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Sample records for biomarker revealing high

  1. Metabolomics reveals metabolic biomarkers of Crohn's disease

    Energy Technology Data Exchange (ETDEWEB)

    Jansson, J.K.; Willing, B.; Lucio, M.; Fekete, A.; Dicksved, J.; Halfvarson, J.; Tysk, C.; Schmitt-Kopplin, P.

    2009-06-01

    The causes and etiology of Crohn's disease (CD) are currently unknown although both host genetics and environmental factors play a role. Here we used non-targeted metabolic profiling to determine the contribution of metabolites produced by the gut microbiota towards disease status of the host. Ion Cyclotron Resonance Fourier Transform Mass Spectrometry (ICR-FT/MS) was used to discern the masses of thousands of metabolites in fecal samples collected from 17 identical twin pairs, including healthy individuals and those with CD. Pathways with differentiating metabolites included those involved in the metabolism and or synthesis of amino acids, fatty acids, bile acids and arachidonic acid. Several metabolites were positively or negatively correlated to the disease phenotype and to specific microbes previously characterized in the same samples. Our data reveal novel differentiating metabolites for CD that may provide diagnostic biomarkers and/or monitoring tools as well as insight into potential targets for disease therapy and prevention.

  2. Biomarkers in Transit Reveal the Nature of Fluvial Integration

    Science.gov (United States)

    Ponton, C.; West, A.; Feakins, S. J.; Galy, V.

    2013-12-01

    suggest that OC from high elevations may be proportionally overrepresented relative to areal extent, with possibly important implications for biomarker isotope composition; 3) timescales of different biomarkers vary considerably; 4) the composition of OC varies downstream and with depth stratification within large rivers. We filtered >1000L of river water in this remote location during the wet season, and are presently replicating that study during the dry season, providing a seasonal comparison of OC transport in this major river system.

  3. Comparative Genomics Reveals Biomarkers to Identify Lactobacillus Species.

    Science.gov (United States)

    Koul, Shikha; Kalia, Vipin Chandra

    2016-09-01

    Bacteria possessing multiple copies of 16S rRNA (rrs) gene demonstrate high intragenomic heterogeneity. It hinders clear distinction at species level and even leads to overestimation of the bacterial diversity. Fifty completely sequenced genomes belonging to 19 species of Lactobacillus species were found to possess 4-9 copies of rrs each. Multiple sequence alignment of 268 rrs genes from all the 19 species could be classified into 20 groups. Lactobacillus sanfranciscensis TMW 1.1304 was the only species where all the 7 copies of rrs were exactly similar and thus formed a distinct group. In order to circumvent the problem of high heterogeneity arising due to multiple copies of rrs, 19 additional genes (732-3645 nucleotides in size) common to Lactobacillus genomes, were selected and digested with 10 Type II restriction endonucleases (RE), under in silico conditions. The following unique gene-RE combinations: recA (1098 nts)-HpyCH4 V, CviAII, BfuCI and RsaI were found to be useful in identifying 29 strains representing 17 species. Digestion patterns of genes-ruvB (1020 nts), dnaA (1368 nts), purA (1290 nts), dnaJ (1140 nts), and gyrB (1944 nts) in combination with REs-AluI, BfuCI, CviAI, Taq1, and Tru9I allowed clear identification of an additional 14 strains belonging to 8 species. Digestion pattern of genes recA, ruvB, dnaA, purA, dnaJ and gyrB can be used as biomarkers for identifying different species of Lactobacillus. PMID:27407290

  4. Serum Glycoprotein Biomarker Discovery and Qualification Pipeline Reveals Novel Diagnostic Biomarker Candidates for Esophageal Adenocarcinoma.

    Science.gov (United States)

    Shah, Alok K; Cao, Kim-Anh Lê; Choi, Eunju; Chen, David; Gautier, Benoît; Nancarrow, Derek; Whiteman, David C; Saunders, Nicholas A; Barbour, Andrew P; Joshi, Virendra; Hill, Michelle M

    2015-11-01

    We report an integrated pipeline for efficient serum glycoprotein biomarker candidate discovery and qualification that may be used to facilitate cancer diagnosis and management. The discovery phase used semi-automated lectin magnetic bead array (LeMBA)-coupled tandem mass spectrometry with a dedicated data-housing and analysis pipeline; GlycoSelector (http://glycoselector.di.uq.edu.au). The qualification phase used lectin magnetic bead array-multiple reaction monitoring-mass spectrometry incorporating an interactive web-interface, Shiny mixOmics (http://mixomics-projects.di.uq.edu.au/Shiny), for univariate and multivariate statistical analysis. Relative quantitation was performed by referencing to a spiked-in glycoprotein, chicken ovalbumin. We applied this workflow to identify diagnostic biomarkers for esophageal adenocarcinoma (EAC), a life threatening malignancy with poor prognosis in the advanced setting. EAC develops from metaplastic condition Barrett's esophagus (BE). Currently diagnosis and monitoring of at-risk patients is through endoscopy and biopsy, which is expensive and requires hospital admission. Hence there is a clinical need for a noninvasive diagnostic biomarker of EAC. In total 89 patient samples from healthy controls, and patients with BE or EAC were screened in discovery and qualification stages. Of the 246 glycoforms measured in the qualification stage, 40 glycoforms (as measured by lectin affinity) qualified as candidate serum markers. The top candidate for distinguishing healthy from BE patients' group was Narcissus pseudonarcissus lectin (NPL)-reactive Apolipoprotein B-100 (p value = 0.0231; AUROC = 0.71); BE versus EAC, Aleuria aurantia lectin (AAL)-reactive complement component C9 (p value = 0.0001; AUROC = 0.85); healthy versus EAC, Erythroagglutinin Phaseolus vulgaris (EPHA)-reactive gelsolin (p value = 0.0014; AUROC = 0.80). A panel of 8 glycoforms showed an improved AUROC of 0.94 to discriminate EAC from BE. Two biomarker candidates

  5. The human oral metaproteome reveals potential biomarkers for caries disease.

    Science.gov (United States)

    Belda-Ferre, Pedro; Williamson, James; Simón-Soro, Áurea; Artacho, Alejandro; Jensen, Ole N; Mira, Alex

    2015-10-01

    Tooth decay is considered the most prevalent human disease worldwide. We present the first metaproteomic study of the oral biofilm, using different mass spectrometry approaches that have allowed us to quantify individual peptides in healthy and caries-bearing individuals. A total of 7771 bacterial and 853 human proteins were identified in 17 individuals, which provide the first available protein repertoire of human dental plaque. Actinomyces and Coryneybacterium represent a large proportion of the protein activity followed by Rothia and Streptococcus. Those four genera account for 60-90% of total diversity. Healthy individuals appeared to have significantly higher amounts of L-lactate dehydrogenase and the arginine deiminase system, both implicated in pH buffering. Other proteins found to be at significantly higher levels in healthy individuals were involved in exopolysaccharide synthesis, iron metabolism and immune response. We applied multivariate analysis in order to find the minimum set of proteins that better allows discrimination of healthy and caries-affected dental plaque samples, detecting seven bacterial and five human protein functions that allow determining the health status of the studied individuals with an estimated specificity and sensitivity over 96%. We propose that future validation of these potential biomarkers in larger sample size studies may serve to develop diagnostic tests of caries risk that could be used in tooth decay prevention. PMID:26272225

  6. 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;

    potential BT biomarkers for optimized breeding. Male pigs (n=48) with low, medium and high genetic merit of BT were selected and tissues from liver and testis were subjected to transcriptomic profiling by RNA-Seq. The reads were mapped to the Sus scrofa reference genome (Ensembl, ver. 79) which resulted...... 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...... and enrichment analysis and semantic filtering revealed the GO terms “catalytic activity” and “transferase activity” to be overrepresented (p hormones. Extraction of hub...

  7. Genome-wide Expression Profiling Reveals S100B as Biomarker for Invasive Aspergillosis

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    Andreas eDix

    2016-03-01

    Full Text Available Invasive aspergillosis (IA is a devastating opportunistic infection and its treatment constitutes a considerable burden for the health care system. Immunocompromised patients are at an increased risk for IA, which is mainly caused by the species Aspergillus fumigatus. An early and reliable diagnosis is required to initiate the appropriate antifungal therapy. However, diagnostic sensitivity and accuracy still needs to be improved, which can be achieved at least partly by the definition of new biomarkers. Besides the direct detection of the pathogen by the current diagnostic methods, the analysis of the host response is a promising strategy towards this aim. Following this approach, we sought to identify new biomarkers for IA. For this purpose, we analyzed gene expression profiles of haematological patients and compared profiles of patients suffering from IA with non-IA patients. Based on microarray data, we applied a comprehensive feature selection using a random forest classifier. We identified the transcript coding for the S100 calcium-binding protein B (S100B as a potential new biomarker for the diagnosis of IA. Considering the expression of this gene, we were able to classify samples from patients with IA with 82.3% sensitivity and 74.6% specificity. Moreover, we validated the expression of S100B in a real-time reverse transcription polymerase chain reaction (RT-PCR assay and we also found a down-regulation of S100B in A. fumigatus stimulated DCs. An influence on the IL1B and CXCL1 downstream levels was demonstrated by this S100B knockdown. In conclusion, this study covers an effective feature selection revealing a key regulator of the human immune response during IA. S100B may represent an additional diagnostic marker that in combination with the established techniques may improve the accuracy of IA diagnosis.

  8. Genome-Wide Expression Profiling Reveals S100B as Biomarker for Invasive Aspergillosis.

    Science.gov (United States)

    Dix, Andreas; Czakai, Kristin; Springer, Jan; Fliesser, Mirjam; Bonin, Michael; Guthke, Reinhard; Schmitt, Anna L; Einsele, Hermann; Linde, Jörg; Löffler, Jürgen

    2016-01-01

    Invasive aspergillosis (IA) is a devastating opportunistic infection and its treatment constitutes a considerable burden for the health care system. Immunocompromised patients are at an increased risk for IA, which is mainly caused by the species Aspergillus fumigatus. An early and reliable diagnosis is required to initiate the appropriate antifungal therapy. However, diagnostic sensitivity and accuracy still needs to be improved, which can be achieved at least partly by the definition of new biomarkers. Besides the direct detection of the pathogen by the current diagnostic methods, the analysis of the host response is a promising strategy toward this aim. Following this approach, we sought to identify new biomarkers for IA. For this purpose, we analyzed gene expression profiles of hematological patients and compared profiles of patients suffering from IA with non-IA patients. Based on microarray data, we applied a comprehensive feature selection using a random forest classifier. We identified the transcript coding for the S100 calcium-binding protein B (S100B) as a potential new biomarker for the diagnosis of IA. Considering the expression of this gene, we were able to classify samples from patients with IA with 82.3% sensitivity and 74.6% specificity. Moreover, we validated the expression of S100B in a real-time reverse transcription polymerase chain reaction (RT-PCR) assay and we also found a down-regulation of S100B in A. fumigatus stimulated DCs. An influence on the IL1B and CXCL1 downstream levels was demonstrated by this S100B knockdown. In conclusion, this study covers an effective feature selection revealing a key regulator of the human immune response during IA. S100B may represent an additional diagnostic marker that in combination with the established techniques may improve the accuracy of IA diagnosis. PMID:27047454

  9. Carbon sources in the Beaufort Sea revealed by molecular lipid biomarkers and compound specific isotope analysis

    Directory of Open Access Journals (Sweden)

    I. Tolosa

    2012-10-01

    Full Text Available Molecular lipid biomarkers (hydrocarbons, alcohols, sterols and fatty acids and compound specific isotope analysis of suspended particulate organic matter (SPM and surface sediments of the Mackenzie Shelf and slope (Southeast Beaufort Sea, Arctic Ocean, were studied in summer 2009. The concentrations of the molecular lipid markers, characteristic of known organic matter sources, were grouped and used as proxies to evaluate the relative importance of fresh algal, detrital algal, fossil, C3 terrestrial plants, bacterial and zooplankton material in the sedimentary organic matter (OM.

    Fossil and detrital algal contributions were the major fractions of the freshwater SPM from the Mackenzie River with ~34% each of the total molecular biomarkers. Fresh algal, C3 terrestrial, bacterial and zooplanktonic components represented much lower percentages, 17, 10, 4 and < 1%, respectively. In marine SPM from the Mackenzie slope, the major contributions were fresh and detrital algal components (> 80% with a minor contribution of fossil and C3 terrestrial biomarkers. Characterization of the sediments revealed a major sink of refractory algal material mixed with some fresh algal material, fossil hydrocarbons and a small input of C3 terrestrial sources. In particular, the sediments from the shelf and at the mouth of the Amundsen Gulf presented the highest contribution of detrital algal material (60–75% whereas those from the slope contained the highest proportion of fossil (40% and C3 terrestrial plant material (10%. Overall, considering that the detrital algal material is marine derived, autochthonous sources contributed more than allochthonous sources to the OM lipid pool. Using the ratio of an allochthonous biomarker (normalized to total organic carbon, TOC found in the sediments to those measured at the river mouth water, we estimated that the fraction of terrestrial material preserved in the

  10. Identification of novel serum peptide biomarkers for high-altitude adaptation: a comparative approach

    Science.gov (United States)

    Yang, Juan; Li, Wenhua; Liu, Siyuan; Yuan, Dongya; Guo, Yijiao; Jia, Cheng; Song, Tusheng; Huang, Chen

    2016-05-01

    We aimed to identify serum biomarkers for screening individuals who could adapt to high-altitude hypoxia at sea level. HHA (high-altitude hypoxia acclimated; n = 48) and HHI (high-altitude hypoxia illness; n = 48) groups were distinguished at high altitude, routine blood tests were performed for both groups at high altitude and at sea level. Serum biomarkers were identified by comparing serum peptidome profiling between HHI and HHA groups collected at sea level. Routine blood tests revealed the concentration of hemoglobin and red blood cells were significantly higher in HHI than in HHA at high altitude. Serum peptidome profiling showed that ten significantly differentially expressed peaks between HHA and HHI at sea level. Three potential serum peptide peaks (m/z values: 1061.91, 1088.33, 4057.63) were further sequence identified as regions of the inter-α trypsin inhibitor heavy chain H4 fragment (ITIH4 347-356), regions of the inter-α trypsin inhibitor heavy chain H1 fragment (ITIH1 205-214), and isoform 1 of fibrinogen α chain precursor (FGA 588-624). Expression of their full proteins was also tested by ELISA in HHA and HHI samples collected at sea level. Our study provided a novel approach for identifying potential biomarkers for screening people at sea level who can adapt to high altitudes.

  11. Identification of novel serum peptide biomarkers for high-altitude adaptation: a comparative approach

    Science.gov (United States)

    Yang, Juan; Li, Wenhua; Liu, Siyuan; Yuan, Dongya; Guo, Yijiao; Jia, Cheng; Song, Tusheng; Huang, Chen

    2016-05-01

    We aimed to identify serum biomarkers for screening individuals who could adapt to high-altitude hypoxia at sea level. HHA (high-altitude hypoxia acclimated; n = 48) and HHI (high-altitude hypoxia illness; n = 48) groups were distinguished at high altitude, routine blood tests were performed for both groups at high altitude and at sea level. Serum biomarkers were identified by comparing serum peptidome profiling between HHI and HHA groups collected at sea level. Routine blood tests revealed the concentration of hemoglobin and red blood cells were significantly higher in HHI than in HHA at high altitude. Serum peptidome profiling showed that ten significantly differentially expressed peaks between HHA and HHI at sea level. Three potential serum peptide peaks (m/z values: 1061.91, 1088.33, 4057.63) were further sequence identified as regions of the inter-α trypsin inhibitor heavy chain H4 fragment (ITIH4 347–356), regions of the inter-α trypsin inhibitor heavy chain H1 fragment (ITIH1 205–214), and isoform 1 of fibrinogen α chain precursor (FGA 588–624). Expression of their full proteins was also tested by ELISA in HHA and HHI samples collected at sea level. Our study provided a novel approach for identifying potential biomarkers for screening people at sea level who can adapt to high altitudes.

  12. Computational imaging reveals mitochondrial morphology as a biomarker of cancer phenotype and drug response

    Science.gov (United States)

    Giedt, Randy J.; Fumene Feruglio, Paolo; Pathania, Divya; Yang, Katherine S.; Kilcoyne, Aoife; Vinegoni, Claudio; Mitchison, Timothy J.; Weissleder, Ralph

    2016-09-01

    Mitochondria, which are essential organelles in resting and replicating cells, can vary in number, mass and shape. Past research has primarily focused on short-term molecular mechanisms underlying fission/fusion. Less is known about longer-term mitochondrial behavior such as the overall makeup of cell populations’ morphological patterns and whether these patterns can be used as biomarkers of drug response in human cells. We developed an image-based analytical technique to phenotype mitochondrial morphology in different cancers, including cancer cell lines and patient-derived cancer cells. We demonstrate that (i) cancer cells of different origins, including patient-derived xenografts, express highly diverse mitochondrial phenotypes; (ii) a given phenotype is characteristic of a cell population and fairly constant over time; (iii) mitochondrial patterns correlate with cell metabolic measurements and (iv) therapeutic interventions can alter mitochondrial phenotypes in drug-sensitive cancers as measured in pre- versus post-treatment fine needle aspirates in mice. These observations shed light on the role of mitochondrial dynamics in the biology and drug response of cancer cells. On the basis of these findings, we propose that image-based mitochondrial phenotyping can provide biomarkers for assessing cancer phenotype and drug response.

  13. Computational imaging reveals mitochondrial morphology as a biomarker of cancer phenotype and drug response

    Science.gov (United States)

    Giedt, Randy J.; Fumene Feruglio, Paolo; Pathania, Divya; Yang, Katherine S.; Kilcoyne, Aoife; Vinegoni, Claudio; Mitchison, Timothy J.; Weissleder, Ralph

    2016-01-01

    Mitochondria, which are essential organelles in resting and replicating cells, can vary in number, mass and shape. Past research has primarily focused on short-term molecular mechanisms underlying fission/fusion. Less is known about longer-term mitochondrial behavior such as the overall makeup of cell populations’ morphological patterns and whether these patterns can be used as biomarkers of drug response in human cells. We developed an image-based analytical technique to phenotype mitochondrial morphology in different cancers, including cancer cell lines and patient-derived cancer cells. We demonstrate that (i) cancer cells of different origins, including patient-derived xenografts, express highly diverse mitochondrial phenotypes; (ii) a given phenotype is characteristic of a cell population and fairly constant over time; (iii) mitochondrial patterns correlate with cell metabolic measurements and (iv) therapeutic interventions can alter mitochondrial phenotypes in drug-sensitive cancers as measured in pre- versus post-treatment fine needle aspirates in mice. These observations shed light on the role of mitochondrial dynamics in the biology and drug response of cancer cells. On the basis of these findings, we propose that image-based mitochondrial phenotyping can provide biomarkers for assessing cancer phenotype and drug response. PMID:27609668

  14. 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; Drigo, Sandra Aparecida; Rogatto, Silvia Regina

    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

  15. 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.

  16. Evaluation of Current and New Biomarkers in Severe Preeclampsia: A Microarray Approach Reveals the VSIG4 Gene as a Potential Blood Biomarker

    OpenAIRE

    Textoris, Julien; Ivorra, Delphine; Ben Amara, Amira; Sabatier, Florence; Ménard, Jean-Pierre; Heckenroth, Hélène; Bretelle, Florence; Mege, Jean-Louis

    2013-01-01

    Preeclampsia is a placental disease characterized by hypertension and proteinuria in pregnant women, and it is associated with a high maternal and neonatal morbidity. However, circulating biomarkers that are able to predict the prognosis of preeclampsia are lacking. Thirty-eight women were included in the current study. They consisted of 19 patients with preeclampsia (13 with severe preeclampsia and 6 with non-severe preeclampsia) and 19 gestational age-matched women with normal pregnancies a...

  17. Novel serum protein biomarker panel revealed by mass spectrometry and its prognostic value in breast cancer

    OpenAIRE

    Chung, Liping; Moore, Katrina; Phillips, Leo; Boyle, Frances M.; Marsh, Deborah J.; Baxter, Robert C.

    2014-01-01

    Introduction Serum profiling using proteomic techniques has great potential to detect biomarkers that might improve diagnosis and predict outcome for breast cancer patients (BC). This study used surface-enhanced laser desorption/ionization time-of-flight (SELDI-TOF) mass spectrometry (MS) to identify differentially expressed proteins in sera from BC and healthy volunteers (HV), with the goal of developing a new prognostic biomarker panel. Methods Training set serum samples from 99 BC and 51 H...

  18. Biomarker identification and effect estimation on schizophrenia –a high dimensional data analysis

    Directory of Open Access Journals (Sweden)

    Yuanzhang eLi

    2015-05-01

    Full Text Available Biomarkers have been examined in schizophrenia research for decades. Medical morbidity and mortality rates, as well as personal and societal costs, are associated with schizophrenia patients. The identification of biomarkers and alleles, which often have a small effect individually, may help to develop new diagnostic tests for early identification and treatment. Currently, there is not a commonly accepted statistical approach to identify predictive biomarkers from high dimensional data. We used space Decomposition-Gradient-Regression method (DGR to select biomarkers, which are associated with the risk of schizophrenia. Then, we used the gradient scores, generated from the selected biomarkers, as the prediction factor in regression to estimate their effects. We also used an alternative approach, classification and regression tree (CART, to compare the biomarker selected by DGR and found about 70% of the selected biomarkers were the same. However, the advantage of DGR is that it can evaluate individual effects for each biomarker from their combined effect. In DGR analysis of serum specimens of US military service members with a diagnosis of schizophrenia from 1992 to 2005 and their controls, Alpha-1-Antitrypsin (AAT, Interleukin-6 receptor (IL-6r and Connective Tissue Growth Factor (CTGF were selected to identify schizophrenia for males; and Alpha-1-Antitrypsin (AAT, Apolipoprotein B (Apo B and Sortilin were selected for females. If these findings from military subjects are replicated by other studies, they suggest the possibility of a novel biomarker panel as an adjunct to earlier diagnosis and initiation of treatment.

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

    OpenAIRE

    Fabiana Azevedo Voorwald; Fabio Albuquerque Marchi; Rolando Andre Rios Villacis; Carlos Eduardo Fonseca Alves; Gilson Hélio Toniollo; Renee Laufer Amorim; Sandra Aparecida Drigo; Silvia Regina Rogatto

    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)....

  20. Comparisons of microRNA patterns in plasma before and after tumor removal reveal new biomarkers of lung squamous cell carcinoma.

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    Vasily N Aushev

    Full Text Available Lung cancer is the major human malignancy, accounting for 30% of all cancer-related deaths worldwide. Poor survival of lung cancer patients, together with late diagnosis and resistance to classic chemotherapy, highlights the need for identification of new biomarkers for early detection. Among different cancer biomarkers, small non-coding RNAs called microRNAs (miRNAs are considered the most promising, owing to their remarkable stability, their cancer-type specificity, and their presence in body fluids. However, results of multiple previous attempts to identify circulating miRNAs specific for lung cancer are inconsistent, likely due to two main reasons: prominent variability in blood miRNA content among individuals and difficulties in distinguishing tumor-relevant miRNAs in the blood from their non-tumor counterparts. To overcome these impediments, we compared circulating miRNA profiles in patients with lung squamous cell carcinoma (SCC before and after tumor removal, assuming that the levels of all tumor-relevant miRNAs would drop after the surgery. Our results revealed a specific panel of the miRNAs (miR-205, -19a, -19b, -30b, and -20a whose levels decreased strikingly in the blood of patients after lung SCC surgery. Interestingly, miRNA profiling of plasma fractions of lung SCC patients revealed high levels of these miRNA species in tumor-specific exosomes; additionally, some of these miRNAs were also found to be selectively secreted to the medium by cultivated lung cancer cells. These results strengthen the notion that tumor cells secrete miRNA-containing exosomes into circulation, and that miRNA profiling of the exosomal plasma fraction may reveal powerful cancer biomarkers.

  1. The Male Fetal Biomarker INSL3 Reveals Substantial Hormone Exchange between Fetuses in Early Pig Gestation

    OpenAIRE

    Andreas Vernunft; Richard Ivell; Kee Heng; Ravinder Anand-Ivell

    2016-01-01

    The peptide hormone INSL3 is uniquely produced by the fetal testis to promote the transabdominal phase of testicular descent. Because it is fetal sex specific, and is present in only very low amounts in the maternal circulation, INSL3 acts as an ideal biomarker with which to monitor the movement of fetal hormones within the pregnant uterus of a polytocous species, the pig. INSL3 production by the fetal testis begins at around GD30. At GD45 of the ca. 114 day gestation, a time at which testicu...

  2. Biomarkers of isoflavone intake : validity at high intakes

    OpenAIRE

    Mackinnon, L. Jay

    2007-01-01

    Isoflavones are biologically active plant chemicals (phytoestrogens) which are ordinarily present in human diets. There is considerable research interest in their potential to prevent or treat several chronic diseases. Biomarkers can demonstrate compliance during dietary interventions and validate associations between intake of isoflavones and health outcomes. The objectives of this study were to validate 24-hour urine collections, timed spot urine samples and timed plasma s...

  3. Expression profiling reveals novel hypoxic biomarkers in peripheral blood of adult mice exposed to chronic hypoxia.

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    Matias Mosqueira

    Full Text Available Hypoxia induces a myriad of changes including an increase in hematocrit due to erythropoietin (EPO mediated erythropoiesis. While hypoxia is of importance physiologically and clinically, lacunae exist in our knowledge of the systemic and temporal changes in gene expression occurring in blood during the exposure and recovery from hypoxia. To identify these changes expression profiling was conducted on blood obtained from cohorts of C57Bl-10 wild type mice that were maintained at normoxia (NX, exposed for two weeks to normobaric chronic hypoxia (CH or two weeks of CH followed by two weeks of normoxic recovery (REC. Using stringent bioinformatic cut-offs (0% FDR, 2 fold change cut-off, 230 genes were identified and separated into four distinct temporal categories. Class I contained 1 transcript up-regulated in both CH and REC; Class II contained 202 transcripts up-regulated in CH but down-regulated after REC; Class III contained 9 transcripts down-regulated both in CH and REC; Class IV contained 18 transcripts down-regulated after CH exposure but up-regulated after REC. Profiling was independently validated and extended by analyzing expression levels of selected genes as novel biomarkers from our profile (e.g. spectrin alpha-1, ubiquitin domain family-1 and pyrroline-5-carboxylate reductase-1 by performing qPCR at 7 different time points during CH and REC. Our identification and characterization of these genes define transcriptome level changes occurring during chronic hypoxia and normoxic recovery as well as novel blood biomarkers that may be useful in monitoring a variety of physiological and pathological conditions associated with hypoxia.

  4. Analyses of acute kidney injury biomarkers by ultra-high performance liquid chromatography with mass spectrometry.

    Science.gov (United States)

    Al Za'abi, Mohammed; Ali, Badreldin H; ALOthman, Zeid A; Ali, Imran

    2016-01-01

    The newly developed acute kidney injury biomarkers are very important for the early and timely detection of kidney diseases. This review contains details of the analyses of several acute kidney injury biomarkers using ultra-high performance liquid chromatography-mass spectrometry in urine and plasma samples. In this review we attempt to discuss some aspects of the types of the biomarkers, patents, sample preparation, and the analyses. Besides, efforts were also made to discuss the possible uses of superficially porous (core-shell) columns in traditional and inexpensive high-performance liquid chromatography instruments. Additionally, the challenges and the future prospects are also highlighted. The present review will be useful for the academicians, scientists, and clinicians for the early detection of acute kidney injury biomarkers.

  5. The Male Fetal Biomarker INSL3 Reveals Substantial Hormone Exchange between Fetuses in Early Pig Gestation.

    Directory of Open Access Journals (Sweden)

    Andreas Vernunft

    Full Text Available The peptide hormone INSL3 is uniquely produced by the fetal testis to promote the transabdominal phase of testicular descent. Because it is fetal sex specific, and is present in only very low amounts in the maternal circulation, INSL3 acts as an ideal biomarker with which to monitor the movement of fetal hormones within the pregnant uterus of a polytocous species, the pig. INSL3 production by the fetal testis begins at around GD30. At GD45 of the ca. 114 day gestation, a time at which testicular descent is promoted, INSL3 evidently moves from male to female allantoic compartments, presumably impacting also on the female fetal circulation. At later time-points (GD63, GD92 there is less inter-fetal transfer, although there still appears to be significant INSL3, presumably of male origin, in the plasma of female fetuses. This study thus provides evidence for substantial transfer of a peptide hormone between fetuses, and probably also across the placenta, emphasizing the vulnerability of the fetus to extrinsic hormonal influences within the uterus.

  6. Evaluation of current and new biomarkers in severe preeclampsia: a microarray approach reveals the VSIG4 gene as a potential blood biomarker.

    Directory of Open Access Journals (Sweden)

    Julien Textoris

    Full Text Available Preeclampsia is a placental disease characterized by hypertension and proteinuria in pregnant women, and it is associated with a high maternal and neonatal morbidity. However, circulating biomarkers that are able to predict the prognosis of preeclampsia are lacking. Thirty-eight women were included in the current study. They consisted of 19 patients with preeclampsia (13 with severe preeclampsia and 6 with non-severe preeclampsia and 19 gestational age-matched women with normal pregnancies as controls. We measured circulating factors that are associated with the coagulation pathway (including fibrinogen, fibronectin, factor VIII, antithrombin, protein S and protein C, endothelial activation (such as soluble endoglin and CD146, and the release of total and platelet-derived microparticles. These markers enabled us to discriminate the preeclampsia condition from a normal pregnancy but were not sufficient to distinguish severe from non-severe preeclampsia. We then used a microarray to study the transcriptional signature of blood samples. Preeclampsia patients exhibited a specific transcriptional program distinct from that of the control group of women. Interestingly, we also identified a severity-related transcriptional signature. Functional annotation of the upmodulated signature in severe preeclampsia highlighted two main functions related to "ribosome" and "complement". Finally, we identified 8 genes that were specifically upmodulated in severe preeclampsia compared with non-severe preeclampsia and the normotensive controls. Among these genes, we identified VSIG4 as a potential diagnostic marker of severe preeclampsia. The determination of this gene may improve the prognostic assessment of severe preeclampsia.

  7. Proteomic analysis of coronary sinus serum reveals leucine-rich α2-glycoprotein as a novel biomarker of ventricular dysfunction and heart failure.

    LENUS (Irish Health Repository)

    Watson, Chris J

    2011-03-01

    Heart failure (HF) prevention strategies require biomarkers that identify disease manifestation. Increases in B-type natriuretic peptide (BNP) correlate with increased risk of cardiovascular events and HF development. We hypothesize that coronary sinus serum from a high BNP hypertensive population reflects an active pathological process and can be used for biomarker exploration. Our aim was to discover differentially expressed disease-associated proteins that identify patients with ventricular dysfunction and HF.

  8. Biomarkers reveal sea turtles remained in oiled areas following the Deepwater Horizon oil spill

    Science.gov (United States)

    Vander Zanden, Hannah B.; Bolten, Alan B.; Tucker, Anton D.; Hart, Kristen M.; Lamont, Margaret M.; Fujisaki, Ikuko; Reich, Kimberly J.; Addison, David S.; Mansfield, Katherine L.; Phillips, Katrina F.; Pajuelo, Mariela; Bjorndal, Karen A.

    2016-01-01

    Assessments of large-scale disasters, such as the Deepwater Horizon oil spill, are problematic because while measurements of post-disturbance conditions are common, measurements of pre-disturbance baselines are only rarely available. Without adequate observations of pre-disaster organismal and environmental conditions, it is impossible to assess the impact of such catastrophes on animal populations and ecological communities. Here, we use long-term biological tissue records to provide pre-disaster data for a vulnerable marine organism. Keratin samples from the carapace of loggerhead sea turtles record the foraging history for up to 18 years, allowing us to evaluate the effect of the oil spill on sea turtle foraging patterns. Samples were collected from 76 satellite-tracked adult loggerheads in 2011 and 2012, approximately one to two years after the spill. Of the 10 individuals that foraged in areas exposed to surface oil, none demonstrated significant changes in foraging patterns post spill. The observed long-term fidelity to foraging sites indicates that loggerheads in the northern Gulf of Mexico likely remained in established foraging sites, regardless of the introduction of oil and chemical dispersants. More research is needed to address potential long-term health consequences to turtles in this region. Mobile marine organisms present challenges for researchers to monitor effects of environmental disasters, both spatially and temporally. We demonstrate that biological tissues can reveal long-term histories of animal behavior and provide critical pre-disaster baselines following an anthropogenic disturbance or natural disaster.

  9. Multiplexed homogeneous proximity ligation assays for high throughput protein biomarker research in serological material

    DEFF Research Database (Denmark)

    Lundberg, Martin; Thorsen, Stine Buch; Assarsson, Erika;

    2011-01-01

    A high throughput protein biomarker discovery tool has been developed based on multiplexed proximity ligation assays (PLA) in a homogeneous format in the sense of no washing steps. The platform consists of four 24-plex panels profiling 74 putative biomarkers with sub pM sensitivity each consuming...... only 1 micro Litre of human plasma sample. The system uses either matched monoclonal antibody pairs or the more readily available single batches of affinity purified polyclonal antibodies to generate the target specific reagents by covalently linking with unique nucleic acid sequences. These paired...

  10. Microbial ecology of the stratified water column of the Black Sea as revealed by a comprehensive biomarker study

    DEFF Research Database (Denmark)

    Wakeham, Stuart G.; Amann, Rudi; Freemann, Katherine H.;

    2007-01-01

    ) and sulfate reducing bacteria. We also measured a wide range of bacterial and archaeal lipid biomarkers. Depth distributions of diagnostic biomarkers are matched with zonation of microbial processes, including aerobic bacterial oxidation of methane, oxidation of ammonium by bacteria and archaea, metal...... reduction, and sulfide oxidation at the chemocline, and bacterial sulfate reduction and anaerobic oxidation of methane by archaea in the anoxic zone. Cell densities for archaea and sulfate reducing bacteria are estimated based on water column biomarker concentrations and compared with CARD-FISH results....

  11. Raman imaging for high throughput biomarker field detections

    Science.gov (United States)

    Tanaka, Zuki; Beer, Thomas; McKay, Christopher P.; Bonaccorsi, Rosalba; Gu, Claire; Chen, Bin

    2009-08-01

    We explore the feasibility of using Raman imaging as a technique for identifying areas of high astrobiological interest on Mars-like surfaces. This paper will discuss the technique, analysis, and possible deployment of rover mounted instrumentation for identifying biogenic samples from Mars analog environments, such as the Mojave Desert and Lassen Volcanic National Park. We also discuss using this technique for the non-destructive, in situ identification snow algae found in harsh environments.

  12. Functional connectivity classification of autism identifies highly predictive brain features but falls short of biomarker standards

    OpenAIRE

    Mark Plitt; Kelly Anne Barnes; Alex Martin

    2015-01-01

    Objectives: Autism spectrum disorders (ASD) are diagnosed based on early-manifesting clinical symptoms, including markedly impaired social communication. We assessed the viability of resting-state functional MRI (rs-fMRI) connectivity measures as diagnostic biomarkers for ASD and investigated which connectivity features are predictive of a diagnosis. Methods: Rs-fMRI scans from 59 high functioning males with ASD and 59 age- and IQ-matched typically developing (TD) males were used to build ...

  13. DAPK1, MGMT and RARB promoter methylation as biomarkers for high-grade cervical lesions

    OpenAIRE

    Sun, Yin; Li, Shu; Shen, Keng; Ye, Shuang; Cao, Dongyan; Yang, Jiaxin

    2015-01-01

    Gene promoter methylation may be used a potential biomarker for detecting solid tumor including cervical cancer. Here, we used methylation sensitive-high resolution melting (MS-HRM) analysis to detecting promoter methylation ratios of DAPK1, MGMT and RARB gene in patients with different cervical disease grade. The detection of gene promoter methylation was conducted in two hundred fifty patients’ samples including normal cytology (n=48), cervical intraepithelial neoplasia grade 1 (CIN1, n=54)...

  14. A new device for liver cancer biomarker detection with high accuracy

    Directory of Open Access Journals (Sweden)

    Shuaipeng Wang

    2015-06-01

    Full Text Available A novel cantilever array-based bio-sensor was batch-fabricated with IC compatible MEMS technology for precise liver cancer bio-marker detection. A micro-cavity was designed in the free end of the cantilever for local antibody-immobilization, thus adsorption of the cancer biomarker is localized in the micro-cavity, and the adsorption-induced k variation can be dramatically reduced with comparison to that caused by adsorption of the whole lever. The cantilever is pizeoelectrically driven into vibration which is pizeoresistively sensed by Wheatstone bridge. These structural features offer several advantages: high sensitivity, high throughput, high mass detection accuracy, and small volume. In addition, an analytical model has been established to eliminate the effect of adsorption-induced lever stiffness change and has been applied to precise mass detection of cancer biomarker AFP, the detected AFP antigen mass (7.6 pg/ml is quite close to the calculated one (5.5 pg/ml, two orders of magnitude better than the value by the fully antibody-immobilized cantilever sensor. These approaches will promote real application of the cantilever sensors in early diagnosis of cancer.

  15. Novel circulating peptide biomarkers for esophageal squamous cell carcinoma revealed by a magnetic bead-based MALDI-TOFMS assay.

    Science.gov (United States)

    Jia, Kun; Li, Wei; Wang, Feng; Qu, Haixia; Qiao, Yuanyuan; Zhou, Lanping; Sun, Yulin; Ma, Qingwei; Zhao, Xiaohang

    2016-04-26

    Esophageal squamous cell carcinoma (ESCC) is one of the most common malignant neoplasms worldwide. Patients are often diagnosed at advanced stages with poor prognosis due to the absence of obvious early symptoms. Here, we applied a high-throughput serum peptidome analysis to identify circulating peptide markers of ESCC. Weak cationic exchange magnetic beads coupled to matrix-assisted laser desorption/ionization time-of-flight mass spectrometry was used for two-stage proteotypic peptide profiling in complex serum samples collected from 477 cancer patients and healthy controls. We established a genetic algorithm model containing three significantly differentially expressed peptides at 1,925.5, 2,950.6 and 5,900.0 Da with a sensitivity and specificity of 97.00% and 95.92% in the training set and 97.03% and 100.00% in the validation set, respectively. The model's diagnostic capability was significantly better than SCC-Ag and Cyfra 21-1, especially for early stage ESCC, with an achieved sensitivity of 96.94%. Subsequently, these peptides were identified as fragments of AHSG, TSP1 and FGA by linear ion trap-orbitrap hybrid tandem mass spectrometry. Notably, increased tissue and serum levels of TSP1 in ESCC were verified and correlated with disease progression. In addition, tissue TSP1 was an independent poor prognostic factor in ESCC. In conclusion, the newly established circulating peptide panel and identified proteins could serve as potential biomarkers for the early detection and diagnosis of ESCC. Nevertheless, a larger cohort will be required for further unequivocal validation of their clinical application. PMID:26993605

  16. Identification of an epigenetic biomarker panel with high sensitivity and specificity for colorectal cancer and adenomas

    Directory of Open Access Journals (Sweden)

    Lind Guro E

    2011-07-01

    Full Text Available Abstract Background The presence of cancer-specific DNA methylation patterns in epithelial colorectal cells in human feces provides the prospect of a simple, non-invasive screening test for colorectal cancer and its precursor, the adenoma. This study investigates a panel of epigenetic markers for the detection of colorectal cancer and adenomas. Methods Candidate biomarkers were subjected to quantitative methylation analysis in test sets of tissue samples from colorectal cancers, adenomas, and normal colonic mucosa. All findings were verified in independent clinical validation series. A total of 523 human samples were included in the study. Receiver operating characteristic (ROC curve analysis was used to evaluate the performance of the biomarker panel. Results Promoter hypermethylation of the genes CNRIP1, FBN1, INA, MAL, SNCA, and SPG20 was frequent in both colorectal cancers (65-94% and adenomas (35-91%, whereas normal mucosa samples were rarely (0-5% methylated. The combined sensitivity of at least two positives among the six markers was 94% for colorectal cancers and 93% for adenoma samples, with a specificity of 98%. The resulting areas under the ROC curve were 0.984 for cancers and 0.968 for adenomas versus normal mucosa. Conclusions The novel epigenetic marker panel shows very high sensitivity and specificity for both colorectal cancers and adenomas. Our findings suggest this biomarker panel to be highly suitable for early tumor detection.

  17. Highly sensitive microscale in vivo sensor enabled by electrophoretic assembly of nanoparticles for multiple biomarker detection.

    Science.gov (United States)

    Malima, Asanterabi; Siavoshi, Salome; Musacchio, Tiziana; Upponi, Jaydev; Yilmaz, Cihan; Somu, Sivasubramanian; Hartner, William; Torchilin, Vladimir; Busnaina, Ahmed

    2012-11-21

    This paper describes a microscale in vivo sensor platform device for the simultaneous detection of multiple biomarkers. We designed the polymer-based biosensors incorporating multiple active isolated areas, as small as 70 μm × 70 μm, for antigen detection. The fabrication approach involved conventional micro- and nano-fabrication processes followed by site-specific electrophoretic directed assembly of antibody-functionalized nanoparticles. To ensure precise and large-scale manufacturing of these biosensors, we developed a semi-automated system for the attachment of the 250-μm biosensor to a 300-μm catheter probe. Our fabrication and post-processing procedures should enable large-scale production of such biosensor devices at lower manufacturing cost. The principle of detection with these biosensors involved a simple fluorescence-based enzyme-linked immunosorbent assay. These biosensors exhibit high selectivity (ability to selectively detect multiple biomarkers of different diseases), specificity (ability to target generic to specific disease biomarkers), rapid antigen uptake, and low detection limits (for carcinoembryonic antigen, 31.25 pg mL(-1); for nucleosomes, 62.5 pg mL(-1)), laying the foundation for potential early detection of various diseases. PMID:22983480

  18. Cell surface profiling using high-throughput flow cytometry: a platform for biomarker discovery and analysis of cellular heterogeneity.

    Directory of Open Access Journals (Sweden)

    Craig A Gedye

    Full Text Available Cell surface proteins have a wide range of biological functions, and are often used as lineage-specific markers. Antibodies that recognize cell surface antigens are widely used as research tools, diagnostic markers, and even therapeutic agents. The ability to obtain broad cell surface protein profiles would thus be of great value in a wide range of fields. There are however currently few available methods for high-throughput analysis of large numbers of cell surface proteins. We describe here a high-throughput flow cytometry (HT-FC platform for rapid analysis of 363 cell surface antigens. Here we demonstrate that HT-FC provides reproducible results, and use the platform to identify cell surface antigens that are influenced by common cell preparation methods. We show that multiple populations within complex samples such as primary tumors can be simultaneously analyzed by co-staining of cells with lineage-specific antibodies, allowing unprecedented depth of analysis of heterogeneous cell populations. Furthermore, standard informatics methods can be used to visualize, cluster and downsample HT-FC data to reveal novel signatures and biomarkers. We show that the cell surface profile provides sufficient molecular information to classify samples from different cancers and tissue types into biologically relevant clusters using unsupervised hierarchical clustering. Finally, we describe the identification of a candidate lineage marker and its subsequent validation. In summary, HT-FC combines the advantages of a high-throughput screen with a detection method that is sensitive, quantitative, highly reproducible, and allows in-depth analysis of heterogeneous samples. The use of commercially available antibodies means that high quality reagents are immediately available for follow-up studies. HT-FC has a wide range of applications, including biomarker discovery, molecular classification of cancers, or identification of novel lineage specific or stem cell

  19. High-sensitivity measurement of diverse vascular plant-derived biomarkers in high-altitude ice cores

    Science.gov (United States)

    Makou, Matthew C.; Thompson, Lonnie G.; Montluçon, Daniel B.; Eglinton, Timothy I.

    2009-07-01

    Semi-volatile organic compounds derived from burned and fresh vascular plant sources and preserved in high-altitude ice fields were detected and identified through use of recently developed analytical tools. Specifically, stir bar sorptive extraction and thermal desorption coupled with gas chromatography/time-of-flight mass spectrometry allowed measurement of multiple biomarkers in small sample volumes (≤30 ml). Among other compounds of interest, several diterpenoids, which suggest inputs from conifers and conifer burning, were identified in post-industrial era and older Holocene ice from the Sajama site in the Bolivian Andes, but not in a glacial period sample, consistent with aridity changes. Differences in biomarker assemblages between sites support the use of these compounds as regionally constrained recorders of vegetation and climate change. This study represents the first application of these analytical techniques to ice core research and the first indication that records of vegetation fires may be reconstructed from diterpenoids in ice.

  20. High-contrast grating resonators for label-free detection of disease biomarkers

    Science.gov (United States)

    Sun, Tianbo; Kan, Shu; Marriott, Gerard; Chang-Hasnain, Connie

    2016-06-01

    A label-free optical biosensor is described that employs a silicon-based high-contrast grating (HCG) resonator with a spectral linewidth of ~500 pm that is sensitive to ligand-induced changes in surface properties. The device is used to generate thermodynamic and kinetic data on surface-attached antibodies with their respective antigens. The device can detect serum cardiac troponin I, a biomarker of cardiac disease to 100 pg/ml within 4 mins, which is faster, and as sensitive as current enzyme-linked immuno-assays for cTnI.

  1. Promising Urinary Protein Biomarkers for the Early Detection of Hepatocellular Carcinoma among High-Risk Hepatitis C Virus Egyptian Patients.

    Science.gov (United States)

    Abdalla, Moemen Ak; Haj-Ahmad, Yousef

    2012-01-01

    Hepatocellular Carcinoma is a major healthcare problem, representing the third most common cause of cancer-related mortality worldwide. There are 130 million Hepatitis C virus infected patients worldwide who are at a high-risk for developing Hepatocellular Carcinoma. Due to the fact that reliable parameters and/or tools for the early detection of Hepatocellular Carcinoma among high-risk individuals are severely lacking, Hepatocellular Carcinoma patients are always diagnosed at a late stage where surgical solutions or effective treatment are not possible. Urine was collected from 106 Hepatitis C infected patients patients, 32 of whom had already developed Hepatocellular Carcinoma and 74 patients who were diagnosed as Hepatocellular Carcinoma -free at the time of initial sample collection. In addition to these patients, urine samples were also collected from 12 healthy control individuals. Total urinary proteins were isolated from the urine samples and LC-MS/MS was used to identify potential protein HCC biomarker candidates. This was followed by validating relative expression levels of proteins present in urine among all the patients using quantitative real time-PCR. This approach revealed that significant over-expression of three proteins: DJ-1, Chromatin Assembly Factor-1 (CAF-1) and Heat Shock Protein 60 (HSP60), was a characteristic event among Hepatocellular Carcinoma - post Hepatitis C virus infected patients. As a single-based Hepatocellular Carcinoma biomarker, CAF-1 over-expression identified Hepatocellular Carcinoma among Hepatitis C virus infected patients with a specificity of 90%, sensitivity of 66% and with an overall diagnostic accuracy of 78%. Moreover, the CAF-1/HSP60 tandem identified Hepatocellular Carcinoma among Hepatitis C virus infected patients with a specificity of 92%, sensitivity of 61% and with an overall diagnostic accuracy of 77%. PMID:23074380

  2. Promising Urinary Protein Biomarkers for the Early Detection of Hepatocellular Carcinoma among High-Risk Hepatitis C Virus Egyptian Patients

    Directory of Open Access Journals (Sweden)

    Moemen AK Abdalla, Yousef Haj-Ahmad

    2012-01-01

    Full Text Available Hepatocellular Carcinoma is a major healthcare problem, representing the third most common cause of cancer-related mortality worldwide. There are 130 million Hepatitis C virus infected patients worldwide who are at a high-risk for developing Hepatocellular Carcinoma. Due to the fact that reliable parameters and/or tools for the early detection of Hepatocellular Carcinoma among high-risk individuals are severely lacking, Hepatocellular Carcinoma patients are always diagnosed at a late stage where surgical solutions or effective treatment are not possible. Urine was collected from 106 Hepatitis C infected patients patients, 32 of whom had already developed Hepatocellular Carcinoma and 74 patients who were diagnosed as Hepatocellular Carcinoma -free at the time of initial sample collection. In addition to these patients, urine samples were also collected from 12 healthy control individuals. Total urinary proteins were isolated from the urine samples and LC-MS/MS was used to identify potential protein HCC biomarker candidates. This was followed by validating relative expression levels of proteins present in urine among all the patients using quantitative real time-PCR. This approach revealed that significant over-expression of three proteins: DJ-1, Chromatin Assembly Factor-1 (CAF-1 and Heat Shock Protein 60 (HSP60, was a characteristic event among Hepatocellular Carcinoma - post Hepatitis C virus infected patients. As a single-based Hepatocellular Carcinoma biomarker, CAF-1 over-expression identified Hepatocellular Carcinoma among Hepatitis C virus infected patients with a specificity of 90%, sensitivity of 66% and with an overall diagnostic accuracy of 78%. Moreover, the CAF-1/HSP60 tandem identified Hepatocellular Carcinoma among Hepatitis C virus infected patients with a specificity of 92%, sensitivity of 61% and with an overall diagnostic accuracy of 77%.

  3. Age of Terrestrial Biomarkers in Fluvial Transit Across the Andes-Amazon Reveal Timescales of Carbon Storage and Turnover

    Science.gov (United States)

    Ponton, C.; Feakins, S. J.; West, A. J.; Galy, V.

    2014-12-01

    Environmental signatures carried by fluvially-exported terrestrial organic matter are shaped by storage, remineralization and replacement at various spatial and temporal scales. Uncertainties in the timescales of these processes are key caveats in the accurate interpretation of sedimentary records. As part of a multi-isotope leaf wax biomarker project, we report the age of biomarkers transported by rivers from mountain to floodplain across the Andes-Amazon transition in southern Peru. We tracked the age of organic carbon using the radiocarbon (14ΔC) composition of plant leaf waxes extracted from particulate organic carbon (POC) in river suspended sediments. Leaf waxes from POC are younger in mountain headwaters (1000 yrs). Downstream aging is associated with the greater storage potential and residence times in lowland mineral soils and sedimentary sequences that include Pleistocene age eroding river terraces. Given three key observations that 1) carbon loading in suspended sediment does not substantively change from Andes to Amazon, 2) ~80% of sediment is sourced in the Andes, and 3) age increases downstream (this study); we find proof of the decoupling of organic carbon from sediment, which we attribute to loss of Andean carbon and replacement during transport.

  4. Differential gene expression profiling of Listeria monocytogenes in Cacciatore and Felino salami to reveal potential stress resistance biomarkers.

    Science.gov (United States)

    Mataragas, M; Rovetto, F; Bellio, A; Alessandria, V; Rantsiou, K; Decastelli, L; Cocolin, L

    2015-04-01

    The current study reports a) the in situ transcriptional profiles of Listeria monocytogenes in response to fermented sausage stress and b) an approach in which in situ RT-qPCR data have been combined with advanced statistical techniques to discover potential stress resistance or cell viability biomarkers. Gene expression profiling of the pathogen has been investigated using RT-qPCR to understand how L. monocytogenes responds to the conditions encountered during the fermentation and ripening of sausages. A cocktail of five L. monocytogenes strains was inoculated into the batter of Cacciatore and Felino sausages. The RT-qPCR data showed that the acidic and osmotic stress-related genes were up-regulated. The transcripts of the lmo0669 gene increased during the fermentation and ripening of Cacciatore, whereas gbuA and lmo1421 were up-regulated during the ripening of Felino and Cacciatore, respectively. sigB expression was induced in both sausages throughout the whole process. Finally, the virulence-related gene prfA was down-regulated during the fermentation of Cacciatore. The multivariate gene expression profiling analysis suggested that sigB and lmo1421 or sigB and gbuA could be used as different types of stress resistance biomarkers to track, for example, stress resistance or cell viability in fermented sausages with short (Cacciatore) or long (Felino) maturation times, respectively. PMID:25475310

  5. Biomarker screening of oral cancer cell lines revealed sub-populations of CD133-, CD44-, CD24- and ALDH1- positive cancer stem cells

    Directory of Open Access Journals (Sweden)

    Kendall K

    2013-05-01

    Full Text Available Head and neck squamous cell carcinoma (HNSCC ranks sixth worldwide for cancer-related mortality. For the past several decades the mainstay of treatment for HNSCC has been surgery and external beam radiation, although more recent trials combining chemotherapy and radiation have demonstrated improvements. However, cancer recurrence and treatment failures continue to occur in a significant percentage of patients. Recent advances in tumor biology have led to the discovery that many cancers, including HNSCC, may contain subpopulations of cells with stem cell-like properties that may explain relapse and recurrence. The objective of this study was to screen existing oral cancer cell lines for biomarkers specific for cells with stem cell-like properties. RNA was isolated for RT-PCR screening using primers for specific mRNA of the biomarkers: CD44, CD24, CD133, NANOG, Nestin, ALDH1, and ABCG2 in CAL27, SCC25 and SCC15 cells. This analysis revealed that some oral cancer cell lines (CAL27 and SCC25 may contain small subpopulations of adhesion- and contact-independent cells (AiDC that also express tumor stem cell markers, including CD44, CD133, and CD24. In addition, CAL27 cells also expressed the intracellular tumor stem cell markers, ALDH1 and ABCG2. Isolation and culture of the adhesion- and contact-independent cells from CAL27 and SCC25 populations revealed differential proliferation rates and more robust inhibition by the MEK inhibitor PD98059, as well as the chemotherapeutic agents Cisplatin and Paclitaxel, within the AiDC CAL27 cells. At least one oral cancer cell line (CAL27 contained subpopulations of cells that express specific biomarkers associated with tumor stem cells which were morphologically and phenotypically distinct from other cells within this cell line.

  6. Evaluation of high intensity focused ultrasound ablation of prostate tumor with hyperpolarized 13C imaging biomarkers

    Science.gov (United States)

    Lee, Jessie E.; Diederich, Chris J.; Salgaonkar, Vasant A.; Bok, Robert; Taylor, Andrew G.; Kurhanewicz, John

    2015-03-01

    Real-time hyperpolarized (HP) 13C MR can be utilized during high-intensity focal ultrasound (HIFU) therapy to improve treatment delivery strategies, provide treatment verification, and thus reduce the need for more radical therapies for lowand intermediate-risk prostate cancers. The goal is to develop imaging biomarkers specific to thermal therapies of prostate cancer using HIFU, and to predict the success of thermal coagulation and identify tissues potentially sensitized to adjuvant treatment by sub-ablative hyperthermic heat doses. Mice with solid prostate tumors received HIFU treatment (5.6 MHz, 160W/cm2, 60 s), and the MR imaging follow-ups were performed on a wide-bore 14T microimaging system. 13C-labeled pyruvate and urea were used to monitor tumor metabolism and perfusion accordingly. After treatment, the ablated tumor tissue had a loss in metabolism and perfusion. In the regions receiving sub-ablative heat dose, a timedependent change in metabolism and perfusion was observed. The untreated regions behaved as a normal untreated TRAMP prostate tumor would. This promising preliminary study shows the potential of using 13C MR imaging as biomarkers of HIFU/thermal therapies.

  7. High-field magnetic resonance imaging of brain iron: birth of a biomarker?

    Science.gov (United States)

    Schenck, John F; Zimmerman, Earl A

    2004-11-01

    The brain has an unusually high concentration of iron, which is distributed in an unusual pattern unlike that in any other organ. The physiological role of this iron and the reasons for this pattern of distribution are not yet understood. There is increasing evidence that several neurodegenerative diseases are associated with altered brain iron metabolism. Understanding these dysmetabolic conditions may provide important information for their diagnosis and treatment. For many years the iron distribution in the human brain could be studied effectively only under postmortem conditions. This situation was changed dramatically by the finding that T2-weighted MR imaging at high field strength (initially 1.5 T) appears to demonstrate the pattern of iron distribution in normal brains and that this imaging technique can detect changes in brain iron concentrations associated with disease states. Up to the present time this imaging capability has been utilized in many research applications but it has not yet been widely applied in the routine diagnosis and management of neurodegenerative disorders. However, recent advances in the basic science of brain iron metabolism, the clinical understanding of neurodegenerative diseases and in MRI technology, particularly in the availability of clinical scanners operating at the higher field strength of 3 T, suggest that iron-dependent MR imaging may soon provide biomarkers capable of characterizing the presence and progression of important neurological disorders. Such biomarkers may be of crucial assistance in the development and utilization of effective new therapies for Alzheimer's and Parkinson's diseases, multiple sclerosis and other iron-related CNS disorders which are difficult to diagnose and treat.

  8. Carbon sources in suspended particles and surface sediments from the Beaufort Sea revealed by molecular lipid biomarkers and compound-specific isotope analysis

    Directory of Open Access Journals (Sweden)

    I. Tolosa

    2013-03-01

    Full Text Available Molecular lipid biomarkers (hydrocarbons, alcohols, sterols and fatty acids and compound-specific isotope analysis of suspended particulate organic matter (SPM and surface sediments of the Mackenzie Shelf and slope (southeast Beaufort Sea, Arctic Ocean were studied in summer 2009. The concentrations of the molecular lipid markers, characteristic of known organic matter sources, were grouped and used as proxies to evaluate the relative importance of fresh algal, detrital algal, fossil, C3 terrestrial plants, bacterial and zooplankton material in the organic matter (OM of this area. Fossil and detrital algal contributions were the major fractions of the freshwater SPM from the Mackenzie River with ~34% each of the total molecular biomarkers. Fresh algal, C3 terrestrial, bacterial and zooplanktonic components represented much lower percentages, 17, 10, 4 and 80%, with a minor contribution of fossil and C3 terrestrial biomarkers. Characterization of the sediments revealed a major sink of refractory algal material mixed with some fresh algal material, fossil hydrocarbons and a small input of C3 terrestrial sources. In particular, the sediments from the shelf and at the mouth of the Amundsen Gulf presented the highest contribution of detrital algal material (60–75%, whereas those from the slope contained the highest proportion of fossil (40% and C3 terrestrial plant material (10%. Overall, considering that the detrital algal material is marine derived, autochthonous sources contributed more than allochthonous sources to the OM lipid pool. Using the ratio of an allochthonous biomarker (normalized to total organic carbon, TOC found in the sediments to those measured at the river mouth water, we estimated that the fraction of terrestrial material preserved in the sediments accounted for 30–40% of the total carbon in the inner shelf sediments, 17% in the outer shelf and Amundsen Gulf and up to 25% in the slope sediments. These estimates are low

  9. The low-abundance transcriptome reveals novel biomarkers, specific intracellular pathways and targetable genes associated with advanced gastric cancer.

    Science.gov (United States)

    Bizama, Carolina; Benavente, Felipe; Salvatierra, Edgardo; Gutiérrez-Moraga, Ana; Espinoza, Jaime A; Fernández, Elmer A; Roa, Iván; Mazzolini, Guillermo; Sagredo, Eduardo A; Gidekel, Manuel; Podhajcer, Osvaldo L

    2014-02-15

    Studies on the low-abundance transcriptome are of paramount importance for identifying the intimate mechanisms of tumor progression that can lead to novel therapies. The aim of the present study was to identify novel markers and targetable genes and pathways in advanced human gastric cancer through analyses of the low-abundance transcriptome. The procedure involved an initial subtractive hybridization step, followed by global gene expression analysis using microarrays. We observed profound differences, both at the single gene and gene ontology levels, between the low-abundance transcriptome and the whole transcriptome. Analysis of the low-abundance transcriptome led to the identification and validation by tissue microarrays of novel biomarkers, such as LAMA3 and TTN; moreover, we identified cancer type-specific intracellular pathways and targetable genes, such as IRS2, IL17, IFNγ, VEGF-C, WISP1, FZD5 and CTBP1 that were not detectable by whole transcriptome analyses. We also demonstrated that knocking down the expression of CTBP1 sensitized gastric cancer cells to mainstay chemotherapeutic drugs. We conclude that the analysis of the low-abundance transcriptome provides useful insights into the molecular basis and treatment of cancer. PMID:23907728

  10. New sepsis biomarkers

    Institute of Scientific and Technical Information of China (English)

    Dolores Limongi; Cartesio DAgostini; Marco Ciotti

    2016-01-01

    Sepsis remains a leading cause of death in the intensive care units and in all age groups worldwide. Early recognition and diagnosis are key to achieving improved outcomes. Therefore, novel biomarkers that might better inform clinicians treating such patients are surely needed. The main attributes of successful biomarkers would be high sensitivity, specificity, possibility of bedside monitoring and financial accessibility. A panel of sepsis biomarkers along with currently used laboratory tests will facilitate earlier diagnosis, timely treatment and improved outcome may be more effective than single biomarkers. In this review, we summarize the most recent advances on sepsis biomarkers evaluated in clinical and experimental studies.

  11. Determination of gouty arthritis' biomarkers in human urine using reversed-phase high-performance liquid chromatography

    Institute of Scientific and Technical Information of China (English)

    Lei-Wen Xiang; Jing Li; Jin-Ming Lin; Hai-Fang Li

    2014-01-01

    Creatinine, uric acid, hypoxanthine and xanthine are important diagnostic biomarkers in human urine for gouty arthritis or renal disease diacrisis. A simple method for simultaneous determination of these biomarkers in urine based on reversed-phase high-performance liquid chromatography (RP-HPLC) with ultraviolet (UV) detector was proposed. After pretreatment by dilution, centrifugation and filtration, the biomarkers in urine samples were separated by ODS-BP column by elution with methanol/50 mM NaH2PO4 buffer solution at pH 5.26 (5:95). Good linearity between peak areas and concentrations of standards was obtained for the biomarkers with correlation coefficients in the range of 0.9957-0.9993. The proposed analytical method has satisfactory repeatability (the recovery of data in a range of creatinine, uric acid, hypoxanthine and xanthine was 93.49-97.90%, 95.38-96.45%, 112.46-115.78%and 90.82-97.13%with standard deviation of o5%, respectively) and the limits of detection (LODs, S/N Z 3) for creatinine, uric acid, hypoxanthine, and xanthine were 0.010, 0.025, 0.050 and 0.025 mg/L, respectively. The established method was proved to be simple, accurate, sensitive and reliable for the quantitation of gouty arthritis' biomarkers in human urine samples. The ratio of creatinine to uric acid was found to be a possible factor for assessment of gouty arthritis.

  12. Proteomic analysis of coronary sinus serum reveals leucine-rich alpha2-glycoprotein as a novel biomarker of ventricular dysfunction and heart failure.

    LENUS (Irish Health Repository)

    Watson, Chris J

    2012-02-01

    BACKGROUND: Heart failure (HF) prevention strategies require biomarkers that identify disease manifestation. Increases in B-type natriuretic peptide (BNP) correlate with increased risk of cardiovascular events and HF development. We hypothesize that coronary sinus serum from a high BNP hypertensive population reflects an active pathological process and can be used for biomarker exploration. Our aim was to discover differentially expressed disease-associated proteins that identify patients with ventricular dysfunction and HF. METHODS AND RESULTS: Coronary sinus serum from 11 asymptomatic, hypertensive patients underwent quantitative differential protein expression analysis by 2-dimensional difference gel electrophoresis. Proteins were identified using mass spectrometry and then studied by enzyme-linked immunosorbent assay in sera from 40 asymptomatic, hypertensive patients and 105 patients across the spectrum of ventricular dysfunction (32 asymptomatic left ventricular diastolic dysfunction, 26 diastolic HF, and 47 systolic HF patients). Leucine-rich alpha2-glycoprotein (LRG) was consistently overexpressed in high BNP serum. LRG levels correlate significantly with BNP in hypertensive, asymptomatic left ventricular diastolic dysfunction, diastolic HF, and systolic HF patient groups (P<\\/=0.05). LRG levels were able to identify HF independent of BNP. LRG correlates with coronary sinus serum levels of tumor necrosis factor-alpha (P=0.009) and interleukin-6 (P=0.021). LRG is expressed in myocardial tissue and correlates with transforming growth factor-betaR1 (P<0.001) and alpha-smooth muscle actin (P=0.025) expression. CONCLUSIONS: LRG was identified as a serum biomarker that accurately identifies patients with HF. Multivariable modeling confirmed that LRG is a stronger identifier of HF than BNP and this is independent of age, sex, creatinine, ischemia, beta-blocker therapy, and BNP.

  13. Diatom-specific highly branched isoprenoids as biomarkers in Antarctic consumers.

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    Aurélie Goutte

    Full Text Available The structure, functioning and dynamics of polar marine ecosystems are strongly influenced by the extent of sea ice. Ice algae and pelagic phytoplankton represent the primary sources of nutrition for higher trophic-level organisms in seasonally ice-covered areas, but their relative contributions to polar marine consumers remain largely unexplored. Here, we investigated the potential of diatom-specific lipid markers and highly branched isoprenoids (HBIs for estimating the importance of these two carbon pools in an Antarctic pelagic ecosystem. Using GC-MS analysis, we studied HBI biomarkers in key marine species over three years in Adélie Land, Antarctica: euphausiids (ice krill Euphausia crystallorophias and Antarctic krill E. superba, fish (bald notothens Pagothenia borchgrevinki and Antarctic silverfish Pleuragramma antarcticum and seabirds (Adélie penguins Pygoscelis adeliae, snow petrels Pagodroma nivea and cape petrels Daption capense. This study provides the first evidence of the incorporation of HBI lipids in Antarctic pelagic consumers. Specifically, a di-unsaturated HBI (diene of sea ice origin was more abundant in ice-associated species than in pelagic species, whereas a tri-unsaturated HBI (triene of phytoplanktonic origin was more abundant in pelagic species than in ice-associated species. Moreover, the relative abundances of diene and triene in seabird tissues and eggs were higher during a year of good sea ice conditions than in a year of poor ice conditions. In turn, the higher contribution of ice algal derived organic matter to the diet of seabirds was related to earlier breeding and higher breeding success. HBI biomarkers are a promising tool for estimating the contribution of organic matter derived from ice algae in pelagic consumers from Antarctica.

  14. Diatom-specific highly branched isoprenoids as biomarkers in Antarctic consumers.

    Science.gov (United States)

    Goutte, Aurélie; Cherel, Yves; Houssais, Marie-Noëlle; Klein, Vincent; Ozouf-Costaz, Catherine; Raccurt, Mireille; Robineau, Camille; Massé, Guillaume

    2013-01-01

    The structure, functioning and dynamics of polar marine ecosystems are strongly influenced by the extent of sea ice. Ice algae and pelagic phytoplankton represent the primary sources of nutrition for higher trophic-level organisms in seasonally ice-covered areas, but their relative contributions to polar marine consumers remain largely unexplored. Here, we investigated the potential of diatom-specific lipid markers and highly branched isoprenoids (HBIs) for estimating the importance of these two carbon pools in an Antarctic pelagic ecosystem. Using GC-MS analysis, we studied HBI biomarkers in key marine species over three years in Adélie Land, Antarctica: euphausiids (ice krill Euphausia crystallorophias and Antarctic krill E. superba), fish (bald notothens Pagothenia borchgrevinki and Antarctic silverfish Pleuragramma antarcticum) and seabirds (Adélie penguins Pygoscelis adeliae, snow petrels Pagodroma nivea and cape petrels Daption capense). This study provides the first evidence of the incorporation of HBI lipids in Antarctic pelagic consumers. Specifically, a di-unsaturated HBI (diene) of sea ice origin was more abundant in ice-associated species than in pelagic species, whereas a tri-unsaturated HBI (triene) of phytoplanktonic origin was more abundant in pelagic species than in ice-associated species. Moreover, the relative abundances of diene and triene in seabird tissues and eggs were higher during a year of good sea ice conditions than in a year of poor ice conditions. In turn, the higher contribution of ice algal derived organic matter to the diet of seabirds was related to earlier breeding and higher breeding success. HBI biomarkers are a promising tool for estimating the contribution of organic matter derived from ice algae in pelagic consumers from Antarctica. PMID:23418580

  15. Highly selective biomarkers for pesticides developed in Eisenia fetida using SELDI-TOF MS.

    Science.gov (United States)

    Park, Doo-San; Jeon, Hwang-Ju; Park, Eun-Sil; Bae, In Kyung; Kim, Yong-Eun; Lee, Sung-Eun

    2015-03-01

    The repeated use of pesticides, and their subsequent residues, has contributed to severe adverse effects on the environment, including risks to human health. Therefore, it is important to assess the quality of the environment to ensure it remains free from pesticide residues. The six pesticides tested in this study showed high mortality on Eisenia fetida with LC50 values ranging from 7.7 to 37.9 g L(-1). The strongest lethal effect resulted from the organochlorine insecticide endosulfan (LC50=7.7 g L(-1)). Following exposure to the carbamate pesticides, acetylcholinesterase activity in E. fetida decreased dramatically in comparison to the control. Carboxylesterase activity was only lowered in E. fetida exposed to propoxur, when compared to the control. The remaining five pesticides had no significant effect on carboxylesterase activity in E. fetida. In order to discover pesticide-specific biomarkers with differentially expressed proteins after exposure to pesticides, protein patterns of pesticide-treated E. fetida were analyzed using SELDI-TOF MS with Q10 ProteinChips. Protein patterns were compared with their intensities at the same mass-to-charge ratios (m/z). All 42 peaks had intensities with associated p-values less than 0.089, and 40 of these peaks had associated p-values of 0.05. Using SELDI-TOF MS technology, selective biomarkers for the six pesticides tested were found in E. fetida; four proteins with 5425, 5697, 9523, and 9868 m/z were consistently observed in the earthworms following exposure to the carbamates.

  16. Differences in abundances of cell-signalling proteins in blood reveal novel biomarkers for early detection of clinical Alzheimer's disease.

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    Mateus Rocha de Paula

    Full Text Available BACKGROUND: In November 2007 a study published in Nature Medicine proposed a simple test based on the abundance of 18 proteins in blood to predict the onset of clinical symptoms of Alzheimer's Disease (AD two to six years before these symptoms manifest. Later, another study, published in PLoS ONE, showed that only five proteins (IL-1, IL-3, EGF, TNF- and G-CSF have overall better prediction accuracy. These classifiers are based on the abundance of 120 proteins. Such values were standardised by a Z-score transformation, which means that their values are relative to the average of all others. METHODOLOGY: The original datasets from the Nature Medicine paper are further studied using methods from combinatorial optimisation and Information Theory. We expand the original dataset by also including all pair-wise differences of z-score values of the original dataset ("metafeatures". Using an exact algorithm to solve the resulting Feature Set problem, used to tackle the feature selection problem, we found signatures that contain either only features, metafeatures or both, and evaluated their predictive performance on the independent test set. CONCLUSIONS: It was possible to show that a specific pattern of cell signalling imbalance in blood plasma has valuable information to distinguish between NDC and AD samples. The obtained signatures were able to predict AD in patients that already had a Mild Cognitive Impairment (MCI with up to 84% of sensitivity, while maintaining also a strong prediction accuracy of 90% on a independent dataset with Non Demented Controls (NDC and AD samples. The novel biomarkers uncovered with this method now confirms ANG-2, IL-11, PDGF-BB, CCL15/MIP-1; and supports the joint measurement of other signalling proteins not previously discussed: GM-CSF, NT-3, IGFBP-2 and VEGF-B.

  17. Novel diagnostic biomarkers for prostate cancer

    Directory of Open Access Journals (Sweden)

    Chikezie O. Madu, Yi Lu

    2010-01-01

    Full Text Available Prostate cancer is the most frequently diagnosed malignancy in American men, and a more aggressive form of the disease is particularly prevalent among African Americans. The therapeutic success rate for prostate cancer can be tremendously improved if the disease is diagnosed early. Thus, a successful therapy for this disease depends heavily on the clinical indicators (biomarkers for early detection of the presence and progression of the disease, as well as the prediction after the clinical intervention. However, the current clinical biomarkers for prostate cancer are not ideal as there remains a lack of reliable biomarkers that can specifically distinguish between those patients who should be treated adequately to stop the aggressive form of the disease and those who should avoid overtreatment of the indolent form.A biomarker is a characteristic that is objectively measured and evaluated as an indicator of normal biologic processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention. A biomarker reveals further information to presently existing clinical and pathological analysis. It facilitates screening and detecting the cancer, monitoring the progression of the disease, and predicting the prognosis and survival after clinical intervention. A biomarker can also be used to evaluate the process of drug development, and, optimally, to improve the efficacy and safety of cancer treatment by enabling physicians to tailor treatment for individual patients. The form of the prostate cancer biomarkers can vary from metabolites and chemical products present in body fluid to genes and proteins in the prostate tissues.Current advances in molecular techniques have provided new tools facilitating the discovery of new biomarkers for prostate cancer. These emerging biomarkers will be beneficial and critical in developing new and clinically reliable indicators that will have a high specificity for the diagnosis and prognosis of

  18. Novel diagnostic biomarkers for prostate cancer.

    Science.gov (United States)

    Madu, Chikezie O; Lu, Yi

    2010-10-06

    Prostate cancer is the most frequently diagnosed malignancy in American men, and a more aggressive form of the disease is particularly prevalent among African Americans. The therapeutic success rate for prostate cancer can be tremendously improved if the disease is diagnosed early. Thus, a successful therapy for this disease depends heavily on the clinical indicators (biomarkers) for early detection of the presence and progression of the disease, as well as the prediction after the clinical intervention. However, the current clinical biomarkers for prostate cancer are not ideal as there remains a lack of reliable biomarkers that can specifically distinguish between those patients who should be treated adequately to stop the aggressive form of the disease and those who should avoid overtreatment of the indolent form.A biomarker is a characteristic that is objectively measured and evaluated as an indicator of normal biologic processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention. A biomarker reveals further information to presently existing clinical and pathological analysis. It facilitates screening and detecting the cancer, monitoring the progression of the disease, and predicting the prognosis and survival after clinical intervention. A biomarker can also be used to evaluate the process of drug development, and, optimally, to improve the efficacy and safety of cancer treatment by enabling physicians to tailor treatment for individual patients. The form of the prostate cancer biomarkers can vary from metabolites and chemical products present in body fluid to genes and proteins in the prostate tissues.Current advances in molecular techniques have provided new tools facilitating the discovery of new biomarkers for prostate cancer. These emerging biomarkers will be beneficial and critical in developing new and clinically reliable indicators that will have a high specificity for the diagnosis and prognosis of prostate cancer. The

  19. A vegetable/fruit concentrate with high antioxidant capacity has no effect on biomarkers of antioxidant status in male smokers

    NARCIS (Netherlands)

    Berg, R. van den; Vliet, T. van; Broekmans, W.M.R.; Cnubben, N.H.P.; Vaes, W.H.J.; Roza, L.; Haenen, G.R.M.M.; Bast, A.; Berg, H. van den

    2001-01-01

    The potential benefits of a high fruit and vegetable intake on the antioxidant status and on relevant biomarkers of oxidative damage to lipids, proteins and DNA and on (functional) markers of oxidative stress were evaluated. A randomized, free living, open placebo-controlled cross-over trial of 3 wk

  20. Differential profiling of breast cancer plasma proteome by isotope-coded affinity tagging method reveals biotinidase as a breast cancer biomarker

    Directory of Open Access Journals (Sweden)

    Yu Myeong-Hee

    2010-03-01

    Full Text Available Abstract Background Breast cancer is one of the leading causes of women's death worldwide. It is important to discover a reliable biomarker for the detection of breast cancer. Plasma is the most ideal source for cancer biomarker discovery since many cells cross-communicate through the secretion of soluble proteins into blood. Methods Plasma proteomes obtained from 6 breast cancer patients and 6 normal healthy women were analyzed by using the isotope-coded affinity tag (ICAT labeling approach and tandem mass spectrometry. All the plasma samples used were depleted of highly abundant 6 plasma proteins by immune-affinity column chromatography before ICAT labeling. Several proteins showing differential abundance level were selected based on literature searches and their specificity to the commercially available antibodies, and then verified by immunoblot assays. Results A total of 155 proteins were identified and quantified by ICAT method. Among them, 33 proteins showed abundance changes by more than 1.5-fold between the plasmas of breast cancer patients and healthy women. We chose 5 proteins for the follow-up confirmation in the individual plasma samples using immunoblot assay. Four proteins, α1-acid glycoprotein 2, monocyte differentiation antigen CD14, biotinidase (BTD, and glutathione peroxidase 3, showed similar abundance ratio to ICAT result. Using a blind set of plasmas obtained from 21 breast cancer patients and 21 normal healthy controls, we confirmed that BTD was significantly down-regulated in breast cancer plasma (Wilcoxon rank-sum test, p = 0.002. BTD levels were lowered in all cancer grades (I-IV except cancer grade zero. The area under the receiver operating characteristic curve of BTD was 0.78. Estrogen receptor status (p = 0.940 and progesterone receptor status (p = 0.440 were not associated with the plasma BTD levels. Conclusions Our study suggests that BTD is a potential serological biomarker for the detection of breast cancer.

  1. IMAC fractionation in combination with LC-MS reveals H2B and NIF-1 peptides as potential bladder cancer biomarkers.

    Science.gov (United States)

    Frantzi, Maria; Zoidakis, Jerome; Papadopoulos, Theofilos; Zürbig, Petra; Katafigiotis, Ioannis; Stravodimos, Konstantinos; Lazaris, Andreas; Giannopoulou, Ioanna; Ploumidis, Achilles; Mischak, Harald; Mullen, William; Vlahou, Antonia

    2013-09-01

    Improvement in bladder cancer (BC) management requires more effective diagnosis and prognosis of disease recurrence and progression. Urinary biomarkers attract special interest because of the noninvasive means of urine collection. Proteomic analysis of urine entails the adoption of a fractionation methodology to reduce sample complexity. In this study, we applied immobilized metal affinity chromatography in combination with high-resolution LC-MS/MS for the discovery of native urinary peptides potentially associated with BC aggressiveness. This approach was employed toward urine samples from patients with invasive BC, noninvasive BC, and benign urogenital diseases. A total of 1845 peptides were identified, corresponding to a total of 638 precursor proteins. Specific enrichment for proteins involved in nucleosome assembly and for zinc-finger transcription factors was observed. The differential expression of two candidate biomarkers, histone H2B and NIF-1 (zinc finger 335) in BC, was verified in independent sets of urine samples by ELISA and by immunohistochemical analysis of BC tissue. The results collectively support changes in the expression of both of these proteins with tumor progression, suggesting their potential role as markers for discriminating BC stages. In addition, the data indicate a possible involvement of NIF-1 in BC progression, likely as a suppressor and through interactions with Sox9 and HoxA1.

  2. Proteomic analysis in type 2 diabetes patients before and after a very low calorie diet reveals potential disease state and intervention specific biomarkers.

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    Maria A Sleddering

    Full Text Available Very low calorie diets (VLCD with and without exercise programs lead to major metabolic improvements in obese type 2 diabetes patients. The mechanisms underlying these improvements have so far not been elucidated fully. To further investigate the mechanisms of a VLCD with or without exercise and to uncover possible biomarkers associated with these interventions, blood samples were collected from 27 obese type 2 diabetes patients before and after a 16-week VLCD (Modifast ∼ 450 kcal/day. Thirteen of these patients followed an exercise program in addition to the VCLD. Plasma was obtained from 27 lean and 27 obese controls as well. Proteomic analysis was performed using mass spectrometry (MS and targeted multiple reaction monitoring (MRM and a large scale isobaric tags for relative and absolute quantitation (iTRAQ approach. After the 16-week VLCD, there was a significant decrease in body weight and HbA1c in all patients, without differences between the two intervention groups. Targeted MRM analysis revealed differences in several proteins, which could be divided in diabetes-associated (fibrinogen, transthyretin, obesity-associated (complement C3, and diet-associated markers (apolipoproteins, especially apolipoprotein A-IV. To further investigate the effects of exercise, large scale iTRAQ analysis was performed. However, no proteins were found showing an exercise effect. Thus, in this study, specific proteins were found to be differentially expressed in type 2 diabetes patients versus controls and before and after a VLCD. These proteins are potential disease state and intervention specific biomarkers.Controlled-Trials.com ISRCTN76920690.

  3. Adaptation to High Ethanol Reveals Complex Evolutionary Pathways

    Science.gov (United States)

    Das, Anupam; Espinosa-Cantú, Adriana; De Maeyer, Dries; Arslan, Ahmed; Van Pee, Michiel; van der Zande, Elisa; Meert, Wim; Yang, Yudi; Zhu, Bo; Marchal, Kathleen; DeLuna, Alexander; Van Noort, Vera; Jelier, Rob; Verstrepen, Kevin J.

    2015-01-01

    Tolerance to high levels of ethanol is an ecologically and industrially relevant phenotype of microbes, but the molecular mechanisms underlying this complex trait remain largely unknown. Here, we use long-term experimental evolution of isogenic yeast populations of different initial ploidy to study adaptation to increasing levels of ethanol. Whole-genome sequencing of more than 30 evolved populations and over 100 adapted clones isolated throughout this two-year evolution experiment revealed how a complex interplay of de novo single nucleotide mutations, copy number variation, ploidy changes, mutator phenotypes, and clonal interference led to a significant increase in ethanol tolerance. Although the specific mutations differ between different evolved lineages, application of a novel computational pipeline, PheNetic, revealed that many mutations target functional modules involved in stress response, cell cycle regulation, DNA repair and respiration. Measuring the fitness effects of selected mutations introduced in non-evolved ethanol-sensitive cells revealed several adaptive mutations that had previously not been implicated in ethanol tolerance, including mutations in PRT1, VPS70 and MEX67. Interestingly, variation in VPS70 was recently identified as a QTL for ethanol tolerance in an industrial bio-ethanol strain. Taken together, our results show how, in contrast to adaptation to some other stresses, adaptation to a continuous complex and severe stress involves interplay of different evolutionary mechanisms. In addition, our study reveals functional modules involved in ethanol resistance and identifies several mutations that could help to improve the ethanol tolerance of industrial yeasts. PMID:26545090

  4. Accumulated metabolites of hydroxybutyric acid serve as diagnostic and prognostic biomarkers of ovarian high-grade serous carcinomas

    Science.gov (United States)

    Hilvo, Mika; de Santiago, Ines; Gopalacharyulu, Peddinti; Schmitt, Wolfgang D.; Budczies, Jan; Kuhberg, Marc; Dietel, Manfred; Aittokallio, Tero; Markowetz, Florian; Denkert, Carsten; Sehouli, Jalid; Frezza, Christian

    2016-01-01

    Ovarian cancer is a heterogeneous disease of low prevalence, but poor survival. Early diagnosis is critical for survival, but is often challenging because the symptoms of ovarian cancer are subtle and become apparent only during advanced stages of the disease. Therefore, the identification of robust biomarkers of early disease is a clinical priority. Metabolomic profiling is an emerging diagnostic tool enabling the detection of biomarkers reflecting alterations in tumor metabolism, a hallmark of cancer. In this study, we performed metabolomic profiling of serum and tumor tissue from 158 patients with high-grade serous ovarian cancer (HGSOC) and 100 control patients with benign or non-neoplastic lesions. We report metabolites of hydroxybutyric acid (HBA) as novel diagnostic and prognostic biomarkers associated with tumor burden and patient survival. The accumulation of HBA metabolites caused by HGSOC was also associated with reduced expression of succinic semialdehyde dehydrogenase (encoded by ALDH5A1), and with the presence of an epithelial-to-mesenchymal transition (EMT) gene signature, implying a role for these metabolic alterations in cancer cell migration and invasion. In conclusion, our findings represent the first comprehensive metabolomics analysis in HGSOC and propose a new set of metabolites as biomarkers of disease with diagnostic and prognostic capabilities. PMID:26685161

  5. High-Sensitivity and Low-Toxicity Fucose Probe for Glycan Imaging and Biomarker Discovery.

    Science.gov (United States)

    Kizuka, Yasuhiko; Funayama, Sho; Shogomori, Hidehiko; Nakano, Miyako; Nakajima, Kazuki; Oka, Ritsuko; Kitazume, Shinobu; Yamaguchi, Yoshiki; Sano, Masahiro; Korekane, Hiroaki; Hsu, Tsui-Ling; Lee, Hsiu-Yu; Wong, Chi-Huey; Taniguchi, Naoyuki

    2016-07-21

    Fucose, a terminal sugar in glycoconjugates, critically regulates various physiological and pathological phenomena, including cancer development and inflammation. However, there are currently no probes for efficient labeling and detection of this sugar. We chemically synthesized a novel series of alkynyl-fucose analogs as probe candidates and found that 7-alkynyl-fucose gave the highest labeling efficiency and low cytotoxicity. Among the fucose analogs, 7-alkynyl-fucose was the best substrate against all five fucosyltransferases examined. We confirmed its conversion to the corresponding guanosine diphosphate derivative in cells and found that cellular glycoproteins were labeled much more efficiently with 7-alkynyl-fucose than with an existing probe. 7-Alkynyl-fucose was detected in the N-glycan core by mass spectrometry, and 7-alkynyl-fucose-modified proteins mostly disappeared in core-fucose-deficient mouse embryonic fibroblasts, suggesting that this analog mainly labeled core fucose in these cells. These results indicate that 7-alkynyl-fucose is a highly sensitive and powerful tool for basic glycobiology research and clinical application for biomarker discovery. PMID:27447047

  6. High-Sensitivity and Low-Toxicity Fucose Probe for Glycan Imaging and Biomarker Discovery.

    Science.gov (United States)

    Kizuka, Yasuhiko; Funayama, Sho; Shogomori, Hidehiko; Nakano, Miyako; Nakajima, Kazuki; Oka, Ritsuko; Kitazume, Shinobu; Yamaguchi, Yoshiki; Sano, Masahiro; Korekane, Hiroaki; Hsu, Tsui-Ling; Lee, Hsiu-Yu; Wong, Chi-Huey; Taniguchi, Naoyuki

    2016-07-21

    Fucose, a terminal sugar in glycoconjugates, critically regulates various physiological and pathological phenomena, including cancer development and inflammation. However, there are currently no probes for efficient labeling and detection of this sugar. We chemically synthesized a novel series of alkynyl-fucose analogs as probe candidates and found that 7-alkynyl-fucose gave the highest labeling efficiency and low cytotoxicity. Among the fucose analogs, 7-alkynyl-fucose was the best substrate against all five fucosyltransferases examined. We confirmed its conversion to the corresponding guanosine diphosphate derivative in cells and found that cellular glycoproteins were labeled much more efficiently with 7-alkynyl-fucose than with an existing probe. 7-Alkynyl-fucose was detected in the N-glycan core by mass spectrometry, and 7-alkynyl-fucose-modified proteins mostly disappeared in core-fucose-deficient mouse embryonic fibroblasts, suggesting that this analog mainly labeled core fucose in these cells. These results indicate that 7-alkynyl-fucose is a highly sensitive and powerful tool for basic glycobiology research and clinical application for biomarker discovery.

  7. DAPK1, MGMT and RARB promoter methylation as biomarkers for high-grade cervical lesions

    Science.gov (United States)

    Sun, Yin; Li, Shu; Shen, Keng; Ye, Shuang; Cao, Dongyan; Yang, Jiaxin

    2015-01-01

    Gene promoter methylation may be used a potential biomarker for detecting solid tumor including cervical cancer. Here, we used methylation sensitive-high resolution melting (MS-HRM) analysis to detecting promoter methylation ratios of DAPK1, MGMT and RARB gene in patients with different cervical disease grade. The detection of gene promoter methylation was conducted in two hundred fifty patients’ samples including normal cytology (n=48), cervical intraepithelial neoplasia grade 1 (CIN1, n=54), cervical intraepithelial neoplasia grade 2 (CIN2, n=47), cervical intraepithelial neoplasia grade 3 (CIN3, n=56) and cervical squamous cell carcinomas (SCS, n=45). We found there were a significant positive correlation between the promoter methylation status of DAPK1 and cervical disease grade (P=0.022). In addition, the methylated promoters of DAPK1 combined with MGMT, MGMT combined with RARB, DAPK1 combined with RARB were positive correlated with cervical disease grade (P < 0.05). All three genes promoters methylated were positive correlated with cervical disease grade (P < 0.001). Receiver operating characteristic (ROC) curves was conducted to evaluate whether the three genes methylation could be used to be a potential marker for diagnosing high grade cervical disease (HSIL and SCC). The cutoff values for the methylation rates of all these genes were 0-5%. Regrettably, only the methylation of MGMT combined with DAPK1 gave 43.4% sensitivity and 68.6% specificity. The current results indicated that MS-HRM-based testing for DNA methylations of MGMT plus DAPK1 genes holds some promise for high grade cervical disease screening. PMID:26823825

  8. Proteomic Analysis of Plasma from California Sea Lions (Zalophus californianus Reveals Apolipoprotein E as a Candidate Biomarker of Chronic Domoic Acid Toxicosis.

    Directory of Open Access Journals (Sweden)

    Benjamin A Neely

    Full Text Available Domoic acid toxicosis (DAT in California sea lions (Zalophus californianus is caused by exposure to the marine biotoxin domoic acid and has been linked to massive stranding events and mortality. Diagnosis is based on clinical signs in addition to the presence of domoic acid in body fluids. Chronic DAT further is characterized by reoccurring seizures progressing to status epilepticus. Diagnosis of chronic DAT is often slow and problematic, and minimally invasive tests for DAT have been the focus of numerous recent biomarker studies. The goal of this study was to retrospectively profile plasma proteins in a population of sea lions with chronic DAT and those without DAT using two dimensional gel electrophoresis to discover whether individual, multiple, or combinations of protein and clinical data could be utilized to identify sea lions with DAT. Using a training set of 32 sea lion sera, 20 proteins and their isoforms were identified that were significantly different between the two groups (p<0.05. Interestingly, 11 apolipoprotein E (ApoE charge forms were decreased in DAT samples, indicating that ApoE charge form distributions may be important in the progression of DAT. In order to develop a classifier of chronic DAT, an independent blinded test set of 20 sea lions, seven with chronic DAT, was used to validate models utilizing ApoE charge forms and eosinophil counts. The resulting support vector machine had high sensitivity (85.7% with 92.3% negative predictive value and high specificity (92.3% with 85.7% positive predictive value. These results suggest that ApoE and eosinophil counts along with machine learning can perform as a robust and accurate tool to diagnose chronic DAT. Although this analysis is specifically focused on blood biomarkers and routine clinical data, the results demonstrate promise for future studies combining additional variables in multidimensional space to create robust classifiers.

  9. Determination of gouty arthritis' biomarkers in human urine using reversed-phase high-performance liquid chromatography

    Directory of Open Access Journals (Sweden)

    Lei-Wen Xiang

    2014-04-01

    Full Text Available Creatinine, uric acid, hypoxanthine and xanthine are important diagnostic biomarkers in human urine for gouty arthritis or renal disease diacrisis. A simple method for simultaneous determination of these biomarkers in urine based on reversed-phase high-performance liquid chromatography (RP-HPLC with ultraviolet (UV detector was proposed. After pretreatment by dilution, centrifugation and filtration, the biomarkers in urine samples were separated by ODS-BP column by elution with methanol/50 mM NaH2PO4 buffer solution at pH 5.26 (5:95. Good linearity between peak areas and concentrations of standards was obtained for the biomarkers with correlation coefficients in the range of 0.9957–0.9993. The proposed analytical method has satisfactory repeatability (the recovery of data in a range of creatinine, uric acid, hypoxanthine and xanthine was 93.49–97.90%, 95.38–96.45%, 112.46–115.78% and 90.82–97.13% with standard deviation of <5%, respectively and the limits of detection (LODs, S/N≥3 for creatinine, uric acid, hypoxanthine, and xanthine were 0.010, 0.025, 0.050 and 0.025 mg/L, respectively. The established method was proved to be simple, accurate, sensitive and reliable for the quantitation of gouty arthritis' biomarkers in human urine samples. The ratio of creatinine to uric acid was found to be a possible factor for assessment of gouty arthritis.

  10. A TMA de-arraying method for high throughput biomarker discovery in tissue research.

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    Yinhai Wang

    Full Text Available BACKGROUND: Tissue MicroArrays (TMAs represent a potential high-throughput platform for the analysis and discovery of tissue biomarkers. As TMA slides are produced manually and subject to processing and sectioning artefacts, the layout of TMA cores on the final slide and subsequent digital scan (TMA digital slide is often disturbed making it difficult to associate cores with their original position in the planned TMA map. Additionally, the individual cores can be greatly altered and contain numerous irregularities such as missing cores, grid rotation and stretching. These factors demand the development of a robust method for de-arraying TMAs which identifies each TMA core, and assigns them to their appropriate coordinates on the constructed TMA slide. METHODOLOGY: This study presents a robust TMA de-arraying method consisting of three functional phases: TMA core segmentation, gridding and mapping. The segmentation of TMA cores uses a set of morphological operations to identify each TMA core. Gridding then utilises a Delaunay Triangulation based method to find the row and column indices of each TMA core. Finally, mapping correlates each TMA core from a high resolution TMA whole slide image with its name within a TMAMap. CONCLUSION: This study describes a genuine robust TMA de-arraying algorithm for the rapid identification of TMA cores from digital slides. The result of this de-arraying algorithm allows the easy partition of each TMA core for further processing. Based on a test group of 19 TMA slides (3129 cores, 99.84% of cores were segmented successfully, 99.81% of cores were gridded correctly and 99.96% of cores were mapped with their correct names via TMAMaps. The gridding of TMA cores were also extensively tested using a set of 113 pseudo slide (13,536 cores with a variety of irregular grid layouts including missing cores, rotation and stretching. 100% of the cores were gridded correctly.

  11. High-Dimensional Medial Lobe Morphometry: An Automated MRI Biomarker for the New AD Diagnostic Criteria

    Directory of Open Access Journals (Sweden)

    Simon Duchesne

    2014-01-01

    Full Text Available Introduction. Medial temporal lobe atrophy assessment via magnetic resonance imaging (MRI has been proposed in recent criteria as an in vivo diagnostic biomarker of Alzheimer’s disease (AD. However, practical application of these criteria in a clinical setting will require automated MRI analysis techniques. To this end, we wished to validate our automated, high-dimensional morphometry technique to the hypothetical prediction of future clinical status from baseline data in a cohort of subjects in a large, multicentric setting, compared to currently known clinical status for these subjects. Materials and Methods. The study group consisted of 214 controls, 371 mild cognitive impairment (147 having progressed to probable AD and 224 stable, and 181 probable AD from the Alzheimer’s Disease Neuroimaging Initiative, with data acquired on 58 different 1.5 T scanners. We measured the sensitivity and specificity of our technique in a hierarchical fashion, first testing the effect of intensity standardization, then between different volumes of interest, and finally its generalizability for a large, multicentric cohort. Results. We obtained 73.2% prediction accuracy with 79.5% sensitivity for the prediction of MCI progression to clinically probable AD. The positive predictive value was 81.6% for MCI progressing on average within 1.5 (0.3 s.d. year. Conclusion. With high accuracy, the technique’s ability to identify discriminant medial temporal lobe atrophy has been demonstrated in a large, multicentric environment. It is suitable as an aid for clinical diagnostic of AD.

  12. Toward rapid, high-sensitivity, volume-constrained biomarker quantification and validation using backscattering interferometry.

    Science.gov (United States)

    Olmsted, Ian R; Hassanein, Mohamed; Kussrow, Amanda; Hoeksema, Megan; Li, Ming; Massion, Pierre P; Bornhop, Darryl J

    2014-08-01

    Realizing personalized medicine, which promises to enable early disease detection, efficient diagnostic staging, and therapeutic efficacy monitoring, hinges on biomarker quantification in patient samples. Yet, the lack of a sensitive technology and assay methodology to rapidly validate biomarker candidates continues to be a bottleneck for clinical translation. In our first direct and quantitative comparison of backscattering interferometry (BSI) to fluorescence sensing by ELISA, we show that BSI could aid in overcoming this limitation. The analytical validation study was performed against ELISA for two biomarkers for lung cancer detection: Cyfra 21-1 and Galectin-7. Spiked serum was used for calibration and comparison of analytical figures of merit, followed by analysis of blinded patient samples. Using the ELISA antibody as the probe chemistry in a mix-and-read assay, BSI provided significantly lower detection limits for spiked serum samples with each of the biomarkers. The limit of quantification (LOQ) for Cyrfa-21-1 was measured to be 230 pg/mL for BSI versus 4000 pg/mL for ELISA, and for Galectin-7, it was 13 pg/mL versus 500 pg/mL. The coefficient of variation for 5 day, triplicate determinations was Cyfra 21-1 in a blinded patient sample analysis. The label-free and free-solution operation of BSI allowed for a significant improvement in analysis speed, with greater ease, improved LOQ values, and excellent day-to-day reproducibility. In this unoptimized format, BSI required 5.5-fold less sample quantity needed for ELISA (a 10 point calibration curve measured in triplicate required 36 μL of serum for BSI vs 200 μL for ELISA). The results indicate that the BSI platform can enable rapid, sensitive analytical validation of serum biomarkers and should significantly impact the validation bottleneck of biomarkers. PMID:24954171

  13. Optimized high-throughput microRNA expression profiling provides novel biomarker assessment of clinical prostate and breast cancer biopsies

    OpenAIRE

    Fedele Vita; Scott Gary K; Wong Linda; Sensinger Kelly; Bowers Jessica; Benz Christopher C; Mattie Michael D; Ginzinger David; Getts Robert; Haqq Chris

    2006-01-01

    Abstract Background Recent studies indicate that microRNAs (miRNAs) are mechanistically involved in the development of various human malignancies, suggesting that they represent a promising new class of cancer biomarkers. However, previously reported methods for measuring miRNA expression consume large amounts of tissue, prohibiting high-throughput miRNA profiling from typically small clinical samples such as excision or core needle biopsies of breast or prostate cancer. Here we describe a no...

  14. Respiratory Toxicity Biomarkers

    Science.gov (United States)

    The advancement in high throughput genomic, proteomic and metabolomic techniques have accelerated pace of lung biomarker discovery. A recent growth in the discovery of new lung toxicity/disease biomarkers have led to significant advances in our understanding of pathological proce...

  15. Functional connectivity classification of autism identifies highly predictive brain features but falls short of biomarker standards

    Directory of Open Access Journals (Sweden)

    Mark Plitt

    2015-01-01

    Conclusions: While individuals can be classified as having ASD with statistically significant accuracy from their rs-fMRI scans alone, this method falls short of biomarker standards. Classification methods provided further evidence that ASD functional connectivity is characterized by dysfunction of large-scale functional networks, particularly those involved in social information processing.

  16. High-Throughput Proteomic Approaches to the Elucidation of Potential Biomarkers of Chronic Allograft Injury (CAI

    Directory of Open Access Journals (Sweden)

    Hilary Cassidy

    2013-09-01

    Full Text Available This review focuses on the role of OMICs technologies, concentrating in particular on proteomics, in biomarker discovery in chronic allograft injury (CAI. CAI is the second most prevalent cause of allograft dysfunction and loss in the first decade post-transplantation, after death with functioning graft (DWFG. The term CAI, sometimes referred to as chronic allograft nephropathy (CAN, describes the deterioration of renal allograft function and structure as a result of immunological processes (chronic antibody-mediated rejection, and other non-immunological factors such as calcineurin inhibitor (CNI induced nephrotoxicity, hypertension and infection. Current methods for assessing allograft function are costly, insensitive and invasive; traditional kidney function measurements such as serum creatinine and glomerular filtration rate (GFR display poor predictive abilities, while the current “gold-standard” involving histological diagnosis with a renal biopsy presents its own inherent risks to the overall health of the allograft. As early as two years post-transplantation, protocol biopsies have shown more than 50% of allograft recipients have mild CAN; ten years post-transplantation more than 50% of the allograft recipients have progressed to severe CAN which is associated with diminishing graft function. Thus, there is a growing medical requirement for minimally invasive biomarkers capable of identifying the early stages of the disease which would allow for timely intervention. Proteomics involves the study of the expression, localization, function and interaction of the proteome. Proteomic technologies may be powerful tools used to identify novel biomarkers which would predict CAI in susceptible individuals. In this paper we will review the use of proteomics in the elucidation of novel predictive biomarkers of CAI in clinical, animal and in vitro studies.

  17. Applying petroleum biomarkers as a tool for confirmation of petroleum hydrocarbons in high organic content soils

    Energy Technology Data Exchange (ETDEWEB)

    O' Sullivan, G.; Martin, E.J.; Waddell, J.; Sandau, C.D. [TRIUM Environmental Solutions, Cochrane, AB (Canada); Denham, G. [Nexen Inc., Calgary, AB (Canada); Samis, M.W. [Great Plains Environmental Management Ltd., Medecine Hat, AB (Canada)

    2009-10-01

    It is often difficult to separate naturally occurring phytogenic organic materials from petrogenic sources in routine gas chromatography flame ionization detection (GC-FID) analyses. Phytogenic compounds include tannins, waxes, terpenes, fats and oils. This study examined the use of petroleum biomarkers as a means of determining the nature, sources, type and geological conditions of the formation of petroleum hydrocarbons (PHCs). The analysis was conducted at a former well site consisting of low-lying peat marshlands that had the potential to interfere with the delineation of PHC impacts. Fourteen boreholes and 8 hand auger holes were placed at the site. Soil samples were analyzed for salinity, metals, and PHC constituents. Biomarker targets included acyclic isoprenoid compounds, polycyclic aromatic hydrocarbon (PAH) compounds, terpanes, hopanes, and triaromatic steranes. A grain-size analysis showed the presence of peat materials within the saturated zone. Results of the study demonstrated the presence of PHC constituents that exceeded applicable guidelines. The biomarker analysis was used to statistically determine site-specific background levels of hydrocarbons. Nearly 3000 tonnes of soil were excavated from the site. It was concluded that site-specific conditions should be taken into consideration when evaluating reclamation targets. 3 refs., 6 figs.

  18. Highly sensitive covalently functionalized light-addressable potentiometric sensor for determination of biomarker.

    Science.gov (United States)

    Liang, Jintao; Guan, Mingyuan; Huang, Guoyin; Qiu, Hengming; Chen, Zhengcheng; Li, Guiyin; Huang, Yong

    2016-06-01

    A biomarker is related to the biological status of a living organism and shows great promise for the early prediction of a related disease. Herein we presented a novel structured light-addressable potentiometric sensor (LAPS) for the determination of a model biomarker, human immunoglobulin G (hIgG). In this system, the goat anti-human immunoglobulin G antibody was used as recognition element and covalently immobilized on the surface of light-addressable potentiometric sensor chip to capture human immunoglobulin G. Due to the light addressable capability of light-addressable potentiometric sensor, human immunoglobulin G dissolved in the supporting electrolyte solution can be detected by monitoring the potential shifts of the sensor. In order to produce a stable photocurrent, the laser diode controlled by field-programmable gate array was used as the light emitter to drive the light-addressable potentiometric sensor. A linear correlation between the potential shift response and the concentration of human immunoglobulin G was achieved and the corresponding regression equation was ΔV (V)=0.00714ChIgG (μg/mL)-0.0147 with a correlation coefficient of 0.9968 over a range 0-150 μg/mL. Moreover, the light-addressable potentiometric sensor system also showed acceptable stability and reproducibility. All the results demonstrated that the system was more applicable to detection of disease biomarkers with simple operation, multiple-sample format and might hold great promise in various environmental, food, and clinical applications.

  19. Trophic ecology of two cold-water coral species from the Mediterranean Sea revealed by lipid biomarkers and compound-specific isotope analyses

    Science.gov (United States)

    Naumann, Malik S.; Tolosa, Imma; Taviani, Marco; Grover, Renaud; Ferrier-Pagès, Christine

    2015-12-01

    Scleractinian cold-water corals (CWC) act as key ecosystem engineers in deep-sea reef environments worldwide. However, our current understanding of their trophic ecology is still limited, particularly in understudied temperate oceanic regions such as the Mediterranean Sea. Hence, this study investigated the trophic ecology of the CWC Desmophyllum dianthus and Madrepora oculata by employing lipid biomarker techniques and compound-specific isotope analyses on coral tissues, suspended particulate organic matter (sPOM), and surface sediment sampled in a Mediterranean CWC habitat. CWC exhibited high contents of poly- and monounsaturated fatty acids (FA) (≥49 and 32 % of FA, respectively) and cholesterol (≥67 % of sterols), while sPOM and sediment samples were enriched in saturated FA (≥44 % of FA) and sitosterol (≥35 % of sterols). CWC contained some rare very long-chained polyunsaturated FA (>C22) and ergosterol absent in sPOM and sediment samples. Our results indicate that Mediterranean CWC mainly consume living food items, rather than detrital sPOM or resuspended sediment, and provide evidence for preferred feeding on omnivorous and carnivorous zooplankton. Overall, these findings provide new insights to the trophic ecology of two common CWC from the Mediterranean Sea.

  20. Biomarkers for systemic lupus erythematosus.

    Science.gov (United States)

    Ahearn, Joseph M; Liu, Chau-Ching; Kao, Amy H; Manzi, Susan

    2012-04-01

    The urgent need for lupus biomarkers was demonstrated in September 2011 during a Workshop sponsored by the Food and Drug Administration: Potential Biomarkers Predictive of Disease Flare. After 2 days of discussion and more than 2 dozen presentations from thought leaders in both industry and academia, it became apparent that highly sought biomarkers to predict lupus flare have not yet been identified. Even short of the elusive biomarker of flare, few biomarkers for systemic lupus erythematosus (SLE) diagnosis, monitoring, and stratification have been validated and employed for making clinical decisions. This lack of reliable, specific biomarkers for SLE hampers proper clinical management of patients with SLE and impedes development of new lupus therapeutics. As such, the intensity of investigation to identify lupus biomarkers is climbing a steep trajectory, lending cautious optimism that a validated panel of biomarkers for lupus diagnosis, monitoring, stratification, and prediction of flare may soon be in hand.

  1. Wafer-scale high-resolution patterning of reduced graphene oxide films for detection of low concentration biomarkers in plasma

    Science.gov (United States)

    Kim, Jinsik; Chae, Myung-Sic; Lee, Sung Min; Jeong, Dahye; Lee, Byung Chul; Lee, Jeong Hoon; Kim, Youngsoo; Chang, Suk Tai; Hwang, Kyo Seon

    2016-08-01

    Given that reduced graphene oxide (rGO)-based biosensors allow disposable and repeatable biomarker detection at the point of care, we developed a wafer-scale rGO patterning method with mass productivity, uniformity, and high resolution by conventional micro-electro-mechanical systems (MEMS) techniques. Various rGO patterns were demonstrated with dimensions ranging from 5 μm up to several hundred μm. Manufacture of these patterns was accomplished through the optimization of dry etching conditions. The axis-homogeneity and uniformity were also measured to verify the uniform patternability in 4-inch wafer with dry etching. Over 66.2% of uniform rGO patterns, which have deviation of resistance within range of ±10%, formed the entire wafer. We selected amyloid beta (Aβ) peptides in the plasma of APP/PS1 transgenic mice as a study model and measured the peptide level by resistance changes of highly uniform rGO biosensor arrays. Aβ is a pathological hallmark of Alzheimer’s disease and its plasma concentration is in the pg mL‑1 range. The sensor detected the Aβ peptides with ultra-high sensitivity; the LOD was at levels as low as 100 fg mL‑1. Our results provide biological evidences that this wafer-scale high-resolution patterning method can be used in rGO-based electrical diagnostic devices for detection of low-level protein biomarkers in biofluids.

  2. Highly sensitive covalently functionalized light-addressable potentiometric sensor for determination of biomarker.

    Science.gov (United States)

    Liang, Jintao; Guan, Mingyuan; Huang, Guoyin; Qiu, Hengming; Chen, Zhengcheng; Li, Guiyin; Huang, Yong

    2016-06-01

    A biomarker is related to the biological status of a living organism and shows great promise for the early prediction of a related disease. Herein we presented a novel structured light-addressable potentiometric sensor (LAPS) for the determination of a model biomarker, human immunoglobulin G (hIgG). In this system, the goat anti-human immunoglobulin G antibody was used as recognition element and covalently immobilized on the surface of light-addressable potentiometric sensor chip to capture human immunoglobulin G. Due to the light addressable capability of light-addressable potentiometric sensor, human immunoglobulin G dissolved in the supporting electrolyte solution can be detected by monitoring the potential shifts of the sensor. In order to produce a stable photocurrent, the laser diode controlled by field-programmable gate array was used as the light emitter to drive the light-addressable potentiometric sensor. A linear correlation between the potential shift response and the concentration of human immunoglobulin G was achieved and the corresponding regression equation was ΔV (V)=0.00714ChIgG (μg/mL)-0.0147 with a correlation coefficient of 0.9968 over a range 0-150μg/mL. Moreover, the light-addressable potentiometric sensor system also showed acceptable stability and reproducibility. All the results demonstrated that the system was more applicable to detection of disease biomarkers with simple operation, multiple-sample format and might hold great promise in various environmental, food, and clinical applications. PMID:27040210

  3. The Glycan Role in the Glycopeptide Immunogenicity Revealed by Atomistic Simulations and Spectroscopic Experiments on the Multiple Sclerosis Biomarker CSF114(Glc)

    Science.gov (United States)

    Bruno, Agostino; Scrima, Mario; Novellino, Ettore; D'Errico, Gerardino; D'Ursi, Anna Maria; Limongelli, Vittorio

    2015-03-01

    Glycoproteins are often recognized as not-self molecules by antibodies triggering the onset of severe autoimmune diseases such as Multiple Sclerosis (MS). Thus, the development of antigen-mimicking biomarkers represents an attractive strategy for an early diagnosis of the disease. An example is the synthetic glycopeptide CSF114(Glc), which was designed and tested as MS biomarker and whose clinical application was limited by its reduced ability to detect autoantibodies in MS patients. In the attempt to improve the efficacy of CSF114(Glc), we have characterized all the events leading to the final binding of the biomarker to the autoantibody using atomistic simulations, ESR and NMR experiments. The glycosydic moiety plays a primary role in the whole process. In particular, in an environment mimicking that used in the clinical tests the glycopeptide assumes a α-helix structure that is functional for the interaction with the antibody. In this conformation CSF114(Glc) binds the monoclonal antibody mAb8-18C5 similarly to the myelin oligodendrocyte glycoprotein MOG, which is a known MS auto-antigen, thus explaining its diagnostic activity. Our study offers new molecular bases to design more effective biomarkers and provides a most valid protocol to investigate other systems where the environment effect is determinant for the biological activity.

  4. Label-Free LC-MS Profiling of Skeletal Muscle Reveals Heart-Type Fatty Acid Binding Protein as a Candidate Biomarker of Aerobic Capacity.

    Science.gov (United States)

    Malik, Zulezwan Ab; Cobley, James N; Morton, James P; Close, Graeme L; Edwards, Ben J; Koch, Lauren G; Britton, Steven L; Burniston, Jatin G

    2013-12-01

    transcriptome profiling work and show LC-MS is a viable means of profiling the abundance of almost all major metabolic enzymes of skeletal muscle in a highly parallel manner. Moreover, our approach is relatively more time efficient than techniques relying on orthogonal separations, and we demonstrate LC-MS profiling of the HCR/LCR selection model was able to highlight biomarkers that also exhibit differences in trained and untrained human muscle.

  5. Label-Free LC-MS Profiling of Skeletal Muscle Reveals Heart-Type Fatty Acid Binding Protein as a Candidate Biomarker of Aerobic Capacity.

    Science.gov (United States)

    Malik, Zulezwan Ab; Cobley, James N; Morton, James P; Close, Graeme L; Edwards, Ben J; Koch, Lauren G; Britton, Steven L; Burniston, Jatin G

    2013-12-01

    transcriptome profiling work and show LC-MS is a viable means of profiling the abundance of almost all major metabolic enzymes of skeletal muscle in a highly parallel manner. Moreover, our approach is relatively more time efficient than techniques relying on orthogonal separations, and we demonstrate LC-MS profiling of the HCR/LCR selection model was able to highlight biomarkers that also exhibit differences in trained and untrained human muscle. PMID:24772389

  6. Metabolomic profiling of Burkholderia pseudomallei using UHPLC-ESI-Q-TOF-MS reveals specific biomarkers including 4-methyl-5-thiazoleethanol and unique thiamine degradation pathway

    OpenAIRE

    Lau, Susanna K. P.; Lam, Ching-Wan; Curreem, Shirly O. T.; Lee, Kim-Chung; Chow, Wang-Ngai; Lau, Candy C. Y.; Sridhar, Siddharth; Wong, Sally C. Y.; Martelli, Paolo; Hui, Suk-Wai; Yuen, Kwok-Yung; Woo, Patrick C. Y.

    2015-01-01

    Background Burkholderia pseudomallei is an emerging pathogen that causes melioidosis, a serious and potentially fatal disease which requires prolonged antibiotics to prevent relapse. However, diagnosis of melioidosis can be difficult, especially in culture-negative cases. While metabolomics represents an uprising tool for studying infectious diseases, there were no reports on its applications to B. pseudomallei. To search for potential specific biomarkers, we compared the metabolomics profile...

  7. Optimized high-throughput microRNA expression profiling provides novel biomarker assessment of clinical prostate and breast cancer biopsies

    Directory of Open Access Journals (Sweden)

    Fedele Vita

    2006-06-01

    Full Text Available Abstract Background Recent studies indicate that microRNAs (miRNAs are mechanistically involved in the development of various human malignancies, suggesting that they represent a promising new class of cancer biomarkers. However, previously reported methods for measuring miRNA expression consume large amounts of tissue, prohibiting high-throughput miRNA profiling from typically small clinical samples such as excision or core needle biopsies of breast or prostate cancer. Here we describe a novel combination of linear amplification and labeling of miRNA for highly sensitive expression microarray profiling requiring only picogram quantities of purified microRNA. Results Comparison of microarray and qRT-PCR measured miRNA levels from two different prostate cancer cell lines showed concordance between the two platforms (Pearson correlation R2 = 0.81; and extension of the amplification, labeling and microarray platform was successfully demonstrated using clinical core and excision biopsy samples from breast and prostate cancer patients. Unsupervised clustering analysis of the prostate biopsy microarrays separated advanced and metastatic prostate cancers from pooled normal prostatic samples and from a non-malignant precursor lesion. Unsupervised clustering of the breast cancer microarrays significantly distinguished ErbB2-positive/ER-negative, ErbB2-positive/ER-positive, and ErbB2-negative/ER-positive breast cancer phenotypes (Fisher exact test, p = 0.03; as well, supervised analysis of these microarray profiles identified distinct miRNA subsets distinguishing ErbB2-positive from ErbB2-negative and ER-positive from ER-negative breast cancers, independent of other clinically important parameters (patient age; tumor size, node status and proliferation index. Conclusion In sum, these findings demonstrate that optimized high-throughput microRNA expression profiling offers novel biomarker identification from typically small clinical samples such as breast

  8. High sensitivity C-reactive protein: a biomarker for heart failure in children with univentricular heart disease

    Directory of Open Access Journals (Sweden)

    Lowenthal A

    2012-08-01

    Full Text Available Alexander Lowenthal,1 Luz Natal-Hernandez,1 Shiri Lowenthal,1 Nancy K Hills,2 Harold S Bernstein1,3,41Department of Pediatrics, 2Clinical and Translational Science Institute, 3Cardiovascular Research Institute, 4Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California San Francisco, San Francisco, CA, USAAbstract: Children with univentricular congenital heart disease are at increased risk for developing heart failure. However, detecting early heart failure in these patients is especially difficult because few objective measures have been validated in this cohort. The aim of this study is to determine the usefulness of high sensitivity C-reactive protein (hsCRP as a biomarker for detecting heart failure in univentricular heart disease patients, and to define the impact of univentricular morphology and stage of palliation on its utility. A cross-sectional observational study of children with univentricular congenital heart disease aged 1 month to 7 years was conducted. The presence of heart failure was defined as a Ross score > 2. The association of hsCRP with heart failure was assessed using logistic regression and receiver operating characteristic curves. Of the 50 included children, 16 (32% had clinical heart failure. A doubling of hsCRP resulted in a 0.31 unit increase in Ross score (95% confidence interval: –0.07, 0.56; P = 0.01 with a c-statistic of 68%. When stratified by ventricular morphology, the left univentricular morphology group exceeded the threshold of ≥75% (c-statistic = 81% as did those at stage II of palliation (c-statistic = 85%. A cut point of ≥0.8 mg/mL correctly classified 75% of patients with left univentricular morphology, and 73% of patients regardless of morphology at stage II of palliation. From these results, we conclude that hsCRP is a useful biomarker of clinical heart failure in univentricular patients with left ventricular morphology at all stages of surgical

  9. Sequencing of 50 human exomes reveals adaptation to high altitude

    DEFF Research Database (Denmark)

    Yi, Xin; Liang, Yu; Huerta-Sanchez, Emilia;

    2010-01-01

    Residents of the Tibetan Plateau show heritable adaptations to extreme altitude. We sequenced 50 exomes of ethnic Tibetans, encompassing coding sequences of 92% of human genes, with an average coverage of 18x per individual. Genes showing population-specific allele frequency changes, which...... represent strong candidates for altitude adaptation, were identified. The strongest signal of natural selection came from endothelial Per-Arnt-Sim (PAS) domain protein 1 (EPAS1), a transcription factor involved in response to hypoxia. One single-nucleotide polymorphism (SNP) at EPAS1 shows a 78% frequency...... difference between Tibetan and Han samples, representing the fastest allele frequency change observed at any human gene to date. This SNP's association with erythrocyte abundance supports the role of EPAS1 in adaptation to hypoxia. Thus, a population genomic survey has revealed a functionally important locus...

  10. Highly ionized region surrounding SN Refsdal revealed by MUSE

    Science.gov (United States)

    Karman, W.; Grillo, C.; Balestra, I.; Rosati, P.; Caputi, K. I.; Di Teodoro, E.; Fraternali, F.; Gavazzi, R.; Mercurio, A.; Prochaska, J. X.; Rodney, S.; Treu, T.

    2016-01-01

    Supernova (SN) Refsdal is the first multiply imaged, highly magnified, and spatially resolved SN ever observed. The SN exploded in a highly magnified spiral galaxy at z = 1.49 behind the Frontier Fields cluster MACS1149, and provides a unique opportunity to study the environment of SNe at high z. We exploit the time delay between multiple images to determine the properties of the SN and its environment before, during, and after the SN exploded. We use the integral-field spectrograph MUSE on the VLT to simultaneously target all observed and model-predicted positions of SN Refsdal. We find Mg II emission at all positions of SN Refsdal, accompanied by weak Fe II* emission at two positions. The measured ratios of [O II] to Mg II emission of 10-20 indicate a high degree of ionization with low metallicity. Because the same high degree of ionization is found in all images, and our spatial resolution is too coarse to resolve the region of influence of SN Refsdal, we conclude that this high degree of ionization has been produced by previous SNe or a young and hot stellar population. We find no variability of the [O II] line over a period of 57 days. This suggests that there is no variation in the [O II] luminosity of the SN over this period, or that the SN has a small contribution to the integrated [O II] emission over the scale resolved by our observations.

  11. Label-Free LC-MS Profiling of Skeletal Muscle Reveals Heart-Type Fatty Acid Binding Protein as a Candidate Biomarker of Aerobic Capacity

    Directory of Open Access Journals (Sweden)

    Zulezwan A. Malik

    2013-12-01

    .54-fold (p = 0.0064 more abundant in HCR than LCR soleus. This discovery was verified using selective reaction monitoring (SRM of the y5 ion (551.21 m/z of the doubly-charged peptide SLGVGFATR (454.19 m/z of residues 23–31 of FABPH. SRM was conducted on technical replicates of each biological sample and exhibited a coefficient of variation of 20%. The abundance of FABPH measured by SRM was 2.84-fold greater (p = 0.0095 in HCR muscle. In addition, SRM of FABPH was performed in vastus lateralis samples of young and elderly humans with different habitual activity levels (collected during a previous study finding FABPH abundance was 2.23-fold greater (p = 0.0396 in endurance-trained individuals regardless of differences in age. In summary, our findings in HCR/LCR rats provide protein-level confirmation for earlier transcriptome profiling work and show LC-MS is a viable means of profiling the abundance of almost all major metabolic enzymes of skeletal muscle in a highly parallel manner. Moreover, our approach is relatively more time efficient than techniques relying on orthogonal separations, and we demonstrate LC-MS profiling of the HCR/LCR selection model was able to highlight biomarkers that also exhibit differences in trained and untrained human muscle.

  12. Resonance strategies revealed in recorded tenor high notes

    NARCIS (Netherlands)

    Schutte, HK; Miller, DG; Duijnstee, M

    2005-01-01

    With careers that depend to a large extent on the amplitude and sonorous beauty of their voices, opera singers must pay special attention to high notes, where the wide spacing of the harmonics of the voice source intensifies the critical importance of the tuning of the resonances of the vocal tract.

  13. Preeclampsia, biomarkers, syncytiotrophoblast stress, and placental capacity.

    Science.gov (United States)

    Redman, Christopher W G; Staff, Anne Cathrine

    2015-10-01

    The maternal syndrome of preeclampsia is mediated by dysfunctional syncytiotrophoblast (STB). When this is stressed by uteroplacental malperfusion, its signaling to the mother changes, as part of a highly coordinated stress response. The STB signals are both proinflammatory and dysangiogenic such that the preeclamptic mother has a stronger vascular inflammatory response than normal, with an antiangiogenic bias. Angiogenic factors have limitations as preeclampsia biomarkers, especially for prediction and diagnosis of preeclampsia at term. However, if they are recognized as markers of STB stress, their physiological changes at term demonstrate that STB stress develops in all pregnancies. The biomarkers reveal that the duration of pregnancies is restricted by placental capacity, such that there is increasing placental dysfunction, at and beyond term. This capacity includes limitations imposed by the size of the uterus, the capacity of the uteroplacental circulation and, possibly, the supply of villous progenitor trophoblast cells. Limited placental capacity explains the increasing risks of postmaturity, including preeclampsia. Early-onset preeclampsia is predictable because STB stress and changes in its biomarkers are intrinsic to poor placentation, an early pregnancy pathology. Prediction of preeclampsia at term is not good because there is no early STB pathology. Moreover, biomarkers cannot accurately diagnose term preeclampsia against a background of universal STB dysfunction, which may or may not be clinically revealed before spontaneous or induced delivery. In this sense, postterm pregnancy is, at best, a pseudonormal state. However, the markers may prove useful in screening for women with more severe problems of postmaturity.

  14. Biomarkers of alcohol misuse: recent advances and future prospects.

    Science.gov (United States)

    Jastrzębska, Iwona; Zwolak, Agnieszka; Szczyrek, Michał; Wawryniuk, Agnieszka; Skrzydło-Radomańska, Barbara; Daniluk, Jadwiga

    2016-01-01

    Alcohol abuse and dependence are highly prevalent in many cultures and contribute considerably to the global burden of health and social issues. The current inability to accurately characterise long-term drinking behaviours is a major obstacle to alcoholism diagnosis and treatment. Therefore, it is of great importance to develop objective diagnostic tools to discern subjects with excessive alcohol use and alcoholism or to confirm abstinence. Research over past years has revealed several biochemical compounds with considerable potential for accurate reflection of alcohol intake. This review will address the issue of alcohol biomarker definition, the types of molecules used as so-called traditional biomarkers, and the compounds that can serve as novel biomarker candidates or components of biomarker panels. PMID:27350834

  15. Highly specific changes in antioxidant levels and lipid peroxidation in Parkinson's disease and its progression: Disease and staging biomarkers and new drug targets.

    Science.gov (United States)

    de Farias, Carine Coneglian; Maes, Michael; Bonifácio, Kamila Landucci; Bortolasci, Chiara Cristina; de Souza Nogueira, André; Brinholi, Francis Fregonesi; Matsumoto, Andressa Keiko; do Nascimento, Matheus Amarante; de Melo, Lúcio Baena; Nixdorf, Suzana Lucy; Lavado, Edson Lopes; Moreira, Estefânia Gastaldello; Barbosa, Décio Sabbatini

    2016-03-23

    There is evidence that immune-inflammatory, stress of reactive oxygen and nitrogen species (IO&NS) processes play a role in the neurodegenerative processes observed in Parkinson's disease (PD). The aim of the present study was to investigate peripheral IO&NS biomarkers in PD. We included 56 healthy individuals and 56 PD patients divided in two groups: early PD stage and late PD stage. Plasma lipid hydroperoxides (LOOH), malondialdehyde (MDA), nitric oxide metabolites (NOx), sulfhydryl (SH) groups, catalase (CAT) activity, superoxide dismutase (SOD) activity, paraoxonase (PON)1 activity, total radical trapping antioxidant parameter (TRAP) and C-reactive protein (CRP) were measured. PD is characterized by increased LOOH, MDA and SOD activity and lowered CAT activity. A combination of five O&NS biomarkers highly significantly predicts PD with a sensitivity of 94.5% and a specificity of 86.8% (i.e., MDA, SOD activity, TRAP, SH-groups and CAT activity). The single best biomarker of PD is MDA, while LOOH and SOD activity are significantly associated with late PD stage, but not early PD stage. Antiparkinson drugs did not affect O&NS biomarkers, but levodopa+carbidopa significantly increased CRP. It is suggested that MDA may serve as a disease biomarker, while LOOH and SOD activity are associated with late PD stage characteristic. New treatments for PD should not only target dopamine but also lipid peroxidation. PMID:26861200

  16. Population variation revealed high-altitude adaptation of Tibetan mastiffs.

    Science.gov (United States)

    Li, Yan; Wu, Dong-Dong; Boyko, Adam R; Wang, Guo-Dong; Wu, Shi-Fang; Irwin, David M; Zhang, Ya-Ping

    2014-05-01

    With the assistance of their human companions, dogs have dispersed into new environments during the expansion of human civilization. Tibetan Mastiff (TM), a native of the Tibetan Plateau, was derived from the domesticated Chinese native dog and, like Tibetans, has adapted to the extreme environment of high altitude. Here, we genotyped genome-wide single-nucleotide polymorphisms (SNPs) from 32 TMs and compared them with SNPs from 20 Chinese native dogs and 14 gray wolves (Canis lupus). We identified 16 genes with signals of positive selection in the TM, with 12 of these candidate genes associated with functions that have roles in adaptation to high-altitude adaptation, such as EPAS1, SIRT7, PLXNA4, and MAFG that have roles in responses to hypoxia. This study provides important information on the genetic diversity of the TM and potential mechanisms for adaptation to hypoxia. PMID:24520091

  17. Effects of Orlistat and herbal mixture extract on brain, testes functions and oxidative stress biomarkers in a rat model of high fat diet

    OpenAIRE

    Galaly, Sanaa R; Hozayen, Walaa G.; Amin, Kamal A; Shimaa M. Ramadan

    2014-01-01

    This study was designed to assess the effectiveness of herbal mixture extracts of pumpkin seed oil, peanuts shell and Orlistat on brain, testes functions, oxidative stress biomarkers and histopathological changes in male albino rats administered high fat diet. Fifty male rats were divided into four groups: 1st administered normal diet, 2nd administered high fat diet, 3rd administered high fat diet with Orlistat and 4th administered high fat diet with herbal mix. A group of rats were fed wi...

  18. Grazing Occultation reveals Gravity Wave Breaking in Pluto's High Atmosphere

    Science.gov (United States)

    Kern, Susan D.; McCarthy, D. W.; Kulesa, C. A.; Hubbard, W. B.; Person, M. J.; Elliot, J. L.; Gulbis, A. A.

    2007-10-01

    Occultation observations of the star P445.3 (2UCAC 25823784; McDonald & Elliot 2000, AJ 120, 1599) by (134340) Pluto on 2007 March 18.453 UT were simultaneously collected in visible and H-band wavelengths from the 6.5-m MMT (Mt. Hopkins) in Arizona. The event was grazing and slow (6.77 km/s), lasting 4 minutes. These conditions facilitated the detection of large-scale, nearly limb-aligned features in Pluto's atmosphere over a pressure range of 0.1-0.7 μbar (0.01-0.07 Pa; radius range of 1500-1350 km). The data are high signal-to-noise and show these features to be fully resolved and achromatic. The scintillation increases with depth in Pluto's atmosphere and indicates a high-frequency cutoff operating on a broad-band spectrum of gravity waves generated deeper in Pluto's atmosphere. The data are in excellent agreement with atmospheric gravity wave theory (Fritts 1984, RGSP 22, 275). Observations reported here were obtained at the MMT Observatory, a joint facility of The University of Arizona and the Smithsonian Institution. The integration and alignment of both cameras was funded by the Astronomy Camp science education program. We also acknowledge support from NASA's Planetary Astronomy Program via grants NNG04GE48G and NNG04GF25G.

  19. Network-Based Logistic Classification with an Enhanced L1/2 Solver Reveals Biomarker and Subnetwork Signatures for Diagnosing Lung Cancer

    Directory of Open Access Journals (Sweden)

    Hai-Hui Huang

    2015-01-01

    Full Text Available Identifying biomarker and signaling pathway is a critical step in genomic studies, in which the regularization method is a widely used feature extraction approach. However, most of the regularizers are based on L1-norm and their results are not good enough for sparsity and interpretation and are asymptotically biased, especially in genomic research. Recently, we gained a large amount of molecular interaction information about the disease-related biological processes and gathered them through various databases, which focused on many aspects of biological systems. In this paper, we use an enhanced L1/2 penalized solver to penalize network-constrained logistic regression model called an enhanced L1/2 net, where the predictors are based on gene-expression data with biologic network knowledge. Extensive simulation studies showed that our proposed approach outperforms L1 regularization, the old L1/2 penalized solver, and the Elastic net approaches in terms of classification accuracy and stability. Furthermore, we applied our method for lung cancer data analysis and found that our method achieves higher predictive accuracy than L1 regularization, the old L1/2 penalized solver, and the Elastic net approaches, while fewer but informative biomarkers and pathways are selected.

  20. Revealing proton shape fluctuations with incoherent diffraction at high energy

    Science.gov (United States)

    Mäntysaari, Heikki; Schenke, Björn

    2016-08-01

    The differential cross section of exclusive diffractive vector meson production in electron proton collisions carries important information on the geometric structure of the proton. More specifically, the coherent cross section as a function of the transferred transverse momentum is sensitive to the size of the proton, while the incoherent or proton dissociative cross section is sensitive to fluctuations of the gluon distribution in coordinate space. We show that at high energies the experimentally measured coherent and incoherent cross sections for the production of J /Ψ mesons are very well reproduced within the color glass condensate framework when strong geometric fluctuations of the gluon distribution in the proton are included. For ρ meson production, we also find reasonable agreement. We study in detail the dependence of our results on various model parameters, including the average proton shape, analyze the effect of saturation scale and color charge fluctuations and constrain the degree of geometric fluctuations.

  1. Revealing proton shape fluctuations with incoherent diffraction at high energy

    CERN Document Server

    Mäntysaari, Heikki

    2016-01-01

    The differential cross section of exclusive diffractive vector meson production in electron proton collisions carries important information on the geometric structure of the proton. More specifically, the coherent cross section as a function of the transferred transverse momentum is sensitive to the size of the proton, while the incoherent, or proton dissociative cross section is sensitive to fluctuations of the gluon distribution in coordinate space. We show that at high energies the experimentally measured coherent and incoherent cross sections for the production of $J/\\Psi$ mesons are very well reproduced within the color glass condensate framework when strong geometric fluctuations of the gluon distribution in the proton are included. For $\\rho$ meson production we also find reasonable agreement. We study in detail the dependence of our results on various model parameters, including the average proton shape, analyze the effect of saturation scale and color charge fluctuations and constrain the degree of g...

  2. Biomarker Identification Using Text Mining

    Directory of Open Access Journals (Sweden)

    Hui Li

    2012-01-01

    Full Text Available Identifying molecular biomarkers has become one of the important tasks for scientists to assess the different phenotypic states of cells or organisms correlated to the genotypes of diseases from large-scale biological data. In this paper, we proposed a text-mining-based method to discover biomarkers from PubMed. First, we construct a database based on a dictionary, and then we used a finite state machine to identify the biomarkers. Our method of text mining provides a highly reliable approach to discover the biomarkers in the PubMed database.

  3. Biomarkers in Prostate Cancer Epidemiology

    Directory of Open Access Journals (Sweden)

    Mudit Verma

    2011-09-01

    Full Text Available Understanding the etiology of a disease such as prostate cancer may help in identifying populations at high risk, timely intervention of the disease, and proper treatment. Biomarkers, along with exposure history and clinical data, are useful tools to achieve these goals. Individual risk and population incidence of prostate cancer result from the intervention of genetic susceptibility and exposure. Biochemical, epigenetic, genetic, and imaging biomarkers are used to identify people at high risk for developing prostate cancer. In cancer epidemiology, epigenetic biomarkers offer advantages over other types of biomarkers because they are expressed against a person’s genetic background and environmental exposure, and because abnormal events occur early in cancer development, which includes several epigenetic alterations in cancer cells. This article describes different biomarkers that have potential use in studying the epidemiology of prostate cancer. We also discuss the characteristics of an ideal biomarker for prostate cancer, and technologies utilized for biomarker assays. Among epigenetic biomarkers, most reports indicate GSTP1 hypermethylation as the diagnostic marker for prostate cancer; however, NKX2-5, CLSTN1, SPOCK2, SLC16A12, DPYS, and NSE1 also have been reported to be regulated by methylation mechanisms in prostate cancer. Current challenges in utilization of biomarkers in prostate cancer diagnosis and epidemiologic studies and potential solutions also are discussed.

  4. A Validated High-Let Radiation Specific Biomarker in the Mayak Worker Cohort

    Energy Technology Data Exchange (ETDEWEB)

    David J. Brenner, Ph.D., D.Sc.; Tamara Azizova, M.D.

    2006-12-11

    Our goal (see Project Objectives) is to deliver a dosimetry system which will enable both a Pu body burden of 0.3 kBq, and a 30 cGy {gamma} ray dose, to be separately estimated with a confidence limit of {+-}30%. In terms of the numbers analyzed and the data we have accrued, we have direct quantitative evidence that we are on track to providing such a comprehensive independent dosimetry system for Mayak workers. We had previously demonstrated that intra-chromosomal aberrations measured in peripheral blood lymphocytes can be used as a sensitive long-lived low-background quantitative biomarker of densely-ionizing radiation dose in individuals exposed many years ago. We propose to calibrate the system such that it can be used to estimate both the densely-ionizing internal plutonium exposure and the sparsely-ionizing external exposure in Mayak workers exposed to different combinations of these over a prolonged period, mostly many years ago. Our objective is to deliver a dosimetry system (set of calibration parameters) which will enable both a comparatively low Pu body burden of 0.3 kBq, and a comparatively low 30 cGy {gamma} ray dose (one of these or both of these) to be estimated with a confidence limit of {+-}30% (higher doses will of course be estimated with smaller confidence intervals and still lower doses with larger confidence intervals). (1) Draw blood, make metaphase slides and measure numbers of intra- and inter-chromosome aberrations (using the mBAND and mFISH techniques) in - (A) 255 healthy former Mayak workers who were exposed various combinations of internal and external exposures. The individuals were chosen from the data base of healthy former workers through computer simulation to optimize estimates of the dosimetry parameters. The individuals have both internal and external dose estimates from the SUBI Doses-99 system. (B) 85 healthy non-exposed controls with ages, gender, and smoking status, chosen based on computer simulation to optimize estimates

  5. Longitudinal micro-CT provides biomarkers of lung disease that can be used to assess the effect of therapy in preclinical mouse models, and reveal compensatory changes in lung volume.

    Science.gov (United States)

    Vande Velde, Greetje; Poelmans, Jennifer; De Langhe, Ellen; Hillen, Amy; Vanoirbeek, Jeroen; Himmelreich, Uwe; Lories, Rik J

    2016-01-01

    In vivo lung micro-computed tomography (micro-CT) is being increasingly embraced in pulmonary research because it provides longitudinal information on dynamic disease processes in a field in which ex vivo assessment of experimental disease models is still the gold standard. To optimize the quantitative monitoring of progression and therapy of lung diseases, we evaluated longitudinal changes in four different micro-CT-derived biomarkers [aerated lung volume, lung tissue (including lesions) volume, total lung volume and mean lung density], describing normal development, lung infections, inflammation, fibrosis and therapy. Free-breathing mice underwent micro-CT before and repeatedly after induction of lung disease (bleomycin-induced fibrosis, invasive pulmonary aspergillosis, pulmonary cryptococcosis) and therapy (imatinib). The four lung biomarkers were quantified. After the last time point, we performed pulmonary function tests and isolated the lungs for histology. None of the biomarkers remained stable during longitudinal follow-up of adult healthy mouse lungs, implying that biomarkers should be compared with age-matched controls upon intervention. Early inflammation and progressive fibrosis led to a substantial increase in total lung volume, which affects the interpretation of aerated lung volume, tissue volume and mean lung density measures. Upon treatment of fibrotic lung disease, the improvement in aerated lung volume and function was not accompanied by a normalization of the increased total lung volume. Significantly enlarged lungs were also present in models of rapidly and slowly progressing lung infections. The data suggest that total lung volume changes could partly reflect a compensatory mechanism that occurs during disease progression in mice. Our findings underscore the importance of quantifying total lung volume in addition to aerated lung or lesion volumes to accurately document growth and potential compensatory mechanisms in mouse models of lung

  6. Individual variability in cardiac biomarker release after 30 min of high-intensity rowing in elite and amateur athletes.

    Science.gov (United States)

    Legaz-Arrese, Alejandro; López-Laval, Isaac; George, Keith; Puente-Lanzarote, Juan José; Moliner-Urdiales, Diego; Ayala-Tajuelo, Vicente Javier; Mayolas-Pi, Carmen; Reverter-Masià, Joaquín

    2015-09-01

    This study had two objectives: (i) to examine individual variation in the pattern of cardiac troponin I (cTnI) and N-terminal pro-brain natriuretic peptide (NT-proBNP) release in response to high-intensity rowing exercise, and (ii) to establish whether individual heterogeneity in biomarker appearance was influenced by athletic status (elite vs. amateur). We examined cTnI and NT-proBNP in 18 elite and 14 amateur rowers before and 5 min, 1, 3, 6, 12, and 24 h after a 30-min maximal rowing test. Compared with pre-exercise levels, peak postexercise cTnI (pre: 0.014 ± 0.030 μg·L(-1); peak post: 0.058 ± 0.091 μg·L(-1); p = 0.000) and NT-proBNP (pre: 15 ± 11 ng·L(-1); peak post: 31 ± 19 ng·L(-1); p = 0.000) were elevated. Substantial individual heterogeneity in peak and time-course data was noted for cTnI. Peak cTnI exceeded the upper reference limit (URL) in 9 elite and 3 amateur rowers. No rower exceeded the URL for NT-proBNP. Elite rowers had higher baseline (0.019 ± 0.038 vs. 0.008 ± 0.015 μg·L(-1); p = 0.003) and peak postexercise cTnI (0.080 ± 0.115 vs. 0.030 ± 0.029 μg·L(-1); p = 0.022) than amateur rowers, but the change with exercise was similar between groups. There were no significant differences in baseline and peak postexercise NT-proBNP between groups. In summary, marked individuality in the cTnI response to a short but high-intensity rowing bout was observed. Athletic status did not seem to affect the change in cardiac biomarkers in response to high-intensity exercise. PMID:26307519

  7. Modeling pulmonary alveolar microlithiasis by epithelial deletion of the Npt2b sodium phosphate cotransporter reveals putative biomarkers and strategies for treatment.

    Science.gov (United States)

    Saito, Atsushi; Nikolaidis, Nikolaos M; Amlal, Hassane; Uehara, Yasuaki; Gardner, Jason C; LaSance, Kathleen; Pitstick, Lori B; Bridges, James P; Wikenheiser-Brokamp, Kathryn A; McGraw, Dennis W; Woods, Jason C; Sabbagh, Yves; Schiavi, Susan C; Altinişik, Göksel; Jakopović, Marko; Inoue, Yoshikazu; McCormack, Francis X

    2015-11-11

    Pulmonary alveolar microlithiasis (PAM) is a rare, autosomal recessive lung disorder associated with progressive accumulation of calcium phosphate microliths. Inactivating mutations in SLC34A2, which encodes the NPT2b sodium-dependent phosphate cotransporter, has been proposed as a cause of PAM. We show that epithelial deletion of Npt2b in mice results in a progressive pulmonary process characterized by diffuse alveolar microlith accumulation, radiographic opacification, restrictive physiology, inflammation, fibrosis, and an unexpected alveolar phospholipidosis. Cytokine and surfactant protein elevations in the alveolar lavage and serum of PAM mice and confirmed in serum from PAM patients identify serum MCP-1 (monocyte chemotactic protein 1) and SP-D (surfactant protein D) as potential biomarkers. Microliths introduced by adoptive transfer into the lungs of wild-type mice produce marked macrophage-rich inflammation and elevation of serum MCP-1 that peaks at 1 week and resolves at 1 month, concomitant with clearance of stones. Microliths isolated by bronchoalveolar lavage readily dissolve in EDTA, and therapeutic whole-lung EDTA lavage reduces the burden of stones in the lungs. A low-phosphate diet prevents microlith formation in young animals and reduces lung injury on the basis of reduction in serum SP-D. The burden of pulmonary calcium deposits in established PAM is also diminished within 4 weeks by a low-phosphate diet challenge. These data support a causative role for Npt2b in the pathogenesis of PAM and the use of the PAM mouse model as a preclinical platform for the development of biomarkers and therapeutic strategies. PMID:26560359

  8. miR-22-5p revealed as a potential biomarker involved in the acute phase of myocardial infarction via profiling of circulating microRNAs.

    Science.gov (United States)

    Maciejak, Agata; Kiliszek, Marek; Opolski, Grzegorz; Segiet, Agnieszka; Matlak, Krzysztof; Dobrzycki, Slawomir; Tulacz, Dorota; Sygitowicz, Grazyna; Burzynska, Beata; Gora, Monika

    2016-09-01

    Acute myocardial infarction (AMI) is a life-threatening episode of coronary artery disease. Recently, circulating myocardial-derived microRNAs (miRNAs) have been reported as potential biomarkers of infarction. The present study aimed to identify differentially expressed miRNAs in patients with ST-segment elevation myocardial infarction that could be potentially dysregulated in response to early myocardial damage. miRNA expression profile analysis was performed using the Serum/Plasma Focus miRNA Polymerase Chain Reaction (PCR) panel of Exiqon A/S (Vedbaek, Denmark) on plasma samples of patients on the first day of AMI (admission) and on samples from the identical patients collected six months following AMI. Selected miRNAs were validated by reverse transcription‑quantitative PCR (RT‑qPCR) using independent patients with AMI and a control group of patients with a stable coronary artery disease. Thirty‑two species of plasma miRNA were differentially expressed (P<0.05) on admission compared with six months following AMI. Subsequent validation in an independent patient group confirmed that miR‑133b and miR‑22‑5p were significantly up‑regulated in the serum of patients with AMI. The receiver operating characteristic (ROC) curve analysis demonstrated a diagnostic utility for miR-22-5p, which has not previously been reported to be associated with AMI. Among the selected miRNAs, miR‑22‑5p represents a novel promising biomarker for the diagnosis of AMI. PMID:27484208

  9. Eight week exposure to a high sugar high fat diet results in adiposity gain and alterations in metabolic biomarkers in baboons (Papio hamadryas sp.

    Directory of Open Access Journals (Sweden)

    Tejero M Elizabeth

    2010-10-01

    Full Text Available Abstract Background Baboons (Papio hamadryas Sp. develop features of the cardiometabolic syndrome and represent a clinically-relevant animal model in which to study the aetiology of the disorder. To further evaluate the baboon as a model for the study of the cardiometabolic syndrome, we developed a high sugar high fat diet and hypothesized that it could be used to induce adiposity gain and affect associated circulating biomarkers. Methods We developed a diet enriched with monosaccharides and saturated fatty acids that was composed of solid and liquid energy sources. We provided a group of baboons (n = 9 ad libitum access to this diet for 8 weeks. Concurrently, a control group (n = 6 was maintained with ad libitum access to a low sugar low fat baseline diet and normal water for 8 weeks. Body composition was determined by dual-energy X-ray absorptiometry and circulating metabolic biomarkers were measured using standard methodology before and after the 8 week study period. Results Neither body composition nor circulating biomarkers changed in the control group. Following the 8 weeks, the intervention group had a significant increase in fat mass (1.71 ± 0.98 vs. 3.23 ± 1.70 kg, p = 0.004, triglyceride (55 ± 13 vs. 109 ± 67 mg/dL, p = 0.006,, and leptin (1.19 ± 1.40 vs. 3.29 ± 2.32 ng/mL, p = 0.001 and a decline in adiponectin concentrations (33530 ± 9744 vs. 23330 ± 7863 ng/mL, p = 0.002. Percentage haemoglobin A1C (4.0 ± 0.3 vs. 6.0 ± 1.4, p = 0.002 also increased in the intervention group. Conclusions Our findings indicate that when exposed to a high sugar high fat diet, young adult male baboons develop increased body fat and triglyceride concentrations, altered adipokine concentrations, and evidence of altered glucose metabolism. Our findings are in keeping with observations in humans and further demonstrate the potential utility of this highly clinically-relevant animal model for studying diet-induced metabolic dysregulation.

  10. Proteomics in Discovery of Hepatocellular Carcinoma Biomarkers

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective: To discover new proteomic biomarkers of hepatocellular carcinoma. Methods: Surface enhanced laser desorption/ionization time-of-flight (SELDI-TOF) mass spectrometry was used to discover biomarkers for differentiating hepatocellular carcinoma and chronic liver disease. A population of 50 patients with hepatocellular carcinoma and 33 patients with chronic liver disease was studied. Results: Twelve proteomic biomarkers of hepatocellular carcinoma were detected in this study. Three proteomic biomarkers were highly expressed in hepatocellular carcinoma and nine proteomic biomarkers were highly expressed in chronic liver disease. The most valuable proteomic biomarker with m/z=11498 had no similar diagnostic value as α-fetoprotein. Conclusion:Some of the twelve proteomic biomarkers may become new biomarkers of hepatocellular carcinoma.

  11. Mark-recapture using tetracycline and genetics reveal record-high bear density

    Science.gov (United States)

    Peacock, E.; Titus, K.; Garshelis, D.L.; Peacock, M.M.; Kuc, M.

    2011-01-01

    We used tetracycline biomarking, augmented with genetic methods to estimate the size of an American black bear (Ursus americanus) population on an island in Southeast Alaska. We marked 132 and 189 bears that consumed remote, tetracycline-laced baits in 2 different years, respectively, and observed 39 marks in 692 bone samples subsequently collected from hunters. We genetically analyzed hair samples from bait sites to determine the sex of marked bears, facilitating derivation of sex-specific population estimates. We obtained harvest samples from beyond the study area to correct for emigration. We estimated a density of 155 independent bears/100 km2, which is equivalent to the highest recorded for this species. This high density appears to be maintained by abundant, accessible natural food. Our population estimate (approx. 1,000 bears) could be used as a baseline and to set hunting quotas. The refined biomarking method for abundance estimation is a useful alternative where physical captures or DNA-based estimates are precluded by cost or logistics. Copyright ?? 2011 The Wildlife Society.

  12. Proteomics tools reveal startlingly high amounts of oxytocin in plasma and serum.

    Science.gov (United States)

    Brandtzaeg, Ole Kristian; Johnsen, Elin; Roberg-Larsen, Hanne; Seip, Knut Fredrik; MacLean, Evan L; Gesquiere, Laurence R; Leknes, Siri; Lundanes, Elsa; Wilson, Steven Ray

    2016-01-01

    The neuropeptide oxytocin (OT) is associated with a plethora of social behaviors, and is a key topic at the intersection of psychology and biology. However, tools for measuring OT are still not fully developed. We describe a robust nano liquid chromatography-mass spectrometry (nanoLC-MS) platform for measuring the total amount of OT in human plasma/serum. OT binds strongly to plasma proteins, but a reduction/alkylation (R/A) procedure breaks this bond, enabling ample detection of total OT. The method (R/A + robust nanoLC-MS) was used to determine total OT plasma/serum levels to startlingly high concentrations (high pg/mL-ng/mL). Similar results were obtained when combining R/A and ELISA. Compared to measuring free OT, measuring total OT can have advantages in e.g. biomarker studies. PMID:27528413

  13. Proteomics tools reveal startlingly high amounts of oxytocin in plasma and serum

    Science.gov (United States)

    Brandtzaeg, Ole Kristian; Johnsen, Elin; Roberg-Larsen, Hanne; Seip, Knut Fredrik; Maclean, Evan L.; Gesquiere, Laurence R.; Leknes, Siri; Lundanes, Elsa; Wilson, Steven Ray

    2016-08-01

    The neuropeptide oxytocin (OT) is associated with a plethora of social behaviors, and is a key topic at the intersection of psychology and biology. However, tools for measuring OT are still not fully developed. We describe a robust nano liquid chromatography-mass spectrometry (nanoLC-MS) platform for measuring the total amount of OT in human plasma/serum. OT binds strongly to plasma proteins, but a reduction/alkylation (R/A) procedure breaks this bond, enabling ample detection of total OT. The method (R/A + robust nanoLC-MS) was used to determine total OT plasma/serum levels to startlingly high concentrations (high pg/mL-ng/mL). Similar results were obtained when combining R/A and ELISA. Compared to measuring free OT, measuring total OT can have advantages in e.g. biomarker studies.

  14. Proteomics tools reveal startlingly high amounts of oxytocin in plasma and serum

    Science.gov (United States)

    Brandtzaeg, Ole Kristian; Johnsen, Elin; Roberg-Larsen, Hanne; Seip, Knut Fredrik; MacLean, Evan L.; Gesquiere, Laurence R.; Leknes, Siri; Lundanes, Elsa; Wilson, Steven Ray

    2016-01-01

    The neuropeptide oxytocin (OT) is associated with a plethora of social behaviors, and is a key topic at the intersection of psychology and biology. However, tools for measuring OT are still not fully developed. We describe a robust nano liquid chromatography-mass spectrometry (nanoLC-MS) platform for measuring the total amount of OT in human plasma/serum. OT binds strongly to plasma proteins, but a reduction/alkylation (R/A) procedure breaks this bond, enabling ample detection of total OT. The method (R/A + robust nanoLC-MS) was used to determine total OT plasma/serum levels to startlingly high concentrations (high pg/mL-ng/mL). Similar results were obtained when combining R/A and ELISA. Compared to measuring free OT, measuring total OT can have advantages in e.g. biomarker studies. PMID:27528413

  15. Glucosylsphingosine is a highly sensitive and specific biomarker for primary diagnostic and follow-up monitoring in Gaucher disease in a non-Jewish, Caucasian cohort of Gaucher disease patients.

    Directory of Open Access Journals (Sweden)

    Arndt Rolfs

    Full Text Available BACKGROUND: Gaucher disease (GD is the most common lysosomal storage disorder (LSD. Based on a deficient β-glucocerebrosidase it leads to an accumulation of glucosylceramide. Standard diagnostic procedures include measurement of enzyme activity, genetic testing as well as analysis of chitotriosidase and CCL18/PARC as biomarkers. Even though chitotriosidase is the most well-established biomarker in GD, it is not specific for GD. Furthermore, it may be false negative in a significant percentage of GD patients due to mutation. Additionally, chitotriosidase reflects the changes in the course of the disease belatedly. This further enhances the need for a reliable biomarker, especially for the monitoring of the disease and the impact of potential treatments. METHODOLOGY: Here, we evaluated the sensitivity and specificity of the previously reported biomarker Glucosylsphingosine with regard to different control groups (healthy control vs. GD carriers vs. other LSDs. FINDINGS: Only GD patients displayed elevated levels of Glucosylsphingosine higher than 12 ng/ml whereas the comparison controls groups revealed concentrations below the pathological cut-off, verifying the specificity of Glucosylsphingosine as a biomarker for GD. In addition, we evaluated the biomarker before and during enzyme replacement therapy (ERT in 19 patients, demonstrating a decrease in Glucosylsphingosine over time with the most pronounced reduction within the first 6 months of ERT. Furthermore, our data reveals a correlation between the medical consequence of specific mutations and Glucosylsphingosine. INTERPRETATION: In summary, Glucosylsphingosine is a very promising, reliable and specific biomarker for GD.

  16. NeuroRDF: semantic integration of highly curated data to prioritize biomarker candidates in Alzheimer's disease

    OpenAIRE

    Iyappan, Anandhi; Kawalia, Shweta Bagewadi; Raschka, Tamara; Hofmann-Apitius, Martin; Senger, Philipp

    2016-01-01

    Background Neurodegenerative diseases are incurable and debilitating indications with huge social and economic impact, where much is still to be learnt about the underlying molecular events. Mechanistic disease models could offer a knowledge framework to help decipher the complex interactions that occur at molecular and cellular levels. This motivates the need for the development of an approach integrating highly curated and heterogeneous data into a disease model of different regulatory data...

  17. The expression profile of phosphatidylinositol in high spatial resolution imaging mass spectrometry as a potential biomarker for prostate cancer.

    Directory of Open Access Journals (Sweden)

    Takayuki Goto

    Full Text Available High-resolution matrix-assisted laser desorption/ionization imaging mass spectrometry (HR-MALDI-IMS is an emerging application for the comprehensive and detailed analysis of the spatial distribution of ionized molecules in situ on tissue slides. HR-MALDI-IMS in negative mode in a mass range of m/z 500-1000 was performed on optimal cutting temperature (OCT compound-embedded human prostate tissue samples obtained from patients with prostate cancer at the time of radical prostatectomy. HR-MALDI-IMS analysis of the 14 samples in the discovery set identified 26 molecules as highly expressed in the prostate. Tandem mass spectrometry (MS/MS showed that these molecules included 14 phosphatidylinositols (PIs, 3 phosphatidylethanolamines (PEs and 3 phosphatidic acids (PAs. Among the PIs, the expression of PI(18:0/18:1, PI(18:0/20:3 and PI(18:0/20:2 were significantly higher in cancer tissue than in benign epithelium. A biomarker algorithm for prostate cancer was formulated by analyzing the expression profiles of PIs in cancer tissue and benign epithelium of the discovery set using orthogonal partial least squares discriminant analysis (OPLS-DA. The sensitivity and specificity of this algorithm for prostate cancer diagnosis in the 24 validation set samples were 87.5 and 91.7%, respectively. In conclusion, HR-MALDI-IMS identified several PIs as being more highly expressed in prostate cancer than benign prostate epithelium. These differences in PI expression profiles may serve as a novel diagnostic tool for prostate cancer.

  18. Jets or high velocity flows revealed in high-cadence spectrometer and imager co-observations?

    CERN Document Server

    Madjarska, M S; Innes, D; Curdt, W

    2007-01-01

    We report on active region EUV dynamic events observed simultaneously at high-cadence with SUMER/SoHO and TRACE. Although the features appear in the TRACE Fe ix/x 171A images as jets seen in projection on the solar disk, the SUMER spectral line profiles suggest that the plasma has been driven along a curved large scale magnetic structure, a pre-existing loop. The SUMER observations were carried out in spectral lines covering a large temperature range from 10^4 K to 10^6 K. The spectral analysis revealed that a sudden heating from an energy deposition is followed by a high velocity plasma flow. The Doppler velocities were found to be in the range from 90 to 160 km/s. The heating process has a duration which is below the SUMER exposure time of 25 s while the lifetime of the events is from 5 to 15 min. The additional check on soft X-ray Yohkoh images shows that the features most probably reach 3 MK (X-ray) temperatures. The spectroscopic analysis showed no existence of cold material during the events.

  19. Claspin as a biomarker of human papillomavirus-related high grade lesions of uterine cervix

    Directory of Open Access Journals (Sweden)

    Benevolo Maria

    2012-06-01

    Full Text Available Abstract Background Claspin is a nuclear protein involved in DNA replication and damage response and is a key mediator for the S-phase checkpoint. Claspin expression is significantly high in several human solid tumors. Furthermore, high levels of claspin have been found in cervical cancer cell lines. Nevertheless, no data are available regarding claspin expression in cervical tissues. Methods In order to investigate whether claspin immunoreactivity is related to the lesion severity and High-Risk (HR HPV infection, we analyzed claspin expression by immunohistochemistry in a series of cervical biopsies which represent the steps occurring during cervical carcinogenesis (normal tissues, Cervical Intraepithelial Neoplasias 1, 2 and 3, Squamous Cell Carcinomas. All patients also had a cervico-vaginal sample for HPV testing, collected immediately before the colposcopy-guided biopsy. The HR-HPV DNA detection was performed by the HR-HPV Hybrid Capture 2 test. HPV genotyping was performed using the Linear Array HPV Genotyping Test. Results Our results evidenced a constant and significant increase of the rate of claspin positivity from the normal tissues to carcinomas (pχ2trend 2  Conclusions Our findings indicate that in vivo claspin expression is significantly related to HR-HPV infection and lesion grade both in histological and cytological samples. Therefore, the analysis of claspin expression could be clinically relevant in the diagnosis of HPV-related cervical lesions, in particular when applied to cervico-vaginal cytology. Moreover, giving information on the proliferation rate of each lesion, claspin immunostaining may contribute to the evaluation of progression risk, thus being helpful in patient management. Nevertheless, only large prospective studies may clarify the true clinical usefulness of claspin expression in distinguishing lesions with different progression potential.

  20. Rapid and High-Throughput Detection and Quantitation of Radiation Biomarkers in Human and Nonhuman Primates by Differential Mobility Spectrometry-Mass Spectrometry

    Science.gov (United States)

    Chen, Zhidan; Coy, Stephen L.; Pannkuk, Evan L.; Laiakis, Evagelia C.; Hall, Adam B.; Fornace, Albert J.; Vouros, Paul

    2016-10-01

    Radiation exposure is an important public health issue due to a range of accidental and intentional threats. Prompt and effective large-scale screening and appropriate use of medical countermeasures (MCM) to mitigate radiation injury requires rapid methods for determining the radiation dose. In a number of studies, metabolomics has identified small-molecule biomarkers responding to the radiation dose. Differential mobility spectrometry-mass spectrometry (DMS-MS) has been used for similar compounds for high-throughput small-molecule detection and quantitation. In this study, we show that DMS-MS can detect and quantify two radiation biomarkers, trimethyl-L-lysine (TML) and hypoxanthine. Hypoxanthine is a human and nonhuman primate (NHP) radiation biomarker and metabolic intermediate, whereas TML is a radiation biomarker in humans but not in NHP, which is involved in carnitine synthesis. They have been analyzed by DMS-MS from urine samples after a simple strong cation exchange-solid phase extraction (SCX-SPE). The dramatic suppression of background and chemical noise provided by DMS-MS results in an approximately 10-fold reduction in time, including sample pretreatment time, compared with liquid chromatography-mass spectrometry (LC-MS). DMS-MS quantitation accuracy has been verified by validation testing for each biomarker. Human samples are not yet available, but for hypoxanthine, selected NHP urine samples (pre- and 7-d-post 10 Gy exposure) were analyzed, resulting in a mean change in concentration essentially identical to that obtained by LC-MS (fold-change 2.76 versus 2.59). These results confirm the potential of DMS-MS for field or clinical first-level rapid screening for radiation exposure.

  1. Rapid and High-Throughput Detection and Quantitation of Radiation Biomarkers in Human and Nonhuman Primates by Differential Mobility Spectrometry-Mass Spectrometry

    Science.gov (United States)

    Chen, Zhidan; Coy, Stephen L.; Pannkuk, Evan L.; Laiakis, Evagelia C.; Hall, Adam B.; Fornace, Albert J.; Vouros, Paul

    2016-07-01

    Radiation exposure is an important public health issue due to a range of accidental and intentional threats. Prompt and effective large-scale screening and appropriate use of medical countermeasures (MCM) to mitigate radiation injury requires rapid methods for determining the radiation dose. In a number of studies, metabolomics has identified small-molecule biomarkers responding to the radiation dose. Differential mobility spectrometry-mass spectrometry (DMS-MS) has been used for similar compounds for high-throughput small-molecule detection and quantitation. In this study, we show that DMS-MS can detect and quantify two radiation biomarkers, trimethyl-L-lysine (TML) and hypoxanthine. Hypoxanthine is a human and nonhuman primate (NHP) radiation biomarker and metabolic intermediate, whereas TML is a radiation biomarker in humans but not in NHP, which is involved in carnitine synthesis. They have been analyzed by DMS-MS from urine samples after a simple strong cation exchange-solid phase extraction (SCX-SPE). The dramatic suppression of background and chemical noise provided by DMS-MS results in an approximately 10-fold reduction in time, including sample pretreatment time, compared with liquid chromatography-mass spectrometry (LC-MS). DMS-MS quantitation accuracy has been verified by validation testing for each biomarker. Human samples are not yet available, but for hypoxanthine, selected NHP urine samples (pre- and 7-d-post 10 Gy exposure) were analyzed, resulting in a mean change in concentration essentially identical to that obtained by LC-MS (fold-change 2.76 versus 2.59). These results confirm the potential of DMS-MS for field or clinical first-level rapid screening for radiation exposure.

  2. Assessment of meat authenticity using bioinformatics, targeted peptide biomarkers and high-resolution mass spectrometry.

    Science.gov (United States)

    Ruiz Orduna, Alberto; Husby, Erik; Yang, Charles T; Ghosh, Dipankar; Beaudry, Francis

    2015-01-01

    In recent years a significant increase of food fraud has been observed, ranging from false label claims to the use of additives and fillers to increase profitability. Recently in 2013 horse and pig DNAs were detected in beef products sold from several retailers. Mass spectrometry (MS) has become the workhorse in protein research, and the detection of marker proteins could serve for both animal species and tissue authentication. Meat species authenticity is performed in this paper using a well-defined proteogenomic annotation, carefully chosen surrogate tryptic peptides and analysis using a hybrid quadrupole-Orbitrap MS. Selected mammalian meat samples were homogenised and proteins were extracted and digested with trypsin. The samples were analysed using a high-resolution MS. Chromatography was achieved using a 30-min linear gradient along with a BioBasic C8 100 × 1 mm column at a flow rate of 75 µl min(-1). The MS was operated in full-scan high resolution and accurate mass. MS/MS spectra were collected for selected proteotypic peptides. Muscular proteins were methodically analysed in silico in order to generate tryptic peptide mass lists and theoretical MS/MS spectra. Following a comprehensive bottom-up proteomic analysis, we detected and identified a proteotypic myoglobin tryptic peptide (120-134) for each species with observed m/z below 1.3 ppm compared with theoretical values. Moreover, proteotypic peptides from myosin-1, myosin-2 and β-haemoglobin were also identified. This targeted method allowed comprehensive meat speciation down to 1% (w/w) of undesired product. PMID:26241836

  3. Assessment of meat authenticity using bioinformatics, targeted peptide biomarkers and high-resolution mass spectrometry.

    Science.gov (United States)

    Ruiz Orduna, Alberto; Husby, Erik; Yang, Charles T; Ghosh, Dipankar; Beaudry, Francis

    2015-01-01

    In recent years a significant increase of food fraud has been observed, ranging from false label claims to the use of additives and fillers to increase profitability. Recently in 2013 horse and pig DNAs were detected in beef products sold from several retailers. Mass spectrometry (MS) has become the workhorse in protein research, and the detection of marker proteins could serve for both animal species and tissue authentication. Meat species authenticity is performed in this paper using a well-defined proteogenomic annotation, carefully chosen surrogate tryptic peptides and analysis using a hybrid quadrupole-Orbitrap MS. Selected mammalian meat samples were homogenised and proteins were extracted and digested with trypsin. The samples were analysed using a high-resolution MS. Chromatography was achieved using a 30-min linear gradient along with a BioBasic C8 100 × 1 mm column at a flow rate of 75 µl min(-1). The MS was operated in full-scan high resolution and accurate mass. MS/MS spectra were collected for selected proteotypic peptides. Muscular proteins were methodically analysed in silico in order to generate tryptic peptide mass lists and theoretical MS/MS spectra. Following a comprehensive bottom-up proteomic analysis, we detected and identified a proteotypic myoglobin tryptic peptide (120-134) for each species with observed m/z below 1.3 ppm compared with theoretical values. Moreover, proteotypic peptides from myosin-1, myosin-2 and β-haemoglobin were also identified. This targeted method allowed comprehensive meat speciation down to 1% (w/w) of undesired product.

  4. A large multi-centre European study validates high-sensitivity C-reactive protein (hsCRP) as a clinical biomarker for the diagnosis of diabetes subtypes

    DEFF Research Database (Denmark)

    Thanabalasingham, G.; Shah, N.; Vaxillaire, M.;

    2011-01-01

    An accurate molecular diagnosis of diabetes subtype confers clinical benefits; however, many individuals with monogenic diabetes remain undiagnosed. Biomarkers could help to prioritise patients for genetic investigation. We recently demonstrated that high-sensitivity C-reactive protein (hs......CRP) levels are lower in UK patients with hepatocyte nuclear factor 1 alpha (HNF1A)-MODY than in other diabetes subtypes. In this large multi-centre study we aimed to assess the clinical validity of hsCRP as a diagnostic biomarker, examine the genotype-phenotype relationship and compare different hsCRP assays....... High-sensitivity CRP levels were analysed in individuals with HNF1A-MODY (n = 457), glucokinase (GCK)-MODY (n = 404), hepatocyte nuclear factor 4 alpha (HNF4A)-MODY (n = 54) and type 2 diabetes (n = 582) from seven European centres. Three common assays for hsCRP analysis were evaluated. We excluded 121...

  5. Effect of moderate- versus high-intensity exercise on vascular function, biomarkers and quality of life in heart transplant recipients

    DEFF Research Database (Denmark)

    Dall, Christian H; Gustafsson, Finn; Christensen, Stefan B;

    2015-01-01

    continued moderate training (CON) on vascular function, biomarkers and health-related quality of life (HRQoL) in HTx recipients. METHODS: A randomized, controlled crossover trial of stable HTx recipients >12 months after transplantation was done on patients with 12 weeks of HIIT or 12 weeks of CON, followed...... by a 5-month washout and crossover. Outcomes included endothelial function, arterial stiffness, biomarkers, HRQoL and markers of anxiety and depression. RESULTS: Sixteen HTx recipients (mean age 52 years, 75% male) completed the study. HIIT increased VO2peak more than CON (between-group difference, p

  6. Application of a high throughput method of biomarker discovery to improvement of the EarlyCDT(®-Lung Test.

    Directory of Open Access Journals (Sweden)

    Isabel K Macdonald

    Full Text Available BACKGROUND: The National Lung Screening Trial showed that CT screening for lung cancer led to a 20% reduction in mortality. However, CT screening has a number of disadvantages including low specificity. A validated autoantibody assay is available commercially (EarlyCDT®-Lung to aid in the early detection of lung cancer and risk stratification in patients with pulmonary nodules detected by CT. Recent advances in high throughput (HTP cloning and expression methods have been developed into a discovery pipeline to identify biomarkers that detect autoantibodies. The aim of this study was to demonstrate the successful clinical application of this strategy to add to the EarlyCDT-Lung panel in order to improve its sensitivity and specificity (and hence positive predictive value, (PPV. METHODS AND FINDINGS: Serum from two matched independent cohorts of lung cancer patients were used (n = 100 and n = 165. Sixty nine proteins were initially screened on an abridged HTP version of the autoantibody ELISA using protein prepared on small scale by a HTP expression and purification screen. Promising leads were produced in shake flask culture and tested on the full assay. These results were analyzed in combination with those from the EarlyCDT-Lung panel in order to provide a set of re-optimized cut-offs. Five proteins that still displayed cancer/normal differentiation were tested for reproducibility and validation on a second batch of protein and a separate patient cohort. Addition of these proteins resulted in an improvement in the sensitivity and specificity of the test from 38% and 86% to 49% and 93% respectively (PPV improvement from 1 in 16 to 1 in 7. CONCLUSION: This is a practical example of the value of investing resources to develop a HTP technology. Such technology may lead to improvement in the clinical utility of the EarlyCDT--Lung test, and so further aid the early detection of lung cancer.

  7. Stress Biomarkers, Mood States, and Sleep during a Major Competition: "Success" and "Failure" Athlete's Profile of High-Level Swimmers.

    Science.gov (United States)

    Chennaoui, Mounir; Bougard, Clément; Drogou, Catherine; Langrume, Christophe; Miller, Christian; Gomez-Merino, Danielle; Vergnoux, Frédéric

    2016-01-01

    The aim of this study was to evaluate stress markers, mood states, and sleep indicators in high-level swimmers during a major 7-days competition according to the outcomes. Nine swimmers [six men and three women (age: 22 ± 2 and 22 ± 4 years, respectively)] were examined. Before (PRE) and after (POST) each race (series, semi-finals, and finals), salivary concentrations of cortisol, α-amylase (sAA), and chromogranin-A (CgA) were determined. Mood states were assessed by the profile of mood state (POMS) questionnaire completed before and after the 7-days, and self-reported sleep diaries were completed daily. In the "failure" group, cortisol and sAA significantly increased between PRE-POST measurements (p < 0.05), while sCgA was not changed. Significant overall decrease of cortisol (-52.6%) and increase of sAA (+68.7%) was shown in the "failure group." In this group, fatigue, confusion and depression scores, and sleep duration before the finals increased. The results in the "success" group show tendencies for increased cortisol and sCgA concentrations in response to competition, while sAA was not changed. Cortisol levels before the semi-finals and finals and sCgA levels before the finals were positively correlated to the fatigue score in the "failure" group only (r = 0.89). sAA levels before and after the semi-finals were negatively correlated to sleep duration measured in the subsequent night (r = -0.90). In conclusion, the stress of the competition could trigger a negative mood profile and sleep disturbance which correspond to different responses of biomarkers related to the hypothalamo-pituitary-adrenal axis and the sympathetic nervous system (SNS) activity, cortisol, sAA, and CgA. PMID:27014092

  8. Biomarkers in Acute Lung Injury

    OpenAIRE

    Bhargava, Maneesh; Wendt, Chris

    2012-01-01

    Acute Respiratory Distress Syndrome (ARDS) and Acute Lung Injury (ALI) result in high permeability pulmonary edema causing hypoxic respiratory failure with high morbidity and mortality. As the population ages, the incidence of ALI is expected to rise. Over the last decade, several studies have identified biomarkers in plasma and bronchoalveolar lavage fluid providing important insights into the mechanisms involved in the pathophysiology of ALI. Several biomarkers have been validated in subjec...

  9. Biomarkers in Prostate Cancer Epidemiology

    OpenAIRE

    Mudit Verma; Mukesh Verma; Payal Patel

    2011-01-01

    Understanding the etiology of a disease such as prostate cancer may help in identifying populations at high risk, timely intervention of the disease, and proper treatment. Biomarkers, along with exposure history and clinical data, are useful tools to achieve these goals. Individual risk and population incidence of prostate cancer result from the intervention of genetic susceptibility and exposure. Biochemical, epigenetic, genetic, and imaging biomarkers are used to identify people at high ris...

  10. Dissecting the Syndrome of Schizophrenia: Progress toward Clinically Useful Biomarkers

    Directory of Open Access Journals (Sweden)

    Brian Dean

    2011-01-01

    Full Text Available The search for clinically useful biomarkers has been one of the holy grails of schizophrenia research. This paper will outline the evolving notion of biomarkers and then outline outcomes from a variety of biomarkers discovery strategies. In particular, the impact of high-throughput screening technologies on biomarker discovery will be highlighted and how new or improved technologies may allow the discovery of either diagnostic biomarkers for schizophrenia or biomarkers that will be useful in determining appropriate treatments for people with the disorder. History tells those involved in biomarker research that the discovery and validation of useful biomarkers is a long process and current progress must always be viewed in that light. However, the approval of the first biomarker screen with some value in predicting responsiveness to antipsychotic drugs suggests that biomarkers can be identified and that these biomarkers that will be useful in diagnosing and treating people with schizophrenia.

  11. Dissecting the Syndrome of Schizophrenia: Progress toward Clinically Useful Biomarkers.

    Science.gov (United States)

    Dean, Brian

    2011-01-01

    The search for clinically useful biomarkers has been one of the holy grails of schizophrenia research. This paper will outline the evolving notion of biomarkers and then outline outcomes from a variety of biomarkers discovery strategies. In particular, the impact of high-throughput screening technologies on biomarker discovery will be highlighted and how new or improved technologies may allow the discovery of either diagnostic biomarkers for schizophrenia or biomarkers that will be useful in determining appropriate treatments for people with the disorder. History tells those involved in biomarker research that the discovery and validation of useful biomarkers is a long process and current progress must always be viewed in that light. However, the approval of the first biomarker screen with some value in predicting responsiveness to antipsychotic drugs suggests that biomarkers can be identified and that these biomarkers that will be useful in diagnosing and treating people with schizophrenia.

  12. Warming and environmental changes in the eastern North Sea Basin during the Palaeocene–Eocene Thermal Maximum as revealed by biomarker lipids

    OpenAIRE

    Schoon, P. L.; Heilmann-Clausen, C.; Schultz, B.P.; Sinninghe Damsté, J.S.; Schouten, S.

    2015-01-01

    Analysis of sediments deposited at different latitudes around the world during the Palaeocene–Eocene Thermal Maximum (PETM; ~56 Ma) have revealed a globally profound warming phase, regionally varying from 5–8 °C. Such records from Europe have not yet been obtained. We studied the variations in sea surface and continental mean annual air temperatures (SST and MAT, respectively) and the distribution patterns and stable carbon isotopes of higher plant derived n-alkanes in two proximal PETM secti...

  13. Biomarkers in Barrett's esophagus.

    Science.gov (United States)

    Reid, Brian J; Blount, Patricia L; Rabinovitch, Peter S

    2003-04-01

    future. Biopsy repositories are now readily available for phase 3 studies that can evaluate and compare biomarkers. There are initiatives for multi-institutional Barrett's Centers of Excellence that could provide rapid progress in biomarker evaluation. In addition to new candidate biomarkers, the human genome project has provided high-throughput methodologies and methods for computer analysis of data, which can provide the volume and quality control required for clinically useful biomarkers. Currently, 17p (p53) LOH has progressed the furthest among molecular biomarkers. The authors do not recommend its routine clinical use at the present time, however. Finally, it is likely that clinicians will want to follow the results of clinical treatment-response studies and epidemiologic studies that evaluate relationship between clinical interventions or environmental risk and protective factors and surrogate endpoints, especially if the endpoints are progessing well along the phases of biomarker validation. These studies are likely to be of clinical interest because they may becoming the basis for randomized clinical trials to prevent cancer in BE.

  14. Utility of Biomarkers for Early Detection of Malignant Mesothelioma in a High-risk Population — EDRN Public Portal

    Science.gov (United States)

    A prospective study to evaluate the utility of various biomarkers in the context of an MM Early Detection Program. The study cohort will be composed of workers at a company with known asbestos exposure. Historically, a considerable number of workers at this company have developed MM.

  15. Neuroimaging Biomarkers for Psychosis

    Science.gov (United States)

    Hager, Brandon M.

    2015-01-01

    Background Biomarkers provide clinicians with a predictable model for the diagnosis, treatment and follow-up of medical ailments. Psychiatry has lagged behind other areas of medicine in the identification of biomarkers for clinical diagnosis and treatment. In this review, we investigated the current state of neuroimaging as it pertains to biomarkers for psychosis. Methods We reviewed systematic reviews and meta-analyses of the structural (sMRI), functional (fMRI), diffusion-tensor (DTI), Positron emission tomography (PET) and spectroscopy (MRS) studies of subjects at-risk or those with an established schizophrenic illness. Only articles reporting effect-sizes and confidence intervals were included in an assessment of robustness. Results Out of the identified meta-analyses and systematic reviews, 21 studies met the inclusion criteria for assessment. There were 13 sMRI, 4 PET, 3 MRS, and 1 DTI studies. The search terms included in the current review encompassed familial high risk (FHR), clinical high risk (CHR), First episode (FES), Chronic (CSZ), schizophrenia spectrum disorders (SSD), and healthy controls (HC). Conclusions Currently, few neuroimaging biomarkers can be considered ready for diagnostic use in patients with psychosis. At least in part, this may be related to the challenges inherent in the current symptom-based approach to classifying these disorders. While available studies suggest a possible value of imaging biomarkers for monitoring disease progression, more systematic research is needed. To date, the best value of imaging data in psychoses has been to shed light on questions of disease pathophysiology, especially through the characterization of endophenotypes. PMID:25883891

  16. Serum High-Sensitivity Cardiac Troponin T Is a Significant Biomarker of Left-Ventricular Diastolic Dysfunction in Subjects with Non-Diabetic Chronic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Masashi Kitagawa

    2011-10-01

    Full Text Available Background: Chronic kidney disease (CKD is associated with left-ventricular (LV diastolic dysfunction (LVDD which progresses to diastolic heart failure. However, biomarkers predicting LVDD in patients with CKD are largely unknown. Methods: In 93 patients with non-diabetic CKD, the relationships among echocardiography, high-sensitivity cardiac troponin T (hs-cTnT, B-type natriuretic peptide (BNP, and renal function were evaluated. LV mass index, peak early diastolic mitral filling velocity (E, peak early diastolic mitral annular velocity (E′, and E/E′ were recorded. Results: The E′ values were significantly decreased and E/E′, BNP, and hs-cTnT increased with increasing CKD stage. The CKD patients with LVDD with E′ Conclusions: These data suggest that hs-cTnT may be a useful biomarker of LVDD in non- diabetic CKD patients.

  17. [Novel biomarkers for diabetic nephropathy].

    Science.gov (United States)

    Araki, Shin-ichi

    2014-02-01

    Diabetic nephropathy is a leading cause of end-stage renal disease worldwide. An early clinical sign of this complication is an increase of urinary albumin excretion, called microalbuminuria, which is not only a predictor of the progression of nephropathy, but also an independent risk factor for cardiovascular disease. Although microalbuminuria is clinically important to assess the prognosis of diabetic patients, it may be insufficient as an early and specific biomarker of diabetic nephropathy because of a large day-to-day variation and lack of a good correlation of microalbuminuria with renal dysfunction and pathohistological changes. Thus, more sensitive and specific biomarkers are needed to improve the diagnostic capability of identifying patients at high risk. The factors involved in renal tubulo-interstitial damage, the production and degradation of extracellular matrix, microinflammation, etc., are investigated as candidate molecules. Despite numerous efforts so far, the assessment of these biomarkers is still a subject of ongoing investigations. Recently, a variety of omics and quantitative techniques in systems biology are rapidly emerging in the field of biomarker discovery, including proteomics, transcriptomics, and metabolomics, and they have been applied to search for novel putative biomarkers of diabetic nephropathy. Novel biomarkers or their combination with microalbuminuria provide a better diagnostic accuracy than microalbuminuria alone, and may be useful for establishing personal medicine. Furthermore, the identification of novel biomarkers may provide insight into the mechanisms underlying diabetic nephropathy.

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

    Science.gov (United States)

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

    2016-04-01

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

  19. Imaging-based biomarkers of cognitive performance in older adults constructed via high-dimensional pattern regression applied to MRI and PET.

    Directory of Open Access Journals (Sweden)

    Ying Wang

    Full Text Available In this study, we used high-dimensional pattern regression methods based on structural (gray and white matter; GM and WM and functional (positron emission tomography of regional cerebral blood flow; PET brain data to identify cross-sectional imaging biomarkers of cognitive performance in cognitively normal older adults from the Baltimore Longitudinal Study of Aging (BLSA. We focused on specific components of executive and memory domains known to decline with aging, including manipulation, semantic retrieval, long-term memory (LTM, and short-term memory (STM. For each imaging modality, brain regions associated with each cognitive domain were generated by adaptive regional clustering. A relevance vector machine was adopted to model the nonlinear continuous relationship between brain regions and cognitive performance, with cross-validation to select the most informative brain regions (using recursive feature elimination as imaging biomarkers and optimize model parameters. Predicted cognitive scores using our regression algorithm based on the resulting brain regions correlated well with actual performance. Also, regression models obtained using combined GM, WM, and PET imaging modalities outperformed models based on single modalities. Imaging biomarkers related to memory performance included the orbito-frontal and medial temporal cortical regions with LTM showing stronger correlation with the temporal lobe than STM. Brain regions predicting executive performance included orbito-frontal, and occipito-temporal areas. The PET modality had higher contribution to most cognitive domains except manipulation, which had higher WM contribution from the superior longitudinal fasciculus and the genu of the corpus callosum. These findings based on machine-learning methods demonstrate the importance of combining structural and functional imaging data in understanding complex cognitive mechanisms and also their potential usage as biomarkers that predict cognitive

  20. Dietary biomarkers: advances, limitations and future directions

    Directory of Open Access Journals (Sweden)

    Hedrick Valisa E

    2012-12-01

    Full Text Available Abstract The subjective nature of self-reported dietary intake assessment methods presents numerous challenges to obtaining accurate dietary intake and nutritional status. This limitation can be overcome by the use of dietary biomarkers, which are able to objectively assess dietary consumption (or exposure without the bias of self-reported dietary intake errors. The need for dietary biomarkers was addressed by the Institute of Medicine, who recognized the lack of nutritional biomarkers as a knowledge gap requiring future research. The purpose of this article is to review existing literature on currently available dietary biomarkers, including novel biomarkers of specific foods and dietary components, and assess the validity, reliability and sensitivity of the markers. This review revealed several biomarkers in need of additional validation research; research is also needed to produce sensitive, specific, cost-effective and noninvasive dietary biomarkers. The emerging field of metabolomics may help to advance the development of food/nutrient biomarkers, yet advances in food metabolome databases are needed. The availability of biomarkers that estimate intake of specific foods and dietary components could greatly enhance nutritional research targeting compliance to national recommendations as well as direct associations with disease outcomes. More research is necessary to refine existing biomarkers by accounting for confounding factors, to establish new indicators of specific food intake, and to develop techniques that are cost-effective, noninvasive, rapid and accurate measures of nutritional status.

  1. Chronic exposure of killifish to a highly polluted environment desensitizes estrogen-responsive reproductive and biomarker genes

    Energy Technology Data Exchange (ETDEWEB)

    Bugel, Sean M., E-mail: Sean.Bugel@oregonstate.edu [Department of Environmental and Molecular Toxicology, Environmental Health Sciences Center, Oregon State University, Corvallis, OR 97331 (United States); Bonventre, Josephine A. [Department of Environmental and Molecular Toxicology, Environmental Health Sciences Center, Oregon State University, Corvallis, OR 97331 (United States); White, Lori A. [Department of Biochemistry and Microbiology, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901 (United States); Tanguay, Robert L. [Department of Environmental and Molecular Toxicology, Environmental Health Sciences Center, Oregon State University, Corvallis, OR 97331 (United States); Cooper, Keith R. [Department of Biochemistry and Microbiology, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901 (United States)

    2014-07-01

    Highlights: • Reproductive biomarker genes in Newark Bay killifish are desensitized to estrogen. • Gene desensitization indicates pre-transcriptional effects on estrogen signaling. • Desensitization does not have a metabolic or epigenetic basis (gene methylation). • Modulation of vitellogenin and choriogenin genes correlates with reproductive impacts. • Choriogenin L appears less prone to false negatives and may be a sensitive biomarker. - Abstract: Reproductive and endocrine disruption is commonly reported in aquatic species exposed to complex contaminant mixtures. We previously reported that Atlantic killifish (Fundulus heteroclitus) from the chronically contaminated Newark Bay, NJ, exhibit multiple endocrine disrupting effects, including inhibition of vitellogenesis (yolk protein synthesis) in females and false negative vitellogenin biomarker responses in males. Here, we characterized the effects on estrogen signaling and the transcriptional regulation of estrogen-responsive genes in this model population. First, a dose–response study tested the hypothesis that reproductive biomarkers (vtg1, vtg2, chg H, chg Hm, chg L) in Newark Bay killifish are relatively less sensitive to 17β-estradiol at the transcriptional level, relative to a reference (Tuckerton, NJ) population. The second study assessed expression for various metabolism (cyp1a, cyp3a30, mdr) and estrogen receptor (ER α, ER βa, ER βb) genes under basal and estrogen treatment conditions in both populations. Hepatic metabolism of 17β-estradiol was also evaluated in vitro as an integrated endpoint for adverse effects on metabolism. In the third study, gene methylation was evaluated for promoters of vtg1 (8 CpGs) and vtg2 (10 CpGs) in both populations, and vtg1 promoter sequences were examined for single nucleotide polymorphism (SNPs). Overall, these studies show that multi-chemical exposures at Newark Bay have desensitized all reproductive biomarkers tested to estrogen. For example, at 10 ng

  2. Characterization of long non-coding RNA-associated ceRNA network to reveal potential prognostic lncRNA biomarkers in human ovarian cancer.

    Science.gov (United States)

    Zhou, Meng; Wang, Xiaojun; Shi, Hongbo; Cheng, Liang; Wang, Zhenzhen; Zhao, Hengqiang; Yang, Lei; Sun, Jie

    2016-03-15

    Accumulating evidence has underscored the important roles of long non-coding RNAs (lncRNAs) acting as competing endogenous RNAs (ceRNAs) in cancer initiation and progression. In this study, we used an integrative computational method to identify miRNA-mediated ceRNA crosstalk between lncRNAs and mRNAs, and constructed global and progression-related lncRNA-associated ceRNA networks (LCeNETs) in ovarian cancer (OvCa) based on "ceRNA hypothesis". The constructed LCeNETs exhibited small world, modular architecture and high functional specificity for OvCa. Known OvCa-related genes tended to be hubs and occurred preferentially in the functional modules. Ten lncRNA ceRNAs were identified as potential candidates associated with stage progression in OvCa using ceRNA-network driven method. Finally, we developed a ten-lncRNA signature which classified patients into high- and low-risk subgroups with significantly different survival outcomes. Our study will provide novel insight for better understanding of ceRNA-mediated gene regulation in progression of OvCa and facilitate the identification of novel diagnostic and therapeutic lncRNA ceRNAs for OvCa. PMID:26863568

  3. Saliva: A diagnostic biomarker of periodontal diseases.

    Science.gov (United States)

    Patil, Priti Basgauda; Patil, Basgauda Ramesh

    2011-10-01

    Early detection of disease plays a crucial role in successful therapy. Early diagnosis and management reduces the severity and possible complications of the disease process. To overcome this challenge, medical researchers are devoted to finding molecular disease biomarkers that reveal a hidden lethal threat before the disease becomes complicated. Saliva, an important physiologic fluid, containing a highly complex mixture of substances, is rapidly gaining popularity as a diagnostic tool. Periodontal disease is a chronic disease of the oral cavity comprising a group of inflammatory conditions affecting the supporting structures of the dentition. In the field of periodontology, traditional clinical criteria are often insufficient for determining sites of active disease, for monitoring the response to therapy, or for measuring the degree of susceptibility to future disease progression. Saliva, as a mirror of oral and systemic health, is a valuable source for clinically relevant information because it contains biomarkers specific for the unique physiologic aspects of periodontal diseases. This review highlights the various potentials of saliva as a diagnostic biomarker for periodontal diseases.

  4. Molecular profiling reveals diversity of stress signal transduction cascades in highly penetrant Alzheimer's disease human skin fibroblasts.

    Directory of Open Access Journals (Sweden)

    Graziella Mendonsa

    Full Text Available The serious and growing impact of the neurodegenerative disorder Alzheimer's disease (AD as an individual and societal burden raises a number of key questions: Can a blanket test for Alzheimer's disease be devised forecasting long-term risk for acquiring this disorder? Can a unified therapy be devised to forestall the development of AD as well as improve the lot of present sufferers? Inflammatory and oxidative stresses are associated with enhanced risk for AD. Can an AD molecular signature be identified in signaling pathways for communication within and among cells during inflammatory and oxidative stress, suggesting possible biomarkers and therapeutic avenues? We postulated a unique molecular signature of dysfunctional activity profiles in AD-relevant signaling pathways in peripheral tissues, based on a gain of function in G-protein-coupled bradykinin B2 receptor (BKB2R inflammatory stress signaling in skin fibroblasts from AD patients that results in tau protein Ser hyperphosphorylation. Such a signaling profile, routed through both phosphorylation and proteolytic cascades activated by inflammatory and oxidative stresses in highly penetrant familial monogenic forms of AD, could be informative for pathogenesis of the complex multigenic sporadic form of AD. Comparing stimulus-specific cascades of signal transduction revealed a striking diversity of molecular signaling profiles in AD human skin fibroblasts that express endogenous levels of mutant presenilins PS-1 or PS-2 or the Trisomy 21 proteome. AD fibroblasts bearing the PS-1 M146L mutation associated with highly aggressive AD displayed persistent BKB2R signaling plus decreased ERK activation by BK, correctible by gamma-secretase inhibitor Compound E. Lack of these effects in the homologous PS-2 mutant cells indicates specificity of presenilin gamma-secretase catalytic components in BK signaling biology directed toward MAPK activation. Oxidative stress revealed a JNK-dependent survival

  5. Intraperitoneal administration of high doses of polyethylene glycol (PEG) causes hepatic subcapsular necrosis and low-grade peritonitis with a rise in hepatic biomarkers

    International Nuclear Information System (INIS)

    Polyethylene glycols (PEGs) are commonly employed as excipients in preclinical studies and in vitro experiments to dissolve poorly hydrosoluble drugs. Their use is generally considered safe in both animals and humans; however, limited data is available concerning the safety of PEGs when administered parenterally. The results of our investigation demonstrate that PEG-400 can have an irritant effect on serosal surfaces and causes subcapsular hepatocellular necrosis in mice when administered intraperitoneally at a high dose (4 mL/kg). Accordingly, levels of serum biomarkers of liver injury need to be carefully interpreted in studies where PEG is administered intraperitoneally and always in association with the results of the histological assessment

  6. Defining molecular and cellular responses after low and high linear energy transfer radiations to develop biomarkers of carcinogenic risk or therapeutic outcome.

    Science.gov (United States)

    Story, Michael; Ding, Liang-hao; Brock, William A; Ang, K Kian; Alsbeih, Ghazi; Minna, John; Park, Seongmi; Das, Amit

    2012-11-01

    The variability in radiosensitivity across the human population is governed in part by genetic factors. The ability to predict therapeutic response, identify individuals at greatest risk for adverse clinical responses after therapeutic radiation doses, or identify individuals at high risk for carcinogenesis from environmental or medical radiation exposures has a medical and economic impact on both the individual and society at large. As radiotherapy incorporates particles, particularly particles larger than protons, into therapy, the need for such discriminators, (i.e., biomarkers) will become ever more important. Cellular assays for survival, DNA repair, or chromatid/chromosomal analysis have been used to identify at-risk individuals, but they are not clinically applicable. Newer approaches, such as genome-wide analysis of gene expression or single nucleotide polymorphisms and small copy number variations within chromosomes, are examples of technologies being applied to the discovery process. Gene expression analysis of primary or immortalized human cells suggests that there are distinct gene expression patterns associated with radiation exposure to both low and high linear energy transfer radiations and that those most radiosensitive are discernible by their basal gene expression patterns. However, because the genetic alterations that drive radio response may be subtle and cumulative, the need for large sample sizes of specific cell or tissue types is required. A systems biology approach will ultimately be necessary. Potential biomarkers from cell lines or animal models will require validation in a human setting where possible and before being considered as a credible biomarker some understanding of the molecular mechanism is necessary.

  7. Fibrosis biomarkers in workers exposed to MWCNTs.

    Science.gov (United States)

    Fatkhutdinova, Liliya M; Khaliullin, Timur O; Vasil'yeva, Olga L; Zalyalov, Ramil R; Mustafin, Ilshat G; Kisin, Elena R; Birch, M Eileen; Yanamala, Naveena; Shvedova, Anna A

    2016-05-15

    Multi-walled carbon nanotubes (MWCNT) with their unique physico-chemical properties offer numerous technological advantages and are projected to drive the next generation of manufacturing growth. As MWCNT have already found utility in different industries including construction, engineering, energy production, space exploration and biomedicine, large quantities of MWCNT may reach the environment and inadvertently lead to human exposure. This necessitates the urgent assessment of their potential health effects in humans. The current study was carried out at NanotechCenter Ltd. Enterprise (Tambov, Russia) where large-scale manufacturing of MWCNT along with relatively high occupational exposure levels was reported. The goal of this small cross-sectional study was to evaluate potential biomarkers during occupational exposure to MWCNT. All air samples were collected at the workplaces from both specific areas and personal breathing zones using filter-based devices to quantitate elemental carbon and perform particle analysis by TEM. Biological fluids of nasal lavage, induced sputum and blood serum were obtained from MWCNT-exposed and non-exposed workers for assessment of inflammatory and fibrotic markers. It was found that exposure to MWCNTs caused significant increase in IL-1β, IL6, TNF-α, inflammatory cytokines and KL-6, a serological biomarker for interstitial lung disease in collected sputum samples. Moreover, the level of TGF-β1 was increased in serum obtained from young exposed workers. Overall, the results from this study revealed accumulation of inflammatory and fibrotic biomarkers in biofluids of workers manufacturing MWCNTs. Therefore, the biomarkers analyzed should be considered for the assessment of health effects of occupational exposure to MWCNT in cross-sectional epidemiological studies. PMID:26902652

  8. High Resolution Discovery Proteomics Reveals Candidate Disease Progression Markers of Alzheimer's Disease in Human Cerebrospinal Fluid.

    Directory of Open Access Journals (Sweden)

    Ronald C Hendrickson

    Full Text Available Disease modifying treatments for Alzheimer's disease (AD constitute a major goal in medicine. Current trends suggest that biomarkers reflective of AD neuropathology and modifiable by treatment would provide supportive evidence for disease modification. Nevertheless, a lack of quantitative tools to assess disease modifying treatment effects remains a major hurdle. Cerebrospinal fluid (CSF biochemical markers such as total tau, p-tau and Ab42 are well established markers of AD; however, global quantitative biochemical changes in CSF in AD disease progression remain largely uncharacterized. Here we applied a high resolution open discovery platform, dMS, to profile a cross-sectional cohort of lumbar CSF from post-mortem diagnosed AD patients versus those from non-AD/non-demented (control patients. Multiple markers were identified to be statistically significant in the cohort tested. We selected two markers SME-1 (p<0.0001 and SME-2 (p = 0.0004 for evaluation in a second independent longitudinal cohort of human CSF from post-mortem diagnosed AD patients and age-matched and case-matched control patients. In cohort-2, SME-1, identified as neuronal secretory protein VGF, and SME-2, identified as neuronal pentraxin receptor-1 (NPTXR, in AD were 21% (p = 0.039 and 17% (p = 0.026 lower, at baseline, respectively, than in controls. Linear mixed model analysis in the longitudinal cohort estimate a decrease in the levels of VGF and NPTXR at the rate of 10.9% and 6.9% per year in the AD patients, whereas both markers increased in controls. Because these markers are detected by mass spectrometry without the need for antibody reagents, targeted MS based assays provide a clear translation path for evaluating selected AD disease-progression markers with high analytical precision in the clinic.

  9. High rates of hybridisation reveal fragile reproductive barriers between endangered Australian sea snakes

    DEFF Research Database (Denmark)

    Sanders, Kate L; Redsted Rasmussen, Arne; Guinea, Michael L.

    2014-01-01

    The viviparous sea snakes include 62 ecologically diverse species, many of which are of very recent evolutionary origin and have overlapping distributions. Peak sea snake diversity and endemism is recorded from the isolated emergent reefs of the Timor Sea in Northwest Australia. However, nine...... designations, but revealed high frequencies of hybrids on all four reefs and individuals of pure A. fuscus ancestry only at Scott and (historically) Ashmore. Most unexpectedly, 95% of snakes sampled at Hibernia were hybrids that resembled A. laevis in phenotype, revealing a collapse of reproductive barriers...

  10. Peculiarities of high-overtone transition probabilities in carbon monoxide revealed by high-precision calculation

    Energy Technology Data Exchange (ETDEWEB)

    Medvedev, Emile S., E-mail: esmedved@orc.ru [The Institute of Problems of Chemical Physics, Russian Academy of Sciences, Prospect Akademika Semenova 1, 142432 Chernogolovka (Russian Federation); Meshkov, Vladimir V.; Stolyarov, Andrey V. [Department of Chemistry, Lomonosov Moscow State University, Leninskie gory 1/3, 119991 Moscow (Russian Federation); Gordon, Iouli E. [Atomic and Molecular Physics Division, Harvard-Smithsonian Center for Astrophysics, 60 Garden St, Cambridge, Massachusetts 02138 (United States)

    2015-10-21

    In the recent work devoted to the calculation of the rovibrational line list of the CO molecule [G. Li et al., Astrophys. J., Suppl. Ser. 216, 15 (2015)], rigorous validation of the calculated parameters including intensities was carried out. In particular, the Normal Intensity Distribution Law (NIDL) [E. S. Medvedev, J. Chem. Phys. 137, 174307 (2012)] was employed for the validation purposes, and it was found that, in the original CO line list calculated for large changes of the vibrational quantum number up to Δn = 41, intensities with Δn > 11 were unphysical. Therefore, very high overtone transitions were removed from the published list in Li et al. Here, we show how this type of validation is carried out and prove that the quadruple precision is indispensably required to predict the reliable intensities using the conventional 32-bit computers. Based on these calculations, the NIDL is shown to hold up for the 0 → n transitions till the dissociation limit around n = 83, covering 45 orders of magnitude in the intensity. The low-intensity 0 → n transition predicted in the work of Medvedev [Determination of a new molecular constant for diatomic systems. Normal intensity distribution law for overtone spectra of diatomic and polyatomic molecules and anomalies in overtone absorption spectra of diatomic molecules, Institute of Chemical Physics, Russian Academy of Sciences, Chernogolovka, 1984] at n = 5 is confirmed, and two additional “abnormal” intensities are found at n = 14 and 23. Criteria for the appearance of such “anomalies” are formulated. The results could be useful to revise the high-overtone molecular transition probabilities provided in spectroscopic databases.

  11. Peculiarities of high-overtone transition probabilities in carbon monoxide revealed by high-precision calculation

    Science.gov (United States)

    Medvedev, Emile S.; Meshkov, Vladimir V.; Stolyarov, Andrey V.; Gordon, Iouli E.

    2015-10-01

    In the recent work devoted to the calculation of the rovibrational line list of the CO molecule [G. Li et al., Astrophys. J., Suppl. Ser. 216, 15 (2015)], rigorous validation of the calculated parameters including intensities was carried out. In particular, the Normal Intensity Distribution Law (NIDL) [E. S. Medvedev, J. Chem. Phys. 137, 174307 (2012)] was employed for the validation purposes, and it was found that, in the original CO line list calculated for large changes of the vibrational quantum number up to Δn = 41, intensities with Δn > 11 were unphysical. Therefore, very high overtone transitions were removed from the published list in Li et al. Here, we show how this type of validation is carried out and prove that the quadruple precision is indispensably required to predict the reliable intensities using the conventional 32-bit computers. Based on these calculations, the NIDL is shown to hold up for the 0 → n transitions till the dissociation limit around n = 83, covering 45 orders of magnitude in the intensity. The low-intensity 0 → n transition predicted in the work of Medvedev [Determination of a new molecular constant for diatomic systems. Normal intensity distribution law for overtone spectra of diatomic and polyatomic molecules and anomalies in overtone absorption spectra of diatomic molecules, Institute of Chemical Physics, Russian Academy of Sciences, Chernogolovka, 1984] at n = 5 is confirmed, and two additional "abnormal" intensities are found at n = 14 and 23. Criteria for the appearance of such "anomalies" are formulated. The results could be useful to revise the high-overtone molecular transition probabilities provided in spectroscopic databases.

  12. Peculiarities of high-overtone transition probabilities in carbon monoxide revealed by high-precision calculation

    International Nuclear Information System (INIS)

    In the recent work devoted to the calculation of the rovibrational line list of the CO molecule [G. Li et al., Astrophys. J., Suppl. Ser. 216, 15 (2015)], rigorous validation of the calculated parameters including intensities was carried out. In particular, the Normal Intensity Distribution Law (NIDL) [E. S. Medvedev, J. Chem. Phys. 137, 174307 (2012)] was employed for the validation purposes, and it was found that, in the original CO line list calculated for large changes of the vibrational quantum number up to Δn = 41, intensities with Δn > 11 were unphysical. Therefore, very high overtone transitions were removed from the published list in Li et al. Here, we show how this type of validation is carried out and prove that the quadruple precision is indispensably required to predict the reliable intensities using the conventional 32-bit computers. Based on these calculations, the NIDL is shown to hold up for the 0 → n transitions till the dissociation limit around n = 83, covering 45 orders of magnitude in the intensity. The low-intensity 0 → n transition predicted in the work of Medvedev [Determination of a new molecular constant for diatomic systems. Normal intensity distribution law for overtone spectra of diatomic and polyatomic molecules and anomalies in overtone absorption spectra of diatomic molecules, Institute of Chemical Physics, Russian Academy of Sciences, Chernogolovka, 1984] at n = 5 is confirmed, and two additional “abnormal” intensities are found at n = 14 and 23. Criteria for the appearance of such “anomalies” are formulated. The results could be useful to revise the high-overtone molecular transition probabilities provided in spectroscopic databases

  13. Separating the Drivers from the Driven: Integrative Network and Pathway Approaches Aid Identification of Disease Biomarkers from High-Throughput Data

    Science.gov (United States)

    McDermott, Jason E.; Costa, Michelle; Janszen, Derek; Singhal, Mudita; Tilton, Susan C.

    2010-01-01

    The recent advances in high-throughput data acquisition have driven a revolution in the study of human disease and determination of molecular biomarkers of disease states. It has become increasingly clear that many of the most important human diseases arise as the result of a complex interplay between several factors including environmental factors, such as exposure to toxins or pathogens, diet, lifestyle, and the genetics of the individual patient. Recent research has begun to describe these factors in the context of networks which describe relationships between biological components, such as genes, proteins and metabolites, and have made progress towards the understanding of disease as a dysfunction of the entire system, rather than, for example, mutations in single genes. We provide a summary of some of the recent work in this area, focusing on how the integration of different kinds of complementary data, and analysis of biological networks and pathways can lead to discovery of robust, specific and useful biomarkers of disease and how these methods can help shed light on the mechanisms and etiology of the diseases being studied. PMID:20534910

  14. Biomarkers in Computational Toxicology

    Science.gov (United States)

    Biomarkers are a means to evaluate chemical exposure and/or the subsequent impacts on toxicity pathways that lead to adverse health outcomes. Computational toxicology can integrate biomarker data with knowledge of exposure, chemistry, biology, pharmacokinetics, toxicology, and e...

  15. Higher surface mass balance of the Greenland ice sheet revealed by high-resolution climate modeling

    OpenAIRE

    Ettema, J.; M. R. van den Broeke; van Meijgaard, E.; Van De Berg, W. J.; Bamber, Jonathan L.; Box, J. E.; Bales, R. C.

    2009-01-01

    High-resolution (∼11 km) regional climate modeling shows total annual precipitation on the Greenland ice sheet for 1958-2007 to be up to 24% and surface mass balance up to 63% higher than previously thought. The largest differences occur in coastal southeast Greenland, where the much higher resolution facilitates capturing snow accumulation peaks that past five-fold coarser resolution regional climate models missed. The surface mass balance trend over the full 1958-2007 period reveals the cla...

  16. Analysis of 27 vascular-related proteins reveals that NT-proBNP is a potential biomarker for Alzheimer’s disease and mild cognitive impairment: A pilot-study

    Science.gov (United States)

    Marksteiner, Josef; Imarhiagbe, Douglas; Defrancesco, Michaela; Deisenhammer, Eberhard A.; Kemmler, Georg; Humpel, Christian

    2015-01-01

    Alzheimer’s disease (AD) is a severe neurodegenerative disease. Cerebrovascular changes often accompany AD-related pathology. Despite a considerable progress in the diagnostic accuracy of AD, no blood biomarkers have been established so far. The aim of the present study was to search for changes in plasma levels of 27 vascular-related proteins of healthy controls, patients with mild cognitive impairment (MCI) and AD. In a sample of 80 participants we showed that out of these 27 proteins, six proteins were slightly changed (up to 1.5×) in AD (alpha2-macroglobulin, apolipoprotein-A1, plasminogen activator inhibitor, RAGE, Tissue Inhibitors of Metalloproteinases-1 and Trombospondin-2) and one marker (serum amyloid A) was enhanced up to 6× but with a very high variance. However, N-terminal pro-brain natriuretic peptide (NT-proBNP) was significantly enhanced both in MCI and AD patients (1.9×). In a second analysis of a sample of 110 subjects including younger healthy controls, we confirmed that NT-proBNP has the potential to be a stable candidate protein for both diagnosis and AD disease progression. PMID:24333505

  17. Combination of biomarkers

    DEFF Research Database (Denmark)

    Thurfjell, Lennart; Lötjönen, Jyrki; Lundqvist, Roger;

    2012-01-01

    The New National Institute on Aging-Alzheimer's Association diagnostic guidelines for Alzheimer's disease (AD) incorporate biomarkers in the diagnostic criteria and suggest division of biomarkers into two categories: Aβ accumulation and neuronal degeneration or injury.......The New National Institute on Aging-Alzheimer's Association diagnostic guidelines for Alzheimer's disease (AD) incorporate biomarkers in the diagnostic criteria and suggest division of biomarkers into two categories: Aβ accumulation and neuronal degeneration or injury....

  18. High-resolution blood-pool-contrast-enhanced MR angiography in glioblastoma: tumor-associated neovascularization as a biomarker for patient survival. A preliminary study

    Energy Technology Data Exchange (ETDEWEB)

    Puig, Josep; Blasco, Gerard; Remollo, Sebastian; Hernandez, David; Pedraza, Salvador [Hospital Universitari Dr Josep Trueta, Research Unit of Diagnostic Imaging Institute (IDI), Department of Radiology [Girona Biomedical Research Institute] IDIBGI, Girona (Spain); Daunis-i-Estadella, Josep; Mateu, Gloria [University of Girona, Department of Computer Science, Applied Mathematics and Statistics, Girona (Spain); Alberich-Bayarri, Angel [La Fe Polytechnics and University Hospital, Biomedical Imaging Research Group (GIBI230), La Fe Health Research Institute, Valencia (Spain); Essig, Marco [University of Manitoba, Department of Radiology, Winnipeg (Canada); Jain, Rajan [NYU School of Medicine, Division of Neuroradiology, Department of Radiology, New York, NY (United States); Puigdemont, Montserrat [Hospital Universitari Dr Josep Trueta, Catalan Institute of Oncology (ICO), Hospital Cancer Registry, Girona (Spain); Sanchez-Gonzalez, Javier [Philips Healthcare Iberica, Madrid (Spain); Wintermark, Max [Stanford University, Department of Radiology, Neuroradiology Division, Palo Alto, CA (United States)

    2016-01-15

    The objective of the study was to determine whether tumor-associated neovascularization on high-resolution gadofosveset-enhanced magnetic resonance angiography (MRA) is a useful biomarker for predicting survival in patients with newly diagnosed glioblastomas. Before treatment, 35 patients (25 men; mean age, 64 ± 14 years) with glioblastoma underwent MRI including first-pass dynamic susceptibility contrast (DSC) perfusion and post-contrast T1WI sequences with gadobutrol (0.1 mmol/kg) and, 48 h later, high-resolution MRA with gadofosveset (0.03 mmol/kg). Volumes of interest for contrast-enhancing lesion (CEL), non-CEL, and contralateral normal-appearing white matter were obtained, and DSC perfusion and DWI parameters were evaluated. Prognostic factors were assessed by Kaplan-Meier survival and Cox proportional hazards model. Eighteen (51.42 %) glioblastomas were hypervascular on high-resolution MRA. Hypervascular glioblastomas were associated with higher CEL volume and lower Karnofsky score. Median survival rates for patients with hypovascular and hypervascular glioblastomas treated with surgery, radiotherapy, and chemotherapy were 15 and 9.75 months, respectively (P < 0.001). Tumor-associated neovascularization was the best predictor of survival at 5.25 months (AUC = 0.794, 81.2 % sensitivity, 77.8 % specificity, 76.5 % positive predictive value, 82.4 % negative predictive value) and yielded the highest hazard ratio (P < 0.001). Tumor-associated neovascularization detected on high-resolution blood-pool-contrast-enhanced MRA of newly diagnosed glioblastoma seems to be a useful biomarker that correlates with worse survival. (orig.)

  19. High-resolution blood-pool-contrast-enhanced MR angiography in glioblastoma: tumor-associated neovascularization as a biomarker for patient survival. A preliminary study

    International Nuclear Information System (INIS)

    The objective of the study was to determine whether tumor-associated neovascularization on high-resolution gadofosveset-enhanced magnetic resonance angiography (MRA) is a useful biomarker for predicting survival in patients with newly diagnosed glioblastomas. Before treatment, 35 patients (25 men; mean age, 64 ± 14 years) with glioblastoma underwent MRI including first-pass dynamic susceptibility contrast (DSC) perfusion and post-contrast T1WI sequences with gadobutrol (0.1 mmol/kg) and, 48 h later, high-resolution MRA with gadofosveset (0.03 mmol/kg). Volumes of interest for contrast-enhancing lesion (CEL), non-CEL, and contralateral normal-appearing white matter were obtained, and DSC perfusion and DWI parameters were evaluated. Prognostic factors were assessed by Kaplan-Meier survival and Cox proportional hazards model. Eighteen (51.42 %) glioblastomas were hypervascular on high-resolution MRA. Hypervascular glioblastomas were associated with higher CEL volume and lower Karnofsky score. Median survival rates for patients with hypovascular and hypervascular glioblastomas treated with surgery, radiotherapy, and chemotherapy were 15 and 9.75 months, respectively (P < 0.001). Tumor-associated neovascularization was the best predictor of survival at 5.25 months (AUC = 0.794, 81.2 % sensitivity, 77.8 % specificity, 76.5 % positive predictive value, 82.4 % negative predictive value) and yielded the highest hazard ratio (P < 0.001). Tumor-associated neovascularization detected on high-resolution blood-pool-contrast-enhanced MRA of newly diagnosed glioblastoma seems to be a useful biomarker that correlates with worse survival. (orig.)

  20. High Expression of LAMP3 Is a Novel Biomarker of Poor Prognosis in Patients with Esophageal Squamous Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Xiaoyu Liao

    2015-07-01

    Full Text Available Lysosomal-associated membrane protein 3 (LAMP3, identified as a molecular marker of mature dendritic cells, is one of the LAMP family members. Its expression was induced by hypoxia, and was associated with hypoxia mediated metastasis in breast and cervical cancers. However, epithelial expression of LAMP3 and its prognostic value in esophageal squamous cell carcinoma (ESCC is still unknown. In the current study, mRNA expression of LAMP3 in 157 ESCC tissues and 50 adjacent normal tissues was detected by quantitative real-time PCR (qRT-PCR. LAMP3 protein expression in 46 paired cancerous and normal tissues was detected by immunohistochemistry (IHC. Then, DNA copy number was examined to observe its potential correlation with mRNA expression. The results showed that both mRNA and protein expression level of LAMP3 was significantly higher in cancerous tissues compared with normal controls (p < 0.001. LAMP3 DNA copy number was amplified in 70% of ESCC tissues and positive correlated with mRNA expression (p = 0.037. Furthermore, patients with higher LAMP3 expression had worse overall survival (HR = 1.90, 95% CI = 1.17–3.09, p = 0.010 and disease-free survival (HR = 1.80, 95% CI = 1.18–2.74, p = 0.006. In conclusion, our results suggest that epithelial LAMP3 expression is an independent prognostic biomarker for ESCC.

  1. Biomarkers of silicosis: Potential candidates

    Directory of Open Access Journals (Sweden)

    Tiwari R

    2005-01-01

    Full Text Available Silica dust is widely prevalent in the atmosphere and more common than the other types of dust, thus making silicosis the most frequently occurring pneumoconiosis. In India also, studies carried out by National Institute of Occupational Health have shown high prevalence of silicosis in small factories and even in nonoccupational exposed subjects. The postero-anterior chest radiographs remain the key tool in diagnosing and assessing the extent and severity of interstitial lung disease. Although Computed Tomography detects finer anatomical structure than radiography it could not get popularity because of its cost. On the basis of histological features of silicosis many potential biomarkers such as Cytokines, Tumor Necrosis Factor, Interleukin 1, Angiotensin Converting Enzyme, Serum Copper, Fas ligand (FasL, etc. have been tried. However, further studies are needed to establish these potential biomarkers as true biomarker of silicosis.

  2. Searching for native tree species and respective potential biomarkers for future assessment of pollution effects on the highly diverse Atlantic Forest in SE-Brazil

    International Nuclear Information System (INIS)

    This study summarizes the first effort to search for bioindicator tree species and respective potential biomarkers for future assessment of potential mixed pollution effects on the highly diverse Atlantic Forest in SE-Brazil. Leaves of the three most abundant species inventoried in a phytosociological survey (Croton floribundus, Piptadenia gonoacantha and Astronium graveolens) were collected in four forest remnants during winter and summer (2012). Their potential bioindicator attributes were highlighted using a screening of morphological, chemical and biochemical markers. The leaf surface structure and/or epicuticular wax composition pointed the accumulator properties of C. floribundus and P. gonoacantha. C. floribundus is a candidate for assessing potential accumulation of Cu, Cd, Mn, Ni, S and Zn. P. gonoacantha is a candidate to monitor polycyclic aromatic hydrocarbons. Increased levels of secondary metabolites and decreased antioxidant capacity in leaves of A. graveolens may support its value as a bioindicator for oxidative pollutants by visible dark stipplings. - Highlights: • We searched for tree species from Atlantic Forest for future air pollution monitoring in Brazil. • Croton floribundus, Astronium graveolens and Piptadenia gonoacantha were possible bioindicators. • P. gonoachanta was a potential bioindicator of polycyclic aromatic hydrocarbons. • C. floribundus was a potential bioindicator of heavy metals and sulfur. • A. graveolens may be used for monitoring oxidative pollutants, due to its biochemical leaf traits. - Inherent characteristics of the most abundant native tree species were potential biomarkers for assessing pollution effects on the highly diverse Atlantic Forest in SE-Brazil

  3. Prediction of transition from ultra-high risk to first-episode psychosis using a probabilistic model combining history, clinical assessment and fatty-acid biomarkers

    Science.gov (United States)

    Clark, S R; Baune, B T; Schubert, K O; Lavoie, S; Smesny, S; Rice, S M; Schäfer, M R; Benninger, F; Feucht, M; Klier, C M; McGorry, P D; Amminger, G P

    2016-01-01

    Current criteria identifying patients with ultra-high risk of psychosis (UHR) have low specificity, and less than one-third of UHR cases experience transition to psychosis within 3 years of initial assessment. We explored whether a Bayesian probabilistic multimodal model, combining baseline historical and clinical risk factors with biomarkers (oxidative stress, cell membrane fatty acids, resting quantitative electroencephalography (qEEG)), could improve this specificity. We analyzed data of a UHR cohort (n=40) with a 1-year transition rate of 28%. Positive and negative likelihood ratios were calculated for predictor variables with statistically significant receiver operating characteristic curves (ROCs), which excluded oxidative stress markers and qEEG parameters as significant predictors of transition. We clustered significant variables into historical (history of drug use), clinical (Positive and Negative Symptoms Scale positive, negative and general scores and Global Assessment of Function) and biomarker (total omega-3, nervonic acid) groups, and calculated the post-test probability of transition for each group and for group combinations using the odds ratio form of Bayes' rule. Combination of the three variable groups vastly improved the specificity of prediction (area under ROC=0.919, sensitivity=72.73%, specificity=96.43%). In this sample, our model identified over 70% of UHR patients who transitioned within 1 year, compared with 28% identified by standard UHR criteria. The model classified 77% of cases as very high or low risk (P>0.9, <0.1) based on history and clinical assessment, suggesting that a staged approach could be most efficient, reserving fatty-acid markers for 23% of cases remaining at intermediate probability following bedside interview. PMID:27648919

  4. Highly selective and automated online SPE LC-MS3 method for determination of cortisol and cortisone in human hair as biomarker for stress related diseases.

    Science.gov (United States)

    Quinete, Natalia; Bertram, Jens; Reska, Marcus; Lang, Jessica; Kraus, Thomas

    2015-03-01

    Hair analysis has been increasingly used to establish long-term biomarkers of exposure to both endogenous and exogenous substances, with a special emphasis on steroidal hormones. Hair cortisol and cortisone have been associated to physiological and psychological strains, anxiety and depression. Hair is a very complex matrix, which might jeopardize analyte detection at low concentrations. A new, highly selective and sensitive method based on fragments of second order, MS(3) (MS/MS/MS), was developed and validated for the analysis of hair cortisol and cortisone. An online solid phase extraction was performed on a C8 restricted access material (RAM) phase following by separation on a reversed-phase C18 column using methanol and 0.02% ammonium hydroxide as mobile phase. The developed method required minimal sample preparation and the injection of only 50 µL of sample leading to a LOQ of 2 pg mg(-1). Good linear responses were observed in the range 2-200 pg mg(-1) (R(2)>0.99) and extraction recoveries ranged between 77-125% and 70-123% for cortisol and cortisone, respectively. Intra- and inter-assay coefficients of variation were between 1.4 and 14%. In order to evaluate the applicability of the method, preliminary tests (N=33) were conducted in 3 cm hair samples (close to scalp) of healthy volunteers with an age range of 4-63. Average concentrations in hair were 12.7±14 pg mg(-1) and 41.6±42 pg mg(-1) for cortisol and cortisone, respectively. Further investigations on cortisol and cortisone as biomarkers for chronic psychological strain will be assessed as a next step. PMID:25618673

  5. Cytokines as Biomarkers in Rheumatoid Arthritis

    Directory of Open Access Journals (Sweden)

    Agata Burska

    2014-01-01

    Full Text Available RA is a complex disease that develops as a series of events often referred to as disease continuum. RA would benefit from novel biomarker development for diagnosis where new biomarkers are still needed (even if progresses have been made with the inclusion of ACPA into the ACR/EULAR 2010 diagnostic criteria and for prognostic notably in at risk of evolution patients with autoantibody-positive arthralgia. Risk biomarkers for rapid evolution or cardiovascular complications are also highly desirable. Monitoring biomarkers would be useful in predicting relapse. Finally, predictive biomarkers for therapy outcome would allow tailoring therapy to the individual. Increasing numbers of cytokines have been involved in RA pathology. Many have the potential as biomarkers in RA especially as their clinical utility is already established in other diseases and could be easily transferable to rheumatology. We will review the current knowledge’s relation to cytokine used as biomarker in RA. However, given the complexity and heterogeneous nature of RA, it is unlikely that a single cytokine may provide sufficient discrimination; therefore multiple biomarker signatures may represent more realistic approach for the future of personalised medicine in RA.

  6. Pyrosequencing reveals highly diverse and species-specific microbial communities in sponges from the Red Sea

    KAUST Repository

    Lee, Onon

    2010-11-18

    Marine sponges are associated with a remarkable array of microorganisms. Using a tag pyrosequencing technology, this study was the first to investigate in depth the microbial communities associated with three Red Sea sponges, Hyrtios erectus, Stylissa carteri and Xestospongia testudinaria. We revealed highly diverse sponge-associated bacterial communities with up to 1000 microbial operational taxonomic units (OTUs) and richness estimates of up to 2000 species. Altogether, 26 bacterial phyla were detected from the Red Sea sponges, 11 of which were absent from the surrounding sea water and 4 were recorded in sponges for the first time. Up to 100 OTUs with richness estimates of up to 300 archaeal species were revealed from a single sponge species. This is by far the highest archaeal diversity ever recorded for sponges. A non-negligible proportion of unclassified reads was observed in sponges. Our results demonstrated that the sponge-associated microbial communities remained highly consistent in the same sponge species from different locations, although they varied at different degrees among different sponge species. A significant proportion of the tag sequences from the sponges could be assigned to one of the sponge-specific clusters previously defined. In addition, the sponge-associated microbial communities were consistently divergent from those present in the surrounding sea water. Our results suggest that the Red Sea sponges possess highly sponge-specific or even sponge-species-specific microbial communities that are resistant to environmental disturbance, and much of their microbial diversity remains to be explored. © 2011 International Society for Microbial Ecology All rights reserved.

  7. Deep RNA sequencing at single base-pair resolution reveals high complexity of the rice transcriptome

    DEFF Research Database (Denmark)

    Zhang, Guojie; Guo, Guangwu; Hu, Xueda;

    2010-01-01

    Understanding the dynamics of eukaryotic transcriptome is essential for studying the complexity of transcriptional regulation and its impact on phenotype. However, comprehensive studies of transcriptomes at single base resolution are rare, even for modern organisms, and lacking for rice. Here, we...... present the first transcriptome atlas for eight organs of cultivated rice. Using high-throughput paired-end RNA-seq, we unambiguously detected transcripts expressing at an extremely low level, as well as a substantial number of novel transcripts, exons, and untranslated regions. An analysis of alternative...... fusion events are more common than expected. In-depth analysis revealed a multitude of fusion transcripts that might be by-products of alternative splicing. Validation and chimeric transcript structural analysis provided evidence that some of these transcripts are likely to be functional in the cell...

  8. Multilocus genotypic data reveal high genetic diversity and low population genetic structure of Iranian indigenous sheep.

    Science.gov (United States)

    Vahidi, S M F; Faruque, M O; Falahati Anbaran, M; Afraz, F; Mousavi, S M; Boettcher, P; Joost, S; Han, J L; Colli, L; Periasamy, K; Negrini, R; Ajmone-Marsan, P

    2016-08-01

    Iranian livestock diversity is still largely unexplored, in spite of the interest in the populations historically reared in this country located near the Fertile Crescent, a major livestock domestication centre. In this investigation, the genetic diversity and differentiation of 10 Iranian indigenous fat-tailed sheep breeds were investigated using 18 microsatellite markers. Iranian breeds were found to host a high level of diversity. This conclusion is substantiated by the large number of alleles observed across loci (average 13.83, range 7-22) and by the high within-breed expected heterozygosity (average 0.75, range 0.72-0.76). Iranian sheep have a low level of genetic differentiation, as indicated by the analysis of molecular variance, which allocated a very small proportion (1.67%) of total variation to the between-population component, and by the small fixation index (FST  = 0.02). Both Bayesian clustering and principal coordinates analysis revealed the absence of a detectable genetic structure. Also, no isolation by distance was observed through comparison of genetic and geographical distances. In spite of high within-breed variation, signatures of inbreeding were detected by the FIS indices, which were positive in all and statistically significant in three breeds. Possible factors explaining the patterns observed, such as considerable gene flow and inbreeding probably due to anthropogenic activities in the light of population management and conservation programmes, are discussed. PMID:26953226

  9. High Redshift Dust Obscured Galaxies, A Morphology-SED Connection Revealed by Keck Adaptive Optics

    CERN Document Server

    Melbourne, J; Brand, K; Desai, V; Armus, L; Dey, Arjun; Jannuzi, B T; Houck, J R; Matthews, K; Soifer, B T

    2009-01-01

    A simple optical to mid-IR color selection, R-[24] > 14, i.e. f_nu(24) / f_nu(R) > 1000, identifies highly dust obscured galaxies (DOGs) with typical redshifts of z~2 +/- 0.5. Extreme mid-IR luminosities (L_{IR} > 10^{12-14}) suggest that DOGs are powered by a combination of AGN and star formation, possibly driven by mergers. In an effort to compare their photometric properties with their rest frame optical morphologies, we obtained high spatial resolution (0.05 -0.1") Keck Adaptive Optics (AO) K'-band images of 15 DOGs. The images reveal a wide range of morphologies, including: small exponential disks (8 of 15), small ellipticals (4 of 15), and unresolved sources (2 of 15). One particularly diffuse source could not be classified because of low signal to noise ratio. We find a statistically significant correlation between galaxy concentration and mid-IR luminosity, with the most luminous DOGs exhibiting higher concentration and smaller physical size. DOGs with high concentration also tend to have spectral ene...

  10. Rapid ester biosynthesis screening reveals a high activity alcohol-O-acyltransferase (AATase) from tomato fruit.

    Science.gov (United States)

    Lin, Jyun-Liang; Zhu, Jie; Wheeldon, Ian

    2016-05-01

    Ethyl and acetate esters are naturally produced in various yeasts, plants, and bacteria. The biosynthetic pathways that produce these esters share a common reaction step, the condensation of acetyl/acyl-CoA with an alcohol by alcohol-O-acetyl/acyltransferase (AATase). Recent metabolic engineering efforts exploit AATase activity to produce fatty acid ethyl esters as potential diesel fuel replacements as well as short- and medium-chain volatile esters as fragrance and flavor compounds. These efforts have been limited by the lack of a rapid screen to quantify ester biosynthesis. Enzyme engineering efforts have also been limited by the lack of a high throughput screen for AATase activity. Here, we developed a high throughput assay for AATase activity and used this assay to discover a high activity AATase from tomato fruit, Solanum lycopersicum (Atf-S.l). Atf1-S.l exhibited broad specificity towards acyl-CoAs with chain length from C4 to C10 and was specific towards 1-pentanol. The AATase screen also revealed new acyl-CoA substrate specificities for Atf1, Atf2, Eht1, and Eeb1 from Saccharomyces cerevisiae, and Atf-C.m from melon fruit, Cucumis melo, thus increasing the pool of characterized AATases that can be used in ester biosynthesis of ester-based fragrance and flavor compounds as well as fatty acid ethyl ester biofuels. PMID:26814045

  11. Biomarkers for lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Zangar, Richard C.; Varnum, Susan M.

    2014-09-02

    A biomarker, method, test kit, and diagnostic system for detecting the presence of lymphoma in a person are disclosed. The lymphoma may be Hodgkin's lymphoma or non-Hodgkin's lymphoma. The person may be a high-risk subject. In one embodiment, a plasma sample from a person is obtained. The level of at least one protein listed in Table S3 in the plasma sample is measured. The level of at least one protein in the plasma sample is compared with the level in a normal or healthy subject. The lymphoma is diagnosed based upon the level of the at least one protein in the plasma sample in comparison to the normal or healthy level.

  12. An Ultra-High Fluorescence Enhancement and High Throughput Assay for Revealing Expression and Internalization of Chemokine Receptor CXCR4.

    Science.gov (United States)

    He, Hua; Wang, Xiaojuan; Cheng, Tiantian; Xia, Yongqing; Lao, Jun; Ge, Baosheng; Ren, Hao; Khan, Naseer Ullah; Huang, Fang

    2016-04-18

    Revealing chemokine receptor CXCR4 expression, distribution, and internalization levels in different cancers helps to evaluate cancer progression or prognosis and to set personalized treatment strategy. We here describe a sensitive and high-throughput immunoassay for determining CXCR4 expression and distribution in cancer cells. The assay is accessible to a wide range of users in an ordinary lab only by dip-coating poly(styrene-co-N-isopropylacrylamide) spheres on the glass substrate. The self- assembled spheres form three-dimensional photonic colloidal crystals which enhance the fluorescence of CF647 and Alexa Fluor 647 by a factor of up to 1000. CXCR4 in cells is detected by using the sandwich immunoassay, where the primary antibody recognizes CXCR4 and the secondary antibody is labeled with CF647. With the newly established assay, we quantified the total expression of CXCR4, its distribution on the cell membrane and cytoplasm, and revealed their internalization level upon SDF-1α activation in various cancer cells, even for those with extremely low expression level. PMID:26879206

  13. Unprecedented high-resolution view of bacterial operon architecture revealed by RNA sequencing.

    Science.gov (United States)

    Conway, Tyrrell; Creecy, James P; Maddox, Scott M; Grissom, Joe E; Conkle, Trevor L; Shadid, Tyler M; Teramoto, Jun; San Miguel, Phillip; Shimada, Tomohiro; Ishihama, Akira; Mori, Hirotada; Wanner, Barry L

    2014-01-01

    We analyzed the transcriptome of Escherichia coli K-12 by strand-specific RNA sequencing at single-nucleotide resolution during steady-state (logarithmic-phase) growth and upon entry into stationary phase in glucose minimal medium. To generate high-resolution transcriptome maps, we developed an organizational schema which showed that in practice only three features are required to define operon architecture: the promoter, terminator, and deep RNA sequence read coverage. We precisely annotated 2,122 promoters and 1,774 terminators, defining 1,510 operons with an average of 1.98 genes per operon. Our analyses revealed an unprecedented view of E. coli operon architecture. A large proportion (36%) of operons are complex with internal promoters or terminators that generate multiple transcription units. For 43% of operons, we observed differential expression of polycistronic genes, despite being in the same operons, indicating that E. coli operon architecture allows fine-tuning of gene expression. We found that 276 of 370 convergent operons terminate inefficiently, generating complementary 3' transcript ends which overlap on average by 286 nucleotides, and 136 of 388 divergent operons have promoters arranged such that their 5' ends overlap on average by 168 nucleotides. We found 89 antisense transcripts of 397-nucleotide average length, 7 unannotated transcripts within intergenic regions, and 18 sense transcripts that completely overlap operons on the opposite strand. Of 519 overlapping transcripts, 75% correspond to sequences that are highly conserved in E. coli (>50 genomes). Our data extend recent studies showing unexpected transcriptome complexity in several bacteria and suggest that antisense RNA regulation is widespread. Importance: We precisely mapped the 5' and 3' ends of RNA transcripts across the E. coli K-12 genome by using a single-nucleotide analytical approach. Our resulting high-resolution transcriptome maps show that ca. one-third of E. coli operons are

  14. Protective effect of Garcinia against renal oxidative stress and biomarkers induced by high fat and sucrose diet

    OpenAIRE

    Abd Eltawab Mohamed A; Kamel Hamdy H; Amin Kamal A

    2011-01-01

    Abstract Background Obesity became major health problem in the world, the objective of this work was to examine the effect of high sucrose and high fat diet to induce obesity on antioxidant defense system, biochemical changes in blood and tissue of control, non treated and treated groups by administration of Garcinia cambogia, and explore the mechanisms that link obesity with altered renal function Methods Rats were fed a standard control diet for 12 week (wk) or a diet containing 65% high su...

  15. Direct label-free electrical immunodetection of transplant rejection protein biomarker in physiological buffer using floating gate AlGaN/GaN high electron mobility transistors.

    Science.gov (United States)

    Tulip, Fahmida S; Eteshola, Edward; Desai, Suchita; Mostafa, Salwa; Roopa, Subramanian; Evans, Boyd; Islam, Syed Kamrul

    2014-06-01

    Monokine induced by interferon gamma (MIG/CXCL9) is used as an immune biomarker for early monitoring of transplant or allograft rejection. This paper demonstrates a direct electrical, label-free detection method of recombinant human MIG with anti-MIG IgG molecules in physiologically relevant buffer environment. The sensor platform used is a biologically modified GaN-based high electron mobility transistor (HEMT) device. Biomolecular recognition capability was provided by using high affinity anti-MIG monoclonal antibody to form molecular affinity interface receptors on short N-hydroxysuccinimide-ester functionalized disulphide (DSP) self-assembled monolayers (SAMs) on the gold sensing gate of the HEMT device. A floating gate configuration has been adopted to eliminate the influences of external gate voltage. Preliminary test results with the proposed chemically treated GaN HEMT biosensor show that MIG can be detected for a wide range of concentration varying from 5 ng/mL to 500 ng/mL.

  16. Migration of Frosts from High-Albedo Regions of Pluto: what New Horizons Reveals

    Science.gov (United States)

    Buratti, Bonnie J.; Stern, S. A.; Weaver, Hal A.; Young, Leslie A.; Olkin, Cathy B.; Ennico, Kimberly; Binzel, Richard P.; Zangari, Amanda; Earle, Alissa M.

    2015-11-01

    With its high eccentricity and obliquity, Pluto should exhibit seasonal volatile transport on its surface. Several lines of evidence support this transport: doubling of Pluto’s atmospheric pressure over the past two decades (Young et al., 2013, Ap. J. 766, L22; Olkin et al., 2015, Icarus 246, 230); changes in its historical rotational light curve, once all variations due to viewing geometry have been modelled (Buratti et al., 2015; Ap. J. 804, L6); and changes in HST albedo maps (Buie et al., 2010, Astron. J. 139, 1128). New Horizons LORRI images reveal that the region of greatest albedo change is not the polar cap(s) of Pluto, but the feature informally named Tombaugh Regio (TR). This feature has a normal reflectance as high as ~0.8 in some places, and it is superposed on older, lower-albedo pre-existing terrain with an albedo of only ~0.10. This contrast is larger than any other body in the Solar System, except for Iapetus. This albedo dichotomy leads to a complicated system of cold-trapping and thermal segregation, beyond the simple picture of seasonal volatile transport. Whatever the origin of TR, it initially acted as a cold trap, as the temperature differential between the high and low albedo regions could be enormous, possibly approaching 20K, based on their albedo differences and assuming their normalized phase curves are similar. This latter assumption will be refined as the full New Horizons data set is returned.Over six decades of ground-based photometry suggest that TR has been decreasing in albedo over the last 25 years. Possible causes include changing insolation angles, or sublimation from the edges where the high-albedo material impinges on a much warmer substrate.Funding by the NASA New Horizons Project acknowledged.

  17. DNA Barcoding Reveals High Cryptic Diversity of the Freshwater Halfbeak Genus Hemirhamphodon from Sundaland

    Science.gov (United States)

    Zainal Abidin, Muchlisin; Pulungan, Chaidir Parlindungan

    2016-01-01

    DNA barcoding of the cytochrome oxidase subunit I (COI) gene was utilized to assess the species diversity of the freshwater halfbeak genus Hemirhamphodon. A total of 201 individuals from 46 locations in Peninsular Malaysia, north Borneo (Sarawak) and Sumatra were successfully amplified for 616 base pairs of the COI gene revealing 231 variable and 213 parsimony informative sites. COI gene trees showed that most recognized species form monophyletic clades with high bootstrap support. Pairwise within species comparisons exhibited a wide range of intraspecific diversity from 0.0% to 14.8%, suggesting presence of cryptic diversity. This finding was further supported by barcode gap analysis, ABGD and the constructed COI gene trees. In particular, H. pogonognathus from Kelantan (northeast Peninsular Malaysia) diverged from the other H. pogonognathus groups with distances ranging from 7.8 to 11.8%, exceeding the nearest neighbor taxon. High intraspecific diversity was also observed in H. byssus and H. kuekanthali, but of a lower magnitude. This study also provides insights into endemism and phylogeographic structuring, and limited support for the Paleo-drainage divergence hypothesis as a driver of speciation in the genus Hemirhamphodon. PMID:27657915

  18. Histopathology reveals correlative and unique phenotypes in a high-throughput mouse phenotyping screen

    Directory of Open Access Journals (Sweden)

    Hibret A. Adissu

    2014-05-01

    Full Text Available The Mouse Genetics Project (MGP at the Wellcome Trust Sanger Institute aims to generate and phenotype over 800 genetically modified mouse lines over the next 5 years to gain a better understanding of mammalian gene function and provide an invaluable resource to the scientific community for follow-up studies. Phenotyping includes the generation of a standardized biobank of paraffin-embedded tissues for each mouse line, but histopathology is not routinely performed. In collaboration with the Pathology Core of the Centre for Modeling Human Disease (CMHD we report the utility of histopathology in a high-throughput primary phenotyping screen. Histopathology was assessed in an unbiased selection of 50 mouse lines with (n=30 or without (n=20 clinical phenotypes detected by the standard MGP primary phenotyping screen. Our findings revealed that histopathology added correlating morphological data in 19 of 30 lines (63.3% in which the primary screen detected a phenotype. In addition, seven of the 50 lines (14% presented significant histopathology findings that were not associated with or predicted by the standard primary screen. Three of these seven lines had no clinical phenotype detected by the standard primary screen. Incidental and strain-associated background lesions were present in all mutant lines with good concordance to wild-type controls. These findings demonstrate the complementary and unique contribution of histopathology to high-throughput primary phenotyping of mutant mice.

  19. Histopathology reveals correlative and unique phenotypes in a high-throughput mouse phenotyping screen.

    Science.gov (United States)

    Adissu, Hibret A; Estabel, Jeanne; Sunter, David; Tuck, Elizabeth; Hooks, Yvette; Carragher, Damian M; Clarke, Kay; Karp, Natasha A; Newbigging, Susan; Jones, Nora; Morikawa, Lily; White, Jacqueline K; McKerlie, Colin

    2014-05-01

    The Mouse Genetics Project (MGP) at the Wellcome Trust Sanger Institute aims to generate and phenotype over 800 genetically modified mouse lines over the next 5 years to gain a better understanding of mammalian gene function and provide an invaluable resource to the scientific community for follow-up studies. Phenotyping includes the generation of a standardized biobank of paraffin-embedded tissues for each mouse line, but histopathology is not routinely performed. In collaboration with the Pathology Core of the Centre for Modeling Human Disease (CMHD) we report the utility of histopathology in a high-throughput primary phenotyping screen. Histopathology was assessed in an unbiased selection of 50 mouse lines with (n=30) or without (n=20) clinical phenotypes detected by the standard MGP primary phenotyping screen. Our findings revealed that histopathology added correlating morphological data in 19 of 30 lines (63.3%) in which the primary screen detected a phenotype. In addition, seven of the 50 lines (14%) presented significant histopathology findings that were not associated with or predicted by the standard primary screen. Three of these seven lines had no clinical phenotype detected by the standard primary screen. Incidental and strain-associated background lesions were present in all mutant lines with good concordance to wild-type controls. These findings demonstrate the complementary and unique contribution of histopathology to high-throughput primary phenotyping of mutant mice.

  20. Microsatellite variability reveals high genetic diversity and low genetic differentiation in a critical giant panda population

    Institute of Scientific and Technical Information of China (English)

    Jiandong YANG; Zhihe ZHANG; Fujun SHEN; Xuyu YANG; Liang ZHANG; Limin CHEN; Wenping ZHANG; Qing ZHU; Rong HOU

    2011-01-01

    Understanding present patterns of genetic diversity is critical in order to design effective conservation and management strategies for endangered species.Tangjiahe Nature Reserve (NR) is one of the most important national reserves for giant pandas Ailuropoda melanoleuca in China.Previous studies have shown that giant pandas in Tangjiahe NR may be threatened by population decline and fragmentation.Here we used 10 microsatellite DNA markers to assess the genetic variability in the Tangjiahe population.The results indicate a low level of genetic differentiation between the Hongshihe and Motianling subpopulations in the reserve.Assignment tests using the Bayesian clustering method in STRUCTURE identified one genetic cluster from 42 individuals of the two subpopulations.All individuals from the same subpopulation were assigned to one cluster.This indicates high gene flow between subpopulations.F statistic analyses revealed a low Fls-value of 0.024 in the total population and implies a randomly mating population in Tangjiahe NR.Additionally,our data show a high level of genetic diversity for the Tangjiahe population.Mean allele number (A),Allelic richness (AR) and mean expected heterozygosity (HE) for the Tangiiahe population was 5.9,5.173 and 0.703,respectively.This wild giant panda population can be restored through concerted effort [Current Zoology 57 (6):717-724,2011].

  1. Westerly moisture transport to the middle of Himalayas revealed from the high deuterium excess

    Institute of Scientific and Technical Information of China (English)

    TIAN Lide; YAO Tandong; J.W.C.White; YU Wusheng; WANG Ninglian

    2005-01-01

    Previous studies found extremely high d-excess in both ice core and glacial melt water in Dasuopu glacier, Xixiabangma, middle of Himalayas. These values are much higher than the global average and those measured in southwest monsoon precipitation. The d-excess variation in over one year at Nyalam station will clarify this phenomenon. Studies show that the high d-excess is related to the seasonal variation of moisture transport to this region. The d-excess values are low during the southwest monsoon active periods, when moisture originated from the humid ocean surface. The d-excess values are higher in non-monsoon months, when moisture is derived from westerly transport. Winter and spring precipitation accounts for a substantial portion of the annual precipitation, resulting in higher d-excess in the yearly precipitation in the middle of Himalayas than other parts of the southern Tibetan Plateau. This finding reveals that the precipitation in the middle of Himalayas is not purely from southwest monsoon, but a large portion from the westerly transport, which is very important for ice core study in this area.

  2. Single nucleus genome sequencing reveals high similarity among nuclei of an endomycorrhizal fungus.

    Directory of Open Access Journals (Sweden)

    Kui Lin

    2014-01-01

    Full Text Available Nuclei of arbuscular endomycorrhizal fungi have been described as highly diverse due to their asexual nature and absence of a single cell stage with only one nucleus. This has raised fundamental questions concerning speciation, selection and transmission of the genetic make-up to next generations. Although this concept has become textbook knowledge, it is only based on studying a few loci, including 45S rDNA. To provide a more comprehensive insight into the genetic makeup of arbuscular endomycorrhizal fungi, we applied de novo genome sequencing of individual nuclei of Rhizophagus irregularis. This revealed a surprisingly low level of polymorphism between nuclei. In contrast, within a nucleus, the 45S rDNA repeat unit turned out to be highly diverged. This finding demystifies a long-lasting hypothesis on the complex genetic makeup of arbuscular endomycorrhizal fungi. Subsequent genome assembly resulted in the first draft reference genome sequence of an arbuscular endomycorrhizal fungus. Its length is 141 Mbps, representing over 27,000 protein-coding gene models. We used the genomic sequence to reinvestigate the phylogenetic relationships of Rhizophagus irregularis with other fungal phyla. This unambiguously demonstrated that Glomeromycota are more closely related to Mucoromycotina than to its postulated sister Dikarya.

  3. The high resolution structure of tyrocidine A reveals an amphipathic dimer.

    Science.gov (United States)

    Loll, Patrick J; Upton, Elizabeth C; Nahoum, Virginie; Economou, Nicoleta J; Cocklin, Simon

    2014-05-01

    Tyrocidine A, one of the first antibiotics ever to be discovered, is a cyclic decapeptide that binds to membranes of target bacteria, disrupting their integrity. It is active against a broad spectrum of Gram-positive organisms, and has recently engendered interest as a potential scaffold for the development of new drugs to combat antibiotic-resistant pathogens. We present here the X-ray crystal structure of tyrocidine A at a resolution of 0.95Å. The structure reveals that tyrocidine forms an intimate and highly amphipathic homodimer made up of four beta strands that associate into a single, highly curved antiparallel beta sheet. We used surface plasmon resonance and potassium efflux assays to demonstrate that tyrocidine binds tightly to mimetics of bacterial membranes with an apparent dissociation constant (K(D)) of 10 μM, and efficiently permeabilizes bacterial cells at concentrations equal to and below the K(D). Using variant forms of tyrocidine in which the fluorescent probe p-cyano-phenylalanine had been inserted on either the polar or apolar face of the molecule, we performed fluorescence quenching experiments, using both water-soluble and membrane-embedded quenchers. The quenching results, together with the structure, strongly support a membrane association model in which the convex, apolar face of tyrocidine's beta sheet is oriented toward the membrane interior, while the concave, polar face is presented to the aqueous phase.

  4. High heregulin expression is associated with activated HER3 and may define an actionable biomarker in patients with squamous cell carcinomas of the head and neck.

    Directory of Open Access Journals (Sweden)

    David S Shames

    Full Text Available PURPOSE: Tumors with oncogenic dependencies on the HER family of receptor tyrosine kinases (RTKs often respond well to targeted inhibition. Our previous work suggested that many cell lines derived from squamous cell carcinomas of the head and neck (SCCHNs depend on autocrine signaling driven by HER2/3 dimerization and high-level co-expression of HRG. Additionally, results from a Phase I trial of MEHD7495A, a dual-action antibody that blocks ligand binding to EGFR and HER3, suggest that high-level HRG expression was associated with clinical response in SCCHN patients. Here we explore the hypothesis that high-level HRG expression defines a subpopulation of SCCHNs with activated HER3. EXPERIMENTAL DESIGN: qRT-PCR expression profiling was performed on >750 tumors of diverse origin, including >150 therapy-naïve, primary, and recurrent SCCHNs. Activated HER3, defined by immunoprecipitation of phospho-HER3, was compared to HRG expression in SCCHN samples. Paracrine versus autocrine expression was evaluated using RNA-in situ hybridization. RESULTS: SCCHN tumors express the highest levels of HRG compared to a diverse collection of other tumor types. We show that high HRG expression is associated with activated HER3, whereas low HRG expression is associated with low HER3 activation in SCCHN tumors. Furthermore, HRG expression is higher in recurrent SCCHN compared to patient-matched therapy naïve specimens. CONCLUSIONS: HRG expression levels define a biologically distinct subset of SCCHN patients. We propose that high-level expression of HRG is associated with constitutive activation of HER3 in SCCHN and thus defines an actionable biomarker for interventions targeting HER3.

  5. Biomarkers in Autism

    Directory of Open Access Journals (Sweden)

    Robert eHendren

    2014-08-01

    Full Text Available Autism spectrum disorders (ASD are complex, heterogeneous disorders caused by an interaction between genetic vulnerability and environmental factors. In an effort to better target the underlying roots of ASD for diagnosis and treatment, efforts to identify reliable biomarkers in genetics, neuroimaging, gene expression and measures of the body’s metabolism are growing. For this article, we review the published studies of potential biomarkers in autism and conclude that while there is increasing promise of finding biomarkers that can help us target treatment, there are none with enough evidence to support routine clinical use unless medical illness is suspected. Promising biomarkers include those for mitochondrial function, oxidative stress, and immune function. Genetic clusters are also suggesting the potential for useful biomarkers.

  6. Metagenomic approach reveals variation of microbes with arsenic and antimony metabolism genes from highly contaminated soil.

    Directory of Open Access Journals (Sweden)

    Jinming Luo

    Full Text Available Microbes have great potential for arsenic (As and antimony (Sb bioremediation in heavily contaminated soil because they have the ability to biotransform As and Sb to species that have less toxicity or are more easily removed. In this study, we integrated a metagenomic method with physicochemical characterization to elucidate the composition of microbial community and functional genes (related to As and Sb in a high As (range from 34.11 to 821.23 mg kg-1 and Sb (range from 226.67 to 3923.07 mg kg-1 contaminated mine field. Metagenomic analysis revealed that microbes from 18 phyla were present in the 5 samples of soil contaminated with high As and Sb. Moreover, redundancy analysis (RDA of the relationship between the 18 phyla and the concentration of As and Sb demonstrated that 5 phyla of microbes, i.e. Actinobacteria, Firmicutes, Nitrospirae, Tenericutes and Gemmatimonadetes were positively correlated with As and Sb concentration. The distribution, diversity and abundance of functional genes (including arsC, arrA, aioA, arsB and ACR3 were much higher for the samples containing higher As and Sb concentrations. Based on correlation analysis, the results showed a positive relationship between arsC-like (R2 = 0.871 and aioA-like (R2 = 0.675 gene abundance and As concentration, and indicated that intracellular As(V reduction and As(III oxidation could be the dominant As detoxification mechanism enabling the microbes to survive in the environment. This study provides a direct and reliable reference on the diversity of microbial community and functional genes in an extremely high concentration As- and Sb-contaminated environment.

  7. Searching for native tree species and respective potential biomarkers for future assessment of pollution effects on the highly diverse Atlantic Forest in SE-Brazil.

    Science.gov (United States)

    Domingos, Marisa; Bulbovas, Patricia; Camargo, Carla Z S; Aguiar-Silva, Cristiane; Brandão, Solange E; Dafré-Martinelli, Marcelle; Dias, Ana Paula L; Engela, Marcela R G S; Gagliano, Janayne; Moura, Barbara B; Alves, Edenise S; Rinaldi, Mirian C S; Gomes, Eduardo P C; Furlan, Claudia M; Figueiredo, Ana Maria G

    2015-07-01

    This study summarizes the first effort to search for bioindicator tree species and respective potential biomarkers for future assessment of potential mixed pollution effects on the highly diverse Atlantic Forest in SE-Brazil. Leaves of the three most abundant species inventoried in a phytosociological survey (Croton floribundus, Piptadenia gonoacantha and Astronium graveolens) were collected in four forest remnants during winter and summer (2012). Their potential bioindicator attributes were highlighted using a screening of morphological, chemical and biochemical markers. The leaf surface structure and/or epicuticular wax composition pointed the accumulator properties of C. floribundus and P. gonoacantha. C. floribundus is a candidate for assessing potential accumulation of Cu, Cd, Mn, Ni, S and Zn. P. gonoacantha is a candidate to monitor polycyclic aromatic hydrocarbons. Increased levels of secondary metabolites and decreased antioxidant capacity in leaves of A. graveolens may support its value as a bioindicator for oxidative pollutants by visible dark stipplings. PMID:25818087

  8. Role of Topoisomerases in Pediatric High Grade Osteosarcomas: TOP2A Gene Is One of the Unique Molecular Biomarkers of Chemoresponse

    Energy Technology Data Exchange (ETDEWEB)

    Nguyen, Aurelia; Lasthaus, Christelle; Guerin, Eric [Laboratoire de Biochimie et Biologie Moléculaire, CHRU Hautepierre, Avenue Molière, Strasbourg Cedex 67098 (France); EA4438, Groupe Marqueurs Moléculaires de Progression Tumorale et de Sensibilisation aux Drogues Anti-Cancéreuses, University of Strasbourg, 3 Avenue Molière, Strasbourg 67000 (France); Marcellin, Luc [Laboratoire d’Anatomie Pathologique, CHRU Hautepierre, Avenue Molière, Strasbourg Cedex 67098 (France); Pencreach, Erwan; Gaub, Marie-Pierre [Laboratoire de Biochimie et Biologie Moléculaire, CHRU Hautepierre, Avenue Molière, Strasbourg Cedex 67098 (France); EA4438, Groupe Marqueurs Moléculaires de Progression Tumorale et de Sensibilisation aux Drogues Anti-Cancéreuses, University of Strasbourg, 3 Avenue Molière, Strasbourg 67000 (France); Guenot, Dominique [Laboratoire de Biochimie et Biologie Moléculaire, CHRU Hautepierre, Avenue Molière, Strasbourg Cedex 67098 (France); Entz-Werle, Natacha, E-mail: Natacha.entz-werle@chru-strasbourg.fr [Laboratoire de Biochimie et Biologie Moléculaire, CHRU Hautepierre, Avenue Molière, Strasbourg Cedex 67098 (France); Service de Pédiatrie Onco-Hématologie, CHRU Hautepierre, Avenue Molière, Strasbourg Cedex 67098 (France)

    2013-06-04

    Currently, the treatment of pediatric high-grade osteosarcomas systematically includes one topoisomerase IIα inhibitor. This chemotherapy is usually adapted to the response to the neo-adjuvant therapy after surgery. The current and unique marker of chemoresponsiveness is the percentage of viable residual cells in the surgical resection. This late patient management marker has to be evaluated earlier in the therapeutic history of the patients on initial biopsy. Therefore, new biomarkers, especially those involved in the topoisomerase IIα inhibitor response might be good candidates. Therefore, our study was designed to target TOP1, TOP2A and TOP2B genes in 105 fresh-frozen diagnostic biopsies by allelotyping and real-time quantitative PCR. Our analyses in those pediatric osteosarcomas, homogeneously treated, highlighted the frequent involvement of topo-isomerase genes. The main and most important observation was the statistical link between the presence of TOP2A amplification and the good response to neo-adjuvant chemotherapy. Compared to adult cancers, the 17q21 amplicon, including TOP2A and ERBB2 genes, seems to be differentially implicated in the osteosarcoma chemoresponsiveness. Surprisingly, there is no ERBB2 gene co-amplification and the patients harboring TOP2A amplification tend to show a worse survival, so TOP2A analyses remain a preliminary, but a good molecular approach for the evaluation at diagnosis of pediatric osteosarcoma chemoresponsiveness.

  9. High sensitive troponin T and heart fatty acid binding protein: Novel biomarker in heart failure with normal ejection fraction?: A cross-sectional study

    Directory of Open Access Journals (Sweden)

    Barroso Michael

    2011-07-01

    Full Text Available Abstract Background High sensitive troponin T (hsTnT and heart fatty acid binding protein (hFABP are both markers of myocardial injury and predict adverse outcome in patients with systolic heart failure (SHF. We tested whether hsTnT and hFABP plasma levels are elevated in patients with heart failure with normal ejection fraction (HFnEF. Methods We analyzed hsTnT, hFABP and N-terminal brain natriuretic peptide in 130 patients comprising 49 HFnEF patients, 51 patients with asymptomatic left ventricular diastolic dysfunction (LVDD, and 30 controls with normal diastolic function. Patients were classified to have HFnEF when the diagnostic criteria as recommended by the European Society of Cardiology were met. Results Levels of hs TnT and hFABP were significantly higher in patients with asymptomatic LVDD and HFnEF (both p Conclusion In HFnEF patients, hsTnT and hFABP are elevated independent of coronary artery disease, suggesting that ongoing myocardial damage plays a critical role in the pathophysiology. A combination of biomarkers and echocardiographic parameters might improve diagnostic accuracy and risk stratification of patients with HFnEF.

  10. Role of Topoisomerases in Pediatric High Grade Osteosarcomas: TOP2A Gene Is One of the Unique Molecular Biomarkers of Chemoresponse

    International Nuclear Information System (INIS)

    Currently, the treatment of pediatric high-grade osteosarcomas systematically includes one topoisomerase IIα inhibitor. This chemotherapy is usually adapted to the response to the neo-adjuvant therapy after surgery. The current and unique marker of chemoresponsiveness is the percentage of viable residual cells in the surgical resection. This late patient management marker has to be evaluated earlier in the therapeutic history of the patients on initial biopsy. Therefore, new biomarkers, especially those involved in the topoisomerase IIα inhibitor response might be good candidates. Therefore, our study was designed to target TOP1, TOP2A and TOP2B genes in 105 fresh-frozen diagnostic biopsies by allelotyping and real-time quantitative PCR. Our analyses in those pediatric osteosarcomas, homogeneously treated, highlighted the frequent involvement of topo-isomerase genes. The main and most important observation was the statistical link between the presence of TOP2A amplification and the good response to neo-adjuvant chemotherapy. Compared to adult cancers, the 17q21 amplicon, including TOP2A and ERBB2 genes, seems to be differentially implicated in the osteosarcoma chemoresponsiveness. Surprisingly, there is no ERBB2 gene co-amplification and the patients harboring TOP2A amplification tend to show a worse survival, so TOP2A analyses remain a preliminary, but a good molecular approach for the evaluation at diagnosis of pediatric osteosarcoma chemoresponsiveness

  11. Role of Topoisomerases in Pediatric High Grade Osteosarcomas: TOP2A Gene Is One of the Unique Molecular Biomarkers of Chemoresponse

    Directory of Open Access Journals (Sweden)

    Natacha Entz-Werle

    2013-06-01

    Full Text Available Currently, the treatment of pediatric high-grade osteosarcomas systematically includes one topoisomerase IIα inhibitor. This chemotherapy is usually adapted to the response to the neo-adjuvant therapy after surgery. The current and unique marker of chemoresponsiveness is the percentage of viable residual cells in the surgical resection. This late patient management marker has to be evaluated earlier in the therapeutic history of the patients on initial biopsy. Therefore, new biomarkers, especially those involved in the topoisomerase IIα inhibitor response might be good candidates. Therefore, our study was designed to target TOP1, TOP2A and TOP2B genes in 105 fresh-frozen diagnostic biopsies by allelotyping and real-time quantitative PCR. Our analyses in those pediatric osteosarcomas, homogeneously treated, highlighted the frequent involvement of topo-isomerase genes. The main and most important observation was the statistical link between the presence of TOP2A amplification and the good response to neo-adjuvant chemotherapy. Compared to adult cancers, the 17q21 amplicon, including TOP2A and ERBB2 genes, seems to be differentially implicated in the osteosarcoma chemoresponsiveness. Surprisingly, there is no ERBB2 gene co-amplification and the patients harboring TOP2A amplification tend to show a worse survival, so TOP2A analyses remain a preliminary, but a good molecular approach for the evaluation at diagnosis of pediatric osteosarcoma chemoresponsiveness.

  12. High Dietary Iron and Radiation Exposure Increase Biomarkers of Oxidative Stress in Blood and Liver of Rats

    Science.gov (United States)

    Morgan, Jennifer L. L.; Theriot, Corey A.; Wu, Honglu; Smith, Scott M.; Zwart, Sara R.

    2012-01-01

    Radiation exposure and increased iron (Fe) status independently cause oxidative damage that can result in protein, lipid, and DNA oxidation. During space flight astronauts are exposed to both increased radiation and increased Fe stores. Increased body Fe results from a decrease in red blood cell mass and the typically high Fe content of the food system. In this study we investigated the combined effects of radiation exposure (0.375 Gy of Cs-137 every other day for 16 days for a total of 3 Gy) and high dietary Fe (650 mg Fe/kg diet compared to 45 mg Fe/kg for controls) in Sprague-Dawley rats (n=8/group). Liver and serum Fe were significantly increased in the high dietary Fe groups. Likewise, radiation treatment increased serum ferritin and Fe concentrations. These data indicate that total body Fe stores increase with both radiation exposure and excess dietary Fe. Hematocrit decreased in the group exposed to radiation, providing a possible mechanism for the shift in Fe indices after radiation exposure. Markers of oxidative stress were also affected by both radiation and high dietary Fe, evidenced by increased liver glutathione peroxidase (GPX) and serum catalase as well as decreased serum GPX. We thus found preliminary indications of synergistic effects of radiation exposure and increased dietary Fe, warranting further study. This study was funded by the NASA Human Research Project.

  13. In situ Expression of Functional Genes Reveals Nitrogen Cycling at High Temperatures in Terrestrial Hydrothermal Systems

    Science.gov (United States)

    Loiacono, S. T.; Meyer-Dombard, D. R.

    2011-12-01

    An essential element for life, nitrogen occurs in all living organisms and is critical for the synthesis of amino acids, proteins, nucleic acids, and other forms of biomass. Thus, nitrogen cycling likely plays a vital role in microbial metabolic processes as well as nutrient availability. For microorganisms in "extreme" environments, this means developing adaptations that allow them to survive in harsh conditions and still perform the metabolisms essential to sustain life. Recent studies have screened biofilms and thermal sediments of Yellowstone National Park (YNP) thermal features for the presence of nifH genes, which code for a key enzyme in the nitrogen fixation process [1-4]. Furthermore, analysis of nitrogen isotopes in biofilms across a temperature and chemical gradient revealed that nitrogen fixation likely varies across the chemosynthetic/photosynthetic ecotone [5]. Although research has evaluated and confirmed the presence of nifH genes in various thermophilic microbial communities, the existence of a gene in the DNA of an organism does not verify its use. Instead, other methods, such as culturing, isotope tracer assays, and gene expression studies are required to provide direct evidence of biological nitrogen fixation. Culturing and isotope tracer approaches have successfully revealed high-temperature biological nitrogen fixation in both marine hydrothermal vent microbial communities [6] and in acidic, terrestrial hydrothermal sediment [3]. Transcriptomics-based techniques (using mRNA extracted from samples to confirm in situ expression of targeted genes) have been much more limited in number, and only a few studies have, to date, investigated in situ expression of the nifH gene in thermophilic microbial communities [2, 7]. This study explores the presence and expression of nifH genes in several features of the Lower Geyser Basin (LGB) of YNP. Nucleic acids from chemosynthetic and photosynthetic microbial communities were extracted and then amplified

  14. Revealing the beneficial effect of protease supplementation to high gravity beer fermentations using "-omics" techniques

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    Workman Chris

    2011-04-01

    Full Text Available Abstract Background Addition of sugar syrups to the basic wort is a popular technique to achieve higher gravity in beer fermentations, but it results in dilution of the free amino nitrogen (FAN content in the medium. The multicomponent protease enzyme Flavourzyme has beneficial effect on the brewer's yeast fermentation performance during high gravity fermentations as it increases the initial FAN value and results in higher FAN uptake, higher specific growth rate, higher ethanol yield and improved flavour profile. Results In the present study, transcriptome and metabolome analysis were used to elucidate the effect on the addition of the multicomponent protease enzyme Flavourzyme and its influence on the metabolism of the brewer's yeast strain Weihenstephan 34/70. The study underlines the importance of sufficient nitrogen availability during the course of beer fermentation. The applied metabolome and transcriptome analysis allowed mapping the effect of the wort sugar composition on the nitrogen uptake. Conclusion Both the transcriptome and the metabolome analysis revealed that there is a significantly higher impact of protease addition for maltose syrup supplemented fermentations, while addition of glucose syrup to increase the gravity in the wort resulted in increased glucose repression that lead to inhibition of amino acid uptake and hereby inhibited the effect of the protease addition.

  15. Bayesian coalescent inference reveals high evolutionary rates and diversification of Zika virus populations.

    Science.gov (United States)

    Fajardo, Alvaro; Soñora, Martín; Moreno, Pilar; Moratorio, Gonzalo; Cristina, Juan

    2016-10-01

    Zika virus (ZIKV) is a member of the family Flaviviridae. In 2015, ZIKV triggered an epidemic in Brazil and spread across Latin America. By May of 2016, the World Health Organization warns over spread of ZIKV beyond this region. Detailed studies on the mode of evolution of ZIKV strains are extremely important for our understanding of the emergence and spread of ZIKV populations. In order to gain insight into these matters, a Bayesian coalescent Markov Chain Monte Carlo analysis of complete genome sequences of recently isolated ZIKV strains was performed. The results of these studies revealed a mean rate of evolution of 1.20 × 10(-3) nucleotide substitutions per site per year (s/s/y) for ZIKV strains enrolled in this study. Several variants isolated in China are grouped together with all strains isolated in Latin America. Another genetic group composed exclusively by Chinese strains were also observed, suggesting the co-circulation of different genetic lineages in China. These findings indicate a high level of diversification of ZIKV populations. Strains isolated from microcephaly cases do not share amino acid substitutions, suggesting that other factors besides viral genetic differences may play a role for the proposed pathogenesis caused by ZIKV infection. J. Med. Virol. 88:1672-1676, 2016. © 2016 Wiley Periodicals, Inc. PMID:27278855

  16. Highly distinct chromosomal structures in cowpea (Vigna unguiculata), as revealed by molecular cytogenetic analysis.

    Science.gov (United States)

    Iwata-Otsubo, Aiko; Lin, Jer-Young; Gill, Navdeep; Jackson, Scott A

    2016-05-01

    Cowpea (Vigna unguiculata (L.) Walp) is an important legume, particularly in developing countries. However, little is known about its genome or chromosome structure. We used molecular cytogenetics to characterize the structure of pachytene chromosomes to advance our knowledge of chromosome and genome organization of cowpea. Our data showed that cowpea has highly distinct chromosomal structures that are cytologically visible as brightly DAPI-stained heterochromatic regions. Analysis of the repetitive fraction of the cowpea genome present at centromeric and pericentromeric regions confirmed that two retrotransposons are major components of pericentromeric regions and that a 455-bp tandem repeat is found at seven out of 11 centromere pairs in cowpea. These repeats likely evolved after the divergence of cowpea from common bean and form chromosomal structure unique to cowpea. The integration of cowpea genetic and physical chromosome maps reveals potential regions of suppressed recombination due to condensed heterochromatin and a lack of pairing in a few chromosomal termini. This study provides fundamental knowledge on cowpea chromosome structure and molecular cytogenetics tools for further chromosome studies. PMID:26758200

  17. Dengue virus surveillance in Singapore reveals high viral diversity through multiple introductions and in situ evolution.

    Science.gov (United States)

    Lee, Kim-Sung; Lo, Sharon; Tan, Sharon Siok-Yin; Chua, Rachel; Tan, Li-Kiang; Xu, Helen; Ng, Lee-Ching

    2012-01-01

    Dengue fever, a vector-borne disease, has caused tremendous burden to countries in the tropics and sub tropics. Over the past 20 years, dengue epidemics have become more widespread, severe and frequent. This study aims to understand the dynamics of dengue viruses in cosmopolitan Singapore. Envelope protein gene sequences of all four dengue serotypes (DENV-1-DENV-4) obtained from human sera in Singapore (2008-2010) revealed that constant viral introductions and in situ evolution contribute to viral diversity in Singapore and play important roles in shaping the epidemiology of dengue in the island state. The diversity of dengue viruses reported here could be a reflection of the on-going dengue situation in the region given Singapore's location in a dengue hyperendemic region and its role as the regional hub for travels and trade. Though cosmopolitan genotype of DENV-2 has remained as the predominant strain circulating in Singapore, we uncovered evidence of in situ evolution which could possibly result in viruses with improved fitness. While we have previously shown that a switch in the predominant dengue serotype could serve as a warning for an impending outbreak, our current data shows that a replacement of a predominant viral clade, even in the absence of a switch in predominant serotype, could signal a possible increase in dengue transmission. The circulating dengue viruses in Singapore are highly diverse, a situation which could offer ample opportunities for selection of strains of higher fitness, thus increasing the risk of outbreaks despite a low Aedes population.

  18. Bayesian coalescent inference reveals high evolutionary rates and diversification of Zika virus populations.

    Science.gov (United States)

    Fajardo, Alvaro; Soñora, Martín; Moreno, Pilar; Moratorio, Gonzalo; Cristina, Juan

    2016-10-01

    Zika virus (ZIKV) is a member of the family Flaviviridae. In 2015, ZIKV triggered an epidemic in Brazil and spread across Latin America. By May of 2016, the World Health Organization warns over spread of ZIKV beyond this region. Detailed studies on the mode of evolution of ZIKV strains are extremely important for our understanding of the emergence and spread of ZIKV populations. In order to gain insight into these matters, a Bayesian coalescent Markov Chain Monte Carlo analysis of complete genome sequences of recently isolated ZIKV strains was performed. The results of these studies revealed a mean rate of evolution of 1.20 × 10(-3) nucleotide substitutions per site per year (s/s/y) for ZIKV strains enrolled in this study. Several variants isolated in China are grouped together with all strains isolated in Latin America. Another genetic group composed exclusively by Chinese strains were also observed, suggesting the co-circulation of different genetic lineages in China. These findings indicate a high level of diversification of ZIKV populations. Strains isolated from microcephaly cases do not share amino acid substitutions, suggesting that other factors besides viral genetic differences may play a role for the proposed pathogenesis caused by ZIKV infection. J. Med. Virol. 88:1672-1676, 2016. © 2016 Wiley Periodicals, Inc.

  19. Character State Reconstruction of Call Diversity in the Neoconocephalus Katydids Reveals High Levels of Convergence.

    Science.gov (United States)

    Frederick, Katy; Schul, Johannes

    2016-01-01

    The katydid genus Neoconocephalus is characterized by high diversity of the acoustic communication system. Both male signals and female preferences have been thoroughly studied in the past. This study used Bayesian character state reconstruction to elucidate the evolutionary history of diverse call traits, based on an existing, well supported phylogenetic hypothesis. The most common male call pattern consisted of continuous calls comprising one fast pulse rate; this pattern is the likely ancestral state in this genus. Three lines of call divergence existed among the species of the genus. First, four species had significantly slower pulse rates. Second, five species had alternating pulse periods, resulting in a double pulse rhythm. Third, several species had discontinuous calls, when pulses were grouped into rhythmically repeated verses. Bayesian character state reconstruction revealed that the double-pulse pattern likely evolved convergently five times; the slow pulse rate also evolved four times independently. Discontinuous calls have evolved twice and occur in two clades; each of which contains reversals to the ancestral continuous calls. Pairwise phylogenetically independent contrast analyses among the three call traits found no significant correlations among the character states of the different traits, supporting the independent evolution of the three call traits. PMID:27110432

  20. High Resolution Genomic Scans Reveal Genetic Architecture Controlling Alcohol Preference in Bidirectionally Selected Rat Model.

    Science.gov (United States)

    Lo, Chiao-Ling; Lossie, Amy C; Liang, Tiebing; Liu, Yunlong; Xuei, Xiaoling; Lumeng, Lawrence; Zhou, Feng C; Muir, William M

    2016-08-01

    Investigations on the influence of nature vs. nurture on Alcoholism (Alcohol Use Disorder) in human have yet to provide a clear view on potential genomic etiologies. To address this issue, we sequenced a replicated animal model system bidirectionally-selected for alcohol preference (AP). This model is uniquely suited to map genetic effects with high reproducibility, and resolution. The origin of the rat lines (an 8-way cross) resulted in small haplotype blocks (HB) with a corresponding high level of resolution. We sequenced DNAs from 40 samples (10 per line of each replicate) to determine allele frequencies and HB. We achieved ~46X coverage per line and replicate. Excessive differentiation in the genomic architecture between lines, across replicates, termed signatures of selection (SS), were classified according to gene and region. We identified SS in 930 genes associated with AP. The majority (50%) of the SS were confined to single gene regions, the greatest numbers of which were in promoters (284) and intronic regions (169) with the least in exon's (4), suggesting that differences in AP were primarily due to alterations in regulatory regions. We confirmed previously identified genes and found many new genes associated with AP. Of those newly identified genes, several demonstrated neuronal function involved in synaptic memory and reward behavior, e.g. ion channels (Kcnf1, Kcnn3, Scn5a), excitatory receptors (Grin2a, Gria3, Grip1), neurotransmitters (Pomc), and synapses (Snap29). This study not only reveals the polygenic architecture of AP, but also emphasizes the importance of regulatory elements, consistent with other complex traits. PMID:27490364

  1. Metagenomes from high-temperature chemotrophic systems reveal geochemical controls on microbial community structure and function.

    Directory of Open Access Journals (Sweden)

    William P Inskeep

    Full Text Available The Yellowstone caldera contains the most numerous and diverse geothermal systems on Earth, yielding an extensive array of unique high-temperature environments that host a variety of deeply-rooted and understudied Archaea, Bacteria and Eukarya. The combination of extreme temperature and chemical conditions encountered in geothermal environments often results in considerably less microbial diversity than other terrestrial habitats and offers a tremendous opportunity for studying the structure and function of indigenous microbial communities and for establishing linkages between putative metabolisms and element cycling. Metagenome sequence (14-15,000 Sanger reads per site was obtained for five high-temperature (>65 degrees C chemotrophic microbial communities sampled from geothermal springs (or pools in Yellowstone National Park (YNP that exhibit a wide range in geochemistry including pH, dissolved sulfide, dissolved oxygen and ferrous iron. Metagenome data revealed significant differences in the predominant phyla associated with each of these geochemical environments. Novel members of the Sulfolobales are dominant in low pH environments, while other Crenarchaeota including distantly-related Thermoproteales and Desulfurococcales populations dominate in suboxic sulfidic sediments. Several novel archaeal groups are well represented in an acidic (pH 3 Fe-oxyhydroxide mat, where a higher O2 influx is accompanied with an increase in archaeal diversity. The presence or absence of genes and pathways important in S oxidation-reduction, H2-oxidation, and aerobic respiration (terminal oxidation provide insight regarding the metabolic strategies of indigenous organisms present in geothermal systems. Multiple-pathway and protein-specific functional analysis of metagenome sequence data corroborated results from phylogenetic analyses and clearly demonstrate major differences in metabolic potential across sites. The distribution of functional genes involved in

  2. Motor agency: a new and highly sensitive measure to reveal agency disturbances in early psychosis.

    Directory of Open Access Journals (Sweden)

    Hélène Wilquin

    Full Text Available BACKGROUND: Early diagnosis of young adults at risk of schizophrenia is essential for preventive approaches of the illness. Nevertheless, classic screening instruments are difficult to use because of the non-specific nature of the signs at this pre-onset phase of illness. The objective of the present contribution was to propose an innovating test that can probe the more specific symptom of psychosis, i.e., the sense of agency, which is defined as being the immediate experience of oneself as the cause of an action. More specifically, we tested whether motor agency is abnormal in early psychosis. METHODS: Thirty-two young symptomatic patients and their age-matched controls participated in the study. 15 of these patients were at ultra high-risk for developing psychosis (UHR, and 17 patients were suffering from first-episode psychosis (FEP. Patients' neurocognitive capacities were assessed through the use of seven neuropsychological tests. A motor agency task was also introduced to obtain an objective indicator of the degree of sense of agency, by contrasting force levels applied during other and self-produced collisions between a hand-held objet and a pendulum. RESULTS: As reported in the literature for adult controls, healthy adolescents used more efficient force levels in self than in other-imposed collisions. For both UHR and FEP patients, abnormally high levels of grip force were used for self-produced collisions, leading to an absence of difference between self and other. The normalized results revealed that motor agency differentiated patients from controls with a higher level of sensitivity than the more classic neuropsychological test battery. CONCLUSIONS: This study is in favour of the existence of an abnormal sense of agency early in the psychotic illness. Because it is quick and none verbal, motor agency may be a valuable tool to use in complement to classic interviews, especially when investigating complex ineffable experiences that are

  3. [Biomarkers in Alzheimer's disease].

    Science.gov (United States)

    García-Ribas, G; López-Sendón Moreno, J L; García-Caldentey, J

    2014-04-01

    The new diagnostic criteria for Alzheimer's disease (AD) include brain imaging and cerebrospinal fluid (CSF) biomarkers, with the aim of increasing the certainty of whether a patient has an ongoing AD neuropathologic process or not. Three CSF biomarkers, Aß42, total tau, and phosphorylated tau, reflect the core pathological features of AD. It is already known that these pathological processes of AD starts decades before the first symptoms, so these biomarkers may provide means of early disease detection. At least three stages of AD could be identified: preclinical AD, mild cognitive impairment due to AD, and dementia due to AD. In this review, we aim to summarize the CSF biomarker data available for each of these stages. We also review the actual research on blood-based biomarkers. Recent studies on healthy elderly subjects and on carriers of dominantly inherited AD mutations have also found biomarker changes that allow separate groups in these preclinical stages. These studies may aid for segregate populations in clinical trials and objectively evaluate if there are changes over the pathological processes of AD. Limits to widespread use of CSF biomarkers, apart from the invasive nature of the process itself, is the higher coefficient of variation for the analyses between centres. It requires strict pre-analytical and analytical procedures that may make feasible multi-centre studies and global cut-off points for the different stages of AD.

  4. Metabolic products as biomarkers

    Science.gov (United States)

    Melancon, M.J.; Alscher, R.; Benson, W.; Kruzynski, G.; Lee, R.F.; Sikka, H.C.; Spies, R.B.; Huggett, Robert J.; Kimerle, Richard A.; Mehrle, Paul M.=; Bergman, Harold L.

    1992-01-01

    Ideally, endogenous biomarkers would indicate both exposure and environmental effects of toxic chemicals; however, such comprehensive biochemical and physiological indices are currently being developed and, at the present time, are unavailable for use in environmental monitoring programs. Continued work is required to validate the use of biochemical and physiological stress indices as useful components of monitoring programs. Of the compounds discussed only phytochelatins and porphyrins are currently in biomarkers in a useful state; however, glutathione,metallothioneins, stress ethylene, and polyamines are promising as biomarkers in environmental monitoring.

  5. Biomarkers in Severe Asthma.

    Science.gov (United States)

    Wan, Xiao Chloe; Woodruff, Prescott G

    2016-08-01

    Biomarkers have been critical for studies of disease pathogenesis and the development of new therapies in severe asthma. In particular, biomarkers of type 2 inflammation have proven valuable for endotyping and targeting new biological agents. Because of these successes in understanding and marking type 2 inflammation, lack of knowledge regarding non-type 2 inflammatory mechanisms in asthma will soon be the major obstacle to the development of new treatments and management strategies in severe asthma. Biomarkers can play a role in these investigations as well by providing insight into the underlying biology in human studies of patients with severe asthma. PMID:27401625

  6. High throughput HPLC-ESI(-)-MS/MS methodology for mercapturic acid metabolites of 1,3-butadiene: Biomarkers of exposure and bioactivation.

    Science.gov (United States)

    Kotapati, Srikanth; Esades, Amanda; Matter, Brock; Le, Chap; Tretyakova, Natalia

    2015-11-01

    1,3-Butadiene (BD) is an important industrial and environmental carcinogen present in cigarette smoke, automobile exhaust, and urban air. The major urinary metabolites of BD in humans are 2-(N-acetyl-L-cystein-S-yl)-1-hydroxybut-3-ene/1-(N-acetyl-L-cystein-S-yl)-2-hydroxybut-3-ene (MHBMA), 4-(N-acetyl-L-cystein-S-yl)-1,2-dihydroxybutane (DHBMA), and 4-(N-acetyl-L-cystein-S-yl)-1,2,3-trihydroxybutyl mercapturic acid (THBMA), which are formed from the electrophilic metabolites of BD, 3,4-epoxy-1-butene (EB), hydroxymethyl vinyl ketone (HMVK), and 3,4-epoxy-1,2-diol (EBD), respectively. In the present work, a sensitive high-throughput HPLC-ESI(-)-MS/MS method was developed for simultaneous quantification of MHBMA and DHBMA in small volumes of human urine (200 μl). The method employs a 96 well Oasis HLB SPE enrichment step, followed by isotope dilution HPLC-ESI(-)-MS/MS analysis on a triple quadrupole mass spectrometer. The validated method was used to quantify MHBMA and DHBMA in urine of workers from a BD monomer and styrene-butadiene rubber production facility (40 controls and 32 occupationally exposed to BD). Urinary THBMA concentrations were also determined in the same samples. The concentrations of all three BD-mercapturic acids and the metabolic ratio (MHBMA/(MHBMA+DHBMA+THBMA)) were significantly higher in the occupationally exposed group as compared to controls and correlated with BD exposure, with each other, and with BD-hemoglobin biomarkers. This improved high throughput methodology for MHBMA and DHBMA will be useful for future epidemiological studies in smokers and occupationally exposed workers. PMID:25727266

  7. A cross sectional study of two independent cohorts identifies serum biomarkers for facioscapulohumeral muscular dystrophy (FSHD).

    Science.gov (United States)

    Petek, Lisa M; Rickard, Amanda M; Budech, Christopher; Poliachik, Sandra L; Shaw, Dennis; Ferguson, Mark R; Tawil, Rabi; Friedman, Seth D; Miller, Daniel G

    2016-07-01

    Measuring the severity and progression of facioscapulohumeral muscular dystrophy (FSHD) is particularly challenging because muscle weakness progresses over long periods of time and can be sporadic. Biomarkers are essential for measuring disease burden and testing treatment strategies. We utilized the sensitive, specific, high-throughput SomaLogic proteomics platform of 1129 proteins to identify proteins with levels that correlate with FSHD severity in a cross-sectional study of two independent cohorts. We discovered biomarkers that correlate with clinical severity and disease burden measured by magnetic resonance imaging. Sixty-eight proteins in the Rochester cohort (n = 48) and 51 proteins in the Seattle cohort (n = 30) had significantly different levels in FSHD-affected individuals when compared with controls (p-value ≤ .005). A subset of these varied by at least 1.5 fold and four biomarkers were significantly elevated in both cohorts. Levels of creatine kinase MM and MB isoforms, carbonic anhydrase III, and troponin I type 2 reliably predicted the disease state and correlated with disease severity. Other novel biomarkers were also discovered that may reveal mechanisms of disease pathology. Assessing the levels of these biomarkers during clinical trials may add significance to other measures of quantifying disease progression or regression. PMID:27185459

  8. A multilocus assay reveals high nucleotide diversity and limited differentiation among Scandinavian willow grouse (Lagopus lagopus

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    Quintela Maria

    2008-12-01

    Full Text Available Abstract Background There is so far very little data on autosomal nucleotide diversity in birds, except for data from the domesticated chicken and some passerines species. Estimates of nucleotide diversity reported so far in birds have been high (~10-3 and a likely explanation for this is the generally higher effective population sizes compared to mammals. In this study, the level of nucleotide diversity has been examined in the willow grouse, a non-domesticated bird species from the order Galliformes, which also holds the chicken. The willow grouse (Lagopus lagopus has an almost circumpolar distribution but is absent from Greenland and the north Atlantic islands. It primarily inhabits tundra, forest edge habitats and sub-alpine vegetation. Willow grouse are hunted throughout its range, and regionally it is a game bird of great cultural and economical importance. Results We sequenced 18 autosomal protein coding loci from approximately 15–18 individuals per population. We found a total of 127 SNP's, which corresponds to 1 SNP every 51 bp. 26 SNP's were amino acid replacement substitutions. Total nucleotide diversity (πt was between 1.30 × 10-4 and 7.66 × 10-3 (average πt = 2.72 × 10-3 ± 2.06 × 10-3 and silent nucleotide diversity varied between 4.20 × 10-4and 2.76 × 10-2 (average πS = 9.22 × 10-3 ± 7.43 × 10-4. The synonymous diversity is approximately 20 times higher than in humans and two times higher than in chicken. Non-synonymous diversity was on average 18 times lower than the synonymous diversity and varied between 0 and 4.90 × 10-3 (average πa = 5.08 × 10-4 ± 7.43 × 103, which suggest that purifying selection is strong in these genes. FST values based on synonymous SNP's varied between -5.60 × 10-4 and 0.20 among loci and revealed low levels of differentiation among the four localities, with an overall value of FST = 0.03 (95% CI: 0.006 – 0.057 over 60 unlinked loci. Non-synonymous SNP's gave similar results. Low

  9. Early Detection Biomarkers for Ovarian Cancer

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    Sreeja Sarojini

    2012-01-01

    Full Text Available Despite the widespread use of conventional and contemporary methods to detect ovarian cancer development, ovarian cancer remains a common and commonly fatal gynecological malignancy. The identification and validation of early detection biomarkers highly specific to ovarian cancer, which would permit development of minimally invasive screening methods for detecting early onset of the disease, are urgently needed. Current practices for early detection of ovarian cancer include transvaginal ultrasonography, biomarker analysis, or a combination of both. In this paper we review recent research on novel and robust biomarkers for early detection of ovarian cancer and provide specific details on their contributions to tumorigenesis. Promising biomarkers for early detection of ovarian cancer include KLK6/7, GSTT1, PRSS8, FOLR1, ALDH1, and miRNAs.

  10. Cardiorenal biomarkers in acute heart failure

    Institute of Scientific and Technical Information of China (English)

    Rajiv Choudhary; Dipika Gopal; Ben A. Kipper; Alejandro De La Parra Landa; Hermineh Aramin

    2012-01-01

    Managing patients with heart failure (HF) is a challenging task within itself, but the presence of associated worsening renal function can greatly increase mortality and morbidity. Early diagnosis and treatment is the key to prevent re-hospitalizations and reduce healthcare costs. Biomarkers have long been established as highly sensitive and specific tools in diagnosing and prognosticating patients with HF. Reflecting distinct pathophysiological events and ongoing cellular insult, biomarkers have been proven superior to conventional laboratory tests. Availability of better assays and rapid analysis has allowed the use of biomarkers as point-of-care tests in the emergency department and at the patient's bed-side. Acute HF patients often go on to develop worsening renal function, termed as acute cardiorenal syndrome. The growing breadth of studies has shown the implications of combining multiple biomarkers to better chart outcomes and produce desirable results in such patients.

  11. Genetic biomarkers in hypertrophic cardiomyopathy.

    Science.gov (United States)

    Coats, Caroline J; Elliott, Perry M

    2013-08-01

    Hypertrophic cardiomyopathy is a common inherited heart muscle disorder associated with sudden cardiac death, arrhythmias and heart failure. Genetic mutations can be identified in approximately 60% of patients; these are commonest in genes that encode proteins of the cardiac sarcomere. Similar to other Mendelian diseases these mutations are characterized by incomplete penetrance and variable clinical expression. Our knowledge of this genetic diversity is rapidly evolving as high-throughput DNA sequencing technology is now used to characterize an individual patient's disease. In addition, the genomic basis of several multisystem diseases associated with a hypertrophic cardiomyopathy phenotype has been elucidated. Genetic biomarkers can be helpful in making an accurate diagnosis and in identifying relatives at risk of developing the condition. In the clinical setting, genetic testing and genetic screening should be used pragmatically with appropriate counseling. Here we review the current role of genetic biomarkers in hypertrophic cardiomyopathy, highlight recent progress in the field and discuss future challenges.

  12. Revealing molecular structure and dynamics through high harmonic generation driven by mid-IR fields

    Science.gov (United States)

    Marangos, Jonathan

    2010-03-01

    High harmonic generation (HHG) from molecules has recently been shown to be a promising tool for measuring instantaneous molecular structure, sub-femtosecond domain structural rearrangements in molecules and even hole dynamics initiated by laser field ionisation. To fully exploit this promise it is essential that we can; (1) systematically decouple structural and dynamic effects so that both may simultaneously be determined in the measurement, (2) can extend the method of molecular HHG imaging to a wide range of molecules. Here we demonstrate important steps towards both these objectives. Up until now HHG imaging measurements have been restricted to drive laser wavelengths close to 800nm, due to the availability of CPA titanium sapphire lasers, which dictates the use of relatively high intensities (> 2.5 x 10^14 Wcm-2) if a harmonic spectrum spanning to ˜70 eV is to be observed which is required for extracting structural data from most small molecules. By using a mid-IR laser (at 1300 nm) we show that with an intensity ˜ 1 x 10^14 W cm-2 we can observe a wide molecular harmonic spectrum spanning to ˜ 70 eV even in molecules where ionization saturation would clamp the cut-off to much lower energies if an 800nm field were used. Thus we have been able to observe evidence for two-centre interference in two new molecules, N2O and C2H2 for the first time. Moreover we can use the ability to observe a broad harmonic spectrum over a large range of intensities to reveal the subtle interplay between structural and dynamic effects in CO2 and so provide a new window into hole dynamics. [4pt] In collaboration with R. Torres, Blackett Laboratory, Imperial College London; O. Smirnova, Max-Born-Institute, Berlin; T. Siegel and L. Brugnera, Blackett Laboratory, Imperial College London; I. Procino and Jonathan G. Underwood, Department of Physics and Astronomy, University College London; C. Altucci and R. Velotta, CNSIM and Dipartimento di Scienze Fisiche, Universita di Napoli

  13. Validation of New Cancer Biomarkers

    DEFF Research Database (Denmark)

    Duffy, Michael J; Sturgeon, Catherine M; Söletormos, Georg;

    2015-01-01

    in advancing a newly discovered cancer candidate biomarker from pilot studies to clinical application. Four main steps are necessary for a biomarker to reach the clinic: analytical validation of the biomarker assay, clinical validation of the biomarker test, demonstration of clinical value from performance...... of the biomarker test, and regulatory approval. In addition to these 4 steps, all biomarker studies should be reported in a detailed and transparent manner, using previously published checklists and guidelines. Finally, all biomarker studies relating to demonstration of clinical value should be registered before...

  14. Data Mining Approaches for Genomic Biomarker Development: Applications Using Drug Screening Data from the Cancer Genome Project and the Cancer Cell Line Encyclopedia.

    Directory of Open Access Journals (Sweden)

    David G Covell

    Full Text Available Developing reliable biomarkers of tumor cell drug sensitivity and resistance can guide hypothesis-driven basic science research and influence pre-therapy clinical decisions. A popular strategy for developing biomarkers uses characterizations of human tumor samples against a range of cancer drug responses that correlate with genomic change; developed largely from the efforts of the Cancer Cell Line Encyclopedia (CCLE and Sanger Cancer Genome Project (CGP. The purpose of this study is to provide an independent analysis of this data that aims to vet existing and add novel perspectives to biomarker discoveries and applications. Existing and alternative data mining and statistical methods will be used to a evaluate drug responses of compounds with similar mechanism of action (MOA, b examine measures of gene expression (GE, copy number (CN and mutation status (MUT biomarkers, combined with gene set enrichment analysis (GSEA, for hypothesizing biological processes important for drug response, c conduct global comparisons of GE, CN and MUT as biomarkers across all drugs screened in the CGP dataset, and d assess the positive predictive power of CGP-derived GE biomarkers as predictors of drug response in CCLE tumor cells. The perspectives derived from individual and global examinations of GEs, MUTs and CNs confirm existing and reveal unique and shared roles for these biomarkers in tumor cell drug sensitivity and resistance. Applications of CGP-derived genomic biomarkers to predict the drug response of CCLE tumor cells finds a highly significant ROC, with a positive predictive power of 0.78. The results of this study expand the available data mining and analysis methods for genomic biomarker development and provide additional support for using biomarkers to guide hypothesis-driven basic science research and pre-therapy clinical decisions.

  15. Data Mining Approaches for Genomic Biomarker Development: Applications Using Drug Screening Data from the Cancer Genome Project and the Cancer Cell Line Encyclopedia.

    Science.gov (United States)

    Covell, David G

    2015-01-01

    Developing reliable biomarkers of tumor cell drug sensitivity and resistance can guide hypothesis-driven basic science research and influence pre-therapy clinical decisions. A popular strategy for developing biomarkers uses characterizations of human tumor samples against a range of cancer drug responses that correlate with genomic change; developed largely from the efforts of the Cancer Cell Line Encyclopedia (CCLE) and Sanger Cancer Genome Project (CGP). The purpose of this study is to provide an independent analysis of this data that aims to vet existing and add novel perspectives to biomarker discoveries and applications. Existing and alternative data mining and statistical methods will be used to a) evaluate drug responses of compounds with similar mechanism of action (MOA), b) examine measures of gene expression (GE), copy number (CN) and mutation status (MUT) biomarkers, combined with gene set enrichment analysis (GSEA), for hypothesizing biological processes important for drug response, c) conduct global comparisons of GE, CN and MUT as biomarkers across all drugs screened in the CGP dataset, and d) assess the positive predictive power of CGP-derived GE biomarkers as predictors of drug response in CCLE tumor cells. The perspectives derived from individual and global examinations of GEs, MUTs and CNs confirm existing and reveal unique and shared roles for these biomarkers in tumor cell drug sensitivity and resistance. Applications of CGP-derived genomic biomarkers to predict the drug response of CCLE tumor cells finds a highly significant ROC, with a positive predictive power of 0.78. The results of this study expand the available data mining and analysis methods for genomic biomarker development and provide additional support for using biomarkers to guide hypothesis-driven basic science research and pre-therapy clinical decisions.

  16. Biomarker time out.

    Science.gov (United States)

    Petzold, Axel; Bowser, Robert; Calabresi, Paolo; Zetterberg, Henrik; Uitdehaag, Bernard M J

    2014-10-01

    The advancement of knowledge relies on scientific investigations. The timing between asking a question and data collection defines if a study is prospective or retrospective. Prospective studies look forward from a point in time, are less prone to bias and are considered superior to retrospective studies. This conceptual framework conflicts with the nature of biomarker research. New candidate biomarkers are discovered in a retrospective manner. There are neither resources nor time for prospective testing in all cases. Relevant sources for bias are not covered. Ethical questions arise through the time penalty of an overly dogmatic concept. The timing of sample collection can be separated from testing biomarkers. Therefore the moment of formulating a hypothesis may be after sample collection was completed. A conceptual framework permissive to asking research questions without the obligation to bow to the human concept of calendar time would simplify biomarker research, but will require new safeguards against bias.

  17. Biomarkers in Airway Diseases

    Directory of Open Access Journals (Sweden)

    Janice M Leung

    2013-01-01

    Full Text Available The inherent limitations of spirometry and clinical history have prompted clinicians and scientists to search for surrogate markers of airway diseases. Although few biomarkers have been widely accepted into the clinical armamentarium, the authors explore three sources of biomarkers that have shown promise as indicators of disease severity and treatment response. In asthma, exhaled nitric oxide measurements can predict steroid responsiveness and sputum eosinophil counts have been used to titrate anti-inflammatory therapies. In chronic obstructive pulmonary disease, inflammatory plasma biomarkers, such as fibrinogen, club cell secretory protein-16 and surfactant protein D, can denote greater severity and predict the risk of exacerbations. While the multitude of disease phenotypes in respiratory medicine make biomarker development especially challenging, these three may soon play key roles in the diagnosis and management of airway diseases.

  18. Biomarkers for immune thrombocytopenia

    OpenAIRE

    Yu, Lingjia; Zhang, Chunmei; Zhang, Liping; Shi, Yongyu; Ji, Xuebin

    2015-01-01

    Immune thrombocytopenia is an autoimmune disease with abnormal biomarkers. Immune thrombocytopenia pathogenesis is a complicated process in which the patient’s immune system is activated by platelet autoantigens resulting in immune mediated platelet destruction or suppression of platelet production. The autoantibodies produced by autoreactive B cells against self antigens are considered to play a crucial role. In addition, biomarkers such as transforming growth factor-beta1,Toll-like receptor...

  19. Biomarkers for neuromyelitis optica.

    Science.gov (United States)

    Chang, Kuo-Hsuan; Ro, Long-Sun; Lyu, Rong-Kuo; Chen, Chiung-Mei

    2015-02-01

    Neuromyelitis optica (NMO) is an acquired, heterogeneous inflammatory disorder, which is characterized by recurrent optic neuritis and longitudinally extensive spinal cord lesions. The discovery of the serum autoantibody marker, anti-aquaporin 4 (anti-AQP4) antibody, revolutionizes our understanding of pathogenesis of NMO. In addition to anti-AQP4 antibody, other biomarkers for NMO are also reported. These candidate biomarkers are particularly involved in T helper (Th)17 and astrocytic damages, which play a critical role in the development of NMO lesions. Among them, IL-6 in the peripheral blood is associated with anti-AQP4 antibody production. Glial fibrillary acidic protein (GFAP) in CSF demonstrates good correlations with clinical severity of NMO relapses. Detecting these useful biomarkers may be useful in the diagnosis and evaluation of disease activity of NMO. Development of compounds targeting these biomarkers may provide novel therapeutic strategies for NMO. This article will review the related biomarker studies in NMO and discuss the potential therapeutics targeting these biomarkers.

  20. Poor efficacy of the phosphorylated high-molecular-weight neurofilament heavy subunit serum level, a biomarker of axonal damage, as a marker of chemotherapy-induced peripheral neuropathy

    Science.gov (United States)

    SUMITANI, MASAHIKO; OGATA, TORU; NATORI, AKINA; HOZUMI, JUN; SHIMOJO, NOBUTAKE; KIDA, KUMIKO; YAMAUCHI, HIDEKO; YAMAUCHI, TERUO

    2016-01-01

    The phosphorylated form of the high-molecular-weight neurofilament heavy subunit (pNF-H) is a major structural protein in axons. The pNF-H level is elevated in the serum of certain patients with central nervous disorders, including chemotherapy-induced cognitive impairment. The present study was conducted to elucidate the potential role of pNF-H as a marker of chemotherapy-induced peripheral neuropathy (CIPN). A total of 71 patients with early breast cancer in various stages of treatment (following 1, 3 or 7 cycles of chemotherapy, or a previous history of breast cancer chemotherapy) were assessed with a self-administered PainDETECT questionnaire [pain location, pain intensity on an 11-point numeric rating scale (NRS), and various pain qualities] and a single serum pNF-H measurement. Patients were divided into two groups based on the presence or absence of bilateral symmetric pain in the distal portions of the extremities [CIPN(+) or CIPN(−)]. The χ2 and Mann-Whitney tests were used for statistical analyses. Among the participants, only 8 patients complained of CIPN. Their pain intensity was 3.5±1.9 (mean ± standard deviation) compared with 1.5±1.8 in the CIPN(−) group (P<0.01). The NRS of numbness in the CIPN(+) group was significantly higher (2.4±1.4) than that of the CIPN(−) group (1.0±1.0). Increased pNF-H levels were observed in 37.5% of the CIPN(+) patients and in 23.8% of CIPN(−) patients (P=0.40). In conclusion, CIPN is observed in the most distal portions of the peripheral nerves that are composed of dendrites but not axons. Although serum pNF-H is a biomarker of axonal damage, it is not useful as a marker of CIPN. PMID:27284419

  1. Stress biomarkers, mood states and sleep during a major competition: success and failure athlete’s profile of high-level swimmers.

    Directory of Open Access Journals (Sweden)

    MOUNIR eCHENNAOUI

    2016-03-01

    Full Text Available The aim of this study was to evaluate stress markers, mood states and sleep indicators in high-level swimmers during a major 7-days competition according to the outcomes. Nine swimmers (6 men and 3 women (age: 22 ± 2 years and 22 ± 4 years, respectively were examined. Before (PRE and after (POST each race (series, semi-finals and finals, salivary concentrations of cortisol, α-amylase (sAA and chromogranin-A (CgA were determined. Mood states were assessed by the profile of mood state (POMS questionnaire completed before and after the 7-days, and self-reported sleep diaries were completed daily. In the failure group, cortisol and sAA significantly increased between PRE-POST measurements (p<0.05, while sCgA was not changed. Significant overall decrease of cortisol (-52.6% and increase of sAA (+68.7% was shown in the failure group. In this group, fatigue, confusion and depression scores and sleep duration before the finals increased. The results in the success group show tendencies for increased cortisol and sCgA concentrations in response to competition, while sAA was not changed. Cortisol levels before the semi-finals and finals and sCgA levels before the finals were positively correlated to the fatigue score in the failure group only (r=0.89. sAA levels before and after the semi-finals were negatively correlated to sleep duration measured in the subsequent night (r=-0.90. In conclusion, the stress of the competition could trigger a negative mood profile and sleep disturbance which correspond to different responses of biomarkers related to the hypothalamo-pituitary-adrenal axis and the sympathetic nervous system activity, cortisol, sAA and CgA.

  2. Stress Biomarkers, Mood States, and Sleep during a Major Competition: “Success” and “Failure” Athlete's Profile of High-Level Swimmers

    Science.gov (United States)

    Chennaoui, Mounir; Bougard, Clément; Drogou, Catherine; Langrume, Christophe; Miller, Christian; Gomez-Merino, Danielle; Vergnoux, Frédéric

    2016-01-01

    The aim of this study was to evaluate stress markers, mood states, and sleep indicators in high-level swimmers during a major 7-days competition according to the outcomes. Nine swimmers [six men and three women (age: 22 ± 2 and 22 ± 4 years, respectively)] were examined. Before (PRE) and after (POST) each race (series, semi-finals, and finals), salivary concentrations of cortisol, α-amylase (sAA), and chromogranin-A (CgA) were determined. Mood states were assessed by the profile of mood state (POMS) questionnaire completed before and after the 7-days, and self-reported sleep diaries were completed daily. In the “failure” group, cortisol and sAA significantly increased between PRE-POST measurements (p < 0.05), while sCgA was not changed. Significant overall decrease of cortisol (-52.6%) and increase of sAA (+68.7%) was shown in the “failure group.” In this group, fatigue, confusion and depression scores, and sleep duration before the finals increased. The results in the “success” group show tendencies for increased cortisol and sCgA concentrations in response to competition, while sAA was not changed. Cortisol levels before the semi-finals and finals and sCgA levels before the finals were positively correlated to the fatigue score in the “failure” group only (r = 0.89). sAA levels before and after the semi-finals were negatively correlated to sleep duration measured in the subsequent night (r = −0.90). In conclusion, the stress of the competition could trigger a negative mood profile and sleep disturbance which correspond to different responses of biomarkers related to the hypothalamo-pituitary-adrenal axis and the sympathetic nervous system (SNS) activity, cortisol, sAA, and CgA. PMID:27014092

  3. Lung Cancer Signature Biomarkers: tissue specific semantic similarity based clustering of Digital Differential Display (DDD data

    Directory of Open Access Journals (Sweden)

    Srivastava Mousami

    2012-11-01

    Full Text Available Abstract Background The tissue-specific Unigene Sets derived from more than one million expressed sequence tags (ESTs in the NCBI, GenBank database offers a platform for identifying significantly and differentially expressed tissue-specific genes by in-silico methods. Digital differential display (DDD rapidly creates transcription profiles based on EST comparisons and numerically calculates, as a fraction of the pool of ESTs, the relative sequence abundance of known and novel genes. However, the process of identifying the most likely tissue for a specific disease in which to search for candidate genes from the pool of differentially expressed genes remains difficult. Therefore, we have used ‘Gene Ontology semantic similarity score’ to measure the GO similarity between gene products of lung tissue-specific candidate genes from control (normal and disease (cancer sets. This semantic similarity score matrix based on hierarchical clustering represents in the form of a dendrogram. The dendrogram cluster stability was assessed by multiple bootstrapping. Multiple bootstrapping also computes a p-value for each cluster and corrects the bias of the bootstrap probability. Results Subsequent hierarchical clustering by the multiple bootstrapping method (α = 0.95 identified seven clusters. The comparative, as well as subtractive, approach revealed a set of 38 biomarkers comprising four distinct lung cancer signature biomarker clusters (panel 1–4. Further gene enrichment analysis of the four panels revealed that each panel represents a set of lung cancer linked metastasis diagnostic biomarkers (panel 1, chemotherapy/drug resistance biomarkers (panel 2, hypoxia regulated biomarkers (panel 3 and lung extra cellular matrix biomarkers (panel 4. Conclusions Expression analysis reveals that hypoxia induced lung cancer related biomarkers (panel 3, HIF and its modulating proteins (TGM2, CSNK1A1, CTNNA1, NAMPT/Visfatin, TNFRSF1A, ETS1, SRC-1, FN1, APLP2, DMBT1

  4. Novel oligonucleotide primers reveal a high diversity of microbes which drive phosphorous turnover in soil.

    Science.gov (United States)

    Bergkemper, Fabian; Kublik, Susanne; Lang, Friederike; Krüger, Jaane; Vestergaard, Gisle; Schloter, Michael; Schulz, Stefanie

    2016-06-01

    Phosphorus (P) is of central importance for cellular life but likewise a limiting macronutrient in numerous environments. Certainly microorganisms have proven their ability to increase the phosphorus bioavailability by mineralization of organic-P and solubilization of inorganic-P. On the other hand they efficiently take up P and compete with other biota for phosphorus. However the actual microbial community that is associated to the turnover of this crucial macronutrient in different ecosystems remains largely anonymous especially taking effects of seasonality and spatial heterogeneity into account. In this study seven oligonucleotide primers are presented which target genes coding for microbial acid and alkaline phosphatases (phoN, phoD), phytases (appA), phosphonatases (phnX) as well as the quinoprotein glucose dehydrogenase (gcd) and different P transporters (pitA, pstS). Illumina amplicon sequencing of soil genomic DNA underlined the high rate of primer specificity towards the respective target gene which usually ranged between 98% and 100% (phoN: 87%). As expected the primers amplified genes from a broad diversity of distinct microorganisms. Using DNA from a beech dominated forest soil, the highest microbial diversity was detected for the alkaline phosphatase (phoD) gene which was amplified from 15 distinct phyla respectively 81 families. Noteworthy the primers also allowed amplification of phoD from 6 fungal orders. The genes coding for acid phosphatase (phoN) and the quinoprotein glucose dehydrogenase (gcd) were amplified from 20 respectively 17 different microbial orders. In comparison the phytase and phosphonatase (appA, phnX) primers covered 13 bacterial orders from 2 different phyla respectively. Although the amplified microbial diversity was apparently limited both primers reliably detected all orders that contributed to the P turnover in the investigated soil as revealed by a previous metagenomic approach. Genes that code for microbial P transporter

  5. Dissociable brain biomarkers of fluid intelligence.

    Science.gov (United States)

    Paul, Erick J; Larsen, Ryan J; Nikolaidis, Aki; Ward, Nathan; Hillman, Charles H; Cohen, Neal J; Kramer, Arthur F; Barbey, Aron K

    2016-08-15

    Cognitive neuroscience has long sought to understand the biological foundations of human intelligence. Decades of research have revealed that general intelligence is correlated with two brain-based biomarkers: the concentration of the brain biochemical N-acetyl aspartate (NAA) measured by proton magnetic resonance spectroscopy (MRS) and total brain volume measured using structural MR imaging (MRI). However, the relative contribution of these biomarkers in predicting performance on core facets of human intelligence remains to be well characterized. In the present study, we sought to elucidate the role of NAA and brain volume in predicting fluid intelligence (Gf). Three canonical tests of Gf (BOMAT, Number Series, and Letter Sets) and three working memory tasks (Reading, Rotation, and Symmetry span tasks) were administered to a large sample of healthy adults (n=211). We conducted exploratory factor analysis to investigate the factor structure underlying Gf independent from working memory and observed two Gf components (verbal/spatial and quantitative reasoning) and one working memory component. Our findings revealed a dissociation between two brain biomarkers of Gf (controlling for age and sex): NAA concentration correlated with verbal/spatial reasoning, whereas brain volume correlated with quantitative reasoning and working memory. A follow-up analysis revealed that this pattern of findings is observed for males and females when analyzed separately. Our results provide novel evidence that distinct brain biomarkers are associated with specific facets of human intelligence, demonstrating that NAA and brain volume are independent predictors of verbal/spatial and quantitative facets of Gf. PMID:27184204

  6. High-Resolution AUV Mapping Reveals Structural Details of Submarine Inflated Lava Flows

    Science.gov (United States)

    Paduan, J.; Clague, D. A.; Caress, D. W.; Thomas, H.; Thompson, D.; Conlin, D.

    2009-12-01

    The MBARI mapping AUV D. Allan B. has now been used to map volcanic terrain at mid-ocean ridges, back-arc spreading centers, and seamounts. These include the summit caldera and upper south rift zone at Axial Volcano, the summit of Davidson Seamount, the Endeavour hydrothermal fields, the Northeast Lau Spreading Center and West Mata Volcano, and, most recently, the CoAxial, North Cleft and North Gorda historic eruption sites on the Juan de Fuca and Gorda Ridges. ROV and submersible dives at most of these sites have provided groundtruth for the textures and features revealed in the roughly 1-m resolution maps. A prominent feature in the maps from four of the sites are inflated flows that did not deflate or drain. These resemble subaerial tumuli but differ in being located on level terrain, apparently atop or very near eruptive vents instead of being in the distal portions of flows. The largest inflated flow at Axial Volcano is on the caldera floor. The main part is 500 by 300 m, and up to 30 m high, with a lobe that extends another 750 m in a sinuous path. It and two nearby, medium-sized inflated flows were first described from sidescan imagery and a submersible dive by Appelgate and Embley (Bull. Volcanol., 54, 447-458, 1992). The AUV maps show clearly the smooth, gently domed relief of the large inflated flow and its sinuous shape on the seafloor, the medium-sized nearby inflated flows, and several additional smaller ones. Particularly striking is a network of 4 to 10 m deep cracks along the crest of each inflation. The cracks occur 30 to 50 m from the margins on all sides of the wider parts of the inflated flows, and become medial cracks along the entire length of the narrow parts, which are nearly triangular in cross-section. An inflation pit 35 m in diameter has a depth equal to the surrounding lava fields. ROV Doc Ricketts dove on these flows in August 2009 and photographed the deeply cracked, uplifted, once flat-lying lineated and ropy sheet flows that form

  7. Downslope Asymmetry in Rainsplash Transport of Sand Revealed With High-Speed Imaging

    Science.gov (United States)

    Furbish, D. J.; Schmeeckle, M. W.; Borosund, M. N.

    2004-12-01

    An understanding of rainsplash detachment and transport is required to formulate theories for a host of hillslope processes, including downslope rainsplash transport, rill development and destruction, and sheetwash transport resulting initially from rainsplash. Net downslope transport of soil particles by rainsplash results from a bias in the number and/or length of particle trajectories. The relative contributions of these attributes of particle motion bear on formulations relating rainsplash transport rates to surface slope angle, as the directional asymmetry of trajectories depends on details of motion during drop impact, including drop incidence angle, whereas the bias in trajectory lengths mostly obtains for geometrical reasons. To clarify these attributes of particle motions initiated by rain drop impacts, we are conducting experiments that allow us to directly visualize them. Specifically, in a first set of experiments we have obtained high-speed video imagery of water-drop impacts and associated motions of medium sand particles on varying slopes under dry and moist (drained) conditions. Drops with diameters of 3 mm were released from a height of 5 m onto a sand target. The target consisted of a circular hole (diameter of 2.5 cm, depth of 1.9 cm) drilled into a wooden block. The quartz sand was angular with a nominal diameter 0.35 mm. In each run the sand surface was initially smooth and flush with the surrounding target surface. Moist conditions were obtained by filling the target hole with sand, wetting it, then allowing the sand to fully drain. Target slopes were 0, 10, 20 and 30 degrees. Images of the drop impacts and particle motions were obtained with a high-speed digital video camera running at 500 frames per second. The videos reveal a clear radial symmetry in particle trajectories at 0 degrees, and only a slight asymmetry at 10 degrees. Noticeable asymmetry occurs at 20 degrees and, at 30 degrees, virtually no particles move upslope. During drop

  8. The Pharmacogenomic HLA Biomarker Associated to Adverse Abacavir Reactions: Comparative Analysis of Different Genotyping Methods

    OpenAIRE

    Zampatti, Stefania; Novelli, Giuseppe; Cascella, Raffaella; Giardina, Emiliano; Stocchi, Laura; Pirazzoli, Antonella

    2012-01-01

    Many pharmacogenomic biomarkers (PGBM) were identified and translated into clinical practice, affecting the usage of drugs via label updates. In this context, abacavir is one of the most brilliant examples of pharmacogenetic studies translated into clinical practice. Pharmacogenetic studies have revealed that abacavir HSRs are highly associated with the major histocompatibility complex class I. Large studies established the effectiveness of prospective HLA-B*57:01 screening to prevent HSRs to...

  9. Potential Blood-based Biomarkers for Concussion.

    Science.gov (United States)

    Papa, Linda

    2016-09-01

    Mounting research in the field of sports concussion biomarkers has led to a greater understanding of the effects of brain injury from sports. A recent systematic review of clinical studies examining biomarkers of brain injury following sports-related concussion established that almost all studies have been published either in or after the year 2000. In an effort to prevent chronic traumatic encephalopathy and long-term consequences of concussion, early diagnostic and prognostic tools are becoming increasingly important; particularly in sports and in military personnel, where concussions are common occurrences. Early and tailored management of athletes following a concussion with biomarkers could provide them with the best opportunity to avoid further injury. Should blood-based biomarkers for concussion be validated and become widely available, they could have many roles. For instance, a point-of-care test could be used on the field by trained sport medicine professionals to help detect a concussion. In the clinic or hospital setting, it could be used by clinicians to determine the severity of concussion and be used to screen players for neuroimaging (computed tomography and/or magnetic resonance imaging) and further neuropsychological testing. Furthermore, biomarkers could have a role in monitoring progression of injury and recovery and in managing patients at high risk of repeated injury by being incorporated into guidelines for return to duty, work, or sports activities. There may even be a role for biomarkers as surrogate measures of efficacy in the assessment of new treatments and therapies for concussion. PMID:27482776

  10. Biomarker Discovery by Novel Sensors Based on Nanoproteomics Approaches

    Directory of Open Access Journals (Sweden)

    Manuel Fuentes

    2012-02-01

    Full Text Available During the last years, proteomics has facilitated biomarker discovery by coupling high-throughput techniques with novel nanosensors. In the present review, we focus on the study of label-based and label-free detection systems, as well as nanotechnology approaches, indicating their advantages and applications in biomarker discovery. In addition, several disease biomarkers are shown in order to display the clinical importance of the improvement of sensitivity and selectivity by using nanoproteomics approaches as novel sensors.

  11. Emerging Risk Biomarkers in Cardiovascular Diseases and Disorders

    OpenAIRE

    Ravi Kant Upadhyay

    2015-01-01

    Present review article highlights various cardiovascular risk prediction biomarkers by incorporating both traditional risk factors to be used as diagnostic markers and recent technologically generated diagnostic and therapeutic markers. This paper explains traditional biomarkers such as lipid profile, glucose, and hormone level and physiological biomarkers based on measurement of levels of important biomolecules such as serum ferritin, triglyceride to HDLp (high density lipoproteins) ratio, l...

  12. Revealing structural and dynamical properties of high density lipoproteins through molecular simulations

    DEFF Research Database (Denmark)

    Koivuniemi, A.; Vattulainen, I.

    2012-01-01

    essentially atomistic considerations of HDL particles over microsecond time scales, thereby proving substantial added value to experimental research. In this article, we discuss recent highlights concerning the structure and dynamics of HDL particles as revealed by atomistic and coarse-grained molecular...

  13. High temperature garnet growth in New England: regional temperature-time trends revealed

    Science.gov (United States)

    Sullivan, N.; Ostwald, C.; Chu, X.; Baxter, E. F.; Ague, J. J.; Eckert, J. O.

    2013-12-01

    A series of localized ultrahigh-temperature (UHT)/high-temperature (HT) granulite facies regions have been identified within the regional amphibolite facies metamorphic zone of the Central Maine Terrane stretching from north-central New Hampshire, through central Massachusetts, and into northeastern Connecticut. Here, we aim to constrain the age and peak temperature of metamorphism at three localities within this region: Bristol, NH, Phillipston, MA and Willington, CT. Garnet-forming reactions are linked directly to peak metamorphic temperatures through thermodynamic modeling and/or Zr-in-rutile thermometry. Precise garnet geochronology allows us to identify the timing of these peak temperatures, as well as the duration of garnet growth. Geochronologic and thermodynamic work was done on 12 samples collected throughout a ~5 km2 metamorphic 'hotspot' previously identified in Bristol, NH (Chamberlain and Rumble, 1988; Journal of Petrology). The highest temperature assemblage within this hotspot is characterized by the presence of garnet + sillimanite + K-feldspar + cordierite and reached temperatures >820οC. The lowest temperature periphery of the hotspot is characterized by sillimanite + muscovite + K-feldspar + minor garnet and reached a maximum temperature of 650οC. Bulk garnet ages from samples within the hotspot range significantly from at least 400.0 × 2.5 Ma to 352.7 × 1.8 Ma with the youngest ages associated with the lower temperature samples. This collection of ages indicates a prolonged period (~50 Ma) of >650οC temperatures interspersed by period(s) of garnet growth. Zoned garnet geochronology will help reveal whether garnet growth and related heating was continuous or episodic. Further south, in Phillipston, MA, zoned garnet geochronology performed on a 2.5 cm diameter garnet porphyroblast indicates garnet growth spanning 389 - 363 Ma, reaching peak temperatures at the end of that time span of 920-940οC, followed by a younger event recorded in

  14. Procalcitonin as an adjunctive biomarker in sepsis

    Directory of Open Access Journals (Sweden)

    Mahua Sinha

    2011-01-01

    Full Text Available Sepsis can sometimes be difficult to substantiate, and its distinction from non-infectious conditions in critically ill patients is often a challenge. Serum procalcitonin (PCT assay is one of the biomarkers of sepsis. The present study was aimed to assess the usefulness of PCT assay in critically ill patients with suspected sepsis. The study included 40 patients from the intensive care unit with suspected sepsis. Sepsis was confirmed clinically and/or by positive blood culture. Serum PCT was assayed semi-quantitatively by rapid immunochromatographic technique (within 2 hours of sample receipt. Among 40 critically ill patients, 21 had clinically confirmed sepsis. There were 12 patients with serum PCT ≥10 ng/ml (8, blood culture positive; 1, rickettsia; 2, post-antibiotic blood culture sterile; and 1, non-sepsis; 7 patients with PCT 2-10 ng/ml (4, blood culture positive; 1, falciparum malaria; 2, post-antibiotic blood culture sterile; 3 patients with PCT of 0.5 to 2 ng/ml (sepsis in 1 patient; and 18 patients with PCT < 0.5 ng/ml (sepsis in 2 patients. Patients with PCT ≥ 2 ng/ml had statistically significant correlation with the presence of sepsis (P<0.0001. The PCT assay revealed moderate sensitivity (86% and high specificity (95% at a cut-off ≥ 2 ng/ml. The PCT assay was found to be a useful biomarker of sepsis in this study. The assay could be performed and reported rapidly and provided valuable information before availability of culture results. This might assist in avoiding unwarranted antibiotic usage.

  15. Nonnegative spline regression of incomplete tracing data reveals high resolution neural connectivity

    CERN Document Server

    Harris, Kameron Decker; Shea-Brown, Eric

    2016-01-01

    Whole-brain neural connectivity data are now available from viral tracing experiments, which reveal the connections between a source injection site and elsewhere in the brain. These hold the promise of revealing spatial patterns of connectivity throughout the mammalian brain. To achieve this goal, we seek to fit a weighted, nonnegative adjacency matrix among 100 {\\mu}m brain "voxels" using viral tracer data. Despite a multi-year experimental effort, the problem remains severely underdetermined: Injection sites provide incomplete coverage, and the number of voxels is orders of magnitude larger than the number of injections. Furthermore, projection data are missing within the injection site because local connections there are not separable from the injection signal. We use a novel machine-learning algorithm to meet these challenges and develop a spatially explicit, voxel-scale connectivity map of the mouse visual system. Our method combines three features: a matrix completion loss for missing data, a smoothing ...

  16. High-Resolution Dissection of Phagosome Maturation Reveals Distinct Membrane Trafficking Phases

    OpenAIRE

    Gotthardt, Daniel; Warnatz, Hans Jörg; Henschel, Oliver; Brückert, Franz; Schleicher, Michael; Soldati, Thierry

    2002-01-01

    Molecular mechanisms of endocytosis in the genetically and biochemically tractable professional phagocyte Dictyostelium discoideum reveal a striking degree of similarity to higher eukaryotic cells. Pulse-chase feeding with latex beads allowed purification of phagosomes at different stages of maturation. Gentle ATP stripping of an actin meshwork entrapping contaminating organelles resulted in a 10-fold increase in yield and purity, as confirmed by electron microscopy. Temporal profiling of sig...

  17. High-resolution dissection of phagosome maturation reveals distinct membrane trafficking phases

    OpenAIRE

    Gotthardt, Daniel; Warnatz, Hans Jörg; Henschel, Oliver; Brückert, Franz; Schleicher, Michael; Soldati, Thierry

    2002-01-01

    Molecular mechanisms of endocytosis in the genetically and biochemically tractable professional phagocyte Dictyostelium discoideum reveal a striking degree of similarity to higher eukaryotic cells. Pulse-chase feeding with latex beads allowed purification of phagosomes at different stages of maturation. Gentle ATP stripping of an actin meshwork entrapping contaminating organelles resulted in a 10-fold increase in yield and purity, as confirmed by electron microscopy. Temporal profiling of sig...

  18. Mass spectrometry for biomarker development

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Chaochao; Liu, Tao; Baker, Erin Shammel; Rodland, Karin D.; Smith, Richard D.

    2015-06-19

    Biomarkers potentially play a crucial role in early disease diagnosis, prognosis and targeted therapy. In the past decade, mass spectrometry based proteomics has become increasingly important in biomarker development due to large advances in technology and associated methods. This chapter mainly focuses on the application of broad (e.g. shotgun) proteomics in biomarker discovery and the utility of targeted proteomics in biomarker verification and validation. A range of mass spectrometry methodologies are discussed emphasizing their efficacy in the different stages in biomarker development, with a particular emphasis on blood biomarker development.

  19. DETECTION OF CANCER BIOMARKERS WITH NANOTECHNOLOGY

    Directory of Open Access Journals (Sweden)

    Lei Zhang

    2013-01-01

    Full Text Available Early detection of cancer biomarkers with high precision is critically important for cancer therapy. A variety of sensors based on different nanostructured materials have attracted intensive research interest due to their potential for highly sensitive and selective detection of cancer biomarkers. This review covers the use of a variety of nanostructured materials, including carbon nanotubes, silicon nanowires, gold nanoparticles and quantum dots, in the fabrication of sensors. Emphases are placed on how the detection systems work and what detection limits can be achieved. Some assays described in this review outperform established methods for cancer biomarker detection. It is highly promising that these sensors would soon move into commercial-scale production and find routine use in hospitals.

  20. YKL-40: a new biomarker in cardiovascular disease?

    DEFF Research Database (Denmark)

    Mathiasen, Anders Bruun; Henningsen, Kristoffer Mads Aaris; Harutyunyan, Marina Jurjevna;

    2010-01-01

    . But in spite of improved treatments, many patients are still plagued by a high frequency of angina symptoms, hospitalizations and a poor prognosis. There is a need for new independent or supplementary biomarkers that can help to predict cardiovascular disease and cardiovascular events earlier and more...... precisely, and thus accompany existing biomarkers in both primary and secondary cardiovascular prevention. One such potential new biomarker is the protein YKL-40. As an independent biomarker in both cardiovascular diseases and noncardiovascular diseases, current evidence suggests YKL-40 to be most useful...

  1. Potential Peripheral Biomarkers for the Diagnosis of Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Seema Patel

    2011-01-01

    Full Text Available Advances in the discovery of a peripheral biomarker for the diagnosis of Alzheimer's would provide a way to better detect the onset of this debilitating disease in a manner that is both noninvasive and universally available. This paper examines the current approaches that are being used to discover potential biomarker candidates available in the periphery. The search for a peripheral biomarker that could be utilized diagnostically has resulted in an extensive amount of studies that employ several biological approaches, including the assessment of tissues, genomics, proteomics, epigenetics, and metabolomics. Although a definitive biomarker has yet to be confirmed, advances in the understanding of the mechanisms of the disease and major susceptibility factors have been uncovered and reveal promising possibilities for the future discovery of a useful biomarker.

  2. Biomarkers of the Dementia

    Directory of Open Access Journals (Sweden)

    Mikio Shoji

    2011-01-01

    Full Text Available Recent advances in biomarker studies on dementia are summarized here. CSF Aβ40, Aβ42, total tau, and phosphorylated tau are the most sensitive biomarkers for diagnosis of Alzheimer's disease (AD and prediction of onset of AD from mild cognitive impairment (MCI. Based on this progress, new diagnostic criteria for AD, MCI, and preclinical AD were proposed by National Institute of Aging (NIA and Alzheimer's Association in August 2010. In these new criteria, progress in biomarker identification and amyloid imaging studies in the past 10 years have added critical information. Huge contributions of basic and clinical studies have established clinical evidence supporting these markers. Based on this progress, essential therapy for cure of AD is urgently expected.

  3. High Resolution Discovery Proteomics Reveals Candidate Disease Progression Markers of Alzheimer’s Disease in Human Cerebrospinal Fluid

    Science.gov (United States)

    Lee, Anita Y. H.; Song, Qinghua; Liaw, Andy; Wiener, Matt; Paweletz, Cloud P.; Seeburger, Jeffrey L.; Li, Jenny; Meng, Fanyu; Deyanova, Ekaterina G.; Mazur, Matthew T.; Settlage, Robert E.; Zhao, Xuemei; Southwick, Katie; Du, Yi; Holder, Dan; Sachs, Jeffrey R.; Laterza, Omar F.; Dallob, Aimee; Chappell, Derek L.; Snyder, Karen; Modur, Vijay; King, Elizabeth; Joachim, Catharine; Bondarenko, Andrey Y.; Shearman, Mark; Soper, Keith A.; Smith, A. David; Potter, William Z.; Koblan, Ken S.; Sachs, Alan B.

    2015-01-01

    Disease modifying treatments for Alzheimer’s disease (AD) constitute a major goal in medicine. Current trends suggest that biomarkers reflective of AD neuropathology and modifiable by treatment would provide supportive evidence for disease modification. Nevertheless, a lack of quantitative tools to assess disease modifying treatment effects remains a major hurdle. Cerebrospinal fluid (CSF) biochemical markers such as total tau, p-tau and Ab42 are well established markers of AD; however, global quantitative biochemical changes in CSF in AD disease progression remain largely uncharacterized. Here we applied a high resolution open discovery platform, dMS, to profile a cross-sectional cohort of lumbar CSF from post-mortem diagnosed AD patients versus those from non-AD/non-demented (control) patients. Multiple markers were identified to be statistically significant in the cohort tested. We selected two markers SME-1 (p<0.0001) and SME-2 (p = 0.0004) for evaluation in a second independent longitudinal cohort of human CSF from post-mortem diagnosed AD patients and age-matched and case-matched control patients. In cohort-2, SME-1, identified as neuronal secretory protein VGF, and SME-2, identified as neuronal pentraxin receptor-1 (NPTXR), in AD were 21% (p = 0.039) and 17% (p = 0.026) lower, at baseline, respectively, than in controls. Linear mixed model analysis in the longitudinal cohort estimate a decrease in the levels of VGF and NPTXR at the rate of 10.9% and 6.9% per year in the AD patients, whereas both markers increased in controls. Because these markers are detected by mass spectrometry without the need for antibody reagents, targeted MS based assays provide a clear translation path for evaluating selected AD disease-progression markers with high analytical precision in the clinic. PMID:26270474

  4. Biomarkers of necrotising soft tissue infections

    DEFF Research Database (Denmark)

    Hansen, Marco Bo; Simonsen, Ulf; Garred, Peter;

    2015-01-01

    INTRODUCTION: The mortality and amputation rates are still high in patients with necrotising soft tissue infections (NSTIs). It would be ideal to have a set of biomarkers that enables the clinician to identify high-risk patients with NSTI on admission. The objectives of this study are to evaluate...

  5. Multilocus sequence analysis of nectar pseudomonads reveals high genetic diversity and contrasting recombination patterns.

    Directory of Open Access Journals (Sweden)

    Sergio Alvarez-Pérez

    Full Text Available The genetic and evolutionary relationships among floral nectar-dwelling Pseudomonas 'sensu stricto' isolates associated to South African and Mediterranean plants were investigated by multilocus sequence analysis (MLSA of four core housekeeping genes (rrs, gyrB, rpoB and rpoD. A total of 35 different sequence types were found for the 38 nectar bacterial isolates characterised. Phylogenetic analyses resulted in the identification of three main clades [nectar groups (NGs 1, 2 and 3] of nectar pseudomonads, which were closely related to five intrageneric groups: Pseudomonas oryzihabitans (NG 1; P. fluorescens, P. lutea and P. syringae (NG 2; and P. rhizosphaerae (NG 3. Linkage disequilibrium analysis pointed to a mostly clonal population structure, even when the analysis was restricted to isolates from the same floristic region or belonging to the same NG. Nevertheless, signatures of recombination were observed for NG 3, which exclusively included isolates retrieved from the floral nectar of insect-pollinated Mediterranean plants. In contrast, the other two NGs comprised both South African and Mediterranean isolates. Analyses relating diversification to floristic region and pollinator type revealed that there has been more unique evolution of the nectar pseudomonads within the Mediterranean region than would be expected by chance. This is the first work analysing the sequence of multiple loci to reveal geno- and ecotypes of nectar bacteria.

  6. Identifying Modular Flows on Multilayer Networks Reveals Highly Overlapping Organization in Interconnected Systems

    Science.gov (United States)

    De Domenico, Manlio; Lancichinetti, Andrea; Arenas, Alex; Rosvall, Martin

    2015-01-01

    To comprehend interconnected systems across the social and natural sciences, researchers have developed many powerful methods to identify functional modules. For example, with interaction data aggregated into a single network layer, flow-based methods have proven useful for identifying modular dynamics in weighted and directed networks that capture constraints on flow processes. However, many interconnected systems consist of agents or components that exhibit multiple layers of interactions, possibly from several different processes. Inevitably, representing this intricate network of networks as a single aggregated network leads to information loss and may obscure the actual organization. Here, we propose a method based on a compression of network flows that can identify modular flows both within and across layers in nonaggregated multilayer networks. Our numerical experiments on synthetic multilayer networks, with some layers originating from the same interaction process, show that the analysis fails in aggregated networks or when treating the layers separately, whereas the multilayer method can accurately identify modules across layers that originate from the same interaction process. We capitalize on our findings and reveal the community structure of two multilayer collaboration networks with topics as layers: scientists affiliated with the Pierre Auger Observatory and scientists publishing works on networks on the arXiv. Compared to conventional aggregated methods, the multilayer method uncovers connected topics and reveals smaller modules with more overlap that better capture the actual organization.

  7. Proteome-based biomarkers in pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Chen Sun; Ann H Rosendahl; Daniel Ansari; Roland Andersson

    2011-01-01

    Pancreatic cancer, as a highly malignant cancer and the fourth cause of cancer-related death in world, is characterized by dismal prognosis, due to rapid disease progression, highly invasive tumour phenotype, and resistance to chemotherapy. Despite significant advances in treatment of the disease during the past decade,the survival rate is little improved. A contributory factor to the poor outcome is the lack of appropriate sensitive and specific biomarkers for early diagnosis. Furthermore, biomarkers for targeting, directing and assessing therapeutic intervention, as well as for detection of residual or recurrent cancer are also needed. Thus, the identification of adequate biomarkers in pancreatic cancer is of extreme importance. Recently, accompanying the development of proteomic technology and devices, more and more potential biomarkers have appeared and are being reported. In this review, we provide an overview of the role of proteome-based biomarkers in pancreatic cancer, including tissue, serum, juice, urine and cell lines. We also discuss the possible mechanism and prospects in the future. That information hopefully might be helpful for further research in the field.

  8. Using Aptamers for Cancer Biomarker Discovery

    Directory of Open Access Journals (Sweden)

    Yun Min Chang

    2013-01-01

    Full Text Available Aptamers are single-stranded synthetic DNA- or RNA-based oligonucleotides that fold into various shapes to bind to a specific target, which includes proteins, metals, and molecules. Aptamers have high affinity and high specificity that are comparable to that of antibodies. They are obtained using iterative method, called (Systematic Evolution of Ligands by Exponential Enrichment SELEX and cell-based SELEX (cell-SELEX. Aptamers can be paired with recent advances in nanotechnology, microarray, microfluidics, and other technologies for applications in clinical medicine. One particular area that aptamers can shed a light on is biomarker discovery. Biomarkers are important in diagnosis and treatment of cancer. In this paper, we will describe ways in which aptamers can be used to discover biomarkers for cancer diagnosis and therapeutics.

  9. Serum biomarker tests are useful in delineating between patients with gastric atrophy and normal, healthy stomach

    Institute of Scientific and Technical Information of China (English)

    Katsunori Iijima; Yasuhiko Abe; Ryosuke Kikuchi; Tomoyuki Koike; Shuichi Ohara; Pentti Sipponen; Tooru Shimosegawa

    2009-01-01

    AIM: To study the value of serum biomarker tests to differentiate between patients with healthy or diseased stomach mucosa: i.e. those with Helicobacter pylori (H pylori) gastritis or atrophic gastritis, who have a high risk of gastric cancer or peptic ulcer diseases.METHODS: Among 162 Japanese outpatients, pepsinogenⅠ(PgⅠ) and Ⅱ(Pg Ⅱ) were measuredusing a conventional Japanese technique, and the European GastroPanel examination (PgⅠand Pg Ⅱ,gastrin-17 and H pylori antibodies). Gastroscopy with gastric biopsies was performed to classify the patients into those with healthy stomach mucosa, H pylori nonatrophic gastritis or atrophic gastritis. RESULTS: Pg Ⅰ and Pg Ⅱ assays with the GastroPanel and the Japanese method showed a highly significant correlation. For methodological reasons, however, serum Pg Ⅰ, but not Pg Ⅱ, was twice as high with the GastroPanel test as with the Japanese test.The biomarker assays revealed that 5% of subjects had advanced atrophic corpus gastritis which was also verified by endoscopic biopsies. GastroPanel examination revealed an additional seven patients who had either advanced atrophic gastritis limited to the antrum or antrum-predominant H pylori gastritis.When compared to the endoscopic biopsy findings,the GastroPanel examination classified the patients into groups with "healthy" or "diseased" stomach mucosa with 94% accuracy, 95% sensitivity and 93% specificity.CONCLUSION: Serum biomarker tests can be used to differentiate between subjects with healthy and diseased gastric mucosa with high accuracy.

  10. Protein biomarker enrichment by biomarker antibody complex elution for immunoassay biosensing.

    Science.gov (United States)

    Sabatte, Gwenola; Feitsma, Harma; Evers, Toon H; Prins, Menno W J

    2011-11-15

    It is very challenging to perform sample enrichment for protein biomarkers because proteins can easily change conformation and denature. In this paper we demonstrate protein enrichment suited for high-sensitivity integrated immuno-biosensing. The method enhances the concentration of the biomarkers and simultaneously removes matrix components that could interfere with the immunoassay. Biomarkers are captured using antibody coated magnetic particles and the biomarker antibody complexes are released by enzymatic elution. The eluted complexes are subsequently detected in a sandwich immunoassay biosensor. A scaling study of the enrichment process demonstrates an enrichment factor of 15 in buffer and plasma. We analyze the enrichment factor in terms of the three basic steps of the assay (capture, concentration, elution) and we quantify their respective efficiencies. The process is suited for integration into bio-analytical tools.

  11. High-Resolution Mapping of Protein Concentration Reveals Principles of Proteome Architecture and Adaptation

    Directory of Open Access Journals (Sweden)

    Emmanuel D. Levy

    2014-05-01

    Full Text Available A single yeast cell contains a hundred million protein molecules. How these proteins are organized to orchestrate living processes is a central question in biology. To probe this organization in vivo, we measured the local concentration of proteins based on the strength of their nonspecific interactions with a neutral reporter protein. We first used a cytosolic reporter and measured local concentrations for ∼2,000 proteins in S. cerevisiae, with accuracy comparable to that of mass spectrometry. Localizing the reporter to membranes specifically increased the local concentration measured for membrane proteins. Comparing the concentrations measured by both reporters revealed that encounter frequencies between proteins are primarily dictated by their abundances. However, to change these encounter frequencies and restructure the proteome, as in adaptation, we find that changes in localization have more impact than changes in abundance. These results highlight how protein abundance and localization contribute to proteome organization and reorganization.

  12. The donor of Aquila X-1 revealed by high angular resolution near-infrared spectroscopy

    CERN Document Server

    Sánchez, D Mata; Casares, J; Jiménez-Ibarra, F

    2016-01-01

    The low mass X-ray binary Aquila X-1 is one of the most active neutron star X-ray transients. Despite it has a relatively bright quiescent optical counterpart, the detection of its companion has been hampered by the presence of a nearby interloper star. Using the infrared integral field spectrograph SINFONI on the VLT-8.2m telescope, we unambiguously single out Aquila X-1 from the interloper. Phase-resolved near infrared spectroscopy reveals absorption features from a K4 +- 2 companion star moving at a projected velocity of K_2= 139 +- 4 km/s. We here present the first dynamical solution and associated fundamental parameters of Aquila X-1, imposing new constraints to the orbital inclination (36 deg < i < 49 deg) and the distance (d = 6 +- 2 kpc) to this prototypical neutron star transient.

  13. The complete primary structure of Cw*1701 reveals a highly divergent HLA class I molecule.

    Science.gov (United States)

    Herrero, M J; Vilches, C; de Pablo, R; Puente, S; Kreisler, M

    1997-03-01

    Genotyping of the HLA-C locus by PCR-SSP has previously shown 100% association of B41 and B42 with a new allelic variant. Partial sequencing studies (exons 2-4) demonstrated that this PCR-SSP variant corresponded to the new allele Cw*1701. In this study we have characterized the whole coding region of Cw*1701 from a Bubi individual of Equatorial Guinea. Our results partially confirm the previously reported sequence and reveal that Cw*1701 has many new polymorphisms at several exons, including a 18-bp insertion in exon 5. Cw*1701 is thus a most unusual HLA-C molecule defining a third allelic lineage of this locus.

  14. Biogeochemistry of methane-related carbonates: an insight from the lipid biomarkers

    Science.gov (United States)

    Makarova, M.; Stadnitskaia, A.; Ivanov, M. K.; Sinninghe Damsté, J. S.

    2009-04-01

    Anaerobic oxidation of methane (AOM) is the main process inducing the formation of authigenic carbonates at the seafloor due to an increase of alkalinity level resulted from the production of bicarbonate ions. AOM is a process accomplished by a consortium of methanogenic archaea and sulfate reducing bacteria (SRB) (Boetius et al., 2000; Hinrichs and Boetius, 2002) but the metabolic interactions of these prokaryotes are still unclear. We studied lipid biomarkers present in authigenic carbonates to reveal molecular patterns that can provide insight in the composition of microbial communities involved in AOM. Methane-derived carbonate crusts and surrounded sediment were collected from different seepage and mud volcano areas with diverse geological history and present-day fluid venting environments: the Western Black Sea, Nile Deep Sea fan (Eastern Mediterranean), and the Gulf of Cadiz (NE Atlantic). Gas chromatography, gas chromatography - mass spectrometry, isotope ratio monitoring gas chromatography mass spectrometry, and high performance liquid chromatography - mass spectrometry were applied to provide biomarker information. The carbonates exhibited diverse range of 13C-depleted lipid biomarkers, which indicate that they harbour a diverse microbial community. The biomarker composition revealed the presence of two distinct types of ANaerobic MEthanotrophic archaea: ANME-1 and ANME-2. However, the composition of archaeal lipids indicated difference in the community structures from crusts to crust. Distinct sets of biomarkers indicated different environments characterized by high and low methane partial pressures during the formation of these carbonates. Lipid biomarkers from non-identified sulfate reducing bacteria, i.e. non-isoprenoidal dialkyl glycerol diethers, were also detected almost in all carbonates although their content varied. Our investigation supports the role of methanotrophic archaea and SRB in the formation of authigenic carbonates. We show that

  15. Tumor antigens as proteogenomic biomarkers in invasive ductal carcinomas

    DEFF Research Database (Denmark)

    Olsen, Lars Rønn; Campos, Benito; Winther, Ole;

    2014-01-01

    Background: The majority of genetic biomarkers for human cancers are defined by statistical screening of high-throughput genomics data. While a large number of genetic biomarkers have been proposed for diagnostic and prognostic applications, only a small number have been applied in the clinic. Si...

  16. P64QUANTITATIVE MGMT METHYLATION ANALYSIS BY PYROSEQUENCING REVEALS A STRONG CORRELATION BETWEEN 1P/19Q CO-DELETION AND HIGH LEVEL METHYLATION IN HIGH GRADE GLIOMAS

    Science.gov (United States)

    Laxton, R.; Doey, L.; Aizpurua, M.; Bodi, I.; King, A.; Chandler, C.; Bhangoo, R.; Beaney, R.; Brazil, L.; Ashkan, K.; Al-Sarraj, S.

    2014-01-01

    INTRODUCTION: Pyrosequencing is a method that allows MGMT methylation to be measured in a quantitative manner. MGMT methylation, along with 1p/19q co-deletion and IDH1 mutation, is an important biomarker in high grade gliomas. MGMT methylation indicates an improved response to temozolomide chemotherapy; patients with 1p/19q co-deleted anaplastic oligodendrogliomas benefit from the addition of chemotherapy to radiotherapy. Aim: To compare the average MGMT promoter methylation level of high grade gliomas and correlate it with other clinical parameters and markers including IDH1&2 mutation and 1p/19q co-deletion. METHOD: For 171 high grade gliomas MGMT methylation analysis was performed by pyrosequencing, mutations to IDH1 and IDH2 genes were also detected by pyrosequencing, or immunohistochemistry (n = 166). Screening for 1p/19q deletion was by fluorescence in situ hybridisation (n = 46). Statistical analysis was performed using R-Stats v2.15.2. RESULTS: The results show that higher methylation was correlated with lower grade and mutation to either IDH1 or IDH2 (27.0% vs. 16.6% p = 0.008; and 27.5 vs. 16.1 p = 0.002 respectively). Interestingly 1p/19q co-deletion versus non co-deletion was associated with a particularly high level of methylation (42.2% vs. 17.7% p = 0.001). No significant differences were seen for age or gender. CONCLUSION: The results offer a potential explanation for the improved prognosis seen in glioma patients with 1p/19q co-deletion and when combined with IDH mutation status may provide an extra control to confirm true 1p/19q co-deletion.

  17. Acute kidney injury in children: Enhancing diagnosis with novel biomarkers

    Directory of Open Access Journals (Sweden)

    Samuel Nkachukwu Uwaezuoke

    2016-07-01

    Full Text Available This narrative review aims to appraise the sensitivity and specificity of novel biomarkers in identifying acute kidney injury (AKI in children. Serum creatinine represents a poor traditional biomarker for AKI due to some limitations. Although alternative reliable biomarkers that would better identify individuals at high risk for developing AKI, identify AKI early enough, monitor its progression and patients' recovery, as well as identify those patients at higher risk for poor outcomes are not yet available in renal care, the search-light has recently been focused on various novel biomarkers, some of which could provide this information in time ahead. Several studies have established their predictive value. However, none of them could solely fulfill all the criteria of the ideal biomarker. Therefore, to increase their sensitivity and specificity and enhance the diagnosis of AKI, constellations of different biomarkers with specific features are probably required. In future, the diagnostic evaluation of AKI in intensive care units will have to undergo a paradigm shift from serum creatinine as the traditional biomarker to tissue-specific injury biomarkers. A panel of these novel biomarkers employed at the bedside setting will ultimately revolutionize the diagnosis and prognostication of AKI in children.

  18. A magma-hydrothermal system beneath Hakone volcano, central Japan, revealed by highly resolved velocity structures

    Science.gov (United States)

    Yukutake, Yohei; Honda, Ryou; Harada, Masatake; Arai, Ryuta; Matsubara, Makoto

    2015-05-01

    High-resolution images of subsurface structures are necessary to understand the transport processes of crustal fluids from deep magma sources and their relationship to earthquake swarms in active volcanic regions. Based on a seismic tomography approach, we have developed a new model for the magma-hydrothermal system beneath Hakone volcano, central Japan, where shallow earthquake swarms and crustal deformation associated with inflation of an open-crack source are often observed. By applying travel-time data for local earthquakes to a tomographic inversion, we obtained highly resolved seismic velocity structures that show a region of low P-wave velocity (Vp), low S-wave velocity (Vs), and high Vp/Vs ratios at depths of 10-20 km beneath the volcano, corresponding to the location of the open-crack source. We suggest that the high Vp/Vs ratios represent a deep magma chamber with a high concentration of melt and/or fluids. Deep low-frequency earthquakes, located just beneath this high Vp/Vs zone, may indicate that magmatic fluids are supplied from below. Above the high Vp/Vs zone, a region of low Vp, low Vs, and low Vp/Vs ratios exists at depths of 3-10 km, suggesting the presence of crack-filled water or CO2 supplied from the inferred deep magma chamber. Many earthquake swarms occur in this low Vp/Vs zone, indicating that crustal fluids play an important role in generating the swarms. Similar relationships between magma reservoirs, overlying hydrothermal systems, and swarm activity have been reported from other volcanic areas and thus may be a ubiquitous feature beneath active volcanoes.

  19. Proteomic Biomarkers of Atherosclerosis

    Directory of Open Access Journals (Sweden)

    Natacha Diaz-Prieto

    2008-01-01

    Full Text Available Biomarkers provide a powerful approach to understanding the spectrum of cardiovascular diseases. They have application in screening, diagnostic, prognostication, prediction of recurrences and monitoring of therapy. The “omics” tool are becoming very useful in the development of new biomarkers in cardiovascular diseases. Among them, proteomics is especially fitted to look for new proteins in health and disease and is playing a significant role in the development of new diagnostic tools in cardiovascular diagnosis and prognosis. This review provides an overview of progress in applying proteomics to atherosclerosis. First, we describe novel proteins identified analysing atherosclerotic plaques directly. Careful analysis of proteins within the atherosclerotic vascular tissue can provide a repertoire of proteins involved in vascular remodelling and atherogenesis. Second, we discuss recent data concerning proteins secreted by atherosclerotic plaques. The definition of the atheroma plaque secretome resides in that proteins secreted by arteries can be very good candidates of novel biomarkers. Finally we describe proteins that have been differentially expressed (versus controls by individual cells which constitute atheroma plaques (endothelial cells, vascular smooth muscle cells, macrophages and foam cells as well as by circulating cells (monocytes, platelets or novel biomarkers present in plasma.

  20. Proteomic Biomarkers of Atherosclerosis.

    Science.gov (United States)

    Vivanco, F; Padial, L R; Darde, V M; de la Cuesta, F; Alvarez-Llamas, G; Diaz-Prieto, Natacha; Barderas, M G

    2008-01-01

    SUMMARY: Biomarkers provide a powerful approach to understanding the spectrum of cardiovascular diseases. They have application in screening, diagnostic, prognostication, prediction of recurrences and monitoring of therapy. The "omics" tool are becoming very useful in the development of new biomarkers in cardiovascular diseases. Among them, proteomics is especially fitted to look for new proteins in health and disease and is playing a significant role in the development of new diagnostic tools in cardiovascular diagnosis and prognosis. This review provides an overview of progress in applying proteomics to atherosclerosis. First, we describe novel proteins identified analysing atherosclerotic plaques directly. Careful analysis of proteins within the atherosclerotic vascular tissue can provide a repertoire of proteins involved in vascular remodelling and atherogenesis. Second, we discuss recent data concerning proteins secreted by atherosclerotic plaques. The definition of the atheroma plaque secretome resides in that proteins secreted by arteries can be very good candidates of novel biomarkers. Finally we describe proteins that have been differentially expressed (versus controls) by individual cells which constitute atheroma plaques (endothelial cells, vascular smooth muscle cells, macrophages and foam cells) as well as by circulating cells (monocytes, platelets) or novel biomarkers present in plasma. PMID:19578499

  1. Emerging Biomarkers in Glioblastoma

    Energy Technology Data Exchange (ETDEWEB)

    McNamara, Mairéad G.; Sahebjam, Solmaz; Mason, Warren P., E-mail: warren.mason@uhn.ca [Pencer Brain Tumor Centre, Princess Margaret Cancer Centre, 610 University Avenue, Toronto, Ontario M5G 2M9 (Canada)

    2013-08-22

    Glioblastoma, the most common primary brain tumor, has few available therapies providing significant improvement in survival. Molecular signatures associated with tumor aggressiveness as well as with disease progression and their relation to differences in signaling pathways implicated in gliomagenesis have recently been described. A number of biomarkers which have potential in diagnosis, prognosis and prediction of response to therapy have been identified and along with imaging modalities could contribute to the clinical management of GBM. Molecular biomarkers including O(6)-methlyguanine-DNA-methyltransferase (MGMT) promoter and deoxyribonucleic acid (DNA) methylation, loss of heterozygosity (LOH) of chromosomes 1p and 19q, loss of heterozygosity 10q, isocitrate dehydrogenase (IDH) mutations, epidermal growth factor receptor (EGFR), epidermal growth factor, latrophilin, and 7 transmembrane domain-containing protein 1 on chromosome 1 (ELTD1), vascular endothelial growth factor (VEGF), tumor suppressor protein p53, phosphatase and tensin homolog (PTEN), p16INK4a gene, cytochrome c oxidase (CcO), phospholipid metabolites, telomerase messenger expression (hTERT messenger ribonucleic acid [mRNA]), microRNAs (miRNAs), cancer stem cell markers and imaging modalities as potential biomarkers are discussed. Inclusion of emerging biomarkers in prospective clinical trials is warranted in an effort for more effective personalized therapy in the future.

  2. A highly-ionized region surrounding SN Refsdal revealed by MUSE

    CERN Document Server

    Karman, W; Balestra, I; Rosati, P; Caputi, K I; Di Teodoro, E; Fraternali, F; Gavazzi, R; Mercurio, A; Prochaska, J X; Rodney, S; Treu, T

    2016-01-01

    Supernova (SN) Refsdal is the first multiply-imaged, highly-magnified, and spatially-resolved SN ever observed. The SN exploded in a highly-magnified spiral galaxy at z=1.49 behind the Frontier Fields Cluster MACS1149, and provides a unique opportunity to study the environment of SNe at high z. We exploit the time delay between multiple images to determine the properties of the SN and its environment, before, during, and after the SN exploded. We use the integral-field spectrograph MUSE on the VLT to simultaneously target all observed and model-predicted positions of SN Refsdal. We find MgII emission at all positions of SN Refsdal, accompanied by weak FeII* emission at two positions. The measured ratios of [OII] to MgII emission of 10-20 indicate a high degree of ionization with low metallicity. Because the same high degree of ionization is found in all images, it cannot be caused by SN Refsdal, but rather by previous SNe or a young and hot stellar population. We find no variability of the [OII] line over a p...

  3. Off like a shot: scaling of ballistic tongue projection reveals extremely high performance in small chameleons.

    Science.gov (United States)

    Anderson, Christopher V

    2016-01-04

    Stretching elastic tissues and using their recoil to power movement allows organisms to release energy more rapidly than by muscle contraction directly, thus amplifying power output. Chameleons employ such a mechanism to ballistically project their tongue up to two body lengths, achieving power outputs nearly three times greater than those possible via muscle contraction. Additionally, small organisms tend to be capable of greater performance than larger species performing similar movements. To test the hypothesis that small chameleon species outperform larger species during ballistic tongue projection, performance was examined during feeding among 20 chameleon species in nine genera. This revealed that small species project their tongues proportionately further than large species, achieving projection distances of 2.5 body lengths. Furthermore, feedings with peak accelerations of 2,590 m s(-2), or 264 g, and peak power output values of 14,040 W kg(-1) are reported. These values represent the highest accelerations and power outputs reported for any amniote movement, highlighting the previously underestimated performance capability of the family. These findings show that examining movements in smaller animals may expose movements harbouring cryptic power amplification mechanisms and illustrate how varying metabolic demands may help drive morphological evolution.

  4. Extreme precipitation and climate gradients in Patagonia revealed by high-resolution regional atmospheric climate modeling

    NARCIS (Netherlands)

    Lenaerts, J.T.M.; van den Broeke, M.R.; van Wessem, J.M.; van de Berg, W.J.; van Meijgaard, E.; van Ulft, L.H.; Schaefer, M.

    2014-01-01

    This study uses output of a high-resolution (5.5 km) regional atmospheric climate model to describe the present-day (1979–2012) climate of Patagonia, with a particular focus on the surface mass balance (SMB) of the Patagonian ice fields. Through a comparison with available in situ observations, it i

  5. Genetic analysis of long-lived families reveals novel variants influencing high density-lipoprotein cholesterol

    DEFF Research Database (Denmark)

    Feitosa, Mary F; Wojczynski, Mary K; Straka, Robert;

    2014-01-01

    The plasma levels of high-density lipoprotein cholesterol (HDL) have an inverse relationship to the risks of atherosclerosis and cardiovascular disease (CVD), and have also been associated with longevity. We sought to identify novel loci for HDL that could potentially provide new insights...

  6. Genetic analysis of Phytophthora infestans populations in the Nordic European countries reveals high genetic variability

    DEFF Research Database (Denmark)

    Brurberg, May Bente; Elameen, Abdelhameed; Le, Ving Hong;

    2011-01-01

    Late blight, caused by the oomycete Phytophthora infestans, is the most important disease of potato (Solanum tuberosum). The pathogen is highly adaptable and to get an overview of the genetic variation in the Nordic countries, Denmark, Finland, Norway and Sweden we have analyzed 200 isolates from...

  7. Bacillus pumilus reveals a remarkably high resistance to hydrogen peroxide provoked oxidative stress

    NARCIS (Netherlands)

    Handtke, S.; Schroeter, R.; Jurgen, B.; Methling, K.; Schluter, R.; Albrecht, D.; Hijum, S.A.F.T. van; Bongaerts, J.; Maurer, K.H.; Lalk, M.; Schweder, T.; Hecker, M.; Voigt, B.

    2014-01-01

    Bacillus pumilus is characterized by a higher oxidative stress resistance than other comparable industrially relevant Bacilli such as B. subtilis or B. licheniformis. In this study the response of B. pumilus to oxidative stress was investigated during a treatment with high concentrations of hydrogen

  8. Single nucleus genome sequencing reveals high similarity among nuclei of an endomycorrhizal fungus

    NARCIS (Netherlands)

    Lin, K.; Limpens, E.H.M.; Zhang, Z.; Ivanov, S.; Saunders, D.G.O.; Mu, D.; Pang, E.; Cao, H.; Cha, H.; Lin, T.; Zhou, Q.; Shang, Y.; Li, Y.; Sharma, T.C.; Velzen, van R.; Ruijter, de N.C.A.; Aanen, D.K.; Win, J.; Kamoun, S.; Bisseling, T.; Geurts, R.; Huang, S.W.

    2014-01-01

    Nuclei of arbuscular endomycorrhizal fungi have been described as highly diverse due to their asexual nature and absence of a single cell stage with only one nucleus. This has raised fundamental questions concerning speciation, selection and transmission of the genetic make-up to next generations. A

  9. Revealing the Hidden Wave: Using the Very Small Radio Telescope to Teach High School Physics

    Science.gov (United States)

    Doherty, Michael; Fish, Vincent L.; Needles, Madeleine

    2011-01-01

    Scientists and teachers have worked together to produce teaching materials for the Very Small Radio Telescope (VSRT), an easy-to-use, low-cost apparatus that can be used in multiple laboratory experiments in high school and university physics and astronomy classes. In this article, we describe the motivation for the VSRT and several of the…

  10. Sustained high basal motion of the Greenland ice sheet revealed by borehole deformation

    DEFF Research Database (Denmark)

    Ryser, Claudia; Luethi, Martin P.; Andrews, Lauren C.;

    2014-01-01

    Ice deformation and basal motion characterize the dynamical behavior of the Greenland ice sheet (GrIS). We evaluate the contribution of basal motion from ice deformation measurements in boreholes drilled to the bed at two sites in the western marginal zone of the GrIS. We find a sustained high am...

  11. Sequence characteristics of T4-like bacteriophage IME08 benome termini revealed by high throughput sequencing

    Directory of Open Access Journals (Sweden)

    An Xiaoping

    2011-04-01

    Full Text Available Abstract Background T4 phage is a model species that has contributed broadly to our understanding of molecular biology. T4 DNA replication and packaging share various mechanisms with human double-stranded DNA viruses such as herpes virus. The literature indicates that T4-like phage genomes have permuted terminal sequences, and are generated by a DNA terminase in a sequence-independent manner; Methods genomic DNA of T4-like bacteriophage IME08 was subjected to high throughput sequencing, and the read sequences with extraordinarily high occurrences were analyzed; Results we demonstrate that both the 5' and 3' termini of the IME08 genome starts with base G or A. The presence of a consensus sequence TTGGA|G around the breakpoint of the high frequency read sequences suggests that the terminase cuts the branched pre-genome in a sequence-preferred manner. Our analysis also shows that terminal cleavage is asymmetric, with one end cut at a consensus sequence, and the other end generated randomly. The sequence-preferred cleavage may produce sticky-ends, but with each end being packaged with different efficiencies; Conclusions this study illustrates how high throughput sequencing can be used to probe replication and packaging mechanisms in bacteriophages and/or viruses.

  12. High throughput olfactory conditioning and memory retention test reveal variation in Nasonia parasitic wasps

    NARCIS (Netherlands)

    Hoedjes, K.M.; Steidle, J.L.M.; Werren, J.H.; Vet, L.E.M.; Smid, H.M.

    2012-01-01

    Most of our knowledge on learning and memory formation results from extensive studies on a small number of animal species. Although features and cellular pathways of learning and memory are highly similar in this diverse group of species, there are also subtle differences. Closely related species of

  13. Highly overlapping winter diet in two sympatric lemming species revealed by DNA metabarcoding.

    Directory of Open Access Journals (Sweden)

    Eeva M Soininen

    Full Text Available Sympatric species are expected to minimize competition by partitioning resources, especially when these are limited. Herbivores inhabiting the High Arctic in winter are a prime example of a situation where food availability is anticipated to be low, and thus reduced diet overlap is expected. We present here the first assessment of diet overlap of high arctic lemmings during winter based on DNA metabarcoding of feces. In contrast to previous analyses based on microhistology, we found that the diets of both collared (Dicrostonyx groenlandicus and brown lemmings (Lemmus trimucronatus on Bylot Island were dominated by Salix while mosses, which were significantly consumed only by the brown lemming, were a relatively minor food item. The most abundant plant taxon, Cassiope tetragona, which alone composes more than 50% of the available plant biomass, was not detected in feces and can thus be considered to be non-food. Most plant taxa that were identified as food items were consumed in proportion to their availability and none were clearly selected for. The resulting high diet overlap, together with a lack of habitat segregation, indicates a high potential for resource competition between the two lemming species. However, Salix is abundant in the winter habitats of lemmings on Bylot Island and the non-Salix portion of the diets differed between the two species. Also, lemming grazing impact on vegetation during winter in the study area is negligible. Hence, it seems likely that the high potential for resource competition predicted between these two species did not translate into actual competition. This illustrates that even in environments with low primary productivity food resources do not necessarily generate strong competition among herbivores.

  14. Biomarkers and infection in the emergency unit.

    Science.gov (United States)

    Hausfater, P

    2014-04-01

    The emergency unit is one of the main places for acute medical care and therefore, has a pivotal role in determining a diagnosis of bacterial infection and initiating antibiotic therapy. There is an unquestionable and growing interest for infection biomarkers because of the polymorphism of septic state presentations in the emergency unit and the lack of accuracy of available biological tools. The C Reactive protein (CRP) is a biomarker of inflammation, not of infection. CRP is highly sensitive but lacks specificity. Moreover, there are few interventional studies evaluating its true added diagnostic value in the emergency unit, therefore preventing using CRP as a biomarker of infection. Serum procalcitonin (PCT) dosage is more specific for the diagnosis of bacterial infection. PCT levels do not increase or only slightly in non-bacterial inflammatory syndromes. PCT also provides prognostic information and risk stratification assessment in the emergency unit. Moreover, many authors of interventional studies have validated the contribution of PCT in decision taking for antibiotic therapy when suspecting low respiratory tract infection. It is currently the first-line biomarker of infection in the emergency unit. Other biomarkers such as presepsin (sCD14) may be contributive for the diagnosis and prognosis. PMID:24556451

  15. Biomarkers for wound healing and their evaluation.

    Science.gov (United States)

    Patel, S; Maheshwari, A; Chandra, A

    2016-01-01

    A biological marker (biomarker) is a substance used as an indicator of biological state. Advances in genomics, proteomics and molecular pathology have generated many candidate biomarkers with potential clinical value. Research has identified several cellular events and mediators associated with wound healing that can serve as biomarkers. Macrophages, neutrophils, fibroblasts and platelets release cytokines molecules including TNF-α, interleukins (ILs) and growth factors, of which platelet-derived growth factor (PDGF) holds the greatest importance. As a result, various white cells and connective tissue cells release both matrix metalloproteinases (MMPs) and the tissue inhibitors of metalloproteinases (TIMPs). Studies have demonstrated that IL-1, IL-6, and MMPs, levels above normal, and an abnormally high MMP/TIMP ratio are often present in non-healing wounds. Clinical examination of wounds for these mediators could predict which wounds will heal and which will not, suggesting use of these chemicals as biomarkers of wound healing. There is also evidence that the application of growth factors like PDGF will alleviate the recuperating process of chronic, non-healing wounds. Finding a specific biomarker for wound healing status would be a breakthrough in this field and helping treat impaired wound healing.

  16. Biomarkers in the Management of Difficult Asthma.

    Science.gov (United States)

    Schleich, Florence; Sophie, Demarche; Renaud, Louis

    2016-01-01

    Difficult asthma is a heterogeneous disease of the airways including various types of bronchial inflammation and various degrees of airway remodeling. Therapeutic response of severe asthmatics can be predicted by the use of biomarkers of Type2-high or Type2-low inflammation. Based on sputum cell analysis, four inflammatory phenotypes have been described. As induced sputum is timeconsuming and expensive technique, surrogate biomarkers are useful in clinical practice. Eosinophilic phenotype is likely to reflect ongoing adaptive immunity in response to allergen. Several biomarkers of eosinophilic asthma are easily available in clinical practice (blood eosinophils, serum IgE, exhaled nitric oxyde, serum periostin). Neutrophilic asthma is thought to reflect innate immune system activation in response to pollutants or infectious agents while paucigranulocytic asthma is thought to be not inflammatory and characterized by smooth muscle dysfunction. We currently lack of user-friendly biomarkers of neutrophilic asthma and airway remodeling. In this review, we summarize the biomarkers available for the management of difficult asthma. PMID:26467509

  17. Are circulating microRNAs peripheral biomarkers for Alzheimer's disease?

    Science.gov (United States)

    Kumar, Subodh; Reddy, P Hemachandra

    2016-09-01

    Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by memory loss, multiple cognitive abnormalities and intellectual impairments. Currently, there are no drugs or agents that can delay and/or prevent the progression of disease in elderly individuals, and there are no peripheral biomarkers that can detect AD early in its pathogenesis. Research has focused on identifying biomarkers for AD so that treatment can be begun as soon as possible in order to restrict or prevent intellectual impairments, memory loss, and other cognitive abnormalities that are associated with the disease. One such potential biomarker is microRNAs that are found in circulatory biofluids, such as blood and blood components, serum and plasma. Blood and blood components are primary sources where miRNAs are released in either cell-free form and then bind to protein components, or are in an encapsulated form with microvesicle particles. Exosomal miRNAs are known to be stable in biofluids and can be detected by high throughput techniques, like microarray and RNA sequencing. In AD brain, enriched miRNAs encapsulated with exosomes crosses the blood brain barrier and secreted in the CSF and blood circulations. This review summarizes recent studies that have identified miRNAs in the blood, serum, plasma, exosomes, cerebral spinal fluids, and extracellular fluids as potential biomarkers of AD. Recent research has revealed only six miRNAs - miR-9, miR-125b, miR-146a, miR-181c, let-7g-5p, and miR-191-5p - that were reported by multiple investigators. Some studies analyzed the diagnostic potential of these six miRNAs through receiver operating curve analysis which indicates the significant area-under-curve values in different biofluid samples. miR-191-5p was found to have the maximum area-under-curve value (0.95) only in plasma and serum samples while smaller area-under-curve values were found for miR-125, miR-181c, miR-191-5p, miR-146a, and miR-9. This article shortlisted the

  18. An Epigenetic Mechanism of High Gdnf Transcription in Glioma Cells Revealed by Specific Sequence Methylation.

    Science.gov (United States)

    Zhang, Bao-Le; Liu, Jie; Lei, Yu; Xiong, Ye; Li, Heng; Lin, Xiaoqian; Yao, Rui-Qin; Gao, Dian-Shuai

    2016-09-01

    Glioma cells express high levels of GDNF. When investigating its transcriptional regulation mechanism, we observed increased or decreased methylation of different cis-acting elements in the gdnf promoter II. However, it is difficult to determine the contributions of methylation changes of each cis-acting element to the abnormally high transcription of gdnf gene. To elucidate the contributions of methylation changes of specific cis-acting elements to the regulation of gdnf transcription, we combined gene site-directed mutation, molecular cloning, and dual luciferase assay to develop the "specific sequence methylation followed by plasmid recircularization" method to alter methylation levels of specific cis-acting elements in the gdnf promoter in living cells and assess gene transcriptional activity. This method successfully introduced artificial changes in the methylation of different cis-acting elements in the gdnf promoter II. Moreover, compared with unmethylated gdnf promoter II, both silencer II hypermethylation plus enhancer II unmethylation and hypermethylation of the entire promoter II (containing enhancer II and silencer II) significantly enhanced gdnf transcriptional activity (P  0.05). Enhancer II hypermethylation plus silencer II unmethylation did not significantly affect gene transcription (P > 0.05). Furthermore, we found significantly increased DNA methylation in the silencer II of the gdnf gene in high-grade astroglioma cells with abnormally high gdnf gene expression (P < 0.01). The absence of silencer II significantly increased gdnf promoter II activity in U251 cells (P < 0.01). In conclusion, our specific sequence methylation followed by plasmid recircularization method successfully altered the methylation levels of a specific cis-acting element in a gene promoter in living cells. This method allows in-depth investigation of the impact of methylation changes of different cis-acting elements in the same promoter on gene transcriptional

  19. Proteomic analysis of Ketogulonicigenium vulgare under glutathione reveals high demand for thiamin transport and antioxidant protection.

    Directory of Open Access Journals (Sweden)

    Qian Ma

    Full Text Available Ketogulonicigenium vulgare, though grows poorly when mono-cultured, has been widely used in the industrial production of the precursor of vitamin C with the coculture of Bacillus megaterium. Various efforts have been made to clarify the synergic pattern of this artificial microbial community and to improve the growth and production ability of K. vulgare, but there is still no sound explanation. In previous research, we found that the addition of reduced glutathione into K. vulgare monoculture could significantly improve its growth and productivity. By performing SEM and TEM, we observed that after adding GSH into K. vulgare monoculture, cells became about 4-6 folds elongated, and formed intracytoplasmic membranes (ICM. To explore the molecular mechanism and provide insights into the investigation of the synergic pattern of the co-culture system, we conducted a comparative iTRAQ-2-D-LC-MS/MS-based proteomic analysis of K. vulgare grown under reduced glutathione. Principal component analysis of proteomic data showed that after the addition of glutathione, proteins for thiamin/thiamin pyrophosphate (TPP transport, glutathione transport and the maintenance of membrane integrity, together with several membrane-bound dehydrogenases had significant up-regulation. Besides, several proteins participating in the pentose phosphate pathway and tricarboxylic acid cycle were also up-regulated. Additionally, proteins combating intracellular reactive oxygen species were also up-regulated, which similarly occurred in K. vulgare when the co-cultured B. megaterium cells lysed from our former research results. This study reveals the demand for transmembrane transport of substrates, especially thiamin, and the demand for antioxidant protection of K. vulgare.

  20. High quality maize centromere 10 sequence reveals evidence of frequent recombination events

    Directory of Open Access Journals (Sweden)

    Thomas Kai Wolfgruber

    2016-03-01

    Full Text Available The ancestral centromeres of maize contain long stretches of the tandemly arranged CentC repeat. The abundance of tandem DNA repeats and centromeric retrotransposons (CR have presented a significant challenge to completely assembling centromeres using traditional sequencing methods. Here we report a nearly complete assembly of the 1.85 Mb maize centromere 10 from inbred B73 using PacBio technology and BACs from the reference genome project. The error rates estimated from overlapping BAC sequences are 7 x 10-6 and 5 x 10-5 for mismatches and indels, respectively. The number of gaps in the region covered by the reassembly was reduced from 140 in the reference genome to three. Three expressed genes are located between 92 and 477 kb of the inferred ancestral CentC cluster, which lies within the region of highest centromeric repeat density. The improved assembly increased the count of full-length centromeric retrotransposons from 5 to 55 and revealed a 22.7 kb segmental duplication that occurred approximately 121,000 years ago. Our analysis provides evidence of frequent recombination events in the form of partial retrotransposons, deletions within retrotransposons, chimeric retrotransposons, segmental duplications including higher order CentC repeats, a deleted CentC monomer, centromere-proximal inversions, and insertion of mitochondrial sequences. Double-strand DNA break (DSB repair is the most plausible mechanism for these events and may be the major driver of centromere repeat evolution and diversity. This repair appears to be mediated by microhomology, suggesting that tandem repeats may have evolved to facilitate the repair of frequent DSBs in centromeres.

  1. High Quality Maize Centromere 10 Sequence Reveals Evidence of Frequent Recombination Events.

    Science.gov (United States)

    Wolfgruber, Thomas K; Nakashima, Megan M; Schneider, Kevin L; Sharma, Anupma; Xie, Zidian; Albert, Patrice S; Xu, Ronghui; Bilinski, Paul; Dawe, R Kelly; Ross-Ibarra, Jeffrey; Birchler, James A; Presting, Gernot G

    2016-01-01

    The ancestral centromeres of maize contain long stretches of the tandemly arranged CentC repeat. The abundance of tandem DNA repeats and centromeric retrotransposons (CR) has presented a significant challenge to completely assembling centromeres using traditional sequencing methods. Here, we report a nearly complete assembly of the 1.85 Mb maize centromere 10 from inbred B73 using PacBio technology and BACs from the reference genome project. The error rates estimated from overlapping BAC sequences are 7 × 10(-6) and 5 × 10(-5) for mismatches and indels, respectively. The number of gaps in the region covered by the reassembly was reduced from 140 in the reference genome to three. Three expressed genes are located between 92 and 477 kb from the inferred ancestral CentC cluster, which lies within the region of highest centromeric repeat density. The improved assembly increased the count of full-length CR from 5 to 55 and revealed a 22.7 kb segmental duplication that occurred approximately 121,000 years ago. Our analysis provides evidence of frequent recombination events in the form of partial retrotransposons, deletions within retrotransposons, chimeric retrotransposons, segmental duplications including higher order CentC repeats, a deleted CentC monomer, centromere-proximal inversions, and insertion of mitochondrial sequences. Double-strand DNA break (DSB) repair is the most plausible mechanism for these events and may be the major driver of centromere repeat evolution and diversity. In many cases examined here, DSB repair appears to be mediated by microhomology, suggesting that tandem repeats may have evolved to efficiently repair frequent DSBs in centromeres. PMID:27047500

  2. Biomarkers of Aging: From Function to Molecular Biology

    OpenAIRE

    Karl-Heinz Wagner; David Cameron-Smith; Barbara Wessner; Bernhard Franzke

    2016-01-01

    Aging is a major risk factor for most chronic diseases and functional impairments. Within a homogeneous age sample there is a considerable variation in the extent of disease and functional impairment risk, revealing a need for valid biomarkers to aid in characterizing the complex aging processes. The identification of biomarkers is further complicated by the diversity of biological living situations, lifestyle activities and medical treatments. Thus, there has been no identification of a sing...

  3. Revealing properties of single-walled carbon nanotubes under high pressure

    CERN Document Server

    Tang Jie; Sasaki, T; Yudasaka, M; Matsushita, A; Iijima, S

    2002-01-01

    It was found by the x-ray diffraction experiment under hydrostatic pressure that the carbon nanotubes are compressed easily with a high volume compressibility of 0.024 GPa sup - sup 1. The single-walled carbon nanotubes are polygonized when they form bundles of hexagonal close-packed structure and the inter-tubular gap is smaller than the equilibrium spacing of graphite. Under high pressure, further polygonization occurs to accommodate the extra amount of volume reduction. The ratio of the short and the long diagonals in the hexagonalized cross section is found to have changed from 0.991 at zero pressure to 0.982 at 1.5 GPa pressure, when the Bragg reflection from the nanotube lattice diminished. Accompanying polygonization, a discontinuous change in electrical resistivity was observed at 1.5 GPa pressure, suggesting a phase transition had occurred.

  4. Subtle Cognitive Dysfunction in Resolving High Altitude Cerebral Edema Revealed by a Clock Drawing Test.

    Science.gov (United States)

    Quigley, Ian; Zafren, Ken

    2016-06-01

    High altitude cerebral edema (HACE) is a life-threatening condition that can affect people who ascend to altitudes above 2500 m. Altered mental status and the presence of ataxia distinguishes HACE from acute mountain sickness (AMS). We describe a patient with subtle cognitive dysfunction, likely due to HACE that had not fully resolved. When he initially presented, the patient appeared to have normal mental status and was not ataxic. The diagnosis of HACE was missed initially but was made when further history became available. Cognitive dysfunction was then diagnosed based on abnormal performance of a clock drawing test. A formal mental status examination, using a clock drawing test, may be helpful in assessing whether a patient at high altitude with apparently normal mental status and with normal gait has HACE. PMID:26874815

  5. Temporal dynamics of motivation-cognitive control interactions revealed by high-resolution pupillometry

    OpenAIRE

    Kimberly Sarah Chiew; Braver, Todd S.

    2013-01-01

    Motivational manipulations, such as the presence of performance-contingent reward incentives, can have substantial influences on cognitive control. Previous evidence suggests that reward incentives may enhance cognitive performance specifically through increased preparatory, or proactive, control processes. The present study examined reward influences on cognitive control dynamics in the AX-Continuous Performance Task (AX-CPT), using high-resolution pupillometry. In the AX-CPT, contextual cue...

  6. Biases during DNA extraction of activated sludge samples revealed by high throughput sequencing

    OpenAIRE

    Guo, Feng; Zhang, Tong

    2012-01-01

    Standardization of DNA extraction is a fundamental issue of fidelity and comparability in investigations of environmental microbial communities. Commercial kits for soil or feces are often adopted for studies of activated sludge because of a lack of specific kits, but they have never been evaluated regarding their effectiveness and potential biases based on high throughput sequencing. In this study, seven common DNA extraction kits were evaluated, based on not only yield/purity but also seque...

  7. Novel Antibacterial Targets and Compounds Revealed by a High-Throughput Cell Wall Reporter Assay

    OpenAIRE

    Nayar, Asha S.; Dougherty, Thomas J.; Ferguson, Keith E.; Granger, Brett A.; McWilliams, Lisa; Stacey, Clare; Leach, Lindsey J.; Narita, Shin-ichiro; Tokuda, Hajime; Miller, Alita A.; Brown, Dean G.; McLeod, Sarah M.

    2015-01-01

    A high-throughput phenotypic screen based on a Citrobacter freundii AmpC reporter expressed in Escherichia coli was executed to discover novel inhibitors of bacterial cell wall synthesis, an attractive, well-validated target for antibiotic intervention. Here we describe the discovery and characterization of sulfonyl piperazine and pyrazole compounds, each with novel mechanisms of action. E. coli mutants resistant to these compounds display no cross-resistance to antibiotics of other classes. ...

  8. Unprecedented High-Resolution View of Bacterial Operon Architecture Revealed by RNA Sequencing

    OpenAIRE

    Conway, Tyrrell; Creecy, James P.; Maddox, Scott M.; Grissom, Joe E; Conkle, Trevor L.; Shadid, Tyler M.; Teramoto, Jun; San Miguel, Phillip; Shimada, Tomohiro; Ishihama, Akira; Mori, Hirotada; Wanner, Barry L.

    2014-01-01

    ABSTRACT We analyzed the transcriptome of Escherichia coli K-12 by strand-specific RNA sequencing at single-nucleotide resolution during steady-state (logarithmic-phase) growth and upon entry into stationary phase in glucose minimal medium. To generate high-resolution transcriptome maps, we developed an organizational schema which showed that in practice only three features are required to define operon architecture: the promoter, terminator, and deep RNA sequence read coverage. We precisely ...

  9. Elevated rates of gold mining in the Amazon revealed through high-resolution monitoring

    OpenAIRE

    Asner, Gregory P.; Llactayo, William; Tupayachi, Raul; Luna, Ernesto Ráez

    2013-01-01

    Commodity gold prices increased substantially following the 2008 global financial crisis. Gold demand has fueled a massive increase in mining activity, some of which is centered in the Amazon basin. Western Amazonian forests of Peru have become an epicenter for mostly illegal gold mining, but the clandestine nature of mining activities has made monitoring and reporting of forest losses extremely challenging. We combined high-resolution satellite and aircraft-based imaging with field surveys t...

  10. Water Vapor on Betelgeuse as Revealed by TEXES High-Resolution 12 Micron Spectra

    OpenAIRE

    Harper, Graham

    2005-01-01

    PUBLISHED The outer atmosphere of the M supergiant Betelgeuse is puzzling. Published observations of different kinds have shed light on different aspects of the atmosphere, but no unified picture has emerged. They have shown, for example, evidence of a water envelope (MOLsphere) that in some studies is found to be optically thick in the mid-infrared. In this paper, we present high-resolution, mid-infrared spectra of Betelgeuse recorded with the TEXES spectrograph. The spe...

  11. High throughput olfactory conditioning and memory retention test reveal variation in Nasonia parasitic wasps

    OpenAIRE

    Hoedjes, K M; Steidle, J.L.M.; Werren, J H; Vet, L. E. M.; Smid, H M

    2012-01-01

    Most of our knowledge on learning and memory formation results from extensive studies on a small number of animal species. Although features and cellular pathways of learning and memory are highly similar in this diverse group of species, there are also subtle differences. Closely related species of parasitic wasps display substantial variation in memory dynamics and can be instrumental to understanding both the adaptive benefit of and mechanisms underlying this variation. Parasitic wasps of ...

  12. Comparative analysis of the Geobacillus hemicellulose utilization locus reveals a highly variable target for improved hemicellulolysis

    OpenAIRE

    De Maayer, Pieter; Phillip J Brumm; Mead, David A; Don A Cowan

    2014-01-01

    Background Members of the thermophilic genus Geobacillus can grow at high temperatures and produce a battery of thermostable hemicellulose hydrolytic enzymes, making them ideal candidates for the bioconversion of biomass to value-added products. To date the molecular determinants for hemicellulose degradation and utilization have only been identified and partially characterized in one strain, namely Geobacillus stearothermophilus T-6, where they are clustered in a single genetic locus. Result...

  13. Effects of anesthetic agents on brain blood oxygenation level revealed with ultra-high field MRI.

    Directory of Open Access Journals (Sweden)

    Luisa Ciobanu

    Full Text Available During general anesthesia it is crucial to control systemic hemodynamics and oxygenation levels. However, anesthetic agents can affect cerebral hemodynamics and metabolism in a drug-dependent manner, while systemic hemodynamics is stable. Brain-wide monitoring of this effect remains highly challenging. Because T(2*-weighted imaging at ultra-high magnetic field strengths benefits from a dramatic increase in contrast to noise ratio, we hypothesized that it could monitor anesthesia effects on brain blood oxygenation. We scanned rat brains at 7T and 17.2T under general anesthesia using different anesthetics (isoflurane, ketamine-xylazine, medetomidine. We showed that the brain/vessels contrast in T(2*-weighted images at 17.2T varied directly according to the applied pharmacological anesthetic agent, a phenomenon that was visible, but to a much smaller extent at 7T. This variation is in agreement with the mechanism of action of these agents. These data demonstrate that preclinical ultra-high field MRI can monitor the effects of a given drug on brain blood oxygenation level in the absence of systemic blood oxygenation changes and of any neural stimulation.

  14. High extensibility of stress fibers revealed by in vitro micromanipulation with fluorescence imaging

    Energy Technology Data Exchange (ETDEWEB)

    Matsui, Tsubasa S. [Department of Biomolecular Sciences, Tohoku University (Japan); Sato, Masaaki [Department of Biomedical Engineering, Tohoku University (Japan); Department of Bioengineering and Robotics, Tohoku University (Japan); Deguchi, Shinji, E-mail: deguchi@nitech.ac.jp [Department of Bioengineering and Robotics, Tohoku University (Japan)

    2013-05-10

    Highlights: •We isolate contractile stress fibers from vascular smooth muscle cells. •We measure the extensibility of individual stress fibers. •We present the first direct evidence that individual stress fibers are highly extensible. •We quantitatively determine the local strain along the length of stress fibers. •The high extensibility we found is beyond that explained by a conventional model. -- Abstract: Stress fibers (SFs), subcellular bundles of actin and myosin filaments, are physically connected at their ends to cell adhesions. The intracellular force transmitted via SFs plays an essential role in cell adhesion regulation and downstream signaling. However, biophysical properties intrinsic to individual SFs remain poorly understood partly because SFs are surrounded by other cytoplasmic components that restrict the deformation of the embedded materials. To characterize their inherent properties independent of other structural components, we isolated SFs from vascular smooth muscle cells and mechanically stretched them by in vitro manipulation while visualizing strain with fluorescent quantum dots attached along their length. SFs were elongated along their entire length, with the length being approximately 4-fold of the stress-free length. This surprisingly high extensibility was beyond that explained by the tandem connection of actin filaments and myosin II bipolar filaments present in SFs, thus suggesting the involvement of other structural components in their passive biophysical properties.

  15. Electron transport in non-polar liquids as revealed by high pressure studies and Hall mobility measurements

    International Nuclear Information System (INIS)

    Several significant advances have been made recently in our studies of excess electrons in non-polar liquids. These studies provide insight into the transport and chemical reactions of electrons. From high pressure studies, up to 3000 atmospheres, information about volume changes for electron transition is obtained. Hall mobility measurements, which are electron drift studies done in crossed magnetic and electric fields, reveal the transport properties of electrons in the conduction band. 8 refs., 1 tab

  16. Nanomaterials based biosensors for cancer biomarker detection

    Science.gov (United States)

    Malhotra, Bansi D.; Kumar, Saurabh; Mouli Pandey, Chandra

    2016-04-01

    Biosensors have enormous potential to contribute to the evolution of new molecular diagnostic techniques for patients suffering with cancerous diseases. A major obstacle preventing faster development of biosensors pertains to the fact that cancer is a highly complex set of diseases. The oncologists currently rely on a few biomarkers and histological characterization of tumors. Some of the signatures include epigenetic and genetic markers, protein profiles, changes in gene expression, and post-translational modifications of proteins. These molecular signatures offer new opportunities for development of biosensors for cancer detection. In this context, conducting paper has recently been found to play an important role towards the fabrication of a biosensor for cancer biomarker detection. In this paper we will focus on results of some of the recent studies obtained in our laboratories relating to fabrication and application of nanomaterial modified paper based biosensors for cancer biomarker detection.

  17. Biomarkers for sporadic Creutzfeldt-Jakob disease.

    Science.gov (United States)

    Soomro, Sanam; Mohan, Chandra

    2016-06-01

    Sporadic Creutzfeldt-Jakob disease (sCJD) is a rare but fatal type of spongiform encephalopathy with unknown cause. Unfortunately, definitive diagnosis of this disease can only be done by examination of postmortem brain tissue. Presumptive diagnosis is done through a combination of clinical manifestations, radiology results, and cerebrospinal fluid (CSF) testing for CSF 14-3-3. Even with these guidelines, premortem diagnosis of sCJD can be unreliable with high rates of misdiagnosis. This calls for more reliable biomarkers of the disease, allowing for better diagnosis as well as understanding the pathogenesis of sCJD. This review compiles potential genetic, protein, biomolecular, and imaging biomarker studies for sCJD since 2010, highlighting the promise of proteins, cytokines, and composite biomarkers for improving the diagnosis as well as understanding the pathogenesis of this mysterious ailment. PMID:27547775

  18. Expression signature as a biomarker for prenatal diagnosis of trisomy 21.

    Directory of Open Access Journals (Sweden)

    Marija Volk

    Full Text Available A universal biomarker panel with the potential to predict high-risk pregnancies or adverse pregnancy outcome does not exist. Transcriptome analysis is a powerful tool to capture differentially expressed genes (DEG, which can be used as biomarker-diagnostic-predictive tool for various conditions in prenatal setting. In search of biomarker set for predicting high-risk pregnancies, we performed global expression profiling to find DEG in Ts21. Subsequently, we performed targeted validation and diagnostic performance evaluation on a larger group of case and control samples. Initially, transcriptomic profiles of 10 cultivated amniocyte samples with Ts21 and 9 with normal euploid constitution were determined using expression microarrays. Datasets from Ts21 transcriptomic studies from GEO repository were incorporated. DEG were discovered using linear regression modelling and validated using RT-PCR quantification on an independent sample of 16 cases with Ts21 and 32 controls. The classification performance of Ts21 status based on expression profiling was performed using supervised machine learning algorithm and evaluated using a leave-one-out cross validation approach. Global gene expression profiling has revealed significant expression changes between normal and Ts21 samples, which in combination with data from previously performed Ts21 transcriptomic studies, were used to generate a multi-gene biomarker for Ts21, comprising of 9 gene expression profiles. In addition to biomarker's high performance in discriminating samples from global expression profiling, we were also able to show its discriminatory performance on a larger sample set 2, validated using RT-PCR experiment (AUC=0.97, while its performance on data from previously published studies reached discriminatory AUC values of 1.00. Our results show that transcriptomic changes might potentially be used to discriminate trisomy of chromosome 21 in the prenatal setting. As expressional alterations

  19. Aerosol Organic Matter-Trace Metal Relationships Revealed by Ultra-High Resolution Mass Spectrometry

    Science.gov (United States)

    Wozniak, A. S.; Sleighter, R. L.; Morton, P. L.; Landing, W. M.; Shelley, R. U.; Hatcher, P. G.

    2011-12-01

    Atmospheric delivery of aerosols is important for the biogeochemical cycling of organic matter (OM) and trace elements in marine environments. Aerosols over marine environments can be derived from marine sources or transported from continental regions of variable vegetative cover and anthropogenic influence. These different sources are key determinants of aerosol OM composition, as well as trace metal amounts and characteristics. Dust-influenced aerosols typically contain higher amounts of Fe than anthropogenic-influenced aerosols but have lesser % of soluble Fe (%FeS), believed to be the bioavailable form of Fe for marine phytoplankton. Four samples from the 2008 GEOTRACES intercalibration experiments (Miami, FL, USA) were analyzed by electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) and related to both air mass back trajectories and %FeS. Three samples showed aerosol sources from the east consistent with Saharan dust inputs, while the fourth sample was derived in part from air masses to the north, influenced by the North American continent. This North American-influenced sample was collected following the 3 day period with the highest %FeS (1.3-1.7%) of the 11 day intercalibration experiment (mean = 0.4-1.1%). FT-ICR mass spectra showed 795 peaks common to the dust-influenced samples but absent from the North American-influenced sample. These peaks were assigned molecular formulas characterized by CHO and CHON compounds with lower H/C and O/C ratios than the 1257 formulas common to all 4 samples, suggesting that the dust-influenced aerosols carry OM that is less oxygenated and more condensed in structure along with Fe of lesser solubility. Air mass trajectory analyses revealed samples collected during a 2010 cruise in the North Atlantic Ocean to be characterized by European-influenced (anthropogenic), African-influenced (dust), and primarily marine air masses, making them ideal for further exploration of the

  20. Network analysis identifies SOD2 mRNA as a potential biomarker for Parkinson's disease.

    Directory of Open Access Journals (Sweden)

    Jose A Santiago

    Full Text Available Increasing evidence indicates that Parkinson's disease (PD and type 2 diabetes (T2DM share dysregulated molecular networks. We identified 84 genes shared between PD and T2DM from curated disease-gene databases. Nitric oxide biosynthesis, lipid and carbohydrate metabolism, insulin secretion and inflammation were identified as common dysregulated pathways. A network prioritization approach was implemented to rank genes according to their distance to seed genes and their involvement in common biological pathways. Quantitative polymerase chain reaction assays revealed that a highly ranked gene, superoxide dismutase 2 (SOD2, is upregulated in PD patients compared to healthy controls in 192 whole blood samples from two independent clinical trials, the Harvard Biomarker Study (HBS and the Diagnostic and Prognostic Biomarkers in Parkinson's disease (PROBE. The results from this study reinforce the idea that shared molecular networks between PD and T2DM provides an additional source of biologically meaningful biomarkers. Evaluation of this biomarker in de novo PD patients and in a larger prospective longitudinal study is warranted.

  1. HIGH-SPEED SINGLE QUANTUM DOT IMAGING OF IN LIVE CELLS REVEAL HOP DIFFUSION

    DEFF Research Database (Denmark)

    Lagerholm, B. Christoffer; Clausen, Mathias P.

    2011-01-01

    have yet to be independently confirmed. In this work, we show that high-speed single particle tracking with quantum dots (QDs) and using a standard wide-field fluorescence microscope and an EMCCD is possible at image acquisition rates of up to ~2000 Hz. The spatial precision in these experiments is ~40...... nm (as determined from the standard deviation of repeated position measurements of an immobile QD on a cell). Using this system, we show that membrane proteins and lipids, which have been exogenously labeled with functionalized QDs, show examples of three types of motion in the plasma membrane of...

  2. Force measurements on natural membrane nanovesicles reveal a composition-independent, high Young's modulus

    Science.gov (United States)

    Calò, Annalisa; Reguera, David; Oncins, Gerard; Persuy, Marie-Annick; Sanz, Guenhaël; Lobasso, Simona; Corcelli, Angela; Pajot-Augy, Edith; Gomila, Gabriel

    2014-01-01

    Mechanical properties of nano-sized vesicles made up of natural membranes are crucial to the development of stable, biocompatible nanocontainers with enhanced functional, recognition and sensing capabilities. Here we measure and compare the mechanical properties of plasma and inner membrane nanovesicles ~80 nm in diameter obtained from disrupted yeast Saccharomyces cerevisiae cells. We provide evidence of a highly deformable behaviour for these vesicles, able to support repeated wall-to-wall compressions without irreversible deformations, accompanied by a noticeably high Young's modulus (~300 MPa) compared to that obtained for reconstituted artificial liposomes of similar size and approaching that of some virus particles. Surprisingly enough, the results are approximately similar for plasma and inner membrane nanovesicles, in spite of their different lipid compositions, especially on what concerns the ergosterol content. These results point towards an important structural role of membrane proteins in the mechanical response of natural membrane vesicles and open the perspective to their potential use as robust nanocontainers for bioapplications.Mechanical properties of nano-sized vesicles made up of natural membranes are crucial to the development of stable, biocompatible nanocontainers with enhanced functional, recognition and sensing capabilities. Here we measure and compare the mechanical properties of plasma and inner membrane nanovesicles ~80 nm in diameter obtained from disrupted yeast Saccharomyces cerevisiae cells. We provide evidence of a highly deformable behaviour for these vesicles, able to support repeated wall-to-wall compressions without irreversible deformations, accompanied by a noticeably high Young's modulus (~300 MPa) compared to that obtained for reconstituted artificial liposomes of similar size and approaching that of some virus particles. Surprisingly enough, the results are approximately similar for plasma and inner membrane nanovesicles, in

  3. High Velocity Precessing Jets from the Water Fountain IRAS 18286-0959 Revealed by VLBA Observations

    CERN Document Server

    Yung, Bosco; Imai, Hiroshi; Deguchi, Shuji; Diamond, Philip; Kwok, Sun

    2011-01-01

    We report the results of multi-epoch VLBA observations of the 22.2GHz water maser emission associated with the "water fountain" IRAS 18286-0959. We suggest that this object is the second example of a highly collimated bipolar precessing outflow traced by water maser emission, the other is W43A. The detected water emission peaks are distributed over a velocity range from -50km/s to 150km/s. The spatial distribution of over 70% of the identified maser features is found to be highly collimated along a spiral jet (jet 1) extended southeast to northwest, the remaining features appear to trace another spiral jet (jet 2) with a different orientation. The two jets form a "double-helix" pattern which lies across ~200 milliarcseconds. The maser distribution is reasonably fit by a model consisting of two bipolar precessing jets. The 3D velocities of jet 1 and jet 2 are derived to be 138km/s and 99km/s, respectively. The precession period of jet 1 is about 56 years. For jet 2, three possible models are tested and they gi...

  4. High-frequency oscillations in distributed neural networks reveal the dynamics of human decision making

    Directory of Open Access Journals (Sweden)

    Adrian G Guggisberg

    2008-03-01

    Full Text Available We examine the relative timing of numerous brain regions involved in human decisions that are based on external criteria, learned information, personal preferences, or unconstrained internal considerations. Using magnetoencephalography (MEG and advanced signal analysis techniques, we were able to non-invasively reconstruct oscillations of distributed neural networks in the high-gamma frequency band (60–150 Hz. The time course of the observed neural activity suggested that two-alternative forced choice tasks are processed in four overlapping stages: processing of sensory input, option evaluation, intention formation, and action execution. Visual areas are activated fi rst, and show recurring activations throughout the entire decision process. The temporo-occipital junction and the intraparietal sulcus are active during evaluation of external values of the options, 250–500 ms after stimulus presentation. Simultaneously, personal preference is mediated by cortical midline structures. Subsequently, the posterior parietal and superior occipital cortices appear to encode intention, with different subregions being responsible for different types of choice. The cerebellum and inferior parietal cortex are recruited for internal generation of decisions and actions, when all options have the same value. Action execution was accompanied by activation peaks in the contralateral motor cortex. These results suggest that high-gamma oscillations as recorded by MEG allow a reliable reconstruction of decision processes with excellent spatiotemporal resolution.

  5. The architecture of the LkCa 15 transitional disk revealed by high-contrast imaging

    CERN Document Server

    Thalmann, C; Hodapp, K; Janson, M; Grady, C A; Min, M; Ovelar, M de Juan; Carson, J; Brandt, T; Bonnefoy, M; McElwain, M W; Leisenring, J; Dominik, C; Henning, T; Tamura, M

    2014-01-01

    We present four new epochs of Ks-band images of the young pre-transitional disk around LkCa 15, and perform extensive forward modeling to derive the physical parameters of the disk. We find indications of strongly anisotropic scattering (Henyey-Greenstein g = 0.67 [-0.11,+0.18]) and a significantly tapered gap edge ('round wall'), but see no evidence that the inner disk, whose existence is predicted by the spectral energy distribution, shadows the outer regions of the disk visible in our images. We marginally confirm the existence of an offset between the disk center and the star along the line of nodes; however, the magnitude of this offset (x = 27 [-20,+19] mas) is notably lower than that found in our earlier H-band images (Thalmann et al. 2010). Intriguingly, we also find, at high significance, an offset of y = 69 [-25, +49] mas perpendicular to the line of nodes. If confirmed by future observations, this would imply a highly elliptical -- or otherwise asymmetric -- disk gap with an effective eccentricity ...

  6. Recent and episodic volcanic and glacial activity on Mars revealed by the High Resolution Stereo Camera.

    Science.gov (United States)

    Neukum, G; Jaumann, R; Hoffmann, H; Hauber, E; Head, J W; Basilevsky, A T; Ivanov, B A; Werner, S C; van Gasselt, S; Murray, J B; McCord, T

    2004-12-23

    The large-area coverage at a resolution of 10-20 metres per pixel in colour and three dimensions with the High Resolution Stereo Camera Experiment on the European Space Agency Mars Express Mission has made it possible to study the time-stratigraphic relationships of volcanic and glacial structures in unprecedented detail and give insight into the geological evolution of Mars. Here we show that calderas on five major volcanoes on Mars have undergone repeated activation and resurfacing during the last 20 per cent of martian history, with phases of activity as young as two million years, suggesting that the volcanoes are potentially still active today. Glacial deposits at the base of the Olympus Mons escarpment show evidence for repeated phases of activity as recently as about four million years ago. Morphological evidence is found that snow and ice deposition on the Olympus construct at elevations of more than 7,000 metres led to episodes of glacial activity at this height. Even now, water ice protected by an insulating layer of dust may be present at high altitudes on Olympus Mons.

  7. High resolution lunar mascon three dimensional density structure revealed by GRAIL gravity

    Science.gov (United States)

    Jianguo, Yan; Yi, Zhang

    2016-07-01

    In the history of the moon exploration, the most amazing achievement is that some mass concentrated areas were found on the near side of the moon1, 2. These mass concentrated areas, which are referred to mascons, are usually covered with a positive gravity anomaly peak, and surrounded by negative gravity anomalies with low geographical elevation1-7. Here we proposed a gravity inverse method including geological constraint to obtain density structure of the lunar mascons. The method was implemented in spherical coordinates and validated with simulation test. Using this method we obtained high resolution density anomaly structure of lunar near side maria mascons basins and far side highland mascons. The high resolution depth information and density anomalies structure of the lunar mascons are presented for the first time. By comparing the near side maria mascons with far side mascons, we found all the mascons have an annulus density structures in their shallow stratums; the mascon depth information also indicates that the mascon depth on lunar far side is much deeper than that on the near side. These results indicate various origination mechanism between nearside and farside mascons.

  8. Pyrosequencing of antibiotic-contaminated river sediments reveals high levels of resistance and gene transfer elements.

    Directory of Open Access Journals (Sweden)

    Erik Kristiansson

    Full Text Available The high and sometimes inappropriate use of antibiotics has accelerated the development of antibiotic resistance, creating a major challenge for the sustainable treatment of infections world-wide. Bacterial communities often respond to antibiotic selection pressure by acquiring resistance genes, i.e. mobile genetic elements that can be shared horizontally between species. Environmental microbial communities maintain diverse collections of resistance genes, which can be mobilized into pathogenic bacteria. Recently, exceptional environmental releases of antibiotics have been documented, but the effects on the promotion of resistance genes and the potential for horizontal gene transfer have yet received limited attention. In this study, we have used culture-independent shotgun metagenomics to investigate microbial communities in river sediments exposed to waste water from the production of antibiotics in India. Our analysis identified very high levels of several classes of resistance genes as well as elements for horizontal gene transfer, including integrons, transposons and plasmids. In addition, two abundant previously uncharacterized resistance plasmids were identified. The results suggest that antibiotic contamination plays a role in the promotion of resistance genes and their mobilization from environmental microbes to other species and eventually to human pathogens. The entire life-cycle of antibiotic substances, both before, under and after usage, should therefore be considered to fully evaluate their role in the promotion of resistance.

  9. Extracellular DNA amplicon sequencing reveals high levels of benthic eukaryotic diversity in the central Red Sea.

    Science.gov (United States)

    Pearman, John K; Irigoien, Xabier; Carvalho, Susana

    2016-04-01

    The present study aims to characterize the benthic eukaryotic biodiversity patterns at a coarse taxonomic level in three areas of the central Red Sea (a lagoon, an offshore area in Thuwal and a shallow coastal area near Jeddah) based on extracellular DNA. High-throughput amplicon sequencing targeting the V9 region of the 18S rRNA gene was undertaken for 32 sediment samples. High levels of alpha-diversity were detected with 16,089 operational taxonomic units (OTUs) being identified. The majority of the OTUs were assigned to Metazoa (29.2%), Alveolata (22.4%) and Stramenopiles (17.8%). Stramenopiles (Diatomea) and Alveolata (Ciliophora) were frequent in a lagoon and in shallower coastal stations, whereas metazoans (Arthropoda: Maxillopoda) were dominant in deeper offshore stations. Only 24.6% of total OTUs were shared among all areas. Beta-diversity was generally lower between the lagoon and Jeddah (nearshore) than between either of those and the offshore area, suggesting a nearshore-offshore biodiversity gradient. The current approach allowed for a broad-range of benthic eukaryotic biodiversity to be analysed with significantly less labour than would be required by other traditional taxonomic approaches. Our findings suggest that next generation sequencing techniques have the potential to provide a fast and standardised screening of benthic biodiversity at large spatial and temporal scales.

  10. The Architecture of the LkCa 15 Transitional Disk Revealed By High-Contrast Imaging

    Science.gov (United States)

    Thalmann, C.; Mulders, G. D.; Hodapp, K.; Janson, M.; Grady, C.A.; Min, M.; de Juan Ovelar, M.; Carson, J.; Brandt, T.; Bonnefoy, M.; McElwain, M. W.; Leisenring, J.; Dominik, C.; Henning, T.; Tamura, M.

    2014-01-01

    We present four new epochs of Ks-band images of the young pre-transitional disk around LkCa 15 and perform extensive forward modeling to derive the physical parameters of the disk. We find indications of strongly anisotropic scattering (Henyey-Greenstein g = 0.67 (+0.18/-0.11)) and a significantly tapered gap edge ("round wall") but see no evidence that the inner disk, whose existence is predicted by the spectral energy distribution, shadows the outer regions of the disk visible in our images.We marginally confirm the existence of an offset between the disk center and the star along the line of nodes; however, the magnitude of this offset (x = 27 (+19/-20) mas) is notably lower than that found in our earlier H-band images. Intriguingly, we also find an offset of y = 69 (+49/-25) mas perpendicular to the line of nodes at high significance. If confirmed by future observations, this would imply a highly elliptical - or otherwise asymmetric - disk gap with an effective eccentricity of e ˜ 0.3. Such asymmetry would most likely be the result of dynamical sculpting by one or more unseen planets in the system. Finally, we find that the bright arc of scattered light we see in direct imaging observations originates from the near side of the disk and appears brighter than the far side because of strong forward scattering.

  11. Revealing complex function, process and pathway interactions with high-throughput expression and biological annotation data.

    Science.gov (United States)

    Singh, Nitesh Kumar; Ernst, Mathias; Liebscher, Volkmar; Fuellen, Georg; Taher, Leila

    2016-10-20

    The biological relationships both between and within the functions, processes and pathways that operate within complex biological systems are only poorly characterized, making the interpretation of large scale gene expression datasets extremely challenging. Here, we present an approach that integrates gene expression and biological annotation data to identify and describe the interactions between biological functions, processes and pathways that govern a phenotype of interest. The product is a global, interconnected network, not of genes but of functions, processes and pathways, that represents the biological relationships within the system. We validated our approach on two high-throughput expression datasets describing organismal and organ development. Our findings are well supported by the available literature, confirming that developmental processes and apoptosis play key roles in cell differentiation. Furthermore, our results suggest that processes related to pluripotency and lineage commitment, which are known to be critical for development, interact mainly indirectly, through genes implicated in more general biological processes. Moreover, we provide evidence that supports the relevance of cell spatial organization in the developing liver for proper liver function. Our strategy can be viewed as an abstraction that is useful to interpret high-throughput data and devise further experiments.

  12. Sustained High Basal Motion of the Greenland Ice Sheet Revealed by Borehole Deformation

    Science.gov (United States)

    Ryser, Claudia; Luthi, Martin P.; Andrews, Lauren C.; Hoffman, Matthew, J.; Catania, Ginny A.; Hawley, Robert L.; Neumann, Thomas A.; Kristensen, Steen S.

    2014-01-01

    Ice deformation and basal motion characterize the dynamical behavior of the Greenland ice sheet (GrIS). We evaluate the contribution of basal motion from ice deformation measurements in boreholes drilled to the bed at two sites in the western marginal zone of the GrIS. We find a sustained high amount of basal motion contribution to surface velocity of 44-73 percent in winter, and up to 90 percent in summer. Measured ice deformation rates show an unexpected variation with depth that can be explained with the help of an ice-flow model as a consequence of stress transfer from slippery to sticky areas. This effect necessitates the use of high-order ice-flow models, not only in regions of fast-flowing ice streams but in all temperate-based areas of the GrIS. The agreement between modeled and measured deformation rates confirms that the recommended values of the temperature-dependent flow rate factor A are a good choice for ice-sheet models.

  13. Extracellular DNA amplicon sequencing reveals high levels of benthic eukaryotic diversity in the central Red Sea

    KAUST Repository

    Pearman, John K.

    2015-11-01

    The present study aims to characterize the benthic eukaryotic biodiversity patterns at a coarse taxonomic level in three areas of the central Red Sea (a lagoon, an offshore area in Thuwal and a shallow coastal area near Jeddah) based on extracellular DNA. High-throughput amplicon sequencing targeting the V9 region of the 18S rRNA gene was undertaken for 32 sediment samples. High levels of alpha-diversity were detected with 16,089 operational taxonomic units (OTUs) being identified. The majority of the OTUs were assigned to Metazoa (29.2%), Alveolata (22.4%) and Stramenopiles (17.8%). Stramenopiles (Diatomea) and Alveolata (Ciliophora) were frequent in a lagoon and in shallower coastal stations, whereas metazoans (Arthropoda: Maxillopoda) were dominant in deeper offshore stations. Only 24.6% of total OTUs were shared among all areas. Beta-diversity was generally lower between the lagoon and Jeddah (nearshore) than between either of those and the offshore area, suggesting a nearshore–offshore biodiversity gradient. The current approach allowed for a broad-range of benthic eukaryotic biodiversity to be analysed with significantly less labour than would be required by other traditional taxonomic approaches. Our findings suggest that next generation sequencing techniques have the potential to provide a fast and standardised screening of benthic biodiversity at large spatial and temporal scales.

  14. High-speed atomic force microscopy reveals structural dynamics of amyloid β1-42 aggregates.

    Science.gov (United States)

    Watanabe-Nakayama, Takahiro; Ono, Kenjiro; Itami, Masahiro; Takahashi, Ryoichi; Teplow, David B; Yamada, Masahito

    2016-05-24

    Aggregation of amyloidogenic proteins into insoluble amyloid fibrils is implicated in various neurodegenerative diseases. This process involves protein assembly into oligomeric intermediates and fibrils with highly polymorphic molecular structures. These structural differences may be responsible for different disease presentations. For this reason, elucidation of the structural features and assembly kinetics of amyloidogenic proteins has been an area of intense study. We report here the results of high-speed atomic force microscopy (HS-AFM) studies of fibril formation and elongation by the 42-residue form of the amyloid β-protein (Aβ1-42), a key pathogenetic agent of Alzheimer's disease. Our data demonstrate two different growth modes of Aβ1-42, one producing straight fibrils and the other producing spiral fibrils. Each mode depends on initial fibril nucleus structure, but switching from one growth mode to another was occasionally observed, suggesting that fibril end structure fluctuated between the two growth modes. This switching phenomenon was affected by buffer salt composition. Our findings indicate that polymorphism in fibril structure can occur after fibril nucleation and is affected by relatively modest changes in environmental conditions. PMID:27162352

  15. Torque measurements reveal large process differences between materials during high solid enzymatic hydrolysis of pretreated lignocellulose

    Directory of Open Access Journals (Sweden)

    Palmqvist Benny

    2012-08-01

    Full Text Available Abstract Background A common trend in the research on 2nd generation bioethanol is the focus on intensifying the process and increasing the concentration of water insoluble solids (WIS throughout the process. However, increasing the WIS content is not without problems. For example, the viscosity of pretreated lignocellulosic materials is known to increase drastically with increasing WIS content. Further, at elevated viscosities, problems arise related to poor mixing of the material, such as poor distribution of the enzymes and/or difficulties with temperature and pH control, which results in possible yield reduction. Achieving good mixing is unfortunately not without cost, since the power requirements needed to operate the impeller at high viscosities can be substantial. This highly important scale-up problem can easily be overlooked. Results In this work, we monitor the impeller torque (and hence power input in a stirred tank reactor throughout high solid enzymatic hydrolysis (Arundo donax and spruce. Two different process modes were evaluated, where either the impeller speed or the impeller power input was kept constant. Results from hydrolysis experiments at a fixed impeller speed of 10 rpm show that a very rapid decrease in impeller torque is experienced during hydrolysis of pretreated arundo (i.e. it loses its fiber network strength, whereas the fiber strength is retained for a longer time within the spruce material. This translates into a relatively low, rather WIS independent, energy input for arundo whereas the stirring power demand for spruce is substantially larger and quite WIS dependent. By operating the impeller at a constant power input (instead of a constant impeller speed it is shown that power input greatly affects the glucose yield of pretreated spruce whereas the hydrolysis of arundo seems unaffected. Conclusions The results clearly highlight the large differences between the arundo and spruce materials, both in terms of

  16. Surface hardening induced by high flux plasma in tungsten revealed by nano-indentation

    Science.gov (United States)

    Terentyev, D.; Bakaeva, A.; Pardoen, T.; Favache, A.; Zhurkin, E. E.

    2016-08-01

    Surface hardness of tungsten after high flux deuterium plasma exposure has been characterized by nanoindentation. The effect of plasma exposure was rationalized on the basis of available theoretical models. Resistance to plastic penetration is enhanced within the 100 nm sub-surface region, attributed to the pinning of geometrically necessary dislocations on nanometric deuterium cavities - signature of plasma-induced defects and deuterium retention. Sub-surface extension of thereby registered plasma-induced damage is in excellent agreement with the results of alternative measurements. The study demonstrates suitability of nano-indentation to probe the impact of deposition of plasma-induced defects in tungsten on near surface plasticity under ITER-relevant plasma exposure conditions.

  17. Measuring Absolute RNA Copy Numbers at High Temporal Resolution Reveals Transcriptome Kinetics in Development

    Directory of Open Access Journals (Sweden)

    Nick D.L. Owens

    2016-01-01

    Full Text Available Transcript regulation is essential for cell function, and misregulation can lead to disease. Despite technologies to survey the transcriptome, we lack a comprehensive understanding of transcript kinetics, which limits quantitative biology. This is an acute challenge in embryonic development, where rapid changes in gene expression dictate cell fate decisions. By ultra-high-frequency sampling of Xenopus embryos and absolute normalization of sequence reads, we present smooth gene expression trajectories in absolute transcript numbers. During a developmental period approximating the first 8 weeks of human gestation, transcript kinetics vary by eight orders of magnitude. Ordering genes by expression dynamics, we find that “temporal synexpression” predicts common gene function. Remarkably, a single parameter, the characteristic timescale, can classify transcript kinetics globally and distinguish genes regulating development from those involved in cellular metabolism. Overall, our analysis provides unprecedented insight into the reorganization of maternal and embryonic transcripts and redefines our ability to perform quantitative biology.

  18. The high energy X-ray tail of Eta Car revealed by BeppoSAX

    OpenAIRE

    Viotti, R. F.; Antonelli, L. A.; Rossi, C.; Rebecchi, S.

    2004-01-01

    We report on the June 2000 long (100 ks) BeppoSAX exposure that has unveiled above 10 keV a new very high energy component of the X-ray spectrum of Eta Car extending to at least 50 keV. We find that the 2-150 keV spectrum is best reproduced by a thermal + non-thermal model. The thermal component dominates the 2-10 keV spectral range with kT_h=5.5 +/- 0.3 keV and log NH_h=22.68 +/- 0.01. The spectrum displays a prominent iron emission line centred at 6.70 keV. Its equivalent width of 0.94 keV,...

  19. Genome-wide binding of MBD2 reveals strong preference for highly methylated loci.

    Directory of Open Access Journals (Sweden)

    Roberta Menafra

    Full Text Available MBD2 is a subunit of the NuRD complex that is postulated to mediate gene repression via recruitment of the complex to methylated DNA. In this study we adopted an MBD2 tagging-approach to study its genome wide binding characteristics. We show that in vivo MBD2 is mainly recruited to CpG island promoters that are highly methylated. Interestingly, MBD2 binds around 1 kb downstream of the transcription start site of a subset of ∼ 400 CpG island promoters that are characterized by the presence of active histone marks, RNA polymerase II (Pol2 and low to medium gene expression levels and H3K36me3 deposition. These tagged-MBD2 binding sites in MCF-7 show increased methylation in a cohort of primary breast cancers but not in normal breast samples, suggesting a putative role for MBD2 in breast cancer.

  20. Mosquito Surveillance for 15 Years Reveals High Genetic Diversity Among West Nile Viruses in Israel.

    Science.gov (United States)

    Lustig, Yaniv; Hindiyeh, Musa; Orshan, Laor; Weiss, Leah; Koren, Ravit; Katz-Likvornik, Shiri; Zadka, Hila; Glatman-Freedman, Aharona; Mendelson, Ella; Shulman, Lester M

    2016-04-01

    West Nile Virus (WNV) is endemic in Israel and has been the cause of several outbreaks in recent years. In 2000, a countrywide mosquito survey was established to monitor WNV activity and characterize viral genotypes in Israel. We analyzed data from 7135 pools containing 277 186 mosquitoes collected over the past 15 years and, here, report partial sequences of WNV genomes obtained from 102 of the 336 positive mosquito pools. Phylogenetic analysis demonstrated that cluster 4 and the Mediterranean and Eastern European subtypes of cluster 2 within WNV lineage 1 circulated in Israel, as did WNV lineage 2, highlighting a high genetic diversity of WNV genotypes in our region. As a major crossroads for bird migration between Africa and Eurasia and with a long history of human infection, Israel serves as a resource hub for WNV in Africa and Eurasia and provides valuable information on WNV circulation in these regions. PMID:26597260

  1. Visual sensory processing deficits in patients with bipolar disorder revealed through high-density electrical mapping.

    LENUS (Irish Health Repository)

    Yeap, Sherlyn

    2009-11-01

    BACKGROUND: Etiological commonalities are apparent between bipolar disorder and schizophrenia. For example, it is becoming clear that both populations show similar electrophysiological deficits in the auditory domain. Recent studies have also shown robust visual sensory processing deficits in patients with schizophrenia using the event-related potential technique, but this has not been formally tested in those with bipolar disorder. Our goal here was to assess whether early visual sensory processing in patients with bipolar disorder, as indexed by decreased amplitude of the P1 component of the visual evoked potential (VEP), would show a similar deficit to that seen in those with schizophrenia. Since the P1 deficit has already been established as an endophenotype in schizophrenia, a finding of commonality between disorders would raise the possibility that it represents a measure of common genetic liability. METHODS: We visually presented isolated-check stimuli to euthymic patients with a diagnosis of bipolar disorder and age-matched healthy controls within a simple go\\/no-go task and recorded VEPs using high-density (72-channel) electroencephalography. RESULTS: The P1 VEP amplitude was substantially reduced in patients with bipolar disorder, with an effect size of f = 0.56 (large according to Cohen\\'s criteria). LIMITATIONS: Our sample size was relatively small and as such, did not allow for an examination of potential relations between the physiologic measures and clinical measures. CONCLUSION: This reduction in P1 amplitude among patients with bipolar disorder represents a dysfunction in early visual processing that is highly similar to that found repeatedly in patients with schizophrenia and their healthy first-degree relatives. Since the P1 deficit has been related to susceptibility genes for schizophrenia, our results raise the possibility that the deficit may in fact be more broadly related to the development of psychosis and that it merits further

  2. A novel high-throughput assay for islet respiration reveals uncoupling of rodent and human islets.

    Directory of Open Access Journals (Sweden)

    Jakob D Wikstrom

    Full Text Available BACKGROUND: The pancreatic beta cell is unique in its response to nutrient by increased fuel oxidation. Recent studies have demonstrated that oxygen consumption rate (OCR may be a valuable predictor of islet quality and long term nutrient responsiveness. To date, high-throughput and user-friendly assays for islet respiration are lacking. The aim of this study was to develop such an assay and to examine bioenergetic efficiency of rodent and human islets. METHODOLOGY/PRINCIPAL FINDINGS: The XF24 respirometer platform was adapted to islets by the development of a 24-well plate specifically designed to confine islets. The islet plate generated data with low inter-well variability and enabled stable measurement of oxygen consumption for hours. The F1F0 ATP synthase blocker oligomycin was used to assess uncoupling while rotenone together with myxothiazol/antimycin was used to measure the level of non-mitochondrial respiration. The use of oligomycin in islets was validated by reversing its effect in the presence of the uncoupler FCCP. Respiratory leak averaged to 59% and 49% of basal OCR in islets from C57Bl6/J and FVB/N mice, respectively. In comparison, respiratory leak of INS-1 cells and C2C12 myotubes was measured to 38% and 23% respectively. Islets from a cohort of human donors showed a respiratory leak of 38%, significantly lower than mouse islets. CONCLUSIONS/SIGNIFICANCE: The assay for islet respiration presented here provides a novel tool that can be used to study islet mitochondrial function in a relatively high-throughput manner. The data obtained in this study shows that rodent islets are less bioenergetically efficient than human islets as well as INS1 cells.

  3. Comprehensive Red List assessment reveals exceptionally high extinction risk to Madagascar palms.

    Directory of Open Access Journals (Sweden)

    Mijoro Rakotoarinivo

    Full Text Available The establishment of baseline IUCN Red List assessments for plants is a crucial step in conservation planning. Nowhere is this more important than in biodiversity hotspots that are subject to significant anthropogenic pressures, such as Madagascar. Here, all Madagascar palm species are assessed using the IUCN Red List categories and criteria, version 3.1. Our results indicate that 83% of the 192 endemic species are threatened, nearly four times the proportion estimated for plants globally and exceeding estimates for all other comprehensively evaluated plant groups in Madagascar. Compared with a previous assessment in 1995, the number of Endangered and Critically Endangered species has substantially increased, due to the discovery of 28 new species since 1995, most of which are highly threatened. The conservation status of most species included in both the 1995 and the current assessments has not changed. Where change occurred, more species have moved to lower threat categories than to higher categories, because of improved knowledge of species and their distributions, rather than a decrease in extinction risk. However, some cases of genuine deterioration in conservation status were also identified. Palms in Madagascar are primarily threatened by habitat loss due to agriculture and biological resource use through direct exploitation or collateral damage. The recent extension of Madagascar's protected area network is highly beneficial for palms, substantially increasing the number of threatened species populations included within reserves. Notably, three of the eight most important protected areas for palms are newly designated. However, 28 threatened and data deficient species are not protected by the expanded network, including some Critically Endangered species. Moreover, many species occurring in protected areas are still threatened, indicating that threatening processes persist even in reserves. Definitive implementation of the new protected

  4. High-resolution mapping reveals links of HP1 with active and inactive chromatin components.

    Directory of Open Access Journals (Sweden)

    Elzo de Wit

    2007-03-01

    Full Text Available Heterochromatin protein 1 (HP1 is commonly seen as a key factor of repressive heterochromatin, even though a few genes are known to require HP1-chromatin for their expression. To obtain insight into the targeting of HP1 and its interplay with other chromatin components, we have mapped HP1-binding sites on Chromosomes 2 and 4 in Drosophila Kc cells using high-density oligonucleotide arrays and the DNA adenine methyltransferase identification (DamID technique. The resulting high-resolution maps show that HP1 forms large domains in pericentric regions, but is targeted to single genes on chromosome arms. Intriguingly, HP1 shows a striking preference for exon-dense genes on chromosome arms. Furthermore, HP1 binds along entire transcription units, except for 5' regions. Comparison with expression data shows that most of these genes are actively transcribed. HP1 target genes are also marked by the histone variant H3.3 and dimethylated histone 3 lysine 4 (H3K4me2, which are both typical of active chromatin. Interestingly, H3.3 deposition, which is usually observed along entire transcription units, is limited to the 5' ends of HP1-bound genes. Thus, H3.3 and HP1 are mutually exclusive marks on active chromatin. Additionally, we observed that HP1-chromatin and Polycomb-chromatin are nonoverlapping, but often closely juxtaposed, suggesting an interplay between both types of chromatin. These results demonstrate that HP1-chromatin is transcriptionally active and has extensive links with several other chromatin components.

  5. High efficiency bio-hydrogen production from glucose revealed in an inoculum of heat-pretreated landfill leachate sludge

    International Nuclear Information System (INIS)

    Bio-hydrogen is a promising sustainable energy to replace fossil fuels. This study investigated bio-H2 production from the inoculum of heat-pretreated landfill leachate sludge using glucose as model substrate. The seed sludge pretreated at 65 °C showed the highest amount of H2 at the optimum condition of pH 6 and 37 °C. The maximum H2 yield estimated by the modified Gompertz model was 6.43 mol H2/mol glucose. The high efficient of H2 production is thermodynamically feasible with the Gibbs free energy of −34 kJ/mol. This study reveals that pretreated landfill leachate sludge has considerable potential for H2 production. - Highlights: • Heat retreated landfill leachate sludge revealed high efficient H2 production. • High efficient H2 yield, 6.4 mol H2/mol glucose. • The synergisms between H2-producing bacteria may responsible for the high H2 yield. • High H2 yield is thermodynamically feasible with Gibbs free energy of −34 kJ/mol

  6. Active faults in the deformation zone off Noto Peninsula, Japan, revealed by high- resolution seismic profiles

    Science.gov (United States)

    Inoue, T.; Okamura, Y.; Murakami, F.; Kimura, H.; Ikehara, K.

    2008-12-01

    Recently, a lot of earthquakes occur in Japan. The deformation zone which many faults and folds have concentrated exists on the Japan Sea side of Japan. The 2007 Noto Hanto Earthquake (MJMA 6.9) and 2007 Chuetsu-oki Earthquake (MJMA 6.8) were caused by activity of parts of faults in this deformation zone. The Noto Hanto Earthquake occurred on 25 March, 2007 under the northwestern coast of Noto Peninsula, Ishikawa Prefecture, Japan. This earthquake is located in Quaternary deformation zone that is continued from northern margin of Noto Peninsula to southeast direction (Okamura, 2007a). National Institute of Advanced Industrial Science and Technology (AIST) carried out high-resolution seismic survey using Boomer and 12 channels short streamer cable in the northern part off Noto Peninsula, in order to clarify distribution and activities of active faults in the deformation zone. A twelve channels short streamer cable with 2.5 meter channel spacing developed by AIST and private corporation is designed to get high resolution seismic profiles in shallow sea area. The multi-channel system is possible to equip on a small fishing boat, because the data acquisition system is based on PC and the length of the cable is short and easy to handle. Moreover, because the channel spacing is short, this cable is very effective for a high- resolution seismic profiling survey in the shallow sea, and seismic data obtained by multi-channel cable can be improved by velocity analysis and CDP stack. In the northern part off Noto Peninsula, seismic profiles depicting geologic structure up to 100 meters deep under sea floor were obtained. The most remarkable reflection surface recognized in the seismic profiles is erosion surface at the Last Glacial Maximum (LGM). In the western part, sediments about 30 meters (40 msec) thick cover the erosional surface that is distributed under the shelf shallower than 100m in depth and the sediments thin toward offshore and east. Flexures like deformation in

  7. High-resolution structure of TBP with TAF1 reveals anchoring patterns in transcriptional regulation

    Science.gov (United States)

    Anandapadamanaban, Madhanagopal; Andresen, Cecilia; Helander, Sara; Ohyama, Yoshifumi; Siponen, Marina I.; Lundström, Patrik; Kokubo, Tetsuro; Ikura, Mitsuhiko; Moche, Martin; Sunnerhagen, Maria

    2016-01-01

    The general transcription factor TFIID provides a regulatory platform for transcription initiation. Here we present the crystal structure (1.97 Å) and NMR analysis of yeast TAF1 N-terminal domains TAND1 and TAND2 when bound to yeast TBP, together with mutational data. The yTAF1-TAND1, which in itself acts as a transcriptional activator, binds into the DNA-binding TBP concave surface by presenting similar anchor residues to TBP as E. coli Mot1 but from a distinct structural scaffold. Furthermore, we show how yTAF1-TAND2 employs an aromatic and acidic anchoring pattern to bind a conserved yTBP surface groove traversing the basic helix region, and we find highly similar TBP-binding motifs also presented by the structurally distinct TFIIA, Mot1 and Brf1 proteins. Our identification of these anchoring patterns, which can be easily disrupted or enhanced, provides compelling insight into the competitive multiprotein TBP interplay critical to transcriptional regulation. PMID:23851461

  8. Water Vapor on Betelgeuse as Revealed by TEXES High-Resolution 12 Micron Spectra

    CERN Document Server

    Ryde, N; Richter, M J; Greathouse, T K; Lacy, J H

    2006-01-01

    The outer atmosphere of the M supergiant Betelgeuse is puzzling. Published observations of different kinds have shed light on different aspects of the atmosphere, but no unified picture has emerged. They have shown, for example, evidence of a water envelope (MOLsphere) that in some studies is found to be optically thick in the mid-infrared. In this paper, we present high-resolution, mid-infrared spectra of Betelgeuse recorded with the TEXES spectrograph. The spectra clearly show absorption features of water vapor and OH. We show that a spectrum based on a spherical, hydrostatic model photosphere with T_eff = 3600 K, an effective temperature often assumed for Betelgeuse, fails to model the observed lines. Furthermore, we show that published MOLspheres scenarios are unable to explain our data. However, we are able to model the observed spectrum reasonably well by adopting a cooler outer photospheric structure corresponding to T_mod = 3250 K. The success of this model may indicate the observed mid-infrared lines...

  9. Metabarcoding analysis of home composts reveals distinctive fungal communities with a high number of unassigned sequences.

    Science.gov (United States)

    Langarica-Fuentes, Adrian; Fox, Graeme; Robson, Geoffrey D

    2015-10-01

    Home composting has been strongly advocated in the UK, Europe and North America to divert organic waste away from conventional waste processing. Despite this, little attention has been given to microbial communities and their diversity in these systems. In this study, we examined the diversity of fungal species in 10 different domestic composts by 454 tag-encoded pyrosequencing. We report the recovery of 478 different molecular operational taxonomic units (MOTUs) from the 10 composts with a mean of 176.7 ± 19.6 MOTUs per compost and a mean of 12.9 ± 3.8 unique MOTUs per sample. Microascales (17.21 %), Hypocreales (16.76 %), Sordariales (14.89 %), Eurotiales (11.25 %) and Mortierellales (7.38 %) were the dominant orders in the community, with Pseudallescheria (9.52 %), Penicillium (8.43 %), Mortierella (3.60 %) and Fusarium (3.31 %) being the most abundant genera. Fungal communities in home composts were substantially different to large-scale commercial composts, with thermophilic and thermotolerant fungi present in much lower numbers. Significantly, 46.2 % of all sequences were identified as uncultured fungi or could not be assigned above the family level, suggesting there are a high number of new genera and species in these environments still to be described. PMID:26243286

  10. Leveraging a high resolution microfluidic assay reveals insights into pathogenic fungal spore germination.

    Science.gov (United States)

    Barkal, Layla J; Walsh, Naomi M; Botts, Michael R; Beebe, David J; Hull, Christina M

    2016-05-16

    Germination of spores into actively growing cells is a process essential for survival and pathogenesis of many microbes. Molecular mechanisms governing germination, however, are poorly understood in part because few tools exist for evaluating and interrogating the process. Here, we introduce an assay that leverages developments in microfluidic technology and image processing to quantitatively measure germination with unprecedented resolution, assessing both individual cells and the population as a whole. Using spores from Cryptococcus neoformans, a leading cause of fatal fungal disease in humans, we developed a platform to evaluate spores as they undergo morphological changes during differentiation into vegetatively growing yeast. The assay uses pipet-accessible microdevices that can be arrayed for efficient testing of diverse microenvironmental variables, including temperature and nutrients. We discovered that temperature influences germination rate, a carbon source alone is sufficient to induce germination, and the addition of a nitrogen source sustains it. Using this information, we optimized the assay for use with fungal growth inhibitors to pinpoint stages of germination inhibition. Unexpectedly, the clinical antifungal drugs amphotericin B and fluconazole did not significantly alter the process or timing of the transition from spore to yeast, indicating that vegetative growth and germination are distinct processes in C. neoformans. Finally, we used the high temporal resolution of the assay to determine the precise defect in a slow-germination mutant. Combining advances in microfluidics with a robust fungal molecular genetic system allowed us to identify and alter key temporal, morphological, and molecular events that occur during fungal germination. PMID:27026574

  11. THE NEAREST HIGH-VELOCITY STARS REVEALED BY LAMOST DATA RELEASE 1

    Energy Technology Data Exchange (ETDEWEB)

    Zhong, Jing; Chen, Li; Hou, Jinliang; Shen, Shiyin; Shao, Zhengyi; Li, Jing [Key Laboratory for Research in Galaxies and Cosmology, Shanghai Astronomical Observatory, Chinese Academy of Sciences, 80 Nandan Road, Shanghai 200030 (China); Liu, Chao; Luo, Ali; Shi, Jianrong; Zhang, Haotong; Yang, Ming; Deng, Licai [Key Laboratory of Optical Astronomy, National Astronomical Observatories, Chinese Academy of Sciences, Datun Road 20A, Beijing 100012 (China); De Grijs, Richard [Kavli Institute for Astronomy and Astrophysics and Department of Astronomy, Peking University, Yi He Yuan Lu 5, Hai Dian District, Beijing 100871 (China); Jin, Ge [University of Science and Technology of China, Hefei 230026 (China); Zhang, Yong; Hou, Yonghui; Zhang, Zhenchao, E-mail: jzhong@shao.ac.cn [Nanjing Institute of Astronomical Optics and Technology, National Astronomical Observatories, Chinese Academy of Sciences, Nanjing 210042 (China)

    2014-07-01

    We report the discovery of 28 candidate high-velocity stars (HVSs) at heliocentric distances of less than 3 kpc, based on the Large Sky Area Multi-Object Fiber Spectroscopic Telescope (LAMOST) Data Release 1. Our sample of HVS candidates covers a much broader color range than the equivalent ranges discussed in previous studies and comprises the first and largest sample of HVSs in the immediate solar neighborhood, at heliocentric distances less than 1-3 kpc. The observed as well as the derived parameters for all candidates are sufficiently accurate to allow us to ascertain their nature as genuine HVSs, of which a subset of 12 objects represents the most promising candidates. Our results also highlight the great potential of discovering statistically large numbers of HVSs of different spectral types in LAMOST survey data. This will ultimately enable us to achieve a better understanding of the nature of Galactic HVSs and their ejection mechanisms, and to constrain the structure of the Galaxy.

  12. Temporal dynamics of motivation-cognitive control interactions revealed by high-resolution pupillometry

    Directory of Open Access Journals (Sweden)

    Kimberly Sarah Chiew

    2013-01-01

    Full Text Available Motivational manipulations, such as the presence of performance-contingent reward incentives, can have substantial influences on cognitive control. Previous evidence suggests that reward incentives may enhance cognitive performance specifically through increased preparatory, or proactive, control processes. The present study examined reward influences on cognitive control dynamics in the AX-Continuous Performance Task (AX-CPT, using high-resolution pupillometry. In the AX-CPT, contextual cues must be actively maintained over a delay in order to appropriately respond to ambiguous target probes. A key feature of the task is that it permits dissociable characterization of preparatory, proactive control processes (i.e., utilization of context and reactive control processes (i.e., target-evoked interference resolution. Task performance profiles suggested that reward incentives enhanced proactive control (context utilization. Critically, pupil dilation was also increased on reward incentive trials during context maintenance periods, suggesting trial-specific shifts in proactive control, particularly when context cues indicated the need to overcome the dominant target response bias. Reward incentives had both transient (i.e., trial-by-trial and sustained (i.e., block-based effects on pupil dilation, which may reflect distinct underlying processes. The transient pupillary effects were present even when comparing against trials matched in task performance, suggesting a unique motivational influence of reward incentives. These results suggest that pupillometry may be a useful technique for investigating reward motivational signals and their dynamic influence on cognitive control.

  13. THE NEAREST HIGH-VELOCITY STARS REVEALED BY LAMOST DATA RELEASE 1

    International Nuclear Information System (INIS)

    We report the discovery of 28 candidate high-velocity stars (HVSs) at heliocentric distances of less than 3 kpc, based on the Large Sky Area Multi-Object Fiber Spectroscopic Telescope (LAMOST) Data Release 1. Our sample of HVS candidates covers a much broader color range than the equivalent ranges discussed in previous studies and comprises the first and largest sample of HVSs in the immediate solar neighborhood, at heliocentric distances less than 1-3 kpc. The observed as well as the derived parameters for all candidates are sufficiently accurate to allow us to ascertain their nature as genuine HVSs, of which a subset of 12 objects represents the most promising candidates. Our results also highlight the great potential of discovering statistically large numbers of HVSs of different spectral types in LAMOST survey data. This will ultimately enable us to achieve a better understanding of the nature of Galactic HVSs and their ejection mechanisms, and to constrain the structure of the Galaxy

  14. Novel and highly diverse fungal endophytes in soybean revealed by the consortium of two different techniques.

    Science.gov (United States)

    de Souza Leite, Tiago; Cnossen-Fassoni, Andréia; Pereira, Olinto Liparini; Mizubuti, Eduardo Seiti Gomide; de Araújo, Elza Fernandes; de Queiroz, Marisa Vieira

    2013-02-01

    Fungal endophytes were isolated from the leaves of soybean cultivars in Brazil using two different isolation techniques - fragment plating and the innovative dilution-to-extinction culturing - to increase the species richness, frequency of isolates and diversity. A total of 241 morphospecies were obtained corresponding to 62 taxa that were identified by analysis of the internal transcribed spacer (ITS) of the ribosomal DNA (rDNA). The Phylum Ascomycota predominated, representing 99% and 95.2% of isolates in the Monsoy and Conquista cultivars, respectively, whereas the Phylum Basidiomycota represented 1% and 4.8% of isolates, respectively. The genera Ampelomyces, Annulohypoxylon, Guignardia, Leptospora, Magnaporthe, Ophiognomonia, Paraconiothyrium, Phaeosphaeriopsis, Rhodotorula, Sporobolomyces, and Xylaria for the first time were isolated from soybean; this suggests that soybean harbours novel and highly diverse fungi. The yeasts genera Rhodotorula and Sporobolomyces (subphylum Pucciniomycotina) represent the Phylum Basidiomycota. The species richness was greater when both isolation techniques were used. The diversity of fungal endophytes was similar in both cultivars when the same isolation technique was used except for Hill's index, N1. The use of ITS region sequences allowed the isolates to be grouped according to Order, Class and Phylum. Ampelomyces, Chaetomium, and Phoma glomerata are endophytic species that may play potential roles in the biological control of soybean pathogens. This study is one of the first to apply extinction-culturing to isolate fungal endophytes in plant leaves, thus contributing to the development and improvement of this technique for future studies.

  15. High-resolution telomere fluorescence in situ hybridization reveals intriguing anomalies in germ cell tumors.

    Science.gov (United States)

    Shekhani, Mohammed Talha; Barber, John R; Bezerra, Stephania M; Heaphy, Christopher M; Gonzalez Roibon, Nilda Diana; Taheri, Diana; Reis, Leonardo O; Guner, Gunes; Joshu, Corinne E; Netto, George J; Meeker, Alan K

    2016-08-01

    Testicular germ cell tumor (TGCT) is the most common malignancy of young men. Most patients are completely cured, which distinguishes these from most other malignancies. Orchiectomy specimens (n=76) were evaluated using high-resolution (single-cell discriminative) telomere-specific fluorescence in situ hybridization (FISH) with simultaneous Oct4 immunofluorescence to describe telomere length phenotype in TGCT neoplastic cells. For the first time, the TGCT precursor lesion, germ cell neoplasia in situ (GCNIS) is also evaluated in depth. The intensity of the signals from cancerous cells was compared to the same patient's reference cells-namely, healthy germ cells (defined as "medium" length) and interstitial/somatic cells (defined as "short" telomere length). We observed short telomeres in most GCNIS and pure seminomas (P=.006 and P=.0005, respectively). In contrast, nonseminomas displayed longer telomeres. Lesion-specific telomere lengths were documented in mixed tumor cases. Embryonal carcinoma (EC) demonstrated the longest telomeres. A fraction of EC displays the telomerase-independent alternative lengthening of telomeres (ALT) phenotype (24% of cases). Loss of ATRX or DAXX nuclear expression was strongly associated with ALT; however, nuclear expression of both proteins was retained in half of ALT-positive ECs. The particular distribution of telomere lengths among TGCT and GCNIS precursors implicate telomeres anomalies in pathogenesis. These results may advise management decisions as well. PMID:27085557

  16. Genomic analysis of six new Geobacillus strains reveals highly conserved carbohydrate degradation architectures and strategies

    Directory of Open Access Journals (Sweden)

    Phillip eBrumm

    2015-05-01

    Full Text Available In this work we report the whole genome sequences of six new Geobacillus xylanolytic strains along with the genomic analysis of their capability to degrade carbohydrates.. The six sequenced Geobacillus strains described here have a range of GC contents from 43.9% to 52.5% and clade with named Geobacillus species throughout the entire genus. We have identified a ~200 kb unique super-cluster in all six strains, containing five to eight distinct carbohydrate degradation clusters in a single genomic region, a feature not seen in other genera. The Geobacillus strains rely on a small number of secreted enzymes located within distinct clusters for carbohydrate utilization, in contrast to most biomass-degrading organisms which contain numerous secreted enzymes located randomly throughout the genomes. All six strains are able to utilize fructose, arabinose, xylose, mannitol, gluconate, xylan, and α-1,6-glucosides. The gene clusters for utilization of these seven substrates have identical organization and the individual proteins have a high percent identity to their homologs. The strains show significant differences in their ability to utilize inositol, sucrose, lactose, α-mannosides, α-1,4-glucosides and arabinan.

  17. Coseismic landslides reveal near-surface rock strength in a high-relief tectonically active setting

    Science.gov (United States)

    Gallen, Sean F; Clark, Marin K; Godt, Jonathan W.

    2014-01-01

    We present quantitative estimates of near-surface rock strength relevant to landscape evolution and landslide hazard assessment for 15 geologic map units of the Longmen Shan, China. Strength estimates are derived from a novel method that inverts earthquake peak ground acceleration models and coseismic landslide inventories to obtain material proper- ties and landslide thickness. Aggregate rock strength is determined by prescribing a friction angle of 30° and solving for effective cohesion. Effective cohesion ranges are from 70 kPa to 107 kPa for 15 geologic map units, and are approximately an order of magnitude less than typical laboratory measurements, probably because laboratory tests on hand-sized specimens do not incorporate the effects of heterogeneity and fracturing that likely control near-surface strength at the hillslope scale. We find that strength among the geologic map units studied varies by less than a factor of two. However, increased weakening of units with proximity to the range front, where precipitation and active fault density are the greatest, suggests that cli- matic and tectonic factors overwhelm lithologic differences in rock strength in this high-relief tectonically active setting.

  18. High Throughput Sequencing of T Cell Antigen Receptors Reveals a Conserved TCR Repertoire

    Science.gov (United States)

    Hou, Xianliang; Lu, Chong; Chen, Sisi; Xie, Qian; Cui, Guangying; Chen, Jianing; Chen, Zhi; Wu, Zhongwen; Ding, Yulong; Ye, Ping; Dai, Yong; Diao, Hongyan

    2016-01-01

    Abstract The T-cell receptor (TCR) repertoire is a mirror of the human immune system that reflects processes caused by infections, cancer, autoimmunity, and aging. Next-generation sequencing has become a powerful tool for deep TCR profiling. Herein, we used this technology to study the repertoire features of TCR beta chain in the blood of healthy individuals. Peripheral blood samples were collected from 10 healthy donors. T cells were isolated with anti-human CD3 magnetic beads according to the manufacturer's protocol. We then combined multiplex-PCR, Illumina sequencing, and IMGT/High V-QUEST to analyze the characteristics and polymorphisms of the TCR. Most of the individual T cell clones were present at very low frequencies, suggesting that they had not undergone clonal expansion. The usage frequencies of the TCR beta variable, beta joining, and beta diversity gene segments were similar among T cells from different individuals. Notably, the usage frequency of individual nucleotides and amino acids within complementarity-determining region (CDR3) intervals was remarkably consistent between individuals. Moreover, our data show that terminal deoxynucleotidyl transferase activity was biased toward the insertion of G (31.92%) and C (27.14%) over A (21.82%) and T (19.12%) nucleotides. Some conserved features could be observed in the composition of CDR3, which may inform future studies of human TCR gene recombination. PMID:26962778

  19. Biomarkers for pancreatic carcinogenesis

    OpenAIRE

    Hustinx, S.R.

    2007-01-01

    Pancreatic cancer is a devastating disease. Most pancreatic cancers (approximately 85%) are diagnosed at a late, incurable stage. The poor prognosis and late presentation of pancreatic cancer patients underscore the importance of early detection, which is the sine qua non for the fight against pancreatic cancer. It is hoped for the future that the understanding of genetic alterations will lead to the rapid discovery of an effective biomarker of pancreatic carcinogenesis. In this thesis we vis...

  20. MicroRNAs as potential biomarkers in malignant pleural mesothelioma

    Directory of Open Access Journals (Sweden)

    Santoni-Rugiu E

    2015-12-01

    Full Text Available Eric Santoni-Rugiu, Morten Andersen, Morten Grauslund Laboratory of Molecular Pathology, Department of Pathology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark Abstract: Malignant pleural mesothelioma (MPM, a highly lethal cancer strictly related to asbestos exposure, is usually characterized by delayed diagnosis, resistance to current therapies, and dismal prognosis. MPM is difficult to distinguish histologically from nonmalignant reactive mesothelial proliferations (RMPs as there are no clinically validated immunohistochemical markers yet and the main diagnostic criterion remains deep invasion into the pleura and underlying fat tissue, which is often not appreciable in small pleural biopsies. In this regard, microRNAs (miRNAs, given their size and stability, are particularly attractive biomarkers in formalin-fixed paraffin-embedded tissue specimens for routine pathology. Moreover, circulating miRNAs appear to be promising biomarkers for early detection and monitoring of patients with MPM. Here, we review the studies mostly performed by miRNA arrays and reverse transcription-quantitative polymerase chain reaction in formalin-fixed paraffin-embedded or frozen tissue samples, MPM cell lines, and blood/plasma/serum samples that have highlighted the potential of miRNAs as biomarkers in MPM. Certain studies have pointed to the ability of miRNAs to distinguish the different histological MPM subtypes or separate MPM from lung adenocarcinoma, and other investigations have revealed that miRNAs can aid in differentiating MPM from RMP or have prognostic value in predicting the patient outcome. Mechanistic aspects of the involvement of miRNAs in mesothelioma genesis and possible use of miRNAs as future therapeutic targets in MPM are also emphasized. Finally, limitations of the data currently obtained due to the drawbacks of reverse transcription-quantitative polymerase chain reaction, heterogeneity of MPM tissue samples, and

  1. Phylogenetic analysis reveals a high prevalence of Sporothrix brasiliensis in feline sporotrichosis outbreaks.

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    Anderson Messias Rodrigues

    Full Text Available Sporothrix schenckii, previously assumed to be the sole agent of human and animal sporotrichosis, is in fact a species complex. Recently recognized taxa include S. brasiliensis, S. globosa, S. mexicana, and S. luriei, in addition to S. schenckii sensu stricto. Over the last decades, large epidemics of sporotrichosis occurred in Brazil due to zoonotic transmission, and cats were pointed out as key susceptible hosts. In order to understand the eco-epidemiology of feline sporotrichosis and its role in human sporotrichosis a survey was conducted among symptomatic cats. Prevalence and phylogenetic relationships among feline Sporothrix species were investigated by reconstructing their phylogenetic origin using the calmodulin (CAL and the translation elongation factor-1 alpha (EF1α loci in strains originated from Rio de Janeiro (RJ, n = 15, Rio Grande do Sul (RS, n = 10, Paraná (PR, n = 4, São Paulo (SP, n =3 and Minas Gerais (MG, n = 1. Our results showed that S. brasiliensis is highly prevalent among cats (96.9% with sporotrichosis, while S. schenckii was identified only once. The genotype of Sporothrix from cats was found identical to S. brasiliensis from human sources confirming that the disease is transmitted by cats. Sporothrix brasiliensis presented low genetic diversity compared to its sister taxon S. schenckii. No evidence of recombination in S. brasiliensis was found by split decomposition or PHI-test analysis, suggesting that S. brasiliensis is a clonal species. Strains recovered in states SP, MG and PR share the genotype of the RJ outbreak, different from the RS clone. The occurrence of separate genotypes among strains indicated that the Brazilian S. brasiliensis epidemic has at least two distinct sources. We suggest that cats represent a major host and the main source of cat and human S. brasiliensis infections in Brazil.

  2. Ten years of satellite observations reveal highly variable sulphur dioxide emissions at Anatahan Volcano, Mariana Islands

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    McCormick, Brendan; Popp, Christoph; Andrews, Benjamin; Cottrell, Elizabeth

    2015-07-01

    Satellite remote sensing enables continuous multiyear observations of volcanic activity in remote settings. Anatahan (Mariana Islands) is a remote volcano in the western North Pacific. Available ground-based measurements of sulphur dioxide (SO2) gas emissions at Anatahan place it among thelargest volcanic SO2 sources worldwide. These ground-based measurements, however, are restricted to eruptive intervals. Anatahan's activity since 2003 has been dominated temporally by prolonged periods of quiescence. Using 10 years of satellite observations from OMI, AIRS, SCIAMACHY, and GOME-2, we report highly variable SO2 emissions within and between eruptive and quiescent intervals at Anatahan. We find close correspondence between levels of activity reported at the volcano and levels of SO2 emissions detected from space. Eruptive SO2 emission rates have a mean value of ˜6400 t d-1, but frequently are in excess of 20,000 t d-1. Conversely, SO2 emissions during quiescent intervals are below the detection limit of space-based sensors and therefore are not likely to exceed ˜300 t d-1. We show that while Anatahan occupies a quiescent state for 85% of the past 10 years, only ˜15% of total SO2 emissions over this interval occur during quiescence, with the remaining ˜85% released in short duration but intense syn-eruptive degassing. We propose that the integration of multiyear satellite data sets and activity histories are a powerful complement to targeted ground-based campaign measurements in better describing the long-term degassing behavior of remote volcanoes.

  3. High Resolution Time-resolved UCLES Spectroscopy of AE Aqr: I. The Secondary Star Revealed

    Science.gov (United States)

    Echevarria, J.; Diego, F.; Mills, D.; Connon Smith, R.

    2006-06-01

    High-dispersion time-resolved spectroscopy of the cataclysmic variable AE Aqr has been obtained. The emission lines have a complex structure that make difficult to measure the motion of the white dwarf. The cross correlation for the absorption lines shows a clear asymmetric profile as expected from a heated side of the red star. The spectral type for the secondary star varies from K2 to K5; there are clear indications that the temperature varies as a function of star longitude. The radial velocity analysis yield Kab = 165.2 ± 0.6 Km s-1 for the cross-correlated secondary star. The rotational velocity of the red star has been measured as a function of orbital period. It shows ellipsoidal variations with a period half the orbital period. The rotational velocities vary within the range Vrot sin i = 105 ± 3 Km s-1 and Vrot sin i = 130 ± 3 Km s-1. The former can be used to constrain the white dwarf semi-amplitude value to yield Kem = 139 ± 4 Km s-1 consistent with derived values from published radial velocity measurements. From a variation in the absorption line strength of 30%, we constrain the inclination angle to i = 58° ± 3. The estimated masses of the binary are: Mw = 1.07 ± 0.07 M? and Mr = 0.90 ± 0.05 M?. If this is correct we should expect a spectral type of G5 if the secondary star is a main sequence star. We suggest that the discrepancy is explained if the star has a radius 40% greater than a main sequence star for a mass of 0.90 M?.

  4. Phylogenetic analysis reveals a high prevalence of Sporothrix brasiliensis in feline sporotrichosis outbreaks.

    Science.gov (United States)

    Rodrigues, Anderson Messias; de Melo Teixeira, Marcus; de Hoog, G Sybren; Schubach, Tânia Maria Pacheco; Pereira, Sandro Antonio; Fernandes, Geisa Ferreira; Bezerra, Leila Maria Lopes; Felipe, Maria Sueli; de Camargo, Zoilo Pires

    2013-01-01

    Sporothrix schenckii, previously assumed to be the sole agent of human and animal sporotrichosis, is in fact a species complex. Recently recognized taxa include S. brasiliensis, S. globosa, S. mexicana, and S. luriei, in addition to S. schenckii sensu stricto. Over the last decades, large epidemics of sporotrichosis occurred in Brazil due to zoonotic transmission, and cats were pointed out as key susceptible hosts. In order to understand the eco-epidemiology of feline sporotrichosis and its role in human sporotrichosis a survey was conducted among symptomatic cats. Prevalence and phylogenetic relationships among feline Sporothrix species were investigated by reconstructing their phylogenetic origin using the calmodulin (CAL) and the translation elongation factor-1 alpha (EF1α) loci in strains originated from Rio de Janeiro (RJ, n = 15), Rio Grande do Sul (RS, n = 10), Paraná (PR, n = 4), São Paulo (SP, n =3) and Minas Gerais (MG, n = 1). Our results showed that S. brasiliensis is highly prevalent among cats (96.9%) with sporotrichosis, while S. schenckii was identified only once. The genotype of Sporothrix from cats was found identical to S. brasiliensis from human sources confirming that the disease is transmitted by cats. Sporothrix brasiliensis presented low genetic diversity compared to its sister taxon S. schenckii. No evidence of recombination in S. brasiliensis was found by split decomposition or PHI-test analysis, suggesting that S. brasiliensis is a clonal species. Strains recovered in states SP, MG and PR share the genotype of the RJ outbreak, different from the RS clone. The occurrence of separate genotypes among strains indicated that the Brazilian S. brasiliensis epidemic has at least two distinct sources. We suggest that cats represent a major host and the main source of cat and human S. brasiliensis infections in Brazil.

  5. Microsatellites reveal a high population structure in Triatoma infestans from Chuquisaca, Bolivia.

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    Juan Carlos Pizarro

    Full Text Available BACKGROUND: For Chagas disease, the most serious infectious disease in the Americas, effective disease control depends on elimination of vectors through spraying with insecticides. Molecular genetic research can help vector control programs by identifying and characterizing vector populations and then developing effective intervention strategies. METHODS AND FINDINGS: The population genetic structure of Triatoma infestans (Hemiptera: Reduviidae, the main vector of Chagas disease in Bolivia, was investigated using a hierarchical sampling strategy. A total of 230 adults and nymphs from 23 localities throughout the department of Chuquisaca in Southern Bolivia were analyzed at ten microsatellite loci. Population structure, estimated using analysis of molecular variance (AMOVA to estimate F(ST (infinite alleles model and R(ST (stepwise mutation model, was significant between western and eastern regions within Chuquisaca and between insects collected in domestic and peri-domestic habitats. Genetic differentiation at three different hierarchical geographic levels was significant, even in the case of adjacent households within a single locality (R(ST = 0.14, F(ST = 0.07. On the largest geographic scale, among five communities up to 100 km apart, R(ST = 0.12 and F(ST = 0.06. Cluster analysis combined with assignment tests identified five clusters within the five communities. CONCLUSIONS: Some houses are colonized by insects from several genetic clusters after spraying, whereas other households are colonized predominately by insects from a single cluster. Significant population structure, measured by both R(ST and F(ST, supports the hypothesis of poor dispersal ability and/or reduced migration of T. infestans. The high degree of genetic structure at small geographic scales, inferences from cluster analysis and assignment tests, and demographic data suggest reinfesting vectors are coming from nearby and from recrudescence (hatching of eggs that were laid

  6. Contrast discrimination at high contrasts reveals the influence of local light adaptation on contrast processing.

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    Kingdom, F A; Whittle, P

    1996-03-01

    Previous measurements of contrast discrimination threshold, delta C, as a function of pedestal contrast, C, for sine-wave gratings have shown a power law relationship between delta C and C at suprathreshold levels of C. However, these studies have rarely used contrasts greater than 50%. Whittle (1986), using incremental and decremental patches, found that delta C increased with C only up to about 50%. At higher contrasts it decreased. Since a periodic stimulus can be considered to be composed of increments and decrements, we thought we might find such an inverse U-shaped function for gratings if we used contrasts up to 100%. We tested this for both sine-wave and square-wave stimuli at spatial frequencies from 0.0625 to 8.0 c/deg. We found that for frequencies up to 0.5 c/deg, delta C in nearly all cases 'dipped down' after about C = 50% contrast. At 4.0 and 8.0 c/deg, however, no dip-down occurred. Additional experiments showed that the dip-down was unlikely to be due to cortical long-term adaptation and most likely an effect of localized light adaptation to the dark bars. We argue that the absence of dip-down at high spatial frequencies was mainly due to the attenuation of contrast by the optics of the eye. As for the results of Whittle (1986), a Weber's Law in W = (Lmax-Lmin)/Lmin describes the inverse U-shaped contrast discrimination function well. Two other contrast expressions also linearize the data on log-log plots. We show how some familiar notions about the physiological operation of localized light adaptation can easily account for the form of the contrast discrimination function. Finally we estimate the number of discriminable steps in contrast from detection threshold to maximum contrast for the various spatial frequencies tested.

  7. Generation of superparamagnetic liposomes revealed as highly efficient MRI contrast agents for in vivo imaging.

    Science.gov (United States)

    Martina, Marie-Sophie; Fortin, Jean-Paul; Ménager, Christine; Clément, Olivier; Barratt, Gillian; Grabielle-Madelmont, Cécile; Gazeau, Florence; Cabuil, Valérie; Lesieur, Sylviane

    2005-08-01

    Maghemite (gamma-Fe2O3) nanocrystals stable at neutral pH and in isotonic aqueous media were synthesized and encapsulated within large unilamellar vesicles of egg phosphatidylcholine (EPC) and distearoyl-SN-glycero-3-phosphoethanolamine-N-[methoxy(poly(ethylene glycol))-2000] (DSPE-PEG(2000), 5 mol %), formed by film hydration coupled with sequential extrusion. The nonentrapped particles were removed by flash gel exclusion chromatography. The magnetic-fluid-loaded liposomes (MFLs) were homogeneous in size (195 +/- 33 hydrodynamic diameters from quasi-elastic light scattering). Iron loading was varied from 35 up to 167 Fe(III)/lipid mol %. Physical and superparamagnetic characteristics of the iron oxide particles were preserved after liposome encapsulation as shown by cryogenic transmission electron microscopy and magnetization curve recording. In biological media, MFLs were highly stable and avoided ferrofluid flocculation while being nontoxic toward the J774 macrophage cell line. Moreover, steric stabilization ensured by PEG-surface-grafting significantly reduced liposome association with the macrophages. The ratios of the transversal (r2) and longitudinal (r1) magnetic resonance (MR) relaxivities of water protons in MFL dispersions (6 < r2/r1 < 18) ranked them among the best T2 contrast agents, the higher iron loading the better the T2 contrast enhancement. Magnetophoresis demonstrated the possible guidance of MFLs by applying a magnetic field gradient. Mouse MR imaging assessed MFLs efficiency as contrast agents in vivo: MR angiography performed 24 h after intravenous injection of the contrast agent provided the first direct evidence of the stealthiness of PEG-ylated magnetic-fluid-loaded liposomes. PMID:16045355

  8. Revealing molecular mechanisms by integrating high-dimensional functional screens with protein interaction data.

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    Angela Simeone

    2014-09-01

    Full Text Available Functional genomics screens using multi-parametric assays are powerful approaches for identifying genes involved in particular cellular processes. However, they suffer from problems like noise, and often provide little insight into molecular mechanisms. A bottleneck for addressing these issues is the lack of computational methods for the systematic integration of multi-parametric phenotypic datasets with molecular interactions. Here, we present Integrative Multi Profile Analysis of Cellular Traits (IMPACT. The main goal of IMPACT is to identify the most consistent phenotypic profile among interacting genes. This approach utilizes two types of external information: sets of related genes (IMPACT-sets and network information (IMPACT-modules. Based on the notion that interacting genes are more likely to be involved in similar functions than non-interacting genes, this data is used as a prior to inform the filtering of phenotypic profiles that are similar among interacting genes. IMPACT-sets selects the most frequent profile among a set of related genes. IMPACT-modules identifies sub-networks containing genes with similar phenotype profiles. The statistical significance of these selections is subsequently quantified via permutations of the data. IMPACT (1 handles multiple profiles per gene, (2 rescues genes with weak phenotypes and (3 accounts for multiple biases e.g. caused by the network topology. Application to a genome-wide RNAi screen on endocytosis showed that IMPACT improved the recovery of known endocytosis-related genes, decreased off-target effects, and detected consistent phenotypes. Those findings were confirmed by rescreening 468 genes. Additionally we validated an unexpected influence of the IGF-receptor on EGF-endocytosis. IMPACT facilitates the selection of high-quality phenotypic profiles using different types of independent information, thereby supporting the molecular interpretation of functional screens.

  9. Large-scale mitochondrial DNA analysis of the domestic goat reveals six haplogroups with high diversity.

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    Saeid Naderi

    Full Text Available BACKGROUND: From the beginning of domestication, the transportation of domestic animals resulted in genetic and demographic processes that explain their present distribution and genetic structure. Thus studying the present genetic diversity helps to better understand the history of domestic species. METHODOLOGY/PRINCIPAL FINDINGS: The genetic diversity of domestic goats has been characterized with 2430 individuals from all over the old world, including 946 new individuals from regions poorly studied until now (mainly the Fertile Crescent. These individuals represented 1540 haplotypes for the HVI segment of the mitochondrial DNA (mtDNA control region. This large-scale study allowed the establishment of a clear nomenclature of the goat maternal haplogroups. Only five of the six previously defined groups of haplotypes were divergent enough to be considered as different haplogroups. Moreover a new mitochondrial group has been localized around the Fertile Crescent. All groups showed very high haplotype diversity. Most of this diversity was distributed among groups and within geographic regions. The weak geographic structure may result from the worldwide distribution of the dominant A haplogroup (more than 90% of the individuals. The large-scale distribution of other haplogroups (except one, may be related to human migration. The recent fragmentation of local goat populations into discrete breeds is not detectable with mitochondrial markers. The estimation of demographic parameters from mismatch analyses showed that all groups had a recent demographic expansion corresponding roughly to the period when domestication took place. But even with a large data set it remains difficult to give relative dates of expansion for different haplogroups because of large confidence intervals. CONCLUSIONS/SIGNIFICANCE: We propose standard criteria for the definition of the different haplogroups based on the result of mismatch analysis and on the use of sequences of

  10. Biomarkers of Ovarian Reserve

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    William E. Roudebush

    2008-01-01

    Full Text Available The primary function of the female ovary is the production of a mature and viable oocyte capable of fertilization and subsequent embryo development and implantation. At birth, the ovary contains a finite number of oocytes available for folliculogenesis. This finite number of available oocytes is termed “the ovarian reserve”. The determination of ovarian reserve is important in the assessment and treatment of infertility. As the ovary ages, the ovarian reserve will decline. Infertility affects approximately 15-20% of reproductive aged couples. The most commonly used biomarker assay to assess ovarian reserve is the measurement of follicle stimulating hormone (FSH on day 3 of the menstrual cycle. However, antimüllerian hormone and inhibin-B are other biomarkers of ovarian reserve that are gaining in popularity since they provide direct determination of ovarian status, whereas day 3 FSH is an indirect measurement. This review examines the physical tools and the hormone biomarkers used to evaluate ovarian reserve.

  11. Physiological and proteomic analyses of leaves from the halophyte Tangut Nitraria reveals diverse response pathways critical for high salinity tolerance

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    Tielong eCheng

    2015-02-01

    Full Text Available Soil salinization poses a serious threat to the environment and agricultural productivity worldwide. Studies on the physiological and molecular mechanisms of salinity tolerance in halophytic plants provide valuable information to enhance their salt tolerance. Tangut Nitraria is a widely distributed halophyte in saline–alkali soil in the northern areas of China. In this study, we used a proteomic approach to investigate the molecular pathways of the high salt tolerance of T. Nitraria. We analyzed the changes in biomass, photosynthesis, and redox-related enzyme activities in T. Nitraria leaves from plant seedlings treated with high salt concentration. Comparative proteomic analysis of the leaves revealed that the expression of 71 proteins was significantly altered after salinity treatments of T. Nitraria. These salinity-responsive proteins were mainly involved in photosynthesis, redox homeostasis, stress/defense, carbohydrate and energy metabolism, protein metabolism, signal transduction, and membrane transport. Results showed that the reduction of photosynthesis under salt stress was attributed to the down-regulation of the enzymes and proteins involved in the light reaction and Calvin cycle. Protein–protein interaction analysis revealed that the proteins involved in redox homeostasis, photosynthesis, and energy metabolism constructed two types of response networks to high salt stress. T. Nitraria plants developed diverse mechanisms for scavenging reactive oxygen species in their leaves to cope with stress induced by high salinity. This study provides important information regarding the salt tolerance of the halophyte T. Nitraria.

  12. Circulating (CD3−CD19+CD20−IgD−CD27highCD38high) Plasmablasts: A Promising Cellular Biomarker for Immune Activity for Anti-PLA2R1 Related Membranous Nephropathy?

    Science.gov (United States)

    Beukinga, Ingrid; Willard-Gallo, Karen; Nortier, Joëlle; Pradier, Olivier

    2016-01-01

    Membranous nephropathy (MN) is a kidney specific autoimmune disease mainly mediated by anti-phospholipase A2 receptor 1 autoantibody (PLA2R1 Ab). The adequate assessment of chimeric anti-CD20 monoclonal antibody, rituximab (RTX), efficacy is still needed to improve clinical outcome of patient with MN. We evaluated the modification of plasmablasts (CD3−CD19+CD20−IgD−CD27highCD38high), a useful biomarker of RTX response in other autoimmune diseases, and memory (CD3−CD19+CD20+IgD−CD27+CD38−) and naive (CD3−CD19+CD20+IgD+CD27−CD38low) B cells by fluorescence-activated cell sorter analysis in PLA2R1 related MN in one patient during the 4 years of follow-up after RTX. RTX induced complete disappearance of CD19+ B cells, plasmablasts, and memory B cells as soon as day 15. Despite severe CD19+ lymphopenia, plasmablasts and memory B cells reemerged early before naive B cells (days 45, 90, and 120, resp.). During the follow-up, plasmablasts decreased more rapidly than memory B cells but still remained elevated as compared to day 0 of RTX. Concomitantly, anti-PLA2R1 Ab increased progressively. Our single case report suggests that, besides monitoring of serum anti-PLA2R1 Ab level, enumeration of circulating plasmablasts and memory B cells represents an attractive and complementary tool to assess immunological activity and efficacy of RTX induced B cells depletion in anti-PLA2R1 Ab related MN. PMID:27493452

  13. Scrutinizing the Biomarkers for the Neglected Chagas Disease: How Remarkable!

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    Pinho, Rosa T.; Waghabi, Mariana C.; Cardillo, Fabíola; Mengel, José; Antas, Paulo R. Z.

    2016-01-01

    Biomarkers or biosignature profiles have become accessible over time in population-based studies for Chagas disease. Thus, the identification of consistent and reliable indicators of the diagnosis and prognosis of patients with heart failure might facilitate the prioritization of therapeutic management to those with the highest chance of contracting this disease. The purpose of this paper is to review the recent state and the upcoming trends in biomarkers for human Chagas disease. As an emerging concept, we propose a classification of biomarkers based on plasmatic-, phenotype-, antigenic-, genetic-, and management-related candidates. The available data revisited here reveal the lessons learned thus far and the existing challenges that still lie ahead to enable biomarkers to be employed consistently in risk evaluation for this disease. There is a strong need for biomarker validation, particularly for biomarkers that are specific to the clinical forms of Chagas disease. The current failure to achieve the eradication of the transmission of this disease has produced determination to solve this validation issue. Finally, it would be strategic to develop a wide variety of biomarkers and to test them in both preclinical and clinical trials. PMID:27563302

  14. A SNP based high-density linkage map of Apis cerana reveals a high recombination rate similar to Apis mellifera.

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    Yuan Yuan Shi

    Full Text Available BACKGROUND: The Eastern honey bee, Apis cerana Fabricius, is distributed in southern and eastern Asia, from India and China to Korea and Japan and southeast to the Moluccas. This species is also widely kept for honey production besides Apis mellifera. Apis cerana is also a model organism for studying social behavior, caste determination, mating biology, sexual selection, and host-parasite interactions. Few resources are available for molecular research in this species, and a linkage map was never constructed. A linkage map is a prerequisite for quantitative trait loci mapping and for analyzing genome structure. We used the Chinese honey bee, Apis cerana cerana to construct the first linkage map in the Eastern honey bee. RESULTS: F2 workers (N = 103 were genotyped for 126,990 single nucleotide polymorphisms (SNPs. After filtering low quality and those not passing the Mendel test, we obtained 3,000 SNPs, 1,535 of these were informative and used to construct a linkage map. The preliminary map contains 19 linkage groups, we then mapped the 19 linkage groups to 16 chromosomes by comparing the markers to the genome of A. mellfiera. The final map contains 16 linkage groups with a total of 1,535 markers. The total genetic distance is 3,942.7 centimorgans (cM with the largest linkage group (180 loci measuring 574.5 cM. Average marker interval for all markers across the 16 linkage groups is 2.6 cM. CONCLUSION: We constructed a high density linkage map for A. c. cerana with 1,535 markers. Because the map is based on SNP markers, it will enable easier and faster genotyping assays than randomly amplified polymorphic DNA or microsatellite based maps used in A. mellifera.

  15. Post-glacial variability of sea ice cover, river run-off and biological production in the western Laptev Sea (Arctic Ocean) - A high-resolution biomarker study

    Science.gov (United States)

    Hörner, T.; Stein, R.; Fahl, K.; Birgel, D.

    2016-07-01

    Multi-proxy biomarker measurements were applied on two sediment cores (PS51/154, PS51/159) to reconstruct sea ice cover (IP25), biological production (brassicasterol, dinosterol) and river run-off (campesterol, β-sitosterol) in the western Laptev Sea over the last ∼17 ka with unprecedented temporal resolution. The absence of IP25 from 17.2 to 15.5 ka, in combination with minimum concentration of phytoplankton biomarkers, suggests that the western Laptev Sea shelf was mostly covered with permanent sea ice. Very minor river run-off and restricted biological production occurred during this cold interval. From ∼16 ka until 7.5 ka, a long-term decrease of terrigenous (riverine) organic matter and a coeval increase of marine organic matter reflect the gradual establishment of fully marine conditions in the western Laptev Sea, caused by the onset of the post-glacial transgression. Intensified river run-off and reduced sea ice cover characterized the time interval between 15.2 and 12.9 ka, including the Bølling/Allerød warm period (14.7-12.9 ka). Prominent peaks of the DIP25 Index coinciding with maximum abundances of subpolar foraminifers, are interpreted as pulses of Atlantic water inflow on the western Laptev Sea shelf. After the warm period, a sudden return to severe sea ice conditions with strongest ice-coverage between 11.9 and 11 ka coincided with the Younger Dryas (12.9-11.6 ka). At the onset of the Younger Dryas, a distinct alteration of the ecosystem (reflected in a distinct drop in terrigenous and phytoplankton biomarkers) was detected. During the last 7 ka, the sea ice proxies reflect a cooling of the Laptev Sea spring/summer season. This cooling trend was superimposed by a short-term variability in sea ice coverage, probably representing Bond cycles (1500 ± 500 ka) that are related to solar activity changes. Hence, atmospheric circulation changes were apparently able to affect the sea ice conditions on the Laptev Sea shelf under modern sea level

  16. Urinary Sugars--A Biomarker of Total Sugars Intake.

    Science.gov (United States)

    Tasevska, Natasha

    2015-07-01

    Measurement error in self-reported sugars intake may explain the lack of consistency in the epidemiologic evidence on the association between sugars and disease risk. This review describes the development and applications of a biomarker of sugars intake, informs its future use and recommends directions for future research. Recently, 24 h urinary sucrose and fructose were suggested as a predictive biomarker for total sugars intake, based on findings from three highly controlled feeding studies conducted in the United Kingdom. From this work, a calibration equation for the biomarker that provides an unbiased measure of sugars intake was generated that has since been used in two US-based studies with free-living individuals to assess measurement error in dietary self-reports and to develop regression calibration equations that could be used in future diet-disease analyses. Further applications of the biomarker include its use as a surrogate measure of intake in diet-disease association studies. Although this biomarker has great potential and exhibits favorable characteristics, available data come from a few controlled studies with limited sample sizes conducted in the UK. Larger feeding studies conducted in different populations are needed to further explore biomarker characteristics and stability of its biases, compare its performance, and generate a unique, or population-specific biomarker calibration equations to be applied in future studies. A validated sugars biomarker is critical for informed interpretation of sugars-disease association studies.

  17. Exploration of new HCC biomarkers

    Directory of Open Access Journals (Sweden)

    Regina M. Santella

    2007-02-01

    Full Text Available

    Analysis of plasma/serum for levels of viral antigens or antibodies to viral proteins has been used extensively as an early biomarker of potential risk of HCC. In addition, detection of elevated levels of alpha-fetoprotein is commonly used for early identification of HCC. Unfortunately, both of these approaches are not highly sensitive or specific. As a result, there is continuing investigation to identify additional biomarkers that may help in the early identification of cases. The use of DNA isolated from plasma or serum for detection of gene specific methylation has been discussed previously. In addition, tumor DNA isolated from blood has been analyzed for the presence of p53 mutations and found in a subset of cases to be present years prior to diagnosis as for methylated DNA. The general level of DNA present in blood has also been suggested as a potential biomarker of cancer.

    Among the newer methods being tested are the detection of specific mutations in HBV. In many cases of HCC in China and Africa a double mutation, an A to T transversion at nucleotide 1762 and a G to A transition at nucleotide 1764 (1762T/1764A have been found. These mutations have been associated with increased severity of HBV infection and cirrhosis suggesting that they might be a useful biomarker for high risk subjects.

    The field of proteomics also holds promise for the development of new biomarkers. A number of groups are developing mass spectrometry methods for the identification of serum/plasma proteomic patterns that will distinguish bloods of HCC cases from those of controls. While some interesting preliminary data have been developed for several cancers, much additional work needs to be done in this area

  18. Chiral biomarkers and microfossils in carbonaceous meteorites

    Science.gov (United States)

    Hoover, Richard B.

    2010-09-01

    Homochirality of the biomolecules (D-sugars of DNA and RNA and L-amino acids of proteins) is a fundamental property of all life on Earth. Abiotic mechanisms yield racemic mixtures (D/L=1) of chiral molecules and after the death of an organism, the enantiopure chiral biomolecules slowly racemize. Several independent investigators have now established that the amino acids present in CI1 and CM2 carbonaceous meteorites have a moderate to strong excess of the L-enantiomer. Stable isotope data have established that these amino acids are both indigenous and extraterrestrial. Carbonaceous meteorites also contain many other strong chemical biomarkers including purines and pyrimidines (nitrogen heterocycles of nucleic acids); pristine and phytane (components of the chlorophyll pigment) and morphological biomarkers (microfossils of filamentous cyanobacteria). Energy dispersive X-ray Spectroscopy (EDS) analysis reveals that nitrogen is below the detectability level in most of the meteorite filaments as well as in Cambrian Trilobites and filaments of 2.7 Gya Archaean cyanobacteria from Karelia. The deficiency of nitrogen in the filaments and the total absence of sugars, of twelve of the life-critical protein amino acids, and two of the nucleobases of DNA and RNA provide clear and convincing evidence that these filaments are not modern biological contaminants. This paper reviews the chiral, chemical biomarkers morphological biomarkers and microfossils in carbonaceous meteorites. This paper reviews chiral and morphological biomarkers and discusses the missing nitrogen, sugars, protein amino acids, and nucleobases as "bio-discriminators" that exclude modern biological contaminants as a possible explanation for the permineralized cyanobacterial filaments found in the meteorites.

  19. High Throughput ELISAs to Measure a Unique Glycan on Transferrin in Cerebrospinal Fluid: A Possible Extension toward Alzheimer's Disease Biomarker Development

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    Keiro Shirotani

    2011-01-01

    Full Text Available We have established high-throughput lectin-antibody ELISAs to measure different glycans on transferrin (Tf in cerebrospinal fluid (CSF using lectins and an anti-transferrin antibody (TfAb. Lectin blot and precipitation analysis of CSF revealed that PVL (Psathyrella velutina lectin bound an unique N-acetylglucosamine-terminated N-glycans on “CSF-type” Tf whereas SSA (Sambucus sieboldiana agglutinin bound α2,6-N-acetylneuraminic acid-terminated N-glycans on “serum-type” Tf. PVL-TfAb ELISA of 0.5 μL CSF samples detected “CSF-type” Tf but not “serum-type” Tf whereas SSA-TfAb ELISA detected “serum-type” Tf but not “CSF-type” Tf, demonstrating the specificity of the lectin-TfAb ELISAs. In idiopathic normal pressure hydrocephalus (iNPH, a senile dementia associated with ventriculomegaly, amounts of the SSA-reactive Tf were significantly higher than in non-iNPH patients, indicating that Tf glycan analysis by the high-throughput lectin-TfAb ELISAs could become practical diagnostic tools for iNPH. The lectin-antibody ELISAs of CSF proteins might be useful for diagnosis of the other neurological diseases.

  20. [Key laboratory diagnostic biomarkers of coronary atherosclerosis].

    Science.gov (United States)

    Ragino, Iu I; Cherniavskiĭ, A M; Eremenko, N V; Shakhtshneĭder, E V; Polonskaia, Ia V; Tsymbal, S Iu; Ivanova, M V; Voevoda, M I

    2011-01-01

    Laboratory lipid and lipoprotein biomarkers (total cholesterol - CH, triglycerides - TG, low-density and high-density lipoprotein cholesterol- LDL-CH, HDL-CH, apolipoproteins B and A1 - apoB, apoA1), carbohydrate biomarkers (plasma glucose, basal insulin), high sensitive C-reactive protein (hsCRP) and oxidative biomarkers (basal level of lipid peroxidation [LPO] products in LDL, LDL resistance to oxidation in vitro, oxidative modification of apoLDL and level of LDL lipophilic antioxidants) were studied in 388 men aged 42-70 years: 96 citizens of Western Siberia with angiographically documented coronary atherosclerosis and coronary heart disease (CHD); 292 men of population sample of citizens of Novosibirsk, including 44 men with CHD confirmed by standardized criteria and methods. Significant associations were found of coronary atherosclerosis and CHD with laboratory diagnostic biomarkers like blood levels of HDL-CH, TG, apoB, apoA1, basal insulin, hsCRP and basal level of LPO products in LDL and LDL resistance to oxidation. PMID:21627612

  1. High-resolution bathymetry reveals contrasting landslide activity shaping the walls of the Mid-Atlantic Ridge axial valley

    OpenAIRE

    CANNAT, Mathilde; Mangeney, Anne; Ondreas, Helene; Fouquet, Yves; Normand, Alain

    2013-01-01

    Axial valleys are found along most slow-spreading mid-ocean ridges and are one of the most prominent topographic features on Earth. In this paper, we present the first deep-tow swath bathymetry for the axial valley walls of the Mid-Atlantic Ridge. These data allow us to analyze axial valley wall morphology with a very high resolution (0.5 to 1 m compared to 50 m for shipboard multibeam bathymetry), revealing the role played by landslides. Slow-spreading ridge axial valleys also commonly expos...

  2. Swift reveals the eclipsing nature of the high mass X-ray binary IGR~J16195-4945

    OpenAIRE

    Cusumano, G.; La Parola, V.; Segreto, A.; D'Aì, A.

    2016-01-01

    IGR J16195-4945 is a hard X-ray source discovered by INTEGRAL during the Core Program observations performed in 2003. We analyzed the X-ray emission of this source exploiting the Swift-BAT survey data from December 2004 to March 2015, and all the available Swift-XRT pointed observations. The source is detected at a high significance level in the 123-month BAT survey data, with an average 15-150 keV flux of the source of ~1.6 mCrab. The timing analysis on the BAT data reveals with a significan...

  3. Primary Sjӧgren's syndrome: Clinical phenotypes, outcome and the development of biomarkers.

    Science.gov (United States)

    Goules, Andreas V; Tzioufas, Athanasios G

    2016-07-01

    Primary Sjӧgren's syndrome (pSS) is a complex autoimmune disease with distinct clinical phenotypes and variable outcomes. The systemic form of the disease is characterized by immune complex mediated manifestations and is complicated by lymphoma as a result of a polyclonal B cell hyperactivity that is evolving into B cell malignancy. In the past decades, well-established clinical and serological markers have been described in the literature to identify high-risk patients and to predict lymphoma development. However, specific biologic treatments have proven ineffective to control the disease. Significant research effort has been made to reveal the major underlying biological events in this subgroup and identify biomarkers for early diagnosis, prognosis and response to treatment. In this review, we summarize the current data for the proposed histological, molecular and genetic biomarkers.

  4. Relationship between inflammatory and coagulation biomarkers and cardiac autonomic function in HIV-infected individuals

    DEFF Research Database (Denmark)

    Young, Lari C; Roediger, Mollie P; Grandits, Greg;

    2014-01-01

    AIM: To examine the relationship between inflammatory and coagulation biomarkers and cardiac autonomic function (CAF) as measured by heart rate variability in persons with HIV. MATERIALS & METHODS: This analysis included 4073 HIV-infected persons from the Strategies for Management of Antiretroviral...... Therapy study. We examined the association between IL-6, high-sensitivity C-reactive protein (hsCRP) and D-dimer with heart rate variability measures (SDNN and rMSSD), both cross-sectionally and longitudinally. RESULTS: Cross-sectional analysis revealed significant inverse associations between IL-6, hs......CRP and d-dimer with SDNN and rMSSD (p longitudinal analysis failed to show a significant association between baseline IL-6, hsCRP and d-dimer with change in CAF over time. CONCLUSION: Cross-sectionally, higher levels of inflammatory and coagulation biomarkers were...

  5. Preservation of hydrocarbons and biomarkers in oil trapped inside fluid inclusions for >2 billion years

    Science.gov (United States)

    George, Simon C.; Volk, Herbert; Dutkiewicz, Adriana; Ridley, John; Buick, Roger

    2008-02-01

    Oil-bearing fluid inclusions occur in a ca. 2.45 Ga fluvial metaconglomerate of the Matinenda Formation at Elliot Lake, Canada. The oil, most likely derived from the conformably overlying deltaic McKim Formation, was trapped in quartz and feldspar during diagenesis and early metamorphism of the host rock, probably before ca. 2.2 Ga. Molecular geochemical analyses of the oil reveal a wide range of compounds, including CH 4, CO 2, n-alkanes, isoprenoids, monomethylalkanes, aromatic hydrocarbons, low molecular weight cyclic hydrocarbons, and trace amounts of complex multi-ring biomarkers. Maturity ratios show that the oil was generated in the oil window, with no evidence of extensive thermal cracking. This is remarkable, given that the oils were exposed to upper prehnite-pumpellyite facies metamorphism (280-350 °C) either during migration or after entrapment. The fluid inclusions are closed systems, with high fluid pressures, and contain no clays or other minerals or metals that might catalyse oil-to-gas cracking. These three attributes may all contribute to the thermal stability of the included oil and enable survival of biomarkers and molecular ratios over billions of years. The biomarker geochemistry of the oil in the Matinenda Formation fluid inclusions enables inferences about the organisms that contributed to the organic matter deposited in the Palaeoproterozoic source rocks from which the analysed oil was generated and expelled. The presence of biomarkers produced by cyanobacteria and eukaryotes that are derived from and trapped in rocks deposited before ca. 2.2 Ga is consistent with an earlier evolution of oxygenic photosynthesis and suggests that some aquatic settings had become sufficiently oxygenated for sterol biosynthesis by this time. The extraction of biomarker molecules from Palaeoproterozoic oil-bearing fluid inclusions thus establishes a new method, using low detection limits and system blank levels, to trace evolution through Earth's early history

  6. Gene expression in the scleractinian Acropora microphthalma exposed to high solar irradiance reveals elements of photoprotection and coral bleaching.

    Directory of Open Access Journals (Sweden)

    Antonio Starcevic

    Full Text Available BACKGROUND: The success of tropical reef-building corals depends on the metabolic co-operation between the animal host and the photosynthetic performance of endosymbiotic algae residing within its cells. To examine the molecular response of the coral Acropora microphthalma to high levels of solar irradiance, a cDNA library was constructed by PCR-based suppression subtractive hybridisation (PCR-SSH from mRNA obtained by transplantation of a colony from a depth of 12.7 m to near-surface solar irradiance, during which the coral became noticeably paler from loss of endosymbionts in sun-exposed tissues. METHODOLOGY/PRINCIPAL FINDINGS: A novel approach to sequence annotation of the cDNA library gave genetic evidence for a hypothetical biosynthetic pathway branching from the shikimic acid pathway that leads to the formation of 4-deoxygadusol. This metabolite is a potent antioxidant and expected precursor of the UV-protective mycosporine-like amino acids (MAAs, which serve as sunscreens in coral phototrophic symbiosis. Empirical PCR based evidence further upholds the contention that the biosynthesis of these MAA sunscreens is a 'shared metabolic adaptation' between the symbiotic partners. Additionally, gene expression induced by enhanced solar irradiance reveals a cellular mechanism of light-induced coral bleaching that invokes a Ca(2+-binding synaptotagmin-like regulator of SNARE protein assembly of phagosomal exocytosis, whereby algal partners are lost from the symbiosis. CONCLUSIONS/SIGNIFICANCE: Bioinformatics analyses of DNA sequences obtained by differential gene expression of a coral exposed to high solar irradiance has revealed the identification of putative genes encoding key steps of the MAA biosynthetic pathway. Revealed also by this treatment are genes that implicate exocytosis as a cellular process contributing to a breakdown in the metabolically essential partnership between the coral host and endosymbiotic algae, which manifests as coral

  7. The High-throughput sequencing of Sillago japonica mitochondrial genome reveals the phylogenetic position within the genus Sillago.

    Science.gov (United States)

    Niu, Sufang; Wu, Renxie; Liu, Yong; Wang, Xuefeng

    2016-09-01

    The complete mitogenome of Sillago japonica was determined through high-throughput DNA sequencing technology. The circular mtDNA molecule was 16 645 bp in size and encoded 13 protein-coding genes, 2 rRNAs, 22 tRNAs and 2 non-coding regions, with the gene arrangement and content identical to other typical vertebrate mitogenomes. The identity analysis revealed that the mitogenome sequence of S. japonica shared a relatively high sequence identity to S. asiatica (81.5%) compared with S. aeolus (77.5%), S. indica (77.1%), and S. sihama (76.3%). The neighbor-joining tree of complete mitogenome sequence showed that S. japonica firstly clustered together with S. asiatica, then grouped with S. indica and S. sihama, and finally gathered with S. aeolus. Taken together, the results absolutely supported the evolutionary position of S. japonica and provided new insights into phylogenetic relationships of Sillago.

  8. Fluid injection induced seismicity reveals a NE dipping fault in the southeastern sector of the High Agri Valley (southern Italy)

    Science.gov (United States)

    Stabile, T. A.; Giocoli, A.; Perrone, A.; Piscitelli, S.; Lapenna, V.

    2014-08-01

    On 2 June 2006 the wastewater produced during the oil and gas field exploitation in High Agri Valley (southern Italy) started to be managed by disposal through pumping the fluids back into the subsurface at the Costa Molina 2 (CM2) injection well, located in the southeastern sector of the valley. The onset of microearthquakes (Ml ≤ 2) after 4 days at about 1.3 km SW of CM2 well suggests fluid injection induced seismicity by the diffusion of pore pressure. Moreover, the space-time evolution of 196 high-resolution relocated events reveals a previously unmapped NE dipping fault. We investigate the physical processes related to the fluid injection induced seismicity and delineate the previously unmapped fault by jointly analyzing seismicity data, geological observations, fluid injection data, the stratigraphic log of the CM2 well, and the electrical resistivity tomography survey carried out in the study area.

  9. Genome-wide analysis of the world's sheep breeds reveals high levels of historic mixture and strong recent selection.

    Science.gov (United States)

    Kijas, James W; Lenstra, Johannes A; Hayes, Ben; Boitard, Simon; Porto Neto, Laercio R; San Cristobal, Magali; Servin, Bertrand; McCulloch, Russell; Whan, Vicki; Gietzen, Kimberly; Paiva, Samuel; Barendse, William; Ciani, Elena; Raadsma, Herman; McEwan, John; Dalrymple, Brian

    2012-02-01

    Through their domestication and subsequent selection, sheep have been adapted to thrive in a diverse range of environments. To characterise the genetic consequence of both domestication and selection, we genotyped 49,034 SNP in 2,819 animals from a diverse collection of 74 sheep breeds. We find the majority of sheep populations contain high SNP diversity and have retained an effective population size much higher than most cattle or dog breeds, suggesting domestication occurred from a broad genetic base. Extensive haplotype sharing and generally low divergence time between breeds reveal frequent genetic exchange has occurred during the development of modern breeds. A scan of the genome for selection signals revealed 31 regions containing genes for coat pigmentation, skeletal morphology, body size, growth, and reproduction. We demonstrate the strongest selection signal has occurred in response to breeding for the absence of horns. The high density map of genetic variability provides an in-depth view of the genetic history for this important livestock species.

  10. Genome-wide analysis of the world's sheep breeds reveals high levels of historic mixture and strong recent selection.

    Directory of Open Access Journals (Sweden)

    James W Kijas

    2012-02-01

    Full Text Available Through their domestication and subsequent selection, sheep have been adapted to thrive in a diverse range of environments. To characterise the genetic consequence of both domestication and selection, we genotyped 49,034 SNP in 2,819 animals from a diverse collection of 74 sheep breeds. We find the majority of sheep populations contain high SNP diversity and have retained an effective population size much higher than most cattle or dog breeds, suggesting domestication occurred from a broad genetic base. Extensive haplotype sharing and generally low divergence time between breeds reveal frequent genetic exchange has occurred during the development of modern breeds. A scan of the genome for selection signals revealed 31 regions containing genes for coat pigmentation, skeletal morphology, body size, growth, and reproduction. We demonstrate the strongest selection signal has occurred in response to breeding for the absence of horns. The high density map of genetic variability provides an in-depth view of the genetic history for this important livestock species.

  11. High-Throughput siRNA Screening to Reveal GATA-2 Upstream Transcriptional Mechanisms in Hematopoietic Cells.

    Directory of Open Access Journals (Sweden)

    Yo Saito

    Full Text Available Hematopoietic stem cells can self-renew and differentiate into all blood cell types. The transcription factor GATA-2 is expressed in both hematopoietic stem and progenitor cells and is essential for cell proliferation, survival, and differentiation. Recently, evidence from studies of aplastic anemia, MonoMAC syndrome, and lung cancer has demonstrated a mechanistic link between GATA-2 and human pathophysiology. GATA-2-dependent disease processes have been extensively analyzed; however, the transcriptional mechanisms upstream of GATA-2 remain less understood. Here, we conducted high-throughput small-interfering-RNA (siRNA library screening and showed that YN-1, a human erythroleukemia cell line, expressed high levels of GATA-2 following the activation of the hematopoietic-specific 1S promoter. As transient luciferase reporter assay in YN-1 cells revealed the highest promoter activity in the 1S promoter fused with GATA-2 intronic enhancer (+9.9 kb/1S; therefore, we established a cell line capable of stably expressing +9.9 kb/1S-Luciferase. Subsequently, we screened 995 transcription factor genes and revealed that CITED2 acts as a GATA-2 activator in human hematopoietic cells. These results provide novel insights into and further identify the regulatory mechanism of GATA-2.

  12. Accurate and High-Coverage Immune Repertoire Sequencing Reveals Characteristics of Antibody Repertoire Diversification in Young Children with Malaria

    Science.gov (United States)

    Jiang, Ning

    Accurately measuring the immune repertoire sequence composition, diversity, and abundance is important in studying repertoire response in infections, vaccinations, and cancer immunology. Using molecular identifiers (MIDs) to tag mRNA molecules is an effective method in improving the accuracy of immune repertoire sequencing (IR-seq). However, it is still difficult to use IR-seq on small amount of clinical samples to achieve a high coverage of the repertoire diversities. This is especially challenging in studying infections and vaccinations where B cell subpopulations with fewer cells, such as memory B cells or plasmablasts, are often of great interest to study somatic mutation patterns and diversity changes. Here, we describe an approach of IR-seq based on the use of MIDs in combination with a clustering method that can reveal more than 80% of the antibody diversity in a sample and can be applied to as few as 1,000 B cells. We applied this to study the antibody repertoires of young children before and during an acute malaria infection. We discovered unexpectedly high levels of somatic hypermutation (SHM) in infants and revealed characteristics of antibody repertoire development in young children that would have a profound impact on immunization in children.

  13. Biomarkers in canine parvovirus enteritis.

    Science.gov (United States)

    Schoeman, J P; Goddard, A; Leisewitz, A L

    2013-07-01

    Canine parvovirus (CPV) enteritis has, since its emergence in 1978, remained a common and important cause of morbidity and mortality in young dogs. The continued incidence of parvoviral enteritis is partly due to the virus' capability to evolve into more virulent and resistant variants with significant local gastrointestinal and systemic inflammatory sequelae. This paper reviews current knowledge on historical-, signalment-, and clinical factors as well as several haematological-, biochemical- and endocrine parameters that can be used as diagnostic and prognostic biomarkers in CPV enteritis. These factors include season of presentation, purebred nature, bodyweight, vomiting, leukopaenia, lymphopaenia, thrombocytopaenia, hypercoagulability, hypercortisolaemia, hypothyroxinaemia, hypoalbuminaemia, elevated C-reactive protein and tumour necrosis factor, hypocholesterolaemia and hypocitrullinaemia. Factors contributing to the manifestations of CPV infection are multiple with elements of host, pathogen, secondary infections, underlying stressors and environment affecting severity and outcome. The availability of several prognosticators has made identification of patients at high risk of death and their subsequent targeted management more rewarding.

  14. MRI plaque imaging reveals high-risk carotid plaques especially in diabetic patients irrespective of the degree of stenosis

    Directory of Open Access Journals (Sweden)

    Holzer K

    2010-11-01

    Full Text Available Abstract Background Plaque imaging based on magnetic resonance imaging (MRI represents a new modality for risk assessment in atherosclerosis. It allows classification of carotid plaques in high-risk and low-risk lesion types (I-VIII. Type 2 diabetes mellitus (DM 2 represents a known risk factor for atherosclerosis, but its specific influence on plaque vulnerability is not fully understood. This study investigates whether MRI-plaque imaging can reveal differences in carotid plaque features of diabetic patients compared to nondiabetics. Methods 191 patients with moderate to high-grade carotid artery stenosis were enrolled after written informed consent was obtained. Each patient underwent MRI-plaque imaging using a 1.5-T scanner with phased-array carotid coils. The carotid plaques were classified as lesion types I-VIII according to the MRI-modified AHA criteria. For 36 patients histology data was available. Results Eleven patients were excluded because of insufficient MR-image quality. DM 2 was diagnosed in 51 patients (28.3%. Concordance between histology and MRI-classification was 91.7% (33/36 and showed a Cohen's kappa value of 0.81 with a 95% CI of 0.98-1.15. MRI-defined high-risk lesion types were overrepresented in diabetic patients (n = 29; 56.8%. Multiple logistic regression analysis revealed association between DM 2 and MRI-defined high-risk lesion types (OR 2.59; 95% CI [1.15-5.81], independent of the degree of stenosis. Conclusion DM 2 seems to represent a predictor for the development of vulnerable carotid plaques irrespective of the degree of stenosis and other risk factors. MRI-plaque imaging represents a new tool for risk stratification of diabetic patients. See Commentary: http://www.biomedcentral.com/1741-7015/8/78/abstract

  15. High resolution genetic mapping by genome sequencing reveals genome duplication and tetraploid genetic structure of the diploid Miscanthus sinensis.

    Directory of Open Access Journals (Sweden)

    Xue-Feng Ma

    Full Text Available We have created a high-resolution linkage map of Miscanthus sinensis, using genotyping-by-sequencing (GBS, identifying all 19 linkage groups for the first time. The result is technically significant since Miscanthus has a very large and highly heterozygous genome, but has no or limited genomics information to date. The composite linkage map containing markers from both parental linkage maps is composed of 3,745 SNP markers spanning 2,396 cM on 19 linkage groups with a 0.64 cM average resolution. Comparative genomics analyses of the M. sinensis composite linkage map to the genomes of sorghum, maize, rice, and Brachypodium distachyon indicate that sorghum has the closest syntenic relationship to Miscanthus compared to other species. The comparative results revealed that each pair of the 19 M. sinensis linkages aligned to one sorghum chromosome, except for LG8, which mapped to two sorghum chromosomes (4 and 7, presumably due to a chromosome fusion event after genome duplication. The data also revealed several other chromosome rearrangements relative to sorghum, including two telomere-centromere inversions of the sorghum syntenic chromosome 7 in LG8 of M. sinensis and two paracentric inversions of sorghum syntenic chromosome 4 in LG7 and LG8 of M. sinensis. The results clearly demonstrate, for the first time, that the diploid M. sinensis is tetraploid origin consisting of two sub-genomes. This complete and high resolution composite linkage map will not only serve as a useful resource for novel QTL discoveries, but also enable informed deployment of the wealth of existing genomics resources of other species to the improvement of Miscanthus as a high biomass energy crop. In addition, it has utility as a reference for genome sequence assembly for the forthcoming whole genome sequencing of the Miscanthus genus.

  16. Early biomarkers of joint damage in rheumatoid and psoriatic arthritis.

    LENUS (Irish Health Repository)

    Mc Ardle, Angela

    2015-01-01

    Joint destruction, as evidenced by radiographic findings, is a significant problem for patients suffering from rheumatoid arthritis and psoriatic arthritis. Inherently irreversible and frequently progressive, the process of joint damage begins at and even before the clinical onset of disease. However, rheumatoid and psoriatic arthropathies are heterogeneous in nature and not all patients progress to joint damage. It is therefore important to identify patients susceptible to joint destruction in order to initiate more aggressive treatment as soon as possible and thereby potentially prevent irreversible joint damage. At the same time, the high cost and potential side effects associated with aggressive treatment mean it is also important not to over treat patients and especially those who, even if left untreated, would not progress to joint destruction. It is therefore clear that a protein biomarker signature that could predict joint damage at an early stage would support more informed clinical decisions on the most appropriate treatment regimens for individual patients. Although many candidate biomarkers for rheumatoid and psoriatic arthritis have been reported in the literature, relatively few have reached clinical use and as a consequence the number of prognostic biomarkers used in rheumatology has remained relatively static for several years. It has become evident that a significant challenge in the transition of biomarker candidates to clinical diagnostic assays lies in the development of suitably robust biomarker assays, especially multiplexed assays, and their clinical validation in appropriate patient sample cohorts. Recent developments in mass spectrometry-based targeted quantitative protein measurements have transformed our ability to rapidly develop multiplexed protein biomarker assays. These advances are likely to have a significant impact on the validation of biomarkers in the future. In this review, we have comprehensively compiled a list of candidate

  17. Potential Serological Biomarkers of Cerebral Malaria

    Directory of Open Access Journals (Sweden)

    Naomi W. Lucchi

    2011-01-01

    Full Text Available Biomarkers have been used to diagnose and prognosticate the progress and outcome of many chronic diseases such as neoplastic and non communicable diseases. However, only recently did the field of malaria research move in the direction of actively identifying biomarkers that can accurately discriminate the severe forms of malaria. Malaria continues to be a deadly disease, killing close to a million people (mostly children every year. One life-threatening complication of malaria is cerebral malaria (CM. Studies carried out in Africa have demonstrated that even with the best treatment, as high as 15–30% of CM patients die and about 10–24% of CM survivors suffer short-or long-term neurological impairment. The transition from mild malaria to CM can be sudden and requires immediate intervention. Currently, there is no biological test available to confirm the diagnosis of CM and its complications. It is hoped that development of biomarkers to identify CM patients and potential risk for adverse outcomes would greatly enhance better intervention and clinical management to improve the outcomes. We review here what is currently known regarding biomarkers for CM outcomes.

  18. Biomarkers in Pediatric ARDS: Future Directions

    Directory of Open Access Journals (Sweden)

    Benjamin E Orwoll

    2016-06-01

    Full Text Available Acute respiratory distress syndrome (ARDS is common among mechanically ventilated children, and accompanies up to 30% of all PICU deaths. Though ARDS diagnosis is based on clinical criteria, biological markers of acute lung damage have been extensively studied in adults and children. Biomarkers of inflammation, alveolar epithelial and capillary endothelial disruption, disordered coagulation, and associated derangements measured in the circulation and other body fluids such as brochoalveolar lavage have improved our understanding of pathobiology of ARDS. The biochemical signature of ARDS has been increasingly well described in adult populations, and this has led to the identification of molecular phenotypes to augment clinical classifications. However, there is a paucity of data from pediatric ARDS patients. Biomarkers and molecular phenotypes have the potential to identify patients at high risk of poor outcomes, and perhaps inform the development of targeted therapies for specific groups of patients. Additionally, because of the lower incidence of and mortality from ARDS in pediatric patients relative to adults and lack of robust clinical predictors of outcome, there is an ongoing interest in biological markers as surrogate outcome measures. The recent definition of pediatric ARDS (pARDS provides additional impetus for measurement of established and novel biomarkers in future pediatric studies in order to further characterize this disease process. This chapter will review the currently available literature and discuss potential future directions for investigation into biomarkers in ARDS among children.

  19. AKAP4 is a circulating biomarker for non-small cell lung cancer

    Science.gov (United States)

    Gumireddy, Kiranmai; Li, Anping; Chang, David H.; Liu, Qin; Kossenkov, Andrew V.; Yan, Jinchun; Korst, Robert J.; Nam, Brian T.; Xu, Hua; Zhang, Lin; Ganepola, Ganepola A.P.; Showe, Louise C.; Huang, Qihong

    2015-01-01

    Cancer testis antigens (CTAs) are widely expressed in tumor tissues, circulating tumor cells (CTCs) and in cancer derived exosomes that are frequently engulfed by lymphoid cells. To determine whether tumor derived CTA mRNAs could be detected in RNA from purified peripheral blood mononuclear cells (PBMC) of non-small cell lung cancer (NSCLC) patients, we assayed for the expression of 116 CTAs in PBMC RNA in a discovery set and identified AKAP4 as a potential NSCLC biomarker. We validated AKAP4 as a highly accurate biomarker in a cohort of 264 NSCLCs and 135 controls from 2 different sites including a subset of controls with high risk lung nodules. When all (264) lung cancers were compared with all (135) controls the area under the ROC curve (AUC) was 0.9714. When 136 stage I NSCLC lung cancers are compared with all controls the AUC is 0.9795 and when all lung cancer patients were compared to 27 controls with histologically confirmed benign lung nodules, a comparison of significant clinical importance, the AUC was 0.9825. AKAP4 expression increases significantly with tumor stage, but independent of age, gender, smoking history or cancer subtype. Follow-up studies in a small number of resected NSCLC patients revealed a decrease of AKAP4 expression post-surgical resection that remained low in patients in remission and increased with tumor recurrence. AKAP4 is a highly accurate biomarker for the detection of early stage lung cancer. PMID:26160834

  20. A biomarker panel (Bioscore incorporating monocytic surface and soluble TREM-1 has high discriminative value for ventilator-associated pneumonia: a prospective observational study.

    Directory of Open Access Journals (Sweden)

    Vimal Grover

    Full Text Available Ventilator-associated pneumonia (VAP increases mortality in critical illness. However, clinical diagnostic uncertainty persists. We hypothesised that measuring cell-surface and soluble inflammatory markers, incorporating Triggering Receptor Expressed by Myeloid cells (TREM-1, would improve diagnostic accuracy.A single centre prospective observational study, set in a University Hospital medical-surgical intensive Care unit, recruited 91 patients into 3 groups: 27 patients with VAP, 33 ventilated controls without evidence of pulmonary sepsis (non-VAP, and 31 non-ventilated controls (NVC, without clinical infection, attending for bronchoscopy. Paired samples of Bronchiolo-alveolar lavage fluid (BALF and blood from each subject were analysed for putative biomarkers of infection: Cellular (TREM-1, CD11b and CD62L and soluble (IL-1β, IL-6, IL-8, sTREM-1, Procalcitonin. Expression of cellular markers on monocytes and neutrophils were measured by flow cytometry. Soluble inflammatory markers were determined by ELISA. A biomarker panel ('Bioscore', was constructed, tested and validated, using Fisher's discriminant function analysis, to assess its value in distinguishing VAP from non VAP.The expression of TREM-1 on monocytes (mTREM-1 and neutrophils (nTREM-1 and concentrations of IL-1β, IL-8, and sTREM-1 in BALF were significantly higher in VAP compared with non-VAP and NVC (p<0.001. The BALF/blood mTREM-1 was significantly higher in VAP patients compared to non-VAP and NVC (0.8 v 0.4 v 0.3 p<0.001. A seven marker Bioscore (BALF/blood ratio mTREM-1 and mCD11b, BALF sTREM-1, IL-8 and IL-1β, and serum CRP and IL-6 correctly identified 88.9% of VAP cases and 100% of non-VAP cases.A 7-marker bioscore, incorporating cellular and soluble TREM-1, accurately discriminates VAP from non-pulmonary infection.

  1. Cardiac Biomarkers and Cycling Race

    Directory of Open Access Journals (Sweden)

    Caroline Le Goff, Jean-François Kaux, Sébastien Goffaux, Etienne Cavalier

    2015-06-01

    Full Text Available In cycling as in other types of strenuous exercise, there exists a risk of sudden death. It is important both to understand its causes and to see if the behavior of certain biomarkers might highlight athletes at risk. Many reports describe changes in biomarkers after strenuous exercise (Nie et al., 2011, but interpreting these changes, and notably distinguishing normal physiological responses from pathological changes, is not easy. Here we have focused on the kinetics of different cardiac biomarkers: creatin kinase (CK, creating kinase midbrain (CK-MB, myoglobin (MYO, highly sensitive troponin T (hs-TnT and N-terminal brain natriuretic peptide (NT-proBNP. The population studied was a group of young trained cyclists participating in a 177-km cycling race. The group of individuals was selected for maximal homogeneity. Their annual training volume was between 10,000 and 16,000 kilometers. The rhythm of races is comparable and averages 35 km/h, depending on the race’s difficulty. The cardiac frequency was recorded via a heart rate monitor. Three blood tests were taken. The first blood test, T0, was taken approximately 2 hours before the start of the race and was intended to gather values which would act as references for the following tests. The second blood test, T1, was realized within 5 minutes of their arrival. The third and final blood test, T3, was taken 3 hours following their arrival. The CK, CK-MB, MYO, hs-TnT and NT-proBNP were measured on the Roche Diagnostic modular E (Manhein, Germany. For the statistical analysis, an ANOVA and post hoc test of Scheffé were calculated with the Statistica Software version 9.1. We noticed an important significant variation in the cardiac frequency between T0 and T1 (p < 0.0001, T0 and T3 (p < 0.0001, and T1 and T3 (p < 0.01. Table 1 shows the results obtained for the different biomarkers. CK and CK-MB showed significant variation between T0-T1 and T0-T3 (p < 0.0001. Myoglobin increased significantly

  2. IL-8 and cathepsin B as melanoma serum biomarkers.

    Science.gov (United States)

    Zhang, Hongtao; Fu, Ting; McGettigan, Suzanne; Kumar, Suresh; Liu, Shujing; Speicher, David; Schuchter, Lynn; Xu, Xiaowei

    2011-01-01

    Melanoma accounts for only a small portion of skin cancer but it is associated with high mortality. Melanoma serum biomarkers that may aid early diagnosis or guide therapy are needed clinically. However, studies of serum biomarkers have often been hampered by the serum interference that causes false readouts in immunological tests. Here we show that, after using a special buffer to eliminate the serum interference, IL-8 and cathepsin B levels were significantly elevated in melanoma patients (p < 0.05). More importantly, the combination of IL-8 and cathepsin B were also studied as a prognosis marker for melanoma mortality. Our study provides a novel approach to examine serum biomarkers. PMID:21673904

  3. Profiling serologic biomarkers in cirrhotic patients via high-throughput Fourier transform infrared spectroscopy: toward a new diagnostic tool of hepatocellular carcinoma.

    Science.gov (United States)

    Zhang, Xiaoqing; Thiéfin, Gérard; Gobinet, Cyril; Untereiner, Valérie; Taleb, Imane; Bernard-Chabert, Brigitte; Heurgué, Alexandra; Truntzer, Caroline; Ducoroy, Patrick; Hillon, Patrick; Sockalingum, Ganesh D

    2013-11-01

    Identification of novel serum biomarkers of hepatocellular carcinoma (HCC) is needed for early-stage disease detection and to improve patients' survival. The aim of this study was to evaluate the potential of serum Fourier transform infrared (FTIR) spectroscopy for differentiating sera from cirrhotic patients with and without HCC. Serum samples were collected from 2 sets of patients: cirrhotic patients with HCC (n = 39) and without HCC (n = 40). The FTIR spectra (10 per sample) were acquired in the transmission mode, and data homogeneity was tested by cluster analysis to exclude outliers. After data preprocessing by extended multiplicative signal correction and principal component analysis, the Support Vector Machine (SVM) method was applied using a leave-one-out cross-validation algorithm to classify the spectra into 2 classes of cirrhotic patients with and without HCC. When SVM was applied to all spectra (n = 790), the sensitivity and the specificity for the diagnosis of HCC were, respectively, 82.02% and 82.5%. When applied to the subset of spectra excluding the outliers (n = 739), SVM classification led to a sensitivity and specificity of 87.18% and 85%, respectively. Using median spectra for each patient instead of all replicates, the sensitivity and specificity were 84.62% and 82.50%, respectively. The overall accuracy rate was 82%-86%. In conclusion, this study suggests that FTIR spectroscopy combined with advanced methods of pattern analysis shows potential for differentiating sera from cirrhotic patients with and without HCC.

  4. CORRELATION OF INFLAMMATION BIOMARKERS WITH THE TRADITIONAL RISK FACTORS IN PATIENTS WITH ACUTE CORONARY SYNDROME

    Directory of Open Access Journals (Sweden)

    I. S. Skopec

    2016-05-01

    Full Text Available Actuality of cardiovascular diseases today determines the high interest to study pathogenesis of atherosclerosis and to searching new risk factors which could help to optimize primary and secondary prevention. Study the correlation between biomarkers of inflammation and traditional risk factors (TRF in patients with different forms of ischemic heart disease is really important today.Aim. To determine the correlation between TRF and the level of biomarkers of the inflammation and endothelial dysfunction in patients with acute coronary syndrome (ACS. Material and methods. Patients (n=62 aged from 24 to 50 years (mean age 43.98±4.73, who were admitted to the hospital due to ACS, were included into the study. Correlations between TRF and the levels of biomarkers of the inflammation and endothelial dysfunction were assessed. The following biomarkers levels were determined: high-sensitivity C-reactive protein (hsCRP, homocysteine, soluble vascular cell (sVCAM-1 and intracellular (sICAM-1 adhesion molecule type 1, soluble E-selectin (sE-selectin, nitrate, neopterin, matrix metalloproteinase type 3 (MMP-3.Results. TRF, including modifiable ones, were often revealed in patients of the studied group. Some correlations between TRF and high concentrations of inflammatory biomarkers were determined. Patients with the family history of early cardiovascular diseases had higher concentration of sVCAM-1 (1047.78±516.98 ng/ml in comparison with the patients without this TRF (705.57±239.28 ng/ml, p=0.017. Patients with arterial hypertension had higher level of MMP-3 (9.31±3.63 ng/ml versus patients without hypertension (5.02±3.66 ng/ml, р=0.011. Patients with abdominal obesity compared with patients without this TRF demonstrated higher concentration of nitrate in acute (208.45±91.85 ng/ml vs 154.53 ng/ml, р=0.028 and long-term (193.53±40.02 ng/ml vs 173.48 ng/ml, р=0.028 periods of ASC.Conclusion. The study showed the significant correlation between

  5. High-throughput sequencing reveals differential expression of miRNAs in prehierarchal follicles of laying and brooding geese.

    Science.gov (United States)

    Yu, Jing; He, Ke; Ren, Ting; Lou, Yaping; Zhao, Ayong

    2016-07-01

    Broodiness is the primary factor influencing egg production in geese, in which several genes and miRNAs participate. Detailed spatiotemporal profiles of miRNAs encompassing follicle development levels, however, are lacking. In this study, we collected preovulatory follicles (classified as small white follicles, large white follicles, and small yellow follicles) from brooding and laying geese and aimed to analyze microRNA (miRNA or miR) during folliculogenesis. High-throughput sequencing and bioinformatics analysis were used to identify the miRNAs involved in follicle development. The let7 family, miR-10 family, and miR-143 family were abundant in these libraries, and they have been suggested to play a housekeeping role during folliculogenesis. Joint comparisons revealed 23 upregulated and 21 downregulated miRNAs (in at least two comparisons of follicles during brooding and laying, P < 0.1) in the laying stage. Unlike reproduction pathways reported for ovaries, GO and KEGG analysis suggested pathways for cell apoptosis and proliferation, such as the regulation of actin cytoskeleton, endocytosis, axon guidance, pathways in cancer, tight junctions, focal adhesion, the MAPK signaling pathway, cytokine-cytokine receptor interactions, and the Wnt signaling pathway in folliculogenesis. This study revealed the miRNAs that were directly involved in follicular atresia, and our results added to the understanding of the functional involvement of miRNAs during specific stages of follicle development. PMID:27199452

  6. Molecular Techniques Revealed Highly Diverse Microbial Communities in Natural Marine Biofilms on Polystyrene Dishes for Invertebrate Larval Settlement

    KAUST Repository

    Lee, On On

    2014-01-09

    Biofilm microbial communities play an important role in the larval settlement response of marine invertebrates. However, the underlying mechanism has yet to be resolved, mainly because of the uncertainties in characterizing members in the communities using traditional 16S rRNA gene-based molecular methods and in identifying the chemical signals involved. In this study, pyrosequencing was used to characterize the bacterial communities in intertidal and subtidal marine biofilms developed during two seasons. We revealed highly diverse biofilm bacterial communities that varied with season and tidal level. Over 3,000 operational taxonomic units with estimates of up to 8,000 species were recovered in a biofilm sample, which is by far the highest number recorded in subtropical marine biofilms. Nineteen phyla were found, of which Cyanobacteria and Proteobacteria were the most dominant one in the intertidal and subtidal biofilms, respectively. Apart from these, Actinobacteria, Bacteroidetes, and Planctomycetes were the major groups recovered in both intertidal and subtidal biofilms, although their relative abundance varied among samples. Full-length 16S rRNA gene clone libraries were constructed for the four biofilm samples and showed similar bacterial compositions at the phylum level to those revealed by pyrosequencing. Laboratory assays confirmed that cyrids of the barnacle Balanus amphitrite preferred to settle on the intertidal rather than subtidal biofilms. This preference was independent of the biofilm bacterial density or biomass but was probably related to the biofilm community structure, particularly, the Proteobacterial and Cyanobacterial groups. © 2014 Springer Science+Business Media New York.

  7. The spider hemolymph clot proteome reveals high concentrations of hemocyanin and von Willebrand factor-like proteins.

    Science.gov (United States)

    Sanggaard, Kristian W; Dyrlund, Thomas F; Bechsgaard, Jesper S; Scavenius, Carsten; Wang, Tobias; Bilde, Trine; Enghild, Jan J

    2016-02-01

    Arthropods include chelicerates, crustaceans, and insects that all have open circulation systems and thus require different properties of their coagulation system than vertebrates. Although the clotting reaction in the chelicerate horseshoe crab (Family: Limulidae) has been described in details, the overall protein composition of the resulting clot has not been analyzed for any of the chelicerates. The largest class among the chelicerates is the arachnids, which includes spiders, ticks, mites, and scorpions. Here, we use a mass spectrometry-based approach to characterize the spider hemolymph clot proteome from the Brazilian whiteknee tarantula, Acanthoscurria geniculata. We focused on the insoluble part of the clot and demonstrated high concentrations of proteins homologous to the hemostasis-related and multimerization-prone von Willebrand factor. These proteins, which include hemolectins and vitellogenin homologous, were previously identified as essential components of the hemolymph clot in crustaceans and insects. Their presence in the spider hemolymph clot suggests that the origin of these proteins' function in coagulation predates the split between chelicerates and mandibulata. The clot proteome reveals that the major proteinaceous component is the oxygen-transporting and phenoloxidase-displaying abundant hemolymph protein hemocyanin, suggesting that this protein also plays a role in clot biology. Furthermore, quantification of the peptidome after coagulation revealed the simultaneous activation of both the innate immune system and the coagulation system. In general, many of the identified clot-proteins are related to the innate immune system, and our results support the previously suggested crosstalk between immunity and coagulation in arthropods.

  8. The spider hemolymph clot proteome reveals high concentrations of hemocyanin and von Willebrand factor-like proteins.

    Science.gov (United States)

    Sanggaard, Kristian W; Dyrlund, Thomas F; Bechsgaard, Jesper S; Scavenius, Carsten; Wang, Tobias; Bilde, Trine; Enghild, Jan J

    2016-02-01

    Arthropods include chelicerates, crustaceans, and insects that all have open circulation systems and thus require different properties of their coagulation system than vertebrates. Although the clotting reaction in the chelicerate horseshoe crab (Family: Limulidae) has been described in details, the overall protein composition of the resulting clot has not been analyzed for any of the chelicerates. The largest class among the chelicerates is the arachnids, which includes spiders, ticks, mites, and scorpions. Here, we use a mass spectrometry-based approach to characterize the spider hemolymph clot proteome from the Brazilian whiteknee tarantula, Acanthoscurria geniculata. We focused on the insoluble part of the clot and demonstrated high concentrations of proteins homologous to the hemostasis-related and multimerization-prone von Willebrand factor. These proteins, which include hemolectins and vitellogenin homologous, were previously identified as essential components of the hemolymph clot in crustaceans and insects. Their presence in the spider hemolymph clot suggests that the origin of these proteins' function in coagulation predates the split between chelicerates and mandibulata. The clot proteome reveals that the major proteinaceous component is the oxygen-transporting and phenoloxidase-displaying abundant hemolymph protein hemocyanin, suggesting that this protein also plays a role in clot biology. Furthermore, quantification of the peptidome after coagulation revealed the simultaneous activation of both the innate immune system and the coagulation system. In general, many of the identified clot-proteins are related to the innate immune system, and our results support the previously suggested crosstalk between immunity and coagulation in arthropods. PMID:26621385

  9. Emerging biomarkers in psoriatic arthritis.

    Science.gov (United States)

    Paek, So Yeon; Han, Ling; Weiland, Matthew; Lu, Chuan-Jian; McKinnon, Kathleen; Zhou, Li; Lim, Henry W; Elder, James T; Mi, Qing-Sheng

    2015-12-01

    Psoriasis is an immune-mediated skin disease which affects 2-4% of the worldwide population. Approximately 20-30% of patients with psoriasis develop psoriatic arthritis (PsA), a frequently destructive and disabling condition. As skin manifestations precede joint symptoms in nearly all patients with PsA, identification of biomarkers for early prediction of joint damage is an important clinical need. Because not all patients with PsA respond to treatment in the same fashion, identification of biomarkers capable of predicting therapeutic response is also imperative. Here, we review existing literature and discuss current investigations to identify potential biomarkers for PsA disease activity, with particular emphasis on microRNAs as novel markers of interest. Serum (soluble) biomarkers, peripheral osteoclast precursor as cellular biomarkers, and genetic loci associated with skin and joint disease are also reviewed. PMID:26602058

  10. Epigenetic biomarkers in liver cancer.

    Science.gov (United States)

    Banaudha, Krishna K; Verma, Mukesh

    2015-01-01

    Liver cancer (hepatocellular carcinoma or HCC) is a major cancer worldwide. Research in this field is needed to identify biomarkers that can be used for early detection of the disease as well as new approaches to its treatment. Epigenetic biomarkers provide an opportunity to understand liver cancer etiology and evaluate novel epigenetic inhibitors for treatment. Traditionally, liver cirrhosis, proteomic biomarkers, and the presence of hepatitis viruses have been used for the detection and diagnosis of liver cancer. Promising results from microRNA (miRNA) profiling and hypermethylation of selected genes have raised hopes of identifying new biomarkers. Some of these epigenetic biomarkers may be useful in risk assessment and for screening populations to identify who is likely to develop cancer. Challenges and opportunities in the field are discussed in this chapter.

  11. Diagnostic Validity of Serum and Peritoneal TNF-alpha, high sensitivity CRP and Plasma Cell-Free Nuclear DNA (ccf nDNA as Biomarkers of Pelvic Endometriosis- A Case Control Study

    Directory of Open Access Journals (Sweden)

    Ahmed F Koura, MSc*, Mohamed A Yehia, Waleed H ElTantawy, Adel S Salah El Din, Dina El-Sayed ElShennawy

    2013-04-01

    Full Text Available Introduction: Endometriosis is a disease defined by the presence of endometrial glands and stroma located outside the uterine cavity. These ectopic implants can be found throughout the pelvis, on and within the ovaries, abutting the uterine ligaments, occupying the rectovaginal septum, invading the intestinal serosa, and along the parietal peritoneum. Endometrial implantation at distant sites such as the pleura, lung, within surgical scars, and along the diaphragm also has been reported. (1. It results often in subfertility and pain, occurs mainly in women of reproductive age (16–50 years and has a progressive character in at least 50%, but the rate and risk factors for progression are unknown. Endometriosis can be classified into four stages: minimal, mild, moderate and severe. The gold standard for the diagnosis of endometriosis is laparoscopic inspection, ideally with histological confirmation. (2, however, is an invasive technique and should be performed only after imaging techniques prove insufficient for confident diagnosis. (3 Lack of a non-invasive diagnostic test contributes to the long delay between onset of symptoms and diagnosis of endometriosis. (2 Additional tools are needed for non-invasive classifications in order to reduce the number of unnecessary laparoscopies without adversely affecting outcomes. Finding specific and more sensitive biomarkers in endometriosis is critical, because endometriosis is usually diagnosed only in advanced stages, and there is a high rate of morbidity for this disease. (4 Aim of the work: The aim of the current study is to assess the validity of serum and peritoneal high sensitivity CRP and TNF-alpha and plasma cell-free nuclear DNA (ccf nDNA as biomarkers in early diagnosis of pelvic endometriosis.Methods: This study was conducted at the Obstetrics & Gynecology department, Maternity Hospital, Ain Shams University. This is a case control study of 120 women scheduled for diagnostic laparoscopy

  12. Circulating Biomarker Panels in Alzheimer's Disease.

    Science.gov (United States)

    Zafari, Sachli; Backes, Christina; Meese, Eckart; Keller, Andreas

    2015-01-01

    The early diagnosis of diseases frequently represents an important unmet clinical need supporting in-time treatment of pathologies. This also applies to neurodegenerative diseases such as Alzheimer's disease (AD), the most common form of dementia, estimated to affect millions of individuals worldwide. The respective diagnostic and prognostic markers, especially for the preclinical stages of AD, are expected to improve patients' outcome significantly. In the last decades, many approaches to detecting AD have been developed, including markers to discover changes in amyloid-β levels [from cerebrospinal fluid (CSF) or using positron emission tomography] or other brain imaging technologies such as structural magnetic resonance imaging (MRI), functional-connectivity MRI or task-related functional MRI. A major challenge is the detection of AD using minimally or even noninvasive biomarkers from body fluids such as plasma or serum. Circulating biomarker candidates based on mRNAs or proteins measured from blood cells, plasma or serum have been proposed for various pathologies including AD. As for other diseases, there is a tendency to use marker signatures obtained by high-throughput approaches, which allow the generation of profiles of hundreds to thousands of biomarkers simultaneously [microarrays, mass spectrometry or next-generation sequencing (NGS)]. Beyond mRNAs and proteins, recent approaches have measured small noncoding RNA (so-called microRNA) profiles in AD patients' blood samples using NGS or array-based technologies. Generally, the development of marker panels is in its early stages and requires further, substantial clinical validation. In this review, we provide an overview of different circulating AD biomarkers, starting with a brief summary of CSF markers and focusing on novel biomarker signatures such as small noncoding RNA profiles.

  13. High-Resolution Profiling of Drosophila Replication Start Sites Reveals a DNA Shape and Chromatin Signature of Metazoan Origins

    Directory of Open Access Journals (Sweden)

    Federico Comoglio

    2015-05-01

    Full Text Available At every cell cycle, faithful inheritance of metazoan genomes requires the concerted activation of thousands of DNA replication origins. However, the genetic and chromatin features defining metazoan replication start sites remain largely unknown. Here, we delineate the origin repertoire of the Drosophila genome at high resolution. We address the role of origin-proximal G-quadruplexes and suggest that they transiently stall replication forks in vivo. We dissect the chromatin configuration of replication origins and identify a rich spatial organization of chromatin features at initiation sites. DNA shape and chromatin configurations, not strict sequence motifs, mark and predict origins in higher eukaryotes. We further examine the link between transcription and origin firing and reveal that modulation of origin activity across cell types is intimately linked to cell-type-specific transcriptional programs. Our study unravels conserved origin features and provides unique insights into the relationship among DNA topology, chromatin, transcription, and replication initiation across metazoa.

  14. A High-Dimensional Atlas of Human T Cell Diversity Reveals Tissue-Specific Trafficking and Cytokine Signatures.

    Science.gov (United States)

    Wong, Michael Thomas; Ong, David Eng Hui; Lim, Frances Sheau Huei; Teng, Karen Wei Weng; McGovern, Naomi; Narayanan, Sriram; Ho, Wen Qi; Cerny, Daniela; Tan, Henry Kun Kiaang; Anicete, Rosslyn; Tan, Bien Keem; Lim, Tony Kiat Hon; Chan, Chung Yip; Cheow, Peng Chung; Lee, Ser Yee; Takano, Angela; Tan, Eng-Huat; Tam, John Kit Chung; Tan, Ern Yu; Chan, Jerry Kok Yen; Fink, Katja; Bertoletti, Antonio; Ginhoux, Florent; Curotto de Lafaille, Maria Alicia; Newell, Evan William

    2016-08-16

    Depending on the tissue microenvironment, T cells can differentiate into highly diverse subsets expressing unique trafficking receptors and cytokines. Studies of human lymphocytes have primarily focused on a limited number of parameters in blood, representing an incomplete view of the human immune system. Here, we have utilized mass cytometry to simultaneously analyze T cell trafficking and functional markers across eight different human tissues, including blood, lymphoid, and non-lymphoid tissues. These data have revealed that combinatorial expression of trafficking receptors and cytokines better defines tissue specificity. Notably, we identified numerous T helper cell subsets with overlapping cytokine expression, but only specific cytokine combinations are secreted regardless of tissue type. This indicates that T cell lineages defined in mouse models cannot be clearly distinguished in humans. Overall, our data uncover a plethora of tissue immune signatures and provide a systemic map of how T cell phenotypes are altered throughout the human body. PMID:27521270

  15. Visualization of multivalent histone modification in a single cell reveals highly concerted epigenetic changes on differentiation of embryonic stem cells

    DEFF Research Database (Denmark)

    Hattori, Naoko; Niwa, Tohru; Kimura, Kana;

    2013-01-01

    . Bivalent modification was clearly visualized by iChmo in wild-type embryonic stem cells (ESCs) known to have it, whereas rarely in Suz12 knockout ESCs and mouse embryonic fibroblasts known to have little of it. iChmo was applied to analysis of epigenetic and phenotypic changes of heterogeneous cell......Combinations of histone modifications have significant biological roles, such as maintenance of pluripotency and cancer development, but cannot be analyzed at the single cell level. Here, we visualized a combination of histone modifications by applying the in situ proximity ligation assay, which...... population, namely, ESCs at an early stage of differentiation, and this revealed that the bivalent modification disappeared in a highly concerted manner, whereas phenotypic differentiation proceeded with large variations among cells. Also, using this method, we were able to visualize a combination...

  16. Structural properties of GaN(0001) epitaxial layers revealed by high resolution X-ray diffraction

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    High-resolution X-ray diffraction has been used to analyze GaN(0001) epitaxial layers on sapphire substrates. Several structural properties of GaN, including the lattice constants, strains, and dislocation densities are revealed by the technique of X-ray dffraction (XRD). Lattice constants calculated from the omega/2theta scan are c=0.5185 nm and a=0.3157 nm. Also, the in-plane strain is -1.003%, while out of the plane, the epitaxial film is almost relaxed. Several methods are used to deduce the mosaicity and dislocation density of GaN, showing that the edge type dislocations are the overwhelming majority.

  17. A High-Dimensional Atlas of Human T Cell Diversity Reveals Tissue-Specific Trafficking and Cytokine Signatures.

    Science.gov (United States)

    Wong, Michael Thomas; Ong, David Eng Hui; Lim, Frances Sheau Huei; Teng, Karen Wei Weng; McGovern, Naomi; Narayanan, Sriram; Ho, Wen Qi; Cerny, Daniela; Tan, Henry Kun Kiaang; Anicete, Rosslyn; Tan, Bien Keem; Lim, Tony Kiat Hon; Chan, Chung Yip; Cheow, Peng Chung; Lee, Ser Yee; Takano, Angela; Tan, Eng-Huat; Tam, John Kit Chung; Tan, Ern Yu; Chan, Jerry Kok Yen; Fink, Katja; Bertoletti, Antonio; Ginhoux, Florent; Curotto de Lafaille, Maria Alicia; Newell, Evan William

    2016-08-16

    Depending on the tissue microenvironment, T cells can differentiate into highly diverse subsets expressing unique trafficking receptors and cytokines. Studies of human lymphocytes have primarily focused on a limited number of parameters in blood, representing an incomplete view of the human immune system. Here, we have utilized mass cytometry to simultaneously analyze T cell trafficking and functional markers across eight different human tissues, including blood, lymphoid, and non-lymphoid tissues. These data have revealed that combinatorial expression of trafficking receptors and cytokines better defines tissue specificity. Notably, we identified numerous T helper cell subsets with overlapping cytokine expression, but only specific cytokine combinations are secreted regardless of tissue type. This indicates that T cell lineages defined in mouse models cannot be clearly distinguished in humans. Overall, our data uncover a plethora of tissue immune signatures and provide a systemic map of how T cell phenotypes are altered throughout the human body.

  18. High-density PhyloChip profiling of stimulated aquifer microbial communities reveals a complex response to acetate amendment

    Energy Technology Data Exchange (ETDEWEB)

    Handley, Kim M. [Univ. of California, Berkeley, CA (United States); Wrighton, Kelly C. [Univ. of California, Berkeley, CA (United States); Piceno, Yvette M. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Andersen, Gary L. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); DeSantis, Todd Z. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Williams, Kenneth H. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Wilkins, Michael J. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); N' Guessan, A. Lucie [Univ. of Massachusetts, Amherst, MA (United States); Peacock, Aaron [Haley & Aldrich, Oak Ridge, TN (United States); Bargar, John [SLAC National Accelerator Lab., Menlo Park, CA (United States). Stanford Synchrotron Radiation Lightsource (SSRL); Long, Philip E. [Energy and Environment Directorate, Pacific Northwest National Laboratory, Richland, WA, 99353, USA; Banfield, Jillian F.

    2012-04-13

    There is increasing interest in harnessing the functional capacities of indigenous microbial communities to transform and remediate a wide range of environmental contaminants. Information about which community members respond to stimulation can guide the interpretation and development of remediation approaches. To comprehensively determine community membership and abundance patterns among a suite of samples associated with uranium bioremediation experiments we employed a high-density microarray (PhyloChip). Samples were unstimulated, naturally reducing, or collected during Fe(III) (early) and sulfate reduction (late biostimulation) from an acetate re-amended/amended aquifer in Rifle, Colorado, and from laboratory experiments using field-collected materials. Deep community sampling with PhyloChip identified hundreds-to-thousands of operational taxonomic units (OTUs) present during amendment, and revealed close similarity among highly enriched taxa from drill-core and groundwater well-deployed column sediment. Overall, phylogenetic data suggested stimulated community membership was most affected by a carryover effect between annual stimulation events. Nevertheless, OTUs within the Fe(III)- and sulfate-reducing lineages, Desulfuromonadales and Desulfobacterales, were repeatedly stimulated. Less consistent, co-enriched taxa represented additional lineages associated with Fe(III) and sulfate reduction (for example, Desulfovibrionales; Syntrophobacterales; Peptococcaceae) and autotrophic sulfur oxidation (Sulfurovum; Campylobacterales). These data imply complex membership among highly stimulated taxa, and by inference biogeochemical responses to acetate, a non-fermentable substrate.

  19. MicroRNA expression profiling in skeletal muscle reveals different regulatory patterns in high and low responders to resistance training.

    Science.gov (United States)

    Ogasawara, Riki; Akimoto, Takayuki; Umeno, Tokushi; Sawada, Shuji; Hamaoka, Takafumi; Fujita, Satoshi

    2016-04-01

    Large variability exists in muscle adaptive response to resistance exercise (RE) training between individuals. Recent studies have revealed a significant role for microRNAs (miRNAs) in skeletal muscle plasticity. In this study, we investigated how RE affects miRNA expression and whether the variability of muscle hypertrophy to RE training may be attributed to differential miRNA regulation in the skeletal muscle. To screen high and low responders to RE, we had 18 young men perform arm curl exercise training. After screening, all the men performed 12 wk of lower body RE training, but only the high or low responders participated in the acute RE test before training. Muscle biopsies were obtained from the vastus lateralis muscle at baseline, 3 h after acute RE, and after the training period. Total RNA was extracted from the skeletal muscle, and miRNA expression (800 miRNAs) was analyzed. RE training increased the cross-sectional area of the biceps brachii (-1.7-26.1%), quadriceps (2.2-16.8%), and hamstrings (1.6-18.4%). Eighty-five and 102 miRNAs were differentially expressed after acute and chronic RE, respectively (P muscle between high and low responders, indicating that the expression patterns of several miRNAs are altered by acute or chronic RE, and that miRNAs are involved in skeletal muscle adaptation to RE training.

  20. AstroSat/LAXPC reveals the high energy variability of GRS 1915+105 in the chi class

    CERN Document Server

    Yadav, J S; Chauhan, Jai Verdhan; Agrawal, P C; Antia, H M; Pahari, Mayukh; Dedhia, Dhiraj; Katoch, Tilak; Madhwani, P; Manchanda, R K; Paul, B; Shah, Parag; Ishwara-Chandra, C H

    2016-01-01

    We present the first quick look analysis of data from nine {\\it AstroSat}'s LAXPC observations of GRS 1915+105 during March 2016 when the source had the characteristics of being in Radio-quiet $\\chi$ class. We find that a simple empirical model of a disk blackbody emission, with Comptonization and a broad Gaussian Iron line can fit the time averaged 3--80 keV spectrum with a systematic uncertainty of 1.5\\% and a background flux uncertainty of 4\\%. A simple deadtime-corrected Poisson noise level spectrum matches well with the observed high frequency power spectra till 50 kHz and as expected the data show no significant high frequency ($> 20$ Hz) features. Energy dependent power spectra reveal a strong low frequency (2 - 8 Hz) Quasi-periodic oscillation (LFQPO) and its harmonic along with broad band noise. The QPO frequency changes rapidly with flux (nearly 4 Hz in ~ 5 hours). With increasing QPO frequency, an excess noise component appears significantly in the high energy regime (> 8 keV). At the QPO frequenci...

  1. High-throughput cell-based screening reveals a role for ZNF131 as a repressor of ERalpha signaling

    Directory of Open Access Journals (Sweden)

    Du Peige

    2008-10-01

    Full Text Available Abstract Background Estrogen receptor α (ERα is a transcription factor whose activity is affected by multiple regulatory cofactors. In an effort to identify the human genes involved in the regulation of ERα, we constructed a high-throughput, cell-based, functional screening platform by linking a response element (ERE with a reporter gene. This allowed the cellular activity of ERα, in cells cotransfected with the candidate gene, to be quantified in the presence or absence of its cognate ligand E2. Results From a library of 570 human cDNA clones, we identified zinc finger protein 131 (ZNF131 as a repressor of ERα mediated transactivation. ZNF131 is a typical member of the BTB/POZ family of transcription factors, and shows both ubiquitous expression and a high degree of sequence conservation. The luciferase reporter gene assay revealed that ZNF131 inhibits ligand-dependent transactivation by ERα in a dose-dependent manner. Electrophoretic mobility shift assay clearly demonstrated that the interaction between ZNF131 and ERα interrupts or prevents ERα binding to the estrogen response element (ERE. In addition, ZNF131 was able to suppress the expression of pS2, an ERα target gene. Conclusion We suggest that the functional screening platform we constructed can be applied for high-throughput genomic screening candidate ERα-related genes. This in turn may provide new insights into the underlying molecular mechanisms of ERα regulation in mammalian cells.

  2. Genomic and epigenomic analysis of high-risk prostate cancer reveals changes in hydroxymethylation and TET1

    Science.gov (United States)

    Spans, Lien; Van den Broeck, Thomas; Smeets, Elien; Prekovic, Stefan; Thienpont, Bernard; Lambrechts, Diether; Karnes, R. Jeffrey; Erho, Nicholas; Alshalalfa, Mohammed; Davicioni, Elai; Helsen, Christine; Gevaert, Thomas; Tosco, Lorenzo; Haustermans, Karin; Lerut, Evelyne; Joniau, Steven; Claessens, Frank

    2016-01-01

    The clinical heterogeneity of prostate cancer (PCa) makes it difficult to identify those patients that could benefit from more aggressive treatments. As a contribution to a better understanding of the genomic changes in the primary tumor that are associated with the development of high-risk disease, we performed exome sequencing and copy number determination of a clinically homogeneous cohort of 47 high-risk PCas. We confirmed recurrent mutations in SPOP, PTEN and TP53 among the 850 point mutations we detected. In seven cases, we discovered genomic aberrations in the TET1 (Ten-Eleven Translocation 1) gene which encodes a DNA hydroxymethylase than can modify methylated cytosines in genomic DNA and thus is linked with gene expression changes. TET1 protein levels were reduced in tumor versus non-tumor prostate tissue in 39 of 40 cases. The clinical relevance of changes in TET1 levels was demonstrated in an independent PCa cohort, in which low TET1 mRNA levels were significantly associated with worse metastases-free survival. We also demonstrate a strong reduction in hydroxymethylated DNA in tumor tissue in 27 of 41 cases. Furthermore, we report the first exploratory (h)MeDIP-Seq analyses of eight high-risk PCa samples. This reveals a large heterogeneity in hydroxymethylation changes in tumor versus non-tumor genomes which can be linked with cell polarity. PMID:27014907

  3. Fungi Sailing the Arctic Ocean: Speciose Communities in North Atlantic Driftwood as Revealed by High-Throughput Amplicon Sequencing.

    Science.gov (United States)

    Rämä, Teppo; Davey, Marie L; Nordén, Jenni; Halvorsen, Rune; Blaalid, Rakel; Mathiassen, Geir H; Alsos, Inger G; Kauserud, Håvard

    2016-08-01

    High amounts of driftwood sail across the oceans and provide habitat for organisms tolerating the rough and saline environment. Fungi have adapted to the extremely cold and saline conditions which driftwood faces in the high north. For the first time, we applied high-throughput sequencing to fungi residing in driftwood to reveal their taxonomic richness, community composition, and ecology in the North Atlantic. Using pyrosequencing of ITS2 amplicons obtained from 49 marine logs, we found 807 fungal operational taxonomic units (OTUs) based on clustering at 97 % sequence similarity cut-off level. The phylum Ascomycota comprised 74 % of the OTUs and 20 % belonged to Basidiomycota. The richness of basidiomycetes decreased with prolonged submersion in the sea, supporting the general view of ascomycetes being more extremotolerant. However, more than one fourth of the fungal OTUs remained unassigned to any fungal class, emphasising the need for better DNA reference data from the marine habitat. Different fungal communities were detected in coniferous and deciduous logs. Our results highlight that driftwood hosts a considerably higher fungal diversity than currently known. The driftwood fungal community is not a terrestrial relic but a speciose assemblage of fungi adapted to the stressful marine environment and different kinds of wooden substrates found in it. PMID:27147245

  4. The role of metabolic biomarkers in drug toxicity studies.

    Science.gov (United States)

    Schnackenberg, Laura K; Beger, Richard D

    2008-01-01

    ABSTRACT Metabolic profiling is a technique that can potentially provide more sensitive and specific biomarkers of toxicity than the current clinical measures benefiting preclinical and clinical drug studies. Both nuclear magnetic resonance (NMR) and mass spectrometry (MS) platforms have been used for metabolic profiling studies of drug toxicity. Not only can both techniques provide novel biomarker(s) of toxicity but the combination of both techniques gives a broader range of metabolites evaluated. Changes in metabolic patterns can provide insight into mechanism(s) of toxicity and help to eliminate a potentially toxic new chemical entity earlier in the developmental process. Metabolic profiling offers numerous advantages in toxicological research and screening as sample collection and preparation are relatively simple. Further, sample throughput, reproducibility, and accuracy are high. The area of drug toxicity of therapeutic compounds has already been impacted by metabolic profiling studies and will continue to be impacted as new, more specific biomarker(s) are found. In order for a biomarker or pattern of biomarkers to be accepted, it must be shown that they originate from the target tissue of interest. Metabolic profiling studies are amenable to any biofluid or tissue sample making it possible to link the changes noted in urine for instance as originating from renal injury. Additionally, the ease of sample collection makes it possible to follow a single animal or subject over time in order to determine whether and when the toxicity resolves itself. This review focuses on the advantages of metabolic profiling for drug toxicity studies.

  5. In situ evaluation of cadmium biomarkers in green algae

    Energy Technology Data Exchange (ETDEWEB)

    Simon, Dana F.; Davis, Thomas A. [Department of Chemistry, University of Montreal, P.O. Box 6128, Succursale Centre-ville, Montreal, Quebec H3C 3J7 (Canada); Tercier-Waeber, Mary-Lou [Analytical and Biophysical Environmental Chemistry, University of Geneva, Sciences II, 30 Quai Ernest-Ansermet, 1211 Geneva 4 (Switzerland); England, Roxane [Department of Chemistry, University of Montreal, P.O. Box 6128, Succursale Centre-ville, Montreal, Quebec H3C 3J7 (Canada); Wilkinson, Kevin J., E-mail: kj.wilkinson@umontreal.ca [Department of Chemistry, University of Montreal, P.O. Box 6128, Succursale Centre-ville, Montreal, Quebec H3C 3J7 (Canada)

    2011-10-15

    In situ measurements provide data that are the highly representative of the natural environment. In this paper, laboratory-determined biomarkers of Cd stress that were previously identified for the green alga Chlamydomonas reinhardtii, were tested in two French rivers: a contaminated site on the Riou Mort River and an 'uncontaminated' reference site on the Lot River. Transcript abundance levels were determined by real time qPCR for biomarkers thought to be Cd sensitive. Transcript levels were significantly higher (>5 fold) for organisms exposed to the contaminated site as compared to those exposed at the uncontaminated site. Biomarker mRNA levels were best correlated to free Cd (Cd{sup 2+}) rather than intracellular Cd, suggesting that they may be useful indicators of in situ stress. The paper shows that biomarker expression levels increased with time, were sensitive to metal levels and metal speciation and were higher in the 'contaminated' as opposed to the 'reference' site. - Highlights: > Biomarkers of Cd stress were tested in a contaminated and a reference site. > The organism was viable under exposure conditions and metal accumulation occurred. > Biomarker levels were correlated to Cd{sup 2+} and were higher in the contaminated site. - Algal transcription levels of several biomarkers were studied in two natural waters in situ.

  6. Biomarkers and imaging: physics and chemistry for noninvasive analyses.

    Science.gov (United States)

    Moyer, Brian R; Barrett, John A

    2009-05-01

    The era of 'modern medicine' has changed its name to 'molecular medicine', and reflects a new age based on personalized medicine utilizing molecular biomarkers in the diagnosis, staging and monitoring of therapy. Alzheimer's disease has a classical biomarker determined at autopsy with the histologic staining of amyloid accumulation in the brain. Today we can diagnose Alzheimer's disease using the same classical pathologic biomarker, but now using a noninvasive imaging probe to image the amyloid deposition in a patient and potentially provide treatment strategies and measure their effectiveness. Molecular medicine is the exploitation of biomarkers to detect disease before overt expression of pathology. Physicians can now find, fight and follow disease using imaging, and the need for other disease biomarkers is in high demand. This review will discuss the innovative physical and molecular biomarker probes now being developed for imaging systems and we will introduce the concepts needed for validation and regulatory acceptance of surrogate biomarkers in the detection and treatment of disease. PMID:21083171

  7. Comprehensive profiling of mercapturic acid metabolites from dietary acrylamide as short-term exposure biomarkers for evaluation of toxicokinetics in rats and daily internal exposure in humans using isotope dilution ultra-high performance liquid chromatography tandem mass spectrometry.

    Science.gov (United States)

    Zhang, Yu; Wang, Qiao; Cheng, Jun; Zhang, Jingshun; Xu, Jiaojiao; Ren, Yiping

    2015-09-24

    Mercapturic acid metabolites from dietary acrylamide are important short-term exposure biomarkers for evaluating the in vivo toxicity of acrylamide. Most of studies have focused on the measurement of two metabolites, N-acetyl-S-(2-carbamoylethyl)-L-cysteine (AAMA) and N-acetyl-S-(2-carbamoyl-2-hydroxyethyl)-L-cysteine (GAMA). Thus, the comprehensive profile of acrylamide urinary metabolites cannot be fully understood. We developed an isotope dilution ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method for the simultaneous determination of all four mercapturic acid adducts of acrylamide and its primary metabolite glycidamide under the electroscopy ionization negative (ESI-) mode in the present study. The limit of detection (LOD) and limit of quantification (LOQ) of the analytes ranged 0.1-0.3 ng/mL and 0.4-1.0 ng/mL, respectively. The recovery rates with low, intermediate and high spiking levels were calculated as 95.5%-105.4%, 98.2%-114.0% and 92.2%-108.9%, respectively. Acceptable within-laboratory reproducibility (RSDrats. Meanwhile, results of human urine analysis indicated that the levels of N-acetyl-S-(2-carbamoylethyl)-L-cysteine-sulfoxide (AAMA-sul), which did not appear in the mercapturic acid metabolites in rodents, were more than the sum of GAMA and N-acetyl-S-(1-carbamoyl-2-hydroxyethyl)-L-cysteine (iso-GAMA). Thus, AAMA-sul may alternatively become a specific biomarker for investigating the acrylamide exposure in humans. Current proposed method provides a substantial methodology support for comprehensive profiling of toxicokinetics and daily internal exposure evaluations of acrylamide in vivo.

  8. An Infrared Fiber-Optic Raman Sensor for Field Detecting of Organic Biomarkers Project

    Data.gov (United States)

    National Aeronautics and Space Administration — High throughput, fast detection and characterization of inorganic and organic biomarkers have become important challenge for future lunar robotic rover exploration...

  9. Crystallographic analysis reveals the structural basis of the high-affinity binding of iophenoxic acid to human serum albumin

    Directory of Open Access Journals (Sweden)

    Chung Chun-wa

    2011-04-01

    Full Text Available Abstract Background Iophenoxic acid is an iodinated radiocontrast agent that was withdrawn from clinical use because of its exceptionally long half-life in the body, which was due in part to its high-affinity binding to human serum albumin (HSA. It was replaced by Iopanoic acid, which has an amino rather than a hydroxyl group at position 3 on the iodinated benzyl ring and, as a result, binds to albumin with lower affinity and is excreted more rapidly from the body. To understand how iophenoxic acid binds so tightly to albumin, we wanted to examine the structural basis of its interaction with HSA. Results We have determined the co-crystal structure of HSA in complex with iophenoxic acid at 2.75 Å resolution, revealing a total of four binding sites, two of which - in drugs sites 1 and 2 on the protein - are likely to be occupied at clinical doses. High-affinity binding of iophenoxic acid occurs at drug site 1. The structure reveals that polar and apolar groups on the compound are involved in its interactions with drug site 1. In particular, the 3-hydroxyl group makes three hydrogen bonds with the side-chains of Tyr 150 and Arg 257. The mode of binding to drug site 2 is similar except for the absence of a binding partner for the hydroxyl group on the benzyl ring of the compound. Conclusions The HSA-iophenoxic acid structure indicates that high-affinity binding to drug site 1 is likely to be due to extensive desolvation of the compound, coupled with the ability of the binding pocket to provide a full set of salt-bridging or hydrogen bonding partners for its polar groups. Consistent with this interpretation, the structure also suggests that the lower-affinity binding of iopanoic acid arises because replacement of the 3-hydroxyl by an amino group eliminates hydrogen bonding to Arg 257. This finding underscores the importance of polar interactions in high-affinity binding to albumin.

  10. Simultaneous detection of multiple biomarkers with over three orders of concentration difference using phase change nanoparticles.

    Science.gov (United States)

    Wang, Chaoming; Sun, Zhaoyong; Ma, Liyuan; Su, Ming

    2011-03-15

    A big challenge for multiplexed detection of cancer biomarkers is that biomarker concentrations in body fluid differs several orders of magnitude. Existing techniques are not suitable to detect low- and high-concentration biomarkers (protein and DNA) at the same time, and liquid chromatography or electrophoresis is used to separate or purify target biomarkers before analysis. This paper describes a new broad-range biomarker assay using solid to liquid phase change nanoparticles, where a panel of metallic nanoparticles (i.e., metals and eutectic alloys) are modified with a panel of ligands to establish a one-to-one correspondence and attached onto ligand-modified substrates by forming sandwiched complexes. The melting peak and fusion enthalpy of phase change nanoparticles during thermal analysis reflect the type and concentration of biomarkers, respectively. The thermal readout condition can be adjusted in such a way that multiple biomarkers with concentration difference over 3 orders of magnitude have been simultaneously detected under the same condition.

  11. Prognostic clinical and molecular biomarkers of renal disease in type 2 diabetes

    DEFF Research Database (Denmark)

    Pena, Michelle J; de Zeeuw, Dick; Mischak, Harald;

    2015-01-01

    biomarker panels are thus required. There is also a paucity of studies that assess the effect of treatments on novel biomarker panels and determine whether initial treatment-induced changes in novel biomarkers predict changes in long-term renal outcomes. Such studies can not only improve our healthcare but......Diabetic kidney disease occurs in ∼ 25-40% of patients with type 2 diabetes. Given the high risk of progressive renal function loss and end-stage renal disease, early identification of patients with a renal risk is important. Novel biomarkers may aid in improving renal risk stratification. In this...... metabolomics biomarkers. We focus on multiple biomarker panels since the molecular processes of renal disease progression in type 2 diabetes are heterogeneous, rendering it unlikely that a single biomarker significantly adds to clinical risk prediction. A limited number of prospective studies of multiple...

  12. Highly Sensitive and Selective Immuno-capture/Electrochemical Assay of Acetylcholinesterase Activity in Red Blood Cells: A Biomarker of Exposure to Organophosphorus Pesticides and Nerve Agents

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Aiqiong; Du, Dan; Lin, Yuehe

    2012-02-09

    Acetylcholinesterase (AChE) enzyme activity in red blood cells (RBCs) is a useful biomarker for biomonitoring of exposures to organophosphorus (OP) pesticides and chemical nerve agents. In this paper, we reported a new method for AChE activity assay based on selective immuno-capture of AChE from biological samples followed by enzyme activity assay of captured AChE using a disposable electrochemical sensor. The electrochemical sensor is based on multiwalled carbon nanotubes-gold nanocomposites (MWCNTs-Au) modified screen printed carbon electrode (SPCE). Upon the completion of immunoreaction, the target AChE (including active and inhibited) is captured onto the electrode surface and followed by an electrochemical detection of enzymatic activity in the presence of acetylthiocholine. A linear response is obtained over standard AChE concentration range from 0.1 to 10 nM. To demonstrate the capability of this new biomonitoring method, AChE solutions dosed with different concentration of paraoxon were used to validate the new AChE assay method. AChE inhibition in OP dosed solutions was proportional to its concentration from 0.2 to 50 nM. The new AChE activity assay method for biomonitoring of OP exposure was further validated with in-vitro paraoxon-dosed RBC samples. The established electrochemical sensing platform for AChE activity assay not only avoids the problem of overlapping substrate specificity with esterases by using selective antibody, but also eliminates potential interference from other electroactive species in biological samples. It offers a new approach for sensitive, selective, and rapid AChE activity assay for biomonitoring of exposures to OPs.

  13. Biomarkers of manganese intoxication.

    Science.gov (United States)

    Zheng, Wei; Fu, Sherleen X; Dydak, Ulrike; Cowan, Dallas M

    2011-01-01

    Manganese (Mn), upon absorption, is primarily sequestered in tissue and intracellular compartments. For this reason, blood Mn concentration does not always accurately reflect Mn concentration in the targeted tissue, particularly in the brain. The discrepancy between Mn concentrations in tissue or intracellular components means that blood Mn is a poor biomarker of Mn exposure or toxicity under many conditions and that other biomarkers must be established. For group comparisons of active workers, blood Mn has some utility for distinguishing exposed from unexposed subjects, although the large variability in mean values renders it insensitive for discriminating one individual from the rest of the study population. Mn exposure is known to alter iron (Fe) homeostasis. The Mn/Fe ratio (MIR) in plasma or erythrocytes reflects not only steady-state concentrations of Mn or Fe in tested individuals, but also a biological response (altered Fe homeostasis) to Mn exposure. Recent human studies support the potential value for using MIR to distinguish individuals with Mn exposure. Additionally, magnetic resonance imaging (MRI), in combination with noninvasive assessment of γ-aminobutyric acid (GABA) by magnetic resonance spectroscopy (MRS), provides convincing evidence of Mn exposure, even without clinical symptoms of Mn intoxication. For subjects with long-term, low-dose Mn exposure or for those exposed in the past but not the present, neither blood Mn nor MRI provides a confident distinction for Mn exposure or intoxication. While plasma or erythrocyte MIR is more likely a sensitive measure, the cut-off values for MIR among the general population need to be further tested and established. Considering the large accumulation of Mn in bone, developing an X-ray fluorescence spectroscopy or neutron-based spectroscopy method may create yet another novel non-invasive tool for assessing Mn exposure and toxicity. PMID:20946915

  14. Biomarkers of Mercury Exposure in the Amazon

    OpenAIRE

    Nathália Santos Serrão de Castro; Marcelo de Oliveira Lima

    2014-01-01

    Mercury exposure in the Amazon has been studied since the 1980s decade and the assessment of human mercury exposure in the Amazon is difficult given that the natural occurrence of this metal is high and the concentration of mercury in biological samples of this population exceeds the standardized value of normality established by WHO. Few studies have focused on the discovery of mercury biomarkers in the region's population. In this way, some studies have used genetics as well as immunologica...

  15. Cytokines as diagnostic biomarkers in canine pyometra and sepsis

    OpenAIRE

    Karlsson, Iulia

    2015-01-01

    Sepsis is a syndrome with high morbidity, mortality and astronomical health care costs and it is challenging to diagnose both in humans and animals due to the lack of suitable diagnostic biomarkers. Although several types of proteins have been suggested as diagnostic biomarkers of sepsis, none of them were shown to be reliable for routine use in the clinical practice. Dogs with uterine bacterial infection called pyometra often develop sepsis and have been suggested as a natural model of sepsi...

  16. Sample phenotype clusters in high-density oligonucleotide microarray data sets are revealed using Isomap, a nonlinear algorithm

    Directory of Open Access Journals (Sweden)

    Malyj Wasyl

    2005-08-01

    Full Text Available Abstract Background Life processes are determined by the organism's genetic profile and multiple environmental variables. However the interaction between these factors is inherently non-linear 1. Microarray data is one representation of the nonlinear interactions among genes and genes and environmental factors. Still most microarray studies use linear methods for the interpretation of nonlinear data. In this study, we apply Isomap, a nonlinear method of dimensionality reduction, to analyze three independent large Affymetrix high-density oligonucleotide microarray data sets. Results Isomap discovered low-dimensional structures embedded in the Affymetrix microarray data sets. These structures correspond to and help to interpret biological phenomena present in the data. This analysis provides examples of temporal, spatial, and functional processes revealed by the Isomap algorithm. In a spinal cord injury data set, Isomap discovers the three main modalities of the experiment – location and severity of the injury and the time elapsed after the injury. In a multiple tissue data set, Isomap discovers a low-dimensional structure that corresponds to anatomical locations of the source tissues. This model is capable of describing low- and high-resolution differences in the same model, such as kidney-vs.-brain and differences between the nuclei of the amygdala, respectively. In a high-throughput drug screening data set, Isomap discovers the monocytic and granulocytic differentiation of myeloid cells and maps several chemical compounds on the two-dimensional model. Conclusion Visualization of Isomap models provides useful tools for exploratory analysis of microarray data sets. In most instances, Isomap models explain more of the variance present in the microarray data than PCA or MDS. Finally, Isomap is a promising new algorithm for class discovery and class prediction in high-density oligonucleotide data sets.

  17. Assessment of the sources of sedimentary organic matter in the Bohai Sea and the northern Yellow Sea using biomarker proxies

    Science.gov (United States)

    Xing, Lei; Hou, Di; Wang, Xinchen; Li, Li; Zhao, Meixun

    2016-07-01

    To evaluate the applicability of source proxies and to assess the sources of sedimentary organic matter in the Bohai Sea (BS) and the northern Yellow Sea (NYS), we analyzed total organic carbon (TOC), total nitrogen (TN), δ13C of TOC, n-alkanes, phytoplankton biomarkers, and glycerol dialkyl glycerol tetraethers (GDGTs) including branched GDGTs (brGDGTs) in 60 surface sediment samples covering the BS and the NYS. Spatial distribution comparison and principal component analysis indicate that with the exception of brGDGTs, terrestrial biomarkers have different spatial distribution pattern from marine biomarkers, suggesting that the sources control the distributions of these biomarkers in spite of hydrodynamic forcing. Significantly positive correlation (R2 = 0.5) between TOC normalized brGDGTs content and TOC normalized crenarchaeol content suggested in situ production of brGDGTs in the BS and the NYS. The δ13C values, TMBR [terrestrial and marine biomarker ratio: (C27 + C29 + C31n-alkanes)/[(C27 + C29 + C31n-alkanes) + (brassicasterol + dinosterol + alkenones)] ] and BIT (branched isoprenoid tetratether index) proxy indicated high terrestrial organic matter (TOM) input near the Huanghe River Estuary, while TOC/TON did not reveal similar distribution pattern. Quantitative estimates of TOM using a binary model revealed much higher TOM percentage from δ13C (avg. 58%) and TMBR (avg. 31%) than from BIT (avg. 7.4%). Our results suggest that, owing to significant in situ production of brGDGTs, the BIT is not a good proxy for indicating soil OM contribution in marine sediments from the BS and the NYS.

  18. High-throughput sequencing reveals differing immune responses in the intestinal mucosa of two inbred lines afflicted with necrotic enteritis.

    Science.gov (United States)

    Truong, Anh Duc; Hong, Yeong Ho; Lillehoj, Hyun S

    2015-08-15

    We investigated the necrotic enteritis (NE)-induced transcripts of immune-related genes in the intestinal mucosa of two highly inbred White Leghorn chicken lines, line 6.3 and line 7.2, which share the same MHC haplotype and show different levels of NE susceptibility using high-throughput RNA sequencing (RNA-Seq) technology. NE was induced by the previously described co-infection model using Eimeria maxima and Clostridium perfringens. The RNA-Seq generated over 38 million sequence reads for Marek's disease (MD)-resistant line 6.3 and over 40 million reads for the MD-susceptible line 7.2. Alignment of these sequences with the Gallus gallus genome database revealed the expression of over 29,900 gene transcripts induced by NE in these two lines, among which 7,841 genes were significantly upregulated and 2,919 genes were downregulated in line 6.3 chickens and 6,043 genes were significantly upregulated and 2,764 genes were downregulated in NE-induced line 7.2 compared with their uninfected controls. Analysis of 560 differentially expressed genes (DEGs) using the gene ontology database revealed annotations for 246 biological processes, 215 molecular functions, and 81 cellular components. Among the 53 cytokines and 96 cytokine receptors, 15 cytokines and 29 cytokine receptors were highly expressed in line 6.3, whereas the expression of 15 cytokines and 15 cytokine receptors was higher in line 7.2 than in line 6.3 (fold change ≥ 2, p<0.01). In a hierarchical cluster analysis of novel mRNAs, the novel mRNA transcriptome showed higher expression in line 6.3 than in line 7.2, which is consistent with the expression profile of immune-related target genes. In qRT-PCR and RNA-Seq analysis, all the genes examined showed similar responses to NE (correlation coefficient R=0.85-0.89, p<0.01) in both lines 6.3 and 7.2. This study is the first report describing NE-induced DEGs and novel transcriptomes using RNA-seq data from two inbred chicken lines showing different levels of NE

  19. Pyrosequencing reveals high-temperature cellulolytic microbial consortia in Great Boiling Spring after in situ lignocellulose enrichment.

    Directory of Open Access Journals (Sweden)

    Joseph P Peacock

    Full Text Available To characterize high-temperature cellulolytic microbial communities, two lignocellulosic substrates, ammonia fiber-explosion-treated corn stover and aspen shavings, were incubated at average temperatures of 77 and 85°C in the sediment and water column of Great Boiling Spring, Nevada. Comparison of 109,941 quality-filtered 16S rRNA gene pyrosequences (pyrotags from eight enrichments to 37,057 quality-filtered pyrotags from corresponding natural samples revealed distinct enriched communities dominated by phylotypes related to cellulolytic and hemicellulolytic Thermotoga and Dictyoglomus, cellulolytic and sugar-fermenting Desulfurococcales, and sugar-fermenting and hydrogenotrophic Archaeoglobales. Minor enriched populations included close relatives of hydrogenotrophic Thermodesulfobacteria, the candidate bacterial phylum OP9, and candidate archaeal groups C2 and DHVE3. Enrichment temperature was the major factor influencing community composition, with a negative correlation between temperature and richness, followed by lignocellulosic substrate composition. This study establishes the importance of these groups in the natural degradation of lignocellulose at high temperatures and suggests that a substantial portion of the diversity of thermophiles contributing to consortial cellulolysis may be contained within lineages that have representatives in pure culture.

  20. Microbial community structure of two freshwater sponges using Illumina MiSeq sequencing revealed high microbial diversity.

    Science.gov (United States)

    Gaikwad, Swapnil; Shouche, Yogesh S; Gade, Wasudev N

    2016-12-01

    Sponges are primitive metazoans that are known to harbour diverse and abundant microbes. All over the world attempts are being made to exploit these microbes for their biotechnological potential to produce, bioactive compounds and antimicrobial peptides. However, the majority of the studies are focussed on the marine sponges and studies on the freshwater sponges have been neglected so far. To increase our understanding of the microbial community structure of freshwater sponges, microbiota of two fresh water sponges namely, Eunapius carteri and Corvospongilla lapidosa is explored for the first time using Next Generation Sequencing (NGS) technology. Overall the microbial composition of these sponges comprises of 14 phyla and on an average, more than 2900 OTUs were obtained from C. lapidosa while E. carteri showed 980 OTUs which is higher than OTUs obtained in the marine sponges. Thus, our study showed that, fresh water sponges also posses highly diverse microbial community than previously thought and it is distinct from the marine sponge microbiota. The present study also revealed that microbial community structure of both the sponges is significantly different from each other and their respective water samples. In the present study, we have detected many bacterial lineages belonging to Firmicutes, Actinobacteria, Proteobacteria, Planctomycetes, etc. that are known to produce compounds of biotechnological importance. Overall, this study gives insight into the microbial composition of the freshwater sponges which is highly diverse and needs to be studied further to exploit their biotechnological capabilities. PMID:27299740

  1. Real-time CARS imaging reveals a calpain-dependent pathway for paranodal myelin retraction during high-frequency stimulation.

    Directory of Open Access Journals (Sweden)

    Terry B Huff

    Full Text Available High-frequency electrical stimulation is becoming a promising therapy for neurological disorders, however the response of the central nervous system to stimulation remains poorly understood. The current work investigates the response of myelin to electrical stimulation by laser-scanning coherent anti-Stokes Raman scattering (CARS imaging of myelin in live spinal tissues in real time. Paranodal myelin retraction at the nodes of Ranvier was observed during 200 Hz electrical stimulation. Retraction was seen to begin minutes after the onset of stimulation and continue for up to 10 min after stimulation was ceased, but was found to reverse after a 2 h recovery period. The myelin retraction resulted in exposure of Kv 1.2 potassium channels visualized by immunofluorescence. Accordingly, treating the stimulated tissue with a potassium channel blocker, 4-aminopyridine, led to the appearance of a shoulder peak in the compound action potential curve. Label-free CARS imaging of myelin coupled with multiphoton fluorescence imaging of immuno-labeled proteins at the nodes of Ranvier revealed that high-frequency stimulation induced paranodal myelin retraction via pathologic calcium influx into axons, calpain activation, and cytoskeleton degradation through spectrin break-down.

  2. Amplicon-Based Pyrosequencing Reveals High Diversity of Protistan Parasites in Ships' Ballast Water: Implications for Biogeography and Infectious Diseases.

    Science.gov (United States)

    Pagenkopp Lohan, K M; Fleischer, R C; Carney, K J; Holzer, K K; Ruiz, G M

    2016-04-01

    Ships' ballast water (BW) commonly moves macroorganisms and microorganisms across the world's oceans and along coasts; however, the majority of these microbial transfers have gone undetected. We applied high-throughput sequencing methods to identify microbial eukaryotes, specifically emphasizing the protistan parasites, in ships' BW collected from vessels calling to the Chesapeake Bay (Virginia and Maryland, USA) from European and Eastern Canadian ports. We utilized tagged-amplicon 454 pyrosequencing with two general primer sets, amplifying either the V4 or V9 domain of the small subunit (SSU) of the ribosomal RNA (rRNA) gene complex, from total DNA extracted from water samples collected from the ballast tanks of bulk cargo vessels. We detected a diverse group of protistan taxa, with some known to contain important parasites in marine systems, including Apicomplexa (unidentified apicomplexans, unidentified gregarines, Cryptosporidium spp.), Dinophyta (Blastodinium spp., Euduboscquella sp., unidentified syndinids, Karlodinium spp., Syndinium spp.), Perkinsea (Parvilucifera sp.), Opisthokonta (Ichthyosporea sp., Pseudoperkinsidae, unidentified ichthyosporeans), and Stramenopiles (Labyrinthulomycetes). Further characterization of groups with parasitic taxa, consisting of phylogenetic analyses for four taxa (Cryptosporidium spp., Parvilucifera spp., Labyrinthulomycetes, and Ichthyosporea), revealed that sequences were obtained from both known and novel lineages. This study demonstrates that high-throughput sequencing is a viable and sensitive method for detecting parasitic protists when present and transported in the ballast water of ships. These data also underscore the potential importance of human-aided dispersal in the biogeography of these microbes and emerging diseases in the world's oceans. PMID:26476551

  3. Bacterial pathogens and community composition in advanced sewage treatment systems revealed by metagenomics analysis based on high-throughput sequencing.

    Science.gov (United States)

    Lu, Xin; Zhang, Xu-Xiang; Wang, Zhu; Huang, Kailong; Wang, Yuan; Liang, Weigang; Tan, Yunfei; Liu, Bo; Tang, Junying

    2015-01-01

    This study used 454 pyrosequencing, Illumina high-throughput sequencing and metagenomic analysis to investigate bacterial pathogens and their potential virulence in a sewage treatment plant (STP) applying both conventional and advanced treatment processes. Pyrosequencing and Illumina sequencing consistently demonstrated that Arcobacter genus occupied over 43.42% of total abundance of potential pathogens in the STP. At species level, potential pathogens Arcobacter butzleri, Aeromonas hydrophila and Klebsiella pneumonia dominated in raw sewage, which was also confirmed by quantitative real time PCR. Illumina sequencing also revealed prevalence of various types of pathogenicity islands and virulence proteins in the STP. Most of the potential pathogens and virulence factors were eliminated in the STP, and the removal efficiency mainly depended on oxidation ditch. Compared with sand filtration, magnetic resin seemed to have higher removals in most of the potential pathogens and virulence factors. However, presence of the residual A. butzleri in the final effluent still deserves more concerns. The findings indicate that sewage acts as an important source of environmental pathogens, but STPs can effectively control their spread in the environment. Joint use of the high-throughput sequencing technologies is considered a reliable method for deep and comprehensive overview of environmental bacterial virulence.

  4. Characterization of polymorphisms and isoforms of the Clostridium perfringens phospholipase C gene (plc) reveals high genetic diversity.

    Science.gov (United States)

    Siqueira, Flávia F; Almeida, Marcelle O; Barroca, Tatiana M; Horta, Carolina C R; Carmo, Anderson O; Silva, Rodrigo O S; Pires, Prhiscylla S; Lobato, Francisco C F; Kalapothakis, Evanguedes

    2012-10-12

    Clostridium perfringens phospholipase C (Cp-PLC), also called alpha-toxin, is encoded by the plc gene and has been implicated in several diseases; however, only a few studies have described polymorphisms in this gene. The aim of this study was to analyze polymorphisms in the Cp-PLC nucleotide and amino acid sequences obtained from isolates from different regions and to compare them to Clostridium phospholipase C sequences deposited in the NCBI database. Environmental samples (sediment, poultry feed, sawdust) and stool samples (from poultry, bovine, swine, horse, caprine, bird, dog, rabbit, toucan) were collected from healthy and sick animals. A total of 73 isolates were analyzed with the majority of samples belonging to the toxin type A subtype and possessing the gene encoding for the beta-2 toxin. Comparison of plc gene sequences from respective isolates revealed a high genetic diversity in the nucleotide sequences of mature Cp-PLC. Sequence comparisons identified 30 amino acid substitutions and 34 isoforms including some isoforms with substitutions in amino acids critical to toxin function. Comparison of sequences obtained in this study to Cp-PLC sequences obtained from the NCBI database resulted in the identification of 11 common haplotypes and 22 new isoforms. Phylogenetic analysis of phospholipase C sequences obtained from other Clostridium species identified relationships previously described. This report describes a broad characterization of the genetic diversity in the C. perfringens plc gene resulting in the identification of various isoforms. A better understanding of sequences encoding phospholipase C isoforms may reveal changes associated with protein function and C. perfringens virulence.

  5. Oxygen restriction as challenge test reveals early high-fat-diet-induced changes in glucose and lipid metabolism.

    Science.gov (United States)

    Duivenvoorde, Loes P M; van Schothorst, Evert M; Derous, Davina; van der Stelt, Inge; Masania, Jinit; Rabbani, Naila; Thornalley, Paul J; Keijer, Jaap

    2015-06-01

    Challenge tests stress homeostasis and may reveal deviations in health that remain masked under unchallenged conditions. Ideally, challenge tests are non-invasive and applicable in an early phase of an animal experiment. Oxygen restriction (OxR; based on ambient, mild normobaric hypoxia) is a non-invasive challenge test that measures the flexibility to adapt metabolism. Metabolic inflexibility is one of the hallmarks of the metabolic syndrome. To test whether OxR can be used to reveal early diet-induced health effects, we exposed mice to a low-fat (LF) or high-fat (HF) diet for only 5 days. The response to OxR was assessed by calorimetric measurements, followed by analysis of gene expression in liver and epididymal white adipose tissue (eWAT) and serum markers for e.g. protein glycation and oxidation. Although HF feeding increased body weight, HF and LF mice did not differ in indirect calorimetric values under normoxic conditions and in a fasting state. Exposure to OxR; however, increased oxygen consumption and lipid oxidation in HF mice versus LF mice. Furthermore, OxR induced gluconeogenesis and an antioxidant response in the liver of HF mice, whereas it induced de novo lipogenesis and an antioxidant response in eWAT of LF mice, indicating that HF and LF mice differed in their adaptation to OxR. OxR also increased serum markers of protein glycation and oxidation in HF mice, whereas these changes were absent in LF mice. Cumulatively, OxR is a promising new method to test food products on potential beneficial effects for human health. PMID:24974902

  6. The human oral metaproteome reveals potential biomarkers for caries disease

    DEFF Research Database (Denmark)

    Belda-Ferre, Pedro; Williamson, James; Simón-Soro, Áurea;

    2015-01-01

    diversity. Healthy individuals appeared to have significantly higher amounts of L-lactate dehydrogenase and the arginine deiminase system, both implicated in pH buffering. Other proteins found to be at significantly higher levels in healthy individuals were involved in exopolysaccharide synthesis, iron...... metabolism and immune response. We applied multivariate analysis in order to find the minimum set of proteins that better allows discrimination of healthy and caries-affected dental plaque samples, detecting seven bacterial and five human protein functions that allow determining the health status...

  7. Acute-phase proteins, oxidative stress biomarkers, proinflammatory cytokines, and cardiac troponin in Arabian mares affected with pyometra.

    Science.gov (United States)

    El-Bahr, S M; El-Deeb, W M

    2016-09-01

    New biomarkers are essential for diagnosis of pyometra in mares. In this context, 12 subfertile Arabian mares suffered from pyometra were admitted to the Veterinary Teaching Hospital. The basis for diagnosis of pyometra was positive findings of clinical examination and rectal palpation. Blood samples were collected from diseased animals and from five Arabian healthy mares, which were considered as control group. Acute-phase proteins (APP), oxidative stress biomarkers, proinflammatory cytokines, and cardiac troponin I were estimated in the harvested sera of both groups. Clinical examination revealed purulent yellowish fluid discharged from vagina of affected animals and rectal palpation of the reproductive tract revealed uterine distention. The biochemical analysis of the serum revealed significant increase in cardiac troponin I, creatin kinase, alkaline phosphatase, malondialdehyde, tumor necrosis factor α, interleukins 6, prostaglandin F2α, haptoglobin, and serum amyloid A and significant decrease in reduced glutathione, superoxide dismutase (SOD), total antioxidant capacity, and nitric oxide (NO) of mares affected with pyometra compare to control. Cardiac troponin I was positively correlated with aspartate aminotransferase, creatin kinase, malondialdehyde, alkaline phosphatase, tumor necrosis factor α, interleukins 6, prostaglandin F2α, haptoglobin and serum amyloid A and negatively correlated with glutathione, superoxide dismutase, total antioxidant capacity and nitric oxide in serum of mares affected with pyometra. Moreover, there was high positive correlation between proinflammatory cytokines and APP in serum of mares affected with pyometra. The present study suggests cardiac troponin I together with APP, proinflammatory cytokines, and oxidative stress parameters as biomarkers for pyometra in Arabian mares. PMID:27177966

  8. High richness of ectomycorrhizal fungi and low host specificity in a coastal sand dune ecosystem revealed by network analysis.

    Science.gov (United States)

    Roy-Bolduc, Alice; Laliberté, Etienne; Hijri, Mohamed

    2016-01-01

    Ectomycorrhizal (EM) fungi are ubiquitous in temperate and boreal forests, comprising over 20,000 species forming root symbiotic associations with Pinaceae and woody angiosperms. As much as 100 different EM fungal species can coexist and interact with the same tree species, forming complex multispecies networks in soils. The degree of host specificity and structural properties of these interaction networks (e.g., nestedness and modularity) may influence plant and fungal community assembly and species coexistence, yet their structure has been little studied in northern coniferous forests, where trees depend on EM fungi for nutrient acquisition. We used high-throughput sequencing to characterize the composition and diversity of bulk soil and root-associated fungal communities in four co-occurring Pinaceae in a relic foredune plain located at Îles de la Madeleine, Québec, Canada. We found high EM fungal richness across the four hosts, with a total of 200 EM operational taxonomic units (OTUs), mainly belonging to the Agaricomycetes. Network analysis revealed an antinested pattern in both bulk soil and roots EM fungal communities. However, there was no detectable modularity (i.e., subgroups of interacting species) in the interaction networks, indicating a low level of specificity in these EM associations. In addition, there were no differences in EM fungal OTU richness or community structure among the four tree species. Limited shared resources and competitive exclusion typically restrict the number of taxa coexisting within the same niche. As such, our finding of high EM fungal richness and low host specificity highlights the need for further studies to determine the mechanisms enabling such a large number of EM fungal species to coexist locally on the same hosts. PMID:26811798

  9. Integrated use of biomarkers and condition indices in mussels (Mytilus galloprovincialis) for monitoring pollution and development of biomarker index to assess the potential toxic of coastal sites.

    Science.gov (United States)

    Benali, Imene; Boutiba, Zitouni; Merabet, Amina; Chèvre, Nathalie

    2015-06-15

    In this study, we are interested in spatial and temporal variations of the biological and physiological responses of mussels collected from contrasting marine sites regarding their levels of pollution. We measured both the conditions indices and the enzymatic biomarker expression: acetylcholinesterase (AChE), catalase (CAT) and glutathione S-transferase (GST) activity. The enzymatic biomarkers were chosen because they respond to environmental stress. Results show a significant interactions between biomarker variations and conditions indices in the industrial harbor site throughout the seasons. But no significant changes in the reference site. Furthermore, we classified the sites along the seasons according to their potential ecotoxicity, calculated based on the sum of the normalised values of the biomarkers. The results show a very high biomarker index in the impacted site with irregular changes between seasons. This biomarker index is therefore a valuable tool that could be used to classify the toxic potential of coastal sites.

  10. High-resolution crystal structure of Streptococcus pyogenes β-NAD{sup +} glycohydrolase in complex with its endogenous inhibitor IFS reveals a highly water-rich interface

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Ji Young; An, Doo Ri; Yoon, Hye-Jin [Seoul National University, Seoul 151-747 (Korea, Republic of); Kim, Hyoun Sook [Seoul National University, Seoul 151-747 (Korea, Republic of); Seoul National University, Seoul 151-742 (Korea, Republic of); Lee, Sang Jae [Seoul National University, Seoul 151-742 (Korea, Republic of); Im, Ha Na; Jang, Jun Young [Seoul National University, Seoul 151-747 (Korea, Republic of); Suh, Se Won, E-mail: sewonsuh@snu.ac.kr [Seoul National University, Seoul 151-747 (Korea, Republic of); Seoul National University, Seoul 151-747 (Korea, Republic of)

    2013-11-01

    The crystal structure of the complex between the C-terminal domain of Streptococcus pyogenes β-NAD{sup +} glycohydrolase and an endogenous inhibitor for SPN was determined at 1.70 Å. It reveals that the interface between the two proteins is highly rich in water molecules. One of the virulence factors produced by Streptococcus pyogenes is β-NAD{sup +} glycohydrolase (SPN). S. pyogenes injects SPN into the cytosol of an infected host cell using the cytolysin-mediated translocation pathway. As SPN is toxic to bacterial cells themselves, S. pyogenes possesses the ifs gene that encodes an endogenous inhibitor for SPN (IFS). IFS is localized intracellularly and forms a complex with SPN. This intracellular complex must be dissociated during export through the cell envelope. To provide a structural basis for understanding the interactions between SPN and IFS, the complex was overexpressed between the mature SPN (residues 38–451) and the full-length IFS (residues 1–161), but it could not be crystallized. Therefore, limited proteolysis was used to isolate a crystallizable SPN{sub ct}–IFS complex, which consists of the SPN C-terminal domain (SPN{sub ct}; residues 193–451) and the full-length IFS. Its crystal structure has been determined by single anomalous diffraction and the model refined at 1.70 Å resolution. Interestingly, our high-resolution structure of the complex reveals that the interface between SPN{sub ct} and IFS is highly rich in water molecules and many of the interactions are water-mediated. The wet interface may facilitate the dissociation of the complex for translocation across the cell envelope.

  11. High-frequency monitoring reveals nutrient sources and transport processes in an agriculture-dominated lowland water system

    Directory of Open Access Journals (Sweden)

    B. van der Grift

    2015-08-01

    Full Text Available Many agriculture-dominated lowland water systems worldwide suffer from eutrophication caused by high nutrient loads. Insight in the hydrochemical functioning of embanked polder catchments is highly relevant for improving the water quality in such areas. This paper introduces new insights in nutrient sources and transport processes in a low elevated polder in the Netherlands using high-frequency monitoring technology at the outlet, where the water is pumped into a higher situated lake, combined with a low-frequency water quality monitoring program at six locations within the drainage area. Seasonal trends and short scale temporal dynamics in concentrations indicated that the NO3 concentration at the pumping station originated from N-loss from agricultural lands. The NO3 loads appear as losses with drain water discharge after intensive rainfall events during the winter months due to preferential flow through the cracked clay soil. Transfer function-noise modelling of hourly NO3 concentrations reveals that a large part of the dynamics in NO3 concentrations during the winter months can be related to rainfall. The total phosphorus (TP concentration almost doubled during operation of the pumping station which points to resuspension of particulate P from channel bed sediments induced by changes in water flow due to pumping. Rainfall events that caused peaks in NO3 concentrations did not results in TP concentration peaks. The by rainfall induced and NO3 enriched quick interflow, may also be enriched in TP but this is then buffered in the water system due to sedimentation of particulate P. Increased TP concentrations associated with run-off events is only observed during a rainfall event at the end of a freeze–thaw cycle. All these observations suggest that the P retention potential of polder water systems is highly due to the artificial pumping regime that buffers high flows. As the TP concentration is affected by operation of the pumping station

  12. Enterococcus species diversity and molecular characterization of biomarker genes in Enterococcus faecalis in Port Blair Bay, Andaman and Nicobar Islands, India.

    Science.gov (United States)

    Meena, Balakrishnan; Anburajan, Lawrance; Sathish, Thadikamala; Raghavan, Rangamaran Vijaya; Jha, Dilip Kumar; Venkateshwaran, Pitchiah; Das, Apurba Kumar; Dheenan, Palaiya Sukumaran; Vinithkumar, Nambali Valsalan; Dharani, Gopal; Kirubagaran, Ramalingam

    2015-05-15

    This study was performed to evaluate the abundance and diversity of Enterococcus sp. and the distribution of biomarker genes in Enterococcus faecalis in Port Blair Bay, Andaman and Nicobar Islands. The Enterococcus sp. densities at the seven sampling stations were highly influenced by tidal fluctuations and season. The distributions and diversities of species varied in the inner and outer regions of Port Blair Bay. Among the 1816 total isolates, the occurrence of fecal Enterococcus was high (1.78×10(4) CFU/100 mL) in Phoenix Bay. Moreover, 67.76% of the isolates were identified as Enterococcus, and the most frequently identified species were E. hirae, E. avium and E. faecalis. Assessments of antibiotic resistance and biomarker genes revealed the maximum occurrence in the Aberdeen Bay isolates. The most prevalent biomarker genes observed in the E. faecalis isolates were gelE and asa1, whereas cyl was not found among the isolates. In silico sequence analysis of biomarker genes of E. faecalis also revealed that they are evolutionarily well conserved with those of earlier reports. Further, multivariate analysis distinguished the JB, PB and OS stations from the other stations according to distinctive microbial densities and compositions. In addition, the Shannon-Wiener diversity indices and box-whisker plots further facilitated and supported the multivariate results.

  13. cNEUPRO: Novel Biomarkers for Neurodegenerative Diseases

    Directory of Open Access Journals (Sweden)

    Philipp Spitzer

    2010-01-01

    Full Text Available “clinical NEUroPROteomics of neurodegenerative diseases” (cNEUPRO is a Specific Targeted Research Project (STREP within the sixth framework program of the European Commission dedicated to the search for novel biomarker candidates for Alzheimer's disease and other neurodegenerative diseases. The ultimate goal of cNEUPRO is to identify one or more valid biomarker(s in blood and CSF applicable to support the early and differential diagnosis of dementia disorders. The consortium covers all steps required for the discovery of novel biomarker candidates such as acquisition of high quality CSF and blood samples from relevant patient groups and controls, analysis of body fluids by various methods, and finally assay development and assay validation. Here we report the standardized procedures for diagnosis and preanalytical sample-handling within the project, as well as the status of the ongoing research activities and some first results.

  14. The Present and Future of Prostate Cancer Urine Biomarkers

    Directory of Open Access Journals (Sweden)

    Jeremy Clark

    2013-06-01

    Full Text Available In order to successfully cure patients with prostate cancer (PCa, it is important to detect the disease at an early stage. The existing clinical biomarkers for PCa are not ideal, since they cannot specifically differentiate between those patients who should be treated immediately and those who should avoid over-treatment. Current screening techniques lack specificity, and a decisive diagnosis of PCa is based on prostate biopsy. Although PCa screening is widely utilized nowadays, two thirds of the biopsies performed are still unnecessary. Thus the discovery of non-invasive PCa biomarkers remains urgent. In recent years, the utilization of urine has emerged as an attractive option for the non-invasive detection of PCa. Moreover, a great improvement in high-throughput “omic” techniques has presented considerable opportunities for the identification of new biomarkers. Herein, we will review the most significant urine biomarkers described in recent years, as well as some future prospects in that field.

  15. HCC Biomarkers in China and Taiwan

    Directory of Open Access Journals (Sweden)

    Regina M. Santella

    2007-02-01

    Full Text Available

    A number of different types of biomarkers have been used to understand the etiology and progression of hepatocellular cancer (HCC. Perhaps the most well known are the serum/ plasma markers of HBV or HCV infection. These markers include analysis of viral DNA or proteins or antibodies produced against the viral proteins. HBV surface antigen (HBsAg is most frequently used to determine chronic infection with high or low viral replication, while HBeAg is a measure of chronic infection with high viral replication. Analysis of antibodies includes measurement of anti-HBV core antigen, anti-HBV e antigen and anti-HBsAg. The response to immunization can be monitored by analysis of anti-HBsAg. The other major classes of biomarkers used in studies of HCC are biomarkers of exposure to environmental, lifestyle or dietary carcinogens, biomarkers of oxidative stress and early biologic response. In addition, studies of genetic susceptibility have studied polymorphisms in a number of pathways and their role in HCC risk. The biomarkers of exposure include the measurement of carcinogens in urine and carcinogen-DNA and protein adducts. Examples are measurement of aflatoxin and polycyclic aromatic hydrocarbon metabolites, and DNA and protein adducts.

    Biomarkers of oxidative stress include urinary isoprostanes and 8-oxodeoxyguanosine and oxidized plasma proteins. Most of these assays are immunologic although the use of high performance liquid chromatograph (HPLC as well as gas chromatography/mass spectroscopy (GC/MS have been utilized. In nested case-control studies, many of these markers are associated with elevated risk. For example, elevated aflatoxin and polycyclic aromatic hydrocarbon-albumin adducts, aflatoxin metabolites in urine and urinary isoprostanes were observed in baseline samples from

  16. Effects of increasing temperatures on biomarker responses and accumulation of hazardous substances in rope mussels (Mytilus galloprovincialis) from Bizerte lagoon.

    Science.gov (United States)

    Kamel, Naouel; Burgeot, Thierry; Banni, Mohamed; Chalghaf, Mohamed; Devin, Simon; Minier, Christophe; Boussetta, Hamadi

    2014-05-01

    This study examined the influence of increasing temperatures in spring and summer on biochemical biomarkers in Mytilus galloprovincialis mussels sampled from Bizerte lagoon (northern Tunisia). Spatial and seasonal variations in a battery of seven biomarkers were analyzed in relation to environmental parameters (temperature, salinity, and pH), physiological status (condition and gonad indexes), stress on stress (SoS), and chemical contaminant levels (heavy metals, polycyclic aromatic hydrocarbons (PAHs), and PCBs) in digestive glands. Integrated biological response (IBR) was calculated using seven biomarkers (acetylcholinesterase (AChE), benzo[a]pyrene hydroxylase (BPH), multixenobiotic resistance (MXR), glutathione S-transferase (GST), catalase (CAT), malondialdehyde (MDA), and metallothioneins (MT). Seasonal variations in biological response were determined during a critical period between spring and summer at two sites, where chemical contamination varies by a factor of 2 for heavy metals and a factor 2.5 for PAHs. The analysis of a battery of biomarkers was combined with the measurement of physiological parameters at both sites, in order to quantify a maximum range of metabolic regulation with a temperature increase of 11 °C between May and August. According to our results, the MT, MDA, CAT, and AChE biomarkers showed the highest amplitude during the 11 °C rise, while the BPH, GST, and MXR biomarkers showed the lowest amplitude. Metabolic amplitude measured with the IBR at Menzel Abdelrahmen-the most severely contaminated station-revealed the highest metabolic stress in Bizerte lagoon in August, when temperatures were highest 29.1 °C. This high metabolic rate was quantified for each biomarker in the North African lagoon area and confirmed in August, when the highest IBR index values were obtained at the least contaminated site 2 (IBR = 9.6) and the most contaminated site 1 (IBR = 19.6). The combined effects of chemical contamination and increased salinity

  17. Biomarker in archaeological soils

    Science.gov (United States)

    Wiedner, Katja; Glaser, Bruno; Schneeweiß, Jens

    2015-04-01

    The use of biomarkers in an archaeological context allow deeper insights into the understanding of anthropogenic (dark) earth formation and from an archaeological point of view, a completely new perspective on cultivation practices in the historic past. During an archaeological excavation of a Slavic settlement (10th/11th C. A.D.) in Brünkendorf (Wendland region in Northern Germany), a thick black soil (Nordic Dark Earth) was discovered that resembled the famous terra preta phenomenon. For the humid tropics, terra preta could act as model for sustainable agricultural practices and as example for long-term CO2-sequestration into terrestrial ecosystems. The question was whether this Nordic Dark Earth had similar properties and genesis as the famous Amazonian Dark Earth in order to find a model for sustainable agricultural practices and long term CO2-sequestration in temperate zones. For this purpose, a multi-analytical approach was used to characterize the sandy-textured Nordic Dark Earth in comparison to less anthropogenically influenced soils in the adjacent area in respect of ecological conditions (e.g. amino sugar), input materials (faeces) and the presence of stable soil organic matter (black carbon). Amino sugar analyses showed that Nordic Dark Earth contained higher amounts of microbial residues being dominated by soil fungi. Faecal biomarkers such as stanols and bile acids indicated animal manure from omnivores and herbivores but also human excrements. Black carbon content of about 30 Mg ha-1 in the Nordic Dark Earth was about four times higher compared to the adjacent soil and in the same order of magnitude compared to terra preta. Our data strongly suggest parallels to anthropogenic soil formation in Amazonia and in Europe by input of organic wastes, faecal material and charred organic matter. An obvious difference was that in terra preta input of human-derived faecal material dominated while in NDE human-derived faecal material played only a minor role

  18. Circulating Biomarkers of Immune Activation, Oxidative Stress and Inflammation Characterize Severe Canine Visceral Leishmaniasis

    Science.gov (United States)

    Solcà, Manuela S.; Andrade, Bruno B.; Abbehusen, Melissa Moura Costa; Teixeira, Clarissa R.; Khouri, Ricardo; Valenzuela, Jesus G.; Kamhawi, Shaden; Bozza, Patrícia Torres; Fraga, Deborah Bittencourt Mothé; Borges, Valeria Matos; Veras, Patrícia Sampaio Tavares; Brodskyn, Claudia Ida

    2016-01-01

    Clinical manifestations in canine visceral leishmaniasis (CVL) have not been clearly associated with immunological status or disease progression. We simultaneously assessed biomarkers of inflammation, immune activation, oxidative stress, and anti-sand fly saliva IgG concentrations in dog sera with different clinical manifestations to characterize a biosignature associated with CVL severity. In a cross-sectional exploratory study, a random population of 70 dogs from an endemic area in Brazil was classified according to CVL clinical severity and parasitological evaluation. A panel of biomarkers and anti–sand fly saliva IgG were measured in canine sera. Assessment of protein expression of profile biomarkers identified a distinct biosignature that could cluster separately animal groups with different clinical scores. Increasing severity scores were associated with a gradual decrease of LTB4 and PGE2, and a gradual increase in CXCL1 and CCL2. Discriminant analyses revealed that combined assessment of LTB4, PGE2 and CXCL1 was able to distinguish dogs with different clinical scores. Dogs with the highest clinical score values also exhibited high parasite loads and higher concentrations of anti-saliva antibodies. Our findings suggest CVL clinical severity is tightly associated with a distinct inflammatory profile hallmarked by a differential expression of circulating eicosanoids and chemokines. PMID:27595802

  19. Biomarkers in natural fish populations indicate adverse biological effects of offshore oil production.

    Directory of Open Access Journals (Sweden)

    Lennart Balk

    Full Text Available BACKGROUND: Despite the growing awareness of the necessity of a sustainable development, the global economy continues to depend largely on the consumption of non-renewable energy resources. One such energy resource is fossil oil extracted from the seabed at offshore oil platforms. This type of oil production causes continuous environmental pollution from drilling waste, discharge of large amounts of produced water, and accidental spills. METHODS AND PRINCIPAL FINDINGS: Samples from natural populations of haddock (Melanogrammus aeglefinus and Atlantic cod (Gadus morhua in two North Sea areas with extensive oil production were investigated. Exposure to and uptake of polycyclic aromatic hydrocarbons (PAHs were demonstrated, and biomarker analyses revealed adverse biological effects, including induction of biotransformation enzymes, oxidative stress, altered fatty acid composition, and genotoxicity. Genotoxicity was reflected by a hepatic DNA adduct pattern typical for exposure to a mixture of PAHs. Control material was collected from a North Sea area without oil production and from remote Icelandic waters. The difference between the two control areas indicates significant background pollution in the North Sea. CONCLUSION: It is most remarkable to obtain biomarker responses in natural fish populations in the open sea that are similar to the biomarker responses in fish from highly polluted areas close to a point source. Risk assessment of various threats to the marine fish populations in the North Sea, such as overfishing, global warming, and eutrophication, should also take into account the ecologically relevant impact of offshore oil production.

  20. Circulating Biomarkers of Immune Activation, Oxidative Stress and Inflammation Characterize Severe Canine Visceral Leishmaniasis

    Science.gov (United States)

    Solcà, Manuela S.; Andrade, Bruno B.; Abbehusen, Melissa Moura Costa; Teixeira, Clarissa R.; Khouri, Ricardo; Valenzuela, Jesus G.; Kamhawi, Shaden; Bozza, Patrícia Torres; Fraga, Deborah Bittencourt Mothé; Borges, Valeria Matos; Veras, Patrícia Sampaio Tavares; Brodskyn, Claudia Ida

    2016-09-01

    Clinical manifestations in canine visceral leishmaniasis (CVL) have not been clearly associated with immunological status or disease progression. We simultaneously assessed biomarkers of inflammation, immune activation, oxidative stress, and anti-sand fly saliva IgG concentrations in dog sera with different clinical manifestations to characterize a biosignature associated with CVL severity. In a cross-sectional exploratory study, a random population of 70 dogs from an endemic area in Brazil was classified according to CVL clinical severity and parasitological evaluation. A panel of biomarkers and anti-sand fly saliva IgG were measured in canine sera. Assessment of protein expression of profile biomarkers identified a distinct biosignature that could cluster separately animal groups with different clinical scores. Increasing severity scores were associated with a gradual decrease of LTB4 and PGE2, and a gradual increase in CXCL1 and CCL2. Discriminant analyses revealed that combined assessment of LTB4, PGE2 and CXCL1 was able to distinguish dogs with different clinical scores. Dogs with the highest clinical score values also exhibited high parasite loads and higher concentrations of anti-saliva antibodies. Our findings suggest CVL clinical severity is tightly associated with a distinct inflammatory profile hallmarked by a differential expression of circulating eicosanoids and chemokines.

  1. Urinary Biomarkers of Brain Diseases

    Directory of Open Access Journals (Sweden)

    Manxia An

    2015-12-01

    Full Text Available Biomarkers are the measurable changes associated with a physiological or pathophysiological process. Unlike blood, urine is not subject to homeostatic mechanisms. Therefore, greater fluctuations could occur in urine than in blood, better reflecting the changes in human body. The roadmap of urine biomarker era was proposed. Although urine analysis has been attempted for clinical diagnosis, and urine has been monitored during the progression of many diseases, particularly urinary system diseases, whether urine can reflect brain disease status remains uncertain. As some biomarkers of brain diseases can be detected in the body fluids such as cerebrospinal fluid and blood, there is a possibility that urine also contain biomarkers of brain diseases. This review summarizes the clues of brain diseases reflected in the urine proteome and metabolome.

  2. Biomarkers of latent TB infection

    DEFF Research Database (Denmark)

    Ruhwald, Morten; Ravn, Pernille

    2009-01-01

    For the last 100 years, the tuberculin skin test (TST) has been the only diagnostic tool available for latent TB infection (LTBI) and no biomarker per se is available to diagnose the presence of LTBI. With the introduction of M. tuberculosis-specific IFN-gamma release assays (IGRAs), a new area of...... in vitro immunodiagnostic tests for LTBI based on biomarker readout has become a reality. In this review, we discuss existing evidence on the clinical usefulness of IGRAs and the indefinite number of potential new biomarkers that can be used to improve diagnosis of latent TB infection. We also...... present early data suggesting that the monocyte-derived chemokine inducible protein-10 may be useful as a novel biomarker for the immunodiagnosis of latent TB infection....

  3. High-resolution bathymetry reveals contrasting landslide activity shaping the walls of the Mid-Atlantic Ridge axial valley

    Science.gov (United States)

    Cannat, Mathilde; Mangeney, Anne; OndréAs, HéLèNe; Fouquet, Yves; Normand, Alain

    2013-04-01

    Axial valleys are found along most slow-spreading mid-ocean ridges and are one of the most prominent topographic features on Earth. In this paper, we present the first deep-tow swath bathymetry for the axial valley walls of the Mid-Atlantic Ridge. These data allow us to analyze axial valley wall morphology with a very high resolution (0.5 to 1 m compared to ≥ 50 m for shipboard multibeam bathymetry), revealing the role played by landslides. Slow-spreading ridge axial valleys also commonly expose mantle-derived serpentinized peridotites in the footwalls of large offset normal faults (detachments). In our map of the Ashadze area (lat. 13°N), ultramafic outcrops have an average slope of 18° and behave as sliding deformable rock masses, with little fragmentation. By contrast, the basaltic seafloor in the Krasnov area (lat. 16°38'N) has an average slope of 32° and the erosion of the steep basaltic rock faces leads to extensive fragmentation, forming debris with morphologies consistent with noncohesive granular flow. Comparison with laboratory experiments suggests that the repose angle for this basaltic debris is > 25°. We discuss the interplay between the normal faults that bound the axial valley and the observed mass wasting processes. We propose that, along axial valley walls where serpentinized peridotites are exposed by detachment faults, mass wasting results in average slopes ≤ 20°, even in places where the emergence angle of the detachment is larger.

  4. Boundary layer jet on the lee side of Western Ghats during southwest monsoon as revealed by high resolution sodar winds

    Science.gov (United States)

    Murthy, B. S.; Latha, R.; Sreeja, P.

    2013-12-01

    High resolution winds measured by SOund Detection And Ranging (SODAR) in the atmospheric boundary layer (ABL) over Pune, located on the lee side of the Western Ghats (WG) reveal the presence of Low Level Jet (LLJ) in the atmospheric boundary layer (hereafter called as boundary layer jet, BLJ) during southwest monsoon (June-August) for three consecutive years, viz., 2009, 2010 and 2011. Its prevalence only during the monsoon period, even at monthly scale indicates a possible interconnection to another LLJ, Somali jet, present during this period. An investigation is done to look into the dominant mechanisms those could result in such an occurrence in the lee side of the WG. Baroclinicity, inertial oscillation, upstream topographic blocking and variability of Somali jet are the mechanisms considered. Baroclinicity due to east-west temperature gradient on the leeside to induce thermal wind and inertial oscillation appear to have a little role in LLJ formation. However, Somali jet seems to govern the BLJ on the lee side through its dynamical interaction with the WG causing flow reversal and wave breaking above WG and inducing acceleration of downslope winds. The height and sharpness of Somali jet core on the windward side and its magnitude as well as direction with respect to WG are observed to determine the strength of BLJ on the lee side illustrating the signature of the summer monsoon in the boundary layer over Pune.

  5. Assessing subaqueous mudslide hazard on the Mississippi River delta front, Part 2: Insights revealed through high-resolution geophysical surveying

    Science.gov (United States)

    Obelcz, J.; Xu, K.; Bentley, S. J.; Georgiou, I. Y.; Maloney, J. M.; Miner, M. D.; Hanegan, K.; Keller, G.

    2014-12-01

    The northern Gulf of Mexico, including the subaqueous Mississippi River delta front (MRDF), has been productive for oil and gas development since the early 1900s. In 1969 cyclic seafloor wave loading associated with the passage of Hurricane Camille triggered subaqueous mudflows across the MRDF, destroying several offshore oil platforms. This incident spurred geophysical and geotechnical studies of the MRDF, which found that the delta front is prone to mass failures on gentle gradients (survey area can be classified into four primary sedimentary facies: mudflow gullies, mudflow lobes, undisturbed prodelta, and undisturbed delta front. Subbottom profiles reveal extensive biogenic gas from 20 to about 80 m water depths on the delta front; sidescan data show a variety of bottleneck slides, mudflow gullies and mudflow noses. Previous studies have attempted to constrain the periodicity and magnitude of subaqueous mudslides on the MRDF. However, large age gaps and varied resolution between datasets result in ambiguity regarding the cause and magnitude of observed bathymetric changes. We present high-temporal resolution MRDF bathymetric variations from 2005 (post Hurricane Katrina), 2009 (relatively quiescent storm period), and 2014 (post 2011 Mississippi River flood). These data yield better magnitude and timing estimates of mass movements. This exercise represents a first step towards (1) assembling a comprehensive geologic dataset upon which future MRDF geohazard assessments can be founded, and (2) understanding the dynamics of a massive passive margin deltaic lobe entering a phase of decline.

  6. ALMA reveals optically thin, highly excited CO gas in the jet-driven winds of the galaxy IC5063

    CERN Document Server

    Dasyra, K M; Oosterloo, T; Oonk, J B R; Morganti, R; Salome, P; Vlahakis, N

    2016-01-01

    Using CO (4-3) and (2-1) Atacama Large Millimeter Array (ALMA) data, we prove that the molecular gas in the jet-driven winds of the galaxy IC5063 is more highly excited than the rest of the molecular gas in the disk of the same galaxy. On average, the CO (4-3) / CO (2-1) flux ratio is 1 for the disk and 5 for the jet accelerated or impacted gas. Spatially-resolved maps reveal that in regions associated with winds, the CO (4-3) / CO (2-1) flux ratio significantly exceeds the upper limit of 4 for optically thick gas. It frequently takes values between 5 and 11, and it occasionally further approaches the upper limit of 16 for optically thin gas. Excitation temperatures of 30-100 K are common for the molecules in these regions. If all of the outflowing molecular gas is optically thin, at 30-50 K, then its mass is 2*10^6 M_sun. This lower mass limit is an order of magnitude below the mass derived from the CO (2-1) flux in case of optically thick gas. Our result suggests that molecular wind masses may be overestima...

  7. Phenothiazine Neuroleptics Signal to the Human Insulin Promoter as Revealed by a Novel High-Throughput Screen

    Science.gov (United States)

    KISELYUK, ALICE; FARBER-KATZ, SUZETTE; COHEN, TOM; LEE, SEUNG-HEE; GERON, IFAT; AZIMI, BEHRAD; HEYNEN-GENEL, SUSANNE; SINGER, ODED; PRICE, JEFFREY; MERCOLA, MARK; ITKIN-ANSARI, PAMELA; LEVINE, FRED

    2012-01-01

    A number of diabetogenic stimuli interact to influence insulin promoter activity, making it an attractive target for both mechanistic studies and therapeutic interventions. High-throughput screening (HTS) for insulin promoter modulators has the potential to reveal novel inputs into the control of that central element of the pancreatic β-cell. A cell line from human islets in which the expression of insulin and other β-cell-restricted genes are modulated by an inducible form of the bHLH transcription factor E47 was developed. This cell line, T6PNE, was adapted for HTS by transduction with a vector expressing green fluorescent protein under the control of the human insulin promoter. The resulting cell line was screened against a library of known drugs for those that increase insulin promoter activity. Members of the phenothiazine class of neuroleptics increased insulin gene expression upon short-term exposure. Chronic treatment, however, resulted in suppression of insulin promoter activity, consistent with the effect of phenothiazines observed clinically to induce diabetes in chronically treated patients. In addition to providing insights into previously unrecognized targets and mechanisms of action of phenothiazines, the novel cell line described here provides a broadly applicable platform for mining new molecular drug targets and central regulators of β-cell differentiated function. PMID:20547533

  8. Closing the gaps on human chromosome 19 revealed genes with a high density of repetitive tandemly arrayed elements.

    Energy Technology Data Exchange (ETDEWEB)

    Leem, Sun-Hee; Kouprina, Natalay; Grimwood, Jane; Kim, Jung-Hyun; Mullokandov, Michael; Yoon, Young-Ho; Chae, Ji-Youn; Morgan, Jenna; Lucas, Susan; Richardson, Paul; Detter, Chris; Glavina, Tijana; Rubin, Eddy; Barrett, J. Carl; Larionov, Vladimir

    2003-09-01

    The reported human genome sequence includes about 400 gaps of unknown sequence that were not found in the bacterial artificial chromosome (BAC) and cosmid libraries used for sequencing of the genome. These missing sequences correspond to {approx} 1 percent of euchromatic regions of the human genome. Gap filling is a laborious process because it relies on analysis of random clones of numerous genomic BAC or cosmid libraries. In this work we demonstrate that closing the gaps can be accelerated by a selective recombinational capture of missing chromosomal segments in yeast. The use of both methodologies allowed us to close the four remaining gaps on the human chromosome 19. Analysis of the gap sequences revealed that they contain several abnormalities that could result in instability of the sequences in microbe hosts, including large blocks of micro- and minisatellites and a high density of Alu repeats. Sequencing of the gap regions, in both BAC and YAC forms, allowed us to generate a complete sequence of four genes, including the neuronal cell signaling gene SCK1/SLI. The SCK1/SLI gene contains a record number of minisatellites, most of which are polymorphic and transmitted through meiosis following a Mendelian inheritance. In conclusion, the use of the alternative recombinational cloning system in yeast may greatly accelerate work on closing the remaining gaps in the human genome (as well as in other complex genomes) to achieve the goal of annotation of all human genes.

  9. High-resolution time series of vessel density in Kenyan mangrove trees reveal a link with climate.

    Science.gov (United States)

    Verheyden, Anouk; De Ridder, Fjo; Schmitz, Nele; Beeckman, Hans; Koedam, Nico

    2005-08-01

    Tropical trees are often excluded from dendrochronological investigations because of a lack of distinct growth ring boundaries, causing a gap in paleoclimate reconstructions from tropical regions. The potential use of time series of vessel features (density, diameter, surface area and hydraulic conductivity) combined with spectral analysis as a proxy for environmental conditions in the mangrove Rhizophora mucronata was investigated. Intra-annual differences in the vessel features revealed a trade-off between hydraulic efficiency (large vessels) during the rainy season and hydraulic safety (small, more numerous vessels) during the dry season. In addition to the earlywood-latewood variations, a semiannual signal was discovered in the vessel density and diameters after Fourier transformation. The similarity in the Fourier spectra of the vessel features and the climate data, in particular mean relative humidity and precipitation, provides strong evidence for a climatic driving force for the intra-annual variability of the vessel features. The high-resolution approach used in this study, in combination with spectral analysis, may have great potential for the study of climate variability in tropical regions. PMID:15998396

  10. Swift reveals the eclipsing nature of the high mass X-ray binary IGR~J16195-4945

    CERN Document Server

    Cusumano, G; Segreto, A; D'Aì, A

    2016-01-01

    IGR J16195-4945 is a hard X-ray source discovered by INTEGRAL during the Core Program observations performed in 2003. We analyzed the X-ray emission of this source exploiting the Swift-BAT survey data from December 2004 to March 2015, and all the available Swift-XRT pointed observations. The source is detected at a high significance level in the 123-month BAT survey data, with an average 15-150 keV flux of the source of ~1.6 mCrab. The timing analysis on the BAT data reveals with a significance higher than 6 standard deviations the presence of a modulated signal with a period of 3.945 d, that we interpret as the orbital period of the binary system. The folded light curve shows a flat profile with a narrow full eclipse lasting ~3.5% of the orbital period. We requested phase-constrained XRT observations to obtain a more detailed characterization of the eclipse in the soft X-ray range. Adopting resonable guess values for the mass and radius of the companion star, we derive a semi-major orbital axis of ~31 R_sun,...

  11. Natural high pCO2 increases autotrophy in Anemonia viridis (Anthozoa) as revealed from stable isotope (C, N) analysis.

    Science.gov (United States)

    Horwitz, Rael; Borell, Esther M; Yam, Ruth; Shemesh, Aldo; Fine, Maoz

    2015-01-01

    Contemporary cnidarian-algae symbioses are challenged by increasing CO2 concentrations (ocean warming and acidification) affecting organisms' biological performance. We examined the natural variability of carbon and nitrogen isotopes in the symbiotic sea anemone Anemonia viridis to investigate dietary shifts (autotrophy/heterotrophy) along a natural pCO2 gradient at the island of Vulcano, Italy. δ(13)C values for both algal symbionts (Symbiodinium) and host tissue of A. viridis became significantly lighter with increasing seawater pCO2. Together with a decrease in the difference between δ(13)C values of both fractions at the higher pCO2 sites, these results indicate there is a greater net autotrophic input to the A. viridis carbon budget under high pCO2 conditions. δ(15)N values and C/N ratios did not change in Symbiodinium and host tissue along the pCO2 gradient. Additional physiological parameters revealed anemone protein and Symbiodinium chlorophyll a remained unaltered among sites. Symbiodinium density was similar among sites yet their mitotic index increased in anemones under elevated pCO2. Overall, our findings show that A. viridis is characterized by a higher autotrophic/heterotrophic ratio as pCO2 increases. The unique trophic flexibility of this species may give it a competitive advantage and enable its potential acclimation and ecological success in the future under increased ocean acidification. PMID:25739995

  12. Decapitation of high-altitude glaciers on the Tibetan Plateau revealed by ice core tritium and mercury records

    Directory of Open Access Journals (Sweden)

    S. C. Kang

    2015-01-01

    Full Text Available Two ice cores were retrieved from high elevations (~ 5800 m a.s.l. at Mt. Nyainqentanglha and Mt. Geladaindong in the southern to inland Tibetan Plateau. The combined analysis of tritium (3H, 210Pb, mercury tracers, along with other chemical records, revealed that the two coring sites had not received net ice accumulation since at least the 1950s and 1980s, respectively, implying an annual ice loss rate of more than several hundred millimeter water equivalent over these periods. Both mass balance modeling at the sites and in situ data from nearby glaciers confirmed a continuously negative mass balance (or mass loss in the region due to the dramatic warming in the last decades. Along with a recent report on Naimona'nyi Glacier in the Himalaya, the findings suggest that glacier decapitation (i.e., the loss of the accumulation zone is a wide-spread phenomenon from the southern to inland Tibetan Plateau even at the summit regions. This raises concerns over the rapid rate of glacier ice loss and associated changes in surface glacier runoff, water availability, and sea levels.

  13. Suzaku Observations of Luminous Quasars: Revealing the Nature of High-Energy Blazar Emission in Quiescent States

    CERN Document Server

    Abdo, A A; Sikora, M; Schady, P; Roming, P; Chester, M M; Maraschi, L

    2010-01-01

    We present the results from the Suzaku X-ray observations of five flat-spectrum radio quasars (FSRQs), namely PKS0208-512, Q0827+243, PKS1127-145, PKS1510-089 and 3C 454.3. All these sources were additionally monitored simultaneously or quasi-simultaneously by the Fermi satellite in gamma-rays and the Swift UVOT in the UV and optical bands, respectively. We constructed their broad-band spectra covering the frequency range from 10^14 Hz up to 10^25 Hz, and those reveal the nature of high-energy emission of luminous blazars in their low-activity states. The analyzed X-ray spectra are well fitted by a power-law model with photoelectric absorption. In the case of PKS0208-512, PKS1127-145, and 3C 454.3, the X-ray continuum showed indication of hard-ening at low-energies. Moreover, when compared with the previous X-ray observations, we see a significantly increasing contribution of low-energy photons to the total X-ray fluxes when the sources are getting fainter. The same behavior can be noted in the Suzaku data al...

  14. High-resolution CO observation of the carbon star CIT 6 revealing the spiral structure and a nascent bipolar outflow

    CERN Document Server

    Kim, Hyosun; Hirano, Naomi; Zhao-Geisler, Ronny; Trejo, Alfonso; Yen, Hsi-Wei; Taam, Ronald E; Kemper, Francisca; Kim, Jongsoo; Byun, Do-Young; Liu, Tie

    2015-01-01

    CIT 6 is a carbon star in the transitional phase from the asymptotic giant branch (AGB) to the protoplanetary nebulae (pPN). Observational evidences of two point sources in the optical, circumstellar arc segments in an HC$_3$N line emission, and a bipolar nebula in near-infrared provide strong support for the presence of a binary companion. Hence, CIT 6 is very attractive for studying the role of companions in the AGB-pPN transition. We have carried out high resolution $^{12}$CO $J=2-1$ and $^{13}$CO $J=2-1$ observations of CIT 6 with the Submillimeter Array combined with the Submillimeter Telescope (single-dish) data. The $^{12}$CO channel maps reveal a spiral-shell pattern connecting the HC$_3$N segments in a continuous form, and an asymmetric outflow corresponding to the near-infrared bipolar nebula. Rotation of the $^{12}$CO channel peak position may be related to the inner spiral winding and/or the bipolar outflow. An eccentric orbit binary is suggested for the presences of an anisotropic mass loss to th...

  15. High-frequency monitoring reveals nutrient sources and transport processes in an agriculture-dominated lowland water system

    Science.gov (United States)

    van der Grift, Bas; Broers, Hans Peter; Berendrecht, Wilbert; Rozemeijer, Joachim; Osté, Leonard; Griffioen, Jasper

    2016-05-01

    Many agriculture-dominated lowland water systems worldwide suffer from eutrophication caused by high nutrient loads. Insight in the hydrochemical functioning of embanked polder catchments is highly relevant for improving the water quality in such areas or for reducing export loads to downstream water bodies. This paper introduces new insights in nutrient sources and transport processes in a polder in the Netherlands situated below sea level using high-frequency monitoring technology at the outlet, where the water is pumped into a higher situated lake, combined with a low-frequency water quality monitoring programme at six locations within the drainage area. Seasonal trends and short-scale temporal dynamics in concentrations indicated that the NO3 concentration at the pumping station originated from N loss from agricultural lands. The NO3 loads appear as losses via tube drains after intensive rainfall events during the winter months due to preferential flow through the cracked clay soil. Transfer function-noise modelling of hourly NO3 concentrations reveals that a large part of the dynamics in NO3 concentrations during the winter months can be related to rainfall. The total phosphorus (TP) concentration and turbidity almost doubled during operation of the pumping station, which points to resuspension of particulate P from channel bed sediments induced by changes in water flow due to pumping. Rainfall events that caused peaks in NO3 concentrations did not results in TP concentration peaks. The rainfall induced and NO3 enriched quick interflow, may also be enriched in TP but retention of TP due to sedimentation of particulate P then results in the absence of rainfall induced TP concentration peaks. Increased TP concentrations associated with run-off events is only observed during a rainfall event at the end of a freeze-thaw cycle. All these observations suggest that the P retention potential of polder water systems is primarily due to the artificial pumping regime

  16. Assessing subaqueous mudslide hazard on the Mississippi River delta front, Part 2: Insights revealed through high-resolution geophysical surveying

    Science.gov (United States)

    Obelcz, J.; Xu, K.; Bentley, S. J.; Georgiou, I. Y.; Maloney, J. M.; Miner, M. D.; Hanegan, K.; Keller, G.

    2014-12-01

    The northern Gulf of Mexico, including the subaqueous Mississippi River delta front (MRDF), has been productive for oil and gas development since the early 1900s. In 1969 cyclic seafloor wave loading associated with the passage of Hurricane Camille triggered subaqueous mudflows across the MRDF, destroying several offshore oil platforms. This incident spurred geophysical and geotechnical studies of the MRDF, which found that the delta front is prone to mass failures on gentle gradients (<0.5°) due to (1) high rates of fine-grained sedimentation and associated underconsolidation, (2) excess sediment pore pressure attributed to in-situ biogenic gas production, and (3) the frequent passage of tropical cyclones. In June 2014, a geophysical pilot study was conducted 8 km southwest of Southwest Pass, the distributary that currently receives the largest fraction of Mississippi River sediment supply. The resultant dataset encompasses 216 km of subbottom Chirp seismic profiles and a 60 km2 grid of bathymetry and sidescan data. Preliminary interpretation of these data shows the survey area can be classified into four primary sedimentary facies: mudflow gullies, mudflow lobes, undisturbed prodelta, and undisturbed delta front. Subbottom profiles reveal extensive biogenic gas from 20 to about 80 m water depths on the delta front; sidescan data show a variety of bottleneck slides, mudflow gullies and mudflow noses. Previous studies have attempted to constrain the periodicity and magnitude of subaqueous mudslides on the MRDF. However, large age gaps and varied resolution between datasets result in ambiguity regarding the cause and magnitude of observed bathymetric changes. We present high-temporal resolution MRDF bathymetric variations from 2005 (post Hurricane Katrina), 2009 (relatively quiescent storm period), and 2014 (post 2011 Mississippi River flood). These data yield better magnitude and timing estimates of mass movements. This exercise represents a first step towards (1

  17. High-density PhyloChip profiling of stimulated aquifer microbial communities reveals a complex response to acetate amendment

    Energy Technology Data Exchange (ETDEWEB)

    Handley, Kim M.; Wrighton, Kelly E.; Piceno, Y. M.; Anderson, Gary L.; DeSantis, Todd; Williams, Kenneth H.; Wilkins, Michael J.; N' Guessan, A. L.; Peacock, Aaron; Bargar, John R.; Long, Philip E.; Banfield, Jillian F.

    2012-06-13

    There is increasing interest in harnessing the functional diversity of indigenous microbial communities to transform and remediate a wide range of environmental contaminants. Understanding the response of communities to stimulation, including flanking taxa, presents important opportunities for optimizing remediation approaches. We used high-density PhyloChip microarray analysis to comprehensively determine community membership and abundance patterns amongst a suite of samples from U(VI) bioremediation experiments. Samples were unstimulated or collected during Fe(III) and sulfate reduction from an acetate-augmented aquifer in Rifle, Colorado, and from laboratory experiments using field-collected materials. Results showed the greatest diversity in abundant SRB lineages was present in naturally-reduced sediment. Desulfuromonadales and Desulfobacterales were consistently identified as the dominant Fe(III)- and sulfate-reducing bacteria (IRB and SRB) throughout acetate amendment experiments. Stimulated communities also exhibited a high degree of functional redundancy amongst enriched flanking members. Not surprisingly, competition for both sulfate and iron was evident amongst abundant taxa, but the distribution and abundance of these ancillary SRB (Peptococcaceae, Desulfovibrionales and Syntrophobacterales), and lineages containing IRB (excluding Desulfobacteraceae) was heterogeneous amongst sample types. Interesting, amongst the most abundant taxa, particularly during sulfate reduction, were Epsilonproteobacteria that perform microaerobic or nitrate-dependant sulfur oxidation, and a number of bacteria other than Geobacteraceae that may enzymatically reduce U(VI). Finally, in depth community probing with PhyloChip determined the efficacy of experimental approaches, notably revealing striking similarity amongst stimulated sediment (from drill cores and in-situ columns) and groundwater communities, and demonstrating that sediment-packed in-situ (down-well) columns served

  18. Sports-related testing protocols are required to reveal trunk stability adaptations in high-level athletes.

    Science.gov (United States)

    Barbado, David; Barbado, Luis C; Elvira, Jose L L; Dieën, Jaap H van; Vera-Garcia, Francisco J

    2016-09-01

    Trunk/core stability is considered a key component of training programs, because it could contribute to prevention of low-back and lower-limb injuries and to sports performance. Based on the specificity principle, sports-related trunk stability tests would be required in elite sports performance. However, there may be some generic qualities underlying trunk stability that can be assessed with nonspecific protocols, which are broadly used in sport and rehabilitation. To assess whether specific tests are needed in a high-performance context, we analyzed the influence of specialization in sports with large but qualitatively different balance control demands (judo and kayaking) on trunk stability and compared high-performance athletes with recreational athletes without a specific training history. Twenty-five judokas, sixteen kayakers and thirty-seven recreational athletes performed two trunk stability protocols: sudden loading, to assess trunk responses to external and unexpected perturbations; stable and unstable sitting, to assess the participant's ability to control trunk while sitting. Within-session test-retest reliability analyses were performed to support the between-groups comparison. Judokas showed lower angular displacement (0.199rad) against posterior loading than kayakers (0.221rad) probably because they are frequently challenged by higher sudden loads while they are pushed or pulled. Kayakers showed lower error (7.33mm), probably because they train and compete seated on unstable surfaces. Importantly, judokas and kayakers obtained better results than recreational athletes only in those tests designed according to the specific demands of each sport (psport training induces specific trunk stability adaptations, which are not revealed through nonspecific tests.

  19. RNA-Seq Analysis of Abdominal Fat Reveals Differences between Modern Commercial Broiler Chickens with High and Low Feed Efficiencies.

    Directory of Open Access Journals (Sweden)

    Zhu Zhuo

    Full Text Available For economic and environmental reasons, chickens with superior feed efficiency (FE are preferred in the broiler chicken industry. High FE (HFE chickens typically have reduced abdominal fat, the major adipose tissue in chickens. In addition to its function of energy storage, adipose tissue is a metabolically active organ that also possesses endocrine and immune regulatory functions. It plays a central role in maintaining energy homeostasis. Comprehensive understanding of the gene expression in the adipose tissue and the biological basis of FE are of significance to optimize selection and breeding strategies. Through gene expression profiling of abdominal fat from high and low FE (LFE commercial broiler chickens, the present study aimed to characterize the differences of gene expression between HFE and LFE chickens. mRNA-seq analysis was carried out on the total RNA of abdominal fat from 10 HFE and 12 LFE commercial broiler chickens, and 1.48 billion of 75-base sequence reads were generated in total. On average, 11,565 genes were expressed (>5 reads/gene/sample in the abdominal fat tissue, of which 286 genes were differentially expressed (DE at q (False Discover Rate 1.3 between HFE and LFE chickens. Expression levels from RNA-seq were confirmed with the NanoString nCounter analysis system. Functional analysis showed that the DE genes were significantly (p < 0.01 enriched in lipid metabolism, coagulation, and immune regulation pathways. Specifically, the LFE chickens had higher expression of lipid synthesis genes and lower expression of triglyceride hydrolysis and cholesterol transport genes. In conclusion, our study reveals the overall differences of gene expression in the abdominal fat from HFE and LFE chickens, and the results suggest that the divergent expression of lipid metabolism genes represents the major differences.

  20. Sports-related testing protocols are required to reveal trunk stability adaptations in high-level athletes.

    Science.gov (United States)

    Barbado, David; Barbado, Luis C; Elvira, Jose L L; Dieën, Jaap H van; Vera-Garcia, Francisco J

    2016-09-01

    Trunk/core stability is considered a key component of training programs, because it could contribute to prevention of low-back and lower-limb injuries and to sports performance. Based on the specificity principle, sports-related trunk stability tests would be required in elite sports performance. However, there may be some generic qualities underlying trunk stability that can be assessed with nonspecific protocols, which are broadly used in sport and rehabilitation. To assess whether specific tests are needed in a high-performance context, we analyzed the influence of specialization in sports with large but qualitatively different balance control demands (judo and kayaking) on trunk stability and compared high-performance athletes with recreational athletes without a specific training history. Twenty-five judokas, sixteen kayakers and thirty-seven recreational athletes performed two trunk stability protocols: sudden loading, to assess trunk responses to external and unexpected perturbations; stable and unstable sitting, to assess the participant's ability to control trunk while sitting. Within-session test-retest reliability analyses were performed to support the between-groups comparison. Judokas showed lower angular displacement (0.199rad) against posterior loading than kayakers (0.221rad) probably because they are frequently challenged by higher sudden loads while they are pushed or pulled. Kayakers showed lower error (7.33mm), probably because they train and compete seated on unstable surfaces. Importantly, judokas and kayakers obtained better results than recreational athletes only in those tests designed according to the specific demands of each sport (p<0.050). In conclusion, specific-sport training induces specific trunk stability adaptations, which are not revealed through nonspecific tests. PMID:27395448

  1. Comparative analyses of six solanaceous transcriptomes reveal a high degree of sequence conservation and species-specific transcripts

    Directory of Open Access Journals (Sweden)

    Ouyang Shu

    2005-09-01

    Full Text Available Abstract Background The Solanaceae is a family of closely related species with diverse phenotypes that have been exploited for agronomic purposes. Previous studies involving a small number of genes suggested sequence conservation across the Solanaceae. The availability of large collections of Expressed Sequence Tags (ESTs for the Solanaceae now provides the opportunity to assess sequence conservation and divergence on a genomic scale. Results All available ESTs and Expressed Transcripts (ETs, 449,224 sequences for six Solanaceae species (potato, tomato, pepper, petunia, tobacco and Nicotiana benthamiana, were clustered and assembled into gene indices. Examination of gene ontologies revealed that the transcripts within the gene indices encode a similar suite of biological processes. Although the ESTs and ETs were derived from a variety of tissues, 55–81% of the sequences had significant similarity at the nucleotide level with sequences among the six species. Putative orthologs could be identified for 28–58% of the sequences. This high degree of sequence conservation was supported by expression profiling using heterologous hybridizations to potato cDNA arrays that showed similar expression patterns in mature leaves for all six solanaceous species. 16–19% of the transcripts within the six Solanaceae gene indices did not have matches among Solanaceae, Arabidopsis, rice or 21 other plant gene indices. Conclusion Results from this genome scale analysis confirmed a high level of sequence conservation at the nucleotide level of the coding sequence among Solanaceae. Additionally, the results indicated that part of the Solanaceae transcriptome is likely to be unique for each species.

  2. High-throughput SHAPE analysis reveals structures in HIV-1 genomic RNA strongly conserved across distinct biological states.

    Directory of Open Access Journals (Sweden)

    Kevin A Wilkinson

    2008-04-01

    Full Text Available Replication and pathogenesis of the human immunodeficiency virus (HIV is tightly linked to the structure of its RNA genome, but genome structure in infectious virions is poorly understood. We invent high-throughput SHAPE (selective 2'-hydroxyl acylation analyzed by primer extension technology, which uses many of the same tools as DNA sequencing, to quantify RNA backbone flexibility at single-nucleotide resolution and from which robust structural information can be immediately derived. We analyze the structure of HIV-1 genomic RNA in four biologically instructive states, including the authentic viral genome inside native particles. Remarkably, given the large number of plausible local structures, the first 10% of the HIV-1 genome exists in a single, predominant conformation in all four states. We also discover that noncoding regions functioning in a regulatory role have significantly lower (p-value < 0.0001 SHAPE reactivities, and hence more structure, than do viral coding regions that function as the template for protein synthesis. By directly monitoring protein binding inside virions, we identify the RNA recognition motif for the viral nucleocapsid protein. Seven structurally homologous binding sites occur in a well-defined domain in the genome, consistent with a role in directing specific packaging of genomic RNA into nascent virions. In addition, we identify two distinct motifs that are targets for the duplex destabilizing activity of this same protein. The nucleocapsid protein destabilizes local HIV-1 RNA structure in ways likely to facilitate initial movement both of the retroviral reverse transcriptase from its tRNA primer and of the ribosome in coding regions. Each of the three nucleocapsid interaction motifs falls in a specific genome domain, indicating that local protein interactions can be organized by the long-range architecture of an RNA. High-throughput SHAPE reveals a comprehensive view of HIV-1 RNA genome structure, and further

  3. HIGH-RESOLUTION CO OBSERVATION OF THE CARBON STAR CIT 6 REVEALING THE SPIRAL STRUCTURE AND A NASCENT BIPOLAR OUTFLOW

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hyosun; Liu, Sheng-Yuan; Hirano, Naomi; Zhao-Geisler, Ronny; Trejo, Alfonso; Yen, Hsi-Wei; Taam, Ronald E.; Kemper, Francisca [Academia Sinica Institute of Astronomy and Astrophysics, P.O. Box 23-141, Taipei 10617, Taiwan (China); Kim, Jongsoo; Byun, Do-Young; Liu, Tie, E-mail: hkim@asiaa.sinica.edu.tw [Korea Astronomy and Space Science Institute, 776, Daedeokdae-ro, Yuseong-gu, Daejeon 305-348 (Korea, Republic of)

    2015-11-20

    CIT 6 is a carbon star in the transitional phase from the asymptotic giant branch (AGB) to the protoplanetary nebulae (pPNs). Observational evidences of two point sources in the optical, circumstellar arc segments in an HC{sub 3}N line emission, and a bipolar nebula in near-infrared provide strong support for the presence of a binary companion. Hence, CIT 6 is very attractive for studying the role of companions in the AGB–pPN transition. We have carried out high-resolution {sup 12}CO J = 2–1 and {sup 13}CO J = 2–1 observations of CIT 6 with the Submillimeter Array combined with the Submillimeter Telescope (single-dish) data. The {sup 12}CO channel maps reveal a spiral-shell pattern connecting the HC{sub 3}N segments in a continuous form and an asymmetric outflow corresponding to the near-infrared bipolar nebula. Rotation of the {sup 12}CO channel peak position may be related to the inner spiral winding and/or the bipolar outflow. An eccentric orbit binary is suggested for the presence of an anisotropic mass loss to the west and a double spiral pattern. The lack of interarm emission to the west may indicate a feature corresponding to the periastron passage of a highly eccentric orbit of the binary. Spatially averaged radial and spectral profiles of {sup 12}CO J = 2–1 and {sup 13}CO J = 2–1 are compared with simple spherical radiative transfer models, suggesting a change of {sup 12}CO/{sup 13}CO abundance ratio from ∼30 to ∼50 inward in the CSE of CIT 6. The millimeter continuum emission is decomposed into extended dust thermal emission (spectral index ∼ −2.4) and compact emission from radio photosphere (spectral index ∼ −2.0)

  4. Cardiac Biomarkers and Cycling Race

    OpenAIRE

    Caroline Le Goff, Jean-François Kaux, Sébastien Goffaux, Etienne Cavalier

    2015-01-01

    In cycling as in other types of strenuous exercise, there exists a risk of sudden death. It is important both to understand its causes and to see if the behavior of certain biomarkers might highlight athletes at risk. Many reports describe changes in biomarkers after strenuous exercise (Nie et al., 2011), but interpreting these changes, and notably distinguishing normal physiological responses from pathological changes, is not easy. Here we have focused on the kinetics of different cardiac bi...

  5. Analysis of biomarker data a practical guide

    CERN Document Server

    Looney, Stephen W

    2015-01-01

    A "how to" guide for applying statistical methods to biomarker data analysis Presenting a solid foundation for the statistical methods that are used to analyze biomarker data, Analysis of Biomarker Data: A Practical Guide features preferred techniques for biomarker validation. The authors provide descriptions of select elementary statistical methods that are traditionally used to analyze biomarker data with a focus on the proper application of each method, including necessary assumptions, software recommendations, and proper interpretation of computer output. In addition, the book discusses

  6. Neuroimmune biomarkers in schizophrenia.

    Science.gov (United States)

    Tomasik, Jakub; Rahmoune, Hassan; Guest, Paul C; Bahn, Sabine

    2016-09-01

    Schizophrenia is a heterogeneous psychiatric disorder with a broad spectrum of clinical and biological manifestations. Due to the lack of objective tests, the accurate diagnosis and selection of effective treatments for schizophrenia remains challenging. Numerous technologies have been employed in search of schizophrenia biomarkers. These studies have suggested that neuroinflammatory processes may play a role in schizophrenia pathogenesis, at least in a subgroup of patients. The evidence indicates alterations in both pro- and anti-inflammatory molecules in the central nervous system, which have also been found in peripheral tissues and may correlate with schizophrenia symptoms. In line with these findings, certain immunomodulatory interventions have shown beneficial effects on psychotic symptoms in schizophrenia patients, in particular those with distinct immune signatures. In this review, we evaluate these findings and their potential for more targeted drug interventions and the development of companion diagnostics. Although currently no validated markers exist for schizophrenia patient stratification or the prediction of treatment efficacy, we propose that utilisation of inflammatory markers for diagnostic and theranostic purposes may lead to novel therapeutic approaches and deliver more effective care for schizophrenia patients. PMID:25124519

  7. Oxidative stress biomarker responses to an acute session of hypertrophy-resistance traditional interval training and circuit training.

    Science.gov (United States)

    Deminice, Rafael; Sicchieri, Tiago; Mialich, Mirele S; Milani, Francine; Ovidio, Paula P; Jordao, Alceu A

    2011-03-01

    We have studied circuit resistance schemes with high loads as a time-effective alternative to hypertrophy-traditional resistance training. However, the oxidative stress biomarker responses to high-load circuit training are unknown. The aim of the present study was to compare oxidative stress biomarker response with an acute session of hypertrophy-resistance circuit training and traditional interval training. A week after the 1 repetition maximum (1RM) test, 11 healthy and well-trained male participants completed hypertrophy-resistance acute sessions of traditional interval training (3 × 10 repetitions at 75% of the 1RM, with 90-second passive rest) and circuit training (3 × 10 repetitions at 75% of the 1RM, in alternating performance of 2 exercises with different muscle groups) in a randomized and cross-over design. Venous blood samples were collected before (pre) and 10 minutes after (post) the resistance training sessions for oxidative stress biomarker assays. As expected, the time used to complete the circuit training (20.2 ± 1.6) was half of that needed to complete the traditional interval training (40.3 ± 1.8). Significant increases (p < 0.05) in thiobarbituric acid reactive substances (40%), creatine kinase (CK) (67%), glutathione (14%), and uric acid (25%) were detected posttraditional interval training session in relation to pre. In relation to circuit training, a significant increase in CK (33%) activity postsession in relation to pre was observed. Statistical analysis did not reveal any other change in the oxidative stress biomarker after circuit training. In conclusion, circuit resistance-hypertrophy training scheme proposed in the current study promoted lower oxidative stress biomarkers and antioxidant modulations compared with resistance traditional interval training.

  8. Cerebrospinal Fluid Biomarkers of Simian Immunodeficiency Virus Encephalitis : CSF Biomarkers of SIV Encephalitis.

    Science.gov (United States)

    Bissel, Stephanie J; Kofler, Julia; Nyaundi, Julia; Murphey-Corb, Michael; Wisniewski, Stephen R; Wiley, Clayton A

    2016-06-01

    Antiretroviral therapy has led to increased survival of HIV-infected patients but also increased prevalence of HIV-associated neurocognitive disorders. We previously identified YKL40 as a potential cerebrospinal fluid (CSF) biomarker of lentiviral central nervous system (CNS) disease in HIV-infected patients and in the macaque model of HIV encephalitis. The aim of this study was to define the specificity and sensitivity along with the predictive value of YKL40 as a biomarker of encephalitis and to assess its relationship to CSF viral load. CSF YKL40 and SIV RNA concentrations were analyzed over the course of infection in 19 SIV-infected pigtailed macaques and statistical analyses were performed to evaluate the relationship to encephalitis. Using these relationships, CSF alterations of 31 neuroimmune markers were studied pre-infection, during acute and asymptomatic infection, at the onset of encephalitis, and at necropsy. YKL40 CSF concentrations above 1122 ng/ml were found to be a specific and sensitive biomarker for the presence of encephalitis and were highly correlated with CSF viral load. Macaques that developed encephalitis had evidence of chronic CNS immune activation during early, asymptomatic, and end stages of infection. At the onset of encephalitis, CSF demonstrated a rise of neuroimmune markers associated with macrophage recruitment, activation and interferon response. CSF YKL40 concentration and viral load are valuable biomarkers to define the onset of encephalitis. Chronic CNS immune activation precedes the development of encephalitis while some responses suggest protection from CNS lentiviral disease. PMID:27059917

  9. Biomarkers in Alzheimer’s disease

    Directory of Open Access Journals (Sweden)

    Mario eRiverol

    2011-07-01

    Full Text Available Alzheimer’s disease (AD is the most common form of dementia in the elderly, and it is characterized by progressive impairment in multiple cognitive domains of sufficient severity to interfere with individuals’ daily living activities. Historically, the diagnosis of AD has been based on the identification of a clinical syndrome, and accuracy studies of the current clinical criteria conducted in referral clinics have shown high sensitivity for AD. However, the identification of the disease is still not perfect, and there is growing evidence that the use of biomarkers will increase our ability to better indentify the underlying biology of AD, especially in its early stages. These biomarkers will improve the detection of the patients suitable for research studies and drug trials, and they will contribute to a better management of the disease in the clinical practice. In this review, we discuss the most studied biomarkers in AD: cerebrospinal fluid proteins, structural magnetic resonance imaging (MRI, functional neuroimaging techniques, and amyloid imaging.

  10. Biomarkers and Pharmacogenetics in Pancreatic Cancer

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    Xunhai Xu

    2011-07-01

    Full Text Available Appropriate identification and validation of biomarkers as well as pharmacogenetics are important in formulating patient-oriented, individualized chemotherapy or biological therapy in cancer patients. These markers can be especially valuable in pancreatic cancer, where high mortality and complex disease biology are frequently encountered. Recently, several advances have been made to further our knowledge in this specific area of pancreatic cancer. In the 2011 American Society of Clinical Oncology (ASCO Annual Meeting, researchers have presented several interesting results in biomarkers development: the identifications of 9 single nucleotide polymorphisms (SNPs that is associated with positive efficacy of gemcitabine (Abstract #4022; the introduction of circulating tumor cells as a prognostic markers in pancreatic adenocarcinoma (Abstract #e14657; the re-affirmation of plasma cytidine deaminase (CDA as a positive predictive markers for gemcitabine efficacy, as well as the postulations that CDA*3 as a potential genotype marker to predict gemcitabine responses (Abstract #e14645; and finally the retrospective tumor tissues analysis in the Arbeitsgemeinschaft Internistische Onkologie (AIO trial in an attempt for epidermal growth factor receptor (EGFR pathway biomarker identifications (Abstract #4047

  11. Biomarkers for cardiac cachexia: reality or utopia.

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    Martins, Telma; Vitorino, Rui; Amado, Francisco; Duarte, José Alberto; Ferreira, Rita

    2014-09-25

    Cardiac cachexia is a serious complication of chronic heart failure, characterized by significant weight loss and body wasting. Chronic heart failure-related muscle wasting results from a chronic imbalance in the activation of anabolic or catabolic pathways, caused by a series of immunological, metabolic, and neurohormonal processes. In spite of the high morbidity and mortality associated to this condition, there is no universally accepted definition or specific biomarkers for cardiac cachexia, which makes its diagnosis and treatment difficult. Several hormonal, inflammatory and oxidative stress molecules have been proposed as serological markers of prognosis in cardiac cachexia but with doubtful success. As individual biomarkers may have limited sensitivity and specificity, multimarker strategies involving mediators of the biological processes modulated by cardiac cachexia will strongly contribute for the diagnosis and management of the disease, as well as for the establishment of new therapeutic targets. An integrated analysis of the biomarkers proposed so far for cardiac cachexia is made in the present review, highlighting the biological processes to which they are related. PMID:24978823

  12. A photoacoustic immunoassay for biomarker detection.

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    Zhao, Yunfei; Cao, Mingfeng; McClelland, John F; Shao, Zengyi; Lu, Meng

    2016-11-15

    Challenges in protein biomarker analysis include insufficient sensitivity for detecting low-abundance biomarkers, poor measurement reproducibility, and the high costs and large footprints of detection systems. To address these issues, a new detection modality was developed for analyzing protein biomarkers based on the plasmon-enhanced photoacoustic (PA) effect. The detection modality employed a heterogeneous immunoassay scheme and used gold nanoparticles (AuNPs) as the signal reporter. Due to their localized plasmon resonance, AuNPs can strongly interact with intensity-modulated laser excitation and generate strong PA signals, which are subsequently sensed and quantified using a microphone. As an example, the performance of the PA immunoassay was evaluated by detecting the human interleukin 8 chemokine. The PA immunoassay provided approximately 143× lower limit of detection (LOD) than observed with the gold standard enzyme-linked immunosorbent assay - a decrease from 23pg/mL to 0.16pg/mL. In addition to the significant performance improvement in terms of the LOD, the PA immunoassay also offers advantages in terms of compatibility with low-cost instruments and the long-term stability of assay results. PMID:27183276

  13. Renal biomarkers in domestic species.

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    Hokamp, Jessica A; Nabity, Mary B

    2016-03-01

    Current conventional tests of kidney damage and function in blood (serum creatinine and urea nitrogen) and urine (urine protein creatinine ratio and urine specific gravity) are widely used for diagnosis and monitoring of kidney disease. However, they all have important limitations, and additional markers of glomerular filtration rate and glomerular and tubular damage are desirable, particularly for earlier detection of renal disease when therapy is most effective. Additionally, urinary markers of kidney damage and function may help localize damage to the affected portion of the kidney. In general, the presence of high- and intermediate-molecular weight proteins in the urine are indicative of glomerular damage, while low-molecular weight proteins and enzymes in the urine suggest tubular damage due to decreased reabsorption of proteins, direct tubular damage, or both. This review aims to discuss many of these new blood and urinary biomarkers in domestic veterinary species, focusing primarily on dogs and cats, how they may be used for diagnosis of renal disease, and their limitations. Additionally, a brief discussion of serum creatinine is presented, highlighting its limitations and important considerations for its improved interpretation in domestic species based on past literature and recent studies. PMID:26918420

  14. Serum biomarkers in Acute Respiratory Distress Syndrome an ailing prognosticator

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    Pneumatikos Ioannis

    2005-06-01

    Full Text Available Abstract The use of biomarkers in medicine lies in their ability to detect disease and support diagnostic and therapeutic decisions. New research and novel understanding of the molecular basis of the disease reveals an abundance of exciting new biomarkers who present a promise for use in the everyday clinical practice. The past fifteen years have seen the emergence of numerous clinical applications of several new molecules as biologic markers in the research field relevant to acute respiratory distress syndrome (translational research. The scope of this review is to summarize the current state of knowledge about serum biomarkers in acute lung injury and acute respiratory distress syndrome and their potential value as prognostic tools and present some of the future perspectives and challenges.

  15. Proteomic analysis of the excretory-secretory products from larval stages of Ascaris suum reveals high abundance of glycosyl hydrolases.

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    Tao Wang

    Full Text Available BACKGROUND: Ascaris lumbricoides and Ascaris suum are socioeconomically important and widespread parasites of humans and pigs, respectively. The excretory-secretory (ES molecules produced and presented at the parasite-host interface during the different phases of tissue invasion and migration are likely to play critical roles in the induction and development of protective immune and other host responses. METHODOLOGY/PRINCIPAL FINDINGS: The aim of this study was to identify the ES proteins of the different larval stages (L3-egg, L3-lung and L4 by LC-MS/MS. In total, 106 different proteins were identified, 20 in L3-egg, 45 in L3-lung stage and 58 in L4. Although most of the proteins identified were stage-specific, 15 were identified in the ES products of at least two stages. Two proteins, i.e. a 14-3-3-like protein and a serpin-like protein, were present in the ES products from the three different larval stages investigated. Interestingly, a comparison of ES products from L4 with those of L3-egg and L3-lung showed an abundance of metabolic enzymes, particularly glycosyl hydrolases. Further study indicated that most of these glycolytic enzymes were transcriptionally upregulated from L4 onwards, with a peak in the adult stage, particularly in intestinal tissue. This was also confirmed by enzymatic assays, showing the highest glycosidase activity in protein extracts from adult worms gut. CONCLUSIONS/SIGNIFICANCE: The present proteomic analysis provides important information on the host-parasite interaction and the biology of the migratory stages of A. suum. In particular, the high transcriptional upregulation of glycosyl hydrolases from the L4 stage onwards reveals that the degradation of complex carbohydrates forms an essential part of the energy metabolism of this parasite once it establishes in the small intestine.

  16. Bacterial communities in women with bacterial vaginosis: high resolution phylogenetic analyses reveal relationships of microbiota to clinical criteria.

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    Sujatha Srinivasan

    Full Text Available BACKGROUND: Bacterial vaginosis (BV is a common condition that is associated with numerous adverse health outcomes and is characterized by poorly understood changes in the vaginal microbiota. We sought to describe the composition and diversity of the vaginal bacterial biota in women with BV using deep sequencing of the 16S rRNA gene coupled with species-level taxonomic identification. We investigated the associations between the presence of individual bacterial species and clinical diagnostic characteristics of BV. METHODOLOGY/PRINCIPAL FINDINGS: Broad-range 16S rRNA gene PCR and pyrosequencing were performed on vaginal swabs from 220 women with and without BV. BV was assessed by Amsel's clinical criteria and confirmed by Gram stain. Taxonomic classification was performed using phylogenetic placement tools that assigned 99% of query sequence reads to the species level. Women with BV had heterogeneous vaginal bacterial communities that were usually not dominated by a single taxon. In the absence of BV, vaginal bacterial communities were dominated by either Lactobacillus crispatus or Lactobacillus iners. Leptotrichia amnionii and Eggerthella sp. were the only two BV-associated bacteria (BVABs significantly associated with each of the four Amsel's criteria. Co-occurrence analysis revealed the presence of several sub-groups of BVABs suggesting metabolic co-dependencies. Greater abundance of several BVABs was observed in Black women without BV. CONCLUSIONS/SIGNIFICANCE: The human vaginal bacterial biota is heterogeneous and marked by greater species richness and diversity in women with BV; no species is universally present. Different bacterial species have different associations with the four clinical criteria, which may account for discrepancies often observed between Amsel and Nugent (Gram stain diagnostic criteria. Several BVABs exhibited race-dependent prevalence when analyzed in separate groups by BV status which may contribute to increased

  17. Identification of β-hematin inhibitors in a high-throughput screening effort reveals scaffolds with in vitro antimalarial activity

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    Rebecca D. Sandlin

    2014-12-01

    Full Text Available The emergence of drug resistant strains of Plasmodium spp. creates a critical need for the development of novel antimalarials. Formation of hemozoin, a crystalline heme detoxification process vital to parasite survival serves as an important drug target. The quinoline antimalarials including chloroquine and amodiaquine owe their antimalarial activity to inhibition of hemozoin formation. Though in vivo formation of hemozoin occurs within the presence of neutral lipids, the lipophilic detergent NP-40 was previously shown to serve as a surrogate in the β-hematin (synthetic hemozoin formation process. Consequently, an NP-40 mediated β-hematin formation assay was developed for use in high-throughput screening. Here, the assay was utilized to screen 144,330 compounds for the identification of inhibitors of crystallization, resulting in 530 hits. To establish the effectiveness of these target-based β-hematin inhibitors against Plasmodium falciparum, each hit was further tested in cultures of parasitized red blood cells. This effort revealed that 171 of the β-hematin inhibitors are also active against the parasite. Dose–response data identified 73 of these β-hematin inhibitors have IC50 values ⩽5 μM, including 25 compounds with nanomolar activity against P. falciparum. A scaffold-based analysis of this data identified 14 primary scaffolds that represent 46% of the 530 total hits. Representative compounds from each of the classes were further assessed for hemozoin inhibitory activity in P. falciparum infected human erythrocytes. Each of the hit compounds tested were found to be positive inhibitors, while a negative control did not perturb this biological pathway in culture.

  18. High-density SNP genotyping of tomato (Solanum lycopersicum L. reveals patterns of genetic variation due to breeding.

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    Sung-Chur Sim

    Full Text Available The effects of selection on genome variation were investigated and visualized in tomato using a high-density single nucleotide polymorphism (SNP array. 7,720 SNPs were genotyped on a collection of 426 tomato accessions (410 inbreds and 16 hybrids and over 97% of the markers were polymorphic in the entire collection. Principal component analysis (PCA and pairwise estimates of F(st supported that the inbred accessions represented seven sub-populations including processing, large-fruited fresh market, large-fruited vintage, cultivated cherry, landrace, wild cherry, and S. pimpinellifolium. Further divisions were found within both the contemporary processing and fresh market sub-populations. These sub-populations showed higher levels of genetic diversity relative to the vintage sub-population. The array provided a large number of polymorphic SNP markers across each sub-population, ranging from 3,159 in the vintage accessions to 6,234 in the cultivated cherry accessions. Visualization of minor allele frequency revealed regions of the genome that distinguished three representative sub-populations of cultivated tomato (processing, fresh market, and vintage, particularly on chromosomes 2, 4, 5, 6, and 11. The PCA loadings and F(st outlier analysis between these three sub-populations identified a large number of candidate loci under positive selection on chromosomes 4, 5, and 11. The extent of linkage disequilibrium (LD was examined within each chromosome for these sub-populations. LD decay varied between chromosomes and sub-populations, with large differences reflective of breeding history. For example, on chromosome 11, decay occurred over 0.8 cM for processing accessions and over 19.7 cM for fresh market accessions. The observed SNP variation and LD decay suggest that different patterns of genetic variation in cultivated tomato are due to introgression from wild species and selection for market specialization.

  19. Novel technologies and emerging biomarkers for personalized cancer immunotherapy.

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    Yuan, Jianda; Hegde, Priti S; Clynes, Raphael; Foukas, Periklis G; Harari, Alexandre; Kleen, Thomas O; Kvistborg, Pia; Maccalli, Cristina; Maecker, Holden T; Page, David B; Robins, Harlan; Song, Wenru; Stack, Edward C; Wang, Ena; Whiteside, Theresa L; Zhao, Yingdong; Zwierzina, Heinz; Butterfield, Lisa H; Fox, Bernard A

    2016-01-01

    The culmination of over a century's work to understand the role of the immune system in tumor control has led to the recent advances in cancer immunotherapies that have resulted in durable clinical responses in patients with a variety of malignancies. Cancer immunotherapies are rapidly changing traditional treatment paradigms and expanding the therapeutic landscape for cancer patients. However, despite the current success of these therapies, not all patients respond to immunotherapy and even those that do often experience toxicities. Thus, there is a growing need to identify predictive and prognostic biomarkers that enhance our understanding of the mechanisms underlying the complex interactions between the immune system and cancer. Therefore, the Society for Immunotherapy of Cancer (SITC) reconvened an Immune Biomarkers Task Force to review state of the art technologies, identify current hurdlers, and make recommendations for the field. As a product of this task force, Working Group 2 (WG2), consisting of international experts from academia and industry, assembled to identify and discuss promising technologies for biomarker discovery and validation. Thus, this WG2 consensus paper will focus on the current status of emerging biomarkers for immune checkpoint blockade therapy and discuss novel technologies as well as high dimensional data analysis platforms that will be pivotal for future biomarker research. In addition, this paper will include a brief overview of the current challenges with recommendations for future biomarker discovery.

  20. Emerging Risk Biomarkers in Cardiovascular Diseases and Disorders

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    Ravi Kant Upadhyay

    2015-01-01

    Full Text Available Present review article highlights various cardiovascular risk prediction biomarkers by incorporating both traditional risk factors to be used as diagnostic markers and recent technologically generated diagnostic and therapeutic markers. This paper explains traditional biomarkers such as lipid profile, glucose, and hormone level and physiological biomarkers based on measurement of levels of important biomolecules such as serum ferritin, triglyceride to HDLp (high density lipoproteins ratio, lipophorin-cholesterol ratio, lipid-lipophorin ratio, LDL cholesterol level, HDLp and apolipoprotein levels, lipophorins and LTPs ratio, sphingolipids, Omega-3 Index, and ST2 level. In addition, immunohistochemical, oxidative stress, inflammatory, anatomical, imaging, genetic, and therapeutic biomarkers have been explained in detail with their investigational specifications. Many of these biomarkers, alone or in combination, can play important role in prediction of risks, its types, and status of morbidity. As emerging risks are found to be affiliated with minor and microlevel factors and its diagnosis at an earlier stage could find CVD, hence, there is an urgent need of new more authentic, appropriate, and reliable diagnostic and therapeutic markers to confirm disease well in time to start the clinical aid to the patients. Present review aims to discuss new emerging biomarkers that could facilitate more authentic and fast diagnosis of CVDs, HF (heart failures, and various lipid abnormalities and disorders in the future.

  1. Emerging risk biomarkers in cardiovascular diseases and disorders.

    Science.gov (United States)

    Upadhyay, Ravi Kant

    2015-01-01

    Present review article highlights various cardiovascular risk prediction biomarkers by incorporating both traditional risk factors to be used as diagnostic markers and recent technologically generated diagnostic and therapeutic markers. This paper explains traditional biomarkers such as lipid profile, glucose, and hormone level and physiological biomarkers based on measurement of levels of important biomolecules such as serum ferritin, triglyceride to HDLp (high density lipoproteins) ratio, lipophorin-cholesterol ratio, lipid-lipophorin ratio, LDL cholesterol level, HDLp and apolipoprotein levels, lipophorins and LTPs ratio, sphingolipids, Omega-3 Index, and ST2 level. In addition, immunohistochemical, oxidative stress, inflammatory, anatomical, imaging, genetic, and therapeutic biomarkers have been explained in detail with their investigational specifications. Many of these biomarkers, alone or in combination, can play important role in prediction of risks, its types, and status of morbidity. As emerging risks are found to be affiliated with minor and microlevel factors and its diagnosis at an earlier stage could find CVD, hence, there is an urgent need of new more authentic, appropriate, and reliable diagnostic and therapeutic markers to confirm disease well in time to start the clinical aid to the patients. Present review aims to discuss new emerging biomarkers that could facilitate more authentic and fast diagnosis of CVDs, HF (heart failures), and various lipid abnormalities and disorders in the future. PMID:25949827

  2. Direct comparison of mice null for liver or intestinal fatty acid-binding proteins reveals highly divergent phenotypic responses to high fat feeding.

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    Gajda, Angela M; Zhou, Yin Xiu; Agellon, Luis B; Fried, Susan K; Kodukula, Sarala; Fortson, Walter; Patel, Khamoshi; Storch, Judith

    2013-10-18

    The enterocyte expresses two fatty acid-binding proteins (FABP), intestinal FABP (IFABP; FABP2) and liver FABP (LFABP; FABP1). LFABP is also expressed in liver. Despite ligand transport and binding differences, it has remained uncertain whether these intestinally coexpressed proteins, which both bind long chain fatty acids (FA), are functionally distinct. Here, we directly compared IFABP(-/-) and LFABP(-/-) mice fed high fat diets containing long chain saturated or unsaturated fatty acids, reasoning that providing an abundance of dietary lipid would reveal unique functional properties. The results showed that mucosal lipid metabolism was indeed differentially modified, with significant decreases in FA incorporation into triacylglycerol (TG) relative to phospholipid (PL) in IFABP(-/-) mice, whereas LFABP(-/-) mice had reduced monoacylglycerol incorporation in TG relative to PL, as well as reduced FA oxidation. Interestingly, striking differences were found in whole body energy homeostasis; LFABP(-/-) mice fed high fat diets became obese relative to WT, whereas IFABP(-/-) mice displayed an opposite, lean phenotype. Fuel utilization followed adiposity, with LFABP(-/-) mice preferentially utilizing lipids, and IFABP(-/-) mice preferentially metabolizing carbohydrate for energy production. Changes in body weight and fat may arise, in part, from altered food intake; mucosal levels of the endocannabinoids 2-arachidonoylglycerol and arachidonoylethanolamine were elevated in LFABP(-/-), perhaps contributing to increased energy intake. This direct comparison provides evidence that LFABP and IFABP have distinct roles in intestinal lipid metabolism; differential intracellular functions in intestine and in liver, for LFABP(-/-) mice, result in divergent downstream effects at the systemic level. PMID:23990461