, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB Nijmegen (Netherlands)

    2013-06-01

    Diclofenac (DF) is a widely used non-steroidal anti-inflammatory drug for the treatment of rheumatic disorders, but is often associated with liver injury. We applied urinary proteomic profiling using MALDI-TOF MS to identify biomarkers for DF-induced hepatotoxicity in mice. Female CH3/HeOUJIco mice were treated with 75 mg/kg bw DF by oral gavage and 24 h urine was collected. Proteins identified in urine of DF-treated mice included epidermal growth factor, transthyretin, kallikrein, clusterin, fatty acid binding protein 1 and urokinase, which are related to liver regeneration but also to kidney injury. Both organs showed enhanced levels of oxidative stress (TBARS, p < 0.01). Kidney injury was confirmed by histology and increased Kim1 and Il-6 mRNA expression levels (p < 0.001 and p < 0.01). Liver histology and plasma ALT levels in DF-treated mice were not different from control, but mRNA expression of Stat3 (p < 0.001) and protein expression of PCNA (p < 0.05) were increased, indicating liver regeneration. In conclusion, urinary proteome analysis revealed that DF treatment in mice induced kidney and liver injury. Within 24 h, however, the liver was able to recover by activating tissue regeneration processes. Hence, the proteins found in urine of DF-treated mice represent kidney damage rather than hepatic injury. - Highlights: • The urinary proteome shows biological processes involved in adverse drug reactions. • Urine proteins of DF-treated mice relate to kidney injury rather than liver injury. • Liver regeneration, not liver injury, is apparent 24h after oral DF administration. • Pretreatment with LPS does not enhance DF-induced liver injury in mice.

  7. Gender Profiles of Workplace Individual and Organizational Deviance

    Directory of Open Access Journals (Sweden)

    Lily Chernyak-Hai

    2018-03-01

    Full Text Available Employees’ workplace deviant behaviors have a harmful potential for organizations in many respects. Past research has indicated that individual variables may account for personal differences in work deviance. One of the prevalent findings is that men display direct aggression more frequently than women. Yet, most of the past studies have reported results providing information on the magnitude of a general behavioral tendency of each gender, leading to rough distinctions. Unlike the previous studies, we focused on examining profiles of the role of gender in interpersonal and organizational deviance, utilizing Profile Analysis via Multidimensional Scaling that allowed us to compare specific deviance behavior indicators between males and females included in the profiles. The current exploratory study reveals that gender differences in aggressive workplace behavior are not only those apparent in inter-personal relations but also when directed towards the organization. Moreover, the reported results point to specific behavioral profiles of men and women that could not be revealed using the mean difference analyses.

  8. Differential co-expression and regulation analyses reveal different mechanisms underlying major depressive disorder and subsyndromal symptomatic depression.

    Science.gov (United States)

    Xu, Fan; Yang, Jing; Chen, Jin; Wu, Qingyuan; Gong, Wei; Zhang, Jianguo; Shao, Weihua; Mu, Jun; Yang, Deyu; Yang, Yongtao; Li, Zhiwei; Xie, Peng

    2015-04-03

    Recent depression research has revealed a growing awareness of how to best classify depression into depressive subtypes. Appropriately subtyping depression can lead to identification of subtypes that are more responsive to current pharmacological treatment and aid in separating out depressed patients in which current antidepressants are not particularly effective. Differential co-expression analysis (DCEA) and differential regulation analysis (DRA) were applied to compare the transcriptomic profiles of peripheral blood lymphocytes from patients with two depressive subtypes: major depressive disorder (MDD) and subsyndromal symptomatic depression (SSD). Six differentially regulated genes (DRGs) (FOSL1, SRF, JUN, TFAP4, SOX9, and HLF) and 16 transcription factor-to-target differentially co-expressed gene links or pairs (TF2target DCLs) appear to be the key differential factors in MDD; in contrast, one DRG (PATZ1) and eight TF2target DCLs appear to be the key differential factors in SSD. There was no overlap between the MDD target genes and SSD target genes. Venlafaxine (Efexor™, Effexor™) appears to have a significant effect on the gene expression profile of MDD patients but no significant effect on the gene expression profile of SSD patients. DCEA and DRA revealed no apparent similarities between the differential regulatory processes underlying MDD and SSD. This bioinformatic analysis may provide novel insights that can support future antidepressant R&D efforts.

  9. Microarray glycan profiling reveals algal fucoidan epitopes in diverse marine metazoans

    DEFF Research Database (Denmark)

    Asunción Salmeán, Armando; Hervé, Cécile; Jørgensen, Bodil

    2017-01-01

    Despite the biological importance and pharmacological potential of glycans from marine organisms, there are many unanswered questions regarding their distribution, function, and evolution. Here we describe microarray-based glycan profiling of a diverse selection of marine animals using antibodies...... raised against fucoidan isolated from a brown alga. We demonstrate the presence of two fucoidan epitopes in six animals belonging to three phyla including Porifera, Molusca, and Chordata. We studied the spatial distribution of these epitopes in Cliona celata ("boring sponge") and identified...

  10. Circular RNA expression profiling of human granulosa cells during maternal aging reveals novel transcripts associated with assisted reproductive technology outcomes.

    Directory of Open Access Journals (Sweden)

    Jing Cheng

    Full Text Available Circular RNAs (circRNAs are a unique class of endogenous RNAs which could be used as potential diagnostic and prognostic biomarkers of many diseases. Our study aimed to investigate circRNA profiles in human granulosa cells (GCs during maternal aging and to uncover age-related circRNA variations that potentially reflect decreased oocyte competence. CircRNAs in GCs from in vitro fertilization (IVF patients with young age (YA, ≤ 30 years and advanced age (AA, ≥ 38 years were profiled by microarray, and validated in 20 paired samples. The correlation between circRNAs expression and clinical characteristics was analyzed in additional 80 samples. Chip-based analysis revealed 46 up-regulated and 11 down-regulated circRNAs in AA samples (fold change > 2.0. Specifically, circRNA_103829, circRNA_103827 and circRNA_104816 were validated to be up-regulated, while circRNA_101889 was down-regulated in AA samples. After adjustment for gonadotropin treatment, only circRNA_103827 and circRNA_104816 levels were positively associated with maternal age (partial r = 0.332, P = 0.045; partial r = 0.473, P = 0.003; respectively. Moreover, circRNA_103827 and circRNA_104816 expressions in GCs were negatively correlated with the number of top quality embryos (r = -0.235, P = 0.036; r = -0.221, P = 0.049; respectively. Receiver operating characteristic (ROC curve analysis indicated that the performance of circRNA_103827 for live birth prediction reached 0.698 [0.570-0.825], with 77.2% sensitivity and 60.9% specificity (P = 0.006, and that of circRNA_104816 was 0.645 [0.507-0.783] (P = 0.043. Bioinformatics analysis revealed that both circRNAs were potentially involved in glucose metabolism, mitotic cell cycle, and ovarian steroidogenesis. Therefore, age-related up-regulation of circRNA_103827 and circRNA_104816 might be potential indicators of compromised follicular micro-environment which could be used to predict IVF prognosis, and improve female infertility

  11. Diffusion Profiling via a Histogram Approach Distinguishes Low-grade from High-grade Meningiomas, Can Reflect the Respective Proliferative Potential and Progesterone Receptor Status.

    Science.gov (United States)

    Gihr, Georg Alexander; Horvath-Rizea, Diana; Garnov, Nikita; Kohlhof-Meinecke, Patricia; Ganslandt, Oliver; Henkes, Hans; Meyer, Hans Jonas; Hoffmann, Karl-Titus; Surov, Alexey; Schob, Stefan

    2018-02-01

    Presurgical grading, estimation of growth kinetics, and other prognostic factors are becoming increasingly important for selecting the best therapeutic approach for meningioma patients. Diffusion-weighted imaging (DWI) provides microstructural information and reflects tumor biology. A novel DWI approach, histogram profiling of apparent diffusion coefficient (ADC) volumes, provides more distinct information than conventional DWI. Therefore, our study investigated whether ADC histogram profiling distinguishes low-grade from high-grade lesions and reflects Ki-67 expression and progesterone receptor status. Pretreatment ADC volumes of 37 meningioma patients (28 low-grade, 9 high-grade) were used for histogram profiling. WHO grade, Ki-67 expression, and progesterone receptor status were evaluated. Comparative and correlative statistics investigating the association between histogram profiling and neuropathology were performed. The entire ADC profile (p10, p25, p75, p90, mean, median) was significantly lower in high-grade versus low-grade meningiomas. The lower percentiles, mean, and modus showed significant correlations with Ki-67 expression. Skewness and entropy of the ADC volumes were significantly associated with progesterone receptor status and Ki-67 expression. ROC analysis revealed entropy to be the most accurate parameter distinguishing low-grade from high-grade meningiomas. ADC histogram profiling provides a distinct set of parameters, which help differentiate low-grade versus high-grade meningiomas. Also, histogram metrics correlate significantly with histological surrogates of the respective proliferative potential. More specifically, entropy revealed to be the most promising imaging biomarker for presurgical grading. Both, entropy and skewness were significantly associated with progesterone receptor status and Ki-67 expression and therefore should be investigated further as predictors for prognostically relevant tumor biological features. Since absolute ADC

  12. Probing Genomic Aspects of the Multi-Host Pathogen Clostridium perfringens Reveals Significant Pangenome Diversity, and a Diverse Array of Virulence Factors

    Directory of Open Access Journals (Sweden)

    Raymond Kiu

    2017-12-01

    Full Text Available Clostridium perfringens is an important cause of animal and human infections, however information about the genetic makeup of this pathogenic bacterium is currently limited. In this study, we sought to understand and characterise the genomic variation, pangenomic diversity, and key virulence traits of 56 C. perfringens strains which included 51 public, and 5 newly sequenced and annotated genomes using Whole Genome Sequencing. Our investigation revealed that C. perfringens has an “open” pangenome comprising 11667 genes and 12.6% of core genes, identified as the most divergent single-species Gram-positive bacterial pangenome currently reported. Our computational analyses also defined C. perfringens phylogeny (16S rRNA gene in relation to some 25 Clostridium species, with C. baratii and C. sardiniense determined to be the closest relatives. Profiling virulence-associated factors confirmed presence of well-characterised C. perfringens-associated exotoxins genes including α-toxin (plc, enterotoxin (cpe, and Perfringolysin O (pfo or pfoA, although interestingly there did not appear to be a close correlation with encoded toxin type and disease phenotype. Furthermore, genomic analysis indicated significant horizontal gene transfer events as defined by presence of prophage genomes, and notably absence of CRISPR defence systems in >70% (40/56 of the strains. In relation to antimicrobial resistance mechanisms, tetracycline resistance genes (tet and anti-defensins genes (mprF were consistently detected in silico (tet: 75%; mprF: 100%. However, pre-antibiotic era strain genomes did not encode for tet, thus implying antimicrobial selective pressures in C. perfringens evolutionary history over the past 80 years. This study provides new genomic understanding of this genetically divergent multi-host bacterium, and further expands our knowledge on this medically and veterinary important pathogen.

  13. Influence of laser beam profile on electromagnetically induced absorption

    International Nuclear Information System (INIS)

    Cuk, S. M.; Radonjic, M.; Krmpot, A. J.; Nikolic, S. N.; Grujic, Z. D.; Jelenkovic, B. M.

    2010-01-01

    We compared, experimentally and theoretically, Hanle electromagnetically induced absorption (EIA) obtained using Gaussian and Π-shaped laser beams 3 mm in diameter. The study was done by measuring the transmission of a laser locked to the F g =2→F e =3 transition at the D 2 line of 87 Rb in a vacuum cell. EIA linewidths obtained for the two laser profiles were significantly different in the range of laser intensities 1-4 mW/cm 2 . EIA with the Π-shaped laser beam has a broad intensity maximum and linewidths larger than those obtained with the Gaussian beam profile. We also studied Hanle EIA by measuring the transmission of selected segments of the entire laser beam by placing a small movable aperture in front of the detector. Waveforms so obtained in Hanle EIA resonances were strongly influenced both by the radial distance of the transmitted segment from the beam center and by the radial profile of the laser beam. We show that outer regions of Gaussian beam, and central regions of the Π-shaped beam generate the narrowest lines. The different behaviors of EIA owing to different beam profiles revealed by both theory and experiment indicate the importance of the radial profile of the laser beam for proper modeling of coherent effects in alkali metal vapors.

  14. Effects of Perfluorooctanoic Acid on Metabolic Profiles in Brain and Liver of Mouse Revealed by a High-throughput Targeted Metabolomics Approach

    Science.gov (United States)

    Yu, Nanyang; Wei, Si; Li, Meiying; Yang, Jingping; Li, Kan; Jin, Ling; Xie, Yuwei; Giesy, John P.; Zhang, Xiaowei; Yu, Hongxia

    2016-04-01

    Perfluorooctanoic acid (PFOA), a perfluoroalkyl acid, can result in hepatotoxicity and neurobehavioral effects in animals. The metabolome, which serves as a connection among transcriptome, proteome and toxic effects, provides pathway-based insights into effects of PFOA. Since understanding of changes in the metabolic profile during hepatotoxicity and neurotoxicity were still incomplete, a high-throughput targeted metabolomics approach (278 metabolites) was used to investigate effects of exposure to PFOA for 28 d on brain and liver of male Balb/c mice. Results of multivariate statistical analysis indicated that PFOA caused alterations in metabolic pathways in exposed individuals. Pathway analysis suggested that PFOA affected metabolism of amino acids, lipids, carbohydrates and energetics. Ten and 18 metabolites were identified as potential unique biomarkers of exposure to PFOA in brain and liver, respectively. In brain, PFOA affected concentrations of neurotransmitters, including serotonin, dopamine, norepinephrine, and glutamate in brain, which provides novel insights into mechanisms of PFOA-induced neurobehavioral effects. In liver, profiles of lipids revealed involvement of β-oxidation and biosynthesis of saturated and unsaturated fatty acids in PFOA-induced hepatotoxicity, while alterations in metabolism of arachidonic acid suggesting potential of PFOA to cause inflammation response in liver. These results provide insight into the mechanism and biomarkers for PFOA-induced effects.

  15. Temporal expression profiling of plasma proteins reveals oxidative stress in early stages of Type 1 Diabetes progression

    International Nuclear Information System (INIS)

    Liu, Chih-Wei; Bramer, Lisa; Computational Modeling); Webb-Robertson, Bobbie-Jo; Computational Modeling); Waugh, Kathleen; Rewers, Marian J.; Zhang, Qibin; Biochemistry)

    2017-01-01

    We report that blood markers other than islet autoantibodies are greatly needed to indicate the pancreatic beta cell destruction process as early as possible, and more accurately reflect the progression of Type 1 Diabetes Mellitus (T1D). To this end, a longitudinal proteomic profiling of human plasma using TMT-10plex-based LC-MS/MS analysis was performed to track temporal proteomic changes of T1D patients (n = 11) across 9 serial time points, spanning the period of T1D natural progression, in comparison with those of the matching healthy controls (n = 10). To our knowledge, the current study represents the largest (> 2000 proteins measured) longitudinal expression profiles of human plasma proteome in T1D research. By applying statistical trend analysis on the temporal expression patterns between T1D and controls, and Benjamini-Hochberg procedure for multiple-testing correction, 13 protein groups were regarded as having statistically significant differences during the entire follow-up period. Moreover, 16 protein groups, which play pivotal roles in response to oxidative stress, have consistently abnormal expression trend before seroconversion to islet autoimmunity. Importantly, the expression trends of two key reactive oxygen species-decomposing enzymes, Catalase and Superoxide dismutase were verified independently by ELISA.

  16. An Andean-type retro-arc foreland system beneath northwest South China revealed by SINOPROBE profiling

    Science.gov (United States)

    Li, Jianhua; Dong, Shuwen; Cawood, Peter A.; Zhao, Guochun; Johnston, Stephen T.; Zhang, Yueqiao; Xin, Yujia

    2018-05-01

    In the Mesozoic, South China was situated along the convergent margin between the Asian and Pacific plates, providing an excellent laboratory to understand the interactions between deformation, sedimentation and magmatism in a retroarc environment. The crustal architecture of northwest South China is displayed along the ∼600-km-long SINOPROBE deep seismic reflection profiles and reveals from east to west: (1) highly folded and truncated reflectors in the upper crust of the Yangtze Fold Zone, which correspond to thin- and thick-skinned thrust systems, and document large-scale intraplate structural imbrication and shortening; (2) a crustal-scale flat-ramp-flat structure, termed the Main Yangtze decollement, which forms a weak, viscous layer to accommodate strain decoupling and material transport in the thin- and thick-skinned systems; and (3) nearly flat-lying reflectors in the Sichuan Basin, which support interpretation of the basin as a weakly deformed depocentre. The Yangtze Fold Zone and the Sichuan Basin represent a retro-arc foreland basin system that is >800 km away from the continental-margin magmatic arc. We suggest that tectonic processes across the arc and retro-arc systems, including arc magma flare-up, basin sedimentation, retroarc thrust propagation, lithosphere underthrusting, root foundering, and extension-related magmatism were interrelated and governed mass transfer. Age data and geological relations link the tectonic processes to evolving geodynamics of the subducting Paleo-Pacific plate.

  17. Characterization of Enzymatic profiles of Aedes aegypti strains from the State of Rio Grande do Norte, Brazil

    Directory of Open Access Journals (Sweden)

    Renan Flávio de França Nunes

    2016-01-01

    Full Text Available Abstract This study was conducted in four strains of Aedes aegypti mosquitoes to evaluate the enzymatic activity profiles in the city of Mossoró, Rio Grande do Norte, and correlate them with biochemical mechanisms of resistance to insecticides. Mosquitos were used to quantify the following detoxification enzymes: Mixed-Function Oxidase (MFO, PNPA-esterase (PNPA-EST, and Acetylcholinesterase (AChE. The profiles were compared statistically with profiles from the Rockefeller strain, through the Kruskal-Wallis test and Dunn's multiple comparisons (p 15% and 50%. The statistical analysis revealed significant differences in the MFO and AChE profiles, which are fundamental in the determination of profiles of resistance to insecticides. Three populations were classified as “Substantially changed” for MFO. The altered enzymatic activity showed that the changes could have an important role in exposing resistance to insecticides.

  18. Transcriptional profiling reveals the expression of novel genes in response to various stimuli in the human dermatophyte Trichophyton rubrum

    Directory of Open Access Journals (Sweden)

    Aquino-Ferreira Roseli

    2010-02-01

    Full Text Available Abstract Background Cutaneous mycoses are common human infections among healthy and immunocompromised hosts, and the anthropophilic fungus Trichophyton rubrum is the most prevalent microorganism isolated from such clinical cases worldwide. The aim of this study was to determine the transcriptional profile of T. rubrum exposed to various stimuli in order to obtain insights into the responses of this pathogen to different environmental challenges. Therefore, we generated an expressed sequence tag (EST collection by constructing one cDNA library and nine suppression subtractive hybridization libraries. Results The 1388 unigenes identified in this study were functionally classified based on the Munich Information Center for Protein Sequences (MIPS categories. The identified proteins were involved in transcriptional regulation, cellular defense and stress, protein degradation, signaling, transport, and secretion, among other functions. Analysis of these unigenes revealed 575 T. rubrum sequences that had not been previously deposited in public databases. Conclusion In this study, we identified novel T. rubrum genes that will be useful for ORF prediction in genome sequencing and facilitating functional genome analysis. Annotation of these expressed genes revealed metabolic adaptations of T. rubrum to carbon sources, ambient pH shifts, and various antifungal drugs used in medical practice. Furthermore, challenging T. rubrum with cytotoxic drugs and ambient pH shifts extended our understanding of the molecular events possibly involved in the infectious process and resistance to antifungal drugs.

  19. [Addictive, criminal and psychopathological profile of a sample of women in prison].

    Science.gov (United States)

    Villagrá Lanza, Patricia; González Menéndez, Ana; Fernández García, Paula; Casares, Ma José; Martín Martín, José Luis; Rodríguez Lamelas, Filomena

    2011-01-01

    This study examines the addictive, criminal and psychopathological profile of a sample of 59 women incarcerated in the Villabona prison in Asturias (a region in northern Spain). The instruments administered were the EuropASI, the SCL-90-R and a semi-structured interview. Results showed that the profile is a young, single women with family dependents serving an average of 5 years' imprisonment. Of the total sample, 64.4% met criteria for a substance abuse disorder. We found a statistically significant relationship between the variables use-nonuse and type of crime: women who used substances had committed the most crimes against property and against the socioeconomic order. As regards psychopathology, 44.06% of the sample fulfilled the requirements for clinical case according to Derogatis' (1994) criteria. The results of the SCL-90-R showed that the predominant psychological disorders were, in the following order, depression, somatization, obsessive-compulsive disorder and paranoid ideation. Moreover, in the group of female users, 47.4% had dual pathology. Our results revealed a statistically significant relationship between clinical case and substance use. Finally, statistically significant differences were found between the user and nonuser groups in the EuropASI severity profile. Highest scores were found for the medical, psychiatric and family areas in the user group.

  20. Regional two-dimensional magnetotelluric profile in West Bohemia/Vogtland reveals deep conductive channel into the earthquake swarm region

    Science.gov (United States)

    Muñoz, Gerard; Weckmann, Ute; Pek, Josef; Kováčiková, Světlana; Klanica, Radek

    2018-03-01

    The West Bohemia/Vogtland region, characterized by the intersection of the Eger (Ohře) Rift and the Mariánské Lázně fault, is a geodynamically active area exhibiting repeated occurrence of earthquake swarms, massive CO2 emanations and mid Pleistocene volcanism. The Eger Rift is the only known intra-continental region in Europe where such deep seated, active lithospheric processes currently take place. We present an image of electrical resistivity obtained from two-dimensional inversion of magnetotelluric (MT) data acquired along a regional profile crossing the Eger Rift. At the near surface, the Cheb basin and the aquifer feeding the mofette fields of Bublák and Hartoušov have been imaged as part of a region of very low resistivity. The most striking resistivity feature, however, is a deep reaching conductive channel which extends from the surface into the lower crust spatially correlated with the hypocentres of the seismic events of the Nový Kostel Focal Zone. This channel has been interpreted as imaging a pathway from a possible mid-crustal fluid reservoir to the surface. The resistivity model reinforces the relation between the fluid circulation along deep-reaching faults and the generation of the earthquakes. Additionally, a further conductive channel has been revealed to the south of the profile. This other feature could be associated to fossil hydrothermal alteration related to Mýtina and/or Neualbenreuth Maar structures or alternatively could be the signature of a structure associated to the suture between the Saxo-Thuringian and Teplá-Barrandian zones, whose surface expression is located only a few kilometres away.

  1. Genetic aspects of auto-immune profiles of healthy chickens.

    Science.gov (United States)

    Parmentier, Henk K; van der Vaart, Priscilla S; Nieuwland, Mike G B; Savelkoul, Huub F J

    2017-09-01

    Auto-antibody profiles binding liver antigens differed between chicken lines divergently selected for specific antibody responses to SRBC, and were affected by ageing suggesting both genetic and environmental effects. Presence and levels of IgM and IgG antibodies binding chicken liver cell lysate (CLL) fragments in plasma at 5 weeks of age from 10 individual full sibs and their parents from 5 H srbc and 5 L srbc line families was studied to reveal genetic relations. Non-genetic maternal effects were studied by comparing auto-antibody profiles of 36 weeks old hens from 2 other unrelated lines with the profiles from their chicks at hatch. IgM and IgG antibodies from parents and progeny from both H srbc and L srbc lines bound CLL fragments. Significant line and generation differences and their interactions were found for both isotypes. Higher staining of CLL fragments was usually found for H srbc line birds. Lines were clustered by auto-antibody profiles, but staining by birds of both lines in both generations was very individual for IgG and IgM. The current data with full sibs therefore not supported a genetic basis for auto-antibody profiles. IgG but not IgM auto-antibody profiles of chicks correlated with maternal auto-antibody profiles. The results suggest that the auto-antibody repertoire of healthy chickens is largely stochastically initiated and may be affected by environmental challenges during ageing, but genetic mechanisms may underlie staining intensity of individual bound CLL fragments. The present results suggest that identification of fragments or profiles to be used at early age for genetic selection for health traits is not feasible yet. Secondly, the IgM profile of neonatal chickens seems non-organised independent of the maternal profile, but the neonatal IgG profile is much more related with the maternal profile. Consequences of these findings for disease susceptibility or breeding for optimal health are discussed. Copyright © 2017 Elsevier Ltd. All

  2. Metabolite Profiling of Red Sea Corals

    KAUST Repository

    Ortega, Jovhana Alejandra

    2016-01-01

    that provide insights into the specific nature of the symbiosis. Our analysis also revealed aquatic pollutants, which suggests that metabolite profiling might be used for monitoring pollution levels and assessing environmental impact.

  3. Phytochemical and antioxidant profiles of leaves from different Sorbus L. species.

    Science.gov (United States)

    Raudonė, Lina; Raudonis, Raimondas; Gaivelytė, Kristina; Pukalskas, Audrius; Viškelis, Pranas; Venskutonis, Petras Rimantas; Janulis, Valdimaras

    2015-02-01

    Leaves of Sorbus L. have been used in various traditional medicine systems. Phenolic compounds determine the main pharmacological effects of Sorbus L. In this study, phytochemical and antioxidant profiles of Sorbus anglica, Sorbus aria, Sorbus arranensis, Sorbus aucuparia, Sorbus austriaca, Sorbus caucasica, Sorbus commixta, Sorbus discolor, Sorbus gracilis, Sorbus hostii, Sorbus semi-incisa and Sorbus tianschanica were determined. Twenty four constituents were identified in Sorbus L. species using ultra high performance liquid chromatography coupled to quadruple and time-of-flight mass spectrometers. Post-column FRAP assay identified compounds with reducing activity and revealed significantly greatest total antioxidant activity of 175.30 μmol TE/g DW, 169.20 μmol TE/g DW and 148.11 μmol TE/g DW in S. commixta, S. discolor and S. gracilis leaf samples, respectively, with neochlorogenic and chlorogenic acids being most significant contributors. Characteristic fingerprints of phytochemical and antioxidant profiles could be applied for the quality evaluation of various raw materials of Sorbus L. species.

  4. Quantitative 1D saturation profiles on chalk by NMR

    DEFF Research Database (Denmark)

    Olsen, Dan; Topp, Simon; Stensgaard, Anders

    1996-01-01

    Quantitative one-dimensional saturation profiles showing the distribution of water and oil in chalk core samples are calculated from NMR measurements utilizing a 1D CSI spectroscopy pulse sequence. Saturation profiles may be acquired under conditions of fluid flow through the sample. Results reveal...

  5. Kompetenční profil kaskadéra

    OpenAIRE

    Šittová, Magdalena

    2017-01-01

    Title: Competency profile of stuntman Objectives: The main aim of this thesis is to create the competency profile of the ideal stuntman. This competency profile should reveal key personality traits, qual- ities and abilities and in the future should help to choose a new stunt people. Methods: The thesis uses interviews with leading Czech stuntmen. The list of competencies based on interviews and written sources was distributed by questionnaires. To as- sess the importance has been selected 4 ...

  6. Gene expression profiles of glucose toxicity-exposed islet microvascular endothelial cells.

    Science.gov (United States)

    Liu, Mingming; Lu, Wenbao; Hou, Qunxing; Wang, Bing; Sheng, Youming; Wu, Qingbin; Li, Bingwei; Liu, Xueting; Zhang, Xiaoyan; Li, Ailing; Zhang, Honggang; Xiu, Ruijuan

    2018-03-25

    Islet microcirculation is mainly composed by IMECs. The aim of the study was to investigate the differences in gene expression profiles of IMECs upon glucose toxicity exposure and insulin treatment. IMECs were treated with 5.6 mmol L -1 glucose, 35 mmol L -1 glucose, and 35 mmol L -1 glucose plus 10 -8  mol L -1 insulin, respectively. Gene expression profiles were determined by microarray and verified by qPCR. GO terms and KEGG analysis were performed to assess the potential roles of differentially expressed genes. The interaction and expression tendency of differentially expressed genes were analyzed by Path-Net algorithm. Compared with glucose toxicity-exposed IMECs, 1574 mRNAs in control group and 2870 mRNAs in insulin-treated IMECs were identified with differential expression, respectively. GO and KEGG pathway analysis revealed that these genes conferred roles in regulation of apoptosis, proliferation, migration, adhesion, and metabolic process etc. Additionally, MAPK signaling pathway and apoptosis were the dominant nodes in Path-Net. IMECs survival and function pathways were significantly changed, and the expression tendency of genes from euglycemia and glucose toxicity exposure to insulin treatment was revealed and enriched in 7 patterns. Our study provides a microcirculatory framework for gene expression profiles of glucose toxicity-exposed IMECs. © 2018 John Wiley & Sons Ltd.

  7. Biochemical association of metabolic profile and microbiome in chronic pressure ulcer wounds.

    Directory of Open Access Journals (Sweden)

    Mary Cloud B Ammons

    Full Text Available Chronic, non-healing wounds contribute significantly to the suffering of patients with co-morbidities in the clinical population with mild to severely compromised immune systems. Normal wound healing proceeds through a well-described process. However, in chronic wounds this process seems to become dysregulated at the transition between resolution of inflammation and re-epithelialization. Bioburden in the form of colonizing bacteria is a major contributor to the delayed headlining in chronic wounds such as pressure ulcers. However how the microbiome influences the wound metabolic landscape is unknown. Here, we have used a Systems Biology approach to determine the biochemical associations between the taxonomic and metabolomic profiles of wounds colonized by bacteria. Pressure ulcer biopsies were harvested from primary chronic wounds and bisected into top and bottom sections prior to analysis of microbiome by pyrosequencing and analysis of metabolome using 1H nuclear magnetic resonance (NMR spectroscopy. Bacterial taxonomy revealed that wounds were colonized predominantly by three main phyla, but differed significantly at the genus level. While taxonomic profiles demonstrated significant variability between wounds, metabolic profiles shared significant similarity based on the depth of the wound biopsy. Biochemical association between taxonomy and metabolic landscape indicated significant wound-to-wound similarity in metabolite enrichment sets and metabolic pathway impacts, especially with regard to amino acid metabolism. To our knowledge, this is the first demonstration of a statistically robust correlation between bacterial colonization and metabolic landscape within the chronic wound environment.

  8. Significance of Measuringigf- Levels in Adolescent Patients with Type 1 Diabetes Mellitus as a Prognostic Marker of Glycemic and Lipid Profile Control

    International Nuclear Information System (INIS)

    Ibrahim, I.; Fathy, H.; Tawfik, M.S.; Elesseily, E.S.

    2016-01-01

    The study aimed at evaluating the effect of elevated serum insulin-like growth factor-1( IGF-1), which is a by-product of growth hormone in the body on glycemic control (assessed by measuring HbA1c) and lipid profiles in adolescent patients (aged between 12 and 18 years) suffering from diabetes mellitus Type 1 (childhood onset diabetes mellitus ). Thirty patients with diabetes mellitus type one were enrolled in the study within the age range mentioned (mean age was 15.2 ± 3). These patients had high-normal IGF-1 levels according to the normal standard range for their age group). A second group of thirty patients with diabetes mellitus type 1 with normal IGF-1 levels (mean age was 14.6 ± 2.5) were also enrolled for this study. A third group included thirty age and sex matched healthy controls. HbA1-c was measured in all of the patients involved in the study as well as serum IGF-1. Lipid profiles were as sassed and they included total cholesterol, low density lipoproteins (LDL) High density lipoproteins (HDL) and serum triglycerides. A significant elevation in HbA1c levels was observed in diabetes mellitus type 1 patients with normal levels of IGF-1 as compared to patients with diabetes mellitus type 1 with high normal IGF-1 levels or normal control subjects (mean HbA1c levels for group 2 as compared to groups 1 and 3 were 9.20 ±0.64 vs. 7.01 ±0.56 vs. 5.11 ±0.57 respectively, p<0.01). A significant negative correlation was established between serum IGF levels and HbA1c (r= - 0.46, p=0.0 2). These results required the reassessment of management protocols for patients be longing to Group 2. Serum total cholesterol levels, LDL-C, and triglycerides were significantly higher in the second group as compared to the other groups while HDL levels in the same group were found to be significantly lower. A significant negative correlation was established between serum LDL-C levels and IGF- levels measured in all participants (r= - 0.41, p=0.02). This study concluded that

  9. Profiles of adolescent religiousness using latent profile analysis: Implications for psychopathology.

    Science.gov (United States)

    Longo, Gregory S; Bray, Bethany C; Kim-Spoon, Jungmeen

    2017-03-01

    Prior research has documented robust associations between adolescent religiousness/spirituality (R/S) and psychopathology outcomes including externalizing and internalizing symptomatology, yet no previous studies have examined these associations with adolescent R/S profiles using a person-centred approach. We examined whether there are identifiable subgroups characterized by unique multidimensional patterns of R/S experiences and how these experiences may be related to externalizing and internalizing symptomatology. The sample consisted of 220 Appalachian adolescents between 12 and 18 years old who were primarily White and primarily Christian. Latent profile analysis revealed three profiles of adolescent R/S: high religiousness (28.4%), introjectors (47.6%), and low religiousness (24.0%). These profiles were differentially related to internalizing and externalizing symptomatology such that the high religiousness group was significantly lower than the introjectors with respect to internalizing and externalizing symptomatology and lower than the low religiousness group in externalizing symptomatology. Implications and suggestions for future research using person-centred approaches to better understand differential developmental trajectories of religious development are provided. Statement of contribution What is already known Prior research has demonstrated a negative relationship between adolescent religiousness and spirituality (R/S) and psychopathology. Numerous studies document the differential relationships between aspects of R/S and psychopathology; however, few have done so from a person-centred perspective. There are several theories that outline how R/S to study R/S when paying specific attention to culture. Saroglou's Big Four dimensions of religion (believing, bonding, behaving, and belonging) posits that these four dimensions (1) are able to delimit religion from proximal constructs; (2) translate major distinct dimensions of religiousness; (3) can be

  10. The study for the profiles of mixed dentition

    International Nuclear Information System (INIS)

    Park, Tae Won

    1978-01-01

    The study was to analyze on the hard and soft tissue profiles in mixed dentition. The subject consisted of 100 males and 100 females from 9 to 12 years of age and with a normal occlusion and acceptable profiles. On the bases of SnH line and SnV line, the author traced all the cephalograms and calculated the mean value and standard deviation in each measuring category and evaluated the sexual difference, the proper limit of development. The obtained results were as follows; 1. Individual variations of the lower facial part were larger the upper facial part in depth and height. 2. Sexual difference of lower facial part was significant in depth and height. 3. All the measured values to the SnH and SnV line were larger in male than in female but revealed resemblance in the profilogram. 4. The measured values of the region of nose, upper lip and point A showed stable tendency.

  11. Lateral facial profile may reveal the risk for sleep disordered breathing in children--the PANIC-study.

    Science.gov (United States)

    Ikävalko, Tiina; Närhi, Matti; Lakka, Timo; Myllykangas, Riitta; Tuomilehto, Henri; Vierola, Anu; Pahkala, Riitta

    2015-01-01

    To evaluate the lateral view photography of the face as a tool for assessing morphological properties (i.e. facial convexity) as a risk factor for sleep disordered breathing (SDB) in children and to test how reliably oral health and non-oral healthcare professionals can visually discern the lateral profile of the face from the photographs. The present study sample consisted of 382 children 6-8 years of age who were participants in the Physical Activity and Nutrition in Children (PANIC) Study. Sleep was assessed by a sleep questionnaire administered by the parents. SDB was defined as apnoeas, frequent or loud snoring or nocturnal mouth breathing observed by the parents. The facial convexity was assessed with three different methods. First, it was clinically evaluated by the reference orthodontist (T.I.). Second, lateral view photographs were taken to visually sub-divide the facial profile into convex, normal or concave. The photos were examined by a reference orthodontist and seven different healthcare professionals who work with children and also by a dental student. The inter- and intra-examiner consistencies were calculated by Kappa statistics. Three soft tissue landmarks of the facial profile, soft tissue Glabella (G`), Subnasale (Sn) and soft tissue Pogonion (Pg`) were digitally identified to analyze convexity of the face and the intra-examiner reproducibility of the reference orthodontist was determined by calculating intra-class correlation coefficients (ICCs). The third way to express the convexity of the face was to calculate the angle of facial convexity (G`-Sn-Pg`) and to group it into quintiles. For analysis the lowest quintile (≤164.2°) was set to represent the most convex facial profile. The prevalence of the SDB in children with the most convex profiles expressed with the lowest quintile of the angle G`-Sn-Pg` (≤164.2°) was almost 2-fold (14.5%) compared to those with normal profile (8.1%) (p = 0.084). The inter-examiner Kappa values between the

  12. Molecular profiling reveals biologically discrete subsets and pathways of progression in diffuse glioma

    Science.gov (United States)

    Ceccarelli, Michele; Barthel, Floris P.; Malta, Tathiane M.; Sabedot, Thais S.; Salama, Sofie R.; Murray, Bradley A.; Morozova, Olena; Newton, Yulia; Radenbaugh, Amie; Pagnotta, Stefano M.; Anjum, Samreen; Wang, Jiguang; Manyam, Ganiraju; Zoppoli, Pietro; Ling, Shiyung; Rao, Arjun A.; Grifford, Mia; Cherniack, Andrew D.; Zhang, Hailei; Poisson, Laila; Carlotti, Carlos Gilberto; Pretti da Cunha Tirapelli, Daniela; Rao, Arvind; Mikkelsen, Tom; Lau, Ching C.; Yung, W.K. Alfred; Rabadan, Raul; Huse, Jason; Brat, Daniel J.; Lehman, Norman L.; Barnholtz-Sloan, Jill S.; Zheng, Siyuan; Hess, Kenneth; Rao, Ganesh; Meyerson, Matthew; Beroukhim, Rameen; Cooper, Lee; Akbani, Rehan; Wrensch, Margaret; Haussler, David; Aldape, Kenneth D.; Laird, Peter W.; Gutmann, David H.; Noushmehr, Houtan; Iavarone, Antonio; Verhaak, Roel G.W.

    2015-01-01

    SUMMARY Therapy development for adult diffuse glioma is hindered by incomplete knowledge of somatic glioma driving alterations and suboptimal disease classification. We defined the complete set of genes associated with 1,122 diffuse grade II-III-IV gliomas from The Cancer Genome Atlas and used molecular profiles to improve disease classification, identify molecular correlations, and provide insights into the progression from low- to high-grade disease. Whole genome sequencing data analysis determined that ATRX but not TERT promoter mutations are associated with increased telomere length. Recent advances in glioma classification based on IDH mutation and 1p/19q co-deletion status were recapitulated through analysis of DNA methylation profiles, which identified clinically relevant molecular subsets. A subtype of IDH-mutant glioma was associated with DNA demethylation and poor outcome; a group of IDH-wildtype diffuse glioma showed molecular similarity to pilocytic astrocytoma and relatively favorable survival. Understanding of cohesive disease groups may aid improved clinical outcomes. PMID:26824661

  13. Biologic and clinical significance of molecular profiling in Chronic Lymphocytic Leukemia.

    Science.gov (United States)

    Butler, Tom; Gribben, J G

    2010-05-01

    CLL is extremely heterogeneous in its clinical course, with some patients living decades with no need for treatment whilst others have a rapidly aggressive clinical course. A major focus of research has been to try to identify those biological factors that influence this heterogeneity. The goal of therapy has been to maintain the best quality of life and treat only when patients become symptomatic from their disease. For the majority of patients this means following a "watch and wait" approach to determine the rate of progression of the disease and assess for development of symptoms. Any alteration to this approach will require identification of criteria that define patients sufficiently "high-risk" that they gain benefit by introduction of early therapy. The use of molecular profiling to suggest particular therapies is currently appropriate only in defining the treatment of the minority of patients with 17p deletions or p53 mutations and in all other circumstances remains a clinical trial question. Copyright 2010 Elsevier Ltd. All rights reserved.

  14. HC-Pro silencing suppressor significantly alters the gene expression profile in tobacco leaves and flowers

    Directory of Open Access Journals (Sweden)

    Lehto Kirsi

    2011-04-01

    -adenosyl-L-methionine (SAM were also decreased in these plants, apparently leading to decreased transmethylation capacity. The proteome analysis using 2D-PAGE indicated significantly altered proteome profile, which may have been both due to altered transcript levels, decreased translation, and increased proteosomal/protease activity. Conclusion Expression of the HC-Pro RSS mimics transcriptional changes previously shown to occur in plants infected with intact viruses (e.g. Tobacco etch virus, TEV. The results indicate that the HC-Pro RSS contributes a significant part of virus-plant interactions by changing the levels of multiple cellular RNAs and proteins.

  15. MicroRNA Expression Profile in Penile Cancer Revealed by Next-Generation Small RNA Sequencing.

    Directory of Open Access Journals (Sweden)

    Li Zhang

    Full Text Available Penile cancer (PeCa is a relatively rare tumor entity but possesses higher morbidity and mortality rates especially in developing countries. To date, the concrete pathogenic signaling pathways and core machineries involved in tumorigenesis and progression of PeCa remain to be elucidated. Several studies suggested miRNAs, which modulate gene expression at posttranscriptional level, were frequently mis-regulated and aberrantly expressed in human cancers. However, the miRNA profile in human PeCa has not been reported before. In this present study, the miRNA profile was obtained from 10 fresh penile cancerous tissues and matched adjacent non-cancerous tissues via next-generation sequencing. As a result, a total of 751 and 806 annotated miRNAs were identified in normal and cancerous penile tissues, respectively. Among which, 56 miRNAs with significantly different expression levels between paired tissues were identified. Subsequently, several annotated miRNAs were selected randomly and validated using quantitative real-time PCR. Compared with the previous publications regarding to the altered miRNAs expression in various cancers and especially genitourinary (prostate, bladder, kidney, testis cancers, the most majority of deregulated miRNAs showed the similar expression pattern in penile cancer. Moreover, the bioinformatics analyses suggested that the putative target genes of differentially expressed miRNAs between cancerous and matched normal penile tissues were tightly associated with cell junction, proliferation, growth as well as genomic instability and so on, by modulating Wnt, MAPK, p53, PI3K-Akt, Notch and TGF-β signaling pathways, which were all well-established to participate in cancer initiation and progression. Our work presents a global view of the differentially expressed miRNAs and potentially regulatory networks of their target genes for clarifying the pathogenic transformation of normal penis to PeCa, which research resource also

  16. Untargeted metabolomic profiling plasma samples of patients with lung cancer for searching significant metabolites by HPLC-MS method

    Science.gov (United States)

    Dementeva, N.; Ivanova, K.; Kokova, D.; Kurzina, I.; Ponomaryova, A.; Kzhyshkowska, J.

    2017-09-01

    Lung cancer is one of the most common types of cancer leading to death. Consequently, the search and the identification of the metabolites associated with the risk of developing cancer are very valuable. For the purpose, untargeted metabolic profiling of the plasma samples collected from the patients with lung cancer (n = 100) and the control group (n = 100) was conducted. After sample preparation, the plasma samples were analyzed using LC-MS method. Biostatistics methods were applied to pre-process the data for elicitation of dominating metabolites which responded to the difference between the case and the control groups. At least seven significant metabolites were evaluated and annotated. The most part of identified metabolites are connected with lipid metabolism and their combination could be useful for follow-up studies of lung cancer pathogenesis.

  17. Survey of French spine surgeons reveals significant variability in spine trauma practices in 2013.

    Science.gov (United States)

    Lonjon, G; Grelat, M; Dhenin, A; Dauzac, C; Lonjon, N; Kepler, C K; Vaccaro, A R

    2015-02-01

    In France, attempts to define common ground during spine surgery meetings have revealed significant variability in clinical practices across different schools of surgery and the two specialities involved in spine surgery, namely, neurosurgery and orthopaedic surgery. To objectively characterise this variability by performing a survey based on a fictitious spine trauma case. Our working hypothesis was that significant variability existed in trauma practices and that this variability was related to a lack of strong scientific evidence in spine trauma care. We performed a cross-sectional survey based on a clinical vignette describing a 31-year-old male with an L1 burst fracture and neurologic symptoms (numbness). Surgeons received the vignette and a 14-item questionnaire on the management of this patient. For each question, surgeons had to choose among five possible answers. Differences in answers across surgeons were assessed using the Index of Qualitative Variability (IQV), in which 0 indicates no variability and 1 maximal variability. Surgeons also received a questionnaire about their demographics and surgical experience. Of 405 invited spine surgeons, 200 responded to the survey. Five questions had an IQV greater than 0.9, seven an IQV between 0.5 and 0.9, and two an IQV lower than 0.5. Variability was greatest about the need for MRI (IQV=0.93), degree of urgency (IQV=0.93), need for fusion (IQV=0.92), need for post-operative bracing (IQV=0.91), and routine removal of instrumentation (IQV=0.94). Variability was lowest for questions about the need for surgery (IQV=0.42) and use of the posterior approach (IQV=0.36). Answers were influenced by surgeon specialty, age, experience level, and type of centre. Clinical practice regarding spine trauma varies widely in France. Little published evidence is available on which to base recommendations that would diminish this variability. Copyright © 2015. Published by Elsevier Masson SAS.

  18. Metabolomics reveals variation and correlation among different tissues of olive (Olea europaea L.

    Directory of Open Access Journals (Sweden)

    Rao Guodong

    2017-09-01

    Full Text Available Metabolites in olives are associated with nutritional value and physiological properties. However, comprehensive information regarding the olive metabolome is limited. In this study, we identified 226 metabolites from three different tissues of olive using a non-targeted metabolomic profiling approach, of which 76 named metabolites were confirmed. Further statistical analysis revealed that these 76 metabolites covered different types of primary metabolism and some of the secondary metabolism pathways. One-way analysis of variance (ANOVA statistical assay was performed to calculate the variations within the detected metabolites, and levels of 65 metabolites were differentially expressed in different samples. Hierarchical cluster analysis (HCA dendrograms showed variations among different tissues that were similar to the metabolite profiles observed in new leaves and fruit. Additionally, 5776 metabolite-metabolite correlations were detected by a Pearson correlation coefficient approach. Screening of the calculated correlations revealed 3136, 3025, and 5184 were determined to metabolites and had significant correlations in three different combinations, respectively. This work provides the first comprehensive metabolomic of olive, which will provide new insights into understanding the olive metabolism, and potentially help advance studies in olive metabolic engineering.

  19. Comprehensive genomic profiling reveals inactivating SMARCA4 mutations and low tumor mutational burden in small cell carcinoma of the ovary, hypercalcemic-type.

    Science.gov (United States)

    Lin, Douglas I; Chudnovsky, Yakov; Duggan, Bridget; Zajchowski, Deborah; Greenbowe, Joel; Ross, Jeffrey S; Gay, Laurie M; Ali, Siraj M; Elvin, Julia A

    2017-12-01

    Small cell carcinoma of the ovary, hypercalcemic-type (SCCOHT) is a rare, extremely aggressive neoplasm that usually occurs in young women and is characterized by deleterious germline or somatic SMARCA4 mutations. We performed comprehensive genomic profiling (CGP) to potentially identify additional clinically and pathophysiologically relevant genomic alterations in SCCOHT. CGP assessment of all classes of coding alterations in up to 406 genes commonly altered in cancer and intronic regions for up to 31 genes commonly rearranged in cancer was performed on 18 SCCOHT cases (16 exhibiting classic morphology and 2 cases exhibiting exclusive a large cell variant morphology). In addition, a retrospective database search for clinically advanced ovarian tumors with genomic profiles similar to SCCOHT yielded 3 additional cases originally diagnosed as non-SCCOHT. CGP revealed inactivating SMARCA4 alterations and low tumor mutational burden (TMB) (<6mutations/Mb) in 94% (15/16) of SCCOHT with classic morphology. In contrast, both (2/2) cases exhibiting only large cell variant morphology were hypermutated (TMB scores of 90 and 360mut/Mb) and were wildtype for SMARCA4. In our retrospective search, an index ovarian cancer patient harboring inactivating SMARCA4 alterations, initially diagnosed as endometrioid carcinoma, was re-classified as SCCOHT and responded to an SCCOHT chemotherapy regimen. The vast majority of SCCOHT demonstrate genomic SMARCA4 loss with only rare co-occurring alterations. Our data support a role for CGP in the diagnosis and management of SCCOHT and of other lesions with overlapping histological and clinical features, since identifying the former by genomic profile suggests benefit from an appropriate regimen and treatment decisions, as illustrated by an index patient. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Crustal structure revealed by a deep seismic sounding profile of Baijing-Gaoming-Jinwan in the Pearl River Delta

    Science.gov (United States)

    Zhang, Xiang; Ye, Xiuwei; Lv, Jinshui; Sun, Jinlong; Wang, Xiaona

    2018-02-01

    The Pearl River Estuary area, located in the middle part of the southern China coastal seismic belt, has long been considered a potential source of strong earthquakes above magnitude 7.0. To scientifically assess the potential strong earthquake risk in this area, a three-dimensional artificial seismic sounding experiment, consisting of a receiving array and seabed seismograph, was performed to reveal the deep crustal structure in this region. We used artificial ship-borne air-gun excitation shots as sources, and fixed and mobile stations as receivers to record seismic data from May to August 2015. This paper presents results along a line from the western side of the Pearl River Estuary to the western side of the Baijing-Gaoming-Jinwan profile. A two-dimensional velocity structure was constructed using seismic travel-time tomography. The inversion results show that the Moho depth is 27 km in the coastal area and 30 km in the northwest of the Pearl River Estuary area, indicating that the crust thins from land to sea. Two structural discontinuities and multiple low-velocity anomalies appear in the crustal section. Inside both discontinuity zones, a low-velocity layer, with a minimum velocity of 6.05 km s-1, exists at a depth of about 15 km, and another, with a minimum velocity of 6.37 km s-1, exists at a depth of about 21.5 km between the middle and lower crust. These low velocities suggest that the discontinuities may consist of partly molten material. Earthquakes with magnitudes higher than 5.0 occurred in the low-velocity layer along the profile. The deep Kaiping-Enping fault, rooted in the crust, may be one of the most important channels for deep material upwelling and is related to tectonic movement since the Cretaceous in the Pearl River Delta tectonic rift basin.

  1. Corrosion issues of powder coated AA6060 aluminium profiles

    DEFF Research Database (Denmark)

    Din, Rameez Ud; Valgarðsson, Smári; Jellesen, Morten Stendahl

    2015-01-01

    In this study detailed microstructural investigation of the reason for unexpected corrosion of powder coated aluminium alloy AA6060 windows profiles has been performed. The results from this study reveals that the failure of the window profiles was originated from the surface defects present...... on the extruded AA6060 aluminium profile after metallurgical process prior to powder coating. Surface defects are produced due to intermetallic particles in the alloy, which disturb the flow during the extrusion process. The corrosion mechanism leading to the failure of the powder coated AA6060 aluminium profiles...

  2. Gas-Chromatography Mass-Spectrometry (GC-MS Based Metabolite Profiling Reveals Mannitol as a Major Storage Carbohydrate in the Coccolithophorid Alga Emiliania huxleyi

    Directory of Open Access Journals (Sweden)

    Alisdair R. Fernie

    2013-03-01

    Full Text Available Algae are divergent organisms having a wide variety of evolutional histories. Although most of them share photosynthetic activity, their pathways of primary carbon metabolism are rather diverse among species. Here we developed a method for gas chromatography-mass spectroscopy (GC-MS based metabolite profiling for the coccolithophorid alga Emiliania huxleyi, which is one of the most abundant microalgae in the ocean, in order to gain an overview of the pathway of primary metabolism within this alga. Following method optimization, twenty-six metabolites could be detected by this method. Whilst most proteogenic amino acids were detected, no peaks corresponding to malate and fumarate were found. The metabolite profile of E. huxleyi was, however, characterized by a prominent accumulation of mannitol reaching in excess of 14 nmol 106 cells−1. Similarly, the accumulation of the 13C label during short term H13CO3− feeding revealed a massive redistribution of label into mannitol as well as rapid but saturating label accumulation into glucose and several amino acids including aspartate, glycine and serine. These results provide support to previous work suggesting that this species adopts C3 photosynthesis and that mannitol functions as a carbon store in E. huxleyi.

  3. Motivational profiles in physical education and their relation to the theory of planned behavior.

    Science.gov (United States)

    Moreno-Murcia, Juan Antonio; Cervelló Gimeno, Eduardo; Hernández, Elisa Huéscar; Pedreño, Noelia Belan-do; Rodríguez Marín, Jesús Jesus

    2013-01-01

    The aim of this study was to establish motivational profiles for doing physical activity according to the variables from the theory of planned action in a sample of 698 students aged 14 to 16. The instruments used were the Questionnaire of Behavioral Regulation in Sport (BRQ-R) and the Questionnaire of the Theory of Planned Behavior (TCP). Cluster analysis revealed two motivational profiles: a "self-determined "profile with high scores in intrinsic motivation and low scores in extrinsic motivation and amotivation, and a "non self- determined "profile with low scores in intrinsic motivation and high scores in extrinsic motivation and amotivation. Positive significant differences in attitudes, norms, and intent to control were found for the self-determined profile related to "non self-determined "profile. Key PointsA "self-determined "profile was found with higher scores for the four types of intrinsic motivations (general, knowledge, stimulation and achievement) and identified regulation than for introjected and external regulation.A "non self-determined "profile was found with higher scores for external, introjected regulation and amotivation than for the four types of intrinsic motivation (general, knowledge, stimulation and achievement).In the context of the "non self-determined profile "we could encourage programs that adapt to these needs in such a way that they contribute to increasing the rates of doing physical activity in the population.

  4. A Latent Profile Analysis of Latino Parenting: The Infusion of Cultural Values on Family Conflict.

    Science.gov (United States)

    Ayón, Cecilia; Williams, Lela Rankin; Marsiglia, Flavio F; Ayers, Stephanie; Kiehne, Elizabeth

    The purpose of the present study was to (a) examine how acculturation and social support inform Latinos' parenting behaviors, controlling for gender and education; (b) describe parenting styles among Latino immigrants while accounting for cultural elements; and (c) test how these parenting styles are associated with family conflict. A 3 step latent profile analysis with the sample ( N = 489) revealed best fit with a 4 profile model ( n = 410) of parenting: family parenting ( n = 268, 65%), child-centered parenting ( n = 68, 17%), moderate parenting ( n = 60, 15%), and disciplinarian parenting ( n = 14, 3%). Parents' gender, acculturation, and social support significantly predicted profile membership. Disciplinarian and moderate parenting were associated with more family conflict. Recommendations include integrating culturally based parenting practices as a critical element to family interventions to minimize conflict and promote positive youth development.

  5. Proteomic Profiling in the Brain of CLN1 Disease Model Reveals Affected Functional Modules.

    Science.gov (United States)

    Tikka, Saara; Monogioudi, Evanthia; Gotsopoulos, Athanasios; Soliymani, Rabah; Pezzini, Francesco; Scifo, Enzo; Uusi-Rauva, Kristiina; Tyynelä, Jaana; Baumann, Marc; Jalanko, Anu; Simonati, Alessandro; Lalowski, Maciej

    2016-03-01

    Neuronal ceroid lipofuscinoses (NCL) are the most commonly inherited progressive encephalopathies of childhood. Pathologically, they are characterized by endolysosomal storage with different ultrastructural features and biochemical compositions. The molecular mechanisms causing progressive neurodegeneration and common molecular pathways linking expression of different NCL genes are largely unknown. We analyzed proteome alterations in the brains of a mouse model of human infantile CLN1 disease-palmitoyl-protein thioesterase 1 (Ppt1) gene knockout and its wild-type age-matched counterpart at different stages: pre-symptomatic, symptomatic and advanced. For this purpose, we utilized a combination of laser capture microdissection-based quantitative liquid chromatography tandem mass spectrometry (MS) and matrix-assisted laser desorption/ionization time-of-flight MS imaging to quantify/visualize the changes in protein expression in disease-affected brain thalamus and cerebral cortex tissue slices, respectively. Proteomic profiling of the pre-symptomatic stage thalamus revealed alterations mostly in metabolic processes and inhibition of various neuronal functions, i.e., neuritogenesis. Down-regulation in dynamics associated with growth of plasma projections and cellular protrusions was further corroborated by findings from RNA sequencing of CLN1 patients' fibroblasts. Changes detected at the symptomatic stage included: mitochondrial functions, synaptic vesicle transport, myelin proteome and signaling cascades, such as RhoA signaling. Considerable dysregulation of processes related to mitochondrial cell death, RhoA/Huntington's disease signaling and myelin sheath breakdown were observed at the advanced stage of the disease. The identified changes in protein levels were further substantiated by bioinformatics and network approaches, immunohistochemistry on brain tissues and literature knowledge, thus identifying various functional modules affected in the CLN1 childhood

  6. Transcriptome profiling of a curdlan-producing Agrobacterium reveals conserved regulatory mechanisms of exopolysaccharide biosynthesis

    Directory of Open Access Journals (Sweden)

    Ruffing Anne M

    2012-02-01

    Full Text Available Abstract Background The ability to synthesize exopolysaccharides (EPS is widespread among microorganisms, and microbial EPS play important roles in biofilm formation, pathogen persistence, and applications in the food and medical industries. Although it is well established that EPS synthesis is invariably in response to environmental cues, it remains largely unknown how various environmental signals trigger activation of the biochemical synthesis machinery. Results We report here the transcriptome profiling of Agrobacterium sp. ATCC 31749, a microorganism that produces large amounts of a glucose polymer known as curdlan under nitrogen starvation. Transcriptome analysis revealed a nearly 100-fold upregulation of the curdlan synthesis operon upon transition to nitrogen starvation, thus establishing the prominent role that transcriptional regulation plays in the EPS synthesis. In addition to known mechanisms of EPS regulation such as activation by c-di-GMP, we identify novel mechanisms of regulation in ATCC 31749, including RpoN-independent NtrC regulation and intracellular pH regulation by acidocalcisomes. Furthermore, we show evidence that curdlan synthesis is also regulated by conserved cell stress responses, including polyphosphate accumulation and the stringent response. In fact, the stringent response signal, pppGpp, appears to be indispensible for transcriptional activation of curdlan biosynthesis. Conclusions This study identifies several mechanisms regulating the synthesis of curdlan, an EPS with numerous applications. These mechanisms are potential metabolic engineering targets for improving the industrial production of curdlan from Agrobacterium sp. ATCC 31749. Furthermore, many of the genes identified in this study are highly conserved across microbial genomes, and we propose that the molecular elements identified in this study may serve as universal regulators of microbial EPS synthesis.

  7. Rhizosphere Protists Change Metabolite Profiles in Zea mays

    Directory of Open Access Journals (Sweden)

    Anke Kuppardt

    2018-05-01

    Full Text Available Plant growth and productivity depend on the interactions of the plant with the associated rhizosphere microbes. Rhizosphere protists play a significant role in this respect: considerable efforts have been made in the past to reveal the impact of protist-bacteria interactions on the remobilization of essential nutrients for plant uptake, or the grazing induced changes on plant-growth promoting bacteria and the root-architecture. However, the metabolic responses of plants to the presence of protists or to protist-bacteria interactions in the rhizosphere have not yet been analyzed. Here we studied in controlled laboratory experiments the impact of bacterivorous protists in the rhizosphere on maize plant growth parameters and the bacterial community composition. Beyond that we investigated the induction of plant biochemical responses by separately analyzing above- and below-ground metabolite profiles of maize plants incubated either with a soil bacterial inoculum or with a mixture of soil bacteria and bacterivorous protists. Significantly distinct leaf and root metabolite profiles were obtained from plants which grew in the presence of protists. These profiles showed decreased levels of a considerable number of metabolites typical for the plant stress reaction, such as polyols, a number of carbohydrates and metabolites connected to phenolic metabolism. We assume that this decrease in plant stress is connected to the grazing induced shifts in rhizosphere bacterial communities as shown by distinct T-RFLP community profiles. Protist grazing had a clear effect on the overall bacterial community composition, richness and evenness in our microcosms. Given the competition of plant resource allocation to either defense or growth, we propose that a reduction in plant stress levels caused directly or indirectly by protists may be an additional reason for corresponding positive effects on plant growth.

  8. Rhizosphere Protists Change Metabolite Profiles in Zea mays.

    Science.gov (United States)

    Kuppardt, Anke; Fester, Thomas; Härtig, Claus; Chatzinotas, Antonis

    2018-01-01

    Plant growth and productivity depend on the interactions of the plant with the associated rhizosphere microbes. Rhizosphere protists play a significant role in this respect: considerable efforts have been made in the past to reveal the impact of protist-bacteria interactions on the remobilization of essential nutrients for plant uptake, or the grazing induced changes on plant-growth promoting bacteria and the root-architecture. However, the metabolic responses of plants to the presence of protists or to protist-bacteria interactions in the rhizosphere have not yet been analyzed. Here we studied in controlled laboratory experiments the impact of bacterivorous protists in the rhizosphere on maize plant growth parameters and the bacterial community composition. Beyond that we investigated the induction of plant biochemical responses by separately analyzing above- and below-ground metabolite profiles of maize plants incubated either with a soil bacterial inoculum or with a mixture of soil bacteria and bacterivorous protists. Significantly distinct leaf and root metabolite profiles were obtained from plants which grew in the presence of protists. These profiles showed decreased levels of a considerable number of metabolites typical for the plant stress reaction, such as polyols, a number of carbohydrates and metabolites connected to phenolic metabolism. We assume that this decrease in plant stress is connected to the grazing induced shifts in rhizosphere bacterial communities as shown by distinct T-RFLP community profiles. Protist grazing had a clear effect on the overall bacterial community composition, richness and evenness in our microcosms. Given the competition of plant resource allocation to either defense or growth, we propose that a reduction in plant stress levels caused directly or indirectly by protists may be an additional reason for corresponding positive effects on plant growth.

  9. Partial venom gland transcriptome of a Drosophila parasitoid wasp, Leptopilina heterotoma, reveals novel and shared bioactive profiles with stinging Hymenoptera

    Science.gov (United States)

    Heavner, Mary E.; Gueguen, Gwenaelle; Rajwani, Roma; Pagan, Pedro E.; Small, Chiyedza; Govind, Shubha

    2013-01-01

    Analysis of natural host-parasite relationships reveals the evolutionary forces that shape the delicate and unique specificity characteristic of such interactions. The accessory long gland-reservoir complex of the wasp Leptopilina heterotoma (Figitidae) produces venom with virus-like particles. Upon delivery, venom components delay host larval development and completely block host immune responses. The host range of this Drosophila endoparasitoid notably includes the highly-studied model organism, Drosophila melanogaster. Categorization of 827 unigenes, using similarity as an indicator of putative homology, reveals that approximately 25% are novel or classified as hypothetical proteins. Most of the remaining unigenes are related to processes involved in signaling, cell cycle, and cell physiology including detoxification, protein biogenesis, and hormone production. Analysis of L. heterotoma’s predicted venom gland proteins demonstrates conservation among endo- and ectoparasitoids within the Apocrita (e.g., this wasp and the jewel wasp Nasonia vitripennis) and stinging aculeates (e.g., the honey bee and ants). Enzyme and KEGG pathway profiling predicts that kinases, esterases, and hydrolases may contribute to venom activity in this unique wasp. To our knowledge, this investigation marks the first functional genomic study for a natural parasitic wasp of Drosophila. Our findings will help explain how L. heterotoma shuts down its hosts’ immunity and shed light on the molecular basis of a natural arms race between these insects. PMID:23688557

  10. Extrapancreatic Autoantibody Profiles in Type I Diabetes

    Science.gov (United States)

    Burbelo, Peter D.; Lebovitz, Evan E.; Bren, Kathleen E.; Bayat, Ahmad; Paviol, Scott; Wenzlau, Janet M.; Barriga, Katherine J.; Rewers, Marian; Harlan, David M.; Iadarola, Michael J.

    2012-01-01

    Type I diabetes (T1D) is an autoimmune disease characterized by destruction of insulin-producing β-cells in the pancreas. Although several islet cell autoantigens are known, the breadth and spectrum of autoantibody targets has not been fully explored. Here the luciferase immunoprecipitation systems (LIPS) antibody profiling technology was used to study islet and other organ-specific autoantibody responses in parallel. Examination of an initial cohort of 93 controls and 50 T1D subjects revealed that 16% of the diabetic subjects showed anti-gastric ATPase autoantibodies which did not correlate with autoantibodies against GAD65, IA2, or IA2-β. A more detailed study of a second cohort with 18 potential autoantibody targets revealed marked heterogeneity in autoantibody responses against islet cell autoantigens including two polymorphic variants of ZnT8. A subset of T1D subjects exhibited autoantibodies against several organ-specific targets including gastric ATPase (11%), thyroid peroxidase (14%), and anti-IgA autoantibodies against tissue transglutaminase (12%). Although a few T1D subjects showed autoantibodies against a lung-associated protein KCNRG (6%) and S100-β (8%), no statistically significant autoantibodies were detected against several cytokines. Analysis of the overall autoantibody profiles using a heatmap revealed two major subgroups of approximately similar numbers, consisting of T1D subjects with and without organ-specific autoantibodies. Within the organ-specific subgroup, there was minimal overlap among anti-gastric ATPase, anti-thyroid peroxidase, and anti-transglutaminase seropositivity, and these autoantibodies did not correlate with islet cell autoantibodies. Examination of a third cohort, comprising prospectively collected longitudinal samples from high-risk individuals, revealed that anti-gastric ATPase autoantibodies were present in several individuals prior to detection of islet autoantibodies and before clinical onset of T1D. Taken together

  11. [Profiles of resilience and quality of life in people with acquired disability due to traffic accidents].

    Science.gov (United States)

    Suriá Martínez, Raquel

    2015-09-01

    To identify distinct profiles of resilience in people with spinal cord injuries due to traffic accidents and to determine whether the profiles identified are related to differences in subjective well-being. The Resilience Scale (Wagnild and Young, 1993) and an adapted quality of life scale (GENCAT) were administered to 98 people with physical disabilities due to traffic accidents. Cluster analyses identified three different resilience profiles: a high-resilience group, a low-resilience group, and a group showing a predominance of high scores in self and life acceptance and social competence. The results also revealed statistically significant differences among profiles in most domains of subjective well-being. The results suggest the need to study resilience in greater depth and to design programs to enhance quality of life among people with disabilities due to traffic accidents. Copyright © 2014 SESPAS. Published by Elsevier Espana. All rights reserved.

  12. Accurate and robust phylogeny estimation based on profile distances: a study of the Chlorophyceae (Chlorophyta

    Directory of Open Access Journals (Sweden)

    Rahmann Sven

    2004-06-01

    Full Text Available Abstract Background In phylogenetic analysis we face the problem that several subclade topologies are known or easily inferred and well supported by bootstrap analysis, but basal branching patterns cannot be unambiguously estimated by the usual methods (maximum parsimony (MP, neighbor-joining (NJ, or maximum likelihood (ML, nor are they well supported. We represent each subclade by a sequence profile and estimate evolutionary distances between profiles to obtain a matrix of distances between subclades. Results Our estimator of profile distances generalizes the maximum likelihood estimator of sequence distances. The basal branching pattern can be estimated by any distance-based method, such as neighbor-joining. Our method (profile neighbor-joining, PNJ then inherits the accuracy and robustness of profiles and the time efficiency of neighbor-joining. Conclusions Phylogenetic analysis of Chlorophyceae with traditional methods (MP, NJ, ML and MrBayes reveals seven well supported subclades, but the methods disagree on the basal branching pattern. The tree reconstructed by our method is better supported and can be confirmed by known morphological characters. Moreover the accuracy is significantly improved as shown by parametric bootstrap.

  13. Circuit-wide Transcriptional Profiling Reveals Brain Region-Specific Gene Networks Regulating Depression Susceptibility.

    Science.gov (United States)

    Bagot, Rosemary C; Cates, Hannah M; Purushothaman, Immanuel; Lorsch, Zachary S; Walker, Deena M; Wang, Junshi; Huang, Xiaojie; Schlüter, Oliver M; Maze, Ian; Peña, Catherine J; Heller, Elizabeth A; Issler, Orna; Wang, Minghui; Song, Won-Min; Stein, Jason L; Liu, Xiaochuan; Doyle, Marie A; Scobie, Kimberly N; Sun, Hao Sheng; Neve, Rachael L; Geschwind, Daniel; Dong, Yan; Shen, Li; Zhang, Bin; Nestler, Eric J

    2016-06-01

    Depression is a complex, heterogeneous disorder and a leading contributor to the global burden of disease. Most previous research has focused on individual brain regions and genes contributing to depression. However, emerging evidence in humans and animal models suggests that dysregulated circuit function and gene expression across multiple brain regions drive depressive phenotypes. Here, we performed RNA sequencing on four brain regions from control animals and those susceptible or resilient to chronic social defeat stress at multiple time points. We employed an integrative network biology approach to identify transcriptional networks and key driver genes that regulate susceptibility to depressive-like symptoms. Further, we validated in vivo several key drivers and their associated transcriptional networks that regulate depression susceptibility and confirmed their functional significance at the levels of gene transcription, synaptic regulation, and behavior. Our study reveals novel transcriptional networks that control stress susceptibility and offers fundamentally new leads for antidepressant drug discovery. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Proteomics reveals the effects of sustained weight loss on the human plasma proteome

    DEFF Research Database (Denmark)

    Geyer, Philipp E; Wewer Albrechtsen, Nicolai J; Tyanova, Stefka

    2016-01-01

    Sustained weight loss is a preferred intervention in a wide range of metabolic conditions, but the effects on an individual's health state remain ill-defined. Here, we investigate the plasma proteomes of a cohort of 43 obese individuals that had undergone 8 weeks of 12% body weight loss followed...... by a year of weight maintenance. Using mass spectrometry-based plasma proteome profiling, we measured 1,294 plasma proteomes. Longitudinal monitoring of the cohort revealed individual-specific protein levels with wide-ranging effects of losing weight on the plasma proteome reflected in 93 significantly...

  15. Surface activity, lipid profiles and their implications in cervical cancer.

    Directory of Open Access Journals (Sweden)

    Preetha A

    2005-01-01

    Full Text Available Background: The profiles of lipids in normal and cancerous tissues may differ revealing information about cancer development and progression. Lipids being surface active, changes in lipid profiles can manifest as altered surface activity profiles. Langmuir monolayers offer a convenient model for evaluating surface activity of biological membranes. Aims: The aims of this study were to quantify phospholipids and their effects on surface activity of normal and cancerous human cervical tissues as well as to evaluate the role of phosphatidylcholine (PC and sphingomyelin (SM in cervical cancer using Langmuir monolayers. Methods and Materials: Lipid quantification was done using thin layer chromatography and phosphorus assay. Surface activity was evaluated using Langmuir monolayers. Monolayers were formed on the surface of deionized water by spreading tissue organic phase corresponding to 1 mg of tissue and studying their surface pressure-area isotherms at body temperature. The PC and SM contents of cancerous human cervical tissues were higher than those of the normal human cervical tissues. Role of PC and SM were evaluated by adding varying amounts of these lipids to normal cervical pooled organic phase. Statistical analysis: Student′s t-test (p < 0.05 and one-way analysis of variance (ANOVA was used. Results: Our results reveals that the phosphatidylglycerol level in cancerous cervical tissue was nearly five folds higher than that in normal cervical tissue. Also PC and sphingomyelin SM were found to be the major phospholipid components in cancerous and normal cervical tissues respectively. The addition of either 1.5 µg DPPC or 0.5 µg SM /mg of tissue to the normal organic phase changed its surface activity profile to that of the cancerous tissues. Statistically significant surface activity parameters showed that PC and SM have remarkable roles in shifting the normal cervical lipophilic surface activity towards that of cancerous lipophilic

  16. Profiling microRNAs in lung tissue from pigs infected with Actinobacillus pleuropneumoniae

    DEFF Research Database (Denmark)

    Podolska, Agnieszka; Anthon, Christian; Bak, Mads

    2012-01-01

    significantly up-regulated in the necrotic sample and 12 were down-regulated. The expression analysis of a number of candidates revealed microRNAs of potential importance in the innate immune response. MiR-155, a known key player in inflammation, was found expressed in both samples. Moreover, miR-664-5p, mi......R-451 and miR-15a appear as very promising candidates for microRNAs involved in response to pathogen infection. Conclusions: This is the first study revealing significant differences in composition and expression profiles of miRNAs in lungs infected with a bacterial pathogen. Our results extend......Background: MicroRNAs (miRNAs) are a class of non-protein-coding genes that play a crucial regulatory role in mammalian development and disease. Whereas a large number of miRNAs have been annotated at the structural level during the latest years, functional annotation is sparse. Actinobacillus...

  17. Correlations Between Anthropometry and Lipid Profile in Women With PCOS.

    Science.gov (United States)

    Kiranmayee, Donthu; Kavya, Kothapalli; Himabindu, Yalamanchali; Sriharibabu, Manne; Madhuri, Gadi Leela Jaya; Venu, Swargam

    2017-01-01

    Polycystic ovary syndrome (PCOS) is the most common endocrinopathy in reproductive age women and is associated with both reproductive and metabolic abnormalities. Recent studies have demonstrated an early onset of abnormal cardiovascular risk profile in women with PCOS. Abnormal lipid profile patterns are common in women with PCOS, and these abnormalities are not uniform in all populations. Anthropometry is a simple and commonly used research tool for assessing metabolic risk in women with PCOS. Therefore, this study examined the correlations between anthropometric parameters and lipid profile in women with PCOS. The objectives of the study were (1) To study the anthropometric profile of women with PCOS, (2) To examine the lipid profile pattern of these women with PCOS and (3) To see whether there exists any correlation between these anthropometric parameters and lipid profile. This observational cross-sectional study examined anthropometry and lipid profile in 86 married women with PCOS in the age group of 18-35 years and correlated them by using Pearson's correlation coefficient. More than 80% of the women with PCOS demonstrated abnormal anthropometric parameters, and in more than 70% women, lipid abnormalities such as low levels of high-density lipoprotein (HDL) cholesterol and high levels of triglycerides and low-density lipoprotein cholesterol were observed. Significant positive correlations were seen between body mass index (BMI) and triglycerides ( P ≤ 0.001) and waist circumference (WC) and triglycerides ( P ≤ 0.029). Negative correlations were observed between BMI and HDL cholesterol ( P ≤ 0.013). This study revealed that BMI and WC are the most important anthropometric parameters correlated to dyslipidemia in the south Indian women with PCOS.

  18. Searching mixed DNA profiles directly against profile databases.

    Science.gov (United States)

    Bright, Jo-Anne; Taylor, Duncan; Curran, James; Buckleton, John

    2014-03-01

    DNA databases have revolutionised forensic science. They are a powerful investigative tool as they have the potential to identify persons of interest in criminal investigations. Routinely, a DNA profile generated from a crime sample could only be searched for in a database of individuals if the stain was from single contributor (single source) or if a contributor could unambiguously be determined from a mixed DNA profile. This meant that a significant number of samples were unsuitable for database searching. The advent of continuous methods for the interpretation of DNA profiles offers an advanced way to draw inferential power from the considerable investment made in DNA databases. Using these methods, each profile on the database may be considered a possible contributor to a mixture and a likelihood ratio (LR) can be formed. Those profiles which produce a sufficiently large LR can serve as an investigative lead. In this paper empirical studies are described to determine what constitutes a large LR. We investigate the effect on a database search of complex mixed DNA profiles with contributors in equal proportions with dropout as a consideration, and also the effect of an incorrect assignment of the number of contributors to a profile. In addition, we give, as a demonstration of the method, the results using two crime samples that were previously unsuitable for database comparison. We show that effective management of the selection of samples for searching and the interpretation of the output can be highly informative. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  19. Comprehensive gene expression profiling reveals synergistic functional networks in cerebral vessels after hypertension or hypercholesterolemia.

    Directory of Open Access Journals (Sweden)

    Wei-Yi Ong

    Full Text Available Atherosclerotic stenosis of cerebral arteries or intracranial large artery disease (ICLAD is a major cause of stroke especially in Asians, Hispanics and Africans, but relatively little is known about gene expression changes in vessels at risk. This study compares comprehensive gene expression profiles in the middle cerebral artery (MCA of New Zealand White rabbits exposed to two stroke risk factors i.e. hypertension and/or hypercholesterolemia, by the 2-Kidney-1-Clip method, or dietary supplementation with cholesterol. Microarray and Ingenuity Pathway Analyses of the MCA of the hypertensive rabbits showed up-regulated genes in networks containing the node molecules: UBC (ubiquitin, P38 MAPK, ERK, NFkB, SERPINB2, MMP1 and APP (amyloid precursor protein; and down-regulated genes related to MAPK, ERK 1/2, Akt, 26 s proteasome, histone H3 and UBC. The MCA of hypercholesterolemic rabbits showed differentially expressed genes that are surprisingly, linked to almost the same node molecules as the hypertensive rabbits, despite a relatively low percentage of 'common genes' (21 and 7% between the two conditions. Up-regulated common genes were related to: UBC, SERPINB2, TNF, HNF4A (hepatocyte nuclear factor 4A and APP, and down-regulated genes, related to UBC. Increased HNF4A message and protein were verified in the aorta. Together, these findings reveal similar nodal molecules and gene pathways in cerebral vessels affected by hypertension or hypercholesterolemia, which could be a basis for synergistic action of risk factors in the pathogenesis of ICLAD.

  20. Comprehensive Gene Expression Profiling Reveals Synergistic Functional Networks in Cerebral Vessels after Hypertension or Hypercholesterolemia

    Science.gov (United States)

    Ong, Wei-Yi; Ng, Mary Pei-Ern; Loke, Sau-Yeen; Jin, Shalai; Wu, Ya-Jun; Tanaka, Kazuhiro; Wong, Peter Tsun-Hon

    2013-01-01

    Atherosclerotic stenosis of cerebral arteries or intracranial large artery disease (ICLAD) is a major cause of stroke especially in Asians, Hispanics and Africans, but relatively little is known about gene expression changes in vessels at risk. This study compares comprehensive gene expression profiles in the middle cerebral artery (MCA) of New Zealand White rabbits exposed to two stroke risk factors i.e. hypertension and/or hypercholesterolemia, by the 2-Kidney-1-Clip method, or dietary supplementation with cholesterol. Microarray and Ingenuity Pathway Analyses of the MCA of the hypertensive rabbits showed up-regulated genes in networks containing the node molecules: UBC (ubiquitin), P38 MAPK, ERK, NFkB, SERPINB2, MMP1 and APP (amyloid precursor protein); and down-regulated genes related to MAPK, ERK 1/2, Akt, 26 s proteasome, histone H3 and UBC. The MCA of hypercholesterolemic rabbits showed differentially expressed genes that are surprisingly, linked to almost the same node molecules as the hypertensive rabbits, despite a relatively low percentage of ‘common genes’ (21 and 7%) between the two conditions. Up-regulated common genes were related to: UBC, SERPINB2, TNF, HNF4A (hepatocyte nuclear factor 4A) and APP, and down-regulated genes, related to UBC. Increased HNF4A message and protein were verified in the aorta. Together, these findings reveal similar nodal molecules and gene pathways in cerebral vessels affected by hypertension or hypercholesterolemia, which could be a basis for synergistic action of risk factors in the pathogenesis of ICLAD. PMID:23874591

  1. A Click Chemistry-Based Proteomic Approach Reveals that 1,2,4-Trioxolane and Artemisinin Antimalarials Share a Common Protein Alkylation Profile.

    Science.gov (United States)

    Ismail, Hanafy M; Barton, Victoria E; Panchana, Matthew; Charoensutthivarakul, Sitthivut; Biagini, Giancarlo A; Ward, Stephen A; O'Neill, Paul M

    2016-05-23

    In spite of the recent increase in endoperoxide antimalarials under development, it remains unclear if all these chemotypes share a common mechanism of action. This is important since it will influence cross-resistance risks between the different classes. Here we investigate this proposition using novel clickable 1,2,4-trioxolane activity based protein-profiling probes (ABPPs). ABPPs with potent antimalarial activity were able to alkylate protein target(s) within the asexual erythrocytic stage of Plasmodium falciparum (3D7). Importantly, comparison of the alkylation fingerprint with that generated from an artemisinin ABPP equivalent confirms a highly conserved alkylation profile, with both endoperoxide classes targeting proteins in the glycolytic, hemoglobin degradation, antioxidant defence, protein synthesis and protein stress pathways, essential biological processes for plasmodial survival. The alkylation signatures of the two chemotypes show significant overlap (ca. 90 %) both qualitatively and semi-quantitatively, suggesting a common mechanism of action that raises concerns about potential cross-resistance liabilities.

  2. Profiles in coping: responses to sexual harassment across persons, organizations, and cultures.

    Science.gov (United States)

    Cortina, Lilia M; Wasti, S Arzu

    2005-01-01

    This study explicates the complexity of sexual harassment coping behavior among 4 diverse samples of working women: (a) working-class Hispanic Americans, (b) working-class Anglo Americans, (c) professional Turks, and (d) professional Anglo Americans. K-means cluster analysis revealed 3 common harassment coping profiles: (a) detached, (b) avoidant negotiating, and (c) support seeking. The authors then tested an integrated framework of coping profile determinants, involving social power, stressor severity, social support, and culture. Analysis of variance, chi-square, and discriminant function results identified significant determinants at each of the 4 levels of this ecological model. These findings underscore the importance of focusing on whole patterns of experience--and considering influences at the level of the individual employee and multiple levels of the surrounding context--when studying how women cope with workplace sexual harassment.

  3. Personalized Proteome Profiles of Healthy and Tumor Human Colon Organoids Reveal Both Individual Diversity and Basic Features of Colorectal Cancer.

    Science.gov (United States)

    Cristobal, Alba; van den Toorn, Henk W P; van de Wetering, Marc; Clevers, Hans; Heck, Albert J R; Mohammed, Shabaz

    2017-01-03

    Diseases at the molecular level are complex and patient dependent, necessitating development of strategies that enable precision treatment to optimize clinical outcomes. Organoid technology has recently been shown to have the potential to recapitulate the in vivo characteristics of the original individual's tissue in a three-dimensional in vitro culture system. Here, we present a quantitative mass-spectrometry-based proteomic analysis and a comparative transcriptomic analysis of human colorectal tumor and healthy organoids derived, in parallel, from seven patients. Although gene and protein signatures can be derived to distinguish the tumor organoid population from healthy organoids, our data clearly reveal that each patient possesses a distinct organoid signature at the proteomic level. We demonstrate that a personalized patient-specific organoid proteome profile can be related to the diagnosis of a patient and with future development contribute to the generation of personalized therapies. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  4. Molecular profiling of interspecific lowland rice populations derived ...

    African Journals Online (AJOL)

    STORAGESEVER

    2008-12-03

    Dec 3, 2008 ... Molecular profiling of interspecific lowland rice populations ... Both cluster and principal component analyses revealed two major groups ...... simulations. Theor ... inheritance, chromosomal location, and population dynamics.

  5. Identifying significant temporal variation in time course microarray data without replicates

    Directory of Open Access Journals (Sweden)

    Porter Weston

    2009-03-01

    Full Text Available Abstract Background An important component of time course microarray studies is the identification of genes that demonstrate significant time-dependent variation in their expression levels. Until recently, available methods for performing such significance tests required replicates of individual time points. This paper describes a replicate-free method that was developed as part of a study of the estrous cycle in the rat mammary gland in which no replicate data was collected. Results A temporal test statistic is proposed that is based on the degree to which data are smoothed when fit by a spline function. An algorithm is presented that uses this test statistic together with a false discovery rate method to identify genes whose expression profiles exhibit significant temporal variation. The algorithm is tested on simulated data, and is compared with another recently published replicate-free method. The simulated data consists both of genes with known temporal dependencies, and genes from a null distribution. The proposed algorithm identifies a larger percentage of the time-dependent genes for a given false discovery rate. Use of the algorithm in a study of the estrous cycle in the rat mammary gland resulted in the identification of genes exhibiting distinct circadian variation. These results were confirmed in follow-up laboratory experiments. Conclusion The proposed algorithm provides a new approach for identifying expression profiles with significant temporal variation without relying on replicates. When compared with a recently published algorithm on simulated data, the proposed algorithm appears to identify a larger percentage of time-dependent genes for a given false discovery rate. The development of the algorithm was instrumental in revealing the presence of circadian variation in the virgin rat mammary gland during the estrous cycle.

  6. Microarray Glycan Profiling Reveals Algal Fucoidan Epitopes in Diverse Marine Metazoans

    Directory of Open Access Journals (Sweden)

    Armando A. Salmeán

    2017-09-01

    Full Text Available Despite the biological importance and pharmacological potential of glycans from marine organisms, there are many unanswered questions regarding their distribution, function, and evolution. Here we describe microarray-based glycan profiling of a diverse selection of marine animals using antibodies raised against fucoidan isolated from a brown alga. We demonstrate the presence of two fucoidan epitopes in six animals belonging to three phyla including Porifera, Molusca, and Chordata. We studied the spatial distribution of these epitopes in Cliona celata (“boring sponge” and identified their restricted localization on the surface of internal chambers. Our results show the potential of high-throughput screening and probes commonly used in plant and algal cell wall biology to study the diversity and distribution of glycan structures in metazoans.

  7. Shotgun microbial profiling of fossil remains

    DEFF Research Database (Denmark)

    Der Sarkissian, Clio; Ermini, Luca; Jónsson, Hákon

    2014-01-01

    the specimen of interest, but instead reflect environmental organisms that colonized the specimen after death. Here, we characterize the microbial diversity recovered from seven c. 200- to 13 000-year-old horse bones collected from northern Siberia. We use a robust, taxonomy-based assignment approach...... to identify the microorganisms present in ancient DNA extracts and quantify their relative abundance. Our results suggest that molecular preservation niches exist within ancient samples that can potentially be used to characterize the environments from which the remains are recovered. In addition, microbial...... community profiling of the seven specimens revealed site-specific environmental signatures. These microbial communities appear to comprise mainly organisms that colonized the fossils recently. Our approach significantly extends the amount of useful data that can be recovered from ancient specimens using...

  8. Criminal profiling as expert witness evidence: The implications of the profiler validity research.

    Science.gov (United States)

    Kocsis, Richard N; Palermo, George B

    The use and development of the investigative tool colloquially known as criminal profiling has steadily increased over the past five decades throughout the world. Coupled with this growth has been a diversification in the suggested range of applications for this technique. Possibly the most notable of these has been the attempted transition of the technique from a tool intended to assist police investigations into a form of expert witness evidence admissible in legal proceedings. Whilst case law in various jurisdictions has considered with mutual disinclination the evidentiary admissibility of criminal profiling, a disjunction has evolved between these judicial examinations and the scientifically vetted research testing the accuracy (i.e., validity) of the technique. This article offers an analysis of the research directly testing the validity of the criminal profiling technique and the extant legal principles considering its evidentiary admissibility. This analysis reveals that research findings concerning the validity of criminal profiling are surprisingly compatible with the extant legal principles. The overall conclusion is that a discrete form of crime behavioural analysis is supported by the profiler validity research and could be regarded as potentially admissible expert witness evidence. Finally, a number of theoretical connections are also identified concerning the skills and qualifications of individuals who may feasibly provide such expert testimony. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. ETMB-RBF: discrimination of metal-binding sites in electron transporters based on RBF networks with PSSM profiles and significant amino acid pairs.

    Science.gov (United States)

    Ou, Yu-Yen; Chen, Shu-An; Wu, Sheng-Cheng

    2013-01-01

    Cellular respiration is the process by which cells obtain energy from glucose and is a very important biological process in living cell. As cells do cellular respiration, they need a pathway to store and transport electrons, the electron transport chain. The function of the electron transport chain is to produce a trans-membrane proton electrochemical gradient as a result of oxidation-reduction reactions. In these oxidation-reduction reactions in electron transport chains, metal ions play very important role as electron donor and acceptor. For example, Fe ions are in complex I and complex II, and Cu ions are in complex IV. Therefore, to identify metal-binding sites in electron transporters is an important issue in helping biologists better understand the workings of the electron transport chain. We propose a method based on Position Specific Scoring Matrix (PSSM) profiles and significant amino acid pairs to identify metal-binding residues in electron transport proteins. We have selected a non-redundant set of 55 metal-binding electron transport proteins as our dataset. The proposed method can predict metal-binding sites in electron transport proteins with an average 10-fold cross-validation accuracy of 93.2% and 93.1% for metal-binding cysteine and histidine, respectively. Compared with the general metal-binding predictor from A. Passerini et al., the proposed method can improve over 9% of sensitivity, and 14% specificity on the independent dataset in identifying metal-binding cysteines. The proposed method can also improve almost 76% sensitivity with same specificity in metal-binding histidine, and MCC is also improved from 0.28 to 0.88. We have developed a novel approach based on PSSM profiles and significant amino acid pairs for identifying metal-binding sites from electron transport proteins. The proposed approach achieved a significant improvement with independent test set of metal-binding electron transport proteins.

  10. Profiling the Mobile Customer

    DEFF Research Database (Denmark)

    Jessen, Pernille Wegener; King, Nancy J.

    2010-01-01

    of significant concerns about privacy and data protection. This second article in a two part series on "Profiling the Mobile Customer" explores how to best protect consumers' privacy and personal data through available mechanisms that include industry self-regulation, privacy-enhancing technologies...... discusses the current limitations of using technology to protect consumers from privacy abuses related to profiling. Concluding that industry self-regulation and available privacy-enhancing technologies will not be adequate to close important privacy gaps related to consumer profiling without legislative...

  11. WISC-III cognitive profiles in children with developmental dyslexia: specific cognitive disability and diagnostic utility.

    Science.gov (United States)

    Moura, Octávio; Simões, Mário R; Pereira, Marcelino

    2014-02-01

    This study analysed the usefulness of the Wechsler Intelligence Scale for Children-Third Edition in identifying specific cognitive impairments that are linked to developmental dyslexia (DD) and the diagnostic utility of the most common profiles in a sample of 100 Portuguese children (50 dyslexic and 50 normal readers) between the ages of 8 and 12 years. Children with DD exhibited significantly lower scores in the Verbal Comprehension Index (except the Vocabulary subtest), Freedom from Distractibility Index (FDI) and Processing Speed Index subtests, with larger effect sizes than normal readers in Information, Arithmetic and Digit Span. The Verbal-Performance IQs discrepancies, Bannatyne pattern and the presence of FDI; Arithmetic, Coding, Information and Digit Span subtests (ACID) and Symbol Search, Coding, Arithmetic and Digit Span subtests (SCAD) profiles (full or partial) in the lowest subtests revealed a low diagnostic utility. However, the receiver operating characteristic curve and the optimal cut-off score analyses of the composite ACID; FDI and SCAD profiles scores showed moderate accuracy in correctly discriminating dyslexic readers from normal ones. These results suggested that in the context of a comprehensive assessment, the Wechsler Intelligence Scale for Children-Third Edition provides some useful information about the presence of specific cognitive disabilities in DD. Practitioner Points. Children with developmental dyslexia revealed significant deficits in the Wechsler Intelligence Scale for Children-Third Edition subtests that rely on verbal abilities, processing speed and working memory. The composite Arithmetic, Coding, Information and Digit Span subtests (ACID); Freedom from Distractibility Index and Symbol Search, Coding, Arithmetic and Digit Span subtests (SCAD) profile scores showed moderate accuracy in correctly discriminating dyslexics from normal readers. Wechsler Intelligence Scale for Children-Third Edition may provide some useful

  12. Protein expression profiling of inflammatory mediators in human temporal lobe epilepsy reveals co-activation of multiple chemokines and cytokines

    Directory of Open Access Journals (Sweden)

    Kan Anne A

    2012-08-01

    Full Text Available Abstract Mesial temporal lobe epilepsy (mTLE is a chronic and often treatment-refractory brain disorder characterized by recurrent seizures originating from the hippocampus. The pathogenic mechanisms underlying mTLE remain largely unknown. Recent clinical and experimental evidence supports a role of various inflammatory mediators in mTLE. Here, we performed protein expression profiling of 40 inflammatory mediators in surgical resection material from mTLE patients with and without hippocampal sclerosis, and autopsy controls using a multiplex bead-based immunoassay. In mTLE patients we identified 21 upregulated inflammatory mediators, including 10 cytokines and 7 chemokines. Many of these upregulated mediators have not previously been implicated in mTLE (for example, CCL22, IL-7 and IL-25. Comparing the three patient groups, two main hippocampal expression patterns could be distinguished, pattern I (for example, IL-10 and IL-25 showing increased expression in mTLE + HS patients compared to mTLE-HS and controls, and pattern II (for example, CCL4 and IL-7 showing increased expression in both mTLE groups compared to controls. Upregulation of a subset of inflammatory mediators (for example, IL-25 and IL-7 could not only be detected in the hippocampus of mTLE patients, but also in the neocortex. Principle component analysis was used to cluster the inflammatory mediators into several components. Follow-up analyses of the identified components revealed that the three patient groups could be discriminated based on their unique expression profiles. Immunocytochemistry showed that IL-25 IR (pattern I and CCL4 IR (pattern II were localized in astrocytes and microglia, whereas IL-25 IR was also detected in neurons. Our data shows co-activation of multiple inflammatory mediators in hippocampus and neocortex of mTLE patients, indicating activation of multiple pro- and anti-epileptogenic immune pathways in this disease.

  13. Phase-I monitoring of standard deviations in multistage linear profiles

    Science.gov (United States)

    Kalaei, Mahdiyeh; Soleimani, Paria; Niaki, Seyed Taghi Akhavan; Atashgar, Karim

    2018-03-01

    In most modern manufacturing systems, products are often the output of some multistage processes. In these processes, the stages are dependent on each other, where the output quality of each stage depends also on the output quality of the previous stages. This property is called the cascade property. Although there are many studies in multistage process monitoring, there are fewer works on profile monitoring in multistage processes, especially on the variability monitoring of a multistage profile in Phase-I for which no research is found in the literature. In this paper, a new methodology is proposed to monitor the standard deviation involved in a simple linear profile designed in Phase I to monitor multistage processes with the cascade property. To this aim, an autoregressive correlation model between the stages is considered first. Then, the effect of the cascade property on the performances of three types of T 2 control charts in Phase I with shifts in standard deviation is investigated. As we show that this effect is significant, a U statistic is next used to remove the cascade effect, based on which the investigated control charts are modified. Simulation studies reveal good performances of the modified control charts.

  14. Family Profiles of Cohesion and Parenting Practices and Latino Youth Adjustment.

    Science.gov (United States)

    Bámaca-Colbert, Mayra Y; Gonzales-Backen, Melinda; Henry, Carolyn S; Kim, Peter S Y; Roblyer, Martha Zapata; Plunkett, Scott W; Sands, Tovah

    2017-08-10

    Using a sample of 279 (52% female) Latino youth in 9th grade (M = 14.57, SD = .56), we examined profiles of family cohesion and parenting practices and their relation to youth adjustment. The results of latent profile analyses revealed four family profiles: Engaged, Supportive, Intrusive, and Disengaged. Latino youth in the Supportive family profile showed most positive adjustment (highest self-esteem and lowest depressive symptoms), followed by youth in the Engaged family profile. Youth in the Intrusive and Disengaged profiles showed the lowest levels of positive adjustment. The findings contribute to the current literature on family dynamics, family profiles, and youth psychological adjustment within specific ethnic groups. © 2017 Family Process Institute.

  15. Motivational profiles of slovenian high school students and their academic performance outcomes.

    Science.gov (United States)

    Vrtačnik, Margareta; Juriševič, Mojca; Savec, Vesna Ferk

    2010-09-01

    Self-determination theory defines motivation as a multidimensional concept, with autonomous and controlled motivation as central factors of broader distinctions. Previous research has proven that academic achievements are positively correlated with autonomous motivation. Students from 10 Slovenian grammar schools were involved in empirical study, in which a cluster analysis revealed two motivational profiles: a low quantity motivation group (low controlled and autonomous motivation) and a good quality motivation group (high autonomous and low or average controlled motivation). Statistically significant differences between the two identified motivational profiles were found for students' general as well as chemistry performance in three grades of schooling. Furthermore, a good quality motivation group is also more in favour of autonomy-supportive teaching methods used in chemistry classes. Examination of students' opinions about important chemistry topics, and on the other hand, unimportant ones, and not connected with life, reveals that the basic reason for distinction might lie in the chemistry teacher's approach used while presenting these topics. Some chemistry teachers are not using an autonomy-supportive way of teaching which would contribute to better teaching outcomes; therefore a need for further research on Slovenian chemistry teachers' motivation and their teaching approaches was recognized.

  16. Gene Expression Profiling Reveals Potential Players of Left-Right Asymmetry in Female Chicken Gonads.

    Science.gov (United States)

    Wan, Zhiyi; Lu, Yanan; Rui, Lei; Yu, Xiaoxue; Yang, Fang; Tu, Chengfang; Li, Zandong

    2017-06-20

    Most female birds develop only a left ovary, whereas males develop bilateral testes. The mechanism underlying this process is still not completely understood. Here, we provide a comprehensive transcriptional analysis of female chicken gonads and identify novel candidate side-biased genes. RNA-Seq analysis was carried out on total RNA harvested from the left and right gonads on embryonic day 6 (E6), E12, and post-hatching day 1 (D1). By comparing the gene expression profiles between the left and right gonads, 347 differentially expressed genes (DEGs) were obtained on E6, 3730 were obtained on E12, and 2787 were obtained on D1. Side-specific genes were primarily derived from the autosome rather than the sex chromosome. Gene ontology and pathway analysis showed that the DEGs were most enriched in the Piwi-interactiing RNA (piRNA) metabolic process, germ plasm, chromatoid body, P granule, neuroactive ligand-receptor interaction, microbial metabolism in diverse environments, and methane metabolism. A total of 111 DEGs, five gene ontology (GO) terms, and three pathways were significantly different between the left and right gonads among all the development stages. We also present the gene number and the percentage within eight development-dependent expression patterns of DEGs in the left and right gonads of female chicken.

  17. Transcriptional profiling in response to terminal drought stress reveals differential responses along the wheat genome

    Directory of Open Access Journals (Sweden)

    Ferrari Francesco

    2009-06-01

    Full Text Available Abstract Background Water stress during grain filling has a marked effect on grain yield, leading to a reduced endosperm cell number and thus sink capacity to accumulate dry matter. The bread wheat cultivar Chinese Spring (CS, a Chinese Spring terminal deletion line (CS_5AL-10 and the durum wheat cultivar Creso were subjected to transcriptional profiling after exposure to mild and severe drought stress at the grain filling stage to find evidences of differential stress responses associated to different wheat genome regions. Results The transcriptome analysis of Creso, CS and its deletion line revealed 8,552 non redundant probe sets with different expression levels, mainly due to the comparisons between the two species. The drought treatments modified the expression of 3,056 probe sets. Besides a set of genes showing a similar drought response in Creso and CS, cluster analysis revealed several drought response features that can be associated to the different genomic structure of Creso, CS and CS_5AL-10. Some drought-related genes were expressed at lower level (or not expressed in Creso (which lacks the D genome or in the CS_5AL-10 deletion line compared to CS. The chromosome location of a set of these genes was confirmed by PCR-based mapping on the D genome (or the 5AL-10 region. Many clusters were characterized by different level of expression in Creso, CS and CS_AL-10, suggesting that the different genome organization of the three genotypes may affect plant adaptation to stress. Clusters with similar expression trend were grouped and functional classified to mine the biological mean of their activation or repression. Genes involved in ABA, proline, glycine-betaine and sorbitol pathways were found up-regulated by drought stress. Furthermore, the enhanced expression of a set of transposons and retrotransposons was detected in CS_5AL-10. Conclusion Bread and durum wheat genotypes were characterized by a different physiological reaction to water

  18. Microenvironment alters epigenetic and gene expression profiles in Swarm rat chondrosarcoma tumors

    International Nuclear Information System (INIS)

    Hamm, Christopher A; Wang, Deli; Malchenko, Sergey; Fatima Bonaldo, Maria de; Casavant, Thomas L; Hendrix, Mary JC; Soares, Marcelo B; Stevens, Jeff W; Xie, Hehuang; Vanin, Elio F; Morcuende, Jose A; Abdulkawy, Hakeem; Seftor, Elisabeth A; Sredni, Simone T; Bischof, Jared M

    2010-01-01

    Chondrosarcomas are malignant cartilage tumors that do not respond to traditional chemotherapy or radiation. The 5-year survival rate of histologic grade III chondrosarcoma is less than 30%. An animal model of chondrosarcoma has been established - namely, the Swarm Rat Chondrosarcoma (SRC) - and shown to resemble the human disease. Previous studies with this model revealed that tumor microenvironment could significantly influence chondrosarcoma malignancy. To examine the effect of the microenvironment, SRC tumors were initiated at different transplantation sites. Pyrosequencing assays were utilized to assess the DNA methylation of the tumors, and SAGE libraries were constructed and sequenced to determine the gene expression profiles of the tumors. Based on the gene expression analysis, subsequent functional assays were designed to determine the relevancy of the specific genes in the development and progression of the SRC. The site of transplantation had a significant impact on the epigenetic and gene expression profiles of SRC tumors. Our analyses revealed that SRC tumors were hypomethylated compared to control tissue, and that tumors at each transplantation site had a unique expression profile. Subsequent functional analysis of differentially expressed genes, albeit preliminary, provided some insight into the role that thymosin-β4, c-fos, and CTGF may play in chondrosarcoma development and progression. This report describes the first global molecular characterization of the SRC model, and it demonstrates that the tumor microenvironment can induce epigenetic alterations and changes in gene expression in the SRC tumors. We documented changes in gene expression that accompany changes in tumor phenotype, and these gene expression changes provide insight into the pathways that may play a role in the development and progression of chondrosarcoma. Furthermore, specific functional analysis indicates that thymosin-β4 may have a role in chondrosarcoma metastasis

  19. Microenvironment alters epigenetic and gene expression profiles in Swarm rat chondrosarcoma tumors

    Directory of Open Access Journals (Sweden)

    Hamm Christopher A

    2010-09-01

    Full Text Available Abstract Background Chondrosarcomas are malignant cartilage tumors that do not respond to traditional chemotherapy or radiation. The 5-year survival rate of histologic grade III chondrosarcoma is less than 30%. An animal model of chondrosarcoma has been established - namely, the Swarm Rat Chondrosarcoma (SRC - and shown to resemble the human disease. Previous studies with this model revealed that tumor microenvironment could significantly influence chondrosarcoma malignancy. Methods To examine the effect of the microenvironment, SRC tumors were initiated at different transplantation sites. Pyrosequencing assays were utilized to assess the DNA methylation of the tumors, and SAGE libraries were constructed and sequenced to determine the gene expression profiles of the tumors. Based on the gene expression analysis, subsequent functional assays were designed to determine the relevancy of the specific genes in the development and progression of the SRC. Results The site of transplantation had a significant impact on the epigenetic and gene expression profiles of SRC tumors. Our analyses revealed that SRC tumors were hypomethylated compared to control tissue, and that tumors at each transplantation site had a unique expression profile. Subsequent functional analysis of differentially expressed genes, albeit preliminary, provided some insight into the role that thymosin-β4, c-fos, and CTGF may play in chondrosarcoma development and progression. Conclusion This report describes the first global molecular characterization of the SRC model, and it demonstrates that the tumor microenvironment can induce epigenetic alterations and changes in gene expression in the SRC tumors. We documented changes in gene expression that accompany changes in tumor phenotype, and these gene expression changes provide insight into the pathways that may play a role in the development and progression of chondrosarcoma. Furthermore, specific functional analysis indicates that

  20. ICRF power-deposition profiles, heating and confinement of monster sawtooth and peaked-density profile discharges in JET

    International Nuclear Information System (INIS)

    Bhatnagar, V.P.; Taroni, A.; Ellis, J.J.; Jacquinot, J.; Start, D.F.H.

    1989-01-01

    The ion cyclotron resonance heating of monster sawtooth (period greater than the energy confinement time) and pellet-fueled peaked-density profiles in limiter discharges of JET Tokamak are studied. The monster sawtooth is a characteristic JET regime which is related to fast ions generated during the minority ion heating. In the ICRF heating of peaked-density profile discharges, we find typically the T i0 is higher roughly by a factor of 2 and T e0 roughly by 35% at a fixed P TOT /n e0 when compared to non-peaked profile cases. Here, T e0 and T i0 are central electron and ion temperatures, respectively, n e0 is the central electron density and P TOT is the total input power. The ion heating is improved in the pellet case, in part, due to a higher collisionality between the background ions and the energetic minority, but more significantly by a reduction of local ion energy transport in the central region. The transport-code simulation of these discharges reveals that there is a reduction of both χ e and χ i in the central region of the plasma in the ICRF heated peaked-profile discharges where χ e and χ i are the electron and ion heat conductivities, respectively. The improvement of confinement is not explained quantitatively by any of the existing η i -driven turbulence theories as the n i parameter (η i = d ln T i /d ln n i where T i is the ion temperature and n i is the ion density), instead of dropping below the critical value, remains above it for most of the duration of the improved confinement phase. The physical mechanism(s) that plays a role in this improvement is not yet clear. (author)

  1. RNA profiles of porcine embryos during genome activation reveal complex metabolic switch sensitive to in vitro conditions

    DEFF Research Database (Denmark)

    Østrup, Olga; Olbricht, Gayla; Østrup, Esben

    2013-01-01

    produced in vitro. Overall, our data are in good accordance with previously published, genome-wide profiling data in other species. Moreover, comparison with mouse and human embryos showed striking overlap in functional annotation of transcripts during the EGA, suggesting conserved basic mechanisms...... a handful of reports characterize changing transcriptome profiles and resulting metabolic changes in cleavage stage embryos. The aims of the current study were to investigate RNA profiles of in vivo developed (ivv) and in vitro produced (ivt) porcine embryos before (2-cell stage) and after (late 4-cell...... from oocyte and are imposed either before oocyte aspiration or during in vitro maturation. IVT embryos have altered content of apoptotic factors, cell cycle regulation factors and spindle components, and transcription factors, which all may contribute to reduced developmental competence of embryos...

  2. A reliability index for assessment of crack profile reconstructed from ECT signals using a neural-network approach

    International Nuclear Information System (INIS)

    Yusa, Noritaka; Chen, Zhenmao; Miya, Kenzo; Cheng, Weiying

    2002-01-01

    This paper proposes a reliability parameter to enhance an version scheme developed by authors. The scheme is based upon an artificial neural network that simulates mapping between eddy current signals and crack profiles. One of the biggest advantages of the scheme is that it can deal with conductive cracks, which is necessary to reconstruct natural cracks. However, it has one significant disadvantage: the reliability of reconstructed profiles was unknown. The parameter provides an index for assessment of the crack profile and overcomes this disadvantage. After the parameter is validated by reconstruction of simulated cracks, it is applied to reconstruction of natural cracks that occurred in steam generator tubes of a pressurized water reactor. It is revealed that the parameter is applicable to not only simulated cracks but also natural ones. (author)

  3. Metabolite Profiling of Red Sea Corals

    KAUST Repository

    Ortega, Jovhana Alejandra

    2016-12-01

    Looking at the metabolite profile of an organism provides insights into the metabolomic state of a cell and hence also into pathways employed. Little is known about the metabolites produced by corals and their algal symbionts. In particular, corals from the central Red Sea are understudied, but interesting study objects, as they live in one of the warmest and most saline environments and can provide clues as to the adjustment of corals to environmental change. In this study, we applied gas chromatography – mass spectrometry (GC–MS) metabolite profiling to analyze the metabolic profile of four coral species and their associated symbionts: Fungia granulosa, Acropora hemprichii, Porites lutea, and Pocillopora verrucosa. We identified and quantified 102 compounds among primary and secondary metabolites across all samples. F. granulosa and its symbiont showed a total of 59 metabolites which were similar to the 51 displayed by P. verrucosa. P. lutea and A. hemprichii both harbored 40 compounds in conjunction with their respective isolated algae. Comparing across species, 28 metabolites were exclusively present in algae, while 38 were exclusive to corals. A principal component and cluster analyses revealed that metabolite profiles clustered between corals and algae, but each species harbored a distinct catalog of metabolites. The major classes of compounds were carbohydrates and amino acids. Taken together, this study provides a first description of metabolites of Red Sea corals and their associated symbionts. As expected, the metabolites of coral hosts differ from their algal symbionts, but each host and algal species harbor a unique set of metabolites. This corroborates that host-symbiont species pairs display a fine-tuned complementary metabolism that provide insights into the specific nature of the symbiosis. Our analysis also revealed aquatic pollutants, which suggests that metabolite profiling might be used for monitoring pollution levels and assessing

  4. Multidimensional profiles of health locus of control in Hispanic Americans.

    Science.gov (United States)

    Champagne, Brian R; Fox, Rina S; Mills, Sarah D; Sadler, Georgia Robins; Malcarne, Vanessa L

    2016-10-01

    Latent profile analysis identified health locus of control profiles among 436 Hispanic Americans who completed the Multidimensional Health Locus of Control scales. Results revealed four profiles: Internally Oriented-Weak, -Moderate, -Strong, and Externally Oriented. The profile groups were compared on sociocultural and demographic characteristics, health beliefs and behaviors, and physical and mental health outcomes. The Internally Oriented-Strong group had less cancer fatalism, religiosity, and equity health attributions, and more alcohol consumption than the other three groups; the Externally Oriented group had stronger equity health attributions and less alcohol consumption. Deriving multidimensional health locus of control profiles through latent profile analysis allows examination of the relationships of health locus of control subtypes to health variables. © The Author(s) 2015.

  5. Understanding Biases in Ribosome Profiling Experiments Reveals Signatures of Translation Dynamics in Yeast.

    Directory of Open Access Journals (Sweden)

    Jeffrey A Hussmann

    2015-12-01

    Full Text Available Ribosome profiling produces snapshots of the locations of actively translating ribosomes on messenger RNAs. These snapshots can be used to make inferences about translation dynamics. Recent ribosome profiling studies in yeast, however, have reached contradictory conclusions regarding the average translation rate of each codon. Some experiments have used cycloheximide (CHX to stabilize ribosomes before measuring their positions, and these studies all counterintuitively report a weak negative correlation between the translation rate of a codon and the abundance of its cognate tRNA. In contrast, some experiments performed without CHX report strong positive correlations. To explain this contradiction, we identify unexpected patterns in ribosome density downstream of each type of codon in experiments that use CHX. These patterns are evidence that elongation continues to occur in the presence of CHX but with dramatically altered codon-specific elongation rates. The measured positions of ribosomes in these experiments therefore do not reflect the amounts of time ribosomes spend at each position in vivo. These results suggest that conclusions from experiments in yeast using CHX may need reexamination. In particular, we show that in all such experiments, codons decoded by less abundant tRNAs were in fact being translated more slowly before the addition of CHX disrupted these dynamics.

  6. MicroRNA profiling reveals dysregulated microRNAs and their target gene regulatory networks in cemento-ossifying fibroma.

    Science.gov (United States)

    Pereira, Thaís Dos Santos Fontes; Brito, João Artur Ricieri; Guimarães, André Luiz Sena; Gomes, Carolina Cavaliéri; de Lacerda, Júlio Cesar Tanos; de Castro, Wagner Henriques; Coimbra, Roney Santos; Diniz, Marina Gonçalves; Gomez, Ricardo Santiago

    2018-01-01

    Cemento-ossifying fibroma (COF) is a benign fibro-osseous neoplasm of uncertain pathogenesis, and its treatment results in morbidity. MicroRNAs (miRNA) are small non-coding RNAs that regulate gene expression and may represent therapeutic targets. The purpose of the study was to generate a comprehensive miRNA profile of COF compared to normal bone. Additionally, the most relevant pathways and target genes of differentially expressed miRNA were investigated by in silico analysis. Nine COF and ten normal bone samples were included in the study. miRNA profiling was carried out by using TaqMan® OpenArray® Human microRNA panel containing 754 validated human miRNAs. We identified the most relevant miRNAs target genes through the leader gene approach, using STRING and Cytoscape software. Pathways enrichment analysis was performed using DIANA-miRPath. Eleven miRNAs were downregulated (hsa-miR-95-3p, hsa-miR-141-3p, hsa-miR-205-5p, hsa-miR-223-3p, hsa-miR-31-5p, hsa-miR-944, hsa-miR-200b-3p, hsa-miR-135b-5p, hsa-miR-31-3p, hsa-miR-223-5p and hsa-miR-200c-3p), and five were upregulated (hsa-miR-181a-5p, hsa-miR-181c-5p, hsa-miR-149-5p, hsa-miR-138-5p and hsa-miR-199a-3p) in COF compared to normal bone. Eighteen common target genes were predicted, and the leader genes approach identified the following genes involved in human COF: EZH2, XIAP, MET and TGFBR1. According to the biology of bone and COF, the most relevant KEGG pathways revealed by enrichment analysis were proteoglycans in cancer, miRNAs in cancer, pathways in cancer, p53-, PI3K-Akt-, FoxO- and TGF-beta signalling pathways, which were previously found to be differentially regulated in bone neoplasms, odontogenic tumours and osteogenesis. miRNA dysregulation occurs in COF, and EZH2, XIAP, MET and TGFBR1 are potential targets for functional analysis validation. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. Metabolomic Profiling as a Possible Reverse Engineering Tool for Estimating Processing Conditions of Dry-Cured Hams.

    Science.gov (United States)

    Sugimoto, Masahiro; Obiya, Shinichi; Kaneko, Miku; Enomoto, Ayame; Honma, Mayu; Wakayama, Masataka; Soga, Tomoyoshi; Tomita, Masaru

    2017-01-18

    Dry-cured hams are popular among consumers. To increase the attractiveness of the product, objective analytical methods and algorithms to evaluate the relationship between observable properties and consumer acceptability are required. In this study, metabolomics, which is used for quantitative profiling of hundreds of small molecules, was applied to 12 kinds of dry-cured hams from Japan and Europe. In total, 203 charged metabolites, including amino acids, organic acids, nucleotides, and peptides, were successfully identified and quantified. Metabolite profiles were compared for the samples with different countries of origin and processing methods (e.g., smoking or use of a starter culture). Principal component analysis of the metabolite profiles with sensory properties revealed significant correlations for redness, homogeneity, and fat whiteness. This approach could be used to design new ham products by objective evaluation of various features.

  8. Ayurvedic Profiling of Alzheimer's Disease.

    Science.gov (United States)

    Bredesen, Dale E; Rao, Rammohan V

    2017-05-01

    Alzheimer's disease (AD) is an age-associated, progressive neurodegenerative disease that is characterized by severe memory loss, personality changes, and an overall decline in cognitive function. The cause of AD is not yet completely defined and efforts to find a cure for it have so far been disappointing. AD is one of the most significant health care problems nationally and globally. Recently, we described a personalized therapeutic approach called metabolic enhancement for neurodegeneration (MEND) that successfully reversed the cognitive decline in patients with early AD. The magnitude of the improvement was exceptional, providing testimony to the fact that a personalized and programmatic approach to cognitive decline is highly effective. Ayurveda is a personalized system of traditional medicine native to India and the Indian subcontinent. Although a direct reference to AD in the ancient Ayurvedic literature is missing, concepts including forgetfulness, memory loss, and brain cell loss have been described. Using the clinical information and the metabolic profiling of AD individuals we recently reported using the MEND program, we now describe in this commentary, 3 subtypes of AD based on the Ayurvedic interpretation. Ayurvedic profiling of patients with AD reveals 3 readily distinguishable subtypes, namely Vata, Pitta, and Krimi, which will prove useful in patients with cognitive decline and those at risk for such decline from the standpoint of specific subtype-based Ayurvedic intervention.

  9. Significant effect of topographic normalization of airborne LiDAR data on the retrieval of plant area index profile in mountainous forests

    Science.gov (United States)

    Liu, Jing; Skidmore, Andrew K.; Heurich, Marco; Wang, Tiejun

    2017-10-01

    As an important metric for describing vertical forest structure, the plant area index (PAI) profile is used for many applications including biomass estimation and wildlife habitat assessment. PAI profiles can be estimated with the vertically resolved gap fraction from airborne LiDAR data. Most research utilizes a height normalization algorithm to retrieve local or relative height by assuming the terrain to be flat. However, for many forests this assumption is not valid. In this research, the effect of topographic normalization of airborne LiDAR data on the retrieval of PAI profile was studied in a mountainous forest area in Germany. Results show that, although individual tree height may be retained after topographic normalization, the spatial arrangement of trees is changed. Specifically, topographic normalization vertically condenses and distorts the PAI profile, which consequently alters the distribution pattern of plant area density in space. This effect becomes more evident as the slope increases. Furthermore, topographic normalization may also undermine the complexity (i.e., canopy layer number and entropy) of the PAI profile. The decrease in PAI profile complexity is not solely determined by local topography, but is determined by the interaction between local topography and the spatial distribution of each tree. This research demonstrates that when calculating the PAI profile from airborne LiDAR data, local topography needs to be taken into account. We therefore suggest that for ecological applications, such as vertical forest structure analysis and modeling of biodiversity, topographic normalization should not be applied in non-flat areas when using LiDAR data.

  10. Profiling metals in Cordyceps sinensis by using inductively coupled plasma mass spectrometry.

    Science.gov (United States)

    Wei, Xin; Hu, Hankun; Zheng, Baogeng; Arslan, Zikri; Huang, Hung-Chung; Mao, Weidong; Liu, Yi-Ming

    2017-01-28

    Cordyceps sinensis ( C. sinensis ) is a natural product that has diverse nutritional and medicinal values. Since the availability of natural C. sinensis becomes limited its authentication and quality control is of high significance. Herein we report on profiling of metals in C. sinensis by using inductively coupled plasma mass spectrometry (ICP-MS). The analysis reveals that C. sinensis contains a wide array of essential elements, including P, Mg, Zn, Cu, Fe, etc. Toxic metals detected are Cd, Pb, and As. In all five samples analyzed Pb contents are below 2.0 ppm. Arsenic level in C. sinensis caterpillar is significantly higher than that in its mycelium and varies from 3.0 to 32 ppm likely due to soil contamination. It's for the first time demonstrated in this work that clustering analysis on the proposed metal profiles consisting of 24 elements is very useful to identify "abnormal" C. sinensis samples, thus adding another dimension to the effective means for authentication and quality assessment of this highly demanded previous natural product.

  11. Translational profiling in childhood acute lymphoblastic leukemia: no evidence for glucocorticoid regulation of mRNA translation.

    Science.gov (United States)

    Aneichyk, Tatsiana; Bindreither, Daniel; Mantinger, Christine; Grazio, Daniela; Goetsch, Katrin; Kofler, Reinhard; Rainer, Johannes

    2013-12-01

    Glucocorticoids (GCs) are natural stress induced steroid hormones causing cell cycle arrest and cell death in lymphoid tissues. Therefore they are the central component in the treatment of lymphoid malignancies, in particular childhood acute lymphoblastic leukemia (chALL). GCs act mainly via regulating gene transcription, which has been intensively studied by us and others. GC control of mRNA translation has also been reported but has never been assessed systematically. In this study we investigate the effect of GCs on mRNA translation on a genome-wide scale. Childhood T- (CCRF-CEM) and precursor B-ALL (NALM6) cells were exposed to GCs and subjected to "translational profiling", a technique combining sucrose-gradient fractionation followed by Affymetrix Exon microarray analysis of mRNA from different fractions, to assess the translational efficiency of the expressed genes. Analysis of GC regulation in ribosome-bound fractions versus transcriptional regulation revealed no significant differences, i.e., GC did not entail a significant shift between ribosomal bound and unbound mRNAs. In the present study we analyzed for the first time possible effects of GC on the translational efficiency of expressed genes in two chALL model systems employing whole genome polysome profiling. Our results did not reveal significant differences in translational efficiency of expressed genes thereby arguing against a potential widespread regulatory effect of GCs on translation at least in the investigated in vitro systems.

  12. 77 FR 34121 - Culturally Significant Objects Imported for Exhibition Determinations: “Revealing the African...

    Science.gov (United States)

    2012-06-08

    ... exhibition ``Revealing the African Presence in Renaissance Europe'' imported from abroad for temporary... exhibit objects at The Walters Art Museum, Baltimore, MD, from on or about October 14, 2012, until on or about January 21, 2013; at the Princeton University Art Museum, Princeton, NJ, from on or about February...

  13. High throughput analysis reveals dissociable gene expression profiles in two independent neural systems involved in the regulation of social behavior

    Directory of Open Access Journals (Sweden)

    Stevenson Tyler J

    2012-10-01

    Full Text Available Abstract Background Production of contextually appropriate social behaviors involves integrated activity across many brain regions. Many songbird species produce complex vocalizations called ‘songs’ that serve to attract potential mates, defend territories, and/or maintain flock cohesion. There are a series of discrete interconnect brain regions that are essential for the successful production of song. The probability and intensity of singing behavior is influenced by the reproductive state. The objectives of this study were to examine the broad changes in gene expression in brain regions that control song production with a brain region that governs the reproductive state. Results We show using microarray cDNA analysis that two discrete brain systems that are both involved in governing singing behavior show markedly different gene expression profiles. We found that cortical and basal ganglia-like brain regions that control the socio-motor production of song in birds exhibit a categorical switch in gene expression that was dependent on their reproductive state. This pattern is in stark contrast to the pattern of expression observed in a hypothalamic brain region that governs the neuroendocrine control of reproduction. Subsequent gene ontology analysis revealed marked variation in the functional categories of active genes dependent on reproductive state and anatomical localization. HVC, one cortical-like structure, displayed significant gene expression changes associated with microtubule and neurofilament cytoskeleton organization, MAP kinase activity, and steroid hormone receptor complex activity. The transitions observed in the preoptic area, a nucleus that governs the motivation to engage in singing, exhibited variation in functional categories that included thyroid hormone receptor activity, epigenetic and angiogenetic processes. Conclusions These findings highlight the importance of considering the temporal patterns of gene expression

  14. GRAPHIC COMPETENCE AS A COMPONENT OF TRAINING FUTURE ENGINEERING TEACHERS OF COMPUTER PROFILE

    Directory of Open Access Journals (Sweden)

    Yuliya Kozak

    2016-06-01

    Full Text Available The article analysis the system of professional training of future engineering teachers of computer type at the pedagogical universities, including graphical content preparation. It is established that the modernization of this system of training engineering teachers of computer profile is extremely important because of increasing demands for total graphics education, which in terms of mass communication, the need to compress a significant amount of information and opportunities provided by new information technologies, becomes so important as second literacy. The article reveals the essential characteristics of the concept of graphic competence as important component of the modernization of the education system, and an attempt to find promising ways of further work to effective solving of the issue of formation of graphic competence of engineering teachers of computer profile.

  15. Molecular profiling reveals frequent gain of MYCN and anaplasia-specific loss of 4q and 14q in Wilms tumor.

    Science.gov (United States)

    Williams, Richard D; Al-Saadi, Reem; Natrajan, Rachael; Mackay, Alan; Chagtai, Tasnim; Little, Suzanne; Hing, Sandra N; Fenwick, Kerry; Ashworth, Alan; Grundy, Paul; Anderson, James R; Dome, Jeffrey S; Perlman, Elizabeth J; Jones, Chris; Pritchard-Jones, Kathy

    2011-12-01

    Anaplasia in Wilms tumor, a distinctive histology characterized by abnormal mitoses, is associated with poor patient outcome. While anaplastic tumors frequently harbour TP53 mutations, little is otherwise known about their molecular biology. We have used array comparative genomic hybridization (aCGH) and cDNA microarray expression profiling to compare anaplastic and favorable histology Wilms tumors to determine their common and differentiating features. In addition to changes on 17p, consistent with TP53 deletion, recurrent anaplasia-specific genomic loss and under-expression were noted in several other regions, most strikingly 4q and 14q. Further aberrations, including gain of 1q and loss of 16q were common to both histologies. Focal gain of MYCN, initially detected by high resolution aCGH profiling in 6/61 anaplastic samples, was confirmed in a significant proportion of both tumor types by a genomic quantitative PCR survey of over 400 tumors. Overall, these results are consistent with a model where anaplasia, rather than forming an entirely distinct molecular entity, arises from the general continuum of Wilms tumor by the acquisition of additional genomic changes at multiple loci. Copyright © 2011 Wiley Periodicals, Inc.

  16. Pathophysiological Significance of Dermatan Sulfate Proteoglycans Revealed by Human Genetic Disorders

    Directory of Open Access Journals (Sweden)

    Shuji Mizumoto

    2017-03-01

    Full Text Available The indispensable roles of dermatan sulfate-proteoglycans (DS-PGs have been demonstrated in various biological events including construction of the extracellular matrix and cell signaling through interactions with collagen and transforming growth factor-β, respectively. Defects in the core proteins of DS-PGs such as decorin and biglycan cause congenital stromal dystrophy of the cornea, spondyloepimetaphyseal dysplasia, and Meester-Loeys syndrome. Furthermore, mutations in human genes encoding the glycosyltransferases, epimerases, and sulfotransferases responsible for the biosynthesis of DS chains cause connective tissue disorders including Ehlers-Danlos syndrome and spondyloepimetaphyseal dysplasia with joint laxity characterized by skin hyperextensibility, joint hypermobility, and tissue fragility, and by severe skeletal disorders such as kyphoscoliosis, short trunk, dislocation, and joint laxity. Glycobiological approaches revealed that mutations in DS-biosynthetic enzymes cause reductions in enzymatic activities and in the amount of synthesized DS and also disrupt the formation of collagen bundles. This review focused on the growing number of glycobiological studies on recently reported genetic diseases caused by defects in the biosynthesis of DS and DS-PGs.

  17. Effect of masticatory stimulation on the quantity and quality of saliva and the salivary metabolomic profile.

    Directory of Open Access Journals (Sweden)

    Nobuyuki Okuma

    Full Text Available This study characterized the changes in quality and quantity of saliva, and changes in the salivary metabolomic profile, to understand the effects of masticatory stimulation.Stimulated and unstimulated saliva samples were collected from 55 subjects and salivary hydrophilic metabolites were comprehensively quantified using capillary electrophoresis-time-of-flight mass spectrometry.In total, 137 metabolites were identified and quantified. The concentrations of 44 metabolites in stimulated saliva were significantly higher than those in unstimulated saliva. Pathway analysis identified the upregulation of the urea cycle and synthesis and degradation pathways of glycine, serine, cysteine and threonine in stimulated saliva. A principal component analysis revealed that the effect of masticatory stimulation on salivary metabolomic profiles was less dependent on sample population sex, age, and smoking. The concentrations of only 1 metabolite in unstimulated saliva, and of 3 metabolites stimulated saliva, showed significant correlation with salivary secretion volume, indicating that the salivary metabolomic profile and salivary secretion volume were independent factors.Masticatory stimulation affected not only salivary secretion volume, but also metabolite concentration patterns. A low correlation between the secretion volume and these patterns supports the conclusion that the salivary metabolomic profile may be a new indicator to characterize masticatory stimulation.

  18. HPV type-related chromosomal profiles in high-grade cervical intraepithelial neoplasia

    Directory of Open Access Journals (Sweden)

    Bierkens Mariska

    2012-01-01

    Full Text Available Abstract Background The development of cervical cancer and its high-grade precursor lesions (Cervical Intraepithelial Neoplasia grade 2/3 [CIN2/3] result from a persistent infection with high-risk human papillomavirus (hrHPV types and the accumulation of (epigenetic host cell aberrations. Epidemiological studies have demonstrated variable CIN2/3 and cancer risks between different hrHPV types. Recent genomic profiling studies revealed substantial heterogeneity in the chromosomal aberrations detected in morphologically indistinguishable CIN2/3 suggestive of varying cancer risk. The current study aimed to investigate whether CIN2/3 with different hrHPV types vary with respect to their chromosomal profiles, both in terms of the number of aberrations and chromosomal loci affected. Methods Chromosomal profiles were determined of 43 p16INK4a-immunopositive CIN2/3 of women with long-term hrHPV infection (≥ 5 years. Sixteen lesions harboured HPV16, 3 HPV18, 14 HPV31, 1 HPV33, 4 HPV45, 1 HPV51, 2 HPV52 and 2 HPV58. Results Unsupervised hierarchical clustering analysis of the chromosomal profiles revealed two major clusters, characterised by either few or multiple chromosomal aberrations, respectively. A majority of 87.5% of lesions with HPV16 were in the cluster with relatively few aberrations, whereas no such unbalanced distribution was seen for lesions harbouring other hrHPV types. Analysis of the two most prevalent types (HPV16 and HPV31 in this data set revealed a three-fold increase in the number of losses in lesions with HPV31 compared to HPV16-positive lesions. In particular, losses at chromosomes 2q, 4p, 4q, 6p, 6q, 8q & 17p and gain at 1p & 1q were significantly more frequent in HPV31-positive lesions (FDR Conclusions Chromosomal aberrations in CIN2/3 are at least in part related to the hrHPV type present. The relatively low number of chromosomal aberrations observed in HPV16-positive CIN2/3 suggests that the development of these lesions is

  19. Integrative analysis and expression profiling of secondary cell wall genes in C4 biofuel model Setaria italica reveals targets for lignocellulose bioengineering

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    Mehanathan eMuthamilarasan

    2015-11-01

    Full Text Available Several underutilized grasses have excellent potential for use as bioenergy feedstock due to their lignocellulosic biomass. Genomic tools have enabled identification of lignocellulose biosynthesis genes in several sequenced plants. However, the non-availability of whole genome sequence of bioenergy grasses hinders the study on bioenergy genomics and their genomics-assisted crop improvement. Foxtail millet (Setaria italica L.; Si is a model crop for studying systems biology of bioenergy grasses. In the present study, a systematic approach has been used for identification of gene families involved in cellulose (CesA/Csl, callose (Gsl and monolignol biosynthesis (PAL, C4H, 4CL, HCT, C3H, CCoAOMT, F5H, COMT, CCR, CAD and construction of physical map of foxtail millet. Sequence alignment and phylogenetic analysis of identified proteins showed that monolignol biosynthesis proteins were highly diverse, whereas CesA/Csl and Gsl proteins were homologous to rice and Arabidopsis. Comparative mapping of foxtail millet lignocellulose biosynthesis genes with other C4 panicoid genomes revealed maximum homology with switchgrass, followed by sorghum and maize. Expression profiling of candidate lignocellulose genes in response to different abiotic stresses and hormone treatments showed their differential expression pattern, with significant higher expression of SiGsl12, SiPAL2, SiHCT1, SiF5H2 and SiCAD6 genes. Further, due to the evolutionary conservation of grass genomes, the insights gained from the present study could be extrapolated for identifying genes involved in lignocellulose biosynthesis in other biofuel species for further characterization.

  20. Integrative analysis and expression profiling of secondary cell wall genes in C4 biofuel model Setaria italica reveals targets for lignocellulose bioengineering.

    Science.gov (United States)

    Muthamilarasan, Mehanathan; Khan, Yusuf; Jaishankar, Jananee; Shweta, Shweta; Lata, Charu; Prasad, Manoj

    2015-01-01

    Several underutilized grasses have excellent potential for use as bioenergy feedstock due to their lignocellulosic biomass. Genomic tools have enabled identification of lignocellulose biosynthesis genes in several sequenced plants. However, the non-availability of whole genome sequence of bioenergy grasses hinders the study on bioenergy genomics and their genomics-assisted crop improvement. Foxtail millet (Setaria italica L.; Si) is a model crop for studying systems biology of bioenergy grasses. In the present study, a systematic approach has been used for identification of gene families involved in cellulose (CesA/Csl), callose (Gsl) and monolignol biosynthesis (PAL, C4H, 4CL, HCT, C3H, CCoAOMT, F5H, COMT, CCR, CAD) and construction of physical map of foxtail millet. Sequence alignment and phylogenetic analysis of identified proteins showed that monolignol biosynthesis proteins were highly diverse, whereas CesA/Csl and Gsl proteins were homologous to rice and Arabidopsis. Comparative mapping of foxtail millet lignocellulose biosynthesis genes with other C4 panicoid genomes revealed maximum homology with switchgrass, followed by sorghum and maize. Expression profiling of candidate lignocellulose genes in response to different abiotic stresses and hormone treatments showed their differential expression pattern, with significant higher expression of SiGsl12, SiPAL2, SiHCT1, SiF5H2, and SiCAD6 genes. Further, due to the evolutionary conservation of grass genomes, the insights gained from the present study could be extrapolated for identifying genes involved in lignocellulose biosynthesis in other biofuel species for further characterization.

  1. Separation of Hepatitis C genotype 4a into IgG-depleted and IgG-enriched fractions reveals a unique quasispecies profile.

    LENUS (Irish Health Repository)

    Moreau, Isabelle

    2012-02-03

    BACKGROUND: Hepatitis C virus (HCV) circulates in an infected individual as a heterogeneous mixture of closely related viruses called quasispecies. The E1\\/E2 region of the HCV genome is hypervariable (HVR1) and is targeted by the humoral immune system. Hepatitis C virions are found in two forms: antibody associated or antibody free. The objective of this study was to investigate if separation of Hepatitis C virions into antibody enriched and antibody depleted fractions segregates quasispecies populations into distinctive swarms. RESULTS: A HCV genotype 4a specimen was fractionated into IgG-depleted and IgG-enriched fractions by use of Albumin\\/IgG depletion spin column. Clonal analysis of these two fractions was performed and then compared to an unfractionated sample. Following sequence analysis it was evident that the antibody depleted fraction was significantly more heterogeneous than the antibody enriched fraction, revealing a unique quasispecies profile. An in-frame 3 nt insertion was observed in 26% of clones in the unfractionated population and in 64% of clones in the IgG-depleted fraction. In addition, an in-frame 3 nt indel event was observed in 10% of clones in the unfractionated population and in 9% of clones in the IgG-depleted fraction. Neither of these latter events, which are rare occurrences in genotype 4a, was identified in the IgG-enriched fraction. CONCLUSION: In conclusion, the homogeneity of the IgG-enriched species is postulated to represent a sequence that was strongly recognised by the humoral immune system at the time the sample was obtained. The heterogeneous nature of the IgG-depleted fraction is discussed in the context of humoral escape.

  2. Neonatal maternal deprivation response and developmental changes in gene expression revealed by hypothalamic gene expression profiling in mice.

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    Feng Ding

    Full Text Available Neonatal feeding problems are observed in several genetic diseases including Prader-Willi syndrome (PWS. Later in life, individuals with PWS develop hyperphagia and obesity due to lack of appetite control. We hypothesized that failure to thrive in infancy and later-onset hyperphagia are related and could be due to a defect in the hypothalamus. In this study, we performed gene expression microarray analysis of the hypothalamic response to maternal deprivation in neonatal wild-type and Snord116del mice, a mouse model for PWS in which a cluster of imprinted C/D box snoRNAs is deleted. The neonatal starvation response in both strains was dramatically different from that reported in adult rodents. Genes that are affected by adult starvation showed no expression change in the hypothalamus of 5 day-old pups after 6 hours of maternal deprivation. Unlike in adult rodents, expression levels of Nanos2 and Pdk4 were increased, and those of Pgpep1, Ndp, Brms1l, Mett10d, and Snx1 were decreased after neonatal deprivation. In addition, we compared hypothalamic gene expression profiles at postnatal days 5 and 13 and observed significant developmental changes. Notably, the gene expression profiles of Snord116del deletion mice and wild-type littermates were very similar at all time points and conditions, arguing against a role of Snord116 in feeding regulation in the neonatal period.

  3. Genomic profiling of plasmablastic lymphoma using array comparative genomic hybridization (aCGH: revealing significant overlapping genomic lesions with diffuse large B-cell lymphoma

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    Lu Xin-Yan

    2009-11-01

    Full Text Available Abstract Background Plasmablastic lymphoma (PL is a subtype of diffuse large B-cell lymphoma (DLBCL. Studies have suggested that tumors with PL morphology represent a group of neoplasms with clinopathologic characteristics corresponding to different entities including extramedullary plasmablastic tumors associated with plasma cell myeloma (PCM. The goal of the current study was to evaluate the genetic similarities and differences among PL, DLBCL (AIDS-related and non AIDS-related and PCM using array-based comparative genomic hybridization. Results Examination of genomic data in PL revealed that the most frequent segmental gain (> 40% include: 1p36.11-1p36.33, 1p34.1-1p36.13, 1q21.1-1q23.1, 7q11.2-7q11.23, 11q12-11q13.2 and 22q12.2-22q13.3. This correlated with segmental gains occurring in high frequency in DLBCL (AIDS-related and non AIDS-related cases. There were some segmental gains and some segmental loss that occurred in PL but not in the other types of lymphoma suggesting that these foci may contain genes responsible for the differentiation of this lymphoma. Additionally, some segmental gains and some segmental loss occurred only in PL and AIDS associated DLBCL suggesting that these foci may be associated with HIV infection. Furthermore, some segmental gains and some segmental loss occurred only in PL and PCM suggesting that these lesions may be related to plasmacytic differentiation. Conclusion To the best of our knowledge, the current study represents the first genomic exploration of PL. The genomic aberration pattern of PL appears to be more similar to that of DLBCL (AIDS-related or non AIDS-related than to PCM. Our findings suggest that PL may remain best classified as a subtype of DLBCL at least at the genome level.

  4. Metabolic Profiles of Brain Metastases

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    Tone F. Bathen

    2013-01-01

    Full Text Available Metastasis to the brain is a feared complication of systemic cancer, associated with significant morbidity and poor prognosis. A better understanding of the tumor metabolism might help us meet the challenges in controlling brain metastases. The study aims to characterize the metabolic profile of brain metastases of different origin using high resolution magic angle spinning (HR-MAS magnetic resonance spectroscopy (MRS to correlate the metabolic profiles to clinical and pathological information. Biopsy samples of human brain metastases (n = 49 were investigated. A significant correlation between lipid signals and necrosis in brain metastases was observed (p < 0.01, irrespective of their primary origin. The principal component analysis (PCA showed that brain metastases from malignant melanomas cluster together, while lung carcinomas were metabolically heterogeneous and overlap with other subtypes. Metastatic melanomas have higher amounts of glycerophosphocholine than other brain metastases. A significant correlation between microscopically visible lipid droplets estimated by Nile Red staining and MR visible lipid signals was observed in metastatic lung carcinomas (p = 0.01, indicating that the proton MR visible lipid signals arise from cytoplasmic lipid droplets. MRS-based metabolomic profiling is a useful tool for exploring the metabolic profiles of metastatic brain tumors.

  5. Does Lipid Profile Affect Thrombin Generation During Ramadan Fasting in Patients With Cardiovascular Risks?

    Science.gov (United States)

    Sassi, Mouna; Chakroun, Taher; Chouchène, Saoussen; Hellara, Ilhem; Boubaker, Hamdi; Grissa, Mohamed Habib; Khochtali, Ines; Hassine, Mohsen; Addad, Faouzi; Elalamy, Ismail; Nouira, Semir

    2017-11-01

    There is evidence that diet and variation in lipid metabolism can influence blood coagulation, but little is known about the effect of Ramadan fasting on plasmatic coagulation pattern. We investigated the effect of Ramadan fasting on thrombin generation (TG) in patients with cardiovascular disease (CVD) risks, and we aimed to assess the effect of lipid profile on TG parameters. The study was conducted in 36 adults having at least 2 CVD risks and in 30 healthy controls. Coagulation pattern was assessed by both classical clotting times and TG test. A complete lipid profile was performed simultaneously. Patients were invited 2 times: 1 week before Ramadan and during the last week of the Ramadan. The TG parameters were not different in patients with CVD risks compared to healthy controls. Fasting had no effect on plasmatic coagulation parameters and on TG profile. Individual analysis of the mean rate index (MRI) of TG revealed 3 groups: group 1 with no modification of MRI, group 2 with a significant increase in MRI (81.64 nM/min vs 136.07 nM/min; P fasting did not influence the global coagulation pattern in patients with CVD risks. Whereas, a significant increase in the propagation phase of TG was associated with a significant increase in cholesterol levels, which was not found with the other TG parameters.

  6. Integrated analysis of microRNA and gene expression profiles reveals a functional regulatory module associated with liver fibrosis.

    Science.gov (United States)

    Chen, Wei; Zhao, Wenshan; Yang, Aiting; Xu, Anjian; Wang, Huan; Cong, Min; Liu, Tianhui; Wang, Ping; You, Hong

    2017-12-15

    -receptor interaction" were remarked significant (adjusted pfunctional miRNA-gene regulatory module that contains 7 miRNAs, 22 genes and 42 miRNA-gene connections. Gene interaction analysis based on String database revealed that 8 out of 22 genes were highly clustered. Finally, we experimentally confirmed a functional regulatory module containing 5 miRNAs (miR-130b-3p, miR-148a-3p, miR-345-5p, miR-378a-3p, and miR-422a) and 6 genes (COL6A1, COL6A2, COL6A3, PIK3R3, COL1A1, CCND2) associated with liver fibrosis. Our integrated analysis of miRNA and gene expression profiles highlighted a functional miRNA-gene regulatory module associated with liver fibrosis, which, to some extent, may provide important clues to better understand the underlying pathogenesis of liver fibrosis. Copyright © 2017. Published by Elsevier B.V.

  7. Global Expression Profiling and Pathway Analysis of Mouse Mammary Tumor Reveals Strain and Stage Specific Dysregulated Pathways in Breast Cancer Progression.

    Science.gov (United States)

    Mei, Yan; Yang, Jun-Ping; Lang, Yan-Hong; Peng, Li-Xia; Yang, Ming-Ming; Liu, Qin; Meng, Dong-Fang; Zheng, Li-Sheng; Qiang, Yuan-Yuan; Xu, Liang; Li, Chang-Zhi; Wei, Wen-Wen; Niu, Ting; Peng, Xing-Si; Yang, Qin; Lin, Fen; Hu, Hao; Xu, Hong-Fa; Huang, Bi-Jun; Wang, Li-Jing; Qian, Chao-Nan

    2018-05-01

    It is believed that the alteration of tissue microenvironment would affect cancer initiation and progression. However, little is known in terms of the underlying molecular mechanisms that would affect the initiation and progression of breast cancer. In the present study, we use two murine mammary tumor models with different speeds of tumor initiation and progression for whole genome expression profiling to reveal the involved genes and signaling pathways. The pathways regulating PI3K-Akt signaling and Ras signaling were activated in Fvb mice and promoted tumor progression. Contrastingly, the pathways regulating apoptosis and cellular senescence were activated in Fvb.B6 mice and suppressed tumor progression. We identified distinct patterns of oncogenic pathways activation at different stages of breast cancer, and uncovered five oncogenic pathways that were activated in both human and mouse breast cancers. The genes and pathways discovered in our study would be useful information for other researchers and drug development.

  8. Diffusion profiling of tumor volumes using a histogram approach can predict proliferation and further microarchitectural features in medulloblastoma.

    Science.gov (United States)

    Schob, Stefan; Beeskow, Anne; Dieckow, Julia; Meyer, Hans-Jonas; Krause, Matthias; Frydrychowicz, Clara; Hirsch, Franz-Wolfgang; Surov, Alexey

    2018-05-31

    Medulloblastomas are the most common central nervous system tumors in childhood. Treatment and prognosis strongly depend on histology and transcriptomic profiling. However, the proliferative potential also has prognostical value. Our study aimed to investigate correlations between histogram profiling of diffusion-weighted images and further microarchitectural features. Seven patients (age median 14.6 years, minimum 2 years, maximum 20 years; 5 male, 2 female) were included in this retrospective study. Using a Matlab-based analysis tool, histogram analysis of whole apparent diffusion coefficient (ADC) volumes was performed. ADC entropy revealed a strong inverse correlation with the expression of the proliferation marker Ki67 (r = - 0.962, p = 0.009) and with total nuclear area (r = - 0.888, p = 0.044). Furthermore, ADC percentiles, most of all ADCp90, showed significant correlations with Ki67 expression (r = 0.902, p = 0.036). Diffusion histogram profiling of medulloblastomas provides valuable in vivo information which potentially can be used for risk stratification and prognostication. First of all, entropy revealed to be the most promising imaging biomarker. However, further studies are warranted.

  9. Comprehensive Genomic Profiling of 282 Pediatric Low- and High-Grade Gliomas Reveals Genomic Drivers, Tumor Mutational Burden, and Hypermutation Signatures.

    Science.gov (United States)

    Johnson, Adrienne; Severson, Eric; Gay, Laurie; Vergilio, Jo-Anne; Elvin, Julia; Suh, James; Daniel, Sugganth; Covert, Mandy; Frampton, Garrett M; Hsu, Sigmund; Lesser, Glenn J; Stogner-Underwood, Kimberly; Mott, Ryan T; Rush, Sarah Z; Stanke, Jennifer J; Dahiya, Sonika; Sun, James; Reddy, Prasanth; Chalmers, Zachary R; Erlich, Rachel; Chudnovsky, Yakov; Fabrizio, David; Schrock, Alexa B; Ali, Siraj; Miller, Vincent; Stephens, Philip J; Ross, Jeffrey; Crawford, John R; Ramkissoon, Shakti H

    2017-12-01

    Pediatric brain tumors are the leading cause of death for children with cancer in the U.S. Incorporating next-generation sequencing data for both pediatric low-grade (pLGGs) and high-grade gliomas (pHGGs) can inform diagnostic, prognostic, and therapeutic decision-making. We performed comprehensive genomic profiling on 282 pediatric gliomas (157 pHGGs, 125 pLGGs), sequencing 315 cancer-related genes and calculating the tumor mutational burden (TMB; mutations per megabase [Mb]). In pLGGs, we detected genomic alterations (GA) in 95.2% (119/125) of tumors. BRAF was most frequently altered (48%; 60/125), and FGFR1 missense (17.6%; 22/125), NF1 loss of function (8.8%; 11/125), and TP53 (5.6%; 7/125) mutations were also detected. Rearrangements were identified in 35% of pLGGs, including KIAA1549-BRAF , QKI-RAF1 , FGFR3-TACC3 , CEP85L-ROS1 , and GOPC-ROS1 fusions. Among pHGGs, GA were identified in 96.8% (152/157). The genes most frequently mutated were TP53 (49%; 77/157), H3F3A (37.6%; 59/157), ATRX (24.2%; 38/157), NF1 (22.2%; 35/157), and PDGFRA (21.7%; 34/157). Interestingly, most H3F3A mutations (81.4%; 35/43) were the variant K28M. Midline tumor analysis revealed H3F3A mutations (40%; 40/100) consisted solely of the K28M variant. Pediatric high-grade gliomas harbored oncogenic EML4-ALK , DGKB-ETV1 , ATG7-RAF1 , and EWSR1-PATZ1 fusions. Six percent (9/157) of pHGGs were hypermutated (TMB >20 mutations per Mb; range 43-581 mutations per Mb), harboring mutations deleterious for DNA repair in MSH6, MSH2, MLH1, PMS2, POLE , and POLD1 genes (78% of cases). Comprehensive genomic profiling of pediatric gliomas provides objective data that promote diagnostic accuracy and enhance clinical decision-making. Additionally, TMB could be a biomarker to identify pediatric glioblastoma (GBM) patients who may benefit from immunotherapy. By providing objective data to support diagnostic, prognostic, and therapeutic decision-making, comprehensive genomic profiling is necessary for

  10. Proteomic profiles reveal age-related changes in coelomic fluid of sea urchin species with different life spans.

    Science.gov (United States)

    Bodnar, Andrea

    2013-05-01

    Sea urchins have a different life history from humans and traditional model organisms used to study the process of aging. Sea urchins grow indeterminately, reproduce throughout their life span and some species have been shown to exhibit negligible senescence with no increase in mortality rate at advanced ages. Despite these properties, different species of sea urchins are reported to have very different natural life spans providing a unique model to investigate cellular mechanisms underlying life span determination and negligible senescence. To gain insight into the biological changes that accompany aging in these animals, proteomic profiles were examined in coelomic fluid from young and old sea urchins of three species with different life spans: short-lived Lytechinus variegatus, long-lived Strongylocentrotus franciscanus and Strongylocentrotus purpuratus which has an intermediate life span. The proteomic profiles of cell-free coelomic fluid were complex with many proteins exhibiting different forms and extensive post-translational modifications. Approximately 20% of the protein spots on 2-D gels showed more than two-fold change with age in each of the species. Changes that are consistent with age in all three species may prove to be useful biomarkers for age-determination for these commercially fished marine invertebrates and also may provide clues to mechanisms of negligible senescence. Among the proteins that change with age, the ectodomain of low-density lipoprotein receptor-related protein 4 (LRP4) was significantly increased in the coelomic fluid of all three sea urchin species suggesting that the Wnt signaling pathway should be further investigated for its role in negligible senescence. Copyright © 2012 Elsevier Inc. All rights reserved.

  11. Gene Expression Profiling Reveals Potential Players of Left-Right Asymmetry in Female Chicken Gonads

    Directory of Open Access Journals (Sweden)

    Zhiyi Wan

    2017-06-01

    Full Text Available Most female birds develop only a left ovary, whereas males develop bilateral testes. The mechanism underlying this process is still not completely understood. Here, we provide a comprehensive transcriptional analysis of female chicken gonads and identify novel candidate side-biased genes. RNA-Seq analysis was carried out on total RNA harvested from the left and right gonads on embryonic day 6 (E6, E12, and post-hatching day 1 (D1. By comparing the gene expression profiles between the left and right gonads, 347 differentially expressed genes (DEGs were obtained on E6, 3730 were obtained on E12, and 2787 were obtained on D1. Side-specific genes were primarily derived from the autosome rather than the sex chromosome. Gene ontology and pathway analysis showed that the DEGs were most enriched in the Piwi-interactiing RNA (piRNA metabolic process, germ plasm, chromatoid body, P granule, neuroactive ligand-receptor interaction, microbial metabolism in diverse environments, and methane metabolism. A total of 111 DEGs, five gene ontology (GO terms, and three pathways were significantly different between the left and right gonads among all the development stages. We also present the gene number and the percentage within eight development-dependent expression patterns of DEGs in the left and right gonads of female chicken.

  12. Proteome-metabolome profiling of ovarian cancer ascites reveals novel components involved in intercellular communication.

    Science.gov (United States)

    Shender, Victoria O; Pavlyukov, Marat S; Ziganshin, Rustam H; Arapidi, Georgij P; Kovalchuk, Sergey I; Anikanov, Nikolay A; Altukhov, Ilya A; Alexeev, Dmitry G; Butenko, Ivan O; Shavarda, Alexey L; Khomyakova, Elena B; Evtushenko, Evgeniy; Ashrafyan, Lev A; Antonova, Irina B; Kuznetcov, Igor N; Gorbachev, Alexey Yu; Shakhparonov, Mikhail I; Govorun, Vadim M

    2014-12-01

    Ovarian cancer ascites is a native medium for cancer cells that allows investigation of their secretome in a natural environment. This medium is of interest as a promising source of potential biomarkers, and also as a medium for cell-cell communication. The aim of this study was to elucidate specific features of the malignant ascites metabolome and proteome. In order to omit components of the systemic response to ascites formation, we compared malignant ascites with cirrhosis ascites. Metabolome analysis revealed 41 components that differed significantly between malignant and cirrhosis ascites. Most of the identified cancer-specific metabolites are known to be important signaling molecules. Proteomic analysis identified 2096 and 1855 proteins in the ovarian cancer and cirrhosis ascites, respectively; 424 proteins were specific for the malignant ascites. Functional analysis of the proteome demonstrated that the major differences between cirrhosis and malignant ascites were observed for the cluster of spliceosomal proteins. Additionally, we demonstrate that several splicing RNAs were exclusively detected in malignant ascites, where they probably existed within protein complexes. This result was confirmed in vitro using an ovarian cancer cell line. Identification of spliceosomal proteins and RNAs in an extracellular medium is of particular interest; the finding suggests that they might play a role in the communication between cancer cells. In addition, malignant ascites contains a high number of exosomes that are known to play an important role in signal transduction. Thus our study reveals the specific features of malignant ascites that are associated with its function as a medium of intercellular communication. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  13. An examination of the spatial variability of CO2 in the profile of managed forest soils

    International Nuclear Information System (INIS)

    Black, M.; Kellman, L.; Beltrami, H.

    2005-01-01

    Soil carbon dioxide (CO 2 ) profiles are typically used in soil-gas exchange studies. Although surface flux measuring methods may be more efficient for deriving surface soil CO 2 exchange budgets, they do not provide enough information about the generation of gas through depth. This poses a challenge in quantifying the CO 2 generated from different zones and soil carbon pools through time. The combination of subsurface concentration profiles and estimates of soil diffusivity reveal where CO 2 is being generated in the soil. This combined approach offers greater awareness into processes controlling CO 2 production in soils through depth, and clarifies how soil CO 2 exchange processes in these ecosystems can be changed by management regimes and climate change. Although information about spatial variability in subsurface concentrations within forested soils is limited, it is assumed to be high because of the high spatial variability in soil CO 2 flux estimates and the large variation in vegetation distribution and topography within sites. In this study, the soil CO 2 profile was monitored during the fall of 2004 at depths of 0, 5, 20 and 35 cm at 10 microsites of a clear-cut and an 80 year old intact mixed forest in Atlantic Canada. Microsites were about 10 meters apart and represented a range of microtopographical conditions that typically encompass extremes in soil CO 2 profile patterns. Preliminary results reveal predictable patterns in concentration profiles through depth, and increasing CO 2 concentration with depth, consistent with a large soil source of CO 2 . The significant variability in the soil carbon profile between microsites in the clear-cut and intact forest sites will be investigated to determine if distinct microsite patterns can be identified. The feasibility of using this method for providing process-based versus soil C exchange budgeting information at forested sites will also be examined

  14. Attenuated UV Radiation Alters Volatile Profile in Cabernet Sauvignon Grapes under Field Conditions.

    Science.gov (United States)

    Liu, Di; Gao, Yuan; Li, Xiao-Xi; Li, Zheng; Pan, Qiu-Hong

    2015-09-17

    This study aimed to explore the effect of attenuated UV radiation around grape clusters on the volatile profile of Cabernet Sauvignon grapes (Vitis vinifera L. cv.) under field conditions. Grape bunches were wrapped with two types of polyester films that cut off 89% (film A) and 99% (film B) invisible sunlight of less than 380 nm wavelength, respectively. Solar UV radiation reaching the grape berry surface was largely attenuated, and an increase in the concentrations of amino acid-derived benzenoid volatiles and fatty acid-derived esters was observed in the ripening grapes. Meanwhile, the attenuated UV radiation significantly reduced the concentrations of fatty acid-derived aldehydes and alcohols and isoprenoid-derived norisoprenoids. No significant impact was observed for terpenes. In most case, these positive or negative effects were stage-dependent. Reducing UV radiation from the onset of veraison to grape harvest, compared to the other stages, caused a larger alteration in the grape volatile profile. Partial Least Square Discriminant Analysis (PLS-DA) revealed that (E)-2-hexenal, 4-methyl benzaldehyde, 2-butoxyethyl acetate, (E)-2-heptenal, styrene, α-phenylethanol, and (Z)-3-hexen-1-ol acetate were affected most significantly by the attenuated UV radiation.

  15. Attenuated UV Radiation Alters Volatile Profile in Cabernet Sauvignon Grapes under Field Conditions

    Directory of Open Access Journals (Sweden)

    Di Liu

    2015-09-01

    Full Text Available This study aimed to explore the effect of attenuated UV radiation around grape clusters on the volatile profile of Cabernet Sauvignon grapes (Vitis vinifera L. cv. under field conditions. Grape bunches were wrapped with two types of polyester films that cut off 89% (film A and 99% (film B invisible sunlight of less than 380 nm wavelength, respectively. Solar UV radiation reaching the grape berry surface was largely attenuated, and an increase in the concentrations of amino acid-derived benzenoid volatiles and fatty acid-derived esters was observed in the ripening grapes. Meanwhile, the attenuated UV radiation significantly reduced the concentrations of fatty acid-derived aldehydes and alcohols and isoprenoid-derived norisoprenoids. No significant impact was observed for terpenes. In most case, these positive or negative effects were stage-dependent. Reducing UV radiation from the onset of veraison to grape harvest, compared to the other stages, caused a larger alteration in the grape volatile profile. Partial Least Square Discriminant Analysis (PLS-DA revealed that (E-2-hexenal, 4-methyl benzaldehyde, 2-butoxyethyl acetate, (E-2-heptenal, styrene, α-phenylethanol, and (Z-3-hexen-1-ol acetate were affected most significantly by the attenuated UV radiation.

  16. Lipid reducing activity and toxicity profiles of a library of polyphenol derivatives.

    Science.gov (United States)

    Urbatzka, Ralph; Freitas, Sara; Palmeira, Andreia; Almeida, Tiago; Moreira, João; Azevedo, Carlos; Afonso, Carlos; Correia-da-Silva, Marta; Sousa, Emilia; Pinto, Madalena; Vasconcelos, Vitor

    2018-05-10

    Obesity is an increasing epidemic worldwide and novel treatments are urgently needed. Polyphenols are natural compounds derived from plants, which are known in particular for their antioxidant properties. However, some polyphenols were described to possess anti-obesity activities in vitro and in vivo. In this study, we aimed to screen a library of 85 polyphenol derivatives for their lipid reducing activity and toxicity. Compounds were analyzed at 5 μM with the zebrafish Nile red fluorescence fat metabolism assay and for general toxicity in vivo. To improve the safety profile, compounds were screened at 50 μM in murine preadipocytes in vitro for cytotoxicity. Obtained activity data were used to create a 2D-QSAR (quantitative structure activity relationship) model. 38 polyphenols showed strong lipid reducing activity. Toxicity analysis revealed that 18 of them did not show any toxicity in vitro or in vivo. QSAR analysis revealed the importance of the number of rings, fractional partial positively charged surface area, relative positive charge, relative number of oxygen atoms, and partial negative surface area for lipid-reducing activity. The five most potent compounds with EC 50 values in the nanomolar range for lipid reducing activity and without any toxic effects are strong candidates for future research and development into anti-obesity drugs. Molecular profiling for fasn, sirt1, mtp and ppary revealed one compound that reduced significantly fasn mRNA expression. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  17. GC-MS metabolic profiling of Cabernet Sauvignon and Merlot cultivars during grapevine berry development and network analysis reveals a stage- and cultivar-dependent connectivity of primary metabolites.

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    Cuadros-Inostroza, Alvaro; Ruíz-Lara, Simón; González, Enrique; Eckardt, Aenne; Willmitzer, Lothar; Peña-Cortés, Hugo

    Information about the total chemical composition of primary metabolites during grape berry development is scarce, as are comparative studies trying to understand to what extent metabolite modifications differ between cultivars during ripening. Thus, correlating the metabolic profiles with the changes occurring in berry development and ripening processes is essential to progress in their comprehension as well in the development of new approaches to improve fruit attributes. Here, the developmental metabolic profiling analysis across six stages from flowering to fully mature berries of two cultivars, Cabernet Sauvignon and Merlot, is reported at metabolite level. Based on a gas chromatography-mass spectrometry untargeted approach, 115 metabolites were identified and relative quantified in both cultivars. Sugars and amino acids levels show an opposite behaviour in both cultivars undergoing a highly coordinated shift of metabolite associated to primary metabolism during the stages involved in growth, development and ripening of berries. The changes are characteristic for each stage, the most pronounced ones occuring at fruit setting and pre-Veraison. They are associated to a reduction of the levels of metabolites present in the earlier corresponding stage, revealing a required catabolic activity of primary metabolites for grape berry developmental process. Network analysis revealed that the network connectivity of primary metabolites is stage- and cultivar-dependent, suggesting differences in metabolism regulation between both cultivars as the maturity process progresses. Furthermore, network analysis may represent an appropriate method to display the association between primary metabolites during berry developmental processes among different grapevine cultivars and for identifying potential biologically relevant metabolites.

  18. Improved annotation of antibiotic resistance determinants reveals microbial resistomes cluster by ecology.

    Science.gov (United States)

    Gibson, Molly K; Forsberg, Kevin J; Dantas, Gautam

    2015-01-01

    Antibiotic resistance is a dire clinical problem with important ecological dimensions. While antibiotic resistance in human pathogens continues to rise at alarming rates, the impact of environmental resistance on human health is still unclear. To investigate the relationship between human-associated and environmental resistomes, we analyzed functional metagenomic selections for resistance against 18 clinically relevant antibiotics from soil and human gut microbiota as well as a set of multidrug-resistant cultured soil isolates. These analyses were enabled by Resfams, a new curated database of protein families and associated highly precise and accurate profile hidden Markov models, confirmed for antibiotic resistance function and organized by ontology. We demonstrate that the antibiotic resistance functions that give rise to the resistance profiles observed in environmental and human-associated microbial communities significantly differ between ecologies. Antibiotic resistance functions that most discriminate between ecologies provide resistance to β-lactams and tetracyclines, two of the most widely used classes of antibiotics in the clinic and agriculture. We also analyzed the antibiotic resistance gene composition of over 6000 sequenced microbial genomes, revealing significant enrichment of resistance functions by both ecology and phylogeny. Together, our results indicate that environmental and human-associated microbial communities harbor distinct resistance genes, suggesting that antibiotic resistance functions are largely constrained by ecology.

  19. The significance and robustness of a plasma free amino acid (PFAA) profile-based multiplex function for detecting lung cancer

    International Nuclear Information System (INIS)

    Shingyoji, Masato; Mitsushima, Toru; Yamakado, Minoru; Kimura, Hideki; Iizasa, Toshihiko; Higashiyama, Masahiko; Imamura, Fumio; Saruki, Nobuhiro; Imaizumi, Akira; Yamamoto, Hiroshi; Daimon, Takashi; Tochikubo, Osamu

    2013-01-01

    We have recently reported on the changes in plasma free amino acid (PFAA) profiles in lung cancer patients and the efficacy of a PFAA-based, multivariate discrimination index for the early detection of lung cancer. In this study, we aimed to verify the usefulness and robustness of PFAA profiling for detecting lung cancer using new test samples. Plasma samples were collected from 171 lung cancer patients and 3849 controls without apparent cancer. PFAA levels were measured by high-performance liquid chromatography (HPLC)–electrospray ionization (ESI)–mass spectrometry (MS). High reproducibility was observed for both the change in the PFAA profiles in the lung cancer patients and the discriminating performance for lung cancer patients compared to previously reported results. Furthermore, multivariate discriminating functions obtained in previous studies clearly distinguished the lung cancer patients from the controls based on the area under the receiver-operator characteristics curve (AUC of ROC = 0.731 ~ 0.806), strongly suggesting the robustness of the methodology for clinical use. Moreover, the results suggested that the combinatorial use of this classifier and tumor markers improves the clinical performance of tumor markers. These findings suggest that PFAA profiling, which involves a relatively simple plasma assay and imposes a low physical burden on subjects, has great potential for improving early detection of lung cancer

  20. Major urinary protein (MUP) profiles show dynamic changes rather than individual 'barcode' signatures.

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    Thoß, M; Luzynski, K C; Ante, M; Miller, I; Penn, D J

    2015-06-30

    House mice ( Mus musculus) produce a variable number of major urinary proteins (MUPs), and studies suggest that each individual produces a unique MUP profile that provides a distinctive odor signature controlling individual and kin recognition. This 'barcode hypothesis' requires that MUP urinary profiles show high individual variability within populations and also high individual consistency over time, but tests of these assumptions are lacking. We analyzed urinary MUP profiles of 66 wild-caught house mice from eight populations using isoelectric focusing. We found that MUP profiles of wild male house mice are not individually unique, and though they were highly variable, closer inspection revealed that the variation strongly depended on MUP band type. The prominent ('major) bands were surprisingly homogenous (and hence most MUPs are not polymorphic), but we also found inconspicuous ('minor') bands that were highly variable and therefore potential candidates for individual fingerprints. We also examined changes in urinary MUP profiles of 58 males over time (from 6 to 24 weeks of age), and found that individual MUP profiles and MUP concentration were surprisingly dynamic, and showed significant changes after puberty and during adulthood. Contrary to what we expected, however, the minor bands were the most variable over time, thus no good candidates for individual fingerprints. Although MUP profiles do not provide individual fingerprints, we found that MUP profiles were more similar among siblings than non-kin despite considerable fluctuation. Our findings show that MUP profiles are not highly stable over time, they do not show strong individual clustering, and thus challenge the barcode hypothesis. Within-individual dynamics of MUP profiles indicate a different function of MUPs in individual recognition than previously assumed and advocate an alternative hypothesis ('dynamic changes' hypothesis).

  1. Large-scale expression analysis reveals distinct microRNA profiles at different stages of human neurodevelopment.

    Directory of Open Access Journals (Sweden)

    Brandon Smith

    Full Text Available BACKGROUND: MicroRNAs (miRNAs are short non-coding RNAs predicted to regulate one third of protein coding genes via mRNA targeting. In conjunction with key transcription factors, such as the repressor REST (RE1 silencing transcription factor, miRNAs play crucial roles in neurogenesis, which requires a highly orchestrated program of gene expression to ensure the appropriate development and function of diverse neural cell types. Whilst previous studies have highlighted select groups of miRNAs during neural development, there remains a need for amenable models in which miRNA expression and function can be analyzed over the duration of neurogenesis. PRINCIPAL FINDINGS: We performed large-scale expression profiling of miRNAs in human NTera2/D1 (NT2 cells during retinoic acid (RA-induced transition from progenitors to fully differentiated neural phenotypes. Our results revealed dynamic changes of miRNA patterns, resulting in distinct miRNA subsets that could be linked to specific neurodevelopmental stages. Moreover, the cell-type specific miRNA subsets were very similar in NT2-derived differentiated cells and human primary neurons and astrocytes. Further analysis identified miRNAs as putative regulators of REST, as well as candidate miRNAs targeted by REST. Finally, we confirmed the existence of two predicted miRNAs; pred-MIR191 and pred-MIR222 associated with SLAIN1 and FOXP2, respectively, and provided some evidence of their potential co-regulation. CONCLUSIONS: In the present study, we demonstrate that regulation of miRNAs occurs in precise patterns indicative of their roles in cell fate commitment, progenitor expansion and differentiation into neurons and glia. Furthermore, the similarity between our NT2 system and primary human cells suggests their roles in molecular pathways critical for human in vivo neurogenesis.

  2. Comparative transcriptional profiling of tildipirosin-resistant and sensitive Haemophilus parasuis.

    Science.gov (United States)

    Lei, Zhixin; Fu, Shulin; Yang, Bing; Liu, Qianying; Ahmed, Saeed; Xu, Lei; Xiong, Jincheng; Cao, Jiyue; Qiu, Yinsheng

    2017-08-08

    Numerous studies have been conducted to examine the molecular mechanism of Haemophilus parasuis resistance to antibiotic, but rarely to tildipirosin. In the current study, transcriptional profiling was applied to analyse the variation in gene expression of JS0135 and tildipirosin-resistant JS32. The growth curves showed that JS32 had a higher growth rate but fewer bacteria than JS0135. The cell membranes of JS32 and a resistant clinical isolate (HB32) were observed to be smoother than those of JS0135. From the comparative gene expression profile 349 up- and 113 downregulated genes were observed, covering 37 GO and 63 KEGG pathways which are involved in biological processes (11), cellular components (17), molecular function (9), cellular processes (1), environmental information processing (4), genetic information processing (9) and metabolism (49) affected in JS32. In addition, the relative overexpression of genes of the metabolism pathway (HAPS_RS09315, HAPS_RS09320), ribosomes (HAPS_RS07815) and ABC transporters (HAPS_RS10945) was detected, particularly the metabolism pathway, and verified with RT-qPCR. Collectively, the gene expression profile in connection with tildipirosin resistance factors revealed unique and highly resistant determinants of H. parasuis to macrolides that warrant further attention due to the significant threat of bacterial resistance.

  3. Metabolite Profiling of Candidatus Liberibacter Infection in Hamlin Sweet Oranges.

    Science.gov (United States)

    Hung, Wei-Lun; Wang, Yu

    2018-04-18

    Huanglongbing (HLB), also known as citrus greening disease, caused by Candidatus Liberibacter asiaticus (CLas), is considered the most serious citrus disease in the world. CLas infection has been shown to greatly affect metabolite profiles in citrus fruits. However, because of uneven distribution of CLas throughout the tree and a minimum bacterial titer requirement for polymerase chain reaction (PCR) detection, the infected trees may test false negative. To prevent this, metabolites of healthy Hamlin oranges (CLas-) obtained from the citrus undercover protection systems (CUPS) were investigated. Comparison of the metabolite profile of juice obtained from CLas- and CLas+ (asymptomatic and symptomatic) trees revealed significant differences in both volatile and nonvolatile metabolites. However, no consistent pattern could be observed in alcohols, esters, sesquiterpenes, sugars, flavanones, and limonoids as compared to previous studies. These results suggest that CLas may affect metabolite profiles of citrus fruits earlier than detecting infection by PCR. Citric acid, nobiletin, malic acid, and phenylalanine were identified as the metabolic biomarkers associated with the progression of HLB. Thus, the differential metabolites found in this study may serve as the biomarkers of HLB in its early stage, and the metabolite signature of CLas infection may provide useful information for developing a potential treatment strategy.

  4. miRNome Expression Analysis Reveals New Players on Leprosy Immune Physiopathology

    Directory of Open Access Journals (Sweden)

    Claudio Guedes Salgado

    2018-03-01

    Full Text Available Leprosy remains as a public health problem and its physiopathology is still not fully understood. MicroRNAs (miRNA are small RNA non-coding that can interfere with mRNA to regulate gene expression. A few studies using DNA chip microarrays have explored the expression of miRNA in leprosy patients using a predetermined set of genes as targets, providing interesting findings regarding the regulation of immune genes. However, using a predetermined set of genes restricted the possibility of finding new miRNAs that might be involved in different mechanisms of disease. Thus, we examined the miRNome of tuberculoid (TT and lepromatous (LL patients using both blood and lesional biopsies from classical leprosy patients (LP who visited the Dr. Marcello Candia Reference Unit in Sanitary Dermatology in the State of Pará and compared them with healthy subjects. Using a set of tools to correlate significantly differentially expressed miRNAs with their gene targets, we identified possible interactions and networks of miRNAs that might be involved in leprosy immunophysiopathology. Using this approach, we showed that the leprosy miRNA profile in blood is distinct from that in lesional skin as well as that four main groups of genes are the targets of leprosy miRNA: (1 recognition and phagocytosis, with activation of immune effector cells, where the immunosuppressant profile of LL and immunoresponsive profile of TT are clearly affected by miRNA expression; (2 apoptosis, with supportive data for an antiapoptotic leprosy profile based on BCL2, MCL1, and CASP8 expression; (3 Schwann cells (SCs, demyelination and epithelial–mesenchymal transition (EMT, supporting a role for different developmental or differentiation gene families, such as Sox, Zeb, and Hox; and (4 loss of sensation and neuropathic pain, revealing that RHOA, ROCK1, SIGMAR1, and aquaporin-1 (AQP1 may be involved in the loss of sensation or leprosy pain, indicating possible new therapeutic targets

  5. Significant role of cationic polymers in drug delivery systems.

    Science.gov (United States)

    Farshbaf, Masoud; Davaran, Soodabeh; Zarebkohan, Amir; Annabi, Nasim; Akbarzadeh, Abolfazl; Salehi, Roya

    2017-11-06

    Cationic polymers are characterized as the macromolecules that possess positive charges, which can be either inherently in the polymer side chains and/or its backbone. Based on their origins, cationic polymers are divided in two category including natural and synthetic, in which the possessed positive charges are as result of primary, secondary or tertiary amine functional groups that could be protonated in particular situations. Cationic polymers have been employed commonly as drug delivery agents due to their superior encapsulation efficacy, enhanced bioavailability, low toxicity and improved release profile. In this paper, we focus on the most prominent examples of cationic polymers which have been revealed to be applicable in drug delivery systems and we also discuss their general synthesis and surface modification methods as well as their controlled release profile in drug delivery.

  6. Beware of Selfies: The Impact of Photo Type on Impression Formation Based on Social Networking Profiles.

    Science.gov (United States)

    Krämer, Nicole C; Feurstein, Markus; Kluck, Jan P; Meier, Yannic; Rother, Marius; Winter, Stephan

    2017-01-01

    Users of social networking sites such as Facebook frequently post self-portraits on their profiles. While research has begun to analyze the motivations for posting such pictures, less is known about how selfies are evaluated by recipients. Although producers of selfies typically aim to create a positive impression, selfies may also be regarded as narcissistic and therefore fail to achieve the intended goal. The aim of this study is to examine the potentially ambivalent reception of selfies compared to photos taken by others based on the Brunswik lens model Brunswik (1956). In a between-subjects online experiment ( N = 297), Facebook profile mockups were shown which differed with regard to picture type (selfie vs. photo taken by others), gender of the profile owner (female vs. male), and number of individuals within a picture (single person vs. group). Results revealed that selfies were indeed evaluated more negatively than photos taken by others. Persons in selfies were rated as less trustworthy, less socially attractive, less open to new experiences, more narcissistic and more extroverted than the same persons in photos taken by others. In addition, gender differences were observed in the perception of pictures. Male profile owners were rated as more narcissistic and less trustworthy than female profile owners, but there was no significant interaction effect of type of picture and gender. Moreover, a mediation analysis of presumed motives for posting selfies revealed that negative evaluations of selfie posting individuals were mainly driven by the perceived motivation of impression management. Findings suggest that selfies are likely to be evaluated less positively than producers of selfies might suppose.

  7. Expression profiling on soybean leaves reveals integration of ER- and osmotic-stress pathways

    Directory of Open Access Journals (Sweden)

    Dewey Ralph E

    2007-11-01

    Full Text Available Abstract Background Despite the potential of the endoplasmic reticulum (ER stress response to accommodate adaptive pathways, its integration with other environmental-induced responses is poorly understood in plants. We have previously demonstrated that the ER-stress sensor binding protein (BiP from soybean exhibits an unusual response to drought. The members of the soybean BiP gene family are differentially regulated by osmotic stress and soybean BiP confers tolerance to drought. While these results may reflect crosstalk between the osmotic and ER-stress signaling pathways, the lack of mutants, transcriptional response profiles to stresses and genome sequence information of this relevant crop has limited our attempts to identify integrated networks between osmotic and ER stress-induced adaptive responses. As a fundamental step towards this goal, we performed global expression profiling on soybean leaves exposed to polyethylene glycol treatment (osmotic stress or to ER stress inducers. Results The up-regulated stress-specific changes unmasked the major branches of the ER-stress response, which include enhancing protein folding and degradation in the ER, as well as specific osmotically regulated changes linked to cellular responses induced by dehydration. However, a small proportion (5.5% of total up-regulated genes represented a shared response that seemed to integrate the two signaling pathways. These co-regulated genes were considered downstream targets based on similar induction kinetics and a synergistic response to the combination of osmotic- and ER-stress-inducing treatments. Genes in this integrated pathway with the strongest synergistic induction encoded proteins with diverse roles, such as plant-specific development and cell death (DCD domain-containing proteins, an ubiquitin-associated (UBA protein homolog and NAC domain-containing proteins. This integrated pathway diverged further from characterized specific branches of ER-stress as

  8. ADME-Tox profiles of some food additives and pesticides

    Science.gov (United States)

    Craciun, Dana; Modra, Dorina; Isvoran, Adriana

    2015-12-01

    Within this study we compute the Absorption, Distribution, Metabolism, Excretion and Toxicity (ADME-Tox) profiles of several commonly used food additives and some pesticides. As expected, all the food additives considered in this study provided to be safe, their ADME-Tox profiles indicating that they have a good oral bioavailability and they do not produce phosphoslipidosis. The ADME-Tox profiles of the pesticides indicate that, with a few exceptions, they are highly toxic (some of them being not approved in the EU, but still used in other countries) and may cause many diseases. Our results are in good agreement with published data concerning the considered food additives and pesticides revealing that the ADME-Tox profiling method may be successfully used to test other chemicals than drug candidates.

  9. Single-cell multiplexed cytokine profiling of CD19 CAR-T cells reveals a diverse landscape of polyfunctional antigen-specific response.

    Science.gov (United States)

    Xue, Qiong; Bettini, Emily; Paczkowski, Patrick; Ng, Colin; Kaiser, Alaina; McConnell, Timothy; Kodrasi, Olja; Quigley, Máire F; Heath, James; Fan, Rong; Mackay, Sean; Dudley, Mark E; Kassim, Sadik H; Zhou, Jing

    2017-11-21

    It remains challenging to characterize the functional attributes of chimeric antigen receptor (CAR)-engineered T cell product targeting CD19 related to potency and immunotoxicity ex vivo, despite promising in vivo efficacy in patients with B cell malignancies. We employed a single-cell, 16-plex cytokine microfluidics device and new analysis techniques to evaluate the functional profile of CD19 CAR-T cells upon antigen-specific stimulation. CAR-T cells were manufactured from human PBMCs transfected with the lentivirus encoding the CD19-BB-z transgene and expanded with anti-CD3/anti-CD28 coated beads. The enriched CAR-T cells were stimulated with anti-CAR or control IgG beads, stained with anti-CD4 RPE and anti-CD8 Alexa Fluor 647 antibodies, and incubated for 16 h in a single-cell barcode chip (SCBC). Each SCBC contains ~12,000 microchambers, covered with a glass slide that was pre-patterned with a complete copy of a 16-plex antibody array. Protein secretions from single CAR-T cells were captured and subsequently analyzed using proprietary software and new visualization methods. We demonstrate a new method for single-cell profiling of CD19 CAR-T pre-infusion products prepared from 4 healthy donors. CAR-T single cells exhibited a marked heterogeneity of cytokine secretions and polyfunctional (2+ cytokine) subsets specific to anti-CAR bead stimulation. The breadth of responses includes anti-tumor effector (Granzyme B, IFN-γ, MIP-1α, TNF-α), stimulatory (GM-CSF, IL-2, IL-8), regulatory (IL-4, IL-13, IL-22), and inflammatory (IL-6, IL-17A) functions. Furthermore, we developed two new bioinformatics tools for more effective polyfunctional subset visualization and comparison between donors. Single-cell, multiplexed, proteomic profiling of CD19 CAR-T product reveals a diverse landscape of immune effector response of CD19 CAR-T cells to antigen-specific challenge, providing a new platform for capturing CAR-T product data for correlative analysis. Additionally, such high

  10. Integrated Analysis of Dysregulated ncRNA and mRNA Expression Profiles in Humans Exposed to Carbon Nanotubes.

    Directory of Open Access Journals (Sweden)

    Anna A Shvedova

    Full Text Available As the application of carbon nanotubes (CNT in consumer products continues to rise, studies have expanded to determine the associated risks of exposure on human and environmental health. In particular, several lines of evidence indicate that exposure to multi-walled carbon nanotubes (MWCNT could pose a carcinogenic risk similar to asbestos fibers. However, to date the potential markers of MWCNT exposure are not yet explored in humans.In the present study, global mRNA and ncRNA expression profiles in the blood of exposed workers, having direct contact with MWCNT aerosol for at least 6 months (n = 8, were compared with expression profiles of non-exposed (n = 7 workers (e.g., professional and/or technical staff from the same manufacturing facility.Significant changes in the ncRNA and mRNA expression profiles were observed between exposed and non-exposed worker groups. An integrative analysis of ncRNA-mRNA correlations was performed to identify target genes, functional relationships, and regulatory networks in MWCNT-exposed workers. The coordinated changes in ncRNA and mRNA expression profiles revealed a set of miRNAs and their target genes with roles in cell cycle regulation/progression/control, apoptosis and proliferation. Further, the identified pathways and signaling networks also revealed MWCNT potential to trigger pulmonary and cardiovascular effects as well as carcinogenic outcomes in humans, similar to those previously described in rodents exposed to MWCNTs.This study is the first to investigate aberrant changes in mRNA and ncRNA expression profiles in the blood of humans exposed to MWCNT. The significant changes in several miRNAs and mRNAs expression as well as their regulatory networks are important for getting molecular insights into the MWCNT-induced toxicity and pathogenesis in humans. Further large-scale prospective studies are necessary to validate the potential applicability of such changes in mRNAs and miRNAs as prognostic markers

  11. Ribosome Profiling Reveals Pervasive Translation Outside of Annotated Protein-Coding Genes

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    Nicholas T. Ingolia

    2014-09-01

    Full Text Available Ribosome profiling suggests that ribosomes occupy many regions of the transcriptome thought to be noncoding, including 5′ UTRs and long noncoding RNAs (lncRNAs. Apparent ribosome footprints outside of protein-coding regions raise the possibility of artifacts unrelated to translation, particularly when they occupy multiple, overlapping open reading frames (ORFs. Here, we show hallmarks of translation in these footprints: copurification with the large ribosomal subunit, response to drugs targeting elongation, trinucleotide periodicity, and initiation at early AUGs. We develop a metric for distinguishing between 80S footprints and nonribosomal sources using footprint size distributions, which validates the vast majority of footprints outside of coding regions. We present evidence for polypeptide production beyond annotated genes, including the induction of immune responses following human cytomegalovirus (HCMV infection. Translation is pervasive on cytosolic transcripts outside of conserved reading frames, and direct detection of this expanded universe of translated products enables efforts at understanding how cells manage and exploit its consequences.

  12. A genome scan revealed significant associations of growth traits with a major QTL and GHR2 in tilapia

    Science.gov (United States)

    Liu, Feng; Sun, Fei; Xia, Jun Hong; Li, Jian; Fu, Gui Hong; Lin, Grace; Tu, Rong Jian; Wan, Zi Yi; Quek, Delia; Yue, Gen Hua

    2014-01-01

    Growth is an important trait in animal breeding. However, the genetic effects underpinning fish growth variability are still poorly understood. QTL mapping and analysis of candidate genes are effective methods to address this issue. We conducted a genome-wide QTL analysis for growth in tilapia. A total of 10, 7 and 8 significant QTLs were identified for body weight, total length and standard length at 140 dph, respectively. The majority of these QTLs were sex-specific. One major QTL for growth traits was identified in the sex-determining locus in LG1, explaining 71.7%, 67.2% and 64.9% of the phenotypic variation (PV) of body weight, total length and standard length, respectively. In addition, a candidate gene GHR2 in a QTL was significantly associated with body weight, explaining 13.1% of PV. Real-time qPCR revealed that different genotypes at the GHR2 locus influenced the IGF-1 expression level. The markers located in the major QTL for growth traits could be used in marker-assisted selection of tilapia. The associations between GHR2 variants and growth traits suggest that the GHR2 gene should be an important gene that explains the difference in growth among tilapia species. PMID:25435025

  13. Tamarix microRNA Profiling Reveals New Insight into Salt Tolerance

    Directory of Open Access Journals (Sweden)

    Jianwen Wang

    2018-04-01

    Full Text Available The halophyte tamarisk (Tamarix is extremely salt tolerant, making it an ideal material for salt tolerance-related studies. Although many salt-responsive genes of Tamarix were identified in previous studies, there are no reports on the role of post-transcriptional regulation in its salt tolerance. We constructed six small RNA libraries of Tamarix chinensis roots with NaCl treatments. High-throughput sequencing of the six libraries was performed and microRNA expression profiles were constructed. We investigated salt-responsive microRNAs to uncover the microRNA-mediated genes regulation. From these analyses, 251 conserved and 18 novel microRNA were identified from all small RNAs. From 191 differentially expressed microRNAs, 74 co-expressed microRNAs were identified as salt-responsive candidate microRNAs. The most enriched GO (gene ontology terms for the 157 genes targeted by differentially expressed microRNAs suggested that transcriptions factors were highly active. Two hub microRNAs (miR414, miR5658, which connected by several target genes into an organic microRNA regulatory network, appeared to be the key regulators of post-transcriptional salt-stress responses. As the first survey on the tamarisk small RNAome, this study improves the understanding of tamarisk salt-tolerance mechanisms and will contribute to the molecular-assisted resistance breeding.

  14. Active Learning Strategies for Phenotypic Profiling of High-Content Screens.

    Science.gov (United States)

    Smith, Kevin; Horvath, Peter

    2014-06-01

    High-content screening is a powerful method to discover new drugs and carry out basic biological research. Increasingly, high-content screens have come to rely on supervised machine learning (SML) to perform automatic phenotypic classification as an essential step of the analysis. However, this comes at a cost, namely, the labeled examples required to train the predictive model. Classification performance increases with the number of labeled examples, and because labeling examples demands time from an expert, the training process represents a significant time investment. Active learning strategies attempt to overcome this bottleneck by presenting the most relevant examples to the annotator, thereby achieving high accuracy while minimizing the cost of obtaining labeled data. In this article, we investigate the impact of active learning on single-cell-based phenotype recognition, using data from three large-scale RNA interference high-content screens representing diverse phenotypic profiling problems. We consider several combinations of active learning strategies and popular SML methods. Our results show that active learning significantly reduces the time cost and can be used to reveal the same phenotypic targets identified using SML. We also identify combinations of active learning strategies and SML methods which perform better than others on the phenotypic profiling problems we studied. © 2014 Society for Laboratory Automation and Screening.

  15. Searching for a neurologic injury's Wechsler Adult Intelligence Scale-Third Edition profile.

    Science.gov (United States)

    Gonçalves, Marta A; Moura, Octávio; Castro-Caldas, Alexandre; Simões, Mário R

    2017-01-01

    This study aimed to investigate the presence of a Wechsler Adult Intelligence Scale-Third Edition (WAIS-III) cognitive profile in a Portuguese neurologic injured sample. The Portuguese WAIS-III was administered to 81 mixed neurologic patients and 81 healthy matched controls selected from the Portuguese standardization sample. Although the mixed neurologic injury group performed significantly lower than the healthy controls for the majority of the WAIS-III scores (i.e., composite measures, discrepancies, and subtests), the mean scores were within the normal range and, therefore, at risk of being unobserved in a clinical evaluation. ROC curves analysis showed poor to acceptable diagnostic accuracy for the WAIS-III composite measures and subtests (Working Memory Index and Digit Span revealed the highest accuracy for discriminating between participants, respectively). Multiple regression analysis showed that both literacy and the presence of brain injury were significant predictors for all of the composite measures. In addition, multiple regression analysis also showed that literacy, age of injury onset, and years of survival predicted all seven composite measures for the mixed neurologic injured group. Despite the failure to find a WAIS-III cognitive profile for mixed neurologic patients, the results showed a significant influence of brain lesion and literacy in the performance of the WAIS-III.

  16. tRNA modification profiles of the fast-proliferating cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Dong, Chao; Niu, Leilei; Song, Wei [State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Department of Obstetrics and Gynecology, Peking University Third Hospital, Peking University, Beijing 100191 (China); Xiong, Xin; Zhang, Xianhua [Departmentof Pharmacy, Peking University Third Hospital, Peking University, Beijing 100191 (China); Zhang, Zhenxi; Yang, Yi; Yi, Fan [State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Department of Obstetrics and Gynecology, Peking University Third Hospital, Peking University, Beijing 100191 (China); Zhan, Jun; Zhang, Hongquan [Department of Anatomy, Histology and Embryology, Laboratory of Molecular Cell Biology and Tumor Biology, Peking University, Beijing 100191 (China); Yang, Zhenjun; Zhang, Li-He [State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Department of Obstetrics and Gynecology, Peking University Third Hospital, Peking University, Beijing 100191 (China); Zhai, Suodi [Departmentof Pharmacy, Peking University Third Hospital, Peking University, Beijing 100191 (China); Li, Hua, E-mail: huali88@sina.com [State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Department of Obstetrics and Gynecology, Peking University Third Hospital, Peking University, Beijing 100191 (China); Ye, Min, E-mail: yemin@bjmu.edu.cn [State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Department of Obstetrics and Gynecology, Peking University Third Hospital, Peking University, Beijing 100191 (China); Du, Quan, E-mail: quan.du@pku.edu.cn [State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Department of Obstetrics and Gynecology, Peking University Third Hospital, Peking University, Beijing 100191 (China)

    2016-08-05

    Despite the recent progress in RNA modification study, a comprehensive modification profile is still lacking for mammalian cells. Using a quantitative HPLC/MS/MS assay, we present here a study where RNA modifications are examined in term of the major RNA species. With paired slow- and fast-proliferating cell lines, distinct RNA modification profiles are first revealed for diverse RNA species. Compared to mRNAs, increased ribose and nucleobase modifications are shown for the highly-structured tRNAs and rRNAs, lending support to their contribution to the formation of high-order structures. This study also reveals a dynamic tRNA modification profile in the fast-proliferating cells. In addition to cultured cells, this unique tRNA profile has been further confirmed with endometrial cancers and their adjacent normal tissues. Taken together, the results indicate that tRNA is a actively regulated RNA species in the fast-proliferating cancer cells, and suggest that they may play a more active role in biological process than expected. -- Highlights: •RNA modifications were first examined in term of the major RNA species. •A dynamic tRNA modifications was characterized for the fast-proliferating cells. •The unique tRNA profile was confirmed with endometrial cancers and their adjacent normal tissues. •tRNA was predicted as an actively regulated RNA species in the fast-proliferating cancer cells.

  17. tRNA modification profiles of the fast-proliferating cancer cells

    International Nuclear Information System (INIS)

    Dong, Chao; Niu, Leilei; Song, Wei; Xiong, Xin; Zhang, Xianhua; Zhang, Zhenxi; Yang, Yi; Yi, Fan; Zhan, Jun; Zhang, Hongquan; Yang, Zhenjun; Zhang, Li-He; Zhai, Suodi; Li, Hua; Ye, Min; Du, Quan

    2016-01-01

    Despite the recent progress in RNA modification study, a comprehensive modification profile is still lacking for mammalian cells. Using a quantitative HPLC/MS/MS assay, we present here a study where RNA modifications are examined in term of the major RNA species. With paired slow- and fast-proliferating cell lines, distinct RNA modification profiles are first revealed for diverse RNA species. Compared to mRNAs, increased ribose and nucleobase modifications are shown for the highly-structured tRNAs and rRNAs, lending support to their contribution to the formation of high-order structures. This study also reveals a dynamic tRNA modification profile in the fast-proliferating cells. In addition to cultured cells, this unique tRNA profile has been further confirmed with endometrial cancers and their adjacent normal tissues. Taken together, the results indicate that tRNA is a actively regulated RNA species in the fast-proliferating cancer cells, and suggest that they may play a more active role in biological process than expected. -- Highlights: •RNA modifications were first examined in term of the major RNA species. •A dynamic tRNA modifications was characterized for the fast-proliferating cells. •The unique tRNA profile was confirmed with endometrial cancers and their adjacent normal tissues. •tRNA was predicted as an actively regulated RNA species in the fast-proliferating cancer cells.

  18. Metabonomics reveals metabolite changes in biliary atresia infants.

    Science.gov (United States)

    Zhou, Kejun; Xie, Guoxiang; Wang, Jun; Zhao, Aihua; Liu, Jiajian; Su, Mingming; Ni, Yan; Zhou, Ying; Pan, Weihua; Che, Yanran; Zhang, Ting; Xiao, Yongtao; Wang, Yang; Wen, Jie; Jia, Wei; Cai, Wei

    2015-06-05

    Biliary atresia (BA) is a rare neonatal cholestatic disorder caused by obstruction of extra- and intra-hepatic bile ducts. If untreated, progressive liver cirrhosis will lead to death within 2 years. Early diagnosis and operation improve the outcome significantly. Infants with neonatal hepatitis syndrome (NHS) present similar symptoms, confounding the early diagnosis of BA. The lack of noninvasive diagnostic methods to differentiate BA from NHS greatly delays the surgery of BA infants, thus deteriorating the outcome. Here we performed a metabolomics study in plasma of BA, NHS, and healthy infants using gas chromatography-time-of-flight mass spectrometry. Scores plots of orthogonal partial least-squares discriminant analysis clearly separated BA from NHS and healthy infants. Eighteen metabolites were found to be differentially expressed between BA and NHS, among which seven (l-glutamic acid, l-ornithine, l-isoleucine, l-lysine, l-valine, l-tryptophan, and l-serine) were amino acids. The altered amino acids were quantitatively verified using ultraperformance liquid chromatography-tandem mass spectrometry. Ingenuity pathway analysis revealed the network of "Cellular Function and Maintenance, Hepatic System Development and Function, Neurological Disease" was altered most significantly. This study suggests that plasma metabolic profiling has great potential in differentiating BA from NHS, and amino acid metabolism is significantly different between the two diseases.

  19. Image-based compound profiling reveals a dual inhibitor of tyrosine kinase and microtubule polymerization

    OpenAIRE

    Tanabe, Kenji

    2016-01-01

    Small-molecule compounds are widely used as biological research tools and therapeutic drugs. Therefore, uncovering novel targets of these compounds should provide insights that are valuable in both basic and clinical studies. I developed a method for image-based compound profiling by quantitating the effects of compounds on signal transduction and vesicle trafficking of epidermal growth factor receptor (EGFR). Using six signal transduction molecules and two markers of vesicle trafficking, 570...

  20. Current density profile evolution in JET

    International Nuclear Information System (INIS)

    Stubberfield, P.M.; Balet, B.; Campbell, D.; Challis, C.D.; Cordey, J.G.; O'Rourke, J.; Hammett, G.; Schmidt, G.L.

    1989-01-01

    Simulation studies have been made of the current density profile evolution in discharges where the bootstrap current is expected to be significant. The changes predicted in the total current profile have been confirmed by comparison with experimental results. (author) 8 refs., 6 figs

  1. Facebook: Personality and privacy on profiles

    OpenAIRE

    Casado Riera, Carla; Oberst, Ursula; Carbonell, Xavier

    2015-01-01

    The aim of this study was to study the possible relationship between the privacy settings in Facebook profiles and two personality dimensions, extraversion and neuroticism, in relation to gender. The Privacy on Facebook Questionnaire and the Eysenck Personality Inventory was applied to a sample of 92 womenand 70 men, all users of Facebook. No significant relationship was found between extraversion or neuroticism and the privacy settings of Facebook profiles, but the results showed significant...

  2. Major urinary protein (MUP) profiles show dynamic changes rather than individual ‘barcode’ signatures

    Science.gov (United States)

    Thoß, M.; Luzynski, K.C.; Ante, M.; Miller, I.; Penn, D.J.

    2016-01-01

    House mice (Mus musculus) produce a variable number of major urinary proteins (MUPs), and studies suggest that each individual produces a unique MUP profile that provides a distinctive odor signature controlling individual and kin recognition. This ‘barcode hypothesis’ requires that MUP urinary profiles show high individual variability within populations and also high individual consistency over time, but tests of these assumptions are lacking. We analyzed urinary MUP profiles of 66 wild-caught house mice from eight populations using isoelectric focusing. We found that MUP profiles of wild male house mice are not individually unique, and though they were highly variable, closer inspection revealed that the variation strongly depended on MUP band type. The prominent (‘major) bands were surprisingly homogenous (and hence most MUPs are not polymorphic), but we also found inconspicuous (‘minor’) bands that were highly variable and therefore potential candidates for individual fingerprints. We also examined changes in urinary MUP profiles of 58 males over time (from 6 to 24 weeks of age), and found that individual MUP profiles and MUP concentration were surprisingly dynamic, and showed significant changes after puberty and during adulthood. Contrary to what we expected, however, the minor bands were the most variable over time, thus no good candidates for individual fingerprints. Although MUP profiles do not provide individual fingerprints, we found that MUP profiles were more similar among siblings than non-kin despite considerable fluctuation. Our findings show that MUP profiles are not highly stable over time, they do not show strong individual clustering, and thus challenge the barcode hypothesis. Within-individual dynamics of MUP profiles indicate a different function of MUPs in individual recognition than previously assumed and advocate an alternative hypothesis (‘dynamic changes’ hypothesis). PMID:26973837

  3. Carotta: Revealing Hidden Confounder Markers in Metabolic Breath Profiles

    Directory of Open Access Journals (Sweden)

    Anne-Christin Hauschild

    2015-06-01

    Full Text Available Computational breath analysis is a growing research area aiming at identifying volatile organic compounds (VOCs in human breath to assist medical diagnostics of the next generation. While inexpensive and non-invasive bioanalytical technologies for metabolite detection in exhaled air and bacterial/fungal vapor exist and the first studies on the power of supervised machine learning methods for profiling of the resulting data were conducted, we lack methods to extract hidden data features emerging from confounding factors. Here, we present Carotta, a new cluster analysis framework dedicated to uncovering such hidden substructures by sophisticated unsupervised statistical learning methods. We study the power of transitivity clustering and hierarchical clustering to identify groups of VOCs with similar expression behavior over most patient breath samples and/or groups of patients with a similar VOC intensity pattern. This enables the discovery of dependencies between metabolites. On the one hand, this allows us to eliminate the effect of potential confounding factors hindering disease classification, such as smoking. On the other hand, we may also identify VOCs associated with disease subtypes or concomitant diseases. Carotta is an open source software with an intuitive graphical user interface promoting data handling, analysis and visualization. The back-end is designed to be modular, allowing for easy extensions with plugins in the future, such as new clustering methods and statistics. It does not require much prior knowledge or technical skills to operate. We demonstrate its power and applicability by means of one artificial dataset. We also apply Carotta exemplarily to a real-world example dataset on chronic obstructive pulmonary disease (COPD. While the artificial data are utilized as a proof of concept, we will demonstrate how Carotta finds candidate markers in our real dataset associated with confounders rather than the primary disease (COPD

  4. Gene expression profiles of prohibitin in testes of Octopus tankahkeei (ot-phb) revealing its possible role during spermiogenesis.

    Science.gov (United States)

    Mao, Hai-Tao; Wang, Da-Hui; Lan, Zhou; Zhou, Hong; Yang, Wan-Xi

    2012-05-01

    Prohibitin is essential for intracellular homeostasis and stabilization of mitochondrial respiratory chain complexes. To explore its functions during spermiogenesis of Octopus tankahkeei (O. tankahkeei), we have cloned and sequenced the cDNA of this mammalian PHB homologue (termed ot-PHB) from the testes of O. tankahkeei. The 1165 bp ot-phb cDNA contains a 100 bp 5' UTR, a 882 bp open reading frame and a 183 bp 3' UTR. The putative ot-PHB protein owns a transmembrane domain from 6 to 31 amino acid (aa) and a putative PHB domain from 26 to 178 aa. Protein alignment demonstrated that ot-PHB had 73.3, 73.6, 74.0, 75.1, and 45.4% identity with its homologues in Homo sapiens, Mus muculus, Danio rerio, Xenopus tropicalis and Trypanosoma brucei, respectively. Tissue distribution profile analysis revealed its presence in all the tissues examined. In situ hybridization in spermiogenic cells demonstrated that ot-phb was expressed moderately at the beginning of the spermiogenesis. The abundance of transcripts increased in intermediate spermatids and in drastically remodeling final spermatids. In mature spermatozoa, the residuary transcripts concentrated around the chondriosomal mantle where mitochondria assemble around. In summary, the expression of ot-phb during spermiogenesis implicates a potential function of this protein during mitochondrial ubiquitination. It is the first time to implicate the role of prohibitin in cephalopod spermiogenesis.

  5. Seasonal effect on physiological, reproductive and fertility profiles in breeding mithun bulls

    Directory of Open Access Journals (Sweden)

    P Perumal

    2017-01-01

    Full Text Available Objective: To analyse the seasonal effect on physiological parameters, reproductive profiles and in vitro fertility in breeding mithun bulls.Methods: A total of ten adult mithun bulls age of 5 to 6 years old with good body condition (score 5-6 were selected from ICAR-NRC on Mithun, Jharnapani, Nagaland, India. The seasons were categorised into winter, spring, summer and autumn seasons based on the meteorological data and sunshine hours. The physiological parameters, reproductive profiles and in vitro fertility parameters were assessed during different seasons in mithun under the semi-intensive system of management.Results: The statistical analysis revealed that these experimental parameters were differed significantly (P<0.05 among the seasons and in overall spring and winter seasons were more beneficial in mithun breeding programme, although, the breeding in mithun occurred throughout the year with variation.Conclusions: It is concluded that collection & preservation of mithun semen and artificial insemination in mithun species during the season of spring and winter has significant beneficial effect in terms of semen production, freezability and fertility for artificial breeding programme in mithun under the semi-intensive system.

  6. Expression Profiling of Mitogen-Activated Protein Kinase Genes Reveals Their Evolutionary and Functional Diversity in Different Rubber Tree (Hevea brasiliensis Cultivars

    Directory of Open Access Journals (Sweden)

    Xiang Jin

    2017-10-01

    Full Text Available Rubber tree (Hevea brasiliensis is the only commercially cultivated plant for producing natural rubber, one of the most essential industrial raw materials. Knowledge of the evolutionary and functional characteristics of kinases in H. brasiliensis is limited because of the long growth period and lack of well annotated genome information. Here, we reported mitogen-activated protein kinases in H. brasiliensis (HbMPKs by manually checking and correcting the rubber tree genome. Of the 20 identified HbMPKs, four members were validated by proteomic data. Protein motif and phylogenetic analyses classified these members into four known groups comprising Thr-Glu-Tyr (TEY and Thr-Asp-Tyr (TDY domains, respectively. Evolutionary and syntenic analyses suggested four duplication events: HbMPK3/HbMPK6, HbMPK8/HbMPK9/HbMPK15, HbMPK10/HbMPK12 and HbMPK11/HbMPK16/HbMPK19. Expression profiling of the identified HbMPKs in roots, stems, leaves and latex obtained from three cultivars with different latex yield ability revealed tissue- and variety-expression specificity of HbMPK paralogues. Gene expression patterns under osmotic, oxidative, salt and cold stresses, combined with cis-element distribution analyses, indicated different regulation patterns of HbMPK paralogues. Further, Ka/Ks and Tajima analyses suggested an accelerated evolutionary rate in paralogues HbMPK10/12. These results revealed HbMPKs have diverse functions in natural rubber biosynthesis, and highlighted the potential possibility of using MPKs to improve stress tolerance in future rubber tree breeding.

  7. Tailoring in risk communication by linking risk profiles and communication preferences: The case of speeding of young car drivers.

    Science.gov (United States)

    Geber, Sarah; Baumann, Eva; Klimmt, Christoph

    2016-12-01

    Speeding is one of the most relevant risk behaviors for serious and fatal accidents, particularly among young drivers. This study presents a tailoring strategy for anti-speeding communication. By referring to their motivational dispositions toward speeding derived from motivational models of health behavior, young car drivers were segmented into different risk groups. In order to ensure that risk communication efforts would actually be capable to target these groups, the linkage between the risk profiles and communication preferences were explored. The study was conducted on the basis of survey data of 1168 German car drivers aged between 17 and 24 years. The data reveal four types of risk drivers significantly differing in their motivational profiles. Moreover, the findings show significant differences in communication habits and media use between these risk groups. By linking the risk profiles and communication preferences, implications for tailoring strategies of road safety communication campaigns are derived. Promising segmentation and targeting strategies are discussed also beyond the current case of anti-speeding campaigns. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Histological staining methods preparatory to laser capture microdissection significantly affect the integrity of the cellular RNA.

    Science.gov (United States)

    Wang, Hongyang; Owens, James D; Shih, Joanna H; Li, Ming-Chung; Bonner, Robert F; Mushinski, J Frederic

    2006-04-27

    Gene expression profiling by microarray analysis of cells enriched by laser capture microdissection (LCM) faces several technical challenges. Frozen sections yield higher quality RNA than paraffin-imbedded sections, but even with frozen sections, the staining methods used for histological identification of cells of interest could still damage the mRNA in the cells. To study the contribution of staining methods to degradation of results from gene expression profiling of LCM samples, we subjected pellets of the mouse plasma cell tumor cell line TEPC 1165 to direct RNA extraction and to parallel frozen sectioning for LCM and subsequent RNA extraction. We used microarray hybridization analysis to compare gene expression profiles of RNA from cell pellets with gene expression profiles of RNA from frozen sections that had been stained with hematoxylin and eosin (H&E), Nissl Stain (NS), and for immunofluorescence (IF) as well as with the plasma cell-revealing methyl green pyronin (MGP) stain. All RNAs were amplified with two rounds of T7-based in vitro transcription and analyzed by two-color expression analysis on 10-K cDNA microarrays. The MGP-stained samples showed the least introduction of mRNA loss, followed by H&E and immunofluorescence. Nissl staining was significantly more detrimental to gene expression profiles, presumably owing to an aqueous step in which RNA may have been damaged by endogenous or exogenous RNAases. RNA damage can occur during the staining steps preparatory to laser capture microdissection, with the consequence of loss of representation of certain genes in microarray hybridization analysis. Inclusion of RNAase inhibitor in aqueous staining solutions appears to be important in protecting RNA from loss of gene transcripts.

  9. Differential expression of OPN, VEGF-A, and HIF-1α and its clinical significance in hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    ZHENG Yan

    2013-01-01

    Full Text Available ObjectiveTo investigate the expression patterns of osteopontin (OPN, vascular endothelial growth factor-A (VEGF-A, and hypoxia-inducible factor-1α(HIF-1α in primary hepatocellular carcinoma (HCC and determine the clinical significance of this differential expression profile. MethodsImmunohistochemical staining of OPN, VEGF-A, and HIF-1α was carried out on primary HCC tissues from 90 patients, HCC-adjacent cirrhosis tissues from 20 of those patients, and normal liver tissues from 15 healthy controls. Correlations between expression levels and HCC clinicopathological characteristics were assessed by Spearman's correlation coefficient. ResultsThe majority of HCC tissues showed positive immunostaining for OPN (69/90, 76.67%, VEGF-A (64/90, 71.11%, and HIF-1α (66/90, 73.33%. OPN- and VEGF-A-positivity were significantly higher than the results from the cirrhosis tissues and normal tissues. HIF-1α-positivity was similar between the HCC and cirrhosis tissues, but both were significantly different from the normal tissues. The differential expressions of OPN, VEGF-A, and HIF-1α were significantly correlated with tumor thrombus, capsular integrity, tumor differentiation and stage, and metastasis (P<0.05. ConclusionHCC tissues overexpress OPN, VEGF-A, and HIF-1α and this differential profile may be related to HCC progression. Future investigations of this triad of factors may provide novel insights into the biological characteristics of HCC and reveal important targets of molecular therapy.

  10. Metabolic Profiling Reveals Effects of Age, Sexual Development and Neutering in Plasma of Young Male Cats.

    Science.gov (United States)

    Allaway, David; Gilham, Matthew S; Colyer, Alison; Jönsson, Thomas J; Swanson, Kelly S; Morris, Penelope J

    2016-01-01

    Neutering is a significant risk factor for obesity in cats. The mechanisms that promote neuter-associated weight gain are not well understood but following neutering, acute changes in energy expenditure and energy consumption have been observed. Metabolic profiling (GC-MS and UHPLC-MS-MS) was used in a longitudinal study to identify changes associated with age, sexual development and neutering in male cats fed a nutritionally-complete dry diet to maintain an ideal body condition score. At eight time points, between 19 and 52 weeks of age, fasted blood samples were taken from kittens neutered at either 19 weeks of age (Early Neuter (EN), n = 8) or at 31 weeks of age (Conventional Neuter (CN), n = 7). Univariate and multivariate analyses were used to compare plasma metabolites (n = 370) from EN and CN cats. Age was the primary driver of variance in the plasma metabolome, including a developmental change independent of neuter group between 19 and 21 weeks in lysolipids and fatty acid amides. Changes associated with sexual development and its subsequent loss were also observed, with differences at some time points observed between EN and CN cats for 45 metabolites (FDR pcats was the most significantly altered pathway, increasing during sexual development and decreasing acutely following neutering. Felinine is a testosterone-regulated, felid-specific glutathione derivative secreted in urine. Alterations in tryptophan, histidine and tocopherol metabolism observed in peripubertal cats may be to support physiological functions of glutathione following diversion of S-amino acids for urinary felinine secretion.

  11. Profiling of REST-dependent microRNAs reveals dynamic modes of expression

    Directory of Open Access Journals (Sweden)

    Zhengliang eGao

    2012-05-01

    Full Text Available Multipotent neural stem cells (NSCs possess the ability to self-renew and differentiate into both neurons and glia. However, the detailed mechanisms underlying NSC fate decisions are not well understood. Recent work suggest that the interaction between cell-type specific transcription factors and microRNAs (miRNAs is important as resident neural stem/progenitor cells give rise to functionally mature neurons. Recently, we demonstrated that the transcriptional repressor REST (RE1-silencing transcription factor is essential to prevent precocious neuronal differentiation and maintain NSC self-renewal in the adult hippocampus. Here we show that REST is required for orchestrating the expression of distinct subsets of miRNAs in primary mouse NSC cultures, a physiologically relevant cell type. Using miRNA array profiling, we identified known REST-regulated miRNA genes, as well as previously uncharacterized REST-dependent miRNAs. Interestingly, REST-regulated miRNAs undergo dynamic expression changes under differentiation conditions over time, but not under proliferation conditions. These results suggest that REST functions in a context-dependent manner through its target miRNAs for mediating neuronal production.

  12. Approximate Stokes Drift Profiles and their use in Ocean Modelling

    Science.gov (United States)

    Breivik, Oyvind; Bidlot, Jea-Raymond; Janssen, Peter A. E. M.; Mogensen, Kristian

    2016-04-01

    Deep-water approximations to the Stokes drift velocity profile are explored as alternatives to the monochromatic profile. The alternative profiles investigated rely on the same two quantities required for the monochromatic profile, viz the Stokes transport and the surface Stokes drift velocity. Comparisons against parametric spectra and profiles under wave spectra from the ERA-Interim reanalysis and buoy observations reveal much better agreement than the monochromatic profile even for complex sea states. That the profiles give a closer match and a more correct shear has implications for ocean circulation models since the Coriolis-Stokes force depends on the magnitude and direction of the Stokes drift profile and Langmuir turbulence parameterizations depend sensitively on the shear of the profile. Of the two Stokes drift profiles explored here, the profile based on the Phillips spectrum is by far the best. In particular, the shear near the surface is almost identical to that influenced by the f-5 tail of spectral wave models. The NEMO general circulation ocean model was recently extended to incorporate the Stokes-Coriolis force along with two other wave-related effects. The ECWMF coupled atmosphere-wave-ocean ensemble forecast system now includes these wave effects in the ocean model component (NEMO).

  13. Toxicological profile for uranium. Final report

    International Nuclear Information System (INIS)

    1990-12-01

    The ATSDR Toxicological Profile for Uranium is intended to characterize succinctly the toxicological and health effects information for the substance. It identifies and reviews the key literature that describes the substances's toxicological properties. Other literature is presented but described in less detail. The profile is not intended to be an exhaustive document; however, more comprehensive sources of specialty information are referenced. The profile begins with a public health statement, which describes in nontechnical language the substance's relevant toxicological properties. Following the statement is material that presents levels of significant human exposure and, where known, significant health effects. The adequacy of information to determine the substance's health effects is described. Research gaps in nontoxic and health effects information are described. Research gaps that are of significance to the protection of public health will be identified in a separate effort. The focus of the document is on health and toxicological information

  14. Toxicological profile for radon. Final report

    International Nuclear Information System (INIS)

    1990-12-01

    The ATSDR Toxicological Profile for Radon is intended to characterize succinctly the toxicological and health effects information for the substance. It identifies and reviews the key literature that describes the substance's toxicological properties. Other literature is presented but described in less detail. The profile is not intended to be an exhaustive document; however, more comprehensive sources of specialty information are referenced. The profile begins with a public health statement, which describes in nontechnical language the substance's relevant toxicological properties. Following the statement is material that presents levels of significant human exposure and, where known, significant health effects. The adequacy of information to determine the substance's health effects is described. Research gaps in nontoxic and health effects information are described. Research gaps that are of significance to the protection of public health will be identified in a separate effort. The focus of the document is on health and toxicological information

  15. Toxicological profile for plutonium. Final report

    International Nuclear Information System (INIS)

    1990-12-01

    The ATSDR Toxicological Profile for Plutonium is intended to characterize succinctly the toxicological and health effects information for the substance. It identifies and reviews the key literature that describes the substance's toxicological properties. Other literature is presented but described in less detail. The profile is not intended to be an exhaustive document; however, more comprehensive sources of specialty information are referenced. The profile begins with a public health statement, which describes in nontechnical language the substance's relevant toxicological properties. Following the statement is material that presents levels of significant human exposure and, where known, significant health effects. The adequacy of information to determine the substance's health effects is described. Research gaps in nontoxic and health effects information are described. Research gaps that are of significance to the protection of public health will be identified in a separate effort. The focus of the document is on health and toxicological information

  16. Toxicological profile for radium. Final report

    International Nuclear Information System (INIS)

    1990-12-01

    The ATSDR Toxicological Profile for Radium is intended to characterize succinctly the toxicological and health effects information for the substance. It identifies and reviews the key literature that describes the substances' toxicological properties. Other literature is presented but described in less detail. The profile is not intended to be an exhaustive document; however, more comprehensive sources of specialty information are referenced. The profile begins with a public health statement, which describes in nontechnical language the substance's relevant toxicological properties. Following the statement is material that presents levels of significant human exposure and, where known, significant health effects. The adequacy of information to determine the substance's health effects is described. Research gaps in nontoxic and health effects information are described. Research gaps that are of significance to the protection of public health will be identified in a separate effort. The focus of the document is on health and toxicological information

  17. High frequency longitudinal profiling reveals hydrologic controls on solute sourcing, transport and processing in a karst river

    Science.gov (United States)

    Hensley, R. T.; Cohen, M. J.; Spangler, M.; Gooseff, M. N.

    2017-12-01

    The lower Santa Fe River is a large, karst river of north Florida, fed by numerous artesian springs and also containing multiple sink-rise systems. We performed repeated longitudinal profiles collecting very high frequency measurements of multiple stream parameters including temperature, dissolved oxygen, carbon dioxide, pH, dissolved organic matter, nitrate, ammonium, phosphate and turbidity. This high frequency dataset provided a spatially explicit understanding of solute sources and coupled biogeochemical processing rates along the 25 km study reach. We noted marked changes in river profiles as the river transitioned from low to high flow during the onset of the wet season. The role of lateral inflow from springs as the primary solute source was greatly reduced under high flow conditions. Effects of sink-rise systems, which under low flow conditions allow the majority of flow to bypass several kilometer long sections of the main channel, virtually disappeared under high flow conditions. Impeded light transmittance at high flow reduced primary production and by extension assimilatory nutrient uptake. This study demonstrates how high frequency longitudinal profiling can be used to observe how hydrologic conditions can alter groundwater-surface water interactions and modulate the sourcing, transport and biogeochemical processing of stream solutes.

  18. Glutaminemia prognostic significance in critical surgical patients - An analysis of plasma aminogram profile.

    Science.gov (United States)

    Costa, Beatriz Pinto; Martins, Paulo; Verissimo, Carla; Simões, Marta; Tomé, Marisa; Grazina, Manuela; Pimentel, Jorge; Sousa, Francisco Castro

    2017-07-28

    Glutamine depletion is common in the critically-ill patients. Glutaminemia lower than 420 μmol/l has been considered as an independent predictive factor of mortality, but the indications for exogenous glutamine supplementation remain controversial. This study intends to determine the glutaminemia profile in critical surgical patients and to investigate its correlation with the severity indexes and the prognosis. A prospective study of 28 adult critical surgical patients was performed. Plasma amino acid concentrations were quantified, by ion exchange chromatography, at the moment of admission and at the first and third days, and compared with those of 11 reference healthy individuals. Severity indexes and parameters of prognosis were registered. In critical surgical patients, mean glutaminemia at admission was lower than that of control individuals (385.1 ± 123.1 versus515 ± 57.9 μmol/l, p = 0.002) and decreased until the third day (p = 0.042). Prevalence of severe hypoglutaminemia (definition of the indications for glutamine supplementation.

  19. Comparative transcriptional profiling of human Merkel cells and Merkel cell carcinoma.

    Science.gov (United States)

    Mouchet, Nicolas; Coquart, Nolwenn; Lebonvallet, Nicolas; Le Gall-Ianotto, Christelle; Mogha, Ariane; Fautrel, Alain; Boulais, Nicholas; Dréno, Brigitte; Martin, Ludovic; Hu, Weiguo; Galibert, Marie-Dominique; Misery, Laurent

    2014-12-01

    Merkel cell carcinoma is believed to be derived from Merkel cells after infection by Merkel cell polyomavirus (MCPyV) and other poorly understood events. Transcriptional profiling using cDNA microarrays was performed on cells from MCPy-negative and MCPy-positive Merkel cell carcinomas and isolated normal Merkel cells. This microarray revealed numerous significantly upregulated genes and some downregulated genes. The extensive list of genes that were identified in these experiments provides a large body of potentially valuable information of Merkel cell carcinoma carcinogenesis and could represent a source of potential targets for cancer therapy. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. Different continuous cropping spans significantly affect microbial community membership and structure in a vanilla-grown soil as revealed by deep pyrosequencing.

    Science.gov (United States)

    Xiong, Wu; Zhao, Qingyun; Zhao, Jun; Xun, Weibing; Li, Rong; Zhang, Ruifu; Wu, Huasong; Shen, Qirong

    2015-07-01

    In the present study, soil bacterial and fungal communities across vanilla continuous cropping time-series fields were assessed through deep pyrosequencing of 16S ribosomal RNA (rRNA) genes and internal transcribed spacer (ITS) regions. The results demonstrated that the long-term monoculture of vanilla significantly altered soil microbial communities. Soil fungal diversity index increased with consecutive cropping years, whereas soil bacterial diversity was relatively stable. Bray-Curtis dissimilarity cluster and UniFrac-weighted principal coordinate analysis (PCoA) revealed that monoculture time was the major determinant for fungal community structure, but not for bacterial community structure. The relative abundances (RAs) of the Firmicutes, Actinobacteria, Bacteroidetes, and Basidiomycota phyla were depleted along the years of vanilla monoculture. Pearson correlations at the phyla level demonstrated that Actinobacteria, Armatimonadetes, Bacteroidetes, Verrucomicrobia, and Firmicutes had significant negative correlations with vanilla disease index (DI), while no significant correlation for fungal phyla was observed. In addition, the amount of the pathogen Fusarium oxysporum accumulated with increasing years and was significantly positively correlated with vanilla DI. By contrast, the abundance of beneficial bacteria, including Bradyrhizobium and Bacillus, significantly decreased over time. In sum, soil weakness and vanilla stem wilt disease after long-term continuous cropping can be attributed to the alteration of the soil microbial community membership and structure, i.e., the reduction of the beneficial microbes and the accumulation of the fungal pathogen.

  1. Metabolomic profiling reveals a role for CPT1c in neuronal oxidative metabolism.

    Science.gov (United States)

    Lee, Jieun; Wolfgang, Michael J

    2012-10-25

    Carnitine Palmitoyltransferase-1c (CPT1c) is a neuron specific homologue of the carnitine acyltransferase family of enzymes. CPT1 isoenzymes transfer long chain acyl groups to carnitine. This constitutes a rate setting step for mitochondrial fatty acid beta-oxidation by facilitating the initial step in acyl transfer to the mitochondrial matrix. In general, neurons do not heavily utilize fatty acids for bioenergetic needs and definitive enzymatic activity has been unable to be demonstrated for CPT1c. Although there are studies suggesting an enzymatic role of CPT1c, its role in neurochemistry remains elusive. In order to better understand how CPT1c functions in neural metabolism, we performed unbiased metabolomic profiling on wild-type (WT) and CPT1c knockout (KO) mouse brains. Consistent with the notion that CPT1c is not involved in fatty acid beta-oxidation, there were no changes in metabolites associated with fatty acid oxidation. Endocannabinoids were suppressed in the CPT1c KO, which may explain the suppression of food intake seen in CPT1c KO mice. Although products of beta-oxidation were unchanged, small changes in carnitine and carnitine metabolites were observed. Finally, we observed changes in redox homeostasis including a greater than 2-fold increase in oxidized glutathione. This indicates that CPT1c may play a role in neural oxidative metabolism. Steady-state metabolomic analysis of CPT1c WT and KO mouse brains identified a small number of metabolites that differed between CPT1c WT and KO mice. The subtle changes in a broad range of metabolites in vivo indicate that CPT1c does not play a significant or required role in fatty acid oxidation; however, it could play an alternative role in neuronal oxidative metabolism.

  2. Metabolomic profiling reveals a role for CPT1c in neuronal oxidative metabolism

    Directory of Open Access Journals (Sweden)

    Lee Jieun

    2012-10-01

    Full Text Available Abstract Background Carnitine Palmitoyltransferase-1c (CPT1c is a neuron specific homologue of the carnitine acyltransferase family of enzymes. CPT1 isoenzymes transfer long chain acyl groups to carnitine. This constitutes a rate setting step for mitochondrial fatty acid beta-oxidation by facilitating the initial step in acyl transfer to the mitochondrial matrix. In general, neurons do not heavily utilize fatty acids for bioenergetic needs and definitive enzymatic activity has been unable to be demonstrated for CPT1c. Although there are studies suggesting an enzymatic role of CPT1c, its role in neurochemistry remains elusive. Results In order to better understand how CPT1c functions in neural metabolism, we performed unbiased metabolomic profiling on wild-type (WT and CPT1c knockout (KO mouse brains. Consistent with the notion that CPT1c is not involved in fatty acid beta-oxidation, there were no changes in metabolites associated with fatty acid oxidation. Endocannabinoids were suppressed in the CPT1c KO, which may explain the suppression of food intake seen in CPT1c KO mice. Although products of beta-oxidation were unchanged, small changes in carnitine and carnitine metabolites were observed. Finally, we observed changes in redox homeostasis including a greater than 2-fold increase in oxidized glutathione. This indicates that CPT1c may play a role in neural oxidative metabolism. Conclusions Steady-state metabolomic analysis of CPT1c WT and KO mouse brains identified a small number of metabolites that differed between CPT1c WT and KO mice. The subtle changes in a broad range of metabolites in vivo indicate that CPT1c does not play a significant or required role in fatty acid oxidation; however, it could play an alternative role in neuronal oxidative metabolism.

  3. OBSERVATIONS AND SIMULATIONS OF THE Na i D{sub 1} LINE PROFILES IN AN M-CLASS SOLAR FLARE

    Energy Technology Data Exchange (ETDEWEB)

    Kuridze, D.; Mathioudakis, M.; Jess, D. B.; Grant, S. D. T.; Kawate, T.; Keenan, F. P. [Astrophysics Research Centre, School of Mathematics and Physics, Queen’s University Belfast, Belfast BT7 1NN (United Kingdom); Christian, D. J. [Department of Physics and Astronomy, California State University, Northridge, CA 91330 (United States); Kowalski, A. F.; Allred, J. C. [NASA/Goddard Space Flight Center, Code 671, Greenbelt, MD 20771 (United States); Simões, P. J. A. [SUPA School of Physics and Astronomy, University of Glasgow, Glasgow G12 8QQ (United Kingdom)

    2016-12-01

    We study the temporal evolution of the Na i D{sub 1} line profiles in the M3.9 flare SOL2014-06-11T21:03 UT, using observations at high spectral resolution obtained with the Interferometric Bidimensional Spectrometer instrument on the Dunn Solar Telescope combined with radiative hydrodynamic simulations. Our results show a significant increase in the intensities of the line core and wings during the flare. The analysis of the line profiles from the flare ribbons reveals that the Na i D{sub 1} line has a central reversal with excess emission in the blue wing (blue asymmetry). We combine RADYN and RH simulations to synthesize Na i D{sub 1} line profiles of the flaring atmosphere and find good agreement with the observations. Heating with a beam of electrons modifies the radiation field in the flaring atmosphere and excites electrons from the ground state 3s {sup 2}S to the first excited state 3p {sup 2}P, which in turn modifies the relative population of the two states. The change in temperature and the population density of the energy states make the sodium line profile revert from absorption into emission. Furthermore, the rapid changes in temperature break the pressure balance between the different layers of the lower atmosphere, generating upflow/downflow patterns. Analysis of the simulated spectra reveals that the asymmetries of the Na i D{sub 1} flare profile are produced by the velocity gradients in the lower solar atmosphere.

  4. Metabolome and proteome profiling of complex I deficiency induced by rotenone.

    Science.gov (United States)

    Gielisch, Ina; Meierhofer, David

    2015-01-02

    Complex I (CI; NADH dehydrogenase) deficiency causes mitochondrial diseases, including Leigh syndrome. A variety of clinical symptoms of CI deficiency are known, including neurodegeneration. Here, we report an integrative study combining liquid chromatography-mass spectrometry (LC-MS)-based metabolome and proteome profiling in CI deficient HeLa cells. We report a rapid LC-MS-based method for the relative quantification of targeted metabolome profiling with an additional layer of confidence by applying multiple reaction monitoring (MRM) ion ratios for further identity confirmation and robustness. The proteome was analyzed by label-free quantification (LFQ). More than 6000 protein groups were identified. Pathway and network analyses revealed that the respiratory chain was highly deregulated, with metabolites such as FMN, FAD, NAD(+), and ADP, direct players of the OXPHOS system, and metabolites of the TCA cycle decreased up to 100-fold. Synthesis of functional iron-sulfur clusters, which are of central importance for the electron transfer chain, and degradation products like bilirubin were also significantly reduced. Glutathione metabolism on the pathway level, as well as individual metabolite components such as NADPH, glutathione (GSH), and oxidized glutathione (GSSG), was downregulated. Overall, metabolome and proteome profiles in CI deficient cells correlated well, supporting our integrated approach.

  5. A chronological expression profile of gene activity during embryonic mouse brain development.

    Science.gov (United States)

    Goggolidou, P; Soneji, S; Powles-Glover, N; Williams, D; Sethi, S; Baban, D; Simon, M M; Ragoussis, I; Norris, D P

    2013-12-01

    The brain is a functionally complex organ, the patterning and development of which are key to adult health. To help elucidate the genetic networks underlying mammalian brain patterning, we conducted detailed transcriptional profiling during embryonic development of the mouse brain. A total of 2,400 genes were identified as showing differential expression between three developmental stages. Analysis of the data identified nine gene clusters to demonstrate analogous expression profiles. A significant group of novel genes of as yet undiscovered biological function were detected as being potentially relevant to brain development and function, in addition to genes that have previously identified roles in the brain. Furthermore, analysis for genes that display asymmetric expression between the left and right brain hemispheres during development revealed 35 genes as putatively asymmetric from a combined data set. Our data constitute a valuable new resource for neuroscience and neurodevelopment, exposing possible functional associations between genes, including novel loci, and encouraging their further investigation in human neurological and behavioural disorders.

  6. Regulators of Long-Term Memory Revealed by Mushroom Body-Specific Gene Expression Profiling in Drosophila melanogaster.

    Science.gov (United States)

    Widmer, Yves F; Bilican, Adem; Bruggmann, Rémy; Sprecher, Simon G

    2018-06-20

    Memory formation is achieved by genetically tightly controlled molecular pathways that result in a change of synaptic strength and synapse organization. While for short-term memory traces rapidly acting biochemical pathways are in place, the formation of long-lasting memories requires changes in the transcriptional program of a cell. Although many genes involved in learning and memory formation have been identified, little is known about the genetic mechanisms required for changing the transcriptional program during different phases of long-term memory formation. With Drosophila melanogaster as a model system we profiled transcriptomic changes in the mushroom body, a memory center in the fly brain, at distinct time intervals during appetitive olfactory long-term memory formation using the targeted DamID technique. We describe the gene expression profiles during these phases and tested 33 selected candidate genes for deficits in long-term memory formation using RNAi knockdown. We identified 10 genes that enhance or decrease memory when knocked-down in the mushroom body. For vajk-1 and hacd1 , the two strongest hits, we gained further support for their crucial role in appetitive learning and forgetting. These findings show that profiling gene expression changes in specific cell-types harboring memory traces provides a powerful entry point to identify new genes involved in learning and memory. The presented transcriptomic data may further be used as resource to study genes acting at different memory phases. Copyright © 2018, Genetics.

  7. Metabolomic Profiling in Individuals with a Failing Kidney Allograft.

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    Roberto Bassi

    Full Text Available Alteration of certain metabolites may play a role in the pathophysiology of renal allograft disease.To explore metabolomic abnormalities in individuals with a failing kidney allograft, we analyzed by liquid chromatography-mass spectrometry (LC-MS/MS; for ex vivo profiling of serum and urine and two dimensional correlated spectroscopy (2D COSY; for in vivo study of the kidney graft 40 subjects with varying degrees of chronic allograft dysfunction stratified by tertiles of glomerular filtration rate (GFR; T1, T2, T3. Ten healthy non-allograft individuals were chosen as controls.LC-MS/MS analysis revealed a dose-response association between GFR and serum concentration of tryptophan, glutamine, dimethylarginine isomers (asymmetric [A]DMA and symmetric [S]DMA and short-chain acylcarnitines (C4 and C12, (test for trend: T1-T3 = p<0.05; p = 0.01; p<0.001; p = 0.01; p = 0.01; p<0.05, respectively. The same association was found between GFR and urinary levels of histidine, DOPA, dopamine, carnosine, SDMA and ADMA (test for trend: T1-T3 = p<0.05; p<0.01; p = 0.001; p<0.05; p = 0.001; p<0.001; p<0.01, respectively. In vivo 2D COSY of the kidney allograft revealed significant reduction in the parenchymal content of choline, creatine, taurine and threonine (all: p<0.05 in individuals with lower GFR levels.We report an association between renal function and altered metabolomic profile in renal transplant individuals with different degrees of kidney graft function.

  8. Audiologist-patient communication profiles in hearing rehabilitation appointments.

    Science.gov (United States)

    Meyer, Carly; Barr, Caitlin; Khan, Asaduzzaman; Hickson, Louise

    2017-08-01

    To profile the communication between audiologists and patients in initial appointments on a biomedical-psychosocial continuum; and explore the associations between these profiles and 1) characteristics of the appointment and 2) patients' decisions to pursue hearing aids. Sixty-three initial hearing assessment appointments were filmed and audiologist-patient communication was coded using the Roter Interaction Analysis System. A hierarchical cluster analysis was conducted to profile audiologist-patient communication, after which regression modelling and Chi-squared analyses were conducted. Two distinct audiologist-patient communication profiles were identified during both the history taking phase (46=biopsychosocial profile, 15=psychosocial profile) and diagnosis and management planning phase (45=expanded biomedical profile, 11=narrowly biomedical profile). Longer appointments were significantly more likely to be associated with an expanded biomedical interaction during the diagnosis and management planning phase. No significant associations were found between audiologist-patient communication profile and patients' decisions to pursue hearing aids. Initial audiology consultations appear to remain clinician-centred. Three quarters of appointments began with a biopsychosocial interaction; however, 80% ended with an expanded biomedical interaction. Findings suggest that audiologists could consider modifying their communication in initial appointments to more holistically address the needs of patients. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. RNA-Seq and molecular docking reveal multi-level pesticide resistance in the bed bug

    Directory of Open Access Journals (Sweden)

    Mamidala Praveen

    2012-01-01

    Full Text Available Abstract Background Bed bugs (Cimex lectularius are hematophagous nocturnal parasites of humans that have attained high impact status due to their worldwide resurgence. The sudden and rampant resurgence of C. lectularius has been attributed to numerous factors including frequent international travel, narrower pest management practices, and insecticide resistance. Results We performed a next-generation RNA sequencing (RNA-Seq experiment to find differentially expressed genes between pesticide-resistant (PR and pesticide-susceptible (PS strains of C. lectularius. A reference transcriptome database of 51,492 expressed sequence tags (ESTs was created by combining the databases derived from de novo assembled mRNA-Seq tags (30,404 ESTs and our previous 454 pyrosequenced database (21,088 ESTs. The two-way GLMseq analysis revealed ~15,000 highly significant differentially expressed ESTs between the PR and PS strains. Among the top 5,000 differentially expressed ESTs, 109 putative defense genes (cuticular proteins, cytochrome P450s, antioxidant genes, ABC transporters, glutathione S-transferases, carboxylesterases and acetyl cholinesterase involved in penetration resistance and metabolic resistance were identified. Tissue and development-specific expression of P450 CYP3 clan members showed high mRNA levels in the cuticle, Malpighian tubules, and midgut; and in early instar nymphs, respectively. Lastly, molecular modeling and docking of a candidate cytochrome P450 (CYP397A1V2 revealed the flexibility of the deduced protein to metabolize a broad range of insecticide substrates including DDT, deltamethrin, permethrin, and imidacloprid. Conclusions We developed significant molecular resources for C. lectularius putatively involved in metabolic resistance as well as those participating in other modes of insecticide resistance. RNA-Seq profiles of PR strains combined with tissue-specific profiles and molecular docking revealed multi-level insecticide

  10. Diagnostic and Prognostic Significance of Lipid Profiles in Holstein Dairy Cattle with Displaced Abomasum: Before and After Surgical Operation

    Directory of Open Access Journals (Sweden)

    Arafat Khalphallah

    2016-01-01

    Full Text Available The study aimed to describe the pattern of changes in clinical findings and lipid metabolism profiles in dairy cattle with displacement of the abomasum (DA from day 0 until day 30 after operation. The study was conducted on DA cattle (n= 25 belonged to dairy farms in Hokkaido area, Japan. Cows were examined and sampled at days 0 (operation, 7 and 30. They were clinically and biochemically examined to estimate BCS and many serum biochemical constituents such as lecithin:cholesterol acyltransferase (LCAT and apolipoprotein B-100 (apoB-100, β-hydroxybutyric acid (BHBA, non-esterified fatty acids (NEFAs and aspartate amino transferase (AST. Based on blood BHBA at day 0, DA cows were classified into three categories; DA only (<1.2 mmol/l, DA with subclinical ketosis (DA SCK (1.2-2.4 mmol/l and DA with clinical ketosis (DA CK (≥2.5 mmol/l. The changes in the pattern of serum biochemical constituents throughout this study indicated recovery of diseased cows and significant effect of surgical operation. Serum biochemical constituents returned to their physiological values indicating that these cows were restoring their normal physiological status. This was reflected through a significant (P<0.05 elevation of LCAT, apoB-100, and cholesterol and a significant (P<0.05 reduction in AST, NEFAs and BHBA (Not in DA group, in all DA groups particularly at day 30 when their values compared with those at day 0. The current study also recorded no remarkable changes (P>0.05 between the diseased groups except for NEFA and BHBA (at day 0 between DA group and the other two groups at any of the three sampling days.

  11. Transcriptome Profiling of the Abdominal Skin of Larimichthys crocea in Light Stress

    Science.gov (United States)

    Han, Zhaofang; Lv, Changhuan; Xiao, Shijun; Ye, Kun; Zhang, Dongling; Tsai, Huai Jen; Wang, Zhiyong

    2018-04-01

    Large yellow croaker ( Larimichthys crocea), one of the most important marine fish species in China, can change its abdominal skin color when it is shifted from light to dark or from dark to light, providing us an opportunity of investigating the molecular responding mechanism of teleost in light stress. The gene expression profile of fish under light stress is rarely documented. In this research, the transcriptome profiles of the abdominal skin of L. crocea exposed to light or dark for 0 h, 0.5 h and 2 h were produced by next-generation sequencing (NGS). The cluster results demonstrated that stress period, rather than light intensity ( e.g., light or dark), is the major influencing factor. Differently expressed genes (DEGs) were identified between 0 h and 0.5 h groups, between 0 h and 2 h groups, between 0.5 h light and 0.5 h dark, and between 2 h light and 2 h dark, respectively. The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) annotation revealed that the genes relating to immunity, energy metabolism, and cytoskeletal protein binding were significantly enriched. The detailed analysis of transcriptome profiles also revealed regular gene expression trends, indicating that the elaborate gene regulation networks underlined the molecular responses of the fish to light stress. This transcriptome analysis suggested that systematic and complicated regulatory cascades were functionally activated in response to external stress, and coloration change caused by light stress was mainly attributed to the change in the density of chromatophores for L. crocea. This study also provided valuable information for skin coloration or light stress research on other marine fish species.

  12. Temporal gene expression profiling reveals CEBPD as a candidate regulator of brain disease in prosaposin deficient mice

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    Ran Huimin

    2008-08-01

    Full Text Available Abstract Background Prosaposin encodes, in tandem, four small acidic activator proteins (saposins with specificities for glycosphingolipid (GSL hydrolases in lysosomes. Extensive GSL storage occurs in various central nervous system regions in mammalian prosaposin deficiencies. Results Our hypomorphic prosaposin deficient mouse, PS-NA, exhibited 45% WT levels of brain saposins and showed neuropathology that included neuronal GSL storage and Purkinje cell loss. Impairment of neuronal function was observed as early as 6 wks as demonstrated by the narrow bridges tests. Temporal transcriptome microarray analyses of brain tissues were conducted with mRNA from three prosaposin deficient mouse models: PS-NA, prosaposin null (PS-/- and a V394L/V394L glucocerebrosidase mutation combined with PS-NA (4L/PS-NA. Gene expression alterations in cerebrum and cerebellum were detectable at birth preceding the neuronal deficits. Differentially expressed genes encompassed a broad spectrum of cellular functions. The number of down-regulated genes was constant, but up-regulated gene numbers increased with age. CCAAT/enhancer-binding protein delta (CEBPD was the only up-regulated transcription factor in these two brain regions of all three models. Network analyses revealed that CEBPD has functional relationships with genes in transcription, pro-inflammation, cell death, binding, myelin and transport. Conclusion These results show that: 1 Regionally specific gene expression abnormalities precede the brain histological and neuronal function changes, 2 Temporal gene expression profiles provide insights into the molecular mechanism during the GSL storage disease course, and 3 CEBPD is a candidate regulator of brain disease in prosaposin deficiency to participate in modulating disease acceleration or progression.

  13. Values profile of health career students from Southern Chile

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    Alex Véliz Burgos

    2017-02-01

    Full Text Available Objective: Higher education institutions must include curricular strategies that enable students to make decisions according to the values and principles related to their professions. The objective of this study was to determine the values profile expressed by health career students from Southern Chile. Materials and methods: This is a quantitative cross-sectional descriptive study with a purposive sample of 242 (M = 20.1 years old nursing, psychology and kinesiology students to whom the Schwartz Value Survey was applied. Software SPSS 20.0 was used to perform a hierarchical clustering analysis and verify the values dimensions associated with each other. One-way ANOVA with post-hoc tests were conducted to verify the means differences among the scores of the values subscales. Results: Two large homogeneous clusters of values were identified. One consisted of the dimensions of Conformity, Security, Achievement, Tradition and Benevolence, and the other one of the dimensions of Hedonism and Stimulation. During the analysis of means, significant statistical differences were observed between the groups in the dimensions of Universalism, Power, Self-Direction, Benevolence, Conformity, Tradition and Achievement (p < 0.01. The most outstanding means differences were those between psychology and nursing students. In the dimensions of Power, Conformity and Tradition, kinesiology and nursing students showed higher means than psychology students (p < 0.01. Conclusions: The results reveal health career students’ values profile. The next step should be to compare those profiles with the values profile of graduates from each discipline, in order to contribute to the strengthening of the dimensions which students from each career consider important for their professional performance.

  14. Phenylpropanoid profiling reveals a class of hydroxycinnamoyl glucaric acid conjugates in Isatis tinctoria leaves.

    Science.gov (United States)

    Nguyen, Thi-Kieu-Oanh; Jamali, Arash; Grand, Eric; Morreel, Kris; Marcelo, Paulo; Gontier, Eric; Dauwe, Rebecca

    2017-12-01

    The brassicaceous herb, Isatis tinctoria, is an ancient medicinal plant whose rosette leaf extracts have anti-inflammatory and anti-allergic activity. Brassicaceae are known to accumulate a variety of phenylpropanoids in their rosette leaves acting as antioxidants and a UV-B shield, and these compounds often have pharmacological potential. Nevertheless, knowledge about the phenylpropanoid content of I. tinctoria leaves remains limited to the characterization of a number of flavonoids. In this research, we profiled the methanol extracts of I. tinctoria fresh leaf extracts by liquid chromatography - mass spectrometry (LC-MS) and focused on the phenylpropanoid derivatives. We report the structural characterization of 99 compounds including 18 flavonoids, 21 mono- or oligolignols, 2 benzenoids, and a wide spectrum of 58 hydroxycinnamic acid esters. Besides the sinapate esters of malate, glucose and gentiobiose, which are typical of brassicaceous plants, these conjugates comprised a large variety of glucaric acid esters that have not previously been reported in plants. Feeding with 13 C 6 -glucaric acid showed that glucaric acid is an acyl acceptor of an as yet unknown acyltransferase activity in I. tinctoria rosette leaves. The large amount of hydroxycinnamic acid derivatives changes radically our view of the woad metabolite profile and potentially contributes to the pharmacological activity of I. tinctoria leaf extracts. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Diagnosis of adenylosuccinate lyase deficiency by metabolomic profiling in plasma reveals a phenotypic spectrum

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    Taraka R. Donti

    2016-09-01

    Full Text Available Adenylosuccinate lyase (ADSL deficiency is a rare autosomal recessive neurometabolic disorder that presents with a broad-spectrum of neurological and physiological symptoms. The ADSL gene produces an enzyme with binary molecular roles in de novo purine synthesis and purine nucleotide recycling. The biochemical phenotype of ADSL deficiency, accumulation of SAICAr and succinyladenosine (S-Ado in biofluids of affected individuals, serves as the traditional target for diagnosis with targeted quantitative urine purine analysis employed as the predominate method of detection. In this study, we report the diagnosis of ADSL deficiency using an alternative method, untargeted metabolomic profiling, an analytical scheme capable of generating semi-quantitative z-score values for over 1000 unique compounds in a single analysis of a specimen. Using this method to analyze plasma, we diagnosed ADSL deficiency in four patients and confirmed these findings with targeted quantitative biochemical analysis and molecular genetic testing. ADSL deficiency is part of a large a group of neurometabolic disorders, with a wide range of severity and sharing a broad differential diagnosis. This phenotypic similarity among these many inborn errors of metabolism (IEMs has classically stood as a hurdle in their initial diagnosis and subsequent treatment. The findings presented here demonstrate the clinical utility of metabolomic profiling in the diagnosis of ADSL deficiency and highlights the potential of this technology in the diagnostic evaluation of individuals with neurologic phenotypes.

  16. Analysis of global gene expression in Brachypodium distachyon reveals extensive network plasticity in response to abiotic stress.

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    Henry D Priest

    Full Text Available Brachypodium distachyon is a close relative of many important cereal crops. Abiotic stress tolerance has a significant impact on productivity of agriculturally important food and feedstock crops. Analysis of the transcriptome of Brachypodium after chilling, high-salinity, drought, and heat stresses revealed diverse differential expression of many transcripts. Weighted Gene Co-Expression Network Analysis revealed 22 distinct gene modules with specific profiles of expression under each stress. Promoter analysis implicated short DNA sequences directly upstream of module members in the regulation of 21 of 22 modules. Functional analysis of module members revealed enrichment in functional terms for 10 of 22 network modules. Analysis of condition-specific correlations between differentially expressed gene pairs revealed extensive plasticity in the expression relationships of gene pairs. Photosynthesis, cell cycle, and cell wall expression modules were down-regulated by all abiotic stresses. Modules which were up-regulated by each abiotic stress fell into diverse and unique gene ontology GO categories. This study provides genomics resources and improves our understanding of abiotic stress responses of Brachypodium.

  17. 78 FR 55772 - Culturally Significant Object Imported for Exhibition Determinations: “Beauty Revealed: Images of...

    Science.gov (United States)

    2013-09-11

    ..., 1965 (79 Stat. 985; 22 U.S.C. 2459), Executive Order 12047 of March 27, 1978, the Foreign Affairs...). The mailing address is U.S. Department of State, SA-5, L/PD, Fifth Floor (Suite 5H03), Washington, DC... Determinations: ``Beauty Revealed: Images of Women in Qing Dynasty Chinese Painting'' SUMMARY: Notice is hereby...

  18. Burnout, work engagement and workaholism among highly educated employees: Profiles, antecedents and outcomes

    Directory of Open Access Journals (Sweden)

    Hely Innanen

    2014-06-01

    Full Text Available The present study examined the longitudinal profiles of burnout, engagement and workaholism among highly educated employees. First, the latent profile modeling indicated two latent classes: Engaged and Exhausted-Workaholic. Second, the results revealed that employees with the Engaged profile experienced high levels of energy and dedication, whereas employees with the Exhausted-Workaholic profile experienced exhaustion, cynicism and workaholism. Social pessimism in the transition from high education to work predicted poor subjective well-being at work. Further, workaholism decreased during the career among members of the Exhausted-Workaholic profile suggesting positive direction during career. Finally, Engaged employees experienced detachment and relaxation, life satisfaction and rewards.

  19. SubID, a non-median dichotomization tool for heterogeneous populations, reveals the pan-cancer significance of INPP4B and its regulation by EVI1 in AML.

    Directory of Open Access Journals (Sweden)

    Irakli Dzneladze

    Full Text Available Our previous studies demonstrated that INPP4B, a member of the PI3K/Akt signaling pathway, is overexpressed in a subset of AML patients and is associated with lower response to chemotherapy and shorter survival. INPP4B expression analysis in AML revealed a right skewed frequency distribution with 25% of patients expressing significantly higher levels than the majority. The 75% low/25% high cut-off revealed the prognostic power of INPP4B expression status in AML, which would not have been apparent with a standard median cut-off approach. Our identification of a clinically relevant non-median cut-off for INPP4B indicated a need for a generalizable non-median dichotomization approach to optimally study clinically relevant genes. To address this need, we developed Subgroup Identifier (SubID, a tool which examines the relationship between a continuous variable (e.g. gene expression, and a test parameter (e.g. CoxPH or Fisher's exact P values. In our study, Fisher's exact SubID was used to reveal EVI1 as a transcriptional regulator of INPP4B in AML; a finding which was validated in vitro. Next, we used CoxPH SubID to conduct a pan-cancer analysis of INPP4B's prognostic significance. Our analysis revealed that INPP4Blow is associated with shorter survival in kidney clear cell, liver hepatocellular, and bladder urothelial carcinomas. Conversely, INPP4Blow was shown to be associated with increased survival in pancreatic adenocarcinoma in three independent datasets. Overall, our study describes the development and application of a novel subgroup identification tool used to identify prognostically significant rare subgroups based upon gene expression, and for investigating the association between a gene with skewed frequency distribution and potentially important upstream and downstream genes that relate to the index gene.

  20. SubID, a non-median dichotomization tool for heterogeneous populations, reveals the pan-cancer significance of INPP4B and its regulation by EVI1 in AML.

    Science.gov (United States)

    Dzneladze, Irakli; Woolley, John F; Rossell, Carla; Han, Youqi; Rashid, Ayesha; Jain, Michael; Reimand, Jüri; Minden, Mark D; Salmena, Leonardo

    2018-01-01

    Our previous studies demonstrated that INPP4B, a member of the PI3K/Akt signaling pathway, is overexpressed in a subset of AML patients and is associated with lower response to chemotherapy and shorter survival. INPP4B expression analysis in AML revealed a right skewed frequency distribution with 25% of patients expressing significantly higher levels than the majority. The 75% low/25% high cut-off revealed the prognostic power of INPP4B expression status in AML, which would not have been apparent with a standard median cut-off approach. Our identification of a clinically relevant non-median cut-off for INPP4B indicated a need for a generalizable non-median dichotomization approach to optimally study clinically relevant genes. To address this need, we developed Subgroup Identifier (SubID), a tool which examines the relationship between a continuous variable (e.g. gene expression), and a test parameter (e.g. CoxPH or Fisher's exact P values). In our study, Fisher's exact SubID was used to reveal EVI1 as a transcriptional regulator of INPP4B in AML; a finding which was validated in vitro. Next, we used CoxPH SubID to conduct a pan-cancer analysis of INPP4B's prognostic significance. Our analysis revealed that INPP4Blow is associated with shorter survival in kidney clear cell, liver hepatocellular, and bladder urothelial carcinomas. Conversely, INPP4Blow was shown to be associated with increased survival in pancreatic adenocarcinoma in three independent datasets. Overall, our study describes the development and application of a novel subgroup identification tool used to identify prognostically significant rare subgroups based upon gene expression, and for investigating the association between a gene with skewed frequency distribution and potentially important upstream and downstream genes that relate to the index gene.

  1. Molecular portrait of breast cancer in China reveals comprehensive transcriptomic likeness to Caucasian breast cancer and low prevalence of luminal A subtype

    International Nuclear Information System (INIS)

    Huang, Xiaoyan; Dugo, Matteo; Callari, Maurizio; Sandri, Marco; De Cecco, Loris; Valeri, Barbara; Carcangiu, Maria Luisa; Xue, Jingyan; Bi, Rui; Veneroni, Silvia; Daidone, Maria Grazia; Ménard, Sylvie; Tagliabue, Elda; Shao, Zhimin; Wu, Jiong; Orlandi, Rosaria

    2015-01-01

    The recent dramatic increase in breast cancer incidence across China with progressive urbanization and economic development has signaled the urgent need for molecular and clinical detailing of breast cancer in the Chinese population. Our analyses of a unique transethnic collection of breast cancer frozen specimens from Shanghai Fudan Cancer Center (Chinese Han) profiled simultaneously with an analogous Caucasian Italian series revealed consistent transcriptomic data lacking in batch effects. The prevalence of Luminal A subtype was significantly lower in Chinese series, impacting the overall prevalence of estrogen receptor (ER)-positive disease in a large cohort of Chinese/Caucasian patients. Unsupervised and supervised comparison of gene and microRNA (miRNA) profiles of Chinese and Caucasian samples revealed extensive similarity in the comprehensive taxonomy of transcriptional elements regulating breast cancer biology. Partition of gene expression data using gene lists relevant to breast cancer as “intrinsic” and “extracellular matrix” genes identified Chinese and Caucasian subgroups with equivalent global gene and miRNA profiles. These findings indicate that in the Chinese and Caucasian groups, breast neoplasia and the surrounding stromal characteristics undergo the same differentiation and molecular processes. Transcriptional similarity across transethnic cohorts may simplify translational medicine approaches and clinical management of breast cancer patients worldwide

  2. Carbon profiles of remote Australian Indigenous communities: A base for opportunities

    International Nuclear Information System (INIS)

    Stewart, J.; Anda, M.; Harper, R.J.

    2016-01-01

    A decision-making model was constructed to assist remote Australian Indigenous communities select appropriate climate change mitigation programs. The Resilient Community and Livelihood Asset Integration Model (ReCLAIM) comprises six steps that focus on community assets and aspirations. The second of these steps is to determine the baseline carbon profiles of communities based on six sources of carbon emissions: materials, construction processes, stationary energy, transport, water systems and waste. The methodology employed an annualised lifecycle analysis of housing materials and construction, and an annual inventory of other emission sources. Profiles were calculated for two remote communities and compared to the Australian average and also average electricity consumption by remote communities in the Northern Territory. The results, expressed in tonnes of carbon dioxide equivalent (tCO_2-e), showed that average household carbon profiles of the two communities (6.3 and 4.1 tCO_2-e/capita/yr) were generally lower than the Australian average (7.3 tCO_2-e/capita/yr). The stationary energy results revealed that infrastructure and building design could raise fuel consumption and costs, and therefore carbon emissions, despite modest lifestyles. The carbon emission categories differed between the two communities highlighting the need for an individualised approach to understanding the drivers of carbon emissions and mitigation responses. - Highlights: •We model carbon profiles of two remote Aboriginal communities. •Community carbon profiles were lower than the Australian average. •We compare stationary energy with a 72-community sample average. •Low-carbon communities are possible with renewable energy systems. •Building design and energy source can impact significantly on emissions.

  3. Gene expression profile analysis of Ligon lintless-1 (Li1) mutant reveals important genes and pathways in cotton leaf and fiber development.

    Science.gov (United States)

    Ding, Mingquan; Jiang, Yurong; Cao, Yuefen; Lin, Lifeng; He, Shae; Zhou, Wei; Rong, Junkang

    2014-02-10

    Ligon lintless-1 (Li1) is a monogenic dominant mutant of Gossypium hirsutum (upland cotton) with a phenotype of impaired vegetative growth and short lint fibers. Despite years of research involving genetic mapping and gene expression profile analysis of Li1 mutant ovule tissues, the gene remains uncloned and the underlying pathway of cotton fiber elongation is still unclear. In this study, we report the whole genome-level deep-sequencing analysis of leaf tissues of the Li1 mutant. Differentially expressed genes in leaf tissues of mutant versus wild-type (WT) plants are identified, and the underlying pathways and potential genes that control leaf and fiber development are inferred. The results show that transcription factors AS2, YABBY5, and KANDI-like are significantly differentially expressed in mutant tissues compared with WT ones. Interestingly, several fiber development-related genes are found in the downregulated gene list of the mutant leaf transcriptome. These genes include heat shock protein family, cytoskeleton arrangement, cell wall synthesis, energy, H2O2 metabolism-related genes, and WRKY transcription factors. This finding suggests that the genes are involved in leaf morphology determination and fiber elongation. The expression data are also compared with the previously published microarray data of Li1 ovule tissues. Comparative analysis of the ovule transcriptomes of Li1 and WT reveals that a number of pathways important for fiber elongation are enriched in the downregulated gene list at different fiber development stages (0, 6, 9, 12, 15, 18dpa). Differentially expressed genes identified in both leaf and fiber samples are aligned with cotton whole genome sequences and combined with the genetic fine mapping results to identify a list of candidate genes for Li1. Copyright © 2013 Elsevier B.V. All rights reserved.

  4. Comprehensive transcriptional profiling of NaCl-stressed Arabidopsis roots reveals novel classes of responsive genes

    Directory of Open Access Journals (Sweden)

    Deyholos Michael K

    2006-10-01

    Full Text Available Abstract Background Roots are an attractive system for genomic and post-genomic studies of NaCl responses, due to their primary importance to agriculture, and because of their relative structural and biochemical simplicity. Excellent genomic resources have been established for the study of Arabidopsis roots, however, a comprehensive microarray analysis of the root transcriptome following NaCl exposure is required to further understand plant responses to abiotic stress and facilitate future, systems-based analyses of the underlying regulatory networks. Results We used microarrays of 70-mer oligonucleotide probes representing 23,686 Arabidopsis genes to identify root transcripts that changed in relative abundance following 6 h, 24 h, or 48 h of hydroponic exposure to 150 mM NaCl. Enrichment analysis identified groups of structurally or functionally related genes whose members were statistically over-represented among up- or down-regulated transcripts. Our results are consistent with generally observed stress response themes, and highlight potentially important roles for underappreciated gene families, including: several groups of transporters (e.g. MATE, LeOPT1-like; signalling molecules (e.g. PERK kinases, MLO-like receptors, carbohydrate active enzymes (e.g. XTH18, transcription factors (e.g. members of ZIM, WRKY, NAC, and other proteins (e.g. 4CL-like, COMT-like, LOB-Class 1. We verified the NaCl-inducible expression of selected transcription factors and other genes by qRT-PCR. Conclusion Micorarray profiling of NaCl-treated Arabidopsis roots revealed dynamic changes in transcript abundance for at least 20% of the genome, including hundreds of transcription factors, kinases/phosphatases, hormone-related genes, and effectors of homeostasis, all of which highlight the complexity of this stress response. Our identification of these transcriptional responses, and groups of evolutionarily related genes with either similar or divergent

  5. Transcriptomic profiling-based mutant screen reveals three new transcription factors mediating menadione resistance in Neurospora crassa.

    Science.gov (United States)

    Zhu, Jufen; Yu, Xinxu; Xie, Baogui; Gu, Xiaokui; Zhang, Zhenying; Li, Shaojie

    2013-06-01

    To gain insight into the regulatory mechanisms of oxidative stress responses in filamentous fungi, the genome-wide transcriptional response of Neurospora crassa to menadione was analysed by digital gene expression (DGE) profiling, which identified 779 upregulated genes and 576 downregulated genes. Knockout mutants affecting 130 highly-upregulated genes were tested for menadione sensitivity, which revealed that loss of the transcription factor siderophore regulation (SRE) (a transcriptional repressor for siderophore biosynthesis), catatase-3, cytochrome c peroxidase or superoxide dismutase 1 copper chaperone causes hypersensitivity to menadione. Deletion of sre dramatically increased transcription of the siderophore biosynthesis gene ono and the siderophore iron transporter gene sit during menadione stress, suggesting that SRE is required for repression of iron uptake under oxidative stress conditions. Contrary to its phenotype, the sre deletion mutant showed higher transcriptional levels of genes encoding reactive oxygen species (ROS) scavengers than wild type during menadione stress, which implies that the mutant suffers a higher level of oxidative stress than wild type. Uncontrolled iron uptake in the sre mutant might exacerbate cellular oxidative stress. This is the first report of a negative regulator of iron assimilation participating in the fungal oxidative stress response. In addition to SRE, eight other transcription factor genes were also menadione-responsive but their single gene knockout mutants showed wild-type menadione sensitivity. Two of them, named as mit-2 (menadione induced transcription factor-2) and mit-4 (menadione induced transcription factor-4), were selected for double mutant analysis. The double mutant was hypersensitive to menadione. Similarly, the double mutation of mit-2 and sre also had additive effects on menadione sensitivity, suggesting multiple transcription factors mediate oxidative stress resistance in an additive manner

  6. Relationships of damaged starch granules and particle size distribution with pasting and thermal profiles of milled MR263 rice flour.

    Science.gov (United States)

    Asmeda, R; Noorlaila, A; Norziah, M H

    2016-01-15

    This research was conducted to investigate the effects of different grinding techniques (dry, semi-wet and wet) of milled rice grains on the damaged starch and particle size distribution of flour produced from a new variety, MR263, specifically related to the pasting and thermal profiles. The results indicated that grinding techniques significantly (price flour. Wet grinding process yields flour with lowest percentage of starch damage (7.37%) and finest average particle size (8.52μm). Pasting and gelatinization temperature was found in the range of 84.45-89.63°C and 59.86-75.31°C, respectively. Dry ground flour attained the lowest pasting and gelatinization temperature as shown by the thermal and pasting profiles. Correlation analysis revealed that percentage of damaged starch granules had a significant, negative relationship with pasting temperature while average particle size distribution had a significant, strong negative relationship with gelatinization temperature. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Integration of miRNA and protein profiling reveals coordinated neuroadaptations in the alcohol-dependent mouse brain.

    Directory of Open Access Journals (Sweden)

    Giorgio Gorini

    Full Text Available The molecular mechanisms underlying alcohol dependence involve different neurochemical systems and are brain region-dependent. Chronic Intermittent Ethanol (CIE procedure, combined with a Two-Bottle Choice voluntary drinking paradigm, represents one of the best available animal models for alcohol dependence and relapse drinking. MicroRNAs, master regulators of the cellular transcriptome and proteome, can regulate their targets in a cooperative, combinatorial fashion, ensuring fine tuning and control over a large number of cellular functions. We analyzed cortex and midbrain microRNA expression levels using an integrative approach to combine and relate data to previous protein profiling from the same CIE-subjected samples, and examined the significance of the data in terms of relative contribution to alcohol consumption and dependence. MicroRNA levels were significantly altered in CIE-exposed dependent mice compared with their non-dependent controls. More importantly, our integrative analysis identified modules of coexpressed microRNAs that were highly correlated with CIE effects and predicted target genes encoding differentially expressed proteins. Coexpressed CIE-relevant proteins, in turn, were often negatively correlated with specific microRNA modules. Our results provide evidence that microRNA-orchestrated translational imbalances are driving the behavioral transition from alcohol consumption to dependence. This study represents the first attempt to combine ex vivo microRNA and protein expression on a global scale from the same mammalian brain samples. The integrative systems approach used here will improve our understanding of brain adaptive changes in response to drug abuse and suggests the potential therapeutic use of microRNAs as tools to prevent or compensate multiple neuroadaptations underlying addictive behavior.

  8. Microarray expression profiling of human dental pulp from single subject.

    Science.gov (United States)

    Tete, Stefano; Mastrangelo, Filiberto; Scioletti, Anna Paola; Tranasi, Michelangelo; Raicu, Florina; Paolantonio, Michele; Stuppia, Liborio; Vinci, Raffaele; Gherlone, Enrico; Ciampoli, Cristian; Sberna, Maria Teresa; Conti, Pio

    2008-01-01

    Microarray is a recently developed simultaneous analysis of expression patterns of thousand of genes. The aim of this research was to evaluate the expression profile of human healthy dental pulp in order to find the presence of genes activated and encoding for proteins involved in the physiological process of human dental pulp. We report data obtained by analyzing expression profiles of human tooth pulp from single subjects, using an approach based on the amplification of the total RNA. Experiments were performed on a high-density array able to analyse about 21,000 oligonucleotide sequences of about 70 bases in duplicate, using an approach based on the amplification of the total RNA from the pulp of a single tooth. Obtained data were analyzed using the S.A.M. system (Significance Analysis of Microarray) and genes were merged according to their molecular functions and biological process by the Onto-Express software. The microarray analysis revealed 362 genes with specific pulp expression. Genes showing significant high expression were classified in genes involved in tooth development, protoncogenes, genes of collagen, DNAse, Metallopeptidases and Growth factors. We report a microarray analysis, carried out by extraction of total RNA from specimens of healthy human dental pulp tissue. This approach represents a powerful tool in the study of human normal and pathological pulp, allowing minimization of the genetic variability due to the pooling of samples from different individuals.

  9. Label-Free LC-MS Profiling of Skeletal Muscle Reveals Heart-Type Fatty Acid Binding Protein as a Candidate Biomarker of Aerobic Capacity

    Directory of Open Access Journals (Sweden)

    Zulezwan A. Malik

    2013-12-01

    Full Text Available Two-dimensional gel electrophoresis provides robust comparative analysis of skeletal muscle, but this technique is laborious and limited by its inability to resolve all proteins. In contrast, orthogonal separation by SDS-PAGE and reverse-phase liquid chromatography (RPLC coupled to mass spectrometry (MS affords deep mining of the muscle proteome, but differential analysis between samples is challenging due to the greater level of fractionation and the complexities of quantifying proteins based on the abundances of their tryptic peptides. Here we report simple, semi-automated and time efficient (i.e., 3 h per sample proteome profiling of skeletal muscle by 1-dimensional RPLC electrospray ionisation tandem MS. Solei were analysed from rats (n = 5, in each group bred as either high- or low-capacity runners (HCR and LCR, respectively that exhibited a 6.4-fold difference (1,625 ± 112 m vs. 252 ± 43 m, p < 0.0001 in running capacity during a standardized treadmill test. Soluble muscle proteins were extracted, digested with trypsin and individual biological replicates (50 ng of tryptic peptides subjected to LC-MS profiling. Proteins were identified by triplicate LC-MS/MS analysis of a pooled sample of each biological replicate. Differential expression profiling was performed on relative abundances (RA of parent ions, which spanned three orders of magnitude. In total, 207 proteins were analysed, which encompassed almost all enzymes of the major metabolic pathways in skeletal muscle. The most abundant protein detected was type I myosin heavy chain (RA = 5,843 ± 897 and the least abundant protein detected was heat shock 70 kDa protein (RA = 2 ± 0.5. Sixteen proteins were significantly (p < 0.05 more abundant in HCR muscle and hierarchal clustering of the profiling data highlighted two protein subgroups, which encompassed proteins associated with either the respiratory chain or fatty acid oxidation. Heart-type fatty acid binding protein (FABPH was 1

  10. Transcriptomic and metabolomic profiling of Zymomonas mobilis during aerobic and anaerobic fermentations

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    Palumbo Anthony V

    2009-01-01

    Full Text Available Abstract Background Zymomonas mobilis ZM4 (ZM4 produces near theoretical yields of ethanol with high specific productivity and recombinant strains are able to ferment both C-5 and C-6 sugars. Z. mobilis performs best under anaerobic conditions, but is an aerotolerant organism. However, the genetic and physiological basis of ZM4's response to various stresses is understood poorly. Results In this study, transcriptomic and metabolomic profiles for ZM4 aerobic and anaerobic fermentations were elucidated by microarray analysis and by high-performance liquid chromatography (HPLC, gas chromatography (GC and gas chromatography-mass spectrometry (GC-MS analyses. In the absence of oxygen, ZM4 consumed glucose more rapidly, had a higher growth rate, and ethanol was the major end-product. Greater amounts of other end-products such as acetate, lactate, and acetoin were detected under aerobic conditions and at 26 h there was only 1.7% of the amount of ethanol present aerobically as there was anaerobically. In the early exponential growth phase, significant differences in gene expression were not observed between aerobic and anaerobic conditions via microarray analysis. HPLC and GC analyses revealed minor differences in extracellular metabolite profiles at the corresponding early exponential phase time point. Differences in extracellular metabolite profiles between conditions became greater as the fermentations progressed. GC-MS analysis of stationary phase intracellular metabolites indicated that ZM4 contained lower levels of amino acids such as alanine, valine and lysine, and other metabolites like lactate, ribitol, and 4-hydroxybutanoate under anaerobic conditions relative to aerobic conditions. Stationary phase microarray analysis revealed that 166 genes were significantly differentially expressed by more than two-fold. Transcripts for Entner-Doudoroff (ED pathway genes (glk, zwf, pgl, pgk, and eno and gene pdc, encoding a key enzyme leading to ethanol

  11. Histological staining methods preparatory to laser capture microdissection significantly affect the integrity of the cellular RNA

    Directory of Open Access Journals (Sweden)

    Li Ming-Chung

    2006-04-01

    Full Text Available Abstract Background Gene expression profiling by microarray analysis of cells enriched by laser capture microdissection (LCM faces several technical challenges. Frozen sections yield higher quality RNA than paraffin-imbedded sections, but even with frozen sections, the staining methods used for histological identification of cells of interest could still damage the mRNA in the cells. To study the contribution of staining methods to degradation of results from gene expression profiling of LCM samples, we subjected pellets of the mouse plasma cell tumor cell line TEPC 1165 to direct RNA extraction and to parallel frozen sectioning for LCM and subsequent RNA extraction. We used microarray hybridization analysis to compare gene expression profiles of RNA from cell pellets with gene expression profiles of RNA from frozen sections that had been stained with hematoxylin and eosin (H&E, Nissl Stain (NS, and for immunofluorescence (IF as well as with the plasma cell-revealing methyl green pyronin (MGP stain. All RNAs were amplified with two rounds of T7-based in vitro transcription and analyzed by two-color expression analysis on 10-K cDNA microarrays. Results The MGP-stained samples showed the least introduction of mRNA loss, followed by H&E and immunofluorescence. Nissl staining was significantly more detrimental to gene expression profiles, presumably owing to an aqueous step in which RNA may have been damaged by endogenous or exogenous RNAases. Conclusion RNA damage can occur during the staining steps preparatory to laser capture microdissection, with the consequence of loss of representation of certain genes in microarray hybridization analysis. Inclusion of RNAase inhibitor in aqueous staining solutions appears to be important in protecting RNA from loss of gene transcripts.

  12. The Urine Proteome Profile Is Different in Neuromyelitis Optica Compared to Multiple Sclerosis: A Clinical Proteome Study.

    Directory of Open Access Journals (Sweden)

    Helle H Nielsen

    Full Text Available Inflammatory demyelinating diseases of the CNS comprise a broad spectrum of diseases like neuromyelitis optica (NMO, NMO spectrum disorders (NMO-SD and multiple sclerosis (MS. Despite clear classification criteria, differentiation can be difficult. We hypothesized that the urine proteome may differentiate NMO from MS.The proteins in urine samples from anti-aquaporin 4 (AQP4 seropositive NMO/NMO-SD patients (n = 32, patients with MS (n = 46 and healthy subjects (HS, n = 31 were examined by quantitative liquid chromatography-tandem mass spectrometry (LC-MS/MS after trypsin digestion and iTRAQ labelling. Immunoglobulins (Ig in the urine were validated by nephelometry in an independent cohort (n = 9-10 pr. groups.The analysis identified a total of 1112 different proteins of which 333 were shared by all 109 subjects. Cluster analysis revealed differences in the urine proteome of NMO/NMO-SD compared to HS and MS. Principal component analysis also suggested that the NMO/NMO-SD proteome profile was useful for classification. Multivariate regression analysis revealed a 3-protein profile for the NMO/NMO-SD versus HS discrimination, a 6-protein profile for NMO/NMO-SD versus MS discrimination and an 11-protein profile for MS versus HS discrimination. All protein panels yielded highly significant ROC curves (AUC in all cases >0.85, p≤0.0002. Nephelometry confirmed the presence of increased Ig-light chains in the urine of patients with NMO/NMO-SD.The urine proteome profile of patients with NMO/NMO-SD is different from MS and HS. This may reflect differences in the pathogenesis of NMO/NMO-SD versus MS and suggests that urine may be a potential source of biomarkers differentiating NMO/NMO-SD from MS.

  13. Anti-cancer agents in Saudi Arabian herbals revealed by automated high-content imaging

    KAUST Repository

    Hajjar, Dina

    2017-06-13

    Natural products have been used for medical applications since ancient times. Commonly, natural products are structurally complex chemical compounds that efficiently interact with their biological targets, making them useful drug candidates in cancer therapy. Here, we used cell-based phenotypic profiling and image-based high-content screening to study the mode of action and potential cellular targets of plants historically used in Saudi Arabia\\'s traditional medicine. We compared the cytological profiles of fractions taken from Juniperus phoenicea (Arar), Anastatica hierochuntica (Kaff Maryam), and Citrullus colocynthis (Hanzal) with a set of reference compounds with established modes of action. Cluster analyses of the cytological profiles of the tested compounds suggested that these plants contain possible topoisomerase inhibitors that could be effective in cancer treatment. Using histone H2AX phosphorylation as a marker for DNA damage, we discovered that some of the compounds induced double-strand DNA breaks. Furthermore, chemical analysis of the active fraction isolated from Juniperus phoenicea revealed possible anti-cancer compounds. Our results demonstrate the usefulness of cell-based phenotypic screening of natural products to reveal their biological activities.

  14. Antimicrobial susceptibility profiles and prevalence of ESBLS among ...

    African Journals Online (AJOL)

    Genetic relatedness of the MDR isolates was apparently influenced by the resistance profiles, hotel type and clinical characteristics. Conclusion: This study revealed that apparently healthy people working in the hospitality industry carry MDR E. coli that could potentially be transmitted to the general public. Infections by such ...

  15. Gene expression profiling of canine osteosarcoma reveals genes associated with short and long survival times

    Directory of Open Access Journals (Sweden)

    Rao Nagesha AS

    2009-09-01

    Full Text Available Abstract Background Gene expression profiling of spontaneous tumors in the dog offers a unique translational opportunity to identify prognostic biomarkers and signaling pathways that are common to both canine and human. Osteosarcoma (OS accounts for approximately 80% of all malignant bone tumors in the dog. Canine OS are highly comparable with their human counterpart with respect to histology, high metastatic rate and poor long-term survival. This study investigates the prognostic gene profile among thirty-two primary canine OS using canine specific cDNA microarrays representing 20,313 genes to identify genes and cellular signaling pathways associated with survival. This, the first report of its kind in dogs with OS, also demonstrates the advantages of cross-species comparison with human OS. Results The 32 tumors were classified into two prognostic groups based on survival time (ST. They were defined as short survivors (dogs with poor prognosis: surviving fewer than 6 months and long survivors (dogs with better prognosis: surviving 6 months or longer. Fifty-one transcripts were found to be differentially expressed, with common upregulation of these genes in the short survivors. The overexpressed genes in short survivors are associated with possible roles in proliferation, drug resistance or metastasis. Several deregulated pathways identified in the present study, including Wnt signaling, Integrin signaling and Chemokine/cytokine signaling are comparable to the pathway analysis conducted on human OS gene profiles, emphasizing the value of the dog as an excellent model for humans. Conclusion A molecular-based method for discrimination of outcome for short and long survivors is useful for future prognostic stratification at initial diagnosis, where genes and pathways associated with cell cycle/proliferation, drug resistance and metastasis could be potential targets for diagnosis and therapy. The similarities between human and canine OS makes the

  16. Gene expression profile identifies potential biomarkers for human intervertebral disc degeneration.

    Science.gov (United States)

    Guo, Wei; Zhang, Bin; Li, Yan; Duan, Hui-Quan; Sun, Chao; Xu, Yun-Qiang; Feng, Shi-Qing

    2017-12-01

    The present study aimed to reveal the potential genes associated with the pathogenesis of intervertebral disc degeneration (IDD) by analyzing microarray data using bioinformatics. Gene expression profiles of two regions of the intervertebral disc were compared between patients with IDD and controls. GSE70362 containing two groups of gene expression profiles, 16 nucleus pulposus (NP) samples from patients with IDD and 8 from controls, and 16 annulus fibrosus (AF) samples from patients with IDD and 8 from controls, was downloaded from the Gene Expression Omnibus database. A total of 93 and 114 differentially expressed genes (DEGs) were identified in NP and AF samples, respectively, using a limma software package for the R programming environment. Gene Ontology (GO) function enrichment analysis was performed to identify the associated biological functions of DEGs in IDD, which indicated that the DEGs may be involved in various processes, including cell adhesion, biological adhesion and extracellular matrix organization. Pathway enrichment analysis using the Kyoto Encyclopedia of Genes and Genomes (KEGG) demonstrated that the identified DEGs were potentially involved in focal adhesion and the p53 signaling pathway. Further analysis revealed that there were 35 common DEGs observed between the two regions (NP and AF), which may be further regulated by 6 clusters of microRNAs (miRNAs) retrieved with WebGestalt. The genes in the DEG‑miRNA regulatory network were annotated using GO function and KEGG pathway enrichment analysis, among which extracellular matrix organization was the most significant disrupted biological process and focal adhesion was the most significant dysregulated pathway. In addition, the result of protein‑protein interaction network modules demonstrated the involvement of inflammatory cytokine interferon signaling in IDD. These findings may not only advance the understanding of the pathogenesis of IDD, but also identify novel potential

  17. Improvement of Lipid Profile and Antioxidant Status of Hyperlipidaemic Albino Rats by Gamma-irradiated Safflower (Carthamus tinctorius L.)

    International Nuclear Information System (INIS)

    Hamza, R.G.; Farag, M.F.

    2011-01-01

    Hyper-Lipidemia is a dominant risk factor that contributes to the development and progression of atherosclerosis. Safflower is rich in the essential omega-6 and omega-3 polyunsaturated fatty acids and phenolic compounds which are known to be effective for the treatment of hyper- lipidemia. This study was performed to examine the efficacy of safflower to ameliorate the induced hyper-lipidemia in rats. The results obtained revealed that rats fed on high fat diet (HFD) significantly induced an increase in lipid profile, glucose and some liver enzymes as well as elevation of malondialdehyde (MDA) associated with a significant decrease in high density lipoprotein (HDL-C), glutathione (GSH) content and some antioxidant enzymes activity. However, when rats received HFD containing either raw or irradiated safflower (1% w/w), a significant improvement in the above mentioned parameters was seen. In conclusion, safflower supplementation in diet of rats pointed out to a promising role of safflower, a natural product, on antioxidant enzymes, liver function and lipid profile of hyper-lipidemic rats, regardless if it is irradiated or not

  18. Performance profiling for brachytherapy applications

    Science.gov (United States)

    Choi, Wonqook; Cho, Kihyeon; Yeo, Insung

    2018-05-01

    In many physics applications, a significant amount of software (e.g. R, ROOT and Geant4) is developed on novel computing architectures, and much effort is expended to ensure the software is efficient in terms of central processing unit (CPU) time and memory usage. Profiling tools are used during the evaluation process to evaluate the efficiency; however, few such tools are able to accommodate low-energy physics regions. To address this limitation, we developed a low-energy physics profiling system in Geant4 to profile the CPU time and memory of software applications in brachytherapy applications. This paper describes and evaluates specific models that are applied to brachytherapy applications in Geant4, such as QGSP_BIC_LIV, QGSP_BIC_EMZ, and QGSP_BIC_EMY. The physics range in this tool allows it to be used to generate low energy profiles in brachytherapy applications. This was a limitation in previous studies, which caused us to develop a new profiling tool that supports profiling in the MeV range, in contrast to the TeV range that is supported by existing high-energy profiling tools. In order to easily compare the profiling results between low-energy and high-energy modes, we employed the same software architecture as that in the SimpliCarlo tool developed at the Fermilab National Accelerator Laboratory (FNAL) for the Large Hadron Collider (LHC). The results show that the newly developed profiling system for low-energy physics (less than MeV) complements the current profiling system used for high-energy physics (greater than TeV) applications.

  19. The alteration of the urinary steroid profile under the stress

    Directory of Open Access Journals (Sweden)

    A Gronowska

    2010-03-01

    Full Text Available In the second part of twentieth century anabolic-androgenic steroids were introduced into doping practice and received continuously increasing significance. In order to prove the usage of doping substances, the determination of steroid profile in the urine came into practice. Several factors may be responsible for alterations in the normal steroid profile for example age, sex and diet. The aim of this study was to find out, whether the psychological stress may cause modifications in the steroid profile and T/Et ratio. The effect of physical activity was also considered. The steroid profile was determined in the group of 34 students being in non-stress conditions and under stress immediately before an important university exam. The intensity of stress was rated by self-reported questionnaire. The GC/MS method was applied to determine the steroid profile in the urine samples. The results of the experiment have shown that psychological stress may cause significant changes in the steroid profile, especially in females. Physical activity, independently of stress significantly modified the steroid profile. In summary, observed changes in steroid profile suggest, that major fluctuations of T/Et and A/E ratios under the influence of stressogenic factors and physical activity are unlikely.

  20. Circulating microRNA Profile throughout the menstrual cycle.

    Directory of Open Access Journals (Sweden)

    Kadri Rekker

    Full Text Available Normal physiological variables, such as age and gender, contribute to alterations in circulating microRNA (miRNA expression levels. The changes in the female body during the menstrual cycle can also be reflected in plasma miRNA expression levels. Therefore, this study aimed to determine the plasma miRNA profile of healthy women during the menstrual cycle and to assess which circulating miRNAs are derived from blood cells. The plasma miRNA expression profiles in nine healthy women were determined by quantitative real time PCR using Exiqon Human Panel I assays from four time-points of the menstrual cycle. This platform was also used for studying miRNAs from pooled whole blood RNA samples at the same four time-points. Our results indicated that circulating miRNA expression levels in healthy women were not significantly altered by the processes occurring during the menstrual cycle. No significant differences in plasma miRNA expression levels were observed between the menstrual cycle time-points, but the number of detected miRNAs showed considerable variation among the studied individuals. miRNA analysis from whole blood samples revealed that majority of miRNAs in plasma are derived from blood cells. The most abundant miRNA in plasma and blood was hsa-miR-451a, but a number of miRNAs were only detected in one or the other sample type. In conclusion, our data suggest that the changes in the female body during the menstrual cycle do not affect the expression of circulating miRNAs at measurable levels.

  1. Inflammatory Mediator Profiling of n-butanol Exposed Upper Airways in Individuals with Multiple Chemical Sensitivity

    DEFF Research Database (Denmark)

    Dantoft, Thomas Meinertz; Skovbjerg, Sine; Andersson, Linus

    2015-01-01

    Multiple Chemical Sensitivity (MCS) is a chronic condition characterized by reports of recurrent symptoms in response to low level exposure to various chemical substances. Recent findings suggests that dysregulation of the immune system may play a role in MCS pathophysiology. The aim of this study...... inflammatory mediator profiles (P>0.05) at baseline. Likewise, direct comparison of mediator levels in the MCS group and controls after n-butanol exposure revealed no significant group differences. We demonstrate no abnormal upper airway inflammatory mediator levels in MCS subjects before or after a symptom...

  2. (1H-NMR spectroscopy revealed Mycobacterium tuberculosis caused abnormal serum metabolic profile of cattle.

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    Yingyu Chen

    Full Text Available To re-evaluate virulence of Mycobacterium tuberculosis (M. tb in cattle, we experimentally infected calves with M. tb andMycobacterium bovisvia intratracheal injection at a dose of 2.0×10(7 CFU and observed the animals for 33 weeks. The intradermal tuberculin test and IFN-γin vitro release assay showed that both M. tb and M. bovis induced similar responses. Immunohistochemical staining of pulmonary lymph nodes indicated that the antigen MPB83 of both M. tb and M. bovis were similarly distributed in the tissue samples. Histological examinations showed all of the infected groups exhibited neutrophil infiltration to similar extents. Although the infected cattle did not develop granulomatous inflammation, the metabolic profiles changed significantly, which were characterized by a change in energy production pathways and increased concentrations of N-acetyl glycoproteins. Glycolysis was induced in the infected cattle by decreased glucose and increased lactate content, and enhanced fatty acid β-oxidation was induced by decreased TG content, and decreased gluconeogenesis indicated by the decreased concentration of glucogenic and ketogenic amino acids promoted utilization of substances other than glucose as energy sources. In addition, an increase in acute phase reactive serum glycoproteins, together with neutrophil infiltration and increased of IL-1β production indicated an early inflammatory response before granuloma formation. In conclusion, this study indicated that both M. tb and M.bovis were virulent to cattle. Therefore, it is likely that cattle with M. tb infections would be critical to tuberculosis transmission from cattle to humans. Nuclear magnetic resonance was demonstrated to be an efficient method to systematically evaluate M. tb and M. bovi sinfection in cattle.

  3. Relationships between physical education students' motivational profiles, enjoyment, state anxiety, and self-reported physical activity.

    Science.gov (United States)

    Yli-Piipari, Sami; Watt, Anthony; Jaakkola, Timo; Liukkonen, Jarmo; Nurmi, Jari-Erik

    2009-01-01

    The purpose of this study was to analyze motivational profiles based on the self-determination theory (Deci and Ryan, 2000) and how these profiles are related to physical education students' enjoyment, state anxiety, and physical activity. The participants, 429 sixth grade students (girls = 216; boys = 213) completed SMS, Sport Enjoyment Scale, PESAS, and Physical Activity Scale. Cluster analyses identified two motivational profiles: 1) the "High motivation profile", in which the students had high intrinsic and extrinsic motivation, and low levels of amotivation, and 2) the "Low motivation profile", in which the students had low intrinsic and extrinsic motivation, and low levels of amotivation. The students in the first cluster enjoyed physical education more and were physically more active. The results revealed that students may be motivated towards physical education lessons both intrinsically and extrinsically, and still experience enjoyment in physical education. Key pointsTWO MOTIVATIONAL PROFILES WERE REVEALED: 1) the "High motivation profile", in which the students had high intrinsic and extrinsic motivation, and low levels of amotivation, and 2) the "Low motivation profile", in which the students had low intrinsic and extrinsic motivation, and low levels of amotivation.The students in the first profile enjoyed physical education more and were physically more active than the students in the second profile.Moreover, the representatives of the "High motivation profile "experienced greater anxiety toward physical education than the representatives of the "Low motivation profile"These findings raised an interesting question whether students engaging in physical education benefit more from the presence of both self-determined and non-self-determined forms of motivation, or are the benefits higher if students are primarily self-determined?

  4. Profiling post-centrifugation delay of serum and plasma with antibody bead arrays.

    Science.gov (United States)

    Qundos, Ulrika; Hong, Mun-Gwan; Tybring, Gunnel; Divers, Mark; Odeberg, Jacob; Uhlen, Mathias; Nilsson, Peter; Schwenk, Jochen M

    2013-12-16

    Several biobanking initiatives have emerged to create extensive collections of specimen for biomedical studies and various analytical platforms. An affinity proteomic analysis with antibody suspension bead arrays was conducted to investigate the influence of the pre-analytical time and temperature conditions on blood derived samples. Serum and EDTA plasma prepared from 16 individuals was centrifuged and aliquots were kept either at 4°C or in ambient temperature for 1h and up to 36h prior to first storage. Multiplexed protein profiles of post-centrifugation delay were generated in 384 biotinylated samples using 373 antibodies that targeted 343 unique proteins. Very few profiles were observed as significantly altered by the studied temperature and time intervals. Single binder and sandwich assays revealed decreasing levels of caldesmon 1 (CALD1) related to EDTA standard tubes and prolonged post-centrifugation delay of 36h. Indications from changes in CALD1 levels require further confirmation in independent material, but the current data suggests that samples should preferentially be frozen during the day of collection when to be profiled with antibody arrays selected for this study. Affinity-based profiling of serum and plasma by microarray assays can provide unique opportunities for the discovery of biomarkers. It is though often not known how differences in sample handling after collection influence the downstream analysis. By profiling three types of blood preparations for alterations in protein profiles with respect to time and temperature post centrifugation, we addressed an important component in the analysis and of such specimen. We believe that this analysis adds valuable information to be considered when biobanking blood derived samples. This article is part of a Special Issue entitled: Standardization and Quality Control in Proteomics. Copyright © 2013 The Authors. Published by Elsevier B.V. All rights reserved.

  5. Accelerated Profile HMM Searches.

    Directory of Open Access Journals (Sweden)

    Sean R Eddy

    2011-10-01

    Full Text Available Profile hidden Markov models (profile HMMs and probabilistic inference methods have made important contributions to the theory of sequence database homology search. However, practical use of profile HMM methods has been hindered by the computational expense of existing software implementations. Here I describe an acceleration heuristic for profile HMMs, the "multiple segment Viterbi" (MSV algorithm. The MSV algorithm computes an optimal sum of multiple ungapped local alignment segments using a striped vector-parallel approach previously described for fast Smith/Waterman alignment. MSV scores follow the same statistical distribution as gapped optimal local alignment scores, allowing rapid evaluation of significance of an MSV score and thus facilitating its use as a heuristic filter. I also describe a 20-fold acceleration of the standard profile HMM Forward/Backward algorithms using a method I call "sparse rescaling". These methods are assembled in a pipeline in which high-scoring MSV hits are passed on for reanalysis with the full HMM Forward/Backward algorithm. This accelerated pipeline is implemented in the freely available HMMER3 software package. Performance benchmarks show that the use of the heuristic MSV filter sacrifices negligible sensitivity compared to unaccelerated profile HMM searches. HMMER3 is substantially more sensitive and 100- to 1000-fold faster than HMMER2. HMMER3 is now about as fast as BLAST for protein searches.

  6. Peripheral blood RNA gene expression profiling in illicit methcathinone users reveals effect on immune system

    Directory of Open Access Journals (Sweden)

    Katrin eSikk

    2011-08-01

    Full Text Available Methcathinone (ephedrone is relatively easily accessible for abuse. Its users develop an extrapyramidal syndrome and it is not known if this is caused by methcathinone itself, by side-ingredients (manganese, or both. In the present study we aimed to clarify molecular mechanisms underlying this condition. We analyzed whole genome gene expression patterns of peripheral blood from 20 methcathinone users and 20 matched controls. Gene expression profile data was analyzed by Bayesian modelling and functional annotation. In order to verify the genechip results we performed quantitative real-time (RT PCR in selected genes. 326 out of analyzed 28,869 genes showed statistically significant differential expression with FDR adjusted p-values below 0.05. Quantitative RT-PCR confirmed differential expression for the most of selected genes. Functional annotation and network analysis indicated that most of the genes were related to activation immunological disease, cellular movement and cardiovascular disease gene network (enrichment score 42. As HIV and HCV infections were confounding factors, we performed additional stratification of patients. A similar functional activation of the immunological disease pathway was evident when we compared patients according to the injection status (past versus current users, balanced for HIV and HCV infection. However, this difference was not large therefore the major effect was related to the HIV status of the patients. Mn-methcathinone abusers have blood transcriptional patterns mostly caused by their HIV and HCV infections.

  7. Effect of N′-nitrosodimethylamine on red blood cell rheology and proteomic profiles of brain in male albino rats

    Science.gov (United States)

    Ahmad, Areeba; Fatima, Ravish; Maheshwari, Veena; Ahmad, Riaz

    2011-01-01

    We investigated the effects of N'-nitrosodimethylamine (NDMA) induced toxicity on red blood cell rheology in male rats and identified bands in proteomic profiles of brain which can be used as novel markers. Polyacrylamide gel electrophoresis (PAGE) profiles exhibited constitutive as well as induced expression of the polypeptides. Remarkably, the molecular weight range of the polypeptides (8–150 kDa) corresponded to that of the family of heat shock proteins. Our results revealed significant changes in blood parameters and showed the presence of acanthocytes, tear drop cells, spicules and cobot rings in the treated categories. Lactate dehydrogenase and esterase zymograms displayed a shift to anaerobic metabolism generating hypoxia-like conditions. This study strongly suggests that NDMA treatment causes acute toxicity leading to cell membrane destruction and alters protein profiles in rats. It is therefore recommended that caution should be exercised in using NDMA to avoid risks, and if at all necessary strategies should be designed to combat such conditions. PMID:22058653

  8. The relationship between technology leadership roles and profiles of school principals and technology integration in primary school classrooms

    Directory of Open Access Journals (Sweden)

    Mustafa SAMANCIOĞLU

    2015-12-01

    Full Text Available The purpose of this study was to investigate the relationship between technology leadership behaviors of school principals and teachers’ level of technology integration, and to determine technology leadership profiles based on teacher views and examine their association with technology integration. The researchers administered two questionnaires to 352 teachers working at sixteen primary schools in a large city in southeastern Turkey. The results revealed a positive, but weak relationship between technology leadership and technology integration. Furthermore, it was concluded that there were positive but weak relationships among technology integration and human centeredness, communication and collaboration, vision and support sub-dimensions of technology leadership. Two technology leadership profiles (high-TLP=65.6% and low-TLP=34.4% were constructed as a result of cluster analysis. A statistically significant difference was detected between teachers’ technology integration perceptions which were categorized into two profiles. The paper concludes by suggestions for implications to strengthen the link between technology leadership and technology integration.

  9. Major Upgrades to the AIRS Version-6 Ozone Profile Methodology

    Science.gov (United States)

    Susskind, Joel; Blaisdell, John; Iredell, Lena

    2015-01-01

    This research is a continuation of part of what was shown at the last AIRS Science Team Meeting in the talk Improved Water Vapor and Ozone Profiles in SRT AIRS Version-6.X and the AIRS February 11, 2015 NetMeeting Further improvements in water vapor and ozone profiles compared to Version-6.AIRS Version-6 was finalized in late 2012 and is now operational. Version-6 contained many significant improvements in retrieval methodology compared to Version-5. However, Version-6 retrieval methodology used for the water vapor profile q(p) and ozone profile O3(p) retrievals is basically unchanged from Version-5, or even from Version-4. Subsequent research has made significant improvements in both water vapor and O3 profiles compared to Version-6. This talk will concentrate on O3 profile retrievals. Improvements in water vapor profile retrievals are given in a separate presentation.

  10. Neurochemical binding profiles of novel indole and benzofuran MDMA analogues.

    Science.gov (United States)

    Shimshoni, Jakob A; Winkler, Ilan; Golan, Ezekiel; Nutt, David

    2017-01-01

    3,4-Methylenedioxy-N-methylamphetamine (MDMA) has been shown to be effective in the treatment of post-traumatic stress disorder (PTSD) in numerous clinical trials. In the present study, we have characterized the neurochemical binding profiles of three MDMA-benzofuran analogues (1-(benzofuran-5-yl)-propan-2-amine, 5-APB; 1-(benzofuran-6-yl)-N-methylpropan-2-amine, 6-MAPB; 1-(benzofuran-5-yl)-N-methylpropan-2-amine, 5-MAPB) and one MDMA-indole analogue (1-(1H-indol-5-yl)-2-methylamino-propan-1-ol, 5-IT). These compounds were screened as potential second-generation anti-PTSD drugs, against a battery of human and non-human receptors, transporters, and enzymes, and their potencies as 5-HT 2 receptor agonist and monoamine uptake inhibitors determined. All MDMA analogues displayed high binding affinities for 5-HT 2a,b,c and NE α2 receptors, as well as significant 5-HT, DA, and NE uptake inhibition. 5-APB revealed significant agonist activity at the 5-HT 2a,b,c receptors, while 6-MAPB, 5-MAPB, and 5-IT exhibited significant agonist activity at the 5-HT 2c receptor. There was a lack of correlation between the results of functional uptake and the monoamine transporter binding assay. MDMA analogues emerged as potent and selective monoamine oxidase A inhibitors. Based on 6-MAPB favorable pharmacological profile, it was further subjected to IC 50 determination for monoamine transporters. Overall, all MDMA analogues displayed higher monoamine receptor/transporter binding affinities and agonist activity at the 5-HT 2a,c receptors as compared to MDMA.

  11. Load profiles analysis for electricity market

    Directory of Open Access Journals (Sweden)

    Radu Porumb

    2014-04-01

    Full Text Available In the wake of electric power system transition towards smart grids, and the adoption of the electric market schemes, electric utilities are facing the need of a better load profiles understanding for their customers. In this work, some key objectives were addresses, such as definition of the mathematical model for calculating the hourly energy specific, identification of the three target groups for users who have developed consumer profiles, definition of the two types of significant load and assessment of the impact of using consumer profiles on users.

  12. Yeast Interspecies Comparative Proteomics Reveals Divergence in Expression Profiles and Provides Insights into Proteome Resource Allocation and Evolutionary Roles of Gene Duplication*

    Science.gov (United States)

    Kito, Keiji; Ito, Haruka; Nohara, Takehiro; Ohnishi, Mihoko; Ishibashi, Yuko; Takeda, Daisuke

    2016-01-01

    Omics analysis is a versatile approach for understanding the conservation and diversity of molecular systems across multiple taxa. In this study, we compared the proteome expression profiles of four yeast species (Saccharomyces cerevisiae, Saccharomyces mikatae, Kluyveromyces waltii, and Kluyveromyces lactis) grown on glucose- or glycerol-containing media. Conserved expression changes across all species were observed only for a small proportion of all proteins differentially expressed between the two growth conditions. Two Kluyveromyces species, both of which exhibited a high growth rate on glycerol, a nonfermentative carbon source, showed distinct species-specific expression profiles. In K. waltii grown on glycerol, proteins involved in the glyoxylate cycle and gluconeogenesis were expressed in high abundance. In K. lactis grown on glycerol, the expression of glycolytic and ethanol metabolic enzymes was unexpectedly low, whereas proteins involved in cytoplasmic translation, including ribosomal proteins and elongation factors, were highly expressed. These marked differences in the types of predominantly expressed proteins suggest that K. lactis optimizes the balance of proteome resource allocation between metabolism and protein synthesis giving priority to cellular growth. In S. cerevisiae, about 450 duplicate gene pairs were retained after whole-genome duplication. Intriguingly, we found that in the case of duplicates with conserved sequences, the total abundance of proteins encoded by a duplicate pair in S. cerevisiae was similar to that of protein encoded by nonduplicated ortholog in Kluyveromyces yeast. Given the frequency of haploinsufficiency, this observation suggests that conserved duplicate genes, even though minor cases of retained duplicates, do not exhibit a dosage effect in yeast, except for ribosomal proteins. Thus, comparative proteomic analyses across multiple species may reveal not only species-specific characteristics of metabolic processes under

  13. Protective effect of ascorbic acid on netilmicin-induced lipid profile and peroxidation parameters in rabbit blood plasma.

    Science.gov (United States)

    Devbhuti, Pritesh; Sikdar, Debasis; Saha, Achintya; Sengupta, Chandana

    2011-01-01

    A drug may cause alteration in blood-lipid profile and induce lipid peroxidation phenomena on administration in the body. Antioxidant may play beneficial role to control the negative alteration in lipid profile and lipid peroxidation. In view of this context, the present in vivo study was carried out to evaluate the role of ascorbic acid as antioxidant on netilmicin-induced alteration of blood lipid profile and peroxidation parameters. Rabbits were used as experimental animals and blood was collected to estimate blood-lipid profiles, such as total cholesterol (TCh), high density lipoprotein cholesterol (HDL-Ch), low density lipoprotein cholesterol (LDL-Ch), very low density lipoprotein cholesterol (VLDL-Ch), triglycerides (Tg), phospholipids (PL), and total lipids (TL), as well as peroxidation parameters, such as malondialdehyde (MDA), 4-hydroxy-2-nonenal (HNE), reduced glutathione (GSH) and nitric oxide (NO). The results revealed that netilmicin caused significant enhancement of MDA, HNE, TCh, LDL-Ch, VLDL-Ch, Tg levels and reduction in GSH, NO, HDL-Ch, PL, TL levels. On co-administration, ascorbic acid was found to be effective in reducing netilmicin-induced negative alterations of the above parameters.

  14. Toxicological profile for thorium. Draft report (Final)

    International Nuclear Information System (INIS)

    1990-10-01

    The ATSDR Toxicological Profile for Thorium is intended to characterize succinctly the toxicological and health effects information for the substance. It identifies and reviews the key literature that describes the substance's toxicological properties. Other literature is presented but described in less detail. The profile is not intended to be an exhaustive document; however, more comprehensive sources of specialty information are referenced. The profile begins with a public health statement, which describes in nontechnical language the substance's relevant toxicological properties. Following the statement is material that presents levels of significant human exposure and, where known, significant health effects. The adequacy of information to determine the substance's health effects is described. Research gaps in nontoxic and health effects information are described. Research gaps that are of significance to the protection of public health will be identified in a separate effort. The focus of the document is on health and toxicological information

  15. Full investigation of patients with polycystic ovary syndrome (PCOS) presenting to four different clinical specialties reveals significant differences and undiagnosed morbidity.

    Science.gov (United States)

    Sivayoganathan, Dhakshana; Maruthini, Deivanayagam; Glanville, Julie M; Balen, Adam H

    2011-12-01

    This study aimed to compare the spectrum of polycystic ovary syndrome (PCOS) symptoms in patients from four different specialist clinics. A prospective cross-sectional observational study. The study was conducted at the infertility, gynaecology, endocrine and dermatology clinics at Leeds General Infirmary, U.K. Seventy women presenting with features of PCOS: 20 from infertility, 17 from gynaecology, 17 from dermatology and 16 from endocrine clinics. Participants were assessed for symptoms and signs of PCOS and underwent a full endocrine and metabolic profile and a pelvic ultrasound scan. All subjects had experienced menstrual problems, 81% were overweight, 86% had polycystic ovaries on ultrasound, 56% had hirsutism, 53% had acne, 23% had acanthosis nigricans, 16% had alopecia and 38% had previously undiagnosed impaired glucose tolerance (IGT) or diabetes. A significant difference between the four clinic groups existed with regard to menstrual patterns (p = 0.0234), frequency distribution of presenting symptoms and the percentages of patients with PCOS who had already been diagnosed as having PCOS (p = 0.0088). This study emphasizes the importance of understanding the full spectrum of PCOS as presented to different specialty clinics. Not only is the syndrome under diagnosed but also are the significant associated morbidities such as IGT and type 2 diabetes. Different specialists need to appreciate the spectrum of health problems for women with PCOS that may extend beyond the specific symptoms that precipitated the initial referral.

  16. Caracterization of the motor profile of students with autistic disorder

    Directory of Open Access Journals (Sweden)

    Paola Matiko Okuda

    2010-12-01

    Full Text Available Thematic focus: The motor abnormalities may be part of so-called comorbidities that can coexist with autistic disorder. Objective: To characterize the motor profile of students with autistic disorder. Method: the study included six children with autistic disorder in elementary school, male, aged 5 years and 5 months and 10 years and 9 months. After signing the consent form by parents or guardians, the students were submitted to the Motor Development Scale for assessment of fine motor, gross motor performance, balance, body scheme, spatial organization, temporal organization and laterality. Results: The results revealed a significant difference between the motor age and chronological age. According to the classification of the Scale of Motor Development, students in this study showed motor development lower than expected for age. Conclusion: The students with autistic disorder in this study presented a profile of Developmental Coordination Disorder in comorbidity, showing that participants of this research presented difficulties in activities that required skills such as handwriting. Thus, motor and psychomotor needs of these students were focused on educational and clinical environment to reduce the impact of behavioral and social manifestations.

  17. A strong anti-inflammatory signature revealed by liver transcription profiling of Tmprss6-/- mice.

    Directory of Open Access Journals (Sweden)

    Michela Riba

    Full Text Available Control of systemic iron homeostasis is interconnected with the inflammatory response through the key iron regulator, the antimicrobial peptide hepcidin. We have previously shown that mice with iron deficiency anemia (IDA-low hepcidin show a pro-inflammatory response that is blunted in iron deficient-high hepcidin Tmprss6 KO mice. The transcriptional response associated with chronic hepcidin overexpression due to genetic inactivation of Tmprss6 is unknown. By using whole genome transcription profiling of the liver and analysis of spleen immune-related genes we identified several functional pathways differentially expressed in Tmprss6 KO mice, compared to IDA animals and thus irrespective of the iron status. In the effort of defining genes potentially targets of Tmprss6 we analyzed liver gene expression changes according to the genotype and independently of treatment. Tmprss6 inactivation causes down-regulation of liver pathways connected to immune and inflammatory response as well as spleen genes related to macrophage activation and inflammatory cytokines production. The anti-inflammatory status of Tmprss6 KO animals was confirmed by the down-regulation of pathways related to immunity, stress response and intracellular signaling in both liver and spleen after LPS treatment. Opposite to Tmprss6 KO mice, Hfe(-/- mice are characterized by iron overload with inappropriately low hepcidin levels. Liver expression profiling of Hfe(-/- deficient versus iron loaded mice show the opposite expression of some of the genes modulated by the loss of Tmprss6. Altogether our results confirm the anti-inflammatory status of Tmprss6 KO mice and identify new potential target pathways/genes of Tmprss6.

  18. Low-profile natural and metamaterial antennas analysis methods and applications

    CERN Document Server

    Nakano, Hisamatsu

    2017-01-01

    This book presents the full range of low-profile antennas that use novel elements and take advantage of new concepts in antenna implementation, including metamaterials. Typically formed by constructing lattices of simple elements, metamaterials possess electromagnetic properties not found in naturally occurring materials, and show great promise in a number of low-profile antenna implementations. Introductory chapters define various natural and metamaterial-based antennas and provide the fundamentals of writing computer programs based on the method of moments (MoM) and the finite-difference time-domain method (FDTDM). Chapters then discuss low-profile natural antennas classified into base station antennas, mobile card antennas, beam-forming antennas, and satellite-satellite and earth-satellite communications antennas. Final chapters look at various properties of low-profile metamaterial-based ant nnas, revealing the strengths and limitations of the metamaterial-based straight line antenna (metaline antenna), m...

  19. Hidden profiles and concealed information: strategic information sharing and use in group decision making.

    Science.gov (United States)

    Toma, Claudia; Butera, Fabrizio

    2009-06-01

    Two experiments investigated the differential impact of cooperation and competition on strategic information sharing and use in a three-person group decision-making task. Information was distributed in order to create a hidden profile so that disconfirmation of group members' initial preferences was required to solve the task. Experiment 1 revealed that competition, compared to cooperation, led group members to withhold unshared information, a difference that was not significant for shared information. In competition, compared to cooperation, group members were also more reluctant to disconfirm their initial preferences. Decision quality was lower in competition than in cooperation, this effect being mediated by disconfirmation use and not by information sharing. Experiment 2 replicated these findings and revealed the role of mistrust in predicting strategic information sharing and use in competition. These results support a motivated information processing approach of group decision making.

  20. DNA microarray analyses reveal a post-irradiation differential time-dependent gene expression profile in yeast cells exposed to X-rays and gamma-rays.

    Science.gov (United States)

    Kimura, Shinzo; Ishidou, Emi; Kurita, Sakiko; Suzuki, Yoshiteru; Shibato, Junko; Rakwal, Randeep; Iwahashi, Hitoshi

    2006-07-21

    Ionizing radiation (IR) is the most enigmatic of genotoxic stress inducers in our environment that has been around from the eons of time. IR is generally considered harmful, and has been the subject of numerous studies, mostly looking at the DNA damaging effects in cells and the repair mechanisms therein. Moreover, few studies have focused on large-scale identification of cellular responses to IR, and to this end, we describe here an initial study on the transcriptional responses of the unicellular genome model, yeast (Saccharomyces cerevisiae strain S288C), by cDNA microarray. The effect of two different IR, X-rays, and gamma (gamma)-rays, was investigated by irradiating the yeast cells cultured in YPD medium with 50 Gy doses of X- and gamma-rays, followed by resuspension of the cells in YPD for time-course experiments. The samples were collected for microarray analysis at 20, 40, and 80 min after irradiation. Microarray analysis revealed a time-course transcriptional profile of changed gene expressions. Up-regulated genes belonged to the functional categories mainly related to cell cycle and DNA processing, cell rescue defense and virulence, protein and cell fate, and metabolism (X- and gamma-rays). Similarly, for X- and gamma-rays, the down-regulated genes belonged to mostly transcription and protein synthesis, cell cycle and DNA processing, control of cellular organization, cell fate, and C-compound and carbohydrate metabolism categories, respectively. This study provides for the first time a snapshot of the genome-wide mRNA expression profiles in X- and gamma-ray post-irradiated yeast cells and comparatively interprets/discusses the changed gene functional categories as effects of these two radiations vis-à-vis their energy levels.

  1. Gene expression profiling and secretome analysis differentiate adult-derived human liver stem/progenitor cells and human hepatic stellate cells.

    Directory of Open Access Journals (Sweden)

    Silvia Berardis

    Full Text Available Adult-derived human liver stem/progenitor cells (ADHLSC are obtained after primary culture of the liver parenchymal fraction. The cells are of fibroblastic morphology and exhibit a hepato-mesenchymal phenotype. Hepatic stellate cells (HSC derived from the liver non-parenchymal fraction, present a comparable morphology as ADHLSC. Because both ADHLSC and HSC are described as liver stem/progenitor cells, we strived to extensively compare both cell populations at different levels and to propose tools demonstrating their singularity. ADHLSC and HSC were isolated from the liver of four different donors, expanded in vitro and followed from passage 5 until passage 11. Cell characterization was performed using immunocytochemistry, western blotting, flow cytometry, and gene microarray analyses. The secretion profile of the cells was evaluated using Elisa and multiplex Luminex assays. Both cell types expressed α-smooth muscle actin, vimentin, fibronectin, CD73 and CD90 in accordance with their mesenchymal origin. Microarray analysis revealed significant differences in gene expression profiles. HSC present high expression levels of neuronal markers as well as cytokeratins. Such differences were confirmed using immunocytochemistry and western blotting assays. Furthermore, both cell types displayed distinct secretion profiles as ADHLSC highly secreted cytokines of therapeutic and immuno-modulatory importance, like HGF, interferon-γ and IL-10. Our study demonstrates that ADHLSC and HSC are distinct liver fibroblastic cell populations exhibiting significant different expression and secretion profiles.

  2. Expression and secretory profile of buffalo fetal fibroblasts and Wharton's jelly feeder layers.

    Science.gov (United States)

    Parmar, Mehtab S; Mishra, Smruti Ranjan; Somal, Anjali; Pandey, Sriti; Kumar, G Sai; Sarkar, Mihir; Chandra, Vikash; Sharma, G Taru

    2017-05-01

    The present study examined the comparative expression and secretory profile of vital signaling molecules in buffalo fetal fibroblasts (BFF) and Wharton's jelly (BWJ) feeder layers at different passages. Both feeder layers were expanded up to 8th passage. Signaling molecules viz. bone morphogenetic protein 4 (BMP4), fibroblast growth factor 2 (FGF2), leukemia inhibitory factor (LIF) and transforming growth factor beta 1 (TGFB1) and pluripotency-associated transcriptional factors (POU5F1, SOX2, NANOG, KLF4, MYC and FOXD3) were immunolocalized in the both feeder types. A clear variation in the expression pattern of key signaling molecules with passaging was registered in both feeders compared to primary culture (0 passage). The conditioned media (CM) was collected from different passages (2, 4, 6, 8) of both the feeder layers and was quantified using enzyme-linked immunosorbent assay (ELISA). Concomitant to expression profile, protein quantification also revealed differences in the concentration of signaling molecules at different time points. Conjointly, expression and secretory profile revealed that 2nd passage of BFF and 6th passage of BWJ exhibit optimal levels of key signaling molecules thus may be selected as best passages for embryonic stem cells (ESCs) propagation. Further, the effect of mitomycin-C (MMC) treatment on the expression profile of signaling molecules in the selected passages of BFF and BWJ revealed that MMC modulates the expression profile of these molecules. In conclusion, the results indicate that feeder layers vary in expression and secretory pattern of vital signaling molecules with passaging. Based on these findings, the appropriate feeder passages may be selected for the quality propagation of buffalo ESCs. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Rice Bran Fermented with Saccharomyces boulardii Generates Novel Metabolite Profiles with Bioactivity

    Science.gov (United States)

    2011-01-01

    Emerging evidence supporting chronic disease fighting properties of rice bran has advanced the development of stabilized rice bran for human use as a functional food and dietary supplement. A global and targeted metabolomic investigation of stabilized rice bran fermented with Saccharomyces boulardii was performed in three rice varieties. Metabolites from S. boulardii-fermented rice bran were detected by gas chromatography−mass spectrometry (GC−MS) and assessed for bioactivity compared to nonfermented rice bran in normal and malignant lymphocytes. Global metabolite profiling revealed significant differences in the metabolome that led to discovery of candidate compounds modulated by S. boulardii fermentation. Fermented rice bran extracts from three rice varieties reduced growth of human B lymphomas compared to each variety’s nonfermented control and revealed that fermentation differentially altered bioactive compounds. These data support that integration of global and targeted metabolite analysis can be utilized for assessing health properties of rice bran phytochemicals that are enhanced by yeast fermentation and that differ across rice varieties. PMID:21306106

  4. Correlation between species-specific metabolite profiles and bioactivities of blueberries (Vaccinium spp.).

    Science.gov (United States)

    Lee, Sarah; Jung, Eun Sung; Do, Seon-Gil; Jung, Ga-Young; Song, Gwanpil; Song, Jung-Min; Lee, Choong Hwan

    2014-03-05

    Metabolite profiling of three blueberry species (Vaccinium bracteatum Thunb., V. oldhamii Miquel., and V. corymbosum L.) was performed using gas chromatography-time-of-flight-mass spectrometry (GC-TOF-MS) and ultraperformance liquid chromatography-quadrupole-time-of-flight-mass spectrometry (UPLC-Q-TOF-MS) combined multivariate analysis. Partial least-squares discriminant analysis clearly showed metabolic differences among species. GC-TOF-MS analysis revealed significant differences in amino acids, organic acids, fatty acids, sugars, and phenolic acids among the three blueberry species. UPLC-Q-TOF-MS analysis indicated that anthocyanins were the major metabolites distinguishing V. bracteatum from V. oldhamii. The contents of anthocyanins such as glycosides of cyanidin were high in V. bracteatum, while glycosides of delphinidin, petunidin, and malvidin were high in V. oldhamii. Antioxidant activities assessed using ABTS and DPPH assays showed the greatest activity in V. oldhamii and revealed the highest correlation with total phenolic, total flavonoid, and total anthocyanin contents and their metabolites.

  5. Family-based Association Analyses of Imputed Genotypes Reveal Genome-Wide Significant Association of Alzheimer’s disease with OSBPL6, PTPRG and PDCL3

    Science.gov (United States)

    Herold, Christine; Hooli, Basavaraj V.; Mullin, Kristina; Liu, Tian; Roehr, Johannes T; Mattheisen, Manuel; Parrado, Antonio R.; Bertram, Lars; Lange, Christoph; Tanzi, Rudolph E.

    2015-01-01

    The genetic basis of Alzheimer's disease (AD) is complex and heterogeneous. Over 200 highly penetrant pathogenic variants in the genes APP, PSEN1 and PSEN2 cause a subset of early-onset familial Alzheimer's disease (EOFAD). On the other hand, susceptibility to late-onset forms of AD (LOAD) is indisputably associated to the ε4 allele in the gene APOE, and more recently to variants in more than two-dozen additional genes identified in the large-scale genome-wide association studies (GWAS) and meta-analyses reports. Taken together however, although the heritability in AD is estimated to be as high as 80%, a large proportion of the underlying genetic factors still remain to be elucidated. In this study we performed a systematic family-based genome-wide association and meta-analysis on close to 15 million imputed variants from three large collections of AD families (~3,500 subjects from 1,070 families). Using a multivariate phenotype combining affection status and onset age, meta-analysis of the association results revealed three single nucleotide polymorphisms (SNPs) that achieved genome-wide significance for association with AD risk: rs7609954 in the gene PTPRG (P-value = 3.98·10−08), rs1347297 in the gene OSBPL6 (P-value = 4.53·10−08), and rs1513625 near PDCL3 (P-value = 4.28·10−08). In addition, rs72953347 in OSBPL6 (P-value = 6.36·10−07) and two SNPs in the gene CDKAL1 showed marginally significant association with LOAD (rs10456232, P-value: 4.76·10−07; rs62400067, P-value: 3.54·10−07). In summary, family-based GWAS meta-analysis of imputed SNPs revealed novel genomic variants in (or near) PTPRG, OSBPL6, and PDCL3 that influence risk for AD with genome-wide significance. PMID:26830138

  6. miRNA and mRNA Expression Profiles Reveal Insight into Chitosan-Mediated Regulation of Plant Growth.

    Science.gov (United States)

    Zhang, Xiaoqian; Li, Kecheng; Xing, Ronge; Liu, Song; Chen, Xiaolin; Yang, Haoyue; Li, Pengcheng

    2018-04-18

    Chitosan has been numerously studied as a plant growth regulator and stress tolerance inducer. To investigate the roles of chitosan as bioregulator on plant and unravel its possible metabolic responses mechanisms, we simultaneously investigated mRNAs and microRNAs (miRNAs) expression profiles of wheat seedlings in response to chitosan heptamer. We found 400 chitosan-responsive differentially expressed genes, including 268 up-regulated and 132 down-regulated mRNAs, many of which were related to photosynthesis, primary carbon and nitrogen metabolism, defense responses, and transcription factors. Moreover, miRNAs also participate in chitosan-mediated regulation on plant growth. We identified 87 known and 21 novel miRNAs, among which 56 miRNAs were induced or repressed by chitosan heptamer, such as miRNA156, miRNA159a, miRNA164, miRNA171a, miRNA319, and miRNA1127. The integrative analysis of miRNA and mRNA expression profiles in this case provides fundamental information for further investigation of regulation mechanisms of chitosan on plant growth and will facilitate its application in agriculture.

  7. Modular organization of the white spruce (Picea glauca) transcriptome reveals functional organization and evolutionary signatures.

    Science.gov (United States)

    Raherison, Elie S M; Giguère, Isabelle; Caron, Sébastien; Lamara, Mebarek; MacKay, John J

    2015-07-01

    Transcript profiling has shown the molecular bases of several biological processes in plants but few studies have developed an understanding of overall transcriptome variation. We investigated transcriptome structure in white spruce (Picea glauca), aiming to delineate its modular organization and associated functional and evolutionary attributes. Microarray analyses were used to: identify and functionally characterize groups of co-expressed genes; investigate expressional and functional diversity of vascular tissue preferential genes which were conserved among Picea species, and identify expression networks underlying wood formation. We classified 22 857 genes as variable (79%; 22 coexpression groups) or invariant (21%) by profiling across several vegetative tissues. Modular organization and complex transcriptome restructuring among vascular tissue preferential genes was revealed by their assignment to coexpression groups with partially overlapping profiles and partially distinct functions. Integrated analyses of tissue-based and temporally variable profiles identified secondary xylem gene networks, showed their remodelling over a growing season and identified PgNAC-7 (no apical meristerm (NAM), Arabidopsis transcription activation factor (ATAF) and cup-shaped cotyledon (CUC) transcription factor 007 in Picea glauca) as a major hub gene specific to earlywood formation. Reference profiling identified comprehensive, statistically robust coexpressed groups, revealing that modular organization underpins the evolutionary conservation of the transcriptome structure. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.

  8. A Profile-Based Framework for Factorial Similarity and the Congruence Coefficient.

    Science.gov (United States)

    Hartley, Anselma G; Furr, R Michael

    2017-01-01

    We present a novel profile-based framework for understanding factorial similarity in the context of exploratory factor analysis in general, and for understanding the congruence coefficient (a commonly used index of factor similarity) specifically. First, we introduce the profile-based framework articulating factorial similarity in terms of 3 intuitive components: general saturation similarity, differential saturation similarity, and configural similarity. We then articulate the congruence coefficient in terms of these components, along with 2 additional profile-based components, and we explain how these components resolve ambiguities that can be-and are-found when using the congruence coefficient. Finally, we present secondary analyses revealing that profile-based components of factorial are indeed linked to experts' actual evaluations of factorial similarity. Overall, the profile-based approach we present offers new insights into the ways in which researchers can examine factor similarity and holds the potential to enhance researchers' ability to understand the congruence coefficient.

  9. Biomarkers for early and late stage chronic allograft nephropathy by proteogenomic profiling of peripheral blood.

    Directory of Open Access Journals (Sweden)

    Sunil M Kurian

    2009-07-01

    Full Text Available Despite significant improvements in life expectancy of kidney transplant patients due to advances in surgery and immunosuppression, Chronic Allograft Nephropathy (CAN remains a daunting problem. A complex network of cellular mechanisms in both graft and peripheral immune compartments complicates the non-invasive diagnosis of CAN, which still requires biopsy histology. This is compounded by non-immunological factors contributing to graft injury. There is a pressing need to identify and validate minimally invasive biomarkers for CAN to serve as early predictors of graft loss and as metrics for managing long-term immunosuppression.We used DNA microarrays, tandem mass spectroscopy proteomics and bioinformatics to identify genomic and proteomic markers of mild and moderate/severe CAN in peripheral blood of two distinct cohorts (n = 77 total of kidney transplant patients with biopsy-documented histology.Gene expression profiles reveal over 2400 genes for mild CAN, and over 700 for moderate/severe CAN. A consensus analysis reveals 393 (mild and 63 (moderate/severe final candidates as CAN markers with predictive accuracy of 80% (mild and 92% (moderate/severe. Proteomic profiles show over 500 candidates each, for both stages of CAN including 302 proteins unique to mild and 509 unique to moderate/severe CAN.This study identifies several unique signatures of transcript and protein biomarkers with high predictive accuracies for mild and moderate/severe CAN, the most common cause of late allograft failure. These biomarkers are the necessary first step to a proteogenomic classification of CAN based on peripheral blood profiling and will be the targets of a prospective clinical validation study.

  10. Dissociative features in posttraumatic stress disorder: A latent profile analysis.

    Science.gov (United States)

    Műllerová, Jana; Hansen, Maj; Contractor, Ateka A; Elhai, Jon D; Armour, Cherie

    2016-09-01

    The fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) characterizes the dissociative subtype of posttraumatic stress disorder (PTSD) in terms of the individual meeting the criteria for PTSD and additionally reporting symptoms of depersonalization and/or derealization. The current study aimed to examine whether a dissociative PTSD profile may include alternative features of dissociation and whether it could be differentiated from a nondissociative PTSD profile on certain psychopathologies and demographics. Data from 309 trauma-exposed participants, collected through Amazon Mechanical Turk, were subjected to latent profile analysis. Regression analyses were used to examine the predictors of latent classes. Three discrete profiles named Baseline, PTSD, and Dissociative profile were uncovered. All examined features of dissociation were significantly elevated in the Dissociative profile. Anxiety, male sex, being employed, and having a minority racial background significantly predicted the Dissociative profile relative to the PTSD profile. The study points to the importance of alternative symptoms of dissociation in the dissociative PTSD subtype beyond the symptoms of depersonalization and derealization. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  11. Self-disclosure on Facebook: How much do we really reveal?

    Directory of Open Access Journals (Sweden)

    Stephanie Day

    Full Text Available This paper investigates the use of the social networking site Facebook to self-disclose and analyses the responses of a small group of Facebook users surveyed about their own willingness to self-disclose. An online survey was used to ask Facebook users about their level of Facebook use, what types of personal information they are willing to reveal and the frequency of these personal revelations. The survey also asked the participants to take a look at their publicly viewable profile and the types of information revealed there. Results indicated that overall, most people tended to be cautious about the types of information they revealed, posted mainly positive statements about themselves and were aware of personal privacy issues.

  12. Multi-substrate terpene synthases: their occurrence and physiological significance

    Directory of Open Access Journals (Sweden)

    Leila Pazouki

    2016-07-01

    Full Text Available Terpene synthases are responsible for synthesis of a large number of terpenes in plants using substrates provided by two distinct metabolic pathways, the mevalonate-dependent pathway that is located in cytosol and has been suggested to be responsible for synthesis of sesquiterpenes (C15, and 2-C-methyl-D-erythritol-4-phosphate pathway located in plastids and suggested to be responsible for the synthesis of hemi- (C5, mono- (C10 and diterpenes (C20. Recent advances in characterization of genes and enzymes responsible for substrate and end product biosynthesis as well as efforts in metabolic engineering have demonstrated existence of a number of multi-substrate terpene synthases. This review summarizes the progress in the characterization of such multi-substrate terpene synthases and suggests that the presence of multi-substrate use might have been significantly underestimated. Multi-substrate use could lead to important changes in terpene product profiles upon substrate profile changes under perturbation of metabolism in stressed plants as well as under certain developmental stages. We therefore argue that multi-substrate use can be significant under physiological conditions and can result in complicate modifications in terpene profiles.

  13. Small interference RNA profiling reveals the essential role of human membrane trafficking genes in mediating the infectious entry of dengue virus

    Directory of Open Access Journals (Sweden)

    Chu Justin

    2010-02-01

    Full Text Available Abstract Background Dengue virus (DENV is the causative agent of Dengue fever and the life-threatening Dengue Haemorrhagic fever or Dengue shock syndrome. In the absence of anti-viral agents or vaccine, there is an urgent need to develop an effective anti-viral strategy against this medically important viral pathogen. The initial interplay between DENV and the host cells may represent one of the potential anti-viral targeting sites. Currently the involvements of human membrane trafficking host genes or factors that mediate the infectious cellular entry of dengue virus are not well defined. Results In this study, we have used a targeted small interfering RNA (siRNA library to identify and profile key cellular genes involved in processes of endocytosis, cytoskeletal dynamics and endosome trafficking that are important and essential for DENV infection. The infectious entry of DENV into Huh7 cells was shown to be potently inhibited by siRNAs targeting genes associated with clathrin-mediated endocytosis. The important role of clathrin-mediated endocytosis was confirmed by the expression of well-characterized dominant-negative mutants of genes in this pathway and by using the clathrin endocytosis inhibitor chlorpromazine. Furthermore, DENV infection was shown to be sensitive to the disruption of human genes in regulating the early to late endosomal trafficking as well as the endosomal acidic pH. The importance and involvement of both actin and microtubule dynamics in mediating the infectious entry of DENV was also revealed in this study. Conclusions Together, the findings from this study have provided a detail profiling of the human membrane trafficking cellular genes and the mechanistic insight into the interplay of these host genes with DENV to initiate an infection, hence broadening our understanding on the entry pathway of this medically important viral pathogen. These data may also provide a new potential avenue for development of anti

  14. Wave propagation simulation of radio occultations based on ECMWF refractivity profiles

    DEFF Research Database (Denmark)

    von Benzon, Hans-Henrik; Høeg, Per

    2015-01-01

    This paper describes a complete radio occultation simulation environment, including realistic refractivity profiles, wave propagation modeling, instrument modeling, and bending angle retrieval. The wave propagator is used to simulate radio occultation measurements. The radio waves are propagated...... of radio occultations. The output from the wave propagator simulator is used as input to a Full Spectrum Inversion retrieval module which calculates geophysical parameters. These parameters can be compared to the ECMWF atmospheric profiles. The comparison can be used to reveal system errors and get...... a better understanding of the physics. The wave propagation simulations will in this paper also be compared to real measurements. These radio occultations have been exposed to the same atmospheric conditions as the radio occultations simulated by the wave propagator. This comparison reveals that precise...

  15. Profiles in coping: responses to sexual harassment across persons, organizations and cultures

    OpenAIRE

    Cortina, Lilia M.; Wasti, S. Arzu

    2005-01-01

    This study explicates the complexity of sexual harassment coping behavior among 4 diverse samples of working women: (a) working-class Hispanic Americans, (b) working-class Anglo Americans, (c) professional Turks, and (d) professional Anglo Americans. K-means cluster analysis revealed 3 common harassment coping profiles: (a) detached, (b) avoidant negotiating, and (c) support seeking. The authors then tested an integrated framework of coping profile determinants, involving social power, stress...

  16. Effects of Different Grinding Methods on Morphological, Textural Properties and Pasting Profiles of MR220 Rice Flour

    International Nuclear Information System (INIS)

    Noorlaila Ahmad; Asmeda Rajab; Norziah Mohd Hani

    2016-01-01

    Three different grinding techniques (dry, semi-wet, and wet) were employed in rice flour production. Investigation on the effects of the grinding techniques on starch damage percentage, particle size distribution, pasting profiles, morphological and textural properties of rice flours produced were evaluated. Wet grinding resulted in significantly (p<0.05) has lower percentage of damaged starch (3.24 %) than other grinding methods. Morphological studies (microscopy and particle size analysis) have reflected significant differences among rice flours granule shapes. The granules displaying different shapes of polygonal, round and angular forms, with some as an individual granule while others tend to attached together. Wet grinding technique also yielded flour that exhibit significantly (p<0.05) with higher gel hardness (16.62 g). Pasting profiles showed that pasting temperature for rice flour produce using these three grinding methods varied between 80.15 - 80.42 degree Celcius. Results revealed that the three grinding techniques clearly affected the physicochemical properties of rice flour. The results from this study play an important role in the selection criteria of rice flour with desirable pasting and textural properties for manufacturing rice-based product. (author)

  17. Network analysis of genomic alteration profiles reveals co-altered functional modules and driver genes for glioblastoma.

    Science.gov (United States)

    Gu, Yunyan; Wang, Hongwei; Qin, Yao; Zhang, Yujing; Zhao, Wenyuan; Qi, Lishuang; Zhang, Yuannv; Wang, Chenguang; Guo, Zheng

    2013-03-01

    The heterogeneity of genetic alterations in human cancer genomes presents a major challenge to advancing our understanding of cancer mechanisms and identifying cancer driver genes. To tackle this heterogeneity problem, many approaches have been proposed to investigate genetic alterations and predict driver genes at the individual pathway level. However, most of these approaches ignore the correlation of alteration events between pathways and miss many genes with rare alterations collectively contributing to carcinogenesis. Here, we devise a network-based approach to capture the cooperative functional modules hidden in genome-wide somatic mutation and copy number alteration profiles of glioblastoma (GBM) from The Cancer Genome Atlas (TCGA), where a module is a set of altered genes with dense interactions in the protein interaction network. We identify 7 pairs of significantly co-altered modules that involve the main pathways known to be altered in GBM (TP53, RB and RTK signaling pathways) and highlight the striking co-occurring alterations among these GBM pathways. By taking into account the non-random correlation of gene alterations, the property of co-alteration could distinguish oncogenic modules that contain driver genes involved in the progression of GBM. The collaboration among cancer pathways suggests that the redundant models and aggravating models could shed new light on the potential mechanisms during carcinogenesis and provide new indications for the design of cancer therapeutic strategies.

  18. Physicochemical Profiles of the Marketed Agrochemicals and Clues for Agrochemical Lead Discovery and Screening Library Development.

    Science.gov (United States)

    Rao, Hanbing; Huangfu, Changxin; Wang, Yanying; Wang, Xianxiang; Tang, Tiansheng; Zeng, Xianyin; Li, Zerong; Chen, Yuzong

    2015-05-01

    Combinatorial chemistry, high-throughput and virtual screening technologies have been extensively used for discovering agrochemical leads from chemical libraries. The knowledge of the physicochemical properties of the marketed agrochemicals is useful for guiding the design and selection of such libraries. Since the earlier profiling of marketed agrochemicals, the number and types of marketed agrochemicals have significantly increased. Recent studies have shown the change of some physicochemical properties of oral drugs with time. There is a need to also profile the physicochemical properties of the marketed agrochemicals. In this work, we analyzed the key physicochemical properties of 1751 marketed agrochemicals in comparison with the previously-analyzed herbicides and insecticides, 106 391 natural products and 57 548 diverse synthetic libraries compounds. Our study revealed the distribution profiles and evolution trend of different types of agrochemicals that in many respects are broadly similar to the reported profiles for oral drugs, with the most marked difference being that agrochemicals have a lower number of hydrogen bond donors. The derived distribution patterns provided the rule of thumb guidelines for selecting potential agrochemical leads and also provided clues for further improving the libraries for agrochemical lead discovery. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Effects of mask imperfections on InP etching profiles

    International Nuclear Information System (INIS)

    Huo, D.T.C.; Yan, M.F.; Wynn, J.D.; Wilt, D.P.

    1990-01-01

    The authors have demonstrated that the quality of etch masks has a significant effect on the InP etching profiles. In particular, the authors have shown that mask imperfections can cause defective etching profiles, such as vertical sidewalls and extra mask undercutting in InP. The authors also discovered that the geometry of these defective profiles is determined by the orientation of the substrate relative to the direction of the mask imperfections. Along a left-angle 110 right-angle line mask defect, the downward etching process changes the left-angle 110 right-angle v-grooves to vertical sidewalls without extra undercutting. For v-grooves aligned along the left-angle 110 right-angle direction, defects on the mask give a significant extra undercutting without changing the etching profile

  20. The history of nursing in the home: revealing the significance of place in the expression of moral agency.

    Science.gov (United States)

    Peter, Elizabeth

    2002-06-01

    The history of nursing in the home: revealing the significance of place in the expression of moral agency The relationship between place and moral agency in home care nursing is explored in this paper. The notion of place is argued to have relevance to moral agency beyond moral context. This argument is theoretically located in feminist ethics and human geography and is supported through an examination of historical documents (1900-33) that describe the experiences and insights of American home care/private duty nurses or that are related to nursing ethics. Specifically, the role of place in inhibiting and enhancing care, justice, good relationships, and power in the practice of private duty nurses is explored. Several implications for current nursing ethics come out of this analysis. (i) The moral agency of nurses is highly nuanced. It is not only structured by nurses' relationships to patients and health professionals, i.e. moral context, it is also structured by the place of nursing care. (ii) Place has the potential to limit and enhance the power of nurses. (iii) Some aspects of nursing's conception of the good, such as what constitutes a good nurse-patient relationship, are historically and geographically relative.

  1. Character profiles and life satisfaction.

    Science.gov (United States)

    Park, Hwanjin; Suh, Byung Seong; Kim, Won Sool; Lee, Hye-Kyung; Park, Seon-Cheol; Lee, Kounseok

    2015-04-01

    There is a surge of interest in subjective well-being (SWB), which concerns how individuals feel about their happiness. Life satisfaction tends to be influenced by individual psychological traits and external social factors. The aim of this study was to examine the relationship between individual character and SWB. Data from 3522 university students were analyzed in this study. Character profiles were evaluated using the Temperament and Character Inventory-Revised Short version (TCI-RS). Life satisfaction was assessed using the Satisfaction with Life Scale (SWLS). All statistical tests regarding the correlations between each character profile and life satisfaction were conducted using ANOVAs, t-tests, multiple linear regression models and correlation analyses. The creative (SCT) profile was associated with the highest levels of life satisfaction, whereas the depressive (sct) profile was associated with the lowest levels of life satisfaction. Additionally, high self-directedness, self-transcendence and cooperation were associated with high life satisfaction. The results of gender-adjusted multiple regression analysis showed that the effects of self-directedness were the strongest in the assessment of one's quality of life, followed by self-transcendence and cooperativeness, in that order. All of the three-character profiles were significantly correlated with one's quality of life, and the character profiles of TCI-RS explained 27.6% of life satisfaction in total. Among the three-character profiles, the self-directedness profile was most associated with life satisfaction. Our study was cross-sectional, and self-reported data from students at a single university were analyzed. The results of this study showed that, among the character profiles, the effects of self-directedness were the strongest for predicting life satisfaction. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Earth-mass haloes and the emergence of NFW density profiles

    Science.gov (United States)

    Angulo, Raul E.; Hahn, Oliver; Ludlow, Aaron D.; Bonoli, Silvia

    2017-11-01

    We simulate neutralino dark matter (χDM) haloes from their initial collapse, at ˜ earth mass, up to a few percent solar. Our results confirm that the density profiles of the first haloes are described by a ˜r-1.5 power law. As haloes grow in mass, their density profiles evolve significantly. In the central regions, they become shallower and reach on average ˜r-1, the asymptotic form of an NFW profile. Using non-cosmological controlled simulations, we observe that temporal variations in the gravitational potential caused by major mergers lead to a shallowing of the inner profile. This transformation is more significant for shallower initial profiles and for a higher number of merging systems. Depending on the merger details, the resulting profiles can be shallower or steeper than NFW in their inner regions. Interestingly, mergers have a much weaker effect when the profile is given by a broken power law with an inner slope of -1 (such as NFW or Hernquist profiles). This offers an explanation for the emergence of NFW-like profiles: after their initial collapse, r-1.5 χDM haloes suffer copious major mergers, which progressively shallows the profile. Once an NFW-like profile is established, subsequent merging does not change the profile anymore. This suggests that halo profiles are not universal but rather a combination of (1) the physics of the formation of the microhaloes and (2) their early merger history - both set by the properties of the dark matter particle - as well as (3) the resilience of NFW-like profiles to perturbations.

  3. Genome-wide identification of Bcl11b gene targets reveals role in brain-derived neurotrophic factor signaling.

    Directory of Open Access Journals (Sweden)

    Bin Tang

    Full Text Available B-cell leukemia/lymphoma 11B (Bcl11b is a transcription factor showing predominant expression in the striatum. To date, there are no known gene targets of Bcl11b in the nervous system. Here, we define targets for Bcl11b in striatal cells by performing chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq in combination with genome-wide expression profiling. Transcriptome-wide analysis revealed that 694 genes were significantly altered in striatal cells over-expressing Bcl11b, including genes showing striatal-enriched expression similar to Bcl11b. ChIP-seq analysis demonstrated that Bcl11b bound a mixture of coding and non-coding sequences that were within 10 kb of the transcription start site of an annotated gene. Integrating all ChIP-seq hits with the microarray expression data, 248 direct targets of Bcl11b were identified. Functional analysis on the integrated gene target list identified several zinc-finger encoding genes as Bcl11b targets, and further revealed a significant association of Bcl11b to brain-derived neurotrophic factor/neurotrophin signaling. Analysis of ChIP-seq binding regions revealed significant consensus DNA binding motifs for Bcl11b. These data implicate Bcl11b as a novel regulator of the BDNF signaling pathway, which is disrupted in many neurological disorders. Specific targeting of the Bcl11b-DNA interaction could represent a novel therapeutic approach to lowering BDNF signaling specifically in striatal cells.

  4. Metabonomics revealed xanthine oxidase-induced oxidative stress and inflammation in the pathogenesis of diabetic nephropathy.

    Science.gov (United States)

    Liu, Jingping; Wang, Chengshi; Liu, Fang; Lu, Yanrong; Cheng, Jingqiu

    2015-03-01

    Diabetic nephropathy (DN) is a serious complication of diabetes mellitus (DM), which is a major public health problem in the world. To reveal the metabolic changes associated with DN, we analyzed the serum, urine, and renal extracts obtained from control and streptozotocin (STZ)-induced DN rats by (1)H NMR-based metabonomics and multivariate data analysis. A significant difference between control and DN rats was revealed in metabolic profiles, and we identified several important DN-related metabolites including increased levels of allantoin and uric acid (UA) in the DN rats, suggesting that disturbed purine metabolism may be involved in the DN. Combined with conventional histological and biological methods, we further demonstrated that xanthine oxidase (XO), a key enzyme for purine catabolism, was abnormally activated in the kidney of diabetic rats by hyperglycemia. The highly activated XO increased the level of intracellular ROS, which caused renal injury by direct oxidative damage to renal cells, and indirect inducing inflammatory responses via activating NF-κB signaling pathway. Our study highlighted that metabonomics is a promising tool to reveal the metabolic changes and the underlying mechanism involved in the pathogenesis of DN.

  5. Microarray analysis of gene expression profiles in ripening pineapple fruits.

    Science.gov (United States)

    Koia, Jonni H; Moyle, Richard L; Botella, Jose R

    2012-12-18

    Pineapple (Ananas comosus) is a tropical fruit crop of significant commercial importance. Although the physiological changes that occur during pineapple fruit development have been well characterized, little is known about the molecular events that occur during the fruit ripening process. Understanding the molecular basis of pineapple fruit ripening will aid the development of new varieties via molecular breeding or genetic modification. In this study we developed a 9277 element pineapple microarray and used it to profile gene expression changes that occur during pineapple fruit ripening. Microarray analyses identified 271 unique cDNAs differentially expressed at least 1.5-fold between the mature green and mature yellow stages of pineapple fruit ripening. Among these 271 sequences, 184 share significant homology with genes encoding proteins of known function, 53 share homology with genes encoding proteins of unknown function and 34 share no significant homology with any database accession. Of the 237 pineapple sequences with homologs, 160 were up-regulated and 77 were down-regulated during pineapple fruit ripening. DAVID Functional Annotation Cluster (FAC) analysis of all 237 sequences with homologs revealed confident enrichment scores for redox activity, organic acid metabolism, metalloenzyme activity, glycolysis, vitamin C biosynthesis, antioxidant activity and cysteine peptidase activity, indicating the functional significance and importance of these processes and pathways during pineapple fruit development. Quantitative real-time PCR analysis validated the microarray expression results for nine out of ten genes tested. This is the first report of a microarray based gene expression study undertaken in pineapple. Our bioinformatic analyses of the transcript profiles have identified a number of genes, processes and pathways with putative involvement in the pineapple fruit ripening process. This study extends our knowledge of the molecular basis of pineapple fruit

  6. Metabolic profile in different cathegories of diary cowst

    OpenAIRE

    Ulchar Igor; Celeska Irena; Ilievska Ksenija; Mitrov Dine; Dzhadzhovski Igor

    2008-01-01

    Knowing the values of the metabolic profile is important for prevention of so-called "production diseases" which have significant negative impact on the milk production. The aim of these investigations was determination of the metabolic profile and its referent values in the diary cows in several farms. Investigations included four categories of diary cows: pregnant heifers, cows in early lactation, cows in late lactation and dry cows. Discussion explains both significant differences of value...

  7. Fetal mesenchymal stromal cells differentiating towards chondrocytes acquire a gene expression profile resembling human growth plate cartilage.

    Directory of Open Access Journals (Sweden)

    Sandy A van Gool

    Full Text Available We used human fetal bone marrow-derived mesenchymal stromal cells (hfMSCs differentiating towards chondrocytes as an alternative model for the human growth plate (GP. Our aims were to study gene expression patterns associated with chondrogenic differentiation to assess whether chondrocytes derived from hfMSCs are a suitable model for studying the development and maturation of the GP. hfMSCs efficiently formed hyaline cartilage in a pellet culture in the presence of TGFβ3 and BMP6. Microarray and principal component analysis were applied to study gene expression profiles during chondrogenic differentiation. A set of 232 genes was found to correlate with in vitro cartilage formation. Several identified genes are known to be involved in cartilage formation and validate the robustness of the differentiating hfMSC model. KEGG pathway analysis using the 232 genes revealed 9 significant signaling pathways correlated with cartilage formation. To determine the progression of growth plate cartilage formation, we compared the gene expression profile of differentiating hfMSCs with previously established expression profiles of epiphyseal GP cartilage. As differentiation towards chondrocytes proceeds, hfMSCs gradually obtain a gene expression profile resembling epiphyseal GP cartilage. We visualized the differences in gene expression profiles as protein interaction clusters and identified many protein clusters that are activated during the early chondrogenic differentiation of hfMSCs showing the potential of this system to study GP development.

  8. Comparison of serum lipid profile in non alcoholic fatty liver disease

    International Nuclear Information System (INIS)

    Latif, A.; Ain, Q.U.A.; Ahmed, N.; Shafiq, A.M.; Sapna, K.

    2017-01-01

    Objective: To compare serum lipid profile in different ultrasonographic grades of non alcoholic fatty liver disease (NAFLD). Study Design: Cross sectional study. Place and Duration of Study: PNS SHIFA hospital, Karachi, from Oct 2015 to Jul 2016. Material and Methods: Seventy three adults of either gender were consecutively inducted after diagnosis of non alcoholic fatty liver disease (NAFLD) on ultrasonography (USG). These individuals were further classified into grade I, II and III of NAFLD depending on US findings. Fasting blood sample of all the subjects was analyzed for serum fasting lipid profile comprising of total cholesterol (TC), triglycerides (TG), high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C). Serum non HDL cholesterol (nonHDL-C) was calculated by subtracting HDL-C from TC. Results: Among 73 subjects with NAFLD, 42.5%, 37% and 20.5% had grade I, II and III NAFLD respectively. All parameters showed significant increase in frequency of abnormal results with increasing grade of NAFLD except TG. Significant difference was found in mean TC (p=0.000), LDL-C (p=0.000), HDL-C (p=0.005) and nonHDL-C (p=0.000) between grades of NAFLD. Post hoc analysis revealed that only mean nonHDL-C was significantly different amongst all the grades of NAFLD. Conclusion: The increasing severity of NAFLD was found associated with increased frequency of dyslipidemia. Though most frequent dyslipidemia in NAFLD was low serum HDL-C followed by hypertriglyceridemia, only serum nonHDL-C was statistically different amongst all the grades of NAFLD. (author)

  9. The adipokine leptin increases skeletal muscle mass and significantly alters skeletal muscle miRNA expression profile in aged mice

    International Nuclear Information System (INIS)

    Hamrick, Mark W.; Herberg, Samuel; Arounleut, Phonepasong; He, Hong-Zhi; Shiver, Austin; Qi, Rui-Qun; Zhou, Li; Isales, Carlos M.

    2010-01-01

    Research highlights: → Aging is associated with muscle atrophy and loss of muscle mass, known as the sarcopenia of aging. → We demonstrate that age-related muscle atrophy is associated with marked changes in miRNA expression in muscle. → Treating aged mice with the adipokine leptin significantly increased muscle mass and the expression of miRNAs involved in muscle repair. → Recombinant leptin therapy may therefore be a novel approach for treating age-related muscle atrophy. -- Abstract: Age-associated loss of muscle mass, or sarcopenia, contributes directly to frailty and an increased risk of falls and fractures among the elderly. Aged mice and elderly adults both show decreased muscle mass as well as relatively low levels of the fat-derived hormone leptin. Here we demonstrate that loss of muscle mass and myofiber size with aging in mice is associated with significant changes in the expression of specific miRNAs. Aging altered the expression of 57 miRNAs in mouse skeletal muscle, and many of these miRNAs are now reported to be associated specifically with age-related muscle atrophy. These include miR-221, previously identified in studies of myogenesis and muscle development as playing a role in the proliferation and terminal differentiation of myogenic precursors. We also treated aged mice with recombinant leptin, to determine whether leptin therapy could improve muscle mass and alter the miRNA expression profile of aging skeletal muscle. Leptin treatment significantly increased hindlimb muscle mass and extensor digitorum longus fiber size in aged mice. Furthermore, the expression of 37 miRNAs was altered in muscles of leptin-treated mice. In particular, leptin treatment increased the expression of miR-31 and miR-223, miRNAs known to be elevated during muscle regeneration and repair. These findings suggest that aging in skeletal muscle is associated with marked changes in the expression of specific miRNAs, and that nutrient-related hormones such as leptin

  10. The adipokine leptin increases skeletal muscle mass and significantly alters skeletal muscle miRNA expression profile in aged mice

    Energy Technology Data Exchange (ETDEWEB)

    Hamrick, Mark W., E-mail: mhamrick@mail.mcg.edu [Department of Cellular Biology and Anatomy, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); Department of Orthopaedic Surgery, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); Herberg, Samuel; Arounleut, Phonepasong [Department of Cellular Biology and Anatomy, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); Department of Orthopaedic Surgery, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); He, Hong-Zhi [Henry Ford Immunology Program, Henry Ford Health System, Detroit, MI (United States); Department of Dermatology, Henry Ford Health System, Detroit, MI (United States); Shiver, Austin [Department of Cellular Biology and Anatomy, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); Department of Orthopaedic Surgery, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); Qi, Rui-Qun [Henry Ford Immunology Program, Henry Ford Health System, Detroit, MI (United States); Department of Dermatology, Henry Ford Health System, Detroit, MI (United States); Zhou, Li [Henry Ford Immunology Program, Henry Ford Health System, Detroit, MI (United States); Department of Dermatology, Henry Ford Health System, Detroit, MI (United States); Department of Internal Medicine, Henry Ford Health System, Detroit, MI (United States); Isales, Carlos M. [Department of Cellular Biology and Anatomy, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); Department of Orthopaedic Surgery, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); others, and

    2010-09-24

    Research highlights: {yields} Aging is associated with muscle atrophy and loss of muscle mass, known as the sarcopenia of aging. {yields} We demonstrate that age-related muscle atrophy is associated with marked changes in miRNA expression in muscle. {yields} Treating aged mice with the adipokine leptin significantly increased muscle mass and the expression of miRNAs involved in muscle repair. {yields} Recombinant leptin therapy may therefore be a novel approach for treating age-related muscle atrophy. -- Abstract: Age-associated loss of muscle mass, or sarcopenia, contributes directly to frailty and an increased risk of falls and fractures among the elderly. Aged mice and elderly adults both show decreased muscle mass as well as relatively low levels of the fat-derived hormone leptin. Here we demonstrate that loss of muscle mass and myofiber size with aging in mice is associated with significant changes in the expression of specific miRNAs. Aging altered the expression of 57 miRNAs in mouse skeletal muscle, and many of these miRNAs are now reported to be associated specifically with age-related muscle atrophy. These include miR-221, previously identified in studies of myogenesis and muscle development as playing a role in the proliferation and terminal differentiation of myogenic precursors. We also treated aged mice with recombinant leptin, to determine whether leptin therapy could improve muscle mass and alter the miRNA expression profile of aging skeletal muscle. Leptin treatment significantly increased hindlimb muscle mass and extensor digitorum longus fiber size in aged mice. Furthermore, the expression of 37 miRNAs was altered in muscles of leptin-treated mice. In particular, leptin treatment increased the expression of miR-31 and miR-223, miRNAs known to be elevated during muscle regeneration and repair. These findings suggest that aging in skeletal muscle is associated with marked changes in the expression of specific miRNAs, and that nutrient

  11. CDBG Performance Profiles - PY12

    Data.gov (United States)

    Department of Housing and Urban Development — These profiles significantly increase the amount of information that is available about the performance of CDBG grantees. It is important that our grantees, all our...

  12. DNA Profiling Success Rates from Degraded Skeletal Remains in Guatemala.

    Science.gov (United States)

    Johnston, Emma; Stephenson, Mishel

    2016-07-01

    No data are available regarding the success of DNA Short Tandem Repeat (STR) profiling from degraded skeletal remains in Guatemala. Therefore, DNA profiling success rates relating to 2595 skeletons from eleven cases at the Forensic Anthropology Foundation of Guatemala (FAFG) are presented. The typical postmortem interval was 30 years. DNA was extracted from bone powder and amplified using Identifiler and Minifler. DNA profiling success rates differed between cases, ranging from 50.8% to 7.0%, the overall success rate for samples was 36.3%. The best DNA profiling success rates were obtained from femur (36.2%) and tooth (33.7%) samples. DNA profiles were significantly better from lower body bones than upper body bones (p = <0.0001). Bone samples from males gave significantly better profiles than samples from females (p = <0.0001). These results are believed to be related to bone density. The findings are important for designing forensic DNA sampling strategies in future victim recovery investigations. © 2016 American Academy of Forensic Sciences.

  13. Label-Free LC-MS Profiling of Skeletal Muscle Reveals Heart-Type Fatty Acid Binding Protein as a Candidate Biomarker of Aerobic Capacity.

    Science.gov (United States)

    Malik, Zulezwan Ab; Cobley, James N; Morton, James P; Close, Graeme L; Edwards, Ben J; Koch, Lauren G; Britton, Steven L; Burniston, Jatin G

    2013-12-01

    Two-dimensional gel electrophoresis provides robust comparative analysis of skeletal muscle, but this technique is laborious and limited by its inability to resolve all proteins. In contrast, orthogonal separation by SDS-PAGE and reverse-phase liquid chromatography (RPLC) coupled to mass spectrometry (MS) affords deep mining of the muscle proteome, but differential analysis between samples is challenging due to the greater level of fractionation and the complexities of quantifying proteins based on the abundances of their tryptic peptides. Here we report simple, semi-automated and time efficient ( i.e ., 3 h per sample) proteome profiling of skeletal muscle by 1-dimensional RPLC electrospray ionisation tandem MS. Solei were analysed from rats (n = 5, in each group) bred as either high- or low-capacity runners (HCR and LCR, respectively) that exhibited a 6.4-fold difference (1,625 ± 112 m vs . 252 ± 43 m, p ions, which spanned three orders of magnitude. In total, 207 proteins were analysed, which encompassed almost all enzymes of the major metabolic pathways in skeletal muscle. The most abundant protein detected was type I myosin heavy chain (RA = 5,843 ± 897) and the least abundant protein detected was heat shock 70 kDa protein (RA = 2 ± 0.5). Sixteen proteins were significantly ( p ion (551.21 m/z ) of the doubly-charged peptide SLGVGFATR (454.19 m/z ) of residues 23-31 of FABPH. SRM was conducted on technical replicates of each biological sample and exhibited a coefficient of variation of 20%. The abundance of FABPH measured by SRM was 2.84-fold greater ( p = 0.0095) in HCR muscle. In addition, SRM of FABPH was performed in vastus lateralis samples of young and elderly humans with different habitual activity levels (collected during a previous study) finding FABPH abundance was 2.23-fold greater ( p = 0.0396) in endurance-trained individuals regardless of differences in age. In summary, our findings in HCR/LCR rats provide protein-level confirmation for

  14. Comprehensive analysis of miRNAs expression profiles revealed potential key miRNA/mRNAs regulating colorectal cancer stem cell self-renewal.

    Science.gov (United States)

    Xu, Peng; Wang, Junhua; Sun, Bo; Xiao, Zhongdang

    2018-05-20

    Self-renewal is essential for the malignant biological behaviors of colorectal cancer stem cells. While the self-renewal molecular mechanisms of colorectal cancer stem cells are not yet fully understood. Recently, miRNAs are reported to be relevant to the self-renewal ability of cancer stem cells. In this study, we first isolated colorectal cancer stem cell from colorectal cancer cell line HCT-116 by 1% low serum culture. Then we conducted a comprehensive analysis based on the miRNAs profiles data of both colorectal cancer stem cells and normal cultured colorectal cancer cells. Pathway analysis revealed multiple pathways including Jak-STAT, TGF-beta, PI3K-Akt and MAPK signaling pathway that are correlated to colorectal cancer. Further, we constructed a miRNA-mRNA network, based on which, several miRNA/mRNA pairs were ranked according to their impact index to the self-renewal of colorectal cancer stem cells. Further biological experiment showed that up-regulation of miR-92a-3p led to cell cycle arrest and reduced colony formation. This work provides clues to find the new potential biomarkers for colorectal cancer stem cell diagnosis and select effective miRNAs for targeted therapy. Copyright © 2018 Elsevier B.V. All rights reserved.

  15. Kozeny-Carman permeability relationship with disintegration process predicted from early dissolution profiles of immediate release tablets.

    Science.gov (United States)

    Kumari, Parveen; Rathi, Pooja; Kumar, Virender; Lal, Jatin; Kaur, Harmeet; Singh, Jasbir

    2017-07-01

    This study was oriented toward the disintegration profiling of the diclofenac sodium (DS) immediate-release (IR) tablets and development of its relationship with medium permeability k perm based on Kozeny-Carman equation. Batches (L1-L9) of DS IR tablets with different porosities and specific surface area were prepared at different compression forces and evaluated for porosity, in vitro dissolution and particle-size analysis of the disintegrated mass. The k perm was calculated from porosities and specific surface area, and disintegration profiles were predicted from the dissolution profiles of IR tablets by stripping/residual method. The disintegration profiles were subjected to exponential regression to find out the respective disintegration equations and rate constants k d . Batches L1 and L2 showed the fastest disintegration rates as evident from their bi-exponential equations while the rest of the batches L3-L9 exhibited the first order or mono-exponential disintegration kinetics. The 95% confidence interval (CI 95% ) revealed significant differences between k d values of different batches except L4 and L6. Similar results were also spotted for dissolution profiles of IR tablets by similarity (f 2 ) test. The final relationship between k d and k perm was found to be hyperbolic, signifying the initial effect of k perm on the disintegration rate. The results showed that disintegration profiling is possible because a relationship exists between k d and k perm . The later being relatable with porosity and specific surface area can be determined by nondestructive tests.

  16. Alteration of the fecal microbiota and serum metabolite profiles in dogs with idiopathic inflammatory bowel disease

    Science.gov (United States)

    Minamoto, Yasushi; Otoni, Cristiane C; Steelman, Samantha M; Büyükleblebici, Olga; Steiner, Jörg M; Jergens, Albert E; Suchodolski, Jan S

    2015-01-01

    Idiopathic inflammatory bowel disease (IBD) is a common cause of chronic gastrointestinal (GI) disease in dogs. The combination of an underlying host genetic susceptibility, an intestinal dysbiosis, and dietary/environmental factors are suspected as main contributing factors in the pathogenesis of canine IBD. However, actual mechanisms of the host-microbe interactions remain elusive. The aim of this study was to compare the fecal microbiota and serum metabolite profiles between healthy dogs (n = 10) and dogs with IBD before and after 3 weeks of medical therapy (n = 12). Fecal microbiota and metabolite profiles were characterized by 454-pyrosequencing of 16 S rRNA genes and by an untargeted metabolomics approach, respectively. Significantly lower bacterial diversity and distinct microbial communities were observed in dogs with IBD compared to the healthy control dogs. While Gammaproteobacteria were overrepresented, Erysipelotrichia, Clostridia, and Bacteroidia were underrepresented in dogs with IBD. The functional gene content was predicted from the 16 S rRNA gene data using PICRUSt, and revealed overrepresented bacterial secretion system and transcription factors, and underrepresented amino acid metabolism in dogs with IBD. The serum metabolites 3-hydroxybutyrate, hexuronic acid, ribose, and gluconic acid lactone were significantly more abundant in dogs with IBD. Although a clinical improvement was observed after medical therapy in all dogs with IBD, this was not accompanied by significant changes in the fecal microbiota or in serum metabolite profiles. These results suggest the presence of oxidative stress and a functional alteration of the GI microbiota in dogs with IBD, which persisted even in the face of a clinical response to medical therapy. PMID:25531678

  17. Alteration of the fecal microbiota and serum metabolite profiles in dogs with idiopathic inflammatory bowel disease.

    Science.gov (United States)

    Minamoto, Yasushi; Otoni, Cristiane C; Steelman, Samantha M; Büyükleblebici, Olga; Steiner, Jörg M; Jergens, Albert E; Suchodolski, Jan S

    2015-01-01

    Idiopathic inflammatory bowel disease (IBD) is a common cause of chronic gastrointestinal (GI) disease in dogs. The combination of an underlying host genetic susceptibility, an intestinal dysbiosis, and dietary/environmental factors are suspected as main contributing factors in the pathogenesis of canine IBD. However, actual mechanisms of the host-microbe interactions remain elusive. The aim of this study was to compare the fecal microbiota and serum metabolite profiles between healthy dogs (n = 10) and dogs with IBD before and after 3 weeks of medical therapy (n = 12). Fecal microbiota and metabolite profiles were characterized by 454-pyrosequencing of 16 S rRNA genes and by an untargeted metabolomics approach, respectively. Significantly lower bacterial diversity and distinct microbial communities were observed in dogs with IBD compared to the healthy control dogs. While Gammaproteobacteria were overrepresented, Erysipelotrichia, Clostridia, and Bacteroidia were underrepresented in dogs with IBD. The functional gene content was predicted from the 16 S rRNA gene data using PICRUSt, and revealed overrepresented bacterial secretion system and transcription factors, and underrepresented amino acid metabolism in dogs with IBD. The serum metabolites 3-hydroxybutyrate, hexuronic acid, ribose, and gluconic acid lactone were significantly more abundant in dogs with IBD. Although a clinical improvement was observed after medical therapy in all dogs with IBD, this was not accompanied by significant changes in the fecal microbiota or in serum metabolite profiles. These results suggest the presence of oxidative stress and a functional alteration of the GI microbiota in dogs with IBD, which persisted even in the face of a clinical response to medical therapy.

  18. A novel protodioscin-enriched fenugreek seed extract (Trigonella foenum-graecum, family Fabaceae improves free testosterone level and sperm profile in healthy volunteers

    Directory of Open Access Journals (Sweden)

    Debasis Bagchi

    2017-03-01

    Full Text Available Background: A novel, patent-pending 20% protodioscin-enriched extract has been developed in our laboratories from fenugreek seeds(Furosap®. We assessed the efficacy of Furosap®in 50 male volunteers (age: 35-65 yearson free and total increased testosterone levels, sperm profile, mental alertness, cardiovascular health, mood, libido,and quality of life. Methods: Furosap®(500 mg/day/subjectwas administered to the 50 male volunteers over a period of 12 weeks in aone-arm, open-labelled study, to determine the efficacy on free and total testosterone levels, sperm profile andsperm morphology, libido and erectile dysfunction, mood and mental alertness and broad spectrum safety parameters. Institution Review Board approval was obtained for this study and the study was registered at the clinicaltrials.gov(NCT02702882.Results: A statistically significant increase in freetestosterone levels were observed in these volunteers following supplementation of Furosap®. Sperm morphology, sperm counts, mental alertness, mood, cardiovascular health,and libidoperformancewere significantly improved. Extensive blood chemistry analyses revealed broad spectrum safety. No significant changes were observed in serum lipid function, cholesterol, triglyceride, HDL and LDLlevels,andhemogram.Conclusions: Results confirmedthat this protodioscin-enriched extract from fenugreek seeds (Furosapis safe and efficacious in boosting serum free testosterone levels, healthy sperm profile, mental alertness, cardiovascular health,and overall performance in male volunteers

  19. Flow profiling of a surface-acoustic-wave nanopump

    Science.gov (United States)

    Guttenberg, Z.; Rathgeber, A.; Keller, S.; Rädler, J. O.; Wixforth, A.; Kostur, M.; Schindler, M.; Talkner, P.

    2004-11-01

    The flow profile in a capillary gap and the pumping efficiency of an acoustic micropump employing surface acoustic waves is investigated both experimentally and theoretically. Ultrasonic surface waves on a piezoelectric substrate strongly couple to a thin liquid layer and generate a quadrupolar streaming pattern within the fluid. We use fluorescence correlation spectroscopy and fluorescence microscopy as complementary tools to investigate the resulting flow profile. The velocity was found to depend on the applied power approximately linearly and to decrease with the inverse third power of the distance from the ultrasound generator on the chip. The found properties reveal acoustic streaming as a promising tool for the controlled agitation during microarray hybridization.

  20. Yeast-yeast interactions revealed by aromatic profile analysis of Sauvignon Blanc wine fermented by single or co-culture of non-Saccharomyces and Saccharomyces yeasts.

    Science.gov (United States)

    Sadoudi, Mohand; Tourdot-Maréchal, Raphaëlle; Rousseaux, Sandrine; Steyer, Damien; Gallardo-Chacón, Joan-Josep; Ballester, Jordi; Vichi, Stefania; Guérin-Schneider, Rémi; Caixach, Josep; Alexandre, Hervé

    2012-12-01

    There has been increasing interest in the use of selected non-Saccharomyces yeasts in co-culture with Saccharomyces cerevisiae. The main reason is that the multistarter fermentation process is thought to simulate indigenous fermentation, thus increasing wine aroma complexity while avoiding the risks linked to natural fermentation. However, multistarter fermentation is characterised by complex and largely unknown interactions between yeasts. Consequently the resulting wine quality is rather unpredictable. In order to better understand the interactions that take place between non-Saccharomyces and Saccharomyces yeasts during alcoholic fermentation, we analysed the volatile profiles of several mono-culture and co-cultures. Candida zemplinina, Torulaspora delbrueckii and Metschnikowia pulcherrima were used to conduct fermentations either in mono-culture or in co-culture with S. cerevisiae. Up to 48 volatile compounds belonging to different chemical families were quantified. For the first time, we show that C. zemplinina is a strong producer of terpenes and lactones. We demonstrate by means of multivariate analysis that different interactions exist between the co-cultures studied. We observed a synergistic effect on aromatic compound production when M. pulcherrima was in co-culture with S. cerevisiae. However a negative interaction was observed between C. zemplinina and S. cerevisiae, which resulted in a decrease in terpene and lactone content. These interactions are independent of biomass production. The aromatic profiles of T. delbrueckii and S. cerevisiae in mono-culture and in co-culture are very close, and are biomass-dependent, reflecting a neutral interaction. This study reveals that a whole family of compounds could be altered by such interactions. These results suggest that the entire metabolic pathway is affected by these interactions. Copyright © 2012 Elsevier Ltd. All rights reserved.

  1. GAUSSIAN RANDOM FIELD: PHYSICAL ORIGIN OF SERSIC PROFILES

    International Nuclear Information System (INIS)

    Cen, Renyue

    2014-01-01

    While the Sersic profile family provides adequate fits for the surface brightness profiles of observed galaxies, its physical origin is unknown. We show that if the cosmological density field is seeded by random Gaussian fluctuations, as in the standard cold dark matter model, galaxies with steep central profiles have simultaneously extended envelopes of shallow profiles in the outskirts, whereas galaxies with shallow central profiles are accompanied by steep density profiles in the outskirts. These properties are in accord with those of the Sersic profile family. Moreover, galaxies with steep central profiles form their central regions in smaller denser subunits that possibly merge subsequently, which naturally leads to the formation of bulges. In contrast, galaxies with shallow central profiles form their central regions in a coherent fashion without significant substructure, a necessary condition for disk galaxy formation. Thus, the scenario is self-consistent with respect to the correlation between observed galaxy morphology and the Sersic index. We further predict that clusters of galaxies should display a similar trend, which should be verifiable observationally

  2. Mercury and omega-3 fatty acid profiles in freshwater fish of the Dehcho Region, Northwest Territories: Informing risk benefit assessments.

    Science.gov (United States)

    Laird, Matthew J; Henao, Juan J Aristizabal; Reyes, Ellen S; Stark, Ken D; Low, George; Swanson, Heidi K; Laird, Brian D

    2018-05-17

    Traditional foods have significant nutritional, sociocultural and economic value in subarctic First Nations communities of the Northwest Territories, and play a crucial role in promoting cultural continuity and sovereignty. Omega-3 polyunsaturated fatty acids (N-3 PUFAs), including eicosapentaenoic (EPA) and docosahexaenoic acid (DHA), carry significant benefits for neurocognitive development and cardiovascular health. However, the health risks posed by methylmercury may serve to undermine the benefits of fish consumption in Northern Indigenous communities. The objective of this study was to characterize profiles for mercury (Hg) and fatty acids in fish species harvested across lakes of the Dehcho Region, in the Mackenzie Valley of the Northwest Territories, to better understand the risks and benefits associated with traditional foods. Hg levels increased with trophic position, with the highest levels found in Burbot, Lake Trout, Walleye, and Northern Pike. Lake Trout, along with planktivorous species including Lake Whitefish, Cisco, and Sucker, demonstrated higher N-3 PUFAs than other species. Negative associations were observed between Hg and N-3 PUFAs in Lake Trout, Northern Pike, Walleye and Burbot. Further stratifying these relationships revealed significant interactions by lake. Significant differences observed in fatty acid and Hg profiles across lakes underscore the importance of considering both species- and lake-specific findings. This growing dataset of freshwater fish of the Dehcho will inform future efforts to characterize human Hg exposure profiles using probabilistic dose reconstruction models. Copyright © 2018 Elsevier B.V. All rights reserved.

  3. Transcriptome profiling of Nasonia vitripennis testis reveals novel transcripts expressed from the selfish B chromosome, paternal sex ratio.

    Science.gov (United States)

    Akbari, Omar S; Antoshechkin, Igor; Hay, Bruce A; Ferree, Patrick M

    2013-09-04

    A widespread phenomenon in nature is sex ratio distortion of arthropod populations caused by microbial and genetic parasites. Currently little is known about how these agents alter host developmental processes to favor one sex or the other. The paternal sex ratio (PSR) chromosome is a nonessential, paternally transmitted centric fragment that segregates in natural populations of the jewel wasp, Nasonia vitripennis. To persist, PSR is thought to modify the hereditary material of the developing sperm, with the result that all nuclear DNA other than the PSR chromosome is destroyed shortly after fertilization. This results in the conversion of a fertilized embryo--normally a female--into a male, thereby insuring transmission of the "selfish" PSR chromosome, and simultaneously leading to wasp populations that are male-biased. To begin to understand this system at the mechanistic level, we carried out transcriptional profiling of testis from WT and PSR-carrying males. We identified a number of transcripts that are differentially expressed between these conditions. We also discovered nine transcripts that are uniquely expressed from the PSR chromosome. Four of these PSR-specific transcripts encode putative proteins, whereas the others have very short open reading frames and no homology to known proteins, suggesting that they are long noncoding RNAs. We propose several different models for how these transcripts could facilitate PSR-dependent effects. Our analyses also revealed 15.71 MB of novel transcribed regions in the N. vitripennis genome, thus increasing the current annotation of total transcribed regions by 53.4%. Finally, we detected expression of multiple meiosis-related genes in the wasp testis, despite the lack of conventional meiosis in the male sex.

  4. Interstrain polymorphisms of isoenzyme profiles and mitochondrial DNA fingerprints among seven strains assigned to Acanthamoeba polyphaga.

    Science.gov (United States)

    Kong, H H; Park, J H; Chung, D I

    1995-12-01

    Interstrain polymorphisms of isoenzyme profiles and mitochondrial (Mt) DNA fingerprints were observed among seven strains of Acanthamoeba isolated from different sources and morphologically assigned to A. polyphaga. Mt DNA fingerprints by eight restriction endonucleases (Bgl II, Sca I, Cla I, EcoR I, Xba I, Kpn I, Sal I, and Sst I) revealed considerable interstrain polymorphisms. Isoenzyme profiles revealed considerable interstrain polymorphisms for acid phosphatase, lactate dehydrogenase, and glucose-6-phosphate dehydrogenase while those for glucose phosphate isomerase, leucine aminopeptidase, and malate dehydrogenase showed similarity. Despite of the interstrain polymorphisms, the isoenzyme profiles and Mt DNA fingerprints of the strain Ap were found to be identical with those of the strain Jones. Mt DNA fingerprinting was found to be highly applicable for the strain identification, characterization, and differentiation.

  5. Policy required for entry of DNA profiles onto the National Forensic DNA Database of South Africa

    Directory of Open Access Journals (Sweden)

    Laura J. Heathfield

    2014-07-01

    Full Text Available The recent Criminal Law (Forensic Procedures Amendment Act (2013 provides a definition for forensic DNA profiles and, in so doing, states that medical information about an individual may not be revealed through a forensic DNA profile. Yet chromosomal abnormalities can exhibit as tri-allelic patterns on DNA profiles and such information can expose medical conditions such as Down syndrome. This short report highlights this concern and suggests a policy be created for the entering of such DNA profiles onto the National Forensic DNA database of South Africa.

  6. Functional gene profiling through metaRNAseq approach reveals diet-dependent variation in rumen microbiota of buffalo (Bubalus bubalis).

    Science.gov (United States)

    Hinsu, Ankit T; Parmar, Nidhi R; Nathani, Neelam M; Pandit, Ramesh J; Patel, Anand B; Patel, Amrutlal K; Joshi, Chaitanya G

    2017-04-01

    Recent advances in next generation sequencing technology have enabled analysis of complex microbial community from genome to transcriptome level. In the present study, metatranscriptomic approach was applied to elucidate functionally active bacteria and their biological processes in rumen of buffalo (Bubalus bubalis) adapted to different dietary treatments. Buffaloes were adapted to a diet containing 50:50, 75:25 and 100:0 forage to concentrate ratio, each for 6 weeks, before ruminal content sample collection. Metatranscriptomes from rumen fiber adherent and fiber-free active bacteria were sequenced using Ion Torrent PGM platform followed by annotation using MG-RAST server and CAZYmes (Carbohydrate active enzymes) analysis toolkit. In all the samples Bacteroidetes was the most abundant phylum followed by Firmicutes. Functional analysis using KEGG Orthology database revealed Metabolism as the most abundant category at level 1 within which Carbohydrate metabolism was dominating. Diet treatments also exerted significant differences in proportion of enzymes involved in metabolic pathways for VFA production. Carbohydrate Active Enzyme(CAZy) analysis revealed the abundance of genes encoding glycoside hydrolases with the highest representation of GH13 CAZy family in all the samples. The findings provide an overview of the activities occurring in the rumen as well as active bacterial population and the changes occurring through different dietary treatments. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Transcriptome profiling of brown adipose tissue during cold exposure reveals extensive regulation of glucose metabolism

    DEFF Research Database (Denmark)

    Hao, Qin; Yadav, Rachita; Basse, Astrid L.

    2015-01-01

    We applied digital gene expression profiling to determine the transcriptome of brown and white adipose tissues (BAT and WAT, respectively) during cold exposure. Male C57BL/6J mice were exposed to cold for 2 or 4 days. A notable induction of genes related to glucose uptake, glycolysis, glycogen...... exposure, we propose a model for the intermediary glucose metabolism in activated BAT: 1) fluxes through glycolysis and the pentose phosphate pathway are induced, the latter providing reducing equivalents for de novo fatty acid synthesis; 2) glycerol synthesis from glucose is increased, facilitating...

  8. Cardioprotective and Metabolomic Profiling of Selected Medicinal Plants against Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Nadia Afsheen

    2018-01-01

    Full Text Available In this research work, the antioxidant and metabolomic profiling of seven selected medicinally important herbs including Rauvolfia serpentina, Terminalia arjuna, Coriandrum sativum, Elettaria cardamom, Piper nigrum, Allium sativum, and Crataegus oxyacantha was performed. The in vivo cardioprotective potential of these medicinal plants was evaluated against surgically induced oxidative stress through left anterior descending coronary artery ligation (LADCA in dogs. The antioxidant profiling of these plants was done through DPPH and DNA protection assay. The C. oxyacantha and T. arjuna showed maximum antioxidant potential, while the E. cardamom showed poor antioxidative strength even at its high concentration. Different concentrations of extracts of the said plants exhibited the protection of plasmid DNA against H2O2 damage as compared to the plasmid DNA merely treated with H2O2. The metabolomic profiling through LC-MS analysis of these antioxidants revealed the presence of active secondary metabolites responsible for their antioxidant potential. During in vivo analysis, blood samples of all treatment groups were drawn at different time intervals to analyze the cardiac and hemodynamic parameters. The results depicted that the group pretreated with HC4 significantly sustained the level of CK-MB, SGOT, and LDH as well as hemodynamic parameters near to normal. The histopathological examination also confirmed the cardioprotective potential of HC4. Thus, the HC4 being safe and inexpensive cardioprotective herbal combination could be considered as an alternate of synthetic drugs.

  9. Cardioprotective and Metabolomic Profiling of Selected Medicinal Plants against Oxidative Stress

    Science.gov (United States)

    Afsheen, Nadia; Jahan, Nazish; Ijaz, Misbah; Manzoor, Asad; Khan, Khalid Mahmood; Hina, Saman

    2018-01-01

    In this research work, the antioxidant and metabolomic profiling of seven selected medicinally important herbs including Rauvolfia serpentina, Terminalia arjuna, Coriandrum sativum, Elettaria cardamom, Piper nigrum, Allium sativum, and Crataegus oxyacantha was performed. The in vivo cardioprotective potential of these medicinal plants was evaluated against surgically induced oxidative stress through left anterior descending coronary artery ligation (LADCA) in dogs. The antioxidant profiling of these plants was done through DPPH and DNA protection assay. The C. oxyacantha and T. arjuna showed maximum antioxidant potential, while the E. cardamom showed poor antioxidative strength even at its high concentration. Different concentrations of extracts of the said plants exhibited the protection of plasmid DNA against H2O2 damage as compared to the plasmid DNA merely treated with H2O2. The metabolomic profiling through LC-MS analysis of these antioxidants revealed the presence of active secondary metabolites responsible for their antioxidant potential. During in vivo analysis, blood samples of all treatment groups were drawn at different time intervals to analyze the cardiac and hemodynamic parameters. The results depicted that the group pretreated with HC4 significantly sustained the level of CK-MB, SGOT, and LDH as well as hemodynamic parameters near to normal. The histopathological examination also confirmed the cardioprotective potential of HC4. Thus, the HC4 being safe and inexpensive cardioprotective herbal combination could be considered as an alternate of synthetic drugs. PMID:29576858

  10. Electron density and temperature profile diagnostics for C-2 field reversed configuration plasmas

    Energy Technology Data Exchange (ETDEWEB)

    Deng, B. H.; Kinley, J. S.; Schroeder, J. [Tri Alpha Energy, Inc., Rancho Santa Margarita, California 92688 (United States)

    2012-10-15

    The 9-point Thomson scattering diagnostic system for the C-2 field reversed configuration plasmas is improved and the measured electron temperature profiles are consistent with theoretical expectations. Rayleigh scattering revealed a finite line width of the ruby laser emission, which complicates density calibration. Taking advantage of the plasma wobble motion, density profile reconstruction accuracy from the 6-chord two-color CO{sub 2}/HeNe interferometer data is improved.

  11. POSTER: Privacy-Preserving Profile Similarity Computation in Online Social Networks

    NARCIS (Netherlands)

    Jeckmans, Arjan; Tang, Qiang; Hartel, Pieter H.

    2011-01-01

    Currently, none of the existing online social networks (OSNs) enables its users to make new friends without revealing their private information. This leaves the users in a vulnerable position when searching for new friends. We propose a solution which enables a user to compute her profile similarity

  12. A profile of effective leadership in some South African high-poverty schools

    Directory of Open Access Journals (Sweden)

    Gerrit Kamper

    2008-02-01

    Full Text Available The struggle of high-poverty schools for survival is well documented. Some have overcome poverty-related odds and performed exceptionally well, prompting the following research question: What elements constitute a profile of effective leadership in high-poverty schools? Investigations conducted at six successful high-poverty schools revealed the contribution of invitational leadership to this success. I look at the personal traits and capabilities of effective leaders in high-poverty schools, as presented in a leadership profile.

  13. Surface glycosylation profiles of urine extracellular vesicles.

    Directory of Open Access Journals (Sweden)

    Jared Q Gerlach

    Full Text Available Urinary extracellular vesicles (uEVs are released by cells throughout the nephron and contain biomolecules from their cells of origin. Although uEV-associated proteins and RNA have been studied in detail, little information exists regarding uEV glycosylation characteristics. Surface glycosylation profiling by flow cytometry and lectin microarray was applied to uEVs enriched from urine of healthy adults by ultracentrifugation and centrifugal filtration. The carbohydrate specificity of lectin microarray profiles was confirmed by competitive sugar inhibition and carbohydrate-specific enzyme hydrolysis. Glycosylation profiles of uEVs and purified Tamm Horsfall protein were compared. In both flow cytometry and lectin microarray assays, uEVs demonstrated surface binding, at low to moderate intensities, of a broad range of lectins whether prepared by ultracentrifugation or centrifugal filtration. In general, ultracentrifugation-prepared uEVs demonstrated higher lectin binding intensities than centrifugal filtration-prepared uEVs consistent with lesser amounts of co-purified non-vesicular proteins. The surface glycosylation profiles of uEVs showed little inter-individual variation and were distinct from those of Tamm Horsfall protein, which bound a limited number of lectins. In a pilot study, lectin microarray was used to compare uEVs from individuals with autosomal dominant polycystic kidney disease to those of age-matched controls. The lectin microarray profiles of polycystic kidney disease and healthy uEVs showed differences in binding intensity of 6/43 lectins. Our results reveal a complex surface glycosylation profile of uEVs that is accessible to lectin-based analysis following multiple uEV enrichment techniques, is distinct from co-purified Tamm Horsfall protein and may demonstrate disease-specific modifications.

  14. Transcriptome Profiling of the Lungs Reveals Molecular Clock Genes Expression Changes after Chronic Exposure to Ambient Air Particles

    Directory of Open Access Journals (Sweden)

    Pengcheng Song

    2017-01-01

    Full Text Available The symptoms of asthma, breathlessness, insomnia, etc. all have relevance to pulmonary rhythmic disturbances. Epidemiology and toxicology studies have demonstrated that exposure to ambient air particles can result in pulmonary dysfunction. However, there are no data directly supporting a link between air pollution and circadian rhythm disorder. In the present study, we found that breathing highly polluted air resulted in changes of the molecular clock genes expression in lung by transcriptome profiling analyses in a rodent model. Compared to those exposed to filtered air, in both pregnant and offspring rats in the unfiltered group, key clock genes (Per1, Per2, Per3, Rev-erbα and Dbp expression level decreased and Bmal1 expression level increased. In both rat dams and their offspring, after continuous exposure to unfiltered air, we observed significant histologic evidence for both perivascular and peribronchial inflammation, increased tissue and systemic oxidative stress in the lungs. Our results suggest that chronic exposure to particulate matter can induce alterations of clock genes expression, which could be another important pathway for explaining the feedbacks of ambient particle exposure in addition to oxidative stress and inflammation.

  15. Profiling and Quantification of Regioisomeric Caffeoyl Glucoses in Berry Fruits.

    Science.gov (United States)

    Patras, Maria A; Jaiswal, Rakesh; McDougall, Gordon J; Kuhnert, Nikolai

    2018-02-07

    On the basis of a recently developed tandem mass spectrometry-based hierarchical scheme for the identification of regioisomeric caffeoyl glucoses, selected berry fruits were profiled for their caffeoyl glucose ester content. Fresh edible berries profiled, including strawberries, raspberries, blueberries, blackberries, red currant, black currant, lingonberries, gooseberries, and juices of elderberries, goji berries, chokeberries, cranberries, açai berries, sea buckthorn berries, Montmorency sour cherries, and pomegranates, were investigated. 1-Caffeoyl glucose was found to be the predominant isomer in the majority of samples, with further profiling revealing the presence of additional hydroxycinnamoyl glucose esters and O-glycosides with p-coumaroyl, feruloyl, and sinapoyl substituents. A quantitative liquid chromatography-mass spectrometry-based method was developed and validated, and all caffeoyl glucose isomers were quantified for the first time in edible berries.

  16. Liquid Chromatography/Mass Spectrometry Reveals the Effect of Lactobacillus Treatment on the Faecal Metabolite Profile of Rats with Chronic Renal Failure.

    Science.gov (United States)

    Wu, Bin; Jiang, Hongli; He, Quan; Wang, Meng; Xue, Jinhong; Liu, Hua; Shi, Kehui; Wei, Meng; Liang, Shanshan; Zhang, Liwen

    2017-01-01

    Chronic kidney disease is accompanied by changes in the gut microbiome and by an increase in the number of gut pathogenic bacteria. The aim of this study was to investigate the difference of the faecal metabolic profiles in rats with uremia, and to determine whether the altered metabolites in the rats with uremia can be restored by Lactobacillus. Thirty rats were randomly divided into 3 groups: sham, uremia and uremia + probiotic (UP) groups. The rats in uremia and UP groups were prepared through surgical renal mass 5/6 ablation. The rats in the UP group received Lactobacillus LB (1 ml, 109 CFU/ml) through gavage every day for 4 weeks. The rats were fed with a standard diet. Faecal samples were analysed through ultra performance liquid chromatography/mass spectrometry. Statistical analyses were performed using MetaboAnalyst and MATLAB. A total of 99, 324 and 177 significantly different ion peaks were selected between sham and uremia groups; sham and UP groups; and uremia and UP groups, respectively. In the 3 groups, 35 significantly altered metabolites were identified; of the 35 metabolites, 27 initially increased and then decreased; by contrast, 8 metabolites initially decreased and then increased. The 35 metabolites were subjected to pathway analysis in MetaboAnalyst. Faecal metabolites were significantly altered in rats with uremia; these changes were partially reversed by Lactobacillus. © 2016 S. Karger AG, Basel.

  17. Perception of facial profile attractiveness by a Saudi sample

    International Nuclear Information System (INIS)

    Talic, Nabeel; Alshakhs, Mohammad S.

    2008-01-01

    Previous studies have reported different levels of perception of attractiveness among different ethnicities and among varying education-level groups on facial profile rating.To study the perception of facial profile attractiveness among Saudi dentists and lay-individuals. Digital facial profile images with altered degree of prognathism and retrognathism were presented to a sample of 60 Saudi dentists and 60 lay-persons with equal gender distribution. High reliability of repeated assessment of profile images was detected (ICC=0.982). Significant difference in perception of facial profile was found between genders (P<0.05) and among the groups with different education backgrounds (P<0.001). General agreement was established in both sample groups on average facial profile to be the most attractive and on the most retrognathic profile to be the least attractive. (author)

  18. Quantitative microbiome profiling links gut community variation to microbial load.

    Science.gov (United States)

    Vandeputte, Doris; Kathagen, Gunter; D'hoe, Kevin; Vieira-Silva, Sara; Valles-Colomer, Mireia; Sabino, João; Wang, Jun; Tito, Raul Y; De Commer, Lindsey; Darzi, Youssef; Vermeire, Séverine; Falony, Gwen; Raes, Jeroen

    2017-11-23

    Current sequencing-based analyses of faecal microbiota quantify microbial taxa and metabolic pathways as fractions of the sample sequence library generated by each analysis. Although these relative approaches permit detection of disease-associated microbiome variation, they are limited in their ability to reveal the interplay between microbiota and host health. Comparative analyses of relative microbiome data cannot provide information about the extent or directionality of changes in taxa abundance or metabolic potential. If microbial load varies substantially between samples, relative profiling will hamper attempts to link microbiome features to quantitative data such as physiological parameters or metabolite concentrations. Saliently, relative approaches ignore the possibility that altered overall microbiota abundance itself could be a key identifier of a disease-associated ecosystem configuration. To enable genuine characterization of host-microbiota interactions, microbiome research must exchange ratios for counts. Here we build a workflow for the quantitative microbiome profiling of faecal material, through parallelization of amplicon sequencing and flow cytometric enumeration of microbial cells. We observe up to tenfold differences in the microbial loads of healthy individuals and relate this variation to enterotype differentiation. We show how microbial abundances underpin both microbiota variation between individuals and covariation with host phenotype. Quantitative profiling bypasses compositionality effects in the reconstruction of gut microbiota interaction networks and reveals that the taxonomic trade-off between Bacteroides and Prevotella is an artefact of relative microbiome analyses. Finally, we identify microbial load as a key driver of observed microbiota alterations in a cohort of patients with Crohn's disease, here associated with a low-cell-count Bacteroides enterotype (as defined through relative profiling).

  19. Profile and Fate of Bacterial Pathogens in Sewage Treatment Plants Revealed by High-Throughput Metagenomic Approach.

    Science.gov (United States)

    Li, Bing; Ju, Feng; Cai, Lin; Zhang, Tong

    2015-09-01

    The broad-spectrum profile of bacterial pathogens and their fate in sewage treatment plants (STPs) were investigated using high-throughput sequencing based metagenomic approach. This novel approach could provide a united platform to standardize bacterial pathogen detection and realize direct comparison among different samples. Totally, 113 bacterial pathogen species were detected in eight samples including influent, effluent, activated sludge (AS), biofilm, and anaerobic digestion sludge with the abundances ranging from 0.000095% to 4.89%. Among these 113 bacterial pathogens, 79 species were reported in STPs for the first time. Specially, compared to AS in bulk mixed liquor, more pathogen species and higher total abundance were detected in upper foaming layer of AS. This suggests that the foaming layer of AS might impose more threat to onsite workers and citizens in the surrounding areas of STPs because pathogens in foaming layer are easily transferred into air and cause possible infections. The high removal efficiency (98.0%) of total bacterial pathogens suggests that AS treatment process is effective to remove most bacterial pathogens. Remarkable similarities of bacterial pathogen compositions between influent and human gut indicated that bacterial pathogen profiles in influents could well reflect the average bacterial pathogen communities of urban resident guts within the STP catchment area.

  20. A Study of the Vaginal Microbiome in Healthy Canadian Women Utilizing cpn60-Based Molecular Profiling Reveals Distinct Gardnerella Subgroup Community State Types

    Science.gov (United States)

    Wagner, Emily C.; Schellenberg, John J.; Links, Matthew G.; van Schalkwyk, Julie; Reid, Gregor; Hemmingsen, Sean M.; Hill, Janet E.; Money, Deborah

    2015-01-01

    The vaginal microbiota is important in women’s reproductive and overall health. However, the relationships between the structure, function and dynamics of this complex microbial community and health outcomes remain elusive. The objective of this study was to determine the phylogenetic range and abundance of prokaryotes in the vaginal microbiota of healthy, non-pregnant, ethnically diverse, reproductive-aged Canadian women. Socio-demographic, behavioural and clinical data were collected and vaginal swabs were analyzed from 310 women. Detailed profiles of their vaginal microbiomes were generated by pyrosequencing of the chaperonin-60 universal target. Six community state types (CST) were delineated by hierarchical clustering, including three Lactobacillus-dominated CST (L. crispatus, L. iners, L. jensenii), two Gardnerella-dominated (subgroups A and C) and an “intermediate” CST which included a small number of women with microbiomes dominated by seven other species or with no dominant species but minority populations of Streptococcus, Staphylococcus, Peptoniphilus, E. coli and various Proteobacteria in co-dominant communities. The striking correspondence between Nugent score and deep sequencing CST continues to reinforce the basic premise provided by the simpler Gram stain method, while additional analyses reveal detailed cpn60-based phylogeny and estimated abundance in microbial communities from vaginal samples. Ethnicity was the only demographic or clinical characteristic predicting CST, with differences in Asian and White women (p = 0.05). In conclusion, this study confirms previous work describing four cpn60-based subgroups of Gardnerella, revealing previously undescribed CST. The data describe the range of bacterial communities seen in Canadian women presenting with no specific vaginal health concerns, and provides an important baseline for future investigations of clinically important cohorts. PMID:26266808

  1. RASopathies are associated with a distinct personality profile.

    Science.gov (United States)

    Bizaoui, Varoona; Gage, Jessica; Brar, Rita; Rauen, Katherine A; Weiss, Lauren A

    2018-06-01

    Personality is a complex, yet partially heritable, trait. Although some Mendelian diseases like Williams-Beuren syndrome are associated with a particular personality profile, studies have failed to assign the personality features to a single gene or pathway. As a family of monogenic disorders caused by mutations in the Ras/MAPK pathway known to influence social behavior, RASopathies are likely to provide insight into the genetic basis of personality. Eighty subjects diagnosed with cardiofaciocutaneous syndrome, Costello syndrome, neurofibromatosis type 1, and Noonan syndrome were assessed using a parent-report BFQ-C (Big Five Questionnaire for Children) evaluating agreeableness, extraversion, conscientiousness, intellect/openness, and neuroticism, along with 55 unaffected sibling controls. A short questionnaire was added to assess sense of humor. RASopathy subjects and sibling controls were compared for individual components of personality, multidimensional personality profiles, and individual questions using Student tests, analysis of variance, and principal component analysis. RASopathy subjects were given lower scores on average compared to sibling controls in agreeableness, extraversion, conscientiousness, openness, and sense of humor, and similar scores in neuroticism. When comparing the multidimensional personality profile between groups, RASopathies showed a distinct profile from unaffected siblings, but no difference in this global profile was found within RASopathies, revealing a common profile for the Ras/MAPK-related disorders. In addition, several syndrome-specific strengths or weaknesses were observed in individual domains. We describe for the first time an association between a single pathway and a specific personality profile, providing a better understanding of the genetics underlying personality, and new tools for tailoring educational and behavioral approaches for individuals with RASopathies. © 2018 Wiley Periodicals, Inc.

  2. Expression profiling of migrated and invaded breast cancer cells predicts early metastatic relapse and reveals Krüppel-like factor 9 as a potential suppressor of invasive growth in breast cancer

    Science.gov (United States)

    Limame, Ridha; de Beeck, Ken Op; Van Laere, Steven; Croes, Lieselot; De Wilde, Annemieke; Dirix, Luc; Van Camp, Guy; Peeters, Marc; De Wever, Olivier; Lardon, Filip; Pauwels, Patrick

    2014-01-01

    Cell motility and invasion initiate metastasis. However, only a subpopulation of cancer cells within a tumor will ultimately become invasive. Due to this stochastic and transient nature, in an experimental setting, migrating and invading cells need to be isolated from the general population in order to study the gene expression profiles linked to these processes. This report describes microarray analysis on RNA derived from migrated or invaded subpopulations of triple negative breast cancer cells in a Transwell set-up, at two different time points during motility and invasion, pre-determined as “early” and “late” in real-time kinetic assessments. Invasion- and migration-related gene expression signatures were generated through comparison with non-invasive cells, remaining at the upper side of the Transwell membranes. Late-phase signatures of both invasion and migration indicated poor prognosis in a series of breast cancer data sets. Furthermore, evaluation of the genes constituting the prognostic invasion-related gene signature revealed Krüppel-like factor 9 (KLF9) as a putative suppressor of invasive growth in breast cancer. Next to loss in invasive vs non-invasive cell lines, KLF9 also showed significantly lower expression levels in the “early” invasive cell population, in several public expression data sets and in clinical breast cancer samples when compared to normal tissue. Overexpression of EGFP-KLF9 fusion protein significantly altered morphology and blocked invasion and growth of MDA-MB-231 cells in vitro. In addition, KLF9 expression correlated inversely with mitotic activity in clinical samples, indicating anti-proliferative effects. PMID:25593984

  3. Reading Profiles in Multi-Site Data With Missingness.

    Science.gov (United States)

    Eckert, Mark A; Vaden, Kenneth I; Gebregziabher, Mulugeta

    2018-01-01

    Children with reading disability exhibit varied deficits in reading and cognitive abilities that contribute to their reading comprehension problems. Some children exhibit primary deficits in phonological processing, while others can exhibit deficits in oral language and executive functions that affect comprehension. This behavioral heterogeneity is problematic when missing data prevent the characterization of different reading profiles, which often occurs in retrospective data sharing initiatives without coordinated data collection. Here we show that reading profiles can be reliably identified based on Random Forest classification of incomplete behavioral datasets, after the missForest method is used to multiply impute missing values. Results from simulation analyses showed that reading profiles could be accurately classified across degrees of missingness (e.g., ∼5% classification error for 30% missingness across the sample). The application of missForest to a real multi-site dataset with missingness ( n = 924) showed that reading disability profiles significantly and consistently differed in reading and cognitive abilities for cases with and without missing data. The results of validation analyses indicated that the reading profiles (cases with and without missing data) exhibited significant differences for an independent set of behavioral variables that were not used to classify reading profiles. Together, the results show how multiple imputation can be applied to the classification of cases with missing data and can increase the integrity of results from multi-site open access datasets.

  4. Reading Profiles in Multi-Site Data With Missingness

    Directory of Open Access Journals (Sweden)

    Mark A. Eckert

    2018-05-01

    Full Text Available Children with reading disability exhibit varied deficits in reading and cognitive abilities that contribute to their reading comprehension problems. Some children exhibit primary deficits in phonological processing, while others can exhibit deficits in oral language and executive functions that affect comprehension. This behavioral heterogeneity is problematic when missing data prevent the characterization of different reading profiles, which often occurs in retrospective data sharing initiatives without coordinated data collection. Here we show that reading profiles can be reliably identified based on Random Forest classification of incomplete behavioral datasets, after the missForest method is used to multiply impute missing values. Results from simulation analyses showed that reading profiles could be accurately classified across degrees of missingness (e.g., ∼5% classification error for 30% missingness across the sample. The application of missForest to a real multi-site dataset with missingness (n = 924 showed that reading disability profiles significantly and consistently differed in reading and cognitive abilities for cases with and without missing data. The results of validation analyses indicated that the reading profiles (cases with and without missing data exhibited significant differences for an independent set of behavioral variables that were not used to classify reading profiles. Together, the results show how multiple imputation can be applied to the classification of cases with missing data and can increase the integrity of results from multi-site open access datasets.

  5. Prognostic significance of anaplasia and angiogenesis in childhood medulloblastoma: a pediatric oncology group study.

    Science.gov (United States)

    Ozer, Erdener; Sarialioglu, Faik; Cetingoz, Riza; Yüceer, Nurullah; Cakmakci, Handan; Ozkal, Sermin; Olgun, Nur; Uysal, Kamer; Corapcioglu, Funda; Canda, Serefettin

    2004-01-01

    The purpose of this study was to investigate whether quantitative assessment of cytologic anaplasia and angiogenesis may predict the clinical prognosis in medulloblastoma and stratify the patients to avoid both undertreatment and overtreatment. Medulloblastomas from 23 patients belonging to the Pediatric Oncology Group were evaluated with respect to some prognostic variables, including histologic assessment of nodularity and desmoplasia, grading of anaplasia, measurement of nuclear size, mitotic cell count, quantification of angiogenesis, including vascular surface density (VSD) and microvessel number (NVES), and immunohistochemical scoring of vascular endothelial growth factor (VEGF) expression. Univariate and multivariate analyses for prognostic indicators for survival were performed. Univariate analysis revealed that extensive nodularity was a significant favorable prognostic factor, whereas the presence of anaplasia, increased nuclear size, mitotic rate, VSD, and NVES were significant unfavorable prognostic factors. Using multivariate analysis, increased nuclear size was found to be an independent unfavorable prognostic factor for survival. Neither the presence of desmoplasia nor VEGF expression was significantly related to patient survival. Although care must be taken not to overstate the importance of the results of this single-institution preliminary report, pathologic grading of medulloblastomas with respect to grading of anaplasia and quantification of nodularity, nuclear size, and microvessel profiles may be clinically useful for the treatment of medulloblastomas. Further validation of the independent prognostic significance of nuclear size in stratifying patients is required.

  6. LCA profiles for building components:

    DEFF Research Database (Denmark)

    Marsh, Rob

    2016-01-01

    . A full bivariate linear regression analysis is performed, showing statistically significant correlations with strong direct relationships between environmental impact categories. A simplified LCA profile consisting of total primary energy, global warming potential and acidification potential is developed...

  7. Control Actions on Leprosy in Primary Health Care in a Brazilian Capital: Profile of Professionals and Users

    Directory of Open Access Journals (Sweden)

    Anselmo Alves Lustosa

    2018-02-01

    Full Text Available Objective: analyze  profile of users of primary health care services affected by leprosy, as well as the medical professionals and nurses responsible for the follow - up of these patients.   Methods: This is a field study that surveyed the socioeconomic and clinical profile of 26 patients affected by leprosy, attended at the municipal health units of the urban area of ​​Teresina-PI, as well as the professional profile and clinical practices of 15 physicians and 19 nurses responsible for the follow-up of these patients. Results: It was observed a profile of people affected by leprosy, characterized by: individuals aged 50 years or more; predominantly male; with low schooling and income. The clinical characteristics reveal a high prevalence of multibacillary cases of leprosy and with a significant diagnosis of some degree of physical disability. Regarding the profile of the professionals and their clinical behaviors, it was verified that the majority had post-graduation and a long time of experience in primary health care and leprosy control actions, however, it has been shown that they do not always put into practice all actions necessary for the diagnosis and treatment of the disease. Conclusions: The profile of patients with leprosy treated at the municipal health units in the urban area of Teresina was similar to that found in other Brazilian territories, thus evidencing the need to implement public social support policies and more effective diagnostic and therapeutic follow-up practices by reduce the high rates of endemicity of the disease.

  8. Alterations in urine, serum and brain metabolomic profiles exhibit sexual dimorphism during malaria disease progression

    Directory of Open Access Journals (Sweden)

    Sharma Shobhona

    2010-04-01

    Full Text Available Abstract Background Metabolic changes in the host in response to Plasmodium infection play a crucial role in the pathogenesis of malaria. Alterations in metabolism of male and female mice infected with Plasmodium berghei ANKA are reported here. Methods 1H NMR spectra of urine, sera and brain extracts of these mice were analysed over disease progression using Principle Component Analysis and Orthogonal Partial Least Square Discriminant Analysis. Results Analyses of overall changes in urinary profiles during disease progression demonstrate that females show a significant early post-infection shift in metabolism as compared to males. In contrast, serum profiles of female mice remain unaltered in the early infection stages; whereas that of the male mice changed. Brain metabolite profiles do not show global changes in the early stages of infection in either sex. By the late stages urine, serum and brain profiles of both sexes are severely affected. Analyses of individual metabolites show significant increase in lactate, alanine and lysine, kynurenic acid and quinolinic acid in sera of both males and females at this stage. Early changes in female urine are marked by an increase of ureidopropionate, lowering of carnitine and transient enhancement of asparagine and dimethylglycine. Several metabolites when analysed individually in sera and brain reveal significant changes in their levels in the early phase of infection mainly in female mice. Asparagine and dimethylglycine levels decrease and quinolinic acid increases early in sera of infected females. In brain extracts of females, an early rise in levels is also observed for lactate, alanine and glycerol, kynurenic acid, ureidopropionate and 2-hydroxy-2-methylbutyrate. Conclusions These results suggest that P. berghei infection leads to impairment of glycolysis, lipid metabolism, metabolism of tryptophan and degradation of uracil. Characterization of early changes along these pathways may be crucial for

  9. Effects of sex, age, and fasting conditions on plasma lipidomic profiles of fasted Sprague-Dawley rats.

    Directory of Open Access Journals (Sweden)

    Kosuke Saito

    Full Text Available Circulating lipid molecules reflect biological processes in the body and, thus, are useful tools for preclinical estimation of the efficacy and safety of newly developed drugs. However, background information on profiles of circulating lipid molecules in preclinical animal models is limited. Therefore, we examined the effects of multiple factors such as sex (fasted male vs. female, age (fasted 10 vs. 30 weeks old, and feeding conditions (feeding vs. fasting, 16 vs. 22 hr fasting, 10 AM vs. 4 PM blood collection, on the global profiles of lipid molecules in plasma from Sprague-Dawley rats by using a lipidomic approach. Our assay platform determined 262 lipid molecules (68 phospholipids, 20 sphingolipids, 138 neutral lipids, and 36 polyunsaturated fatty acids and their metabolites in rat plasma. Multivariate discriminant analysis (orthogonal partial least squares discriminant analysis and heat maps of statistically significant lipid molecules revealed that the plasma lipid profiles in rats are predominantly influenced by feeding conditions, followed by sex and age. In addition, the fasting duration (16 vs. 22 hr fasting or the time of blood collection (10 AM vs. 4 PM blood collection has limited or no contribution on the profiles of lipid molecules in rat plasma. Our results provide useful, fundamental information for exploring and validating biomarkers in future preclinical studies and may help to establish regulatory standards for such studies.

  10. Implementation of reflectometry as a standard density profile diagnostic on DIII-D

    International Nuclear Information System (INIS)

    Zeng, L.; Doyle, E. J.; Luce, T. C.; Peebles, W. A.

    2001-01-01

    The profile reflectometer system on the DIII-D tokamak has been significantly upgraded in order to improve time coverage, data quality, and profile availability. The performance of the reflectometer system, which utilizes continuous frequency modulated (FMCW) radar techniques, has been improved as follows: First, a new PC-based data acquisition system has been installed, providing higher data sampling rates and larger memory depth. The higher sampling rate enables use of faster frequency sweeps of the FMCW microwave source, improving time resolution, and increasing profile accuracy. The larger memory depth enables longer data records, so that profiles can now be obtained throughout 5 s discharges at 100 Hz profile measurement rates, while continuous sampling at 10 MHz is available for 1 s for high time resolution physics studies. Second, an initial automated between-shots profile analysis capability is now available. Third, availability of the profiles to end users has been significantly improved

  11. Is the subjective perception of lactose intolerance influenced by the psychological profile?

    Science.gov (United States)

    Tomba, C; Baldassarri, A; Coletta, M; Cesana, B M; Basilisco, G

    2012-10-01

    Symptoms of lactose intolerance are often attributed to lactose malabsorption but, as this relationship has not been demonstrated when a small dose of lactose similar to that contained in one cup of milk is ingested by intolerant patients, psychological factors may play a role in altered symptom perception. To assess the hypothesis that the psychological profile influences the symptoms of lactose intolerance. One hundred and two consecutive patients underwent a 15 g lactose hydrogen breath test to assess lactose malabsorption. The patients recorded the presence and severity of symptoms of lactose intolerance during the breath test using visual analogue scales. The psychological profile was assessed using a psychological symptom checklist, and health-related quality of life by means of the short-form health survey. Lactose malabsorption and intolerance were diagnosed in, respectively, 18% and 29% of the patients. The two conditions were not associated, and the severity of intolerance was even less in the patients with malabsorption. Multivariate logistic analysis showed that a high somatisation t-score was significantly associated with lactose intolerance (odds ratio 4.184; 1.704-10.309); the effects of the other psychological variables and of lactose malabsorption were not statistically significant. Health-related quality of life was significantly reduced in the patients with somatisation, but not in those with lactose malabsorption. The symptoms of lactose intolerance during hydrogen breath testing at a low physiological lactose load, are unrelated to lactose malabsorption, but may reveal a tendency towards somatisation that could impair the quality of life. © 2012 Blackwell Publishing Ltd.

  12. Probing the magnetic profile of diluted magnetic semiconductors using polarized neutron reflectivity.

    Science.gov (United States)

    Luo, X; Tseng, L T; Lee, W T; Tan, T T; Bao, N N; Liu, R; Ding, J; Li, S; Lauter, V; Yi, J B

    2017-07-24

    Room temperature ferromagnetism has been observed in the Cu doped ZnO films deposited under an oxygen partial pressure of 10 -3 and 10 -5 torr on Pt (200 nm)/Ti (45 nm)/Si (001) substrates using pulsed laser deposition. Due to the deposition at relatively high temperature (873 K), Cu and Ti atoms diffuse to the surface and interface, which significantly affects the magnetic properties. Depth sensitive polarized neutron reflectometry method provides the details of the composition and magnetization profiles and shows that an accumulation of Cu on the surface leads to an increase in the magnetization near the surface. Our results reveal that the presence of the copper at Zn sites induces ferromagnetism at room temperature, confirming intrinsic ferromagnetism.

  13. Glycomic Analysis of Life Stages of the Human Parasite Schistosoma mansoni Reveals Developmental Expression Profiles of Functional and Antigenic Glycan Motifs.

    Science.gov (United States)

    Smit, Cornelis H; van Diepen, Angela; Nguyen, D Linh; Wuhrer, Manfred; Hoffmann, Karl F; Deelder, André M; Hokke, Cornelis H

    2015-07-01

    Glycans present on glycoproteins and glycolipids of the major human parasite Schistosoma mansoni induce innate as well as adaptive immune responses in the host. To be able to study the molecular characteristics of schistosome infections it is therefore required to determine the expression profiles of glycans and antigenic glycan-motifs during a range of critical stages of the complex schistosome lifecycle. We performed a longitudinal profiling study covering schistosome glycosylation throughout worm- and egg-development using a mass spectrometry-based glycomics approach. Our study revealed that during worm development N-glycans with Galβ1-4(Fucα1-3)GlcNAc (LeX) and core-xylose motifs were rapidly lost after cercariae to schistosomula transformation, whereas GalNAcβ1-4GlcNAc (LDN)-motifs gradually became abundant and predominated in adult worms. LeX-motifs were present on glycolipids up to 2 weeks of schistosomula development, whereas glycolipids with mono- and multifucosylated LDN-motifs remained present up to the adult worm stage. In contrast, expression of complex O-glycans diminished to undetectable levels within days after transformation. During egg development, a rich diversity of N-glycans with fucosylated motifs was expressed, but with α3-core fucose and a high degree of multifucosylated antennae only in mature eggs and miracidia. N-glycan antennae were exclusively LDN-based in miracidia. O-glycans in the mature eggs were also diverse and contained LeX- and multifucosylated LDN, but none of these were associated with miracidia in which we detected only the Galβ1-3(Galβ1-6)GalNAc core glycan. Immature eggs also exhibited short O-glycan core structures only, suggesting that complex fucosylated O-glycans of schistosome eggs are derived primarily from glycoproteins produced by the subshell envelope in the developed egg. Lipid glycans with multifucosylated GlcNAc repeats were present throughout egg development, but with the longer highly fucosylated

  14. Protein profiles of CCL5, HPGDS, and NPSR1 in plasma reveal association with childhood asthma.

    Science.gov (United States)

    Hamsten, C; Häggmark, A; Grundström, J; Mikus, M; Lindskog, C; Konradsen, J R; Eklund, A; Pershagen, G; Wickman, M; Grunewald, J; Melén, E; Hedlin, G; Nilsson, P; van Hage, M

    2016-09-01

    Asthma is a common chronic childhood disease with many different phenotypes that need to be identified. We analyzed a broad range of plasma proteins in children with well-characterized asthma phenotypes to identify potential markers of childhood asthma. Using an affinity proteomics approach, plasma levels of 362 proteins covered by antibodies from the Human Protein Atlas were investigated in a total of 154 children with persistent or intermittent asthma and controls. After screening, chemokine ligand 5 (CCL5) hematopoietic prostaglandin D synthase (HPGDS) and neuropeptide S receptor 1 (NPSR1) were selected for further investigation. Significantly lower levels of both CCL5 and HPGDS were found in children with persistent asthma, while NPSR1 was found at higher levels in children with mild intermittent asthma compared to healthy controls. In addition, the protein levels were investigated in another respiratory disease, sarcoidosis, showing significantly higher NPSR1 levels in sera from sarcoidosis patients compared to healthy controls. Immunohistochemical staining of healthy tissues revealed high cytoplasmic expression of HPGDS in mast cells, present in stroma of both airway epithelia, lung as well as in other organs. High expression of NPSR1 was observed in neuroendocrine tissues, while no expression was observed in airway epithelia or lung. In conclusion, we have utilized a broad-scaled affinity proteomics approach to identify three proteins with altered plasma levels in asthmatic children, representing one of the first evaluations of HPGDS and NPSR1 protein levels in plasma. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. Genomic profiles of lung cancer associated with idiopathic pulmonary fibrosis.

    Science.gov (United States)

    Hwang, Ji An; Kim, Deokhoon; Chun, Sung-Min; Bae, SooHyun; Song, Joon Seon; Kim, Mi Young; Koo, Hyun Jung; Song, Jin Woo; Kim, Woo Sung; Lee, Jae Cheol; Kim, Hyeong Ryul; Choi, Chang-Min; Jang, Se Jin

    2018-01-01

    Little is known about the pathogenesis or molecular profiles of idiopathic pulmonary fibrosis-associated lung cancer (IPF-LC). This study was performed to investigate the genomic profiles of IPF-LC and to explore the possibility of defining potential therapeutic targets in IPF-LC. We assessed genomic profiles of IPF-LC by using targeted exome sequencing (OncoPanel version 2) in 35 matched tumour/normal pairs surgically resected between 2004 and 2014. Germline and somatic variant calling was performed with GATK HaplotypeCaller and MuTect with GATK SomaticIndelocator, respectively. Copy number analysis was conducted with CNVkit, with focal events determined by Genomic Identification of Significant Targets in Cancer 2.0, and pathway analysis (KEGG) with DAVID. Germline mutations in TERT (rs2736100, n = 33) and CDKN1A (rs2395655, n = 27) associated with idiopathic pulmonary fibrosis risk were detected in most samples. A total of 410 somatic mutations were identified, with an average of 11.7 per tumour, including 69 synonymous, 177 missense, 17 nonsense, 1 nonstop and 11 splice-site mutations, and 135 small coding indels. Spectra of the somatic mutations revealed predominant C > T transitions despite an extensive smoking history in most patients, suggesting a potential association between APOBEC-related mutagenesis and the development of IPF-LC. TP53 (22/35, 62.9%) and BRAF (6/35, 17.1%) were found to be significantly mutated in IPF-LC. Recurrent focal amplifications in three chromosomal loci (3q26.33, 7q31.2, and 12q14.3) and 9p21.3 deletion were identified, and genes associated with the JAK-STAT signalling pathway were significantly amplified in IPF-LC (P = 0.012). This study demonstrates that IPF-LC is genetically characterized by the presence of somatic mutations reflecting a variety of environmental exposures on the background of specific germline mutations, and is associated with potentially targetable alterations such as BRAF mutations. Copyright © 2017

  16. Analysis of plasma microRNA expression profiles revealed different cancer susceptibility in healthy young adult smokers and middle-aged smokers.

    Science.gov (United States)

    Shi, Bing; Gao, Hongmin; Zhang, Tianyang; Cui, Qinghua

    2016-04-19

    Cigarette smoking is a world-wide habit and an important risk factor for cancer. It was known that cigarette smoking can change the expression of circulating microRNAs (miRNAs) in healthy middle-aged adults. However, it remains unclear whether cigarette smoking can change the levels of circulating miRNAs in young healthy smokers and whether there are differences in cancer susceptibility for the two cases. In this study, the miRNA expression profiles of 28 smokers and 12 non-smokers were determined by Agilent human MicroRNA array. We further performed bioinformatics analysis for the differentially expressed miRNAs. The result showed that 35 miRNAs were differentially expressed. Among them, 24 miRNAs were up-regulated and 11 miRNAs were down-regulated in smokers. Functional enrichment analysis showed that the deregulated miRNAs are related to immune system and hormones regulation. Strikingly, the up-regulated miRNAs are mostly associated with hematologic cancers, such as lymphoma, leukemia. As a comparison, the up-regulated plasma miRNAs in middle-aged smokers are mostly associated with solid cancers, such as hepatocellular carcinoma and lung cancer, suggesting that smoking could have different influences on young adults and middle-aged adults. In a conclusion, we identified the circulating miRNAs deregulated by cigarette smoking and revealed that the age-dependent deregulated miRNAs tend to be mainly involved in different types of human cancers.

  17. Small RNA profiling reveals phosphorus deficiency as a contributing factor in symptom expression for citrus huanglongbing disease.

    Science.gov (United States)

    Zhao, Hongwei; Sun, Ruobai; Albrecht, Ute; Padmanabhan, Chellappan; Wang, Airong; Coffey, Michael D; Girke, Thomas; Wang, Zonghua; Close, Timothy J; Roose, Mikeal; Yokomi, Raymond K; Folimonova, Svetlana; Vidalakis, Georgios; Rouse, Robert; Bowman, Kim D; Jin, Hailing

    2013-03-01

    Huanglongbing (HLB) is a devastating citrus disease that is associated with bacteria of the genus 'Candidatus Liberibacter' (Ca. L.). Powerful diagnostic tools and management strategies are desired to control HLB. Host small RNAs (sRNA) play a vital role in regulating host responses to pathogen infection and are used as early diagnostic markers for many human diseases, including cancers. To determine whether citrus sRNAs regulate host responses to HLB, sRNAs were profiled from Citrus sinensis 10 and 14 weeks post grafting with Ca. L. asiaticus (Las)-positive or healthy tissue. Ten new microRNAs (miRNAs), 76 conserved miRNAs, and many small interfering RNAs (siRNAs) were discovered. Several miRNAs and siRNAs were highly induced by Las infection, and can be potentially developed into early diagnosis markers of HLB. miR399, which is induced by phosphorus starvation in other plant species, was induced specifically by infection of Las but not Spiroplasma citri that causes citrus stubborn-a disease with symptoms similar to HLB. We found a 35% reduction of phosphorus in Las-positive citrus trees compared to healthy trees. Applying phosphorus oxyanion solutions to HLB-positive sweet orange trees reduced HLB symptom severity and significantly improved fruit production during a 3-year field trial in south-west Florida. Our molecular, physiological, and field data suggest that phosphorus deficiency is linked to HLB disease symptomology.

  18. Metabolic Profiling of Alpine and Ecuadorian Lichens

    Directory of Open Access Journals (Sweden)

    Verena K. Mittermeier

    2015-10-01

    Full Text Available Non-targeted 1H-NMR methods were used to determine metabolite profiles from crude extracts of Alpine and Ecuadorian lichens collected from their natural habitats. In control experiments, the robustness of metabolite detection and quantification was estimated using replicate measurements of Stereocaulon alpinum extracts. The deviations in the overall metabolite fingerprints were low when analyzing S. alpinum collections from different locations or during different annual and seasonal periods. In contrast, metabolite profiles observed from extracts of different Alpine and Ecuadorian lichens clearly revealed genus- and species-specific profiles. The discriminating functions determining cluster formation in principle component analysis (PCA were due to differences in the amounts of genus-specific compounds such as sticticin from the Sticta species, but also in the amounts of ubiquitous metabolites, such as sugar alcohols or trehalose. However, varying concentrations of these metabolites from the same lichen species e.g., due to different environmental conditions appeared of minor relevance for the overall cluster formation in PCA. The metabolic clusters matched phylogenetic analyses using nuclear ribosomal DNA (nrDNA internal transcribed spacer (ITS sequences of lichen mycobionts, as exemplified for the genus Sticta. It can be concluded that NMR-based non-targeted metabolic profiling is a useful tool in the chemo-taxonomy of lichens. The same approach could also facilitate the discovery of novel lichen metabolites on a rapid and systematical basis.

  19. Serum Progesterone and Estradiol-17β Profiles in Nili Ravi Buffaloes (Bubalus bubalis with and without Dystocia

    Directory of Open Access Journals (Sweden)

    Muhammad Amjad Ali, Laeeq Akbar Lodhi and Faiz-ul-Hassan1*

    2012-10-01

    Full Text Available The aim of this study was to compare serum hormone profiles (progesterone and estradiol-17β in buffaloes with dystocia and unassisted calving in three agro-ecological zones of Punjab, Pakistan. One hundred and seventy three buffaloes (n=173 with assisted (dystocia and unassisted calving (normal birth were sampled for study. The results showed that the buffaloes suffering with dystocia had significantly higher (P<0.05 mean serum progesterone level compared with those having normal calving. The comparison amongst the agro-ecological zones revealed that serum progesterone level of dystocia cases in buffaloes of northern irrigated zone was significantly lower (P<0.05 compared with those in the southern irrigated zone and the arid zone, whereas the latter two did not differ between each other. No difference was observed in serum progesterone levels in normal buffaloes when compared amongst three agro-ecological zones. The serum estradiol-17β profile showed a significant (P<0.05 lower level in buffaloes with dystocia as compared to those with normal calving. Mean serum estradiol-17β level in the buffaloes affected with dystocia in the northern irrigated zone was significantly lower (P<0.05 compared to those in the southern irrigated zone and the arid zone wherein the latter two did not differ between each other.

  20. Evolution of anthocyanin profile from grape to wine

    Directory of Open Access Journals (Sweden)

    Margherita Squadrito

    2010-09-01

    Significance and impact of the study: Only in varieties in which the anthocyanin profile of grapes is characterized by low percentages of di-oxygenated side-ring forms is it possible to gain information about the varietal origin of a young wine by comparing the profiles of both grape and wine. However, great care is required.

  1. Diagnostic significance of microRNAs as novel biomarkers for bladder cancer: a meta-analysis of ten articles.

    Science.gov (United States)

    Shi, Hong-Bin; Yu, Jia-Xing; Yu, Jian-Xiu; Feng, Zheng; Zhang, Chao; Li, Guang-Yong; Zhao, Rui-Ning; Yang, Xiao-Bo

    2017-08-03

    Previous studies have revealed the importance of microRNAs' (miRNAs) function as biomarkers in diagnosing human bladder cancer (BC). However, the results are discordant. Consequently, the possibility of miRNAs to be BC biomarkers was summarized in this meta-analysis. In this study, the relevant articles were systematically searched from CBM, PubMed, EMBASE, and Chinese National Knowledge Infrastructure (CNKI). The bivariate model was used to calculate the pooled diagnostic parameters and summary receiver operator characteristic (SROC) curve in this meta-analysis, thereby estimating the whole predictive performance. STATA software was used during the whole analysis. Thirty-one studies from 10 articles, including 1556 cases and 1347 controls, were explored in this meta-analysis. In short, the pooled sensitivity, area under the SROC curve, specificity, positive likelihood ratio, diagnostic odds ratio, and negative likelihood ratio were 0.72 (95%CI 0.66-0.76), 0.80 (0.77-0.84), 0.76 (0.71-0.81), 3.0 (2.4-3.8), 8 (5.0-12.0), and 0.37 (0.30-0.46) respectively. Additionally, sub-group and meta-regression analyses revealed that there were significant differences between ethnicity, miRNA profiling, and specimen sub-groups. These results suggested that Asian population-based studies, multiple-miRNA profiling, and blood-based assays might yield a higher diagnostic accuracy than their counterparts. This meta-analysis demonstrated that miRNAs, particularly multiple miRNAs in the blood, might be novel, useful biomarkers with relatively high sensitivity and specificity and can be used for the diagnosis of BC. However, further prospective studies with more samples should be performed for further validation.

  2. Convolution based profile fitting

    International Nuclear Information System (INIS)

    Kern, A.; Coelho, A.A.; Cheary, R.W.

    2002-01-01

    diffractometers (e.g. BM16 at ESRF and Station 2.3 at Daresbury). In the literature, convolution based profile fitting is normally associated with microstructure analysis where the sample contribution needs to be separated from the instrument contribution in an observed profile. This is no longer the case. Convolution based profile fitting can be also performed on a fully empirical basis to provide better fits to data and a greater variety of profile shapes. With convolution based profile fitting virtually any peak shape and its angular dependence can be modelled. The approach may be based on a physical model (FPA) or performed empirically. The quality of fit by convolution is normally better than using other methods. The uncertainty in derived parameters is therefore reduced. The number of parameters required to describe a pattern is normally smaller than the 'analytical function approach' and therefore parameter correlation is reduced significantly, therefore, increasing profile complexity does not necessarily require an increasing number of parameters. Copyright (2002) Australian X-ray Analytical Association Inc

  3. Velocity dispersion profiles of clusters of galaxies

    International Nuclear Information System (INIS)

    Struble, M.F.

    1979-01-01

    Velocity dispersion as a function of radius, called sigma/sub ls/ profiles, is presented for 13 clusters of galaxies having > or =30 radial velocities from both published and unpublished lists. A list of probable new members and possible outlying members for these clusters is also given. chi 2 and Kolmogoroff--Smirnoff one-sample tests for the goodness of fit of power laws to portions of the profiles indicate two significant structures in some profiles: (1) a local minimum corresponding to the local minimum noted in surface density or surface brightness profiles, and (2) a decrease in sigma/sub ls/ toward the cores. Both of these features are discussed in terms of a comparison with Wielen's N-body simulations. The sigma/sub ls/ profiles are placed in a new classification scheme which lends itself to interpreting clusters in a dynamical age sequence. The velocity field of galaxies at large distances from cluster centers is also discussed

  4. An investigation on the noise reduction performance of profiled rigid median barriers at highways

    Directory of Open Access Journals (Sweden)

    Mohammad Reza Monazzam

    2012-01-01

    Full Text Available Median barriers as a portion of a divided highway are provided to minimize the cross-median crashes. Moreover, median barriers similar to roadside noise barriers could protect people from transportation noise. Thus, there is a need to investigate various median barrier models to identify changes of insertion loss over a simple rigid barrier. In order to estimate the acoustical influence of median barrier′s profile in the shadow zone, different median barrier models are presented and their insertion losses are calculated over a frequency range from 50 to 4000 Hz using a two-dimensional boundary element method. The present investigation has clearly revealed that among the profiled median barriers, T-shape, Y-shape, and L-shape provide better performance than that of the other shapes. It is also found that among inclined barriers, V-shape barrier significantly presents higher values of attenuation. Based on the calculation of different geometrics, it has been shown that a further 2 dB (A in efficiency could be obtained by a better design of the median barrier which is labeled model "L."

  5. Interpretive reliability of two common MMPI-2 profiles

    Directory of Open Access Journals (Sweden)

    Mark A. Deskovitz

    2016-12-01

    Full Text Available Users of multi-scale tests like the MMPI-2 tend not to interpret scales one at a time in a way that would correspond to standard scale-level reliability information. Instead, clinicians integrate inferences from a multitude of scales simultaneously, producing a descriptive narrative that is thought to characterize the examinee. This study was an attempt to measure the reliability of such integrated interpretations using a q-sort research methodology. Participants were 20 MMPI-2 users who responded to E-mail solicitations on professional listservs and in personal emails. Each participant interpreted one of two common MMPI-2 profiles using a q-set of 100 statements designed for MMPI-2 interpretation. To measure the “interpretive reliability” of the MMPI-2 profile interpretations, q-sort descriptions were intercorrelated. Mean pairwise interpretive reliability was .39, lower than expected, and there was no significant difference in reliability between profiles. There was also not a significant difference between within-profile and cross-profile correlations. Q-set item analysis was conducted to determine which individual statements had the most impact on interpretive reliability. Although sampling in this study was limited, implications for the field reliability of MMPI-2 interpretation are sobering.

  6. Comparative genomics reveals mobile pathogenicity chromosomes in Fusarium

    Energy Technology Data Exchange (ETDEWEB)

    Ma, Li Jun; van der Does, H. C.; Borkovich, Katherine A.; Coleman, Jeffrey J.; Daboussi, Marie-Jose; Di Pietro, Antonio; Dufresne, Marie; Freitag, Michael; Grabherr, Manfred; Henrissat, Bernard; Houterman, Petra M.; Kang, Seogchan; Shim, Won-Bo; Wolochuk, Charles; Xie, Xiaohui; Xu, Jin Rong; Antoniw, John; Baker, Scott E.; Bluhm, Burton H.; Breakspear, Andrew; Brown, Daren W.; Butchko, Robert A.; Chapman, Sinead; Coulson, Richard; Coutinho, Pedro M.; Danchin, Etienne G.; Diener, Andrew; Gale, Liane R.; Gardiner, Donald; Goff, Steven; Hammond-Kossack, Kim; Hilburn, Karen; Hua-Van, Aurelie; Jonkers, Wilfried; Kazan, Kemal; Kodira, Chinnappa D.; Koehrsen, Michael; Kumar, Lokesh; Lee, Yong Hwan; Li, Liande; Manners, John M.; Miranda-Saavedra, Diego; Mukherjee, Mala; Park, Gyungsoon; Park, Jongsun; Park, Sook Young; Proctor, Robert H.; Regev, Aviv; Ruiz-Roldan, M. C.; Sain, Divya; Sakthikumar, Sharadha; Sykes, Sean; Schwartz, David C.; Turgeon, Barbara G.; Wapinski, Ilan; Yoder, Olen; Young, Sarah; Zeng, Qiandong; Zhou, Shiguo; Galagan, James; Cuomo, Christina A.; Kistler, H. Corby; Rep, Martijn

    2010-03-18

    Fusarium species are among the most important phytopathogenic and toxigenic fungi, having significant impact on crop production and animal health. Distinctively, members of the F. oxysporum species complex exhibit wide host range but discontinuously distributed host specificity, reflecting remarkable genetic adaptability. To understand the molecular underpinnings of diverse phenotypic traits and their evolution in Fusarium, we compared the genomes of three economically important and phylogenetically related, yet phenotypically diverse plant-pathogenic species, F. graminearum, F. verticillioides and F. oxysporum f. sp. lycopersici. Our analysis revealed greatly expanded lineage-specific (LS) genomic regions in F. oxysporum that include four entire chromosomes, accounting for more than one-quarter of the genome. LS regions are rich in transposons and genes with distinct evolutionary profiles but related to pathogenicity. Experimentally, we demonstrate for the first time the transfer of two LS chromosomes between strains of F. oxysporum, resulting in the conversion of a non-pathogenic strain into a pathogen. Transfer of LS chromosomes between otherwise genetically isolated strains explains the polyphyletic origin of host specificity and the emergence of new pathogenic lineages in the F. oxysporum species complex, putting the evolution of fungal pathogenicity into a new perspective.

  7. Quantitative proteome profiling of human myoma and myometrium tissue reveals kinase expression signatures with potential for therapeutic intervention

    NARCIS (Netherlands)

    Lemeer, Simone; Gholami, Amin Moghaddas; Wu, Zhixiang; Kuster, Bernhard

    2015-01-01

    Uterine leiomyomas are benign tumors affecting a large proportion of the female population. Despite the very high prevalence, the molecular basis for understanding the onset and development of the disease are still poorly understood. In this study, we profiled the proteomes and kinomes of leiomyoma

  8. LOGISTIC FUNCTION PROFILE FIT: A least-squares program for fitting interface profiles to an extended logistic function

    International Nuclear Information System (INIS)

    Kirchhoff, William H.

    2012-01-01

    The extended logistic function provides a physically reasonable description of interfaces such as depth profiles or line scans of surface topological or compositional features. It describes these interfaces with the minimum number of parameters, namely, position, width, and asymmetry. Logistic Function Profile Fit (LFPF) is a robust, least-squares fitting program in which the nonlinear extended logistic function is linearized by a Taylor series expansion (equivalent to a Newton–Raphson approach) with no apparent introduction of bias in the analysis. The program provides reliable confidence limits for the parameters when systematic errors are minimal and provides a display of the residuals from the fit for the detection of systematic errors. The program will aid researchers in applying ASTM E1636-10, “Standard practice for analytically describing sputter-depth-profile and linescan-profile data by an extended logistic function,” and may also prove useful in applying ISO 18516: 2006, “Surface chemical analysis—Auger electron spectroscopy and x-ray photoelectron spectroscopy—determination of lateral resolution.” Examples are given of LFPF fits to a secondary ion mass spectrometry depth profile, an Auger surface line scan, and synthetic data generated to exhibit known systematic errors for examining the significance of such errors to the extrapolation of partial profiles.

  9. Anger profiles in social anxiety disorder.

    Science.gov (United States)

    Versella, Mark V; Piccirillo, Marilyn L; Potter, Carrie M; Olino, Thomas M; Heimberg, Richard G

    2016-01-01

    Individuals with social anxiety disorder (SAD) exhibit elevated levels of anger and anger suppression, which are both associated with increased depression, diminished quality of life, and poorer treatment outcomes. However, little is known about how anger experiences differ among individuals with SAD and whether any heterogeneity might relate to negative outcomes. This investigation sought to empirically define anger profiles among 136 treatment-seeking individuals with SAD and to assess their association with distress and impairment. A latent class analysis was conducted utilizing the trait subscales of the State-Trait Anger Expression Inventory-2 as indicators of class membership. Analysis revealed four distinct anger profiles, with greatest distress and impairment generally demonstrated by individuals with elevated trait anger, a greater tendency to suppress the expression of anger, and diminished ability to adaptively control their anger expression. These results have implications for tailoring more effective interventions for socially anxious individuals. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. DNA methylation profile distinguishes clear cell sarcoma of the kidney from other pediatric renal tumors.

    Directory of Open Access Journals (Sweden)

    Hitomi Ueno

    Full Text Available A number of specific, distinct neoplastic entities occur in the pediatric kidney, including Wilms' tumor, clear cell sarcoma of the kidney (CCSK, congenital mesoblastic nephroma (CMN, rhabdoid tumor of the kidney (RTK, and the Ewing's sarcoma family of tumors (ESFT. By employing DNA methylation profiling using Illumina Infinium HumanMethylation27, we analyzed the epigenetic characteristics of the sarcomas including CCSK, RTK, and ESFT in comparison with those of the non-neoplastic kidney (NK, and these tumors exhibited distinct DNA methylation profiles in a tumor-type-specific manner. CCSK is the most frequently hypermethylated, but least frequently hypomethylated, at CpG sites among these sarcomas, and exhibited 490 hypermethylated and 46 hypomethylated CpG sites in compared with NK. We further validated the results by MassARRAY, and revealed that a combination of four genes was sufficient for the DNA methylation profile-based differentiation of these tumors by clustering analysis. Furthermore, THBS1 CpG sites were found to be specifically hypermethylated in CCSK and, thus, the DNA methylation status of these THBS1 sites alone was sufficient for the distinction of CCSK from other pediatric renal tumors, including Wilms' tumor and CMN. Moreover, combined bisulfite restriction analysis could be applied for the detection of hypermethylation of a THBS1 CpG site. Besides the biological significance in the pathogenesis, the DNA methylation profile should be useful for the differential diagnosis of pediatric renal tumors.

  11. Independent component analysis reveals new and biologically significant structures in micro array data

    Directory of Open Access Journals (Sweden)

    Veerla Srinivas

    2006-06-01

    Full Text Available Abstract Background An alternative to standard approaches to uncover biologically meaningful structures in micro array data is to treat the data as a blind source separation (BSS problem. BSS attempts to separate a mixture of signals into their different sources and refers to the problem of recovering signals from several observed linear mixtures. In the context of micro array data, "sources" may correspond to specific cellular responses or to co-regulated genes. Results We applied independent component analysis (ICA to three different microarray data sets; two tumor data sets and one time series experiment. To obtain reliable components we used iterated ICA to estimate component centrotypes. We found that many of the low ranking components indeed may show a strong biological coherence and hence be of biological significance. Generally ICA achieved a higher resolution when compared with results based on correlated expression and a larger number of gene clusters with significantly enriched for gene ontology (GO categories. In addition, components characteristic for molecular subtypes and for tumors with specific chromosomal translocations were identified. ICA also identified more than one gene clusters significant for the same GO categories and hence disclosed a higher level of biological heterogeneity, even within coherent groups of genes. Conclusion Although the ICA approach primarily detects hidden variables, these surfaced as highly correlated genes in time series data and in one instance in the tumor data. This further strengthens the biological relevance of latent variables detected by ICA.

  12. Shaping the composition profiles in heteroepitaxial quantum dots: Interplay of thermodynamic and kinetic effects

    Directory of Open Access Journals (Sweden)

    C. Georgiou

    2014-07-01

    Full Text Available Atomistic Monte Carlo simulations, coupling thermodynamic and kinetic effects, resolve a longstanding controversy regarding the origin of composition profiles in heteroepitaxial SiGe quantum dots. It is shown that profiles with cores rich in the unstrained (Si component derive from near-equilibrium processes and intraisland diffusion. Profiles with cores rich in the strained (Ge component are of nonequilibrium nature, i.e., they are strain driven but kinetically limited. They are shaped by the distribution of kinetic barriers of atomic diffusion in the islands. The diffusion pathways are clearly revealed for the first time. Geometrical kinetics play a minor role.

  13. Circulating microRNA (miRNA Expression Profiling in Plasma of Patients with Gestational Diabetes Mellitus Reveals Upregulation of miRNA miR-330-3p

    Directory of Open Access Journals (Sweden)

    Guido Sebastiani

    2017-12-01

    Full Text Available Gestational diabetes mellitus (GDM is characterized by insulin resistance accompanied by low/absent beta-cell compensatory adaptation to the increased insulin demand. Although the molecular mechanisms and factors acting on beta-cell compensatory response during pregnancy have been partially elucidated and reported, those inducing an impaired beta-cell compensation and function, thus evolving in GDM, have yet to be fully addressed. MicroRNAs (miRNAs are a class of small endogenous non-coding RNAs, which negatively modulate gene expression through their sequence-specific binding to 3′UTR of mRNA target. They have been described as potent modulators of cell survival and proliferation and, furthermore, as orchestrating molecules of beta-cell compensatory response and function in diabetes. Moreover, it has been reported that miRNAs can be actively secreted by cells and found in many biological fluids (e.g., serum/plasma, thus representing both optimal candidate disease biomarkers and mediators of tissues crosstalk(s. Here, we analyzed the expression profiles of circulating miRNAs in plasma samples obtained from n = 21 GDM patients and from n = 10 non-diabetic control pregnant women (24–33 weeks of gestation using TaqMan array microfluidics cards followed by RT-real-time PCR single assay validation. The results highlighted the upregulation of miR-330-3p in plasma of GDM vs non-diabetics. Furthermore, the analysis of miR-330-3p expression levels revealed a bimodally distributed GDM patients group characterized by high or low circulating miR-330 expression and identified as GDM-miR-330high and GDM-miR-330low. Interestingly, GDM-miR-330high subgroup retained lower levels of insulinemia, inversely correlated to miR-330-3p expression levels, and a significant higher rate of primary cesarean sections. Finally, miR-330-3p target genes analysis revealed major modulators of beta-cell proliferation and of insulin secretion, such as the

  14. Effect of fiber sources on fatty acids profile, glycemic index, and phenolic compound content of in vitro digested fortified wheat bread.

    Science.gov (United States)

    Kurek, Marcin Andrzej; Wyrwisz, Jarosław; Karp, Sabina; Wierzbicka, Agnieszka

    2018-05-01

    In this study, some dietary fiber (DF) sources were investigated as fortifiers of wheat bread: oat (OB), flax (FB), and apple (AB). Adding oat and flax fibers to bread significantly changed the fatty acid profiles. OB was highest in oleic acid (33.83% of lipids) and linoleic acid (24.31% of lipids). Only in FB, γ-linolenic fatty acid was present in a significant amount-18.32%. The bioaccessibility trails revealed that the DF slow down the intake of saturated fatty acids. PUFA were least bioaccessible from all fatty acids groups in the range of (72% in OB to 87% in FB). The control bread had the greatest value (80.5) and was significantly higher than values for OB, FB, and AB in terms of glycemic index. OB, FB and AB addition led to obtain low glycemic index. AB had a significant highest value of total phenolic (897.2 mg/kg) with the lowest values in FB (541.2 mg/kg). The only significant lowering of caloric values in this study was observed in AB. The study could address the gap in the area of research about taking into consideration glycemic index, fatty acid profile and phenolic content in parallel in terms of DF application in breads.

  15. Lipid Profile Status in Mustard Lung Patients and its Relation to Severity of Airflow Obstruction

    Directory of Open Access Journals (Sweden)

    Davood Attaran

    2014-02-01

    Full Text Available Introduction: Chronic obstructive pulmonary disease (COPD secondary to sulfur mustard gas poisoning, known as mustard lung, is a major late pulmonary complications in chemical warfare patients. Serious comorbidities like dyslipidemia are frequently encountered in COPD. The aim of this study was to measure the serum lipid profile and evaluate the relation of lipid parameters with the severity of airway obstruction in mustard lung patients. Materials and Methods: Thirty-six non-smoker mustard lung patients with no history of cardiovascular disease, diabetes mellitus, and dyslipidemia were entered into this cross-sectional study. Control group consisted of 36 healthy non-smoker men were considered in this study. Serum lipid profile was performed in the patients and the controls. Spirometry was done in mustard lung patients. Results: The mean age of the patients was 47±6.80 SD years. The mean duration of COPD was 18.50±7.75 SD years. There were statistically significant differences in mean serum triglycerides and total cholesterol levels between patients and controls (p=0.04 and p=0.03, respectively.The mean levels of lipid parameters were not statistically significant different among the 4 stages of COPD severity (p>0.05. Conclusion: The current study revealed that the serum levels of triglycerides and cholesterol are elevated in mustard lung patients compared with the healthy controls. Since lipid profile abnormalities are considered as a major risk factor for cardiovascular disease, especial attention to this matter is recommended in mustard lung patients

  16. ObStruct: a method to objectively analyse factors driving population structure using Bayesian ancestry profiles.

    Directory of Open Access Journals (Sweden)

    Velimir Gayevskiy

    Full Text Available Bayesian inference methods are extensively used to detect the presence of population structure given genetic data. The primary output of software implementing these methods are ancestry profiles of sampled individuals. While these profiles robustly partition the data into subgroups, currently there is no objective method to determine whether the fixed factor of interest (e.g. geographic origin correlates with inferred subgroups or not, and if so, which populations are driving this correlation. We present ObStruct, a novel tool to objectively analyse the nature of structure revealed in Bayesian ancestry profiles using established statistical methods. ObStruct evaluates the extent of structural similarity between sampled and inferred populations, tests the significance of population differentiation, provides information on the contribution of sampled and inferred populations to the observed structure and crucially determines whether the predetermined factor of interest correlates with inferred population structure. Analyses of simulated and experimental data highlight ObStruct's ability to objectively assess the nature of structure in populations. We show the method is capable of capturing an increase in the level of structure with increasing time since divergence between simulated populations. Further, we applied the method to a highly structured dataset of 1,484 humans from seven continents and a less structured dataset of 179 Saccharomyces cerevisiae from three regions in New Zealand. Our results show that ObStruct provides an objective metric to classify the degree, drivers and significance of inferred structure, as well as providing novel insights into the relationships between sampled populations, and adds a final step to the pipeline for population structure analyses.

  17. Motor carrier industry profile study : financial and operating performance profiles by industry segment, 2001-2002.

    Science.gov (United States)

    2004-09-01

    This report profiles the motor carrier industry and its significant operating segments. It is one of a series of reports analyzing various aspects of the motor carrier industry. Other reports in the series focus on the safety performance of the indus...

  18. Emotional Profile of Women Victims of Domestic Violence.

    Science.gov (United States)

    Avdibegovic, Esmina; Brkic, Maja; Sinanovic, Osman

    2017-06-01

    Research indicates that women victims of domestic violence show significant cognitive changes, emotional numbing, and avoidance of interpersonal relationships. The aim of this research was to analyze emotional profile of women victims of domestic violence, and to determine the relationship between dimensions of emotions and frequency of women exposure to domestic violence. The research was conducted on the sample of 169 women, 111 were victims of domestic violence and 58 were women who did not experience domestic violence. Plutchik's Emotions Profile Index (EPI) was used for measuring of the emotion profile, and the Modified Inventory of Domestic Violence for measuring experiences of different types of violence. Basic socio-demographic data were also collected. Significant differences between women victims of domestic violence and women who did not experience domestic violence were found in a few dimensions of emotional profile. Women victims of domestic violence had higher results in the dimensions of deprivation/depression and aggression/destruction, while women who did not experience domestic violence had higher results in dimensions of reproduction and incorporation. Aggression was in significant negative correlation with reproduction, incorporation and self protection, whereas it was significant positive correlation with deprivation and opposition. There were significant and positive correlation between the dimensions of aggression and deprivation and frequency of all three forms of domestic violence and age of women. According to results obtained in this research, it can be concluded that women victims of domestic violence have significantly more intensive negative emotional dimensions in comparison to women who were not abused. Women victims of domestic violence with higher frequency of abuse describe themselves as more sad, apathetic, lonely, angry, quarrelsome and less sociable. Prominence of negative emotions, deprivation and aggression, can be factor of

  19. Charge-collection efficiency of GaAs field effect transistors fabricated with a low temperature grown buffer layer: dependence on charge deposition profile

    International Nuclear Information System (INIS)

    McMorrow, D.; Knudson, A.R.; Melinger, J.S.; Buchner, S.

    1999-01-01

    The results presented here reveal a surprising dependence of the charge-collection efficiency of LT GaAs FETs (field effect transistors) on the depth profile of the deposited charge. Investigation of the temporal dependence of the signal amplitude, carrier density contours, and potential contours reveals different mechanisms for charge collection arising from carriers deposited above and below the LT GaAs buffer layer, respectively. In particular, carriers deposited below the LT GaAs buffer layer dissipate slowly and give rise to a persistent charge collection that is associated with a bipolar-like gain process. These results may be of significance in understanding the occurrence of single-event upsets from protons, neutrons, and large-angle, glancing heavy-ion strikes. (authors)

  20. Assessment of oral safety profile of aqueous extract blend of three ...

    African Journals Online (AJOL)

    ... did not reveal any pathological changes attributable to treatment with the spice blend extract. Conclusions: These findings indicate that oral consumption of a spice blend of garlic, ginger and cayenne pepper in humans may be safe. Keywords: Spice blend, Toxicity, Histology, Marker enzymes, Medicinal, Safety profile ...