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  1. Transcriptome analysis reveals non-identical microRNA profiles between arterial and venous plasma

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    Xu, Guoheng; Geng, Bin; Cui, Qinghua

    2017-01-01

    Circulating microRNAs presented in venous plasma have been demonstrated as powerful biomarkers for the complex diseases like cancer. Nevertheless, those presented in arterial plasma remained largely unexplored. Here, using microarray technique, we compared microRNA expression profiles of the matched arterial and venous plasma samples from the same male rats. Though the microRNA profiles were largely similar, we identified 24 differentially expressed microRNAs, including 10 arterial highly expressed microRNAs and 14 venous highly expressed microRNAs. The differentially expressed microRNAs were validated by qRT-PCR. Computational analysis of these microRNAs and their targets indicated that arterial highly expressed microRNAs were overrepresented for functional terms like hematopoiesis and diseases like Crohn's Disease and leukemia; while venous highly expressed microRNAs were enriched for cell differentiation function, and diseases like distal myopathies and heart failure. Our analysis also suggested significant correlations between plasma microRNA expression and tissue microRNA expression. Four arterial highly expressed microRNAs also showed enriched expression in specific tissues and would be novel biomarker candidates. PMID:28212530

  2. Transcriptome analysis reveals distinct gene expression profiles in astrocytoma grades II-IV.

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    Narsia, Nato; Ramagiri, Pradeep; Ehrmann, Jiri; Kolar, Zdenek

    2017-09-01

    Astrocytoma is the most prevalent form of primary brain cancer categorized into four histological grades by the World Health Organization. Investigation into individual grades of astrocytoma by previous studies has provided some insight into dysregulation of regulatory networks associated with increasing astrocytoma grades. However, further understanding of key mechanisms that distinguish different astrocytoma grades is required to facilitate targeted therapies. In this study, we utilized a large cohort of publicly available RNA sequencing data from patients with diffuse astrocytoma (grade II), anaplastic astrocytoma (grade III), primary glioblastoma (grade IV), secondary glioblastoma (grade IV), recurrent glioblastoma (grade IV), and normal brain samples to identify genetic similarities and differences between these grades using bioinformatics applications. Our analysis revealed a distinct gene expression pattern between grade II astrocytoma and grade IV glioblastoma (GBM). We also identified genes that were exclusively expressed in each of the astrocytoma grades. Furthermore, we identified known and novel genes involved in key pathways in our study. Gene set enrichment analysis revealed a distinct expression pattern of transcriptional regulators in primary GBM. Further investigation into molecular processes showed that the genes involved in cell proliferation and invasion were shared across all subtypes of astrocytoma. Also, the number of genes involved in metastasis, regulation of cell proliferation, and apoptosis increased with tumor grade. We confirmed existing findings and shed light on some important genes and molecular processes that will improve our understanding of glioma biology.

  3. Expression profiling and functional analysis of Populus WRKY23 reveals a regulatory role in defense.

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    Levée, Valérie; Major, Ian; Levasseur, Caroline; Tremblay, Laurence; MacKay, John; Séguin, Armand

    2009-01-01

    WRKY transcription factors are key regulators that activate and fine-tune stress responses, including defense responses against pathogens. We isolated a poplar (Populus tremulaxPopulus alba) cDNA sequence, PtWRKY23, that encodes the ortholog of Arabidopsis WRKY23 and present the functional analysis of WRKY23, with emphasis on its potential role in resistance to rust infection. To investigate the function of PtWRKY23, we examined PtWRKY23 expression after stress treatments by qRT-PCR and generated PtWRKY23-misexpressing plants. Transgenic plants were assessed for resistance to Melampsora rust and were analyzed using the poplar Affymetrix GeneChip and histological techniques to study the consequences of PtWRKY23 misexpression. PtWRKY23 is rapidly induced by Melampsora infection and elicitor treatments and poplars overexpressing and underexpressing PtWRKY23 were both more susceptible to Melampsora infection than wild type. Transcriptome analysis of PtWRKY23 overexpressors revealed a significant overlap with the Melampsora-infection response. Transcriptome analysis also suggests that PtWRKY23 affects redox homeostasis and cell wall-related metabolism, which was confirmed by analyses that showed that PtWRKY23-misexpressing plants have altered peroxidase activity, apparent H(2)O(2) accumulation and lignin deposition. Our results show that PtWRKY23 affects resistance to Melampsora infection and that this may be caused by deregulation of genes that disrupt redox homeostasis and cell wall metabolism.

  4. Lipid profiling and transcriptomic analysis reveals a functional interplay between estradiol and growth hormone in liver.

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    Leandro Fernández-Pérez

    Full Text Available 17β-estradiol (E2 may interfere with endocrine, metabolic, and gender-differentiated functions in liver in both females and males. Indirect mechanisms play a crucial role because of the E2 influence on the pituitary GH secretion and the GHR-JAK2-STAT5 signaling pathway in the target tissues. E2, through its interaction with the estrogen receptor, exerts direct effects on liver. Hypothyroidism also affects endocrine and metabolic functions of the liver, rendering a metabolic phenotype with features that mimic deficiencies in E2 or GH. In this work, we combined the lipid and transcriptomic analysis to obtain comprehensive information on the molecular mechanisms of E2 effects, alone and in combination with GH, to regulate liver functions in males. We used the adult hypothyroid-orchidectomized rat model to minimize the influence of internal hormones on E2 treatment and to explore its role in male-differentiated functions. E2 influenced genes involved in metabolism of lipids and endo-xenobiotics, and the GH-regulated endocrine, metabolic, immune, and male-specific responses. E2 induced a female-pattern of gene expression and inhibited GH-regulated STAT5b targeted genes. E2 did not prevent the inhibitory effects of GH on urea and amino acid metabolism-related genes. The combination of E2 and GH decreased transcriptional immune responses. E2 decreased the hepatic content of saturated fatty acids and induced a transcriptional program that seems to be mediated by the activation of PPARα. In contrast, GH inhibited fatty acid oxidation. Both E2 and GH replacements reduced hepatic CHO levels and increased the formation of cholesterol esters and triacylglycerols. Notably, the hepatic lipid profiles were endowed with singular fingerprints that may be used to segregate the effects of different hormonal replacements. In summary, we provide in vivo evidence that E2 has a significant impact on lipid content and transcriptome in male liver and that E2 exerts a

  5. Cluster analysis of sputum cytokine-high profiles reveals diversity in T(h)2-high asthma patients.

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    Seys, Sven F; Scheers, Hans; Van den Brande, Paul; Marijsse, Gudrun; Dilissen, Ellen; Van Den Bergh, Annelies; Goeminne, Pieter C; Hellings, Peter W; Ceuppens, Jan L; Dupont, Lieven J; Bullens, Dominique M A

    2017-02-23

    Asthma is characterized by a heterogeneous inflammatory profile and can be subdivided into T(h)2-high and T(h)2-low airway inflammation. Profiling of a broader panel of airway cytokines in large unselected patient cohorts is lacking. Patients (n = 205) were defined as being "cytokine-low/high" if sputum mRNA expression of a particular cytokine was outside the respective 10th/90th percentile range of the control group (n = 80). Unsupervised hierarchical clustering was used to determine clusters based on sputum cytokine profiles. Half of patients (n = 108; 52.6%) had a classical T(h)2-high ("IL-4-, IL-5- and/or IL-13-high") sputum cytokine profile. Unsupervised cluster analysis revealed 5 clusters. Patients with an "IL-4- and/or IL-13-high" pattern surprisingly did not cluster but were equally distributed among the 5 clusters. Patients with an "IL-5-, IL-17A-/F- and IL-25- high" profile were restricted to cluster 1 (n = 24) with increased sputum eosinophil as well as neutrophil counts and poor lung function parameters at baseline and 2 years later. Four other clusters were identified: "IL-5-high or IL-10-high" (n = 16), "IL-6-high" (n = 8), "IL-22-high" (n = 25). Cluster 5 (n = 132) consists of patients without "cytokine-high" pattern or patients with only high IL-4 and/or IL-13. We identified 5 unique asthma molecular phenotypes by biological clustering. Type 2 cytokines cluster with non-type 2 cytokines in 4 out of 5 clusters. Unsupervised analysis thus not supports a priori type 2 versus non-type 2 molecular phenotypes. www.clinicaltrials.gov NCT01224938. Registered 18 October 2010.

  6. Proteomic Profiling Analysis Reveals a Link between Experimental Autoimmune Uveitis and Complement Activation in Rats.

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    Guo, D D; Hu, B; Tang, H Y; Sun, Y Y; Liu, B; Tian, Q M; Bi, H S

    2017-05-01

    Uveitis is an autoimmune disease that usually damages the vision function, leading to poor visual quality in patients. As an autoimmune ocular inflammatory disease, the pathogenesis of uveitis is associated with abnormal expression of some proteins and aberrant regulation of multiple signalling pathways. Nevertheless, the detailed mechanism remains unclear. In this study, we induced an experimental autoimmune uveitis (EAU) model in rats. We determined the levels of C3a and membrane attack complex C5b-9 (soluble C5b-9, sC5b-9) in both plasma and aqueous humour, identified the differentially expressed proteins in plasma by liquid chromatography-tandem mass spectrometry and employed bioinformatics algorithms to analyse differentially expressed proteins in EAU rat plasma. The results demonstrate that there were 168 differentially expressed plasma proteins in EAU rats versus control subjects. The levels of sC5b-9 and C3a were elevated in the plasmas and aqueous humours of EAU rats. Gene ontology enrichment analysis showed that the differentially expressed proteins in EAU rat plasma were mainly involved in metabolic and immune processes. Kyoto encyclopedia of genes and genomes (KEGG) pathway annotation, database for annotation, visualization and integrated discovery (DAVID) and protein-protein interaction analyses revealed that the differentially expressed proteins in EAU rat plasmas were closely associated with complement and coagulation cascades, metabolic pathways, NF-kappa B, PI3K-Akt, Toll-like receptors and autophagy. Overall, the differentially expressed proteins in EAU rat plasmas are mainly involved in the complement and coagulation cascades. The pathogenesis of uveitis closely correlates with complement activation. © 2017 The Foundation for the Scandinavian Journal of Immunology.

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

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    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.

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

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    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

  9. Transcript analysis at DGAT1 reveals different mRNA profiles in river buffaloes with extreme phenotypes for milk fat.

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    Gu, M; Cosenza, G; Nicolae, I; Bota, A; Guo, Y; Di Stasio, L; Pauciullo, A

    2017-10-01

    Buffalo DGAT1 (diacylglycerol O-acyltransferase 1) was mainly investigated for the characterization of the gene itself and for the identification of the K232A polymorphism, similar to what has been accomplished in cattle, although no information has been reported so far at the mRNA level. The importance of DGAT1 for lipid metabolism led us to investigate the transcript profiles of lactating buffaloes characterized as high (9.13 ± 0.23) and low (7.94 ± 0.29) for milk fat percentage, and to explore the genetic diversity at the RNA and DNA level. A total of 336 positive clones for the DGAT1 cDNA were analyzed by PCR and chosen for sequencing according to the differences in length. The clone assembling revealed a very complex mRNA pattern with a total of 21 transcripts differently represented in the 2 groups of animals. Apart from the correct transcript (17 exons long), the skipping of exon 12 is the most significant in terms of distribution of clones with 11.6% difference between the 2 groups, whereas a totally different mRNA profile was found in approximately 12% of clones. The sequencing of genomic DNA allowed the identification of 10 polymorphic sites at the intron level, which clarify, at least partially, the genetic events behind the production of complex mRNA. Genetic diversity was found also at the exon level. The single nucleotide polymorphism c.1053C>T represents the first example of polymorphism in a coding region for the DGAT1 in the Italian Mediterranean breed. To establish whether this polymorphism is present in other buffalo breeds, a quick method based on PCR-RFLP was set up for allelic discrimination in the Italian Mediterranean and the Romanian Murrah (200 animals in total). The alleles were equally represented in the overall population, whereas the analysis of the 2 breeds showed different frequencies, likely indicating diverse genetic structure of the 2 breeds. The T allele might be considered as the ancestral condition of the DGAT1 gene, being

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

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    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 pGenes enriched in these pathways coupled with their regulatory miRNAs formed a functional 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.

  11. Comparative analysis of inflamed and non-inflamed colon biopsies reveals strong proteomic inflammation profile in patients with ulcerative colitis

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    Poulsen, Nina Aagaard; Andersen, Vibeke; Moller, Jens Christian

    2012-01-01

    Background: Accurate diagnostic and monitoring tools for ulcerative colitis (UC) are missing. Our aim was to describe the proteomic profile of UC and search for markers associated with disease exacerbation. Therefore, we aimed to characterize specific proteins associated with inflamed colon mucosa...... annotated by image analysis and 222 of these had a statistically different protein level between inflamed and non-inflamed tissue in the patient group. Principal component analysis clearly grouped non-inflamed samples separately from the inflamed samples indicating that the proteomic signature of colon......, thioredoxins and selenium binding protein). Conclusions: A distinct proteomic profile of inflamed tissue in UC patients was found. Specific proteins involved in energy metabolism and oxidative stress were identified as potential candidate markers for UC....

  12. Genome-wide methylation analysis of DNMT3B gene isoforms revealed specific methylation profiles in breast cell lines.

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    Plourde, Karine V; Labrie, Yvan; Ouellette, Geneviève; Pouliot, Marie-Christine; Durocher, Francine

    2016-09-01

    The goal of this study is to characterize the specific methylation profile triggered by DNMT3B protein isoforms expressed at different levels in breast cell lines. Microarray DNA methylation data were analyzed and associated with functional genome annotation data. A large spectrum of DNMT3B3/DNMT3B2 expression ratio values was observed in parental breast cell lines. According to their methylation profiles, hierarchical clustering of untransfected cell lines revealed clustering based on their ER/PR status. Overexpression of DNMT3B3 triggered methylation changes of thousands of CpG sites in breast cells. Based on the trend of methylation changes, the results suggest an antiproliferative action of the DNMT3B3 isoform through a dominant negative effect on its wild-type counterpart DNMT3B2. This study revealed specific pathways modulated by DNMT3B isoforms, which could regulate cell proliferation and other biological mechanisms. This illustrates the importance of multiple interactions between isoforms in the complexity of methylation processes.

  13. Lectin Microarray Reveals Binding Profiles of Lactobacillus casei Strains in a Comprehensive Analysis of Bacterial Cell Wall Polysaccharides▿†

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    Yasuda, Emi; Tateno, Hiroaki; Hirabarashi, Jun; Iino, Tohru; Sako, Tomoyuki

    2011-01-01

    We previously showed a pivotal role of the polysaccharide (PS) moiety in the cell wall of the Lactobacillus casei strain Shirota (YIT 9029) as a possible immune modulator (E. Yasuda M. Serata, and T. Sako, Appl. Environ. Microbiol. 74:4746-4755, 2008). To distinguish PS structures on the bacterial cell surface of individual strains in relation to their activities, it would be useful to have a rapid and high-throughput methodology. Recently, a new technique called lectin microarray was developed for rapid profiling of glycosylation in eukaryotic polymers and cell surfaces. Here, we report on the development of a simple and sensitive method based on this technology for direct analysis of intact bacterial cell surface glycomes. The method involves labeling bacterial cells with SYTOX Orange before incubation with the lectin microarray. After washing, bound cells are directly detected using an evanescent-field fluorescence scanner in a liquid phase. Using this method, we compared the cell surface glycomes from 16 different strains of L. casei. The patterns of lectin-binding affinity of most strains were found to be unique. There appears to be two types of lectin-binding profiles: the first is characterized by a few lectins, and the other is characterized by multiple lectins with different specificities. We also showed a dramatic change in the lectin-binding profile of a YIT 9029 derivative with a mutation in the cps1C gene, encoding a putative glycosyltransferase. In conclusion, the developed technique provided a novel strategy for rapid profiling and, more importantly, differentiating numerous bacterial strains with relevance to the biological functions of PS. PMID:21602390

  14. Blue whale earplug reveals lifetime contaminant exposure and hormone profiles

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    Trumble, Stephen J.; Robinson, Eleanor M.; Berman-Kowalewski, Michelle; Potter, Charles W.; Usenko, Sascha

    2013-01-01

    Currently, obtaining lifetime chemical profiles (i.e., from birth to death) is extremely rare and difficult for most of Earth’s animals. We have developed a unique approach to quantify hormone and contaminant lifetime profiles for an individual blue whale with a 6-mo resolution using the wax earplug as a natural matrix capable of archiving and preserving these temporal profiles. Using a male blue whale earplug, chemical analysis reveals lifetime patterns of mercury and organic pollutant expos...

  15. "Topological significance" analysis of gene expression and proteomic profiles from prostate cancer cells reveals key mechanisms of androgen response.

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    Adaikkalam Vellaichamy

    2010-06-01

    Full Text Available The problem of prostate cancer progression to androgen independence has been extensively studied. Several studies systematically analyzed gene expression profiles in the context of biological networks and pathways, uncovering novel aspects of prostate cancer. Despite significant research efforts, the mechanisms underlying tumor progression are poorly understood. We applied a novel approach to reconstruct system-wide molecular events following stimulation of LNCaP prostate cancer cells with synthetic androgen and to identify potential mechanisms of androgen-independent progression of prostate cancer.We have performed concurrent measurements of gene expression and protein levels following the treatment using microarrays and iTRAQ proteomics. Sets of up-regulated genes and proteins were analyzed using our novel concept of "topological significance". This method combines high-throughput molecular data with the global network of protein interactions to identify nodes which occupy significant network positions with respect to differentially expressed genes or proteins. Our analysis identified the network of growth factor regulation of cell cycle as the main response module for androgen treatment in LNCap cells. We show that the majority of signaling nodes in this network occupy significant positions with respect to the observed gene expression and proteomic profiles elicited by androgen stimulus. Our results further indicate that growth factor signaling probably represents a "second phase" response, not directly dependent on the initial androgen stimulus.We conclude that in prostate cancer cells the proliferative signals are likely to be transmitted from multiple growth factor receptors by a multitude of signaling pathways converging on several key regulators of cell proliferation such as c-Myc, Cyclin D and CREB1. Moreover, these pathways are not isolated but constitute an interconnected network module containing many alternative routes from inputs

  16. Biomarker Analysis Revealed Distinct Profiles of Innate and Adaptive Immunity in Infants with Ocular Lesions of Congenital Toxoplasmosis

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    Machado, Anderson Silva; Carneiro, Ana Carolina Aguiar Vasconcelos; Béla, Samantha Ribeiro; Andrade, Gláucia Manzan Queiroz; Vasconcelos-Santos, Daniel Vitor; Januário, José Nélio; Coelho-dos-Reis, Jordana G.; Ferro, Eloisa Amália Vieira; Teixeira-Carvalho, Andréa; Vitor, Ricardo Wagner Almeida; Martins-Filho, Olindo Assis; —UFMG-CTBG, UFMG Congenital Toxoplasmosis Brazilian Group

    2014-01-01

    Toxoplasma gondii is the main infectious cause of human posterior retinochoroiditis, the most frequent clinical manifestation of congenital toxoplasmosis. This investigation was performed after neonatal screening to identify biomarkers of immunity associated with immunopathological features of the disease by flow cytometry. The study included infected infants without NRL and with retinochoroidal lesions (ARL, ACRL, and CRL) as well as noninfected individuals (NI). Our data demonstrated that leukocytosis, with increased monocytes and lymphocytes, was a relevant hematological biomarker of ARL. Immunophenotypic analysis also revealed expansion of CD14+CD16+HLA-DRhigh monocytes and CD56dim cytotoxic NK-cells in ARL. Moreover, augmented TCRγ δ + and CD8+ T-cell counts were apparently good biomarkers of morbidity. Biomarker network analysis revealed that complex and intricated networks underscored the negative correlation of monocytes with NK- and B-cells in NRL. The remarkable lack of connections involving B-cells and a relevant shift of NK-cell connections from B-cells toward T-cells observed in ARL were outstanding. A tightly connected biomarker network was observed in CRL, with relevant connections of NK- and CD8+ T-cells with a broad range of cell subsets. Our findings add novel elements to the current knowledge on the innate and adaptive immune responses in congenital toxoplasmosis. PMID:25328286

  17. 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.

  18. Integrative analysis of the transcriptome profiles observed in type 1, type 2 and gestational diabetes mellitus reveals the role of inflammation.

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    Evangelista, Adriane F; Collares, Cristhianna V A; Xavier, Danilo J; Macedo, Claudia; Manoel-Caetano, Fernanda S; Rassi, Diane M; Foss-Freitas, Maria C; Foss, Milton C; Sakamoto-Hojo, Elza T; Nguyen, Catherine; Puthier, Denis; Passos, Geraldo A; Donadi, Eduardo A

    2014-05-23

    Type 1 diabetes (T1D) is an autoimmune disease, while type 2 (T2D) and gestational diabetes (GDM) are considered metabolic disturbances. In a previous study evaluating the transcript profiling of peripheral mononuclear blood cells obtained from T1D, T2D and GDM patients we showed that the gene profile of T1D patients was closer to GDM than to T2D. To understand the influence of demographical, clinical, laboratory, pathogenetic and treatment features on the diabetes transcript profiling, we performed an analysis integrating these features with the gene expression profiles of the annotated genes included in databases containing information regarding GWAS and immune cell expression signatures. Samples from 56 (19 T1D, 20 T2D, and 17 GDM) patients were hybridized to whole genome one-color Agilent 4x44k microarrays. Non-informative genes were filtered by partitioning, and differentially expressed genes were obtained by rank product analysis. Functional analyses were carried out using the DAVID database, and module maps were constructed using the Genomica tool. The functional analyses were able to discriminate between T1D and GDM patients based on genes involved in inflammation. Module maps of differentially expressed genes revealed that modulated genes: i) exhibited transcription profiles typical of macrophage and dendritic cells; ii) had been previously associated with diabetic complications by association and by meta-analysis studies, and iii) were influenced by disease duration, obesity, number of gestations, glucose serum levels and the use of medications, such as metformin. This is the first module map study to show the influence of epidemiological, clinical, laboratory, immunopathogenic and treatment features on the transcription profiles of T1D, T2D and GDM patients.

  19. Differential profiling analysis of miRNAs reveals a regulatory role in low N stress response of Populus.

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    Ren, Yuanyuan; Sun, Fengshuo; Hou, Jia; Chen, Lei; Zhang, Yiyun; Kang, Xiangyang; Wang, Yanwei

    2015-01-01

    Nitrogen (N) is an essential mineral element for plant growth processes, and its availability severely affects the productivity of plants, especially trees. MicroRNAs (miRNAs) are a class of non-coding RNAs approximately 21 nucleotides in length that play important roles in plant growth, development and stress responses. To identify Populus miRNAs and their functions in response to nutrition stress, high-throughput sequencing was performed using Populus tomentosa plantlets treated with or without low concentrations of N. We identified 160 conserved miRNAs, 15 known but non-conserved miRNAs, 2 candidate novel miRNAs and 71 corresponding miRNA*s. Differential expression analysis showed that expression of the 21 conserved miRNA families was significantly altered. Real-time quantitative PCR (qPCR) was used to further validate and analyze the dynamic expression of the identified miRNAs. A total of 218 target genes from the low-N-responsive miRNAs were predicted, and their functions were further annotated in combination with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. These results suggest that miRNAs play important roles in the response of Populus to low N stress. Furthermore, this study provides the first identification and profiles of N stress-responsive miRNAs from trees.

  20. Glycan analysis of Fonsecaea monophora from clinical and environmental origins reveals different structural profile and human antigenic response

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    Juliana Reis Burjack

    2014-10-01

    Full Text Available Dematiaceous fungi constitute a large and heterogeneous group, characterized by having a dark pigment, the dihydroxynaftalen melanin - DHN, inside their cell walls. In nature they are found mainly as soil microbiota or decomposing organic matter, and are spread in tropical and subtropical regions. The fungus Fonsecaea monophora causes chromoblastomycosis in humans, and possesses essential mechanisms that may enhance pathogenicity, proliferation and dissemination inside the host. Glycoconjugates confer important properties to these pathogenic microorganisms. In this work, structural characterization of glycan structures present in two different strains of F. monophora MMHC82 and FE5p4, from clinical and environmental origins, respectively, was performed. Each one were grown on Minimal Medium (MM and Czapeck-Dox (CD medium, and the water soluble cell wall glycoconjugates and exopolysaccharides (EPS were evaluated by NMR, methylation and principal component analysis (PCA. By combining the methylation and 2D NMR analyses, it was possible to visualize the glycosidic profiles of the complex carbohydrate mixtures. Significant differences were observed in β-D-Galf-(1→5 and (1→6 linkages, α- and β-D-Glcp-(1→3, (1→4 and (1→6 units, as well as in α-D-Manp. PCA from 1H-NMR data showed that MMHC82 from CD medium showed a higher variation in the cell wall carbohydrates, mainly related to O-2 substituted β-D-Galf (δ 106.0/5.23 and δ 105.3/5.23 units. In order to investigate the antigenic response of the glycoconjugates, these were screened against serum from chromoblastomycosis patients. The antigen which contained the cell wall of MMHC82 grown in MM had β-D-Manp units that promoted higher antigenic response. The distribution of these fungal species in nature and the knowledge of how cell wall polysaccharides and glycoconjugates structure vary, may contribute to the better understanding and the elucidation of the pathology caused by this

  1. Cysteine Protease Profiles of the Medicinal Plant Calotropis procera R. Br. revealed by de novo transcriptome analysis.

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    Chang Woo Kwon

    Full Text Available Calotropis procera R. Br., a traditional medicinal plant in India, is a promising source of commercial proteases, because the cysteine proteases from the plant exhibit high thermo-stability, broad pH optima, and plasma-clotting activity. Though several proteases such as Procerain, Procerain B, CpCp-1, CpCp-2, and CpCp-3 have been isolated and characterized, the information of their transcripts is limited to cDNAs encoding their mature peptides. Due to this limitation, in this study, to determine the cDNA sequences encoding full open reading frame of these cysteine proteases, transcripts were sequenced with an Illumina Hiseq2000 sequencer. A total of 171,253,393 clean reads were assembled into 106,093 contigs with an average length of 1,614 bp and an N50 of 2,703 bp, and 70,797 contigs with an average length of 1,565 bp and N50 of 2,082 bp using Trinity and Velvet-Oases software, respectively. Among these contigs, we found 20 unigenes related to papain-like cysteine proteases by BLASTX analysis against a non-redundant NCBI protein database. Our expression analysis revealed that the cysteine protease contains an N-terminal pro-peptide domain (inhibitor region, which is necessary for correct folding and proteolytic activity. It was evident that expression yields using an inducible T7 expression system in Escherichia coli were considerably higher with the pro-peptide domain than without the domain, which could contribute to molecular cloning of the Calotropis procera protease as an active form with correct folding.

  2. Cysteine Protease Profiles of the Medicinal Plant Calotropis procera R. Br. revealed by de novo transcriptome analysis.

    Science.gov (United States)

    Kwon, Chang Woo; Park, Kyung-Min; Kang, Byoung-Cheorl; Kweon, Dae-Hyuk; Kim, Myoung-Dong; Shin, Sang Woon; Je, Yeon Ho; Chang, Pahn-Shick

    2015-01-01

    Calotropis procera R. Br., a traditional medicinal plant in India, is a promising source of commercial proteases, because the cysteine proteases from the plant exhibit high thermo-stability, broad pH optima, and plasma-clotting activity. Though several proteases such as Procerain, Procerain B, CpCp-1, CpCp-2, and CpCp-3 have been isolated and characterized, the information of their transcripts is limited to cDNAs encoding their mature peptides. Due to this limitation, in this study, to determine the cDNA sequences encoding full open reading frame of these cysteine proteases, transcripts were sequenced with an Illumina Hiseq2000 sequencer. A total of 171,253,393 clean reads were assembled into 106,093 contigs with an average length of 1,614 bp and an N50 of 2,703 bp, and 70,797 contigs with an average length of 1,565 bp and N50 of 2,082 bp using Trinity and Velvet-Oases software, respectively. Among these contigs, we found 20 unigenes related to papain-like cysteine proteases by BLASTX analysis against a non-redundant NCBI protein database. Our expression analysis revealed that the cysteine protease contains an N-terminal pro-peptide domain (inhibitor region), which is necessary for correct folding and proteolytic activity. It was evident that expression yields using an inducible T7 expression system in Escherichia coli were considerably higher with the pro-peptide domain than without the domain, which could contribute to molecular cloning of the Calotropis procera protease as an active form with correct folding.

  3. 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.

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

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    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.

  5. Comparative transcriptional profiling analysis of the two daughter cells from tobacco zygote reveals the transcriptome differences in the apical and basal cells

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    Hu Tian-Xiang

    2010-08-01

    Full Text Available Abstract Background In angiosperm, after the first asymmetric zygotic cell division, the apical and basal daughter cells follow distinct development pathways. Global transcriptome analysis of these two cells is essential in understanding their developmental differences. However, because of the difficulty to isolate the in vivo apical and basal cells of two-celled proembryo from ovule and ovary in higher plants, the transcriptome analysis of them hasn't been reported. Results In this study, we developed a procedure for isolating the in vivo apical and basal cells of the two-celled proembryo from tobacco (Nicotiana tabacum, and then performed a comparative transcriptome analysis of the two cells by suppression subtractive hybridization (SSH combined with macroarray screening. After sequencing, we identified 797 differentially expressed ESTs corresponding to 299 unigenes. Library sequence analysis successfully identified tobacco homologies of genes involved in embryogenesis and seed development. By quantitative real-time PCR, we validated the differential expression of 40 genes, with 6 transcripts of them specifically expressed in the apical or basal cell. Expression analysis also revealed some transcripts displayed cell specific activation in one of the daughter cells after zygote division. These differential expressions were further validated by in situ hybridization (ISH. Tissue expression pattern analysis also revealed some potential roles of these candidate genes in development. Conclusions The results show that some differential or specific transcripts in the apical and basal cells of two-celled proembryo were successfully isolated, and the identification of these transcripts reveals that these two daughter cells possess distinct transcriptional profiles after zygote division. Further functional work on these differentially or specifically expressed genes will promote the elucidation of molecular mechanism controlling early embryogenesis.

  6. Combining Metabolic Profiling and Gene Expression Analysis to Reveal the Biosynthesis Site and Transport of Ginkgolides in Ginkgo biloba L.

    Science.gov (United States)

    Lu, Xu; Yang, Hua; Liu, Xinguang; Shen, Qian; Wang, Ning; Qi, Lian-wen; Li, Ping

    2017-01-01

    The most unique components of Ginkgo biloba extracts are terpene trilactones (TTLs) including ginkgolides and bilobalide. Study of TTLs biosynthesis has been stagnant in recent years. Metabolic profiling of 40 compounds, including TTLs, flavonoids, and phenolic acids, were globally analyzed in leaf, fibrous root, main root, old stem and young stem extracts of G. biloba. Most of the flavonoids were mainly distributed in the leaf and old stem. Most of phenolic acids were generally distributed among various tissues. The total content of TTLs decreased in the order of the leaf, fibrous root, main root, old stem and young stem. The TTLs were further analyzed in different parts of the main root and old stem. The content of TTLs decreases in the order of the main root periderm, the main root cortex and phloem and the main root xylem. In old stems, the content of TTLs in the cortex and phloem was much higher than both the old stem periderm and xylem. The expression patterns of five key genes in the ginkgolide biosynthetic pathway were measured by real-time quantitative polymerase chain reaction (RT-Q-PCR). Combining metabolic profiling and RT-Q-PCR, the results showed that the fibrous root and main root periderm tissues were the important biosynthesis sites of ginkgolides. Based on the above results, a model of the ginkgolide biosynthesis site and transport pathway in G. biloba was proposed. In this putative model, ginkgolides are synthesized in the fibrous root and main root periderm, and these compounds are then transported through the old stem cortex and phloem to the leaves. PMID:28603534

  7. Transcript profile analysis reveals important roles of jasmonic acid signalling pathway in the response of sweet potato to salt stress.

    Science.gov (United States)

    Zhang, Huan; Zhang, Qian; Zhai, Hong; Li, Yan; Wang, Xiangfeng; Liu, Qingchang; He, Shaozhen

    2017-01-13

    Sweet potato is an important food and bio-energy crop, and investigating the mechanisms underlying salt tolerance will provide information for salt-tolerant breeding of this crop. Here, the root transcriptomes of the salt-sensitive variety Lizixiang and the salt-tolerant line ND98 were compared to identify the genes and pathways involved in salt stress responses. In total, 8,744 and 10,413 differentially expressed genes (DEGs) in Lizixiang and ND98, respectively, were involved in salt responses. A lower DNA methylation level was detected in ND98 than in Lizixiang. In both genotypes, the DEGs, which function in phytohormone synthesis and signalling and ion homeostasis, may underlie the different degrees of salt tolerance. Significant up-regulations of the genes involved in the jasmonic acid (JA) biosynthesis and signalling pathways and ion transport, more accumulation of JA, a higher degree of stomatal closure and a lower level of Na + were found in ND98 compared to Lizixiang. This is the first report on transcriptome responses to salt tolerance in sweet potato. These results reveal that the JA signalling pathway plays important roles in the response of sweet potato to salt stress. This study provides insights into the mechanisms and genes involved in the salt tolerance of sweet potato.

  8. Transcript profile analysis reveals important roles of jasmonic acid signalling pathway in the response of sweet potato to salt stress

    Science.gov (United States)

    Zhang, Huan; Zhang, Qian; Zhai, Hong; Li, Yan; Wang, Xiangfeng; Liu, Qingchang; He, Shaozhen

    2017-01-01

    Sweet potato is an important food and bio-energy crop, and investigating the mechanisms underlying salt tolerance will provide information for salt-tolerant breeding of this crop. Here, the root transcriptomes of the salt-sensitive variety Lizixiang and the salt-tolerant line ND98 were compared to identify the genes and pathways involved in salt stress responses. In total, 8,744 and 10,413 differentially expressed genes (DEGs) in Lizixiang and ND98, respectively, were involved in salt responses. A lower DNA methylation level was detected in ND98 than in Lizixiang. In both genotypes, the DEGs, which function in phytohormone synthesis and signalling and ion homeostasis, may underlie the different degrees of salt tolerance. Significant up-regulations of the genes involved in the jasmonic acid (JA) biosynthesis and signalling pathways and ion transport, more accumulation of JA, a higher degree of stomatal closure and a lower level of Na+ were found in ND98 compared to Lizixiang. This is the first report on transcriptome responses to salt tolerance in sweet potato. These results reveal that the JA signalling pathway plays important roles in the response of sweet potato to salt stress. This study provides insights into the mechanisms and genes involved in the salt tolerance of sweet potato. PMID:28084460

  9. Virome profiling of bats from Myanmar by metagenomic analysis of tissue samples reveals more novel Mammalian viruses.

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    Biao He

    Full Text Available Bats are reservoir animals harboring many important pathogenic viruses and with the capability of transmitting these to humans and other animals. To establish an effective surveillance to monitor transboundary spread of bat viruses between Myanmar and China, complete organs from the thorax and abdomen from 853 bats of six species from two Myanmar counties close to Yunnan province, China, were collected and tested for their virome through metagenomics by Solexa sequencing and bioinformatic analysis. In total, 3,742,314 reads of 114 bases were generated, and over 86% were assembled into 1,649,512 contigs with an average length of 114 bp, of which 26,698 (2% contigs were recognizable viral sequences belonging to 24 viral families. Of the viral contigs 45% (12,086/26,698 were related to vertebrate viruses, 28% (7,443/26,698 to insect viruses, 27% (7,074/26,698 to phages and 95 contigs to plant viruses. The metagenomic results were confirmed by PCR of selected viruses in all bat samples followed by phylogenetic analysis, which has led to the discovery of some novel bat viruses of the genera Mamastrovirus, Bocavirus, Circovirus, Iflavirus and Orthohepadnavirus and to their prevalence rates in two bat species. In conclusion, the present study aims to present the bat virome in Myanmar, and the results obtained further expand the spectrum of viruses harbored by bats.

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

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    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

  11. Gene expression profiling analysis reveals weaning-induced cell cycle arrest and apoptosis in the small intestine of pigs.

    Science.gov (United States)

    Zhu, L H; Xu, J X; Zhu, S W; Cai, X; Yang, S F; Chen, X L; Guo, Q

    2014-03-01

    In swine production, weaning is a critical event for porcine weaning-associated disease, such as postweaning stress syndrome, which involves intestinal dysfunction. However, little is known about the molecular mechanisms of intestinal dysfunction in pigs during weaning. To gain new insight into the interaction between weaning stress and intestinal function, 4 pigs at 25 d of age for each of the weaning and the suckling groups for a total of 40 pigs were used to analyze changes in the genomic expression in the intestines of weaned pigs by microarray analysis. Four hundred forty-five genes showed altered expression after weaning treatment (286 upregulated and 159 downregulated) at the cutoff criteria of the fold change ≥1.5 or 0.05) were observed when compared with the suckling pigs. These selected genes likely indicate that weaning induced cell cycle arrest, enhanced apoptosis, and inhibited cell proliferation. The results of this study provide a basis for understanding the molecular pathogenesis of weaning treatment.

  12. Genetic profiling and surface proteome analysis of human atrial stromal cells and rat ventricular epicardium-derived cells reveals novel insights into their cardiogenic potential

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    Sebastian Temme

    2017-12-01

    Full Text Available Epicardium-derived cells (EPDC and atrial stromal cells (ASC display cardio-regenerative potential, but the molecular details are still unexplored. Signals which induce activation, migration and differentiation of these cells are largely unknown. Here we have isolated rat ventricular EPDC and rat/human ASC and performed genetic and proteomic profiling. EPDC and ASC expressed epicardial/mesenchymal markers (WT-1, Tbx18, CD73, CD90, CD44, CD105, cardiac markers (Gata4, Tbx5, troponin T and also contained phosphocreatine. We used cell surface biotinylation to isolate plasma membrane proteins of rEPDC and hASC, Nano-liquid chromatography with subsequent mass spectrometry and bioinformatics analysis identified 396 rat and 239 human plasma membrane proteins with 149 overlapping proteins. Functional GO-term analysis revealed several significantly enriched categories related to extracellular matrix (ECM, cell migration/differentiation, immunology or angiogenesis. We identified receptors for ephrin and growth factors (IGF, PDGF, EGF, anthrax toxin known to be involved in cardiac repair and regeneration. Functional category enrichment identified clusters around integrins, PI3K/Akt-signaling and various cardiomyopathies. Our study indicates that EPDC and ASC have a similar molecular phenotype related to cardiac healing/regeneration. The cell surface proteome repository will help to further unravel the molecular details of their cardio-regenerative potential and their role in cardiac diseases.

  13. 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.

  14. 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.

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

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    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. Bovine Teat Microbiome Analysis Revealed Reduced Alpha Diversity and Significant Changes in Taxonomic Profiles in Quarters with a History of Mastitis

    Science.gov (United States)

    Falentin, Hélène; Rault, Lucie; Nicolas, Aurélie; Bouchard, Damien S.; Lassalas, Jacques; Lamberton, Philippe; Aubry, Jean-Marc; Marnet, Pierre-Guy; Le Loir, Yves; Even, Sergine

    2016-01-01

    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 infectious episode

  17. 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.

  18. An inverse analysis reveals limitations of the soil-CO2 profile method to calculate CO2 production and efflux for well-structured soils

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    M. D. Corre

    2010-08-01

    Full Text Available Soil respiration is the second largest flux in the global carbon cycle, yet the underlying below-ground process, carbon dioxide (CO2 production, is not well understood because it can not be measured in the field. CO2 production has frequently been calculated from the vertical CO2 diffusive flux divergence, known as "soil-CO2 profile method". This relatively simple model requires knowledge of soil CO2 concentration profiles and soil diffusive properties. Application of the method for a tropical lowland forest soil in Panama gave inconsistent results when using diffusion coefficients (D calculated based on relationships with soil porosity and moisture ("physically modeled" D. Our objective was to investigate whether these inconsistencies were related to (1 the applied interpolation and solution methods and/or (2 uncertainties in the physically modeled profile of D. First, we show that the calculated CO2 production strongly depends on the function used to interpolate between measured CO2 concentrations. Secondly, using an inverse analysis of the soil-CO2 profile method, we deduce which D would be required to explain the observed CO2 concentrations, assuming the model perception is valid. In the top soil, this inversely modeled D closely resembled the physically modeled D. In the deep soil, however, the inversely modeled D increased sharply while the physically modeled D did not. When imposing a constraint during the fit parameter optimization, a solution could be found where this deviation between the physically and inversely modeled D disappeared. A radon (Rn mass balance model, in which diffusion was calculated based on the physically modeled or constrained inversely modeled D, simulated observed Rn profiles reasonably well. However, the CO2 concentrations which corresponded to the constrained inversely modeled D were too small compared to the measurements. We suggest that, in well-structured soils, a missing description of steady state CO2

  19. Gene expression profiling and network analysis reveals lipid and steroid metabolism to be the most favored by TNFalpha in HepG2 cells.

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    Amit K Pandey

    Full Text Available BACKGROUND: The proinflammatory cytokine, TNFalpha, is a crucial mediator of the pathogenesis of several diseases, more so in cases involving the liver wherein it is critical in maintaining liver homeostasis since it is a major determiner of hepatocyte life and death. Gene expression profiling serves as an appropriate strategy to unravel the underlying signatures to envisage such varied responses and considering this, gene transcription profiling was examined in control and TNFalpha treated HepG2 cells. METHODS AND FINDINGS: Microarray experiments between control and TNFalpha treated HepG2 cells indicated that TNFalpha could significantly alter the expression profiling of 140 genes; among those up-regulated, several GO (Gene Ontology terms related to lipid and fat metabolism were significantly (p<0.01 overrepresented indicating a global preference of fat metabolism within the hepatocyte and those within the down-regulated dataset included genes involved in several aspects of the immune response like immunoglobulin receptor activity and IgE binding thereby indicating a compromise in the immune defense mechanism(s. Conserved transcription factor binding sites were identified in identically clustered genes within a common GO term and SREBP-1 and FOXJ2 depicted increased occupation of their respective binding elements in the presence of TNFalpha. The interacting network of "lipid metabolism, small molecule biochemistry" was derived to be significantly overrepresented that correlated well with the top canonical pathway of "biosynthesis of steroids". CONCLUSIONS: TNFalpha alters the transcriptome profiling within HepG2 cells with an interesting catalog of genes being affected and those involved in lipid and steroid metabolism to be the most favored. This study represents a composite analysis of the effects of TNFalpha in HepG2 cells that encompasses the altered transcriptome profiling, the functional analysis of the up- and down- regulated genes and

  20. Genome-wide mRNA analysis reveals a TUBD1 isoform profile as a potential biomarker for diabetic retinopathy development.

    Science.gov (United States)

    Villegas-Ruiz, Vanessa; Hendlmeier, Ferdinand; Buentello-Volante, Beatriz; Rodríguez-Loaiza, José L; Miranda-Duarte, Antonio; Zenteno, Juan C

    2017-02-01

    Diabetic retinopathy (DR) affects approximately one third of all diabetic subjects and is the leading cause of blindness in young to middle-aged adults in the developed world. While early diagnosis is crucial for preventing DR-associated visual loss, the identification of accessible biomarkers that could lead to presymptomatic recognition of the disease is of great clinical importance. The aim of this work was to investigate the possible involvement of alternative splicing events in DR development by performing a genome-wide transcriptional profiling comparing blood-derived RNA from DR subjects and from diabetic-non DR controls. A total of 95 RNA samples, 67 from patients with bilateral DR and 28 from diabetic patients without DR after a period of at least 10 years with type 2 DM, were compared in a genome-wide transcriptome analysis using the GeneChip(®) Human Gene 2.0 ST Array which contains probe sets covering all exons of ∼33,500 coding transcripts of annotated genes. Microarray data analysis followed by RT-PCR and cDNA sequencing identified important differential splicing events in TUBD1 (Tubulin, Delta-1) isoforms between DR and DM samples. Specifically, the co-expression of particular TUBD1 isoforms was significantly associated with NPDR risk (p = 0.039 by Pearson's chi-squared test; OR (CI 95%): 8.1 (1.0-72.7)). Analysis of TUBD1 signal pathways and regulating networks using a MetaCore platform showed that HIF-1, a molecule playing an important role in the pathogenesis of DR, is a direct regulator of TUBD1 expression. In conjunction, our data suggest that TUBD1 mRNA isoform expression profile in peripheral blood could be an accessible biomarker for predicting the risk for diabetic retinopathy development. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. A systematic integrated analysis of brain expression profiles reveals YAP1 and other prioritized hub genes as important upstream regulators in Alzheimer's disease.

    Science.gov (United States)

    Xu, Min; Zhang, Deng-Feng; Luo, Rongcan; Wu, Yong; Zhou, Hejiang; Kong, Li-Li; Bi, Rui; Yao, Yong-Gang

    2018-02-01

    Profiling the spatial-temporal expression pattern and characterizing the regulatory networks of brain tissues are vital for understanding the pathophysiology of Alzheimer's disease (AD). We performed a systematic integrated analysis of expression profiles of AD-affected brain tissues (684 AD and 562 controls). A network-based convergent functional genomic approach was used to prioritize possible regulator genes during AD development, followed by functional characterization. We generated a complete list of differentially expressed genes and hub genes of the transcriptomic network in AD brain and constructed a Web server (www.alzdata.org) for public access. Seventeen hub genes active at the early stages, especially YAP1, were recognized as upstream regulators of the AD network. Cellular assays proved that early alteration of YAP1 could promote AD by influencing the whole transcriptional network. Early expression disturbance of hub genes is an important feature of AD development, and interfering with this process may reverse the disease progression. Copyright © 2017 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

  2. De Novo Transcriptome and Expression Profile Analysis to Reveal Genes and Pathways Potentially Involved in Cantharidin Biosynthesis in the Blister Beetle Mylabris cichorii.

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    Yi Huang

    Full Text Available The dried body of Mylabris cichorii is well-known Chinese traditional medicine. The sesquiterpenoid cantharidin, which is secreted mostly by adult male beetles, has recently been used as an anti-cancer drug. However, little is known about the mechanisms of cantharidin biosynthesis. Furthermore, there is currently no genomic or transcriptomic information for M. cichorii. In this study, we performed de novo assembly transcriptome of M. cichorii using the Illumina Hiseq2000. A single run produced 9.19 Gb of clean nucleotides comprising 29,247 sequences, including 23,739 annotated sequences (about 81%. We also constructed two expression profile libraries (20-25 day-old adult males and 20-25 day-old adult females and discovered 2,465 significantly differentially-expressed genes. Putative genes and pathways involved in the biosynthesis of cantharidin were then characterized. We also found that cantharidin biosynthesis in M. cichorii might only occur via the mevalonate (MVA pathway, not via the methylerythritol 4-phosphate/deoxyxylulose 5-phosphate (MEP/DOXP pathway or a mixture of these. Besides, we considered that cantharidin biosynthesis might be related to the juvenile hormone (JH biosynthesis or degradation. The results of transcriptome and expression profiling analysis provide a comprehensive sequence resource for M. cichorii that could facilitate the in-depth study of candidate genes and pathways involved in cantharidin biosynthesis, and may thus help to improve our understanding of the mechanisms of cantharidin biosynthesis in blister beetles.

  3. Quantitative profiling of glucosinolates by LC-MS analysis reveals several cultivars of cabbage and kale as promising sources of sulforaphane.

    Science.gov (United States)

    Sasaki, Katsunori; Neyazaki, Makiko; Shindo, Kazutoshi; Ogawa, Toshiya; Momose, Masaki

    2012-08-15

    Sulforaphane is an isothiocyanate well known for its potential health benefits. With the aim of finding sulforaphane supply sources, its precursor, glucoraphanin, was widely searched for among Brassica oleracea varieties. Quantitative profiling of seven glucosinolates by LC-MS analysis was performed on 6 cultivars of broccoli, 32 of cabbage and 24 cultivars of kale. The glucoraphanin levels found in three cultivars of cabbage and six cultivars of kale were comparable with, or even higher than, the highest of broccoli (119.4 mg/100g FW). The most promising group belonged to the black kale, Cavolo nero. Use of a C30 column and an ammonium formate buffer in LC-MS and a micro plate solid phase extraction technique was highly effective. Copyright © 2012 Elsevier B.V. All rights reserved.

  4. Roles of microRNAs in immunopathogenesis of non-alcoholic fatty liver disease revealed by integrated analysis of microRNA and mRNA expression profiles.

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    Zhang, Yu-Jun; Hu, Ying; Li, Jing; Chi, Yu-Jing; Jiang, Wei-Wei; Zhang, Feng; Liu, Yu-Lan

    2017-02-01

    The integrative analysis of microRNA and mRNA expression profiles can elucidate microRNA-targeted gene function. We used this technique to elucidate insights into the immunological pathology of non-alcoholic fatty liver disease (NAFLD). We analyzed differentially expressed microRNA and mRNA expression profiles of CD4+ T lymphocytes from the liver and mesenteric lymph nodes (MLNs) of mice with NAFLD using microarrays and RNA sequencing. Normal mice were used as controls. The target genes of microRNAs were predicted by TargetScan. Integrative analysis showed that the mRNAs were overlapped with microRNAs. Furthermore, the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to predict the key genes and pathways. Then, 16 microRNAs and 10 mRNAs were validated by qRT-PCR. Microarray analysis suggested that 170 microRNAs were significantly de-regulated in CD4+ T lymphocytes from the liver between the two groups. Eighty mRNAs corresponded with microRNA targeted genes. KEGG analysis indicated that the MAPK pathway was consistently augmented in the liver of NAFLD mice. miR-23b, let-7e, miR-128 and miR-130b possibly played significant parts in the MAPK pathways. Furthermore, between the two groups, 237 microRNAs were significantly de-regulated in CD4+ T lymphocytes from MLNs. 38 mRNAs coincided with microRNA target genes. The metabolic pathway was consistently enriched in the MLNs of NAFLD mice. miR-206-3p, miR-181a-5p, miR-29c-3p and miR-30d-5p likely play important roles in the regulation of metabolic pathways. The results of this study presented a new perspective on the application of integrative analysis to identify complex regulation means involved in the immunological pathogenesis of NAFLD.

  5. Transcriptome and Expression Profiling Analysis of the Hemocytes Reveals a Large Number of Immune-Related Genes in Mud Crab Scylla paramamosain during Vibrio parahaemolyticus Infection

    Science.gov (United States)

    Xie, Chuping; Chen, Yaping; Sun, Wanwei; Ding, Jun; Zhou, Lizhen; Wang, Shasha; Wang, Shuqi; Zhang, Yueling; Zhu, Dashi; Wen, Xiaobo; Hu, Songnian; Li, Shengkang

    2014-01-01

    Background Mud crab Scylla paramamosain is an economically important marine species in China. However, frequent outbreaks of infectious diseases caused by marine bacteria, such as Vibrio parahaemolyticus, result in great economic losses. Methodology/Principal Findings Comparative de novo transcriptome analysis of S. paramamosain infected with V. parahaemolyticus was carried out to investigate the molecular mechanisms underlying the immune response to pathogenic bacteria by using the Illumina paired-end sequencing platform. A total of 52,934,042 clean reads from the hemocytes of V. parahaemolyticus-infected mud crabs and controls were obtained and assembled into 186,193 contigs. 59,120 unigenes were identified from 81,709 consensus sequences of mud crabs and 48,934 unigenes were matched proteins in the Nr or Swissprot databases. Among these, 10,566 unigenes belong to 3 categories of Gene Ontology, 25,349 to 30 categories of KEGG, and 15,191 to 25 categories of COG database, covering almost all functional categories. By using the Solexa/Illumina's DGE platform, 1213 differentially expressed genes (P<0.05), including 538 significantly up-regulated and 675 down-regulated, were detected in V. parahaemolyticus-infected crabs as compared to that in the controls. Transcript levels of randomly-chosen genes were further measured by quantitative real-time PCR to confirm the expression profiles. Many differentially expressed genes are involved in various immune processes, including stimulation of the Toll pathway, Immune Deficiency (IMD) pathway, Ras-regulated endocytosis, and proPO-activating system. Conclusions/Significance Analysis of the expression profile of crabs under infection provides invaluable new data for biological research in S. paramamosain, such as the identification of novel genes in the hemocytes during V. parahaemolyticus infection. These results will facilitate our comprehensive understanding of the mechanisms involved in the immune response to bacterial

  6. Microarray Expression Profile Analysis of Long Non-Coding RNAs in Umbilical Cord Plasma Reveals their Potential Role in Gestational Diabetes-Induced Macrosomia

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    Zhonghua Shi

    2015-05-01

    Full Text Available Background: Fetal macrosomia and its associated complications are the most frequent and serious morbidities for infants associated with gestational diabetes mellitus (GDM. The associations between long non-coding RNAs (lncRNAs and macrosomia have been rarely reported; therefore, we investigated the umbilical cord lncRNA profiles in GDM macrosomia. Method: Thirty pairs of GDM macrosomia and normal controls were divided into three subgroups randomly, and the umbilical cord vein blood from each subgroup was mixed, and hybridized to a microarray containing probes representing 33,000 lncRNA genes. Quantitative real-time polymerase chain reaction (qPCR was used to validate selected differentially expressed lncRNAs. The gene ontology (GO, pathway and network analysis were performed. Result: The microarray identified 8814 lncRNAs that were expressed in the umbilical cord blood, of which 349 were significantly upregulated and 892 were significantly downregulated (fold-change ≥ 2.0 in GDM group. The highest enriched GOs targeted by downregulated transcripts were biological regulation. Pathway analysis indicated that nine pathways corresponded to downregulated transcripts. Conclusions: Certain lncRNAs that were aberrantly expressed in the umbilical cord blood from GDM macrosomia might play a partial or key role in GDM macrosomia development. This study provided potential targets for treatment of macrosomia and novel insights into macrosomia biology.

  7. Microarray Expression Profile Analysis of Long Non-Coding RNAs in Umbilical Cord Plasma Reveals their Potential Role in Gestational Diabetes-Induced Macrosomia.

    Science.gov (United States)

    Shi, Zhonghua; Zhao, Chun; Long, Wei; Ding, Hongjuan; Shen, Rong

    2015-01-01

    Fetal macrosomia and its associated complications are the most frequent and serious morbidities for infants associated with gestational diabetes mellitus (GDM). The associations between long non-coding RNAs (lncRNAs) and macrosomia have been rarely reported; therefore, we investigated the umbilical cord lncRNA profiles in GDM macrosomia. Thirty pairs of GDM macrosomia and normal controls were divided into three subgroups randomly, and the umbilical cord vein blood from each subgroup was mixed, and hybridized to a microarray containing probes representing 33,000 lncRNA genes. Quantitative real-time polymerase chain reaction (qPCR) was used to validate selected differentially expressed lncRNAs. The gene ontology (GO), pathway and network analysis were performed. The microarray identified 8814 lncRNAs that were expressed in the umbilical cord blood, of which 349 were significantly upregulated and 892 were significantly downregulated (fold-change ≥ 2.0) in GDM group. The highest enriched GOs targeted by downregulated transcripts were biological regulation. Pathway analysis indicated that nine pathways corresponded to downregulated transcripts. Certain lncRNAs that were aberrantly expressed in the umbilical cord blood from GDM macrosomia might play a partial or key role in GDM macrosomia development. This study provided potential targets for treatment of macrosomia and novel insights into macrosomia biology. © 2015 S. Karger AG, Basel.

  8. Blue whale earplug reveals lifetime contaminant exposure and hormone profiles

    Science.gov (United States)

    Trumble, Stephen J.; Robinson, Eleanor M.; Berman-Kowalewski, Michelle; Potter, Charles W.; Usenko, Sascha

    2013-01-01

    Lifetime contaminant and hormonal profiles have been reconstructed for an individual male blue whale (Balaenoptera musculus, Linnaeus 1758) using the earplug as a natural aging matrix that is also capable of archiving and preserving lipophilic compounds. These unprecedented lifetime profiles (i.e., birth to death) were reconstructed with a 6-mo resolution for a wide range of analytes including cortisol (stress hormone), testosterone (developmental hormone), organic contaminants (e.g., pesticides and flame retardants), and mercury. Cortisol lifetime profiles revealed a doubling of cortisol levels over baseline. Testosterone profiles suggest this male blue whale reached sexual maturity at approximately 10 y of age, which corresponds well with and improves on previous estimates. Early periods of the reconstructed contaminant profiles for pesticides (such as dichlorodiphenyltrichloroethanes and chlordanes), polychlorinated biphenyls, and polybrominated diphenyl ethers demonstrate significant maternal transfer occurred at 0–12 mo. The total lifetime organic contaminant burden measured between the earplug (sum of contaminants in laminae layers) and blubber samples from the same organism were similar. Total mercury profiles revealed reduced maternal transfer and two distinct pulse events compared with organic contaminants. The use of a whale earplug to reconstruct lifetime chemical profiles will allow for a more comprehensive examination of stress, development, and contaminant exposure, as well as improve the assessment of contaminant use/emission, environmental noise, ship traffic, and climate change on these important marine sentinels. PMID:24043814

  9. The medical threat of mamba envenoming in sub-Saharan Africa revealed by genus-wide analysis of venom composition, toxicity and antivenomics profiling of available antivenoms.

    Science.gov (United States)

    Ainsworth, Stuart; Petras, Daniel; Engmark, Mikael; Süssmuth, Roderich D; Whiteley, Gareth; Albulescu, Laura-Oana; Kazandjian, Taline D; Wagstaff, Simon C; Rowley, Paul; Wüster, Wolfgang; Dorrestein, Pieter C; Arias, Ana Silvia; Gutiérrez, José M; Harrison, Robert A; Casewell, Nicholas R; Calvete, Juan J

    2017-08-24

    extremely rapid-acting neurotoxins. Previous studies on mamba venoms have focused on the biochemical and pharmacological characterisation of their most relevant toxins to rationalize the common neurological and neuromuscular symptoms of envenomings caused by these species, but there has been little work on overall venom composition or comparisons between them. Only very recently an overview of the composition of the venom of two Dendroaspis species, D. angusticeps and D. polylepis, has been unveiled through venomics approaches. Here we present the first genus-wide transcriptomic-proteomic analysis of mamba venom composition. The transcriptomic analyses described in this paper have contributed 29 (D. polylepis), 23 (D. angusticeps), 40 (D. viridis), 25 (D. j. jamesoni) and 21 (D. j. kaimosae), novel full-length toxin sequences to the non-redundant Dendroaspis sequence database. The mamba genus-wide venomic analysis demonstrated that major D. polylepis venom components are Kunitz-fold family toxins. This feature is unique in relation to the relatively conserved three-finger toxin (3FTx)-dominated venom compositions of the green mambas. Venom variation was interpreted in the context of dietary variation due to the divergent terrestrial ecology of D. polylepis compared to the arboreal niche occupied by all other mambas. Additionally, the degree of cross-reactivity conservation of mamba venoms was assessed by antivenomics against a panel of commercial antivenoms generated for the sub-Saharan Africa market. This study provides a genus-wide overview to infer which available antivenoms may be capable of neutralising human envenomings caused by mambas, irrespective of the species responsible. The information gathered in this study lays the foundations for rationalising the pharmacological profiles of mamba venoms at locus resolution. This understanding will contribute to the generation of a safer and more efficacious pan-Dendroaspis therapeutic antivenom against any mamba

  10. Steroid profiling in doping analysis

    NARCIS (Netherlands)

    Kerkhof, Daniël Henri van de

    2001-01-01

    Profiling androgens in urine samples is used in doping analysis for the detection of abused steroids of endogenous origin. These profiling techniques were originally developed for the analysis of testosterone, mostly by means of the ratio of testosterone to epitestosterone (T/E ratio). A study was

  11. Transcriptome profiling reveals mosaic genomic origins of modern cultivated barley

    Science.gov (United States)

    Dai, Fei; Chen, Zhong-Hua; Wang, Xiaolei; Li, Zefeng; Jin, Gulei; Wu, Dezhi; Cai, Shengguan; Wang, Ning; Wu, Feibo; Nevo, Eviatar; Zhang, Guoping

    2014-01-01

    The domestication of cultivated barley has been used as a model system for studying the origins and early spread of agrarian culture. Our previous results indicated that the Tibetan Plateau and its vicinity is one of the centers of domestication of cultivated barley. Here we reveal multiple origins of domesticated barley using transcriptome profiling of cultivated and wild-barley genotypes. Approximately 48-Gb of clean transcript sequences in 12 Hordeum spontaneum and 9 Hordeum vulgare accessions were generated. We reported 12,530 de novo assembled transcripts in all of the 21 samples. Population structure analysis showed that Tibetan hulless barley (qingke) might have existed in the early stage of domestication. Based on the large number of unique genomic regions showing the similarity between cultivated and wild-barley groups, we propose that the genomic origin of modern cultivated barley is derived from wild-barley genotypes in the Fertile Crescent (mainly in chromosomes 1H, 2H, and 3H) and Tibet (mainly in chromosomes 4H, 5H, 6H, and 7H). This study indicates that the domestication of barley may have occurred over time in geographically distinct regions. PMID:25197090

  12. Correlation-based network analysis of metabolite and enzyme profiles reveals a role of citrate biosynthesis in modulating N and C metabolism in zea mays

    Science.gov (United States)

    To investigate the natural variability of leaf metabolism and enzymatic activity in a maize inbred population, statistical and network analyses were employed on metabolite and enzyme profiles. The test of coefficient of variation showed that sugars and amino acids displayed opposite trends in their ...

  13. The Combined Effects of Ethylene and MeJA on Metabolic Profiling of Phenolic Compounds in Catharanthus roseus Revealed by Metabolomics Analysis.

    Science.gov (United States)

    Liu, Jia; Liu, Yang; Wang, Yu; Zhang, Zhong-Hua; Zu, Yuan-Gang; Efferth, Thomas; Tang, Zhong-Hua

    2016-01-01

    Phenolic compounds belong to a class of secondary metabolites and are implicated in a wide range of responsive mechanisms in plants triggered by both biotic and abiotic elicitors. In this study, we approached the combinational effects of ethylene and MeJA (methyl jasmonate) on phenolic compounds profiles and gene expressions in the medicinal plant Catharanthus roseus. In virtue of a widely non-targeted metabolomics method, we identified a total of 34 kinds of phenolic compounds in the leaves, composed by 7 C6C1-, 11 C6C3-, and 16 C6C3C6 compounds. In addition, 7 kinds of intermediates critical for the biosynthesis of phenolic compounds and alkaloids were identified and discussed with phenolic metabolism. The combinational actions of ethylene and MeJA effectively promoted the total phenolic compounds, especially the C6C1 compounds (such as salicylic acid, benzoic acid) and C6C3 ones (such as cinnamic acid, sinapic acid). In contrast, the C6C3C6 compounds displayed a notably inhibitory trend in this case. Subsequently, the gene-to-metabolite networks were drawn up by searching for correlations between the expression profiles of 5 gene tags and the accumulation profiles of 41 metabolite peaks. Generally, we provide an insight into the controlling mode of ethylene-MeJA combination on phenolic metabolism in C. roseus leaves.

  14. Serum cytokine profiling and enrichment analysis reveal the involvement of immunological and inflammatory pathways in stable patients with chronic obstructive pulmonary disease

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    Bade G

    2014-08-01

    Full Text Available Geetanjali Bade,1 Meraj Alam Khan,2 Akhilesh Kumar Srivastava,1 Parul Khare,1 Krishna Kumar Solaiappan,1 Randeep Guleria,3 Nades Palaniyar,2 Anjana Talwar1 1Department of Physiology, All India Institute of Medical Sciences, New Delhi, India; 2Program in Physiology and Experimental Medicine, The Hospital for Sick Children, Department of Laboratory Medicine and Pathobiology, and Institute of Medical Sciences, Faculty of Medicine, University of Toronto, Toronto, ON, Canada; 3Department of Pulmonary Medicine and Sleep Disorders, All India Institute of Medical Sciences, New Delhi, India Abstract: Chronic obstructive pulmonary disease (COPD is a major global health problem. It results from chronic inflammation and causes irreversible airway damage. Levels of different serum cytokines could be surrogate biomarkers for inflammation and lung function in COPD. We aimed to determine the serum levels of different biomarkers in COPD patients, the association between cytokine levels and various prognostic parameters, and the key pathways/networks involved in stable COPD. In this study, serum levels of 48 cytokines were examined by multiplex assays in 30 subjects (control, n=9; COPD, n=21. Relationships between serum biomarkers and forced expiratory volume in 1 second, peak oxygen uptake, body mass index, dyspnea score, and smoking were assessed. Enrichment pathways and networks analyses were implemented, using a list of cytokines showing differential expression between healthy controls and patients with COPD by Cytoscape and GeneGo Metacore™ softwares (Thomson-Reuters Corporation, New York, NY, USA. Concentrations of cutaneous T-cell attracting chemokine, eotaxin, hepatocyte growth factor, interleukin 6 (IL-6, IL-16, and stem cell factor are significantly higher in COPD patients compared with in control patients. Notably, this study identifies stem cell factor as a biomarker for COPD. Multiple regression analysis predicts that cutaneous T

  15. Integrative RNA- and miRNA-Profile Analysis Reveals a Likely Role of BR and Auxin Signaling in Branch Angle Regulation of B. napus

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    Hongtao Cheng

    2017-05-01

    Full Text Available Oilseed rape (Brassica napus L. is the second largest oilseed crop worldwide and one of the most important oil crops in China. As a component of plant architecture, branch angle plays an important role in yield performance, especially under high-density planting conditions. However, the mechanisms underlying the regulation of branch angle are still largely not understood. Two oilseed rape lines with significantly different branch angles were used to conduct RNA- and miRNA-profiling at two developmental stages, identifying differential expression of a large number of genes involved in auxin- and brassinosteroid (BR-related pathways. Many auxin response genes, including AUX1, IAA, GH3, and ARF, were enriched in the compact line. However, a number of genes involved in BR signaling transduction and biosynthesis were down-regulated. Differentially expressed miRNAs included those involved in auxin signaling transduction. Expression patterns of most target genes were fine-tuned by related miRNAs, such as miR156, miR172, and miR319. Some miRNAs were found to be differentially expressed at both developmental stages, including three miR827 members. Our results provide insight that auxin- and BR-signaling may play a pivotal role in branch angle regulation.

  16. Marker-Assisted Molecular Profiling, Deletion Mutant Analysis, and RNA-Seq Reveal a Disease Resistance Cluster Associated with Uromyces appendiculatus Infection in Common Bean Phaseolus vulgaris L.

    Science.gov (United States)

    Todd, Antonette R; Donofrio, Nicole; Sripathi, Venkateswara R; McClean, Phillip E; Lee, Rian K; Pastor-Corrales, Marcial; Kalavacharla, Venu Kal

    2017-05-23

    Common bean (Phaseolus vulgaris L.) is an important legume, useful for its high protein and dietary fiber. The fungal pathogen Uromyces appendiculatus (Pers.) Unger can cause major loss in susceptible varieties of the common bean. The Ur-3 locus provides race specific resistance to virulent strains or races of the bean rust pathogen along with Crg, (Complements resistance gene), which is required for Ur-3-mediated rust resistance. In this study, we inoculated two common bean genotypes (resistant "Sierra" and susceptible crg) with rust race 53 of U. appendiculatus, isolated leaf RNA at specific time points, and sequenced their transcriptomes. First, molecular markers were used to locate and identify a 250 kb deletion on chromosome 10 in mutant crg (which carries a deletion at the Crg locus). Next, we identified differential expression of several disease resistance genes between Mock Inoculated (MI) and Inoculated (I) samples of "Sierra" leaf RNA within the 250 kb delineated region. Both marker assisted molecular profiling and RNA-seq were used to identify possible transcriptomic locations of interest regarding the resistance in the common bean to race 53. Identification of differential expression among samples in disease resistance clusters in the bean genome may elucidate significant genes underlying rust resistance. Along with preserving favorable traits in the crop, the current research may also aid in global sustainability of food stocks necessary for many populations.

  17. Comparative proteomics, network analysis and post-translational modification identification reveal differential profiles of plasma Con A-bound glycoprotein biomarkers in gastric cancer.

    Science.gov (United States)

    Uen, Yih-Huei; Lin, Kai-Yuan; Sun, Ding-Ping; Liao, Chen-Chung; Hsieh, Ming-Song; Huang, Yung-Kai; Chen, Yen-Wei; Huang, Pei-Hsuan; Chen, Wei-Jung; Tai, Chih-Chun; Lee, Kuan-Wei; Chen, You-Chia; Lin, Ching-Yu

    2013-05-27

    In the study, we used Con A affinity chromatography, 1-D gel electrophoresis, and nano-LC-MS/MS to screen biomarker candidates in plasma samples obtained from 30 patients with gastric cancer and 30 healthy volunteers. First, we pooled plasma samples matched by age and sex. We identified 17 differentially expressed Con A-bound glycoproteins, including 10 upregulated proteins and 7 downregulated proteins; these differences were significant (Student's t-test, p-valueresponse signaling, the complement system, LXR/RXR activation, hematopoiesis from pluripotent stem cells, and primary immunodeficiency signaling. Our results suggest that Con A-bound LRG1 and ITIH3 may not be practically applicable as a robust biomarker for the early detection of gastric cancer. Additionally, three novel PTMs in ITIH3 were identified and include hexose-N-acetyl-hexosamine at asparagine-(41), trimethylation at aspartic acid-(290), and flavin adenine dinucleotide at histidine-(335). Our study was to describe a combinatorial approach of Con A affinity chromatography, 1-D SDS-PAGE, and nano-LC/MS/MS that provides a label-free, comparative glycoproteomic quantification strategy for the investigation of glycoprotein profiles in plasma from gastric cancer patients versus healthy volunteers and to identify glycoprotein biomarkers for the early clinical detection of gastric cancer. Three novel PTMs, HexHexNAc, trimethylation and FAD, in Con A-bound ITIH3 were identified and built in molecular modeling. The aspartic acid-(290) trimethylation site was located in a metal ion-dependent adhesion site (MIDAS motif; (290)-DXSXS…T…D-(313)) that may influence important function for binding protein ligands. Copyright © 2013 Elsevier B.V. All rights reserved.

  18. Whole transcriptome analysis of Acinetobacter baumannii assessed by RNA-sequencing reveals different mRNA expression profiles in biofilm compared to planktonic cells.

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    Soraya Rumbo-Feal

    Full Text Available Acinetobacterbaumannii has emerged as a dangerous opportunistic pathogen, with many strains able to form biofilms and thus cause persistent infections. The aim of the present study was to use high-throughput sequencing techniques to establish complete transcriptome profiles of planktonic (free-living and sessile (biofilm forms of A. baumannii ATCC 17978 and thereby identify differences in their gene expression patterns. Collections of mRNA from planktonic (both exponential and stationary phase cultures and sessile (biofilm cells were sequenced. Six mRNA libraries were prepared following the mRNA-Seq protocols from Illumina. Reads were obtained in a HiScanSQ platform and mapped against the complete genome to describe the complete mRNA transcriptomes of planktonic and sessile cells. The results showed that the gene expression pattern of A. baumannii biofilm cells was distinct from that of planktonic cells, including 1621 genes over-expressed in biofilms relative to stationary phase cells and 55 genes expressed only in biofilms. These differences suggested important changes in amino acid and fatty acid metabolism, motility, active transport, DNA-methylation, iron acquisition, transcriptional regulation, and quorum sensing, among other processes. Disruption or deletion of five of these genes caused a significant decrease in biofilm formation ability in the corresponding mutant strains. Among the genes over-expressed in biofilm cells were those in an operon involved in quorum sensing. One of them, encoding an acyl carrier protein, was shown to be involved in biofilm formation as demonstrated by the significant decrease in biofilm formation by the corresponding knockout strain. The present work serves as a basis for future studies examining the complex network systems that regulate bacterial biofilm formation and maintenance.

  19. Impact of protein supplementation and exercise in preventing changes in gene expression profiling in woman muscles after long-term bedrest as revealed by microarray analysis.

    Science.gov (United States)

    Chopard, Angele; Lecunff, Martine; Danger, Richard; Teusan, Raluca; Jasmin, Bernard J.; Marini, Jean-Francois; Leger, Jean

    Long duration space flights have a dramatic impact on human physiology and under such a condition, skeletal muscles are known to be one of the most affected systems. A thorough understanding of the basic mechanisms leading to muscle impairment under microgravity, which causes significant loss of muscle mass as well as structural disorders, is necessary for the development of efficient space flight countermeasures. This study was conducted under the aegis of the European Space Agency (ESA), the National Aeronautics and Space Administration of the USA (NASA), the Canadian Space Agency (CSA), and the French "Centre National d'Etudes Spatiales" (CNES). It gave us the opportunity to investigate for the first time the effects of prolonged disuse (long-term bedrest, LTBR) on the transcriptome of different muscle types in healthy women (control, n=8), as well as the potential beneficial impact of protein supplementation (nutrition, n=8) and a combined resistance and aerobic exercise training program (exercise, n=8). Pre- (LTBR -8) and post- (LTBR +59) biopsies were obtained from vastus lateralis (VL) and soleus (SOL) muscles from each subject. Skeletal muscle gene expression profiles were obtained using a custom made microarray containing 6681 muscle-relevant genes. 555 differentiallyexpressed and statistically-significant genes were identified in control group following 60 days of LTBR, including 348 specific for SOL, 83 specific for VL, and 124 common for the two types of muscle (p<0.05). After LTBR, both muscle types exhibited a consistent decrease in pathways involved in fatty acid oxidation, ATP synthesis, and oxidative phosphorylation (p<0.05). However, the postural SOL muscle exhibited a higher level of changes with mRNA encoding proteins involved in protein synthesis and activation of protein degradation (mainly ubiquitinproteasome components) (p<0.05). Major changes in muscle function, such as those involved in calcium signaling and muscle structure including

  20. What can digital transcript profiling reveal about human cancers?

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    J.M. Cerutti

    2003-08-01

    Full Text Available Important biological and clinical features of malignancy are reflected in its transcript pattern. Recent advances in gene expression technology and informatics have provided a powerful new means to obtain and interpret these expression patterns. A comprehensive approach to expression profiling is serial analysis of gene expression (SAGE, which provides digital information on transcript levels. SAGE works by counting transcripts and storing these digital values electronically, providing absolute gene expression levels that make historical comparisons possible. SAGE produces a comprehensive profile of gene expression and can be used to search for candidate tumor markers or antigens in a limited number of samples. The Cancer Genome Anatomy Project has created a SAGE database of human gene expression levels for many different tumors and normal reference tissues and provides online tools for viewing, comparing, and downloading expression profiles. Digital expression profiling using SAGE and informatics have been useful for identifying genes that have a role in tumor invasion and other aspects of tumor progression.

  1. Next-Generation Sequencing Analysis Reveals Differential Expression Profiles of MiRNA-mRNA Target Pairs in KSHV-Infected Cells.

    Directory of Open Access Journals (Sweden)

    Coralie Viollet

    Full Text Available Kaposi's sarcoma associated herpesvirus (KSHV causes several tumors, including primary effusion lymphoma (PEL and Kaposi's sarcoma (KS. Cellular and viral microRNAs (miRNAs have been shown to play important roles in regulating gene expression. A better knowledge of the miRNA-mediated pathways affected by KSHV infection is therefore important for understanding viral infection and tumor pathogenesis. In this study, we used deep sequencing to analyze miRNA and cellular mRNA expression in a cell line with latent KSHV infection (SLKK as compared to the uninfected SLK line. This approach revealed 153 differentially expressed human miRNAs, eight of which were independently confirmed by qRT-PCR. KSHV infection led to the dysregulation of ~15% of the human miRNA pool and most of these cellular miRNAs were down-regulated, including nearly all members of the 14q32 miRNA cluster, a genomic locus linked to cancer and that is deleted in a number of PEL cell lines. Furthermore, we identified 48 miRNAs that were associated with a total of 1,117 predicted or experimentally validated target mRNAs; of these mRNAs, a majority (73% were inversely correlated to expression changes of their respective miRNAs, suggesting miRNA-mediated silencing mechanisms were involved in a number of these alterations. Several dysregulated miRNA-mRNA pairs may facilitate KSHV infection or tumor formation, such as up-regulated miR-708-5p, associated with a decrease in pro-apoptotic caspase-2 and leukemia inhibitory factor LIF, or down-regulated miR-409-5p, associated with an increase in the p53-inhibitor MDM2. Transfection of miRNA mimics provided further evidence that changes in miRNAs are driving some observed mRNA changes. Using filtered datasets, we also identified several canonical pathways that were significantly enriched in differentially expressed miRNA-mRNA pairs, such as the epithelial-to-mesenchymal transition and the interleukin-8 signaling pathways. Overall, our data

  2. Genome-wide analysis of AP2/ERF transcription factors in carrot (Daucus carota L.) reveals evolution and expression profiles under abiotic stress.

    Science.gov (United States)

    Li, Meng-Yao; Xu, Zhi-Sheng; Huang, Ying; Tian, Chang; Wang, Feng; Xiong, Ai-Sheng

    2015-12-01

    AP2/ERF is a large transcription factor family that regulates plant physiological processes, such as plant development and stress response. Carrot (Daucus carota L.) is an important economical crop with a genome size of 480 Mb; the draft genome sequencing of this crop has been completed by our group. However, little is known about the AP2/ERF factors in carrot. In this study, a total of 267 putative AP2/ERF factors were identified from the whole-genome sequence of carrot. These AP2/ERF proteins were phylogenetically clustered into five subfamilies based on their similarity to the amino acid sequences from Arabidopsis. The distribution and comparative genome analysis of the AP2/ERF factors among plants showed the AP2/ERF factors had expansion during the evolutionary process, and the AP2 domain was highly conserved during evolution. The number of AP2/ERF factors in land plants expanded during their evolution. A total of 60 orthologous and 145 coorthologous AP2/ERF gene pairs between carrot and Arabidopsis were identified, and the interaction network of orthologous genes was constructed. The expression patterns of eight AP2/ERF family genes from each subfamily (DREB, ERF, AP2, and RAV) were related to abiotic stresses. Yeast one-hybrid and β-galactosidase activity assays confirmed the DRE and GCC box-binding activities of DREB subfamily genes. This study is the first to identify and characterize the AP2/ERF transcription factors in carrot using whole-genome analysis, and the findings may serve as references for future functional research on the transcription factors in carrot.

  3. Molecular analysis of ex-vivo CD133+ GBM cells revealed a common invasive and angiogenic profile but different proliferative signatures among high grade gliomas

    Directory of Open Access Journals (Sweden)

    Garcia Juan L

    2010-08-01

    Full Text Available Abstract Background Gliomas are the most common type of primary brain tumours, and in this group glioblastomas (GBMs are the higher-grade gliomas with fast progression and unfortunate prognosis. Two major aspects of glioma biology that contributes to its awful prognosis are the formation of new blood vessels through the process of angiogenesis and the invasion of glioma cells. Despite of advances, two-year survival for GBM patients with optimal therapy is less than 30%. Even in those patients with low-grade gliomas, that imply a moderately good prognosis, treatment is almost never curative. Recent studies have demonstrated the existence of a small fraction of glioma cells with characteristics of neural stem cells which are able to grow in vitro forming neurospheres and that can be isolated in vivo using surface markers such as CD133. The aim of this study was to define the molecular signature of GBM cells expressing CD133 in comparison with non expressing CD133 cells. This molecular classification could lead to the finding of new potential therapeutic targets for the rationale treatment of high grade GBM. Methods Eight fresh, primary and non cultured GBMs were used in order to study the gene expression signatures from its CD133 positive and negative populations isolated by FACS-sorting. Dataset was generated with Affymetrix U133 Plus 2 arrays and analysed using the software of the Affymetrix Expression Console. In addition, genomic analysis of these tumours was carried out by CGH arrays, FISH studies and MLPA; Results Gene expression analysis of CD133+ vs. CD133- cell population from each tumour showed that CD133+ cells presented common characteristics in all glioblastoma samples (up-regulation of genes involved in angiogenesis, permeability and down-regulation of genes implicated in cell assembly, neural cell organization and neurological disorders. Furthermore, unsupervised clustering of gene expression led us to distinguish between two groups

  4. Hippocampal Proteomic Analysis Reveals Distinct Pathway Deregulation Profiles at Early and Late Stages in a Rat Model of Alzheimer's-Like Amyloid Pathology.

    Science.gov (United States)

    Do Carmo, Sonia; Crynen, Gogce; Paradis, Tiffany; Reed, Jon; Iulita, M Florencia; Ducatenzeiler, Adriana; Crawford, Fiona; Cuello, A Claudio

    2017-05-13

    The cerebral accumulation and cytotoxicity of amyloid beta (Aβ) is central to Alzheimer's pathogenesis. However, little is known about how the amyloid pathology affects the global expression of brain proteins at different disease stages. In order to identify genotype and time-dependent significant changes in protein expression, we employed quantitative proteomics analysis of hippocampal tissue from the McGill-R-Thy1-APP rat model of Alzheimer-like amyloid pathology. McGill transgenic rats were compared to wild-type rats at early and late pathology stages, i.e., when intraneuronal Aβ amyloid burden is conspicuous and when extracellular amyloid plaques are abundant with more pronounced cognitive deficits. After correction for multiple testing, the expression levels of 64 proteins were found to be considerably different in transgenic versus wild-type rats at the pre-plaque stage (3 months), and 86 proteins in the post-plaque group (12 months), with only 9 differentially regulated proteins common to the 2 time-points. This minimal overlap supports the hypothesis that different molecular pathways are affected in the hippocampus at early and late stages of the amyloid pathology throughout its continuum. At early stages, disturbances in pathways related to cellular responses to stress, protein homeostasis, and neuronal structure are predominant, while disturbances in metabolic energy generation dominate at later stages. These results shed new light on the molecular pathways affected by the early accumulation of Aβ and how the evolving amyloid pathology impacts other complex metabolic pathways.

  5. Individual Profiling Using Text Analysis

    Science.gov (United States)

    2016-04-15

    likelihood that it belongs to the input text , although early experiments showed that this added no benefit. Parts–of– speech In early experiments all...tweets were POS tagged as part of the pre– processing step using a Twitter specific part–of– speech tagger [8]. Various studies have identified POS tags as...AFRL-AFOSR-UK-TR-2016-0011 Individual Profiling using Text Analysis 140333 Mark Stevenson UNIVERSITY OF SHEFFIELD, DEPARTMENT OF PSYCHOLOGY Final

  6. Circular RNA profile in gliomas revealed by identification tool UROBORUS

    Science.gov (United States)

    Song, Xiaofeng; Zhang, Naibo; Han, Ping; Moon, Byoung-San; Lai, Rose K.; Wang, Kai; Lu, Wange

    2016-01-01

    Recent evidence suggests that many endogenous circular RNAs (circRNAs) may play roles in biological processes. However, the expression patterns and functions of circRNAs in human diseases are not well understood. Computationally identifying circRNAs from total RNA-seq data is a primary step in studying their expression pattern and biological roles. In this work, we have developed a computational pipeline named UROBORUS to detect circRNAs in total RNA-seq data. By applying UROBORUS to RNA-seq data from 46 gliomas and normal brain samples, we detected thousands of circRNAs supported by at least two read counts, followed by successful experimental validation on 24 circRNAs from the randomly selected 27 circRNAs. UROBORUS is an efficient tool that can detect circRNAs with low expression levels in total RNA-seq without RNase R treatment. The circRNAs expression profiling revealed more than 476 circular RNAs differentially expressed in control brain tissues and gliomas. Together with parental gene expression, we found that circRNA and its parental gene have diversified expression patterns in gliomas and control brain tissues. This study establishes an efficient and sensitive approach for predicting circRNAs using total RNA-seq data. The UROBORUS pipeline can be accessed freely for non-commercial purposes at http://uroborus.openbioinformatics.org/. PMID:26873924

  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. Carotta: Revealing Hidden Confounder Markers in Metabolic Breath Profiles

    Science.gov (United States)

    Hauschild, Anne-Christin; Frisch, Tobias; Baumbach, Jörg Ingo; Baumbach, Jan

    2015-01-01

    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) and bronchial

  9. 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

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

    Science.gov (United States)

    Closek, Collin J; Sunagawa, Shinichi; DeSalvo, Michael K; Piceno, Yvette M; DeSantis, Todd Z; Brodie, Eoin L; Weber, Michele X; Voolstra, Christian R; Andersen, Gary L; Medina, Mónica

    2014-12-01

    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.

  11. 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.

  12. 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.

  13. 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.

  14. In-depth profiling and analysis of host and viral microRNAs in Japanese flounder (Paralichthys olivaceus) infected with megalocytivirus reveal involvement of microRNAs in host-virus interaction in teleost fish.

    Science.gov (United States)

    Zhang, Bao-cun; Zhang, Jian; Sun, Li

    2014-10-08

    MicroRNAs (miRNAs) regulate gene expression by binding to mRNA transcripts in various biological processes. In mammals and birds, miRNAs are known to play vital parts in both host immune defense and viral infection. However, in lower vertebrates such as teleost, systematic investigations on host and viral miRNAs are lacking. In this study, we applied high-throughput sequencing technology to identify and analyze both host and viral miRNAs in Japanese flounder (Paralichthys olivaceus), an economically important teleost fish farmed widely in the world, infected with megalocytivirus at a timescale of 14 days divided into five different time points. The results showed that a total of 381 host miRNAs and 9 viral miRNAs were identified, the latter being all novel miRNAs that have no homologues in the currently available databases. Of the host miRNAs, 251 have been reported previously in flounder and other species, and 130 were discovered for the first time. The expression levels of 121 host miRNAs were significantly altered at 2 d to 14 d post-viral infection (pi), and these miRNAs were therefore classified as differentially expressed host miRNAs. The expression levels of all 9 viral miRNAs increased from 0 d pi to 10 d pi and then dropped from 10 d pi to 14 d pi. For the 121 differentially expressed host miRNAs and the 9 viral miRNAs, 243 and 48 putative target genes, respectively, were predicted in flounder. GO and KEGG enrichment analysis revealed that the putative target genes of both host and viral miRNAs were grouped mainly into the categories of immune response, signal transduction, and apoptotic process. The results of our study provide the first evidences that indicate existence in teleost fish (i) infection-responsive host and viral miRNAs that exhibit dynamic changes in expression profiles during the course of viral infection, and (ii) potential involvement of miRNAs in host-viral interaction.

  15. What your Facebook Profile Picture Reveals about your Personality

    OpenAIRE

    Segalin, Cristina; Celli, Fabio; Polonio, Luca; Kosinski, Michal; Stillwell, David; Sebe, Nicu; Cristani, Marco; Lepri, Bruno

    2017-01-01

    People spend considerable effort managing the impressions they give others. Social psychologists have shown that people manage these impressions differently depending upon their personality. Facebook and other social media provide a new forum for this fundamental process; hence, understanding people's behaviour on social media could provide interesting insights on their personality. In this paper we investigate automatic personality recognition from Facebook profile pictures. We analyze the e...

  16. Expression profiling reveals metabolic and structural components of extraocular muscles.

    Science.gov (United States)

    Fischer, M Dominik; Gorospe, J Rafael; Felder, Edward; Bogdanovich, Sasha; Pedrosa-Domellöf, F; Ahima, Rexford S; Rubinstein, Neal A; Hoffman, Eric P; Khurana, Tejvir S

    2002-01-01

    The extraocular muscles (EOM) are anatomically and physiologically distinct from other skeletal muscles. EOM are preferentially affected in mitochondrial myopathies, but spared in Duchenne's muscular dystrophy. The anatomical and pathophysiological properties of EOM have been attributed to their unique molecular makeup: an allotype. We used expression profiling to define molecular features of the EOM allotype. We found 346 differentially expressed genes in rat EOM compared with tibialis anterior, based on a twofold difference cutoff. Genes required for efficient, fatigue-resistant, oxidative metabolism were increased in EOM, whereas genes for glycogen metabolism were decreased. EOM also showed increased expression of genes related to structural components of EOM such as vessels, nerves, mitochondria, and neuromuscular junctions. Additionally, genes related to specialized functional roles of EOM such as the embryonic and EOM-specific myosin heavy chains and genes for muscle growth, development, and/or regeneration were increased. The EOM expression profile was validated using biochemical, structural, and molecular methods. Characterization of the EOM expression profile begins to define gene transcription patterns associated with the unique anatomical, metabolic, and pathophysiological properties of EOM.

  17. Comparative Systems Biology Reveals Allelic Variation Modulating Tocochromanol Profiles in Barley (Hordeum vulgare L.)

    Science.gov (United States)

    Oliver, Rebekah E.; Islamovic, Emir; Obert, Donald E.; Wise, Mitchell L.; Herrin, Lauri L.; Hang, An; Harrison, Stephen A.; Ibrahim, Amir; Marshall, Juliet M.; Miclaus, Kelci J.; Lazo, Gerard R.; Hu, Gongshe; Jackson, Eric W.

    2014-01-01

    Tocochromanols are recognized for nutritional content, plant stress response, and seed longevity. Here we present a systems biological approach to characterize and develop predictive assays for genes affecting tocochromanol variation in barley. Major QTL, detected in three regions of a SNP linkage map, affected multiple tocochromanol forms. Candidate genes were identified through barley/rice orthology and sequenced in genotypes with disparate tocochromanol profiles. Gene-specific markers, designed based on observed polymorphism, mapped to the originating QTL, increasing R2 values at the respective loci. Polymorphism within promoter regions corresponded to motifs known to influence gene expression. Quantitative PCR analysis revealed a trend of increased expression in tissues grown at cold temperatures. These results demonstrate utility of a novel method for rapid gene identification and characterization, and provide a resource for efficient development of barley lines with improved tocochromanol profiles. PMID:24820172

  18. Dynamic Functional Network Connectivity Reveals Unique and Overlapping Profiles of Insula Subdivisions

    Science.gov (United States)

    Nomi, Jason S.; Farrant, Kristafor; Damaraju, Eswar; Rachakonda, Srinivas; Calhoun, Vince D.; Uddin, Lucina Q.

    2016-01-01

    The human insular cortex consists of functionally diverse subdivisions that engage during tasks ranging from interoception to cognitive control. The multiplicity of functions subserved by insular subdivisions calls for a nuanced investigation of their functional connectivity profiles. Four insula subdivisions (dorsal anterior, dAI; ventral, VI; posterior, PI; middle, MI) derived using a data-driven approach were subjected to static- and dynamic-functional network connectivity (s-FNC and d-FNC) analyses. Static-FNC analyses replicated previous work demonstrating a cognition-emotion-interoception division of the insula, where the dAI is functionally connected to frontal areas, the VI to limbic areas, and the PI and MI to sensorimotor areas. Dynamic-FNC analyses consisted of k-means clustering of sliding windows to identify variable insula connectivity states. The d-FNC analysis revealed that the most frequently occurring dynamic state mirrored the cognition-emotion-interoception division observed from the s-FNC analysis, with less frequently occurring states showing overlapping and unique subdivision connectivity profiles. In two of the states, all subdivisions exhibited largely overlapping profiles, consisting of subcortical, sensory, motor, and frontal connections. Two other states showed the dAI exhibited a unique connectivity profile compared with other insula subdivisions. Additionally, the dAI exhibited the most variable functional connections across the s-FNC and d-FNC analyses, and was the only subdivision to exhibit dynamic functional connections with regions of the default mode network. These results highlight how a d-FNC approach can capture functional dynamics masked by s-FNC approaches, and reveal dynamic functional connections enabling the functional flexibility of the insula across time. PMID:26880689

  19. Urine Glycoprotein Profile Reveals Novel Markers for Chronic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Anuradha Vivekanandan-Giri

    2011-01-01

    Full Text Available Chronic kidney disease (CKD is a significant public health problem, and progression to end-stage renal disease leads to dramatic increases in morbidity and mortality. The mechanisms underlying progression of disease are poorly defined, and current noninvasive markers incompletely correlate with disease progression. Therefore, there is a great need for discovering novel markers for CKD. We utilized a glycoproteomic profiling approach to test the hypothesis that the urinary glycoproteome profile from subjects with CKD would be distinct from healthy controls. N-linked glycoproteins were isolated and enriched from the urine of healthy controls and subjects with CKD. This strategy identified several differentially expressed proteins in CKD, including a diverse array of proteins with endopeptidase inhibitor activity, protein binding functions, and acute-phase/immune-stress response activity supporting the proposal that inflammation may play a central role in CKD. Additionally, several of these proteins have been previously linked to kidney disease implicating a mechanistic role in disease pathogenesis. Collectively, our observations suggest that the human urinary glycoproteome may serve as a discovery source for novel mechanism-based biomarkers of CKD.

  20. 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.

  1. 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

  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. Linear stability analysis reveals exclusion zone for sliding bed transport

    Directory of Open Access Journals (Sweden)

    Talmon Arnold M.

    2015-06-01

    Full Text Available A bend or any another pipe component disturbs solids transport in pipes. Longitudinal pressure profiles downstream of such a component may show a stationary transient harmonic wave, as revealed by a recent settling slurry laboratory experiment. Therefore the fundamental transient response of the two-layer model for fully stratified flow is investigated as a first approach. A linear stability analysis of the sliding bed configuration is conducted. No stationary transient harmonic waves are found in this analysis, but adaptation lengths for exponential recovery are quantified. An example calculation is given for a 0.1 m diameter pipeline.

  4. Multidimensional Profiling Platforms Reveal Metabolic Dysregulation caused by Organophosphorus Pesticides

    Science.gov (United States)

    Medina-Cleghorn, Daniel; Heslin, Ann; Morris, Patrick J.; Mulvihill, Melinda M.; Nomura, Daniel K.

    2014-01-01

    We are environmentally exposed to countless synthetic chemicals on a daily basis with an increasing number of these chemical exposures linked to adverse health effects. However, our understanding of the (patho)physiological effects of these chemicals remains poorly understood, due in-part to a general lack of effort to systematically and comprehensively identify the direct interactions of environmental chemicals with biological macromolecules in mammalian systems in vivo. Here, we have used functional chemoproteomic and metabolomic platforms to broadly identify direct enzyme targets that are inhibited by widely used organophosphorus (OP) pesticides in vivo in mice and to determine metabolic alterations that are caused by these chemicals. We find that these pesticides directly inhibit over 20 serine hydrolases in vivo leading to widespread disruptions in lipid metabolism. Through identifying direct biological targets of OP pesticides, we show heretofore unrecognized modes of toxicity that may be associated with these agents and underscore the utility of utilizing multidimensional profiling approaches to obtain a more complete understanding of toxicities associated with environmental chemicals. PMID:24205821

  5. Exploring Different Types of Academic Delayers: A Latent Profile Analysis

    Science.gov (United States)

    Grunschel, Carola; Patrzek, Justine; Fries, Stefan

    2013-01-01

    In this study, we explored whether there are different types of academic delayers (i.e., types of students who delay academic tasks). Latent profile analysis based on 554 university students' reasons for academic delay revealed four distinct types: inconspicuous, successful pressure-seeking, worried/anxious, and discontent with studies. The types…

  6. Unbiased Metabolite Profiling of Schizophrenia Fibroblasts under Stressful Perturbations Reveals Dysregulation of Plasmalogens and Phosphatidylcholines.

    Science.gov (United States)

    Huang, Joanne H; Park, Hyoungjun; Iaconelli, Jonathan; Berkovitch, Shaunna S; Watmuff, Bradley; McPhie, Donna; Öngür, Dost; Cohen, Bruce M; Clish, Clary B; Karmacharya, Rakesh

    2017-02-03

    We undertook an unbiased metabolite profiling of fibroblasts from schizophrenia patients and healthy controls to identify metabolites and pathways that are dysregulated in disease, seeking to gain new insights into the disease biology of schizophrenia and to discover potential disease-related biomarkers. We measured polar and nonpolar metabolites in the fibroblasts under normal conditions and under two stressful physiological perturbations: growth in low-glucose media and exposure to the steroid hormone dexamethasone. We found that metabolites that were significantly different between schizophrenia and control subjects showed separation of the two groups by partial least-squares discriminant analysis methods. This separation between schizophrenia and healthy controls was more robust with metabolites identified under the perturbation conditions. The most significant individual metabolite differences were also found in the perturbation experiments. Metabolites that were significantly different between schizophrenia and healthy controls included a number of plasmalogens and phosphatidylcholines. We present these results in the context of previous reports of metabolic profiling of brain tissue and plasma in schizophrenia. These results show the applicability of metabolite profiling under stressful perturbations to reveal cellular pathways that may be involved in disease biology.

  7. 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.

  8. Metabolic profiling of the human response to a glucose challenge reveals distinct axes of insulin sensitivity

    Science.gov (United States)

    Shaham, Oded; Wei, Ru; Wang, Thomas J; Ricciardi, Catherine; Lewis, Gregory D; Vasan, Ramachandran S; Carr, Steven A; Thadhani, Ravi; Gerszten, Robert E; Mootha, Vamsi K

    2008-01-01

    Glucose ingestion after an overnight fast triggers an insulin-dependent, homeostatic program that is altered in diabetes. The full spectrum of biochemical changes associated with this transition is currently unknown. We have developed a mass spectrometry-based strategy to simultaneously measure 191 metabolites following glucose ingestion. In two groups of healthy individuals (n=22 and 25), 18 plasma metabolites changed reproducibly, including bile acids, urea cycle intermediates, and purine degradation products, none of which were previously linked to glucose homeostasis. The metabolite dynamics also revealed insulin's known actions along four key axes—proteolysis, lipolysis, ketogenesis, and glycolysis—reflecting a switch from catabolism to anabolism. In pre-diabetics (n=25), we observed a blunted response in all four axes that correlated with insulin resistance. Multivariate analysis revealed that declines in glycerol and leucine/isoleucine (markers of lipolysis and proteolysis, respectively) jointly provide the strongest predictor of insulin sensitivity. This observation indicates that some humans are selectively resistant to insulin's suppression of proteolysis, whereas others, to insulin's suppression of lipolysis. Our findings lay the groundwork for using metabolic profiling to define an individual's 'insulin response profile', which could have value in predicting diabetes, its complications, and in guiding therapy. PMID:18682704

  9. Neurobiological signatures of alcohol dependence revealed by protein profiling.

    Directory of Open Access Journals (Sweden)

    Giorgio Gorini

    Full Text Available Alcohol abuse causes dramatic neuroadaptations in the brain, which contribute to tolerance, dependence, and behavioral modifications. Previous proteomic studies in human alcoholics and animal models have identified candidate alcoholism-related proteins. However, recent evidences suggest that alcohol dependence is caused by changes in co-regulation that are invisible to single protein-based analysis. Here, we analyze global proteomics data to integrate differential expression, co-expression networks, and gene annotations to unveil key neurobiological rearrangements associated with the transition to alcohol dependence modeled by a Chronic Intermittent Ethanol (CIE, two-bottle choice (2BC paradigm. We analyzed cerebral cortices (CTX and midbrains (MB from male C57BL/6J mice subjected to a CIE, 2BC paradigm, which induces heavy drinking and represents one of the best available animal models for alcohol dependence and relapse drinking. CIE induced significant changes in protein levels in dependent mice compared with their non-dependent controls. Multiple protein isoforms showed region-specific differential regulation as a result of post-translational modifications. Our integrative analysis identified modules of co-expressed proteins that were highly correlated with CIE treatment. We found that modules most related to the effects of CIE treatment coordinate molecular imbalances in endocytic- and energy-related pathways, with specific proteins involved, such as dynamin-1. The qRT-PCR experiments validated both differential and co-expression analyses, and the correspondence among our data and previous genomic and proteomic studies in humans and rodents substantiates our findings. The changes identified above may play a key role in the escalation of ethanol consumption associated with dependence. Our approach to alcohol addiction will advance knowledge of brain remodeling mechanisms and adaptive changes in response to drug abuse, contribute to

  10. How Frequently Are Pan-Assay Interference Compounds Active? Large-Scale Analysis of Screening Data Reveals Diverse Activity Profiles, Low Global Hit Frequency, and Many Consistently Inactive Compounds.

    Science.gov (United States)

    Jasial, Swarit; Hu, Ye; Bajorath, Jürgen

    2017-05-11

    Undetected pan-assay interference compounds (PAINS) with false-positive activities in assays often propagate through medicinal chemistry programs and compromise their outcomes. Although a large number of PAINS have been classified, often on the basis of individual studies or chemical experience, little has been done so far to systematically assess their activity profiles. Herein we report a large-scale analysis of the behavior of PAINS in biological screening assays. More than 23 000 extensively tested compounds containing PAINS substructures were detected, and their hit rates were determined. Many consistently inactive compounds were identified. The hit frequency was low overall, with median values of two to five hits for PAINS tested in hundreds of assays. Only confined subsets of PAINS produced abundant hits. The same PAINS substructure was often found in consistently inactive and frequently active compounds, indicating that the structural context in which PAINS occur modulates their effects.

  11. Metabolomics reveals distinct neurochemical profiles associated with stress resilience

    Directory of Open Access Journals (Sweden)

    Brooke N. Dulka

    2017-12-01

    Full Text Available Acute social defeat represents a naturalistic form of conditioned fear and is an excellent model in which to investigate the biological basis of stress resilience. While there is growing interest in identifying biomarkers of stress resilience, until recently, it has not been feasible to associate levels of large numbers of neurochemicals and metabolites to stress-related phenotypes. The objective of the present study was to use an untargeted metabolomics approach to identify known and unknown neurochemicals in select brain regions that distinguish susceptible and resistant individuals in two rodent models of acute social defeat. In the first experiment, male mice were first phenotyped as resistant or susceptible. Then, mice were subjected to acute social defeat, and tissues were immediately collected from the ventromedial prefrontal cortex (vmPFC, basolateral/central amygdala (BLA/CeA, nucleus accumbens (NAc, and dorsal hippocampus (dHPC. Ultra-high performance liquid chromatography coupled with high resolution mass spectrometry (UPLC-HRMS was used for the detection of water-soluble neurochemicals. In the second experiment, male Syrian hamsters were paired in daily agonistic encounters for 2 weeks, during which they formed stable dominant-subordinate relationships. Then, 24 h after the last dominance encounter, animals were exposed to acute social defeat stress. Immediately after social defeat, tissue was collected from the vmPFC, BLA/CeA, NAc, and dHPC for analysis using UPLC-HRMS. Although no single biomarker characterized stress-related phenotypes in both species, commonalities were found. For instance, in both model systems, animals resistant to social defeat stress also show increased concentration of molecules to protect against oxidative stress in the NAc and vmPFC. Additionally, in both mice and hamsters, unidentified spectral features were preliminarily annotated as potential targets for future experiments. Overall, these findings

  12. 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

    2014-12-19

    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.

  13. Revealing genes associated with vitellogenesis in the liver of the zebrafish (Danio rerio by transcriptome profiling

    Directory of Open Access Journals (Sweden)

    Hyslop Terry

    2009-03-01

    Full Text Available Abstract Background In oviparous vertebrates, including fish, vitellogenesis consists of highly regulated pathways involving 17β-estradiol (E2. Previous studies focused on a relatively small number of hepatic expressed genes during vitellogenesis. This study aims to identify hepatic genes involved in vitellogenesis and regulated by E2, by using zebrafish microarray gene expression profiling, and to provide information on functional distinctive genes expressed in the liver of a vitellogenic female, using zebrafish as a model fish. Results Genes associated with vitellogenesis were revealed by the following paired t-tests (SAM comparisons: a two-month old vitellogenic (Vit2 females were compared with non-vitellogenic (NV females, showing 825 differentially expressed transcripts during early stages of vitellogenesis, b four-month old vitellogenic (Vit4 females were compared with NV females, showing 1,046 differentially expressed transcripts during vitellogenesis and c E2-treated males were compared with control males, showing 1,828 differentially expressed transcripts regulated by E2. A Venn diagram revealed 822 common transcripts in the three groups, indicating that these transcripts were involved in vitellogenesis and putatively regulated by E2. In addition, 431 transcripts were differentially expressed in Vit2 and Vit4 females but not in E2-treated males, indicating that they were putatively not up-regulated by E2. Correspondence analysis showed high similarity in expression profiles of Vit2 with Vit4 and of NV females with control males. The E2-treated males differed from the other groups. The repertoire of genes putatively regulated by E2 in vitellogenic females included genes associated with protein synthesis and reproduction. Genes associated with the immune system processes and biological adhesion, were among the genes that were putatively not regulated by E2. E2-treated males expressed a large array of transcripts that were not associated

  14. Entertainment Marketing. Occupational Competency Analysis Profile.

    Science.gov (United States)

    Ohio State Univ., Columbus. Vocational Instructional Materials Lab.

    This Occupational Competency Analysis Profile (OCAP) for entertainment marketing is an employer-verified competency list that evolved from a modified DACUM (Developing a Curriculum) job analysis process involving business, industry, labor, and community agency representatives throughout Ohio. The competency list consists of six units: (1) human…

  15. General Marketing. Occupational Competency Analysis Profile.

    Science.gov (United States)

    Ohio State Univ., Columbus. Vocational Instructional Materials Lab.

    This General Marketing Occupational Competency Analysis Profile (OCAP) is one of a series of competency lists, verified by expert workers, that have evolved from a modified DACUM (Developing a Curriculum) job analysis process involving business, industry, labor, and community agency representatives from throughout Ohio. This OCAP identifies the…

  16. Mutational Profiles Reveal an Aberrant TGF-β-CEA Regulated Pathway in Colon Adenomas.

    Directory of Open Access Journals (Sweden)

    Jian Chen

    Full Text Available Mutational processes and signatures that drive early tumorigenesis are centrally important for early cancer prevention. Yet, to date, biomarkers and risk factors for polyps (adenomas that inordinately and rapidly develop into colon cancer remain poorly defined. Here, we describe surprisingly high mutational profiles through whole-genome sequence (WGS analysis in 2 of 4 pairs of benign colorectal adenoma tissue samples. Unsupervised hierarchical clustered transcriptomic analysis of a further 7 pairs of adenomas reveals distinct mutational signatures regardless of adenoma size. Transitional single nucleotide substitutions of C:G>T:A predominate in the adenoma mutational spectrum. Strikingly, we observe mutations in the TGF-β pathway and CEA-associated genes in 4 out of 11 adenomas, overlapping with the Wnt pathway. Immunohistochemical labeling reveals a nearly 5-fold increase in CEA levels in 23% of adenoma samples with a concomitant loss of TGF-β signaling. We also define a functional role by which the CEA B3 domain interacts with TGFBR1, potentially inactivating the tumor suppressor function of TGF-β signaling. Our study uncovers diverse mutational processes underlying the transition from early adenoma to cancer. This has broad implications for biomarker-driven targeting of CEA/TGF-β in high-risk adenomas and may lead to early detection of aggressive adenoma to CRC progression.

  17. Molecular Expression Profile Reveals Potential Biomarkers and Therapeutic Targets in Canine Endometrial Lesions.

    Directory of Open Access Journals (Sweden)

    Fabiana Azevedo Voorwald

    Full Text Available Cystic endometrial hyperplasia (CEH, mucometra, and pyometra are common uterine diseases in intact dogs, with pyometra being a life threatening disease. This study aimed to determine the gene expression profile of these lesions and potential biomarkers for closed-cervix pyometra, the most severe condition. Total RNA was extracted from 69 fresh endometrium samples collected from 21 healthy female dogs during diestrus, 16 CEH, 15 mucometra and 17 pyometra (eight open and nine closed-cervixes. Global gene expression was detected using the Affymetrix Canine Gene 1.0 ST Array. Unsupervised analysis revealed two clusters, one mainly composed of diestrus and CEH samples and the other by 12/15 mucometra and all pyometra samples. When comparing pyometra with other groups, 189 differentially expressed genes were detected. SLPI, PTGS2/COX2, MMP1, S100A8, S100A9 and IL8 were among the top up-regulated genes detected in pyometra, further confirmed by external expression data. Notably, a particular molecular profile in pyometra from animals previously treated with exogenous progesterone compounds was observed in comparison with pyometra from untreated dogs as well as with other groups irrespective of exogenous hormone treatment status. In addition to S100A8 and S100A9 genes, overexpression of the inflammatory cytokines IL1B, TNF and IL6 as well as LTF were detected in the pyometra from treated animals. Interestingly, closed pyometra was more frequently detected in treated dogs (64% versus 33%, with IL1B, TNF, LBP and CXCL10 among the most relevant overexpressed genes. This molecular signature associated with potential biomarkers and therapeutic targets, such as CXCL10 and COX2, should guide future clinical studies. Based on the gene expression profile we suggested that pyometra from progesterone treated dogs is a distinct molecular entity.

  18. Molecular Expression Profile Reveals Potential Biomarkers and Therapeutic Targets in Canine Endometrial Lesions

    Science.gov (United States)

    Voorwald, Fabiana Azevedo; Marchi, Fabio Albuquerque; Villacis, Rolando Andre Rios; Alves, Carlos Eduardo Fonseca; Toniollo, Gilson Hélio; Amorim, Renee Laufer

    2015-01-01

    Cystic endometrial hyperplasia (CEH), mucometra, and pyometra are common uterine diseases in intact dogs, with pyometra being a life threatening disease. This study aimed to determine the gene expression profile of these lesions and potential biomarkers for closed-cervix pyometra, the most severe condition. Total RNA was extracted from 69 fresh endometrium samples collected from 21 healthy female dogs during diestrus, 16 CEH, 15 mucometra and 17 pyometra (eight open and nine closed-cervixes). Global gene expression was detected using the Affymetrix Canine Gene 1.0 ST Array. Unsupervised analysis revealed two clusters, one mainly composed of diestrus and CEH samples and the other by 12/15 mucometra and all pyometra samples. When comparing pyometra with other groups, 189 differentially expressed genes were detected. SLPI, PTGS2/COX2, MMP1, S100A8, S100A9 and IL8 were among the top up-regulated genes detected in pyometra, further confirmed by external expression data. Notably, a particular molecular profile in pyometra from animals previously treated with exogenous progesterone compounds was observed in comparison with pyometra from untreated dogs as well as with other groups irrespective of exogenous hormone treatment status. In addition to S100A8 and S100A9 genes, overexpression of the inflammatory cytokines IL1B, TNF and IL6 as well as LTF were detected in the pyometra from treated animals. Interestingly, closed pyometra was more frequently detected in treated dogs (64% versus 33%), with IL1B, TNF, LBP and CXCL10 among the most relevant overexpressed genes. This molecular signature associated with potential biomarkers and therapeutic targets, such as CXCL10 and COX2, should guide future clinical studies. Based on the gene expression profile we suggested that pyometra from progesterone treated dogs is a distinct molecular entity. PMID:26222498

  19. Ribosome profiling of mouse embryonic stem cells reveals the complexity and dynamics of mammalian proteomes.

    Science.gov (United States)

    Ingolia, Nicholas T; Lareau, Liana F; Weissman, Jonathan S

    2011-11-11

    The ability to sequence genomes has far outstripped approaches for deciphering the information they encode. Here we present a suite of techniques, based on ribosome profiling (the deep sequencing of ribosome-protected mRNA fragments), to provide genome-wide maps of protein synthesis as well as a pulse-chase strategy for determining rates of translation elongation. We exploit the propensity of harringtonine to cause ribosomes to accumulate at sites of translation initiation together with a machine learning algorithm to define protein products systematically. Analysis of translation in mouse embryonic stem cells reveals thousands of strong pause sites and unannotated translation products. These include amino-terminal extensions and truncations and upstream open reading frames with regulatory potential, initiated at both AUG and non-AUG codons, whose translation changes after differentiation. We also define a class of short, polycistronic ribosome-associated coding RNAs (sprcRNAs) that encode small proteins. Our studies reveal an unanticipated complexity to mammalian proteomes. Copyright © 2011 Elsevier Inc. All rights reserved.

  20. Expression profiling of CD34+ hematopoietic stem/ progenitor cells reveals distinct subtypes of therapy-related acute myeloid leukemia

    OpenAIRE

    Qian, Zhijian; Fernald, Anthony A.; Godley, Lucy A.; Larson, Richard A.; Le Beau, Michelle M.

    2002-01-01

    One of the most serious consequences of cytotoxic cancer therapy is the development of therapy-related acute myeloid leukemia (t-AML), a neoplastic disorder arising from a multipotential hematopoietic stem cell. To gain insights into the molecular basis of this disease, we performed gene expression profiling of CD34+ hematopoietic progenitor cells from t-AML patients. Our analysis revealed that there are distinct subtypes of t-AML that have a characteristic gene expression pattern. Common to ...

  1. SEMINAL FLUID ANALYSIS AND BIOPHYSICAL PROFILE: FINDINGS

    African Journals Online (AJOL)

    SEMINAL FLUID ANALYSIS AND BIOPHYSICAL PROFILE: FINDINGS. AND RELEVANCE IN INFERTILE MALES IN ILORIN, NIGERIA. lOghagbon, E. K., 2Jimoh, A. A. 6., 1Adebisi, S. A.. Department of 1Chemical Pathology / Immunology and 2Obstetrics] Gynaecology. Faculty of Health Sciences, University of Ilorin, Ilorin, ...

  2. Machine Trades. Ohio's Competency Analysis Profile.

    Science.gov (United States)

    Ohio State Univ., Columbus. Vocational Instructional Materials Lab.

    This Ohio Competency Analysis Profile (OCAP), derived from a modified Developing a Curriculum (DACUM) process, is a current comprehensive and verified employer competency program list for machine trades. Each unit (with or without subunits) contains competencies and competency builders that identify the occupational, academic, and employability…

  3. Precision Machining Technologies. Occupational Competency Analysis Profile.

    Science.gov (United States)

    Ohio State Univ., Columbus. Vocational Instructional Materials Lab.

    This Occupational Competency Analysis Profile (OCAP), which is one of a series of OCAPs developed to identify the skills that Ohio employers deem necessary to entering a given occupation/occupational area, lists the occupational, academic, and employability skills required of individuals entering the occupation of precision machinist. The…

  4. Marketing Management. Occupational Competency Analysis Profile.

    Science.gov (United States)

    Ohio State Univ., Columbus. Vocational Instructional Materials Lab.

    This Occupational Competency Analysis Profile (OCAP) contains a competency list verified by expert workers and developed through a modified DACUM (Developing a Curriculum) involving business, industry, labor, and community agency representatives from Ohio. This OCAP identifies the occupational, academic, and employability skills (competencies)…

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

    Directory of Open Access Journals (Sweden)

    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.

  6. Network-based analysis of proteomic profiles

    KAUST Repository

    Wong, Limsoon

    2016-01-26

    Mass spectrometry (MS)-based proteomics is a widely used and powerful tool for profiling systems-wide protein expression changes. It can be applied for various purposes, e.g. biomarker discovery in diseases and study of drug responses. Although RNA-based high-throughput methods have been useful in providing glimpses into the underlying molecular processes, the evidences they provide are indirect. Furthermore, RNA and corresponding protein levels have been known to have poor correlation. On the other hand, MS-based proteomics tend to have consistency issues (poor reproducibility and inter-sample agreement) and coverage issues (inability to detect the entire proteome) that need to be urgently addressed. In this talk, I will discuss how these issues can be addressed by proteomic profile analysis techniques that use biological networks (especially protein complexes) as the biological context. In particular, I will describe several techniques that we have been developing for network-based analysis of proteomics profile. And I will present evidence that these techniques are useful in identifying proteomics-profile analysis results that are more consistent, more reproducible, and more biologically coherent, and that these techniques allow expansion of the detected proteome to uncover and/or discover novel proteins.

  7. 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.

  8. Urinary Metabolomic Profiling Reveals the Effect of Shenfu Decoction on Chronic Heart Failure in Rats

    Directory of Open Access Journals (Sweden)

    Dawei Yang

    2015-06-01

    Full Text Available Shenfu decoction (SFD can be used to treat patients with sign of Yangqi decline or Yang exhaustion related to chronic heart failure (CHF. We conducted a gas chromatography with time-of-flight mass spectrometer (GC/TOF–MS-based metabolomic study to increase the understanding of CHF and assess the efficacies and mechanisms of SFD in treating CHF induced by coronary artery ligation in rats. Based on unsupervised principal component analysis, there was a clear separation between the CHF and sham surgery group, which revealed that CHF disturbed the metabolism of endogenous substances and significantly altered the urine metabolite fingerprints. After SFD treatment, the metabolomics profile found in CHF was significantly reversed, shifting much closer to normal controls and sham surgery group, indicating that SFD has therapeutic effects in CHF, which is in accordance with the hemodynamic assay results. Metabolomic pathway analysis demonstrated that several pathways including fatty acid biosynthesis, fatty acid elongation, steroid biosynthesis, galactose metabolism, and amino acid metabolism were significantly altered in CHF rats. Therefore, we may infer that SFD shows therapeutic efficacy in CHF by restoring these disturbed metabolic pathways, especially those related to energy metabolism. This study offers new methodologies for increasing the understanding of CHF and systematically characterizing the efficacies and mechanisms of SFD in treating CHF.

  9. Metabolic profiling of triple-negative breast cancer cells reveals metabolic vulnerabilities.

    Science.gov (United States)

    Lanning, Nathan J; Castle, Joshua P; Singh, Simar J; Leon, Andre N; Tovar, Elizabeth A; Sanghera, Amandeep; MacKeigan, Jeffrey P; Filipp, Fabian V; Graveel, Carrie R

    2017-01-01

    Among breast cancers, the triple-negative breast cancer (TNBC) subtype has the worst prognosis with no approved targeted therapies and only standard chemotherapy as the backbone of systemic therapy. Unique metabolic changes in cancer progression provide innovative therapeutic opportunities. The receptor tyrosine kinases (RTKs) epidermal growth factor receptor (EGFR), and MET receptor are highly expressed in TNBC, making both promising therapeutic targets. RTK signaling profoundly alters cellular metabolism by increasing glucose consumption and subsequently diverting glucose carbon sources into metabolic pathways necessary to support the tumorigenesis. Therefore, detailed metabolic profiles of TNBC subtypes and their response to tyrosine kinase inhibitors may identify therapeutic sensitivities. We quantified the metabolic profiles of TNBC cell lines representing multiple TNBC subtypes using gas chromatography mass spectrometry. In addition, we subjected MDA-MB-231, MDA-MB-468, Hs578T, and HCC70 cell lines to metabolic flux analysis of basal and maximal glycolytic and mitochondrial oxidative rates. Metabolic pool size and flux measurements were performed in the presence and absence of the MET inhibitor, INC280/capmatinib, and the EGFR inhibitor, erlotinib. Further, the sensitivities of these cells to modulators of core metabolic pathways were determined. In addition, we annotated a rate-limiting metabolic enzymes library and performed a siRNA screen in combination with MET or EGFR inhibitors to validate synergistic effects. TNBC cell line models displayed significant metabolic heterogeneity with respect to basal and maximal metabolic rates and responses to RTK and metabolic pathway inhibitors. Comprehensive systems biology analysis of metabolic perturbations, combined siRNA and tyrosine kinase inhibitor screens identified a core set of TCA cycle and fatty acid pathways whose perturbation sensitizes TNBC cells to small molecule targeting of receptor tyrosine kinases

  10. High throughput transcriptome profiling of lithium stimulated human mesenchymal stem cells reveals priming towards osteoblastic lineage.

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    Neeraj Kumar Satija

    Full Text Available Human mesenchymal stem cells (hMSCs present in the bone marrow are the precursors of osteoblasts, chondrocytes and adipocytes, and hold tremendous potential for osteoregenerative therapy. However, achieving directed differentiation into osteoblasts has been a major concern. The use of lithium for enhancing osteogenic differentiation has been documented in animal models but its effect in humans is not clear. We, therefore, performed high throughput transcriptome analysis of lithium-treated hMSCs to identify altered gene expression and its relevance to osteogenic differentiation. Our results show suppression of proliferation and enhancement of alkaline phosphatase (ALP activity upon lithium treatment of hMSCs under non-osteogenic conditions. Microarray profiling of lithium-stimulated hMSC revealed decreased expression of adipogenic genes (CEBPA, CMKLR1, HSD11B1 and genes involved in lipid biosynthesis. Interestingly, osteoclastogenic factors and immune responsive genes (IL7, IL8, CXCL1, CXCL12, CCL20 were also downregulated. Negative transcriptional regulators of the osteogenic program (TWIST1 and PBX1 were suppressed while genes involved in mineralization like CLEC3B and ATF4 were induced. Gene ontology analysis revealed enrichment of upregulated genes related to mesenchymal cell differentiation and signal transduction. Lithium priming led to enhanced collagen 1 synthesis and osteogenic induction of lithium pretreated MSCs resulted in enhanced expression of Runx2, ALP and bone sialoprotein. However, siRNA-mediated knockdown of RRAD, CLEC3B and ATF4 attenuated lithium-induced osteogenic priming, identifying a role for RRAD, a member of small GTP binding protein family, in osteoblast differentiation. In conclusion, our data highlight the transcriptome reprogramming potential of lithium resulting in higher propensity of lithium "primed" MSCs for osteoblastic differentiation.

  11. High throughput transcriptome profiling of lithium stimulated human mesenchymal stem cells reveals priming towards osteoblastic lineage.

    Science.gov (United States)

    Satija, Neeraj Kumar; Sharma, Deepa; Afrin, Farhat; Tripathi, Rajendra P; Gangenahalli, Gurudutta

    2013-01-01

    Human mesenchymal stem cells (hMSCs) present in the bone marrow are the precursors of osteoblasts, chondrocytes and adipocytes, and hold tremendous potential for osteoregenerative therapy. However, achieving directed differentiation into osteoblasts has been a major concern. The use of lithium for enhancing osteogenic differentiation has been documented in animal models but its effect in humans is not clear. We, therefore, performed high throughput transcriptome analysis of lithium-treated hMSCs to identify altered gene expression and its relevance to osteogenic differentiation. Our results show suppression of proliferation and enhancement of alkaline phosphatase (ALP) activity upon lithium treatment of hMSCs under non-osteogenic conditions. Microarray profiling of lithium-stimulated hMSC revealed decreased expression of adipogenic genes (CEBPA, CMKLR1, HSD11B1) and genes involved in lipid biosynthesis. Interestingly, osteoclastogenic factors and immune responsive genes (IL7, IL8, CXCL1, CXCL12, CCL20) were also downregulated. Negative transcriptional regulators of the osteogenic program (TWIST1 and PBX1) were suppressed while genes involved in mineralization like CLEC3B and ATF4 were induced. Gene ontology analysis revealed enrichment of upregulated genes related to mesenchymal cell differentiation and signal transduction. Lithium priming led to enhanced collagen 1 synthesis and osteogenic induction of lithium pretreated MSCs resulted in enhanced expression of Runx2, ALP and bone sialoprotein. However, siRNA-mediated knockdown of RRAD, CLEC3B and ATF4 attenuated lithium-induced osteogenic priming, identifying a role for RRAD, a member of small GTP binding protein family, in osteoblast differentiation. In conclusion, our data highlight the transcriptome reprogramming potential of lithium resulting in higher propensity of lithium "primed" MSCs for osteoblastic differentiation.

  12. Distinct evolutionary trajectories of primary high-grade serous ovarian cancers revealed through spatial mutational profiling.

    Science.gov (United States)

    Bashashati, Ali; Ha, Gavin; Tone, Alicia; Ding, Jiarui; Prentice, Leah M; Roth, Andrew; Rosner, Jamie; Shumansky, Karey; Kalloger, Steve; Senz, Janine; Yang, Winnie; McConechy, Melissa; Melnyk, Nataliya; Anglesio, Michael; Luk, Margaret T Y; Tse, Kane; Zeng, Thomas; Moore, Richard; Zhao, Yongjun; Marra, Marco A; Gilks, Blake; Yip, Stephen; Huntsman, David G; McAlpine, Jessica N; Shah, Sohrab P

    2013-09-01

    High-grade serous ovarian cancer (HGSC) is characterized by poor outcome, often attributed to the emergence of treatment-resistant subclones. We sought to measure the degree of genomic diversity within primary, untreated HGSCs to examine the natural state of tumour evolution prior to therapy. We performed exome sequencing, copy number analysis, targeted amplicon deep sequencing and gene expression profiling on 31 spatially and temporally separated HGSC tumour specimens (six patients), including ovarian masses, distant metastases and fallopian tube lesions. We found widespread intratumoural variation in mutation, copy number and gene expression profiles, with key driver alterations in genes present in only a subset of samples (eg PIK3CA, CTNNB1, NF1). On average, only 51.5% of mutations were present in every sample of a given case (range 10.2-91.4%), with TP53 as the only somatic mutation consistently present in all samples. Complex segmental aneuploidies, such as whole-genome doubling, were present in a subset of samples from the same individual, with divergent copy number changes segregating independently of point mutation acquisition. Reconstruction of evolutionary histories showed one patient with mixed HGSC and endometrioid histology, with common aetiologic origin in the fallopian tube and subsequent selection of different driver mutations in the histologically distinct samples. In this patient, we observed mixed cell populations in the early fallopian tube lesion, indicating that diversity arises at early stages of tumourigenesis. Our results revealed that HGSCs exhibit highly individual evolutionary trajectories and diverse genomic tapestries prior to therapy, exposing an essential biological characteristic to inform future design of personalized therapeutic solutions and investigation of drug-resistance mechanisms. © 2013 The Authors. Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

  13. Genome-wide analysis, molecular cloning and expression profiling reveal tissue-specifically expressed, feedback-regulated, stress-responsive and alternatively spliced novel genes involved in gibberellin metabolism in Salvia miltiorrhiza.

    Science.gov (United States)

    Du, Qing; Li, Caili; Li, Dongqiao; Lu, Shanfa

    2015-12-21

    Gibberellin (GA), a classical phytohormone, plays significant roles in plant growth and development. It shares the important intermediate diphosphate precursor, GGPP, with the main lipophilic bioactive components, diterpenoid tanshinones in Salvia miltiorrhiza Bunge, one of the most important Traditional Chinese Medicine materials and an emerging model medicinal plant. Analysis of GA metabolism and regulation may help to demonstrate the biological functions of GAs and the crosstalk between GA metabolism and tanshinone biosynthesis in S. miltiorrhiza. However, genes involved in the conversion of ent-kaurene to GAs have not been systematically studied. Through genome-wide prediction and molecular cloning, twenty two candidate gibberellin metabolism pathway genes were systematically identified for the first time. It includes a SmKO, two SmKAOs, six SmGA20oxs, two SmGA3oxs and eleven SmGA2oxs, of which twenty genes are novel. The deduced proteins showed sequence conservation and divergence. Gibberellin metabolism pathway genes exhibited tissue-specific expression patterns and responded differentially to exogenous GA3 treatment, indicating differential regulation of gibberellin metabolism in different tissue types in S. miltiorrhiza. SmKAO1, SmKAO2, SmGA2ox2, and SmGA2ox4-SmGA2ox7 were significantly up-regulated; SmGA20ox2, SmGA3ox1, SmGA2ox1, SmGA2ox8, SmGA2ox10 and SmGA2ox11 were significantly down-regulated; while the responses of many other genes varied among different tissue-types and time-points of GA3 treatment, suggesting the complexity of feedback regulation. Tanshinone biosynthesis-related genes, such as SmCPS1 and SmKSL1, were up-regulated in response to GA3 treatment. Among the 22 identified genes, nine responded to yeast extract and Ag(+)-treatment in S. miltiorrhiza hairy roots. Moreover, tissue-specifically expressed splice variants were identified for SmKO, SmGA20ox3, SmGA2ox3 and SmGA2ox11, of which SmKOv1, SmGA20ox3v and SmGA2ox11v1 were GA3-responsive

  14. Metabolic Profiles Reveal Changes in Wild and Cultivated Soybean Seedling Leaves under Salt Stress.

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    Jing Zhang

    Full Text Available Clarification of the metabolic mechanisms underlying salt stress responses in plants will allow further optimization of crop breeding and cultivation to obtain high yields in saline-alkali land. Here, we characterized 68 differential metabolites of cultivated soybean (Glycine max and wild soybean (Glycine soja under neutral-salt and alkali-salt stresses using gas chromatography-mass spectrometry (GC-MS-based metabolomics, to reveal the physiological and molecular differences in salt tolerance. According to comparisons of growth parameters under the two kinds of salt stresses, the level of inhibition in wild soybean was lower than in cultivated soybean, especially under alkali-salt stress. Moreover, wild soybean contained significantly higher amounts of phenylalanine, asparagine, citraconic acid, citramalic acid, citric acid and α-ketoglutaric acid under neutral-salt stress, and higher amounts of palmitic acid, lignoceric acid, glucose, citric acid and α-ketoglutaric acid under alkali-salt stress, than cultivated soybean. Further investigations demonstrated that the ability of wild soybean to salt tolerance was mainly based on the synthesis of organic and amino acids, and the more active tricarboxylic acid cycle under neutral-salt stress. In addition, the metabolite profiling analysis suggested that the energy generation from β-oxidation, glycolysis and the citric acid cycle plays important roles under alkali-salt stress. Our results extend the understanding of mechanisms involved in wild soybean salt tolerance and provide an important reference for increasing yields and developing salt-tolerant soybean cultivars.

  15. Nicotine-induced protein expression profiling reveals mutually altered proteins across four human cell lines.

    Science.gov (United States)

    Paulo, Joao A; Gygi, Steven P

    2017-01-01

    Mass spectrometry-based proteomic strategies can profile the expression level of proteins in response to external stimuli. Nicotine affects diverse cellular pathways, however, the nicotine-induced alterations on the global proteome across human cell lines have not been fully elucidated. We measured perturbations in protein levels resulting from nicotine treatment in four cell lines-HEK, HeLa, PaSC, and SH-SY5Y-in a single experiment using tandem mass tags (TMT10-plex) and high-resolution mass spectrometry. We quantified 8590 proteins across all cell lines. Of these, nicotine increased the abundance of 31 proteins 1.5-fold or greater in all cell lines. Likewise, considering proteins with altered levels in at least three of the four cell lines, 64 were up-regulated, while one was down-regulated. Gene ontology analysis revealed that ∼40% of these proteins were membrane bound, and functioned in transmembrane signaling and receptor activity. We highlighted proteins, including APP, APLP2, LAPTM4B, and NCOA4, which were dysregulated by nicotine in all cell lines investigated and may have implications in downstream signaling pathways, particularly autophagy. Using the outlined methodology, studies in additional (including primary) cell lines will provide further evidence that alterations in the levels of these proteins are indeed a general response to nicotine and thereby merit further investigation. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

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    Maria Cecilia Fernandes

    2016-05-01

    Full Text Available 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.

  17. Multiregion gene expression profiling reveals heterogeneity in molecular subtypes and immunotherapy response signatures in lung cancer.

    Science.gov (United States)

    Lee, Won-Chul; Diao, Lixia; Wang, Jing; Zhang, Jianhua; Roarty, Emily B; Varghese, Susan; Chow, Chi-Wan; Fujimoto, Junya; Behrens, Carmen; Cascone, Tina; Peng, Weiyi; Kalhor, Neda; Moran, Cesar A; Weissferdt, Annikka; Johnson, Faye M; William, William N; Swisher, Stephen G; Lee, J Jack; Hong, Waun Ki; Heymach, John V; Wistuba, Ignacio I; Futreal, P Andrew; Zhang, Jianjun

    2018-02-06

    Intra-tumor heterogeneity may be present at all molecular levels. Genomic intra-tumor heterogeneity at the exome level has been reported in many cancer types, but comprehensive gene expression intra-tumor heterogeneity has not been well studied. Here, we delineated the gene expression intra-tumor heterogeneity by exploring gene expression profiles of 35 tumor regions from 10 non-small cell lung cancer tumors (three or four regions/tumor), including adenocarcinoma, squamous cell carcinoma, large-cell carcinoma, and pleomorphic carcinoma of the lung. Using Affymetrix Gene 1.0 ST arrays, we generated the gene expression data for every sample. Inter-tumor heterogeneity was generally higher than intra-tumor heterogeneity, but some tumors showed a substantial level of intra-tumor heterogeneity. The analysis of various clinically relevant gene expression signatures including molecular subtype, epithelial-to-mesenchymal transition, and anti-PD-1 resistance signatures also revealed heterogeneity between different regions of the same tumor. The gene expression intra-tumor heterogeneity we observed was associated with heterogeneous tumor microenvironments represented by stromal and immune cells infiltrated. Our data suggest that RNA-based prognostic or predictive molecular tests should be carefully conducted in consideration of the gene expression intra-tumor heterogeneity.

  18. Transcriptome profiling revealed novel transcriptional regulators in maize responses to Ostrinia furnacalis and jasmonic acid.

    Science.gov (United States)

    Wang, Hai; Li, Shengyan; Teng, Shouzhen; Liang, Haisheng; Xin, Hongjia; Gao, Hongjiang; Huang, Dafang; Lang, Zhihong

    2017-01-01

    Chewing insects cause severe yield losses in crop production worldwide. Crop plants counteract chewing insects by transcriptionally promoting a repertoire of defense gene products that are either toxic to, or attractive to the natural enemies of, pest insects. However, the complexity of the transcriptional reprogramming in plant defense response against chewing insects is still not well understood. In this study, the genome-wide early responses in maize seedlings to Asian corn borer (ACB, Ostrinia furnacalis) and also to jasmonic acid(JA), the pivotal phytohormone controlling plant defense response against herbivory, were transcriptionally profiled by RNA-Seq. Clustering of differentially expressed genes (DEGs) along with functional enrichment analysis revealed important biological processes regulated in response to ACB infestation and/or jasmonic acid. Moreover, DEGs with distinct expression patterns were differentially enriched with diverse families of cis-elements on their promoters. Multiple inventories of differentially expressed transcription factors (DETFs) in each DEG group were also analyzed. A transient expression assay using transfected maize protoplastswas established to examine the potential roles of DETFs in maize defense response and JA signaling, and this was used to show that ZmNAC60, an ACB- and JA-inducible DETF, represented a novel positive regulator of JA and defense pathway genes. This study provided a comprehensive transcriptional picture for the early dynamics of maize defense responses and JA signaling, and the identification of DETFs offered potential targets for further functional genomics investigation of master regulators in maize defense responses against herbivory.

  19. The Fatty Acid Profile Analysis of Cyperus laxus Used for Phytoremediation of Soils from Aged Oil Spill-Impacted Sites Revealed That This Is a C18:3 Plant Species

    Science.gov (United States)

    Montes Horcasitas, María del Carmen; Rodríguez Vázquez, Refugio; Esparza García, Fernando José; Pérez Vargas, Josefina; Ariza Castolo, Armando; Ferrera-Cerrato, Ronald; Gómez Guzmán, Octavio

    2015-01-01

    The effect of recalcitrant hydrocarbons on the fatty acid profile from leaf, basal corm, and roots of Cyperus laxus plants cultivated in greenhouse phytoremediation systems of soils from aged oil spill-impacted sites containing from 16 to 340 g/Kg total hydrocarbons (THC) was assessed to investigate if this is a C18:3 species and if the hydrocarbon removal during the phytoremediation process has a relationship with the fatty acid profile of this plant. The fatty acid profile was specific to each vegetative organ and was strongly affected by the hydrocarbons level in the impacted sites. Leaf extracts of plants from uncontaminated soil produced palmitic acid (C16), octadecanoic acid (C18:0), unsaturated oleic acids (C18:1-C18:3), and unsaturated eichosanoic (C20:2-C20:3) acids with a noticeable absence of the unsaturated hexadecatrienoic acid (C16:3); this finding demonstrates, for the first time, that C. laxus is a C18:3 plant. In plants from the phytoremediation systems, the total fatty acid contents in the leaf and the corm were negatively affected by the hydrocarbons presence; however, the effect was positive in root. Interestingly, under contaminated conditions, unusual fatty acids such as odd numbered carbons (C15, C17, C21, and C23) and uncommon unsaturated chains (C20:3n6 and C20:4) were produced together with a remarkable quantity of C22:2 and C24:0 chains in the corm and the leaf. These results demonstrate that weathered hydrocarbons may drastically affect the lipidic composition of C. laxus at the fatty acid level, suggesting that this species adjusts the cover lipid composition in its vegetative organs, mainly in roots, in response to the weathered hydrocarbon presence and uptake during the phytoremediation process. PMID:26473488

  20. The Fatty Acid Profile Analysis of Cyperus laxus Used for Phytoremediation of Soils from Aged Oil Spill-Impacted Sites Revealed That This Is a C18:3 Plant Species.

    Directory of Open Access Journals (Sweden)

    Noemí Araceli Rivera Casado

    Full Text Available The effect of recalcitrant hydrocarbons on the fatty acid profile from leaf, basal corm, and roots of Cyperus laxus plants cultivated in greenhouse phytoremediation systems of soils from aged oil spill-impacted sites containing from 16 to 340 g/Kg total hydrocarbons (THC was assessed to investigate if this is a C18:3 species and if the hydrocarbon removal during the phytoremediation process has a relationship with the fatty acid profile of this plant. The fatty acid profile was specific to each vegetative organ and was strongly affected by the hydrocarbons level in the impacted sites. Leaf extracts of plants from uncontaminated soil produced palmitic acid (C16, octadecanoic acid (C18:0, unsaturated oleic acids (C18:1-C18:3, and unsaturated eichosanoic (C20:2-C20:3 acids with a noticeable absence of the unsaturated hexadecatrienoic acid (C16:3; this finding demonstrates, for the first time, that C. laxus is a C18:3 plant. In plants from the phytoremediation systems, the total fatty acid contents in the leaf and the corm were negatively affected by the hydrocarbons presence; however, the effect was positive in root. Interestingly, under contaminated conditions, unusual fatty acids such as odd numbered carbons (C15, C17, C21, and C23 and uncommon unsaturated chains (C20:3n6 and C20:4 were produced together with a remarkable quantity of C22:2 and C24:0 chains in the corm and the leaf. These results demonstrate that weathered hydrocarbons may drastically affect the lipidic composition of C. laxus at the fatty acid level, suggesting that this species adjusts the cover lipid composition in its vegetative organs, mainly in roots, in response to the weathered hydrocarbon presence and uptake during the phytoremediation process.

  1. Transcriptional profiling of the bladder in urogenital schistosomiasis reveals pathways of inflammatory fibrosis and urothelial compromise.

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    Debalina Ray

    Full Text Available Urogenital schistosomiasis, chronic infection by Schistosoma haematobium, affects 112 million people worldwide. S. haematobium worm oviposition in the bladder wall leads to granulomatous inflammation, fibrosis, and egg expulsion into the urine. Despite the global impact of urogenital schistosomiasis, basic understanding of the associated pathologic mechanisms has been incomplete due to the lack of suitable animal models. We leveraged our recently developed mouse model of urogenital schistosomiasis to perform the first-ever profiling of the early molecular events that occur in the bladder in response to the introduction of S. haematobium eggs. Microarray analysis of bladders revealed rapid, differential transcription of large numbers of genes, peaking three weeks post-egg administration. Many differentially transcribed genes were related to the canonical Type 2 anti-schistosomal immune response, as reflected by the development of egg-based bladder granulomata. Numerous collagen and metalloproteinase genes were differentially transcribed over time, revealing complex remodeling and fibrosis of the bladder that was confirmed by Masson's Trichrome staining. Multiple genes implicated in carcinogenesis pathways, including vascular endothelial growth factor-, oncogene-, and mammary tumor-related genes, were differentially transcribed in egg-injected bladders. Surprisingly, junctional adhesion molecule, claudin and uroplakin genes, key components for maintaining the urothelial barrier, were globally suppressed after bladder exposure to eggs. This occurred in the setting of urothelial hyperplasia and egg shedding in urine. Thus, S. haematobium egg expulsion is associated with intricate modulation of the urothelial barrier on the cellular and molecular level. Taken together, our findings have important implications for understanding host-parasite interactions and carcinogenesis in urogenital schistosomiasis, and may provide clues for novel therapeutic

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

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    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.

  3. A UML Profile for State Analysis

    Science.gov (United States)

    Murray, Alex; Rasmussen, Robert

    2010-01-01

    State Analysis is a systems engineering methodology for the specification and design of control systems, developed at the Jet Propulsion Laboratory. The methodology emphasizes an analysis of the system under control in terms of States and their properties and behaviors and their effects on each other, a clear separation of the control system from the controlled system, cognizance in the control system of the controlled system's State, goal-based control built on constraining the controlled system's States, and disciplined techniques for State discovery and characterization. State Analysis (SA) introduces two key diagram types: State Effects and Goal Network diagrams. The team at JPL developed a tool for performing State Analysis. The tool includes a drawing capability, backed by a database that supports the diagram types and the organization of the elements of the SA models. But the tool does not support the usual activities of software engineering and design - a disadvantage, since systems to which State Analysis can be applied tend to be very software-intensive. This motivated the work described in this paper: the development of a preliminary Unified Modeling Language (UML) profile for State Analysis. Having this profile would enable systems engineers to specify a system using the methods and graphical language of State Analysis, which is easily linked with a larger system model in SysML (Systems Modeling Language), while also giving software engineers engaged in implementing the specified control system immediate access to and use of the SA model, in the same language, UML, used for other software design. That is, a State Analysis profile would serve as a shared modeling bridge between system and software models for the behavior aspects of the system. This paper begins with an overview of State Analysis and its underpinnings, followed by an overview of the mapping of SA constructs to the UML metamodel. It then delves into the details of these mappings and the

  4. Computer imaging software for profile photograph analysis.

    Science.gov (United States)

    Tollefson, Travis T; Sykes, Jonathan M

    2007-01-01

    To describe a novel calibration technique for photographs of different sizes and to test a new method of chin evaluation in relation to established analysis measurements. A photograph analysis and medical record review of 14 patients who underwent combined rhinoplasty and chin correction at an academic center. Patients undergoing concurrent orthognathic surgery, rhytidectomy, or submental liposuction were excluded. Preoperative and postoperative digital photographs were analyzed using computer imaging software with a new method, the soft tissue porion to pogonion distance, and with established measurements, including the cervicomental angle, the mentocervical angle, and the facial convexity angle. The porion to pogonion distance consistently increased after the chin correction procedure (more in the osseous group). All photograph angle measurements changed toward the established normal range postoperatively. Surgery for facial disharmony requires artistic judgment and objective evaluation. Although 3-dimensional video analysis of the face seems promising, its clinical use is limited by cost. For surgeons who use computer imaging software, analysis of profile photographs is the most valuable tool. Even when preoperative and postoperative photographs are of different sizes, relative distance comparisons are possible with a new calibration technique using the constant facial landmarks, the porion and the pupil. The porion-pogonion distance is a simple reproducible measurement that can be used along with established soft tissue measurements as a guide for profile facial analysis.

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

    Science.gov (United States)

    Sampey, Brante P; Freemerman, Alex J; Zhang, Jimmy; Kuan, Pei-Fen; Galanko, Joseph A; O'Connell, Thomas M; Ilkayeva, Olga R; Muehlbauer, Michael J; Stevens, Robert D; Newgard, Christopher B; Brauer, Heather A; Troester, Melissa A; Makowski, Liza

    2012-01-01

    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 leading to Metabolic

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

    Directory of Open Access Journals (Sweden)

    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

  7. Revealed preference analysis of noncooperative household consumption

    NARCIS (Netherlands)

    Cherchye, L.J.H.; Demuynck, T.; de Rock, B.

    2011-01-01

    We develop a revealed preference approach to analyse non-unitary household consumption behaviour that is not cooperative (or Pareto efficient). We derive global necessary and sufficient conditions for data consistency with the model. We show that the conditions can be verified by means of relatively

  8. Proteomic profiling reveals dopaminergic regulation of progenitor cell functions of goldfish radial glial cells in vitro.

    Science.gov (United States)

    Xing, Lei; Martyniuk, Christopher J; Esau, Crystal; Da Fonte, Dillon F; Trudeau, Vance L

    2016-07-20

    Radial glial cells (RGCs) are stem-like cells found in the developing and adult central nervous system. They function as both a scaffold to guide neuron migration and as progenitor cells that support neurogenesis. Our previous study revealed a close anatomical relationship between dopamine neurons and RGCs in the telencephalon of female goldfish. In this study, label-free proteomics was used to identify the proteins in a primary RGC culture and to determine the proteome response to the selective dopamine D1 receptor agonist SKF 38393 (10μM), in order to better understand dopaminergic regulation of RGCs. A total of 689 unique proteins were identified in the RGCs and these were classified into biological and pathological pathways. Proteins such as nucleolin (6.9-fold) and ependymin related protein 1 (4.9-fold) were increased in abundance while proteins triosephosphate isomerase (10-fold) and phosphoglycerate dehydrogenase (5-fold) were decreased in abundance. Pathway analysis revealed that proteins that consistently changed in abundance across biological replicates were related to small molecules such as ATP, lipids and steroids, hormones, glucose, cyclic AMP and Ca(2+). Sub-network enrichment analysis suggested that estrogen receptor signaling, among other transcription factors, is regulated by D1 receptor activation. This suggests that these signaling pathways are correlated to dopaminergic regulation of radial glial cell functions. Most proteins down-regulated by SKF 38393 were involved in cell cycle/proliferation, growth, death, and survival, which suggests that dopamine inhibits the progenitor-related processes of radial glial cells. Examples of differently expressed proteins including triosephosphate isomerase, nucleolin, phosphoglycerate dehydrogenase and capping protein (actin filament) muscle Z-line beta were validated by qPCR and western blot, which were consistent with MS/MS data in the direction of change. This is the first study to characterize the RGC

  9. Complex trait subtypes identification using transcriptome profiling reveals an interaction between two QTL affecting adiposity in chicken

    Directory of Open Access Journals (Sweden)

    Blum Yuna

    2011-11-01

    Full Text Available Abstract Background Integrative genomics approaches that combine genotyping and transcriptome profiling in segregating populations have been developed to dissect complex traits. The most common approach is to identify genes whose eQTL colocalize with QTL of interest, providing new functional hypothesis about the causative mutation. Another approach includes defining subtypes for a complex trait using transcriptome profiles and then performing QTL mapping using some of these subtypes. This approach can refine some QTL and reveal new ones. In this paper we introduce Factor Analysis for Multiple Testing (FAMT to define subtypes more accurately and reveal interaction between QTL affecting the same trait. The data used concern hepatic transcriptome profiles for 45 half sib male chicken of a sire known to be heterozygous for a QTL affecting abdominal fatness (AF on chromosome 5 distal region around 168 cM. Results Using this methodology which accounts for hidden dependence structure among phenotypes, we identified 688 genes that are significantly correlated to the AF trait and we distinguished 5 subtypes for AF trait, which are not observed with gene lists obtained by classical approaches. After exclusion of one of the two lean bird subtypes, linkage analysis revealed a previously undetected QTL on chromosome 5 around 100 cM. Interestingly, the animals of this subtype presented the same q paternal haplotype at the 168 cM QTL. This result strongly suggests that the two QTL are in interaction. In other words, the "q configuration" at the 168 cM QTL could hide the QTL existence in the proximal region at 100 cM. We further show that the proximal QTL interacts with the previous one detected on the chromosome 5 distal region. Conclusion Our results demonstrate that stratifying genetic population by molecular phenotypes followed by QTL analysis on various subtypes can lead to identification of novel and interacting QTL.

  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. 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.

  12. 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.

  13. Metabolomic profiling reveals potential markers and bioprocesses altered in bladder cancer progression.

    Science.gov (United States)

    Putluri, Nagireddy; Shojaie, Ali; Vasu, Vihas T; Vareed, Shaiju K; Nalluri, Srilatha; Putluri, Vasanta; Thangjam, Gagan Singh; Panzitt, Katrin; Tallman, Christopher T; Butler, Charles; Sana, Theodore R; Fischer, Steven M; Sica, Gabriel; Brat, Daniel J; Shi, Huidong; Palapattu, Ganesh S; Lotan, Yair; Weizer, Alon Z; Terris, Martha K; Shariat, Shahrokh F; Michailidis, George; Sreekumar, Arun

    2011-12-15

    Although alterations in xenobiotic metabolism are considered causal in the development of bladder cancer, the precise mechanisms involved are poorly understood. In this study, we used high-throughput mass spectrometry to measure over 2,000 compounds in 58 clinical specimens, identifying 35 metabolites which exhibited significant changes in bladder cancer. This metabolic signature distinguished both normal and benign bladder from bladder cancer. Exploratory analyses of this metabolomic signature in urine showed promise in distinguishing bladder cancer from controls and also nonmuscle from muscle-invasive bladder cancer. Subsequent enrichment-based bioprocess mapping revealed alterations in phase I/II metabolism and suggested a possible role for DNA methylation in perturbing xenobiotic metabolism in bladder cancer. In particular, we validated tumor-associated hypermethylation in the cytochrome P450 1A1 (CYP1A1) and cytochrome P450 1B1 (CYP1B1) promoters of bladder cancer tissues by bisulfite sequence analysis and methylation-specific PCR and also by in vitro treatment of T-24 bladder cancer cell line with the DNA demethylating agent 5-aza-2'-deoxycytidine. Furthermore, we showed that expression of CYP1A1 and CYP1B1 was reduced significantly in an independent cohort of bladder cancer specimens compared with matched benign adjacent tissues. In summary, our findings identified candidate diagnostic and prognostic markers and highlighted mechanisms associated with the silencing of xenobiotic metabolism. The metabolomic signature we describe offers potential as a urinary biomarker for early detection and staging of bladder cancer, highlighting the utility of evaluating metabolomic profiles of cancer to gain insights into bioprocesses perturbed during tumor development and progression.

  14. 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.

  15. Representing high throughput expression profiles via perturbation barcodes reveals compound targets.

    Directory of Open Access Journals (Sweden)

    Tracey M Filzen

    2017-02-01

    Full Text Available High throughput mRNA expression profiling can be used to characterize the response of cell culture models to perturbations such as pharmacologic modulators and genetic perturbations. As profiling campaigns expand in scope, it is important to homogenize, summarize, and analyze the resulting data in a manner that captures significant biological signals in spite of various noise sources such as batch effects and stochastic variation. We used the L1000 platform for large-scale profiling of 978 representative genes across thousands of compound treatments. Here, a method is described that uses deep learning techniques to convert the expression changes of the landmark genes into a perturbation barcode that reveals important features of the underlying data, performing better than the raw data in revealing important biological insights. The barcode captures compound structure and target information, and predicts a compound's high throughput screening promiscuity, to a higher degree than the original data measurements, indicating that the approach uncovers underlying factors of the expression data that are otherwise entangled or masked by noise. Furthermore, we demonstrate that visualizations derived from the perturbation barcode can be used to more sensitively assign functions to unknown compounds through a guilt-by-association approach, which we use to predict and experimentally validate the activity of compounds on the MAPK pathway. The demonstrated application of deep metric learning to large-scale chemical genetics projects highlights the utility of this and related approaches to the extraction of insights and testable hypotheses from big, sometimes noisy data.

  16. Monosomic analysis reveals duplicated chromosomal segments in ...

    Indian Academy of Sciences (India)

    Monosomics for chromosome 2 expressed liguleless leaf phenotype due to hemizygous condition of recessive gene lg. Two monosomic-4 plants were identified after test crossing with monosomic tester (see table 2 in electronic supplemen- tary material). Monosomic-6 plants were identified by the cytological analysis (figure ...

  17. Quantitative interactome analysis reveals a chemoresistant edgotype.

    Science.gov (United States)

    Chavez, Juan D; Schweppe, Devin K; Eng, Jimmy K; Zheng, Chunxiang; Taipale, Alex; Zhang, Yiyi; Takara, Kohji; Bruce, James E

    2015-08-03

    Chemoresistance is a common mode of therapy failure for many cancers. Tumours develop resistance to chemotherapeutics through a variety of mechanisms, with proteins serving pivotal roles. Changes in protein conformations and interactions affect the cellular response to environmental conditions contributing to the development of new phenotypes. The ability to understand how protein interaction networks adapt to yield new function or alter phenotype is limited by the inability to determine structural and protein interaction changes on a proteomic scale. Here, chemical crosslinking and mass spectrometry were employed to quantify changes in protein structures and interactions in multidrug-resistant human carcinoma cells. Quantitative analysis of the largest crosslinking-derived, protein interaction network comprising 1,391 crosslinked peptides allows for 'edgotype' analysis in a cell model of chemoresistance. We detect consistent changes to protein interactions and structures, including those involving cytokeratins, topoisomerase-2-alpha, and post-translationally modified histones, which correlate with a chemoresistant phenotype.

  18. 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

  19. Metabolic profiling of ob/ob mouse fatty liver using HR-MAS (1)H-NMR combined with gene expression analysis reveals alterations in betaine metabolism and the transsulfuration pathway.

    Science.gov (United States)

    Gogiashvili, Mikheil; Edlund, Karolina; Gianmoena, Kathrin; Marchan, Rosemarie; Brik, Alexander; Andersson, Jan T; Lambert, Jörg; Madjar, Katrin; Hellwig, Birte; Rahnenführer, Jörg; Hengstler, Jan G; Hergenröder, Roland; Cadenas, Cristina

    2017-02-01

    Metabolic perturbations resulting from excessive hepatic fat accumulation are poorly understood. Thus, in this study, leptin-deficient ob/ob mice, a mouse model of fatty liver disease, were used to investigate metabolic alterations in more detail. Metabolites were quantified in intact liver tissues of ob/ob (n = 8) and control (n = 8) mice using high-resolution magic angle spinning (HR-MAS) (1)H-NMR. In addition, after demonstrating that HR-MAS (1)H-NMR does not affect RNA integrity, transcriptional changes were measured by quantitative real-time PCR on RNA extracted from the same specimens after HR-MAS (1)H-NMR measurements. Importantly, the gene expression changes obtained agreed with those observed by Affymetrix microarray analysis performed on RNA isolated directly from fresh-frozen tissue. In total, 40 metabolites could be assigned in the spectra and subsequently quantified. Quantification of lactate was also possible after applying a lactate-editing pulse sequence that suppresses the lipid signal, which superimposes the lactate methyl resonance at 1.3 ppm. Significant differences were detected for creatinine, glutamate, glycine, glycolate, trimethylamine-N-oxide, dimethylglycine, ADP, AMP, betaine, phenylalanine, and uridine. Furthermore, alterations in one-carbon metabolism, supported by both metabolic and transcriptional changes, were observed. These included reduced demethylation of betaine to dimethylglycine and the reduced expression of genes coding for transsulfuration pathway enzymes, which appears to preserve methionine levels, but may limit glutathione synthesis. Overall, the combined approach is advantageous as it identifies changes not only at the single gene or metabolite level but also deregulated pathways, thus providing critical insight into changes accompanying fatty liver disease. Graphical abstract A Evaluation of RNA integrity before and after HR-MAS (1)H-NMR of intact mouse liver tissue. B Metabolite concentrations and gene

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

    Directory of Open Access Journals (Sweden)

    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.

  1. HPLC-MS/MS targeted metabolic profiling reveals distinct metabolic profiles from Staphylococcus aureus small-colony variants.

    Science.gov (United States)

    Wang, Chen; Zhu, Jiangjiang

    2017-08-15

    Staphylococcus aureus is a world-wide health threat due to its prevalence and possible resistance to antibiotic treatment. A variety reasons can contribute to S. aureus antibiotic resistance and one group of phenotypes that may be discovered from S. aureus is named small-colony variants (SCVs). This study focused on applying a HPLC-MS/MS based targeted metabolic profiling approach to detect a set of metabolites that are dysregulated during S. aureus SCVs formation. Over one hundred and eighty metabolites were confidently detected and their difference between S. aureus SCVs and wild type control groups was compared via univariate and multivariate statistical analyses. Twenty metabolites, including 3',5'-cyclic AMP, tyrosine and adenine were identified as SCV specific metabolic features in comparison to the control group. Metabolic profile differences between individually isolated SCV were also observed and compared. Principal component analyses demonstrated clear metabolic profile differentiation between wild type control to SCVs. Metabolic pathway impact analysis also identified multiple metabolic pathways, including alanine, aspartate and glutamate metabolism, glycine, serine and threonine metabolism, that were significantly impacted during SCV formation. To the best of our knowledge, our study is the very first report to detect a large set of altered metabolites induced by S. aureus SCV formation. We believe our method can be used in combination with genomic, transcriptomic and proteomic approaches to achieve a better understanding of the unique physiological and metabolic changes during S. aureus SCV formation, and to assist the potential future development of targeted treatment for S. aureus SCV infections. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Analysis of implanted silicon dopant profiles

    Energy Technology Data Exchange (ETDEWEB)

    Prosa, T.J., E-mail: ty.prosa@ametek.com [Cameca Instruments Inc., Madison, WI 53711 (United States); Olson, D.; Geiser, B.; Larson, D.J. [Cameca Instruments Inc., Madison, WI 53711 (United States); Henry, K.; Steel, E. [National Institute of Standards and Technology, Gaithersburg, MD 20899 (United States)

    2013-09-15

    Atom probe tomography implant dose measurements are reported for National Institute of Standards and Technology Standard Reference Material 2134 (arsenic implant). Efforts were taken to manufacture specimens with limited variation in size and shape to minimize variation in physical reconstruction parameters. A tip profile reconstruction was utilized where measurements of tip profile, post-analysis specimen radius and sphere-to-cone radius ratio were required as inputs into the reconstruction process. A variation of 4% is observed in the dose measurement under these conditions. Various considerations necessary to narrow the observed variation in measured dose, toward the limit imposed by counting statistics, are discussed. - Highlights: ► Multiple APT measurements were made on a NIST standard reference implant material. ► Accuracy and precision of APT was assessed on implant dose measurements. ► Dose standard deviations of ∼2% (∼2× counting statistics limit) were achieved. ► SEM exposure was found to affect the ability to successfully analyze these specimens.

  3. Motivational orientations and imagery use: a goal profiling analysis.

    Science.gov (United States)

    Cumming, Jennifer; Hall, Craig; Harwood, Chris; Gammage, Kimberley

    2002-02-01

    The aim of this study was to establish whether different motivational profiles that result from performing a cluster analysis reflect the use of different functions and amounts of imagery. One hundred and five competitive swimmers were recruited to participate in the study. They were asked to complete both the Task and Ego Orientation in Sport Questionnaire (TEOSQ) and the Sport Imagery Questionnaire. The results of a K-means cluster analysis on the TEOSQ scores resulted in a three-cluster solution that maximized between-group differences and minimized within-group differences. A multivariate analysis of variance revealed that the three cluster groups could be distinguished by their use of imagery. Specifically, the results indicated that individuals with a 'complementary balance' between task and ego orientations were more motivated to perform the functions of imagery that would help them to maximize their performance.

  4. Large-scale profiling of signalling pathways reveals an asthma specific signature in bronchial smooth muscle cells

    Science.gov (United States)

    Alexandrova, Elena; Nassa, Giovanni; Corleone, Giacomo; Buzdin, Anton; Aliper, Alexander M.; Terekhanova, Nadezhda; Shepelin, Denis; Zhavoronkov, Alexander; Tamm, Michael; Milanesi, Luciano; Weisz, Alessandro

    2016-01-01

    Background Bronchial smooth muscle (BSM) cells from asthmatic patients maintain in vitro a distinct hyper-reactive (“primed”) phenotype, characterized by increased release of pro-inflammatory factors and mediators, as well as hyperplasia and/or hypertrophy. This “primed” phenotype helps to understand pathogenesis of asthma, as changes in BSM function are essential for manifestation of allergic and inflammatory responses and airway wall remodelling. Objective To identify signalling pathways in cultured primary BSMs of asthma patients and non-asthmatic subjects by genome wide profiling of differentially expressed mRNAs and activated intracellular signalling pathways (ISPs). Methods Transcriptome profiling by cap-analysis-of-gene-expression (CAGE), which permits selection of preferentially capped mRNAs most likely to be translated into proteins, was performed in human BSM cells from asthmatic (n=8) and non-asthmatic (n=6) subjects and OncoFinder tool were then exploited for identification of ISP deregulations. Results CAGE revealed >600 RNAs differentially expressed in asthma vs control cells (p≤0.005), with asthma samples showing a high degree of similarity among them. Comprehensive ISP activation analysis revealed that among 269 pathways analysed, 145 (psignalization. Conclusions These first-time results can now be exploited toward development of novel therapeutic strategies targeting ISP signatures linked to asthma pathophysiology. PMID:26863634

  5. CeFra-seq reveals broad asymmetric mRNA and noncoding RNA distribution profiles in Drosophila and human cells.

    Science.gov (United States)

    Benoit Bouvrette, Louis Philip; Cody, Neal A L; Bergalet, Julie; Lefebvre, Fabio Alexis; Diot, Cédric; Wang, Xiaofeng; Blanchette, Mathieu; Lécuyer, Eric

    2018-01-01

    Cells are highly asymmetrical, a feature that relies on the sorting of molecular constituents, including proteins, lipids, and nucleic acids, to distinct subcellular locales. The localization of RNA molecules is an important layer of gene regulation required to modulate localized cellular activities, although its global prevalence remains unclear. We combine biochemical cell fractionation with RNA-sequencing (CeFra-seq) analysis to assess the prevalence and conservation of RNA asymmetric distribution on a transcriptome-wide scale in Drosophila and human cells. This approach reveals that the majority (∼80%) of cellular RNA species are asymmetrically distributed, whether considering coding or noncoding transcript populations, in patterns that are broadly conserved evolutionarily. Notably, a large number of Drosophila and human long noncoding RNAs and circular RNAs display enriched levels within specific cytoplasmic compartments, suggesting that these RNAs fulfill extra-nuclear functions. Moreover, fraction-specific mRNA populations exhibit distinctive sequence characteristics. Comparative analysis of mRNA fractionation profiles with that of their encoded proteins reveals a general lack of correlation in subcellular distribution, marked by strong cases of asymmetry. However, coincident distribution profiles are observed for mRNA/protein pairs related to a variety of functional protein modules, suggesting complex regulatory inputs of RNA localization to cellular organization. © 2018 Benoit Bouvrette et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

  6. [Analysis of the pragmatic abilities profile in normal preschool children].

    Science.gov (United States)

    Hage, Simone de Rocha Vasconcellos; Resegue, Marta Maria; Viveiros, Daniele Cristina Sedano de; Pacheco, Elaine Florentino

    2007-01-01

    pragmatic abilities in children. to analyze the pragmatic abilities profile in normal preschool children and to verify if significant differences exist regarding the children's different socioeconomic levels. participants of this study were 30 children, with ages between 36 and 47 months, who attended public and private elementary schools - low and medium/high socioeconomic levels respectively. A thirty minute semi-structured conversation between each child and the evaluator was recorded in VHS. For the analysis of the pragmatic abilities profile 20 minutes of each conversation was transcribed. there is a prevalence of verbal over non-verbal and unintelligible utterances; simple over expansive utterances; coherent over incoherent utterances. There was a low occurrence of utterances used to start a conversation. Regarding the use of communicative functions, the informative function prevailed, even though all the others (instrumental, heuristic, naming, narrative, negative, interactive) were used by all of the children. Comparing the performance of children who attended public schools with that of children who attended private schools, statistically significant differences were observed in the number of simple and expansive verbal utterances, and in the use of the narrative function, indicating a better performance of children from private institutions. the analysis of the children's conversational abilities profile revealed that they respond/maintain the conversation instead of initiating it; their utterances are verbal, mostly coherent and simple. Regarding the communicative functions, the most prevalent was the informative function. Sociolinguistic aspects can interfere in the pragmatic abilities of children of different socioeconomic level.

  7. [Basics of esthetic and functional cephalometric analysis of the profile].

    Science.gov (United States)

    Gola, R; Cheynet, F; Guyot, L; Richard, O

    2004-12-01

    We report a new cephalometric method for profile analysis, which uses strictly exobasicranial landmarks: 13 anatomic points, 9 bone points and 4 skin points. The analysis is based on phylogenetic, ontogenetic, anatomic and biomechanical data. Phylogenetic analysis reveals that the occipital plate belongs more to the cranial vault than the base of the skull. Embryology shows that on the midline the facial skull base ends at the spheno-occipital suture and that the overall skull base ends at the basion. The pre-maxillary fuses rapidly to the maxillary, while the pterygoid processes, which belong to the face and not the skull base, fusion very rapidly to the skull base. Revisiting the anatomy of the facial skull base shows that it is prolonged posteriorly medially to meast the synostosic creast and latterally to the glenoid fossae. Further anatomic analysis shows that the dentate and muscular part of the superior level of the facial mass correspond to equivalent parts of the inferior mandibular level. The biomechanical analysis reveals that the anterior pillar passes through the pre-maxillary, ending on the supra-orbital border and the glabella and as such belongs to the face. The posterior pillar follows the pterygoid process ending in the sphenoid. The glabella and these two pillars are taken into account in this new analysis technique.

  8. Mitochondrial DNA analysis reveals a low nucleotide diversity of ...

    African Journals Online (AJOL)

    Mitochondrial DNA analysis reveals a low nucleotide diversity of Caligula japonica in China. ... Mitochondrial DNA analysis reveals a low nucleotide diversity of Caligula japonica in China. Y Li, B Yang, H Wang, R Xia, L Wang, Z Zhang, L Qin, Y Liu ...

  9. Genomic profiling reveals Pitx2 controls expression of mature extraocular muscle contraction-related genes.

    Science.gov (United States)

    Zhou, Yuefang; Gong, Bendi; Kaminski, Henry J

    2012-04-18

    To assess the influence of the Pitx2 transcription factor on the global gene expression profile of extraocular muscle (EOM) of mice. Mice with a conditional knockout of Pitx2, designated Pitx2(Δflox/Δflox) and their control littermates Pitx2(flox/flox), were used. RNA was isolated from EOM obtained at 3, 6, and 12 weeks of age and processed for microarray-based profiling. Pairwise comparisons were performed between mice of the same age and differentially expressed gene lists were generated. Select genes from the profile were validated using real-time quantitative polymerase chain reaction and protein immunoblot. Ultrastructural analysis was performed to evaluate EOM sarcomeric structure. The number of differentially expressed genes was relatively small. Eleven upregulated and 23 downregulated transcripts were identified common to all three age groups in the Pitx2-deficient extraocular muscle compared with littermate controls. These fell into a range of categories including muscle-specific structural genes, transcription factors, and ion channels. The differentially expressed genes were primarily related to muscle contraction. We verified by protein and ultrastructural analysis that myomesin 2 was expressed in the Pitx2-deficient mice, and this was associated with development of M lines evident in their orbital region. The global transcript expression analysis uncovered that Pitx2 primarily regulates a relatively select number of genes associated with muscle contraction. Pitx2 loss led to the development of M line structures, a feature more typical of other skeletal muscle.

  10. Inborn errors of metabolism revealed by organic acid profile analysis ...

    African Journals Online (AJOL)

    Objective: To determine the prevalence and types of inborn errors of amino acid or organic acid metabolism in a group of high risk Egyptian children with clinical signs and symptoms suggestive of inherited metabolic diseases. Subjects and Methods: 117 (79 males ═ 67.5 % and 38 females ═ 32.5 %) high risk patients with ...

  11. Large-scale profiling of signalling pathways reveals an asthma specific signature in bronchial smooth muscle cells.

    Science.gov (United States)

    Alexandrova, Elena; Nassa, Giovanni; Corleone, Giacomo; Buzdin, Anton; Aliper, Alexander M; Terekhanova, Nadezhda; Shepelin, Denis; Zhavoronkov, Alexander; Tamm, Michael; Milanesi, Luciano; Miglino, Nicola; Weisz, Alessandro; Borger, Pieter

    2016-05-03

    Bronchial smooth muscle (BSM) cells from asthmatic patients maintain in vitro a distinct hyper-reactive ("primed") phenotype, characterized by increased release of pro-inflammatory factors and mediators, as well as hyperplasia and/or hypertrophy. This "primed" phenotype helps to understand pathogenesis of asthma, as changes in BSM function are essential for manifestation of allergic and inflammatory responses and airway wall remodelling. To identify signalling pathways in cultured primary BSMs of asthma patients and non-asthmatic subjects by genome wide profiling of differentially expressed mRNAs and activated intracellular signalling pathways (ISPs). Transcriptome profiling by cap-analysis-of-gene-expression (CAGE), which permits selection of preferentially capped mRNAs most likely to be translated into proteins, was performed in human BSM cells from asthmatic (n=8) and non-asthmatic (n=6) subjects and OncoFinder tool were then exploited for identification of ISP deregulations. CAGE revealed >600 RNAs differentially expressed in asthma vs control cells (p≤0.005), with asthma samples showing a high degree of similarity among them. Comprehensive ISP activation analysis revealed that among 269 pathways analysed, 145 (p<0.05) or 103 (p<0.01) are differentially active in asthma, with profiles that clearly characterize BSM cells of asthmatic individuals. Notably, we identified 7 clusters of coherently acting pathways functionally related to the disease, with ISPs down-regulated in asthma mostly targeting cell death-promoting pathways and up-regulated ones affecting cell growth and proliferation, inflammatory response, control of smooth muscle contraction and hypoxia-related signalization. These first-time results can now be exploited toward development of novel therapeutic strategies targeting ISP signatures linked to asthma pathophysiology.

  12. 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

  13. MicroRNA Profiling of CSF Reveals Potential Biomarkers to Detect Alzheimer`s Disease.

    Science.gov (United States)

    Denk, Johannes; Boelmans, Kai; Siegismund, Christine; Lassner, Dirk; Arlt, Sönke; Jahn, Holger

    2015-01-01

    The miRBase-21 database currently lists 1881 microRNA (miRNA) precursors and 2585 unique mature human miRNAs. Since their discovery, miRNAs have proved to present a new level of epigenetic post-transcriptional control of protein synthesis. Initial results point to a possible involvement of miRNA in Alzheimer's disease (AD). We applied OpenArray technology to profile the expression of 1178 unique miRNAs in cerebrospinal fluid (CSF) samples of AD patients (n = 22) and controls (n = 28). Using a Cq of 34 as cut-off, we identified positive signals for 441 miRNAs, while 729 miRNAs could not be detected, indicating that at least 37% of miRNAs are present in the brain. We found 74 miRNAs being down- and 74 miRNAs being up-regulated in AD using a 1.5 fold change threshold. By applying the new explorative "Measure of relevance" method, 6 reliable and 9 informative biomarkers were identified. Confirmatory MANCOVA revealed reliable miR-100, miR-146a and miR-1274a as differentially expressed in AD reaching Bonferroni corrected significance. MANCOVA also confirmed differential expression of informative miR-103, miR-375, miR-505#, miR-708, miR-4467, miR-219, miR-296, miR-766 and miR-3622b-3p. Discrimination analysis using a combination of miR-100, miR-103 and miR-375 was able to detect AD in CSF by positively classifying controls and AD cases with 96.4% and 95.5% accuracy, respectively. Referring to the Ingenuity database we could identify a set of AD associated genes that are targeted by these miRNAs. Highly predicted targets included genes involved in the regulation of tau and amyloid pathways in AD like MAPT, BACE1 and mTOR.

  14. Soil profiles' development and differentiation as revealed by their magnetic signal

    Science.gov (United States)

    Jordanova, Neli; Jordanova, Diana

    2017-04-01

    Soil profiles' development is a major theme in soil science research, as far as it gives basic information on soil genesis and classification. The use of soil magnetic properties as indicators for physical and geochemical conditions during pedogenesis received great attention during the last decade mainly in relation to paleoclimate reconstructions. However, tracking the observed general relationships with respect to degree of soil differentiation would lead to capitalization of this knowledge and its further utilization as pedogenic indicator. Here we present an overview of the observed relationships and depth variations of magnetic characteristics along ten soil profiles of Chernozems, Luvisols and Planosols from Bulgaria. Depending on the general soil group considered, different relationships between depth distribution of the relative amount of superparamagnetic (SP), single domain (SD) and larger pseudo single domain (PSD) to multi domain (MD) ferrimagnetic fractions are revealed. The profiles of the soil group with pronounced accumulation of organic matter in the mineral topsoil (Chernozems and Phaeozems) a systematic shift in the relative maxima of SP- and SD- like concentration proxies is observed with the increase of profile differentiation. In contrast, the group of soils with clay-enriched subsoil horizon (e.g. Luvisols) shows different evolution of the depth distribution of the grain-size proxy parameters. The increase of profile's degradation leads to a decrease in the amount of the SP fraction and a split in its maxima into two depth intervals related to the eluvial and illuvial horizons respectively. Along with this tendency, the maximum of the SD fraction moves to progressively deeper levels of the illuvial horizon. The third soil group of the Planosols is characterized by specific re-distribution of the iron oxides, caused by the oscillating oxidation - reduction fluctuations within the profile. The diagnostic eluvial and illuvial soil horizons are

  15. 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.

  16. Profile Analysis of the Universal Nonverbal Intelligence Test Standardization Sample.

    Science.gov (United States)

    Wilhoit, Brian E.; McCallum, R. Steve

    2002-01-01

    A normative typology was developed and applied using multivariate profile analysis of subtest scores of the Universal Nonverbal Intelligence Test (UNIT) standardization sample. The results yielded a seven-profile cluster solution for the Extended Battery, and a six-profile cluster solution for the Standard Battery. Additionally, the results lend…

  17. {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.

  18. 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.

  19. Diagnosis of adenylosuccinate lyase deficiency by metabolomic profiling in plasma reveals a phenotypic spectrum

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    Olga Østrup

    Full Text Available Fertilization is followed by complex changes in cytoplasmic composition and extensive chromatin reprogramming which results in the abundant activation of totipotent embryonic genome at embryonic genome activation (EGA. While chromatin reprogramming has been widely studied in several species, only 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 stage EGA and determine major metabolic changes that regulate totipotency. The period before EGA was dominated by transcripts responsible for cell cycle regulation, mitosis, RNA translation and processing (including ribosomal machinery, protein catabolism, and chromatin remodelling. Following EGA an increase in the abundance of transcripts involved in transcription, translation, DNA metabolism, histone and chromatin modification, as well as protein catabolism was detected. The further analysis of members of overlapping GO terms revealed that despite that comparable cellular processes are taking place before and after EGA (RNA splicing, protein catabolism, different metabolic pathways are involved. This strongly suggests that a complex metabolic switch accompanies EGA. In vitro conditions significantly altered RNA profiles before EGA, and the character of these changes indicates that they originate 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 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

  1. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  3. Plasma, urine and ligament tissue metabolite profiling reveals potential biomarkers of ankylosing spondylitis using NMR-based metabolic profiles.

    Science.gov (United States)

    Wang, Wei; Yang, Gen-Jin; Zhang, Ju; Chen, Chen; Jia, Zhen-Yu; Li, Jia; Xu, Wei-Dong

    2016-10-22

    Ankylosing spondylitis (AS) is an autoimmune rheumatic disease mostly affecting the axial skeleton. Currently, anti-tumour necrosis factor α (anti-TNF-α) represents an effective treatment for AS that may delay the progression of the disease and alleviate the symptoms if the diagnosis can be made early. Unfortunately, effective diagnostic biomarkers for AS are still lacking; therefore, most patients with AS do not receive timely and effective treatment. The intent of this study was to determine several key metabolites as potential biomarkers of AS using metabolomic methods to facilitate the early diagnosis of AS. First, we collected samples of plasma, urine, and ligament tissue around the hip joint from AS and control groups. The samples were examined by nuclear magnetic resonance spectrometry, and multivariate data analysis was performed to find metabolites that differed between the groups. Subsequently, according to the correlation coefficients, variable importance for the projection (VIP) and P values of the metabolites obtained in the multivariate data analysis, the most crucial metabolites were selected as potential biomarkers of AS. Finally, metabolic pathways involving the potential biomarkers were determined using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, and the metabolic pathway map was drawn. Forty-four patients with AS agreed to provide plasma and urine samples, and 30 provided ligament tissue samples. An equal number of volunteers were recruited for the control group. Multidimensional statistical analysis suggested significant differences between the patients with AS and control subjects, and the models exhibited good discrimination and predictive ability. A total of 20 different metabolites ultimately met the requirements for potential biomarkers. According to KEGG analysis, these marker metabolites were primarily related to fat metabolism, intestinal microbial metabolism, glucose metabolism and choline metabolism pathways, and

  4. Transcript profiling reveals expression differences in wild-type and glabrous soybean lines

    Directory of Open Access Journals (Sweden)

    Stromvik Martina

    2011-10-01

    Full Text Available Abstract Background Trichome hairs affect diverse agronomic characters such as seed weight and yield, prevent insect damage and reduce loss of water but their molecular control has not been extensively studied in soybean. Several detailed models for trichome development have been proposed for Arabidopsis thaliana, but their applicability to important crops such as cotton and soybean is not fully known. Results Two high throughput transcript sequencing methods, Digital Gene Expression (DGE Tag Profiling and RNA-Seq, were used to compare the transcriptional profiles in wild-type (cv. Clark standard, CS and a mutant (cv. Clark glabrous, i.e., trichomeless or hairless, CG soybean isoline that carries the dominant P1 allele. DGE data and RNA-Seq data were mapped to the cDNAs (Glyma models predicted from the reference soybean genome, Williams 82. Extending the model length by 250 bp at both ends resulted in significantly more matches of authentic DGE tags indicating that many of the predicted gene models are prematurely truncated at the 5' and 3' UTRs. The genome-wide comparative study of the transcript profiles of the wild-type versus mutant line revealed a number of differentially expressed genes. One highly-expressed gene, Glyma04g35130, in wild-type soybean was of interest as it has high homology to the cotton gene GhRDL1 gene that has been identified as being involved in cotton fiber initiation and is a member of the BURP protein family. Sequence comparison of Glyma04g35130 among Williams 82 with our sequences derived from CS and CG isolines revealed various SNPs and indels including addition of one nucleotide C in the CG and insertion of ~60 bp in the third exon of CS that causes a frameshift mutation and premature truncation of peptides in both lines as compared to Williams 82. Conclusion Although not a candidate for the P1 locus, a BURP family member (Glyma04g35130 from soybean has been shown to be abundantly expressed in the CS line and very

  5. Finite Element Analysis of PVC window profile &aluminium window profile with and without thermal break

    OpenAIRE

    ENG. Mohammad Buhemdi

    2016-01-01

    Examine a thermal analysis .Numerous analogies exist between thermal and structuralanalysis for PVC window profile &aluminium window profile with and without thermalbreak ,Finite Element Analysis, commonly called FEA, is a method of numerical analysis. FEA isused for solving problems in many engineering disciplines such as machine design,acoustics, electromagnetism, soil mechanics, fluid dynamics, and many others. Inmathematical terms, FEA is a numerical technique used for solving...

  6. Expression profiling of the RPE in zebrafish smarca4 mutant revealed altered signals that potentially affect RPE and retinal differentiation

    Science.gov (United States)

    Ma, Ping; Collery, Ross; Trowbridge, Sara; Zhong, Wenxuan; Leung, Yuk Fai

    2014-01-01

    Purpose The purpose of this study was to develop a framework for analyzing retinal pigment epithelium (RPE) expression profiles from zebrafish eye mutants. Methods The fish model we used was SWI/SNF-related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 4 (smarca4), a retinal dystrophic mutant with a previously described retinal phenotype and expression profiles. Histological and Affymetrix GeneChip analyses were conducted to characterize the RPE defects and underlying differential expression, respectively. Results Histological analysis revealed that smarca4 RPE was formed, but its differentiation was abnormal. In particular, ultrastructural analysis of smarca4 RPE by transmission electron microscopy demonstrated several defects in melanogenesis. The nature of these defects also suggests that the cytoskeletal dynamics, which are tightly linked with melanogenesis, were impaired in smarca4 RPE. To compare the expression profile of normal wild-type (WT) and smarca4 RPE, the gene expression profiles of microdissected retinas and RPE-attached retinas were measured with Affymetrix GeneChip analysis. The RPE expression values were then estimated from these samples by subtracting the retinal expression values from the expression values of the RPE-attached retinas. A factorial analysis was conducted using the expression values of the RPE, retinal, and whole-embryo samples. Specific rules (contrasts) were built using the coefficients of the resulting fitted models to select for three groups of genes: 1) smarca4-regulated RPE genes, 2) smarca4-regulated retinal genes, and 3) smarca4-regulated RPE genes that are not differentially expressed in the retina. Interestingly, the third group consists of 39 genes that are highly related to cytoskeletal dynamics, melanogenesis, and paracrine and intracellular signal transduction. Conclusions Our analytical framework provides an experimental approach to identify differentially-regulated genes in the

  7. 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.

  8. Profiling of metastatic small intestine neuroendocrine tumors reveals characteristic miRNAs detectable in plasma.

    Science.gov (United States)

    Bowden, Michaela; Zhou, Chensheng W; Zhang, Sui; Brais, Lauren; Rossi, Ashley; Naudin, Laurent; Thiagalingam, Arunthi; Sicinska, Ewa; Kulke, Matthew H

    2017-08-15

    Current diagnostic and prognostic blood-based biomarkers for neuroendocrine tumors are limited. MiRNAs have tumor-specific expression patterns, are relatively stable, and can be measured in patient blood specimens. We performed a multi-stage study to identify and validate characteristic circulating miRNAs in patients with metastatic small intestine neuroendocrine tumors, and to assess associations between miRNA levels and survival. Using a 742-miRNA panel, we identified candidate miRNAs similarly expressed in 19 small intestine neuroendocrine tumors and matched plasma samples. We refined our panel in an independent cohort of plasma samples from 40 patients with metastatic small intestine NET and 40 controls, and then validated this panel in a second, large cohort of 120 patients with metastatic small intestine NET and 120 independent controls. miRNA profiling of 19 matched small intestine neuroendocrine tumors and matched plasma samples revealed 31 candidate miRNAs similarly expressed in both tissue and plasma. We evaluated expression of these 31 candidate miRNAs in 40 independent cases and 40 normal controls, and identified 4 miRNAs (miR-21-5p, miR-22-3p, miR-29b-3p, and miR-150-5p) that were differently expressed in cases and controls (p<0.05). We validated these 4 miRNAs in a separate, larger panel of 120 cases and 120 controls. We confirmed that high circulating levels of miR-22-3p (p<0.0001), high levels of miR 21-5p, and low levels of miR-150-5p (p=0.027) were associated with the presence of metastatic small intestine NET. While levels of 29b-3p were lower in cases than in controls in both the initial cohort and the validation cohort, the difference in the validation cohort did not reach statistical significance. We further found that high levels of circulating miR-21-5p, high levels of circulating miR-22-3p and low levels of circulating miR-150-5p were each independently associated with shorter overall survival. A combined analysis using all three markers

  9. 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.

  10. Fractal Analysis of Rock Joint Profiles

    Science.gov (United States)

    Audy, Ondřej; Ficker, Tomáš

    2017-10-01

    Surface reliefs of rock joints are analyzed in geotechnics when shear strength of rocky slopes is estimated. The rock joint profiles actually are self-affine fractal curves and computations of their fractal dimensions require special methods. Many papers devoted to the fractal properties of these profiles were published in the past but only a few of those papers employed a convenient computational method that would have guaranteed a sound value of that dimension. As a consequence, anomalously low dimensions were presented. This contribution deals with two computational modifications that lead to sound fractal dimensions of the self-affine rock joint profiles. These are the modified box-counting method and the modified yard-stick method sometimes called the compass method. Both these methods are frequently applied to self-similar fractal curves but the self-affine profile curves due to their self-affine nature require modified computational procedures implemented in computer programs.

  11. 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.

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

    Science.gov (United States)

    Peres, Nalu T A; Sanches, Pablo R; Falcão, Juliana P; Silveira, Henrique C S; Paião, Fernanda G; Maranhão, Fernanda C A; Gras, Diana E; Segato, Fernando; Cazzaniga, Rodrigo A; Mazucato, Mendelson; Cursino-Santos, Jeny R; Aquino-Ferreira, Roseli; Rossi, Antonio; Martinez-Rossi, Nilce M

    2010-02-08

    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. 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. 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.

  13. Stromal transcriptional profiles reveal hierarchies of anatomical site, serum response and disease and identify disease specific pathways.

    Science.gov (United States)

    Filer, Andrew; Antczak, Philipp; Parsonage, Greg N; Legault, Holly M; O'Toole, Margot; Pearson, Mark J; Thomas, Andrew M; Scheel-Toellner, Dagmar; Raza, Karim; Buckley, Christopher D; Falciani, Francesco

    2015-01-01

    Synovial fibroblasts in persistent inflammatory arthritis have been suggested to have parallels with cancer growth and wound healing, both of which involve a stereotypical serum response programme. We tested the hypothesis that a serum response programme can be used to classify diseased tissues, and investigated the serum response programme in fibroblasts from multiple anatomical sites and two diseases. To test our hypothesis we utilized a bioinformatics approach to explore a publicly available microarray dataset including rheumatoid arthritis (RA), osteoarthritis (OA) and normal synovial tissue, then extended those findings in a new microarray dataset representing matched synovial, bone marrow and skin fibroblasts cultured from RA and OA patients undergoing arthroplasty. The classical fibroblast serum response programme discretely classified RA, OA and normal synovial tissues. Analysis of low and high serum treated fibroblast microarray data revealed a hierarchy of control, with anatomical site the most powerful classifier followed by response to serum and then disease. In contrast to skin and bone marrow fibroblasts, exposure of synovial fibroblasts to serum led to convergence of RA and OA expression profiles. Pathway analysis revealed three inter-linked gene networks characterising OA synovial fibroblasts: Cell remodelling through insulin-like growth factors, differentiation and angiogenesis through _3 integrin, and regulation of apoptosis through CD44. We have demonstrated that Fibroblast serum response signatures define disease at the tissue level, and that an OA specific, serum dependent repression of genes involved in cell adhesion, extracellular matrix remodelling and apoptosis is a critical discriminator between cultured OA and RA synovial fibroblasts.

  14. 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

    2013-09-10

    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 is among the first functional genomic studies 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. Copyright © 2013 Elsevier B.V. All rights reserved.

  15. 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.

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

    OpenAIRE

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

    2015-01-01

    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...

  17. Exploratory factor analysis of the Oral Health Impact Profile.

    Science.gov (United States)

    John, M T; Reissmann, D R; Feuerstahler, L; Waller, N; Baba, K; Larsson, P; Celebić, A; Szabo, G; Rener-Sitar, K

    2014-09-01

    Although oral health-related quality of life (OHRQoL) as measured by the Oral Health Impact Profile (OHIP) is thought to be multidimensional, the nature of these dimensions is not known. The aim of this report was to explore the dimensionality of the OHIP using the Dimensions of OHRQoL (DOQ) Project, an international study of general population subjects and prosthodontic patients. Using the project's Learning Sample (n = 5173), we conducted an exploratory factor analysis on the 46 OHIP items not specifically referring to dentures for 5146 subjects with sufficiently complete data. The first eigenvalue (27·0) of the polychoric correlation matrix was more than ten times larger than the second eigenvalue (2·6), suggesting the presence of a dominant, higher-order general factor. Follow-up analyses with Horn's parallel analysis revealed a viable second-order, four-factor solution. An oblique rotation of this solution revealed four highly correlated factors that we named Oral Function, Oro-facial Pain, Oro-facial Appearance and Psychosocial Impact. These four dimensions and the strong general factor are two viable hypotheses for the factor structure of the OHIP. © 2014 John Wiley & Sons Ltd.

  18. Protein profiling reveals consequences of lifestyle choices on predicted biological aging.

    Science.gov (United States)

    Enroth, Stefan; Enroth, Sofia Bosdotter; Johansson, Åsa; Gyllensten, Ulf

    2015-12-01

    Ageing is linked to a number of changes in how the body and its organs function. On a molecular level, ageing is associated with a reduction of telomere length, changes in metabolic and gene-transcription profiles and an altered DNA-methylation pattern. Lifestyle factors such as smoking or stress can impact some of these molecular processes and thereby affect the ageing of an individual. Here we demonstrate by analysis of 77 plasma proteins in 976 individuals, that the abundance of circulating proteins accurately predicts chronological age, as well as anthropometrical measurements such as weight, height and hip circumference. The plasma protein profile can also be used to identify lifestyle factors that accelerate and decelerate ageing. We found smoking, high BMI and consumption of sugar-sweetened beverages to increase the predicted chronological age by 2-6 years, while consumption of fatty fish, drinking moderate amounts of coffee and exercising reduced the predicted age by approximately the same amount. This method can be applied to dried blood spots and may thus be useful in forensic medicine to provide basic anthropometrical measures for an individual based on a biological evidence sample.

  19. 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

  20. RNA-seq transcriptional profiling of Leishmania amazonensis reveals an arginase-dependent gene expression regulation.

    Directory of Open Access Journals (Sweden)

    Juliana Ide Aoki

    2017-10-01

    Full Text Available Leishmania is a protozoan parasite that alternates its life cycle between the sand-fly vector and the mammalian host. This alternation involves environmental changes and leads the parasite to dynamic modifications in morphology, metabolism, cellular signaling and regulation of gene expression to allow for a rapid adaptation to new conditions. The L-arginine pathway in L. amazonensis is important during the parasite life cycle and interferes in the establishment and maintenance of the infection in mammalian macrophages. Host arginase is an immune-regulatory enzyme that can reduce the production of nitric oxide by activated macrophages, directing the availability of L-arginine to the polyamine pathway, resulting in parasite replication. In this work, we performed transcriptional profiling to identify differentially expressed genes in L. amazonensis wild-type (La-WT versus L. amazonensis arginase knockout (La-arg- promastigotes and axenic amastigotes.A total of 8253 transcripts were identified in La-WT and La-arg- promastigotes and axenic amastigotes, about 60% of them codifying hypothetical proteins and 443 novel transcripts, which did not match any previously annotated genes. Our RNA-seq data revealed that 85% of genes were constitutively expressed. The comparison of transcriptome and metabolome data showed lower levels of arginase and higher levels of glutamate-5-kinase in La-WT axenic amastigotes compared to promastigotes. The absence of arginase activity in promastigotes increased the levels of pyrroline 5-carboxylate reductase, but decreased the levels of arginosuccinate synthase, pyrroline 5-carboxylate dehydrogenase, acetylornithine deacetylase and spermidine synthase transcripts levels. These observations can explain previous metabolomic data pointing to the increase of L-arginine, citrulline and L-glutamate and reduction of aspartate, proline, ornithine and putrescine. Altogether, these results indicate that arginase activity is important

  1. Transcriptional profiling of the pea shoot apical meristem reveals processes underlying its function and maintenance

    Directory of Open Access Journals (Sweden)

    Singh Mohan B

    2008-06-01

    Full Text Available Abstract Background Despite the importance of the shoot apical meristem (SAM in plant development and organ formation, our understanding of the molecular mechanisms controlling its function is limited. Genomic tools have the potential to unravel the molecular mysteries of the SAM, and legume systems are increasingly being used in plant-development studies owing to their unique characteristics such as nitrogen fixation, secondary metabolism, and pod development. Garden pea (Pisum sativum is a well-established classic model species for genetics studies that has been used since the Mendel era. In addition, the availability of a plethora of developmental mutants makes pea an ideal crop legume for genomics studies. This study aims to utilise genomics tools in isolating genes that play potential roles in the regulation of SAM activity. Results In order to identify genes that are differentially expressed in the SAM, we generated 2735 ESTs from three cDNA libraries derived from freshly micro-dissected SAMs from 10-day-old garden peas (Pisum sativum cv Torsdag. Custom-designed oligonucleotide arrays were used to compare the transcriptional profiles of pea SAMs and non-meristematic tissues. A total of 184 and 175 transcripts were significantly up- or down-regulated in the pea SAM, respectively. As expected, close to 61% of the transcripts down-regulated in the SAM were found in the public database, whereas sequences from the same source only comprised 12% of the genes that were expressed at higher levels in the SAM. This highlights the under-representation of transcripts from the meristematic tissues in the current public pea protein database, and demonstrates the utility of our SAM EST collection as an essential genetic resource for revealing further information on the regulation of this developmental process. In addition to unknowns, many of the up-regulated transcripts are known to encode products associated with cell division and proliferation

  2. Transcriptional profiling of the pea shoot apical meristem reveals processes underlying its function and maintenance.

    Science.gov (United States)

    Wong, Chui E; Bhalla, Prem L; Ottenhof, Harald; Singh, Mohan B

    2008-06-30

    Despite the importance of the shoot apical meristem (SAM) in plant development and organ formation, our understanding of the molecular mechanisms controlling its function is limited. Genomic tools have the potential to unravel the molecular mysteries of the SAM, and legume systems are increasingly being used in plant-development studies owing to their unique characteristics such as nitrogen fixation, secondary metabolism, and pod development. Garden pea (Pisum sativum) is a well-established classic model species for genetics studies that has been used since the Mendel era. In addition, the availability of a plethora of developmental mutants makes pea an ideal crop legume for genomics studies. This study aims to utilise genomics tools in isolating genes that play potential roles in the regulation of SAM activity. In order to identify genes that are differentially expressed in the SAM, we generated 2735 ESTs from three cDNA libraries derived from freshly micro-dissected SAMs from 10-day-old garden peas (Pisum sativum cv Torsdag). Custom-designed oligonucleotide arrays were used to compare the transcriptional profiles of pea SAMs and non-meristematic tissues. A total of 184 and 175 transcripts were significantly up- or down-regulated in the pea SAM, respectively. As expected, close to 61% of the transcripts down-regulated in the SAM were found in the public database, whereas sequences from the same source only comprised 12% of the genes that were expressed at higher levels in the SAM. This highlights the under-representation of transcripts from the meristematic tissues in the current public pea protein database, and demonstrates the utility of our SAM EST collection as an essential genetic resource for revealing further information on the regulation of this developmental process. In addition to unknowns, many of the up-regulated transcripts are known to encode products associated with cell division and proliferation, epigenetic regulation, auxin-mediated responses and

  3. RNA-seq transcriptional profiling of Leishmania amazonensis reveals an arginase-dependent gene expression regulation.

    Science.gov (United States)

    Aoki, Juliana Ide; Muxel, Sandra Marcia; Zampieri, Ricardo Andrade; Laranjeira-Silva, Maria Fernanda; Müller, Karl Erik; Nerland, Audun Helge; Floeter-Winter, Lucile Maria

    2017-10-01

    Leishmania is a protozoan parasite that alternates its life cycle between the sand-fly vector and the mammalian host. This alternation involves environmental changes and leads the parasite to dynamic modifications in morphology, metabolism, cellular signaling and regulation of gene expression to allow for a rapid adaptation to new conditions. The L-arginine pathway in L. amazonensis is important during the parasite life cycle and interferes in the establishment and maintenance of the infection in mammalian macrophages. Host arginase is an immune-regulatory enzyme that can reduce the production of nitric oxide by activated macrophages, directing the availability of L-arginine to the polyamine pathway, resulting in parasite replication. In this work, we performed transcriptional profiling to identify differentially expressed genes in L. amazonensis wild-type (La-WT) versus L. amazonensis arginase knockout (La-arg-) promastigotes and axenic amastigotes. A total of 8253 transcripts were identified in La-WT and La-arg- promastigotes and axenic amastigotes, about 60% of them codifying hypothetical proteins and 443 novel transcripts, which did not match any previously annotated genes. Our RNA-seq data revealed that 85% of genes were constitutively expressed. The comparison of transcriptome and metabolome data showed lower levels of arginase and higher levels of glutamate-5-kinase in La-WT axenic amastigotes compared to promastigotes. The absence of arginase activity in promastigotes increased the levels of pyrroline 5-carboxylate reductase, but decreased the levels of arginosuccinate synthase, pyrroline 5-carboxylate dehydrogenase, acetylornithine deacetylase and spermidine synthase transcripts levels. These observations can explain previous metabolomic data pointing to the increase of L-arginine, citrulline and L-glutamate and reduction of aspartate, proline, ornithine and putrescine. Altogether, these results indicate that arginase activity is important in Leishmania

  4. Comprehensive immune profiling reveals substantial immune system alterations in a subset of patients with amyotrophic lateral sclerosis.

    Directory of Open Access Journals (Sweden)

    Michael P Gustafson

    Full Text Available Amyotrophic lateral sclerosis (ALS is a fatal neurodegenerative disease with a median lifespan of 2-3 years after diagnosis. There are few meaningful treatments that alter progression in this disease. Preclinical and clinical studies have demonstrated that neuroinflammation may play a key role in the progression rate of ALS. Despite this, there are no validated biomarkers of neuroinflammation for use in clinical practice or clinical trials. Biomarkers of neuroinflammation could improve patient management, provide new therapeutic targets, and possibly help stratify clinical trial selection and monitoring. However, attempts to identify a singular cause of neuroinflammation have not been successful. Here, we performed multi-parameter flow cytometry to comprehensively assess 116 leukocyte populations and phenotypes from lymphocytes, monocytes, and granulocytes in a cohort of 80 ALS patients. We identified 32 leukocyte phenotypes that were altered in ALS patients compared to age and gender matched healthy volunteers (HV that included phenotypes of both inflammation and immune suppression. Unsupervised hierarchical clustering and principle component analysis of ALS and HV immunophenotypes revealed two distinct immune profiles of ALS patients. ALS patients were clustered into a profile distinct from HVs primarily due to differences in a multiple T cell phenotypes, CD3+CD56+ T cells and HLA-DR on monocytes. Patients clustered into an abnormal immune profile were younger, more likely to have a familial form of the disease, and survived longer than those patients who clustered similarly with healthy volunteers (344 weeks versus 184 weeks; p = 0.012. The data set generated from this study establishes an extensive accounting of immunophenotypic changes readily suitable for biomarker validation studies. The extensive immune system changes measured in this study indicate that normal immune homeostatic mechanisms are disrupted in ALS patients, and that

  5. Mutational Profile of Metastatic Breast Cancers: A Retrospective Analysis.

    Directory of Open Access Journals (Sweden)

    Celine Lefebvre

    2016-12-01

    Full Text Available Major advances have been achieved in the characterization of early breast cancer (eBC genomic profiles. Metastatic breast cancer (mBC is associated with poor outcomes, yet limited information is available on the genomic profile of this disease. This study aims to decipher mutational profiles of mBC using next-generation sequencing.Whole-exome sequencing was performed on 216 tumor-blood pairs from mBC patients who underwent a biopsy in the context of the SAFIR01, SAFIR02, SHIVA, or Molecular Screening for Cancer Treatment Optimization (MOSCATO prospective trials. Mutational profiles from 772 primary breast tumors from The Cancer Genome Atlas (TCGA were used as a reference for comparing primary and mBC mutational profiles. Twelve genes (TP53, PIK3CA, GATA3, ESR1, MAP3K1, CDH1, AKT1, MAP2K4, RB1, PTEN, CBFB, and CDKN2A were identified as significantly mutated in mBC (false discovery rate [FDR] < 0.1. Eight genes (ESR1, FSIP2, FRAS1, OSBPL3, EDC4, PALB2, IGFN1, and AGRN were more frequently mutated in mBC as compared to eBC (FDR < 0.01. ESR1 was identified both as a driver and as a metastatic gene (n = 22, odds ratio = 29, 95% CI [9-155], p = 1.2e-12 and also presented with focal amplification (n = 9 for a total of 31 mBCs with either ESR1 mutation or amplification, including 27 hormone receptor positive (HR+ and HER2 negative (HER2- mBCs (19%. HR+/HER2- mBC presented a high prevalence of mutations on genes located on the mechanistic target of rapamycin (mTOR pathway (TSC1 and TSC2 as compared to HR+/HER2- eBC (respectively 6% and 0.7%, p = 0.0004. Other actionable genes were more frequently mutated in HR+ mBC, including ERBB4 (n = 8, NOTCH3 (n = 7, and ALK (n = 7. Analysis of mutational signatures revealed a significant increase in APOBEC-mediated mutagenesis in HR+/HER2- metastatic tumors as compared to primary TCGA samples (p < 2e-16. The main limitations of this study include the absence of bone metastases and the size of the cohort, which might

  6. Integration of miRNA and mRNA expression profiles reveals microRNA-regulated networks during muscle wasting in cardiac cachexia

    DEFF Research Database (Denmark)

    Moraes, Leonardo N; Fernandez, Geysson J; Vechetti-Júnior, Ivan J

    2017-01-01

    Cardiac cachexia (CC) is a common complication of heart failure (HF) associated with muscle wasting and poor patient prognosis. Although different mechanisms have been proposed to explain muscle wasting during CC, its pathogenesis is still not understood. Here, we described an integrative analysis...... between miRNA and mRNA expression profiles of muscle wasting during CC. Global gene expression profiling identified 1,281 genes and 19 miRNAs differentially expressed in muscle wasting during CC. Several of these deregulated genes are known or putative targets of the altered miRNAs, including miR-29a-3p......, miR-29b-3p, miR-210-5p, miR-214, and miR-489. Gene ontology analysis on integrative mRNA/miRNA expression profiling data revealed miRNA interactions affecting genes that regulate extra-cellular matrix (ECM) organization, proteasome protein degradation, citric acid cycle and respiratory electron...

  7. Plasma proteome profiling of atherosclerotic disease manifestations reveals elevated levels of the cytoskeletal protein vinculin

    DEFF Research Database (Denmark)

    Kristensen, Lars P; Larsen, Martin Røssel; Mickley, Hans

    2014-01-01

    an increased expression profile from group 1 to 4. The top-most elevated protein, vinculin (Vcl) displayed a similar profile. Immunoassays confirmed the expression profile of apo(a) and CRP. A 5-plex SRM-MS assay for Vcl, SAA, CRP, apo(a) and thrombospondin-4 (TSP-4) was developed for multiplex verification...

  8. Proton NMR metabolic profiling of CSF reveals distinct differentiation of meningitis from negative controls.

    Science.gov (United States)

    Chatterji, Tanushri; Singh, Suruchi; Sen, Manodeep; Singh, Ajai Kumar; Agarwal, Gaurav Raj; Singh, Deepak Kumar; Srivastava, Janmejai Kumar; Singh, Alka; Srivastava, Rajeshwar Nath; Roy, Raja

    2017-06-01

    Cerebrospinal fluid (CSF) is an essential bio-fluid of the central nervous system (CNS), playing a vital role in the protection of CNS and performing neuronal function regulation. The chemical composition of CSF varies during onset of meningitis, neurodegenerative disorders (positive controls) and in traumatic cases (negative controls). The study design was broadly categorized into meningitis cases, negative controls and positive controls. Further differentiation among the three groups was carried out using Principal Component Analysis (PCA) followed by supervised Partial Least Square Discriminant Analysis (PLS-DA). The statistical analysis of meningitis vs. negative controls using PLS-DA model resulted in R 2 of 0.97 and Q 2 of 0.85. There was elevation in the levels of ketone bodies, total free amino acids, glutamine, creatine, citrate and choline containing compounds (choline and GPC) in meningitis cases. Similarly, meningitis vs. positive controls resulted in R 2 of 0.80 and Q 2 of 0.60 and showed elevation in the levels of total free amino acids, glutamine, creatine/creatinine and citrate in the meningitis group. Four cases of HIV were identified by PLS-DA model as well as by clinical investigations. On the basis of metabolic profile it was found that negative control CSF samples are more appropriate for differentiation of meningitis than positive control CSF samples. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Multi-elemental profiling and chemo-metric validation revealed nutritional qualities of Zingiber officinale.

    Science.gov (United States)

    Pandotra, Pankaj; Viz, Bhavana; Ram, Gandhi; Gupta, Ajai Prakash; Gupta, Suphla

    2015-04-01

    Ginger rhizome is a valued food, spice and an important ingredient of traditional systems of medicine of India, China and Japan. An Inductively Coupled Plasma-Mass Spectrometry (ICP-MS) based multi-elemental profiling was performed to assess the quantitative complement of elements, nutritional quality and toxicity of 46 ginger germplasms, collected from the north western Himalayan India. The abundance of eighteen elements quantified in the acid digested rhizomes was observed to be K>Mg>Fe>Ca>Na>Mn>Zn>Ba>Cu>Cr>Ni>Pb>Co>Se>As>Be>Cd. Toxic element, Hg was not detected in any of the investigated samples. Chemometric analyses showed positive correlation among most of the elements. No negative correlation was observed in any of the metals under investigation. UPGMA based clustering analysis of the quantitative data grouped all the 46 samples into three major clusters, displaying 88% similarity in their metal composition, while eighteen metals investigated grouped into two major clusters. Quantitatively, all the elements analyzed were below the permissible limits laid down by World Health Organization. The results were further validated by cluster analysis (CA) and principal component analysis (PCA) to understand the ionome of the ginger rhizome. The study suggested raw ginger to be a good source of beneficial elements/minerals like Mg, Ca, Mn, Fe, Cu and Zn and will provide platform for understanding the functional and physiological status of ginger rhizome. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. General Marketing. Ohio's Competency Analysis Profile. Revised.

    Science.gov (United States)

    Ohio State Univ., Columbus. Vocational Instructional Materials Lab.

    Developed through a modified DACUM (Developing a Curriculum) process involving business, industry, labor, and community agency representatives in Ohio, this document is a comprehensive and verified employer competency profile for general marketing occupations. The list contains units (with and without subunits), competencies, and competency…

  11. Nurse Aide. Ohio's Competency Analysis Profile.

    Science.gov (United States)

    Ohio State Univ., Columbus. Vocational Instructional Materials Lab.

    Developed through a modified DACUM (Developing a Curriculum) process involving business, industry, labor, and community agency representatives in Ohio, this document is a comprehensive and verified employer competency profile for nurses' aides. The list contains units (with and without subunits), competencies, and competency builders that identify…

  12. 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

  13. 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.

  14. Kinase Inhibitor Profiling Reveals Unexpected Opportunities to Inhibit Disease-Associated Mutant Kinases

    Directory of Open Access Journals (Sweden)

    Krisna C. Duong-Ly

    2016-02-01

    Full Text Available Small-molecule kinase inhibitors have typically been designed to inhibit wild-type kinases rather than the mutant forms that frequently arise in diseases such as cancer. Mutations can have serious clinical implications by increasing kinase catalytic activity or conferring therapeutic resistance. To identify opportunities to repurpose inhibitors against disease-associated mutant kinases, we conducted a large-scale functional screen of 183 known kinase inhibitors against 76 recombinant mutant kinases. The results revealed lead compounds with activity against clinically important mutant kinases, including ALK, LRRK2, RET, and EGFR, as well as unexpected opportunities for repurposing FDA-approved kinase inhibitors as leads for additional indications. Furthermore, using T674I PDGFRα as an example, we show how single-dose screening data can provide predictive structure-activity data to guide subsequent inhibitor optimization. This study provides a resource for the development of inhibitors against numerous disease-associated mutant kinases and illustrates the potential of unbiased profiling as an approach to compound-centric inhibitor development.

  15. Transcriptomic profiling revealed the regulatory mechanism of Arabidopsis seedlings response to oxidative stress from cryopreservation.

    Science.gov (United States)

    Ren, Li; Zhang, Di; Chen, Guan-qun; Reed, Barbara M; Shen, Xiao-hui; Chen, Huo-ying

    2015-12-01

    Elevated antioxidant status and positive abiotic stress response in dehydration enhance cell resistance to cryoinjury, and controlling oxidative damage via reactive oxygen species homeostasis maintenance leads to high survival. Cryoprotectants are important for cell survival in cryopreservation, but high concentrations can also cause oxidative stress. Adding vitamin C to the cryoprotectant doubled the survival ratio in Arabidopsis thaliana 60-h seedlings (seedlings after 60-h germination) cryopreservation. In this study, the metabolites and transcriptional profiling of 60-h seedlings were analyzed in both the control cryopreservation procedure (CCP) and an improved cryopreservation procedure (ICP) to reveal the mechanism of plant cell response to oxidative stress from cryopreservation. Reactive oxygen species (ROS) and peroxidation levels reached a peak after rapid cooling-warming in CCP, which were higher than that in ICP. In addition, gene regulation was significantly increased in CCP and decreased in ICP during rapid cooling-warming. Before cryogenic treatment, the number of specifically regulated genes was nearly 10 times higher in ICP dehydration than CCP dehydration. Among these genes, DREBs/CBFs were beneficial to cope with cryoinjury, and calcium-binding protein, OXI1, WRKY and MYB family members as key factors in ROS signal transduction activated the ROS-producing and ROS-scavenging networks including AsA-GSH and GPX cycles involved in scavenging H2O2. Finally, elevated antioxidant status and oxidative stress response in the improved dehydration enhanced seedling resistance to cryogenic treatment, maintained ROS homeostasis and improved cell recovery after cryopreservation.

  16. A Quantitative Profiling Tool for Diverse Genomic Data Types Reveals Potential Associations between Chromatin and Pre-mRNA Processing.

    Science.gov (United States)

    Kremsky, Isaac; Bellora, Nicolás; Eyras, Eduardo

    2015-01-01

    High-throughput sequencing, and genome-based datasets in general, are often represented as profiles centered at reference points to study the association of protein binding and other signals to particular regulatory mechanisms. Although these profiles often provide compelling evidence of these associations, they do not provide a quantitative assessment of the enrichment, which makes the comparison between signals and conditions difficult. In addition, a number of biases can confound profiles, but are rarely accounted for in the tools currently available. We present a novel computational method, ProfileSeq, for the quantitative assessment of biological profiles to provide an exact, nonparametric test that specific regions of the test profile have higher or lower signal densities than a control set. The method is applicable to high-throughput sequencing data (ChIP-Seq, GRO-Seq, CLIP-Seq, etc.) and to genome-based datasets (motifs, etc.). We validate ProfileSeq by recovering and providing a quantitative assessment of several results reported before in the literature using independent datasets. We show that input signal and mappability have confounding effects on the profile results, but that normalizing the signal by input reads can eliminate these biases while preserving the biological signal. Moreover, we apply ProfileSeq to ChIP-Seq data for transcription factors, as well as for motif and CLIP-Seq data for splicing factors. In all examples considered, the profiles were robust to biases in mappability of sequencing reads. Furthermore, analyses performed with ProfileSeq reveal a number of putative relationships between transcription factor binding to DNA and splicing factor binding to pre-mRNA, adding to the growing body of evidence relating chromatin and pre-mRNA processing. ProfileSeq provides a robust way to quantify genome-wide coordinate-based signal. Software and documentation are freely available for academic use at https://bitbucket.org/regulatorygenomicsupf/profileseq/.

  17. Transcriptome profiling and comparative analysis of Panax ginseng adventitious roots

    Directory of Open Access Journals (Sweden)

    Murukarthick Jayakodi

    2014-10-01

    Conclusion: This study will provide a comprehensive insight into the transcriptome of ginseng adventitious roots, and a way for successful transcriptome analysis and profiling of resource plants with less genomic information. The transcriptome profiling data generated in this study are available in our newly created adventitious root transcriptome database (http://im-crop.snu.ac.kr/transdb/index.php for public use.

  18. Computational gene expression profiling under salt stress reveals patterns of co-expression.

    Science.gov (United States)

    Sanchita; Sharma, Ashok

    2016-03-01

    Plants respond differently to environmental conditions. Among various abiotic stresses, salt stress is a condition where excess salt in soil causes inhibition of plant growth. To understand the response of plants to the stress conditions, identification of the responsible genes is required. Clustering is a data mining technique used to group the genes with similar expression. The genes of a cluster show similar expression and function. We applied clustering algorithms on gene expression data of Solanum tuberosum showing differential expression in Capsicum annuum under salt stress. The clusters, which were common in multiple algorithms were taken further for analysis. Principal component analysis (PCA) further validated the findings of other cluster algorithms by visualizing their clusters in three-dimensional space. Functional annotation results revealed that most of the genes were involved in stress related responses. Our findings suggest that these algorithms may be helpful in the prediction of the function of co-expressed genes.

  19. Computational gene expression profiling under salt stress reveals patterns of co-expression

    Directory of Open Access Journals (Sweden)

    Sanchita

    2016-03-01

    Full Text Available Plants respond differently to environmental conditions. Among various abiotic stresses, salt stress is a condition where excess salt in soil causes inhibition of plant growth. To understand the response of plants to the stress conditions, identification of the responsible genes is required. Clustering is a data mining technique used to group the genes with similar expression. The genes of a cluster show similar expression and function. We applied clustering algorithms on gene expression data of Solanum tuberosum showing differential expression in Capsicum annuum under salt stress. The clusters, which were common in multiple algorithms were taken further for analysis. Principal component analysis (PCA further validated the findings of other cluster algorithms by visualizing their clusters in three-dimensional space. Functional annotation results revealed that most of the genes were involved in stress related responses. Our findings suggest that these algorithms may be helpful in the prediction of the function of co-expressed genes.

  20. Profiling of human myotubes reveals an intrinsic proteomic signature associated with type 2 diabetes

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    Lubna Al-Khalili

    2014-03-01

    Full Text Available The development of insulin resistance and type 2 diabetes (T2D involves a complex array of metabolic defects in skeletal muscle. An in vitro cell culture system excludes the acute effects of external systemic factors existing in vivo. Thus, we aimed to determine whether intrinsic differences in the protein profile exist in cultured myotubes derived from T2D versus normal glucose tolerant (NGT healthy people. Applying two dimensional difference gel electrophoresis technology (2-D DIGE, the abundance of 47 proteins differed in myotubes derived from T2D patients versus NGT donors. Proteins involved in fatty acid and amino acid metabolism, TCA cycle, mitochondrial function, mRNA processing, DNA repair and cell survival showed higher abundance, while proteins associated with redox signaling (PARK7; Parkinson disease 7, glutathione metabolism (glutathione S-transferase, GST, isoforms T1, P1 and M2, and protein dynamics (heat shock protein, HSP, isoform B1 and 90A showed reduced abundance in myotubes derived from T2D versus NGT donors. Consistent with our proteome analysis results, the level of total glutathione was reduced in myotubes obtained from T2D versus NGT donors. Taken together, our data provide evidence for intrinsic differences in the profile of proteins involved in energy metabolism, cellular oxidative stress, protein dynamics and gene regulation in myotubes derived from T2D patients. These differences thereby suggest a genetic or epigenetic influence on protein content level, which can be further investigated to understand the molecular underpinnings of T2D progression and lead to new therapeutic approaches.

  1. Transcriptional profiling reveals functional dichotomy between human slan+ non-classical monocytes and myeloid dendritic cells.

    Science.gov (United States)

    van Leeuwen-Kerkhoff, Nathalie; Lundberg, Kristina; Westers, Theresia M; Kordasti, Shahram; Bontkes, Hetty J; de Gruijl, Tanja D; Lindstedt, Malin; van de Loosdrecht, Arjan A

    2017-10-01

    Human 6-sulfo LacNac-positive (slan+) cells have been subject to a paradigm debate. They have previously been classified as a distinct dendritic cell (DC) subset. However, evidence has emerged that they may be more related to monocytes than to DCs. To gain deeper insight into the functional specialization of slan+ cells, we have compared them with both conventional myeloid DC subsets (CD1c+ and CD141+) in human peripheral blood (PB). With the use of genome-wide transcriptional profiling, as well as functional tests, we clearly show that slan+ cells form a distinct, non-DC-like population. They cluster away from both DC subsets, and their gene-expression profile evidently suggests involvement in distinct inflammatory processes. An extensive transcriptional meta-analysis confirmed the relationship of slan+ cells with the monocytic compartment rather than with DCs. From a functional perspective, their ability to prime CD4+ and CD8+ T cells is relatively low. Combined with the finding that "antigen presentation by MHC class II" is at the top of under-represented pathways in slan+ cells, this points to a minimal role in directing adaptive T cell immunity. Rather, the higher expression levels of complement receptors on their cell surface, together with their high secretion of IL-1β and IL-6, imply a specific role in innate inflammatory processes, which is consistent with their recent identification as non-classical monocytes. This study extends our knowledge on DC/monocyte subset biology under steady-state conditions and contributes to our understanding of their role in immune-mediated diseases and their potential use in immunotherapeutic strategies. © Society for Leukocyte Biology.

  2. A strong anti-inflammatory signature revealed by liver transcription profiling of Tmprss6-/- mice.

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    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.

  3. Single-cell profiling reveals GPCR heterogeneity and functional patterning during neuroinflammation.

    Science.gov (United States)

    Tischner, Denise; Grimm, Myriam; Kaur, Harmandeep; Staudenraus, Daniel; Carvalho, Jorge; Looso, Mario; Günther, Stefan; Wanke, Florian; Moos, Sonja; Siller, Nelly; Breuer, Johanna; Schwab, Nicholas; Zipp, Frauke; Waisman, Ari; Kurschus, Florian C; Offermanns, Stefan; Wettschureck, Nina

    2017-08-03

    GPCR expression was intensively studied in bulk cDNA of leukocyte populations, but limited data are available with respect to expression in individual cells. Here, we show a microfluidic-based single-cell GPCR expression analysis in primary T cells, myeloid cells, and endothelial cells under naive conditions and during experimental autoimmune encephalomyelitis, the mouse model of multiple sclerosis. We found that neuroinflammation induces characteristic changes in GPCR heterogeneity and patterning, and we identify various functionally relevant subgroups with specific GPCR profiles among spinal cord-infiltrating CD4 T cells, macrophages, microglia, or endothelial cells. Using GPCRs CXCR4, S1P1, and LPHN2 as examples, we show how this information can be used to develop new strategies for the functional modulation of Th17 cells and activated endothelial cells. Taken together, single-cell GPCR expression analysis identifies functionally relevant subpopulations with specific GPCR repertoires and provides a basis for the development of new therapeutic strategies in immune disorders.

  4. Mycotoxigenic Potentials of Fusarium Species in Various Culture Matrices Revealed by Mycotoxin Profiling

    Science.gov (United States)

    Shi, Wen; Tan, Yanglan; Wang, Shuangxia; Gardiner, Donald M.; De Saeger, Sarah; Liao, Yucai; Wang, Cheng; Fan, Yingying; Wang, Zhouping; Wu, Aibo

    2016-01-01

    In this study, twenty of the most common Fusarium species were molecularly characterized and inoculated on potato dextrose agar (PDA), rice and maize medium, where thirty three targeted mycotoxins, which might be the secondary metabolites of the identified fungal species, were detected by liquid chromatography–tandem mass spectrometry (LC-MS/MS). Statistical analysis was performed with principal component analysis (PCA) to characterize the mycotoxin profiles for the twenty fungi, suggesting that these fungi species could be discriminated and divided into three groups as follows. Group I, the fusaric acid producers, were defined into two subgroups, namely subgroup I as producers of fusaric acid and fumonisins, comprising of F. proliferatum, F. verticillioides, F. fujikuroi and F. solani, and subgroup II considered to only produce fusaric acid, including F. temperatum, F. subglutinans, F. musae, F. tricinctum, F. oxysporum, F. equiseti, F. sacchari, F. concentricum, F. andiyazi. Group II, as type A trichothecenes producers, included F. langsethiae, F. sporotrichioides, F. polyphialidicum, while Group III were found to mainly produce type B trichothecenes, comprising of F. culmorum, F. poae, F. meridionale and F. graminearum. A comprehensive picture, which presents the mycotoxin-producing patterns by the selected fungal species in various matrices, is obtained for the first time, and thus from an application point of view, provides key information to explore mycotoxigenic potentials of Fusarium species and forecast the Fusarium infestation/mycotoxins contamination. PMID:28035973

  5. cDNA-AFLP transcriptional profiling reveals genes expressed during flower development in Oncidium Milliongolds.

    Science.gov (United States)

    Qian, X; Gong, M J; Wang, C X; Tian, M

    2014-02-21

    The flower developmental process, which is crucial to the whole lifecycle of higher plants, is influenced by both environmental and endogenous factors. The genus Oncidium is commercially important for cut flower and houseplant industry and is ideal for flower development studies. Using cDNA-amplified restriction fragment length polymorphism analysis, we profiled transcripts that are differentially expressed during flower development of Oncidium Milliongolds. A total of 15,960 transcript-derived fragments were generated, with 114 primer sets. Of these, 1248 were sequenced, producing 993 readable sequences. BLASTX/N analysis showed that 833 of the 993 transcripts showed homology to genes in the NCBI databases, exhibiting functions involved in various processes, such as signal transduction, energy conversion, metabolism, and gene expression regulation. The full-length mRNAs of SUCROSE SYNTHASE 1 (SUS1) and LEAFY (LFY) were cloned, and their expression patterns were characterized. The results showed that the expression levels of SUS1 and LFY were similar during flower development. To confirm the function of SUS1 in flower buds, carbohydrate content and sucrose synthase activity were determined. The results showed that changes in sucrose content and sucrose synthase activity reflected SUS1 expression levels. Collectively, these results indicate that SUS1 influences flower development by regulating LFY expression levels through changing the sucrose content of flower buds.

  6. Qualitative Analysis of Commercial Social Network Profiles

    Science.gov (United States)

    Melendez, Lester; Wolfson, Ouri; Adjouadi, Malek; Rishe, Naphtali

    Social-networking sites have become an integral part of many users' daily internet routine. Commercial enterprises have been quick to recognize this and are subsequently creating profiles for many of their products and services. Commercial enterprises use social network profiles to target and interact with potential customers as well as to provide a gateway for users of the product or service to interact with each other. Many commercial enterprises use the statistics from their product or service's social network profile to tout the popularity and success of the product or service being showcased. They will use statistics such as number of friends, number of daily visits, number of interactions, and other similar measurements to quantify their claims. These statistics are often not a clear indication of the true popularity and success of the product. In this chapter the term product is used to refer to any tangible or intangible product, service, celebrity, personality, film, book, or other entity produced by a commercial enterprise.

  7. Proteomic and transcriptomic analysis reveals evidence for the basis ...

    African Journals Online (AJOL)

    Proteomic and transcriptomic analysis reveals evidence for the basis of salt sensitivity in Thai jasmine rice ( Oryza sativa L. cv. ... African Journal of Biotechnology ... the posttranscriptional mechanisms controlling protein expression levels were not as efficient as in Pokkali, indicating targets for future genetic improvement.

  8. Microarray analysis of gene expression profiles in ripening pineapple fruits

    Directory of Open Access Journals (Sweden)

    Koia Jonni H

    2012-12-01

    Full Text Available Abstract Background 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. Results 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. Conclusions 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

  9. 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

  10. Mass spectrometric profiling reveals association of N-glycan patterns with epithelial ovarian cancer progression.

    Science.gov (United States)

    Chen, Huanhuan; Deng, Zaian; Huang, Chuncui; Wu, Hongmei; Zhao, Xia; Li, Yan

    2017-07-01

    Aberrant changes of N-glycan modifications on proteins have been linked to various diseases including different cancers, suggesting possible avenue for exploring their etiologies based on N-glycomic analysis. Changes in N-glycan patterns during epithelial ovarian cancer development have so far been investigated mainly using serum, plasma, ascites, and cell lines. However, changes in patterns of N-glycans in tumor tissues during epithelial ovarian cancer progression have remained largely undefined. To investigate whether changes in N-glycan patterns correlate with oncogenesis and progression of epithelial ovarian cancer, we profiled N-glycans from formalin-fixed paraffin-embedded tissue slides using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and quantitatively compared among different pathological grades of epithelial ovarian cancer and healthy controls. Our results show that among the 80 compositions of N-glycan detected, expression levels of high-mannose type were higher in epithelial ovarian cancer samples than that observed in healthy controls, accompanied by reduced levels of hybrid-type glycans. By applying receiver operating characteristic analysis, we show that a combined panel composed of four high-mannose and three fucosylated neutral complex N-glycans allows for good discrimination of epithelial ovarian cancer from healthy controls. Furthermore, using a statistical analysis of variance assay, we found that different N-glycan patterns, including 2 high-mannose-type, 2 fucosylated and sialylated complex structures, and 10 fucosylated neutral complex N-glycans, exhibited specific changes in N-glycan abundance across epithelial ovarian cancer grades. Together, our results provide strong evidence that N-glycomic changes are a strong indicator for epithelial ovarian cancer pathological grades and should provide avenues to identify novel biomarkers for epithelial ovarian cancer diagnosis and monitoring.

  11. Global gene expression profiling reveals SPINK1 as a potential hepatocellular carcinoma marker.

    Directory of Open Access Journals (Sweden)

    Aileen Marshall

    Full Text Available Liver cirrhosis is the most important risk factor for hepatocellular carcinoma (HCC but the role of liver disease aetiology in cancer development remains under-explored. We investigated global gene expression profiles from HCC arising in different liver diseases to test whether HCC development is driven by expression of common or different genes, which could provide new diagnostic markers or therapeutic targets.Global gene expression profiling was performed for 4 normal (control livers as well as 8 background liver and 7 HCC from 3 patients with hereditary haemochromatosis (HH undergoing surgery. In order to investigate different disease phenotypes causing HCC, the data were compared with public microarray repositories for gene expression in normal liver, hepatitis C virus (HCV cirrhosis, HCV-related HCC (HCV-HCC, hepatitis B virus (HBV cirrhosis and HBV-related HCC (HBV-HCC. Principal component analysis and differential gene expression analysis were carried out using R Bioconductor. Liver disease-specific and shared gene lists were created and genes identified as highly expressed in hereditary haemochromatosis HCC (HH-HCC were validated using quantitative RT-PCR. Selected genes were investigated further using immunohistochemistry in 86 HCC arising in liver disorders with varied aetiology. Using a 2-fold cut-off, 9 genes were highly expressed in all HCC, 11 in HH-HCC, 270 in HBV-HCC and 9 in HCV-HCC. Six genes identified by microarray as highly expressed in HH-HCC were confirmed by RT qPCR. Serine peptidase inhibitor, Kazal type 1 (SPINK1 mRNA was very highly expressed in HH-HCC (median fold change 2291, p = 0.0072 and was detected by immunohistochemistry in 91% of HH-HCC, 0% of HH-related cirrhotic or dysplastic nodules and 79% of mixed-aetiology HCC.HCC, arising from diverse backgrounds, uniformly over-express a small set of genes. SPINK1, a secretory trypsin inhibitor, demonstrated potential as a diagnostic HCC marker and should be

  12. Microdialysis Sampling from Wound Fluids Enables Quantitative Assessment of Cytokines, Proteins, and Metabolites Reveals Bone Defect-Specific Molecular Profiles.

    Science.gov (United States)

    Förster, Yvonne; Schmidt, Johannes R; Wissenbach, Dirk K; Pfeiffer, Susanne E M; Baumann, Sven; Hofbauer, Lorenz C; von Bergen, Martin; Kalkhof, Stefan; Rammelt, Stefan

    2016-01-01

    Bone healing involves a variety of different cell types and biological processes. Although certain key molecules have been identified, the molecular interactions of the healing progress are not completely understood. Moreover, a clinical routine for predicting the quality of bone healing after a fracture in an early phase is missing. This is mainly due to a lack of techniques to comprehensively screen for cytokines, growth factors and metabolites at their local site of action. Since all soluble molecules of interest are present in the fracture hematoma, its in-depth assessment could reveal potential markers for the monitoring of bone healing. Here, we describe an approach for sampling and quantification of cytokines and metabolites by using microdialysis, combined with solid phase extractions of proteins from wound fluids. By using a control group with an isolated soft tissue wound, we could reveal several bone defect-specific molecular features. In bone defect dialysates the neutrophil chemoattractants CXCL1, CXCL2 and CXCL3 were quantified with either a higher or earlier response compared to dialysate from soft tissue wound. Moreover, by analyzing downstream adaptions of the cells on protein level and focusing on early immune response, several proteins involved in the immune cell migration and activity could be identified to be specific for the bone defect group, e.g. immune modulators, proteases and their corresponding inhibitors. Additionally, the metabolite screening revealed different profiles between the bone defect group and the control group. In summary, we identified potential biomarkers to indicate imbalanced healing progress on all levels of analysis.

  13. Microdialysis Sampling from Wound Fluids Enables Quantitative Assessment of Cytokines, Proteins, and Metabolites Reveals Bone Defect-Specific Molecular Profiles.

    Directory of Open Access Journals (Sweden)

    Yvonne Förster

    Full Text Available Bone healing involves a variety of different cell types and biological processes. Although certain key molecules have been identified, the molecular interactions of the healing progress are not completely understood. Moreover, a clinical routine for predicting the quality of bone healing after a fracture in an early phase is missing. This is mainly due to a lack of techniques to comprehensively screen for cytokines, growth factors and metabolites at their local site of action. Since all soluble molecules of interest are present in the fracture hematoma, its in-depth assessment could reveal potential markers for the monitoring of bone healing. Here, we describe an approach for sampling and quantification of cytokines and metabolites by using microdialysis, combined with solid phase extractions of proteins from wound fluids. By using a control group with an isolated soft tissue wound, we could reveal several bone defect-specific molecular features. In bone defect dialysates the neutrophil chemoattractants CXCL1, CXCL2 and CXCL3 were quantified with either a higher or earlier response compared to dialysate from soft tissue wound. Moreover, by analyzing downstream adaptions of the cells on protein level and focusing on early immune response, several proteins involved in the immune cell migration and activity could be identified to be specific for the bone defect group, e.g. immune modulators, proteases and their corresponding inhibitors. Additionally, the metabolite screening revealed different profiles between the bone defect group and the control group. In summary, we identified potential biomarkers to indicate imbalanced healing progress on all levels of analysis.

  14. Genomic DNA Methylation Analyses Reveal the Distinct Profiles in Castor Bean Seeds with Persistent Endosperms1

    Science.gov (United States)

    Yang, Tianquan; Dong, Xue; Li, De-Zhu

    2016-01-01

    Investigations of genomic DNA methylation in seeds have been restricted to a few model plants. The endosperm genomic DNA hypomethylation has been identified in angiosperm, but it is difficult to dissect the mechanism of how this hypomethylation is established and maintained because endosperm is ephemeral and disappears with seed development in most dicots. Castor bean (Ricinus communis), unlike Arabidopsis (Arabidopsis thaliana), endosperm is persistent throughout seed development, providing an excellent model in which to dissect the mechanism of endosperm genomic hypomethylation in dicots. We characterized the DNA methylation-related genes encoding DNA methyltransferases and demethylases and analyzed their expression profiles in different tissues. We examined genomic methylation including CG, CHG, and CHH contexts in endosperm and embryo tissues using bisulfite sequencing and revealed that the CHH methylation extent in endosperm and embryo was, unexpectedly, substantially higher than in previously studied plants, irrespective of the CHH percentage in their genomes. In particular, we found that the endosperm exhibited a global reduction in CG and CHG methylation extents relative to the embryo, markedly switching global gene expression. However, CHH methylation occurring in endosperm did not exhibit a significant reduction. Combining with the expression of 24-nucleotide small interfering RNAs (siRNAs) mapped within transposable element (TE) regions and genes involved in the RNA-directed DNA methylation pathway, we demonstrate that the 24-nucleotide siRNAs played a critical role in maintaining CHH methylation and repressing the activation of TEs in persistent endosperm development. This study discovered a novel genomic DNA methylation pattern and proposes the potential mechanism occurring in dicot seeds with persistent endosperm. PMID:27208275

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

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    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.

  16. Transcriptional Profiling of Human Endocervical Tissues Reveals Distinct Gene Expression in the Follicular and Luteal Phases of the Menstrual Cycle.

    Science.gov (United States)

    Yildiz-Arslan, Sevim; Coon, John S; Hope, Thomas J; Kim, J Julie

    2016-06-01

    The endocervix plays an important role in providing appropriate protective mechanisms of the upper female reproductive tract (FRT) while at the same time providing the appropriate milieu for sperm transport. Hormone fluctuations throughout the menstrual cycle contribute to changes in the mucosal environment that render the FRT vulnerable to infectious diseases. The objective of this study was to identify genes in human endocervix tissues that were differentially expressed in the follicular versus the luteal phases of the menstrual cycle using gene expression profiling. A microarray using the IIlumina platform was performed with eight endocervix tissues from follicular and four tissues from luteal phases of the menstrual cycle. Data analysis revealed significant differential expression of 110 genes between the two phases, with a P value stress, and immune cell regulation were predominately expressed. Using samples from additional patients' tissues, select genes were confirmed by quantitative real-time PCR; immunohistochemical staining was also done to examine protein levels. This is the first microarray analysis comparing gene expression in endocervix tissues in cycling women. This study identified key genes and molecular pathways that were differentially regulated during the menstrual cycle. © 2016 by the Society for the Study of Reproduction, Inc.

  17. Genome-scale expression and transcription factor binding profiles reveal therapeutic targets in transgenic ERG myeloid leukemia.

    Science.gov (United States)

    Goldberg, Liat; Tijssen, Marloes R; Birger, Yehudit; Hannah, Rebecca L; Kinston, Sarah J; Schütte, Judith; Beck, Dominik; Knezevic, Kathy; Schiby, Ginette; Jacob-Hirsch, Jasmine; Biran, Anat; Kloog, Yoel; Marcucci, Guido; Bloomfield, Clara D; Aplan, Peter D; Pimanda, John E; Göttgens, Berthold; Izraeli, Shai

    2013-10-10

    The ETS transcription factor ERG plays a central role in definitive hematopoiesis, and its overexpression in acute myeloid leukemia (AML) is associated with a stem cell signature and poor prognosis. Yet how ERG causes leukemia is unclear. Here we show that pan-hematopoietic ERG expression induces an early progenitor myeloid leukemia in transgenic mice. Integrated genome-scale analysis of gene expression and ERG binding profiles revealed that ERG activates a transcriptional program similar to human AML stem/progenitor cells and to human AML with high ERG expression. This transcriptional program was associated with activation of RAS that was required for leukemia cells growth in vitro and in vivo. We further show that ERG induces expression of the Pim1 kinase oncogene through a novel hematopoietic enhancer validated in transgenic mice and human CD34(+) normal and leukemic cells. Pim1 inhibition disrupts growth and induces apoptosis of ERG-expressing leukemic cells. The importance of the ERG/PIM1 axis is further underscored by the poorer prognosis of AML highly expressing ERG and PIM1. Thus, integrative genomic analysis demonstrates that ERG causes myeloid progenitor leukemia characterized by an induction of leukemia stem cell transcriptional programs. Pim1 and the RAS pathway are potential therapeutic targets of these high-risk leukemias.

  18. The first succinylome profile of Trichophyton rubrum reveals lysine succinylation on proteins involved in various key cellular processes.

    Science.gov (United States)

    Xu, Xingye; Liu, Tao; Yang, Jian; Chen, Lihong; Liu, Bo; Wei, Candong; Wang, Lingling; Jin, Qi

    2017-08-04

    Dermatophytes, the most common cause of fungal infections, affect millions of individuals worldwide. They pose a major threat to public health because of the severity and longevity of infections caused by dermatophytes and their refractivity to therapy. Trichophyton rubrum (T. rubrum), the most common dermatophyte species, is a promising model organism for dermatophyte research. Post-translational modifications (PTMs) have been shown to be essential for many biological processes, particularly in the regulation of key cellular processes that contribute to pathogenicity. Although PTMs have important roles, little is known about their roles in T. rubrum and other dermatophytes. Succinylation is a new PTM that has recently been identified. In this study, we assessed the proteome-wide succinylation profile of T. rubrum. This study sought to systematically identify the succinylated sites and proteins in T. rubrum and to reveal the roles of succinylated proteins in various cellular processes as well as the differences in the succinylation profiles in different growth stages of the T. rubrum life cycle. A total of 569 succinylated lysine sites were identified in 284 proteins. These succinylated proteins are involved in various cellular processes, such as metabolism, translation and epigenetic regulation. Additionally, 24 proteins related to pathogenicity were found to be succinylated. Comparison of the succinylome at the conidia and mycelia stages revealed that most of the succinylated proteins and sites were growth-stage specific. In addition, the succinylation modifications on histone and ribosomal proteins were significantly different between these two growth stages. Moreover, the sequence features surrounding the succinylated sites were different in the two stages, thus indicating the specific recognition of succinyltransferases in each growth phase. In this study, we explored the first T. rubrum succinylome, which is also the first PTM analysis of dermatophytes

  19. Proteomic Profiling Reveals Upregulated Protein Expression of Hsp70 in Keloids

    Directory of Open Access Journals (Sweden)

    Ju Hee Lee

    2013-01-01

    Full Text Available Background. The biochemical characteristics of keloid-derived fibroblasts differ from those of adjacent normal fibroblasts, and these differences are thought to be the cause of abnormal fibrosis. Therefore, we investigated the characteristic proteins that are differentially expressed in keloid-derived fibroblasts using proteomics tools. Objective. We attempted to investigate the novel proteins that play important roles in the pathophysiology of keloids. Methods. Proteomics analysis was performed to identify differentially expressed proteins in keloid-derived fibroblasts. Keloid-derived fibroblasts and adjacent normal fibroblasts were analyzed with 2-DAGE. We validated these proteins with immunoblot analysis, real-time RT-PCR, and immunohistochemistry. Results. Sixteen differentially expressed protein spots were identified in keloid-derived fibroblasts. Among them, heat shock protein 70 (Hsp70 was specifically upregulated in keloid-derived fibroblasts. Also, immunohistochemistry and western blot analysis revealed increased Hsp70, TGF-β, and PCNA expressions in keloids compared to normal tissue. Conclusion. Hsp70 is overexpressed in keloid fibroblasts and tissue. The overexpression of Hsp70 may be involved in the pathogenesis of keloids, and the inhibition of Hsp70 could be a new therapeutic tool for the treatment of keloids.

  20. Transcriptomic profile reveals gender-specific molecular mechanisms driving multiple sclerosis progression.

    Directory of Open Access Journals (Sweden)

    Haritz Irizar

    Full Text Available BACKGROUND: Although the most common clinical presentation of multiple sclerosis (MS is the so called Relapsing-Remitting MS (RRMS, the molecular mechanisms responsible for its progression are currently unknown. To tackle this problem, a whole-genome gene expression analysis has been performed on RRMS patients. RESULTS: The comparative analysis of the Affymetrix Human Gene 1.0 ST microarray data from peripheral blood leucocytes obtained from 25 patients in remission and relapse and 25 healthy subjects has revealed 174 genes altered in both remission and relapse, a high proportion of them showing what we have called "mirror pattern": they are upregulated in remission and downregulated in relapse or vice versa. The coexpression analysis of these genes has shown that they are organized in three female-specific and one male-specific modules. CONCLUSIONS: The interpretation of the modules of the coexpression network suggests that Epstein-Barr virus (EBV reactivation of B cells happens in MS relapses; however, qPCR expression data of the viral genes supports that hypothesis only in female patients, reinforcing the notion that different molecular processes drive disease progression in females and males. Besides, we propose that the "primed" state showed by neutrophils in women is an endogenous control mechanism triggered to keep EBV reactivation under control through vitamin B12 physiology. Finally, our results also point towards an important sex-specific role of non-coding RNA in MS.

  1. Genome-wide DNA methylation profiling reveals parity-associated hypermethylation of FOXA1.

    Science.gov (United States)

    Ghosh, Sagar; Gu, Fei; Wang, Chou-Miin; Lin, Chun-Lin; Liu, Joseph; Wang, Howard; Ravdin, Peter; Hu, Yanfen; Huang, Tim H M; Li, Rong

    2014-10-01

    Early pregnancy in women by the age of 20 is known to have a profound effect on reduction of lifelong breast cancer risk as compared to their nulliparous counterparts. Additional pregnancies further enhance the protection against breast cancer development. Nationwide trend of delayed pregnancy may contribute to the recently reported increase in the incidence of advanced breast cancer among young women in this country. The underlying mechanism for the parity-associated reduction of breast cancer risk is not clearly understood. The purpose of the current study is to use whole-genome DNA methylation profiling to explore a potential association between parity and epigenetic changes in breast tissue from women with early parity and nulliparity. Breast tissue was collected from age-matched cancer-free women with early parity (age parity-associated hypermethylated genes were further verified by locus-specific pyrosequencing, using an expanded cohort of parous (n = 19) and nulliparous (n = 16) women that included the initial samples used in the global analysis. Our study identified six genes that are hypermethylated in the parous group (P parity-associated hypermethylation at multiple CpG islands of the FOXA1 gene, which encodes a pioneer factor that facilitates chromatin binding of estrogen receptor α. Our work identifies several potential methylation biomarkers for parity-associated breast cancer risk assessment. In addition, the results are consistent with the notion that parity-associated epigenetic silencing of FOXA1 contributes to long-term attenuation of the estrogenic impact on breast cancer development.

  2. Single-cell profiling reveals heterogeneity and functional patterning of GPCR expression in the vascular system.

    Science.gov (United States)

    Kaur, H; Carvalho, J; Looso, M; Singh, P; Chennupati, R; Preussner, J; Günther, S; Albarrán-Juárez, J; Tischner, D; Classen, S; Offermanns, S; Wettschureck, N

    2017-06-16

    G-protein-coupled receptor (GPCR) expression is extensively studied in bulk cDNA, but heterogeneity and functional patterning of GPCR expression in individual vascular cells is poorly understood. Here, we perform a microfluidic-based single-cell GPCR expression analysis in primary smooth muscle cells (SMC) and endothelial cells (EC). GPCR expression is highly heterogeneous in all cell types, which is confirmed in reporter mice, on the protein level and in human cells. Inflammatory activation in murine models of sepsis or atherosclerosis results in characteristic changes in the GPCR repertoire, and we identify functionally relevant subgroups of cells that are characterized by specific GPCR patterns. We further show that dedifferentiating SMC upregulate GPCRs such as Gpr39, Gprc5b, Gprc5c or Gpr124, and that selective targeting of Gprc5b modulates their differentiation state. Taken together, single-cell profiling identifies receptors expressed on pathologically relevant subpopulations and provides a basis for the development of new therapeutic strategies in vascular diseases.

  3. 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.

  4. Metabolic profiling reveals metabolic shifts in Arabidopsis plants grown under different light conditions.

    Science.gov (United States)

    Jänkänpää, Hanna Johansson; Mishra, Yogesh; Schröder, Wolfgang P; Jansson, Stefan

    2012-10-01

    Plants have tremendous capacity to adjust their morphology, physiology and metabolism in response to changes in growing conditions. Thus, analysis solely of plants grown under constant conditions may give partial or misleading indications of their responses to the fluctuating natural conditions in which they evolved. To obtain data on growth condition-dependent differences in metabolite levels, we compared leaf metabolite profiles of Arabidopsis thaliana growing under three constant laboratory light conditions: 30 [low light (LL)], 300 [normal light (NL)] and 600 [high light (HL)]µmol photons m(-2) s(-1). We also shifted plants to the field and followed their metabolite composition for 3 d. Numerous compounds showed light intensity-dependent accumulation, including: many sugars and sugar derivatives (fructose, sucrose, glucose, galactose and raffinose); tricarboxylic acid (TCA) cycle intermediates; and amino acids (ca. 30% of which were more abundant under HL and 60% under LL). However, the patterns differed after shifting NL plants to field conditions. Levels of most identified metabolites (mainly amino acids, sugars and TCA cycle intermediates) rose after 2 h and peaked after 73 h, indicative of a 'biphasic response' and 'circadian' effects. The results provide new insight into metabolomic level mechanisms of plant acclimation, and highlight the role of known protectants under natural conditions. © 2012 Blackwell Publishing Ltd.

  5. Gene co-expression networks and profiles reveal potential biomarkers of boar taint in pigs

    DEFF Research Database (Denmark)

    Drag, Markus; Skinkyté-Juskiené, R.; Do, D. N.

    and enrichment analysis and semantic filtering revealed the GO terms “catalytic activity” and “transferase activity” to be overrepresented (p steroid hormones. Extraction of hub...... active tissue. GOseq was used to find enriched gene ontology (GO) terms and REVIGO was used to filter semantic similarities. In both liver and testis, a GO termed “oxidoreductase activity” was enriched (p steroid metabolism, including androstenone...... synthesis. In testis, >80 DE genes were functionally classified by the PANTHER tool to “Gonadotropin releasing hormone receptor” and “Wnt signaling” pathways which play a role in reproductive maturation and proliferation of spermatogonia, respectively. WGCNA was used to build co-expression modules...

  6. Genome-Wide Transcriptional Profiling Reveals Connective Tissue Mast Cell Accumulation in Bronchopulmonary Dysplasia

    Science.gov (United States)

    Bhattacharya, Soumyaroop; Go, Diana; Krenitsky, Daria L.; Huyck, Heidi L.; Solleti, Siva Kumar; Lunger, Valerie A.; Metlay, Leon; Srisuma, Sorachai; Wert, Susan E.; Pryhuber, Gloria S.

    2012-01-01

    Rationale: Bronchopulmonary dysplasia (BPD) is a major complication of premature birth. Risk factors for BPD are complex and include prenatal infection and O2 toxicity. BPD pathology is equally complex and characterized by inflammation and dysmorphic airspaces and vasculature. Due to the limited availability of clinical samples, an understanding of the molecular pathogenesis of this disease and its causal mechanisms and associated biomarkers is limited. Objectives: Apply genome-wide expression profiling to define pathways affected in BPD lungs. Methods: Lung tissue was obtained at autopsy from 11 BPD cases and 17 age-matched control subjects without BPD. RNA isolated from these tissue samples was interrogated using microarrays. Standard gene selection and pathway analysis methods were applied to the data set. Abnormal expression patterns were validated by quantitative reverse transcriptase–polymerase chain reaction and immunohistochemistry. Measurements and Main Results: We identified 159 genes differentially expressed in BPD tissues. Pathway analysis indicated previously appreciated (e.g., DNA damage regulation of cell cycle) as well as novel (e.g., B-cell development) biological functions were affected. Three of the five most highly induced genes were mast cell (MC)-specific markers. We confirmed an increased accumulation of connective tissue MCTC (chymase expressing) mast cells in BPD tissues. Increased expression of MCTC markers was also demonstrated in an animal model of BPD-like pathology. Conclusions: We present a unique genome-wide expression data set from human BPD lung tissue. Our data provide information on gene expression patterns associated with BPD and facilitated the discovery that MCTC accumulation is a prominent feature of this disease. These observations have significant clinical and mechanistic implications. PMID:22723293

  7. Analysis of paediatric prescribing profiles in two health-funding ...

    African Journals Online (AJOL)

    Setting. Two industry databases, one covering a prepaid health maintenance organisation (HMO), the other providing a chronic medication programme for medical schemes and their members. Main outcome measures. Comparison of prescribing profiles of specialists and GPs. Main results. Data from the HMO revealed that ...

  8. 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

  9. 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.

  10. 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.

  11. Analysis of River Profiles in northwestern Bhutan

    Science.gov (United States)

    de Palézieux, Larissa; Leith, Kerry; Loew, Simon

    2017-04-01

    With large alluvial plains, narrow gorges, prominent knick points, and chains of terraces or cut-off ridges, the deeply-incised valleys in Bhutan reflect an environment of diverse erosional activity. Topography ranges from 97 m to 7570 m, with characteristic postglacial landscapes typically located above ca 4200 m. The lower latitudes below ca 3000 m show high relief and terraced or linear hillslopes indicative of a fluvial origin. Although full channel analyses in the region suggest significant local tectonic contributions to longitudinal river profiles (Adams et al., 2016), we develop a method to isolate rivers in an apparently homogeneous tectonic block in the mid- to upper- elevations. Profiles of rivers in this region show a consistent pattern with a marked topographic step covering 2000 m of elevation change within 10 km. Field observations of knick points, terraces and cut-off ridges associated with the step suggest a regionally consistent signal resulting from changes in relative uplift or erosion rate. Chi plots correlate well for all channels when the base level is chosen to isolate rivers below the main alluvial plain, suggesting similar fluvial erosion histories in upstream regions. Employing third order topographic derivatives (Minár et al., 2013), we identify low angle slope sections/plateaus corresponding to terraces and/or extrapolated ridges that project onto former valley floor levels. Employing similar methods as those used to correlate fluvial knickpoints, these will be used to test for regionally consistent changes in fluvial and hillslope activity that may be tied to major tectonic or climatic changes. REFERENCES Adams, B., Whipple, K. X., Hodges, K. V. & Heimsath, A. M. 2016: In situ development of high-elevation, low-relief landscapes via duplex deformation in the Eastern Himalayan hinterland, Bhutan, in Journal of Geophysical Research: Earth Surface, 925-938. Minár, J., Jenčo, M., Evans, I. S., Minár, J., Kadlec, M., Krcho, J., Pacina

  12. EXPRESSION PROFILING OF FIVE RAT STRAINS REVEAL TRANSCRIPTIONAL MODES IN THE ANTIGEN PROCESSING PATHWAY

    Science.gov (United States)

    Comparative gene expression profiling of rat strains with genetic predisposition to diverse cardiovascular diseases can help decode the transcriptional program that governs cellular behavior. We hypothesized that co-transcribed, intra-pathway, functionally coherent genes can be r...

  13. Proteomic profiling reveals a severely perturbed protein expression pattern in aged skeletal muscle.

    Science.gov (United States)

    O'Connell, Kathleen; Gannon, Joan; Doran, Philip; Ohlendieck, Kay

    2007-08-01

    Extended longevity is often accompanied by frailty and increased susceptibility to a variety of crippling disorders. One of the most striking features of human aging is sarcopenia, which is defined as the age-related decline in skeletal muscle mass and strength. Although various metabolic and functional defects in aging muscle fibres have been described over the last decade, it is not known whether a pathophysiological hierarchy exists within degenerative pathways leading to muscle wasting. Hence, in order to identify novel biomarkers of age-dependent skeletal muscle degeneration, we have here applied mass spectrometry-based proteomics for studying global muscle protein expression patterns. As a model system of sarcopenia, we have employed crude extracts from senescent rat gastrocnemius muscle, as compared to young adult tissue preparations. Using the highly sensitive protein dye Deep Purple for the analysis of the 2-D separated muscle proteome and peptide mass fingerprinting for the identification of individual protein spots, a differential expression pattern was observed for contractile proteins, metabolic factors, regulatory components and heat shock elements. A drastic increase was shown for alpha B-crystallin, myosin light chain MLC-1, phosphoglycerate kinase, adenylate kinase, triosephosphate isomerase, albumin, aconitase and nucleoside-diphosphate kinase in aged fibres. In contrast, the expression of pyruvate kinase, aldolase, creatine kinase, transferrin, alpha-tropomyosin and myosin light chain MLC-3 was decreased in old skeletal muscle. Comparative 2-D immunoblotting of selected candidate proteins has confirmed the effect of aging on the skeletal muscle proteome. These findings demonstrate a severely perturbed protein expression pattern in aged skeletal muscle, which reflects the underlying molecular alterations causing a drastic decline of muscle strength in the senescent organism. In the long-term, the systematic deduction of abnormal protein expression

  14. Metabolic Profiling Reveals Effects of Age, Sexual Development and Neutering in Plasma of Young Male Cats.

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    David Allaway

    Full Text Available 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 p<0.05. Pathway Enrichment Analysis also identified significant effects in 20 pathways, dominated by amino acid, sterol and fatty acid metabolism. Most changes were interpretable within the context of male sexual development, and changed following neutering in the CN group. Felinine metabolism in CN cats 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.

  15. Profiling of Oncogenic Driver Events in Lung Adenocarcinoma Revealed MET Mutation as Independent Prognostic Factor.

    Science.gov (United States)

    Yeung, Sai F; Tong, Joanna H M; Law, Peggy P W; Chung, Lau Y; Lung, Raymond W M; Tong, Carol Y K; Chow, Chit; Chan, Anthony W H; Wan, Innes Y P; Mok, Tony S K; To, Ka F

    2015-09-01

    Oncogenic driver mutations activating receptor tyrosine kinase pathways are promising predictive markers for targeted treatment. We investigated the mutation profile of an updated driver events list on receptor tyrosine kinase/RAS/PI3K axis and the clinicopathologic implications in a cohort of never-smoker predominated Chinese lung adenocarcinoma. We tested 154 lung adenocarcinomas and adenosquamous carcinomas for EGFR, KRAS, HER2, BRAF, PIK3CA, MET, NRAS, MAP2K1, and RIT1 mutations by polymerase chain reaction-direct sequencing. MET amplification and ALK and ROS1 translocations were assessed by fluorescent in situ hybridizations. MET and thyroid transcription factor-1 protein expressions were investigated by immunohistochemistry. Seventy percent of lung adenocarcinomas carried actionable driver events. Alterations on EGFR (43%), KRAS (11.4%), ALK (6%), and MET (5.4%) were frequently found. ROS1 translocation and mutations involving BRAF, HER2, NRAS, and PIK3CA were also detected. No mutation was observed in RIT1 and MAP2K1. Patients with EGFR mutations had a favorable prognosis, whereas those with MET mutations had poorer overall survival. Multivariate analysis further demonstrated that MET mutation was an independent prognostic factor. Although MET protein expression was detected in 65% of lung adenocarcinoma, only 10% of the MET-immunohistochemistry positive tumors harbor MET DNA alterations that drove protein overexpression. Appropriate predictive biomarker is essential for selecting patients who might benefit from specific targeted therapy. Actionable driver events can be detected in two thirds of lung adenocarcinoma. MET DNA alterations define a subset of patients with aggressive diseases that might potentially benefit from anti-MET targeted therapy. High negative predictive values of thyroid transcription factor-1 and MET expression suggest potential roles as surrogate markers for EGFR and/or MET mutations.

  16. Cephalometric profile of Bangladeshis: Tweed's analysis

    Directory of Open Access Journals (Sweden)

    Hasan Md Rizvi

    2017-01-01

    Full Text Available Introduction: Tweed's diagnostic triangle is simple yet provides a definite guideline in treatment planning. The aim of the present study was to establish the Tweed's norms for Bangladeshi people. Methods: The study was conducted for 89 Bangladeshi young adults (45 males and 44 females, aged 19–27 years, having balanced and harmonious facial profiles. Lateral cephalograms taken of these subjects were used for a series of morphometric analyses. Results: All three angular parameters Frankfort-mandibular plane angle (FMA, Frankfort-mandibular incisal angle (FMIA, incise mandibular plane angle (IMPAwere measured and found to be 24.52°, 54.60°, and 100.88°, respectively. The mean FMA has been found to be 24.52° (with a range of 14°–36° which is quite close to Tweed's norm and found to be statistically insignificant. However, IMPA and FMIA values of Bangladeshis found to be statistically significantly different from that of the Caucasians. The linear regression equation of IMPA on FMA was fitted, and the estimated value of IMPA was computed for a given FMA. Conclusion: The results support the idea that treatment objectives of IMPA should be considered according to the facial pattern, i.e., FMA. Ethnic variations of norms cannot be overlooked while outlining goals and planning the treatment.

  17. Transcriptome Profiling of Wild-Type and pga-Knockout Mutant Strains Reveal the Role of Exopolysaccharide in Aggregatibacter actinomycetemcomitans.

    Directory of Open Access Journals (Sweden)

    Mayilvahanan Shanmugam

    Full Text Available Exopolysaccharides have a diverse set of functions in most bacteria including a mechanistic role in protecting bacteria against environmental stresses. Among the many functions attributed to the exopolysaccharides, biofilm formation, antibiotic resistance, immune evasion and colonization have been studied most extensively. The exopolysaccharide produced by many Gram positive as well as Gram negative bacteria including the oral pathogen Aggregatibacter actinomycetemcomitans is the homopolymer of β(1,6-linked N-acetylglucosamine. Recently, we reported that the PGA-deficient mutant of A. actinomycetemcomitans failed to colonize or induce bone resorption in a rat model of periodontal disease, and the colonization genes, apiA and aae, were significantly down regulated in the mutant strain. To understand the role of exopolysaccharide and the pga locus in the global expression of A. actinomycetemcomitans, we have used comparative transcriptome profiling to identify differentially expressed genes in the wild-type strain in relation to the PGA-deficient strain. Transcriptome analysis revealed that about 50% of the genes are differently expressed (P 1.5. Our study demonstrated that the absence of the pga locus affects the genes involved in peptidoglycan recycling, glycogen storage, and virulence. Further, using confocal microscopy and plating assays, we show that the viability of pga mutant strain is significantly reduced during biofilm growth. Thus, this study highlights the importance of pga genes and the exopolysaccharide in the virulence of A. actinomycetemcomitans.

  18. Phenotypic and transcriptional profiling in Entamoeba histolytica reveal costs to fitness and adaptive responses associated with metronidazole resistance

    Directory of Open Access Journals (Sweden)

    Gil M Penuliar

    2015-05-01

    Full Text Available Antimicrobial chemotherapy is critical in the fight against infectious diseases caused by Entamoeba histolytica. Among the drugs available for the treatment of amebiasis, metronidazole (MTZ is considered the drug of choice. Recently, in vitro studies have described MTZ resistance and the potential mechanisms involved. Costs to fitness and adaptive responses associated with resistance, however, have not been investigated. In this study we generated an HM-1 derived strain resistant to 12 µM MTZ (MTZR. We examined its phenotypic and transcriptional profile to determine the consequences and mRNA level changes associated with MTZ resistance. Our results indicated increased cell size and granularity, and decreased rates in cell division, adhesion, phagocytosis, cytopathogenicity, and glucose consumption. Transcriptome analysis revealed 142 differentially expressed genes in MTZR. In contrast to other MTZ resistant parasites, MTZR did not down-regulate pyruvate:ferredoxin oxidoreductase, but showed increased expression of genes for a hypothetical protein (HP1 and several iron-sulfur flavoproteins, and downregulation of genes for leucine-rich proteins. Fisher’s exact test showed 24 significantly enriched GO terms in MTZR, and a 3-way comparison of modulated genes in MTZR against those of MTZR cultured without MTZ and HM-1 cultured with MTZ, showed that 88 genes were specific to MTZR. Overall, our findings suggested that MTZ resistance is associated with specific transcriptional changes and decreased parasite virulence.

  19. Expression profiling of CD34+ hematopoietic stem/ progenitor cells reveals distinct subtypes of therapy-related acute myeloid leukemia.

    Science.gov (United States)

    Qian, Zhijian; Fernald, Anthony A; Godley, Lucy A; Larson, Richard A; Le Beau, Michelle M

    2002-11-12

    One of the most serious consequences of cytotoxic cancer therapy is the development of therapy-related acute myeloid leukemia (t-AML), a neoplastic disorder arising from a multipotential hematopoietic stem cell. To gain insights into the molecular basis of this disease, we performed gene expression profiling of CD34(+) hematopoietic progenitor cells from t-AML patients. Our analysis revealed that there are distinct subtypes of t-AML that have a characteristic gene expression pattern. Common to each of the subgroups are gene expression patterns typical of arrested differentiation in early progenitor cells. Leukemias with a -5/del(5q) have a higher expression of genes involved in cell cycle control (CCNA2, CCNE2, CDC2), checkpoints (BUB1), or growth (MYC), and loss of expression of the gene encoding IFN consensus sequence-binding protein (ICSBP). A second subgroup of t-AML is characterized by down-regulation of transcription factors involved in early hematopoiesis (TAL1, GATA1, and EKLF) and overexpression of proteins involved in signaling pathways in myeloid cells (FLT3) and cell survival (BCL2). Establishing the molecular pathways involved in t-AML may facilitate the identification of selectively expressed genes that can be exploited for the development of urgently needed targeted therapies.

  20. In vivo HMRS and lipidomic profiling reveals comprehensive changes of hippocampal metabolism during aging in mice.

    Science.gov (United States)

    Lin, Lejun; Cao, Bofeng; Xu, Zhiying; Sui, Yanbin; Chen, Jiao; Luan, Qiang; Yang, Ruifang; Li, Shanchun; Li, Ke Feng

    2016-01-29

    Aging is characterized by various cellular changes in the brain. Hippocampus is important for systemic aging and lifespan control. There is still a lack of comprehensive overview of metabolic changes in hippocampus during aging. In this study, we first created an accelerated brain aging mice model through the chronic administration of d-galactose. We then performed a multiplatform metabolomic profiling of mice hippocampus using the combination of in vivo 9.4 T HMRS and in vitro LC-MS/MS based lipidomics. We found N-acetylaspartic acid (NAA), gama-aminobutyric acid (GABA), glutamate/glutamine, taurine, choline, sphingolipids (SMs), phosphatidylethanolamines (PEs), phosphatidylinositols (PIs), phosphatidylglycerols (PGs) and phosphatidylserines (PSs), all of them decreasing with the aging process in mice hippocampus. The changes of sphingolipids and phospholipids were not limited to one single class or molecular species. In contrast, we found the significant accumulation of lactate, myoinositol and phosphatidylcholines (PCs) along with aging in hippocampus. SM (d18:1/20:2), PE (36:2), PG (34:1), PI (36:4), PS (18:0/20:4) and PC (36:0) have the most significant changes along with aging. Network analysis revealed the striking loss of biochemical connectivity and interactions between hippocampal metabolites with aging. The correlation pattern between metabolites in hippocampus could function as biomarkers for aging or diagnosis of aging-related diseases. Copyright © 2015 Elsevier Inc. All rights reserved.

  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. Food Management, Production, and Service. Occupational Competency Analysis Profile.

    Science.gov (United States)

    Ohio State Univ., Columbus. Vocational Instructional Materials Lab.

    This Food Management, Production, and Service Occupational Competency Analysis Profile (OCAP) is one of a series of competency lists, verified by expert workers, that have evolved from a modified DACUM (Developing a Curriculum) job analysis process involving business, industry, labor, and community agency representatives from throughout Ohio. This…

  3. Microarray gene expression profiling and analysis in renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Sadhukhan Provash

    2004-06-01

    Full Text Available Abstract Background Renal cell carcinoma (RCC is the most common cancer in adult kidney. The accuracy of current diagnosis and prognosis of the disease and the effectiveness of the treatment for the disease are limited by the poor understanding of the disease at the molecular level. To better understand the genetics and biology of RCC, we profiled the expression of 7,129 genes in both clear cell RCC tissue and cell lines using oligonucleotide arrays. Methods Total RNAs isolated from renal cell tumors, adjacent normal tissue and metastatic RCC cell lines were hybridized to affymatrix HuFL oligonucleotide arrays. Genes were categorized into different functional groups based on the description of the Gene Ontology Consortium and analyzed based on the gene expression levels. Gene expression profiles of the tissue and cell line samples were visualized and classified by singular value decomposition. Reverse transcription polymerase chain reaction was performed to confirm the expression alterations of selected genes in RCC. Results Selected genes were annotated based on biological processes and clustered into functional groups. The expression levels of genes in each group were also analyzed. Seventy-four commonly differentially expressed genes with more than five-fold changes in RCC tissues were identified. The expression alterations of selected genes from these seventy-four genes were further verified using reverse transcription polymerase chain reaction (RT-PCR. Detailed comparison of gene expression patterns in RCC tissue and RCC cell lines shows significant differences between the two types of samples, but many important expression patterns were preserved. Conclusions This is one of the initial studies that examine the functional ontology of a large number of genes in RCC. Extensive annotation, clustering and analysis of a large number of genes based on the gene functional ontology revealed many interesting gene expression patterns in RCC. Most

  4. Metabolomic Profiles of Body Mass Index in the Framingham Heart Study Reveal Distinct Cardiometabolic Phenotypes.

    Directory of Open Access Journals (Sweden)

    Jennifer E Ho

    Full Text Available Although obesity and cardiometabolic traits commonly overlap, underlying pathways remain incompletely defined. The association of metabolite profiles across multiple cardiometabolic traits may lend insights into the interaction of obesity and metabolic health. We sought to investigate metabolic signatures of obesity and related cardiometabolic traits in the community using broad-based metabolomic profiling.We evaluated the association of 217 assayed metabolites and cross-sectional as well as longitudinal changes in cardiometabolic traits among 2,383 Framingham Offspring cohort participants. Body mass index (BMI was associated with 69 of 217 metabolites (P<0.00023 for all, including aromatic (tyrosine, phenylalanine and branched chain amino acids (valine, isoleucine, leucine. Additional metabolic pathways associated with BMI included the citric acid cycle (isocitrate, alpha-ketoglutarate, aconitate, the tryptophan pathway (kynurenine, kynurenic acid, and the urea cycle. There was considerable overlap in metabolite profiles between BMI, abdominal adiposity, insulin resistance [IR] and dyslipidemia, modest overlap of metabolite profiles between BMI and hyperglycemia, and little overlap with fasting glucose or elevated blood pressure. Metabolite profiles were associated with longitudinal changes in fasting glucose, but the involved metabolites (ornithine, 5-HIAA, aminoadipic acid, isoleucine, cotinine were distinct from those associated with baseline glucose or other traits. Obesity status appeared to "modify" the association of 9 metabolites with IR. For example, bile acid metabolites were strongly associated with IR among obese but not lean individuals, whereas isoleucine had a stronger association with IR in lean individuals.In this large-scale metabolite profiling study, body mass index was associated with a broad range of metabolic alterations. Metabolite profiling highlighted considerable overlap with abdominal adiposity, insulin resistance

  5. Systematic analysis of Ca2+ homeostasis in Saccharomyces cerevisiae based on chemical-genetic interaction profiles

    Science.gov (United States)

    Ghanegolmohammadi, Farzan; Yoshida, Mitsunori; Ohnuki, Shinsuke; Sukegawa, Yuko; Okada, Hiroki; Obara, Keisuke; Kihara, Akio; Suzuki, Kuninori; Kojima, Tetsuya; Yachie, Nozomu; Hirata, Dai; Ohya, Yoshikazu

    2017-01-01

    We investigated the global landscape of Ca2+ homeostasis in budding yeast based on high-dimensional chemical-genetic interaction profiles. The morphological responses of 62 Ca2+-sensitive (cls) mutants were quantitatively analyzed with the image processing program CalMorph after exposure to a high concentration of Ca2+. After a generalized linear model was applied, an analysis of covariance model was used to detect significant Ca2+–cls interactions. We found that high-dimensional, morphological Ca2+–cls interactions were mixed with positive (86%) and negative (14%) chemical-genetic interactions, whereas one-dimensional fitness Ca2+–cls interactions were all negative in principle. Clustering analysis with the interaction profiles revealed nine distinct gene groups, six of which were functionally associated. In addition, characterization of Ca2+–cls interactions revealed that morphology-based negative interactions are unique signatures of sensitized cellular processes and pathways. Principal component analysis was used to discriminate between suppression and enhancement of the Ca2+-sensitive phenotypes triggered by inactivation of calcineurin, a Ca2+-dependent phosphatase. Finally, similarity of the interaction profiles was used to reveal a connected network among the Ca2+ homeostasis units acting in different cellular compartments. Our analyses of high-dimensional chemical-genetic interaction profiles provide novel insights into the intracellular network of yeast Ca2+ homeostasis. PMID:28566553

  6. Oncogene mutation profiling reveals poor prognosis associated with FGFR1/3 mutation in liposarcoma.

    Science.gov (United States)

    Li, Chengfang; Shen, Yaoyuan; Ren, Yan; Liu, Wei; Li, Man; Liang, Weihua; Liu, Chunxia; Li, Feng

    2016-09-01

    Liposarcoma (LPS) is one of the most prevalent soft tissue sarcomas. LPS shows a poor response to radiation and chemotherapy. The causes of death in patients with LPS include locally recurrent and metastatic disease. We sought to examine novel gene mutations and pathways in primary and matched recurrent LPSs to identify potential therapeutic targets. We conducted a high-throughput analysis of 238 known mutations in 19 oncogenes using Sequenom MassARRAY technology. Nucleic acids were extracted from 19 primary and recurrent LPS samples, encompassing 9 dedifferentiated LPSs (DDLPS), 9 myxoid/round cell LPSs, and 1 pleomorphic LPS. Mutation screening revealed missense mutations in 21.1% (4/19) of the LPS specimens, including 4 different genes (FGFR1, FGFR3, PIK3CA, and KIT). Based on histologic subtypes, 22.2% DDLPS (2/9) and 22.2% myxoid cell LPS (2/9) contained gene mutations. Specifically, 3 (23.1%) of 13 primary tumors harbored mutations. Furthermore, although gene mutations were identified in 1 (11.1%) of 9 recurrent LPS samples, the difference between the primary and the recurrence was not statistically significant. Analysis of patient survival data indicated that patients harboring FGFR1/3 mutations experienced reduced overall survival (P<.05). Despite the limited number of samples, our findings provide the first evidence of FGFR1/3 mutations in DDLPS, which were associated with poor clinical outcomes. The FGFR pathway may play an important role in the development and progression of DDLPS and warrants further investigation; moreover, PIK3CA mutation is a common event (11.1%) in myxoid cell LPS. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. An integrated metagenomics pipeline for strain profiling reveals novel patterns of bacterial transmission and biogeography

    Science.gov (United States)

    Nayfach, Stephen; Rodriguez-Mueller, Beltran; Garud, Nandita

    2016-01-01

    We present the Metagenomic Intra-species Diversity Analysis System (MIDAS), which is an integrated computational pipeline for quantifying bacterial species abundance and strain-level genomic variation, including gene content and single-nucleotide polymorphisms (SNPs), from shotgun metagenomes. Our method leverages a database of more than 30,000 bacterial reference genomes that we clustered into species groups. These cover the majority of abundant species in the human microbiome but only a small proportion of microbes in other environments, including soil and seawater. We applied MIDAS to stool metagenomes from 98 Swedish mothers and their infants over one year and used rare SNPs to track strains between hosts. Using this approach, we found that although species compositions of mothers and infants converged over time, strain-level similarity diverged. Specifically, early colonizing bacteria were often transmitted from an infant’s mother, while late colonizing bacteria were often transmitted from other sources in the environment and were enriched for spore-formation genes. We also applied MIDAS to 198 globally distributed marine metagenomes and used gene content to show that many prevalent bacterial species have population structure that correlates with geographic location. Strain-level genetic variants present in metagenomes clearly reveal extensive structure and dynamics that are obscured when data are analyzed at a coarser taxonomic resolution. PMID:27803195

  8. Transcriptional profiling of aging in human muscle reveals a common aging signature.

    Directory of Open Access Journals (Sweden)

    Jacob M Zahn

    2006-07-01

    Full Text Available We analyzed expression of 81 normal muscle samples from humans of varying ages, and have identified a molecular profile for aging consisting of 250 age-regulated genes. This molecular profile correlates not only with chronological age but also with a measure of physiological age. We compared the transcriptional profile of muscle aging to previous transcriptional profiles of aging in the kidney and the brain, and found a common signature for aging in these diverse human tissues. The common aging signature consists of six genetic pathways; four pathways increase expression with age (genes in the extracellular matrix, genes involved in cell growth, genes encoding factors involved in complement activation, and genes encoding components of the cytosolic ribosome, while two pathways decrease expression with age (genes involved in chloride transport and genes encoding subunits of the mitochondrial electron transport chain. We also compared transcriptional profiles of aging in humans to those of the mouse and fly, and found that the electron transport chain pathway decreases expression with age in all three organisms, suggesting that this may be a public marker for aging across species.

  9. Transcriptome Profiling of Taproot Reveals Complex Regulatory Networks during Taproot Thickening in Radish (Raphanus sativus L.).

    Science.gov (United States)

    Yu, Rugang; Wang, Jing; Xu, Liang; Wang, Yan; Wang, Ronghua; Zhu, Xianwen; Sun, Xiaochuan; Luo, Xiaobo; Xie, Yang; Everlyne, Muleke; Liu, Liwang

    2016-01-01

    Radish (Raphanus sativus L.) is one of the most important vegetable crops worldwide. Taproot thickening represents a critical developmental period that determines yield and quality in radish life cycle. To isolate differentially expressed genes (DGEs) involved in radish taproot thickening process and explore the molecular mechanism underlying taproot development, three cDNA libraries from radish taproot collected at pre-cortex splitting stage (L1), cortex splitting stage (L2), and expanding stage (L3) were constructed and sequenced by RNA-Seq technology. More than seven million clean reads were obtained from the three libraries, from which 4,717,617 (L1, 65.35%), 4,809,588 (L2, 68.24%) and 4,973,745 (L3, 69.45%) reads were matched to the radish reference genes, respectively. A total of 85,939 transcripts were generated from three libraries, from which 10,450, 12,325, and 7392 differentially expressed transcripts (DETs) were detected in L1 vs. L2, L1 vs. L3, and L2 vs. L3 comparisons, respectively. Gene Ontology and pathway analysis showed that many DEGs, including EXPA9, Cyclin, CaM, Syntaxin, MADS-box, SAUR, and CalS were involved in cell events, cell wall modification, regulation of plant hormone levels, signal transduction and metabolisms, which may relate to taproot thickening. Furthermore, the integrated analysis of mRNA-miRNA revealed that 43 miRNAs and 92 genes formed 114 miRNA-target mRNA pairs were co-expressed, and three miRNA-target regulatory networks of taproot were constructed from different libraries. Finally, the expression patterns of 16 selected genes were confirmed using RT-qPCR analysis. A hypothetical model of genetic regulatory network associated with taproot thickening in radish was put forward. The taproot formation of radish is mainly attributed to cell differentiation, division and expansion, which are regulated and promoted by certain specific signal transduction pathways and metabolism processes. These results could provide new insights

  10. Transcriptome profiling of taproot reveals complex regulatory networks during taproot thickening in radish (Raphanus sativus L.

    Directory of Open Access Journals (Sweden)

    Rugang Yu

    2016-08-01

    Full Text Available Radish (Raphanus sativus L., is one of the most important vegetable crops worldwide. Taproot thickening represents a critical developmental period that determines yield and quality in radish life cycle. To isolate differentially expressed genes (DGEs involved in radish taproot thickening process and explored the molecular mechanism in underlying taproot development, three cDNA libraries from radish taproot collected at pre-cortex splitting stage (L1, cortex splitting stage (L2 and expanding stage (L3 were constructed and sequenced by RNA-Seq technology. More than seven million clean reads were obtained from the three libraries, respectively, from which 4,717,617 (L1, 65.35%, 4,809,588 (L2, 68.24% and 4,973,745 (L3, 69.45% reads were matched to the radish reference genes. A total of 85,939 transcripts were generated from three libraries, from which 10,450, 12,325 and 7,392 differentially expressed transcripts (DETs were detected in L1 vs. L2, L1 vs. L3, and L2 vs. L3 comparisons, respectively. Gene Ontology and pathway analysis showed that many DEGs, including EXPA9, Cyclin, CaM, Syntaxin, MADS-box, SAUR and CalS were involved in cell events, cell wall modification, regulation of plant hormone levels, signal transduction and metabolisms, which may relate to taproot thickening. Furthermore, the integrated analysis of mRNA-miRNA revealed that 43 miRNAs and 92 genes that formed 114 miRNA-target mRNA pairs were co-expressed, and three miRNA-target regulatory networks of taproot were constructed from different libraries. Finally, the expression patterns of 16 selected genes were confirmed using RT-qPCR analysis. A hypothetical model of genetic regulatory network associated with taproot thickening in radish was put forward. The taproot formation of radish is mainly contributed to cell differentiation, division and expansion, which are regulated and promoted by certain specific signal transduction pathways and metabolism possesses. These results could

  11. Microbiota analysis to reveal temperature abuse of fresh pork

    DEFF Research Database (Denmark)

    Buschhardt, Tasja; Bahl, Martin Iain; Hansen, Tina Beck

    Violations of temperature regulations in the meat chain may affect meat safety. Methods are lacking to estimate whether meat has been subjected to temperature abuse. Exposure to too high temperatures may lead to systematic changes in the diverse bacterial communities of fresh meat. We investigated...... whether temperature induced changes in the community composition on fresh meat surfaces can reflect the temperature-history (combination of time and temperature). Sterile pieces of pork were inoculated with a carcass swab homogenate, to which Salmonella was added. Changes in the meat microbiota were...... was dominated by Pseudomonas only. We also showed that the initial community affects subsequent changes during storage. The results suggest that principal coordinate analysis of beta diversity could be a useful tool to reveal temperature abused meat. Sequence data and culturing data revealed a strong positive...

  12. Quantitative electroencephalography reveals different physiological profiles between benign and remitting-relapsing multiple sclerosis patients

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    Duque Pablo

    2008-11-01

    Full Text Available Abstract Background A possible method of finding physiological markers of multiple sclerosis (MS is the application of EEG quantification (QEEG of brain activity when the subject is stressed by the demands of a cognitive task. In particular, modulations of the spectral content that take place in the EEG of patients with multiple sclerosis remitting-relapsing (RRMS and benign multiple sclerosis (BMS during a visuo-spatial task need to be observed. Methods The sample consisted of 19 patients with RRMS, 10 with BMS, and 21 control subjects. All patients were free of medication and had not relapsed within the last month. The power spectral density (PSD of different EEG bands was calculated by Fast-Fourier-Transformation (FFT, those analysed being delta, theta, alpha, beta and gamma. Z-transformation was performed to observe individual profiles in each experimental group for spectral modulations. Lastly, correlation analyses was performed between QEEG values and other variables from participants in the study (age, EDSS, years of evolution and cognitive performance. Results Nearly half (42% the RRMS patients showed a statistically significant increase of two or more standard deviations (SD compared to the control mean value for the beta-2 and gamma bands (F = 2.074, p = 0.004. These alterations were localized to the anterior regions of the right hemisphere, and bilaterally to the posterior areas of the scalp. None of the BMS patients or control subjects had values outside the range of ± 2 SD. There were no significant correlations between these values and the other variables analysed (age, EDSS, years of evolution or behavioural performance. Conclusion During the attentional processing, changes in the high EEG spectrum (beta-2 and gamma in MS patients exhibit physiological alterations that are not normally detected by spontaneous EEG analysis. The different spectral pattern between pathological and controls groups could represent specific changes for

  13. The sorghum SWEET gene family: stem sucrose accumulation as revealed through transcriptome profiling.

    Science.gov (United States)

    Mizuno, Hiroshi; Kasuga, Shigemitsu; Kawahigashi, Hiroyuki

    2016-01-01

    SWEET is a newly identified family of sugar transporters. Although SWEET transporters have been characterized by using Arabidopsis and rice, very little knowledge of sucrose accumulation in the stem region is available, as these model plants accumulate little sucrose in their stems. To elucidate the expression of key SWEET genes involved in sucrose accumulation of sorghum, we performed transcriptome profiling by RNA-seq, categorization using phylogenetic trees, analysis of chromosomal synteny, and comparison of amino acid sequences between SIL-05 (a sweet sorghum) and BTx623 (a grain sorghum). We identified 23 SWEET genes in the sorghum genome. In the leaf, SbSWEET8-1 was highly expressed and was grouped in the same clade as AtSWEET11 and AtSWEET12 that play a role in the efflux of photosynthesized sucrose. The key genes in sucrose synthesis (SPS3) and that in another step of sugar transport (SbSUT1 and SbSUT2) were also highly expressed, suggesting that sucrose is newly synthesized and actively exported from the leaf. In the stem, SbSWEET4-3 was uniquely highly expressed. SbSWEET4-1, SbSWEET4-2, and SbSWEET4-3 were categorized into the same clade, but their tissue specificities were different, suggesting that SbSWEET4-3 is a sugar transporter with specific roles in the stem. We found a putative SWEET4-3 ortholog in the corresponding region of the maize chromosome, but not the rice chromosome, suggesting that SbSWEET4-3 was copied after the branching of sorghum and maize from rice. In the panicle from the heading through to 36 days afterward, SbSWEET2-1 and SbSWEET7-1 were expressed and grouped in the same clade as rice OsSWEET11/Xa13 that is essential for seed development. SbSWEET9-3 was highly expressed in the panicle only just after heading and was grouped into the same clade as AtSWEET8/RPG1 that is essential for pollen viability. Five of 23 SWEET genes had SNPs that caused nonsynonymous amino acid substitutions between SIL-05 and BTx623. We determined the key

  14. Consumer profile analysis for different types of meat in Spain.

    Science.gov (United States)

    Escriba-Perez, Carmen; Baviera-Puig, Amparo; Buitrago-Vera, Juan; Montero-Vicente, Luis

    2017-07-01

    It is important to analyse the consumer profile of each type of meat to better adapt the marketing mix to each one. To this end, we examined the average consumption frequency of different types of meat based on two methodologies: consumer segmentation using the food-related lifestyle (FRL) framework, giving rise to 4 segments, and analysis of socio-demographic profiles. The variables used were: sex, age, educational level, social class, number of people in the household, presence of children younger than 18 in the home, geographical area and habitual residence. Beef was the only meat type significant in both analyses. Turkey meat only appeared as significant in the FRL analysis. The other meats (chicken, pork, rabbit and lamb) were only significant in the sociodemographic variables analysis. From the outcomes we may conclude that there is no single consumer profile, which rather depends on the type of meat. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Elemental microchemistry, fatty acid profile and geometric morphometrics signatures of goose barnacles (Pollicipes pollicipes reveal their place of origin

    Directory of Open Access Journals (Sweden)

    Rui Albuquerque

    2014-06-01

    Full Text Available Seafood plays an important role in the socioeconomic, gastronomy and cultural heritage of Portuguese coastal communities. In the Iberian Peninsula, the goose barnacle Pollicipes pollicipes is the intertidal biological resource most heavily exploited by man, resulting on overexploitation of stocks. In the MPA of BNR P.pollicipes harvesting is however strictly regulated, making it a good example of marine resources management. Analytical methods able to identify the origin of goose barnacle would be an important tool to help the management of the trade. For such purpose, we investigated whether P. pollicipes have site-specific differences based on its elemental microchemistry (EM, fatty acid profile (FA and capitulum shape (CS. The analysis was performed on specimens collected from 3 sites in the BNR and 7 along a 300 km stretch of the Portuguese coast. For each individual we analysed the largest lateral shell for EM using ICP-MS, the FA content of the muscle using GC-FID, and the CS using geometric morphometrics. Discriminant function analyses (DFA for both EM and FA separately provided a high reclassification success (77.6% and 99% respectively, of cross-validated cases correctly classified, while for EM combined with FA allowed for a 100% reclassification success. DFA analysis based only on CS, revealed a low classification success (29.6%. These results show that EM and FA signatures can be a powerful tool to infer goose barnacles origin. Such “fingerprinting” approach can be used to track and identify goose barnacles origin, helping in establishing an origin certificate and increasing the potential value of biological resources from Portuguese MPAs.

  16. Genome-wide profiling of pluripotent cells reveals a unique molecular signature of human embryonic germ cells.

    Directory of Open Access Journals (Sweden)

    Nikta Pashai

    Full Text Available Human embryonic germ cells (EGCs provide a powerful model for identifying molecules involved in the pluripotent state when compared to their progenitors, primordial germ cells (PGCs, and other pluripotent stem cells. Microarray and Principal Component Analysis (PCA reveals for the first time that human EGCs possess a transcription profile distinct from PGCs and other pluripotent stem cells. Validation with qRT-PCR confirms that human EGCs and PGCs express many pluripotency-associated genes but with quantifiable differences compared to pluripotent embryonic stem cells (ESCs, induced pluripotent stem cells (IPSCs, and embryonal carcinoma cells (ECCs. Analyses also identified a number of target genes that may be potentially associated with their unique pluripotent states. These include IPO7, MED7, RBM26, HSPD1, and KRAS which were upregulated in EGCs along with other pluripotent stem cells when compared to PGCs. Other potential target genes were also found which may contribute toward a primed ESC-like state. These genes were exclusively up-regulated in ESCs, IPSCs and ECCs including PARP1, CCNE1, CDK6, AURKA, MAD2L1, CCNG1, and CCNB1 which are involved in cell cycle regulation, cellular metabolism and DNA repair and replication. Gene classification analysis also confirmed that the distinguishing feature of EGCs compared to ESCs, ECCs, and IPSCs lies primarily in their genetic contribution to cellular metabolism, cell cycle, and cell adhesion. In contrast, several genes were found upregulated in PGCs which may help distinguish their unipotent state including HBA1, DMRT1, SPANXA1, and EHD2. Together, these findings provide the first glimpse into a unique genomic signature of human germ cells and pluripotent stem cells and provide genes potentially involved in defining different states of germ-line pluripotency.

  17. Genome-Wide Profiling of Pluripotent Cells Reveals a Unique Molecular Signature of Human Embryonic Germ Cells

    Science.gov (United States)

    Pashai, Nikta; Hao, Haiping; All, Angelo; Gupta, Siddharth; Chaerkady, Raghothama; De Los Angeles, Alejandro; Gearhart, John D.; Kerr, Candace L.

    2012-01-01

    Human embryonic germ cells (EGCs) provide a powerful model for identifying molecules involved in the pluripotent state when compared to their progenitors, primordial germ cells (PGCs), and other pluripotent stem cells. Microarray and Principal Component Analysis (PCA) reveals for the first time that human EGCs possess a transcription profile distinct from PGCs and other pluripotent stem cells. Validation with qRT-PCR confirms that human EGCs and PGCs express many pluripotency-associated genes but with quantifiable differences compared to pluripotent embryonic stem cells (ESCs), induced pluripotent stem cells (IPSCs), and embryonal carcinoma cells (ECCs). Analyses also identified a number of target genes that may be potentially associated with their unique pluripotent states. These include IPO7, MED7, RBM26, HSPD1, and KRAS which were upregulated in EGCs along with other pluripotent stem cells when compared to PGCs. Other potential target genes were also found which may contribute toward a primed ESC-like state. These genes were exclusively up-regulated in ESCs, IPSCs and ECCs including PARP1, CCNE1, CDK6, AURKA, MAD2L1, CCNG1, and CCNB1 which are involved in cell cycle regulation, cellular metabolism and DNA repair and replication. Gene classification analysis also confirmed that the distinguishing feature of EGCs compared to ESCs, ECCs, and IPSCs lies primarily in their genetic contribution to cellular metabolism, cell cycle, and cell adhesion. In contrast, several genes were found upregulated in PGCs which may help distinguish their unipotent state including HBA1, DMRT1, SPANXA1, and EHD2. Together, these findings provide the first glimpse into a unique genomic signature of human germ cells and pluripotent stem cells and provide genes potentially involved in defining different states of germ-line pluripotency. PMID:22737227

  18. Exon-level transcriptome profiling in murine breast cancer reveals splicing changes specific to tumors with different metastatic abilities.

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    Amandine Bemmo

    2010-08-01

    Full Text Available Breast cancer is the second most frequent type of cancer affecting women. We are increasingly aware that changes in mRNA splicing are associated with various characteristics of cancer. The most deadly aspect of cancer is metastasis, the process by which cancer spreads from the primary tumor to distant organs. However, little is known specifically about the involvement of alternative splicing in the formation of macroscopic metastases. Our study investigates transcript isoform changes that characterize tumors of different abilities to form growing metastases.To identify alternative splicing events (ASEs that are associated with the fully metastatic phenotype in breast cancer, we used Affymetrix Exon Microarrays to profile mRNA isoform variations genome-wide in weakly metastatic (168FARN and 4T07 and highly metastatic (4T1 mammary carcinomas. Statistical analysis identified significant expression changes in 7606 out of 155,994 (4% exons and in 1725 out of 189,460 (1% intronic regions, which affect 2623 out of 16,654 (16% genes. These changes correspond to putative alternative isoforms-several of which are novel-that are differentially expressed between tumors of varying metastatic phenotypes. Gene pathway analysis showed that 1224 of genes expressing alternative isoforms were involved in cell growth, cell interactions, cell proliferation, cell migration and cell death and have been previously linked to cancers and genetic disorders. We chose ten predicted splice variants for RT-PCR validation, eight of which were successfully confirmed (MED24, MFI2, SRRT, CD44, CLK1 and HNRNPH1. These include three novel intron retentions in CD44, a gene in which isoform variations have been previously associated with the metastasis of several cancers.Our findings reveal that various genes are differently spliced and/or expressed in association with the metastatic phenotype of tumor cells. Identification of metastasis-specific isoforms may contribute to the

  19. Proteomic and ionomic profiling reveals significant alterations of protein expression and calcium homeostasis in cystic fibrosis cells.

    Science.gov (United States)

    Ciavardelli, Domenico; D'Orazio, Melania; Pieroni, Luisa; Consalvo, Ada; Rossi, Claudia; Sacchetta, Paolo; Di Ilio, Carmine; Battistoni, Andrea; Urbani, Andrea

    2013-06-01

    Cystic fibrosis (CF) is an autosomal recessive disorder associated with mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene and defective chloride transport across the epithelial cell membranes. Abnormal epithelial ion transport is the primary cause of persistent airway infections and chronic inflammation in CF patients. In order to gain further insight into the mechanisms of epithelial dysfunctions linked to CFTR mutations, we performed and integrated proteomic and ionomic analysis of human bronchial epithelial IB3-1 cells and compared them with a CFTR-complemented isogenic cell line (C38). Aside from changes that were consistent with known effects related to CFTR mutations, such as differences in glycolytic and gluconeogenic pathways and unfolded protein responses, differential proteomics highlighted significant alteration of protein expression and, in particular, of the 14-3-3 signalling pathway that is known to be involved in cellular calcium (Ca) homeostasis. Of note, restoring chloride efflux by acting on Ca cellular homeostasis has been shown to be a promising therapeutic intervention for CF. Ionomic analysis showed significant changes in the IB3-1 element profile compared with C38 cells and in particular we observed an increase of intracellular Ca that significantly correlates with intracellular zinc (Zn) levels, suggesting a synergistic role of Ca and Zn influx. This finding is particularly intriguing because Zn has been reported to be effective in CF treatment increasing Ca influx. Taken together, our proteomic and ionomic data reveal that CFTR mutation sets in motion endogenous mechanisms counteracting impaired chloride transport mainly acting on epithelial ion transport and increasing intracellular Ca, suggesting potential links between protein expression and this response.

  20. The features of Drosophila core promoters revealed by statistical analysis

    Directory of Open Access Journals (Sweden)

    Trifonov Edward N

    2006-06-01

    Full Text Available Abstract Background Experimental investigation of transcription is still a very labor- and time-consuming process. Only a few transcription initiation scenarios have been studied in detail. The mechanism of interaction between basal machinery and promoter, in particular core promoter elements, is not known for the majority of identified promoters. In this study, we reveal various transcription initiation mechanisms by statistical analysis of 3393 nonredundant Drosophila promoters. Results Using Drosophila-specific position-weight matrices, we identified promoters containing TATA box, Initiator, Downstream Promoter Element (DPE, and Motif Ten Element (MTE, as well as core elements discovered in Human (TFIIB Recognition Element (BRE and Downstream Core Element (DCE. Promoters utilizing known synergetic combinations of two core elements (TATA_Inr, Inr_MTE, Inr_DPE, and DPE_MTE were identified. We also establish the existence of promoters with potentially novel synergetic combinations: TATA_DPE and TATA_MTE. Our analysis revealed several motifs with the features of promoter elements, including possible novel core promoter element(s. Comparison of Human and Drosophila showed consistent percentages of promoters with TATA, Inr, DPE, and synergetic combinations thereof, as well as most of the same functional and mutual positions of the core elements. No statistical evidence of MTE utilization in Human was found. Distinct nucleosome positioning in particular promoter classes was revealed. Conclusion We present lists of promoters that potentially utilize the aforementioned elements/combinations. The number of these promoters is two orders of magnitude larger than the number of promoters in which transcription initiation was experimentally studied. The sequences are ready to be experimentally tested or used for further statistical analysis. The developed approach may be utilized for other species.

  1. Developmental Profiling of Spiral Ganglion Neurons Reveals Insights into Auditory Circuit Assembly

    Science.gov (United States)

    Lu, Cindy C.; Appler, Jessica M.; Houseman, E. Andres; Goodrich, Lisa V.

    2011-01-01

    The sense of hearing depends on the faithful transmission of sound information from the ear to the brain by spiral ganglion (SG) neurons. However, how SG neurons develop the connections and properties that underlie auditory processing is largely unknown. We catalogued gene expression in mouse SG neurons from embryonic day 12 (E12), when SG neurons first extend projections, up until postnatal day 15 (P15), after the onset of hearing. For comparison, we also analyzed the closely-related vestibular ganglion (VG). Gene ontology analysis confirmed enriched expression of genes associated with gene regulation and neurite outgrowth at early stages, with the SG and VG often expressing different members of the same gene family. At later stages, the neurons transcribe more genes related to mature function, and exhibit a dramatic increase in immune gene expression. Comparisons of the two populations revealed enhanced expression of TGFβ pathway components in SG neurons and established new markers that consistently distinguish auditory and vestibular neurons. Unexpectedly, we found that Gata3, a transcription factor commonly associated with auditory development, is also expressed in VG neurons at early stages. We therefore defined new cohorts of transcription factors and axon guidance molecules that are uniquely expressed in SG neurons and may drive auditory-specific aspects of their differentiation and wiring. We show that one of these molecules, the receptor guanylyl cyclase Npr2, is required for bifurcation of the SG central axon. Hence, our data set provides a useful resource for uncovering the molecular basis of specific auditory circuit assembly events. PMID:21795542

  2. Metabolite profiling reveals abiotic stress tolerance in Tn5 mutant of Pseudomonas putida.

    Directory of Open Access Journals (Sweden)

    Vasvi Chaudhry

    Full Text Available Pseudomonas is an efficient plant growth-promoting rhizobacteria (PGPR; however, intolerance to drought and high temperature limit its application in agriculture as a bioinoculant. Transposon 5 (Tn5 mutagenesis was used to generate a stress tolerant mutant from a PGPR Pseudomonas putida NBRI1108 isolated from chickpea rhizosphere. A mutant NBRI1108T, selected after screening of nearly 10,000 transconjugants, exhibited significant tolerance towards high temperature and drought. Southern hybridization analysis of EcoRI and XhoI restricted genomic DNA of NBRI1108T confirmed that it had a single Tn5 insertion. The metabolic changes in the polar and non-polar extracts of NBRI1108 and NBRI1108T were examined using 1H, 31P nuclear magnetic resonance (NMR spectroscopy and gas chromatography-mass spectrometry (GC-MS. Thirty six chemically diverse metabolites consisting of amino acids, fatty acids and phospholipids were identified and quantified. Insertion of Tn5 influenced amino acid and phospholipid metabolism and resulted in significantly higher concentration of aspartic acid, glutamic acid, glycinebetaine, glycerophosphatidylcholine (GPC and putrescine in NBRI1108T as compared to that in NBRI1108. The concentration of glutamic acid, glycinebetaine and GPC increased by 34%, 95% and 100%, respectively in the NBRI1108T as compared to that in NBRI1108. High concentration of glycerophosphatidylethanolamine (GPE and undetected GPC in NBRI1108 indicates that biosynthesis of GPE may have taken place via the methylation pathway of phospholipid biosynthesis. However, high GPC and low GPE concentration in NBRI1108T suggest that methylation pathway and phosphatidylcholine synthase (PCS pathway of phospholipid biosynthesis are being followed in the NBRI1108T. Application of multivariate principal component analysis (PCA on the quantified metabolites revealed clear variations in NBRI1108 and NBRI1108T in polar and non-polar metabolites. Identification of abiotic

  3. An Inducible Operon Is Involved in Inulin Utilization in Lactobacillus plantarum Strains, as Revealed by Comparative Proteogenomics and Metabolic Profiling.

    Science.gov (United States)

    Buntin, Nirunya; Hongpattarakere, Tipparat; Ritari, Jarmo; Douillard, François P; Paulin, Lars; Boeren, Sjef; Shetty, Sudarshan A; de Vos, Willem M

    2017-01-15

    The draft genomes of Lactobacillus plantarum strains isolated from Asian fermented foods, infant feces, and shrimp intestines were sequenced and compared to those of well-studied strains. Among 28 strains of L. plantarum, variations in the genomic features involved in ecological adaptation were elucidated. The genome sizes ranged from approximately 3.1 to 3.5 Mb, of which about 2,932 to 3,345 protein-coding sequences (CDS) were predicted. The food-derived isolates contained a higher number of carbohydrate metabolism-associated genes than those from infant feces. This observation correlated to their phenotypic carbohydrate metabolic profile, indicating their ability to metabolize the largest range of sugars. Surprisingly, two strains (P14 and P76) isolated from fermented fish utilized inulin. β-Fructosidase, the inulin-degrading enzyme, was detected in the supernatants and cell wall extracts of both strains. No activity was observed in the cytoplasmic fraction, indicating that this key enzyme was either membrane-bound or extracellularly secreted. From genomic mining analysis, a predicted inulin operon of fosRABCDXE, which encodes β-fructosidase and many fructose transporting proteins, was found within the genomes of strains P14 and P76. Moreover, pts1BCA genes, encoding sucrose-specific IIBCA components involved in sucrose transport, were also identified. The proteomic analysis revealed the mechanism and functional characteristic of the fosRABCDXE operon involved in the inulin utilization of L. plantarum The expression levels of the fos operon and pst genes were upregulated at mid-log phase. FosE and the LPXTG-motif cell wall anchored β-fructosidase were induced to a high abundance when inulin was present as a carbon source. Inulin is a long-chain carbohydrate that may act as a prebiotic, which provides many health benefits to the host by selectively stimulating the growth and activity of beneficial bacteria in the colon. While certain lactobacilli can catabolize

  4. Transcript profiling of crown rootless1 mutant stem base reveals new elements associated with crown root development in rice

    Directory of Open Access Journals (Sweden)

    Van Anh Le Thi

    2011-08-01

    Full Text Available Abstract Background In rice, the major part of the post-embryonic root system is made of stem-derived roots named crown roots (CR. Among the few characterized rice mutants affected in root development, crown rootless1 mutant is unable to initiate crown root primordia. CROWN ROOTLESS1 (CRL1 is induced by auxin and encodes an AS2/LOB-domain transcription factor that acts upstream of the gene regulatory network controlling CR development. Results To identify genes involved in CR development, we compared global gene expression profile in stem bases of crl1 mutant and wild-type (WT plants. Our analysis revealed that 250 and 236 genes are down- and up-regulated respectively in the crl1 mutant. Auxin induces CRL1 expression and consequently it is expected that auxin also alters the expression of genes that are early regulated by CRL1. To identify genes under the early control of CRL1, we monitored the expression kinetics of a selected subset of genes, mainly chosen among those exhibiting differential expression, in crl1 and WT following exogenous auxin treatment. This analysis revealed that most of these genes, mainly related to hormone, water and nutrient, development and homeostasis, were likely not regulated directly by CRL1. We hypothesized that the differential expression for these genes observed in the crl1 mutant is likely a consequence of the absence of CR formation. Otherwise, three CRL1-dependent auxin-responsive genes: FSM (FLATENNED SHOOT MERISTEM/FAS1 (FASCIATA1, GTE4 (GENERAL TRANSCRIPTION FACTOR GROUP E4 and MAP (MICROTUBULE-ASSOCIATED PROTEIN were identified. FSM/FAS1 and GTE4 are known in rice and Arabidopsis to be involved in the maintenance of root meristem through chromatin remodelling and cell cycle regulation respectively. Conclusion Our data showed that the differential regulation of most genes in crl1 versus WT may be an indirect consequence of CRL1 inactivation resulting from the absence of CR in the crl1 mutant. Nevertheless

  5. Mathematical Analysis of Biomolecular Network Reveals Connections Between Diseases

    Science.gov (United States)

    Wang, Guanyu

    2012-02-01

    Connections between cancer and metabolic diseases may consist in the complex network of interactions among a common set of biomolecules. By applying singularity and bifurcation analysis, the phenotypes constrained by the AKT signaling pathway are identified and mapped onto the parameter space, which include cancer and certain metabolic diseases. By considering physiologic properties (sensitivity, robustness and adaptivity) the AKT pathway must possess in order to efficiently sense growth factors and nutrients, the region of normal responses is located. The analysis illuminates the parameter space and reveals system-level mechanisms in regulating biological functions (cell growth, survival, proliferation and metabolism) and how their deregulation may lead to the development of diseases. The analytical expressions summarize the synergistic interactions among many molecules, which provides valuable insights into therapeutic interventions.

  6. Transcriptome and metabolite profiling reveals that prolonged drought modulates the phenylpropanoid and terpenoid pathway in white grapes (Vitis vinifera L.).

    Science.gov (United States)

    Savoi, Stefania; Wong, Darren C J; Arapitsas, Panagiotis; Miculan, Mara; Bucchetti, Barbara; Peterlunger, Enrico; Fait, Aaron; Mattivi, Fulvio; Castellarin, Simone D

    2016-03-21

    Secondary metabolism contributes to the adaptation of a plant to its environment. In wine grapes, fruit secondary metabolism largely determines wine quality. Climate change is predicted to exacerbate drought events in several viticultural areas, potentially affecting the wine quality. In red grapes, water deficit modulates flavonoid accumulation, leading to major quantitative and compositional changes in the profile of the anthocyanin pigments; in white grapes, the effect of water deficit on secondary metabolism is still largely unknown. In this study we investigated the impact of water deficit on the secondary metabolism of white grapes using a large scale metabolite and transcript profiling approach in a season characterized by prolonged drought. Irrigated grapevines were compared to non-irrigated grapevines that suffered from water deficit from early stages of berry development to harvest. A large effect of water deficit on fruit secondary metabolism was observed. Increased concentrations of phenylpropanoids, monoterpenes, and tocopherols were detected, while carotenoid and flavonoid accumulations were differentially modulated by water deficit according to the berry developmental stage. The RNA-sequencing analysis carried out on berries collected at three developmental stages-before, at the onset, and at late ripening-indicated that water deficit affected the expression of 4,889 genes. The Gene Ontology category secondary metabolic process was overrepresented within up-regulated genes at all the stages of fruit development considered, and within down-regulated genes before ripening. Eighteen phenylpropanoid, 16 flavonoid, 9 carotenoid, and 16 terpenoid structural genes were modulated by water deficit, indicating the transcriptional regulation of these metabolic pathways in fruit exposed to water deficit. An integrated network and promoter analyses identified a transcriptional regulatory module that encompasses terpenoid genes, transcription factors, and enriched

  7. Metabolomic profiling reveals potential markers and bioprocesses altered in bladder cancer progression

    National Research Council Canada - National Science Library

    Putluri, Nagireddy; Shojaie, Ali; Vasu, Vihas T; Vareed, Shaiju K; Nalluri, Srilatha; Putluri, Vasanta; Thangjam, Gagan Singh; Panzitt, Katrin; Tallman, Christopher T; Butler, Charles; Sana, Theodore R; Fischer, Steven M; Sica, Gabriel; Brat, Daniel J; Shi, Huidong; Palapattu, Ganesh S; Lotan, Yair; Weizer, Alon Z; Terris, Martha K; Shariat, Shahrokh F; Michailidis, George; Sreekumar, Arun

    2011-01-01

    .... Subsequent enrichment-based bioprocess mapping revealed alterations in phase I/II metabolism and suggested a possible role for DNA methylation in perturbing xenobiotic metabolism in bladder cancer...

  8. Treatment Strategy Profiles in Substance Use Disorder Treatment Programs: A Latent Class Analysis

    Science.gov (United States)

    Aletraris, Lydia; Paino, Maria; Roman, Paul M.

    2015-01-01

    Background Modern treatment options for substance use disorder are diverse. While studies have analyzed the adoption of individual evidence-based practices in treatment centers, little is known about the specific make-up of treatment strategy profiles in treatment centers throughout the United States. The current study used latent class analysis to profile underlying treatment strategies and to evaluate philosophical and structural supports associated with each profile. Methods Utilizing three aggregated and secondary datasets of nationally representative samples of substance use disorder treatment centers (N=775), we employed latent class analysis to determine treatment strategy profiles. Using multinomial logistic regression, we then examined organizational characteristics associated with each profile. Results We found three distinct treatment strategy profiles: Centers that primarily relied on Motivational Interviewing and Motivational Enhancement Therapy, centers that utilized psychosocial and alternative therapies, and centers that employed comprehensive treatments including pharmacotherapy. The multinomial logistic regression revealed that philosophical and structural center characteristics were associated with membership in the comprehensive class. Centers with philosophical orientations conducive to holistic care and pharmacotherapy-acceptance, resource-rich infrastructures, and an entrepreneurial reliance on insured clients were more likely to offer diverse interventions. All associations were significant at the .05 level. Principle Conclusion The findings from this study help us understand the general strategies of treatment centers. From a practical perspective, practitioners and clients should be aware of the variation in treatment center practices where they may offer or receive treatment. PMID:26105707

  9. Biostimulation and microbial community profiling reveal insights on RDX transformation in groundwater.

    Science.gov (United States)

    Wang, Dongping; Boukhalfa, Hakim; Marina, Oana; Ware, Doug S; Goering, Tim J; Sun, Fengjie; Daligault, Hajnalka E; Lo, Chien-Chi; Vuyisich, Momchilo; Starkenburg, Shawn R

    2017-04-01

    . putida strain II-B was specifically enriched in the RDX-degrading samples. Analysis of the accumulation of RDX-degradation products reveals that during active RDX degradation, there is a transient increase in the concentration of the degradation products MNX, DNX, TNX, and NDAB. The accumulation of these degradation products suggests that RDX is degraded via sequential reduction of the nitro functional groups followed by abiotic ring-cleavage. The results suggest that strict anaerobic conditions are needed to stimulate RDX degradation under the TA-16 site-specific conditions. © 2016 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.

  10. Variations in Academic Performance Trajectories during High School Transition: Exploring Change Profiles Via Multidimensional Scaling Growth Profile Analysis

    Science.gov (United States)

    Ding, Cody S.

    2008-01-01

    This study examines the baseline change profiles of academic performance (math and English) trajectories during the high school transition for the students who went from middle school to high school. Using multidimensional scaling growth profile analysis, we identified a no-change group plus 4 other groups with different change profile types: 1…

  11. Comparative analysis of gene expression profiles of OPN signalling ...

    Indian Academy of Sciences (India)

    The results showed that 23, 33, 59 and 74 genes were significantly changed in the above four kinds of liver diseases, respectively. H-clustering analysis showed that the expression profiles of OPN signalling-related genes were notably different in four kinds of liver diseases. Subsequently, a total of above-mentioned 147 ...

  12. Spatial and temporal profiles of growth factor expression during CNS demyelination reveal the dynamics of repair priming.

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    Viktoria Gudi

    Full Text Available Demyelination is the cause of disability in various neurological disorders. It is therefore crucial to understand the molecular regulation of oligodendrocytes, the myelin forming cells in the CNS. Growth factors are known to be essential for the development and maintenance of oligodendrocytes and are involved in the regulation of glial responses in various pathological conditions. We employed the well established murine cuprizone model of toxic demyelination to analyze the expression of 13 growth factors in the CNS during de- and remyelination. The temporal mRNA expression profile during demyelination and the subsequent remyelination were analyzed separately in the corpus callosum and cerebral cortex using laser microdissection and real-time PCR techniques. During demyelination a similar pattern of growth factor mRNA expression was observed in both areas with a strong up-regulation of NRG1 and GDNF and a slight increase of CNTF in the first week of cuprizone treatment. HGF, FGF-2, LIF, IGF-I, and TGF-ß1 were up-regulated mainly during peak demyelination. In contrast, during remyelination there were regional differences in growth factor mRNA expression levels. GDNF, CNTF, HGF, FGF-2, and BDNF were elevated in the corpus callosum but not in the cortex, suggesting tissue differences in the molecular regulation of remyelination in the white and grey matter. To clarify the cellular source we isolated microglia from the cuprizone lesions. GDNF, IGF-1, and FGF mRNA were detected in the microglial fraction with a temporal pattern corresponding to that from whole tissue PCR. In addition, immunohistochemical analysis revealed IGF-1 protein expression also in the reactive astrocytes. CNTF was located in astrocytes. This study identified seven different temporal expression patterns for growth factors in white and grey matter and demonstrated the importance of early tissue priming and exact orchestration of different steps during callosal and cortical de

  13. Bead arrays for antibody and complement profiling reveal joint contribution of antibody isotypes to C3 deposition.

    Directory of Open Access Journals (Sweden)

    Burcu Ayoglu

    Full Text Available The development of antigen arrays has provided researchers with great tools to identify reactivities against self or foreign antigens from body fluids. Yet, these approaches mostly do not address antibody isotypes and their effector functions even though these are key points for a more detailed understanding of disease processes. Here, we present a bead array-based assay for a multiplexed determination of antigen-specific antibody levels in parallel with their properties for complement activation. We measured the deposition of C3 fragments from serum samples to reflect the degree of complement activation via all three complement activation pathways. We utilized the assay on a bead array containing native and citrullinated peptide antigens to investigate the levels of IgG, IgM and IgA autoantibodies along with their complement activating properties in serum samples of 41 rheumatoid arthritis patients and 40 controls. Our analysis revealed significantly higher IgG reactivity against the citrullinated fibrinogen β and filaggrin peptides as well as an IgA reactivity that was exclusive for citrullinated fibrinogen β peptide and C3 deposition in rheumatoid arthritis patients. In addition, we characterized the humoral immune response against the viral EBNA-1 antigen to demonstrate the applicability of this assay beyond autoimmune conditions. We observed that particular buffer compositions were demanded for separate measurement of antibody reactivity and complement activation, as detection of antigen-antibody complexes appeared to be masked due to C3 deposition. We also found that rheumatoid factors of IgM isotype altered C3 deposition and introduced false-positive reactivities against EBNA-1 antigen. In conclusion, the presented bead-based assay setup can be utilized to profile antibody reactivities and immune-complex induced complement activation in a high-throughput manner and could facilitate the understanding and diagnosis of several diseases

  14. Transcriptional Profiling of Coxiella burnetii Reveals Extensive Cell Wall Remodeling in the Small Cell Variant Developmental Form

    Science.gov (United States)

    Sandoz, Kelsi M.; Popham, David L.; Beare, Paul A.; Sturdevant, Daniel E.; Hansen, Bryan; Nair, Vinod; Heinzen, Robert A.

    2016-01-01

    A hallmark of Coxiella burnetii, the bacterial cause of human Q fever, is a biphasic developmental cycle that generates biologically, ultrastructurally, and compositionally distinct large cell variant (LCV) and small cell variant (SCV) forms. LCVs are replicating, exponential phase forms while SCVs are non-replicating, stationary phase forms. The SCV has several properties, such as a condensed nucleoid and an unusual cell envelope, suspected of conferring enhanced environmental stability. To identify genetic determinants of the LCV to SCV transition, we profiled the C. burnetii transcriptome at 3 (early LCV), 5 (late LCV), 7 (intermediate forms), 14 (early SCV), and 21 days (late SCV) post-infection of Vero epithelial cells. Relative to early LCV, genes downregulated in the SCV were primarily involved in intermediary metabolism. Upregulated SCV genes included those involved in oxidative stress responses, arginine acquisition, and cell wall remodeling. A striking transcriptional signature of the SCV was induction (>7-fold) of five genes encoding predicted L,D transpeptidases that catalyze nonclassical 3–3 peptide cross-links in peptidoglycan (PG), a modification that can influence several biological traits in bacteria. Accordingly, of cross-links identified, muropeptide analysis showed PG of SCV with 46% 3–3 cross-links as opposed to 16% 3–3 cross-links for LCV. Moreover, electron microscopy revealed SCV with an unusually dense cell wall/outer membrane complex as compared to LCV with its clearly distinguishable periplasm and inner and outer membranes. Collectively, these results indicate the SCV produces a unique transcriptome with a major component directed towards remodeling a PG layer that likely contributes to Coxiella’s environmental resistance. PMID:26909555

  15. A compendium of antibiotic-induced transcription profiles reveals broad regulation of Pasteurella multocida virulence genes.

    Science.gov (United States)

    Melnikow, E; Schoenfeld, C; Spehr, V; Warrass, R; Gunkel, N; Duszenko, M; Selzer, P M; Ullrich, H J

    2008-10-15

    The transcriptional responses of Pasteurella multocida to eight antibiotics with known mode of actions (MoAs) and one novel antibiotic compound with an unknown MoA were collected to create a compendium of transcriptional profiles for MoA studies. At minimal inhibitory concentration the three bactericidal compounds enrofloxacin, cefquinome and the novel compound had a minor impact on gene regulation with approximately 1% of the P. multocida genome affected, whilst the bacteriostatic compounds florfenicol, tilmicosin, rifampin, trimethoprim and brodimoprim regulated 20% of the genome. Novobiocin was special in that it regulated 40% of all P. multocida genes. Regulation of target genes was observed for novobiocin, rifampin, florfenicol and tilmicosin and signature genes were identified for most antibiotics. The transcriptional profile induced by the novel compound was unrelated to the compendium profiles suggesting a new MoA. The transcription of many P. multocida virulence factors, particularly genes involved in capsule synthesis and export, LPS synthesis, competence, adherence and iron transport were altered in the presence of antibiotics. Virulence gene transcription was mainly negatively affected, however the opposite effect was also observed in the case of rifampin where the up-regulation of the tad locus involved in tight adherence was seen. Novobiocin and trimethoprim caused a marked reduction in the transcription of capsule genes, which correlated with a concomitant reduction of the capsular layer on the surface of P. multocida. The broad negative impact on virulence gene transcription supports the notion that the therapeutic effect of some antibiotics could be a combination of growth and virulence inhibition.

  16. Revealing metabolic phenotypes in plants: inputs from NMR analysis.

    Science.gov (United States)

    Ratcliffe, R G; Shachar-Hill, Y

    2005-02-01

    Assessing the performance of the plant metabolic network, with its varied biosynthetic capacity and its characteristic subcellular compartmentation, remains a considerable challenge. The complexity of the network is such that it is not yet possible to build large-scale predictive models of the fluxes it supports, whether on the basis of genomic and gene expression analysis or on the basis of more traditional measurements of metabolites and their interconversions. This limits the agronomic and biotechnological exploitation of plant metabolism, and it undermines the important objective of establishing a rational metabolic engineering strategy. Metabolic analysis is central to removing this obstacle and currently there is particular interest in harnessing high-throughput and/or large-scale analyses to the task of defining metabolic phenotypes. Nuclear magnetic resonance (NMR) spectroscopy contributes to this objective by providing a versatile suite of analytical techniques for the detection of metabolites and the fluxes between them. The principles that underpin the analysis of plant metabolism by NMR are described, including a discussion of the measurement options for the detection of metabolites in vivo and in vitro, and a description of the stable isotope labelling experiments that provide the basis for metabolic flux analysis. Despite a relatively low sensitivity, NMR is suitable for high-throughput system-wide analyses of the metabolome, providing methods for both metabolite fingerprinting and metabolite profiling, and in these areas NMR can contribute to the definition of plant metabolic phenotypes that are based on metabolic composition. NMR can also be used to investigate the operation of plant metabolic networks. Labelling experiments provide information on the operation of specific pathways within the network, and the quantitative analysis of steady-state labelling experiments leads to the definition of large-scale flux maps for heterotrophic carbon

  17. 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...

  18. Objective Diagnosis of Cervical Cancer by Tissue Protein Profile Analysis

    Science.gov (United States)

    Patil, Ajeetkumar; Bhat, Sujatha; Rai, Lavanya; Kartha, V. B.; Chidangil, Santhosh

    2011-07-01

    Protein profiles of homogenized normal cervical tissue samples from hysterectomy subjects and cancerous cervical tissues from biopsy samples collected from patients with different stages of cervical cancer were recorded using High Performance Liquid Chromatography coupled with Laser Induced Fluorescence (HPLC-LIF). The Protein profiles were subjected to Principle Component Analysis to derive statistically significant parameters. Diagnosis of sample types were carried out by matching three parameters—scores of factors, squared residuals, and Mahalanobis Distance. ROC and Youden's Index curves for calibration standards were used for objective estimation of the optimum threshold for decision making and performance.

  19. Systematic Epigenomic Analysis Reveals Chromatin States Associated with Melanoma Progression

    Directory of Open Access Journals (Sweden)

    Petko Fiziev

    2017-04-01

    Full Text Available The extent and nature of epigenomic changes associated with melanoma progression is poorly understood. Through systematic epigenomic profiling of 35 epigenetic modifications and transcriptomic analysis, we define chromatin state changes associated with melanomagenesis by using a cell phenotypic model of non-tumorigenic and tumorigenic states. Computation of specific chromatin state transitions showed loss of histone acetylations and H3K4me2/3 on regulatory regions proximal to specific cancer-regulatory genes in important melanoma-driving cell signaling pathways. Importantly, such acetylation changes were also observed between benign nevi and malignant melanoma human tissues. Intriguingly, only a small fraction of chromatin state transitions correlated with expected changes in gene expression patterns. Restoration of acetylation levels on deacetylated loci by histone deacetylase (HDAC inhibitors selectively blocked excessive proliferation in tumorigenic cells and human melanoma cells, suggesting functional roles of observed chromatin state transitions in driving hyperproliferative phenotype. Through these results, we define functionally relevant chromatin states associated with melanoma progression.

  20. Systematic Epigenomic Analysis Reveals Chromatin States Associated with Melanoma Progression.

    Science.gov (United States)

    Fiziev, Petko; Akdemir, Kadir C; Miller, John P; Keung, Emily Z; Samant, Neha S; Sharma, Sneha; Natale, Christopher A; Terranova, Christopher J; Maitituoheti, Mayinuer; Amin, Samirkumar B; Martinez-Ledesma, Emmanuel; Dhamdhere, Mayura; Axelrad, Jacob B; Shah, Amiksha; Cheng, Christine S; Mahadeshwar, Harshad; Seth, Sahil; Barton, Michelle C; Protopopov, Alexei; Tsai, Kenneth Y; Davies, Michael A; Garcia, Benjamin A; Amit, Ido; Chin, Lynda; Ernst, Jason; Rai, Kunal

    2017-04-25

    The extent and nature of epigenomic changes associated with melanoma progression is poorly understood. Through systematic epigenomic profiling of 35 epigenetic modifications and transcriptomic analysis, we define chromatin state changes associated with melanomagenesis by using a cell phenotypic model of non-tumorigenic and tumorigenic states. Computation of specific chromatin state transitions showed loss of histone acetylations and H3K4me2/3 on regulatory regions proximal to specific cancer-regulatory genes in important melanoma-driving cell signaling pathways. Importantly, such acetylation changes were also observed between benign nevi and malignant melanoma human tissues. Intriguingly, only a small fraction of chromatin state transitions correlated with expected changes in gene expression patterns. Restoration of acetylation levels on deacetylated loci by histone deacetylase (HDAC) inhibitors selectively blocked excessive proliferation in tumorigenic cells and human melanoma cells, suggesting functional roles of observed chromatin state transitions in driving hyperproliferative phenotype. Through these results, we define functionally relevant chromatin states associated with melanoma progression. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  1. Antifungal Susceptibility Profiles of 1698 Yeast Reference Strains Revealing Potential Emerging Human Pathogens

    Science.gov (United States)

    Desnos-Ollivier, Marie; Robert, Vincent; Raoux-Barbot, Dorothée; Groenewald, Marizeth; Dromer, Françoise

    2012-01-01

    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. PMID:22396754

  2. 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.

  3. 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.

  4. Profiling the dynamics of a human phosphorylome reveals new components in HGF/c-Met signaling.

    Directory of Open Access Journals (Sweden)

    Crystal L Woodard

    Full Text Available Protein phosphorylation is a dynamic and reversible event that greatly influences cellular function. Identifying the key regulatory elements that determine cellular phenotypes during development and oncogenesis requires the ability to dynamically monitor proteome-wide events. Here, we report the development of a new strategy to monitor dynamic changes of protein phosphorylation in cells and tissues using functional protein microarrays as the readout. To demonstrate this technology's ability to identify condition-dependent phosphorylation events, human protein microarrays were incubated with lysates from cells or tissues under activation or inhibition of c-Met, a receptor tyrosine kinase involved in tissue morphogenesis and malignancy. By comparing the differences between the protein phosphorylation profiles obtained using the protein microarrays, we were able to recover many of the proteins that are known to be specifically activated (i.e., phosphorylated upon c-Met activation by the hepatocyte growth factor (HGF. Most importantly, we discovered many proteins that were differentially phosphorylated by lysates from cells or tissues when the c-Met pathway was active. Using phosphorylation-specific antibodies, we were able to validate several candidate proteins as new downstream components of the c-Met signaling pathway in cells. We envision that this new approach, like its DNA microarray counterpart, can be further extended toward profiling dynamics of global protein phosphorylation under many different physiological conditions both in cellulo and in vivo in a high-throughput and cost-effective fashion.

  5. Gene co-expression networks and profiles reveal potential biomarkers of boar taint in pigs

    DEFF Research Database (Denmark)

    Drag, Markus; Skinkyté-Juskiené, Rúta; Do, Duy Ngoc

    Boar taint (BT) is an offensive odour or taste of porcine meat which may occur in entire male pigs due to skatole and androstenone accumulation. To avoid BT, castration of young piglets is performed but this strategy is under debate due to animal welfare concerns. The study aimed to reveal potent...

  6. Defect-Related Physical-Profile-Based X-Ray and Neutron Line Profile Analysis

    Science.gov (United States)

    Ungár, Tamás; Balogh, Levente; Ribárik, Gábor

    2010-05-01

    Diffraction line broadening is caused by different defects present in crystalline materials: (1) small coherent domains, (2) dislocations, (3) other types of microstrains, (4) twin boundaries, (5) stacking faults, (6) chemical inhomogeneities, and (7) grain-to-grain second-order internal stresses. Line profile analysis provides qualitative and quantitative information about defect types and densities, respectively. Line profiles can broaden, be asymmetric, and be shifted, and these features can be anisotropic in terms of hkl indices. A few thumb rules help qualitative selection of lattice defect types. If the breadths do not increase globally with hkl, the defects are of size type, i.e., either the domain size is small or twinning or faulting, or both, is present. Whenever the breadths increase globally, the defects produce microstrains. Physically based profile functions can be determined for the different defect types and hkl anisotropy. The qualitative input about defect types based on different experimental observations allows adequate quantitative evaluation of the densities of different defect types by using physically modeled profile functions.

  7. Proteomic profiling of chikungunya virus-infected human muscle cells: reveal the role of cytoskeleton network in CHIKV replication.

    Science.gov (United States)

    Issac, Too Horng Khit; Tan, Eng Lee; Chu, Justin Jang Hann

    2014-08-28

    Chikungunya virus (CHIKV) is an arthropod-borne, positive-sense, single-stranded RNA virus belonging to genus Alphavirus and family Togaviridae. The clinical manifestations developed upon CHIKV-infection include fever, myositis, arthralgia and maculopapular rash. Thus, the re-emergence of CHIKV has posed serious health threats worldwide. Due to the fact that myositis is induced upon CHIKV-infection, we sought to understand the dynamic proteomic regulation in SJCRH30, a human rhabdomyosarcoma cell line, to gain insights on CHIKV pathogenesis. Two-dimensional gel electrophoresis (2DE) in combination of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) was used to profile differential cellular proteins expression in CHIKV-infected SJCRH30 cells. 2DE analysis on CHIKV-infected cells has revealed 44 protein spots. These spots are found to be involved in various biological pathways such as biomolecules synthesis and metabolism, cell signaling and cellular reorganization. siRNA-mediated gene silencing on selected genes has elucidated the biological significance of these gene-translated host proteins involved in CHIKV-infection. More importantly, the interaction of vimentin with non-structural protein (nsP3) of CHIKV was shown, suggesting the role played by vimentin during CHIKV replication by forming an anchorage network with the CHIKV replication complexes (RCs). Chikungunya virus (CHIKV) is a re-emerging virus that has caused various disease outbreaks in Africa and Asia. The clinical symptoms of CHIKV-infection include fever, skin rash, recurrent joint paint, and myositis. Neuronal implications and death may be resulted from the severe viral infection. Up to date, there are no effective treatments and vaccines against CHIKV-infection. More importantly, little is known about the differential regulation of host proteins upon CHIKV infection, hence deciphering the viral-host cell interactions during viral infection provide critical

  8. Comparative Transcriptome Profiling Reveals Coding and Noncoding RNA Differences in NSCLC from African Americans and European Americans.

    Science.gov (United States)

    Mitchell, Khadijah A; Zingone, Adriana; Toulabi, Leila; Boeckelman, Jacob; Ryan, Bríd M

    2017-12-01

    Purpose: To determine whether racial differences in gene and miRNA expression translates to differences in lung tumor biology with clinical relevance in African Americans (AAs) and European Americans (EAs). Experimental Design: The NCI-Maryland Case Control Study includes seven Baltimore City hospitals and is overrepresented with AA patients (∼40%). Patients that underwent curative NSCLC surgery between 1998 and 2014 were enrolled. Comparative molecular profiling used mRNA ( n = 22 AAs and 19 EAs) and miRNA ( n = 42 AAs and 55 EAs) expression arrays to track differences in paired fresh frozen normal tissues and lung tumor specimens from AAs and EAs. Pathway enrichment, predicted drug response, tumor microenvironment infiltration, cancer immunotherapy antigen profiling, and miRNA target enrichment were assessed. Results: AA-enriched differential gene expression was characterized by stem cell and invasion pathways. Differential gene expression in lung tumors from EAs was primarily characterized by cell proliferation pathways. Population-specific gene expression was partly driven by population-specific miRNA expression profiles. Drug susceptibility predictions revealed a strong inverse correlation between AA resistance and EA sensitivity to the same panel of drugs. Statistically significant differences in M1 and M2 macrophage infiltration were observed in AAs ( P profiling revealed clear differences in lung tumor biology between AAs and EAs. Increased participation by AAs in lung cancer clinical trials are needed to integrate, and leverage, transcriptomic differences with other clinical information to maximize therapeutic benefit in both AAs and EAs. Clin Cancer Res; 23(23); 7412-25. ©2017 AACR . ©2017 American Association for Cancer Research.

  9. The Immersive Virtual Reality Experience: A Typology of Users Revealed Through Multiple Correspondence Analysis Combined with Cluster Analysis Technique.

    Science.gov (United States)

    Rosa, Pedro J; Morais, Diogo; Gamito, Pedro; Oliveira, Jorge; Saraiva, Tomaz

    2016-03-01

    Immersive virtual reality is thought to be advantageous by leading to higher levels of presence. However, and despite users getting actively involved in immersive three-dimensional virtual environments that incorporate sound and motion, there are individual factors, such as age, video game knowledge, and the predisposition to immersion, that may be associated with the quality of virtual reality experience. Moreover, one particular concern for users engaged in immersive virtual reality environments (VREs) is the possibility of side effects, such as cybersickness. The literature suggests that at least 60% of virtual reality users report having felt symptoms of cybersickness, which reduces the quality of the virtual reality experience. The aim of this study was thus to profile the right user to be involved in a VRE through head-mounted display. To examine which user characteristics are associated with the most effective virtual reality experience (lower cybersickness), a multiple correspondence analysis combined with cluster analysis technique was performed. Results revealed three distinct profiles, showing that the PC gamer profile is more associated with higher levels of virtual reality effectiveness, that is, higher predisposition to be immersed and reduced cybersickness symptoms in the VRE than console gamer and nongamer. These findings can be a useful orientation in clinical practice and future research as they help identify which users are more predisposed to benefit from immersive VREs.

  10. Strength analysis of welded corners of PVC window profiles

    Science.gov (United States)

    Postawa, P.; Stachowiak, T.; Gnatowski, A.

    2017-08-01

    The article presents the results of researches which main purpose was to define the influence of welding parameters on strength of welded corners of PVC window profile. PVC profiles of a branded name GENEO® produced by Rehau Company were used for this research. The profiles were made by using a co-extrusion method. The surface of the profile was made of PVC mixture with no additives. Its main task was to get a smooth surface resistant to a smudge. The use of an unfilled polyester provides an aesthetic look and improves the resistance of extrudate to water getting into inner layers. The profile's inner layers have been filled up with glass fibre in order to improve its stiffness and mechanical properties. Window frames with cut corners used for this research, were produced on technological line of EUROCOLOR Company based in Pyskowice (Poland). The main goal of this analysis was to evaluate the influence of the main welding parameter (temperature upsetting) on hardness of welds we received in whole process. A universal testing machine was used for the research.

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

    Science.gov (United States)

    Ingolia, Nicholas T.; Brar, Gloria A.; Stern-Ginossar, Noam; Harris, Michael S.; Talhouarne, Gaëlle J. S.; Jackson, Sarah E.; Wills, Mark R.; Weissman, Jonathan S.

    2014-01-01

    SUMMARY Ribosome profiling suggests that ribosomes occupy many regions of the transcriptome thought to be non-coding, including 5′ UTRs and 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: co-purification 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 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 to understand how cells manage and exploit its consequences. PMID:25159147

  12. 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.

  13. Untargeted metabolite profiling of murine embryos to reveal metabolic perturbations associated with neural tube closure defects.

    Science.gov (United States)

    Hansler, Alex; Chen, Qiuying; Gray, Jason D; Ross, M Elizabeth; Finnell, Richard H; Gross, Steven S

    2014-08-01

    Neural tube closure defects (NTDs) are among the most common congenital malformation in human, typically presenting in liveborns as spina bifida. At least 240 gene mutations in mouse are known to increase the risk of NTD. There is a growing appreciation that environmental factors significantly contribute to NTD expression, and that NTDs likely arise from complex gene-environment interactions. Because maternal folic acid supplementation reduces human NTD risk in some populations by 60 to 70%, it is likely that NTD predisposition is often associated with a defect in folate-dependent one-carbon metabolism. A comprehensive, untargeted metabolic survey of NTD-associated changes in embryo metabolism would provide a valuable test of this assumption. We sought to establish a metabolic profiling platform that is capable of broadly assessing metabolic aberrations associated with NTD-promoting gene mutations in early-stage mouse embryos. A liquid chromatography/mass spectrometry-based untargeted metabolite profiling platform was used to broadly identify significant differences in small molecule levels (50-1000 Da) in NTD-affected embryonic day (E) 9.5 mouse embryos (Lrp6(-) (/) (-) ) versus unaffected (Lrp6(+/+) ) control embryos. Results provide proof-of-principal feasibility for the broad survey of the metabolome of individual E9.5 mouse embryos and identification of metabolic changes associated with NTDs and gene mutations. Levels of 30 different metabolites were altered in association with Lrp6 gene deletion. Some metabolites link to folate-dependent one-carbon transfer reactions, as anticipated, while others await structure elucidation and pathway integration. Whole-embryo metabolomics offers the potential to identify metabolic changes in genetically determined NTD-prone embryos. © 2014 Wiley Periodicals, Inc.

  14. 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

  15. Gene Expression Profiling of Dendritic Cells Reveals Important Mechanisms Associated with Predisposition to Staphylococcus Infections

    Science.gov (United States)

    Toufeer, Mehdi; Bonnefont, Cécile M. D.; Foulon, Eliane; Caubet, Cécile; Tasca, Christian; Aurel, Marie-Rose; Robert-Granié, Christèle; Rupp, Rachel; Foucras, Gilles

    2011-01-01

    Background Staphylococcus aureus is a major pathogen of humans and animals and emerging antibiotic-resistant strains have further increased the concern of this health issue. Host genetics influence susceptibility to S. aureus infections, and the genes determining the outcome of infections should be identified to find alternative therapies to treatment with antibiotics. Here, we used outbred animals from a divergent selection based on susceptibility towards Staphylococcus infection to explore host immunogenetics. Methodology/Principal Findings We investigated how dendritic cells respond to heat-inactivated S. aureus and whether dendritic cells from animals showing different degrees of susceptibility had distinct gene expression profiles. We measured gene expression levels of in vitro S. aureus-stimulated bone marrow-derived dendritic cells at three different time points (0, 3 and 8 hrs) by using 15 k ovine Agilent microarrays. Furthermore, differential expression of a selected number of genes was confirmed by RT-qPCR. Gene signatures of stimulated DCs were obtained and showed that genes involved in the inflammatory process and T helper cell polarization were highly up-regulated upon stimulation. Moreover, a set of 204 genes were statistically differentially expressed between susceptible and resistant animals, and grouped them according to their predisposition to staphylococcal infection. Interestingly, over-expression of the C1q and Ido1 genes was observed in the resistant line and suggested a role of classical pathway of complement and early regulation of inflammation pathways, respectively. On the contrary, over expression of genes involved in the IL1R pathway was observed in susceptible animals. Furthermore, the leucocyte extravasation pathway was also found to be dominant in the susceptible line. Conclusion/Significance We successfully obtained Staphylococcus aureus associated gene expression of ovine BM-DC in an 8-hour kinetics experiment. The distinct

  16. Differential Expression Profiles of the Transcriptome in Breast Cancer Cell Lines Revealed by Next Generation Sequencing

    Directory of Open Access Journals (Sweden)

    Yu Shi

    2017-11-01

    Full Text Available Background/Aims: As MCF-7 and MDA-MB-231 cells are the typical cell lines of two clinical breast tumour subtypes, the aim of the present study was to elucidate the transcriptome differences between MCF-7 and MDA-MB-231 breast cancer cell lines. Methods: The mRNA, miRNA (MicroRNA and lncRNA (Long non-coding RNA expression profiles were examined using NGS (next generation sequencing instrument Illumina HiSeq-2500. GO (Gene Ontology and KEGG (Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed to identify the biological functions of differentially expressed coding RNAs. Subsequently, we constructed an mRNA-ncRNA (non-coding RNA targeting regulatory network. Finally, we performed RT-qPCR (real-time quantitative PCR to confirm the NGS results. Results: There are sharp distinctions of the coding and non-coding RNA profiles between MCF-7 and MDA-MB-231 cell lines. Among the mRNAs and ncRNAs with the most differential expression, SLPI, SOD2, miR-7, miR-143 and miR-145 were highly expressed in MCF-7 cells, while CD55, KRT17, miR-21, miR-10b, miR-9, NEAT1 and PICSAR were over-expressed in MDA-MB-231 cells. Differentially expressed mRNAs are primarily involved in biological processes of locomotion, biological adhesion, ECM-receptor interaction pathway and focal adhesion. In the targeting regulatory network of differentially expressed RNAs, mRNAs and miRNAs are primarily associated with tumour metastasis, but the functions of lncRNAs remain uncharacterized. Conclusion: These results provide a basis for future studies of breast cancer metastasis and drug resistance.

  17. Genomic profiling reveals extensive heterogeneity in somatic DNA copy number aberrations of canine hemangiosarcoma.

    Science.gov (United States)

    Thomas, Rachael; Borst, Luke; Rotroff, Daniel; Motsinger-Reif, Alison; Lindblad-Toh, Kerstin; Modiano, Jaime F; Breen, Matthew

    2014-09-01

    Canine hemangiosarcoma is a highly aggressive vascular neoplasm associated with extensive clinical and anatomical heterogeneity and a grave prognosis. Comprehensive molecular characterization of hemangiosarcoma may identify novel therapeutic targets and advanced clinical management strategies, but there are no published reports of tumor-associated genome instability and disrupted gene dosage in this cancer. We performed genome-wide microarray-based somatic DNA copy number profiling of 75 primary intra-abdominal hemangiosarcomas from five popular dog breeds that are highly predisposed to this disease. The cohort exhibited limited global genomic instability, compared to other canine sarcomas studied to date, and DNA copy number aberrations (CNAs) were predominantly of low amplitude. Recurrent imbalances of several key cancer-associated genes were evident; however, the global penetrance of any single CNA was low and no distinct hallmark aberrations were evident. Copy number gains of dog chromosomes 13, 24, and 31, and loss of chromosome 16, were the most recurrent CNAs involving large chromosome regions, but their relative distribution within and between cases suggests they most likely represent passenger aberrations. CNAs involving CDKN2A, VEGFA, and the SKI oncogene were identified as potential driver aberrations of hemangiosarcoma development, highlighting potential targets for therapeutic modulation. CNA profiles were broadly conserved between the five breeds, although subregional variation was evident, including a near twofold lower incidence of VEGFA gain in Golden Retrievers versus other breeds (22 versus 40 %). These observations support prior transcriptional studies suggesting that the clinical heterogeneity of this cancer may reflect the existence of multiple, molecularly distinct subtypes of canine hemangiosarcoma.

  18. Gene expression profiling of Epstein–Barr virus-positive diffuse large B-cell lymphoma of the elderly reveals alterations of characteristic oncogenetic pathways

    Science.gov (United States)

    Kato, Harumi; Karube, Kennosuke; Yamamoto, Kazuhito; Takizawa, Jun; Tsuzuki, Shinobu; Yatabe, Yasushi; Kanda, Teru; Katayama, Miyuki; Ozawa, Yukiyasu; Ishitsuka, Kenji; Okamoto, Masataka; Kinoshita, Tomohiro; Ohshima, Koichi; Nakamura, Shigeo; Morishima, Yasuo; Seto, Masao

    2014-01-01

    Epstein–Barr virus (EBV)-positive diffuse large B-cell lymphoma (DLBCL) of the elderly (EBV[+]DLBCL-E) is classified as a subtype of DLBCL. Until now, its molecular pathogenesis has remained unknown. To identify pathways characteristic of EBV(+)DLBCL-E, gene expression profiling of five EBV(+)DLBCL-E and seven EBV-negative DLBCL (EBV[−]DLBCL) cases was undertaken using human oligonucleotide microarray analysis. Gene set enrichment analysis and gene ontology analysis showed that gene sets of the Janus kinase-signal transducer and activator of transcription (JAK-STAT) and nuclear factor kappa B (NF-κB) pathways were enriched in EBV(+)DLBCL-E cases. To confirm the results of the expression profiles, in vitro analysis was performed. Expression profiling analysis showed that high activation of the JAK-STAT and NF-κB pathways was induced by EBV infection into DLBCL cell lines. Activation of the NF-κB pathway was confirmed in EBV-infected cell lines using an electrophoretic mobility shift assay. Western blot analysis revealed an increased protein expression level of phosphorylated signal transducer and activator of transcription 3 (STAT3) in an EBV-infected cell line. Protein expression of phosphorylated STAT3 was frequently observed in lymphoma cells of EBV(+)DLBCL-E clinical samples using immunohistochemistry (EBV[+]DLBCL-E: 80.0% [n = 20/25] versus EBV[−]DLBCL: 38.9% [n = 14/36]; P = 0.001). The results of the present study suggest that activation of the JAK-STAT and NF-κB pathways was characteristic of EBV(+)DLBCL-E, which may reflect the nature of EBV-positive tumor cells. Targeting these pathways as therapies might improve clinical outcomes of EBV(+)DLBCL-E. PMID:24581222

  19. Integrative analysis of RNA, translation, and protein levels reveals distinct regulatory variation across humans

    Science.gov (United States)

    Cenik, Can; Cenik, Elif Sarinay; Byeon, Gun W.; Grubert, Fabian; Candille, Sophie I.; Spacek, Damek; Alsallakh, Bilal; Tilgner, Hagen; Araya, Carlos L.; Tang, Hua; Ricci, Emiliano; Snyder, Michael P.

    2015-01-01

    Elucidating the consequences of genetic differences between humans is essential for understanding phenotypic diversity and personalized medicine. Although variation in RNA levels, transcription factor binding, and chromatin have been explored, little is known about global variation in translation and its genetic determinants. We used ribosome profiling, RNA sequencing, and mass spectrometry to perform an integrated analysis in lymphoblastoid cell lines from a diverse group of individuals. We find significant differences in RNA, translation, and protein levels suggesting diverse mechanisms of personalized gene expression control. Combined analysis of RNA expression and ribosome occupancy improves the identification of individual protein level differences. Finally, we identify genetic differences that specifically modulate ribosome occupancy—many of these differences lie close to start codons and upstream ORFs. Our results reveal a new level of gene expression variation among humans and indicate that genetic variants can cause changes in protein levels through effects on translation. PMID:26297486

  20. Small RNA profiling reveals deregulated phosphatase and tensin homolog (PTEN)/phosphoinositide 3-kinase (PI3K)/Akt pathway in bronchial smooth muscle cells from asthmatic patients.

    Science.gov (United States)

    Alexandrova, Elena; Miglino, Nicola; Hashim, Adnan; Nassa, Giovanni; Stellato, Claudia; Tamm, Michael; Baty, Florent; Brutsche, Martin; Weisz, Alessandro; Borger, Pieter

    2016-01-01

    Aberrant expression of small noncoding RNAs (sncRNAs), microRNAs (miRNAs) and PIWI-interacting RNAs (piRNAs) in particular, define several pathologic processes. Asthma is characterized by airway hyperreactivity, chronic inflammation, and airway wall remodeling. Asthma-specific miRNA profiles were reported for bronchial epithelial cells, whereas sncRNA expression in asthmatic bronchial smooth muscle (BSM) cells is almost completely unexplored. We sought to determine whether the primary BSM sncRNA expression profile is altered in asthmatic patients and identify targets of differentially expressed sncRNAs. Small RNA sequencing was used for sncRNA profiling in BSM cells (from 8 asthmatic and 6 nonasthmatic subjects). sncRNA identification and differential expression analysis was performed with iMir software. Experimentally validated miRNA targets were identified by using Ingenuity Pathway Analysis, and putative piRNA targets were identified by using miRanda software. BSM cells from asthmatic patients showed abnormal expression of 32 sncRNAs (26 miRNAs, 5 piRNAs, and 1 small nucleolar RNA). Target prediction for deregulated miRNAs and piRNAs revealed experimentally validated and predicted mRNA targets expressed in the BSM cells. Thirty-eight of these mRNAs represent major targets for deregulated miRNAs and might play important roles in the pathophysiology of asthma. Interestingly, 6 of these mRNAs were previously associated with asthma, considered as novel therapeutic targets for treatment of this disease, or both. Signaling pathway analysis revealed involvement of 38 miRNA-targeted mRNAs in increased cell proliferation through phosphatase and tensin homolog and phosphoinositide 3-kinase/Akt signaling pathways. BSM cells of asthmatic patients are characterized by aberrant sncRNA expression that recapitulates multiple pathologic phenotypes of these cells. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  1. Error analysis for mesospheric temperature profiling by absorptive occultation sensors

    Directory of Open Access Journals (Sweden)

    M. J. Rieder

    Full Text Available An error analysis for mesospheric profiles retrieved from absorptive occultation data has been performed, starting with realistic error assumptions as would apply to intensity data collected by available high-precision UV photodiode sensors. Propagation of statistical errors was investigated through the complete retrieval chain from measured intensity profiles to atmospheric density, pressure, and temperature profiles. We assumed unbiased errors as the occultation method is essentially self-calibrating and straight-line propagation of occulted signals as we focus on heights of 50–100 km, where refractive bending of the sensed radiation is negligible. Throughout the analysis the errors were characterized at each retrieval step by their mean profile, their covariance matrix and their probability density function (pdf. This furnishes, compared to a variance-only estimation, a much improved insight into the error propagation mechanism. We applied the procedure to a baseline analysis of the performance of a recently proposed solar UV occultation sensor (SMAS – Sun Monitor and Atmospheric Sounder and provide, using a reasonable exponential atmospheric model as background, results on error standard deviations and error correlation functions of density, pressure, and temperature profiles. Two different sensor photodiode assumptions are discussed, respectively, diamond diodes (DD with 0.03% and silicon diodes (SD with 0.1% (unattenuated intensity measurement noise at 10 Hz sampling rate. A factor-of-2 margin was applied to these noise values in order to roughly account for unmodeled cross section uncertainties. Within the entire height domain (50–100 km we find temperature to be retrieved to better than 0.3 K (DD / 1 K (SD accuracy, respectively, at 2 km height resolution. The results indicate that absorptive occultations acquired by a SMAS-type sensor could provide mesospheric profiles of fundamental variables such as temperature with

  2. 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.

  3. 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

    2015-01-01

    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. PMID:26966343

  4. [Plasmid profile analysis in identification of epidemic strains of Salmonella enterica serovar Enteritidis].

    Science.gov (United States)

    Miljković-Selimović, Biljana; Lepsanović, Zorica; Babić, Tatjana; Kocić, Branislava; Randelović, Gordana

    2008-04-01

    As illness caused by Sallmonella enterica serovar Enteritidis (S. Enteritidis) occurs not only as sporadic cases but as outbreaks, to reveal the source and routes of spreading of infection it is necessary to identify epidemic strain by the use of some typing methods. To determine whether plasmid profile analysis, as genotyping method, could be applied for the investigation of epidemic strains, isolates of S. Enteritidis, recovered from patient's stools and food associated with outbreaks and those isolated from sporadic cases of diarrhea, were investigated. Investigation of antibiotic resistance was performed by Kirby-Bauer disc-diffusion method. Isolation of plasmid DNA was carried out by Birnboim and Dolly alkaline lysis method, modified by Ish-Horovitz. Out of 276 izolates of S. Enteritidis 94 were isolated from patient's stools and food associated with outbreaks and 182 were isolated from sporadic cases of diarrhea. The presence of 12 plasmid profiles was established. An average correlation degree of plasmid profiles between the strains was 0.84, that implies high degree of similarity of plasmid profiles of epidemic and non epidemic strains isolated at our geographic region for the given period of time. The strains of S. Enteritidis, isolated in outbreaks of enterocolitis as well as from spordic cases of diarrhea in the same period of time and at the same area, frequently exhibit the same plasmid profile characterized by a single plasmid of 38 MDa. Therefore, in most cases plasmid profile analysis is not valuable in the identification of epidemic strains of S. Enteritidis. However, for this purpose plasmid profile analysis could be used when drug-resistant strains of S. Enteritidis are isolated, as they often possess additional resistant plasmids what increases discrimination power of this method.

  5. Plasmid profile analysis in identification of epidemic strains of Salmonella enterica serovar Enteritidis

    Directory of Open Access Journals (Sweden)

    Miljković-Selimović Biljana

    2008-01-01

    Full Text Available Background/Aim. As illness caused by Sallmonella enterica serovar Enteritidis (S. Enteritidis occurs not only as sporadic cases but as outbreaks, to reveal the source and routes of spreading of infection it is necessary to identify epidemic strain by the use of some typing methods. To determine whether plasmid profile analysis, as genotyping method, could be applied for the investigation of epidemic strains, isolates of S. Enteritidis, recovered from patient's stools and food associated with outbreaks and those isolated from sporadic cases of diarrhea, were investigated. Methods. Investigation of antibiotic resistance was performed by Kirby - Bauer disc-diffusion method. Isolation of plasmid DNA was carried out by Birnboim and Dolly alkaline lysis method, modified by Ish-Horovitz. Results. Out of 276 izolates of S. Enteritidis 94 were isolated from patient's stools and food associated with outbreaks and 182 were isolated from sporadic cases of diarrhea. The presence of 12 plasmid profiles was established. An average correlation degree of plasmid profiles between the strains was 0.84, that implies high degree of similarity of plasmid profiles of epidemic and non- epidemic strains isolated at our geographic region for the given period of time. Conclusion. The strains of S. Enteritidis, isolated in outbreaks of enterocolitis as well as from spordic cases of diarrhea in the same period of time and at the same area, frequently exhibit the same plasmid profile characterized by a single plasmid of 38 MDa. Therefore, in most cases plasmid profile analysis is not valuable in the identification of epidemic strains of S. Enteritidis. However, for this purpose plasmid profile analysis could be used when drug-resistant strains of S. Enteritidis are isolated, as they often possess additional resistant plasmids what increases discrimination power of this method.

  6. Heterogeneity revealed by integrated genomic analysis uncovers a molecular switch in malignant uveal melanoma.

    Science.gov (United States)

    de Lange, Mark J; van Pelt, Sake I; Versluis, Mieke; Jordanova, Ekaterina S; Kroes, Wilma G M; Ruivenkamp, Claudia; van der Burg, Sjoerd H; Luyten, Grégorius P M; van Hall, Thorbald; Jager, Martine J; van der Velden, Pieter A

    2015-11-10

    Gene expression profiles as well as genomic imbalances are correlated with disease progression in uveal melanoma (UM). We integrated expression and genomic profiles to obtain insight into the oncogenic mechanisms in development and progression of UM. We used tumor tissue from 64 enucleated eyes of UM patients for profiling. Mutations and genomic imbalances were quantified with digital PCR to study tumor heterogeneity and molecular pathogenesis. Gene expression analysis divided the UM panel into three classes. Class I presented tumors with a good prognosis and a distinct genomic make up that is characterized by 6p gain. The UM with a bad prognosis were subdivided into class IIa and class IIb. These classes presented similar survival risks but could be distinguished by tumor heterogeneity. Class IIa presented homogeneous tumors while class IIb tumors, on average, contained 30% of non-mutant cells. Tumor heterogeneity coincided with expression of a set of immune genes revealing an extensive immune infiltrate in class IIb tumors. Molecularly, class IIa and IIb presented the same genomic configuration and could only be distinguished by 8q copy number. Moreover, UM establish in the void of the immune privileged eye indicating that in IIb tumors the infiltrate is attracted by the UM. Combined our data show that chromosome 8q contains the locus that causes the immune phentotype of UM. UM thereby provides an unique opportunity to study immune attraction by tumors.

  7. Comparative Analysis of 35 Basidiomycete Genomes Reveals Diversity and Uniqueness of the Phylum

    Energy Technology Data Exchange (ETDEWEB)

    Riley, Robert; Salamov, Asaf; Otillar, Robert; Fagnan, Kirsten; Boussau, Bastien; Brown, Daren; Henrissat, Bernard; Levasseur, Anthony; Held, Benjamin; Nagy, Laszlo; Floudas, Dimitris; Morin, Emmanuelle; Manning, Gerard; Baker, Scott; Martin, Francis; Blanchette, Robert; Hibbett, David; Grigoriev, Igor V.

    2013-03-11

    Fungi of the phylum Basidiomycota (basidiomycetes), make up some 37percent of the described fungi, and are important in forestry, agriculture, medicine, and bioenergy. This diverse phylum includes symbionts, pathogens, and saprobes including wood decaying fungi. To better understand the diversity of this phylum we compared the genomes of 35 basidiomycete fungi including 6 newly sequenced genomes. The genomes of basidiomycetes span extremes of genome size, gene number, and repeat content. A phylogenetic tree of Basidiomycota was generated using the Phyldog software, which uses all available protein sequence data to simultaneously infer gene and species trees. Analysis of core genes reveals that some 48percent of basidiomycete proteins are unique to the phylum with nearly half of those (22percent) comprising proteins found in only one organism. Phylogenetic patterns of plant biomass-degrading genes suggest a continuum rather than a sharp dichotomy between the white rot and brown rot modes of wood decay among the members of Agaricomycotina subphylum. There is a correlation of the profile of certain gene families to nutritional mode in Agaricomycotina. Based on phylogenetically-informed PCA analysis of such profiles, we predict that that Botryobasidium botryosum and Jaapia argillacea have properties similar to white rot species, although neither has liginolytic class II fungal peroxidases. Furthermore, we find that both fungi exhibit wood decay with white rot-like characteristics in growth assays. Analysis of the rate of discovery of proteins with no or few homologs suggests the high value of continued sequencing of basidiomycete fungi.

  8. Comparative analysis of fungal genomes reveals different plant cell wall degrading capacity in fungi

    Science.gov (United States)

    2013-01-01

    Background Fungi produce a variety of carbohydrate activity enzymes (CAZymes) for the degradation of plant polysaccharide materials to facilitate infection and/or gain nutrition. Identifying and comparing CAZymes from fungi with different nutritional modes or infection mechanisms may provide information for better understanding of their life styles and infection models. To date, over hundreds of fungal genomes are publicly available. However, a systematic comparative analysis of fungal CAZymes across the entire fungal kingdom has not been reported. Results In this study, we systemically identified glycoside hydrolases (GHs), polysaccharide lyases (PLs), carbohydrate esterases (CEs), and glycosyltransferases (GTs) as well as carbohydrate-binding modules (CBMs) in the predicted proteomes of 103 representative fungi from Ascomycota, Basidiomycota, Chytridiomycota, and Zygomycota. Comparative analysis of these CAZymes that play major roles in plant polysaccharide degradation revealed that fungi exhibit tremendous diversity in the number and variety of CAZymes. Among them, some families of GHs and CEs are the most prevalent CAZymes that are distributed in all of the fungi analyzed. Importantly, cellulases of some GH families are present in fungi that are not known to have cellulose-degrading ability. In addition, our results also showed that in general, plant pathogenic fungi have the highest number of CAZymes. Biotrophic fungi tend to have fewer CAZymes than necrotrophic and hemibiotrophic fungi. Pathogens of dicots often contain more pectinases than fungi infecting monocots. Interestingly, besides yeasts, many saprophytic fungi that are highly active in degrading plant biomass contain fewer CAZymes than plant pathogenic fungi. Furthermore, analysis of the gene expression profile of the wheat scab fungus Fusarium graminearum revealed that most of the CAZyme genes related to cell wall degradation were up-regulated during plant infection. Phylogenetic analysis also

  9. Comparative analysis of fungal genomes reveals different plant cell wall degrading capacity in fungi.

    Science.gov (United States)

    Zhao, Zhongtao; Liu, Huiquan; Wang, Chenfang; Xu, Jin-Rong

    2013-04-23

    Fungi produce a variety of carbohydrate activity enzymes (CAZymes) for the degradation of plant polysaccharide materials to facilitate infection and/or gain nutrition. Identifying and comparing CAZymes from fungi with different nutritional modes or infection mechanisms may provide information for better understanding of their life styles and infection models. To date, over hundreds of fungal genomes are publicly available. However, a systematic comparative analysis of fungal CAZymes across the entire fungal kingdom has not been reported. In this study, we systemically identified glycoside hydrolases (GHs), polysaccharide lyases (PLs), carbohydrate esterases (CEs), and glycosyltransferases (GTs) as well as carbohydrate-binding modules (CBMs) in the predicted proteomes of 103 representative fungi from Ascomycota, Basidiomycota, Chytridiomycota, and Zygomycota. Comparative analysis of these CAZymes that play major roles in plant polysaccharide degradation revealed that fungi exhibit tremendous diversity in the number and variety of CAZymes. Among them, some families of GHs and CEs are the most prevalent CAZymes that are distributed in all of the fungi analyzed. Importantly, cellulases of some GH families are present in fungi that are not known to have cellulose-degrading ability. In addition, our results also showed that in general, plant pathogenic fungi have the highest number of CAZymes. Biotrophic fungi tend to have fewer CAZymes than necrotrophic and hemibiotrophic fungi. Pathogens of dicots often contain more pectinases than fungi infecting monocots. Interestingly, besides yeasts, many saprophytic fungi that are highly active in degrading plant biomass contain fewer CAZymes than plant pathogenic fungi. Furthermore, analysis of the gene expression profile of the wheat scab fungus Fusarium graminearum revealed that most of the CAZyme genes related to cell wall degradation were up-regulated during plant infection. Phylogenetic analysis also revealed a complex

  10. Genome-wide mRNA and miRNA expression profiling reveal multiple regulatory networks in colorectal cancer

    DEFF Research Database (Denmark)

    Vishnubalaji, R; Hamam, R; Abdulla, M-H

    2015-01-01

    Despite recent advances in cancer management, colorectal cancer (CRC) remains the third most common cancer and a major health-care problem worldwide. MicroRNAs have recently emerged as key regulators of cancer development and progression by targeting multiple cancer-related genes; however......, such regulatory networks are not well characterized in CRC. Thus, the aim of this study was to perform global messenger RNA (mRNA) and microRNA expression profiling in the same CRC samples and adjacent normal tissues and to identify potential miRNA-mRNA regulatory networks. Our data revealed 1273 significantly...... in cell proliferation, and migration in vitro. Concordantly, small interfering RNA-mediated knockdown of EZH2 led to similar effects on CRC cell growth in vitro. Therefore, our data have revealed several hundred potential miRNA-mRNA regulatory networks in CRC and suggest targeting relevant networks...

  11. Genome-wide mRNA and miRNA expression profiling reveal multiple regulatory networks in colorectal cancer

    DEFF Research Database (Denmark)

    Vishnubalaji, R; Hamam, R; Abdulla, M-H

    2015-01-01

    Despite recent advances in cancer management, colorectal cancer (CRC) remains the third most common cancer and a major health-care problem worldwide. MicroRNAs have recently emerged as key regulators of cancer development and progression by targeting multiple cancer-related genes; however......, such regulatory networks are not well characterized in CRC. Thus, the aim of this study was to perform global messenger RNA (mRNA) and microRNA expression profiling in the same CRC samples and adjacent normal tissues and to identify potential miRNA-mRNA regulatory networks. Our data revealed 1273 significantly......-β (using SB-431542) pathways led to dose- and time-dependent inhibition of CRC cell growth. Similarly, our data revealed up- (42) and downregulated (61) microRNAs in the same matched samples. Using target prediction and bioinformatics, ~77% of the upregulated genes were predicted to be targeted by microRNAs...

  12. PPARα-independent transcriptional targets of perfluoroalkyl acids revealed by transcript profiling

    Data.gov (United States)

    U.S. Environmental Protection Agency — Microarray datasets used in the analysis. This dataset is associated with the following publication: Rosen, M., K. Das, J. Rooney, B. Abbott, C. Lau, and C. Corton....

  13. Phosphoproteomic Profiling Reveals ALK and MET as Novel Actionable Targets across Synovial Sarcoma Subtypes

    NARCIS (Netherlands)

    Fleuren, E.D.G.; Vlenterie, M.; Graaf, W.T.A. van der; Hillebrandt-Roeffen, M.H.S.; Blackburn, J.; Ma, X.; Chan, H.; Magias, M.C.; Erp, A. van; Houdt, L. van; Cebeci, S.A.S.; Ven, A. van der; Flucke, U.E.; Heyer, E.E.; Thomas, D.M.; Lord, C.J.; Marini, K.D.; Vaghjiani, V.; Mercer, T.R.; Cain, J.E.; Wu, J.; Versleijen-Jonkers, Y.M.H.; Daly, R.J.

    2017-01-01

    Despite intensive multimodal treatment of sarcomas, a heterogeneous group of malignant tumors arising from connective tissue, survival remains poor. Candidate-based targeted treatments have demonstrated limited clinical success, urging an unbiased and comprehensive analysis of oncogenic signaling

  14. The shallow structure of Solfatara Volcano, Italy, revealed by dense, wide-aperture seismic profiling.

    Science.gov (United States)

    Bruno, Pier Paolo G; Maraio, Stefano; Festa, Gaetano

    2017-12-12

    Two active-source, high-resolution seismic profiles were acquired in the Solfatara tuff cone in May and November 2014, with dense, wide-aperture arrays. Common Receiver Surface processing was crucial in improving signal-to-noise ratio and reflector continuity. These surveys provide, for the first time, high-resolution seismic images of the Solfatara crater, depicting a ~400 m deep asymmetrical crater filled by volcanoclastic sediments and rocks and carved within an overall non-reflective pre-eruptive basement showing features consistent with the emplacement of shallow intrusive bodies. Seismic reflection data were interpreted using the trace complex attributes and clearly display several steep and segmented collapse faults, generally having normal kinematics and dipping toward the crater centre. Fault/fracture planes are imaged as sudden amplitude drops that generate narrow low-similarity and high-dip attributes. Uprising fluids degassed by a magmatic source are the most probable cause of the small-scale amplitude reduction. Seismic data also support the interpretation of the shallow structure of the Solfatara crater as a maar. Our results provides a solid framework to constrain the near-surface geological interpretation of such a complex area, which improves our understanding of the temporal changes of the structure in relation with other geophysical and geochemical measurements.

  15. SELDI-TOF-MS Serum Profiling Reveals Predictors of Cardiac MRI Changes in Marathon Runners

    Directory of Open Access Journals (Sweden)

    George D. Wilson

    2012-01-01

    Full Text Available Purpose. To utilize proteomics to discover proteins associated with significant cardiac magnetic resonance imaging (MRI changes in marathon runners. Methods. Serum from 25 runners was analyzed by surface enhanced laser desorption ionization time-of-flight mass spectrometry (SELDI-TOF-MS. Proteomic profiles were compared in serum samples obtained prior to the race, at the finish line and within 7 hours after race to identify dynamic proteins correlated with cardiac MRI changes. Results. 693 protein/peptide clusters were identified using two ProteinChip surface chemistries and, of these, 116 were significantly different between the three time points. We identified 7 different patterns of protein expression change within the runners and 5 prerace protein peaks, 16 finish-line protein levels, and 15 postrace proteins which were correlated with significant postrace cardiac MRI changes. Conclusions. This study has identified baseline levels of proteins which may be predictive of risk of significant cardiac damage following a marathon race. Preliminary identification of the significant proteins suggested the involvement of cytokines and other proteins involved in stress and inflammatory response.

  16. SELDI-TOF-MS Serum Profiling Reveals Predictors of Cardiac MRI Changes in Marathon Runners.

    Science.gov (United States)

    Wilson, George D; Geddes, Timothy J; Pruetz, Barbara L; Thibodeau, Bryan J; Murawka, Amy; Colar, James M; McCullough, Peter A; Trivax, Justin E

    2012-01-01

    Purpose. To utilize proteomics to discover proteins associated with significant cardiac magnetic resonance imaging (MRI) changes in marathon runners. Methods. Serum from 25 runners was analyzed by surface enhanced laser desorption ionization time-of-flight mass spectrometry (SELDI-TOF-MS). Proteomic profiles were compared in serum samples obtained prior to the race, at the finish line and within 7 hours after race to identify dynamic proteins correlated with cardiac MRI changes. Results. 693 protein/peptide clusters were identified using two ProteinChip surface chemistries and, of these, 116 were significantly different between the three time points. We identified 7 different patterns of protein expression change within the runners and 5 prerace protein peaks, 16 finish-line protein levels, and 15 postrace proteins which were correlated with significant postrace cardiac MRI changes. Conclusions. This study has identified baseline levels of proteins which may be predictive of risk of significant cardiac damage following a marathon race. Preliminary identification of the significant proteins suggested the involvement of cytokines and other proteins involved in stress and inflammatory response.

  17. 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.

  18. Ribosome profiling reveals features of normal and disease-associated mitochondrial translation

    Science.gov (United States)

    Rooijers, Koos; Loayza-Puch, Fabricio; Nijtmans, Leo G.; Agami, Reuven

    2013-12-01

    Mitochondria are essential cellular organelles for generation of energy and their dysfunction may cause diabetes, Parkinson’s disease and multi-systemic failure marked by failure to thrive, gastrointestinal problems, lactic acidosis and early lethality. Disease-associated mitochondrial mutations often affect components of the mitochondrial translation machinery. Here we perform ribosome profiling to measure mitochondrial translation at nucleotide resolution. Using a protocol optimized for the retrieval of mitochondrial ribosome protected fragments (RPFs) we show that the size distribution of wild-type mitochondrial RPFs follows a bimodal distribution peaking at 27 and 33 nucleotides, which is distinct from the 30-nucleotide peak of nuclear RPFs. Their cross-correlation suggests generation of mitochondrial RPFs during ribosome progression. In contrast, RPFs from patient-derived mitochondria mutated in tRNA-Tryptophan are centered on tryptophan codons and reduced downstream, indicating ribosome stalling. Intriguingly, long RPFs are enriched in mutated mitochondria, suggesting they characterize stalled ribosomes. Our findings provide the first model for translation in wild-type and disease-triggering mitochondria.

  19. Transcript profiling reveals rewiring of iron assimilation gene expression in Candida albicans and C. dubliniensis.

    LENUS (Irish Health Repository)

    Moran, Gary P

    2012-12-01

    Hyphal growth is repressed in Candida albicans and Candida dubliniensis by the transcription factor Nrg1. Transcript profiling of a C. dubliniensis NRG1 mutant identified a common group of 28 NRG1-repressed genes in both species, including the hypha-specific genes HWP1, ECE1 and the regulator of cell elongation UME6. Unexpectedly, C. dubliniensis NRG1 was required for wild-type levels of expression of 10 genes required for iron uptake including seven ferric reductases, SIT1, FTR1 and RBT5. However, at alkaline pH and during filamentous growth in 10% serum, most of these genes were highly induced in C. dubliniensis. Conversely, RBT5, PGA10, FRE10 and FRP1 did not exhibit induction during hyphal growth when NRG1 is downregulated, indicating that in C. dubliniensis NRG1 is also required for optimal expression of these genes in alkaline environments. In iron-depleted medium at pH 4.5, reduced growth of the NRG1 mutant relative to wild type was observed; however, growth was restored to wild-type levels or greater at pH 6.5, indicating that alkaline induction of iron assimilation gene expression could rescue this phenotype. These data indicate that transcriptional control of iron assimilation and pseudohypha formation has been separated in C. albicans, perhaps promoting growth in a wider range of niches.

  20. SELDI-TOF-MS Serum Profiling Reveals Predictors of Cardiac MRI Changes in Marathon Runners

    Science.gov (United States)

    Wilson, George D.; Geddes, Timothy J.; Pruetz, Barbara L.; Thibodeau, Bryan J.; Murawka, Amy; Colar, James M.; McCullough, Peter A.; Trivax, Justin E.

    2012-01-01

    Purpose. To utilize proteomics to discover proteins associated with significant cardiac magnetic resonance imaging (MRI) changes in marathon runners. Methods. Serum from 25 runners was analyzed by surface enhanced laser desorption ionization time-of-flight mass spectrometry (SELDI-TOF-MS). Proteomic profiles were compared in serum samples obtained prior to the race, at the finish line and within 7 hours after race to identify dynamic proteins correlated with cardiac MRI changes. Results. 693 protein/peptide clusters were identified using two ProteinChip surface chemistries and, of these, 116 were significantly different between the three time points. We identified 7 different patterns of protein expression change within the runners and 5 prerace protein peaks, 16 finish-line protein levels, and 15 postrace proteins which were correlated with significant postrace cardiac MRI changes. Conclusions. This study has identified baseline levels of proteins which may be predictive of risk of significant cardiac damage following a marathon race. Preliminary identification of the significant proteins suggested the involvement of cytokines and other proteins involved in stress and inflammatory response. PMID:22988506

  1. Transcriptome profiling of aging Drosophila photoreceptors reveals gene expression trends that correlate with visual senescence.

    Science.gov (United States)

    Hall, Hana; Medina, Patrick; Cooper, Daphne A; Escobedo, Spencer E; Rounds, Jeremiah; Brennan, Kaelan J; Vincent, Christopher; Miura, Pedro; Doerge, Rebecca; Weake, Vikki M

    2017-11-21

    Aging is associated with functional decline of neurons and increased incidence of both neurodegenerative and ocular disease. Photoreceptor neurons in Drosophila melanogaster provide a powerful model for studying the molecular changes involved in functional senescence of neurons since decreased visual behavior precedes retinal degeneration. Here, we sought to identify gene expression changes and the genomic features of differentially regulated genes in photoreceptors that contribute to visual senescence. To identify gene expression changes that could lead to visual senescence, we characterized the aging transcriptome of Drosophila sensory neurons highly enriched for photoreceptors. We profiled the nuclear transcriptome of genetically-labeled photoreceptors over a 40 day time course and identified increased expression of genes involved in stress and DNA damage response, and decreased expression of genes required for neuronal function. We further show that combinations of promoter motifs robustly identify age-regulated genes, suggesting that transcription factors are important in driving expression changes in aging photoreceptors. However, long, highly expressed and heavily spliced genes are also more likely to be downregulated with age, indicating that other mechanisms could contribute to expression changes at these genes. Lastly, we identify that circular RNAs (circRNAs) strongly increase during aging in photoreceptors. Overall, we identified changes in gene expression in aging Drosophila photoreceptors that could account for visual senescence. Further, we show that genomic features predict these age-related changes, suggesting potential mechanisms that could be targeted to slow the rate of age-associated visual decline.

  2. The complexity and structural diversity of ant venom peptidomes is revealed by mass spectrometry profiling.

    Science.gov (United States)

    Touchard, Axel; Koh, Jennifer M S; Aili, Samira R; Dejean, Alain; Nicholson, Graham M; Orivel, Jérôme; Escoubas, Pierre

    2015-03-15

    Compared with other animal venoms, ant venoms remain little explored. Ants have evolved complex venoms to rapidly immobilize arthropod prey and to protect their colonies from predators and pathogens. Many ants have retained peptide-rich venoms that are similar to those of other arthropod groups. With the goal of conducting a broad and comprehensive survey of ant venom peptide diversity, we investigated the peptide composition of venoms from 82 stinging ant species from nine subfamilies using matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOFMS). We also conducted an in-depth investigation of eight venoms using reversed-phase high-performance liquid chromatography (RP-HPLC) separation coupled with offline MALDI-TOFMS. Our results reveal that the peptide compositions of ant venom peptidomes from both poneroid and formicoid ant clades comprise hundreds of small peptides (4 kDa) are also present in the venom of formicoids. Chemical reduction revealed the presence of disulfide-linked peptides in most ant subfamilies, including peptides structured by one, two or three disulfide bonds as well as dimeric peptides reticulated by three disulfide bonds. The biochemical complexity of ant venoms, associated with an enormous ecological and taxonomic diversity, suggests that stinging ant venoms constitute a promising source of bioactive molecules that could be exploited in the search for novel drug and biopesticide leads. Copyright © 2015 John Wiley & Sons, Ltd.

  3. Extracting body image symptom dimensions among eating disorder patients: the Profile Analysis via Multidimensional Scaling (PAMS) approach.

    Science.gov (United States)

    Olatunji, Bunmi O; Kim, Se-Kang; Wall, David

    2015-09-01

    The present study employs Profile Analysis via Multidimensional Scaling (PAMS), a procedure for extracting dimensions, in order to identify core eating disorder symptoms in a clinical sample. A large sample of patients with eating disorders (N=5193) presenting for treatment completed the Eating Disorders Inventory-2 (EDI-2; Garner, 1991), and PAMS was then employed to estimate individual profile weights that reflect the degree to which an individual's observed symptom profile approximates the pattern of the dimensions. The findings revealed three symptom dimensions: Body Thinness, Body Perfectionism, and Body Awareness. Subsequent analysis using individual level data illustrate that the PAMS profiles properly operate as prototypical profiles that encapsulate all individuals' response patterns. The implications of these dimensional findings for the assessment and diagnosis of eating disorders are discussed. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Flash Study Analysis and The Music Learning Profiles Project

    Directory of Open Access Journals (Sweden)

    Radio Cremata

    2016-08-01

    Full Text Available This paper introduces the Music Learning Profiles Project, and its methodological approach, flash study analysis. Flash study analysis is a method that draws heavily on extant qualitative approaches to education research, to develop broad understandings of music learning in diverse contexts. The Music Learning Profiles Project (MLPP is an international collaboration to collect and curate a large number of flash studies exploring musicking and music learning in a variety of contexts that fall outside traditional school music education. In this paper the authors present context, rationale, and methods for the project, along with indicative preliminary findings. The project aims to provide an expanding online database of music experiences upon which colleagues in music education and ethnomusicology research can draw, and to which they are invited to contribute. The MLPP aims to benefit the music education community and wider society by helping to democratize research to include more diverse experiences of music learning.

  5. Modified ribosome profiling reveals high abundance of ribosome protected mRNA fragments derived from 3' untranslated regions.

    Science.gov (United States)

    Miettinen, Teemu P; Björklund, Mikael

    2015-01-01

    Ribosome profiling identifies ribosome positions on translated mRNAs. A prominent feature of published datasets is the near complete absence of ribosomes in 3' untranslated regions (3'UTR) although substantial ribosome density can be observed on non-coding RNAs. Here we perform ribosome profiling in cultured Drosophila and human cells and show that different features of translation are revealed depending on the nuclease and the digestion conditions used. Most importantly, we observe high abundance of ribosome protected fragments in 3'UTRs of thousands of genes without manipulation of translation termination. Affinity purification of ribosomes indicates that the 3'UTR reads originate from ribosome protected fragments. Association of ribosomes with the 3'UTR may be due to ribosome migration through the stop codon or 3'UTR mRNA binding to ribosomes on the coding sequence. This association depends primarily on the relative length of the 3'UTR and may be related to translational regulation or ribosome recycling, for which the efficiency is known to inversely correlate with 3'UTR length. Together our results indicate that ribosome profiling is highly dependent on digestion conditions and that ribosomes commonly associate with the 3'UTR, which may have a role in translational regulation. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

  6. Modified ribosome profiling reveals high abundance of ribosome protected mRNA fragments derived from 3′ untranslated regions

    Science.gov (United States)

    Miettinen, Teemu P.; Björklund, Mikael

    2015-01-01

    Ribosome profiling identifies ribosome positions on translated mRNAs. A prominent feature of published datasets is the near complete absence of ribosomes in 3′ untranslated regions (3′UTR) although substantial ribosome density can be observed on non-coding RNAs. Here we perform ribosome profiling in cultured Drosophila and human cells and show that different features of translation are revealed depending on the nuclease and the digestion conditions used. Most importantly, we observe high abundance of ribosome protected fragments in 3′UTRs of thousands of genes without manipulation of translation termination. Affinity purification of ribosomes indicates that the 3′UTR reads originate from ribosome protected fragments. Association of ribosomes with the 3′UTR may be due to ribosome migration through the stop codon or 3′UTR mRNA binding to ribosomes on the coding sequence. This association depends primarily on the relative length of the 3′UTR and may be related to translational regulation or ribosome recycling, for which the efficiency is known to inversely correlate with 3′UTR length. Together our results indicate that ribosome profiling is highly dependent on digestion conditions and that ribosomes commonly associate with the 3′UTR, which may have a role in translational regulation. PMID:25550424

  7. Chloride ingress profiles measured by electron probe micro analysis

    DEFF Research Database (Denmark)

    Jensen, Ole mejlhede; Coats, Alison M.; Glasser, Fred P.

    1996-01-01

    Traditional techniques for measuring chloride ingress profiles do not apply well to high performance cement paste systems; the geometric resolution of the traditional measuring techniques is too low. In this paper measurements by Electron Probe Micro Analysis (EPMA) are presented. EPMA...... is demonstated to determine chloride ingress in cement paste on a micrometer scale. Potential chloride ingress routes such as cracks or the paste-aggregate interface may also be characterized by EPMA. Copyright (C) 1996 Elsevier Science Ltd...

  8. Blade Profile Optimization of Kaplan Turbine Using CFD Analysis

    Directory of Open Access Journals (Sweden)

    Aijaz Bashir Janjua

    2013-10-01

    Full Text Available Utilization of hydro-power as renewable energy source is of prime importance in the world now. Hydropower energy is available in abundant in form of falls, canals rivers, dams etc. It means, there are various types of sites with different parameters like flow rate, heads, etc. Depending upon the sites, water turbines are designed and manufactured to avail hydro-power energy. Low head turbines on runof-river are widely used for the purpose. Low head turbines are classified as reaction turbines. For runof river, depending upon the variety of site data, low head Kaplan turbines are selected, designed and manufactured. For any given site requirement, it becomes very essential to design the turbine runner blades through optimization of the CAD model of blades profile. This paper presents the optimization technique carried out on a complex geometry of blade profile through static and dynamic computational analysis. It is used through change of the blade profile geometry at five different angles in the 3D (Three Dimensional CAD model. Blade complex geometry and design have been developed by using the coordinates point system on the blade in PRO-E /CREO software. Five different blade models are developed for analysis purpose. Based on the flow rate and heads, blade profiles are analyzed using ANSYS software to check and compare the output results for optimization of the blades for improved results which show that by changing blade profile angle and its geometry, different blade sizes and geometry can be optimized using the computational techniques with changes in CAD models.

  9. Genomic profiling of ER+ breast cancers after short-term estrogen suppression reveals alterations associated with endocrine resistance.

    Science.gov (United States)

    Giltnane, Jennifer M; Hutchinson, Katherine E; Stricker, Thomas P; Formisano, Luigi; Young, Christian D; Estrada, Monica V; Nixon, Mellissa J; Du, Liping; Sanchez, Violeta; Ericsson, Paula Gonzalez; Kuba, Maria G; Sanders, Melinda E; Mu, Xinmeng J; Van Allen, Eliezer M; Wagle, Nikhil; Mayer, Ingrid A; Abramson, Vandana; Gόmez, Henry; Rizzo, Monica; Toy, Weiyi; Chandarlapaty, Sarat; Mayer, Erica L; Christiansen, Jason; Murphy, Danielle; Fitzgerald, Kerry; Wang, Kai; Ross, Jeffrey S; Miller, Vincent A; Stephens, Phillip J; Yelensky, Roman; Garraway, Levi; Shyr, Yu; Meszoely, Ingrid; Balko, Justin M; Arteaga, Carlos L

    2017-08-09

    Inhibition of proliferation in estrogen receptor-positive (ER+) breast cancers after short-term antiestrogen therapy correlates with long-term patient outcome. We profiled 155 ER+/human epidermal growth factor receptor 2-negative (HER2-) early breast cancers from 143 patients treated with the aromatase inhibitor letrozole for 10 to 21 days before surgery. Twenty-one percent of tumors remained highly proliferative, suggesting that these tumors harbor alterations associated with intrinsic endocrine therapy resistance. Whole-exome sequencing revealed a correlation between 8p11-12 and 11q13 gene amplifications, including FGFR1 and CCND1, respectively, and high Ki67. We corroborated these findings in a separate cohort of serial pretreatment, postneoadjuvant chemotherapy, and recurrent ER+ tumors. Combined inhibition of FGFR1 and CDK4/6 reversed antiestrogen resistance in ER+FGFR1/CCND1 coamplified CAMA1 breast cancer cells. RNA sequencing of letrozole-treated tumors revealed the existence of intrachromosomal ESR1 fusion transcripts and increased expression of gene signatures indicative of enhanced E2F-mediated transcription and cell cycle processes in cancers with high Ki67. These data suggest that short-term preoperative estrogen deprivation followed by genomic profiling can be used to identify druggable alterations that may cause intrinsic endocrine therapy resistance. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  10. Metabolic profiling of Commiphora wightii (guggul) reveals a potential source for pharmaceuticals and nutraceuticals.

    Science.gov (United States)

    Bhatia, Anil; Bharti, Santosh K; Tripathi, Tusha; Mishra, Anuradha; Sidhu, Om P; Roy, Raja; Nautiyal, Chandra Shekhar

    2015-02-01

    Guggul gum resin from Commiphora wightii (syn. Commiphoramukul) has been used for centuries in Ayurveda to treat a variety of ailments. The NMR and GC-MS based non-targeted metabolite profiling identified 118 chemically diverse metabolites including amino acids, fatty acids, organic acids, phenolic acids, pregnane-derivatives, steroids, sterols, sugars, sugar alcohol, terpenoids, and tocopherol from aqueous and non-aqueous extracts of leaves, stem, roots, latex and fruits of C. wightii. Out of 118, 51 structurally diverse aqueous metabolites were characterized by NMR spectroscopy. For the first time quinic acid and myo-inositol were identified as the major metabolites in C. wightii. Very high concentration of quinic acid was found in fruits (553.5 ± 39.38 mg g(-1) dry wt.) and leaves (212.9 ± 10.37 mg g(-1) dry wt.). Similarly, high concentration of myo-inositol (168.8 ± 13.84 mg g(-1) dry wt.) was observed from fruits. The other metabolites of cosmeceutical, medicinal, nutraceutical and industrial significance such as α-tocopherol, n-methylpyrrolidone (NMP), trans-farnesol, prostaglandin F2, protocatechuic, gallic and cinnamic acids were identified from non-aqueous extracts using GC-MS. These important metabolites have thus far not been reported from this plant. Isolation of a fungal endophyte, (Nigrospora sps.) from this plant is the first report. The fungal endophyte produced a substantial quantity of bostrycin and deoxybostrycin known for their antitumor properties. Very high concentrations of quinic acid and myo-inositol in leaves and fruits; a substantial quantity of α-tocopherol and NMP in leaves, trans-farnesol in fruits, bostrycin and deoxybostrycin from its endophyte makes the taxa distinct, since these metabolites with medicinal properties find immense applications as dietary supplements and nutraceuticals. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Comprehensive expression profiling of rice tetraspanin genes reveals diverse roles during development and abiotic stress

    Directory of Open Access Journals (Sweden)

    Balaji eM

    2015-12-01

    Full Text Available Tetraspanin family is comprised of evolutionarily conserved integral membrane proteins. The incredible ability of tetraspanins to form ‘micro domain complexes’ and their preferential targeting to membranes emphasizes their active association with signal recognition and communication with neighboring cells, thus acting as key modulators of signaling cascades. In animals, tetraspanins are associated with multitude of cellular processes. Unlike animals, the biological relevance of tetraspanins in plants has not been well investigated. In Arabidopsis tetraspanins are known to contribute in important plant development processes such as leaf morphogenesis, root and floral organ formation. In the present study we investigated the genomic organization, chromosomal distribution, phylogeny and domain structure of 15 rice tetraspanin proteins (OsTETs. OsTET proteins had similar domain structure and signature ‘GCCK/R’ motif as reported in Arabidopsis. Comprehensive expression profiling of OsTET genes suggested their possible involvement during rice development. While OsTET9 and 10 accumulated predominantly in flowers, OsTET5, 8 and 12 were preferentially expressed in root tissues. Noticeably, seven OsTETs exhibited more than 2-fold up regulation at early stages of flag leaf senescence in rice. Furthermore, several OsTETs were differentially regulated in rice seedlings exposed to abiotic stresses, exogenous treatment of hormones and nutrient deprivation. Transient subcellular localization studies of eight OsTET proteins in tobacco epidermal cells showed that these proteins localized in plasma membrane. The present study provides valuable insights into the possible roles of tetraspanins in regulating development and defining response to abiotic stresses in rice. Targeted proteomic studies would be useful in identification of their interacting partners under different conditions and ultimately their biological function in plants

  12. Mechanistic insights revealed by lipid profiling in monogenic insulin resistance syndromes.

    Science.gov (United States)

    Eiden, Michael; Koulman, Albert; Hatunic, Mensud; West, James A; Murfitt, Steven; Osei, Michael; Adams, Claire; Wang, Xinzhu; Chu, Yajing; Marney, Luke; Roberts, Lee D; O'Rahilly, Stephen; Semple, Robert K; Savage, David B; Griffin, Julian L

    2015-01-01

    Evidence from several recent metabolomic studies suggests that increased concentrations of triacylglycerols with shorter (14-16 carbon atoms), saturated fatty acids are associated with insulin resistance and the risk of type 2 diabetes. Although causality cannot be inferred from association studies, patients in whom the primary cause of insulin resistance can be genetically defined offer unique opportunities to address this challenge. We compared metabolite profiles in patients with congenital lipodystrophy or loss-of-function insulin resistance (INSR gene) mutations with healthy controls. The absence of significant differences in triacylglycerol species in the INSR group suggest that changes previously observed in epidemiological studies are not purely a consequence of insulin resistance. The presence of triacylglycerols with lower carbon numbers and high saturation in patients with lipodystrophy suggests that these metabolite changes may be associated with primary adipose tissue dysfunction. The observed pattern of triacylglycerol species is indicative of increased de novo lipogenesis in the liver. To test this we investigated the distribution of these triacylglycerols in lipoprotein fractions using size exclusion chromatography prior to mass spectrometry. This associated these triacylglycerols with very low-density lipoprotein particles, and hence release of triacylglycerols into the blood from the liver. To test further the hepatic origin of these triacylglycerols we induced de novo lipogenesis in the mouse, comparing ob/ob and wild-type mice on a chow or high fat diet, confirming that de novo lipogenesis induced an increase in relatively shorter, more saturated fatty acids. Overall, these studies highlight hepatic de novo lipogenesis in the pathogenesis of metabolic dyslipidaemia in states where energy intake exceeds the capacity of adipose tissue.

  13. Stage-specific histone modification profiles reveal global transitions in the Xenopus embryonic epigenome.

    Directory of Open Access Journals (Sweden)

    Tobias D Schneider

    Full Text Available Vertebrate embryos are derived from a transitory pool of pluripotent cells. By the process of embryonic induction, these precursor cells are assigned to specific fates and differentiation programs. Histone post-translational modifications are thought to play a key role in the establishment and maintenance of stable gene expression patterns underlying these processes. While on gene level histone modifications are known to change during differentiation, very little is known about the quantitative fluctuations in bulk histone modifications during development. To investigate this issue we analysed histones isolated from four different developmental stages of Xenopus laevis by mass spectrometry. In toto, we quantified 59 modification states on core histones H3 and H4 from blastula to tadpole stages. During this developmental period, we observed in general an increase in the unmodified states, and a shift from histone modifications associated with transcriptional activity to transcriptionally repressive histone marks. We also compared these naturally occurring patterns with the histone modifications of murine ES cells, detecting large differences in the methylation patterns of histone H3 lysines 27 and 36 between pluripotent ES cells and pluripotent cells from Xenopus blastulae. By combining all detected modification transitions we could cluster their patterns according to their embryonic origin, defining specific histone modification profiles (HMPs for each developmental stage. To our knowledge, this data set represents the first compendium of covalent histone modifications and their quantitative flux during normogenesis in a vertebrate model organism. The HMPs indicate a stepwise maturation of the embryonic epigenome, which may be causal to the progressing restriction of cellular potency during development.

  14. Transcriptome profiling reveals the genetic basis of alkalinity tolerance in wheat.

    Science.gov (United States)

    Meng, Chen; Quan, Tai-Yong; Li, Zhong-Yi; Cui, Kang-Li; Yan, Li; Liang, Yu; Dai, Jiu-Lan; Xia, Guang-Min; Liu, Shu-Wei

    2017-01-05

    Soil alkalinity shows significant constraints to crop productivity; however, much less attention has been paid to analyze the effect of soil alkalinity on plant growth and development. Shanrong No. 4 (SR4) is an alkalinity tolerant bread wheat cultivar selected from an asymmetric somatic hybridization between the bread wheat cultivar Jinan 177 (JN177) and tall wheatgrass (Thinopyrum ponticum), which is a suitable material for studying alkalinity tolerant associate genes. The growth of SR4 plant seedlings was less inhibited than that of JN177 when exposed to alkalinity stress conditions. The root cytosolic Na+/K+ ratio in alkalinity stressed SR4 was lower than in JN177, while alkalinity stressed SR4 contained higher level of nutrient elements than in JN177. SR4 plant seedlings accumulated less malondialdehyde (MDA) and reactive oxygen species (ROS), it also showed higher activity of ROS scavenging enzymes than JN177 under alkalinity stress. The root intracellular pH decreased in both alkalinity stressed JN177 and SR4, however, it was much lower in SR4 than in JN177 under alkalinity stress. The transcriptomes of SR4 and JN177 seedlings exposed to alkalinity stress were analyzed by digital gene expression tag profiling method. Alkalinity stress conditions up- and down-regulated a large number of genes in the seedling roots that play the functions in the categories of transcription regulation, signal transduction and protein modification. SR4 expresses a superior tolerance to alkaline stress conditions which is due to its strong absorbing ability for nutrient ions, a strong regulating ability for intracellular and rhizosphere pH and a more active ROS scavenging ability.

  15. Long-term carbon and nitrogen dynamics at SPRUCE revealed through stable isotopes in peat profiles

    Science.gov (United States)

    Hobbie, Erik A.; Chen, Janet; Hanson, Paul J.; Iversen, Colleen M.; McFarlane, Karis J.; Thorp, Nathan R.; Hofmockel, Kirsten S.

    2017-05-01

    Peatlands encode information about past vegetation dynamics, climate, and microbial processes. Here, we used δ15N and δ13C patterns from 16 peat profiles to deduce how the biogeochemistry of the Marcell S1 forested bog in northern Minnesota responded to environmental and vegetation change over the past ˜ 10 000 years. In multiple regression analyses, δ15N and δ13C correlated strongly with depth, plot location, C / N, %N, and each other. Correlations with %N, %C, C / N, and the other isotope accounted for 80 % of variance for δ15N and 38 % of variance for δ13C, reflecting N and C losses. In contrast, correlations with depth and topography (hummock or hollow) reflected peatland successional history and climate. Higher δ15N in plots closer to uplands may reflect upland-derived DON inputs and accompanying shifts in N dynamics in the lagg drainage area surrounding the bog. The Suess effect (declining δ13CO2 since the Industrial Revolution) lowered δ13C in recent surficial samples. High δ15N from -35 to -55 cm probably indicated the depth of ectomycorrhizal activity after tree colonization of the peatland over the last 400 years, as confirmed by the occasional presence of wood down to -35 cm depth. High δ13C at ˜ 4000 years BP (-65 to -105 cm) could reflect a transition at that time to slower rates of peat accumulation, when 13C discrimination during peat decomposition may increase in importance. Low δ13C and high δ15N at -213 and -225 cm ( ˜ 8500 years BP) corresponded to a warm period during a sedge-dominated rich fen stage. The above processes appear to be the primary drivers of the observed isotopic patterns, whereas there was no clear evidence for methane dynamics influencing δ13C patterns.

  16. Cell Surface and Secreted Protein Profiles of Human Thyroid Cancer Cell Lines Reveal Distinct Glycoprotein Patterns

    Science.gov (United States)

    Arcinas, Arthur; Yen, Ten-Yang; Kebebew, Electron; Macher, Bruce A.

    2009-01-01

    Cell surface proteins have been shown to be effective therapeutic targets. In addition, shed forms of these proteins and secreted proteins can serve as biomarkers for diseases, including cancer. Thus, identification of cell surface and secreted proteins has been a prime area of interest in the proteomics field. Most cell surface and secreted proteins are known to be glycosylated and therefore, a proteomics strategy targeting these proteins was applied to obtain proteomic profiles from various thyroid cancer cell lines that represent the range of thyroid cancers of follicular cell origin. In this study, we oxidized the carbohydrates of secreted proteins and those on the cell surface with periodate and isolated them via covalent coupling to hydrazide resin. The glycoproteins obtained were identified from tryptic peptides and N-linked glycopeptides released from the hydrazide resin using 2-dimensional liquid chromatography-tandem mass spectrometry in combination with the gas phase fractionation. Thyroid cancer cell lines derived from papillary thyroid cancer (TPC-1), follicular thyroid cancer (FTC-133), Hürthle cell carcinoma (XTC-1), and anaplastic thyroid cancer (ARO and DRO-1) were evaluated. An average of 150 glycoproteins were identified per cell line, of which more than 57 percent are known cell surface or secreted glycoproteins. The usefulness of the approach for identifying thyroid cancer associated biomarkers was validated by the identification of glycoproteins (e.g. CD44, galectin 3 and metalloproteinase inhibitor 1) that have been found to be useful markers for thyroid cancer. In addition to glycoproteins that are commonly expressed by all of the cell lines, we identified others that are only expressed in the more well-differentiated thyroid cancer cell lines (follicular, Hürthle cell and papillary), or by cell lines derived from undifferentiated tumors that are uniformly fatal forms of thyroid cancer (i.e. anaplastic). Based on the results obtained, a

  17. Genome-wide transcriptome profiling reveals novel insights into Luffa cylindrica browning.

    Science.gov (United States)

    Chen, Xia; Tan, Taiming; Xu, Changcheng; Huang, Shuping; Tan, Jie; Zhang, Min; Wang, Chunli; Xie, Conghua

    2015-08-07

    Luffa cylindrica (sponge gourd) is one of the most popular vegetables in China. Production and consumption of L. cylindrica are limited due to postharvest browning; however, little is known about the genetic regulation of the browning process. In the present study, transcriptome profiles of L. cylindrica cultivars, YLB05 (browning resistant) and XTR05 (browning sensitive), were analyzed using next-generation sequencing to clarify the genes and mechanisms associated with browning. A total of 9.1 Gb of valid data including 116,703 unigenes (>200 bp) were obtained and 39,473 sequences were annotated by alignment against five public databases. Of these, there were 27,407 genes assigned to 747 Gene Ontology functional categories; and 12,350 genes were annotated with 25 Eukaryotic Orthologous Groups (KOG) categories with 343 KOG functional terms. Additionally, by searching against the Kyoto Encyclopedia of Genes and Genomes database, 8689 unigenes were mapped to 189 pathways. Furthermore, there were 24,556 sequences found to be differentially regulated, including 4344 annotated unigenes. Several genes potentially associated with phenolic oxidation, carbohydrate and hormone metabolism were found differentially regulated between the cultivars of different browning sensitivities. Our results suggest that elements involved in enzymatic processes and other pathways might be responsible for L. cylindrica browning. The present study provides a comprehensive transcriptome sequence resource, which will facilitate further studies on gene discovery and exploiting the fruit browning mechanism of L. cylindrica. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. 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

  19. DNA Replication Stress Phosphoproteome Profiles Reveal Novel Functional Phosphorylation Sites on Xrs2 in Saccharomyces cerevisiae.

    Science.gov (United States)

    Huang, Dongqing; Piening, Brian D; Kennedy, Jacob J; Lin, Chenwei; Jones-Weinert, Corey W; Yan, Ping; Paulovich, Amanda G

    2016-05-01

    In response to replication stress, a phospho-signaling cascade is activated and required for coordination of DNA repair and replication of damaged templates (intra-S-phase checkpoint) . How phospho-signaling coordinates the DNA replication stress response is largely unknown. We employed state-of-the-art liquid chromatography tandem-mass spectrometry (LC-MS/MS) approaches to generate high-coverage and quantitative proteomic and phospho-proteomic profiles during replication stress in yeast, induced by continuous exposure to the DNA alkylating agent methyl methanesulfonate (MMS) . We identified 32,057 unique peptides representing the products of 4296 genes and 22,061 unique phosphopeptides representing the products of 3183 genes. A total of 542 phosphopeptides (mapping to 339 genes) demonstrated an abundance change of greater than or equal to twofold in response to MMS. The screen enabled detection of nearly all of the proteins known to be involved in the DNA damage response, as well as many novel MMS-induced phosphorylations. We assessed the functional importance of a subset of key phosphosites by engineering a panel of phosphosite mutants in which an amino acid substitution prevents phosphorylation. In total, we successfully mutated 15 MMS-responsive phosphorylation sites in seven representative genes including APN1 (base excision repair); CTF4 and TOF1 (checkpoint and sister-chromatid cohesion); MPH1 (resolution of homologous recombination intermediates); RAD50 and XRS2 (MRX complex); and RAD18 (PRR). All of these phosphorylation site mutants exhibited MMS sensitivity, indicating an important role in protecting cells from DNA damage. In particular, we identified MMS-induced phosphorylation sites on Xrs2 that are required for MMS resistance in the absence of the MRX activator, Sae2, and that affect telomere maintenance. Copyright © 2016 by the Genetics Society of America.

  20. (1H-NMR spectroscopy revealed Mycobacterium tuberculosis caused abnormal serum metabolic profile of cattle.

    Directory of Open Access Journals (Sweden)

    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.

  1. Transcriptomic profiling of Microplitis demolitor bracovirus reveals host, tissue and stage-specific patterns of activity.

    Science.gov (United States)

    Bitra, Kavita; Zhang, Shu; Strand, Michael R

    2011-09-01

    The polydnaviruses (PDVs) are a family of DNA viruses that are symbiotically associated with parasitoid wasps. The transcription of particular genes or gene-family members have been reported for several PDVs, but no studies have characterized the spatio-temporal patterns of expression for the entire complement of predicted genes in the encapsidated genome of any PDV isolate. The braconid wasp Microplitis demolitor carries the PDV Microplitis demolitor bracovirus (MdBV) and parasitizes larval stage Pseudoplusia (Chrysodeixis) includens. The encapsidated genome consists of 15 genomic segments with 51 predicted ORFs encoding proteins ≥100 aa. A majority of these ORFs form four multimember gene families (ptp, ank, glc and egf) while the remaining ORFs consist of single copy (orph) genes. Here we used RT-PCR and quantitative real-time PCR methods to profile the encapsidated transcriptome of MdBV in P. includens and M. demolitor. Our results indicate that most predicted genes are expressed in P. includens. Spatial patterns of expression in P. includens differed among genes, but temporal patterns of expression were generally similar, with transcript abundance progressively declining between 24 and 120 h. A subset of ptp, ank and orph genes were also expressed in adult female but not male M. demolitor. Only one encapsidated gene (ank-H4) was expressed in all life stages of M. demolitor, albeit at much lower levels than in P. includens. However, another encapsidated gene (orph-B1) was expressed in adult M. demolitor at similar levels to those detected in P. includens.

  2. Sequence analysis reveals mosaic genome of Aichi virus

    Directory of Open Access Journals (Sweden)

    Han Xiaohong

    2011-08-01

    Full Text Available Abstract Aichi virus is a positive-sense and single-stranded RNA virus, which demonstrated to be related to diarrhea of Children. In the present study, phylogenetic and recombination analysis based on the Aichi virus complete genomes available in GenBank reveal a mosaic genome sequence [GenBank: FJ890523], of which the nt 261-852 region (the nt position was based on the aligned sequence file shows close relationship with AB010145/Japan with 97.9% sequence identity, while the other genomic regions show close relationship with AY747174/German with 90.1% sequence identity. Our results will provide valuable hints for future research on Aichi virus diversity. Aichi virus is a member of the Kobuvirus genus of the Picornaviridae family 12 and belongs to a positive-sense and single-stranded RNA virus. Its presence in fecal specimens of children suffering from diarrhea has been demonstrated in several Asian countries 3456, in Brazil and German 7, in France 8 and in Tunisia 9. Some reports showed the high level of seroprevalence in adults 710, suggesting the widespread exposure to Aichi virus during childhood. The genome of Aichi virus contains 8,280 nucleotides and a poly(A tail. The single large open reading frame (nt 713-8014 according to the strain AB010145 encodes a polyprotein of 2,432 amino acids that is cleaved into the typical picornavirus structural proteins VP0, VP3, VP1, and nonstructural proteins 2A, 2B, 2C, 3A, 3B, 3C and 3D 211. Based on the phylogenetic analysis of 519-bp sequences at the 3C-3D (3CD junction, Aichi viruses can be divided into two genotypes A and B with approximately 90% sequence homology 12. Although only six complete genomes of Aichi virus were deposited in GenBank at present, mosaic genomes can be found in strains from different countries.

  3. Sequence analysis reveals mosaic genome of Aichi virus.

    Science.gov (United States)

    Han, Xiaohong; Zhang, Wen; Xue, Yanjun; Shao, Shihe

    2011-08-05

    Aichi virus is a positive-sense and single-stranded RNA virus, which demonstrated to be related to diarrhea of Children. In the present study, phylogenetic and recombination analysis based on the Aichi virus complete genomes available in GenBank reveal a mosaic genome sequence [GenBank: FJ890523], of which the nt 261-852 region (the nt position was based on the aligned sequence file) shows close relationship with AB010145/Japan with 97.9% sequence identity, while the other genomic regions show close relationship with AY747174/German with 90.1% sequence identity. Our results will provide valuable hints for future research on Aichi virus diversity.Aichi virus is a member of the Kobuvirus genus of the Picornaviridae family 12 and belongs to a positive-sense and single-stranded RNA virus. Its presence in fecal specimens of children suffering from diarrhea has been demonstrated in several Asian countries 3456, in Brazil and German 7, in France 8 and in Tunisia 9. Some reports showed the high level of seroprevalence in adults 710, suggesting the widespread exposure to Aichi virus during childhood.The genome of Aichi virus contains 8,280 nucleotides and a poly(A) tail. The single large open reading frame (nt 713-8014 according to the strain AB010145) encodes a polyprotein of 2,432 amino acids that is cleaved into the typical picornavirus structural proteins VP0, VP3, VP1, and nonstructural proteins 2A, 2B, 2C, 3A, 3B, 3C and 3D 211. Based on the phylogenetic analysis of 519-bp sequences at the 3C-3D (3CD) junction, Aichi viruses can be divided into two genotypes A and B with approximately 90% sequence homology 12. Although only six complete genomes of Aichi virus were deposited in GenBank at present, mosaic genomes can be found in strains from different countries.

  4. Mass-spectrometric profiling of cerebrospinal fluid reveals metabolite biomarkers for CNS involvement in varicella zoster virus reactivation.

    Science.gov (United States)

    Kuhn, Maike; Sühs, Kurt-Wolfram; Akmatov, Manas K; Klawonn, Frank; Wang, Junxi; Skripuletz, Thomas; Kaever, Volkhard; Stangel, Martin; Pessler, Frank

    2018-01-17

    Varicella zoster virus (VZV) reactivation spans the spectrum from uncomplicated segmental herpes zoster to life-threatening disseminated CNS infection. Moreover, in the absence of a small animal model for this human pathogen, studies of pathogenesis at the organismal level depend on analysis of human biosamples. Changes in cerebrospinal fluid (CSF) metabolites may reflect critical aspects of host responses and end-organ damage in neuroinfection and neuroinflammation. We therefore applied a targeted metabolomics screen of CSF to three clinically distinct forms of VZV reactivation and infectious and non-infectious disease controls in order to identify biomarkers for CNS involvement in VZV reactivation. Metabolite profiles were determined by targeted liquid chromatography-mass spectrometry in CSF from patients with segmental zoster (shingles, n = 14), facial nerve zoster (n = 16), VZV meningitis/encephalitis (n = 15), enteroviral meningitis (n = 10), idiopathic Bell's palsy (n = 11), and normal pressure hydrocephalus (n = 15). Concentrations of 88 metabolites passing quality assessment clearly separated the three VZV reactivation forms from each other and from the non-infected samples. Internal cross-validation identified four metabolites (SM C16:1, glycine, lysoPC a C26:1, PC ae C34:0) that were particularly associated with VZV meningoencephalitis. SM(OH) C14:1 accurately distinguished facial nerve zoster from Bell's palsy. Random forest construction revealed even more accurate classifiers (signatures comprising 2-4 metabolites) for most comparisons. Some of the most accurate biomarkers correlated only weakly with CSF leukocyte count, indicating that they do not merely reflect recruitment of inflammatory cells but, rather, specific pathophysiological mechanisms. Across all samples, only the sum of hexoses and the amino acids arginine, serine, and tryptophan correlated negatively with leukocyte count. Increased expression of the metabolites

  5. Temporal profiling of the chromatin proteome reveals system-wide responses to replication inhibition

    DEFF Research Database (Denmark)

    Khoudoli, Guennadi A; Gillespie, Peter J; Stewart, Graeme

    2008-01-01

    Although the replication, expression, and maintenance of DNA are well-studied processes, the way that they are coordinated is poorly understood. Here, we report an analysis of the changing association of proteins with chromatin (the chromatin proteome) during progression through interphase of the...

  6. Protein expression profiling of nuclear membrane protein reveals potential biomarker of human hepatocellular carcinoma

    OpenAIRE

    Khan, Rizma; Zahid, Saadia; Wan, Yu-Jui; Forster, Jameson; Karim, A-Bashar; Nawabi, Atta M; Azhar, Abid; Rahman, M; Ahmed, Nikhat

    2013-01-01

    Abstract Background Complex molecular events lead to development and progression of liver cirrhosis to HCC. Differentially expressed nuclear membrane associated proteins are responsible for the functional and structural alteration during the progression from cirrhosis to carcinoma. Although alterations/ post translational modifications in protein expression have been extensively quantified, complementary analysis of nuclear membrane proteome changes h...

  7. Gait profile score and movement analysis profile in patients with Parkinson's disease during concurrent cognitive load

    Science.gov (United States)

    Speciali, Danielli S.; Oliveira, Elaine M.; Cardoso, Jefferson R.; Correa, João C. F.; Baker, Richard; Lucareli, Paulo R. G.

    2014-01-01

    Background: Gait disorders are common in individuals with Parkinson's Disease (PD) and the concurrent performance of motor and cognitive tasks can have marked effects on gait. The Gait Profile Score (GPS) and the Movement Analysis Profile (MAP) were developed in order to summarize the data of kinematics and facilitate understanding of the results of gait analysis. Objective: To investigate the effectiveness of the GPS and MAP in the quantification of changes in gait during a concurrent cognitive load while walking in adults with and without PD. Method: Fourteen patients with idiopathic PD and nine healthy subjects participated in the study. All subjects performed single and dual walking tasks. The GPS/MAP was computed from three-dimensional gait analysis data. Results: Differences were found between tasks for GPS (PGait Variable Score (GVS) (pelvic rotation, knee flexion-extension and ankle dorsiflexion-plantarflexion) (Pgait impairment during the dual task and suggest that GPS/MAP may be used to evaluate the effects of concurrent cognitive load while walking in patients with PD. PMID:25054382

  8. 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.

  9. In vivo Host-Pathogen Interaction as Revealed by Global Proteomic Profiling of Zebrafish Larvae

    Directory of Open Access Journals (Sweden)

    Francisco Díaz-Pascual

    2017-07-01

    immersion. We demonstrated the suitability of zebrafish embryos as a model for in vivo host-pathogen based proteomic studies in P. aeruginosa. Our global proteomic profiling identifies novel molecular signatures that give systematic insight into zebrafish-Pseudomonas interaction.

  10. Whole-genome gene expression profiling revealed genes and pathways potentially involved in regulating interactions of soybean with cyst nematode (Heterodera glycines Ichinohe).

    Science.gov (United States)

    Wan, Jinrong; Vuong, Tri; Jiao, Yongqing; Joshi, Trupti; Zhang, Hongxin; Xu, Dong; Nguyen, Henry T

    2015-03-04

    Soybean cyst nematode (SCN, Heterodera glycines Ichinohe) is the most devastating pathogen of soybean. Many gene expression profiling studies have been conducted to investigate the responses of soybean to the infection by this pathogen using primarily the first-generation soybean genome array that covered approximately 37,500 soybean transcripts. However, no study has been reported yet using the second-generation Affymetrix soybean whole-genome transcript array (Soybean WT array) that represents approximately 66,000 predicted soybean transcripts. In the present work, the gene expression profiles of two soybean plant introductions (PIs) PI 437654 and PI 567516C (both resistant to multiple SCN HG Types) and cultivar Magellan (susceptible to SCN) were compared in the presence or absence of the SCN inoculum at 3 and 8 days post-inoculation using the Soybean WT array. Data analysis revealed that the two resistant soybean lines showed distinctive gene expression profiles from each other and from Magellan not only in response to the SCN inoculation, but also in the absence of SCN. Overall, 1,413 genes and many pathways were revealed to be differentially regulated. Among them, 297 genes were constitutively regulated in the two resistant lines (compared with Magellan) and 1,146 genes were responsive to the SCN inoculation in the three lines, with 30 genes regulated both constitutively and by SCN. In addition to the findings similar to those in the published work, many genes involved in ethylene, protein degradation, and phenylpropanoid pathways were also revealed differentially regulated in the present study. GC-rich elements (e.g., GCATGC) were found over-represented in the promoter regions of certain groups of genes. These have not been observed before, and could be new defense-responsive regulatory elements. Different soybean lines showed different gene expression profiles in the presence and absence of the SCN inoculum. Both inducible and constitutive gene expression

  11. Analysis and test of low profile aluminum aerospace tank dome

    Science.gov (United States)

    Ahmed, R.; Wilhelm, J. M.

    1993-01-01

    In order to increase the structural performance of cryogenic tanks, the aerospace industry is beginning to employ low-profile bulkheads in new generation launch vehicle designs. This report details the analysis and test of one such dome made from 2219 aluminum. Such domes have two potential failure modes under internal pressure, general tensile failure and hoop compression buckling (in regions near the equator). The test determined the buckling load and ultimate tensile load of the hardware and showed that both compared well with the analysis predictions. This effort was conducted under the auspices of NASA and the General Dynamics Cryogenic Tank Technology Program (CTTP).

  12. Dose profile analysis of small fields in intensity modulated radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Medel B, E. [IMSS, Centro Medico Nacional Manuel Avila Camacho, Calle 2 Nte. 2004, Barrio de San Francisco, 72090 Puebla, Pue. (Mexico); Tejeda M, G.; Romero S, K., E-mail: romsakaren@gmail.com [Benemerita Universidad Autonoma de Puebla, Facultad de Ciencias Fisico Matematicas, Av. San Claudio y 18 Sur, Ciudad Universitaria, 72570 Puebla, Pue.(Mexico)

    2015-10-15

    Full text: Small field dosimetry is getting a very important worldwide task nowadays. The use of fields of few centimeters is more common with the introduction of sophisticated techniques of radiation therapy, as Intensity Modulated Radiotherapy (IMRT). In our country the implementation of such techniques is just getting started and whit it the need of baseline data acquisition. The dosimetry under small field conditions represents a challenge for the physicists community. In this work, a dose profile analysis was done, using various types of dosimeters for further comparisons. This analysis includes the study of quality parameters as flatness, symmetry, penumbra, and other in-axis measurements. (Author)

  13. Transcriptome Analysis of Sorbic Acid-Stressed Bacillus subtilis Reveals a Nutrient Limitation Response and Indicates Plasma Membrane Remodeling▿ †

    OpenAIRE

    Beek, Alex Ter; Keijser, Bart J. F.; Boorsma, Andre; Zakrzewska, Anna; Orij, Rick; Smits, Gertien J.; Brul, Stanley

    2007-01-01

    The weak organic acid sorbic acid is a commonly used food preservative, as it inhibits the growth of bacteria, yeasts, and molds. We have used genome-wide transcriptional profiling of Bacillus subtilis cells during mild sorbic acid stress to reveal the growth-inhibitory activity of this preservative and to identify potential resistance mechanisms. Our analysis demonstrated that sorbic acid-stressed cells induce responses normally seen upon nutrient limitation. This is indicated by the strong ...

  14. Deep small RNA sequencing from the nematode Ascaris reveals conservation, functional diversification, and novel developmental profiles

    Science.gov (United States)

    Wang, Jianbin; Czech, Benjamin; Crunk, Amanda; Wallace, Adam; Mitreva, Makedonka; Hannon, Gregory J.; Davis, Richard E.

    2011-01-01

    Eukaryotic cells express several classes of small RNAs that regulate gene expression and ensure genome maintenance. Endogenous siRNAs (endo-siRNAs) and Piwi-interacting RNAs (piRNAs) mainly control gene and transposon expression in the germline, while microRNAs (miRNAs) generally function in post-transcriptional gene silencing in both somatic and germline cells. To provide an evolutionary and developmental perspective on small RNA pathways in nematodes, we identified and characterized known and novel small RNA classes through gametogenesis and embryo development in the parasitic nematode Ascaris suum and compared them with known small RNAs of Caenorhabditis elegans. piRNAs, Piwi-clade Argonautes, and other proteins associated with the piRNA pathway have been lost in Ascaris. miRNAs are synthesized immediately after fertilization in utero, before pronuclear fusion, and before the first cleavage of the zygote. This is the earliest expression of small RNAs ever described at a developmental stage long thought to be transcriptionally quiescent. A comparison of the two classes of Ascaris endo-siRNAs, 22G-RNAs and 26G-RNAs, to those in C. elegans, suggests great diversification and plasticity in the use of small RNA pathways during spermatogenesis in different nematodes. Our data reveal conserved characteristics of nematode small RNAs as well as features unique to Ascaris that illustrate significant flexibility in the use of small RNAs pathways, some of which are likely an adaptation to Ascaris' life cycle and parasitism. PMID:21685128

  15. Proteomic amino-termini profiling reveals targeting information for protein import into complex plastids.

    Directory of Open Access Journals (Sweden)

    Pitter F Huesgen

    Full Text Available In organisms with complex plastids acquired by secondary endosymbiosis from a photosynthetic eukaryote, the majority of plastid proteins are nuclear-encoded, translated on cytoplasmic ribosomes, and guided across four membranes by a bipartite targeting sequence. In-depth understanding of this vital import process has been impeded by a lack of information about the transit peptide part of this sequence, which mediates transport across the inner three membranes. We determined the mature N-termini of hundreds of proteins from the model diatom Thalassiosira pseudonana, revealing extensive N-terminal modification by acetylation and proteolytic processing in both cytosol and plastid. We identified 63 mature N-termini of nucleus-encoded plastid proteins, deduced their complete transit peptide sequences, determined a consensus motif for their cleavage by the stromal processing peptidase, and found evidence for subsequent processing by a plastid methionine aminopeptidase. The cleavage motif differs from that of higher plants, but is shared with other eukaryotes with complex plastids.

  16. Expression profiling of lymph nodes in tuberculosis patients reveal inflammatory milieu at site of infection

    Science.gov (United States)

    Maji, Abhijit; Misra, Richa; Kumar Mondal, Anupam; Kumar, Dhirendra; Bajaj, Divya; Singhal, Anshika; Arora, Gunjan; Bhaduri, Asani; Sajid, Andaleeb; Bhatia, Sugandha; Singh, Sompal; Singh, Harshvardhan; Rao, Vivek; Dash, Debasis; Baby Shalini, E; Sarojini Michael, Joy; Chaudhary, Anil; Gokhale, Rajesh S.; Singh, Yogendra

    2015-01-01

    Extrapulmonary manifestations constitute 15 to 20% of tuberculosis cases, with lymph node tuberculosis (LNTB) as the most common form of infection. However, diagnosis and treatment advances are hindered by lack of understanding of LNTB biology. To identify host response, Mycobacterium tuberculosis infected lymph nodes from LNTB patients were studied by means of transcriptomics and quantitative proteomics analyses. The selected targets obtained by comparative analyses were validated by quantitative PCR and immunohistochemistry. This approach provided expression data for 8,728 transcripts and 102 proteins, differentially regulated in the infected human lymph node. Enhanced inflammation with upregulation of T-helper1-related genes, combined with marked dysregulation of matrix metalloproteinases, indicates tissue damage due to high immunoactivity at infected niche. This expression signature was accompanied by significant upregulation of an immunoregulatory gene, leukotriene A4 hydrolase, at both transcript and protein levels. Comparative transcriptional analyses revealed LNTB-specific perturbations. In contrast to pulmonary TB-associated increase in lipid metabolism, genes involved in fatty-acid metabolism were found to be downregulated in LNTB suggesting differential lipid metabolic signature. This study investigates the tissue molecular signature of LNTB patients for the first time and presents findings that indicate the possible mechanism of disease pathology through dysregulation of inflammatory and tissue-repair processes. PMID:26469538

  17. Proteomic profiling of cereal aphid saliva reveals both ubiquitous and adaptive secreted proteins.

    Directory of Open Access Journals (Sweden)

    Sohail A K Rao

    Full Text Available The secreted salivary proteins from two cereal aphid species, Sitobion avenae and Metopolophium dirhodum, were collected from artificial diets and analysed by tandem mass spectrometry. Protein identification was performed by searching MS data against the official protein set from the current pea aphid (Acyrthosiphon pisum genome assembly and revealed 12 and 7 proteins in the saliva of S. avenae and M. dirhodum, respectively. When combined with a comparable dataset from A. pisum, only three individual proteins were common to all the aphid species; two paralogues of the GMC oxidoreductase family (glucose dehydrogenase; GLD and ACYPI009881, an aphid specific protein previously identified as a putative component of the salivary sheath. Antibodies were designed from translated protein sequences obtained from partial cDNA sequences for ACYPI009881 and both saliva associated GLDs. The antibodies detected all parent proteins in secreted saliva from the three aphid species, but could only detect ACYPI009881, and not saliva associated GLDs, in protein extractions from the salivary glands. This result was confirmed by immunohistochemistry using whole and sectioned salivary glands, and in addition, localised ACYPI009881 to specific cell types within the principal salivary gland. The implications of these findings for the origin of salivary components and the putative role of the proteins identified are discussed in the context of our limited understanding of the functional relationship between aphid saliva and the plants they feed on. The mass spectrometry data have been deposited to the ProteomeXchange and can be accessed under the identifier PXD000113.

  18. Proteomic profiling of cereal aphid saliva reveals both ubiquitous and adaptive secreted proteins.

    Science.gov (United States)

    Rao, Sohail A K; Carolan, James C; Wilkinson, Tom L

    2013-01-01

    The secreted salivary proteins from two cereal aphid species, Sitobion avenae and Metopolophium dirhodum, were collected from artificial diets and analysed by tandem mass spectrometry. Protein identification was performed by searching MS data against the official protein set from the current pea aphid (Acyrthosiphon pisum) genome assembly and revealed 12 and 7 proteins in the saliva of S. avenae and M. dirhodum, respectively. When combined with a comparable dataset from A. pisum, only three individual proteins were common to all the aphid species; two paralogues of the GMC oxidoreductase family (glucose dehydrogenase; GLD) and ACYPI009881, an aphid specific protein previously identified as a putative component of the salivary sheath. Antibodies were designed from translated protein sequences obtained from partial cDNA sequences for ACYPI009881 and both saliva associated GLDs. The antibodies detected all parent proteins in secreted saliva from the three aphid species, but could only detect ACYPI009881, and not saliva associated GLDs, in protein extractions from the salivary glands. This result was confirmed by immunohistochemistry using whole and sectioned salivary glands, and in addition, localised ACYPI009881 to specific cell types within the principal salivary gland. The implications of these findings for the origin of salivary components and the putative role of the proteins identified are discussed in the context of our limited understanding of the functional relationship between aphid saliva and the plants they feed on. The mass spectrometry data have been deposited to the ProteomeXchange and can be accessed under the identifier PXD000113.

  19. Computer vision profiling of neurite outgrowth dynamics reveals spatiotemporal modularity of Rho GTPase signaling.

    Science.gov (United States)

    Fusco, Ludovico; Lefort, Riwal; Smith, Kevin; Benmansour, Fethallah; Gonzalez, German; Barillari, Caterina; Rinn, Bernd; Fleuret, Francois; Fua, Pascal; Pertz, Olivier

    2016-01-04

    Rho guanosine triphosphatases (GTPases) control the cytoskeletal dynamics that power neurite outgrowth. This process consists of dynamic neurite initiation, elongation, retraction, and branching cycles that are likely to be regulated by specific spatiotemporal signaling networks, which cannot be resolved with static, steady-state assays. We present NeuriteTracker, a computer-vision approach to automatically segment and track neuronal morphodynamics in time-lapse datasets. Feature extraction then quantifies dynamic neurite outgrowth phenotypes. We identify a set of stereotypic neurite outgrowth morphodynamic behaviors in a cultured neuronal cell system. Systematic RNA interference perturbation of a Rho GTPase interactome consisting of 219 proteins reveals a limited set of morphodynamic phenotypes. As proof of concept, we show that loss of function of two distinct RhoA-specific GTPase-activating proteins (GAPs) leads to opposite neurite outgrowth phenotypes. Imaging of RhoA activation dynamics indicates that both GAPs regulate different spatiotemporal Rho GTPase pools, with distinct functions. Our results provide a starting point to dissect spatiotemporal Rho GTPase signaling networks that regulate neurite outgrowth. © 2016 Fusco et al.

  20. Gene Essentiality Profiling Reveals Gene Networks and Synthetic Lethal Interactions with Oncogenic Ras.

    Science.gov (United States)

    Wang, Tim; Yu, Haiyan; Hughes, Nicholas W; Liu, Bingxu; Kendirli, Arek; Klein, Klara; Chen, Walter W; Lander, Eric S; Sabatini, David M

    2017-02-23

    The genetic dependencies of human cancers widely vary. Here, we catalog this heterogeneity and use it to identify functional gene interactions and genotype-dependent liabilities in cancer. By using genome-wide CRISPR-based screens, we generate a gene essentiality dataset across 14 human acute myeloid leukemia (AML) cell lines. Sets of genes with correlated patterns of essentiality across the lines reveal new gene relationships, the essential substrates of enzymes, and the molecular functions of uncharacterized proteins. Comparisons of differentially essential genes between Ras-dependent and -independent lines uncover synthetic lethal partners of oncogenic Ras. Screens in both human AML and engineered mouse pro-B cells converge on a surprisingly small number of genes in the Ras processing and MAPK pathways and pinpoint PREX1 as an AML-specific activator of MAPK signaling. Our findings suggest general strategies for defining mammalian gene networks and synthetic lethal interactions by exploiting the natural genetic and epigenetic diversity of human cancer cells. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Transcriptional profiling of mature Arabidopsis trichomes reveals that NOECK encodes the MIXTA-like transcriptional regulator MYB106.

    Science.gov (United States)

    Jakoby, Marc J; Falkenhan, Doris; Mader, Michael T; Brininstool, Ginger; Wischnitzki, Elisabeth; Platz, Nicole; Hudson, Andrew; Hülskamp, Martin; Larkin, John; Schnittger, Arp

    2008-11-01

    Leaf hairs (trichomes) of Arabidopsis (Arabidopsis thaliana) have been extensively used as a model to address general questions in cell and developmental biology. Here, we lay the foundation for a systems-level understanding of the biology of this model cell type by performing genome-wide gene expression analyses. We have identified 3,231 genes that are up-regulated in mature trichomes relative to leaves without trichomes, and we compared wild-type trichomes with two mutants, glabra3 and triptychon, that affect trichome morphology and physiology in contrasting ways. We found that cell wall-related transcripts were particularly overrepresented in trichomes, consistent with their highly elaborated structure. In addition, trichome expression maps revealed high activities of anthocyanin, flavonoid, and glucosinolate pathways, indicative of the roles of trichomes in the biosynthesis of secondary compounds and defense. Interspecies comparisons revealed that Arabidopsis trichomes share many expressed genes with cotton (Gossypium hirsutum) fibers, making them an attractive model to study industrially important fibers. In addition to identifying physiological processes involved in the development of a specific cell type, we also demonstrated the utility of transcript profiling for identifying and analyzing regulatory gene function. One of the genes that are differentially expressed in fibers is the MYB transcription factor GhMYB25. A combination of transcript profiling and map-based cloning revealed that the NOECK gene of Arabidopsis encodes AtMYB106, a MIXTA-like transcription factor and homolog of cotton GhMYB25. However, in contrast to Antirrhinum, in which MIXTA promotes epidermal cell outgrowth, AtMYB106 appears to function as a repressor of cell outgrowth in Arabidopsis.

  2. Biochemical and transcriptomic analyses reveal different metabolite biosynthesis profiles among three color and developmental stages in 'Anji Baicha' (Camellia sinensis).

    Science.gov (United States)

    Li, Chun-Fang; Xu, Yan-Xia; Ma, Jian-Qiang; Jin, Ji-Qiang; Huang, Dan-Juan; Yao, Ming-Zhe; Ma, Chun-Lei; Chen, Liang

    2016-09-08

    The new shoots of the albino tea cultivar 'Anji Baicha' are yellow or white at low temperatures and turn green as the environmental temperatures increase during the early spring. 'Anji Baicha' metabolite profiles exhibit considerable variability over three color and developmental stages, especially regarding the carotenoid, chlorophyll, and theanine concentrations. Previous studies focused on physiological characteristics, gene expression differences, and variations in metabolite abundances in albino tea plant leaves at specific growth stages. However, the molecular mechanisms regulating metabolite biosynthesis in various color and developmental stages in albino tea leaves have not been fully characterized. We used RNA-sequencing to analyze 'Anji Baicha' leaves at the yellow-green, albescent, and re-greening stages. The leaf transcriptomes differed considerably among the three stages. Functional classifications based on Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes enrichment analyses revealed that differentially expressed unigenes were mainly related to metabolic pathways, biosynthesis of secondary metabolites, phenylpropanoid biosynthesis, and carbon fixation in photosynthetic organisms. Chemical analyses revealed higher β-carotene and theanine levels, but lower chlorophyll a levels, in the albescent stage than in the green stage. Furthermore, unigenes involved in carotenoid, chlorophyll, and theanine biosyntheses were identified, and the expression patterns of the differentially expressed unigenes in these biosynthesis pathways were characterized. Through co-expression analyses, we identified the key genes in these pathways. These genes may be responsible for the metabolite biosynthesis differences among the different leaf color and developmental stages of 'Anji Baicha' tea plants. Our study presents the results of transcriptomic and biochemical analyses of 'Anji Baicha' tea plants at various stages. The distinct transcriptome profiles

  3. Transcriptome profile at different physiological stages reveals potential mode for curly fleece in Chinese tan sheep.

    Directory of Open Access Journals (Sweden)

    Xiaolong Kang

    Full Text Available Tan sheep (Ovis aries, a Chinese indigenous breed, has special curly fleece after birth, especially at one month old. However, this unique phenotype disappears gradually with age and the underlying reasons of trait evolvement are still unknown. In this study, skin transcriptome data was used to study this issue. In total 51,215 transcripts including described transcripts and transfrags were identified. Pathway analysis of the top 100 most highly expressed transcripts, which included TCHH and keratin gene family members, such as KRT25, KRT5, KRT71, KRT14 and others, showed pathways known to be relevant to hair/fleece development and function. Six hundred differentially expressed (DE transcripts were detected at two different physiological ages (one-month-old with curly fleece and 48-month-old without curly fleece and were categorized into three major functional groups: cellular component, molecular function, and biological process. The top six functional categories included cell, cell part, cellular process, binding, intracellular, metabolic process. The detected differentially expressed genes were particularly involved in signal, signal peptide, disulfide bond, glycoprotein and secreted terms, respectively. Further splicing isoform analysis showed that the metallothionein 3 isoform was up-regulated in Tan lamb skin, indicating that it may be related to the conformation of curly fleece in Chinese Tan lamb. The hair-related important differentially expressed genes (SPINK4, FGF21, ESRα, EphA3, NTNG1 and GPR110 were confirmed by qPCR analysis. We deduced that the differences existed in expressed transcripts, splice isoforms and GO categories between the two different physiological stages, which might constitute the major reasons for explaining the trait evolvement of curly fleece in Chinese Tan sheep. This study provides some clues for elucidating the molecular mechanism of fleece change with age in Chinese Tan sheep, as well as supplying some

  4. Latent profile analysis of regression-based norms demonstrates relationship of compounding MS symptom burden and negative work events.

    Science.gov (United States)

    Frndak, Seth E; Smerbeck, Audrey M; Irwin, Lauren N; Drake, Allison S; Kordovski, Victoria M; Kunker, Katrina A; Khan, Anjum L; Benedict, Ralph H B

    2016-10-01

    We endeavored to clarify how distinct co-occurring symptoms relate to the presence of negative work events in employed multiple sclerosis (MS) patients. Latent profile analysis (LPA) was utilized to elucidate common disability patterns by isolating patient subpopulations. Samples of 272 employed MS patients and 209 healthy controls (HC) were administered neuroperformance tests of ambulation, hand dexterity, processing speed, and memory. Regression-based norms were created from the HC sample. LPA identified latent profiles using the regression-based z-scores. Finally, multinomial logistic regression tested for negative work event differences among the latent profiles. Four profiles were identified via LPA: a common profile (55%) characterized by slightly below average performance in all domains, a broadly low-performing profile (18%), a poor motor abilities profile with average cognition (17%), and a generally high-functioning profile (9%). Multinomial regression analysis revealed that the uniformly low-performing profile demonstrated a higher likelihood of reported negative work events. Employed MS patients with co-occurring motor, memory and processing speed impairments were most likely to report a negative work event, classifying them as uniquely at risk for job loss.

  5. Gene response profiles for Daphnia pulex exposed to the environmental stressor cadmium reveals novel crustacean metallothioneins

    Directory of Open Access Journals (Sweden)

    Davey Jennifer C

    2007-12-01

    Full Text Available Abstract Background Genomic research tools such as microarrays are proving to be important resources to study the complex regulation of genes that respond to environmental perturbations. A first generation cDNA microarray was developed for the environmental indicator species Daphnia pulex, to identify genes whose regulation is modulated following exposure to the metal stressor cadmium. Our experiments revealed interesting changes in gene transcription that suggest their biological roles and their potentially toxicological features in responding to this important environmental contaminant. Results Our microarray identified genes reported in the literature to be regulated in response to cadmium exposure, suggested functional attributes for genes that share no sequence similarity to proteins in the public databases, and pointed to genes that are likely members of expanded gene families in the Daphnia genome. Genes identified on the microarray also were associated with cadmium induced phenotypes and population-level outcomes that we experimentally determined. A subset of genes regulated in response to cadmium exposure was independently validated using quantitative-realtime (Q-RT-PCR. These microarray studies led to the discovery of three genes coding for the metal detoxication protein metallothionein (MT. The gene structures and predicted translated sequences of D. pulex MTs clearly place them in this gene family. Yet, they share little homology with previously characterized MTs. Conclusion The genomic information obtained from this study represents an important first step in characterizing microarray patterns that may be diagnostic to specific environmental contaminants and give insights into their toxicological mechanisms, while also providing a practical tool for evolutionary, ecological, and toxicological functional gene discovery studies. Advances in Daphnia genomics will enable the further development of this species as a model organism for

  6. Transcriptome analysis reveals dynamic changes in the gene ...

    Indian Academy of Sciences (India)

    Home; Journals; Journal of Genetics; Volume 94; Issue 3 ... Potassium plays a key role in plant development and reproduction. ... Our results indicate that the expression profiles of a large number of genes involved in various plant physiological processes are significantly altered in response to potassium deficiency, which ...

  7. Mass Spectrometry-Based Quantitative Metabolomics Revealed a Distinct Lipid Profile in Breast Cancer Patients

    Directory of Open Access Journals (Sweden)

    Yun Yen

    2013-04-01

    Full Text Available Breast cancer accounts for the largest number of newly diagnosed cases in female cancer patients. Although mammography is a powerful screening tool, about 20% of breast cancer cases cannot be detected by this method. New diagnostic biomarkers for breast cancer are necessary. Here, we used a mass spectrometry-based quantitative metabolomics method to analyze plasma samples from 55 breast cancer patients and 25 healthy controls. A number of 30 patients and 20 age-matched healthy controls were used as a training dataset to establish a diagnostic model and to identify potential biomarkers. The remaining samples were used as a validation dataset to evaluate the predictive accuracy for the established model. Distinct separation was obtained from an orthogonal partial least squares-discriminant analysis (OPLS-DA model with good prediction accuracy. Based on this analysis, 39 differentiating metabolites were identified, including significantly lower levels of lysophosphatidylcholines and higher levels of sphingomyelins in the plasma samples obtained from breast cancer patients compared with healthy controls. Using logical regression, a diagnostic equation based on three metabolites (lysoPC a C16:0, PC ae C42:5 and PC aa C34:2 successfully differentiated breast cancer patients from healthy controls, with a sensitivity of 98.1% and a specificity of 96.0%.

  8. DNA methylation profiling reveals the presence of population-specific signatures correlating with phenotypic characteristics.

    Science.gov (United States)

    Giri, Anil K; Bharadwaj, Soham; Banerjee, Priyanka; Chakraborty, Shraddha; Parekatt, Vaisak; Rajashekar, Donaka; Tomar, Abhishek; Ravindran, Aarthi; Basu, Analabha; Tandon, Nikhil; Bharadwaj, Dwaipayan

    2017-06-01

    Phenotypic characteristics are known to vary substantially among different ethnicities around the globe. These variations are mediated by number of stochastic events and cannot be attributed to genetic architecture alone. DNA methylation is a well-established mechanism that sculpts our epigenome influencing phenotypic variation including disease manifestation. Since DNA methylation is an important determinant for health issues of a population, it demands a thorough investigation of the natural differences in genome wide DNA methylation patterns across different ethnic groups. This study is based on comparative analyses of methylome from five different ethnicities with major focus on Indian subjects. The current study uses hierarchical clustering approaches, principal component analysis and locus specific differential methylation analysis on Illumina 450K methylation data to compare methylome of different ethnic subjects. Our data indicates that the variations in DNA methylation patterns of Indians are less among themselves compared to other global population. It empirically correlated with dietary, cultural and demographical divergences across different ethnic groups. Our work further suggests that Indians included in this study, despite their genetic similarity with the Caucasian population, are in close proximity with Japanese in terms of their methylation signatures.

  9. Cytogenomic profiling of breast cancer brain metastases reveals potential for repurposing targeted therapeutics.

    Science.gov (United States)

    Bollig-Fischer, Aliccia; Michelhaugh, Sharon K; Wijesinghe, Priyanga; Dyson, Greg; Kruger, Adele; Palanisamy, Nallasivam; Choi, Lydia; Alosh, Baraa; Ali-Fehmi, Rouba; Mittal, Sandeep

    2015-06-10

    Breast cancer brain metastases remain a significant clinical problem. Chemotherapy is ineffective and a lack of treatment options result in poor patient outcomes. Targeted therapeutics have proven to be highly effective in primary breast cancer, but lack of molecular genomic characterization of metastatic brain tumors is hindering the development of new treatment regimens. Here we contribute to fill this void by reporting on gene copy number variation (CNV) in 10 breast cancer metastatic brain tumors, assayed by array comparative genomic hybridization (aCGH). Results were compared to a list of cancer genes verified by others to influence cancer. Cancer gene aberrations were identified in all specimens and pathway-level analysis was applied to aggregate data, which identified stem cell pluripotency pathway enrichment and highlighted recurring, significant amplification of SOX2, PIK3CA, NTRK1, GNAS, CTNNB1, and FGFR1. For a subset of the metastatic brain tumor samples (n = 4) we compared patient-matched primary breast cancer specimens. The results of our CGH analysis and validation by alternative methods indicate that oncogenic signals driving growth of metastatic tumors exist in the original cancer. This report contributes support for more rapid development of new treatments of metastatic brain tumors, the use of genomic-based diagnostic tools and repurposed drug treatments.

  10. Transcriptome and metabolome profiling of Narcissus pseudonarcissus 'King Alfred' reveal components of Amaryllidaceae alkaloid metabolism.

    Science.gov (United States)

    Singh, Aparna; Desgagné-Penix, Isabel

    2017-12-11

    Amaryllidaceae alkaloids (AAs) represent a diverse class of plant specialized metabolites and many display potent pharmacological activities. The AA metabolic pathway is poorly understood and resources are minimal. To enable AA pathway elucidation and novel biosynthetic enzymes discovery, we generated comprehensive metabolomic and corresponding transcriptomic datasets from different tissues of Narcissus pseudonarcissus 'King Alfred'. In this study, we performed untargeted UPLC-QTOF-MS metabolite analysis from different tissues, which generated exhaustive list of compounds, including several AAs, most predominant and diverse in bulbs. RNA sequencing of N. pseudonarcissus 'King Alfred' bulbs yielded 195,347 transcripts, after assembly. Top expressed genes belong to process like metabolism, survival, and defense including alkaloid biosynthetic genes. The transcriptome contained complete sequences for all proposed genes encoding AA-biosynthetic enzymes such as tyrosine decarboxylase (TYDC1 and TYDC2), phenylalanine ammonia-lyase (PAL1 and PAL2) and phenolic acids hydroxylases (C4H and C3H) to name a few. Furthermore, transcriptome data were validated using RT-qPCR analysis and expression study in different tissues of N. pseudonarcissus 'King Alfred' was performed. Here, we present the first comprehensive metabolome and transcriptome study from N. pseudonarcissus 'King Alfred' providing invaluable resources for metabolic engineering and biotechnological applications.

  11. Mitochondrial Genome Analysis Reveals Historical Lineages in Yellowstone Bison.

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    David Forgacs

    Full Text Available Yellowstone National Park is home to one of the only plains bison populations that have continuously existed on their present landscape since prehistoric times without evidence of domestic cattle introgression. Previous studies characterized the relatively high levels of nuclear genetic diversity in these bison, but little is known about their mitochondrial haplotype diversity. This study assessed mitochondrial genomes from 25 randomly selected Yellowstone bison and found 10 different mitochondrial haplotypes with a haplotype diversity of 0.78 (± 0.06. Spatial analysis of these mitochondrial DNA (mtDNA haplotypes did not detect geographic population subdivision (FST = -0.06, p = 0.76. However, we identified two independent and historically important lineages in Yellowstone bison by combining data from 65 bison (defined by 120 polymorphic sites from across North America representing a total of 30 different mitochondrial DNA haplotypes. Mitochondrial DNA haplotypes from one of the Yellowstone lineages represent descendants of the 22 indigenous bison remaining in central Yellowstone in 1902. The other mitochondrial DNA lineage represents descendants of the 18 females introduced from northern Montana in 1902 to supplement the indigenous bison population and develop a new breeding herd in the northern region of the park. Comparing modern and historical mitochondrial DNA diversity in Yellowstone bison helps uncover a historical context of park restoration efforts during the early 1900s, provides evidence against a hypothesized mitochondrial disease in bison, and reveals the signature of recent hybridization between American plains bison (Bison bison bison and Canadian wood bison (B. b. athabascae. Our study demonstrates how mitochondrial DNA can be applied to delineate the history of wildlife species and inform future conservation actions.

  12. Mitochondrial Genome Analysis Reveals Historical Lineages in Yellowstone Bison

    Science.gov (United States)

    Derr, James N.

    2016-01-01

    Yellowstone National Park is home to one of the only plains bison populations that have continuously existed on their present landscape since prehistoric times without evidence of domestic cattle introgression. Previous studies characterized the relatively high levels of nuclear genetic diversity in these bison, but little is known about their mitochondrial haplotype diversity. This study assessed mitochondrial genomes from 25 randomly selected Yellowstone bison and found 10 different mitochondrial haplotypes with a haplotype diversity of 0.78 (± 0.06). Spatial analysis of these mitochondrial DNA (mtDNA) haplotypes did not detect geographic population subdivision (FST = -0.06, p = 0.76). However, we identified two independent and historically important lineages in Yellowstone bison by combining data from 65 bison (defined by 120 polymorphic sites) from across North America representing a total of 30 different mitochondrial DNA haplotypes. Mitochondrial DNA haplotypes from one of the Yellowstone lineages represent descendants of the 22 indigenous bison remaining in central Yellowstone in 1902. The other mitochondrial DNA lineage represents descendants of the 18 females introduced from northern Montana in 1902 to supplement the indigenous bison population and develop a new breeding herd in the northern region of the park. Comparing modern and historical mitochondrial DNA diversity in Yellowstone bison helps uncover a historical context of park restoration efforts during the early 1900s, provides evidence against a hypothesized mitochondrial disease in bison, and reveals the signature of recent hybridization between American plains bison (Bison bison bison) and Canadian wood bison (B. b. athabascae). Our study demonstrates how mitochondrial DNA can be applied to delineate the history of wildlife species and inform future conservation actions. PMID:27880780

  13. Microarray analysis reveals novel features of the muscle aging process in men and women.

    Science.gov (United States)

    Liu, Dongmei; Sartor, Maureen A; Nader, Gustavo A; Pistilli, Emidio E; Tanton, Leah; Lilly, Charles; Gutmann, Laurie; IglayReger, Heidi B; Visich, Paul S; Hoffman, Eric P; Gordon, Paul M

    2013-09-01

    To develop a global view of muscle transcriptional differences between older men and women and sex-specific aging, we obtained muscle biopsies from the biceps brachii of young and older men and women and profiled the whole-genome gene expression using microarray. A logistic regression-based method in combination with an intensity-based Bayesian moderated t test was used to identify significant sex- and aging-related gene functional groups. Our analysis revealed extensive sex differences in the muscle transcriptome of older individuals and different patterns of transcriptional changes with aging in men and women. In older women, we observed a coordinated transcriptional upregulation of immune activation, extracellular matrix remodeling, and lipids storage; and a downregulation of mitochondrial biogenesis and function and muscle regeneration. The effect of aging results in sexual dimorphic alterations in the skeletal muscle transcriptome, which may modify the risk for developing musculoskeletal and metabolic diseases in men and women.

  14. Global metabolomic profiling reveals an association of metal fume exposure and plasma unsaturated fatty acids.

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    Yongyue Wei

    Full Text Available Welding-associated air pollutants negatively affect the health of exposed workers; however, their molecular mechanisms in causing disease remain largely unclear. Few studies have systematically investigated the systemic toxic effects of welding fumes on humans.To explore the effects of welding fumes on the plasma metabolome, and to identify biomarkers for risk assessment of welding fume exposure.The two-stage, self-controlled exploratory study included 11 boilermakers from a 2011 discovery panel and 8 boilermakers from a 2012 validation panel. Plasma samples were collected pre- and post-welding fume exposure and analyzed by chromatography/mass spectrometry.Eicosapentaenoic or docosapentaenoic acid metabolic changes post-welding were significantly associated with particulate (PM2.5 exposure (p<0.05. The combined analysis by linear mixed-effects model showed that exposure was associated with a statistically significant decline in metabolite change of eicosapentaenoic acid [β(95% CI = -0.013(-0.022 ≈ -0.004; p = 0.005], docosapentaenoic acid n3 [β(95% CI = -0.010(-0.018 ≈ -0.002; p = 0.017], and docosapentaenoic acid n6 [β(95% CI = -0.007(-0.013 ≈ -0.001; p = 0.021]. Pathway analysis identified an association of the unsaturated fatty acid pathway with exposure (p Study-2011 = 0.025; p Study-2012 = 0.021; p Combined = 0.009. The functional network built by these fatty acids and their interactive genes contained significant enrichment of genes associated with various diseases, including neoplasms, cardiovascular diseases, and lipid metabolism disorders.High-dose exposure of metal welding fumes decreases unsaturated fatty acids with an exposure-response relationship. This alteration in fatty acids is a potential biological mediator and biomarker for exposure-related health disorders.

  15. Metabolite Profiling Reveals Developmental Inequalities in Pinot Noir Berry Tissues Late in Ripening.

    Science.gov (United States)

    Vondras, Amanda M; Commisso, Mauro; Guzzo, Flavia; Deluc, Laurent G

    2017-01-01

    Uneven ripening in Vitis vinifera is increasingly recognized as a phenomenon of interest, with substantial implications for fruit and wine composition and quality. This study sought to determine whether variation late in ripening (∼Modified Eichhorn-Lorenz stage 39) was associated with developmental differences that were observable as fruits within a cluster initiated ripening (véraison). Four developmentally distinct ripening classes of berries were tagged at cluster véraison, sampled at three times late in ripening, and subjected to untargeted HPLC-MS to measure variation in amino acids, sugars, organic acids, and phenolic metabolites in skin, pulp, and seed tissues separately. Variability was described using predominantly two strategies. In the first, multivariate analysis (Orthogonal Projections to Latent Structures-Discriminant Analysis, OPLS-DA) was used to determine whether fruits were still distinguishable per their developmental position at véraison and to identify which metabolites accounted for these distinctions. The same technique was used to assess changes in each tissue over time. In a second strategy and for each annotated metabolite, the variance across the ripening classes at each time point was measured to show whether intra-cluster variance (ICV) was growing, shrinking, or constant over the period observed. Indeed, berries could be segregated by OPLS-DA late in ripening based on their developmental position at véraison, though the four ripening classes were aggregated into two larger ripening groups. Further, not all tissues were dynamic over the period examined. Although pulp tissues could be segregated by time sampled, this was not true for seed and only moderately so for skin. Ripening group differences in seed and skin, rather than the time fruit was sampled, were better able to define berries. Metabolites also experienced significant reductions in ICV between single pairs of time points, but never across the entire experiment

  16. Metabolite Profiling Reveals Developmental Inequalities in Pinot Noir Berry Tissues Late in Ripening

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    Amanda M. Vondras

    2017-06-01

    Full Text Available Uneven ripening in Vitis vinifera is increasingly recognized as a phenomenon of interest, with substantial implications for fruit and wine composition and quality. This study sought to determine whether variation late in ripening (∼Modified Eichhorn-Lorenz stage 39 was associated with developmental differences that were observable as fruits within a cluster initiated ripening (véraison. Four developmentally distinct ripening classes of berries were tagged at cluster véraison, sampled at three times late in ripening, and subjected to untargeted HPLC-MS to measure variation in amino acids, sugars, organic acids, and phenolic metabolites in skin, pulp, and seed tissues separately. Variability was described using predominantly two strategies. In the first, multivariate analysis (Orthogonal Projections to Latent Structures-Discriminant Analysis, OPLS-DA was used to determine whether fruits were still distinguishable per their developmental position at véraison and to identify which metabolites accounted for these distinctions. The same technique was used to assess changes in each tissue over time. In a second strategy and for each annotated metabolite, the variance across the ripening classes at each time point was measured to show whether intra-cluster variance (ICV was growing, shrinking, or constant over the period observed. Indeed, berries could be segregated by OPLS-DA late in ripening based on their developmental position at véraison, though the four ripening classes were aggregated into two larger ripening groups. Further, not all tissues were dynamic over the period examined. Although pulp tissues could be segregated by time sampled, this was not true for seed and only moderately so for skin. Ripening group differences in seed and skin, rather than the time fruit was sampled, were better able to define berries. Metabolites also experienced significant reductions in ICV between single pairs of time points, but never across the entire

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

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    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

  18. Transcriptome Profiling Reveals the Antitumor Mechanism of Polysaccharide from Marine Algae Gracilariopsis lemaneiformis.

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    Yani Kang

    Full Text Available Seaweed is one of the important biomass producers and possesses active metabolites with potential therapeutic effects against tumors. The red alga Gracilariopsis lemaneiformis (Gp. lemaneiformis possesses antitumor activity, and the polysaccharide of Gp. lemaneiformis (PGL has been demonstrated to be an ingredient with marked anticancer activity. However, the anticancer mechanism of PGL remains to be elucidated. In this study, we analyzed the inhibitory effect of PGL on the cell growth of 3 human cancer cell lines and found that PGL inhibited cell proliferation, reduced cell viability, and altered cell morphology in a time- and concentration-dependent manner. Our transcriptome analysis indicates that PGL can regulate the expression of 758 genes, which are involved in apoptosis, the cell cycle, nuclear division, and cell death. Furthermore, we demonstrated that PGL induced apoptosis and cell cycle arrest and modulated the expression of related genes in the A549 cell line. Our work provides a framework to understand the effects of PGL on cancer cells, and can serve as a resource for delineating the antitumor mechanisms of Gp. lemaneiformis.

  19. Molecular and Cellular Profiling of Scalp Psoriasis Reveals Differences and Similarities Compared to Skin Psoriasis.

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    Juan Ruano

    Full Text Available Scalp psoriasis shows a variable clinical spectrum and in many cases poses a great therapeutic challenge. However, it remains unknown whether the immune response of scalp psoriasis differs from understood pathomechanisms of psoriasis in other skin areas. We sought to determine the cellular and molecular phenotype of scalp psoriasis by performing a comparative analysis of scalp and skin using lesional and nonlesional samples from 20 Caucasian subjects with untreated moderate to severe psoriasis and significant scalp involvement and 10 control subjects without psoriasis. Our results suggest that even in the scalp, psoriasis is a disease of the inter-follicular skin. The immune mechanisms that mediate scalp psoriasis were found to be similar to those involved in skin psoriasis. However, the magnitude of dysregulation, number of differentially expressed genes, and enrichment of the psoriatic genomic fingerprint were more prominent in skin lesions. Furthermore, the scalp transcriptome showed increased modulation of several gene-sets, particularly those induced by interferon-gamma, compared with that of skin psoriasis, which was mainly associated with activation of TNFα/L-17/IL-22-induced keratinocyte response genes. We also detected differences in expression of gene-sets involving negative regulation, epigenetic regulation, epidermal differentiation, and dendritic cell or Th1/Th17/Th22-related T-cell processes.

  20. Molecular and Cellular Profiling of Scalp Psoriasis Reveals Differences and Similarities Compared to Skin Psoriasis.

    Science.gov (United States)

    Ruano, Juan; Suárez-Fariñas, Mayte; Shemer, Avner; Oliva, Margeaux; Guttman-Yassky, Emma; Krueger, James G

    2016-01-01

    Scalp psoriasis shows a variable clinical spectrum and in many cases poses a great therapeutic challenge. However, it remains unknown whether the immune response of scalp psoriasis differs from understood pathomechanisms of psoriasis in other skin areas. We sought to determine the cellular and molecular phenotype of scalp psoriasis by performing a comparative analysis of scalp and skin using lesional and nonlesional samples from 20 Caucasian subjects with untreated moderate to severe psoriasis and significant scalp involvement and 10 control subjects without psoriasis. Our results suggest that even in the scalp, psoriasis is a disease of the inter-follicular skin. The immune mechanisms that mediate scalp psoriasis were found to be similar to those involved in skin psoriasis. However, the magnitude of dysregulation, number of differentially expressed genes, and enrichment of the psoriatic genomic fingerprint were more prominent in skin lesions. Furthermore, the scalp transcriptome showed increased modulation of several gene-sets, particularly those induced by interferon-gamma, compared with that of skin psoriasis, which was mainly associated with activation of TNFα/L-17/IL-22-induced keratinocyte response genes. We also detected differences in expression of gene-sets involving negative regulation, epigenetic regulation, epidermal differentiation, and dendritic cell or Th1/Th17/Th22-related T-cell processes.

  1. Molecular and Cellular Profiling of Scalp Psoriasis Reveals Differences and Similarities Compared to Skin Psoriasis

    Science.gov (United States)

    Ruano, Juan; Suárez-Fariñas, Mayte; Shemer, Avner; Oliva, Margeaux

    2016-01-01

    Scalp psoriasis shows a variable clinical spectrum and in many cases poses a great therapeutic challenge. However, it remains unknown whether the immune response of scalp psoriasis differs from understood pathomechanisms of psoriasis in other skin areas. We sought to determine the cellular and molecular phenotype of scalp psoriasis by performing a comparative analysis of scalp and skin using lesional and nonlesional samples from 20 Caucasian subjects with untreated moderate to severe psoriasis and significant scalp involvement and 10 control subjects without psoriasis. Our results suggest that even in the scalp, psoriasis is a disease of the inter-follicular skin. The immune mechanisms that mediate scalp psoriasis were found to be similar to those involved in skin psoriasis. However, the magnitude of dysregulation, number of differentially expressed genes, and enrichment of the psoriatic genomic fingerprint were more prominent in skin lesions. Furthermore, the scalp transcriptome showed increased modulation of several gene-sets, particularly those induced by interferon-gamma, compared with that of skin psoriasis, which was mainly associated with activation of TNFα/L-17/IL-22-induced keratinocyte response genes. We also detected differences in expression of gene-sets involving negative regulation, epigenetic regulation, epidermal differentiation, and dendritic cell or Th1/Th17/Th22-related T-cell processes. PMID:26849645

  2. Gene expression profiling of white adipose tissue reveals paternal transmission of proneness to obesity.

    Science.gov (United States)

    Morita, Sumiyo; Nakabayashi, Kazuhiko; Kawai, Tomoko; Hayashi, Keiko; Horii, Takuro; Kimura, Mika; Kamei, Yasutomi; Ogawa, Yoshihiro; Hata, Kenichiro; Hatada, Izuho

    2016-02-12

    Previously, we found that C57BL/6J (B6) mice are more prone to develop obesity than PWK mice. In addition, we analyzed reciprocal crosses between these mice and found that (PWK × B6) F1 mice, which have B6 fathers, are more likely to develop dietary obesity than (B6 × PWK) F1 mice, which have B6 mothers. These results suggested that diet-induced obesity is paternally transmitted. In this study, we performed transcriptome analysis of adipose tissues of B6, PWK, (PWK × B6) F1, and (B6 × PWK) F1 mice using next-generation sequencing. We found that paternal transmission of diet-induced obesity was correlated with genes involved in adipose tissue inflammation, metal ion transport, and cilia. Furthermore, we analyzed the imprinted genes expressed in white adipose tissue (WAT) and obesity. Expression of paternally expressed imprinted genes (PEGs) was negatively correlated with body weight, whereas expression of maternally expressed imprinted genes (MEGs) was positively correlated. In the obesity-prone B6 mice, expression of PEGs was down-regulated by a high-fat diet, suggesting that abnormally low expression of PEGs contributes to high-fat diet-induced obesity in B6 mice. In addition, using single-nucleotide polymorphisms that differ between B6 and PWK, we identified candidate imprinted genes in WAT.

  3. Functional Sphere Profiling Reveals the Complexity of Neuroblastoma Tumor-Initiating Cell Model

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    Aurélie Coulon

    2011-10-01

    Full Text Available Neuroblastoma (NB is a neural crest-derived childhood tumor characterized by a remarkable phenotypic diversity, ranging from spontaneous regression to fatal metastatic disease. Although the cancer stem cell (CSC model provides a trail to characterize the cells responsible for tumor onset, the NB tumor-initiating cell (TIC has not been identified. In this study, the relevance of the CSC model in NB was investigated by taking advantage of typical functional stem cell characteristics. A predictive association was established between self-renewal, as assessed by serial sphere formation, and clinical aggressiveness in primary tumors. Moreover, cell subsets gradually selected during serial sphere culture harbored increased in vivo tumorigenicity, only highlighted in an orthotopic microenvironment. A microarray time course analysis of serial spheres passages from metastatic cells allowed us to specifically “profile” the NB stem cell-like phenotype and to identify CD133, ABC transporter, and WNT and NOTCH genes as spheres markers. On the basis of combined sphere markers expression, at least two distinct tumorigenic cell subpopulations were identified, also shown to preexist in primary NB. However, sphere markers-mediated cell sorting of parental tumor failed to recapitulate the TIC phenotype in the orthotopic model, highlighting the complexity of the CSC model. Our data support the NB stem-like cells as a dynamic and heterogeneous cell population strongly dependent on microenvironmental signals and add novel candidate genes as potential therapeutic targets in the control of high-risk NB.

  4. Expression profiling of colorectal cancer cells reveals inhibition of DNA replication licensing by extracellular calcium.

    Science.gov (United States)

    Aggarwal, Abhishek; Schulz, Herbert; Manhardt, Teresa; Bilban, Martin; Thakker, Rajesh V; Kallay, Enikö

    2017-06-01

    Colorectal cancer is one of the most common cancers in industrialised societies. Epidemiological studies, animal experiments, and randomized clinical trials have shown that dietary factors can influence all stages of colorectal carcinogenesis, from initiation through promotion to progression. Calcium is one of the factors with a chemoprophylactic effect in colorectal cancer. The aim of this study was to understand the molecular mechanisms of the anti-tumorigenic effects of extracellular calcium ([Ca(2+)]o) in colon cancer cells. Gene expression microarray analysis of colon cancer cells treated for 1, 4, and 24h with 2mM [Ca(2+)]o identified significant changes in expression of 1571 probe sets (ANOVA, pcalcium-sensing receptor (CaSR), a G protein-coupled receptor is a mediator involved in this process. To test whether these results were physiologically relevant, we fed mice with a standard diet containing low (0.04%), intermediate (0.1%), or high (0.9%) levels of dietary calcium. The main molecules regulating replication licensing were inhibited also in vivo, in the colon of mice fed high calcium diet. We show that among the mechanisms behind the chemopreventive effect of [Ca(2+)]o is inhibition of replication licensing, a process often deregulated in neoplastic transformation. Our data suggest that dietary calcium is effective in preventing replicative stress, one of the main drivers of cancer and this process is mediated by the calcium-sensing receptor. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  5. Metabolic Profiling in Chinese Cabbage (Brassica rapa L. subsp. pekinensis) Cultivars Reveals that Glucosinolate Content Is Correlated with Carotenoid Content.

    Science.gov (United States)

    Baek, Seung-A; Jung, Young-Ho; Lim, Sun-Hyung; Park, Sang Un; Kim, Jae Kwang

    2016-06-01

    A total of 38 bioactive compounds, including glucosinolates, carotenoids, tocopherols, sterols, and policosanols, were characterized from nine varieties of Chinese cabbage (Brassica rapa L. subsp. pekinensis) to determine their phytochemical diversity and analyze their abundance relationships. The metabolite profiles were evaluated with principal component analysis (PCA), Pearson correlation analysis, and hierarchical clustering analysis (HCA). PCA and HCA identified two distinct varieties of Chinese cabbage (Cheonsangcheonha and Waldongcheonha) with higher levels of glucosinolates and carotenoids. Pairwise comparisons of the 38 metabolites were calculated using Pearson correlation coefficients. The HCA, which used the correlation coefficients, clustered metabolites that are derived from closely related biochemical pathways. Significant correlations were discovered between chlorophyll and carotenoids. Additionally, aliphatic glucosinolate and carotenoid levels were positively correlated. The Cheonsangcheonha and Waldongcheonha varieties appear to be good candidates for breeding because they have high glucosinolate and carotenoid levels.

  6. Comprehensive and quantitative proteomic analyses of zebrafish plasma reveals conserved protein profiles between genders and between zebrafish and human

    Science.gov (United States)

    Li, Caixia; Tan, Xing Fei; Lim, Teck Kwang; Lin, Qingsong; Gong, Zhiyuan

    2016-01-01

    Omic approaches have been increasingly used in the zebrafish model for holistic understanding of molecular events and mechanisms of tissue functions. However, plasma is rarely used for omic profiling because of the technical challenges in collecting sufficient blood. In this study, we employed two mass spectrometric (MS) approaches for a comprehensive characterization of zebrafish plasma proteome, i.e. conventional shotgun liquid chromatography-tandem mass spectrometry (LC-MS/MS) for an overview study and quantitative SWATH (Sequential Window Acquisition of all THeoretical fragment-ion spectra) for comparison between genders. 959 proteins were identified in the shotgun profiling with estimated concentrations spanning almost five orders of magnitudes. Other than the presence of a few highly abundant female egg yolk precursor proteins (vitellogenins), the proteomic profiles of male and female plasmas were very similar in both number and abundance and there were basically no other highly gender-biased proteins. The types of plasma proteins based on IPA (Ingenuity Pathway Analysis) classification and tissue sources of production were also very similar. Furthermore, the zebrafish plasma proteome shares significant similarities with human plasma proteome, in particular in top abundant proteins including apolipoproteins and complements. Thus, the current study provided a valuable dataset for future evaluation of plasma proteins in zebrafish. PMID:27071722

  7. Suppression subtractive hybridization reveals transcript profiling of Chlorella under heterotrophy to photoautotrophy transition.

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    Jianhua Fan

    Full Text Available BACKGROUND: Microalgae have been extensively investigated and exploited because of their competitive nutritive bioproducts and biofuel production ability. Chlorella are green algae that can grow well heterotrophically and photoautotrophically. Previous studies proved that shifting from heterotrophy to photoautotrophy in light-induced environments causes photooxidative damage as well as distinct physiologic features that lead to dynamic changes in Chlorella intracellular components, which have great potential in algal health food and biofuel production. However, the molecular mechanisms underlying the trophic transition remain unclear. METHODOLOGY/PRINCIPAL FINDINGS: In this study, suppression subtractive hybridization strategy was employed to screen and characterize genes that are differentially expressed in response to the light-induced shift from heterotrophy to photoautotrophy. Expressed sequence tags (ESTs were obtained from 770 and 803 randomly selected clones among the forward and reverse libraries, respectively. Sequence analysis identified 544 unique genes in the two libraries. The functional annotation of the assembled unigenes demonstrated that 164 (63.1% from the forward library and 62 (21.8% from the reverse showed significant similarities with the sequences in the NCBI non-redundant database. The time-course expression patterns of 38 selected differentially expressed genes further confirmed their responsiveness to a diverse trophic status. The majority of the genes enriched in the subtracted libraries were associated with energy metabolism, amino acid metabolism, protein synthesis, carbohydrate metabolism, and stress defense. CONCLUSIONS/SIGNIFICANCE: The data presented here offer the first insights into the molecular foundation underlying the diverse microalgal trophic niche. In addition, the results can be used as a reference for unraveling candidate genes associated with the transition of Chlorella from heterotrophy to

  8. Metatranscriptomic Profiling Reveals Linkages between the Active Rumen Microbiome and Feed Efficiency in Beef Cattle.

    Science.gov (United States)

    Li, Fuyong; Guan, Le Luo

    2017-05-01

    Exploring compositional and functional characteristics of the rumen microbiome can improve the understanding of its role in rumen function and cattle feed efficiency. In this study, we applied metatranscriptomics to characterize the active rumen microbiomes of beef cattle with different feed efficiencies (efficient, n = 10; inefficient, n = 10) using total RNA sequencing. Active bacterial and archaeal compositions were estimated based on 16S rRNAs, and active microbial metabolic functions including carbohydrate-active enzymes (CAZymes) were assessed based on mRNAs from the same metatranscriptomic data sets. In total, six bacterial phyla (Proteobacteria, Firmicutes, Bacteroidetes, Spirochaetes, Cyanobacteria, and Synergistetes), eight bacterial families (Succinivibrionaceae, Prevotellaceae, Ruminococcaceae, Lachnospiraceae, Veillonellaceae, Spirochaetaceae, Dethiosulfovibrionaceae, and Mogibacteriaceae), four archaeal clades (Methanomassiliicoccales, Methanobrevibacter ruminantium, Methanobrevibacter gottschalkii, and Methanosphaera), 112 metabolic pathways, and 126 CAZymes were identified as core components of the active rumen microbiome. As determined by comparative analysis, three bacterial families (Lachnospiraceae, Lactobacillaceae, and Veillonellaceae) tended to be more abundant in low-feed-efficiency (inefficient) animals (P feed-efficiency (efficient) cattle (P 2 with a P value of efficient animals. These findings suggest that the rumen microbiomes of inefficient cattle have more diverse activities than those of efficient cattle, which may be related to the host feed efficiency variation.IMPORTANCE This study applied total RNA-based metatranscriptomics and showed the linkage between the active rumen microbiome and feed efficiency (residual feed intake) in beef cattle. The data generated from the current study provide fundamental information on active rumen microbiome at both compositional and functional levels, which serve as a foundation to study rumen

  9. In vivo transcriptional profiling of Yersinia pestis reveals a novel bacterial mediator of pulmonary inflammation.

    Science.gov (United States)

    Pechous, Roger D; Broberg, Christopher A; Stasulli, Nikolas M; Miller, Virginia L; Goldman, William E

    2015-02-17

    Inhalation of Yersinia pestis results in primary pneumonic plague, a highly lethal and rapidly progressing necrotizing pneumonia. The disease begins with a period of extensive bacterial replication in the absence of disease symptoms, followed by the sudden onset of inflammatory responses that ultimately prove fatal. Very little is known about the bacterial and host factors that contribute to the rapid biphasic progression of pneumonic plague. In this work, we analyzed the in vivo transcription kinetics of 288 bacterial open reading frames previously shown by microarray analysis to be dynamically regulated in the lung. Using this approach combined with bacterial genetics, we were able to identify five Y. pestis genes that contribute to the development of pneumonic plague. Deletion of one of these genes, ybtX, did not alter bacterial survival but attenuated host inflammatory responses during late-stage disease. Deletion of ybtX in another lethal respiratory pathogen, Klebsiella pneumoniae, also resulted in diminished host inflammation during infection. Thus, our in vivo transcriptional screen has identified an important inflammatory mediator that is common to two Gram-negative bacterial pathogens that cause severe pneumonia. Yersinia pestis is responsible for at least three major pandemics, most notably the Black Death of the Middle Ages. Due to its pandemic potential, ease of dissemination by aerosolization, and a history of its weaponization, Y. pestis is categorized by the Centers for Disease Control and Prevention as a tier 1 select agent most likely to be used as a biological weapon. To date, there is no licensed vaccine against Y. pestis. Importantly, an early "silent" phase followed by the rapid onset of nondescript influenza-like symptoms makes timely treatment of pneumonic plague difficult. A more detailed understanding of the bacterial and host factors that contribute to pathogenesis is essential to understanding the progression of pneumonic plague and

  10. Suppression Subtractive Hybridization Reveals Transcript Profiling of Chlorella under Heterotrophy to Photoautotrophy Transition

    Science.gov (United States)

    Huang, Jianke; Wang, Weiliang; Yin, Weibo; Hu, Zanmin; Li, Yuanguang

    2012-01-01

    Background Microalgae have been extensively investigated and exploited because of their competitive nutritive bioproducts and biofuel production ability. Chlorella are green algae that can grow well heterotrophically and photoautotrophically. Previous studies proved that shifting from heterotrophy to photoautotrophy in light-induced environments causes photooxidative damage as well as distinct physiologic features that lead to dynamic changes in Chlorella intracellular components, which have great potential in algal health food and biofuel production. However, the molecular mechanisms underlying the trophic transition remain unclear. Methodology/Principal Findings In this study, suppression subtractive hybridization strategy was employed to screen and characterize genes that are differentially expressed in response to the light-induced shift from heterotrophy to photoautotrophy. Expressed sequence tags (ESTs) were obtained from 770 and 803 randomly selected clones among the forward and reverse libraries, respectively. Sequence analysis identified 544 unique genes in the two libraries. The functional annotation of the assembled unigenes demonstrated that 164 (63.1%) from the forward library and 62 (21.8%) from the reverse showed significant similarities with the sequences in the NCBI non-redundant database. The time-course expression patterns of 38 selected differentially expressed genes further confirmed their responsiveness to a diverse trophic status. The majority of the genes enriched in the subtracted libraries were associated with energy metabolism, amino acid metabolism, protein synthesis, carbohydrate metabolism, and stress defense. Conclusions/Significance The data presented here offer the first insights into the molecular foundation underlying the diverse microalgal trophic niche. In addition, the results can be used as a reference for unraveling candidate genes associated with the transition of Chlorella from heterotrophy to photoautotrophy, which holds

  11. Proteome profiling reveals insights into cold-tolerant growth in sea buckthorn.

    Science.gov (United States)

    He, Caiyun; Gao, Guori; Zhang, Jianguo; Duan, Aiguo; Luo, Hongmei

    2016-01-01

    Low temperature is one of the crucial environmental factors limiting the productivity and distribution of plants. Sea buckthorn ( Hippophae rhamnoides L.), a well recognized multipurpose plant species, live successfully in in cold desert regions. But their molecular mechanisms underlying cold tolerance are not well understood. Physiological and biochemical responses to low-temperature stress were studied in seedlings of sea buckthorn. Differentially expressed protein spots were analyzed using multiplexing fluorescent two-dimensional fluorescence difference gel electrophoresis (2D-DIGE) coupled with matrix-assisted laser desorption/ionization (MALDI) time-of-flight/time-of-flight (TOF/TOF) mass spectrometry (MS), the concentration of phytohormone was measured using enzyme-linked immunosorbent assay, and a spectrophotometric assay was used to measure enzymatic reactions. With the increase of cold stress intensity, the photosynthesis rate, transpiration rate, stomatal conductance in leaves and contents of abscisic acid (ABA) and indole acetic acid (IAA) in roots decreased significantly; however, water-use efficiency, ABA and zeatin riboside in leaves increased significantly, while cell membrane permeability, malondialdehyde and IAA in leaves increased at 7 d and then decreased at 14 d. DIGE and MS/MS analysis identified 32 of 39 differentially expressed protein spots under low-temperature stress, and their functions were mainly involved in metabolism, photosynthesis, signal transduction, antioxidative systems and post-translational modification. The changed protein abundance and corresponding physiological-biochemical response shed light on the molecular mechanisms related to cold tolerance in cold-tolerant plants and provide key candidate proteins for genetic improvement of plants.

  12. 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

  13. Lipidomic Profiling of Saccharomyces cerevisiae and Zygosaccharomyces bailii Reveals Critical Changes in Lipid Composition in Response to Acetic Acid Stress

    Science.gov (United States)

    Riezman, Howard; Olsson, Lisbeth; Bettiga, Maurizio

    2013-01-01

    When using microorganisms as cell factories in the production of bio-based fuels or chemicals from lignocellulosic hydrolysate, inhibitory concentrations of acetic acid, released from the biomass, reduce the production rate. The undissociated form of acetic acid enters the cell by passive diffusion across the lipid bilayer, mediating toxic effects inside the cell. In order to elucidate a possible link between lipid composition and acetic acid stress, the present study presents detailed lipidomic profiling of the major lipid species found in the plasma membrane, including glycerophospholipids, sphingolipids and sterols, in Saccharomyces cerevisiae (CEN.PK 113_7D) and Zygosaccharomyces bailii (CBS7555) cultured with acetic acid. Detailed physiological characterization of the response of the two yeasts to acetic acid has also been performed in aerobic batch cultivations using bioreactors. Physiological characterization revealed, as expected, that Z. bailii is more tolerant to acetic acid than S. cerevisiae. Z. bailii grew at acetic acid concentrations above 24 g L−1, while limited growth of S. cerevisiae was observed after 11 h when cultured with only 12 g L−1 acetic acid. Detailed lipidomic profiling using electrospray ionization, multiple-reaction-monitoring mass spectrometry (ESI-MRM-MS) showed remarkable changes in the glycerophospholipid composition of Z. bailii, including an increase in saturated glycerophospholipids and considerable increases in complex sphingolipids in both S. cerevisiae (IPC 6.2×, MIPC 9.1×, M(IP)2C 2.2×) and Z. bailii (IPC 4.9×, MIPC 2.7×, M(IP)2C 2.7×), when cultured with acetic acid. In addition, the basal level of complex sphingolipids was significantly higher in Z. bailii than in S. cerevisiae, further emphasizing the proposed link between lipid saturation, high sphingolipid levels and acetic acid tolerance. The results also suggest that acetic acid tolerance is associated with the ability of a given strain to generate large

  14. 1H NMR-based profiling reveals differential immune-metabolic networks during influenza virus infection in obese mice.

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    J Justin Milner

    Full Text Available Obese individuals are at greater risk for death from influenza virus infection. Paralleling human evidence, obese mice are also more susceptible to influenza infection mortality. However, the underlying mechanisms driving greater influenza severity in the obese remain unclear. Metabolic profiling has been utilized in infectious disease models to enhance prognostic or diagnostic methods, and to gain insight into disease pathogenesis by providing a more global picture of dynamic infection responses. Herein, metabolic profiling was used to develop a deeper understanding of the complex processes contributing to impaired influenza protection in obese mice and to facilitate generation of new explanatory hypotheses. Diet-induced obese and lean mice were infected with influenza A/Puerto Rico/8/34. 1H nuclear magnetic resonance-based metabolic profiling of urine, feces, lung, liver, mesenteric white adipose tissue, bronchoalveolar lavage fluid and serum revealed distinct metabolic signatures in infected obese mice, including perturbations in nucleotide, vitamin, ketone body, amino acid, carbohydrate, choline and lipid metabolic pathways. Further, metabolic data was integrated with immune analyses to obtain a more comprehensive understanding of potential immune-metabolic interactions. Of interest, uncovered metabolic signatures in urine and feces allowed for discrimination of infection status in both lean and obese mice at an early influenza time point, which holds prognostic and diagnostic implications for this methodology. These results confirm that obesity causes distinct metabolic perturbations during influenza infection and provide a basis for generation of new hypotheses and use of this methodology in detection of putative biomarkers and metabolic patterns to predict influenza infection outcome.

  15. Lipidomic profiling of Saccharomyces cerevisiae and Zygosaccharomyces bailii reveals critical changes in lipid composition in response to acetic acid stress.

    Directory of Open Access Journals (Sweden)

    Lina Lindberg

    Full Text Available When using microorganisms as cell factories in the production of bio-based fuels or chemicals from lignocellulosic hydrolysate, inhibitory concentrations of acetic acid, released from the biomass, reduce the production rate. The undissociated form of acetic acid enters the cell by passive diffusion across the lipid bilayer, mediating toxic effects inside the cell. In order to elucidate a possible link between lipid composition and acetic acid stress, the present study presents detailed lipidomic profiling of the major lipid species found in the plasma membrane, including glycerophospholipids, sphingolipids and sterols, in Saccharomyces cerevisiae (CEN.PK 113_7D and Zygosaccharomyces bailii (CBS7555 cultured with acetic acid. Detailed physiological characterization of the response of the two yeasts to acetic acid has also been performed in aerobic batch cultivations using bioreactors. Physiological characterization revealed, as expected, that Z. bailii is more tolerant to acetic acid than S. cerevisiae. Z. bailii grew at acetic acid concentrations above 24 g L(-1, while limited growth of S. cerevisiae was observed after 11 h when cultured with only 12 g L(-1 acetic acid. Detailed lipidomic profiling using electrospray ionization, multiple-reaction-monitoring mass spectrometry (ESI-MRM-MS showed remarkable changes in the glycerophospholipid composition of Z. bailii, including an increase in saturated glycerophospholipids and considerable increases in complex sphingolipids in both S. cerevisiae (IPC 6.2×, MIPC 9.1×, M(IP2C 2.2× and Z. bailii (IPC 4.9×, MIPC 2.7×, M(IP2C 2.7×, when cultured with acetic acid. In addition, the basal level of complex sphingolipids was significantly higher in Z. bailii than in S. cerevisiae, further emphasizing the proposed link between lipid saturation, high sphingolipid levels and acetic acid tolerance. The results also suggest that acetic acid tolerance is associated with the ability of a given strain to

  16. Metabolomic profiling of beer reveals effect of temperature on non-volatile small molecules during short-term storage.

    Science.gov (United States)

    Heuberger, Adam L; Broeckling, Corey D; Lewis, Matthew R; Salazar, Lauren; Bouckaert, Peter; Prenni, Jessica E

    2012-12-01

    The effect of temperature on non-volatile compounds in beer has not been well characterised during storage. Here, a metabolomics approach was applied to characterise the effect of storage temperature on non-volatile metabolite variation after 16weeks of storage, using fresh beer as a control. The metabolite profile of room temperature stored (RT) and cold temperature stored (CT) beer differed significantly from fresh, with the most substantial variation observed between RT and fresh beer. Metabolites that changed during storage included prenylated flavonoids, purines, and peptides, and all showed reduced quantitative variation under the CT storage conditions. Corresponding sensory panel observations indicated significant beer oxidation after 12 and 16weeks of storage, with higher values reported for RT samples. These data support that temperature affected beer oxidation during short-term storage, and reveal 5-methylthioadenosine (5-MTA) as a candidate non-volatile metabolite marker for beer oxidation and staling. Copyright © 2012 Elsevier Ltd. All rights reserved.

  17. Expression profiling reveals an unexpected growth-stimulating effect of surplus iron on the yeast Saccharomyces cerevisiae.

    Science.gov (United States)

    Du, Yang; Cheng, Wang; Li, Wei-Fang

    2012-08-01

    Iron homeostasis plays a crucial role in growth and division of cells in all kingdoms of life. Although yeast iron metabolism has been extensively studied, little is known about the molecular mechanism of response to surplus iron. In this study, expression profiling of Saccharomyces cerevisiae in the presence of surplus iron revealed a dual effect at 1 and 4 h. A cluster of stress-responsive genes was upregulated via activation of the stress-resistance transcription factor Msn4, which indicated the stress effect of surplus iron on yeast metabolism. Genes involved in aerobic metabolism and several anabolic pathways are also upregulated in iron-surplus conditions, which could significantly accelerate yeast growth. This dual effect suggested that surplus iron might participate in a more complex metabolic network, in addition to serving as a stress inducer. These findings contribute to our understanding of the global response of yeast to the fluctuating availability of iron in the environment.

  18. mRNA profiling reveals determinants of trastuzumab efficiency in HER2-positive breast cancer.

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    Silvia von der Heyde

    Full Text Available Intrinsic and acquired resistance to the monoclonal antibody drug trastuzumab is a major problem in the treatment of HER2-positive breast cancer. A deeper understanding of the underlying mechanisms could help to develop new agents. Our intention was to detect genes and single nucleotide polymorphisms (SNPs affecting trastuzumab efficiency in cell culture. Three HER2-positive breast cancer cell lines with different resistance phenotypes were analyzed. We chose BT474 as model of trastuzumab sensitivity, HCC1954 as model of intrinsic resistance, and BTR50, derived from BT474, as model of acquired resistance. Based on RNA-Seq data, we performed differential expression analyses on these cell lines with and without trastuzumab treatment. Differentially expressed genes between the resistant cell lines and BT474 are expected to contribute to resistance. Differentially expressed genes between untreated and trastuzumab treated BT474 are expected to contribute to drug efficacy. To exclude false positives from the candidate gene set, we removed genes that were also differentially expressed between untreated and trastuzumab treated BTR50. We further searched for SNPs in the untreated cell lines which could contribute to trastuzumab resistance. The analysis resulted in 54 differentially expressed candidate genes that might be connected to trastuzumab efficiency. 90% of 40 selected candidates were validated by RT-qPCR. ALPP, CALCOCO1, CAV1, CYP1A2 and IGFBP3 were significantly higher expressed in the trastuzumab treated than in the untreated BT474 cell line. GDF15, IL8, LCN2, PTGS2 and 20 other genes were significantly higher expressed in HCC1954 than in BT474, while NCAM2, COLEC12, AFF3, TFF3, NRCAM, GREB1 and TFF1 were significantly lower expressed. Additionally, we inferred SNPs in HCC1954 for CAV1, PTGS2, IL8 and IGFBP3. The latter also had a variation in BTR50. 20% of the validated subset have already been mentioned in literature. For half of them we

  19. mRNA Profiling Reveals Determinants of Trastuzumab Efficiency in HER2-Positive Breast Cancer

    Science.gov (United States)

    von der Heyde, Silvia; Wagner, Steve; Czerny, Alexander; Nietert, Manuel; Ludewig, Fabian; Salinas-Riester, Gabriela; Arlt, Dorit; Beißbarth, Tim

    2015-01-01

    Intrinsic and acquired resistance to the monoclonal antibody drug trastuzumab is a major problem in the treatment of HER2-positive breast cancer. A deeper understanding of the underlying mechanisms could help to develop new agents. Our intention was to detect genes and single nucleotide polymorphisms (SNPs) affecting trastuzumab efficiency in cell culture. Three HER2-positive breast cancer cell lines with different resistance phenotypes were analyzed. We chose BT474 as model of trastuzumab sensitivity, HCC1954 as model of intrinsic resistance, and BTR50, derived from BT474, as model of acquired resistance. Based on RNA-Seq data, we performed differential expression analyses on these cell lines with and without trastuzumab treatment. Differentially expressed genes between the resistant cell lines and BT474 are expected to contribute to resistance. Differentially expressed genes between untreated and trastuzumab treated BT474 are expected to contribute to drug efficacy. To exclude false positives from the candidate gene set, we removed genes that were also differentially expressed between untreated and trastuzumab treated BTR50. We further searched for SNPs in the untreated cell lines which could contribute to trastuzumab resistance. The analysis resulted in 54 differentially expressed candidate genes that might be connected to trastuzumab efficiency. 90% of 40 selected candidates were validated by RT-qPCR. ALPP, CALCOCO1, CAV1, CYP1A2 and IGFBP3 were significantly higher expressed in the trastuzumab treated than in the untreated BT474 cell line. GDF15, IL8, LCN2, PTGS2 and 20 other genes were significantly higher expressed in HCC1954 than in BT474, while NCAM2, COLEC12, AFF3, TFF3, NRCAM, GREB1 and TFF1 were significantly lower expressed. Additionally, we inferred SNPs in HCC1954 for CAV1, PTGS2, IL8 and IGFBP3. The latter also had a variation in BTR50. 20% of the validated subset have already been mentioned in literature. For half of them we called and analyzed

  20. Gait profile score and movement analysis profile in patients with Parkinson's disease during concurrent cognitive load

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    Danielli S. Speciali

    2014-08-01

    Full Text Available Background: Gait disorders are common in individuals with Parkinson's Disease (PD and the concurrent performance of motor and cognitive tasks can have marked effects on gait. The Gait Profile Score (GPS and the Movement Analysis Profile (MAP were developed in order to summarize the data of kinematics and facilitate understanding of the results of gait analysis. Objective: To investigate the effectiveness of the GPS and MAP in the quantification of changes in gait during a concurrent cognitive load while walking in adults with and without PD. Method: Fourteen patients with idiopathic PD and nine healthy subjects participated in the study. All subjects performed single and dual walking tasks. The GPS/MAP was computed from three-dimensional gait analysis data. Results: Differences were found between tasks for GPS (P<0.05 and Gait Variable Score (GVS (pelvic rotation, knee flexion-extension and ankle dorsiflexion-plantarflexion (P<0.05 in the PD group. An interaction between task and group was observed for GPS (P<0.01 for the right side (Cohen's ¯d=0.99, left side (Cohen's ¯d=0.91, and overall (Cohen's ¯d=0.88. No interaction was observed only for hip internal-external rotation and foot internal-external progression GVS variables in the PD group. Conclusions: The results showed gait impairment during the dual task and suggest that GPS/MAP may be used to evaluate the effects of concurrent cognitive load while walking in patients with PD.

  1. Power analysis attacks revealing the secrets of smart cards

    CERN Document Server

    Mangard, Stefan; Popp, Thomas

    2008-01-01

    A comprehensive treatment of power analysis attacks and countermeasures. Based on the principle that the only way to defend against power analysis attacks is to understand them, this book explains how power analysis attacks work. It discusses simple and differential power analysis as well as advanced techniques like template attacks.

  2. PROFILE ANALYSIS OF THE EMPLOYEES OF COMMERCIAL BANKS IN ROMANIA

    Directory of Open Access Journals (Sweden)

    Tudor NISTORESCU

    2012-01-01

    Full Text Available In this paper we tried to deliver a profile analysis of the employees from the commercial banks. The banking sector is especially important because it has to finance the entire economy, and therefore it needs competent and well-motivated people. As methodology we realized a survey on a representative number of employees of commercial banks. We used questionnaires measuring motivational factors, the orientation to tasks vs. people questionnaire, the potential leadership questionnaire, the Belbin self-knowledge questionnaire. The results showed that the employee from the Romanian commercial banks has a strong work-ethic and is highly motivated.

  3. Integrated Analysis of Alzheimer's Disease and Schizophrenia Dataset Revealed Different Expression Pattern in Learning and Memory.

    Science.gov (United States)

    Li, Wen-Xing; Dai, Shao-Xing; Liu, Jia-Qian; Wang, Qian; Li, Gong-Hua; Huang, Jing-Fei

    2016-01-01

    Alzheimer's disease (AD) and schizophrenia (SZ) are both accompanied by impaired learning and memory functions. This study aims to explore the expression profiles of learning or memory genes between AD and SZ. We downloaded 10 AD and 10 SZ datasets from GEO-NCBI for integrated analysis. These datasets were processed using RMA algorithm and a global renormalization for all studies. Then Empirical Bayes algorithm was used to find the differentially expressed genes between patients and controls. The results showed that most of the differentially expressed genes were related to AD whereas the gene expression profile was little affected in the SZ. Furthermore, in the aspects of the number of differentially expressed genes, the fold change and the brain region, there was a great difference in the expression of learning or memory related genes between AD and SZ. In AD, the CALB1, GABRA5, and TAC1 were significantly downregulated in whole brain, frontal lobe, temporal lobe, and hippocampus. However, in SZ, only two genes CRHBP and CX3CR1 were downregulated in hippocampus, and other brain regions were not affected. The effect of these genes on learning or memory impairment has been widely studied. It was suggested that these genes may play a crucial role in AD or SZ pathogenesis. The different gene expression patterns between AD and SZ on learning and memory functions in different brain regions revealed in our study may help to understand the different mechanism between two diseases.

  4. 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

  5. Principal component analysis of proteolytic profiles as markers of authenticity of PDO cheeses.

    Science.gov (United States)

    Guerreiro, Joana Santos; Barros, Mário; Fernandes, Paulo; Pires, Preciosa; Bardsley, Ronald

    2013-02-15

    The casein fraction of 13 Portuguese PDO cheeses were analysed using Urea-PAGE and reverse phase-high performance liquid chromatography (RP-HPLC) and then subjected to chemometric evaluation. The chemometric techniques of cluster analysis (CA) and principal component analysis (PCA) were used for the classification studies. Peptide mapping using Urea-PAGE followed by CA revealed two major clusters according to the similarity of the proteolytic profile of the cheeses. PCA results were in accordance with the grouping performed using CA. CA of RP-HPLC results of the matured cheeses revealed the presence of one major cluster comprising samples manufactured with only ovine milk or milk admixtures. When the results of CA technique were compared with the two PCA approaches performed, it was found that the grouping of the samples was similar. Both approaches, revealed the potential of proteolytic profiles (which is an essential aspect of cheese maturation) as markers of authenticity of PDO cheeses in terms of ripening time and milk admixtures not mentioned on the label. Copyright © 2012 Elsevier Ltd. All rights reserved.

  6. Key Elements of Cratonic and Pericratonic Lithospheric Structure Revealed by Deep Seismic Reflection Profiling in North America

    Science.gov (United States)

    Brown, L. D.

    2008-05-01

    Deep seismic reflection profiling collected both by national programs (COCORP in the US; LITHOPROBE in Canada) and regional programs (e.g. GLIMPCE, CDROM,) have traversed most of the major tectonic elements of the North American craton and its Precambrian periphery. Once argued to be relatively bland in terms of reflection character, the craton has turned out to exhibit a rich diversity of fabrics and features of fundamental tectonic significance. Among the more distinctive characteristics are: 1) crustal penetrating zones of pronounced reflectivity that suggest distributed shear fabrics, a likely fingerprint of past crustal flow. The type example is the Grenville Front at the eastern edge of the Superior Province; 2) A sharp contrast in reflectivity across the Moho, exemplified by seismic reflection profiles in the Abitibi-Grenville, Superior and Slave Provinces; 3) Distinct, dipping reflections that penetrate into the mantle from the lower crust, usually interpret as fossil subduction zones; 4) Prominent reflections that delineate thin, extensive sills in the upper to mid crust; 5) Thick layered sequences that mark extensive buried volcano-sedimentary units in the peripheral platforms of the central U.S.; and 6) Apparent continuity of crustal fabrics across the Moho that argue for preservation of Precambrian tectonic structures in the upper mantle, even in Phanerozoic remobilized terranes, and/or evolution of the Moho as a phase change rather than a lithologic contrast in some areas. For the most part, the structural assemblages revealed by deep seismic reflection profiling in the North American craton support a plate tectonic regime in the Archean. Perhaps the most iconic of the deep reflection transects of cratonic North America is the SNORCLE transect of the LITHOPROBE program, which demonstrates not only the intrinsic heterogeneity of the crust and crust-mantle boundary, but a complex assemblage of mantle discontinuities that preserve tectonic fabrics well

  7. Phosphoproteomic Profiling Reveals Epstein-Barr Virus Protein Kinase Integration of DNA Damage Response and Mitotic Signaling.

    Directory of Open Access Journals (Sweden)

    Renfeng Li

    2015-12-01

    Full Text Available Epstein-Barr virus (EBV is etiologically linked to infectious mononucleosis and several human cancers. EBV encodes a conserved protein kinase BGLF4 that plays a key role in the viral life cycle. To provide new insight into the host proteins regulated by BGLF4, we utilized stable isotope labeling by amino acids in cell culture (SILAC-based quantitative proteomics to compare site-specific phosphorylation in BGLF4-expressing Akata B cells. Our analysis revealed BGLF4-mediated hyperphosphorylation of 3,046 unique sites corresponding to 1,328 proteins. Frequency analysis of these phosphosites revealed a proline-rich motif signature downstream of BGLF4, indicating a broader substrate recognition for BGLF4 than its cellular ortholog cyclin-dependent kinase 1 (CDK1. Further, motif analysis of the hyperphosphorylated sites revealed enrichment in ATM, ATR and Aurora kinase substrates while functional analyses revealed significant enrichment of pathways related to the DNA damage response (DDR, mitosis and cell cycle. Phosphorylation of proteins associated with the mitotic spindle assembly checkpoint (SAC indicated checkpoint activation, an event that inactivates the anaphase promoting complex/cyclosome, APC/C. Furthermore, we demonstrated that BGLF4 binds to and directly phosphorylates the key cellular proteins PP1, MPS1 and CDC20 that lie upstream of SAC activation and APC/C inhibition. Consistent with APC/C inactivation, we found that BGLF4 stabilizes the expression of many known APC/C substrates. We also noted hyperphosphorylation of 22 proteins associated the nuclear pore complex, which may contribute to nuclear pore disassembly and SAC activation. A drug that inhibits mitotic checkpoint activation also suppressed the accumulation of extracellular EBV virus. Taken together, our data reveal that, in addition to the DDR, manipulation of mitotic kinase signaling and SAC activation are mechanisms associated with lytic EBV replication. All MS data have been

  8. Profiling of microRNA in human and mouse ES and iPS cells reveals overlapping but distinct microRNA expression patterns.

    Science.gov (United States)

    Razak, Siti Razila Abdul; Ueno, Kazuko; Takayama, Naoya; Nariai, Naoki; Nagasaki, Masao; Saito, Rika; Koso, Hideto; Lai, Chen-Yi; Murakami, Miyako; Tsuji, Koichiro; Michiue, Tatsuo; Nakauchi, Hiromitsu; Otsu, Makoto; Watanabe, Sumiko

    2013-01-01

    Using quantitative PCR-based miRNA arrays, we comprehensively analyzed the expression profiles of miRNAs in human and mouse embryonic stem (ES), induced pluripotent stem (iPS), and somatic cells. Immature pluripotent cells were purified using SSEA-1 or SSEA-4 and were used for miRNA profiling. Hierarchical clustering and consensus clustering by nonnegative matrix factorization showed two major clusters, human ES/iPS cells and other cell groups, as previously reported. Principal components analysis (PCA) to identify miRNAs that segregate in these two groups identified miR-187, 299-3p, 499-5p, 628-5p, and 888 as new miRNAs that specifically characterize human ES/iPS cells. Detailed direct comparisons of miRNA expression levels in human ES and iPS cells showed that several miRNAs included in the chromosome 19 miRNA cluster were more strongly expressed in iPS cells than in ES cells. Similar analysis was conducted with mouse ES/iPS cells and somatic cells, and several miRNAs that had not been reported to be expressed in mouse ES/iPS cells were suggested to be ES/iPS cell-specific miRNAs by PCA. Comparison of the average expression levels of miRNAs in ES/iPS cells in humans and mice showed quite similar expression patterns of human/mouse miRNAs. However, several mouse- or human-specific miRNAs are ranked as high expressers. Time course tracing of miRNA levels during embryoid body formation revealed drastic and different patterns of changes in their levels. In summary, our miRNA expression profiling encompassing human and mouse ES and iPS cells gave various perspectives in understanding the miRNA core regulatory networks regulating pluripotent cells characteristics.

  9. Metabolomic and proteomic profiles reveal the dynamics of primary metabolism during seed development of lotus (Nelumbo nucifera

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    Pingfang eYang

    2016-06-01

    Full Text Available Sacred lotus (Nelumbo nucifera belongs to Nelumbonaceae family. Its seeds are widely consumed in Asia countries as snacks or even medicine. Besides the market values, lotus seed also plays crucial roles in lotus life cycle. Consequently, it is essential to gain a comprehensive understanding of the development of lotus seed. During its development, lotus seed undergoes cell division, expansion, reserve accumulation, desiccation and maturation phases. We observed morphological and biochemical changes from 10 to 25 days after pollination (DAP which was corresponding to the reserve synthesis and accumulation phase. The volume of the seed expanded until 20 DAP with the color of the seed coat changing from yellow-green to dark green and gradually fading again. Starch and protein rapidly accumulated from 15 to 20 DAP. To further reveal the metabolism adaptation, primary metabolites and proteins profiles were obtained using mass spectrometry based platforms. Metabolites and enzymes involved in sugar metabolism, glycolysis, TCA cycle and amino acids metabolism showed sequential dynamics enabling the clear separation of the different metabolic states during lotus seed development. The integration of the data revealed a highly significant metabolic switch at 15 DAP going through a transition of metabolically highly active tissue to the preparation of storage tissue. The results provide reference data set for the evaluation of primary metabolism during lotus seed development.

  10. Genomic aberrations in an African American colorectal cancer cohort reveals a MSI-specific profile and chromosome X amplification in male patients.

    Directory of Open Access Journals (Sweden)

    Hassan Brim

    Full Text Available OBJECTIVE: DNA aberrations that cause colorectal cancer (CRC occur in multiple steps that involve microsatellite instability (MSI and chromosomal instability (CIN. Herein, we studied CRCs from AA patients for their CIN and MSI status. EXPERIMENTAL DESIGN: Array CGH was performed on 30 AA colon tumors. The MSI status was established. The CGH data from AA were compared to published lists of 41 TSG and oncogenes in Caucasians and 68 cancer genes, proposed via systematic sequencing for somatic mutations in colon and breast tumors. The patient-by-patient CGH profiles were organized into a maximum parsimony cladogram to give insights into the tumors' aberrations lineage. RESULTS: The CGH analysis revealed that CIN was independent of age, gender, stage or location. However, both the number and nature of aberrations seem to depend on the MSI status. MSI-H tumors clustered together in the cladogram. The chromosomes with the highest rates of CGH aberrations were 3, 5, 7, 8, 20 and X. Chromosome X was primarily amplified in male patients. A comparison with Caucasians revealed an overall similar aberration profile with few exceptions for the following genes; THRB, RAF1, LPL, DCC, XIST, PCNT, STS and genes on the 20q12-q13 cytoband. Among the 68 CAN genes, all showed some level of alteration in our cohort. CONCLUSION: Chromosome X amplification in male patients with CRC merits follow-up. The observed CIN may play a distinctive role in CRC in AAs. The clustering of MSI-H tumors in global CGH data analysis suggests that chromosomal aberrations are not random.

  11. Profiling School Shooters: Automatic Text-Based Analysis

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    Yair eNeuman

    2015-06-01

    Full Text Available School shooters present a challenge to both forensic psychiatry and law enforcement agencies. The relatively small number of school shooters, their various charateristics, and the lack of in-depth analysis of all of the shooters prior to the shooting add complexity to our understanding of this problem. In this short paper, we introduce a new methodology for automatically profiling school shooters. The methodology involves automatic analysis of texts and the production of several measures relevant for the identification of the shooters. Comparing texts written by six school shooters to 6056 texts written by a comparison group of male subjects, we found that the shooters' texts scored significantly higher on the Narcissistic Personality dimension as well as on the Humilated and Revengeful dimensions. Using a ranking/priorization procedure, similar to the one used for the automatic identification of sexual predators, we provide support for the validity and relevance of the proposed methodology.

  12. Next-generation transcriptome profiling reveals insights into genetic factors contributing to growth differences and temperature adaptation in Australian populations of barramundi (Lates calcarifer).

    Science.gov (United States)

    Newton, James R; Zenger, Kyall R; Jerry, Dean R

    2013-09-01

    Identification of genetically-regulated adaptation in fish is a precursor to understanding how populations will respond to future climate induced stressors like temperature. Australian populations of barramundi (Lates calcarifer) show strong evidence of local adaptation to temperature. However, the phenotypic consequences of this adaptation are unknown and the genetic mechanisms underlying this response are poorly understood. In the current study, two populations of barramundi from temperature extremes of the species Australian distribution were communally reared at cool (22°C), control (28°C) and hot (36°C) water temperatures for 3.5months. Southern populations of barramundi originating from a cooler environment grew significantly faster at 22°C than northern populations of warm adapted barramundi. However, no difference in population growth was present at either 28°C or 36°C. The underlying transcriptome profile of barramundi was examined via Illumina mRNA deep sequencing to determine the major contributing gene categories giving rise to phenotypic differences in barramundi population growth. Gene ontology (GO) analysis revealed enrichment in categories relating to the regulation of peptidase activity as well as microtubule, cytoplasmic and cellular metabolic based processes. Further analysis of the GO category "microtubule based process" with associated genes from the "response to stress" category revealed an apparent re-organization of cytoskeletal elements in response to an induced cold stress in northern barramundi reared at 22°C, when compared with northern barramundi reared at 36°C. Between southern barramundi and northern barramundi reared at 36°C, an analysis of the "endopeptidase inhibitor activity" GO category in conjunction with stress genes indicated a suppression of the complement system in southern barramundi along with an increase in the cellular stress response. The results of the present study show that southern populations of barramundi

  13. Profiling of illicit cocaine seized in China by ICP-MS analysis of inorganic elements.

    Science.gov (United States)

    Liu, Cuimei; Hua, Zhendong; Meng, Xin

    2017-07-01

    For the first time in China, the inorganic element profiling of cocaine specimens was performed at the National Narcotics Laboratory. An inductive coupled plasma-mass spectrometry (ICP-MS) method was developed and validated for simultaneous analysis of 26 inorganic elements, including sodium (Na), magnesium (Mg), aluminuim (Al), potassium (K), calcium (Ca), vanadium (V), chromium (Cr), manganese (Mn), iron (Fe), cobalt (Co), nickel (Ni), copper (Cu), zinc (Zn), arsenic (As), selenium (Se), molybdenum (Mo), silver (Ag), cadmium (Cd), antimony (Sb), barium (Ba), lanthanum (La), cerium (Ce), thallium (Tl), lead (Pb), thorium (Th), and uranium (U) in illicit cocaine samples. Ultrasonic assisted dissolution was applied for sample preparation. Minimum sample preparation and analysis time were required, which was suitable for routine analysis. After the analysis of 183 cocaine samples seized from 2011 to 2015, the element concentration ranges of cocaine sample were obtained. Based on the quantitative data set of 26 inorganic elements in 131 linked/un-linked cocaine samples, fifty combinations of pre-treatment methods and distance/correlation measurements were tested for their potential discrimination power for cocaine profiling, and normalization+standardization+logarithm (N+S+L)/Cosine correlation exhibited the best result. After hierarchical cluster analysis (HCA) analysis of 183 cocaine samples, 21 groups of linked samples were found within and between provinces, which provide intelligence for case connection and revealing of the distribution networks. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Correction: Comparative analysis of fungal genomes reveals different plant cell wall degrading capacity in fungi.

    Science.gov (United States)

    Zhao, Zhongtao; Liu, Huiquan; Wang, Chenfang; Xu, Jin-Rong

    2014-01-03

    families are present in fungi that are not known to have cellulose-degrading ability. In addition, our results also showed that in general, plant pathogenic fungi have the highest number of CAZymes. Biotrophic fungi tend to have fewer CAZymes than necrotrophic and hemibiotrophic fungi. Pathogens of dicots often contain more pectinases than fungi infecting monocots. Interestingly, besides yeasts, many saprophytic fungi that are highly active in degrading plant biomass contain fewer CAZymes than plant pathogenic fungi. Furthermore, analysis of the gene expression profile of the wheat scab fungus Fusarium graminearum revealed that most of the CAZyme genes related to cell wall degradation were up-regulated during plant infection. Phylogenetic analysis also revealed a complex history of lineage-specific expansions and attritions for the PL1 family. Our study provides insights into the variety and expansion of fungal CAZyme classes and revealed the relationship of CAZyme size and diversity with their nutritional strategy and host specificity.

  15. Correction: Comparative analysis of fungal genomes reveals different plant cell wall degrading capacity in fungi

    Science.gov (United States)

    2014-01-01

    . Importantly, cellulases of some GH families are present in fungi that are not known to have cellulose-degrading ability. In addition, our results also showed that in general, plant pathogenic fungi have the highest number of CAZymes. Biotrophic fungi tend to have fewer CAZymes than necrotrophic and hemibiotrophic fungi. Pathogens of dicots often contain more pectinases than fungi infecting monocots. Interestingly, besides yeasts, many saprophytic fungi that are highly active in degrading plant biomass contain fewer CAZymes than plant pathogenic fungi. Furthermore, analysis of the gene expression profile of the wheat scab fungus Fusarium graminearum revealed that most of the CAZyme genes related to cell wall degradation were up-regulated during plant infection. Phylogenetic analysis also revealed a complex history of lineage-specific expansions and attritions for the PL1 family. Conclusions Our study provides insights into the variety and expansion of fungal CAZyme classes and revealed the relationship of CAZyme size and diversity with their nutritional strategy and host specificity. PMID:24422981

  16. Infectomic Analysis of Gene Expression Profiles of Human Brain Microvascular Endothelial Cells Infected with Cryptococcus neoformans

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    Ambrose Jong

    2008-01-01

    Full Text Available In order to dissect the pathogenesis of Cryptococcus neoformans meningoencephalitis, a genomic survey of the changes in gene expression of human brain microvascular endothelial cells infected by C. neoformans was carried out in a time-course study. Principal component analysis (PCA revealed sigificant fluctuations in the expression levels of different groups of genes during the pathogen-host interaction. Self-organizing map (SOM analysis revealed that most genes were up- or downregulated 2 folds or more at least at one time point during the pathogen-host engagement. The microarray data were validated by Western blot analysis of a group of genes, including β-actin, Bcl-x, CD47, Bax, Bad, and Bcl-2. Hierarchical cluster profile showed that 61 out of 66 listed interferon genes were changed at least at one time point. Similarly, the active responses in expression of MHC genes were detected at all stages of the interaction. Taken together, our infectomic approaches suggest that the host cells significantly change the gene profiles and also actively participate in immunoregulations of the central nervous system (CNS during C. neoformans infection.

  17. Differential Network Analysis Reveals Evolutionary Complexity in Secondary Metabolism of Rauvolfia serpentina over Catharanthus roseus

    Science.gov (United States)

    Pathania, Shivalika; Bagler, Ganesh; Ahuja, Paramvir S.

    2016-01-01

    Comparative co-expression analysis of multiple species using high-throughput data is an integrative approach to determine the uniformity as well as diversification in biological processes. Rauvolfia serpentina and Catharanthus roseus, both members of Apocyanacae family, are reported to have remedial properties against multiple diseases. Despite of sharing upstream of terpenoid indole alkaloid pathway, there is significant diversity in tissue-specific synthesis and accumulation of specialized metabolites in these plants. This led us to implement comparative co-expression network analysis to investigate the modules and genes responsible for differential tissue-specific expression as well as species-specific synthesis of metabolites. Toward these goals differential network analysis was implemented to identify candidate genes responsible for diversification of metabolites profile. Three genes were identified with significant difference in connectivity leading to differential regulatory behavior between these plants. These genes may be responsible for diversification of secondary metabolism, and thereby for species-specific metabolite synthesis. The network robustness of R. serpentina, determined based on topological properties, was also complemented by comparison of gene-metabolite networks of both plants, and may have evolved to have complex metabolic mechanisms as compared to C. roseus under the influence of various stimuli. This study reveals evolution of complexity in secondary metabolism of R. serpentina, and key genes that contribute toward diversification of specific metabolites. PMID:27588023

  18. Differential network analysis reveals evolutionary complexity in secondary metabolism of Rauvolfia serpentina over Catharanthus roseus

    Directory of Open Access Journals (Sweden)

    Shivalika Pathania

    2016-08-01

    Full Text Available Comparative co-expression analysis of multiple species using high-throughput data is an integrative approach to determine the uniformity as well as diversification in biological processes. Rauvolfia serpentina and Catharanthus roseus, both members of Apocyanacae family, are reported to have remedial properties against multiple diseases. Despite of sharing upstream of terpenoid indole alkaloid pathway, there is significant diversity in tissue-specific synthesis and accumulation of specialized metabolites in these plants. This led us to implement comparative co-expression network analysis to investigate the modules and genes responsible for differential tissue-specific expression as well as species-specific synthesis of metabolites. Towards these goals differential network analysis was implemented to identify candidate genes responsible for diversification of metabolites profile. Three genes were identified with significant difference in connectivity leading to differential regulatory behavior between these plants. These mechanisms may be responsible for diversification of secondary metabolism, and thereby for species-specific metabolite synthesis. The network robustness of R. serpentina, determined based on topological properties, was also complemented by comparison of gene-metabolite networks of both plants, and may have evolved to have complex metabolic mechanisms as compared to C. roseus under the influence of various stimuli. This study reveals evolution of complexity in secondary metabolism of Rauvolfia serpentina, and key genes that contribute towards diversification of specific metabolites.

  19. Metabolomic Profiling of Extracellular Vesicles and Alternative Normalization Methods Reveal Enriched Metabolites and Strategies to Study Prostate Cancer-Related Changes.

    Science.gov (United States)

    Puhka, Maija; Takatalo, Maarit; Nordberg, Maria-Elisa; Valkonen, Sami; Nandania, Jatin; Aatonen, Maria; Yliperttula, Marjo; Laitinen, Saara; Velagapudi, Vidya; Mirtti, Tuomas; Kallioniemi, Olli; Rannikko, Antti; Siljander, Pia R-M; Af Hällström, Taija Maria

    2017-01-01

    Body fluids are a rich source of extracellular vesicles (EVs), which carry cargo derived from the secreting cells. So far, biomarkers for pathological conditions have been mainly searched from their protein, (mi)RNA, DNA and lipid cargo. Here, we explored the small molecule metabolites from urinary and platelet EVs relative to their matched source samples. As a proof-of-concept study of intra-EV metabolites, we compared alternative normalization methods to profile urinary EVs from prostate cancer patients before and after prostatectomy and from healthy controls. We employed targeted ultra-performance liquid chromatography-tandem mass spectrometry to profile over 100 metabolites in the isolated EVs, original urine samples and platelets. We determined the enrichment of the metabolites in the EVs and analyzed their subcellular origin, pathways and relevant enzymes or transporters through data base searches. EV- and urine-derived factors and ratios between metabolites were tested for normalization of the metabolomics data. Approximately 1 x 1010 EVs were sufficient for detection of metabolite profiles from EVs. The profiles of the urinary and platelet EVs overlapped with each other and with those of the source materials, but they also contained unique metabolites. The EVs enriched a selection of cytosolic metabolites including members from the nucleotide and spermidine pathways, which linked to a number of EV-resident enzymes or transporters. Analysis of the urinary EVs from the patients indicated that the levels of glucuronate, D-ribose 5-phosphate and isobutyryl-L-carnitine were 2-26-fold lower in all pre-prostatectomy samples compared to the healthy control and post-prostatectomy samples (p < 0.05). These changes were only detected from EVs by normalization to EV-derived factors or with metabolite ratios, and not from the original urine samples. Our results suggest that metabolite analysis of EVs from different samples is feasible using a high-throughput platform

  20. Multiple maternal origins of Indonesian crowing chickens revealed by mitochondrial DNA analysis.

    Science.gov (United States)

    Ulfah, Maria; Perwitasari, Dyah; Jakaria, Jakaria; Muladno, Muhammad; Farajallah, Achmad

    2017-03-01

    The utilization of Indonesian crowing chickens is increasing; as such, assessing their genetic structures is important to support the conservation of their genetic resources. This study analyzes the matrilineal evolution of Indonesian crowing chickens based on the mtDNA displacement loop D-loop region to clarify their phylogenetic relationships, possible maternal origin, and possible routes of chicken dispersal. The neighbor-joining tree reveals that the majority of Indonesian crowing chickens belong to haplogroups B, D, and E, but haplogroup D harbored most of them. The Bayesian analysis also reveals that Indonesian crowing chickens derive from Bekisar chicken, a hybrid of the green junglefowl, suggesting the possible contribution of green junglefowl to chicken domestication. There appear at least three maternal lineages of Indonesian chicken origins indicated by the median network profile of mtDNA D-loop haplotypes, namely (1) Chinese; (2) Chinese, Indian, and other Southeast Asian chickens; and (3) Indian, Chinese, Southeast Asian, Japanese, and European chickens. Chicken domestication might be centered in China, India, Indonesia, and other Southeast Asian countries, supporting multiple maternal origins of Indonesian crowing chickens. A systematic breeding program of indigenous chickens will be very important to retain the genetic diversity for future use and conservation.

  1. 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.

  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. Expression profile of the Schistosoma japonicum degradome reveals differential protease expression patterns and potential anti-schistosomal intervention targets.

    Science.gov (United States)

    Liu, Shuai; Cai, Pengfei; Piao, Xianyu; Hou, Nan; Zhou, Xiaosu; Wu, Chuang; Wang, Heng; Chen, Qijun

    2014-10-01

    Blood fluke proteases play pivotal roles in the processes of invasion, nutrition acquisition, immune evasion, and other host-parasite interactions. Hundreds of genes encoding putative proteases have been identified in the recently published schistosome genomes. However, the expression profiles of these proteases in Schistosoma species have not yet been systematically analyzed. We retrieved and culled the redundant protease sequences of Schistosoma japonicum, Schistosoma mansoni, Echinococcus multilocularis, and Clonorchis sinensis from public databases utilizing bioinformatic approaches. The degradomes of the four parasitic organisms and Homo sapiens were then comparatively analyzed. A total of 262 S. japonicum protease sequences were obtained and the expression profiles generated using whole-genome microarray. Four main clusters of protease genes with different expression patterns were identified: proteases up-regulated in hepatic schistosomula and adult worms, egg-specific or predominantly expressed proteases, cercaria-specific or predominantly expressed proteases, and constantly expressed proteases. A subset of protease genes with different expression patterns were further validated using real-time quantitative PCR. The present study represents the most comprehensive analysis of a degradome in Schistosoma species to date. These results provide a firm foundation for future research on the specific function(s) of individual proteases and may help to refine anti-proteolytic strategies in blood flukes.

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

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    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.

  5. Reproducibility of Cognitive Profiles in Psychosis Using Cluster Analysis.

    Science.gov (United States)

    Lewandowski, Kathryn E; Baker, Justin T; McCarthy, Julie M; Norris, Lesley A; Öngür, Dost

    2017-10-18

    Cognitive dysfunction is a core symptom dimension that cuts across the psychoses. Recent findings support classification of patients along the cognitive dimension using cluster analysis; however, data-derived groupings may be highly determined by sampling characteristics and the measures used to derive the clusters, and so their interpretability must be established. We examined cognitive clusters in a cross-diagnostic sample of patients with psychosis and associations with clinical and functional outcomes. We then compared our findings to a previous report of cognitive clusters in a separate sample using a different cognitive battery. Participants with affective or non-affective psychosis (n=120) and healthy controls (n=31) were administered the MATRICS Consensus Cognitive Battery, and clinical and community functioning assessments. Cluster analyses were performed on cognitive variables, and clusters were compared on demographic, cognitive, and clinical measures. Results were compared to findings from our previous report. A four-cluster solution provided a good fit to the data; profiles included a neuropsychologically normal cluster, a globally impaired cluster, and two clusters of mixed profiles. Cognitive burden was associated with symptom severity and poorer community functioning. The patterns of cognitive performance by cluster were highly consistent with our previous findings. We found evidence of four cognitive subgroups of patients with psychosis, with cognitive profiles that map closely to those produced in our previous work. Clusters were associated with clinical and community variables and a measure of premorbid functioning, suggesting that they reflect meaningful groupings: replicable, and related to clinical presentation and functional outcomes. (JINS, 2017, 23, 1-9).

  6. Seasonal Transport in Mars' Mesosphere revealed by Nitric Oxide Nightglow vertical profiles and global images from IUVS/MAVEN

    Science.gov (United States)

    Stiepen, Arnaud; Stewart, Ian; Jain, Sonal; Schneider, Nicholas; Deighan, Justin; Gonzàlez-Galindo, Francisco; Gérard, Jean-Claude; Stevens, Michael; Bougher, Stephen; Milby, Zachariah; Evans, Scott; Chaffin, Michael; McClintock, William; Clarke, John; Holsclaw, Greg; Montmessin, Franck; Lefèvre, Franck; Lo, Daniel; Jakosky, Bruce

    2017-04-01

    We analyze the ultraviolet nightglow in the atmosphere of Mars through Nitric Oxide (NO) δ and γ bands emissions. On the dayside thermosphere of Mars, solar extreme ultraviolet radiation partly dissociates CO2 and N2 molecules. O(3P) and N(4S) atoms are carried by the day-to-night hemispheric transport. They preferentially descend in the nightside mesosphere in the winter hemisphere, where they can radiatively recombine to form NO(C2Π). The excited molecules promptly relax by emitting photons in the UV δ bands and in the γ bands through cascades via the A2Σ, v' = 0 state. These emissions are thus indicators of the N and O atom fluxes transported from the dayside to Mars' nightside and the winter descending circulation pattern from the nightside thermosphere to the mesosphere (e.g. Bertaux et al., 2005 ; Bougher et al., 1990 ; Cox et al., 2008 ; Gagné et al., 2013 ; Gérard et al., 2008 ; Stiepen et al., 2015). Observations of these emissions have been accumulated on a large dataset of nightside disk images and vertical profiles obtained at the limb by the Imaging Ultraviolet Spectrograph (IUVS, McClintock et al., 2015) instrument when the Mars Atmosphere and Volatile EvolutioN (MAVEN) spacecraft is at its apoapsis and its periapsis phases along its orbit, respectively. We present discussion on the variability in the brightness, altitude and topside scale height of the emission with season, geographical position and local time and possible interpretation for local and global changes in the mesosphere dynamics. IUVS images and limb scans reveal unexpected complex structure of the emission. The brightest emission is observed close to the winter pole. The emission is also surprisingly more intense in some sectors located close to the equator : at 120˚ and 150˚ longitude. Observations also reveal spots and streaks, indicating irregularities in the wind circulation pattern and possible impact of waves and tides. The disk images and limb profiles are compared to

  7. Iranian Voice Quality of Life Profile (IVQLP): Factor Analysis.

    Science.gov (United States)

    Dehqan, Ali; Yadegari, Fariba; Scherer, Ronald C; Asgari, Ali; Dabirmoghadam, Payman

    2017-09-01

    An important domain in health-related quality of life evaluations is quality of life perceptions due to having a voice disorder. The objective of this study was to examine the factor structure of the Iranian Voice Quality of Life Profile (IVQLP) based on Exploratory Factor Analysis and confirmatory factor analysis. The study sample consisted of 280 patients (174 males and 106 females) diagnosed with MTD, benign organic disorders such as polyps and nodules, and unilateral vocal fold paralysis and cancer. To evaluate the different dimensions of the IVQLP, a principal component analysis (PCA) was conducted. Confirmatory factor analysis (CFA) was used to investigate the fitting of extracted dimensions and construct validity of the IVQLP. The results showed that the IVQLP has a 4-factor structure. The first factor has 17 items and refers to Emotions. The second factor has 12 items and refers to Individual/Social Relations. The third factor with 6 items refers to Occupation, and the forth with 5 items relates to Psychosomatic characteristics. The conclusion of this study is that the concept of quality of life in Iranian patients with voice disorders is somewhat different from that of Western patients. This difference can be seen in. the large number of items related to an Emotional factor and the identification of a Psychosomatic factor. Copyright © 2017 The Voice Foundation. All rights reserved.

  8. Free choice profiling sensory analysis to discriminate coffees

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    Cíntia Sorane Good Kitzberger

    2016-12-01

    Full Text Available Sensory attributes were evaluated from Arabica coffee genotypes growing in two places in Brazil, Mandaguari and Londrina. Post-harvest and roasted process was standardized. Free choice profiling sensory analysis was apply to investigate the influence of genetic variability and local cultivation (Londrina and Mandaguari, Brazil on the sensory characteristics of coffee genotypes. A sensory panel evaluated coffees from Mandaguari in two groups: one (Sarchimor derived, IPR100, IPR102, IPR105, IPR106 characterized by transparency, coffee colour, green aroma, taste (green, bitter, fermented, astringent and a watery texture, another group (Catuaí, Sarchimor derived, IPR101, IPR103 was characterized by coffee colour, brightness, aroma (coffee, acid, sweet, chocolate, acidity, bitterness, burnt aroma, sweetness and full-bodied. Coffees from Londrina presented brightness, coffee colour, sweet, green, burnt aroma, astringent, bitter, fermented, green taste; and watery texture (Catuaí, IPR97, IPR98, IPR100. Another group (Sarchimor derived, IPR101, IPR102, IPR103, IPR105, IPR106 were associated with turbidity, aroma (green, coffee, sweet, acidity, astringency, bitterness, sweetness and full-bodied. Catuaí, Iapar59, IPR99, IPR101, IPR103 and IPR108 exhibited positive attributes when grown in either locale. Edaphoclimatic conditions play a major role in the sensory profiles of coffee.

  9. 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.

  10. Differential appearance of isoforms and cultivar variation in protein temporal profiles revealed in the maturing barley grain proteome

    DEFF Resea