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Sample records for analysis identifies molecular

  1. Meta-Analysis of Placental Transcriptome Data Identifies a Novel Molecular Pathway Related to Preeclampsia.

    Science.gov (United States)

    van Uitert, Miranda; Moerland, Perry D; Enquobahrie, Daniel A; Laivuori, Hannele; van der Post, Joris A M; Ris-Stalpers, Carrie; Afink, Gijs B

    2015-01-01

    Studies using the placental transcriptome to identify key molecules relevant for preeclampsia are hampered by a relatively small sample size. In addition, they use a variety of bioinformatics and statistical methods, making comparison of findings challenging. To generate a more robust preeclampsia gene expression signature, we performed a meta-analysis on the original data of 11 placenta RNA microarray experiments, representing 139 normotensive and 116 preeclamptic pregnancies. Microarray data were pre-processed and analyzed using standardized bioinformatics and statistical procedures and the effect sizes were combined using an inverse-variance random-effects model. Interactions between genes in the resulting gene expression signature were identified by pathway analysis (Ingenuity Pathway Analysis, Gene Set Enrichment Analysis, Graphite) and protein-protein associations (STRING). This approach has resulted in a comprehensive list of differentially expressed genes that led to a 388-gene meta-signature of preeclamptic placenta. Pathway analysis highlights the involvement of the previously identified hypoxia/HIF1A pathway in the establishment of the preeclamptic gene expression profile, while analysis of protein interaction networks indicates CREBBP/EP300 as a novel element central to the preeclamptic placental transcriptome. In addition, there is an apparent high incidence of preeclampsia in women carrying a child with a mutation in CREBBP/EP300 (Rubinstein-Taybi Syndrome). The 388-gene preeclampsia meta-signature offers a vital starting point for further studies into the relevance of these genes (in particular CREBBP/EP300) and their concomitant pathways as biomarkers or functional molecules in preeclampsia. This will result in a better understanding of the molecular basis of this disease and opens up the opportunity to develop rational therapies targeting the placental dysfunction causal to preeclampsia. PMID:26171964

  2. Multi-tissue microarray analysis identifies a molecular signature of regeneration.

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    Sarah E Mercer

    Full Text Available The inability to functionally repair tissues that are lost as a consequence of disease or injury remains a significant challenge for regenerative medicine. The molecular and cellular processes involved in complete restoration of tissue architecture and function are expected to be complex and remain largely unknown. Unlike humans, certain salamanders can completely regenerate injured tissues and lost appendages without scar formation. A parsimonious hypothesis would predict that all of these regenerative activities are regulated, at least in part, by a common set of genes. To test this hypothesis and identify genes that might control conserved regenerative processes, we performed a comprehensive microarray analysis of the early regenerative response in five regeneration-competent tissues from the newt Notophthalmus viridescens. Consistent with this hypothesis, we established a molecular signature for regeneration that consists of common genes or gene family members that exhibit dynamic differential regulation during regeneration in multiple tissue types. These genes include members of the matrix metalloproteinase family and its regulators, extracellular matrix components, genes involved in controlling cytoskeleton dynamics, and a variety of immune response factors. Gene Ontology term enrichment analysis validated and supported their functional activities in conserved regenerative processes. Surprisingly, dendrogram clustering and RadViz classification also revealed that each regenerative tissue had its own unique temporal expression profile, pointing to an inherent tissue-specific regenerative gene program. These new findings demand a reconsideration of how we conceptualize regenerative processes and how we devise new strategies for regenerative medicine.

  3. Dietary separation of sympatric carnivores identified by molecular analysis of scats.

    Science.gov (United States)

    Farrell, L E; Roman, J; Sunquist, M E

    2000-10-01

    We studied the diets of four sympatric carnivores in the flooding savannas of western Venezuela by analysing predator DNA and prey remains in faeces. DNA was isolated and a portion of the cytochrome b gene of the mitochondrial genome amplified and sequenced from 20 of 34 scats. Species were diagnosed by comparing the resulting sequences to reference sequences generated from the blood of puma (Puma concolor), jaguar (Panthera onca), ocelot (Leopardus pardalus) and crab-eating fox (Cerdocyon thous). Scat size has previously been used to identify predators, but DNA data show that puma and jaguar scats overlap in size, as do those of puma, ocelot and fox. Prey-content analysis suggests minimal prey partitioning between pumas and jaguars. In field testing this technique for large carnivores, two potential limitations emerged: locating intact faecal samples and recovering DNA sequences from samples obtained in the wet season. Nonetheless, this study illustrates the tremendous potential of DNA faecal studies. The presence of domestic dog (Canis familiaris) in one puma scat and of wild pig (Sus scrofa), set as bait, in one jaguar sample exemplifies the forensic possibilities of this noninvasive analysis. In addition to defining the dietary habits of similar size sympatric mammals, DNA identifications from faeces allow wildlife managers to detect the presence of endangered taxa and manage prey for their conservation. PMID:11050553

  4. Molecular Fingerprints to Identify Candida Species

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    Claudia Spampinato

    2013-01-01

    Full Text Available A wide range of molecular techniques have been developed for genotyping Candida species. Among them, multilocus sequence typing (MLST and microsatellite length polymorphisms (MLP analysis have recently emerged. MLST relies on DNA sequences of internal regions of various independent housekeeping genes, while MLP identifies microsatellite instability. Both methods generate unambiguous and highly reproducible data. Here, we review the results achieved by using these two techniques and also provide a brief overview of a new method based on high-resolution DNA melting (HRM. This method identifies sequence differences by subtle deviations in sample melting profiles in the presence of saturating fluorescent DNA binding dyes.

  5. Susceptibility to thyroid autoimmune disease: molecular analysis of HLA-D region genes identifies new markers for goitrous Hashimoto's thyroiditis.

    Science.gov (United States)

    Badenhoop, K; Schwarz, G; Walfish, P G; Drummond, V; Usadel, K H; Bottazzo, G F

    1990-11-01

    Hashimoto's thyroiditis has been shown to be associated with the HLA-specificities DR4 and DR5. Since former association studies yielded variable results, we used novel molecular typing methods to assess predisposing immunogenetic factors. Gene analysis of the HLA-DR-DQ and tumor necrosis factor region was performed in a group of Hashimoto's thyroiditis patients and randomly chosen controls using standards and nomenclature of the 10th International Histocompatibility Workshop. Genomic DNA of patients and controls was analyzed using a cDNA probe of the DQB1 gene. The resulting restriction fragment patterns allowed the determination of newly defined DQw-types 1-9. We find the strongest relative risk conferred by DQw7 (RR = 4.7), that is observed in 36 of 64 patients (56%) and only 21 of 98 controls (21%) (P corr less than 0.002). Comparison of DNA sequence variation in the DQB1 gene, that is found predominantly in Hashimoto's thyroiditis patients, indicates that codons 45 and 57 are critical features in DQw7 which distinguish it from other DQw specificities. The adjacent DQA1 genes also display a significant association with Hashimoto's thyroiditis (DQA1*0201/*0301 heterozygotes were found in 37% of patients and 15% controls, P less than 0.03). No significant association could be found with polymorphisms of the tumor necrosis factor gene. These results provide a new basis for the concept of genetic susceptibility in Hashimoto's thyroiditis and will help to elucidate the underlying autoimmune mechanisms that lead to disease at the functional level. PMID:1977755

  6. Morphological and Molecular Analysis Identifies the Associated Fungus ("Xianghui") of the Medicinal White Jelly Mushroom, Tremella fuciformis, as Annulohypoxylon stygium.

    Science.gov (United States)

    Deng, Youjin; van Peer, Arend Frans; Lan, Fu-Sheng; Wang, Qing-Fu; Jiang, Yuji; Lian, Ling-Dan; Lu, Dong-Min; Xie, Baogui

    2016-01-01

    White jelly mushroom, Tremella fuciformis, is a popular edible mushroom with interesting medicinal properties (e.g., immunostimulating, antidiabetic). The formation of T. fuciformis basidiomes is highly dependent on the presence of a specific host fungus, both in nature and for industrial production. This host has traditionally been indicated as "Xianghui" in China, yet which or how many fungal species Xianghui comprises is unclear, with various authorities claiming different species. At present, Annulohypoxilon archeri is generally assumed to be the main Xianghui species, but this has not yet been confirmed experimentally. The implementation of older, premolecular-based research data (i.e., morphological) with present, sequence-based data to solve the identity remains confusing and studies addressing both identification methods in combination are lacking. The unclear identity of Xianghui is a major obstacle for further understanding of the important relationship between the host(s) and T. fuciformis. In this study, we collected a wild specimen of T. fuciformis together with several nearby stroma of Xianghui, cocultivated T. fuciformis with the Xianghui isolates, and observed basidiome formation. Internal transcribed spacer (ITS) sequence analysis showed that all Xianghui spore isolates belonged to the same species and both morphological analysis of sexual stages and ITS β-tubulin and actin gene sequences of the Xianghui specified it as Annulohypoxylon stygium. The ITS sequences of the newly identified Xianghui further closely matched those of the Xianghui strains used in the mushroom industry, showing that wild and culture spawn Xianghui in China consist of A. stygium. In contrast with previous conclusions, A. stygium, and not A. archeris, seems to be the preferred host of T. fuciformis. PMID:27481159

  7. A transcriptome analysis identifies molecular effectors of unconjugated bilirubin in human neuroblastoma SH-SY5Y cells

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    Giraudi Pablo

    2009-11-01

    Full Text Available Abstract Background The deposition of unconjugated bilirubin (UCB in selected regions of the brain results in irreversible neuronal damage, or Bilirubin Encephalopathy (BE. Although UCB impairs a large number of cellular functions in other tissues, the basic mechanisms of neurotoxicity have not yet been fully clarified. While cells can accumulate UCB by passive diffusion, cell protection may involve multiple mechanisms including the extrusion of the pigment as well as pro-survival homeostatic responses that are still unknown. Results Transcriptome changes induced by UCB exposure in SH-SY5Y neuroblastoma cell line were examined by high density oligonucleotide microarrays. Two-hundred and thirty genes were induced after 24 hours. A Gene Ontology (GO analysis showed that at least 50 genes were directly involved in the endoplasmic reticulum (ER stress response. Validation of selected ER stress genes is shown by quantitative RT-PCR. Analysis of XBP1 splicing and DDIT3/CHOP subcellular localization is presented. Conclusion These results show for the first time that UCB exposure induces ER stress response as major intracellular homeostasis in surviving neuroblastoma cells in vitro.

  8. Integrated physiological, biochemical and molecular analysis identifies important traits and mechanisms associated with differential response of rice genotypes to elevated temperature

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    Boghireddy eSailaja

    2015-11-01

    Full Text Available In changing climate, heat stress caused by high temperature poses a serious threat to rice cultivation. A multiple organizational analysis at physiological, biochemical and molecular level is required to fully understand the impact of elevated temperature in rice. This study was aimed at deciphering the elevated temperature response in eleven popular and mega rice cultivars widely grown in India. Physiological and biochemical traits specifically membrane thermostability (MTS, antioxidants, and photosynthesis were studied at vegetative and reproductive phases which were used to establish a correlation with grain yield under stress. Several useful traits in different genotypes were identified which will be important resource to develop high temperature tolerant rice cultivars. Interestingly, Nagina22 emerged as best performer in terms of yield as well as expression of physiological and biochemical traits at elevated temperature. It showed lesser relative injury, lesser reduction in chlorophyll content, increased super oxide dismutase, catalase and peroxidase activity, lesser reduction in net photosynthetic rate (PN, high transpiration rate (E and other photosynthetic/ fluorescence parameters contributing to least reduction in spikelet fertility and grain yield at elevated temperature. Further, expression of 14 genes including heat shock transcription factors and heat shock proteins was analyzed in Nagina22 (tolerant and Vandana (susceptible at flowering phase, strengthening the fact that N22 performs better at molecular level also during elevated temperature. This study shows that elevated temperature response is complex and involves multiple biological processes which are needed to be characterized to address the challenges of future climate extreme conditions.

  9. Proteomics Analysis to Identify and Characterize the Molecular Signatures of Hepatic Steatosis in Ovariectomized Rats as a Model of Postmenopausal Status

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    Chen-Chung Liao

    2015-10-01

    Full Text Available Postmenopausal women are particularly at increased risk of developing non-alcoholic fatty liver disease (NAFLD. Here we aimed to determine the impact of postmenopausal-induced NAFLD (PM-NAFLD in an ovariectomized rat model. Sixteen six-week-old Sprague-Dawley female rats were randomly divided into two groups (eight per group, for sham-operation (Sham or bilateral ovariectomy (Ovx. Four months after surgery, indices of liver damage and liver histomorphometry were measured. Both serum aspartate aminotransferase (AST and alanine aminotranferease (ALT levels were significantly higher in the Ovx than Sham group. We performed quantitative LC-MS/MS-based proteomic profiling of livers from rats with PM-NAFLD to provide baseline knowledge of the PM-NAFLD proteome and to investigate proteins involved in PM-NAFLD by ingenuity pathways analysis (IPA to provide corroborative evidence for differential regulation of molecular and cellular functions affecting metabolic processes. Of the 586 identified proteins, the levels of 59 (10.0% and 48 (8.2% were significantly higher and lower, respectively, in the Ovx group compared to the Sham group. In conclusion, the changes in regulation of proteins implicated in PM-NAFLD may affect other vital biological processes in the body apart from causing postmenopause-mediated liver dysfunction. Our quantitative proteomics analysis may also suggest potential biomarkers and further clinical applications for PM-NAFLD.

  10. Molecular techniques for identifying North Sea fauna

    OpenAIRE

    Knebelsberger, Thomas; Ditzler, Sandra; Laakmann, Silke; Mohrbeck, Inga; Raupach, Michael J.

    2010-01-01

    Accelerated biodiversity assessment is the key to understanding the relationship between biodiversity and ecosystem functioning, especially in times of rapid climate change and habitat destruction. For the marine fauna of the North Sea, morphological species identification is impaired by the small size of many taxa, morphological convergence, intraspecific variation and larval stages which often elude morphological identification. Accordingly, the use of molecular methods...

  11. Integrated RNA-Seq and sRNA-Seq Analysis Identifies Chilling and Freezing Responsive Key Molecular Players and Pathways in Tea Plant (Camellia sinensis.

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    Chao Zheng

    Full Text Available Tea [Camellia sinensis (L O. Kuntze, Theaceae] is one of the most popular non-alcoholic beverages worldwide. Cold stress is one of the most severe abiotic stresses that limit tea plants' growth, survival and geographical distribution. However, the genetic regulatory network and signaling pathways involved in cold stress responses in tea plants remain unearthed. Using RNA-Seq, DGE and sRNA-Seq technologies, we performed an integrative analysis of miRNA and mRNA expression profiling and their regulatory network of tea plants under chilling (4℃ and freezing (-5℃ stress. Differentially expressed (DE miRNA and mRNA profiles were obtained based on fold change analysis, miRNAs and target mRNAs were found to show both coherent and incoherent relationships in the regulatory network. Furthermore, we compared several key pathways (e.g., 'Photosynthesis', GO terms (e.g., 'response to karrikin' and transcriptional factors (TFs, e.g., DREB1b/CBF1 which were identified as involved in the early chilling and/or freezing response of tea plants. Intriguingly, we found that karrikins, a new group of plant growth regulators, and β-primeverosidase (BPR, a key enzyme functionally relevant with the formation of tea aroma might play an important role in both early chilling and freezing response of tea plants. Quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR analysis further confirmed the results from RNA-Seq and sRNA-Seq analysis. This is the first study to simultaneously profile the expression patterns of both miRNAs and mRNAs on a genome-wide scale to elucidate the molecular mechanisms of early responses of tea plants to cold stress. In addition to gaining a deeper insight into the cold resistant characteristics of tea plants, we provide a good case study to analyse mRNA/miRNA expression and profiling of non-model plant species using next-generation sequencing technology.

  12. Integrated RNA-Seq and sRNA-Seq Analysis Identifies Chilling and Freezing Responsive Key Molecular Players and Pathways in Tea Plant (Camellia sinensis).

    Science.gov (United States)

    Zheng, Chao; Zhao, Lei; Wang, Yu; Shen, Jiazhi; Zhang, Yinfei; Jia, Sisi; Li, Yusheng; Ding, Zhaotang

    2015-01-01

    Tea [Camellia sinensis (L) O. Kuntze, Theaceae] is one of the most popular non-alcoholic beverages worldwide. Cold stress is one of the most severe abiotic stresses that limit tea plants' growth, survival and geographical distribution. However, the genetic regulatory network and signaling pathways involved in cold stress responses in tea plants remain unearthed. Using RNA-Seq, DGE and sRNA-Seq technologies, we performed an integrative analysis of miRNA and mRNA expression profiling and their regulatory network of tea plants under chilling (4℃) and freezing (-5℃) stress. Differentially expressed (DE) miRNA and mRNA profiles were obtained based on fold change analysis, miRNAs and target mRNAs were found to show both coherent and incoherent relationships in the regulatory network. Furthermore, we compared several key pathways (e.g., 'Photosynthesis'), GO terms (e.g., 'response to karrikin') and transcriptional factors (TFs, e.g., DREB1b/CBF1) which were identified as involved in the early chilling and/or freezing response of tea plants. Intriguingly, we found that karrikins, a new group of plant growth regulators, and β-primeverosidase (BPR), a key enzyme functionally relevant with the formation of tea aroma might play an important role in both early chilling and freezing response of tea plants. Quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) analysis further confirmed the results from RNA-Seq and sRNA-Seq analysis. This is the first study to simultaneously profile the expression patterns of both miRNAs and mRNAs on a genome-wide scale to elucidate the molecular mechanisms of early responses of tea plants to cold stress. In addition to gaining a deeper insight into the cold resistant characteristics of tea plants, we provide a good case study to analyse mRNA/miRNA expression and profiling of non-model plant species using next-generation sequencing technology. PMID:25901577

  13. Integrated Physiological, Biochemical, and Molecular Analysis Identifies Important Traits and Mechanisms Associated with Differential Response of Rice Genotypes to Elevated Temperature

    OpenAIRE

    Sailaja, Boghireddy; Subrahmanyam, Desiraju; Neelamraju, Sarla; Vishnukiran, Turaga; Rao, Yadavalli Venkateswara; Vijayalakshmi, Pujarula; Voleti, Sitapati R.; Bhadana, Vijai P.; Mangrauthia, Satendra K.

    2015-01-01

    In changing climatic conditions, heat stress caused by high temperature poses a serious threat to rice cultivation. A multiple organizational analysis at physiological, biochemical, and molecular levels is required to fully understand the impact of elevated temperature in rice. This study was aimed at deciphering the elevated temperature response in 11 popular and mega rice cultivars widely grown in India. Physiological and biochemical traits specifically membrane thermostability (MTS), antio...

  14. Key molecular processes of the diapause to post-diapause quiescence transition in the alfalfa leafcutting bee Megachile rotundata identified by comparative transcriptome analysis

    Science.gov (United States)

    Insect diapause (dormancy) synchronizes an insect’s life cycle to seasonal changes in the abiotic and biotic resources required for development and reproduction. Transcription analysis of Megachile rotundata diapause termination identified 399 post-diapause upregulated and 144 post-diapause down-reg...

  15. Analysis of bulked segregants to identify molecular markers linked with cocoon weight and cocoon shell weight in the silkworm Bombyx mori L

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Two silkworm strains viz, B20 A (high cocoon shell ratio) and C.Nichi (low cocoon shell ratio) were sib mated for 10 generations to determine the homozygosis. Both bulked segregant analysis(BSA) and near isogenic lines (NIL) studies were done to identify the RFLP markers closely linked to cocoon shell parameters. Three hundred and fifty-two random clones were identified as the low copy number sequence and used for identification of Restriction Fragment Length Polymorphic (RFLP) marker linked to cocoon weight and cocoon shell character. In the bulk segregant analysis, DNA from the parents (B20 A, C.Nichi), F1 and F2 progeny of high shell ratio (HSR) and low shell ratio (LSR) were screened for hybridization with the random clones. Polymorphic banding pattern achieved through southern hybridization with different probes indicated the probable correlation of polymorphism with high and low cocoon shell character which are possible landmarks in identifying the putative marker(s) for the cocoon shell character. Out of the 100 probes tried with parents, F1, F2 and their bulks, 10 probes were found to be closely linked to cocoon shell characters.

  16. Genomic analyses identify molecular subtypes of pancreatic cancer.

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    Bailey, Peter; Chang, David K; Nones, Katia; Johns, Amber L; Patch, Ann-Marie; Gingras, Marie-Claude; Miller, David K; Christ, Angelika N; Bruxner, Tim J C; Quinn, Michael C; Nourse, Craig; Murtaugh, L Charles; Harliwong, Ivon; Idrisoglu, Senel; Manning, Suzanne; Nourbakhsh, Ehsan; Wani, Shivangi; Fink, Lynn; Holmes, Oliver; Chin, Venessa; Anderson, Matthew J; Kazakoff, Stephen; Leonard, Conrad; Newell, Felicity; Waddell, Nick; Wood, Scott; Xu, Qinying; Wilson, Peter J; Cloonan, Nicole; Kassahn, Karin S; Taylor, Darrin; Quek, Kelly; Robertson, Alan; Pantano, Lorena; Mincarelli, Laura; Sanchez, Luis N; Evers, Lisa; Wu, Jianmin; Pinese, Mark; Cowley, Mark J; Jones, Marc D; Colvin, Emily K; Nagrial, Adnan M; Humphrey, Emily S; Chantrill, Lorraine A; Mawson, Amanda; Humphris, Jeremy; Chou, Angela; Pajic, Marina; Scarlett, Christopher J; Pinho, Andreia V; Giry-Laterriere, Marc; Rooman, Ilse; Samra, Jaswinder S; Kench, James G; Lovell, Jessica A; Merrett, Neil D; Toon, Christopher W; Epari, Krishna; Nguyen, Nam Q; Barbour, Andrew; Zeps, Nikolajs; Moran-Jones, Kim; Jamieson, Nigel B; Graham, Janet S; Duthie, Fraser; Oien, Karin; Hair, Jane; Grützmann, Robert; Maitra, Anirban; Iacobuzio-Donahue, Christine A; Wolfgang, Christopher L; Morgan, Richard A; Lawlor, Rita T; Corbo, Vincenzo; Bassi, Claudio; Rusev, Borislav; Capelli, Paola; Salvia, Roberto; Tortora, Giampaolo; Mukhopadhyay, Debabrata; Petersen, Gloria M; Munzy, Donna M; Fisher, William E; Karim, Saadia A; Eshleman, James R; Hruban, Ralph H; Pilarsky, Christian; Morton, Jennifer P; Sansom, Owen J; Scarpa, Aldo; Musgrove, Elizabeth A; Bailey, Ulla-Maja Hagbo; Hofmann, Oliver; Sutherland, Robert L; Wheeler, David A; Gill, Anthony J; Gibbs, Richard A; Pearson, John V; Waddell, Nicola; Biankin, Andrew V; Grimmond, Sean M

    2016-03-01

    Integrated genomic analysis of 456 pancreatic ductal adenocarcinomas identified 32 recurrently mutated genes that aggregate into 10 pathways: KRAS, TGF-β, WNT, NOTCH, ROBO/SLIT signalling, G1/S transition, SWI-SNF, chromatin modification, DNA repair and RNA processing. Expression analysis defined 4 subtypes: (1) squamous; (2) pancreatic progenitor; (3) immunogenic; and (4) aberrantly differentiated endocrine exocrine (ADEX) that correlate with histopathological characteristics. Squamous tumours are enriched for TP53 and KDM6A mutations, upregulation of the TP63∆N transcriptional network, hypermethylation of pancreatic endodermal cell-fate determining genes and have a poor prognosis. Pancreatic progenitor tumours preferentially express genes involved in early pancreatic development (FOXA2/3, PDX1 and MNX1). ADEX tumours displayed upregulation of genes that regulate networks involved in KRAS activation, exocrine (NR5A2 and RBPJL), and endocrine differentiation (NEUROD1 and NKX2-2). Immunogenic tumours contained upregulated immune networks including pathways involved in acquired immune suppression. These data infer differences in the molecular evolution of pancreatic cancer subtypes and identify opportunities for therapeutic development.

  17. Molecular field analysis of trophic relationships in soil-dwelling invertebrates to identify mercury, lead and cadmium transmission through forest ecosystems.

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    Šerić Jelaska, Lucija; Jurasović, Jasna; Brown, David S; Vaughan, Ian P; Symondson, William O C

    2014-08-01

    Contamination pathways in complex food chains in soil ecosystems can be difficult to elucidate. Molecular analysis of predator gut content can, however, rapidly reveal previously unidentified trophic interactions between invertebrates and thereby uncover pathways of pollutant spread. Here, we measured concentrations of the toxic metals lead, cadmium and mercury in carabid beetle predators and their prey. Invertebrates were sampled at one control and four heavy metal-polluted sites to reveal the impact of diet composition and seasonal variation in prey availability on metal burden in carabids and metal transfer pathways through forest ecosystems. This is the first report, to our knowledge, of carabid diet composition based on PCR analysis of gut contents at the forest community level, rather than in cultivated fields. Extensive screening using group- and species-specific primers revealed that carabids ate primarily earthworms and slugs, as well as smaller numbers of woodlice and springtails. Metal concentrations in carabids correlated with seasonal changes in diet. Mercury accumulated in beetle predators more than in their slug prey. As earthworms, slugs and carabid beetles are the major prey of many birds and mammals, prey-predator transfer and associated toxicity are major risks at mercury-contaminated sites. Carabids may be useful bioindicators for assessing the impact of pollutants on soil ecosystems, as long as species and seasonal factors are taken into account. PMID:24138157

  18. Analysis of bulked segregants to identify molecular markers linked with cocoon weight and cocoon shell weight in the silkworm Bombyx mori L

    Institute of Scientific and Technical Information of China (English)

    SateeshKumar; 徐孟奎; 陈玉银; Ponnuvel,K.M; Datta,R.K

    2002-01-01

    Two silkworm strains viz, B20 A (high cocoon shell ratio) and C. Nichi (low cocoon shell ratio) were sib mated for 10 generations to determine the homozygoeis. Both bulked segregant analysis (BSA) and near isogenic lines (NIL) studies were done to identify the RFLP markers doaely linked to cocoon shell parameters. Three hundred and fifty-two random clones were identified as the low copy number 'sequeiace and used for identification of Restriction Fragment Length Polyrnorphic (RFLP) marker linked to cocoon weight and cocoon shell character. In the bulk aegregant analysia, DNA from the parents (B20 A, C.Nichi), Fl and F2 progeny of high shell ratio (HSR) and low shell ratio (LSR) were screened for hybridization with the random clones. Polymorphic banding pattern achieved through southern hybridization with different probes indicated the probable correlation of polymorphism with high and low cocoon shell character which are possible landmarks in identifying the putative marker(s) for the cocoon shell character. Out of the 100 probes tried with parents, Fl, F2 and their bulks 10 probes were found to be closely linked to cocoon shell characters.

  19. Morphological, molecular and cross-breeding analysis of geographic populations of coconut-mite associated predatory mites identified as Neoseiulus baraki: evidence for cryptic species?

    Science.gov (United States)

    Famah Sourassou, Nazer; Hanna, Rachid; Zannou, Ignace; Breeuwer, Johannes A J; de Moraes, Gilberto; Sabelis, Maurice W

    2012-05-01

    Surveys were conducted in Brazil, Benin and Tanzania to collect predatory mites as candidates for control of the coconut mite Aceria guerreronis Keifer, a serious pest of coconut fruits. At all locations surveyed, one of the most dominant predators on infested coconut fruits was identified as Neoseiulus baraki Athias-Henriot, based on morphological similarity with regard to taxonomically relevant characters. However, scrutiny of our own and published descriptions suggests that consistent morphological differences may exist between the Benin population and those from the other geographic origins. In this study, we combined three methods to assess whether these populations belong to one species or a few distinct, yet closely related species. First, multivariate analysis of 32 morphological characters showed that the Benin population differed from the other three populations. Second, DNA sequence analysis based on the mitochondrial cytochrome oxidase subunit I (COI) showed the same difference between these populations. Third, cross-breeding between populations was unsuccessful in all combinations. These data provide evidence for the existence of cryptic species. Subsequent morphological research showed that the Benin population can be distinguished from the others by a new character (not included in the multivariate analysis), viz. the number of teeth on the fixed digit of the female chelicera.

  20. A 6-gene signature identifies four molecular subgroups of neuroblastoma

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    Kogner Per

    2011-04-01

    Full Text Available Abstract Background There are currently three postulated genomic subtypes of the childhood tumour neuroblastoma (NB; Type 1, Type 2A, and Type 2B. The most aggressive forms of NB are characterized by amplification of the oncogene MYCN (MNA and low expression of the favourable marker NTRK1. Recently, mutations or high expression of the familial predisposition gene Anaplastic Lymphoma Kinase (ALK was associated to unfavourable biology of sporadic NB. Also, various other genes have been linked to NB pathogenesis. Results The present study explores subgroup discrimination by gene expression profiling using three published microarray studies on NB (47 samples. Four distinct clusters were identified by Principal Components Analysis (PCA in two separate data sets, which could be verified by an unsupervised hierarchical clustering in a third independent data set (101 NB samples using a set of 74 discriminative genes. The expression signature of six NB-associated genes ALK, BIRC5, CCND1, MYCN, NTRK1, and PHOX2B, significantly discriminated the four clusters (p ALK, BIRC5, and PHOX2B, and was significantly associated with higher tumour stage, poor outcome and poor survival compared to the Type 1-corresponding favourable group (INSS stage 4 and/or dead of disease, p Conclusions Based on expression profiling we have identified four molecular subgroups of neuroblastoma, which can be distinguished by a 6-gene signature. The fourth subgroup has not been described elsewhere, and efforts are currently made to further investigate this group's specific characteristics.

  1. Multigene mutational profiling of cholangiocarcinomas identifies actionable molecular subgroups

    Science.gov (United States)

    Mafficini, Andrea; Wood, Laura D.; Corbo, Vincenzo; Melisi, Davide; Malleo, Giuseppe; Vicentini, Caterina; Malpeli, Giorgio; Antonello, Davide; Sperandio, Nicola; Capelli, Paola; Tomezzoli, Anna; Iacono, Calogero; Lawlor, Rita T.; Bassi, Claudio; Hruban, Ralph H.; Guglielmi, Alfredo; Tortora, Giampaolo; de Braud, Filippo; Scarpa, Aldo

    2014-01-01

    One-hundred-fifty-three biliary cancers, including 70 intrahepatic cholangiocarcinomas (ICC), 57 extrahepatic cholangiocarcinomas (ECC) and 26 gallbladder carcinomas (GBC) were assessed for mutations in 56 genes using multigene next-generation sequencing. Expression of EGFR and mTOR pathway genes was investigated by immunohistochemistry. At least one mutated gene was observed in 118/153 (77%) cancers. The genes most frequently involved were KRAS (28%), TP53 (18%), ARID1A (12%), IDH1/2 (9%), PBRM1 (9%), BAP1 (7%), and PIK3CA (7%). IDH1/2 (p=0.0005) and BAP1 (p=0.0097) mutations were characteristic of ICC, while KRAS (p=0.0019) and TP53 (p=0.0019) were more frequent in ECC and GBC. Multivariate analysis identified tumour stage and TP53 mutations as independent predictors of survival. Alterations in chromatin remodeling genes (ARID1A, BAP1, PBRM1, SMARCB1) were seen in 31% of cases. Potentially actionable mutations were seen in 104/153 (68%) cancers: i) KRAS/NRAS/BRAF mutations were found in 34% of cancers; ii) mTOR pathway activation was documented by immunohistochemistry in 51% of cases and by mutations in mTOR pathway genes in 19% of cancers; iii) TGF-ß/Smad signaling was altered in 10.5% cancers; iv) mutations in tyrosine kinase receptors were found in 9% cases. Our study identified molecular subgroups of cholangiocarcinomas that can be explored for specific drug targeting in clinical trials. PMID:24867389

  2. A 6-gene signature identifies four molecular subgroups of neuroblastoma

    LENUS (Irish Health Repository)

    Abel, Frida

    2011-04-14

    Abstract Background There are currently three postulated genomic subtypes of the childhood tumour neuroblastoma (NB); Type 1, Type 2A, and Type 2B. The most aggressive forms of NB are characterized by amplification of the oncogene MYCN (MNA) and low expression of the favourable marker NTRK1. Recently, mutations or high expression of the familial predisposition gene Anaplastic Lymphoma Kinase (ALK) was associated to unfavourable biology of sporadic NB. Also, various other genes have been linked to NB pathogenesis. Results The present study explores subgroup discrimination by gene expression profiling using three published microarray studies on NB (47 samples). Four distinct clusters were identified by Principal Components Analysis (PCA) in two separate data sets, which could be verified by an unsupervised hierarchical clustering in a third independent data set (101 NB samples) using a set of 74 discriminative genes. The expression signature of six NB-associated genes ALK, BIRC5, CCND1, MYCN, NTRK1, and PHOX2B, significantly discriminated the four clusters (p < 0.05, one-way ANOVA test). PCA clusters p1, p2, and p3 were found to correspond well to the postulated subtypes 1, 2A, and 2B, respectively. Remarkably, a fourth novel cluster was detected in all three independent data sets. This cluster comprised mainly 11q-deleted MNA-negative tumours with low expression of ALK, BIRC5, and PHOX2B, and was significantly associated with higher tumour stage, poor outcome and poor survival compared to the Type 1-corresponding favourable group (INSS stage 4 and\\/or dead of disease, p < 0.05, Fisher\\'s exact test). Conclusions Based on expression profiling we have identified four molecular subgroups of neuroblastoma, which can be distinguished by a 6-gene signature. The fourth subgroup has not been described elsewhere, and efforts are currently made to further investigate this group\\'s specific characteristics.

  3. Morphological, molecular and cross-breeding analysis of geographic populations of coconut-mite associated predatory mites identified as Neoseiulus baraki: evidence for cryptic species?

    NARCIS (Netherlands)

    N.F. Sourassou; R. Hanna; I. Zannou; J.A.J. Breeuwer; G. de Moraes; M.W. Sabelis

    2012-01-01

    Surveys were conducted in Brazil, Benin and Tanzania to collect predatory mites as candidates for control of the coconut mite Aceria guerreronis Keifer, a serious pest of coconut fruits. At all locations surveyed, one of the most dominant predators on infested coconut fruits was identified as Neosei

  4. Molecular profiling of Mycobacterium tuberculosis identifies tuberculosinyl nucleoside products of the virulence-associated enzyme Rv3378c

    NARCIS (Netherlands)

    Layre, Emilie; Lee, Ho Jun; Young, David C.; Martinot, Amanda Jezek; Buter, Jeffrey; Minnaard, Adriaan J.; Annand, John W.; Fortune, Sarah M.; Snider, Barry B.; Matsunaga, Isamu; Rubin, Eric J.; Alber, Tom; Moody, D. Branch

    2014-01-01

    To identify lipids with roles in tuberculosis disease, we systematically compared the lipid content of virulent Mycobacterium tuberculosis with the attenuated vaccine strain Mycobacterium bovis bacillus Calmette-Guerin. Comparative lipidomics analysis identified more than 1,000 molecular differences

  5. Molecular analysis of the genus Asparagus based on matK sequences and its application to identify A. racemosus, a medicinally phytoestrogenic species.

    Science.gov (United States)

    Boonsom, Teerawat; Waranuch, Neti; Ingkaninan, Kornkanok; Denduangboripant, Jessada; Sukrong, Suchada

    2012-07-01

    The plant Asparagus racemosus is one of the most widely used sources of phytoestrogens because of its high content of the steroidal saponins, shatavarins I-IV, in roots. The dry root of A. racemosus, known as "Rak-Sam-Sip" in Thai, is one of the most popular herbal medicines, used as an anti-inflammatory, an aphrodisiac and a galactagogue. Recently, the interest in plant-derived estrogens has increased tremendously, making A. racemosus particularly important and a possible target for fraudulent labeling. However, the identification of A. racemosus is generally difficult due to its similar morphology to other Asparagus spp. Thus, accurate authentication of A. racemosus is essential. In this study, 1557-bp nucleotide sequences of the maturase K (matK) gene of eight Asparagus taxa were analyzed. A phylogenetic relationship based on the matK gene was also constructed. Ten polymorphic sites of nucleotide substitutions were found within the matK sequences. A. racemosus showed different nucleotide substitutions to the other species. A polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis of the matK gene was developed to discriminate A. racemosus from others. Only the 650-bp PCR product from A. racemosus could be digested with BssKI into two fragments of 397 and 253-bp while the products of other species remained undigested. Ten commercially crude drugs were analyzed and revealed that eight samples were derived from A. racemosus while two samples of that were not. Thus, the PCR-RFLP analysis of matK gene was shown to be an effective method for authentication of the medicinally phytoestrogenic species, A. racemosus.

  6. Molecular Surveillance Identifies Multiple Transmissions of Typhoid in West Africa

    Science.gov (United States)

    Wong, Vanessa K.; Holt, Kathryn E.; Okoro, Chinyere; Baker, Stephen; Pickard, Derek J.; Marks, Florian; Page, Andrew J.; Olanipekun, Grace; Munir, Huda; Alter, Roxanne; Fey, Paul D.; Feasey, Nicholas A.; Weill, Francois-Xavier; Le Hello, Simon; Hart, Peter J.; Kariuki, Samuel; Breiman, Robert F.; Gordon, Melita A.; Heyderman, Robert S.; Jacobs, Jan; Lunguya, Octavie; Msefula, Chisomo; MacLennan, Calman A.; Keddy, Karen H.; Smith, Anthony M.; Onsare, Robert S.; De Pinna, Elizabeth; Nair, Satheesh; Amos, Ben; Dougan, Gordon; Obaro, Stephen

    2016-01-01

    Background The burden of typhoid in sub-Saharan African (SSA) countries has been difficult to estimate, in part, due to suboptimal laboratory diagnostics. However, surveillance blood cultures at two sites in Nigeria have identified typhoid associated with Salmonella enterica serovar Typhi (S. Typhi) as an important cause of bacteremia in children. Methods A total of 128 S. Typhi isolates from these studies in Nigeria were whole-genome sequenced, and the resulting data was used to place these Nigerian isolates into a worldwide context based on their phylogeny and carriage of molecular determinants of antibiotic resistance. Results Several distinct S. Typhi genotypes were identified in Nigeria that were related to other clusters of S. Typhi isolates from north, west and central regions of Africa. The rapidly expanding S. Typhi clade 4.3.1 (H58) previously associated with multiple antimicrobial resistances in Asia and in east, central and southern Africa, was not detected in this study. However, antimicrobial resistance was common amongst the Nigerian isolates and was associated with several plasmids, including the IncHI1 plasmid commonly associated with S. Typhi. Conclusions These data indicate that typhoid in Nigeria was established through multiple independent introductions into the country, with evidence of regional spread. MDR typhoid appears to be evolving independently of the haplotype H58 found in other typhoid endemic countries. This study highlights an urgent need for routine surveillance to monitor the epidemiology of typhoid and evolution of antimicrobial resistance within the bacterial population as a means to facilitate public health interventions to reduce the substantial morbidity and mortality of typhoid. PMID:27657909

  7. Identifying molecular targets of lifestyle modifications in colon cancer prevention

    Directory of Open Access Journals (Sweden)

    Molly Marie Derry

    2013-05-01

    Full Text Available One in four deaths in the United States is cancer-related, and colorectal cancer (CRC is the second leading cause of cancer-associated deaths. Screening strategies are utilized but have not reduced disease incidence or mortality. In this regard, there is an interest in cancer preventive strategies focusing on lifestyle intervention, where specific etiologic factors involved in cancer initiation, promotion, and progression could be targeted. For example, exposure to dietary carcinogens, such as nitrosamines and polycyclic aromatic hydrocarbons influences colon carcinogenesis. Furthermore, dietary deficiencies could alter sensitivity to genetic damage and influence carcinogen metabolism contributing to CRC. High alcohol consumption increases the risk of mutations including the fact that acetaldehyde, an ethanol metabolite, is classified as a group 1 carcinogen. Tobacco smoke exposure is also a risk factor for cancer development; ~20% of CRCs are associated with smoking. Additionally, obese patients have a higher risk of cancer development, which is further supported by the fact that physical activity decreases CRC risk by 55%. Similarly, chronic inflammatory conditions also increase the risk of CRC development. Moreover, the circadian clock alters digestion and regulates other biochemical, physiological and behavioral processes that could positively influence CRC. Taken together, colon carcinogenesis involves a number of etiological factors, and therefore, to create effective preventive strategies, molecular targets need to be identified and beleaguered prior to disease progression. With this in mind, the following is a comprehensive review identifying downstream target proteins of the above lifestyle risk factors, which are modulated during colon carcinogenesis and could be targeted for CRC prevention by novel agents including phytochemicals.

  8. Molecular analysis and anticancer properties of two identified isolates, Fusarium solani and Emericella nidulans isolated from Wady El-Natron soil in Egypt against Caco-2 (ATCC) cell line

    Institute of Scientific and Technical Information of China (English)

    Hala F Mohamed

    2012-01-01

    Objective: To characterize, identify and investigate the anticancer properties of two new soil fungal isolates, Emericella nidulans and Fusarium solani isolated from Wady El-Natron in Egypt against colon cancer Caco-2 (ATCC) cell line. Methods: Soil sample was cultured and two strains were chosen for morphological and phenotypical characterization. Partial sequences of the 18s rRNA gene and the internal transcribed spacer region ITS of the two isolates were amplified by PCR. Phylogenetic tree construction and analysis of the resulted multiple sequences from the two fugal isolates were also carried out. In vitro anticancer activity of the two strains was done against colon Caco-2 cancer cell line. Reverse transcription – PCR was carried out to detect level of expression of p53 in Caco-2 cell line. Results: HF.1 displayed morphological and genotypic characteristics most similar to that of Fusarium solani while HF.2 was most similar to Emericella nidulans with high similarity of 99% and 97% respectively. The multiple sequence alignment of the two fungal isolates showed that, the maximum identical conserved domains in the 18s rRNA genes were identified with the nucleotide regions of 51st to 399th base pairs, 88th to 525th base pairs respectively. While those in the ITS genes were identified with the nucleotide regions of 88th to 463rdand 51st to 274th. The two isolates showed IC50 value with (6.24±5.21) and (9.84±0.36) μg/mL) concentrations respectively at 28h. Reverse transcription – PCR indicated that these cells showed high level of expression for p53 mRNA. Conclusions: The morphology and molecular analysis identified HF.1 and HF.2 to be Fusarium solani and Emericella nidulans; new isolates of anticancer producing fungi from Wady El-Natroon city in Egypt. Treatment with the two isolates caused P53 expression in Caco-2 cell line. These two isolates can be used as an anticancer agents.

  9. Parameter Trajectory Analysis to Identify Treatment Effects of Pharmacological Interventions

    OpenAIRE

    Tiemann, Christian A.; Vanlier, Joep; Oosterveer, Maaike H.; Albert K Groen; Hilbers, Peter A. J.; Natal A W van Riel

    2013-01-01

    The field of medical systems biology aims to advance understanding of molecular mechanisms that drive disease progression and to translate this knowledge into therapies to effectively treat diseases. A challenging task is the investigation of long-term effects of a (pharmacological) treatment, to establish its applicability and to identify potential side effects. We present a new modeling approach, called Analysis of Dynamic Adaptations in Parameter Trajectories (ADAPT), to analyze the long-t...

  10. Factor analysis identifies subgroups of constipation

    Institute of Scientific and Technical Information of China (English)

    Philip G Dinning; Mike Jones; Linda Hunt; Sergio E Fuentealba; Jamshid Kalanter; Denis W King; David Z Lubowski; Nicholas J Talley; Ian J Cook

    2011-01-01

    AIM: To determine whether distinct symptom groupings exist in a constipated population and whether such grouping might correlate with quantifiable pathophysiological measures of colonic dysfunction. METHODS: One hundred and ninety-one patients presenting to a Gastroenterology clinic with constipation and 32 constipated patients responding to a newspaper advertisement completed a 53-item, wide-ranging selfreport questionnaire. One hundred of these patients had colonic transit measured scintigraphically. Factor analysis determined whether constipation-related symptoms grouped into distinct aspects of symptomatology. Cluster analysis was used to determine whether individual patients naturally group into distinct subtypes. RESULTS: Cluster analysis yielded a 4 cluster solution with the presence or absence of pain and laxative unresponsiveness providing the main descriptors. Amongst all clusters there was a considerable proportion of patients with demonstrable delayed colon transit, irritable bowel syndrome positive criteria and regular stool frequency. The majority of patients with these characteristics also reported regular laxative use. CONCLUSION: Factor analysis identified four constipation subgroups, based on severity and laxative unresponsiveness, in a constipated population. However, clear stratification into clinically identifiable groups remains imprecise.

  11. Molecular Testing of 163 Patients with Morquio A (Mucopolysaccharidosis IVA) Identifies 39 Novel GALNS Mutations

    Science.gov (United States)

    Morrone, A; Tylee, K.L.; Al-Sayed, M; Brusius-Facchin, A.C.; Caciotti, A.; Church, H.J.; Coll, M.J.; Davidson, K.; Fietz, M.J.; Gort, L.; Hegde, M.; Kubaski, F.; Lacerda, L.; Laranjeira, F.; Leistner-Segal, S.; Mooney, S.; Pajares, S.; Pollard, L.; Riberio, I.; Wang, R.Y.; Miller, N.

    2014-01-01

    Morquio A (Mucopolysaccharidosis IVA; MPS IVA) is an autosomal recessive lysosomal storage disorder caused by partial or total deficiency of the enzyme galactosamine-6-sulfate sulfatase (GALNS; also known as N-acetylgalactosamine-6-sulfate sulfatase) encoded by the GALNS gene. Patients who inherit two mutated GALNS gene alleles produce protein with decreased ability to degrade the glycosaminoglycans (GAGs) keratan sulfate and chondroitin 6-sulfate, thereby causing GAG accumulation within lysosomes and consequently pleiotropic disease. GALNS mutations occur throughout the gene and many mutations are identified only in single patients or families, causing difficulties both in mutation detection and interpretation. In this study, molecular analysis of 163 patients with Morquio A identified 99 unique mutations in the GALNS gene believed to negatively impact GALNS protein function, of which 39 are previously unpublished, together with 26 single-nucleotide polymorphisms. Recommendations for the molecular testing of patients, clear reporting of sequence findings, and interpretation of sequencing data are provided. PMID:24726177

  12. Molecular testing of 163 patients with Morquio A (Mucopolysaccharidosis IVA) identifies 39 novel GALNS mutations.

    Science.gov (United States)

    Morrone, A; Tylee, K L; Al-Sayed, M; Brusius-Facchin, A C; Caciotti, A; Church, H J; Coll, M J; Davidson, K; Fietz, M J; Gort, L; Hegde, M; Kubaski, F; Lacerda, L; Laranjeira, F; Leistner-Segal, S; Mooney, S; Pajares, S; Pollard, L; Ribeiro, I; Wang, R Y; Miller, N

    2014-06-01

    Morquio A (Mucopolysaccharidosis IVA; MPS IVA) is an autosomal recessive lysosomal storage disorder caused by partial or total deficiency of the enzyme galactosamine-6-sulfate sulfatase (GALNS; also known as N-acetylgalactosamine-6-sulfate sulfatase) encoded by the GALNS gene. Patients who inherit two mutated GALNS gene alleles have a decreased ability to degrade the glycosaminoglycans (GAGs) keratan sulfate and chondroitin 6-sulfate, thereby causing GAG accumulation within lysosomes and consequently pleiotropic disease. GALNS mutations occur throughout the gene and many mutations are identified only in single patients or families, causing difficulties both in mutation detection and interpretation. In this study, molecular analysis of 163 patients with Morquio A identified 99 unique mutations in the GALNS gene believed to negatively impact GALNS protein function, of which 39 are previously unpublished, together with 26 single-nucleotide polymorphisms. Recommendations for the molecular testing of patients, clear reporting of sequence findings, and interpretation of sequencing data are provided.

  13. Probing molecular mechanisms of the Hsp90 chaperone: biophysical modeling identifies key regulators of functional dynamics.

    Directory of Open Access Journals (Sweden)

    Anshuman Dixit

    Full Text Available Deciphering functional mechanisms of the Hsp90 chaperone machinery is an important objective in cancer biology aiming to facilitate discovery of targeted anti-cancer therapies. Despite significant advances in understanding structure and function of molecular chaperones, organizing molecular principles that control the relationship between conformational diversity and functional mechanisms of the Hsp90 activity lack a sufficient quantitative characterization. We combined molecular dynamics simulations, principal component analysis, the energy landscape model and structure-functional analysis of Hsp90 regulatory interactions to systematically investigate functional dynamics of the molecular chaperone. This approach has identified a network of conserved regions common to the Hsp90 chaperones that could play a universal role in coordinating functional dynamics, principal collective motions and allosteric signaling of Hsp90. We have found that these functional motifs may be utilized by the molecular chaperone machinery to act collectively as central regulators of Hsp90 dynamics and activity, including the inter-domain communications, control of ATP hydrolysis, and protein client binding. These findings have provided support to a long-standing assertion that allosteric regulation and catalysis may have emerged via common evolutionary routes. The interaction networks regulating functional motions of Hsp90 may be determined by the inherent structural architecture of the molecular chaperone. At the same time, the thermodynamics-based "conformational selection" of functional states is likely to be activated based on the nature of the binding partner. This mechanistic model of Hsp90 dynamics and function is consistent with the notion that allosteric networks orchestrating cooperative protein motions can be formed by evolutionary conserved and sparsely connected residue clusters. Hence, allosteric signaling through a small network of distantly connected

  14. Parameter trajectory analysis to identify treatment effects of pharmacological interventions.

    Directory of Open Access Journals (Sweden)

    Christian A Tiemann

    Full Text Available The field of medical systems biology aims to advance understanding of molecular mechanisms that drive disease progression and to translate this knowledge into therapies to effectively treat diseases. A challenging task is the investigation of long-term effects of a (pharmacological treatment, to establish its applicability and to identify potential side effects. We present a new modeling approach, called Analysis of Dynamic Adaptations in Parameter Trajectories (ADAPT, to analyze the long-term effects of a pharmacological intervention. A concept of time-dependent evolution of model parameters is introduced to study the dynamics of molecular adaptations. The progression of these adaptations is predicted by identifying necessary dynamic changes in the model parameters to describe the transition between experimental data obtained during different stages of the treatment. The trajectories provide insight in the affected underlying biological systems and identify the molecular events that should be studied in more detail to unravel the mechanistic basis of treatment outcome. Modulating effects caused by interactions with the proteome and transcriptome levels, which are often less well understood, can be captured by the time-dependent descriptions of the parameters. ADAPT was employed to identify metabolic adaptations induced upon pharmacological activation of the liver X receptor (LXR, a potential drug target to treat or prevent atherosclerosis. The trajectories were investigated to study the cascade of adaptations. This provided a counter-intuitive insight concerning the function of scavenger receptor class B1 (SR-B1, a receptor that facilitates the hepatic uptake of cholesterol. Although activation of LXR promotes cholesterol efflux and -excretion, our computational analysis showed that the hepatic capacity to clear cholesterol was reduced upon prolonged treatment. This prediction was confirmed experimentally by immunoblotting measurements of SR-B1

  15. Quantitative proteomics identify molecular targets that are crucial in larval settlement and metamorphosis of bugula neritina

    KAUST Repository

    Zhang, Huoming

    2011-01-07

    The marine invertebrate Bugula neritina has a biphasic life cycle that consists of a swimming larval stage and a sessile juvenile and adult stage. The attachment of larvae to the substratum and their subsequent metamorphosis have crucial ecological consequences. Despite many studies on this species, little is known about the molecular mechanism of these processes. Here, we report a comparative study of swimming larvae and metamorphosing individuals at 4 and 24 h postattachment using label-free quantitative proteomics. We identified more than 1100 proteins at each stage, 61 of which were differentially expressed. Specifically, proteins involved in energy metabolism and structural molecules were generally down-regulated, whereas proteins involved in transcription and translation, the extracellular matrix, and calcification were strongly up-regulated during metamorphosis. Many tightly regulated novel proteins were also identified. Subsequent analysis of the temporal and spatial expressions of some of the proteins and an assay of their functions indicated that they may have key roles in metamorphosis of B. neritina. These findings not only provide molecular evidence with which to elucidate the substantial changes in morphology and physiology that occur during larval attachment and metamorphosis but also identify potential targets for antifouling treatment. © 2011 American Chemical Society.

  16. Structural Analysis of Molecular Clouds: Dendrograms

    CERN Document Server

    Rosolowsky, E W; Kauffmann, J; Goodman, A A

    2008-01-01

    We demonstrate the utility of dendrograms at representing the essential features of the hierarchical structure of the isosurfaces for molecular line data cubes. The dendrogram of a data cube is an abstraction of the changing topology of the isosurfaces as a function of contour level. The ability to track hierarchical structure over a range of scales makes this analysis philosophically different from local segmentation algorithms like CLUMPFIND. Points in the dendrogram structure correspond to specific volumes in data cubes defined by their bounding isosurfaces. We further refine the technique by measuring the properties associated with each isosurface in the analysis allowing for a multiscale calculation of molecular gas properties. Using COMPLETE 13CO(1-0) data from the L1448 region in Perseus and mock observations of a simulated data cube, we identify regions that have a significant contribution by self-gravity to their energetics on a range of scales. We find evidence for self-gravitation on all spatial sc...

  17. Rice Transcriptome Analysis to Identify Possible Herbicide Quinclorac Detoxification Genes

    Directory of Open Access Journals (Sweden)

    Wenying eXu

    2015-09-01

    Full Text Available Quinclorac is a highly selective auxin-type herbicide, and is widely used in the effective control of barnyard grass in paddy rice fields, improving the world’s rice yield. The herbicide mode of action of quinclorac has been proposed and hormone interactions affect quinclorac signaling. Because of widespread use, quinclorac may be transported outside rice fields with the drainage waters, leading to soil and water pollution and environmental health problems.In this study, we used 57K Affymetrix rice whole-genome array to identify quinclorac signaling response genes to study the molecular mechanisms of action and detoxification of quinclorac in rice plants. Overall, 637 probe sets were identified with differential expression levels under either 6 or 24 h of quinclorac treatment. Auxin-related genes such as GH3 and OsIAAs responded to quinclorac treatment. Gene Ontology analysis showed that genes of detoxification-related family genes were significantly enriched, including cytochrome P450, GST, UGT, and ABC and drug transporter genes. Moreover, real-time RT-PCR analysis showed that top candidate P450 families such as CYP81, CYP709C and CYP72A genes were universally induced by different herbicides. Some Arabidopsis genes for the same P450 family were up-regulated under quinclorac treatment.We conduct rice whole-genome GeneChip analysis and the first global identification of quinclorac response genes. This work may provide potential markers for detoxification of quinclorac and biomonitors of environmental chemical pollution.

  18. Identifiable Data Files - Medicare Provider Analysis and ...

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Medicare Provider Analysis and Review (MEDPAR) File contains data from claims for services provided to beneficiaries admitted to Medicare certified inpatient...

  19. Comprehensive expression profiling of tumor cell lines identifies molecular signatures of melanoma progression.

    Directory of Open Access Journals (Sweden)

    Byungwoo Ryu

    Full Text Available BACKGROUND: Gene expression profiling has revolutionized our ability to molecularly classify primary human tumors and significantly enhanced the development of novel tumor markers and therapies; however, progress in the diagnosis and treatment of melanoma over the past 3 decades has been limited, and there is currently no approved therapy that significantly extends lifespan in patients with advanced disease. Profiling studies of melanoma to date have been inconsistent due to the heterogeneous nature of this malignancy and the limited availability of informative tissue specimens from early stages of disease. METHODOLOGY/PRINCIPLE FINDINGS: In order to gain an improved understanding of the molecular basis of melanoma progression, we have compared gene expression profiles from a series of melanoma cell lines representing discrete stages of malignant progression that recapitulate critical characteristics of the primary lesions from which they were derived. Here we describe the unsupervised hierarchical clustering of profiling data from melanoma cell lines and melanocytes. This clustering identifies two distinctive molecular subclasses of melanoma segregating aggressive metastatic tumor cell lines from less-aggressive primary tumor cell lines. Further analysis of expression signatures associated with melanoma progression using functional annotations categorized these transcripts into three classes of genes: 1 Upregulation of activators of cell cycle progression, DNA replication and repair (CDCA2, NCAPH, NCAPG, NCAPG2, PBK, NUSAP1, BIRC5, ESCO2, HELLS, MELK, GINS1, GINS4, RAD54L, TYMS, and DHFR, 2 Loss of genes associated with cellular adhesion and melanocyte differentiation (CDH3, CDH1, c-KIT, PAX3, CITED1/MSG-1, TYR, MELANA, MC1R, and OCA2, 3 Upregulation of genes associated with resistance to apoptosis (BIRC5/survivin. While these broad classes of transcripts have previously been implicated in the progression of melanoma and other malignancies, the

  20. Molecular markers for identifying a new selected variety of Pacific white shrimp Litopenaeus vannamei

    Science.gov (United States)

    Yu, Yang; Zhang, Xiaojun; Liu, Jingwen; Li, Fuhua; Huang, Hao; Li, Yijun; Liu, Xiaolin; Xiang, Jianhai

    2015-01-01

    Selective breeding of the Pacific white shrimp Litopenaeus vannamei during the last decade has produced new varieties exhibiting high growth rates and disease resistance. However, the identification of new varieties of shrimps from their phenotypic characters is difficult. This study introduces a new approach for identifying varieties of shrimps using molecular markers of microsatellites and mitochondrial control region sequences. The method was employed to identify a new selected variety, Kehai No. 1 (KH-1), from three representative stocks (control group): Zhengda; Tongwei; and a stock collected from Fujian Province, which is now cultured in mainland China. By pooled genotyping of KH-1 and the control group, five microsatellites showing differences between KH-1 and the control group were screened out. Individual genotyping data confirmed the results from pooled genotyping. The genotyping data for the five microsatellites were applied to the assignment analysis of the KH-1 group and the control group using the partial Bayesian assignment method in GENECLASS2. By sequencing the mitochondrial control regions of individuals from the KH-1 and control group, four haplotypes were observed in the KH-1 group, whereas 14 haplotypes were obtained in the control group. By combining the microsatellite assignment analysis with mitochondrial control region analysis, the average accuracy of identification of individuals in the KH-1 group and control group reached 89%. The five selected microsatellite loci and mitochondrial control region sequences were highly polymorphic and could be used to distinguish new selected varieties of L. vannamei from other populations cultured in China.

  1. Dental diagnostics: molecular analysis of oral biofilms.

    Science.gov (United States)

    Hiyari, Sarah; Bennett, Katie M

    2011-01-01

    Dental biofilms are complex, multi-species bacterial communities that colonize the mouth in the form of plaque and are known to cause dental caries and periodontal disease. Biofilms are unique from planktonic bacteria in that they are mutualistic communities with a 3-dimensional structure and complex nutritional and communication pathways. The homeostasis within the biofilm colony can be disrupted, causing a shift in the bacterial composition of the colony and resulting in proliferation of pathogenic species. Because of this dynamic lifestyle, traditional microbiological techniques are inadequate for the study of biofilms. Many of the bacteria present in the oral cavity are viable but not culturable, which severely limits laboratory analysis. However, with the advent of new molecular techniques, the microbial makeup of oral biofilms can be better identified. Some of these techniques include DNA-DNA hybridization, 16S rRNA gene sequencing, denaturing gradient gel electrophoresis, terminal restriction fragment length polymorphism, denaturing high-performance liquid chromatography and pyrosequencing. This review provides an overview of biofilm formation and examines the major molecular techniques currently used in oral biofilm analysis. Future applications of the molecular analysis of oral biofilms in the diagnosis and treatment of caries and periodontal disease are also discussed.

  2. Identifying MMORPG Bots: A Traffic Analysis Approach

    Directory of Open Access Journals (Sweden)

    Wen-Chin Chen

    2008-11-01

    Full Text Available Massively multiplayer online role playing games (MMORPGs have become extremely popular among network gamers. Despite their success, one of MMORPG's greatest challenges is the increasing use of game bots, that is, autoplaying game clients. The use of game bots is considered unsportsmanlike and is therefore forbidden. To keep games in order, game police, played by actual human players, often patrol game zones and question suspicious players. This practice, however, is labor-intensive and ineffective. To address this problem, we analyze the traffic generated by human players versus game bots and propose general solutions to identify game bots. Taking Ragnarok Online as our subject, we study the traffic generated by human players and game bots. We find that their traffic is distinguishable by 1 the regularity in the release time of client commands, 2 the trend and magnitude of traffic burstiness in multiple time scales, and 3 the sensitivity to different network conditions. Based on these findings, we propose four strategies and two ensemble schemes to identify bots. Finally, we discuss the robustness of the proposed methods against countermeasures of bot developers, and consider a number of possible ways to manage the increasingly serious bot problem.

  3. Identifying MMORPG Bots: A Traffic Analysis Approach

    Science.gov (United States)

    Chen, Kuan-Ta; Jiang, Jhih-Wei; Huang, Polly; Chu, Hao-Hua; Lei, Chin-Laung; Chen, Wen-Chin

    2008-12-01

    Massively multiplayer online role playing games (MMORPGs) have become extremely popular among network gamers. Despite their success, one of MMORPG's greatest challenges is the increasing use of game bots, that is, autoplaying game clients. The use of game bots is considered unsportsmanlike and is therefore forbidden. To keep games in order, game police, played by actual human players, often patrol game zones and question suspicious players. This practice, however, is labor-intensive and ineffective. To address this problem, we analyze the traffic generated by human players versus game bots and propose general solutions to identify game bots. Taking Ragnarok Online as our subject, we study the traffic generated by human players and game bots. We find that their traffic is distinguishable by 1) the regularity in the release time of client commands, 2) the trend and magnitude of traffic burstiness in multiple time scales, and 3) the sensitivity to different network conditions. Based on these findings, we propose four strategies and two ensemble schemes to identify bots. Finally, we discuss the robustness of the proposed methods against countermeasures of bot developers, and consider a number of possible ways to manage the increasingly serious bot problem.

  4. Integrating subpathway analysis to identify candidate agents for hepatocellular carcinoma.

    Science.gov (United States)

    Wang, Jiye; Li, Mi; Wang, Yun; Liu, Xiaoping

    2016-01-01

    Hepatocellular carcinoma (HCC) is the second most common cause of cancer-associated death worldwide, characterized by a high invasiveness and resistance to normal anticancer treatments. The need to develop new therapeutic agents for HCC is urgent. Here, we developed a bioinformatics method to identify potential novel drugs for HCC by integrating HCC-related and drug-affected subpathways. By using the RNA-seq data from the TCGA (The Cancer Genome Atlas) database, we first identified 1,763 differentially expressed genes between HCC and normal samples. Next, we identified 104 significant HCC-related subpathways. We also identified the subpathways associated with small molecular drugs in the CMap database. Finally, by integrating HCC-related and drug-affected subpathways, we identified 40 novel small molecular drugs capable of targeting these HCC-involved subpathways. In addition to previously reported agents (ie, calmidazolium), our method also identified potentially novel agents for targeting HCC. We experimentally verified that one of these novel agents, prenylamine, induced HCC cell apoptosis using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, an acridine orange/ethidium bromide stain, and electron microscopy. In addition, we found that prenylamine not only affected several classic apoptosis-related proteins, including Bax, Bcl-2, and cytochrome c, but also increased caspase-3 activity. These candidate small molecular drugs identified by us may provide insights into novel therapeutic approaches for HCC. PMID:27022281

  5. Molecular markers for identifying municipal, domestic and agricultural sources of organic matter in natural waters.

    Science.gov (United States)

    Harwood, John J

    2014-01-01

    Molecular markers can be used to determine the sources of organic pollution in water. This review summarizes progress made during the last two decades in identifying reliable molecular markers to distinguish pollution from sewage, animal production, and other sources. Two artificial sweeteners, sucralose and acesulfame-K, are sufficiently stable to be molecular markers and easily associated with domestic wastewater. Waste from different animal species may be distinguished by profiling fecal sterols and bile acids. Other markers which have been evaluated, including caffeine, detergent components, and compounds commonly leached from landfills are discussed. PMID:24200048

  6. Generalized analysis of molecular variance.

    Directory of Open Access Journals (Sweden)

    Caroline M Nievergelt

    2007-04-01

    Full Text Available Many studies in the fields of genetic epidemiology and applied population genetics are predicated on, or require, an assessment of the genetic background diversity of the individuals chosen for study. A number of strategies have been developed for assessing genetic background diversity. These strategies typically focus on genotype data collected on the individuals in the study, based on a panel of DNA markers. However, many of these strategies are either rooted in cluster analysis techniques, and hence suffer from problems inherent to the assignment of the biological and statistical meaning to resulting clusters, or have formulations that do not permit easy and intuitive extensions. We describe a very general approach to the problem of assessing genetic background diversity that extends the analysis of molecular variance (AMOVA strategy introduced by Excoffier and colleagues some time ago. As in the original AMOVA strategy, the proposed approach, termed generalized AMOVA (GAMOVA, requires a genetic similarity matrix constructed from the allelic profiles of individuals under study and/or allele frequency summaries of the populations from which the individuals have been sampled. The proposed strategy can be used to either estimate the fraction of genetic variation explained by grouping factors such as country of origin, race, or ethnicity, or to quantify the strength of the relationship of the observed genetic background variation to quantitative measures collected on the subjects, such as blood pressure levels or anthropometric measures. Since the formulation of our test statistic is rooted in multivariate linear models, sets of variables can be related to genetic background in multiple regression-like contexts. GAMOVA can also be used to complement graphical representations of genetic diversity such as tree diagrams (dendrograms or heatmaps. We examine features, advantages, and power of the proposed procedure and showcase its flexibility by

  7. Cartography of Pathway Signal Perturbations Identifies Distinct Molecular Pathomechanisms in Malignant and Chronic Lung Diseases.

    Science.gov (United States)

    Arakelyan, Arsen; Nersisyan, Lilit; Petrek, Martin; Löffler-Wirth, Henry; Binder, Hans

    2016-01-01

    Lung diseases are described by a wide variety of developmental mechanisms and clinical manifestations. Accurate classification and diagnosis of lung diseases are the bases for development of effective treatments. While extensive studies are conducted toward characterization of various lung diseases at molecular level, no systematic approach has been developed so far. Here we have applied a methodology for pathway-centered mining of high throughput gene expression data to describe a wide range of lung diseases in the light of shared and specific pathway activity profiles. We have applied an algorithm combining a Pathway Signal Flow (PSF) algorithm for estimation of pathway activity deregulation states in lung diseases and malignancies, and a Self Organizing Maps algorithm for classification and clustering of the pathway activity profiles. The analysis results allowed clearly distinguish between cancer and non-cancer lung diseases. Lung cancers were characterized by pathways implicated in cell proliferation, metabolism, while non-malignant lung diseases were characterized by deregulations in pathways involved in immune/inflammatory response and fibrotic tissue remodeling. In contrast to lung malignancies, chronic lung diseases had relatively heterogeneous pathway deregulation profiles. We identified three groups of interstitial lung diseases and showed that the development of characteristic pathological processes, such as fibrosis, can be initiated by deregulations in different signaling pathways. In conclusion, this paper describes the pathobiology of lung diseases from systems viewpoint using pathway centered high-dimensional data mining approach. Our results contribute largely to current understanding of pathological events in lung cancers and non-malignant lung diseases. Moreover, this paper provides new insight into molecular mechanisms of a number of interstitial lung diseases that have been studied to a lesser extent.

  8. Big data visualization identifies the multidimensional molecular landscape of human gliomas

    Science.gov (United States)

    Bolouri, Hamid; Zhao, Lue Ping; Holland, Eric C.

    2016-01-01

    We show that visualizing large molecular and clinical datasets enables discovery of molecularly defined categories of highly similar patients. We generated a series of linked 2D sample similarity plots using genome-wide single nucleotide alterations (SNAs), copy number alterations (CNAs), DNA methylation, and RNA expression data. Applying this approach to the combined glioblastoma (GBM) and lower grade glioma (LGG) The Cancer Genome Atlas datasets, we find that combined CNA/SNA data divide gliomas into three highly distinct molecular groups. The mutations commonly used in clinical evaluation of these tumors are regionally distributed in these plots. One of the three groups is a mixture of GBM and LGG that shows similar methylation and survival characteristics to GBM. Altogether, our approach identifies eight molecularly defined glioma groups with distinct sequence/expression/methylation profiles. Importantly, we show that regionally clustered samples are enriched for specific drug targets. PMID:27118839

  9. Molecular evolution of rbcL in three gymnosperm families: identifying adaptive and coevolutionary patterns

    LENUS (Irish Health Repository)

    Sen, Lin

    2011-06-03

    Abstract Background The chloroplast-localized ribulose-1, 5-biphosphate carboxylase\\/oxygenase (Rubisco), the primary enzyme responsible for autotrophy, is instrumental in the continual adaptation of plants to variations in the concentrations of CO2. The large subunit (LSU) of Rubisco is encoded by the chloroplast rbcL gene. Although adaptive processes have been previously identified at this gene, characterizing the relationships between the mutational dynamics at the protein level may yield clues on the biological meaning of such adaptive processes. The role of such coevolutionary dynamics in the continual fine-tuning of RbcL remains obscure. Results We used the timescale and phylogenetic analyses to investigate and search for processes of adaptive evolution in rbcL gene in three gymnosperm families, namely Podocarpaceae, Taxaceae and Cephalotaxaceae. To understand the relationships between regions identified as having evolved under adaptive evolution, we performed coevolutionary analyses using the software CAPS. Importantly, adaptive processes were identified at amino acid sites located on the contact regions among the Rubisco subunits and on the interface between Rubisco and its activase. Adaptive amino acid replacements at these regions may have optimized the holoenzyme activity. This hypothesis was pinpointed by evidence originated from our analysis of coevolution that supported the correlated evolution between Rubisco and its activase. Interestingly, the correlated adaptive processes between both these proteins have paralleled the geological variation history of the concentration of atmospheric CO2. Conclusions The gene rbcL has experienced bursts of adaptations in response to the changing concentration of CO2 in the atmosphere. These adaptations have emerged as a result of a continuous dynamic of mutations, many of which may have involved innovation of functional Rubisco features. Analysis of the protein structure and the functional implications of such

  10. New Molecular Features of Colorectal Cancer Identified - Office of Cancer Clinical Proteomics Research

    Science.gov (United States)

    Investigators from the National Cancer Institute's Clinical Proteomic Tumor Analysis Consortium (CPTAC) who comprehensively analyzed 95 human colorectal tumor samples, have determined how gene alterations identified in previous analyses of the same samples

  11. Subtracted diversity array identifies novel molecular markers including retrotransposons for fingerprinting Echinacea species.

    Directory of Open Access Journals (Sweden)

    Alexandra Olarte

    Full Text Available Echinacea, native to the Canadian prairies and the prairie states of the United States, has a long tradition as a folk medicine for the Native Americans. Currently, Echinacea are among the top 10 selling herbal medicines in the U.S. and Europe, due to increasing popularity for the treatment of common cold and ability to stimulate the immune system. However, the genetic relationship within the species of this genus is unclear, making the authentication of the species used for the medicinal industry more difficult. We report the construction of a novel Subtracted Diversity Array (SDA for Echinacea species and demonstrate the potential of this array for isolating highly polymorphic sequences. In order to selectively isolate Echinacea-specific sequences, a Suppression Subtractive Hybridization (SSH was performed between a pool of twenty-four Echinacea genotypes and a pool of other angiosperms and non-angiosperms. A total of 283 subtracted genomic DNA (gDNA fragments were amplified and arrayed. Twenty-seven Echinacea genotypes including four that were not used in the array construction could be successfully discriminated. Interestingly, unknown samples of E. paradoxa and E. purpurea could be unambiguously identified from the cluster analysis. Furthermore, this Echinacea-specific SDA was also able to isolate highly polymorphic retrotransposon sequences. Five out of the eleven most discriminatory features matched to known retrotransposons. This is the first time retrotransposon sequences have been used to fingerprint Echinacea, highlighting the potential of retrotransposons as based molecular markers useful for fingerprinting and studying diversity patterns in Echinacea.

  12. Gene expression profiling identifies molecular pathways associated with collagen VI deficiency and provides novel therapeutic targets.

    Directory of Open Access Journals (Sweden)

    Sonia Paco

    Full Text Available Ullrich congenital muscular dystrophy (UCMD, caused by collagen VI deficiency, is a common congenital muscular dystrophy. At present, the role of collagen VI in muscle and the mechanism of disease are not fully understood. To address this we have applied microarrays to analyse the transcriptome of UCMD muscle and compare it to healthy muscle and other muscular dystrophies. We identified 389 genes which are differentially regulated in UCMD relative to controls. In addition, there were 718 genes differentially expressed between UCMD and dystrophin deficient muscle. In contrast, only 29 genes were altered relative to other congenital muscular dystrophies. Changes in gene expression were confirmed by real-time PCR. The set of regulated genes was analysed by Gene Ontology, KEGG pathways and Ingenuity Pathway analysis to reveal the molecular functions and gene networks associated with collagen VI defects. The most significantly regulated pathways were those involved in muscle regeneration, extracellular matrix remodelling and inflammation. We characterised the immune response in UCMD biopsies as being mainly mediated via M2 macrophages and the complement pathway indicating that anti-inflammatory treatment may be beneficial to UCMD as for other dystrophies. We studied the immunolocalisation of ECM components and found that biglycan, a collagen VI interacting proteoglycan, was reduced in the basal lamina of UCMD patients. We propose that biglycan reduction is secondary to collagen VI loss and that it may be contributing towards UCMD pathophysiology. Consequently, strategies aimed at over-expressing biglycan and restore the link between the muscle cell surface and the extracellular matrix should be considered.

  13. RNA sequencing of Populus x canadensis roots identifies key molecular mechanisms underlying physiological adaption to excess zinc.

    Directory of Open Access Journals (Sweden)

    Andrea Ariani

    Full Text Available Populus x canadensis clone I-214 exhibits a general indicator phenotype in response to excess Zn, and a higher metal uptake in roots than in shoots with a reduced translocation to aerial parts under hydroponic conditions. This physiological adaptation seems mainly regulated by roots, although the molecular mechanisms that underlie these processes are still poorly understood. Here, differential expression analysis using RNA-sequencing technology was used to identify the molecular mechanisms involved in the response to excess Zn in root. In order to maximize specificity of detection of differentially expressed (DE genes, we consider the intersection of genes identified by three distinct statistical approaches (61 up- and 19 down-regulated and validate them by RT-qPCR, yielding an agreement of 93% between the two experimental techniques. Gene Ontology (GO terms related to oxidation-reduction processes, transport and cellular iron ion homeostasis were enriched among DE genes, highlighting the importance of metal homeostasis in adaptation to excess Zn by P. x canadensis clone I-214. We identified the up-regulation of two Populus metal transporters (ZIP2 and NRAMP1 probably involved in metal uptake, and the down-regulation of a NAS4 gene involved in metal translocation. We identified also four Fe-homeostasis transcription factors (two bHLH38 genes, FIT and BTS that were differentially expressed, probably for reducing Zn-induced Fe-deficiency. In particular, we suggest that the down-regulation of FIT transcription factor could be a mechanism to cope with Zn-induced Fe-deficiency in Populus. These results provide insight into the molecular mechanisms involved in adaption to excess Zn in Populus spp., but could also constitute a starting point for the identification and characterization of molecular markers or biotechnological targets for possible improvement of phytoremediation performances of poplar trees.

  14. Molecular forensic science analysis of nuclear materials

    Science.gov (United States)

    Reilly, Dallas David

    Concerns over the proliferation and instances of nuclear material in the environment have increased interest in the expansion of nuclear forensics analysis and attribution programs. A new related field, molecular forensic science (MFS) has helped meet this expansion by applying common scientific analyses to nuclear forensics scenarios. In this work, MFS was applied to three scenarios related to nuclear forensics analysis. In the first, uranium dioxide was synthesized and aged at four sets of static environmental conditions and studied for changes in chemical speciation. The second highlighted the importance of bulk versus particle characterizations by analyzing a heterogeneous industrially prepared sample with similar techniques. In the third, mixed uranium/plutonium hot particles were collected from the McGuire Air Force Base BOMARC Site and analyzed for chemical speciation and elemental surface composition. This work has identified new signatures and has indicated unexpected chemical behavior under various conditions. These findings have lead to an expansion of basic actinide understanding, proof of MFS as a tool for nuclear forensic science, and new areas for expansion in these fields.

  15. Molecular analysis of holoprosencephaly in South America

    Directory of Open Access Journals (Sweden)

    Clarice Pagani Savastano

    2014-01-01

    Full Text Available Holoprosencephaly (HPE is a spectrum of brain and facial malformations primarily reflecting genetic factors, such as chromosomal abnormalities and gene mutations. Here, we present a clinical and molecular analysis of 195 probands with HPE or microforms; approximately 72% of the patients were derived from the Latin American Collaborative Study of Congenital Malformations (ECLAMC, and 82% of the patients were newborns. Alobar HPE was the predominant brain defect in almost all facial defect categories, except for patients without oral cleft and median or lateral oral clefts. Ethmocephaly, cebocephaly, and premaxillary agenesis were primarily observed among female patients. Premaxillary agenesis occurred in six of the nine diabetic mothers. Recurrence of HPE or microform was approximately 19%. The frequency of microdeletions, detected using Multiplex Ligation-dependant Probe Amplification (MLPA was 17% in patients with a normal karyotype. Cytogenetics or QF-PCR analyses revealed chromosomal anomalies in 27% of the probands. Mutational analyses in genes SHH, ZIC2, SIX3 and TGIF were performed in 119 patients, revealing eight mutations in SHH, two mutations in SIX3 and two mutations in ZIC2. Thus, a detailed clinical description of new HPE cases with identified genetic anomalies might establish genotypic and phenotypic correlations and contribute to the development of additional strategies for the analysis of new cases.

  16. Molecular epidemiology identifies HIV transmission networks associated with younger age and heterosexual exposure among Korean individuals.

    Science.gov (United States)

    Chin, Bum Sik; Chaillon, Antoine; Mehta, Sanjay R; Wertheim, Joel O; Kim, Gayeon; Shin, Hyoung-Shik; Smith, Davey M

    2016-10-01

    To evaluate if HIV transmission networks could be elucidated from data collected in a short time frame, 131 HIV-1 pol sequences were analyzed which were generated from treatment-naïve Korean individuals who were sequentially identified over 1 year. A transmission linkage was inferred when there was a genetic distance <1.5% and a total of 16 clusters, involving 39/131 (29.8%), were identified. Younger age and heterosexual exposure were independently related with clustering in the inferred network, which demonstrated that molecular epidemiology with currently generated data (i.e., drug resistance genotypes) can be used to identify local transmission networks, even over a short timeframe. J. Med. Virol. 88:1832-1835, 2016. © 2016 Wiley Periodicals, Inc. PMID:26990771

  17. Peptide aptamer identified by molecular docking targeting translationally controlled tumor protein in leukemia cells.

    Science.gov (United States)

    Kadioglu, Onat; Efferth, Thomas

    2016-08-01

    Bioinformatics screening and molecular docking analyses were utilized to select high affinity peptides targeting translationally controlled tumor protein (TCTP). Selected peptide aptamers were tested towards cancer cell lines with different levels of TCTP expression. One peptide (WGQWPYHC) revealed specific cytotoxicity according to the TCTP expression in tumor cells without affecting normal cells. Western blot analysis showed peptide-induced down-regulation of TCTP as primary target as well as of cell-cycle related downstream proteins (CDK2, CDK6, Cyclin D3) in MOLT-4 leukemia cells. "WGQWPYHC" deserves further analysis for targeted therapy of TCTP-expressing tumor cells. Graphical abstract Molecular docking on TCTP, cytotoxicity toward MOLT-4 leukemia cell line and downregulation of CDK2, CDK6, CyclinD3 and TCTP proteins. PMID:26972431

  18. BIOELECTRICAL IMPEDANCE VECTOR ANALYSIS IDENTIFIES SARCOPENIA IN NURSING HOME RESIDENTS

    Science.gov (United States)

    Loss of muscle mass and water shifts between body compartments are contributing factors to frailty in the elderly. The body composition changes are especially pronounced in institutionalized elderly. We investigated the ability of single-frequency bioelectrical impedance analysis (BIA) to identify b...

  19. Sequencing and molecular modeling identifies candidate members of Caliciviridae family in bats.

    Science.gov (United States)

    Kemenesi, Gábor; Gellért, Ákos; Dallos, Bianka; Görföl, Tamás; Boldogh, Sándor; Estók, Péter; Marton, Szilvia; Oldal, Miklós; Martella, Vito; Bányai, Krisztián; Jakab, Ferenc

    2016-07-01

    Emerging viral diseases represent an ongoing challenge for globalized world and bats constitute an immense, partially explored, reservoir of potentially zoonotic viruses. Caliciviruses are important human and animal pathogens and, as observed for human noroviruses, they may impact on human health on a global scale. By screening fecal samples of bats in Hungary, calicivirus RNA was identified in the samples of Myotis daubentonii and Eptesicus serotinus bats. In order to characterize more in detail the bat caliciviruses, large portions of the genome sequence of the viruses were determined. Phylogenetic analyses and molecular modeling identified firmly the two viruses as candidate members within the Caliciviridae family, with one calicivirus strain resembling members of the Sapovirus genus and the other bat calicivirus being more related to porcine caliciviruses of the proposed genus Valovirus. This data serves the effort for detecting reservoir hosts for potential emerging viruses and recognize important evolutionary relationships. PMID:27085289

  20. Messina: a novel analysis tool to identify biologically relevant molecules in disease.

    Directory of Open Access Journals (Sweden)

    Mark Pinese

    Full Text Available BACKGROUND: Morphologically similar cancers display heterogeneous patterns of molecular aberrations and follow substantially different clinical courses. This diversity has become the basis for the definition of molecular phenotypes, with significant implications for therapy. Microarray or proteomic expression profiling is conventionally employed to identify disease-associated genes, however, traditional approaches for the analysis of profiling experiments may miss molecular aberrations which define biologically relevant subtypes. METHODOLOGY/PRINCIPAL FINDINGS: Here we present Messina, a method that can identify those genes that only sometimes show aberrant expression in cancer. We demonstrate with simulated data that Messina is highly sensitive and specific when used to identify genes which are aberrantly expressed in only a proportion of cancers, and compare Messina to contemporary analysis techniques. We illustrate Messina by using it to detect the aberrant expression of a gene that may play an important role in pancreatic cancer. CONCLUSIONS/SIGNIFICANCE: Messina allows the detection of genes with profiles typical of markers of molecular subtype, and complements existing methods to assist the identification of such markers. Messina is applicable to any global expression profiling data, and to allow its easy application has been packaged into a freely-available stand-alone software package.

  1. Spectroscope and molecular model identify the behavior of doxorubicin-SPION binding to bovine hemoglobin.

    Science.gov (United States)

    Liu, Yihong; Liu, Rutao

    2015-08-01

    To provide reference for the bio-safety evaluation of doxorubicin-loaded SPION, the interaction of bovine hemoglobin (BHb) with the drug delivery was investigated by multi-spectroscopic techniques and molecular modeling calculation. Multi-spectroscopic results indicated that DOX-SPION unfolded the conformation of BHb, decreased the content of α-helix from 38.89% to 35.08%, which verified the changes of protein's secondary structure quantificationally. Stern-Volmer analysis and molecular model showed there were two static interaction modes corresponding to the two reaction steps: DOX first immobilized on the particle adhered to the external region of BHb, leading to the increasing exposure of chromophore group, rendering particles to bond to the original hemoglobin central cavity (Site 2) in sequence. They finally generated a stable bioconjugate via hydrogen bonds. This work indicated that the drug delivery has deleterious effects on the frame conformation of BHb, affecting its physiological function. PMID:26033525

  2. Turcot syndrome confirmed with molecular analysis.

    Science.gov (United States)

    Lebrun, C; Olschwang, S; Jeannin, S; Vandenbos, F; Sobol, H; Frenay, M

    2007-04-01

    Turcot syndrome is clinically characterized by the occurrence of primary brain tumor and colorectal tumor and has, in previous reports, been shown associated with germline mutations in the genes APC, MLH1, MHS6, and PMS2. To date, only few families have been documented by molecular analysis. We report two new families with Turcot syndrome to illustrate and review its characteristics and facilitate diagnosis. Molecular analysis revealed two germline mutations, one in the MLH1 gene and one in MSH2. The latter has never been describe in the literature. Personal and familial relevant anamnestic data from patients with glioma might aid in the diagnosis of genetic disorders. The subsequent molecular characterization may contribute to the appropriate care of affected patients and asymptomatic gene carriers. PMID:17389002

  3. Electroretinogram analysis of relative spectral sensitivity in genetically identified dichromatic macaques

    OpenAIRE

    Hanazawa, Akitoshi; Mikami, Akichika; Angelika, Puti Sulistyo; Takenaka, Osamu; Goto, Shunji; Onishi, Akishi; Koike, Satoshi; Yamamori, Tetsuo; Kato, Keichiro; Kondo, Aya; Suryobroto, Bambang; Farajallah, Achmad; Komatsu, Hidehiko

    2001-01-01

    The retinas of macaque monkeys usually contain three types of photopigment, providing them with trichromatic color vision homologous to that of humans. However, we recently used molecular genetic analysis to identify several macaques with a dichromatic genotype. The affected X chromosome of these animals contains a hybrid gene of long-wavelength-sensitive (L) and middle-wavelength-sensitive (M) photopigments instead of separate genes encoding L and M photopigments. The product of the hybrid g...

  4. Gene expression analysis identifies global gene dosage sensitivity in cancer

    DEFF Research Database (Denmark)

    Fehrmann, Rudolf S. N.; Karjalainen, Juha M.; Krajewska, Malgorzata;

    2015-01-01

    Many cancer-associated somatic copy number alterations (SCNAs) are known. Currently, one of the challenges is to identify the molecular downstream effects of these variants. Although several SCNAs are known to change gene expression levels, it is not clear whether each individual SCNA affects gene...... expression. We reanalyzed 77,840 expression profiles and observed a limited set of 'transcriptional components' that describe well-known biology, explain the vast majority of variation in gene expression and enable us to predict the biological function of genes. On correcting expression profiles...... for these components, we observed that the residual expression levels (in 'functional genomic mRNA' profiling) correlated strongly with copy number. DNA copy number correlated positively with expression levels for 99% of all abundantly expressed human genes, indicating global gene dosage sensitivity. By applying...

  5. Use of Photogrammetry and Biomechanical Gait analysis to Identify Individuals

    DEFF Research Database (Denmark)

    Larsen, Peter Kastmand; Simonsen, Erik Bruun; Lynnerup, Niels

    found. Especially the variables located in the frontal plane are interesting due to large inter-individual differences in time course patterns. The variables with high recognition rates seem preferable for use in forensic gait analysis and as input variables to waveform analysis techniques...... such as principal component analysis resulting in marginal scores, which are difficult to interpret individually. Finally, a new gait model is presented based on functional principal component analysis with potentials for detecting individual gait patterns where time course patterns can be marginally interpreted......Photogrammetry and recognition of gait patterns are valuable tools to help identify perpetrators based on surveillance recordings. We have found that stature but only few other measures have a satisfying reproducibility for use in forensics. Several gait variables with high recognition rates were...

  6. Latent cluster analysis of ALS phenotypes identifies prognostically differing groups.

    Directory of Open Access Journals (Sweden)

    Jeban Ganesalingam

    Full Text Available BACKGROUND: Amyotrophic lateral sclerosis (ALS is a degenerative disease predominantly affecting motor neurons and manifesting as several different phenotypes. Whether these phenotypes correspond to different underlying disease processes is unknown. We used latent cluster analysis to identify groupings of clinical variables in an objective and unbiased way to improve phenotyping for clinical and research purposes. METHODS: Latent class cluster analysis was applied to a large database consisting of 1467 records of people with ALS, using discrete variables which can be readily determined at the first clinic appointment. The model was tested for clinical relevance by survival analysis of the phenotypic groupings using the Kaplan-Meier method. RESULTS: The best model generated five distinct phenotypic classes that strongly predicted survival (p<0.0001. Eight variables were used for the latent class analysis, but a good estimate of the classification could be obtained using just two variables: site of first symptoms (bulbar or limb and time from symptom onset to diagnosis (p<0.00001. CONCLUSION: The five phenotypic classes identified using latent cluster analysis can predict prognosis. They could be used to stratify patients recruited into clinical trials and generating more homogeneous disease groups for genetic, proteomic and risk factor research.

  7. Advanced computational biology methods identify molecular switches for malignancy in an EGF mouse model of liver cancer.

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    Philip Stegmaier

    Full Text Available The molecular causes by which the epidermal growth factor receptor tyrosine kinase induces malignant transformation are largely unknown. To better understand EGFs' transforming capacity whole genome scans were applied to a transgenic mouse model of liver cancer and subjected to advanced methods of computational analysis to construct de novo gene regulatory networks based on a combination of sequence analysis and entrained graph-topological algorithms. Here we identified transcription factors, processes, key nodes and molecules to connect as yet unknown interacting partners at the level of protein-DNA interaction. Many of those could be confirmed by electromobility band shift assay at recognition sites of gene specific promoters and by western blotting of nuclear proteins. A novel cellular regulatory circuitry could therefore be proposed that connects cell cycle regulated genes with components of the EGF signaling pathway. Promoter analysis of differentially expressed genes suggested the majority of regulated transcription factors to display specificity to either the pre-tumor or the tumor state. Subsequent search for signal transduction key nodes upstream of the identified transcription factors and their targets suggested the insulin-like growth factor pathway to render the tumor cells independent of EGF receptor activity. Notably, expression of IGF2 in addition to many components of this pathway was highly upregulated in tumors. Together, we propose a switch in autocrine signaling to foster tumor growth that was initially triggered by EGF and demonstrate the knowledge gain form promoter analysis combined with upstream key node identification.

  8. Identifying Organizational Inefficiencies with Pictorial Process Analysis (PPA

    Directory of Open Access Journals (Sweden)

    David John Patrishkoff

    2013-11-01

    Full Text Available Pictorial Process Analysis (PPA was created by the author in 2004. PPA is a unique methodology which offers ten layers of additional analysis when compared to standard process mapping techniques.  The goal of PPA is to identify and eliminate waste, inefficiencies and risk in manufacturing or transactional business processes at 5 levels in an organization. The highest level being assessed is the process management, followed by the process work environment, detailed work habits, process performance metrics and general attitudes towards the process. This detailed process assessment and analysis is carried out during process improvement brainstorming efforts and Kaizen events. PPA creates a detailed visual efficiency rating for each step of the process under review.  A selection of 54 pictorial Inefficiency Icons (cards are available for use to highlight major inefficiencies and risks that are present in the business process under review. These inefficiency icons were identified during the author's independent research on the topic of why things go wrong in business. This paper will highlight how PPA was developed and show the steps required to conduct Pictorial Process Analysis on a sample manufacturing process. The author has successfully used PPA to dramatically improve business processes in over 55 different industries since 2004.  

  9. Molecular dynamics study to identify the reactive sites of a liquid squalane surface.

    Science.gov (United States)

    Köhler, Sven P K; Reed, Stewart K; Westacott, Robin E; McKendrick, Kenneth G

    2006-06-22

    Molecular dynamics simulations of liquid squalane, C30H62, were performed, focusing in particular on the liquid-vacuum interface. These theoretical studies were aimed at identifying potentially reactive sites on the surface, knowledge of which is important for a number of inelastic and reactive scattering experiments. A united atom force field (Martin, M. G.; Siepmann, J. I. J. Phys. Chem. B 1999, 103, 4508-4517) was used, and the simulations were analyzed with respect to their interfacial properties. A modest but clearly identifiable preference for methyl groups to protrude into the vacuum has been found at lower temperatures. This effect decreases when going to higher temperatures. Additional simulations tracking the flight paths of projectiles directed at a number of randomly chosen surfaces extracted from the molecular dynamics simulations were performed. The geometrical parameters for these calculations were chosen to imitate a typical abstraction reaction, such as the reaction between ground-state oxygen atoms and hydrocarbons. Despite the preference for methyl groups to protrude further into the vacuum, Monte Carlo tracking simulations suggest, on geometric grounds, that primary and secondary hydrogen atoms are roughly equally likely to react with incoming gas-phase atoms. These geometric simulations also indicate that a substantial fraction of the scattered products is likely to undergo at least one secondary collision with hydrocarbon side chains. These results help to interpret the outcome of previous measurements of the internal and external energy distribution of the gas-phase OH products of the interfacial reaction between oxygen atoms and liquid squalane.

  10. Molecular analysis of retinoblastoma in pediatrics

    International Nuclear Information System (INIS)

    Inactivation of RB protein produced by mutation of RB-1 gene is critical to the pathogenesis of Retinoblastoma. Since other factors besides this gene are thought to be involved in this mechanism, we performed the molecular analysis of Retinoblastoma for loss of RB-1 gene and N-myc gene amplification. Loss of RB-1 gene was found in five(56%) among nine patients with Retinoblastoma and total loss of the gene in one patient. We also found total loss of RB-1 gene in WERI cell line and a more than 100 fold amplification of N-myc in Y-79 cell line. The analysis of the relationship between molecular events and clinical characteristics such as age, sex, tumor laterality did not reveal any specific correlation. We suggest this method can be a useful tool for initially screening a large number of tumors and for genetic counseling and early detection of the tumor. (Author)

  11. Proteogenomic Analysis Identifies a Novel Human SHANK3 Isoform

    Directory of Open Access Journals (Sweden)

    Fahad Benthani

    2015-05-01

    Full Text Available Mutations of the SHANK3 gene have been associated with autism spectrum disorder. Individuals harboring different SHANK3 mutations display considerable heterogeneity in their cognitive impairment, likely due to the high SHANK3 transcriptional diversity. In this study, we report a novel interaction between the Mutated in colorectal cancer (MCC protein and a newly identified SHANK3 protein isoform in human colon cancer cells and mouse brain tissue. Hence, our proteogenomic analysis identifies a new human long isoform of the key synaptic protein SHANK3 that was not predicted by the human reference genome. Taken together, our findings describe a potential new role for MCC in neurons, a new human SHANK3 long isoform and, importantly, highlight the use of proteomic data towards the re-annotation of GC-rich genomic regions.

  12. A Transposon Screen Identifies Genetic Determinants of Vibrio cholerae Resistance to High-Molecular-Weight Antibiotics.

    Science.gov (United States)

    Dörr, Tobias; Delgado, Fernanda; Umans, Benjamin D; Gerding, Matthew A; Davis, Brigid M; Waldor, Matthew K

    2016-08-01

    Gram-negative bacteria are notoriously resistant to a variety of high-molecular-weight antibiotics due to the limited permeability of their outer membrane (OM). The basis of OM barrier function and the genetic factors required for its maintenance remain incompletely understood. Here, we employed transposon insertion sequencing to identify genes required for Vibrio cholerae resistance to vancomycin and bacitracin, antibiotics that are thought to be too large to efficiently penetrate the OM. The screen yielded several genes whose protein products are predicted to participate in processes important for OM barrier functions and for biofilm formation. In addition, we identified a novel factor, designated vigA (for vancomycin inhibits growth), that has not previously been characterized or linked to outer membrane function. The vigA open reading frame (ORF) codes for an inner membrane protein, and in its absence, cells became highly sensitive to glycopeptide antibiotics (vancomycin and ramoplanin) and bacitracin but not to other large antibiotics or detergents. In contrast to wild-type (WT) cells, the vigA mutant was stained with fluorescent vancomycin. These observations suggest that VigA specifically prevents the periplasmic accumulation of certain large antibiotics without exerting a general role in the maintenance of OM integrity. We also observed marked interspecies variability in the susceptibilities of Gram-negative pathogens to glycopeptides and bacitracin. Collectively, our findings suggest that the OM barrier is not absolute but rather depends on specific OM-antibiotic interactions. PMID:27216069

  13. Lineage mapping identifies molecular and architectural similarities between the larval and adult Drosophila central nervous system

    Science.gov (United States)

    Lacin, Haluk; Truman, James W

    2016-01-01

    Neurogenesis in Drosophila occurs in two phases, embryonic and post-embryonic, in which the same set of neuroblasts give rise to the distinct larval and adult nervous systems, respectively. Here, we identified the embryonic neuroblast origin of the adult neuronal lineages in the ventral nervous system via lineage-specific GAL4 lines and molecular markers. Our lineage mapping revealed that neurons born late in the embryonic phase show axonal morphology and transcription factor profiles that are similar to the neurons born post-embryonically from the same neuroblast. Moreover, we identified three thorax-specific neuroblasts not previously characterized and show that HOX genes confine them to the thoracic segments. Two of these, NB2-3 and NB3-4, generate leg motor neurons. The other neuroblast is novel and appears to have arisen recently during insect evolution. Our findings provide a comprehensive view of neurogenesis and show how proliferation of individual neuroblasts is dictated by temporal and spatial cues. DOI: http://dx.doi.org/10.7554/eLife.13399.001 PMID:26975248

  14. Molecular analysis of 11 galactosemia patients.

    OpenAIRE

    Reichardt, J K

    1991-01-01

    Galactosemia is a human inborn error of galactose metabolism due to deficiency of galactose-1-phosphate uridyl transferase. In this paper, I describe the molecular analysis of genomic DNA, mRNA and protein from 11 different galactosemic patients by Southern, Northern and Western blotting. The results of these experiments lead me to conclude that galactosemia is caused mostly by missense mutations. The unusual preponderance of missense mutations in galactosemia led me to investigate its cause....

  15. Identifying clinical course patterns in SMS data using cluster analysis

    DEFF Research Database (Denmark)

    Kent, Peter; Kongsted, Alice

    2012-01-01

    ABSTRACT: BACKGROUND: Recently, there has been interest in using the short message service (SMS or text messaging), to gather frequent information on the clinical course of individual patients. One possible role for identifying clinical course patterns is to assist in exploring clinically important...... clinically interpretable and different from those of the whole group. Similar patterns were obtained when the number of SMS time points was reduced to monthly. The advantages and disadvantages of this method were contrasted to that of first transforming SMS data by spline analysis. CONCLUSIONS: This study...

  16. Lidar point density analysis: implications for identifying water bodies

    Science.gov (United States)

    Worstell, Bruce B.; Poppenga, Sandra; Evans, Gayla A.; Prince, Sandra

    2014-01-01

    Most airborne topographic light detection and ranging (lidar) systems operate within the near-infrared spectrum. Laser pulses from these systems frequently are absorbed by water and therefore do not generate reflected returns on water bodies in the resulting void regions within the lidar point cloud. Thus, an analysis of lidar voids has implications for identifying water bodies. Data analysis techniques to detect reduced lidar return densities were evaluated for test sites in Blackhawk County, Iowa, and Beltrami County, Minnesota, to delineate contiguous areas that have few or no lidar returns. Results from this study indicated a 5-meter radius moving window with fewer than 23 returns (28 percent of the moving window) was sufficient for delineating void regions. Techniques to provide elevation values for void regions to flatten water features and to force channel flow in the downstream direction also are presented.

  17. Cluster analysis of clinical data identifies fibromyalgia subgroups.

    Directory of Open Access Journals (Sweden)

    Elisa Docampo

    Full Text Available INTRODUCTION: Fibromyalgia (FM is mainly characterized by widespread pain and multiple accompanying symptoms, which hinder FM assessment and management. In order to reduce FM heterogeneity we classified clinical data into simplified dimensions that were used to define FM subgroups. MATERIAL AND METHODS: 48 variables were evaluated in 1,446 Spanish FM cases fulfilling 1990 ACR FM criteria. A partitioning analysis was performed to find groups of variables similar to each other. Similarities between variables were identified and the variables were grouped into dimensions. This was performed in a subset of 559 patients, and cross-validated in the remaining 887 patients. For each sample and dimension, a composite index was obtained based on the weights of the variables included in the dimension. Finally, a clustering procedure was applied to the indexes, resulting in FM subgroups. RESULTS: VARIABLES CLUSTERED INTO THREE INDEPENDENT DIMENSIONS: "symptomatology", "comorbidities" and "clinical scales". Only the two first dimensions were considered for the construction of FM subgroups. Resulting scores classified FM samples into three subgroups: low symptomatology and comorbidities (Cluster 1, high symptomatology and comorbidities (Cluster 2, and high symptomatology but low comorbidities (Cluster 3, showing differences in measures of disease severity. CONCLUSIONS: We have identified three subgroups of FM samples in a large cohort of FM by clustering clinical data. Our analysis stresses the importance of family and personal history of FM comorbidities. Also, the resulting patient clusters could indicate different forms of the disease, relevant to future research, and might have an impact on clinical assessment.

  18. Use of discriminant analysis to identify propensity for purchasing properties

    Directory of Open Access Journals (Sweden)

    Ricardo Floriani

    2015-03-01

    Full Text Available Properties usually represent a milestone for people and families due to the high added-value when compared with family income. The objective of this study is the proposition of a discrimination model, by a discriminant analysis of people with characteristics (according to independent variables classified as potential buyers of properties, as well as to identify the interest in the use of such property, if it will be assigned to housing or leisure activities such as a cottage or beach house, and/or for investment. Thus, the following research question is proposed: What are the characteristics that better describe the profile of people which intend to acquire properties? The study justifies itself by its economic relevance in the real estate industry, as well as to the players of the real estate Market that may develop products based on the profile of potential customers. As a statistical technique, discriminant analysis was applied to the data gathered by questionnaire, which was sent via e-mail. Three hundred and thirty four responses were gathered. Based on this study, it was observed that it is possible to identify the intention for acquired properties, as well the purpose for acquiring it, for housing or investments.

  19. Longitudinal Metagenomic Analysis of Hospital Air Identifies Clinically Relevant Microbes

    Science.gov (United States)

    King, Paula; Pham, Long K.; Waltz, Shannon; Sphar, Dan; Yamamoto, Robert T.; Conrad, Douglas; Taplitz, Randy; Torriani, Francesca

    2016-01-01

    We describe the sampling of sixty-three uncultured hospital air samples collected over a six-month period and analysis using shotgun metagenomic sequencing. Our primary goals were to determine the longitudinal metagenomic variability of this environment, identify and characterize genomes of potential pathogens and determine whether they are atypical to the hospital airborne metagenome. Air samples were collected from eight locations which included patient wards, the main lobby and outside. The resulting DNA libraries produced 972 million sequences representing 51 gigabases. Hierarchical clustering of samples by the most abundant 50 microbial orders generated three major nodes which primarily clustered by type of location. Because the indoor locations were longitudinally consistent, episodic relative increases in microbial genomic signatures related to the opportunistic pathogens Aspergillus, Penicillium and Stenotrophomonas were identified as outliers at specific locations. Further analysis of microbial reads specific for Stenotrophomonas maltophilia indicated homology to a sequenced multi-drug resistant clinical strain and we observed broad sequence coverage of resistance genes. We demonstrate that a shotgun metagenomic sequencing approach can be used to characterize the resistance determinants of pathogen genomes that are uncharacteristic for an otherwise consistent hospital air microbial metagenomic profile. PMID:27482891

  20. Analysis and computational dissection of molecular signature multiplicity.

    Directory of Open Access Journals (Sweden)

    Alexander Statnikov

    2010-05-01

    Full Text Available Molecular signatures are computational or mathematical models created to diagnose disease and other phenotypes and to predict clinical outcomes and response to treatment. It is widely recognized that molecular signatures constitute one of the most important translational and basic science developments enabled by recent high-throughput molecular assays. A perplexing phenomenon that characterizes high-throughput data analysis is the ubiquitous multiplicity of molecular signatures. Multiplicity is a special form of data analysis instability in which different analysis methods used on the same data, or different samples from the same population lead to different but apparently maximally predictive signatures. This phenomenon has far-reaching implications for biological discovery and development of next generation patient diagnostics and personalized treatments. Currently the causes and interpretation of signature multiplicity are unknown, and several, often contradictory, conjectures have been made to explain it. We present a formal characterization of signature multiplicity and a new efficient algorithm that offers theoretical guarantees for extracting the set of maximally predictive and non-redundant signatures independent of distribution. The new algorithm identifies exactly the set of optimal signatures in controlled experiments and yields signatures with significantly better predictivity and reproducibility than previous algorithms in human microarray gene expression datasets. Our results shed light on the causes of signature multiplicity, provide computational tools for studying it empirically and introduce a framework for in silico bioequivalence of this important new class of diagnostic and personalized medicine modalities.

  1. Applying universal scaling laws to identify the best molecular design paradigms for second-order nonlinear optics

    CERN Document Server

    Perez-Moreno, Javier; Kuzyk, Mark G

    2016-01-01

    We apply scaling and the theory of the fundamental limits of the second-order molecular susceptibility to identify material classes with ultralarge nonlinear-optical response. Size effects are removed by normalizing all nonlinearities to get intrinsic values so that the scaling behavior of a series of molecular homologues can be determined. Several new figures of merit are proposed that quantify the desirable properties for molecules that can be designed by adding a sequence of repeat units, and used in the assessment of the data. Three molecular classes are found. They are characterized by sub-scaling, nominal scaling, or super-scaling. Super-scaling homologues most efficiently take advantage of increased size. We apply our approach to data currently available in the literature to identify the best super-scaling molecular paradigms with the aim of identifying desirable traits of new materials.

  2. Integrated Bioinformatics, Environmental Epidemiologic and Genomic Approaches to Identify Environmental and Molecular Links between Endometriosis and Breast Cancer

    Directory of Open Access Journals (Sweden)

    Deodutta Roy

    2015-10-01

    Full Text Available We present a combined environmental epidemiologic, genomic, and bioinformatics approach to identify: exposure of environmental chemicals with estrogenic activity; epidemiologic association between endocrine disrupting chemical (EDC and health effects, such as, breast cancer or endometriosis; and gene-EDC interactions and disease associations. Human exposure measurement and modeling confirmed estrogenic activity of three selected class of environmental chemicals, polychlorinated biphenyls (PCBs, bisphenols (BPs, and phthalates. Meta-analysis showed that PCBs exposure, not Bisphenol A (BPA and phthalates, increased the summary odds ratio for breast cancer and endometriosis. Bioinformatics analysis of gene-EDC interactions and disease associations identified several hundred genes that were altered by exposure to PCBs, phthalate or BPA. EDCs-modified genes in breast neoplasms and endometriosis are part of steroid hormone signaling and inflammation pathways. All three EDCs–PCB 153, phthalates, and BPA influenced five common genes—CYP19A1, EGFR, ESR2, FOS, and IGF1—in breast cancer as well as in endometriosis. These genes are environmentally and estrogen responsive, altered in human breast and uterine tumors and endometriosis lesions, and part of Mitogen Activated Protein Kinase (MAPK signaling pathways in cancer. Our findings suggest that breast cancer and endometriosis share some common environmental and molecular risk factors.

  3. Root productivity of deciduous and evergreen species identified using a molecular approach

    Science.gov (United States)

    Ellsworth, P.; Sternberg, L. O.

    2012-12-01

    identified visually were separated based on each species ' unique banding pattern of restriction fragments. Approximately 2,500 roots were identified using PCR-RFLP and approximately 1,500 more roots were identified visually. Identifying fine roots to species allows for species-level analysis of root productivity in this in situ study.

  4. A Critical Analysis of Anesthesiology Podcasts: Identifying Determinants of Success

    Science.gov (United States)

    Singh, Devin; Matava, Clyde

    2016-01-01

    Background Audio and video podcasts have gained popularity in recent years. Increasingly, podcasts are being used in the field of medicine as a tool to disseminate information. This format has multiple advantages including highly accessible creation tools, low distribution costs, and portability for the user. However, despite its ongoing use in medical education, there are no data describing factors associated with the success or quality of podcasts. Objective The goal of the study was to assess the landscape of anesthesia podcasts in Canada and develop a methodology for evaluating the quality of the podcast. To achieve our objective, we identified the scope of podcasts in anesthesia specifically, constructed an algorithmic model for measuring success, and identified factors linked to both successful podcasts and a peer-review process. Methods Independent reviewers performed a systematic search of anesthesia-related podcasts on iTunes Canada. Data and metrics recorded for each podcast included podcast’s authorship, number posted, podcast series duration, target audience, topics, and social media presence. Descriptive statistics summarized mined data, and univariate analysis was used to identify factors associated with podcast success and a peer-review process. Results Twenty-two podcasts related to anesthesia were included in the final analysis. Less than a third (6/22=27%) were still active. The median longevity of the podcasts’ series was just 13 months (interquartile range: 1-39 months). Anesthesiologists were the target audience for 77% of podcast series with clinical topics being most commonly addressed. We defined a novel algorithm for measuring success: Podcast Success Index. Factors associated with a high Podcast Success Index included podcasts targeting fellows (Spearman R=0.434; P=.04), inclusion of professional topics (Spearman R=0.456-0.603; P=.01-.03), and the use of Twitter as a means of social media (Spearman R=0.453;P=.03). In addition, more

  5. Network stratification analysis for identifying function-specific network layers.

    Science.gov (United States)

    Zhang, Chuanchao; Wang, Jiguang; Zhang, Chao; Liu, Juan; Xu, Dong; Chen, Luonan

    2016-04-22

    A major challenge of systems biology is to capture the rewiring of biological functions (e.g. signaling pathways) in a molecular network. To address this problem, we proposed a novel computational framework, namely network stratification analysis (NetSA), to stratify the whole biological network into various function-specific network layers corresponding to particular functions (e.g. KEGG pathways), which transform the network analysis from the gene level to the functional level by integrating expression data, the gene/protein network and gene ontology information altogether. The application of NetSA in yeast and its comparison with a traditional network-partition both suggest that NetSA can more effectively reveal functional implications of network rewiring and extract significant phenotype-related biological processes. Furthermore, for time-series or stage-wise data, the function-specific network layer obtained by NetSA is also shown to be able to characterize the disease progression in a dynamic manner. In particular, when applying NetSA to hepatocellular carcinoma and type 1 diabetes, we can derive functional spectra regarding the progression of the disease, and capture active biological functions (i.e. active pathways) in different disease stages. The additional comparison between NetSA and SPIA illustrates again that NetSA could discover more complete biological functions during disease progression. Overall, NetSA provides a general framework to stratify a network into various layers of function-specific sub-networks, which can not only analyze a biological network on the functional level but also investigate gene rewiring patterns in biological processes. PMID:26879865

  6. Deep RNA profiling identified CLOCK and molecular clock genes as pathophysiological signatures in collagen VI myopathy.

    Science.gov (United States)

    Scotton, Chiara; Bovolenta, Matteo; Schwartz, Elena; Falzarano, Maria Sofia; Martoni, Elena; Passarelli, Chiara; Armaroli, Annarita; Osman, Hana; Rodolico, Carmelo; Messina, Sonia; Pegoraro, Elena; D'Amico, Adele; Bertini, Enrico; Gualandi, Francesca; Neri, Marcella; Selvatici, Rita; Boffi, Patrizia; Maioli, Maria Antonietta; Lochmüller, Hanns; Straub, Volker; Bushby, Katherine; Castrignanò, Tiziana; Pesole, Graziano; Sabatelli, Patrizia; Merlini, Luciano; Braghetta, Paola; Bonaldo, Paolo; Bernardi, Paolo; Foley, Reghan; Cirak, Sebahattin; Zaharieva, Irina; Muntoni, Francesco; Capitanio, Daniele; Gelfi, Cecilia; Kotelnikova, Ekaterina; Yuryev, Anton; Lebowitz, Michael; Zhang, Xiping; Hodge, Brian A; Esser, Karyn A; Ferlini, Alessandra

    2016-04-15

    Collagen VI myopathies are genetic disorders caused by mutations in collagen 6 A1, A2 and A3 genes, ranging from the severe Ullrich congenital muscular dystrophy to the milder Bethlem myopathy, which is recapitulated by collagen-VI-null (Col6a1(-/-)) mice. Abnormalities in mitochondria and autophagic pathway have been proposed as pathogenic causes of collagen VI myopathies, but the link between collagen VI defects and these metabolic circuits remains unknown. To unravel the expression profiling perturbation in muscles with collagen VI myopathies, we performed a deep RNA profiling in bothCol6a1(-/-)mice and patients with collagen VI pathology. The interactome map identified common pathways suggesting a previously undetected connection between circadian genes and collagen VI pathology. Intriguingly,Bmal1(-/-)(also known asArntl) mice, a well-characterized model displaying arrhythmic circadian rhythms, showed profound deregulation of the collagen VI pathway and of autophagy-related genes. The involvement of circadian rhythms in collagen VI myopathies is new and links autophagy and mitochondrial abnormalities. It also opens new avenues for therapies of hereditary myopathies to modulate the molecular clock or potential gene-environment interactions that might modify muscle damage pathogenesis. PMID:26945058

  7. Luminosity Functions of Spitzer Identified Protostars in Nine Nearby Molecular Clouds

    CERN Document Server

    Kryukova, E; Gutermuth, R A; Pipher, J; Allen, T S; Allen, L E; Myers, P C; Muzerolle, J

    2012-01-01

    We identify protostars in Spitzer surveys of nine star-forming molecular clouds within 1 kpc: Serpens, Perseus, Ophiuchus, Chamaeleon, Lupus, Taurus, Orion, Cep OB3, and Mon R2, which combined host over 700 protostar candidates. Our diverse cloud sample allows us to compare protostar luminosity functions in these varied environments. We combine photometry from 2MASS J, H, and Ks bands and Spitzer IRAC and MIPS 24 micron bands to create 1 - 24 micron spectral energy distributions (SEDs). Using protostars from the c2d survey with well-determined bolometric luminosities (Lbol), we derive a relationship between Lbol, L_MIR (integrated from 1 - 24 microns), and SED slope. Estimations of Lbol for protostar candidates are combined to create luminosity functions for each cloud. Contamination due to edge-on disks, reddened Class II sources, and galaxies is estimated and removed from the luminosity functions. We find that luminosity functions for high mass star forming clouds peak near 1 Lsun and show a tail extending ...

  8. Deep RNA profiling identified CLOCK and molecular clock genes as pathophysiological signatures in collagen VI myopathy.

    Science.gov (United States)

    Scotton, Chiara; Bovolenta, Matteo; Schwartz, Elena; Falzarano, Maria Sofia; Martoni, Elena; Passarelli, Chiara; Armaroli, Annarita; Osman, Hana; Rodolico, Carmelo; Messina, Sonia; Pegoraro, Elena; D'Amico, Adele; Bertini, Enrico; Gualandi, Francesca; Neri, Marcella; Selvatici, Rita; Boffi, Patrizia; Maioli, Maria Antonietta; Lochmüller, Hanns; Straub, Volker; Bushby, Katherine; Castrignanò, Tiziana; Pesole, Graziano; Sabatelli, Patrizia; Merlini, Luciano; Braghetta, Paola; Bonaldo, Paolo; Bernardi, Paolo; Foley, Reghan; Cirak, Sebahattin; Zaharieva, Irina; Muntoni, Francesco; Capitanio, Daniele; Gelfi, Cecilia; Kotelnikova, Ekaterina; Yuryev, Anton; Lebowitz, Michael; Zhang, Xiping; Hodge, Brian A; Esser, Karyn A; Ferlini, Alessandra

    2016-04-15

    Collagen VI myopathies are genetic disorders caused by mutations in collagen 6 A1, A2 and A3 genes, ranging from the severe Ullrich congenital muscular dystrophy to the milder Bethlem myopathy, which is recapitulated by collagen-VI-null (Col6a1(-/-)) mice. Abnormalities in mitochondria and autophagic pathway have been proposed as pathogenic causes of collagen VI myopathies, but the link between collagen VI defects and these metabolic circuits remains unknown. To unravel the expression profiling perturbation in muscles with collagen VI myopathies, we performed a deep RNA profiling in both Col6a1(-/-)mice and patients with collagen VI pathology. The interactome map identified common pathways suggesting a previously undetected connection between circadian genes and collagen VI pathology. Intriguingly, Bmal1(-/-)(also known as Arntl) mice, a well-characterized model displaying arrhythmic circadian rhythms, showed profound deregulation of the collagen VI pathway and of autophagy-related genes. The involvement of circadian rhythms in collagen VI myopathies is new and links autophagy and mitochondrial abnormalities. It also opens new avenues for therapies of hereditary myopathies to modulate the molecular clock or potential gene-environment interactions that might modify muscle damage pathogenesis.

  9. Back to the sea twice: identifying candidate plant genes for molecular evolution to marine life

    Directory of Open Access Journals (Sweden)

    Reusch Thorsten BH

    2011-01-01

    Full Text Available Abstract Background Seagrasses are a polyphyletic group of monocotyledonous angiosperms that have adapted to a completely submerged lifestyle in marine waters. Here, we exploit two collections of expressed sequence tags (ESTs of two wide-spread and ecologically important seagrass species, the Mediterranean seagrass Posidonia oceanica (L. Delile and the eelgrass Zostera marina L., which have independently evolved from aquatic ancestors. This replicated, yet independent evolutionary history facilitates the identification of traits that may have evolved in parallel and are possible instrumental candidates for adaptation to a marine habitat. Results In our study, we provide the first quantitative perspective on molecular adaptations in two seagrass species. By constructing orthologous gene clusters shared between two seagrasses (Z. marina and P. oceanica and eight distantly related terrestrial angiosperm species, 51 genes could be identified with detection of positive selection along the seagrass branches of the phylogenetic tree. Characterization of these positively selected genes using KEGG pathways and the Gene Ontology uncovered that these genes are mostly involved in translation, metabolism, and photosynthesis. Conclusions These results provide first insights into which seagrass genes have diverged from their terrestrial counterparts via an initial aquatic stage characteristic of the order and to the derived fully-marine stage characteristic of seagrasses. We discuss how adaptive changes in these processes may have contributed to the evolution towards an aquatic and marine existence.

  10. Analysis of an Image Secret Sharing Scheme to Identify Cheaters

    Directory of Open Access Journals (Sweden)

    Jung-San LEe

    2010-09-01

    Full Text Available Secret image sharing mechanisms have been widely applied to the military, e-commerce, and communications fields. Zhao et al. introduced the concept of cheater detection into image sharing schemes recently. This functionality enables the image owner and authorized members to identify the cheater in reconstructing the secret image. Here, we provide an analysis of Zhao et al.¡¦s method: an authorized participant is able to restore the secret image by him/herself. This contradicts the requirement of secret image sharing schemes. The authorized participant utilizes an exhaustive search to achieve the attempt, though, simulation results show that it can be done within a reasonable time period.

  11. Identifying avian sources of faecal contamination using sterol analysis.

    Science.gov (United States)

    Devane, Megan L; Wood, David; Chappell, Andrew; Robson, Beth; Webster-Brown, Jenny; Gilpin, Brent J

    2015-10-01

    Discrimination of the source of faecal pollution in water bodies is an important step in the assessment and mitigation of public health risk. One tool for faecal source tracking is the analysis of faecal sterols which are present in faeces of animals in a range of distinctive ratios. Published ratios are able to discriminate between human and herbivore mammal faecal inputs but are of less value for identifying pollution from wildfowl, which can be a common cause of elevated bacterial indicators in rivers and streams. In this study, the sterol profiles of 50 avian-derived faecal specimens (seagulls, ducks and chickens) were examined alongside those of 57 ruminant faeces and previously published sterol profiles of human wastewater, chicken effluent and animal meatwork effluent. Two novel sterol ratios were identified as specific to avian faecal scats, which, when incorporated into a decision tree with human and herbivore mammal indicative ratios, were able to identify sterols from avian-polluted waterways. For samples where the sterol profile was not consistent with herbivore mammal or human pollution, avian pollution is indicated when the ratio of 24-ethylcholestanol/(24-ethylcholestanol + 24-ethylcoprostanol + 24-ethylepicoprostanol) is ≥0.4 (avian ratio 1) and the ratio of cholestanol/(cholestanol + coprostanol + epicoprostanol) is ≥0.5 (avian ratio 2). When avian pollution is indicated, further confirmation by targeted PCR specific markers can be employed if greater confidence in the pollution source is required. A 66% concordance between sterol ratios and current avian PCR markers was achieved when 56 water samples from polluted waterways were analysed.

  12. Social network analysis in identifying influential webloggers: A preliminary study

    Science.gov (United States)

    Hasmuni, Noraini; Sulaiman, Nor Intan Saniah; Zaibidi, Nerda Zura

    2014-12-01

    In recent years, second generation of internet-based services such as weblog has become an effective communication tool to publish information on the Web. Weblogs have unique characteristics that deserve users' attention. Some of webloggers have seen weblogs as appropriate medium to initiate and expand business. These webloggers or also known as direct profit-oriented webloggers (DPOWs) communicate and share knowledge with each other through social interaction. However, survivability is the main issue among DPOW. Frequent communication with influential webloggers is one of the way to keep survive as DPOW. This paper aims to understand the network structure and identify influential webloggers within the network. Proper understanding of the network structure can assist us in knowing how the information is exchanged among members and enhance survivability among DPOW. 30 DPOW were involved in this study. Degree centrality and betweenness centrality measurement in Social Network Analysis (SNA) were used to examine the strength relation and identify influential webloggers within the network. Thus, webloggers with the highest value of these measurements are considered as the most influential webloggers in the network.

  13. LUMINOSITY FUNCTIONS OF SPITZER-IDENTIFIED PROTOSTARS IN NINE NEARBY MOLECULAR CLOUDS

    Energy Technology Data Exchange (ETDEWEB)

    Kryukova, E.; Megeath, S. T.; Allen, T. S. [Department of Physics and Astronomy, University of Toledo, Toledo, OH (United States); Gutermuth, R. A. [Department of Astronomy, University of Massachusetts, Amherst, MA (United States); Pipher, J. [Department of Physics and Astronomy, University of Rochester, Rochester, NY (United States); Allen, L. E. [National Optical Astronomy Observatories, Tucson, AZ (United States); Myers, P. C. [Harvard-Smithsonian Center for Astrophysics, Cambridge, MA (United States); Muzerolle, J. [Space Telescope Science Institute, Baltimore, MD (United States)

    2012-08-15

    We identify protostars in Spitzer surveys of nine star-forming (SF) molecular clouds within 1 kpc: Serpens, Perseus, Ophiuchus, Chamaeleon, Lupus, Taurus, Orion, Cep OB3, and Mon R2, which combined host over 700 protostar candidates. These clouds encompass a variety of SF environments, including both low-mass and high-mass SF regions, as well as dense clusters and regions of sparsely distributed star formation. Our diverse cloud sample allows us to compare protostar luminosity functions in these varied environments. We combine near- and mid-infrared photometry from the Two Micron All Sky Survey and Spitzer to create 1-24 {mu}m spectral energy distributions (SEDs). Using protostars from the c2d survey with well-determined bolometric luminosities, we derive a relationship between bolometric luminosity, mid-IR luminosity (integrated from 1-24 {mu}m), and SED slope. Estimations of the bolometric luminosities for protostar candidates are combined to create luminosity functions for each cloud. Contamination due to edge-on disks, reddened Class II sources, and galaxies is estimated and removed from the luminosity functions. We find that luminosity functions for high-mass SF clouds (Orion, Mon R2, and Cep OB3) peak near 1 L{sub Sun} and show a tail extending toward luminosities above 100 L{sub Sun }. The luminosity functions of the low-mass SF clouds (Serpens, Perseus, Ophiuchus, Taurus, Lupus, and Chamaeleon) do not exhibit a common peak, however the combined luminosity function of these regions peaks below 1 L{sub Sun }. Finally, we examine the luminosity functions as a function of the local surface density of young stellar objects. In the Orion molecular clouds, we find a significant difference between the luminosity functions of protostars in regions of high and low stellar density, the former of which is biased toward more luminous sources. This may be the result of primordial mass segregation, although this interpretation is not unique. We compare our luminosity

  14. Matched molecular pair analysis in drug discovery.

    Science.gov (United States)

    Dossetter, Alexander G; Griffen, Edward J; Leach, Andrew G

    2013-08-01

    Multiple parameter optimisation in drug discovery is difficult, but Matched Molecular Pair Analysis (MMPA) can help. Computer algorithms can process data in an unbiased way to yield design rules and suggest better molecules, cutting the number of design cycles. The approach often makes more suggestions than can be processed manually and methods to deal with this are proposed. However, there is a paucity of contextually specific design rules, which would truly make the technique powerful. By combining extracted information from multiple sources there is an opportunity to solve this problem and advance medicinal chemistry in a matter of months rather than years. PMID:23557664

  15. Genetic and molecular characterization of submergence response identifies Subtol6 as a major submergence tolerance locus in maize.

    Directory of Open Access Journals (Sweden)

    Malachy T Campbell

    Full Text Available Maize is highly sensitive to short term flooding and submergence. Early season flooding reduces germination, survival and growth rate of maize seedlings. We aimed to discover genetic variation for submergence tolerance in maize and elucidate the genetic basis of submergence tolerance through transcriptional profiling and linkage analysis of contrasting genotypes. A diverse set of maize nested association mapping (NAM founder lines were screened, and two highly tolerant (Mo18W and M162W and sensitive (B97 and B73 genotypes were identified. Tolerant lines exhibited delayed senescence and lower oxidative stress levels compared to sensitive lines. Transcriptome analysis was performed on these inbreds to provide genome level insights into the molecular responses to submergence. Tolerant lines had higher transcript abundance of several fermentation-related genes and an unannotated Pyrophosphate-Dependent Fructose-6-Phosphate 1-Phosphotransferase gene during submergence. A coexpression network enriched for CBF (C-REPEAT/DRE BINDING FACTOR: C-REPEAT/DRE BINDING FACTOR genes, was induced by submergence in all four inbreds, but was more activated in the tolerant Mo18W. A recombinant inbred line (RIL population derived from Mo18W and B73 was screened for submergence tolerance. A major QTL named Subtol6 was mapped to chromosome 6 that explains 22% of the phenotypic variation within the RIL population. We identified two candidate genes (HEMOGLOBIN2 and RAV1 underlying Subtol6 based on contrasting expression patterns observed in B73 and Mo18W. Sources of tolerance identified in this study (Subtol6 can be useful to increase survival rate during flooding events that are predicted to increase in frequency with climate change.

  16. Chiral Analysis of Isopulegol by Fourier Transform Molecular Rotational Spectroscopy

    Science.gov (United States)

    Evangelisti, Luca; Seifert, Nathan A.; Spada, Lorenzo; Pate, Brooks

    2016-06-01

    Chiral analysis on molecules with multiple chiral centers can be performed using pulsed-jet Fourier transform rotational spectroscopy. This analysis includes quantitative measurement of diastereomer products and, with the three wave mixing methods developed by Patterson, Schnell, and Doyle (Nature 497, 475-477 (2013)), quantitative determination of the enantiomeric excess of each diastereomer. The high resolution features enable to perform the analysis directly on complex samples without the need for chromatographic separation. Isopulegol has been chosen to show the capabilities of Fourier transform rotational spectroscopy for chiral analysis. Broadband rotational spectroscopy produces spectra with signal-to-noise ratio exceeding 1000:1. The ability to identify low-abundance (0.1-1%) diastereomers in the sample will be described. Methods to rapidly identify rotational spectra from isotopologues at natural abundance will be shown and the molecular structures obtained from this analysis will be compared to theory. The role that quantum chemistry calculations play in identifying structural minima and estimating their spectroscopic properties to aid spectral analysis will be described. Finally, the implementation of three wave mixing techniques to measure the enantiomeric excess of each diastereomer and determine the absolute configuration of the enantiomer in excess will be described.

  17. Applying universal scaling laws to identify the best molecular design paradigms for third-order nonlinear optics

    CERN Document Server

    Perez-Moreno, Javier; Kuzyk, Mark G

    2016-01-01

    The scaling of the fundamental limits of the second hyperpolarizability is used to define the intrinsic second hyperpolarizability, which aids in identifying material classes with ultralarge nonlinear-optical response per unit of molecular size. The intrinsic nonlinear response is a size-independent metric that we apply to comparing classes of molecular homologues, which are made by adding repeat units to extend their lengths. Several new figures of merit are proposed that quantify not only the intrinsic nonlinear response, but also how the second hyperpolarizability increases with size within a molecular class. Scaling types can be classified into sub-scaling, nominal scaling that follows the theory of limits, and super-scaling behavior. Super-scaling homologues that have large intrinsic nonlinearity are the most promising because they efficiently take advantage of increased size. We apply our approach to data in the literature to identify the best super-scaling molecular paradigms and articulate the importa...

  18. Comparative genomic analyses identify common molecular pathways modulated upon exposure to low doses of arsenic and cadmium

    Directory of Open Access Journals (Sweden)

    Fry Rebecca C

    2011-04-01

    Full Text Available Abstract Background Exposure to the toxic metals arsenic and cadmium is associated with detrimental health effects including cancers of various organs. While arsenic and cadmium are well known to cause adverse health effects at high doses, the molecular impact resulting from exposure to environmentally relevant doses of these metals remains largely unexplored. Results In this study, we examined the effects of in vitro exposure to either arsenic or cadmium in human TK6 lymphoblastoid cells using genomics and systems level pathway mapping approaches. A total of 167 genes with differential expression were identified following exposure to either metal with surprisingly no overlap between the two. Real-time PCR was used to confirm target gene expression changes. The gene sets were overlaid onto protein-protein interaction maps to identify metal-induced transcriptional networks. Interestingly, both metal-induced networks were significantly enriched for proteins involved in common biological processes such as tumorigenesis, inflammation, and cell signaling. These findings were further supported by gene set enrichment analysis. Conclusions This study is the first to compare the transcriptional responses induced by low dose exposure to cadmium and arsenic in human lymphoblastoid cells. These results highlight that even at low levels of exposure both metals can dramatically influence the expression of important cellular pathways.

  19. Physical Properties and Galactic Distribution of Molecular Clouds identified in the Galactic Ring Survey

    CERN Document Server

    Roman-Duval, Julia; Heyer, Mark; Rathborne, Jill; Simon, Robert

    2010-01-01

    We derive the physical properties of 580 molecular clouds based on their 12CO and 13CO line emission detected in the University of Massachusetts-Stony Brook (UMSB) and Galactic Ring surveys. We provide a range of values of the physical properties of molecular clouds, and find a power-law correlation between their radii and masses, suggesting that the fractal dimension of the ISM is around 2.36. This relation, M = (228 +/- 18) R^{2.36+/-0.04}, allows us to derive masses for an additional 170 GRS molecular clouds not covered by the UMSB survey. We derive the Galactic surface mass density of molecular gas and examine its spatial variations throughout the Galaxy. We find that the azimuthally averaged Galactic surface density of molecular gas peaks between Galactocentric radii of 4 and 5 kpc. Although the Perseus arm is not detected in molecular gas, the Galactic surface density of molecular gas is enhanced along the positions of the Scutum-Crux and Sagittarius arms. This may indicate that molecular clouds form in...

  20. Physical Properties and Galactic Distribution of Molecular Clouds Identified in the Galactic Ring Survey

    Science.gov (United States)

    Roman-Duval, Julia; Jackson, James M.; Heyer, Mark; Rathborne, Jill; Simon, Robert

    2010-11-01

    We derive the physical properties of 580 molecular clouds based on their 12CO and 13CO line emission detected in the University of Massachusetts-Stony Brook (UMSB) and Galactic Ring surveys. We provide a range of values of the physical properties of molecular clouds, and find a power-law correlation between their radii and masses, suggesting that the fractal dimension of the interstellar medium is around 2.36. This relation, M = (228 ± 18) R 2.36 ± 0.04, allows us to derive masses for an additional 170 Galactic Ring Survey (GRS) molecular clouds not covered by the UMSB survey. We derive the Galactic surface mass density of molecular gas and examine its spatial variations throughout the Galaxy. We find that the azimuthally averaged Galactic surface density of molecular gas peaks between Galactocentric radii of 4 and 5 kpc. Although the Perseus arm is not detected in molecular gas, the Galactic surface density of molecular gas is enhanced along the positions of the Scutum-Crux and Sagittarius arms. This may indicate that molecular clouds form in spiral arms and are disrupted in the inter-arm space. Finally, we find that the CO excitation temperature of molecular clouds decreases away from the Galactic center, suggesting a possible decline in the star formation rate with Galactocentric radius. There is a marginally significant enhancement in the CO excitation temperature of molecular clouds at a Galactocentric radius of about 6 kpc, which in the longitude range of the GRS corresponds to the Sagittarius arm. This temperature increase could be associated with massive star formation in the Sagittarius spiral arm.

  1. Colon cancer molecular subtypes identified by expression profiling and associated to stroma, mucinous type and different clinical behavior

    International Nuclear Information System (INIS)

    Colon cancer patients with the same stage show diverse clinical behavior due to tumor heterogeneity. We aimed to discover distinct classes of tumors based on microarray expression patterns, to analyze whether the molecular classification correlated with the histopathological stages or other clinical parameters and to study differences in the survival. Hierarchical clustering was performed for class discovery in 88 colon tumors (stages I to IV). Pathways analysis and correlations between clinical parameters and our classification were analyzed. Tumor subtypes were validated using an external set of 78 patients. A 167 gene signature associated to the main subtype was generated using the 3-Nearest-Neighbor method. Coincidences with other prognostic predictors were assesed. Hierarchical clustering identified four robust tumor subtypes with biologically and clinically distinct behavior. Stromal components (p < 0.001), nuclear β-catenin (p = 0.021), mucinous histology (p = 0.001), microsatellite-instability (p = 0.039) and BRAF mutations (p < 0.001) were associated to this classification but it was independent of Dukes stages (p = 0.646). Molecular subtypes were established from stage I. High-stroma-subtype showed increased levels of genes and altered pathways distinctive of tumour-associated-stroma and components of the extracellular matrix in contrast to Low-stroma-subtype. Mucinous-subtype was reflected by the increased expression of trefoil factors and mucins as well as by a higher proportion of MSI and BRAF mutations. Tumor subtypes were validated using an external set of 78 patients. A 167 gene signature associated to the Low-stroma-subtype distinguished low risk patients from high risk patients in the external cohort (Dukes B and C:HR = 8.56(2.53-29.01); Dukes B,C and D:HR = 1.87(1.07-3.25)). Eight different reported survival gene signatures segregated our tumors into two groups the Low-stroma-subtype and the other tumor subtypes. We have identified novel

  2. Directional reflectance analysis for identifying counterfeit drugs: Preliminary study.

    Science.gov (United States)

    Wilczyński, Sławomir; Koprowski, Robert; Błońska-Fajfrowska, Barbara

    2016-05-30

    The WHO estimates that up to 10% of drugs on the market may be counterfeit. In order to prevent intensification of the phenomenon of drug counterfeiting, the methods for distinguishing genuine medicines from fake ones need to be developed. The aim of this study was to try to develop simple, reproducible and inexpensive method for distinguishing between original and counterfeit medicines based on the measurement of directional reflectance. The directional reflectance of 6 original Viagra(®) tablets (Pfizer) and 24 (4 different batches) counterfeit tablets (imitating Viagra(®)) was examined in six spectral bands: from 0.9 to 1.1 μm, from 1.9 to 2.6 μm, from 3.0 to 4.0 μm, from 3.0 to 5.0 μm, from 4.0 to 5.0 μm, from 8.0 to 12.0 μm, and for two angles of incidence, 20° and 60°. Directional hemispherical reflectometer was applied to measure directional reflectance. Significant statistical differences between the directional reflectance of the original Viagra(®) and counterfeit tablets were registered. Any difference in the value of directional reflectance for any spectral band or angle of incidence identifies the drug as a fake one. The proposed method of directional reflectance analysis enables to differentiate between the real Viagra(®) and fake tablets. Directional reflectance analysis is a fast (measurement time under 5s), cheap and reproducible method which does not require expensive equipment or specialized laboratory staff. It also seems to be an effective method, however, the effectiveness will be assessed after the extension of research. PMID:26977587

  3. Using Homology Modeling, Molecular Dynamics and Molecular Docking Techniques to Identify Inhibitor Binding Regions of Somatostatin Receptor 1

    Institute of Scientific and Technical Information of China (English)

    LAN Hai-nan; WANG Yue-xi; ZHENG Ming-zhu; HAN Wei-wei; ZHENG Xin

    2013-01-01

    The G protein coupled receptor(GPCR),one of the members in the superfamily,which consists of thousands of integral membrane proteins,exerts a wide variety of physiological functions and responses to a large portion of the drug targets.The 3D structure of somatostatin receptor 1(SSTR1) was modeled and refined by means of homology modeling and molecular dynamics simulation.This model was assessed by Verify-3D and Vadar,which confirmed the reliability of the refined model.The interaction between the inhibitor cysteamine,somatostatin(SST) and SSTRI was investigated by a molecular docking program,Affinity.The binding module not only showed the crucial residues involved in the interaction,but also provided important information about the interaction between SSTR1 on the one hand and ligands on the other,which might be the significant evidence for the structure-based design.

  4. A Sensitivity Analysis Approach to Identify Key Environmental Performance Factors

    Directory of Open Access Journals (Sweden)

    Xi Yu

    2014-01-01

    Full Text Available Life cycle assessment (LCA is widely used in design phase to reduce the product’s environmental impacts through the whole product life cycle (PLC during the last two decades. The traditional LCA is restricted to assessing the environmental impacts of a product and the results cannot reflect the effects of changes within the life cycle. In order to improve the quality of ecodesign, it is a growing need to develop an approach which can reflect the changes between the design parameters and product’s environmental impacts. A sensitivity analysis approach based on LCA and ecodesign is proposed in this paper. The key environmental performance factors which have significant influence on the products’ environmental impacts can be identified by analyzing the relationship between environmental impacts and the design parameters. Users without much environmental knowledge can use this approach to determine which design parameter should be first considered when (redesigning a product. A printed circuit board (PCB case study is conducted; eight design parameters are chosen to be analyzed by our approach. The result shows that the carbon dioxide emission during the PCB manufacture is highly sensitive to the area of PCB panel.

  5. Global secretome analysis identifies novel mediators of bone metastasis

    Institute of Scientific and Technical Information of China (English)

    Mario Andres Blanco; Gary LeRoy; Zia Khan; Ma(s)a Ale(c)kovi(c); Barry M Zee; Benjamin A Garcia; Yibin Kang

    2012-01-01

    Bone is the one of the most common sites of distant metastasis of solid tumors.Secreted proteins are known to influence pathological interactions between metastatic cancer cells and the bone stroma.To comprehensively profile secreted proteins associated with bone metastasis,we used quantitative and non-quantitative mass spectrometry to globally analyze the secretomes of nine cell lines of varying bone metastatic ability from multiple species and cancer types.By comparing the secretomes of parental cells and their bone metastatic derivatives,we identified the secreted proteins that were uniquely associated with bone metastasis in these cell lines.We then incorporated bioinformatic analyses of large clinical metastasis datasets to obtain a list of candidate novel bone metastasis proteins of several functional classes that were strongly associated with both clinical and experimental bone metastasis.Functional validation of selected proteins indicated that in vivo bone metastasis can be promoted by high expression of (1) the salivary cystatins CST1,CST2,and CST4; (2) the plasminogen activators PLAT and PLAU; or (3) the collagen functionality proteins PLOD2 and COL6A1.Overall,our study has uncovered several new secreted mediators of bone metastasis and therefore demonstrated that secretome analysis is a powerful method for identification of novel biomarkers and candidate therapeutic targets.

  6. Correlation between smoking history and molecular pathways in sporadic colorectal cancer: a meta-analysis

    OpenAIRE

    Chen, Ke; Xia, Guanggai; Zhang, Changhua; Sun, Yunwei

    2015-01-01

    Background: Epidemiological studies have shown that smoking increases the risk for colorectal cancer (CRC). Evidence of the guiding significance of smoking history for molecular classification and molecular targeted anti-tumor therapy is not well established. Aims: To provide indirectly evidence, we conducted a systematic meta-analysis of association between smoking history and different molecular classification. Methods: We searched in multiple databases up to January 2014, and identified 27...

  7. Performance Analysis: Work Control Events Identified January - August 2010

    Energy Technology Data Exchange (ETDEWEB)

    De Grange, C E; Freeman, J W; Kerr, C E; Holman, G; Marsh, K; Beach, R

    2011-01-14

    This performance analysis evaluated 24 events that occurred at LLNL from January through August 2010. The analysis identified areas of potential work control process and/or implementation weaknesses and several common underlying causes. Human performance improvement and safety culture factors were part of the causal analysis of each event and were analyzed. The collective significance of all events in 2010, as measured by the occurrence reporting significance category and by the proportion of events that have been reported to the DOE ORPS under the ''management concerns'' reporting criteria, does not appear to have increased in 2010. The frequency of reporting in each of the significance categories has not changed in 2010 compared to the previous four years. There is no change indicating a trend in the significance category and there has been no increase in the proportion of occurrences reported in the higher significance category. Also, the frequency of events, 42 events reported through August 2010, is not greater than in previous years and is below the average of 63 occurrences per year at LLNL since 2006. Over the previous four years, an average of 43% of the LLNL's reported occurrences have been reported as either ''management concerns'' or ''near misses.'' In 2010, 29% of the occurrences have been reported as ''management concerns'' or ''near misses.'' This rate indicates that LLNL is now reporting fewer ''management concern'' and ''near miss'' occurrences compared to the previous four years. From 2008 to the present, LLNL senior management has undertaken a series of initiatives to strengthen the work planning and control system with the primary objective to improve worker safety. In 2008, the LLNL Deputy Director established the Work Control Integrated Project Team to develop the core requirements and graded

  8. Systems Genetics Reveals the Functional Context of PCOS Loci and Identifies Genetic and Molecular Mechanisms of Disease Heterogeneity.

    Directory of Open Access Journals (Sweden)

    Michelle R Jones

    2015-08-01

    Full Text Available Genome wide association studies (GWAS have revealed 11 independent risk loci for polycystic ovary syndrome (PCOS, a common disorder in young women characterized by androgen excess and oligomenorrhea. To put these risk loci and the single nucleotide polymorphisms (SNPs therein into functional context, we measured DNA methylation and gene expression in subcutaneous adipose tissue biopsies to identify PCOS-specific alterations. Two genes from the LHCGR region, STON1-GTF2A1L and LHCGR, were overexpressed in PCOS. In analysis stratified by obesity, LHCGR was overexpressed only in non-obese PCOS women. Although not differentially expressed in the entire PCOS group, INSR was underexpressed in obese PCOS subjects only. Alterations in gene expression in the LHCGR, RAB5B and INSR regions suggest that SNPs in these loci may be functional and could affect gene expression directly or indirectly via epigenetic alterations. We identified reduced methylation in the LHCGR locus and increased methylation in the INSR locus, changes that are concordant with the altered gene expression profiles. Complex patterns of meQTL and eQTL were identified in these loci, suggesting that local genetic variation plays an important role in gene regulation. We propose that non-obese PCOS women possess significant alterations in LH receptor expression, which drives excess androgen secretion from the ovary. Alternatively, obese women with PCOS possess alterations in insulin receptor expression, with underexpression in metabolic tissues and overexpression in the ovary, resulting in peripheral insulin resistance and excess ovarian androgen production. These studies provide a genetic and molecular basis for the reported clinical heterogeneity of PCOS.

  9. Systems Genetics Reveals the Functional Context of PCOS Loci and Identifies Genetic and Molecular Mechanisms of Disease Heterogeneity.

    Science.gov (United States)

    Jones, Michelle R; Brower, Meredith A; Xu, Ning; Cui, Jinrui; Mengesha, Emebet; Chen, Yii-Der I; Taylor, Kent D; Azziz, Ricardo; Goodarzi, Mark O

    2015-08-01

    Genome wide association studies (GWAS) have revealed 11 independent risk loci for polycystic ovary syndrome (PCOS), a common disorder in young women characterized by androgen excess and oligomenorrhea. To put these risk loci and the single nucleotide polymorphisms (SNPs) therein into functional context, we measured DNA methylation and gene expression in subcutaneous adipose tissue biopsies to identify PCOS-specific alterations. Two genes from the LHCGR region, STON1-GTF2A1L and LHCGR, were overexpressed in PCOS. In analysis stratified by obesity, LHCGR was overexpressed only in non-obese PCOS women. Although not differentially expressed in the entire PCOS group, INSR was underexpressed in obese PCOS subjects only. Alterations in gene expression in the LHCGR, RAB5B and INSR regions suggest that SNPs in these loci may be functional and could affect gene expression directly or indirectly via epigenetic alterations. We identified reduced methylation in the LHCGR locus and increased methylation in the INSR locus, changes that are concordant with the altered gene expression profiles. Complex patterns of meQTL and eQTL were identified in these loci, suggesting that local genetic variation plays an important role in gene regulation. We propose that non-obese PCOS women possess significant alterations in LH receptor expression, which drives excess androgen secretion from the ovary. Alternatively, obese women with PCOS possess alterations in insulin receptor expression, with underexpression in metabolic tissues and overexpression in the ovary, resulting in peripheral insulin resistance and excess ovarian androgen production. These studies provide a genetic and molecular basis for the reported clinical heterogeneity of PCOS. PMID:26305227

  10. Systems Genetics Reveals the Functional Context of PCOS Loci and Identifies Genetic and Molecular Mechanisms of Disease Heterogeneity.

    Science.gov (United States)

    Jones, Michelle R; Brower, Meredith A; Xu, Ning; Cui, Jinrui; Mengesha, Emebet; Chen, Yii-Der I; Taylor, Kent D; Azziz, Ricardo; Goodarzi, Mark O

    2015-08-01

    Genome wide association studies (GWAS) have revealed 11 independent risk loci for polycystic ovary syndrome (PCOS), a common disorder in young women characterized by androgen excess and oligomenorrhea. To put these risk loci and the single nucleotide polymorphisms (SNPs) therein into functional context, we measured DNA methylation and gene expression in subcutaneous adipose tissue biopsies to identify PCOS-specific alterations. Two genes from the LHCGR region, STON1-GTF2A1L and LHCGR, were overexpressed in PCOS. In analysis stratified by obesity, LHCGR was overexpressed only in non-obese PCOS women. Although not differentially expressed in the entire PCOS group, INSR was underexpressed in obese PCOS subjects only. Alterations in gene expression in the LHCGR, RAB5B and INSR regions suggest that SNPs in these loci may be functional and could affect gene expression directly or indirectly via epigenetic alterations. We identified reduced methylation in the LHCGR locus and increased methylation in the INSR locus, changes that are concordant with the altered gene expression profiles. Complex patterns of meQTL and eQTL were identified in these loci, suggesting that local genetic variation plays an important role in gene regulation. We propose that non-obese PCOS women possess significant alterations in LH receptor expression, which drives excess androgen secretion from the ovary. Alternatively, obese women with PCOS possess alterations in insulin receptor expression, with underexpression in metabolic tissues and overexpression in the ovary, resulting in peripheral insulin resistance and excess ovarian androgen production. These studies provide a genetic and molecular basis for the reported clinical heterogeneity of PCOS.

  11. A systems biology approach identifies Molecular networks defining skeletal muscle abnormalities in chronic obstructive pulmonary disease.

    OpenAIRE

    Nil Turan; Susana Kalko; Anna Stincone; Kim Clarke; Ayesha Sabah; Katherine Howlett; S John Curnow; Rodriguez, Diego A.; Marta Cascante; Laura O'Neill; Stuart Egginton; Josep Roca; Francesco Falciani

    2011-01-01

    Chronic Obstructive Pulmonary Disease (COPD) is an inflammatory process of the lung inducing persistent airflow limitation. Extensive systemic effects, such as skeletal muscle dysfunction, often characterize these patients and severely limit life expectancy. Despite considerable research efforts, the molecular basis of muscle degeneration in COPD is still a matter of intense debate. In this study, we have applied a network biology approach to model the relationship between muscle molecular an...

  12. Asaia bogorensis peritonitis identified by 16S ribosomal RNA sequence analysis in a patient receiving peritoneal dialysis.

    Science.gov (United States)

    Snyder, Richard W; Ruhe, Jorg; Kobrin, Sidney; Wasserstein, Alan; Doline, Christa; Nachamkin, Irving; Lipschutz, Joshua H

    2004-08-01

    Here the authors report a case of refractory peritonitis leading to multiple hospitalizations and the loss of peritoneal dialysis access in a patient on automated peritoneal dialysis, caused by Asaia bogorensis, a bacterium not previously described as a human pathogen. This organism was identified by sequence analysis of the 16S ribosomal RNA gene. Unusual microbial agents may cause peritonitis, and molecular microbiological techniques are important tools for identifying these agents.

  13. IS element IS16 as a molecular screening tool to identify hospital-associated strains of Enterococcus faecium

    NARCIS (Netherlands)

    Werner, Guido; Fleige, Carola; Geringer, Uta; van Schaik, Willem; Klare, Ingo; Witte, Wolfgang

    2011-01-01

    Background: Hospital strains of Enterococcus faecium could be characterized and typed by various molecular methods (MLST, AFLP, MLVA) and allocated to a distinct clonal complex known as MLST CC17. However, these techniques are laborious, time-consuming and cost-intensive. Our aim was to identify hos

  14. Combination of meta-analysis and graph clustering to identify prognostic markers of ESCC

    Directory of Open Access Journals (Sweden)

    Hongyun Gao

    2012-01-01

    Full Text Available Esophageal squamous cell carcinoma (ESCC is one of the most malignant gastrointestinal cancers and occurs at a high frequency rate in China and other Asian countries. Recently, several molecular markers were identified for predicting ESCC. Notwithstanding, additional prognostic markers, with a clear understanding of their underlying roles, are still required. Through bioinformatics, a graph-clustering method by DPClus was used to detect co-expressed modules. The aim was to identify a set of discriminating genes that could be used for predicting ESCC through graph-clustering and GO-term analysis. The results showed that CXCL12, CYP2C9, TGM3, MAL, S100A9, EMP-1 and SPRR3 were highly associated with ESCC development. In our study, all their predicted roles were in line with previous reports, whereby the assumption that a combination of meta-analysis, graph-clustering and GO-term analysis is effective for both identifying differentially expressed genes, and reflecting on their functions in ESCC.

  15. Combination of meta-analysis and graph clustering to identify prognostic markers of ESCC.

    Science.gov (United States)

    Gao, Hongyun; Wang, Lishan; Cui, Shitao; Wang, Mingsong

    2012-04-01

    Esophageal squamous cell carcinoma (ESCC) is one of the most malignant gastrointestinal cancers and occurs at a high frequency rate in China and other Asian countries. Recently, several molecular markers were identified for predicting ESCC. Notwithstanding, additional prognostic markers, with a clear understanding of their underlying roles, are still required. Through bioinformatics, a graph-clustering method by DPClus was used to detect co-expressed modules. The aim was to identify a set of discriminating genes that could be used for predicting ESCC through graph-clustering and GO-term analysis. The results showed that CXCL12, CYP2C9, TGM3, MAL, S100A9, EMP-1 and SPRR3 were highly associated with ESCC development. In our study, all their predicted roles were in line with previous reports, whereby the assumption that a combination of meta-analysis, graph-clustering and GO-term analysis is effective for both identifying differentially expressed genes, and reflecting on their functions in ESCC.

  16. Galleria mellonella model identifies highly virulent strains among all major molecular types of Cryptococcus gattii.

    Directory of Open Access Journals (Sweden)

    Carolina Firacative

    Full Text Available Cryptococcosis is mainly caused by Cryptococcus neoformans. However, the number of cases due to C. gattii is increasing, affecting mainly immunocompetent hosts. C. gattii is divided into four major molecular types, VGI to VGIV, which differ in their host range, epidemiology, antifungal susceptibility and geographic distribution. Besides studies on the Vancouver Island outbreak strains, which showed that the subtype VGIIa is highly virulent compared to the subtype VGIIb, little is known about the virulence of the other major molecular types. To elucidate the virulence potential of the major molecular types of C. gattii, Galleria mellonella larvae were inoculated with ten globally selected strains per molecular type. Survival rates were recorded and known virulence factors were studied. One VGII, one VGIII and one VGIV strain were more virulent (p 0.05, 21 (five VGI, five VGII, four VGIII and seven VGIV were less virulent (p <0.05 while one strain of each molecular type were avirulent. Cell and capsule size of all strains increased markedly during larvae infection (p <0.001. No differences in growth rate at 37°C were observed. Melanin synthesis was directly related with the level of virulence: more virulent strains produced more melanin than less virulent strains (p <0.05. The results indicate that all C. gattii major molecular types exhibit a range of virulence, with some strains having the potential to be more virulent. The study highlights the necessity to further investigate the genetic background of more and less virulent strains in order to recognize critical features, other than the known virulence factors (capsule, melanin and growth at mammalian body temperature, that maybe crucial for the development and progression of cryptococcosis.

  17. Physical Properties and Galactic Distribution of Molecular Clouds identified in the Galactic Ring Survey

    OpenAIRE

    Roman-Duval, Julia; Jackson, James M.; Heyer, Mark; Rathborne, Jill; Simon, Robert

    2010-01-01

    We derive the physical properties of 580 molecular clouds based on their 12CO and 13CO line emission detected in the University of Massachusetts-Stony Brook (UMSB) and Galactic Ring surveys. We provide a range of values of the physical properties of molecular clouds, and find a power-law correlation between their radii and masses, suggesting that the fractal dimension of the ISM is around 2.36. This relation, M = (228 +/- 18) R^{2.36+/-0.04}, allows us to derive masses for an additional 170 G...

  18. Integrated genomic analysis identifies the mitotic checkpoint kinase WEE1 as a novel therapeutic target in medulloblastoma

    OpenAIRE

    Harris, Peter S; Venkataraman, Sujatha; Alimova, Irina; Birks, Diane K; Balakrishnan, Ilango; Cristiano, Brian; Donson, Andrew M; Dubuc, Adrian M.; Taylor, Michael D.; Foreman, Nicholas K.; Reigan, Philip; Vibhakar, Rajeev

    2014-01-01

    Background Medulloblastoma is the most common type of malignant brain tumor that afflicts children. Although recent advances in chemotherapy and radiation have improved outcomes, high-risk patients do poorly with significant morbidity. Methods To identify new molecular targets, we performed an integrated genomic analysis using structural and functional methods. Gene expression profiling in 16 medulloblastoma patient samples and subsequent gene set enrichment analysis indicated that cell cycle...

  19. Weighted gene co-expression network analysis identifies specific modules and hub genes related to coronary artery disease

    OpenAIRE

    Liu, Jing; Jing, Ling; Tu, Xilin

    2016-01-01

    Background The analysis of the potential molecule targets of coronary artery disease (CAD) is critical for understanding the molecular mechanisms of disease. However, studies of global microarray gene co-expression analysis of CAD still remain limited. Methods Microarray data of CAD (GSE23561) were downloaded from Gene Expression Omnibus, including peripheral blood samples from CAD patients (n = 6) and controls (n = 9). Limma package in R was used to identify the differentially expressed gene...

  20. Correlation analyses of clinical and molecular findings identify candidate biological pathways in systemic juvenile idiopathic arthritis

    Directory of Open Access Journals (Sweden)

    Ling Xuefeng B

    2012-10-01

    Full Text Available Abstract Background Clinicians have long appreciated the distinct phenotype of systemic juvenile idiopathic arthritis (SJIA compared to polyarticular juvenile idiopathic arthritis (POLY. We hypothesized that gene expression profiles of peripheral blood mononuclear cells (PBMC from children with each disease would reveal distinct biological pathways when analyzed for significant associations with elevations in two markers of JIA activity, erythrocyte sedimentation rate (ESR and number of affected joints (joint count, JC. Methods PBMC RNA from SJIA and POLY patients was profiled by kinetic PCR to analyze expression of 181 genes, selected for relevance to immune response pathways. Pearson correlation and Student's t-test analyses were performed to identify transcripts significantly associated with clinical parameters (ESR and JC in SJIA or POLY samples. These transcripts were used to find related biological pathways. Results Combining Pearson and t-test analyses, we found 91 ESR-related and 92 JC-related genes in SJIA. For POLY, 20 ESR-related and 0 JC-related genes were found. Using Ingenuity Systems Pathways Analysis, we identified SJIA ESR-related and JC-related pathways. The two sets of pathways are strongly correlated. In contrast, there is a weaker correlation between SJIA and POLY ESR-related pathways. Notably, distinct biological processes were found to correlate with JC in samples from the earlier systemic plus arthritic phase (SAF of SJIA compared to samples from the later arthritis-predominant phase (AF. Within the SJIA SAF group, IL-10 expression was related to JC, whereas lack of IL-4 appeared to characterize the chronic arthritis (AF subgroup. Conclusions The strong correlation between pathways implicated in elevations of both ESR and JC in SJIA argues that the systemic and arthritic components of the disease are related mechanistically. Inflammatory pathways in SJIA are distinct from those in POLY course JIA, consistent with

  1. Research Advances: Nanoscale Molecular Tweezers; Cinnamon as Pesticide?; Recently Identified Dietary Sources of Antioxidants

    Science.gov (United States)

    King, Angela G.

    2004-12-01

    This Report from Other Journals surveys articles of interest to chemists that have been recently published in other science journals. Topics surveyed include reports that receptors have been designed to act as molecular tweezers; cinnamon has potential in the fight against mosquitoes; and high levels of antioxidants are found in some surprising foods. See Featured Molecules .

  2. Microarrays and RNA-Seq identify molecular mechanisms driving the end of nephron production

    Directory of Open Access Journals (Sweden)

    Potter S Steven

    2011-03-01

    Full Text Available Abstract Background The production of nephrons suddenly ends in mice shortly after birth when the remaining cells of the multi-potent progenitor mesenchyme begin to differentiate into nephrons. We exploited this terminal wave of nephron production using both microarrays and RNA-Seq to serially evaluate gene transcript levels in the progenitors. This strategy allowed us to define the changing gene expression states following induction and the onset of differentiation after birth. Results Microarray and RNA-Seq studies of the progenitors detected a change in the expression profiles of several classes of genes early after birth. One functional class, a class of genes associated with cellular proliferation, was activated. Analysis of proliferation with a nucleotide analog demonstrated in vivo that entry into the S-phase of the cell cycle preceded increases in transcript levels of genetic markers of differentiation. Microarrays and RNA-Seq also detected the onset of expression of markers of differentiation within the population of progenitors prior to detectable Six2 repression. Validation by in situ hybridization demonstrated that the markers were expressed in a subset of Six2 expressing progenitors. Finally, the studies identified a third set of genes that provide indirect evidence of an altered cellular microenvironment of the multi-potential progenitors after birth. Conclusions These results demonstrate that Six2 expression is not sufficient to suppress activation of genes associated with growth and differentiation of nephrons. They also better define the sequence of events after induction and suggest mechanisms contributing to the rapid end of nephron production after birth in mice.

  3. Polymer Molecular Weight Analysis by [Superscript 1]H NMR Spectroscopy

    Science.gov (United States)

    Izunobi, Josephat U.; Higginbotham, Clement L.

    2011-01-01

    The measurement and analysis of molecular weight and molecular weight distribution remain matters of fundamental importance for the characterization and physical properties of polymers. Gel permeation chromatography (GPC) is the most routinely used method for the molecular weight determination of polymers whereas matrix-assisted laser…

  4. A systems biology approach identifies molecular networks defining skeletal muscle abnormalities in chronic obstructive pulmonary disease.

    Directory of Open Access Journals (Sweden)

    Nil Turan

    2011-09-01

    Full Text Available Chronic Obstructive Pulmonary Disease (COPD is an inflammatory process of the lung inducing persistent airflow limitation. Extensive systemic effects, such as skeletal muscle dysfunction, often characterize these patients and severely limit life expectancy. Despite considerable research efforts, the molecular basis of muscle degeneration in COPD is still a matter of intense debate. In this study, we have applied a network biology approach to model the relationship between muscle molecular and physiological response to training and systemic inflammatory mediators. Our model shows that failure to co-ordinately activate expression of several tissue remodelling and bioenergetics pathways is a specific landmark of COPD diseased muscles. Our findings also suggest that this phenomenon may be linked to an abnormal expression of a number of histone modifiers, which we discovered correlate with oxygen utilization. These observations raised the interesting possibility that cell hypoxia may be a key factor driving skeletal muscle degeneration in COPD patients.

  5. Proteomics identifies molecular networks affected by tetradecylthioacetic acid and fish oil supplemented diets

    DEFF Research Database (Denmark)

    Wrzesinski, Krzysztof; León, Ileana R.; Kulej, Katarzyna;

    2013-01-01

    - high fat diet that is thought to contribute to the development of metabolic syndrome - a condition that is strongly associated with diabetes, obesity and heart failure. Fish oil and TTA are known to have beneficial effects for the fatty acid metabolism and have been shown to alleviate some...... of the symptoms of the metabolic syndrome. To date very little is known about the molecular mechanisms behind these beneficial effects and the potential pitfalls of the consumption of those two compounds. Only studies of each compound separately and using only small scale molecular biology approaches have been...... carried out. The results of this work provide an excellent starting point for further studies that will help to understand the metabolic effects of fish oil and TTA and will hopefully help to design dietary programs directed towards reduction of the prevalence of metabolic syndrome and associated diseases....

  6. An efficient algorithm for identifying matches with errors in multiple long molecular sequences.

    Science.gov (United States)

    Leung, M Y; Blaisdell, B E; Burge, C; Karlin, S

    1991-10-20

    An efficient algorithm is described for finding matches, repeats and other word relations, allowing for errors, in large data sets of long molecular sequences. The algorithm entails hashing on fixed-size words in conjunction with the use of a linked list connecting all occurrences of the same word. The average memory and run time requirement both increase almost linearly with the total sequence length. Some results of the program's performance on a database of Escherichia coli DNA sequences are presented.

  7. Molecular applications for identifying microbial pathogens in the post-9/11 era.

    Science.gov (United States)

    Cebula, Thomas A; Brown, Eric W; Jackson, Scott A; Mammel, Mark K; Mukherjee, Amit; LeClerc, J Eugene

    2005-05-01

    Rapid advances in molecular and optical technologies over the past 10 years have dramatically impacted the way biologic research is conducted today. Examples include microarrays, capillary sequencing, optical mapping and real-time sequencing (Pyrosequencing). These technologies are capable of rapidly delivering massive amounts of genetic information and are becoming routine mainstays of many laboratories. Fortunately, advances in scientific computing have provided the enormous computing power necessary to analyze these enormous data sets. The application of molecular technologies should prove useful to the burgeoning field of microbial forensics. In the post-9/11 era, when securing America's food supply is a major endeavor, the need for rapid identification of microbes that accidentally or intentionally find their way into foods is apparent. The principle that distinguishes a microbial forensic investigation from a molecular epidemiology study is that a biocrime has been committed. If proper attribution is to be attained, a link must be made between a particular microbe in the food and the perpetrator who placed it there. Therefore, the techniques used must be able to discriminate individual isolates of a particular microbe. A battery of techniques in development for distinguishing individual isolates of particular foodborne pathogens is discussed.

  8. Market Analysis Identifies Community and School Education Goals.

    Science.gov (United States)

    Lindle, Jane C.

    1989-01-01

    Principals must realize the positive effects that marketing can have on improving schools and building support for them. Market analysis forces clarification of the competing needs and interests present in the community. The four marketing phases are needs assessment, analysis, goal setting, and public relations and advertising. (MLH)

  9. Gene expression signature analysis identifies vorinostat as a candidate therapy for gastric cancer.

    Directory of Open Access Journals (Sweden)

    Sofie Claerhout

    Full Text Available BACKGROUND: Gastric cancer continues to be one of the deadliest cancers in the world and therefore identification of new drugs targeting this type of cancer is thus of significant importance. The purpose of this study was to identify and validate a therapeutic agent which might improve the outcomes for gastric cancer patients in the future. METHODOLOGY/PRINCIPAL FINDINGS: Using microarray technology, we generated a gene expression profile of human gastric cancer-specific genes from human gastric cancer tissue samples. We used this profile in the Broad Institute's Connectivity Map analysis to identify candidate therapeutic compounds for gastric cancer. We found the histone deacetylase inhibitor vorinostat as the lead compound and thus a potential therapeutic drug for gastric cancer. Vorinostat induced both apoptosis and autophagy in gastric cancer cell lines. Pharmacological and genetic inhibition of autophagy however, increased the therapeutic efficacy of vorinostat, indicating that a combination of vorinostat with autophagy inhibitors may therapeutically be more beneficial. Moreover, gene expression analysis of gastric cancer identified a collection of genes (ITGB5, TYMS, MYB, APOC1, CBX5, PLA2G2A, and KIF20A whose expression was elevated in gastric tumor tissue and downregulated more than 2-fold by vorinostat treatment in gastric cancer cell lines. In contrast, SCGB2A1, TCN1, CFD, APLP1, and NQO1 manifested a reversed pattern. CONCLUSIONS/SIGNIFICANCE: We showed that analysis of gene expression signature may represent an emerging approach to discover therapeutic agents for gastric cancer, such as vorinostat. The observation of altered gene expression after vorinostat treatment may provide the clue to identify the molecular mechanism of vorinostat and those patients likely to benefit from vorinostat treatment.

  10. Integrative genome-wide expression profiling identifies three distinct molecular subgroups of renal cell carcinoma with different patient outcome

    International Nuclear Information System (INIS)

    Renal cell carcinoma (RCC) is characterized by a number of diverse molecular aberrations that differ among individuals. Recent approaches to molecularly classify RCC were based on clinical, pathological as well as on single molecular parameters. As a consequence, gene expression patterns reflecting the sum of genetic aberrations in individual tumors may not have been recognized. In an attempt to uncover such molecular features in RCC, we used a novel, unbiased and integrative approach. We integrated gene expression data from 97 primary RCC of different pathologic parameters, 15 RCC metastases as well as 34 cancer cell lines for two-way nonsupervised hierarchical clustering using gene groups suggested by the PANTHER Classification System. We depicted the genomic landscape of the resulted tumor groups by means of Single Nuclear Polymorphism (SNP) technology. Finally, the achieved results were immunohistochemically analyzed using a tissue microarray (TMA) composed of 254 RCC. We found robust, genome wide expression signatures, which split RCC into three distinct molecular subgroups. These groups remained stable even if randomly selected gene sets were clustered. Notably, the pattern obtained from RCC cell lines was clearly distinguishable from that of primary tumors. SNP array analysis demonstrated differing frequencies of chromosomal copy number alterations among RCC subgroups. TMA analysis with group-specific markers showed a prognostic significance of the different groups. We propose the existence of characteristic and histologically independent genome-wide expression outputs in RCC with potential biological and clinical relevance

  11. Conformational analysis of methylphenidate: comparison of molecular orbital and molecular mechanics methods.

    Science.gov (United States)

    Gilbert, Kathleen M; Skawinski, William J; Misra, Milind; Paris, Kristina A; Naik, Neelam H; Buono, Ronald A; Deutsch, Howard M; Venanzi, Carol A

    2004-11-01

    Methylphenidate (MP) binds to the cocaine binding site on the dopamine transporter and inhibits reuptake of dopamine, but does not appear to have the same abuse potential as cocaine. This study, part of a comprehensive effort to identify a drug treatment for cocaine abuse, investigates the effect of choice of calculation technique and of solvent model on the conformational potential energy surface (PES) of MP and a rigid methylphenidate (RMP) analogue which exhibits the same dopamine transporter binding affinity as MP. Conformational analysis was carried out by the AM1 and AM1/SM5.4 semiempirical molecular orbital methods, a molecular mechanics method (Tripos force field with the dielectric set equal to that of vacuum or water) and the HF/6-31G* molecular orbital method in vacuum phase. Although all three methods differ somewhat in the local details of the PES, the general trends are the same for neutral and protonated MP. In vacuum phase, protonation has a distinctive effect in decreasing the regions of space available to the local conformational minima. Solvent has little effect on the PES of the neutral molecule and tends to stabilize the protonated species. The random search (RS) conformational analysis technique using the Tripos force field was found to be capable of locating the minima found by the molecular orbital methods using systematic grid search. This suggests that the RS/Tripos force field/vacuum phase protocol is a reasonable choice for locating the local minima of MP. However, the Tripos force field gave significantly larger phenyl ring rotational barriers than the molecular orbital methods for MP and RMP. For both the neutral and protonated cases, all three methods found the phenyl ring rotational barriers for the RMP conformers/invertamers (denoted as cte, tte, and cta) to be: cte, tte > MP > cta. Solvation has negligible effect on the phenyl ring rotational barrier of RMP. The B3LYP/6-31G* density functional method was used to calculate the

  12. Combined molecular and biochemical approach identifies Aspergillus japonicus and Aspergillus aculeatus as two species

    DEFF Research Database (Denmark)

    Parenicova, L.; Skouboe, P.; Frisvad, Jens Christian;

    2001-01-01

    We examined nine Aspergillus japonicus isolates and 10 Aspergillus aculeatus isolates by using molecular and biochemical markers, including DNA sequences of the ITS1-5.8S rRNA gene-ITS2 region, restriction fragment length polymorphisms (RFLP), and secondary-metabolite profiles. The DNA sequence...... of the internal transcribed spacers (ITS1 and ITS2) and the 5.8S rRNA gene could not be used to distinguish between A. japonicus and A. aculeatus but did show that these two taxa are more closely related to each other than to other species of black aspergilli. Aspergillus niger pyruvate kinase (pkiA) and pectin...

  13. More on contamination: the use of asymmetric molecular behavior to identify authentic ancient human DNA

    DEFF Research Database (Denmark)

    Malmström, Helena; Svensson, Emma M; Gilbert, M Thomas P;

    2007-01-01

    the reliability of one of the proposed criteria, that of appropriate molecular behavior. Using real-time polymerase chain reaction (PCR) and pyrosequencing, we have quantified the relative levels of authentic aDNA and contaminant human DNA sequences recovered from archaeological dog and cattle remains. In doing....... Furthermore, we find that there is a substantial increase in the relative proportions of authentic DNA to contaminant DNA as the PCR target fragment size is decreased. We therefore conclude that the degradation pattern in aDNA provides a quantifiable difference between authentic aDNA and modern contamination...

  14. Rice transcriptome analysis to identify possible herbicide quinclorac detoxification genes

    OpenAIRE

    Xu, Wenying; Di, Chao; Zhou, Shaoxia; Liu, Jia; LI Li; Liu, Fengxia; Yang, Xinling; Ling, Yun; Su, Zhen

    2015-01-01

    Quinclorac is a highly selective auxin-type herbicide and is widely used in the effective control of barnyard grass in paddy rice fields, improving the world's rice yield. The herbicide mode of action of quinclorac has been proposed, and hormone interactions affecting quinclorac signaling has been identified. Because of widespread use, quinclorac may be transported outside rice fields with the drainage waters, leading to soil and water pollution and other environmental health problems. In thi...

  15. Identifiability analysis of the CSTR river water quality model.

    Science.gov (United States)

    Chen, J; Deng, Y

    2006-01-01

    Conceptual river water quality models are widely known to lack identifiability. The causes for that can be due to model structure errors, observational errors and less frequent samplings. Although significant efforts have been directed towards better identification of river water quality models, it is not clear whether a given model is structurally identifiable. Information is also limited regarding the contribution of different unidentifiability sources. Taking the widely applied CSTR river water quality model as an example, this paper presents a theoretical proof that the CSTR model is indeed structurally identifiable. Its uncertainty is thus dominantly from observational errors and less frequent samplings. Given the current monitoring accuracy and sampling frequency, the unidentifiability from sampling frequency is found to be more significant than that from observational errors. It is also noted that there is a crucial sampling frequency between 0.1 and 1 day, over which the simulated river system could be represented by different illusions and the model application could be far less reliable.

  16. Association analysis identifies ZNF750 regulatory variants in psoriasis

    Directory of Open Access Journals (Sweden)

    Birnbaum Ramon Y

    2011-12-01

    Full Text Available Abstract Background Mutations in the ZNF750 promoter and coding regions have been previously associated with Mendelian forms of psoriasis and psoriasiform dermatitis. ZNF750 encodes a putative zinc finger transcription factor that is highly expressed in keratinocytes and represents a candidate psoriasis gene. Methods We examined whether ZNF750 variants were associated with psoriasis in a large case-control population. We sequenced the promoter and exon regions of ZNF750 in 716 Caucasian psoriasis cases and 397 Caucasian controls. Results We identified a total of 47 variants, including 38 rare variants of which 35 were novel. Association testing identified two ZNF750 haplotypes associated with psoriasis (p ZNF750 promoter and 5' UTR variants displayed a 35-55% reduction of ZNF750 promoter activity, consistent with the promoter activity reduction seen in a Mendelian psoriasis family with a ZNF750 promoter variant. However, the rare promoter and 5' UTR variants identified in this study did not strictly segregate with the psoriasis phenotype within families. Conclusions Two haplotypes of ZNF750 and rare 5' regulatory variants of ZNF750 were found to be associated with psoriasis. These rare 5' regulatory variants, though not causal, might serve as a genetic modifier of psoriasis.

  17. The diverse heterogeneity of molecular alterations in prostate cancer identified through next-generation sequencing

    Institute of Scientific and Technical Information of China (English)

    Alexander W Wyatt; Fan Mo; Yuzhuo Wang; Colin C Collins

    2013-01-01

    Prostate cancer is a leading cause of global cancer-related death but attempts to improve diagnoses and develop novel therapies have been confounded by significant patient heterogeneity.In recent years,the application of next-generation sequencing to hundreds of prostate tumours has defined novel molecular subtypes and characterized extensive genomic aberration underlying disease initiation and progression.It is now clear that the heterogeneity observed in the clinic is underpinned by a molecular landscape rife with complexity,where genomic rearrangements and rare mutations combine to amplify transcriptomic diversity.This review dissects our current understanding of prostate cancer ‘omics',including the sentinel role of copy number variation,the growing spectrum of oncogenic fusion genes,the potential influence of chromothripsis,and breakthroughs in defining mutation-associated subtypes.Increasing evidence suggests that genomic lesions frequently converge on specific cellular functions and signalling pathways,yet recurrent gene aberration appears rare.Therefore,it is critical that we continue to define individual tumour genomes,especially in the context of their expressed transcriptome.Only through improved characterisation of tumour to tumour variability can we advance to an age of precision therapy and personalized oncology.

  18. SNR analysis: molecular investigation of an anthrax epidemic

    Directory of Open Access Journals (Sweden)

    Adone Rosanna

    2010-02-01

    Full Text Available Abstract Background In Italy, anthrax is endemic but occurs sporadically. During the summer of 2004, in the Pollino National Park, Basilicata, Southern Italy, an anthrax epidemic consisting of 41 outbreaks occurred; it claimed the lives of 124 animals belonging to different mammal species. This study is a retrospective molecular epidemiological investigation carried out on 53 isolates collected during the epidemic. A 25-loci Multiple Locus VNTR Analysis (MLVA MLVA was initially performed to define genetic relationships, followed by an investigation of genetic diversity between epidemic strains through Single Nucleotide Repeat (SNR analysis. Results 53 Bacillus anthracis strains were isolated. The 25-loci MLVA analysis identified all of them as belonging to a single genotype, while the SNR analysis was able to detect the existence of five subgenotypes (SGTs, allowing a detailed epidemic investigation. SGT-1 was the most frequent (46/53; SGTs 2 (4/53, 3 (1/53 4 (1/53 and 5 (1/53 were detected in the remaining seven isolates. Conclusions The analysis revealed the prevalent spread, during this epidemic, of a single anthrax clone. SGT-1 - widely distributed across the epidemic area and present throughout the period in question - may, thus, be the ancestral form. SGTs 2, 3 and 4 differed from SGT-1 at only one locus, suggesting that they could have evolved directly from the latter during the course of this epidemic. SGT-5 differed from the other SGTs at 2-3 loci. This isolate, thus, appears to be more distantly related to SGT-1 and may not be a direct descendant of the lineage responsible for the majority of cases in this epidemic. These data confirm the importance of molecular typing and subtyping methods for in-depth epidemiological analyses of anthrax epidemics.

  19. Using Rasch Analysis to Identify Uncharacteristic Responses to Undergraduate Assessments

    Science.gov (United States)

    Edwards, Antony; Alcock, Lara

    2010-01-01

    Rasch Analysis is a statistical technique that is commonly used to analyse both test data and Likert survey data, to construct and evaluate question item banks, and to evaluate change in longitudinal studies. In this article, we introduce the dichotomous Rasch model, briefly discussing its assumptions. Then, using data collected in an…

  20. Evaluation of energy system analysis techniques for identifying underground facilities

    Energy Technology Data Exchange (ETDEWEB)

    VanKuiken, J.C.; Kavicky, J.A.; Portante, E.C. [and others

    1996-03-01

    This report describes the results of a study to determine the feasibility and potential usefulness of applying energy system analysis techniques to help detect and characterize underground facilities that could be used for clandestine activities. Four off-the-shelf energy system modeling tools were considered: (1) ENPEP (Energy and Power Evaluation Program) - a total energy system supply/demand model, (2) ICARUS (Investigation of Costs and Reliability in Utility Systems) - an electric utility system dispatching (or production cost and reliability) model, (3) SMN (Spot Market Network) - an aggregate electric power transmission network model, and (4) PECO/LF (Philadelphia Electric Company/Load Flow) - a detailed electricity load flow model. For the purposes of most of this work, underground facilities were assumed to consume about 500 kW to 3 MW of electricity. For some of the work, facilities as large as 10-20 MW were considered. The analysis of each model was conducted in three stages: data evaluation, base-case analysis, and comparative case analysis. For ENPEP and ICARUS, open source data from Pakistan were used for the evaluations. For SMN and PECO/LF, the country data were not readily available, so data for the state of Arizona were used to test the general concept.

  1. Molecular analysis of Boophilus spp. (Acari: Ixodidae) tick strains.

    Science.gov (United States)

    Fuente, J; García-García, J C; González, D M; Izquierdo, G; Ochagavia, M E

    2000-10-01

    Boophilus spp. (Acari: Ixodidae) parasitize cattle and other farm and wild animals in tropical and subtropical regions of the world. Ticks belonging to the genus Boophilus have undergone evolutionary processes associated with habitat adaptation following biogeographical separation, resulting in strains with marked morphological differences. We have characterized at the molecular level B. microplus strains from Latin America and Australia, employing sequences derived from the bm86 coding region, an intron located within the bm86 gene, and DNA short tandem repeats (STR). A B. annulatus strain was employed for comparison. The results indicated that variation within the bm86 coding region is higher between B. microplus strains than between some B. microplus strains and B. annulatus. The sequence of the intron was not informative for phylogenetic analysis, varying among individuals of the same strain. Two STRs were identified in B. microplus (STRs BmM1 and BmM2) and one in B. annulatus (STR Ba1). Southern hybridization experiments with STRs BmM1 and BmM2 as a probe revealed the prevalence of dispersed moderately repeated DNA in the genome of B. microplus. The analysis of polymorphism at STR locus BmM1 evidenced differences within and between populations of B. microplus. These results support at the molecular level the existing differences between B. microplus strains and suggest tools to characterize these populations. PMID:10962158

  2. Arterial tortuosity syndrome : Clinical and molecular findings in 12 newly identified families

    NARCIS (Netherlands)

    Callewaert, B. L.; Willaert, A.; Kerstjens-Frederikse, W. S.; De Backer, J.; Devriendt, K.; Albrecht, B.; Ramos-Arroyo, M. A.; Doco-Fenzy, M.; Hennekam, R. C. M.; Pyeritz, R. E.; Krogmann, O. N.; Gillessen-kaesbach, G.; Wakeling, E. L.; Nik-zainal, S.; Francannet, C.; Mauran, P.; Booth, C.; Barrow, M.; Dekens, R.; Loeys, B. L.; Coucke, P. J.; De Paepe, A. M.

    2008-01-01

    Arterial tortuosity syndrome (ATS) is a rare autosomal recessive connective tissue disease, characterized by widespread arterial involvement with elongation, tortuosity, and aneurysms of the large and middle-sized arteries. Recently, SLC2A10 mutations were identified in this condition. This gene enc

  3. Molecular docking and NMR binding studies to identify novel inhibitors of human phosphomevalonate kinase

    Energy Technology Data Exchange (ETDEWEB)

    Boonsri, Pornthip [Chemical Proteomics Facility at Marquette, Department of Chemistry, Marquette University, Milwaukee, WI 53201 (United States); Department of Chemistry, NANOTEC Center of Nanotechnology, National Nanotechnology Center, Faculty of Science, Kasetsart University, Bangkok 10900 (Thailand); Neumann, Terrence S.; Olson, Andrew L.; Cai, Sheng [Chemical Proteomics Facility at Marquette, Department of Chemistry, Marquette University, Milwaukee, WI 53201 (United States); Herdendorf, Timothy J.; Miziorko, Henry M. [Division of Molecular Biology and Biochemistry, School of Biological Sciences, University of Missouri-Kansas City, Kansas City, MO 64110 (United States); Hannongbua, Supa [Department of Chemistry, NANOTEC Center of Nanotechnology, National Nanotechnology Center, Faculty of Science, Kasetsart University, Bangkok 10900 (Thailand); Sem, Daniel S., E-mail: daniel.sem@cuw.edu [Chemical Proteomics Facility at Marquette, Department of Chemistry, Marquette University, Milwaukee, WI 53201 (United States)

    2013-01-04

    Highlights: Black-Right-Pointing-Pointer Natural and synthetic inhibitors of human phosphomevalonate kinase identified. Black-Right-Pointing-Pointer Virtual screening yielded a hit rate of 15%, with inhibitor K{sub d}'s of 10-60 {mu}M. Black-Right-Pointing-Pointer NMR studies indicate significant protein conformational changes upon binding. -- Abstract: Phosphomevalonate kinase (PMK) phosphorylates mevalonate-5-phosphate (M5P) in the mevalonate pathway, which is the sole source of isoprenoids and steroids in humans. We have identified new PMK inhibitors with virtual screening, using autodock. Promising hits were verified and their affinity measured using NMR-based {sup 1}H-{sup 15}N heteronuclear single quantum coherence (HSQC) chemical shift perturbation and fluorescence titrations. Chemical shift changes were monitored, plotted, and fitted to obtain dissociation constants (K{sub d}). Tight binding compounds with K{sub d}'s ranging from 6-60 {mu}M were identified. These compounds tended to have significant polarity and negative charge, similar to the natural substrates (M5P and ATP). HSQC cross peak changes suggest that binding induces a global conformational change, such as domain closure. Compounds identified in this study serve as chemical genetic probes of human PMK, to explore pharmacology of the mevalonate pathway, as well as starting points for further drug development.

  4. A Network Biology Approach Identifies Molecular Cross-Talk between Normal Prostate Epithelial and Prostate Carcinoma Cells

    Science.gov (United States)

    Trevino, Victor; Cassese, Alberto; Nagy, Zsuzsanna; Zhuang, Xiaodong; Herbert, John; Antzack, Philipp; Clarke, Kim; Davies, Nicholas; Rahman, Ayesha; Campbell, Moray J.; Bicknell, Roy; Vannucci, Marina; Falciani, Francesco

    2016-01-01

    Abstract The advent of functional genomics has enabled the genome-wide characterization of the molecular state of cells and tissues, virtually at every level of biological organization. The difficulty in organizing and mining this unprecedented amount of information has stimulated the development of computational methods designed to infer the underlying structure of regulatory networks from observational data. These important developments had a profound impact in biological sciences since they triggered the development of a novel data-driven investigative approach. In cancer research, this strategy has been particularly successful. It has contributed to the identification of novel biomarkers, to a better characterization of disease heterogeneity and to a more in depth understanding of cancer pathophysiology. However, so far these approaches have not explicitly addressed the challenge of identifying networks representing the interaction of different cell types in a complex tissue. Since these interactions represent an essential part of the biology of both diseased and healthy tissues, it is of paramount importance that this challenge is addressed. Here we report the definition of a network reverse engineering strategy designed to infer directional signals linking adjacent cell types within a complex tissue. The application of this inference strategy to prostate cancer genome-wide expression profiling data validated the approach and revealed that normal epithelial cells exert an anti-tumour activity on prostate carcinoma cells. Moreover, by using a Bayesian hierarchical model integrating genetics and gene expression data and combining this with survival analysis, we show that the expression of putative cell communication genes related to focal adhesion and secretion is affected by epistatic gene copy number variation and it is predictive of patient survival. Ultimately, this study represents a generalizable approach to the challenge of deciphering cell communication

  5. A Network Biology Approach Identifies Molecular Cross-Talk between Normal Prostate Epithelial and Prostate Carcinoma Cells.

    Directory of Open Access Journals (Sweden)

    Victor Trevino

    2016-04-01

    Full Text Available The advent of functional genomics has enabled the genome-wide characterization of the molecular state of cells and tissues, virtually at every level of biological organization. The difficulty in organizing and mining this unprecedented amount of information has stimulated the development of computational methods designed to infer the underlying structure of regulatory networks from observational data. These important developments had a profound impact in biological sciences since they triggered the development of a novel data-driven investigative approach. In cancer research, this strategy has been particularly successful. It has contributed to the identification of novel biomarkers, to a better characterization of disease heterogeneity and to a more in depth understanding of cancer pathophysiology. However, so far these approaches have not explicitly addressed the challenge of identifying networks representing the interaction of different cell types in a complex tissue. Since these interactions represent an essential part of the biology of both diseased and healthy tissues, it is of paramount importance that this challenge is addressed. Here we report the definition of a network reverse engineering strategy designed to infer directional signals linking adjacent cell types within a complex tissue. The application of this inference strategy to prostate cancer genome-wide expression profiling data validated the approach and revealed that normal epithelial cells exert an anti-tumour activity on prostate carcinoma cells. Moreover, by using a Bayesian hierarchical model integrating genetics and gene expression data and combining this with survival analysis, we show that the expression of putative cell communication genes related to focal adhesion and secretion is affected by epistatic gene copy number variation and it is predictive of patient survival. Ultimately, this study represents a generalizable approach to the challenge of deciphering cell

  6. A Network Biology Approach Identifies Molecular Cross-Talk between Normal Prostate Epithelial and Prostate Carcinoma Cells.

    Science.gov (United States)

    Trevino, Victor; Cassese, Alberto; Nagy, Zsuzsanna; Zhuang, Xiaodong; Herbert, John; Antzack, Philipp; Clarke, Kim; Davies, Nicholas; Rahman, Ayesha; Campbell, Moray J; Guindani, Michele; Bicknell, Roy; Vannucci, Marina; Falciani, Francesco

    2016-04-01

    The advent of functional genomics has enabled the genome-wide characterization of the molecular state of cells and tissues, virtually at every level of biological organization. The difficulty in organizing and mining this unprecedented amount of information has stimulated the development of computational methods designed to infer the underlying structure of regulatory networks from observational data. These important developments had a profound impact in biological sciences since they triggered the development of a novel data-driven investigative approach. In cancer research, this strategy has been particularly successful. It has contributed to the identification of novel biomarkers, to a better characterization of disease heterogeneity and to a more in depth understanding of cancer pathophysiology. However, so far these approaches have not explicitly addressed the challenge of identifying networks representing the interaction of different cell types in a complex tissue. Since these interactions represent an essential part of the biology of both diseased and healthy tissues, it is of paramount importance that this challenge is addressed. Here we report the definition of a network reverse engineering strategy designed to infer directional signals linking adjacent cell types within a complex tissue. The application of this inference strategy to prostate cancer genome-wide expression profiling data validated the approach and revealed that normal epithelial cells exert an anti-tumour activity on prostate carcinoma cells. Moreover, by using a Bayesian hierarchical model integrating genetics and gene expression data and combining this with survival analysis, we show that the expression of putative cell communication genes related to focal adhesion and secretion is affected by epistatic gene copy number variation and it is predictive of patient survival. Ultimately, this study represents a generalizable approach to the challenge of deciphering cell communication networks

  7. A Network Biology Approach Identifies Molecular Cross-Talk between Normal Prostate Epithelial and Prostate Carcinoma Cells.

    Science.gov (United States)

    Trevino, Victor; Cassese, Alberto; Nagy, Zsuzsanna; Zhuang, Xiaodong; Herbert, John; Antzack, Philipp; Clarke, Kim; Davies, Nicholas; Rahman, Ayesha; Campbell, Moray J; Guindani, Michele; Bicknell, Roy; Vannucci, Marina; Falciani, Francesco

    2016-04-01

    The advent of functional genomics has enabled the genome-wide characterization of the molecular state of cells and tissues, virtually at every level of biological organization. The difficulty in organizing and mining this unprecedented amount of information has stimulated the development of computational methods designed to infer the underlying structure of regulatory networks from observational data. These important developments had a profound impact in biological sciences since they triggered the development of a novel data-driven investigative approach. In cancer research, this strategy has been particularly successful. It has contributed to the identification of novel biomarkers, to a better characterization of disease heterogeneity and to a more in depth understanding of cancer pathophysiology. However, so far these approaches have not explicitly addressed the challenge of identifying networks representing the interaction of different cell types in a complex tissue. Since these interactions represent an essential part of the biology of both diseased and healthy tissues, it is of paramount importance that this challenge is addressed. Here we report the definition of a network reverse engineering strategy designed to infer directional signals linking adjacent cell types within a complex tissue. The application of this inference strategy to prostate cancer genome-wide expression profiling data validated the approach and revealed that normal epithelial cells exert an anti-tumour activity on prostate carcinoma cells. Moreover, by using a Bayesian hierarchical model integrating genetics and gene expression data and combining this with survival analysis, we show that the expression of putative cell communication genes related to focal adhesion and secretion is affected by epistatic gene copy number variation and it is predictive of patient survival. Ultimately, this study represents a generalizable approach to the challenge of deciphering cell communication networks

  8. Identifying Colluvial Slopes by Airborne LiDAR Analysis

    Science.gov (United States)

    Kasai, M.; Marutani, T.; Yoshida, H.

    2015-12-01

    Colluvial slopes are one of major sources of landslides. Identifying the locations of the slopes will help reduce the risk of disasters, by avoiding building infrastructure and properties nearby, or if they are already there, by applying appropriate counter measures before it suddenly moves. In this study, airborne LiDAR data was analyzed to find their geomorphic characteristics to use for extracting their locations. The study site was set in the suburb of Sapporo City, Hokkaido in Japan. The area is underlain by Andesite and Tuff and prone to landslides. Slope angle and surface roughness were calculated from 5 m resolution DEM. These filters were chosen because colluvial materials deposit at around the angle of repose and accumulation of loose materials was considered to form a peculiar surface texture differentiable from other slope types. Field survey conducted together suggested that colluvial slopes could be identified by the filters with a probability of 80 percent. Repeat LiDAR monitoring of the site by an unmanned helicopter indicated that those slopes detected as colluviums appeared to be moving at a slow rate. In comparison with a similar study from the crushed zone in Japan, the range of slope angle indicative of colluviums agreed with the Sapporo site, while the texture was rougher due to larger debris composing the slopes.

  9. ApoE4-specific Misfolded Intermediate Identified by Molecular Dynamics Simulations.

    Directory of Open Access Journals (Sweden)

    Benfeard Williams

    2015-10-01

    Full Text Available The increased risk of developing Alzheimer's disease (AD is associated with the APOE gene, which encodes for three variants of Apolipoprotein E, namely E2, E3, E4, differing only by two amino acids at positions 112 and 158. ApoE4 is known to be the strongest risk factor for AD onset, while ApoE3 and ApoE2 are considered to be the AD-neutral and AD-protective isoforms, respectively. It has been hypothesized that the ApoE isoforms may contribute to the development of AD by modifying the homeostasis of ApoE physiological partners and AD-related proteins in an isoform-specific fashion. Here we find that, despite the high sequence similarity among the three ApoE variants, only ApoE4 exhibits a misfolded intermediate state characterized by isoform-specific domain-domain interactions in molecular dynamics simulations. The existence of an ApoE4-specific intermediate state can contribute to the onset of AD by altering multiple cellular pathways involved in ApoE-dependent lipid transport efficiency or in AD-related protein aggregation and clearance. We present what we believe to be the first structural model of an ApoE4 misfolded intermediate state, which may serve to elucidate the molecular mechanism underlying the role of ApoE4 in AD pathogenesis. The knowledge of the structure for the ApoE4 folding intermediate provides a new platform for the rational design of alternative therapeutic strategies to fight AD.

  10. ApoE4-specific Misfolded Intermediate Identified by Molecular Dynamics Simulations.

    Science.gov (United States)

    Williams, Benfeard; Convertino, Marino; Das, Jhuma; Dokholyan, Nikolay V

    2015-10-01

    The increased risk of developing Alzheimer's disease (AD) is associated with the APOE gene, which encodes for three variants of Apolipoprotein E, namely E2, E3, E4, differing only by two amino acids at positions 112 and 158. ApoE4 is known to be the strongest risk factor for AD onset, while ApoE3 and ApoE2 are considered to be the AD-neutral and AD-protective isoforms, respectively. It has been hypothesized that the ApoE isoforms may contribute to the development of AD by modifying the homeostasis of ApoE physiological partners and AD-related proteins in an isoform-specific fashion. Here we find that, despite the high sequence similarity among the three ApoE variants, only ApoE4 exhibits a misfolded intermediate state characterized by isoform-specific domain-domain interactions in molecular dynamics simulations. The existence of an ApoE4-specific intermediate state can contribute to the onset of AD by altering multiple cellular pathways involved in ApoE-dependent lipid transport efficiency or in AD-related protein aggregation and clearance. We present what we believe to be the first structural model of an ApoE4 misfolded intermediate state, which may serve to elucidate the molecular mechanism underlying the role of ApoE4 in AD pathogenesis. The knowledge of the structure for the ApoE4 folding intermediate provides a new platform for the rational design of alternative therapeutic strategies to fight AD.

  11. Temperature-based Instanton Analysis: Identifying Vulnerability in Transmission Networks

    Energy Technology Data Exchange (ETDEWEB)

    Kersulis, Jonas [Univ. of Michigan, Ann Arbor, MI (United States); Hiskens, Ian [Univ. of Michigan, Ann Arbor, MI (United States); Chertkov, Michael [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Backhaus, Scott N. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Bienstock, Daniel [Columbia Univ., New York, NY (United States)

    2015-04-08

    A time-coupled instanton method for characterizing transmission network vulnerability to wind generation fluctuation is presented. To extend prior instanton work to multiple-time-step analysis, line constraints are specified in terms of temperature rather than current. An optimization formulation is developed to express the minimum wind forecast deviation such that at least one line is driven to its thermal limit. Results are shown for an IEEE RTS-96 system with several wind-farms.

  12. Identification and in silico analysis of the Citrus HSP70 molecular chaperone gene family

    OpenAIRE

    Fietto, Luciano G.; Maximiller D.L. Costa; Cosme D Cruz; De Souza, Alessandra A.; Machado, Marcos A; Fontes, Elizabeth P. B.

    2007-01-01

    The completion of the genome sequencing of the Arabidopsis thaliana model system provided a powerful molecular tool for comparative analysis of gene families present in the genome of economically relevant plant species. In this investigation, we used the sequences of the Arabidopsis Hsp70 gene family to identify and annotate the Citrus Hsp70 genes represented in the CitEST database. Based on sequence comparison analysis, we identified 18 clusters that were further divided into 5 subgroups enc...

  13. Predicting missing links and identifying spurious links via likelihood analysis

    Science.gov (United States)

    Pan, Liming; Zhou, Tao; Lü, Linyuan; Hu, Chin-Kun

    2016-03-01

    Real network data is often incomplete and noisy, where link prediction algorithms and spurious link identification algorithms can be applied. Thus far, it lacks a general method to transform network organizing mechanisms to link prediction algorithms. Here we use an algorithmic framework where a network’s probability is calculated according to a predefined structural Hamiltonian that takes into account the network organizing principles, and a non-observed link is scored by the conditional probability of adding the link to the observed network. Extensive numerical simulations show that the proposed algorithm has remarkably higher accuracy than the state-of-the-art methods in uncovering missing links and identifying spurious links in many complex biological and social networks. Such method also finds applications in exploring the underlying network evolutionary mechanisms.

  14. A molecular screening approach to identify and characterize inhibitors of glioblastoma stem cells

    OpenAIRE

    Visnyei, Koppany; Onodera, Hideyuki; Damoiseaux, Robert; Saigusa, Kuniyasu; Petrosyan, Syuzanna; De Vries, David; Ferrari, Denise; Saxe, Jonathan; Panosyan, Eduard H.; Masterman-Smith, Michael; Mottahedeh, Jack; Bradley, Kenneth A.; Huang, Jing; Sabatti, Chiara; Nakano, Ichiro

    2011-01-01

    Glioblastoma multiforme (GBM) is amongst the most lethal of all cancers. GBM consist of a heterogeneous population of tumor cells amongst which a tumor initiating and treatment-resistant subpopulation, here termed GBM stem cells (GSC), have been identified as primary therapeutic targets. Here, we describe a high-throughput small molecule screening approach that enables the identification and characterization of chemical compounds that are effective against GSC. The paradigm uses a tissue cult...

  15. Galactosemia: A strategy to identify new biochemical phenotypes and molecular genotypes

    Energy Technology Data Exchange (ETDEWEB)

    Elsas, L.J.; Langley, S.; Steele, E.; Evinger, J.; Brown, A.; Singh, R.; Fernhoff, P.; Hjelm, L.N.; Dembure, P.P.; Fridovich-Keil, J.L. [Emory Univ. School of Medicine, Atlanta, GA (United States)

    1995-03-01

    We describe a stratagem for identifying new mutations in the galactose-1-phosphate uridyl transferase (GALT) gene. GALT enzyme activity and isoforms were defined in erythrocytes from probands and their first-degree relatives. If the biochemical phenotypes segregated in an autosomal recesssive pattern, we screened for common mutations by using multiplex PCR and restriction endonuclease digestions. If common mutant alleles were not present, the 11 exons of the GALT gene were amplified by PCR, and variations from the normal nucleotide sequences were identified by SSCP. The suspected region(s) was then analyzed by direct DNA sequencing. We identified 86 mutant GALT alleles that reduced erythrocyte GALT activity. Seventy-five of these GALT genomes had abnormal SSCP patterns, of which 41 were sequenced, yielding 12 new and 21 previously reported, rare mutations. Among the novel group of 12 new mutations, an unusual biochemical phenotype was found in a family whose newborn proband has classical galactosemia. He had inherited two mutations in cis (N314D-E204K) from his father, whose GALT activity was near normal, and an additional GALT mutation in the splice-acceptor site of intron C (IVSC) from his mother. The substitution of a positively charged E204K mutation created a unique isoform-banding pattern. An asymptomatic sister`s GALT genes carries three mutations (E203K-N314D/N314D) with eight distinct isoform bands. Surprisingly, her erythrocytes have normal GALT activity. We conclude that the synergism of pedigree, biochemical, SSCP, and direct GALT gene analyses is an efficient protocol for identifying new mutations and speculate that E203K and N314D codon changes produce intra-allelic complementation when in cis. 40 refs., 4 figs., 3 tabs.

  16. Molecular Docking and NMR Binding Studies to Identify Novel Inhibitors of Human Phosphomevalonate Kinase

    OpenAIRE

    Boonsri, Pornthip; Neumann, Terrence S.; Olson, Andrew L.; Cai, Sheng; Herdendorf, Timothy J.; Miziorko, Henry M.; Hannongbua, Supa; Sem, Daniel S.

    2012-01-01

    Phosphomevalonate kinase (PMK) phosphorylates mevalonate-5-phosphate (M5P) in the mevalonate pathway, which is the sole source of isoprenoids and steroids in humans. We have identified new PMK inhibitors with virtual screening, using Autodock. Promising hits were verified and their affinity measured using NMR-based 1H-15N Heteronuclear Single Quantum Coherence (HSQC) chemical shift perturbation and fluorescence titrations. Chemical shift changes were monitored, plotted, and fitted to obtain d...

  17. A systems biology pipeline identifies new immune and disease related molecular signatures and networks in human cells during microgravity exposure

    Science.gov (United States)

    Mukhopadhyay, Sayak; Saha, Rohini; Palanisamy, Anbarasi; Ghosh, Madhurima; Biswas, Anupriya; Roy, Saheli; Pal, Arijit; Sarkar, Kathakali; Bagh, Sangram

    2016-05-01

    Microgravity is a prominent health hazard for astronauts, yet we understand little about its effect at the molecular systems level. In this study, we have integrated a set of systems-biology tools and databases and have analysed more than 8000 molecular pathways on published global gene expression datasets of human cells in microgravity. Hundreds of new pathways have been identified with statistical confidence for each dataset and despite the difference in cell types and experiments, around 100 of the new pathways are appeared common across the datasets. They are related to reduced inflammation, autoimmunity, diabetes and asthma. We have identified downregulation of NfκB pathway via Notch1 signalling as new pathway for reduced immunity in microgravity. Induction of few cancer types including liver cancer and leukaemia and increased drug response to cancer in microgravity are also found. Increase in olfactory signal transduction is also identified. Genes, based on their expression pattern, are clustered and mathematically stable clusters are identified. The network mapping of genes within a cluster indicates the plausible functional connections in microgravity. This pipeline gives a new systems level picture of human cells under microgravity, generates testable hypothesis and may help estimating risk and developing medicine for space missions.

  18. Network modeling identifies molecular functions targeted by miR-204 to suppress head and neck tumor metastasis.

    Directory of Open Access Journals (Sweden)

    Younghee Lee

    2010-04-01

    Full Text Available Due to the large number of putative microRNA gene targets predicted by sequence-alignment databases and the relative low accuracy of such predictions which are conducted independently of biological context by design, systematic experimental identification and validation of every functional microRNA target is currently challenging. Consequently, biological studies have yet to identify, on a genome scale, key regulatory networks perturbed by altered microRNA functions in the context of cancer. In this report, we demonstrate for the first time how phenotypic knowledge of inheritable cancer traits and of risk factor loci can be utilized jointly with gene expression analysis to efficiently prioritize deregulated microRNAs for biological characterization. Using this approach we characterize miR-204 as a tumor suppressor microRNA and uncover previously unknown connections between microRNA regulation, network topology, and expression dynamics. Specifically, we validate 18 gene targets of miR-204 that show elevated mRNA expression and are enriched in biological processes associated with tumor progression in squamous cell carcinoma of the head and neck (HNSCC. We further demonstrate the enrichment of bottleneckness, a key molecular network topology, among miR-204 gene targets. Restoration of miR-204 function in HNSCC cell lines inhibits the expression of its functionally related gene targets, leads to the reduced adhesion, migration and invasion in vitro and attenuates experimental lung metastasis in vivo. As importantly, our investigation also provides experimental evidence linking the function of microRNAs that are located in the cancer-associated genomic regions (CAGRs to the observed predisposition to human cancers. Specifically, we show miR-204 may serve as a tumor suppressor gene at the 9q21.1-22.3 CAGR locus, a well established risk factor locus in head and neck cancers for which tumor suppressor genes have not been identified. This new strategy

  19. The Nematoda Filarioidea: critical analysis linking molecular and traditional approaches

    Directory of Open Access Journals (Sweden)

    Bain O.

    2008-09-01

    Full Text Available The molecular analysis of the Filarioidea and the endobacteria Wolbachia is no more limited to the agents of human diseases and the diversified sampling permits a synthesis with the morphological and biological results. The validity of the genera with “uncoherent host range”, such as Mansonella, Litomosoides and Cercopithifilaria, is confirmed and, consequently, their evolution by host-switchings. Dirofilaria and Onchocerca, types of two subfamilies, appear more closely related than with other onchocercids. Waltonellinae from anurans and Oswaldofilariinae from reptiles have a basal position. These filariae, and some others also considered primitive, do not harbour Wolbachia. Evidence for transversal transmission of the bacteria and a second acquisition event is given with the supergroup F, identified in Mansonella, in one of the Cercopithifilaria species and in arthropods.

  20. Shortest-path network analysis is a useful approach toward identifying genetic determinants of longevity.

    Directory of Open Access Journals (Sweden)

    J R Managbanag

    network analysis of aging to be extensively validated in a biological system. The novel longevity genes identified in this study are likely to yield further insight into the molecular mechanisms of aging and age-associated disease.

  1. Molecular markers and imaging tools to identify malignant potential in Barrett’s esophagus

    Institute of Scientific and Technical Information of China (English)

    Michael; Bennett; Hiroshi; Mashimo

    2014-01-01

    Due to its rapidly rising incidence and high mortality, esophageal adenocarcinoma is a major public health concern, particularly in Western countries. The steps involved in the progression from its predisposing condition, gastroesophageal reflux disease, to its premalignant disorder, Barrett’s esophagus, and to cancer, are incompletely understood. Current screening and surveillance methods are limited by the lack of population-wide utility, incomplete sampling of standard biopsies, and subjectivity of evaluation. Advances in endoscopic ablation have raised the hope of effective therapy for eradication of high-risk Barrett’s lesions, but improvements are needed in determining when to apply this treatment and how to follow patients clinically. Researchers have evaluated numerous potential molecular biomarkers with the goal of detecting dysplasia, with varying degrees of success. The combination of biomarker panels with epidemiologic risk factors to yield clinical risk scoring systems is promising. New approaches to sample tissue may also be combined with these biomarkers for less invasive screening and sur-veillance. The development of novel endoscopic imaging tools in recent years has the potential to markedly improve detection of small foci of dysplasia in vivo. Current and future efforts will aim to determine the combination of markers and imaging modalities that will most effectively improve the rate of early detection of highrisk lesions in Barrett’s esophagus.

  2. The use of Multidimensional Data to Identify the Molecular Biomarker for Pancreatic Ductal Adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Liwei Zhuang

    2013-01-01

    Full Text Available Pancreatic ductal adenocarcinoma (PDAC is a lethal disease, and the patient has an extremely poor overall survival with a less than 5% 5-year survival rate. Development of potential biomarkers provides a critical foundation for the diagnosis of PDAC. In this project, we have adopted an integrative approach to simultaneously identify biomarker and generate testable hypothesis from multidimensional omics data. We first examine genes for which expression levels are correlated with survival data. The gene list was screened with TF regulation, predicted miRNA targets information, and KEGG pathways. We identified that 273 candidate genes are correlated with patient survival data. 12 TF regulation gene sets, 11 miRNAs targets gene sets, and 15 KEGG pathways are enriched with these survival genes. Notably, CEBPA/miRNA32/PER2 signaling to the clock rhythm qualifies this pathway as a suitable target for therapeutic intervention in PDAC. PER2 expression was highly associated with survival data, thus representing a novel biomarker for earlier detection of PDAC.

  3. Structure of human phytanoyl-CoA 2-hydroxylase identifies molecular mechanisms of Refsum disease.

    Science.gov (United States)

    McDonough, Michael A; Kavanagh, Kathryn L; Butler, Danica; Searls, Timothy; Oppermann, Udo; Schofield, Christopher J

    2005-12-01

    Refsum disease (RD), a neurological syndrome characterized by adult onset retinitis pigmentosa, anosmia, sensory neuropathy, and phytanic acidaemia, is caused by elevated levels of phytanic acid. Many cases of RD are associated with mutations in phytanoyl-CoA 2-hydroxylase (PAHX), an Fe(II) and 2-oxoglutarate (2OG)-dependent oxygenase that catalyzes the initial alpha-oxidation step in the degradation of phytenic acid in peroxisomes. We describe the x-ray crystallographic structure of PAHX to 2.5 A resolution complexed with Fe(II) and 2OG and predict the molecular consequences of mutations causing RD. Like other 2OG oxygenases, PAHX possesses a double-stranded beta-helix core, which supports three iron binding ligands (His(175), Asp(177), and His(264)); the 2-oxoacid group of 2OG binds to the Fe(II) in a bidentate manner. The manner in which PAHX binds to Fe(II) and 2OG together with the presence of a cysteine residue (Cys(191)) 6.7 A from the Fe(II) and two further histidine residues (His(155) and His(281)) at its active site distinguishes it from that of the other human 2OG oxygenase for which structures are available, factor inhibiting hypoxia-inducible factor. Of the 15 PAHX residues observed to be mutated in RD patients, 11 cluster in two distinct groups around the Fe(II) (Pro(173), His(175), Gln(176), Asp(177), and His(220)) and 2OG binding sites (Trp(193), Glu(197), Ile(199), Gly(204), Asn(269), and Arg(275)). PAHX may be the first of a new subfamily of coenzyme A-binding 2OG oxygenases.

  4. Molecular analysis of deep subsurface bacteria

    International Nuclear Information System (INIS)

    Deep sediments samples from site C10a, in Appleton, and sites, P24, P28, and P29, at the Savannah River Site (SRS), near Aiken, South Carolina were studied to determine their microbial community composition, DNA homology and mol %G+C. Different geological formations with great variability in hydrogeological parameters were found across the depth profile. Phenotypic identification of deep subsurface bacteria underestimated the bacterial diversity at the three SRS sites, since bacteria with the same phenotype have different DNA composition and less than 70% DNA homology. Total DNA hybridization and mol %G+C analysis of deep sediment bacterial isolates suggested that each formation is comprised of different microbial communities. Depositional environment was more important than site and geological formation on the DNA relatedness between deep subsurface bacteria, since more 70% of bacteria with 20% or more of DNA homology came from the same depositional environments. Based on phenotypic and genotypic tests Pseudomonas spp. and Acinetobacter spp.-like bacteria were identified in 85 million years old sediments. This suggests that these microbial communities might have been adapted during a long period of time to the environmental conditions of the deep subsurface

  5. Identifying a preservation zone using multi–criteria decision analysis

    Directory of Open Access Journals (Sweden)

    Farashi, A.

    2016-03-01

    Full Text Available Zoning of a protected area is an approach to partition landscape into various land use units. The management of these landscape units can reduce conflicts caused by human activities. Tandoreh National Park is one of the most biologically diverse, protected areas in Iran. Although the area is generally designed to protect biodiversity, there are many conflicts between biodiversity conservation and human activities. For instance, the area is highly controversial and has been considered as an impediment to local economic development, such as tourism, grazing, road construction, and cultivation. In order to reduce human conflicts with biodiversity conservation in Tandoreh National Park, safe zones need to be established and human activities need to be moved out of the zones. In this study we used a systematic methodology to integrate a participatory process with Geographic Information Systems (GIS using a multi–criteria decision analysis (MCDA technique to guide a zoning scheme for the Tandoreh National Park, Iran. Our results show that the northern and eastern parts of the Tandoreh National Park that were close to rural areas and farmlands returned less desirability for selection as a preservation area. Rocky Mountains were the most important and most destructed areas and abandoned plains were the least important criteria for preservation in the area. Furthermore, the results reveal that the land properties were considered to be important for protection based on the obtaine

  6. Meconium microbiome analysis identifies bacteria correlated with premature birth.

    Directory of Open Access Journals (Sweden)

    Alexandria N Ardissone

    Full Text Available Preterm birth is the second leading cause of death in children under the age of five years worldwide, but the etiology of many cases remains enigmatic. The dogma that the fetus resides in a sterile environment is being challenged by recent findings and the question has arisen whether microbes that colonize the fetus may be related to preterm birth. It has been posited that meconium reflects the in-utero microbial environment. In this study, correlations between fetal intestinal bacteria from meconium and gestational age were examined in order to suggest underlying mechanisms that may contribute to preterm birth.Meconium from 52 infants ranging in gestational age from 23 to 41 weeks was collected, the DNA extracted, and 16S rRNA analysis performed. Resulting taxa of microbes were correlated to clinical variables and also compared to previous studies of amniotic fluid and other human microbiome niches.Increased detection of bacterial 16S rRNA in meconium of infants of <33 weeks gestational age was observed. Approximately 61·1% of reads sequenced were classified to genera that have been reported in amniotic fluid. Gestational age had the largest influence on microbial community structure (R = 0·161; p = 0·029, while mode of delivery (C-section versus vaginal delivery had an effect as well (R = 0·100; p = 0·044. Enterobacter, Enterococcus, Lactobacillus, Photorhabdus, and Tannerella, were negatively correlated with gestational age and have been reported to incite inflammatory responses, suggesting a causative role in premature birth.This provides the first evidence to support the hypothesis that the fetal intestinal microbiome derived from swallowed amniotic fluid may be involved in the inflammatory response that leads to premature birth.

  7. Molecular characterization and LD(50) identify virulent isolates of Staphylococcus epidermidis from adult sepsis.

    Science.gov (United States)

    Herndona, B L; Bialkowska-Hobrzanska, H; Dall, L

    2000-02-01

    Staphylococcus epidermidis plays an important role in infections of patients with implanted prosthetic devices. The exact clinical significance of recovered S. epidermidis from clinical specimens is difficult to assess, as they are inhabitants of the normal skin. In this study, 11 adults with clinical sepsis and blood cultures that grew only S. epidermidis were the host population. Bacterial virulence in vivo was determined by using the mouse LD(50) assay where the intravenous lethality was determined for each patient isolate. Bacterial dose (CFU x 10(9)) that produced lethality in 50% of the animals at 12 h was the value used for comparison. Restriction fragment length polymorphism (RFLP) analysis of chromosomal DNA by pulsed-field gel electrophoresis (PFGE) was used for identification of individual strains and their clonal organization. Confirmation of species assignment was done by RFLP analysis of 16S + 23S rRNA gene regions (ribotyping). Plasmid profile analysis was also conducted. Four of 11 blood isolates from adults with S. epidermidis sepsis had indistinguishable or closely related DNA patterns and were considered clone A. The same clone was previously seen to account for the majority of sepsis in a neonatal intensive care unit. There were significant differences in virulence characteristics of the S. epidermidis isolates. Clone A isolates produced lethality by LD(50) in mice at a dose averaging 2.35; clone B isolate at a dose of 2.54, and the remaining isolates, representing six distinct clones, were lethal to mice at significantly larger doses (3.51-5.17, average 4.16). These data suggest that individual clones of S. epidermidis isolated from septic adults have detectable differences in virulence as defined by an animal bioassay, and the more virulent clone is widespread. PMID:10705046

  8. Molecular and structural analysis of viscoelastic properties

    Science.gov (United States)

    Yapp, Rebecca D.; Kalyanam, Sureshkumar; Insana, Michael F.

    2007-03-01

    Elasticity imaging is emerging as an important tool for breast cancer detection and monitoring of treatment. Viscoelastic image contrast in breast lesions is generated by disease specific processes that modify the molecular structure of connective tissues. We showed previously that gelatin hydrogels exhibit mechanical behavior similar to native collagen found in breast tissue and therefore are suitable as phantoms for elasticity imaging. This paper summarizes our study of the viscoelastic properties of hydrogels designed to discover molecular-scale sources of elasticity image contrast.

  9. Theoretical analysis of cavity saturation spectroscopy of weak molecular absorbance

    Institute of Scientific and Technical Information of China (English)

    Ma Wei-Guang; Dong Lei; Yin Wang-Bao; Jia Suo-Tang

    2005-01-01

    A theoretical analysis of sub-Doppler molecular saturation spectroscopy by use of a confocal Fabry-Perot (CFP)cavity is presented. The effects of gas pressure, cavity length and mirror reflectivity on the saturation dip amplitude are analysed. Such a treatment can provide the optimum conditions and a guidance for the experiment of saturating the weak molecular absorption lines.

  10. Statistical Analysis of Hominoid Molecular Evolution

    OpenAIRE

    Barry, Daniel; Hartigan, J. A.

    1987-01-01

    The core data of molecular biology consists of DNA sequences. We will show how DNA sequences may be used to infer the evolution of the primates, human, chimpanzee, ape, orangutan and gibbon. The underlying probability models are taken to be Markov processes on trees. Some dependencies along the sequence due to the genetic code are also considered.

  11. A molecular screening approach to identify and characterize inhibitors of glioblastoma stem cells.

    Science.gov (United States)

    Visnyei, Koppany; Onodera, Hideyuki; Damoiseaux, Robert; Saigusa, Kuniyasu; Petrosyan, Syuzanna; De Vries, David; Ferrari, Denise; Saxe, Jonathan; Panosyan, Eduard H; Masterman-Smith, Michael; Mottahedeh, Jack; Bradley, Kenneth A; Huang, Jing; Sabatti, Chiara; Nakano, Ichiro; Kornblum, Harley I

    2011-10-01

    Glioblastoma (GBM) is among the most lethal of all cancers. GBM consist of a heterogeneous population of tumor cells among which a tumor-initiating and treatment-resistant subpopulation, here termed GBM stem cells, have been identified as primary therapeutic targets. Here, we describe a high-throughput small molecule screening approach that enables the identification and characterization of chemical compounds that are effective against GBM stem cells. The paradigm uses a tissue culture model to enrich for GBM stem cells derived from human GBM resections and combines a phenotype-based screen with gene target-specific screens for compound identification. We used 31,624 small molecules from 7 chemical libraries that we characterized and ranked based on their effect on a panel of GBM stem cell-enriched cultures and their effect on the expression of a module of genes whose expression negatively correlates with clinical outcome: MELK, ASPM, TOP2A, and FOXM1b. Of the 11 compounds meeting criteria for exerting differential effects across cell types used, 4 compounds showed selectivity by inhibiting multiple GBM stem cells-enriched cultures compared with nonenriched cultures: emetine, n-arachidonoyl dopamine, n-oleoyldopamine (OLDA), and n-palmitoyl dopamine. ChemBridge compounds #5560509 and #5256360 inhibited the expression of the 4 mitotic module genes. OLDA, emetine, and compounds #5560509 and #5256360 were chosen for more detailed study and inhibited GBM stem cells in self-renewal assays in vitro and in a xenograft model in vivo. These studies show that our screening strategy provides potential candidates and a blueprint for lead compound identification in larger scale screens or screens involving other cancer types. PMID:21859839

  12. Breaking a virus: Identifying molecular level failure modes of a viral capsid by multiscale modeling

    Science.gov (United States)

    Krishnamani, V.; Globisch, C.; Peter, C.; Deserno, M.

    2016-07-01

    We use coarse-grained (CG) simulations to study the deformation of empty Cowpea Chlorotic Mottle Virus (CCMV) capsids under uniaxial compression, from the initial elastic response up to capsid breakage. Our CG model is based on the MARTINI force field and has been amended by a stabilizing elastic network, acting only within individual proteins, that was tuned to capture the fluctuation spectrum of capsid protein dimers, obtained from all atom simulations. We have previously shown that this model predicts force-compression curves that match AFM indentation experiments on empty CCMV capsids. Here we investigate details of the actual breaking events when the CCMV capsid finally fails. We present a symmetry classification of all relevant protein contacts and show that they differ significantly in terms of stability. Specifically, we show that interfaces which break readily are precisely those which are believed to form last during assembly, even though some of them might share the same contacts as other non-breaking interfaces. In particular, the interfaces that form pentamers of dimers never break, while the virtually identical interfaces within hexamers of dimers readily do. Since these units differ in the large-scale geometry and, most noticeably, the cone-angle at the center of the 5- or 6-fold vertex, we propose that the hexameric unit fails because it is pre-stressed. This not only suggests that hexamers of dimers form less frequently during the early stages of assembly; it also offers a natural explanation for the well-known β-barrel motif at the hexameric center as a post-aggregation stabilization mechanism. Finally, we identify those amino acid contacts within all key protein interfaces that are most persistent during compressive deformation of the capsid, thereby providing potential targets for mutation studies aiming to elucidate the key contacts upon which overall stability rests.

  13. Analysis of Pigeon (Columba Ovary Transcriptomes to Identify Genes Involved in Blue Light Regulation.

    Directory of Open Access Journals (Sweden)

    Ying Wang

    Full Text Available Monochromatic light is widely applied to promote poultry reproductive performance, yet little is currently known regarding the mechanism by which light wavelengths affect pigeon reproduction. Recently, high-throughput sequencing technologies have been used to provide genomic information for solving this problem. In this study, we employed Illumina Hiseq 2000 to identify differentially expressed genes in ovary tissue from pigeons under blue and white light conditions and de novo transcriptome assembly to construct a comprehensive sequence database containing information on the mechanisms of follicle development. A total of 157,774 unigenes (mean length: 790 bp were obtained by the Trinity program, and 35.83% of these unigenes were matched to genes in a non-redundant protein database. Gene description, gene ontology, and the clustering of orthologous group terms were performed to annotate the transcriptome assembly. Differentially expressed genes between blue and white light conditions included those related to oocyte maturation, hormone biosynthesis, and circadian rhythm. Furthermore, 17,574 SSRs and 533,887 potential SNPs were identified in this transcriptome assembly. This work is the first transcriptome analysis of the Columba ovary using Illumina technology, and the resulting transcriptome and differentially expressed gene data can facilitate further investigations into the molecular mechanism of the effect of blue light on follicle development and reproduction in pigeons and other bird species.

  14. Epigenome-Wide Association Analysis Identified Nine Skin DNA Methylation Loci for Psoriasis.

    Science.gov (United States)

    Zhou, Fusheng; Wang, Wenjun; Shen, Changbing; Li, Hui; Zuo, Xianbo; Zheng, Xiaodong; Yue, Min; Zhang, Cuicui; Yu, Liang; Chen, Mengyun; Zhu, Caihong; Yin, Xianyong; Tang, Mingjun; Li, Yongjiang; Chen, Gang; Wang, Zaixing; Liu, Shengxiu; Zhou, Yi; Zhang, Fengyu; Zhang, Weijia; Li, Caihua; Yang, Sen; Sun, Liangdan; Zhang, Xuejun

    2016-04-01

    Psoriasis is a chronic hyperproliferative and inflammatory skin disease caused by the interplay of genetic and environmental factors. DNA methylation has been linked to psoriasis, but the manner in which this process contributes to the disease is not fully understood. In this study, we carried out a three-stage epigenome-wide association study to identify disease-associated differentially methylated sites using a combination of 262 skin and 48 peripheral blood mononuclear cell samples. We not only revealed genome-wide methylation patterns for psoriasis but also identified strong associations between the skin-specific DNA methylation of nine disease-associated differentially methylated sites and psoriasis (Wilcoxon ranked PBonferroni 0.10). Further analysis revealed that these nine disease-associated differentially methylated sites were not significantly affected by genetic variations, supporting their remarkable contributions to disease status. The expression of CYP2S1, ECE1, EIF2C2, MAN1C1, and DLGAP4 was negatively correlated with DNA methylation. These findings will help us to better understand the molecular mechanism of psoriasis. PMID:26743604

  15. Epigenome-Wide Association Analysis Identified Nine Skin DNA Methylation Loci for Psoriasis.

    Science.gov (United States)

    Zhou, Fusheng; Wang, Wenjun; Shen, Changbing; Li, Hui; Zuo, Xianbo; Zheng, Xiaodong; Yue, Min; Zhang, Cuicui; Yu, Liang; Chen, Mengyun; Zhu, Caihong; Yin, Xianyong; Tang, Mingjun; Li, Yongjiang; Chen, Gang; Wang, Zaixing; Liu, Shengxiu; Zhou, Yi; Zhang, Fengyu; Zhang, Weijia; Li, Caihua; Yang, Sen; Sun, Liangdan; Zhang, Xuejun

    2016-04-01

    Psoriasis is a chronic hyperproliferative and inflammatory skin disease caused by the interplay of genetic and environmental factors. DNA methylation has been linked to psoriasis, but the manner in which this process contributes to the disease is not fully understood. In this study, we carried out a three-stage epigenome-wide association study to identify disease-associated differentially methylated sites using a combination of 262 skin and 48 peripheral blood mononuclear cell samples. We not only revealed genome-wide methylation patterns for psoriasis but also identified strong associations between the skin-specific DNA methylation of nine disease-associated differentially methylated sites and psoriasis (Wilcoxon ranked PBonferroni 0.10). Further analysis revealed that these nine disease-associated differentially methylated sites were not significantly affected by genetic variations, supporting their remarkable contributions to disease status. The expression of CYP2S1, ECE1, EIF2C2, MAN1C1, and DLGAP4 was negatively correlated with DNA methylation. These findings will help us to better understand the molecular mechanism of psoriasis.

  16. GWAS meta-analysis and replication identifies three new susceptibility loci for ovarian cancer.

    Science.gov (United States)

    Pharoah, Paul D P; Tsai, Ya-Yu; Ramus, Susan J; Phelan, Catherine M; Goode, Ellen L; Lawrenson, Kate; Buckley, Melissa; Fridley, Brooke L; Tyrer, Jonathan P; Shen, Howard; Weber, Rachel; Karevan, Rod; Larson, Melissa C; Song, Honglin; Tessier, Daniel C; Bacot, François; Vincent, Daniel; Cunningham, Julie M; Dennis, Joe; Dicks, Ed; Aben, Katja K; Anton-Culver, Hoda; Antonenkova, Natalia; Armasu, Sebastian M; Baglietto, Laura; Bandera, Elisa V; Beckmann, Matthias W; Birrer, Michael J; Bloom, Greg; Bogdanova, Natalia; Brenton, James D; Brinton, Louise A; Brooks-Wilson, Angela; Brown, Robert; Butzow, Ralf; Campbell, Ian; Carney, Michael E; Carvalho, Renato S; Chang-Claude, Jenny; Chen, Y Anne; Chen, Zhihua; Chow, Wong-Ho; Cicek, Mine S; Coetzee, Gerhard; Cook, Linda S; Cramer, Daniel W; Cybulski, Cezary; Dansonka-Mieszkowska, Agnieszka; Despierre, Evelyn; Doherty, Jennifer A; Dörk, Thilo; du Bois, Andreas; Dürst, Matthias; Eccles, Diana; Edwards, Robert; Ekici, Arif B; Fasching, Peter A; Fenstermacher, David; Flanagan, James; Gao, Yu-Tang; Garcia-Closas, Montserrat; Gentry-Maharaj, Aleksandra; Giles, Graham; Gjyshi, Anxhela; Gore, Martin; Gronwald, Jacek; Guo, Qi; Halle, Mari K; Harter, Philipp; Hein, Alexander; Heitz, Florian; Hillemanns, Peter; Hoatlin, Maureen; Høgdall, Estrid; Høgdall, Claus K; Hosono, Satoyo; Jakubowska, Anna; Jensen, Allan; Kalli, Kimberly R; Karlan, Beth Y; Kelemen, Linda E; Kiemeney, Lambertus A; Kjaer, Susanne Krüger; Konecny, Gottfried E; Krakstad, Camilla; Kupryjanczyk, Jolanta; Lambrechts, Diether; Lambrechts, Sandrina; Le, Nhu D; Lee, Nathan; Lee, Janet; Leminen, Arto; Lim, Boon Kiong; Lissowska, Jolanta; Lubiński, Jan; Lundvall, Lene; Lurie, Galina; Massuger, Leon F A G; Matsuo, Keitaro; McGuire, Valerie; McLaughlin, John R; Menon, Usha; Modugno, Francesmary; Moysich, Kirsten B; Nakanishi, Toru; Narod, Steven A; Ness, Roberta B; Nevanlinna, Heli; Nickels, Stefan; Noushmehr, Houtan; Odunsi, Kunle; Olson, Sara; Orlow, Irene; Paul, James; Pejovic, Tanja; Pelttari, Liisa M; Permuth-Wey, Jenny; Pike, Malcolm C; Poole, Elizabeth M; Qu, Xiaotao; Risch, Harvey A; Rodriguez-Rodriguez, Lorna; Rossing, Mary Anne; Rudolph, Anja; Runnebaum, Ingo; Rzepecka, Iwona K; Salvesen, Helga B; Schwaab, Ira; Severi, Gianluca; Shen, Hui; Shridhar, Vijayalakshmi; Shu, Xiao-Ou; Sieh, Weiva; Southey, Melissa C; Spellman, Paul; Tajima, Kazuo; Teo, Soo-Hwang; Terry, Kathryn L; Thompson, Pamela J; Timorek, Agnieszka; Tworoger, Shelley S; van Altena, Anne M; van den Berg, David; Vergote, Ignace; Vierkant, Robert A; Vitonis, Allison F; Wang-Gohrke, Shan; Wentzensen, Nicolas; Whittemore, Alice S; Wik, Elisabeth; Winterhoff, Boris; Woo, Yin Ling; Wu, Anna H; Yang, Hannah P; Zheng, Wei; Ziogas, Argyrios; Zulkifli, Famida; Goodman, Marc T; Hall, Per; Easton, Douglas F; Pearce, Celeste L; Berchuck, Andrew; Chenevix-Trench, Georgia; Iversen, Edwin; Monteiro, Alvaro N A; Gayther, Simon A; Schildkraut, Joellen M; Sellers, Thomas A

    2013-04-01

    Genome-wide association studies (GWAS) have identified four susceptibility loci for epithelial ovarian cancer (EOC), with another two suggestive loci reaching near genome-wide significance. We pooled data from a GWAS conducted in North America with another GWAS from the UK. We selected the top 24,551 SNPs for inclusion on the iCOGS custom genotyping array. We performed follow-up genotyping in 18,174 individuals with EOC (cases) and 26,134 controls from 43 studies from the Ovarian Cancer Association Consortium. We validated the two loci at 3q25 and 17q21 that were previously found to have associations close to genome-wide significance and identified three loci newly associated with risk: two loci associated with all EOC subtypes at 8q21 (rs11782652, P = 5.5 × 10(-9)) and 10p12 (rs1243180, P = 1.8 × 10(-8)) and another locus specific to the serous subtype at 17q12 (rs757210, P = 8.1 × 10(-10)). An integrated molecular analysis of genes and regulatory regions at these loci provided evidence for functional mechanisms underlying susceptibility and implicated CHMP4C in the pathogenesis of ovarian cancer. PMID:23535730

  17. GWAS meta-analysis and replication identifies three new susceptibility loci for ovarian cancer

    Science.gov (United States)

    Pharoah, Paul D. P.; Tsai, Ya-Yu; Ramus, Susan J.; Phelan, Catherine M.; Goode, Ellen L.; Lawrenson, Kate; Price, Melissa; Fridley, Brooke L.; Tyrer, Jonathan P.; Shen, Howard; Weber, Rachel; Karevan, Rod; Larson, Melissa C.; Song, Honglin; Tessier, Daniel C.; Bacot, François; Vincent, Daniel; Cunningham, Julie M.; Dennis, Joe; Dicks, Ed; Aben, Katja K.; Anton-Culver, Hoda; Antonenkova, Natalia; Armasu, Sebastian M.; Baglietto, Laura; Bandera, Elisa V.; Beckmann, Matthias W.; Birrer, Michael J.; Bloom, Greg; Bogdanova, Natalia; Brenton, James D.; Brinton, Louise A.; Brooks-Wilson, Angela; Brown, Robert; Butzow, Ralf; Campbell, Ian; Carney, Michael E; Carvalho, Renato S.; Chang-Claude, Jenny; Chen, Y. Anne; Chen, Zhihua; Chow, Wong-Ho; Cicek, Mine S.; Coetzee, Gerhard; Cook, Linda S.; Cramer, Daniel W.; Cybulski, Cezary; Dansonka-Mieszkowska, Agnieszka; Despierre, Evelyn; Doherty, Jennifer A; Dörk, Thilo; du Bois, Andreas; Dürst, Matthias; Eccles, Diana; Edwards, Robert; Ekici, Arif B.; Fasching, Peter A.; Fenstermacher, David; Flanagan, James; Gao, Yu-Tang; Garcia-Closas, Montserrat; Gentry-Maharaj, Aleksandra; Giles, Graham; Gjyshi, Anxhela; Gore, Martin; Gronwald, Jacek; Guo, Qi; Halle, Mari K; Harter, Philipp; Hein, Alexander; Heitz, Florian; Hillemanns, Peter; Hoatlin, Maureen; Høgdall, Estrid; Høgdall, Claus K.; Hosono, Satoyo; Jakubowska, Anna; Jensen, Allan; Kalli, Kimberly R.; Karlan, Beth Y.; Kelemen, Linda E.; Kiemeney, Lambertus A.; Kjaer, Susanne Krüger; Konecny, Gottfried E.; Krakstad, Camilla; Kupryjanczyk, Jolanta; Lambrechts, Diether; Lambrechts, Sandrina; Le, Nhu D.; Lee, Nathan; Lee, Janet; Leminen, Arto; Lim, Boon Kiong; Lissowska, Jolanta; Lubiński, Jan; Lundvall, Lene; Lurie, Galina; Massuger, Leon F.A.G.; Matsuo, Keitaro; McGuire, Valerie; McLaughlin, John R; Menon, Usha; Modugno, Francesmary; Moysich, Kirsten B.; Nakanishi, Toru; Narod, Steven A.; Ness, Roberta B.; Nevanlinna, Heli; Nickels, Stefan; Noushmehr, Houtan; Odunsi, Kunle; Olson, Sara; Orlow, Irene; Paul, James; Pejovic, Tanja; Pelttari, Liisa M; Permuth-Wey, Jenny; Pike, Malcolm C; Poole, Elizabeth M; Qu, Xiaotao; Risch, Harvey A.; Rodriguez-Rodriguez, Lorna; Rossing, Mary Anne; Rudolph, Anja; Runnebaum, Ingo; Rzepecka, Iwona K; Salvesen, Helga B.; Schwaab, Ira; Severi, Gianluca; Shen, Hui; Shridhar, Vijayalakshmi; Shu, Xiao-Ou; Sieh, Weiva; Southey, Melissa C.; Spellman, Paul; Tajima, Kazuo; Teo, Soo-Hwang; Terry, Kathryn L.; Thompson, Pamela J; Timorek, Agnieszka; Tworoger, Shelley S.; van Altena, Anne M.; Berg, David Van Den; Vergote, Ignace; Vierkant, Robert A.; Vitonis, Allison F.; Wang-Gohrke, Shan; Wentzensen, Nicolas; Whittemore, Alice S.; Wik, Elisabeth; Winterhoff, Boris; Woo, Yin Ling; Wu, Anna H; Yang, Hannah P.; Zheng, Wei; Ziogas, Argyrios; Zulkifli, Famida; Goodman, Marc T.; Hall, Per; Easton, Douglas F; Pearce, Celeste L; Berchuck, Andrew; Chenevix-Trench, Georgia; Iversen, Edwin; Monteiro, Alvaro N.A.; Gayther, Simon A.; Schildkraut, Joellen M.; Sellers, Thomas A.

    2013-01-01

    Genome wide association studies (GWAS) have identified four susceptibility loci for epithelial ovarian cancer (EOC) with another two loci being close to genome-wide significance. We pooled data from a GWAS conducted in North America with another GWAS from the United Kingdom. We selected the top 24,551 SNPs for inclusion on the iCOGS custom genotyping array. Follow-up genotyping was carried out in 18,174 cases and 26,134 controls from 43 studies from the Ovarian Cancer Association Consortium. We validated the two loci at 3q25 and 17q21 previously near genome-wide significance and identified three novel loci associated with risk; two loci associated with all EOC subtypes, at 8q21 (rs11782652, P=5.5×10-9) and 10p12 (rs1243180; P=1.8×10-8), and another locus specific to the serous subtype at 17q12 (rs757210; P=8.1×10-10). An integrated molecular analysis of genes and regulatory regions at these loci provided evidence for functional mechanisms underlying susceptibility that implicates CHMP4C in the pathogenesis of ovarian cancer. PMID:23535730

  18. Molecular systems evaluation of oligomerogenic APP(E693Q) and fibrillogenic APP(KM670/671NL)/PSEN1(Δexon9) mouse models identifies shared features with human Alzheimer's brain molecular pathology.

    Science.gov (United States)

    Readhead, B; Haure-Mirande, J-V; Zhang, B; Haroutunian, V; Gandy, S; Schadt, E E; Dudley, J T; Ehrlich, M E

    2016-08-01

    Identification and characterization of molecular mechanisms that connect genetic risk factors to initiation and evolution of disease pathophysiology represent major goals and opportunities for improving therapeutic and diagnostic outcomes in Alzheimer's disease (AD). Integrative genomic analysis of the human AD brain transcriptome holds potential for revealing novel mechanisms of dysfunction that underlie the onset and/or progression of the disease. We performed an integrative genomic analysis of brain tissue-derived transcriptomes measured from two lines of mice expressing distinct mutant AD-related proteins. The first line expresses oligomerogenic mutant APP(E693Q) inside neurons, leading to the accumulation of amyloid beta (Aβ) oligomers and behavioral impairment, but never develops parenchymal fibrillar amyloid deposits. The second line expresses APP(KM670/671NL)/PSEN1(Δexon9) in neurons and accumulates fibrillar Aβ amyloid and amyloid plaques accompanied by neuritic dystrophy and behavioral impairment. We performed RNA sequencing analyses of the dentate gyrus and entorhinal cortex from each line and from wild-type mice. We then performed an integrative genomic analysis to identify dysregulated molecules and pathways, comparing transgenic mice with wild-type controls as well as to each other. We also compared these results with datasets derived from human AD brain. Differential gene and exon expression analysis revealed pervasive alterations in APP/Aβ metabolism, epigenetic control of neurogenesis, cytoskeletal organization and extracellular matrix (ECM) regulation. Comparative molecular analysis converged on FMR1 (Fragile X Mental Retardation 1), an important negative regulator of APP translation and oligomerogenesis in the post-synaptic space. Integration of these transcriptomic results with human postmortem AD gene networks, differential expression and differential splicing signatures identified significant similarities in pathway dysregulation

  19. MOLECULAR ANALYSIS OF HUMAN SPERMATOZOA: POTENTIAL FOR INFERTILITY RESEARCH

    Science.gov (United States)

    Gordon Research Conference: Mammalian Gametogenesis and Embryogenesis New London, CT, July 1-6, 2000Molecular Analysis of Human Spermatozoa: Potential for Infertility ResearchDavid Miller 1, David Dix2, Robert Reid 3, Stephen A Krawetz 3 1Reproductive ...

  20. Molecular epidemiology of coxsackievirus A16: intratype and prevalent intertype recombination identified.

    Directory of Open Access Journals (Sweden)

    Xiangpeng Chen

    Full Text Available Coxsackievirus A16 (CVA16 is responsible for nearly 50% of all the confirmed hand, foot, and mouth disease (HFMD cases in mainland China, sometimes it could also cause severe complications, and even death. To clarify the genetic characteristics and the epidemic patterns of CVA16 in mainland China, comprehensive bioinfomatics analyses were performed by using 35 CVA16 whole genome sequences from 1998 to 2011, 593 complete CVA16 VP1 sequences from 1981 to 2011, and prototype strains of human enterovirus species A (EV-A. Analysis on complete VP1 sequences revealed that subgenotypes B1a and B1b were prevalent strains and have been co-circulating in many Asian countries since 2000, especially in mainland China for at least 13 years. While the prevalence of subgenotype B1c (totally 20 strains was much limited, only found in Malaysia from 2005 to 2007 and in France in 2010. Genotype B2 only caused epidemic in Japan and Malaysia from 1981 to 2000. Both subgenotypes B1a and B1b were potential recombinant viruses containing sequences from other EV-A donors in the 5'-untranslated region and P2, P3 non-structural protein encoding regions.

  1. Identifying initial molecular targets of PDT: protein and lipid oxidation products

    Science.gov (United States)

    Oleinick, Nancy L.; Kim, Junhwan; Rodriguez, Myriam E.; Xue, Liang-yan; Kenney, Malcolm E.; Anderson, Vernon E.

    2009-06-01

    Photodynamic Therapy (PDT) generates singlet oxygen (1O2) which oxidizes biomolecules in the immediate vicinity of its formation. The phthalocyanine photosensitizer Pc 4 localizes to mitochondria and endoplasmic reticulum, and the primary targets of Pc 4-PDT are expected to be lipids and proteins of those membranes. The initial damage then causes apoptosis in cancer cells via the release of cytochrome c (Cyt-c) from mitochondria into the cytosol, followed by the activation of caspases. That damage also triggers the induction of autophagy, an attempt by the cells to eliminate damaged organelles, or when damage is too extensive, to promote cell death. Cyt-c is bound to the cytosolic side of the mitochondrial inner membrane through association with cardiolipin (CL), a phospholipid containing four unsaturated fatty acids and thus easily oxidized by 1O2 or by other oxidizing agents. Increasing evidence suggests that oxidation of CL loosens its association with Cyt-c, and that the peroxidase activity of Cyt-c can oxidize CL. In earlier studies of Cyt-c in homogeneous medium by MALDI-TOF-MS and LC-ESI-MS, we showed that 1O2 generated by Pc 4-PDT oxidized histidine, methionine, tryptophan, and unexpectedly phenylalanine but not tyrosine. Most of the oxidation products were known to be formed by other oxidizing agents, such as hydroxyl radical, superoxide radical anion, and peroxynitrite. However, two products of histidine were unique to 1O2 and may be useful for reporting the action of 1O2 in cells and tissues. These products, as well as CL oxidation products, have now been identified in liposomes and mitochondria after Pc 4-PDT. In mitochondria, the PDT dose-dependent oxidations can be related to specific changes in mitochondrial function, Bcl-2 photodamage, and Cyt-c release. Thus, the role of PDT-generated 1O2 in oxidizing Cyt-c and CL and the interplay between protein and lipid targets may be highly relevant to understanding one mechanism for cell killing by PDT.

  2. Adaptive Molecular Resolution Approach in Hamiltonian Form: An Asymptotic Analysis

    CERN Document Server

    Zhu, Jinglong; Site, Luigi Delle

    2016-01-01

    Adaptive Molecular Resolution approaches in Molecular Dynamics are becoming relevant tools for the analysis of molecular liquids characterized by the interplay of different physical scales. The essential difference among these methods is in the way the change of molecular resolution is made in a buffer/transition region. In particular a central question concerns the possibility of the existence of a global Hamiltonian which, by describing the change of resolution, is at the same time physically consistent, mathematically well defined and numerically accurate. In this paper we present an asymptotic analysis of the adaptive process complemented by numerical results and show that under certain mathematical conditions a Hamiltonian, which is physically consistent and numerically accurate, may exist. \\blue{Such conditions show that molecular simulations in the current computational implementation require systems of large size and thus a Hamiltonian approach as the one proposed, at this stage, would not be practica...

  3. Pseudo-transition Analysis Identifies the Key Regulators of Dynamic Metabolic Adaptations from Steady-State Data.

    Science.gov (United States)

    Gerosa, Luca; Haverkorn van Rijsewijk, Bart R B; Christodoulou, Dimitris; Kochanowski, Karl; Schmidt, Thomas S B; Noor, Elad; Sauer, Uwe

    2015-10-28

    Hundreds of molecular-level changes within central metabolism allow a cell to adapt to the changing environment. A primary challenge in cell physiology is to identify which of these molecular-level changes are active regulatory events. Here, we introduce pseudo-transition analysis, an approach that uses multiple steady-state observations of (13)C-resolved fluxes, metabolites, and transcripts to infer which regulatory events drive metabolic adaptations following environmental transitions. Pseudo-transition analysis recapitulates known biology and identifies an unexpectedly sparse, transition-dependent regulatory landscape: typically a handful of regulatory events drive adaptation between carbon sources, with transcription mainly regulating TCA cycle flux and reactants regulating EMP pathway flux. We verify these observations using time-resolved measurements of the diauxic shift, demonstrating that some dynamic transitions can be approximated as monotonic shifts between steady-state extremes. Overall, we show that pseudo-transition analysis can explore the vast regulatory landscape of dynamic transitions using relatively few steady-state data, thereby guiding time-consuming, hypothesis-driven molecular validations. PMID:27136056

  4. Molecular Hydrogen Optical Depth Templates for FUSE Data Analysis

    OpenAIRE

    McCandliss, S. R.

    2003-01-01

    The calculation and use of molecular hydrogen optical depth templates to quickly identify and model molecular hydrogen absorption features longward of the Lyman edge at 912 Angstroms are described. Such features are commonly encountered in spectra obtained by the Far Ultraviolet Spectroscopic Explorer and also in spectra obtained by the Space Telescope Imaging Spectrograph, albeit less commonly. Individual templates are calculated containing all the Lyman and Werner transitions originating fr...

  5. Integration of molecular biology tools for identifying promoters and genes abundantly expressed in flowers of Oncidium Gower Ramsey

    Directory of Open Access Journals (Sweden)

    Tung Shu-Yun

    2011-04-01

    Full Text Available Abstract Background Orchids comprise one of the largest families of flowering plants and generate commercially important flowers. However, model plants, such as Arabidopsis thaliana do not contain all plant genes, and agronomic and horticulturally important genera and species must be individually studied. Results Several molecular biology tools were used to isolate flower-specific gene promoters from Oncidium 'Gower Ramsey' (Onc. GR. A cDNA library of reproductive tissues was used to construct a microarray in order to compare gene expression in flowers and leaves. Five genes were highly expressed in flower tissues, and the subcellular locations of the corresponding proteins were identified using lip transient transformation with fluorescent protein-fusion constructs. BAC clones of the 5 genes, together with 7 previously published flower- and reproductive growth-specific genes in Onc. GR, were identified for cloning of their promoter regions. Interestingly, 3 of the 5 novel flower-abundant genes were putative trypsin inhibitor (TI genes (OnTI1, OnTI2 and OnTI3, which were tandemly duplicated in the same BAC clone. Their promoters were identified using transient GUS reporter gene transformation and stable A. thaliana transformation analyses. Conclusions By combining cDNA microarray, BAC library, and bombardment assay techniques, we successfully identified flower-directed orchid genes and promoters.

  6. Molecular analysis of mutants of the Neurospora adenylosuccinate synthetase locus

    Indian Academy of Sciences (India)

    A. Wiest; A. J. McCarthy; R. Schnittker; K. McCluskey

    2012-08-01

    The ad-8 gene of Neurospora crassa, in addition to being used for the study of purine biology, has been extensively studied as a model for gene structure, mutagenesis and intralocus recombination. Because of this there is an extensive collection of well-characterized N. crassa ad-8 mutants in the Fungal Genetics Stock Center collection. Among these are spontaneous mutants and mutants induced with X-ray, UV or chemical mutagens. The specific lesions in these mutants have been genetically mapped at high resolution. We have sequenced the ad-8 locus from 13 of these mutants and identified the molecular nature of the mutation in each strain. We compare the historical fine-structure map to the DNA and amino acid sequence of each allele. The placement of the individual lesions in the fine-structure map was more accurate at the 5′ end of the gene and no mutants were identified in the 3′ untranslated region of this gene. We additionally analysed ad-8+ alleles in 18 N. crassa strains subjected to whole-genome sequence analysis and describe the variability among Neurospora strains and among fungi and other organisms.

  7. Analysis of Maize Crop Leaf using Multivariate Image Analysis for Identifying Soil Deficiency

    Directory of Open Access Journals (Sweden)

    S. Sridevy

    2014-11-01

    Full Text Available Image processing analysis for the soil deficiency identification has become an active area of research in this study. The changes in the color of the leaves are used to analyze and identify the deficiency of soil nutrients such as Nitrogen (N, Phosphorus (P and potassium (K by digital color image analysis. This research study focuses on the image analysis of the maize crop leaf using multivariate image analysis. In this proposed novel approach, initially, a color transformation for the input RGB image is formed and this RGB is converted to HSV because RGB is ideal for color generation but HSV is very suitable for color perception. Then green pixels are masked and removed using specific threshold value by applying histogram equalization. This masking approach is done through specific customized filtering approach which exclusively filters the green color of the leaf. After the filtering step, only the deficiency part of the leaf is taken for consideration. Then, a histogram generation is carried out for the deficiency part of the leaf. Then, Multivariate Image Analysis approach using Independent Component Analysis (ICA is carried out to extract a reference eigenspace from a matrix built by unfolding color data from the deficiency part. Test images are also unfolded and projected onto the reference eigenspace and the result is a score matrix which is used to compute nutrient deficiency based on the T2 statistic. In addition, a multi-resolution scheme by scaling down process is carried out to speed up the process. Finally, based on the training samples, the soil deficiency is identified based on the color of the maize crop leaf.

  8. Differential analysis of ovarian and endometrial cancers identifies a methylator phenotype.

    Directory of Open Access Journals (Sweden)

    Diana L Kolbe

    Full Text Available Despite improved outcomes in the past 30 years, less than half of all women diagnosed with epithelial ovarian cancer live five years beyond their diagnosis. Although typically treated as a single disease, epithelial ovarian cancer includes several distinct histological subtypes, such as papillary serous and endometrioid carcinomas. To address whether the morphological differences seen in these carcinomas represent distinct characteristics at the molecular level we analyzed DNA methylation patterns in 11 papillary serous tumors, 9 endometrioid ovarian tumors, 4 normal fallopian tube samples and 6 normal endometrial tissues, plus 8 normal fallopian tube and 4 serous samples from TCGA. For comparison within the endometrioid subtype we added 6 primary uterine endometrioid tumors and 5 endometrioid metastases from uterus to ovary. Data was obtained from 27,578 CpG dinucleotides occurring in or near promoter regions of 14,495 genes. We identified 36 locations with significant increases or decreases in methylation in comparisons of serous tumors and normal fallopian tube samples. Moreover, unsupervised clustering techniques applied to all samples showed three major profiles comprising mostly normal samples, serous tumors, and endometrioid tumors including ovarian, uterine and metastatic origins. The clustering analysis identified 60 differentially methylated sites between the serous group and the normal group. An unrelated set of 25 serous tumors validated the reproducibility of the methylation patterns. In contrast, >1,000 genes were differentially methylated between endometrioid tumors and normal samples. This finding is consistent with a generalized regulatory disruption caused by a methylator phenotype. Through DNA methylation analyses we have identified genes with known roles in ovarian carcinoma etiology, whereas pathway analyses provided biological insight to the role of novel genes. Our finding of differences between serous and endometrioid

  9. Normal Mode Analysis with Molecular Geometry Restraints: Bridging Molecular Mechanics and Elastic Models

    OpenAIRE

    Lu, Mingyang; Ma, Jianpeng

    2011-01-01

    A new method for normal mode analysis is reported for all-atom structures using molecular geometry restraints (MGR). Similar to common molecular mechanics force fields, the MGR potential contains short- and long-range terms. The short-range terms are defined by molecular geometry, i.e. bond lengths, angles and dihedrals; the long-range term is similar to that in elastic network models. Each interaction term uses a single force constant parameter, and is determined by fitting against a set of ...

  10. Mathematical analysis and calculation of molecular surfaces

    Science.gov (United States)

    Quan, Chaoyu; Stamm, Benjamin

    2016-10-01

    In this article we derive a complete characterization of the Solvent Excluded Surface (SES) for molecular systems including a complete characterization of singularities of the surface. The theory is based on an implicit representation of the SES, which, in turn, is based on the signed distance function to the Solvent Accessible Surface (SAS). All proofs are constructive so that the theory allows for efficient algorithms in order to compute the area of the SES and the volume of the SES-cavity, or to visualize the surface. Further, we propose to refine the notion of SAS and SES in order to take inner holes in a solute molecule into account or not.

  11. Dynamical analysis of highly excited molecular spectra

    Energy Technology Data Exchange (ETDEWEB)

    Kellman, M.E. [Univ. of Oregon, Eugene (United States)

    1993-12-01

    The goal of this program is new methods for analysis of spectra and dynamics of highly excited vibrational states of molecules. In these systems, strong mode coupling and anharmonicity give rise to complicated classical dynamics, and make the simple normal modes analysis unsatisfactory. New methods of spectral analysis, pattern recognition, and assignment are sought using techniques of nonlinear dynamics including bifurcation theory, phase space classification, and quantization of phase space structures. The emphasis is chaotic systems and systems with many degrees of freedom.

  12. Cladistic analysis of molecular and morphological data.

    Science.gov (United States)

    Mishler, B D

    1994-05-01

    Considerable progress has been made recently in phylogenetic reconstruction in a number of groups of organisms. This progress coincides with two major advances in systematics: new sources have been found for potentially informative characters (i.e., molecular data) and (more importantly) new approaches have been developed for extracting historical information from old or new characters (i.e., Hennigian phylogenetic systematics or cladistics). The basic assumptions of cladistics (the existence and splitting of lineages marked by discrete, heritable, and independent characters, transformation of which occurs at a rate slower than divergence of lineages) are discussed and defended. Molecular characters are potentially greater in quantity than (and usually independent of) more traditional morphological characters, yet their great simplicity (i.e., fewer potential character states; problems with determining homology), and difficulty of sufficient sampling (particularly from fossils) can lead to special difficulties. Expectations of the phylogenetic behavior of different types of data are investigated from a theoretical standpoint, based primarily on variation in the central parameter lambda (branch length in terms of expected number of character changes per segment of a tree), which also leads to possibilities for character and character state weighting. Also considered are prospects for representing diverse yet clearly monophyletic clades in larger-scale cladistic analyses, e.g., the exemplar method vs. "compartmentalization" (a new approach involving substituting an inferred "archetype" for a large clade accepted as monophyletic based on previous analyses). It is concluded that parsimony is to be preferred for synthetic, "total evidence" analyses because it appears to be a robust method, is applicable to all types of data, and has an explicit and interpretable evolutionary basis.

  13. Evolution & Phylogenetic Analysis: Classroom Activities for Investigating Molecular & Morphological Concepts

    Science.gov (United States)

    Franklin, Wilfred A.

    2010-01-01

    In a flexible multisession laboratory, students investigate concepts of phylogenetic analysis at both the molecular and the morphological level. Students finish by conducting their own analysis on a collection of skeletons representing the major phyla of vertebrates, a collection of primate skulls, or a collection of hominid skulls.

  14. Differentially expressed genes identified by microarray analysis following leptin treatment of hepatic stellate cells

    Institute of Scientific and Technical Information of China (English)

    ZHONG Li-hua; CHENG Jun; ZHU Li-ying

    2010-01-01

    Background Liver fibrosis is the process through which numerous chronic liver diseases develop into liver cirrhosis. Leptin can activate hepatic stellate cells (HSCs) and play an important role in the formation of liver fibrosis. However, the process by which leptin activates HSCs is complicated, and research on this process is limited. The aim of this study was to explore the related changes in gene expression and the control mechanisms involved in leptin activated HSCs to understand the overall mechanism of liver fibrosis development. Methods We cultivate rat HSCs, with and without stimulation by leptin, and extracted mRNA. Differentially expressed genes were detected by microarray analysis. Results The differentially expressed genes identified included six upregulated genes and six downregulated genes. The representative upregulated genes included short chain dehydrogenase (CY5/CY3=2.265) and pulmonary surfactant protein A1 (CY5/CY3=2.036). The significant downregulated gene encoded hepatic stearoyl coenzyme A desaturase 1 (SCD-1) (CY5/CY3=0.351).Conclusion Leptin might mediate the molecular biological mechanisms of liver fibrosis.

  15. Interactive analysis of systems biology molecular expression data

    Directory of Open Access Journals (Sweden)

    Prabhakar Sunil

    2008-02-01

    Full Text Available Abstract Background Systems biology aims to understand biological systems on a comprehensive scale, such that the components that make up the whole are connected to one another and work through dependent interactions. Molecular correlations and comparative studies of molecular expression are crucial to establishing interdependent connections in systems biology. The existing software packages provide limited data mining capability. The user must first generate visualization data with a preferred data mining algorithm and then upload the resulting data into the visualization package for graphic visualization of molecular relations. Results Presented is a novel interactive visual data mining application, SysNet that provides an interactive environment for the analysis of high data volume molecular expression information of most any type from biological systems. It integrates interactive graphic visualization and statistical data mining into a single package. SysNet interactively presents intermolecular correlation information with circular and heatmap layouts. It is also applicable to comparative analysis of molecular expression data, such as time course data. Conclusion The SysNet program has been utilized to analyze elemental profile changes in response to an increasing concentration of iron (Fe in growth media (an ionomics dataset. This study case demonstrates that the SysNet software is an effective platform for interactive analysis of molecular expression information in systems biology.

  16. In silico analysis of the molecular mechanism of postmenopausal osteoporosis.

    Science.gov (United States)

    Liu, Yanqing; Wang, Yueqiu; Yang, Nailong; Wu, Suning; Lv, Yanhua; Xu, Lili

    2015-11-01

    Postmenopausal osteoporosis (PO) is a common disease in females >50 years of age worldwide and is becoming an increasing burden to society. The present study aimed to assess the molecular mechanism of PO using bioinformatic methods. The gene expression data from patients with PO and normal controls were downloaded from the ArrayExpress database provided by European Bioinformatics Institute. Following the screening of the differentially expressed genes (DEGs) using the Limma package in R language, Kyoto Encyclopedia of Genes and Genomes pathways enrichment analysis was performed using the Database for Annotation, Visualization and Integrated Discovery online tools. Sequentially, modulators of the DEGs, including transcription factors (TFs) and microRNAs, were predicted by the ChIP Enrichment Analysis databases and WEB‑based GEne SeT AnaLysis Toolkit system, respectively. In addition, the protein‑protein interaction network of DEGs was constructed via the search tool for the retrieval of interacting genes and then the functional modules were further analyzed via the clusterMaker package and The Biological Networks Gene Ontology package within the Cytoscape software. A total of 482 DEGs, including 279 upregulated and 203 downregulated DEGs, were screened out. DEGs were predominantly enriched in the pathways of fatty acid metabolism, cardiac muscle contraction and DNA replication. TFs, including SMAD4, in addition to microRNAs, including the microRNA‑125 (miR‑125) family, miR‑331 and miR‑24, may be the modulators of the DEGs in PO. In addition, the five largest modules were identified with TTN, L1G1, ACADM, UQCRC2 and TRIM63 as the hub proteins, and they were associated with the biological processes of muscle contraction, DNA replication initiation, lipid modification, generation of precursor metabolites and energy, and regulation of acetyl‑CoA biosynthetic process, respectively. SMAD4, CACNG1 and TRIM63 are suggested to be important factors in the

  17. Inhibition of acetylcholinesterase by two genistein derivatives: kinetic analysis, molecular docking and molecular dynamics simulation.

    Science.gov (United States)

    Fang, Jiansong; Wu, Ping; Yang, Ranyao; Gao, Li; Li, Chao; Wang, Dongmei; Wu, Song; Liu, Ai-Lin; Du, Guan-Hua

    2014-12-01

    In this study two genistein derivatives (G1 and G2) are reported as inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), and differences in the inhibition of AChE are described. Although they differ in structure by a single methyl group, the inhibitory effect of G1 (IC50=264 nmol/L) on AChE was 80 times stronger than that of G2 (IC50=21,210 nmol/L). Enzyme-kinetic analysis, molecular docking and molecular dynamics (MD) simulations were conducted to better understand the molecular basis for this difference. The results obtained by kinetic analysis demonstrated that G1 can interact with both the catalytic active site and peripheral anionic site of AChE. The predicted binding free energies of two complexes calculated by the molecular mechanics/generalized born surface area (MM/GBSA) method were consistent with the experimental data. The analysis of the individual energy terms suggested that a difference between the net electrostatic contributions (ΔE ele+ΔG GB) was responsible for the binding affinities of these two inhibitors. Additionally, analysis of the molecular mechanics and MM/GBSA free energy decomposition revealed that the difference between G1 and G2 originated from interactions with Tyr124, Glu292, Val294 and Phe338 of AChE. In conclusion, the results reveal significant differences at the molecular level in the mechanism of inhibition of AChE by these structurally related compounds. PMID:26579414

  18. Sex Change in Clownfish: Molecular Insights from Transcriptome Analysis

    KAUST Repository

    Casas, Laura

    2016-10-17

    Sequential hermaphroditism is a unique reproductive strategy among teleosts that is displayed mainly in fish species living in the coral reef environment. The reproductive biology of hermaphrodites has long been intriguing; however, very little is known about the molecular pathways underlying their sex change. Here, we provide the first de novo transcriptome analyses of a hermaphrodite teleost´s undergoing sex change in its natural environment. Our study has examined relative gene expression across multiple groups—rather than just two contrasting conditions— and has allowed us to explore the differential expression patterns throughout the whole process. Our analysis has highlighted the rapid and complex genomic response of the brain associated with sex change, which is subsequently transmitted to the gonads, identifying a large number of candidate genes, some well-known and some novel, involved in the process. The present study provides strong evidence of the importance of the sex steroidogenic machinery during sex change in clownfish, with the aromatase gene playing a central role, both in the brain and the gonad. This work constitutes the first genome-wide study in a social sex-changing species and provides insights into the genetic mechanism governing social sex change and gonadal restructuring in protandrous hermaphrodites.

  19. Circumscribed sebaceous neoplasms: a morphological, immunohistochemical and molecular analysis.

    Science.gov (United States)

    Harvey, Nathan Tobias; Tabone, Tania; Erber, Wendy; Wood, Benjamin Andrew

    2016-08-01

    Sebaceous neoplasms encompass a range of lesions, including benign entities such as sebaceous adenoma and sebaceoma, as well as sebaceous carcinoma. The distinction of sebaceous carcinoma from benign lesions relies on histological identification of architectural or cytological features of malignancy. In this study we have assessed the diagnostic discriminatory ability of mitotic rate and immunohistochemical markers (p53, bcl-2 and p16) in a selected group of well circumscribed sebaceous neoplasms, incorporating examples of sebaceous adenoma, sebaceoma and sebaceous carcinoma. We found that mitotic rate was significantly higher in malignant lesions as compared to benign lesions, but none of the immunohistochemical markers showed a discriminatory expression pattern. In addition, we performed a mutational analysis on the same group of lesions using next generation sequencing (NGS) technology. The most commonly mutated gene was TP53, although there was no correlation between the p53 immunohistochemical results and number or type of TP53 mutation detected. CDKN2A, EGFR, CTNNB1 and KRAS were also commonly mutated across all lesions. No particular gene, mutation profile or individual mutation could be identified which directly correlated with the consensus histological diagnosis. In conclusion, within this diagnostically challenging group of lesions, mitotic activity, but not immunohistochemical labelling for p16 or bcl-2, correlates with diagnostic category. While a number of genes potentially involved in the genesis of sebaceous neoplasia were uncovered, any molecular differences between the histological diagnostic categories remain unclear. PMID:27311873

  20. Sex Change in Clownfish: Molecular Insights from Transcriptome Analysis

    Science.gov (United States)

    Casas, Laura; Saborido-Rey, Fran; Ryu, Taewoo; Michell, Craig; Ravasi, Timothy; Irigoien, Xabier

    2016-01-01

    Sequential hermaphroditism is a unique reproductive strategy among teleosts that is displayed mainly in fish species living in the coral reef environment. The reproductive biology of hermaphrodites has long been intriguing; however, very little is known about the molecular pathways underlying their sex change. Here, we provide the first de novo transcriptome analyses of a hermaphrodite teleost´s undergoing sex change in its natural environment. Our study has examined relative gene expression across multiple groups—rather than just two contrasting conditions— and has allowed us to explore the differential expression patterns throughout the whole process. Our analysis has highlighted the rapid and complex genomic response of the brain associated with sex change, which is subsequently transmitted to the gonads, identifying a large number of candidate genes, some well-known and some novel, involved in the process. The present study provides strong evidence of the importance of the sex steroidogenic machinery during sex change in clownfish, with the aromatase gene playing a central role, both in the brain and the gonad. This work constitutes the first genome-wide study in a social sex-changing species and provides insights into the genetic mechanism governing social sex change and gonadal restructuring in protandrous hermaphrodites. PMID:27748421

  1. Molecular docking and dynamic studies of human growth factor receptorbound protein (Grb 2 insights to identify novel inhibitors

    Directory of Open Access Journals (Sweden)

    Sandeep S

    2016-10-01

    Full Text Available Background: Human growth factor receptor bound protein-2 (Grb 2 involves in initiation of kinase signaling by Son of Sevenless (SOS and activates mitogen activated protein kinase pathway. Grb2 overexpress during cancerous condition hence it emerged as a potent target for various cancers. Material and Methods: Seven pharmacophores were developed from seven co-crystal structures of Grb2 and applied for common pharmacophore hypothesis. Two common pharmacophore hypothesis (CPH models were screened and hits were applied for docking and free energy [G] calculations. Results: Two leads were proposed from docking and G analysis. Energy of the system, RMSD, RMSF, hydrogen bonds and water bridges of lead1 was better than the co-crystal ligand during 50 ns molecular dynamics simulations. Discussion: Two leads are interacting with Src homology 2 (SH2 domain of Grb2 and blocking the function of Grb2.

  2. Molecular genetic analysis of human alcohol dehydrogenase

    OpenAIRE

    Duester, G; Wesley Hatfield, G.; Smith, M.

    1985-01-01

    Human alcohol dehydrogenase (ADH) consists of a complex group of isozymes encoded by at least five non-identical genes, two of which have previously been shown through enzymatic analysis to possess polymorphic variants. Using a cDNA probe the ADH2gene encoding the β subunit of human ADH was mapped to human chromosome 4. The cDNA probe for ADH2 was also used to detect a restriction fragment length polymorphism present in human populations. This polymorphism may help establish whether certain A...

  3. Molecular sieves analysis by elastic recoil detection

    International Nuclear Information System (INIS)

    The opportunity of water determination in zeolites via hydrogen detection using the elastic recoil detection analysis (ERDA) was investigated. The radiation effect upon the desorption rate of hydrogen in miscellaneous types of zeolites, e.g. Y-Faujasite, ZSM-5, SK, etc. and in a natural clay, e.g. an Algerian bentonite was discussed. Quantitative measurements were carried out in order to determine the amount and distribution shape of hydrogen in each material. Various explanations dealing with hydration and constitution water in such a crystalline framework were proposed. The experimental results are in a good agreement with the corresponding theoretical values

  4. Genome-wide meta-analysis identifies new susceptibility loci for migraine

    DEFF Research Database (Denmark)

    Anttila, Verneri; Winsvold, Bendik S; Gormley, Padhraig;

    2013-01-01

    Migraine is the most common brain disorder, affecting approximately 14% of the adult population, but its molecular mechanisms are poorly understood. We report the results of a meta-analysis across 29 genome-wide association studies, including a total of 23,285 individuals with migraine (cases) an...

  5. Genome-wide meta-analysis identifies new susceptibility loci for migraine

    NARCIS (Netherlands)

    Anttila, Verneri; Winsvold, Bendik S.; Gormley, Padhraig; Kurth, Tobias; Bettella, Francesco; McMahon, George; Kallela, Mikko; Malik, Rainer; de Vries, Boukje; Terwindt, Gisela; Medland, Sarah E.; Todt, Unda; McArdle, Wendy L.; Quaye, Lydia; Koiranen, Markku; Ikram, M. Arfan; Lehtimaki, Terho; Stam, Anine H.; Ligthart, Lannie; Wedenoja, Juho; Dunham, Ian; Neale, Benjamin M.; Palta, Priit; Hamalainen, Eija; Schuerks, Markus; Rose, Lynda M.; Buring, Julie E.; Ridker, Paul M.; Steinberg, Stacy; Stefansson, Hreinn; Jakobsson, Finnbogi; Lawlor, Debbie A.; Evans, David M.; Ring, Susan M.; Farkkila, Markus; Artto, Ville; Kaunisto, Mari A.; Freilinger, Tobias; Schoenen, Jean; Frants, Rune R.; Pelzer, Nadine; Weller, Claudia M.; Zielman, Ronald; Heath, Andrew C.; Madden, Pamela A. F.; Montgomery, Grant W.; Martin, Nicholas G.; Borck, Guntram; Goebel, Hartmut; Heinze, Axel; Heinze-Kuhn, Katja; Williams, Frances M. K.; Hartikainen, Anna-Liisa; Pouta, Anneli; van den Ende, Joyce; Uitterlinden, Andre G.; Hofman, Albert; Amin, Najaf; Hottenga, Jouke-Jan; Vink, Jacqueline M.; Heikkila, Kauko; Alexander, Michael; Muller-Myhsok, Bertram; Schreiber, Stefan; Meitinger, Thomas; Wichmann, Heinz Erich; Aromaa, Arpo; Eriksson, Johan G.; Traynor, Bryan J.; Trabzuni, Daniah; Rossin, Elizabeth; Lage, Kasper; Jacobs, Suzanne B. R.; Gibbs, J. Raphael; Birney, Ewan; Kaprio, Jaakko; Penninx, Brenda W.; Boomsma, Dorret I.; van Duijn, Cornelia; Raitakari, Olli; Jarvelin, Marjo-Riitta; Zwart, John-Anker; Cherkas, Lynn; Strachan, David P.; Kubisch, Christian; Ferrari, Michel D.; van den Maagdenberg, Arn M. J. M.; Dichgans, Martin; Wessman, Maija; Smith, George Davey; Stefansson, Kari; Daly, Mark J.; Nyholt, Dale R.; Chasman, Daniel I.; Palotie, Aarno

    2013-01-01

    Migraine is the most common brain disorder, affecting approximately 14% of the adult population, but its molecular mechanisms are poorly understood. We report the results of a meta-analysis across 29 genome-wide association studies, including a total of 23,285 individuals with migraine (cases) and 9

  6. Molecular Eigensolution Symmetry Analysis and Fine Structure

    Directory of Open Access Journals (Sweden)

    William G. Harter

    2013-01-01

    Full Text Available Spectra of high-symmetry molecules contain fine and superfine level cluster structure related to J-tunneling between hills and valleys on rovibronic energy surfaces (RES. Such graphic visualizations help disentangle multi-level dynamics, selection rules, and state mixing effects including widespread violation of nuclear spin symmetry species. A review of RES analysis compares it to that of potential energy surfaces (PES used in Born-Oppenheimer approximations. Both take advantage of adiabatic coupling in order to visualize Hamiltonian eigensolutions. RES of symmetric and D2 asymmetric top rank-2-tensor Hamiltonians are compared with Oh spherical top rank-4-tensor fine-structure clusters of 6-fold and 8-fold tunneling multiplets. Then extreme 12-fold and 24-fold multiplets are analyzed by RES plots of higher rank tensor Hamiltonians. Such extreme clustering is rare in fundamental bands but prevalent in hot bands, and analysis of its superfine structure requires more efficient labeling and a more powerful group theory. This is introduced using elementary examples involving two groups of order-6 (C6 and D3~C3v, then applied to families of Oh clusters in SF6 spectra and to extreme clusters.

  7. Confirming an integrated pathology of diabetes and its complications by molecular biomarker-target network analysis.

    Science.gov (United States)

    Zhao, Zide; Zhang, Yingying; Gai, Fengchun; Wang, Ying

    2016-09-01

    Despite ongoing research into diabetes and its complications, the underlying molecular associations remain to be elucidated. The systematic identification of molecular interactions in associated diseases may be approached using a network analysis strategy. The biomarker-target interrelated molecules associated with diabetes and its complications were identified via the Comparative Toxicogenomics Database (CTD); the Search Tool for Recurring Instances of Neighboring Genes was utilized for network construction. Functional enrichment analysis was performed with Database for Annotation, Visualization and Integrated Discovery software to investigate connections between diabetes and its complications. A total of 142 (including 122 biomarkers, 10 therapeutic targets and 10 overlapping molecules) biomarker-target interrelated molecules associated with diabetes and its complications were identified via the CTD database, and analysis of the network yielded 1,087 biological processes and fifteen Kyoto Encyclopedia of Genes and Genomes pathways with significant P‑values. Various critical aspects of the networks were examined in the present study: a) Intermolecular horizontal and vertical combinations in biomarkers and therapeutic targets associated with diabetes and its complicationb) network topology properties associated with molecular pathological responsec) contribution of key molecules to integrated regulation; and d) crosstalk between multiple pathways. Based on a multi-dimensional analysis, it was concluded that the integrated molecular pathological development of diabetes and its complications does not proceed randomly, which suggests a requirement for integrated, multi-target intervention. PMID:27430657

  8. Identifying cell and molecular stress after radiation in a three-dimensional (3-D) model of oral mucositis

    International Nuclear Information System (INIS)

    Research highlights: → We irradiated a 3-D human oral cell culture of keratinocytes and fibroblasts with 12 and 2 Gy. → 6 h after irradiation the histopathology and apoptosis of the 3-D culture were evaluated. Microarrays were used to assess the gene expression in the irradiated 3-D tissue. → 12 Gy induced significant histopathologic changes and cellular apoptosis. → 12 Gy significantly affected genes of the NF-kB pathway, inflammatory cytokines and DAMPs. -- Abstract: Mucositis is a debilitating adverse effect of chemotherapy and radiation treatment. It is important to develop a simple and reliable in vitro model, which can routinely be used to screen new drugs for prevention and treatment of mucositis. Furthermore, identifying cell and molecular stresses especially in the initiation phase of mucositis in this model will help towards this end. We evaluated a three-dimensional (3-D) human oral cell culture that consisted of oral keratinocytes and fibroblasts as a model of oral mucositis. The 3-D cell culture model was irradiated with 12 or 2 Gy. Six hours after the irradiation we evaluated microscopic sections of the cell culture for evidence of morphologic changes including apoptosis. We used microarrays to compare the expression of several genes from the irradiated tissue with identical genes from tissue that was not irradiated. We found that irradiation with 12 Gy induced significant histopathologic effects including cellular apoptosis. Irradiation significantly affected the expression of several genes of the NF-kB pathway and several inflammatory cytokines, such as IL-1B, 1L-8, NF-kB1, and FOS compared to tissue that was not irradiated. We identified significant upregulation of several genes that belong to damage-associated molecular patterns (DAMPs) such as HMB1, S100A13, SA10014, and SA10016 in the 3-D tissues that received 12 Gy but not in tissues that received 2 Gy. In conclusion, this model quantifies radiation damage and this is an important first

  9. Identifying cell and molecular stress after radiation in a three-dimensional (3-D) model of oral mucositis

    Energy Technology Data Exchange (ETDEWEB)

    Lambros, Maria Polikandritou, E-mail: mlambros@westernu.edu [Department of Pharmaceutical Sciences, College of Pharmacy, Western University of Health Sciences, Pomona, CA 91766 (United States); Parsa, Cyrus [Department of Clinical Sciences, College of Osteopathic Medicine, Western University of Health Sciences, Pomona, CA 91766 (United States); Mulamalla, HariChandana [Department of Pharmaceutical Sciences, College of Pharmacy, Western University of Health Sciences, Pomona, CA 91766 (United States); Orlando, Robert [Department of Clinical Sciences, College of Osteopathic Medicine, Western University of Health Sciences, Pomona, CA 91766 (United States); Lau, Bernard [Center for Advancement of Drug Research and Evaluation (CADRE), Western University of Health Sciences, Pomona, CA 91766 (United States); Huang, Ying [Department of Pharmaceutical Sciences, College of Pharmacy, Western University of Health Sciences, Pomona, CA 91766 (United States); Center for Advancement of Drug Research and Evaluation (CADRE), Western University of Health Sciences, Pomona, CA 91766 (United States); Pon, Doreen [Department of Pharmacy Practice and Administration, College of Pharmacy, Western University of Health Sciences, Pomona, CA 91766 (United States); Chow, Moses [Department of Pharmacy Practice and Administration, College of Pharmacy, Western University of Health Sciences, Pomona, CA 91766 (United States); Center for Advancement of Drug Research and Evaluation (CADRE), Western University of Health Sciences, Pomona, CA 91766 (United States)

    2011-02-04

    Research highlights: {yields} We irradiated a 3-D human oral cell culture of keratinocytes and fibroblasts with 12 and 2 Gy. {yields} 6 h after irradiation the histopathology and apoptosis of the 3-D culture were evaluated. Microarrays were used to assess the gene expression in the irradiated 3-D tissue. {yields} 12 Gy induced significant histopathologic changes and cellular apoptosis. {yields} 12 Gy significantly affected genes of the NF-kB pathway, inflammatory cytokines and DAMPs. -- Abstract: Mucositis is a debilitating adverse effect of chemotherapy and radiation treatment. It is important to develop a simple and reliable in vitro model, which can routinely be used to screen new drugs for prevention and treatment of mucositis. Furthermore, identifying cell and molecular stresses especially in the initiation phase of mucositis in this model will help towards this end. We evaluated a three-dimensional (3-D) human oral cell culture that consisted of oral keratinocytes and fibroblasts as a model of oral mucositis. The 3-D cell culture model was irradiated with 12 or 2 Gy. Six hours after the irradiation we evaluated microscopic sections of the cell culture for evidence of morphologic changes including apoptosis. We used microarrays to compare the expression of several genes from the irradiated tissue with identical genes from tissue that was not irradiated. We found that irradiation with 12 Gy induced significant histopathologic effects including cellular apoptosis. Irradiation significantly affected the expression of several genes of the NF-kB pathway and several inflammatory cytokines, such as IL-1B, 1L-8, NF-kB1, and FOS compared to tissue that was not irradiated. We identified significant upregulation of several genes that belong to damage-associated molecular patterns (DAMPs) such as HMB1, S100A13, SA10014, and SA10016 in the 3-D tissues that received 12 Gy but not in tissues that received 2 Gy. In conclusion, this model quantifies radiation damage and this

  10. Protein analysis based on molecular beacon probes and biofunctionalized nanoparticles

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    With the completion of the human genome-sequencing project, there has been a resulting change in the focus of studies from genomics to proteomics. By utilizing the inherent advantages of molecular beacon probes and biofunctionalized nanoparticles, a series of novel principles, methods and techniques have been exploited for bioanalytical and biomedical studies. This review mainly discusses the applications of molecular beacon probes and biofunctionalized nanoparticles-based technologies for realtime, in-situ, highly sensitive and highly selective protein analysis, including the nonspecific or specific protein detection and separation, protein/DNA interaction studies, cell surface protein recognition, and antigen-antibody binding process-based bacteria assays. The introduction of molecular beacon probes and biofunctionalized nanoparticles into the protein analysis area would necessarily advance the proteomics research.

  11. Theoretical analysis of dynamic processes for interacting molecular motors

    International Nuclear Information System (INIS)

    Biological transport is supported by the collective dynamics of enzymatic molecules that are called motor proteins or molecular motors. Experiments suggest that motor proteins interact locally via short-range potentials. We investigate the fundamental role of these interactions by carrying out an analysis of a new class of totally asymmetric exclusion processes, in which interactions are accounted for in a thermodynamically consistent fashion. This allows us to explicitly connect microscopic features of motor proteins with their collective dynamic properties. A theoretical analysis that combines various mean-field calculations and computer simulations suggests that the dynamic properties of molecular motors strongly depend on the interactions, and that the correlations are stronger for interacting motor proteins. Surprisingly, it is found that there is an optimal strength of interactions (weak repulsion) that leads to a maximal particle flux. It is also argued that molecular motor transport is more sensitive to attractive interactions. Applications of these results for kinesin motor proteins are discussed. (paper)

  12. A Molecular Iodine Spectral Data Set for Rovibronic Analysis

    Science.gov (United States)

    Williamson, J. Charles; Kuntzleman, Thomas S.; Kafader, Rachael A.

    2013-01-01

    A data set of 7,381 molecular iodine vapor rovibronic transitions between the X and B electronic states has been prepared for an advanced undergraduate spectroscopic analysis project. Students apply standard theoretical techniques to these data and determine the values of three X-state constants (image omitted) and four B-state constants (image…

  13. Transcriptome Analysis of Syringa oblata Lindl. Inflorescence Identifies Genes Associated with Pigment Biosynthesis and Scent Metabolism.

    Directory of Open Access Journals (Sweden)

    Jian Zheng

    Full Text Available Syringa oblata Lindl. is a woody ornamental plant with high economic value and characteristics that include early flowering, multiple flower colors, and strong fragrance. Despite a long history of cultivation, the genetics and molecular biology of S. oblata are poorly understood. Transcriptome and expression profiling data are needed to identify genes and to better understand the biological mechanisms of floral pigments and scents in this species. Nine cDNA libraries were obtained from three replicates of three developmental stages: inflorescence with enlarged flower buds not protruded, inflorescence with corolla lobes not displayed, and inflorescence with flowers fully opened and emitting strong fragrance. Using the Illumina RNA-Seq technique, 319,425,972 clean reads were obtained and were assembled into 104,691 final unigenes (average length of 853 bp, 41.75% of which were annotated in the NCBI non-redundant protein database. Among the annotated unigenes, 36,967 were assigned to gene ontology categories and 19,956 were assigned to eukaryoticorthologous groups. Using the Kyoto Encyclopedia of Genes and Genomes pathway database, 12,388 unigenes were sorted into 286 pathways. Based on these transcriptomic data, we obtained a large number of candidate genes that were differentially expressed at different flower stages and that were related to floral pigment biosynthesis and fragrance metabolism. This comprehensive transcriptomic analysis provides fundamental information on the genes and pathways involved in flower secondary metabolism and development in S. oblata, providing a useful database for further research on S. oblata and other plants of genus Syringa.

  14. Identifying At-Risk Students in General Chemistry via Cluster Analysis of Affective Characteristics

    Science.gov (United States)

    Chan, Julia Y. K.; Bauer, Christopher F.

    2014-01-01

    The purpose of this study is to identify academically at-risk students in first-semester general chemistry using affective characteristics via cluster analysis. Through the clustering of six preselected affective variables, three distinct affective groups were identified: low (at-risk), medium, and high. Students in the low affective group…

  15. Automated Analysis and Classification of Histological Tissue Features by Multi-Dimensional Microscopic Molecular Profiling.

    Directory of Open Access Journals (Sweden)

    Daniel P Riordan

    Full Text Available Characterization of the molecular attributes and spatial arrangements of cells and features within complex human tissues provides a critical basis for understanding processes involved in development and disease. Moreover, the ability to automate steps in the analysis and interpretation of histological images that currently require manual inspection by pathologists could revolutionize medical diagnostics. Toward this end, we developed a new imaging approach called multidimensional microscopic molecular profiling (MMMP that can measure several independent molecular properties in situ at subcellular resolution for the same tissue specimen. MMMP involves repeated cycles of antibody or histochemical staining, imaging, and signal removal, which ultimately can generate information analogous to a multidimensional flow cytometry analysis on intact tissue sections. We performed a MMMP analysis on a tissue microarray containing a diverse set of 102 human tissues using a panel of 15 informative antibody and 5 histochemical stains plus DAPI. Large-scale unsupervised analysis of MMMP data, and visualization of the resulting classifications, identified molecular profiles that were associated with functional tissue features. We then directly annotated H&E images from this MMMP series such that canonical histological features of interest (e.g. blood vessels, epithelium, red blood cells were individually labeled. By integrating image annotation data, we identified molecular signatures that were associated with specific histological annotations and we developed statistical models for automatically classifying these features. The classification accuracy for automated histology labeling was objectively evaluated using a cross-validation strategy, and significant accuracy (with a median per-pixel rate of 77% per feature from 15 annotated samples for de novo feature prediction was obtained. These results suggest that high-dimensional profiling may advance the

  16. A tyrosine-rich cell surface protein in the diatom Amphora coffeaeformis identified through transcriptome analysis and genetic transformation.

    Directory of Open Access Journals (Sweden)

    Matthias T Buhmann

    Full Text Available Diatoms are single-celled eukaryotic microalgae that are ubiquitously found in almost all aquatic ecosystems, and are characterized by their intricately structured SiO2 (silica-based cell walls. Diatoms with a benthic life style are capable of attaching to any natural or man-made submerged surface, thus contributing substantially to both microbial biofilm communities and economic losses through biofouling. Surface attachment of diatoms is mediated by a carbohydrate- and protein- based glue, yet no protein involved in diatom underwater adhesion has been identified so far. In the present work, we have generated a normalized transcriptome database from the model adhesion diatom Amphora coffeaeformis. Using an unconventional bioinformatics analysis we have identified five proteins that exhibit unique amino acid sequences resembling the amino acid composition of the tyrosine-rich adhesion proteins from mussel footpads. Establishing the first method for the molecular genetic transformation of A. coffeaeformis has enabled investigations into the function of one of these proteins, AC3362, through expression as YFP fusion protein. Biochemical analysis and imaging by fluorescence microscopy revealed that AC3362 is not involved in adhesion, but rather plays a role in biosynthesis and/or structural stability of the cell wall. The methods established in the present study have paved the way for further molecular studies on the mechanisms of underwater adhesion and biological silica formation in the diatom A. coffeaeformis.

  17. Gene Expression Meta-Analysis identifies Cytokine Pathways and 5q Aberrations involved in Metastasis of ERBB2 Amplified and Basal Breast Cancer

    DEFF Research Database (Denmark)

    Thomassen, Mads; Tan, Qihua; Burton, Mark;

    2013-01-01

    Background: Breast tumors have been described by molecular subtypes characterized by pervasively different gene expression profiles. The subtypes are associated with different clinical parameters and origin of precursor cells. However, the biological pathways and chromosomal aberrations that differ...... between the subgroups are less well characterized. The molecular subtypes are associated with different risk of metastatic recurrence of the disease. Nevertheless, the performance of these overall patterns to predict outcome is far from optimal, suggesting that biological mechanisms that extend beyond...... the subgroups impact metastasis. Results: We have scrutinized publicly available gene expression datasets and identified molecular subtypes in 1,394 breast tumors with outcome data. By analysis of chromosomal regions and pathways using “Gene set enrichment analysis” followed by a meta-analysis, we identified...

  18. A molecular cytogenetic analysis of introgression in Alstroemeria

    OpenAIRE

    Kamstra, S.A.

    1999-01-01

    This thesis describes the results of a molecular cytogenetic investigation of the process of introgression in Alstroemeria . The aim of this study was to transfer chromosomes or genes from one Alstroemeria species into another. For this, two distantly related species, A. aurea and A. inodora , were hybridized and the resulting hybrids were further backcrossed with the species A. inodora . To monitor the process of introgression accurately it was necessary to identify the individual chromosome...

  19. [Challenge to the Development of Molecular Targeted Therapy against a Novel Target Candidate Identified by Antibody Proteomics Technology].

    Science.gov (United States)

    Nagano, Kazuya

    2016-01-01

    Disease proteomics that systemically analyzes and identifies differentially expressed proteins between healthy and diseased samples is a potentially useful approach for obtaining target proteins for drug development. To date, however, very few target proteins have been identified from this field. A key issue that remains to be resolved is how to correctly identify target proteins from a number of potential candidates. To circumvent this problem, we have developed "antibody proteomics technology" in which a single chain Fv phage antibody library is utilized for proteome analysis. Here, we describe the application of this technology by primarily focusing on Eph receptor A10 (EphA10), a novel breast cancer-related protein that is a promising target for antibody drugs. To establish an effective and safe targeted cancer therapy, it is important that the target is specifically expressed in cancer tissues. Therefore, we attempted to analyze the EphA10 expression profiles. Tissue microarray analysis showed that EphA10 was expressed in all subtypes of breast cancer containing triple negative breast cancer cases. On the other hand, EphA10 was only expressed in testis tissue among 36 kinds of normal tissues. Thus, EphA10 could be a highly cancer-specific protein, making it a promising target for female breast cancer patients. Finally, we examined the anti-tumor effect by anti-EphA10 antibody, aiming for the development of a novel EphA10 targeting therapy. Administration of the antibody showed that tumor volumes were significantly inhibited. Our results suggest that targeting EphA10 in breast cancer cases might be a promising new form of therapy. PMID:26831784

  20. Secretome analysis identifies potential virulence factors of Diplodia corticola, a fungal pathogen involved in cork oak (Quercus suber) decline.

    Science.gov (United States)

    Fernandes, Isabel; Alves, Artur; Correia, António; Devreese, Bart; Esteves, Ana Cristina

    2014-01-01

    The characterisation of the secretome of phytopathogenic fungi may contribute to elucidate the molecular mechanisms of pathogenesis. This is particularly relevant for Diplodia corticola, a fungal plant pathogen belonging to the family Botryosphaeriaceae, whose genome remains unsequenced. This phytopathogenic fungus is recognised as one of the most important pathogens of cork oak, being related to the decline of cork oak forests in the Iberian Peninsula. Unfortunately, secretome analysis of filamentous fungi is limited by the low protein concentration and by the presence of many interfering substances, such as polysaccharides, which affect the separation and analysis by 1D and 2D gel electrophoresis. We compared six protein extraction protocols concerning their suitability for further application with proteomic workflows. The protocols involving protein precipitation were the most efficient, with emphasis on TCA-acetone protocol, allowing us to identify the most abundant proteins on the secretome of this plant pathogen. Approximately 60% of the spots detected were identified, all corresponding to extracellular proteins. Most proteins identified were carbohydrate degrading enzymes and proteases that may be related to D. corticola pathogenicity. Although the secretome was assessed in a noninfection environment, potential virulence factors such as the putative glucan-β-glucosidase, neuraminidase, and the putative ferulic acid esterase were identified. The data obtained forms a useful basis for a deeper understanding of the pathogenicity and infection biology of D. corticola. Moreover, it will contribute to the development of proteomics studies on other members of the Botryosphaeriaceae.

  1. Whole exome analysis identifies dominant COL4A1 mutations in patients with complex ocular phenotypes involving microphthalmia.

    Science.gov (United States)

    Deml, B; Reis, L M; Maheshwari, M; Griffis, C; Bick, D; Semina, E V

    2014-11-01

    Anophthalmia/microphthalmia (A/M) is a developmental ocular malformation defined as complete absence or reduction in size of the eye. A/M is a heterogenous disorder with numerous causative genes identified; however, about half the cases lack a molecular diagnosis. We undertook whole exome sequencing in an A/M family with two affected siblings, two unaffected siblings, and unaffected parents; the ocular phenotype was isolated with only mild developmental delay/learning difficulties reported and a normal brain magnetic resonance imaging (MRI) in the proband at 16 months. No pathogenic mutations were identified in 71 known A/M genes. Further analysis identified a shared heterozygous mutation in COL4A1, c.2317G>A, p.(Gly773Arg) that was not seen in the unaffected parents and siblings. Analysis of 24 unrelated A/M exomes identified a novel c.2122G>A, p.(Gly708Arg) mutation in an additional patient with unilateral microphthalmia, bilateral microcornea and Peters anomaly; the mutation was absent in the unaffected mother and the unaffected father was not available. Mutations in COL4A1 have been linked to a spectrum of human disorders; the most consistent feature is cerebrovascular disease with variable ocular anomalies, kidney and muscle defects. This study expands the spectrum of COL4A1 phenotypes and indicates screening in patients with A/M regardless of MRI findings or presumed inheritance pattern.

  2. Assessing Reliability of Cellulose Hydrolysis Models to Support Biofuel Process Design – Identifiability and Uncertainty Analysis

    DEFF Research Database (Denmark)

    Sin, Gürkan; Meyer, Anne S.; Gernaey, Krist

    2010-01-01

    The reliability of cellulose hydrolysis models is studied using the NREL model. An identifiability analysis revealed that only 6 out of 26 parameters are identifiable from the available data (typical hydrolysis experiments). Attempting to identify a higher number of parameters (as done in the ori...... to analyze the uncertainty of model predictions. This allows judging the fitness of the model to the purpose under uncertainty. Hence we recommend uncertainty analysis as a proactive solution when faced with model uncertainty, which is the case for biofuel process development research....

  3. Analysis of genetic diversity identified by amplified fragment length polymorphism marker in hybrid wheat.

    Science.gov (United States)

    Ejaz, M; Qidi, Z; Gaisheng, Z; Na, N; Huiyan, Z; Qunzhu, W

    2015-01-01

    Amplified fragment length polymorphism markers were used to assess genetic diversity in 10 male sterile wheat crop lines (hetero-cytoplasm with the same nucleus) in relation to a restorer wheat line. These male sterile lines were evaluated using 64 amplified fragment length polymorphism primer combinations, and 13 primers produced polymorphic bands, generating a total 682 fragments. Of the 682 fragments, 113 were polymorphic. The polymorphic information content and marker index values demonstrated the utility of the primer combinations used in the present study. Unweighted pair group method with arithmetic mean and principal coordinate analysis of the genotypic data revealed clustering of accessions based on genetic relationships, and accessions were separated into 2 groups with their restorer line. Jaccard's similarity coefficient values suggested good variability among the male sterile lines, indicating their utility in breeding programs. The fallouts of analysis of molecular variance showed large within-group population variation, accounting for 77% of variation, while among-group comparison accounted for 23% of the total molecular variation, which was statistically significant. The molecular diversity observed in this study will be useful for selecting appropriate accessions for plant improvement and hybridization through molecular-breeding approaches and for developing suitable conservation strategies. PMID:26345825

  4. Molecular characterisation of blaESBL-harbouring conjugative plasmids identified in multi-drug resistant Escherichia coli isolated from food-producing animals and healthy humans

    Directory of Open Access Journals (Sweden)

    Juan eWang

    2013-07-01

    Full Text Available Background: Extended-spectrum β-lactamse (ESBL-encoding genes are frequently mapped to plasmids, yet few of these structures have been characterized at the molecular level, to date.Methods: Eighty-seven ESBL-producing E. coli were isolated from fecal samples of food-producing animals and healthy humans in Switzerland from 2009 to 2011. Plasmid DNA of all isolates was purified. Broth mating assays were carried out individually for 32 isolates to determine if the ESBL marker could be transferred by conjugation. The plasmid sizes were determined by S1 nuclease pulsed-field gel electrophoresis (PFGE and the plasmids were typed by PCR-based replicon typing. Susceptibility tests by disk diffusion followed with a re-analysis S1-nuclease PFGE and PCR reactions were performed to confirm plasmid transfer. Microarray was performed to detect additional antibiotic resistance markers and multi-locus sequence typing (MLST was also performed in selected donor strains. The phylotypes were identified by triplex PCR.Results: About half (n=46 of the 87 isolates carried small (< 20-kb plasmids. All selected 32 isolates contained large plasmids (ranging in sizes from 20- to 600-kb. Eleven plasmid replicon types were detected. Of these, IncFIA (n=5, IncFIB (n=9 and IncK/B (n=4 were common. Nine isolates demonstrated the ability to transfer their cefotaxime resistance marker at high transfer rates. Plasmid profile re-analysis of these transconjugants identified 16 plasmids. IncFIB and IncI1 were the most prevalent replicon types. Phylogenetic grouping showed that five of the nine donor strains belonged to phylogroup B1. Nine different STs were identified in nine tested donor strains.Conclusions: Characterization of these ESBL-encoding conjugative plasmids extends our understanding on these resistance markers in multi-drug resistant E. coli cultured from healthy human and animal sources.

  5. A Numerical Procedure for Model Identifiability Analysis Applied to Enzyme Kinetics

    DEFF Research Database (Denmark)

    Daele, Timothy, Van; Van Hoey, Stijn; Gernaey, Krist;

    2015-01-01

    structure evaluation by assessing the local identifiability characteristics of the parameters. Moreover, such a procedure should be generic to make sure it can be applied independent from the structure of the model. We hereby apply a numerical identifiability approach which is based on the work of Walter...... and Pronzato (1997) and which can be easily set up for any type of model. In this paper the proposed approach is applied to the forward reaction rate of the enzyme kinetics proposed by Shin and Kim(1998). Structural identifiability analysis showed that no local structural model problems were occurring....... In contrast, the practical identifiability analysis revealed that high values of the forward rate parameter Vf led to identifiability problems. These problems were even more pronounced athigher substrate concentrations, which illustrates the importance of a proper experimental designto avoid...

  6. Consolidating metabolite identifiers to enable contextual and multi-platform metabolomics data analysis

    Directory of Open Access Journals (Sweden)

    Saito Kazuki

    2010-04-01

    Full Text Available Abstract Background Analysis of data from high-throughput experiments depends on the availability of well-structured data that describe the assayed biomolecules. Procedures for obtaining and organizing such meta-data on genes, transcripts and proteins have been streamlined in many data analysis packages, but are still lacking for metabolites. Chemical identifiers are notoriously incoherent, encompassing a wide range of different referencing schemes with varying scope and coverage. Online chemical databases use multiple types of identifiers in parallel but lack a common primary key for reliable database consolidation. Connecting identifiers of analytes found in experimental data with the identifiers of their parent metabolites in public databases can therefore be very laborious. Results Here we present a strategy and a software tool for integrating metabolite identifiers from local reference libraries and public databases that do not depend on a single common primary identifier. The program constructs groups of interconnected identifiers of analytes and metabolites to obtain a local metabolite-centric SQLite database. The created database can be used to map in-house identifiers and synonyms to external resources such as the KEGG database. New identifiers can be imported and directly integrated with existing data. Queries can be performed in a flexible way, both from the command line and from the statistical programming environment R, to obtain data set tailored identifier mappings. Conclusions Efficient cross-referencing of metabolite identifiers is a key technology for metabolomics data analysis. We provide a practical and flexible solution to this task and an open-source program, the metabolite masking tool (MetMask, available at http://metmask.sourceforge.net, that implements our ideas.

  7. A novel high-throughput in vivo molecular screen for shade avoidance mutants identifies a novel phyA mutation.

    Science.gov (United States)

    Wang, Xuewen; Roig-Villanova, Irma; Khan, Safina; Shanahan, Hugh; Quail, Peter H; Martinez-Garcia, Jaime F; Devlin, Paul F

    2011-05-01

    The shade avoidance syndrome (SAS) allows plants to anticipate and avoid shading by neighbouring plants by initiating an elongation growth response. The phytochrome photoreceptors are able to detect a reduction in the red:far red ratio in incident light, the result of selective absorption of red and blue wavelengths by proximal vegetation. A shade-responsive luciferase reporter line (PHYB::LUC) was used to carry out a high-throughput screen to identify novel SAS mutants. The dracula 1 (dra1) mutant, that showed no avoidance of shade for the PHYB::LUC response, was the result of a mutation in the PHYA gene. Like previously characterized phyA mutants, dra1 showed a long hypocotyl in far red light and an enhanced hypocotyl elongation response to shade. However, dra1 additionally showed a long hypocotyl in red light. Since phyB levels are relatively unaffected in dra1, this gain-of-function red light phenotype strongly suggests a disruption of phyB signalling. The dra1 mutation, G773E within the phyA PAS2 domain, occurs at a residue absolutely conserved among phyA sequences. The equivalent residue in phyB is absolutely conserved as a threonine. PAS domains are structurally conserved domains involved in molecular interaction. Structural modelling of the dra1 mutation within the phyA PAS2 domain shows some similarity with the structure of the phyB PAS2 domain, suggesting that the interference with phyB signalling may be the result of non-functional mimicry. Hence, it was hypothesized that this PAS2 residue forms a key distinction between the phyA and phyB phytochrome species.

  8. Molecular and functional analyses of a maize autoactive NB-LRR protein identify precise structural requirements for activity.

    Directory of Open Access Journals (Sweden)

    Guan-Feng Wang

    2015-02-01

    Full Text Available Plant disease resistance is often mediated by nucleotide binding-leucine rich repeat (NLR proteins which remain auto-inhibited until recognition of specific pathogen-derived molecules causes their activation, triggering a rapid, localized cell death called a hypersensitive response (HR. Three domains are recognized in one of the major classes of NLR proteins: a coiled-coil (CC, a nucleotide binding (NB-ARC and a leucine rich repeat (LRR domains. The maize NLR gene Rp1-D21 derives from an intergenic recombination event between two NLR genes, Rp1-D and Rp1-dp2 and confers an autoactive HR. We report systematic structural and functional analyses of Rp1 proteins in maize and N. benthamiana to characterize the molecular mechanism of NLR activation/auto-inhibition. We derive a model comprising the following three main features: Rp1 proteins appear to self-associate to become competent for activity. The CC domain is signaling-competent and is sufficient to induce HR. This can be suppressed by the NB-ARC domain through direct interaction. In autoactive proteins, the interaction of the LRR domain with the NB-ARC domain causes de-repression and thus disrupts the inhibition of HR. Further, we identify specific amino acids and combinations thereof that are important for the auto-inhibition/activity of Rp1 proteins. We also provide evidence for the function of MHD2, a previously uncharacterized, though widely conserved NLR motif. This work reports several novel insights into the precise structural requirement for NLR function and informs efforts towards utilizing these proteins for engineering disease resistance.

  9. An RNA interference lethality screen of the human druggable genome to identify molecular vulnerabilities in epithelial ovarian cancer.

    Directory of Open Access Journals (Sweden)

    Geetika Sethi

    Full Text Available Targeted therapies have been used to combat many tumor types; however, few have effectively improved the overall survival in women with epithelial ovarian cancer, begging for a better understanding of this deadly disease and identification of essential drivers of tumorigenesis that can be targeted effectively. Therefore, we used a loss-of-function screening approach to help identify molecular vulnerabilities that may represent key points of therapeutic intervention. We employed an unbiased high-throughput lethality screen using a 24,088 siRNA library targeting over 6,000 druggable genes and studied their effects on growth and/or survival of epithelial ovarian cancer (EOC cell lines. The top 300 "hits" affecting the viability of A1847 cells were rescreened across additional EOC cell lines and non-tumorigenic, human immortalized ovarian epithelial cell lines. Fifty-three gene candidates were found to exhibit effects in all tumorigenic cell lines tested. Extensive validation of these hits refined the list to four high quality candidates (HSPA5, NDC80, NUF2, and PTN. Mechanistic studies show that silencing of three genes leads to increased apoptosis, while HSPA5 silencing appears to alter cell growth through G1 cell cycle arrest. Furthermore, two independent gene expression studies show that NDC80, NUF2 and PTN were significantly aberrantly overexpressed in serous adenocarcinomas. Overall, our functional genomics results integrated with the genomics data provide an important unbiased avenue towards the identification of prospective therapeutic targets for drug discovery, which is an urgent and unmet clinical need for ovarian cancer.

  10. New molecular scaffolds for the design of Mycobacterium tuberculosis type II dehydroquinase inhibitors identified using ligand and receptor based virtual screening.

    Science.gov (United States)

    Kumar, Ashutosh; Siddiqi, Mohammad Imran; Miertus, Stanislav

    2010-04-01

    Using ligand and receptor based virtual screening approaches we have identified potential virtual screening hits targeting type II dehydroquinase from Mycobacterium tuberculosis, an effective and validated anti-mycobacterial target. Initially, we applied a virtual screening workflow based on a combination of 2D structural fingerprints, 3D pharmacophore and molecular docking to identify compounds that rigidly match specific aspects of ligand bioactive conformation. Subsequently, the resulting compounds were ranked and prioritized using receptor interaction fingerprint based scoring and quantitative structure activity relationship model developed using already known actives. The virtual screening hits prioritized belong to several classes of molecular scaffolds with several available substitution positions that could allow chemical modification to enhance binding affinity. Finally, identified hits may be useful to a medicinal chemist or combinatorial chemist to pick up the new molecular starting points for medicinal chemistry optimization for the design of novel type II dehydroquinase inhibitors. PMID:19816720

  11. Basal gene expression by lung CD4+ T cells in chronic obstructive pulmonary disease identifies independent molecular correlates of airflow obstruction and emphysema extent.

    Directory of Open Access Journals (Sweden)

    Christine M Freeman

    Full Text Available Lung CD4+ T cells accumulate as chronic obstructive pulmonary disease (COPD progresses, but their role in pathogenesis remains controversial. To address this controversy, we studied lung tissue from 53 subjects undergoing clinically-indicated resections, lung volume reduction, or transplant. Viable single-cell suspensions were analyzed by flow cytometry or underwent CD4+ T cell isolation, followed either by stimulation with anti-CD3 and cytokine/chemokine measurement, or by real-time PCR analysis. In lung CD4+ T cells of most COPD subjects, relative to lung CD4+ T cells in smokers with normal spirometry: (a stimulation induced minimal IFN-γ or other inflammatory mediators, but many subjects produced more CCL2; (b the T effector memory subset was less uniformly predominant, without correlation with decreased IFN-γ production. Analysis of unstimulated lung CD4+ T cells of all subjects identified a molecular phenotype, mainly in COPD, characterized by markedly reduced mRNA transcripts for the transcription factors controlling TH1, TH2, TH17 and FOXP3+ T regulatory subsets and their signature cytokines. This mRNA-defined CD4+ T cell phenotype did not result from global inability to elaborate mRNA; increased transcripts for inhibitory CD28 family members or markers of anergy; or reduced telomerase length. As a group, these subjects had significantly worse spirometry, but not DLCO, relative to subjects whose lung CD4+ T cells expressed a variety of transcripts. Analysis of mRNA transcripts of unstimulated lung CD4+ T cell among all subjects identified two distinct molecular correlates of classical COPD clinical phenotypes: basal IL-10 transcripts correlated independently and inversely with emphysema extent (but not spirometry; by contrast, unstimulated IFN-γ transcripts correlated independently and inversely with reduced spirometry (but not reduced DLCO or emphysema extent. Aberrant lung CD4+ T cells polarization appears to be common in advanced

  12. Controlling the sense of molecular rotation: classical vs quantum analysis

    CERN Document Server

    Khodorkovsky, Yuri; Hasegawa, Hirokazu; Ohshima, Yasuhiro; Averbukh, Ilya Sh

    2010-01-01

    Recently, it was predicted theoretically and verified experimentally that a pair of delayed and cross-polarized short laser pulses can create molecular ensembles with a well defined sense of rotation (clockwise or counterclockwise). Here we provide a comparative study of the classical and quantum aspects of the underlying mechanism for linear molecules and for symmetric tops, like benzene molecules, that were used for the first experimental demonstration of the effect. Very good quantitative agreement is found between the classical description of the process and the rigorous quantum mechanical analysis at the relevant experimental conditions. Both approaches predict the same optimal values for the delay between pulses and the angle between them, and deliver the same magnitude of the induced oriented angular momentum of the molecular ensemble. As expected, quantum and classical analysis substantially deviate when the delay between pulses is comparable with the period of quantum rotational revivals. However, ti...

  13. TREEFINDER: a powerful graphical analysis environment for molecular phylogenetics

    Directory of Open Access Journals (Sweden)

    von Haeseler Arndt

    2004-06-01

    Full Text Available Abstract Background Most analysis programs for inferring molecular phylogenies are difficult to use, in particular for researchers with little programming experience. Results TREEFINDER is an easy-to-use integrative platform-independent analysis environment for molecular phylogenetics. In this paper the main features of TREEFINDER (version of April 2004 are described. TREEFINDER is written in ANSI C and Java and implements powerful statistical approaches for inferring gene tree and related analyzes. In addition, it provides a user-friendly graphical interface and a phylogenetic programming language. Conclusions TREEFINDER is a versatile framework for analyzing phylogenetic data across different platforms that is suited both for exploratory as well as advanced studies.

  14. Molecular Hydrogen Optical Depth Templates for FUSE Data Analysis

    CERN Document Server

    McCandliss, S R

    2003-01-01

    The calculation and use of molecular hydrogen optical depth templates to quickly identify and model molecular hydrogen absorption features longward of the Lyman edge at 912 Angstroms are described. Such features are commonly encountered in spectra obtained by the Far Ultraviolet Spectroscopic Explorer and also in spectra obtained by the Space Telescope Imaging Spectrograph, albeit less commonly. Individual templates are calculated containing all the Lyman and Werner transitions originating from a single rotational state (J'') of the 0th vibrational level (v'') of the ground electronic state. Templates are provided with 0.01 Angstrom sampling for doppler parameters ranging from 2 <= b <= 20 km s^-1 and rotational states 0 <= J'' <= 15. Optical depth templates for excited vibrational states are also available for select doppler parameters. Each template is calculated for a fiducial column density of log[N(cm^-2)] = 21 and may be scaled to any column less than this value without loss of accuracy. The...

  15. Comparative analysis of Salmonella genomes identifies a metabolic network for escalating growth in the inflamed gut.

    Science.gov (United States)

    Nuccio, Sean-Paul; Bäumler, Andreas J

    2014-03-18

    The Salmonella genus comprises a group of pathogens associated with illnesses ranging from gastroenteritis to typhoid fever. We performed an in silico analysis of comparatively reannotated Salmonella genomes to identify genomic signatures indicative of disease potential. By removing numerous annotation inconsistencies and inaccuracies, the process of reannotation identified a network of 469 genes involved in central anaerobic metabolism, which was intact in genomes of gastrointestinal pathogens but degrading in genomes of extraintestinal pathogens. This large network contained pathways that enable gastrointestinal pathogens to utilize inflammation-derived nutrients as well as many of the biochemical reactions used for the enrichment and biochemical discrimination of Salmonella serovars. Thus, comparative genome analysis identifies a metabolic network that provides clues about the strategies for nutrient acquisition and utilization that are characteristic of gastrointestinal pathogens. IMPORTANCE While some Salmonella serovars cause infections that remain localized to the gut, others disseminate throughout the body. Here, we compared Salmonella genomes to identify characteristics that distinguish gastrointestinal from extraintestinal pathogens. We identified a large metabolic network that is functional in gastrointestinal pathogens but decaying in extraintestinal pathogens. While taxonomists have used traits from this network empirically for many decades for the enrichment and biochemical discrimination of Salmonella serovars, our findings suggest that it is part of a "business plan" for growth in the inflamed gastrointestinal tract. By identifying a large metabolic network characteristic of Salmonella serovars associated with gastroenteritis, our in silico analysis provides a blueprint for potential strategies to utilize inflammation-derived nutrients and edge out competing gut microbes.

  16. Application of atomic absorption in molecular analysis (spectrophotometry)

    International Nuclear Information System (INIS)

    The apparatus of atomic absorption has been considered by all the experts in chemical analysis as one of the most important equipments in actual utilization in such field. Among its several applications one should emphasize direct and indirect metals analyses using flame, graphite furnace, cold vapor generator,... Besides such known applications, the authors have developed at the R and D Center of CSN a patent pendent method for the utilization of such equipment for molecular analysis, in substitution of a sophisticated and specific apparatus. (Author)

  17. Identify the signature genes for diagnose of uveal melanoma by weight gene co-expression network analysis

    Institute of Scientific and Technical Information of China (English)

    Kai; Shi; Zhi-Tong; Bing; Gui-Qun; Cao; Ling; Guo; Ya-Na; Cao; Hai-Ou; Jiang; Mei-Xia; Zhang

    2015-01-01

    AIM: To identify and understand the relationship between co-expression pattern and clinic traits in uveal melanoma, weighted gene co-expression network analysis(WGCNA) is applied to investigate the gene expression levels and patient clinic features. Uveal melanoma is the most common primary eye tumor in adults. Although many studies have identified some important genes and pathways that were relevant to progress of uveal melanoma, the relationship between co-expression and clinic traits in systems level of uveal melanoma is unclear yet. We employ WGCNA to investigate the relationship underlying molecular and phenotype in this study.METHODS: Gene expression profile of uveal melanoma and patient clinic traits were collected from the Gene Expression Omnibus(GEO) database. The gene co-expression is calculated by WGCNA that is the R package software. The package is used to analyze the correlation between pairs of expression levels of genes.The function of the genes were annotated by gene ontology(GO).RESULTS: In this study, we identified four co-expression modules significantly correlated with clinictraits. Module blue positively correlated with radiotherapy treatment. Module purple positively correlates with tumor location(sclera) and negatively correlates with patient age. Module red positively correlates with sclera and negatively correlates with thickness of tumor. Module black positively correlates with the largest tumor diameter(LTD). Additionally, we identified the hug gene(top connectivity with other genes) in each module. The hub gene RPS15 A, PTGDS, CD53 and MSI2 might play a vital role in progress of uveal melanoma.CONCLUSION: From WGCNA analysis and hub gene calculation, we identified RPS15 A, PTGDS, CD53 and MSI2 might be target or diagnosis for uveal melanoma.

  18. 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.

  19. Identifying Innovative Interventions to Promote Healthy Eating Using Consumption-Oriented Food Supply Chain Analysis

    OpenAIRE

    Hawkes, Corinna, ed.

    2009-01-01

    The mapping and analysis of supply chains is a technique increasingly used to address problems in the food system. Yet such supply chain management has not yet been applied as a means of encouraging healthier diets. Moreover, most policies recommended to promote healthy eating focus on the consumer end of the chain. This article proposes a consumption-oriented food supply chain analysis to identify the changes needed in the food supply chain to create a healthier food environment, measured in...

  20. Exploratory data analysis of the dependencies between skin permeability, molecular weight and log P.

    Science.gov (United States)

    Kilian, D; Lemmer, H J R; Gerber, M; du Preez, J L; du Plessis, J

    2016-06-01

    Molecular weight and log P remain the most frequently used physicochemical properties in models that predict skin permeability. However, several reports over the past two decades have suggested that predictions made by these models may not be sufficiently accurate. In this study, exploratory data analysis of the probabilistic dependencies between molecular weight, log P and log Kp was performed on a dataset constructed from the combination of several popular datasets. The results suggest that, in general, molecular weight and log P are poorly correlated to log Kp. However, after employing several exploratory data analysis techniques, regions within the dataset of statistically significant dependence were identified. As an example of the applicability of the information extracted from the exploratory data analyses, a multiple linear regression model was constructed, bounded by the ranges of dependence. This model gave reasonable approximations to log Kp values obtained from skin permeability studies of selected non-steroidal ant-inflammatory drugs (NSAIDs) administered from a buffer solution and a lipid-based drug delivery system. A method of testing whether a given drug falls within the regions of statistical dependence was also presented. Knowing the ranges within which molecular weight and log P are statistically related to log Kp can supplement existing methods of screening, risk analysis or early drug development decision making to add confidence to predictions made regarding skin permeability.

  1. Molecular genetic analysis of regions of the murine genome associated with radiation-induced mutations

    International Nuclear Information System (INIS)

    The authors are exploiting the large array of radiation-induced mutations to develop both detailed molecular and functional maps of selected small model regions (as opposed to specific genes) within the mouse genome. Through the integrated use of recombinant DNA technology and classical genetic and cytogenetic analysis, they hope to relate the structure and function of these regions to the study of both normal and abnormal mammalian development. Over the years, the germ-line mutagenesis program has generated a valuable array of induced mutations at several specific loci scattered throughout the murine genome. Many of these mutations are multilocus deletions of chromosomal DNA. Genetic analysis of these types of lesions has detected passenger mutations of wide-ranging effect and severity, and has generated gross functional maps of entire chromosomal regions. They have initiated a program to expand the molecular analysis of these types of deletion mutations. This program exploits the deletion mutations and other chromosomal rearrangements to obtain molecular clones of wild-type DNA that map to regions absent in mutants carrying the deletions. These clones will then be used to correlate the resultant molecular/physical map of the chromosomal region with the genetic/functional map in both mutant and wild-type individuals. Such correlations are essential to a strategy for identifying as many of the genes as possible in a particular region of the genome and for ascertaining their role(s) in the normal development of the mouse

  2. Molecular analysis of rice plant mutated after space flight

    Science.gov (United States)

    Cheng, Z.; Li, C.; Wei, L.; Xu, D.; Gu, D.; Guan, S.; Zhao, H.; Xin, P.; Sun, Y.

    We have obtained several rice mutants planted from seeds flown on recoverable satellites. Some new traits, such as good yields, diseases resistances and higher nutrient values, have been identified, putatively as consequences of the space environment. Radiation inside the Chinese recoverable satellite was composed of low flux of high energy particles (>40 Mev/u). To study the mechanisms of plant mutations induced by the space environment, we used dry rice seeds as a model to identify the phenotype of mutations, and used the wealth of the rice genome to identify the mutated genes in the mutants. The research included collecting rice plant mutants in the seeds flown on the satellites, identifying the nature of genomic and proteomic alterations, modifications and identifying the functional changes of the specific genes. The study showed that the rice seeds are a good model for exploring biological effect of space environment since 1) it is easy fly the seeds without specific hardware and crew work, 2) it is easy to obtain pure mutant breed lines for cloning DNA sequence in order to compare with the sequence in the wild type, and 3) it is easy to quantitatively analyze genetics using advanced molecular techniques.

  3. Identifying Effective Spelling Interventions Using a Brief Experimental Analysis and Extended Analysis

    Science.gov (United States)

    McCurdy, Merilee; Clure, Lynne F.; Bleck, Amanda A.; Schmitz, Stephanie L.

    2016-01-01

    Spelling is an important skill that is crucial to effective written communication. In this study, brief experimental analysis procedures were used to examine spelling instruction strategies (e.g., whole word correction; word study strategy; positive practice; and cover, copy, and compare) for four students. In addition, an extended analysis was…

  4. Identifying Skill Requirements for GIS Positions: A Content Analysis of Job Advertisements

    Science.gov (United States)

    Hong, Jung Eun

    2016-01-01

    This study identifies the skill requirements for geographic information system (GIS) positions, including GIS analysts, programmers/developers/engineers, specialists, and technicians, through a content analysis of 946 GIS job advertisements from 2007-2014. The results indicated that GIS job applicants need to possess high levels of GIS analysis…

  5. Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis

    NARCIS (Netherlands)

    B.F. Voight (Benjamin); L.J. Scott (Laura); V. Steinthorsdottir (Valgerdur); A.D. Morris (Andrew); C. Dina (Christian); R.P. Welch (Ryan); E. Zeggini (Eleftheria); C. Huth (Cornelia); Y.S. Aulchenko (Yurii); G. Thorleifsson (Gudmar); L.J. McCulloch (Laura); T. Ferreira (Teresa); H. Grallert (Harald); N. Amin (Najaf); G. Wu (Guanming); C.J. Willer (Cristen); S. Raychaudhuri (Soumya); S.A. McCarroll (Steven); C. Langenberg (Claudia); O.M. Hofmann (Oliver); J. Dupuis (Josée); L. Qi (Lu); A.V. Segrè (Ayellet); M. van Hoek (Mandy); P. Navarro (Pau); K.G. Ardlie (Kristin); B. Balkau (Beverley); R. Benediktsson (Rafn); A.J. Bennett (Amanda); R. Blagieva (Roza); E. Boerwinkle (Eric); L.L. Bonnycastle (Lori); K.B. Boström (Kristina Bengtsson); B. Bravenboer (Bert); S. Bumpstead (Suzannah); N.P. Burtt (Noël); G. Charpentier (Guillaume); P.S. Chines (Peter); M. Cornelis (Marilyn); D.J. Couper (David); G. Crawford (Gabe); A.S.F. Doney (Alex); K.S. Elliott (Katherine); M.R. Erdos (Michael); C.S. Fox (Caroline); C.S. Franklin (Christopher); M. Ganser (Martha); C. Gieger (Christian); N. Grarup (Niels); T. Green (Todd); S. Griffin (Simon); C.J. Groves (Christopher); C. Guiducci (Candace); S. Hadjadj (Samy); N. Hassanali (Neelam); C. Herder (Christian); B. Isomaa (Bo); A.U. Jackson (Anne); P.R.V. Johnson (Paul); T. Jørgensen (Torben); W.H.L. Kao (Wen); N. Klopp (Norman); A. Kong (Augustine); P. Kraft (Peter); J. Kuusisto (Johanna); T. Lauritzen (Torsten); M. Li (Man); A. Lieverse (Aloysius); C.M. Lindgren (Cecilia); V. Lyssenko (Valeriya); M. Marre (Michel); T. Meitinger (Thomas); K. Midthjell (Kristian); M.A. Morken (Mario); N. Narisu (Narisu); P. Nilsson (Peter); K.R. Owen (Katharine); F. Payne (Felicity); J.R.B. Perry (John); A.K. Petersen; C. Platou (Carl); C. Proença (Christine); I. Prokopenko (Inga); W. Rathmann (Wolfgang); N.W. Rayner (Nigel William); N.R. Robertson (Neil); G. Rocheleau (Ghislain); M. Roden (Michael); M.J. Sampson (Michael); R. Saxena (Richa); B.M. Shields (Beverley); P. Shrader (Peter); G. Sigurdsson (Gunnar); T. Sparsø (Thomas); K. Strassburger (Klaus); H.M. Stringham (Heather); Q. Sun (Qi); A.J. Swift (Amy); B. Thorand (Barbara); J. Tichet (Jean); T. Tuomi (Tiinamaija); R.M. van Dam (Rob); T.W. van Haeften (Timon); T.W. van Herpt (Thijs); J.V. van Vliet-Ostaptchouk (Jana); G.B. Walters (Bragi); M.N. Weedon (Michael); C. Wijmenga (Cisca); J.C.M. Witteman (Jacqueline); R.N. Bergman (Richard); S. Cauchi (Stephane); F.S. Collins (Francis); A.L. Gloyn (Anna); U. Gyllensten (Ulf); T. Hansen (Torben); W.A. Hide (Winston); G.A. Hitman (Graham); A. Hofman (Albert); D. Hunter (David); K. Hveem (Kristian); M. Laakso (Markku); K.L. Mohlke (Karen); C.N.A. Palmer (Colin); P.P. Pramstaller (Peter Paul); I. Rudan (Igor); E.J.G. Sijbrands (Eric); L.D. Stein (Lincoln); J. Tuomilehto (Jaakko); A.G. Uitterlinden (André); M. Walker (Mark); N.J. Wareham (Nick); G.R. Abecasis (Gonçalo); B.O. Boehm (Bernhard); H. Campbell (Harry); M.J. Daly (Mark); A.T. Hattersley (Andrew); F.B. Hu (Frank); J.B. Meigs (James); J.S. Pankow (James); O. Pedersen (Oluf); H.E. Wichmann (Erich); I. Barroso (Inês); J.C. Florez (Jose); T.M. Frayling (Timothy); L. Groop (Leif); R. Sladek (Rob); U. Thorsteinsdottir (Unnur); J.F. Wilson (James); T. Illig (Thomas); P. Froguel (Philippe); P. Tikka-Kleemola (Päivi); J-A. Zwart (John-Anker); D. Altshuler (David); M. Boehnke (Michael); M.I. McCarthy (Mark); R.M. Watanabe (Richard)

    2010-01-01

    textabstractBy combining genome-wide association data from 8,130 individuals with type 2 diabetes (T2D) and 38,987 controls of European descent and following up previously unidentified meta-analysis signals in a further 34,412 cases and 59,925 controls, we identified 12 new T2D association signals w

  6. Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis

    NARCIS (Netherlands)

    Voight, Benjamin F.; Scott, Laura J.; Steinthorsdottir, Valgerdur; Morris, Andrew P.; Dina, Christian; Welch, Ryan P.; Zeggini, Eleftheria; Huth, Cornelia; Aulchenko, Yurii S.; Thorleifsson, Gudmar; McCulloch, Laura J.; Ferreira, Teresa; Grallert, Harald; Amin, Najaf; Wu, Guanming; Willer, Cristen J.; Raychaudhuri, Soumya; McCarroll, Steve A.; Langenberg, Claudia; Hofmann, Oliver M.; Dupuis, Josee; Qi, Lu; Segre, Ayellet V.; van Hoek, Mandy; Navarro, Pau; Ardlie, Kristin; Balkau, Beverley; Benediktsson, Rafn; Bennett, Amanda J.; Blagieva, Roza; Boerwinkle, Eric; Bonnycastle, Lori L.; Bostrom, Kristina Bengtsson; Bravenboer, Bert; Bumpstead, Suzannah; Burtt, Noisel P.; Charpentier, Guillaume; Chines, Peter S.; Cornelis, Marilyn; Couper, David J.; Crawford, Gabe; Doney, Alex S. F.; Elliott, Katherine S.; Elliott, Amanda L.; Erdos, Michael R.; Fox, Caroline S.; Franklin, Christopher S.; Ganser, Martha; Gieger, Christian; Grarup, Niels; Green, Todd; Griffin, Simon; Groves, Christopher J.; Guiducci, Candace; Hadjadj, Samy; Hassanali, Neelam; Herder, Christian; Isomaa, Bo; Jackson, Anne U.; Johnson, Paul R. V.; Jorgensen, Torben; Kao, Wen H. L.; Klopp, Norman; Kong, Augustine; Kraft, Peter; Kuusisto, Johanna; Lauritzen, Torsten; Li, Man; Lieverse, Aloysius; Lindgren, Cecilia M.; Lyssenko, Valeriya; Marre, Michel; Meitinger, Thomas; Midthjell, Kristian; Morken, Mario A.; Narisu, Narisu; Nilsson, Peter; Owen, Katharine R.; Payne, Felicity; Perry, John R. B.; Petersen, Ann-Kristin; Platou, Carl; Proenca, Christine; Prokopenko, Inga; Rathmann, Wolfgang; Rayner, N. William; Robertson, Neil R.; Rocheleau, Ghislain; Roden, Michael; Sampson, Michael J.; Saxena, Richa; Shields, Beverley M.; Shrader, Peter; Sigurdsson, Gunnar; Sparso, Thomas; Strassburger, Klaus; Stringham, Heather M.; Sun, Qi; Swift, Amy J.; Thorand, Barbara; Tichet, Jean; Tuomi, Tiinamaija; van Dam, Rob M.; van Haeften, Timon W.; van Herpt, Thijs; van Vliet-Ostaptchouk, Jana V.; Walters, G. Bragi; Weedon, Michael N.; Wijmenga, Cisca; Witteman, Jacqueline; Bergman, Richard N.; Cauchi, Stephane; Collins, Francis S.; Gloyn, Anna L.; Gyllensten, Ulf; Hansen, Torben; Hide, Winston A.; Hitman, Graham A.; Hofman, Albert; Hunter, David J.; Hveem, Kristian; Laakso, Markku; Mohlke, Karen L.; Morris, Andrew D.; Palmer, Colin N. A.; Pramstaller, Peter P.; Rudan, Igor; Sijbrands, Eric; Stein, Lincoln D.; Tuomilehto, Jaakko; Uitterlinden, Andre; Walker, Mark; Wareham, Nicholas J.; Watanabe, Richard M.; Abecasis, Goncalo R.; Boehm, Bernhard O.; Campbell, Harry; Daly, Mark J.; Hattersley, Andrew T.; Hu, Frank B.; Meigs, James B.; Pankow, James S.; Pedersen, Oluf; Wichmann, H-Erich; Barroso, Ines; Florez, Jose C.; Frayling, Timothy M.; Groop, Leif; Sladek, Rob; Thorsteinsdottir, Unnur; Wilson, James F.; Illig, Thomas; Froguel, Philippe; van Duijn, Cornelia M.; Stefansson, Kari; Altshuler, David; Boehnke, Michael; McCarthy, Mark I.

    2010-01-01

    By combining genome-wide association data from 8,130 individuals with type 2 diabetes (T2D) and 38,987 controls of European descent and following up previously unidentified meta-analysis signals in a further 34,412 cases and 59,925 controls, we identified 12 new T2D association signals with combined

  7. Genome-wide association study meta-analysis identifies seven new rheumatoid arthritis risk loci

    NARCIS (Netherlands)

    Stahl, Eli A.; Raychaudhuri, Soumya; Remmers, Elaine F.; Xie, Gang; Eyre, Stephen; Thomson, Brian P.; Li, Yonghong; Kurreeman, Fina A. S.; Zhernakova, Alexandra; Hinks, Anne; Guiducci, Candace; Chen, Robert; Alfredsson, Lars; Amos, Christopher I.; Ardlie, Kristin G.; Barton, Anne; Bowes, John; Brouwer, Elisabeth; Burtt, Noel P.; Catanese, Joseph J.; Coblyn, Jonathan; Coenen, Marieke J. H.; Costenbader, Karen H.; Criswell, Lindsey A.; Crusius, J. Bart A.; Cui, Jing; de Bakker, Paul I. W.; De Jager, Philip L.; Ding, Bo; Emery, Paul; Flynn, Edward; Harrison, Pille; Hocking, Lynne J.; Huizinga, Tom W. J.; Kastner, Daniel L.; Ke, Xiayi; Lee, Annette T.; Liu, Xiangdong; Martin, Paul; Morgan, Ann W.; Padyukov, Leonid; Posthumus, Marcel D.; Radstake, Timothy R. D. J.; Reid, David M.; Seielstad, Mark; Seldin, Michael F.; Shadick, Nancy A.; Steer, Sophia; Tak, Paul P.; Thomson, Wendy; van der Helm-van Mil, Annette H. M.; van der Horst-Bruinsma, Irene E.; van der Schoot, C. Ellen; van Riel, Piet L. C. M.; Weinblatt, Michael E.; Wilson, Anthony G.; Wolbink, Gert Jan; Wordsworth, B. Paul; Wijmenga, Cisca; Karlson, Elizabeth W.; Toes, Rene E. M.; de Vries, Niek; Begovich, Ann B.; Worthington, Jane; Siminovitch, Katherine A.; Gregersen, Peter K.; Klareskog, Lars; Plenge, Robert M.

    2010-01-01

    To identify new genetic risk factors for rheumatoid arthritis, we conducted a genome-wide association study meta-analysis of 5,539 autoantibody-positive individuals with rheumatoid arthritis (cases) and 20,169 controls of European descent, followed by replication in an independent set of 6,768 rheum

  8. Bioinformatics analysis identifies several intrinsically disordered human E3 ubiquitin-protein ligases

    DEFF Research Database (Denmark)

    Boomsma, Wouter; Nielsen, Sofie V; Lindorff-Larsen, Kresten;

    2016-01-01

    conduct a bioinformatics analysis to examine >600 human and S. cerevisiae E3 ligases to identify enzymes that are similar to San1 in terms of function and/or mechanism of substrate recognition. An initial sequence-based database search was found to detect candidates primarily based on the homology...

  9. Clinical Trial Registries Are of Minimal Use for Identifying Selective Outcome and Analysis Reporting

    Science.gov (United States)

    Norris, Susan L.; Holmer, Haley K.; Fu, Rongwei; Ogden, Lauren A.; Viswanathan, Meera S.; Abou-Setta, Ahmed M.

    2014-01-01

    Objective: This study aimed to examine selective outcome reporting (SOR) and selective analysis reporting (SAR) in randomized controlled trials (RCTs) and to explore the usefulness of trial registries for identifying SOR and SAR. Study Design and Setting: We selected one "index outcome" for each of three comparative effectiveness reviews…

  10. Genome-wide association scan meta-analysis identifies three loci influencing adiposity and fat distribution

    NARCIS (Netherlands)

    C.M. Lindgren (Cecilia); I.M. Heid (Iris); J.C. Randall (Joshua); C. Lamina (Claudia); V. Steinthorsdottir (Valgerdur); L. Qi (Lu); E.K. Speliotes (Elizabeth); G. Thorleifsson (Gudmar); C.J. Willer (Cristen); B.M. Herrera (Blanca); A.U. Jackson (Anne); N. Lim (Noha); P. Scheet (Paul); N. Soranzo (Nicole); N. Amin (Najaf); Y.S. Aulchenko (Yurii); J.C. Chambers (John); A. Drong (Alexander); J. Luan; H.N. Lyon (Helen); F. Rivadeneira Ramirez (Fernando); S. Sanna (Serena); N. Timpson (Nicholas); M.C. Zillikens (Carola); H.Z. Jing; P. Almgren (Peter); S. Bandinelli (Stefania); A.J. Bennett (Amanda); R.N. Bergman (Richard); L.L. Bonnycastle (Lori); S. Bumpstead (Suzannah); S.J. Chanock (Stephen); L. Cherkas (Lynn); P.S. Chines (Peter); L. Coin (Lachlan); C. Cooper (Charles); G. Crawford (Gabe); A. Doering (Angela); A. Dominiczak (Anna); A.S.F. Doney (Alex); S. Ebrahim (Shanil); P. Elliott (Paul); M.R. Erdos (Michael); K. Estrada Gil (Karol); L. Ferrucci (Luigi); G. Fischer (Guido); N.G. Forouhi (Nita); C. Gieger (Christian); H. Grallert (Harald); C.J. Groves (Christopher); S.M. Grundy (Scott); C. Guiducci (Candace); D. Hadley (David); A. Hamsten (Anders); A.S. Havulinna (Aki); A. Hofman (Albert); R. Holle (Rolf); J.W. Holloway (John); T. Illig (Thomas); B. Isomaa (Bo); L.C. Jacobs (Leonie); K. Jameson (Karen); P. Jousilahti (Pekka); F. Karpe (Fredrik); J. Kuusisto (Johanna); J. Laitinen (Jaana); G.M. Lathrop (Mark); D.A. Lawlor (Debbie); M. Mangino (Massimo); W.L. McArdle (Wendy); T. Meitinger (Thomas); M.A. Morken (Mario); A.P. Morris (Andrew); P. Munroe (Patricia); N. Narisu (Narisu); A. Nordström (Anna); B.A. Oostra (Ben); C.N.A. Palmer (Colin); F. Payne (Felicity); J. Peden (John); I. Prokopenko (Inga); F. Renström (Frida); A. Ruokonen (Aimo); V. Salomaa (Veikko); M.S. Sandhu (Manjinder); L.J. Scott (Laura); A. Scuteri (Angelo); K. Silander (Kaisa); K. Song (Kijoung); X. Yuan (Xin); H.M. Stringham (Heather); A.J. Swift (Amy); T. Tuomi (Tiinamaija); M. Uda (Manuela); P. Vollenweider (Peter); G. Waeber (Gérard); C. Wallace (Chris); G.B. Walters (Bragi); M.N. Weedon (Michael); J.C.M. Witteman (Jacqueline); C. Zhang (Cuilin); M. Caulfield (Mark); F.S. Collins (Francis); G.D. Smith; I.N.M. Day (Ian); P.W. Franks (Paul); A.T. Hattersley (Andrew); F.B. Hu (Frank); M.R. Jarvelin; A. Kong (Augustine); J.S. Kooner (Jaspal); M. Laakso (Markku); E. Lakatta (Edward); V. Mooser (Vincent); L. Peltonen (Leena Johanna); N.J. Samani (Nilesh); T.D. Spector (Timothy); D.P. Strachan (David); T. Tanaka (Toshiko); J. Tuomilehto (Jaakko); A.G. Uitterlinden (André); P. Tikka-Kleemola (Päivi); N.J. Wareham (Nick); H. Watkins (Hugh); D. Waterworth (Dawn); M. Boehnke (Michael); P. Deloukas (Panagiotis); L. Groop (Leif); D.J. Hunter (David); U. Thorsteinsdottir (Unnur); D. Schlessinger (David); H.E. Wichmann (Erich); T.M. Frayling (Timothy); G.R. Abecasis (Gonçalo); J.N. Hirschhorn (Joel); R.J.F. Loos (Ruth); J-A. Zwart (John-Anker); K.L. Mohlke (Karen); I. Barroso (Inês); M.I. McCarthy (Mark)

    2009-01-01

    textabstractTo identify genetic loci influencing central obesity and fat distribution, we performed a meta-analysis of 16 genome-wide association studies (GWAS, N = 38,580) informative for adult waist circumference (WC) and waist-hip ratio (WHR). We selected 26 SNPs for follow-up, for which the evid

  11. Using Latent Class Analysis to Identify Academic and Behavioral Risk Status in Elementary Students

    Science.gov (United States)

    King, Kathleen R.; Lembke, Erica S.; Reinke, Wendy M.

    2016-01-01

    Identifying classes of children on the basis of academic and behavior risk may have important implications for the allocation of intervention resources within Response to Intervention (RTI) and Multi-Tiered System of Support (MTSS) models. Latent class analysis (LCA) was conducted with a sample of 517 third grade students. Fall screening scores in…

  12. Identifying Barriers in Implementing Outcomes-Based Assessment Program Review: A Grounded Theory Analysis

    Science.gov (United States)

    Bresciani, Marilee J.

    2011-01-01

    The purpose of this grounded theory study was to identify the typical barriers encountered by faculty and administrators when implementing outcomes-based assessment program review. An analysis of interviews with faculty and administrators at nine institutions revealed a theory that faculty and administrators' promotion, tenure (if applicable),…

  13. Identifying sustainability issues using participatory SWOT analysis - A case study of egg production in the Netherlands

    NARCIS (Netherlands)

    Mollenhorst, H.; Boer, de I.J.M.

    2004-01-01

    The aim of this paper was to demonstrate how participatory strengths, weaknesses, opportunities and threats (SWOT) analysis can be used to identify relevant economic, ecological and societal (EES) issues for the assessment of sustainable development. This is illustrated by the case of egg production

  14. Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis

    DEFF Research Database (Denmark)

    Voight, Benjamin F; Scott, Laura J; Steinthorsdottir, Valgerdur;

    2010-01-01

    By combining genome-wide association data from 8,130 individuals with type 2 diabetes (T2D) and 38,987 controls of European descent and following up previously unidentified meta-analysis signals in a further 34,412 cases and 59,925 controls, we identified 12 new T2D association signals with combi...

  15. Identifying Contingency Requirements using Obstacle Analysis on an Unpiloted Aerial Vehicle

    Science.gov (United States)

    Lutz, Robyn R.; Nelson, Stacy; Patterson-Hine, Ann; Frost, Chad R.; Tal, Doron

    2005-01-01

    This paper describes experience using Obstacle Analysis to identify contingency requirements on an unpiloted aerial vehicle. A contingency is an operational anomaly, and may or may not involve component failure. The challenges to this effort were: ( I ) rapid evolution of the system while operational, (2) incremental autonomy as capabilities were transferred from ground control to software control and (3) the eventual safety-criticality of such systems as they begin to fly over populated areas. The results reported here are preliminary but show that Obstacle Analysis helped (1) identify new contingencies that appeared as autonomy increased; (2) identify new alternatives for handling both previously known and new contingencies; and (3) investigate the continued validity of existing software requirements for contingency handling. Since many mobile, intelligent systems are built using a development process that poses the same challenges, the results appear to have applicability to other similar systems.

  16. Gene expression meta-analysis identifies chromosomal regions involved in ovarian cancer survival

    DEFF Research Database (Denmark)

    Thomassen, Mads; Jochumsen, Kirsten M; Mogensen, Ole;

    2009-01-01

    the relation of gene expression and chromosomal position to identify chromosomal regions of importance for early recurrence of ovarian cancer. By use of *Gene Set Enrichment Analysis*, we have ranked chromosomal regions according to their association to survival. Over-representation analysis including 1......Ovarian cancer cells exhibit complex karyotypic alterations causing deregulation of numerous genes. Some of these genes are probably causal for cancer formation and local growth, whereas others are causal for metastasis and recurrence. By using publicly available data sets, we have investigated......-4 consecutive cytogenetic bands identified regions with increased expression for chromosome 5q12-14, and a very large region of chromosome 7 with the strongest signal at 7p15-13 among tumors from short-living patients. Reduced gene expression was identified at 4q26-32, 6p12-q15, 9p21-q32, and 11p14-11. We...

  17. DyNet: visualization and analysis of dynamic molecular interaction networks

    Science.gov (United States)

    Goenawan, Ivan H.; Lynn, David J.

    2016-01-01

    Summary: The ability to experimentally determine molecular interactions on an almost proteome-wide scale under different conditions is enabling researchers to move from static to dynamic network analysis, uncovering new insights into how interaction networks are physically rewired in response to different stimuli and in disease. Dynamic interaction data presents a special challenge in network biology. Here, we present DyNet, a Cytoscape application that provides a range of functionalities for the visualization, real-time synchronization and analysis of large multi-state dynamic molecular interaction networks enabling users to quickly identify and analyze the most ‘rewired’ nodes across many network states. Availability and Implementation: DyNet is available at the Cytoscape (3.2+) App Store (http://apps.cytoscape.org/apps/dynet). Contact: david.lynn@sahmri.com. Supplementary Information: Supplementary data are available at Bioinformatics online. PMID:27153624

  18. Metabolites production improvement by identifying minimal genomes and essential genes using flux balance analysis.

    Science.gov (United States)

    Salleh, Abdul Hakim Mohamed; Mohamad, Mohd Saberi; Deris, Safaai; Illias, Rosli Md

    2015-01-01

    With the advancement in metabolic engineering technologies, reconstruction of the genome of host organisms to achieve desired phenotypes can be made. However, due to the complexity and size of the genome scale metabolic network, significant components tend to be invisible. We proposed an approach to improve metabolite production that consists of two steps. First, we find the essential genes and identify the minimal genome by a single gene deletion process using Flux Balance Analysis (FBA) and second by identifying the significant pathway for the metabolite production using gene expression data. A genome scale model of Saccharomyces cerevisiae for production of vanillin and acetate is used to test this approach. The result has shown the reliability of this approach to find essential genes, reduce genome size and identify production pathway that can further optimise the production yield. The identified genes and pathways can be extendable to other applications especially in strain optimisation. PMID:26489144

  19. Analysis of multiple transcriptomes of the African oil palm (Elaeis guineensis) to identify reference genes for RT-qPCR.

    Science.gov (United States)

    Xia, Wei; Mason, Annaliese S; Xiao, Yong; Liu, Zheng; Yang, Yaodong; Lei, Xintao; Wu, Xiaoming; Ma, Zilong; Peng, Ming

    2014-08-20

    The African oil palm (Elaeis guineensis), which is grown in tropical and subtropical regions, is a highly productive oil-bearing crop. For gene expression-based analyses such as reverse transcription-quantitative real time PCR (RT-qPCR), reference genes are essential to provide a baseline with which to quantify relative gene expression. Normalization using reliable reference genes is critical in correctly interpreting expression data from RT-qPCR. In order to identify suitable reference genes in African oil palm, 17 transcriptomes of different tissues obtained from NCBI were systematically assessed for gene expression variation. In total, 53 putative candidate reference genes with coefficient of variation values <3.0 were identified: 18 in reproductive tissue and 35 in vegetative tissue. Analysis for enriched functions showed that approximately 90% of identified genes were clustered in cell component gene functions, and 12 out of 53 genes were traditional housekeeping genes. We selected and validated 16 reference genes chosen from leaf tissue transcriptomes by using RT-qPCR in sets of cold, drought and high salinity treated samples, and ranked expression stability using statistical algorithms geNorm, Normfinder and Bestkeeper. Genes encoding actin, adenine phosphoribosyltransferase and eukaryotic initiation factor 4A genes were the most stable genes over the cold, drought and high salinity stresses. Identification of stably expressed genes as reference gene candidates from multiple transcriptome datasets was found to be reliable and efficient, and some traditional housekeeping genes were more stably expressed than others. We provide a useful molecular genetic resource for future gene expression studies in African oil palm, facilitating molecular genetics approaches for crop improvement in this species.

  20. Analysis of multiple transcriptomes of the African oil palm (Elaeis guineensis) to identify reference genes for RT-qPCR.

    Science.gov (United States)

    Xia, Wei; Mason, Annaliese S; Xiao, Yong; Liu, Zheng; Yang, Yaodong; Lei, Xintao; Wu, Xiaoming; Ma, Zilong; Peng, Ming

    2014-08-20

    The African oil palm (Elaeis guineensis), which is grown in tropical and subtropical regions, is a highly productive oil-bearing crop. For gene expression-based analyses such as reverse transcription-quantitative real time PCR (RT-qPCR), reference genes are essential to provide a baseline with which to quantify relative gene expression. Normalization using reliable reference genes is critical in correctly interpreting expression data from RT-qPCR. In order to identify suitable reference genes in African oil palm, 17 transcriptomes of different tissues obtained from NCBI were systematically assessed for gene expression variation. In total, 53 putative candidate reference genes with coefficient of variation values <3.0 were identified: 18 in reproductive tissue and 35 in vegetative tissue. Analysis for enriched functions showed that approximately 90% of identified genes were clustered in cell component gene functions, and 12 out of 53 genes were traditional housekeeping genes. We selected and validated 16 reference genes chosen from leaf tissue transcriptomes by using RT-qPCR in sets of cold, drought and high salinity treated samples, and ranked expression stability using statistical algorithms geNorm, Normfinder and Bestkeeper. Genes encoding actin, adenine phosphoribosyltransferase and eukaryotic initiation factor 4A genes were the most stable genes over the cold, drought and high salinity stresses. Identification of stably expressed genes as reference gene candidates from multiple transcriptome datasets was found to be reliable and efficient, and some traditional housekeeping genes were more stably expressed than others. We provide a useful molecular genetic resource for future gene expression studies in African oil palm, facilitating molecular genetics approaches for crop improvement in this species. PMID:24862192

  1. Gene expression meta-analysis identifies metastatic pathways and transcription factors in breast cancer

    International Nuclear Information System (INIS)

    Metastasis is believed to progress in several steps including different pathways but the determination and understanding of these mechanisms is still fragmentary. Microarray analysis of gene expression patterns in breast tumors has been used to predict outcome in recent studies. Besides classification of outcome, these global expression patterns may reflect biological mechanisms involved in metastasis of breast cancer. Our purpose has been to investigate pathways and transcription factors involved in metastasis by use of gene expression data sets. We have analyzed 8 publicly available gene expression data sets. A global approach, 'gene set enrichment analysis' as well as an approach focusing on a subset of significantly differently regulated genes, GenMAPP, has been applied to rank pathway gene sets according to differential regulation in metastasizing tumors compared to non-metastasizing tumors. Meta-analysis has been used to determine overrepresentation of pathways and transcription factors targets, concordant deregulated in metastasizing breast tumors, in several data sets. The major findings are up-regulation of cell cycle pathways and a metabolic shift towards glucose metabolism reflected in several pathways in metastasizing tumors. Growth factor pathways seem to play dual roles; EGF and PDGF pathways are decreased, while VEGF and sex-hormone pathways are increased in tumors that metastasize. Furthermore, migration, proteasome, immune system, angiogenesis, DNA repair and several signal transduction pathways are associated to metastasis. Finally several transcription factors e.g. E2F, NFY, and YY1 are identified as being involved in metastasis. By pathway meta-analysis many biological mechanisms beyond major characteristics such as proliferation are identified. Transcription factor analysis identifies a number of key factors that support central pathways. Several previously proposed treatment targets are identified and several new pathways that may

  2. A cross-species genetic analysis identifies candidate genes for mouse anxiety and human bipolar disorder.

    Science.gov (United States)

    Ashbrook, David G; Williams, Robert W; Lu, Lu; Hager, Reinmar

    2015-01-01

    Bipolar disorder (BD) is a significant neuropsychiatric disorder with a lifetime prevalence of ~1%. To identify genetic variants underlying BD genome-wide association studies (GWAS) have been carried out. While many variants of small effect associated with BD have been identified few have yet been confirmed, partly because of the low power of GWAS due to multiple comparisons being made. Complementary mapping studies using murine models have identified genetic variants for behavioral traits linked to BD, often with high power, but these identified regions often contain too many genes for clear identification of candidate genes. In the current study we have aligned human BD GWAS results and mouse linkage studies to help define and evaluate candidate genes linked to BD, seeking to use the power of the mouse mapping with the precision of GWAS. We use quantitative trait mapping for open field test and elevated zero maze data in the largest mammalian model system, the BXD recombinant inbred mouse population, to identify genomic regions associated with these BD-like phenotypes. We then investigate these regions in whole genome data from the Psychiatric Genomics Consortium's bipolar disorder GWAS to identify candidate genes associated with BD. Finally we establish the biological relevance and pathways of these genes in a comprehensive systems genetics analysis. We identify four genes associated with both mouse anxiety and human BD. While TNR is a novel candidate for BD, we can confirm previously suggested associations with CMYA5, MCTP1, and RXRG. A cross-species, systems genetics analysis shows that MCTP1, RXRG, and TNR coexpress with genes linked to psychiatric disorders and identify the striatum as a potential site of action. CMYA5, MCTP1, RXRG, and TNR are associated with mouse anxiety and human BD. We hypothesize that MCTP1, RXRG, and TNR influence intercellular signaling in the striatum. PMID:26190982

  3. A cross-species genetic analysis identifies candidate genes for mouse anxiety and human bipolar disorder

    Directory of Open Access Journals (Sweden)

    David G Ashbrook

    2015-07-01

    Full Text Available Bipolar disorder (BD is a significant neuropsychiatric disorder with a lifetime prevalence of ~1%. To identify genetic variants underlying BD genome-wide association studies (GWAS have been carried out. While many variants of small effect associated with BD have been identified few have yet been confirmed, partly because of the low power of GWAS due to multiple comparisons being made. Complementary mapping studies using murine models have identified genetic variants for behavioral traits linked to BD, often with high power, but these identified regions often contain too many genes for clear identification of candidate genes. In the current study we have aligned human BD GWAS results and mouse linkage studies to help define and evaluate candidate genes linked to BD, seeking to use the power of the mouse mapping with the precision of GWAS. We use quantitative trait mapping for open field test and elevated zero maze data in the largest mammalian model system, the BXD recombinant inbred mouse population, to identify genomic regions associated with these BD-like phenotypes. We then investigate these regions in whole genome data from the Psychiatric Genomics Consortium’s bipolar disorder GWAS to identify candidate genes associated with BD. Finally we establish the biological relevance and pathways of these genes in a comprehensive systems genetics analysis.We identify four genes associated with both mouse anxiety and human BD. While TNR is a novel candidate for BD, we can confirm previously suggested associations with CMYA5, MCTP1 and RXRG. A cross-species, systems genetics analysis shows that MCTP1, RXRG and TNR coexpress with genes linked to psychiatric disorders and identify the striatum as a potential site of action. CMYA5, MCTP1, RXRG and TNR are associated with mouse anxiety and human BD. We hypothesize that MCTP1, RXRG and TNR influence intercellular signaling in the striatum.

  4. Four-month outbreak of invasive meningococcal disease caused by a rare serogroup B strain, identified through the use of molecular PorA subtyping, England, 2013.

    Science.gov (United States)

    Chatt, C; Gajraj, R; Hawker, J; Neal, K; Tahir, M; Lawrence, M; Gray, S J; Lucidarme, J; Carr, A D; Clark, S A; Fowler, T

    2014-01-01

    Molecular PorA subtyping provides information that increasingly requires the adaptation of standard public health approaches to outbreak management. We report an outbreak of a rare subtype of meningococcal infection not previously identified in the United Kingdom (UK). The outbreak occurred in the Warwickshire area in England between February and June 2013. Molecular subtyping allowed the identification of additional cases, prompting an enhanced public health response that included efforts to identify potential social networks that might benefit from chemoprophylaxis. It also prompted swabbing to define nasopharyngeal carriage in the focal nursery and helped explain the unusual epidemiological pattern. Without subtyping to identify a link, the additional cases would have been managed as sporadic cases in accordance with current UK guidance. PMID:25394258

  5. The use of combining ability analysis to identify elite parents for Artemisia annua F1 hybrid production.

    Directory of Open Access Journals (Sweden)

    Theresa Townsend

    Full Text Available Artemisia annua is an important medicinal crop used for the production of the anti-malarial compound artemisinin. In order to assist in the production of affordable high quality artemisinin we have carried out an A. annua breeding programme aimed at improving artemisinin concentration and biomass. Here we report on a combining ability analysis of a diallel cross to identify robust parental lines for hybrid breeding. The parental lines were selected based on a range of phenotypic traits to encourage heterosis. The general combining ability (GCA values for the diallel parental lines correlated to the positive alleles of quantitative trait loci (QTL in the same parents indicating the presence of beneficial alleles that contribute to parental performance. Hybrids generated from crossing specific parental lines with good GCA were identified as having an increase in both artemisinin concentration and biomass when grown either in glasshouse or experimental field trials and compared to controls. This study demonstrates that combining ability as determined by a diallel cross can be used to identify elite parents for the production of improved A. annua hybrids. Furthermore, the selection of material for breeding using this approach was found to be consistent with our QTL-based molecular breeding approach.

  6. Do different neurons age differently? Direct genome-wide analysis of aging in single identified cholinergic neurons

    Directory of Open Access Journals (Sweden)

    Leonid L Moroz

    2010-05-01

    Full Text Available Aplysia californica is a powerful experimental system to study the entire scope of genomic and epigenomic regulation at the resolution of single functionally characterized neurons and is an emerging model in the neurobiology of aging. First, we have identified and cloned a number of evolutionarily conserved genes that are age-related, including components of apoptosis and chromatin remodeling. Second, we performed gene expression profiling of different identified cholinergic neurons between young and aged animals. Our initial analysis indicates that two cholinergic neurons (R2 and LPl1 revealed highly differential genome-wide changes following aging suggesting that on the molecular scale different neurons indeed age differently. Each of neurons tested has a unique subset of genes differentially expressed in older animals, and the majority of differently expressed genes (including those related to apoptosis and Alzheimer’s disease are found in aging neurons of one but not another type. The performed analysis allows us to implicate (i cell specific changes in histones, (ii DNA methylation and (iii regional relocation of RNAs as key processes underlying age-related changes in neuronal functions and synaptic plasticity. These mechanisms can fine-tune the dynamics of long-term chromatin remodeling, or control weakening and the loss of synaptic connections in aging. At the same time our genomic tests revealed evolutionarily conserved gene clusters associated with aging (e.g. apoptosis-, telomere- and redox- dependent processes, insulin and estrogen signaling and water channels.

  7. Proteomic analysis of cerebrospinal fluid in California sea lions (Zalophus californianus) with domoic acid toxicosis identifies proteins associated with neurodegeneration.

    Science.gov (United States)

    Neely, Benjamin A; Soper, Jennifer L; Gulland, Frances M D; Bell, P Darwin; Kindy, Mark; Arthur, John M; Janech, Michael G

    2015-12-01

    Proteomic studies including marine mammals are rare, largely due to the lack of fully sequenced genomes. This has hampered the application of these techniques toward biomarker discovery efforts for monitoring of health and disease in these animals. We conducted a pilot label-free LC-MS/MS study to profile and compare the cerebrospinal fluid from California sea lions with domoic acid toxicosis (DAT) and without DAT. Across 11 samples, a total of 206 proteins were identified (FDRlions with DAT: complement C3, complement factor B, dickkopf-3, malate dehydrogenase 1, neuron cell adhesion molecule 1, gelsolin, and neuronal cell adhesion molecule. Immunoblot analysis found reelin to be depressed in the cerebrospinal fluid from California sea lions with DAT. Mice administered domoic acid also had lower hippocampal reelin protein levels suggesting that domoic acid depresses reelin similar to kainic acid. In summary, proteomic analysis of cerebrospinal fluid in marine mammals is a useful tool to characterize the underlying molecular pathology of neurodegenerative disease. All MS data have been deposited in the ProteomeXchange with identifier PXD002105 (http://proteomecentral.proteomexchange.org/dataset/PXD002105).

  8. Cluster analysis of spontaneous preterm birth phenotypes identifies potential associations among preterm birth mechanisms

    Science.gov (United States)

    Esplin, M Sean; Manuck, Tracy A.; Varner, Michael W.; Christensen, Bryce; Biggio, Joseph; Bukowski, Radek; Parry, Samuel; Zhang, Heping; Huang, Hao; Andrews, William; Saade, George; Sadovsky, Yoel; Reddy, Uma M.; Ilekis, John

    2015-01-01

    Objective We sought to employ an innovative tool based on common biological pathways to identify specific phenotypes among women with spontaneous preterm birth (SPTB), in order to enhance investigators' ability to identify to highlight common mechanisms and underlying genetic factors responsible for SPTB. Study Design A secondary analysis of a prospective case-control multicenter study of SPTB. All cases delivered a preterm singleton at SPTB ≤34.0 weeks gestation. Each woman was assessed for the presence of underlying SPTB etiologies. A hierarchical cluster analysis was used to identify groups of women with homogeneous phenotypic profiles. One of the phenotypic clusters was selected for candidate gene association analysis using VEGAS software. Results 1028 women with SPTB were assigned phenotypes. Hierarchical clustering of the phenotypes revealed five major clusters. Cluster 1 (N=445) was characterized by maternal stress, cluster 2 (N=294) by premature membrane rupture, cluster 3 (N=120) by familial factors, and cluster 4 (N=63) by maternal comorbidities. Cluster 5 (N=106) was multifactorial, characterized by infection (INF), decidual hemorrhage (DH) and placental dysfunction (PD). These three phenotypes were highly correlated by Chi-square analysis [PD and DH (p<2.2e-6); PD and INF (p=6.2e-10); INF and DH (p=0.0036)]. Gene-based testing identified the INS (insulin) gene as significantly associated with cluster 3 of SPTB. Conclusion We identified 5 major clusters of SPTB based on a phenotype tool and hierarchal clustering. There was significant correlation between several of the phenotypes. The INS gene was associated with familial factors underlying SPTB. PMID:26070700

  9. Rat Hepatocytes Weighted Gene Co-Expression Network Analysis Identifies Specific Modules and Hub Genes Related to Liver Regeneration after Partial Hepatectomy

    OpenAIRE

    Yun Zhou; Jiucheng Xu; Yunqing Liu; Juntao Li; Cuifang Chang; Cunshuan Xu

    2014-01-01

    The recovery of liver mass is mainly mediated by proliferation of hepatocytes after 2/3 partial hepatectomy (PH) in rats. Studying the gene expression profiles of hepatocytes after 2/3 PH will be helpful to investigate the molecular mechanisms of liver regeneration (LR). We report here the first application of weighted gene co-expression network analysis (WGCNA) to analyze the biological implications of gene expression changes associated with LR. WGCNA identifies 12 specific gene modules and ...

  10. MALDI-TOF and SELDI-TOF analysis: “tandem” techniques to identify potential biomarker in fibromyalgia

    Directory of Open Access Journals (Sweden)

    A. Lucacchini

    2011-11-01

    Full Text Available Fibromyalgia (FM is characterized by the presence of chronic widespread pain throughout the musculoskeletal system and diffuse tenderness. Unfortunately, no laboratory tests have been appropriately validated for FM and correlated with the subsets and activity. The aim of this study was to apply a proteomic technique in saliva of FM patients: the Surface Enhance Laser Desorption/Ionization Time-of-Flight (SELDI-TOF. For this study, 57 FM patients and 35 HC patients were enrolled. The proteomic analysis of saliva was carried out using SELDI-TOF. The analysis was performed using different chip arrays with different characteristics of binding. The statistical analysis was performed using cluster analysis and the difference between two groups was underlined using Student’s t-test. Spectra analysis highlighted the presence of several peaks differently expressed in FM patients compared with controls. The preliminary results obtained by SELDI-TOF analysis were compared with those obtained in our previous study performed on whole saliva of FM patients by using electrophoresis. The m/z of two peaks, increased in FM patients, seem to overlap well with the molecular weight of calgranulin A and C and Rho GDP-dissociation inhibitor 2, which we had found up-regulated in our previous study. These preliminary results showed the possibility of identifying potential salivary biomarker through salivary proteomic analysis with MALDI-TOF and SELDI-TOF in FM patients. The peaks observed allow us to focus on some of the particular pathogenic aspects of FM, the oxidative stress which contradistinguishes this condition, the involvement of proteins related to the cytoskeletal arrangements, and central sensibilization.

  11. Menkes disease: importance of diagnosis with molecular analysis in the neonatal period

    Directory of Open Access Journals (Sweden)

    Larissa Sampaio de Athayde Costa

    2015-10-01

    Full Text Available Summary Menkes disease is a congenital disorder caused by changes in copper metabolism derived from mutations in the ATP7A gene. It is characterized by physical and neurological alterations. In the neonatal period, these alterations can be nonspecific, which makes early diagnosis a challenge. Diagnosis can be suspected when there are low levels of ceruloplasmin and serum copper. Molecular analysis confirms the diagnosis. Treatment is parenteral administration of copper histidine. We report a familial case with molecular confirmation. The proband had clinical and biochemical suspicious. Treatment with copper histidine was indicated, but initiated at the age of 2 months and 27 days only. He did not present improvements and died at 6 months. The mother became pregnant again, a male fetus was identified and copper histidine was manufactured during pregnancy. He was born healthy, biochemical markers were reduced and treatment was indicated. Molecular analysis was performed confirming mutation in both the mother and the proband, while the other son did not have mutation, so treatment was discontinued. We support the clinical relevance of molecular confirmation for the correct diagnosis and genetic counseling, once clinical findings in the neonatal period are nonspecific and early treatment with parenteral copper histidine must be indicated.

  12. Probabilistic approach to identify sensitive parameter distributions in multimedia pathway analysis.

    Energy Technology Data Exchange (ETDEWEB)

    Kamboj, S.; Gnanapragasam, E.; LePoire, D.; Biwer, B. M.; Cheng, J.; Arnish, J.; Yu, C.; Chen, S. Y.; Mo, T.; Abu-Eid, R.; Thaggard, M.; Environmental Assessment; NRC

    2002-01-01

    Sensitive parameter distributions were identified with the use of probabilistic analysis in the RESRAD computer code. RESRAD is a multimedia pathway analysis code designed to evaluate radiological exposures resulting from radiological contamination in soil. The dose distribution was obtained by using a set of default parameter distribution/values. Most of the variations in the output dose distribution could be attributed to uncertainty in a small set of input parameters that could be considered as sensitive parameter distributions. The identification of the sensitive parameters is a first step in the prioritization of future research and information gathering. When site-specific parameter distribution/values are available for an actual site, the same process should be used with these site-specific data. Regression analysis used to identify sensitive parameters indicated that the dominant pathways depended on the radionuclide and source configurations. However, two parameter distributions were sensitive for many radionuclides: the external shielding factor when external exposure was the dominant pathway and the plant transfer factor when plant ingestion was the dominant pathway. No single correlation or regression coefficient can be used alone to identify sensitive parameters in all the cases. The coefficients are useful guides, but they have to be used in conjunction with other aids, such as scatter plots, and should undergo further analysis.

  13. Molecular orbital analysis of the hydrogen bonded water dimer

    Science.gov (United States)

    Wang, Bo; Jiang, Wanrun; Dai, Xin; Gao, Yang; Wang, Zhigang; Zhang, Rui-Qin

    2016-01-01

    As an essential interaction in nature, hydrogen bonding plays a crucial role in many material formations and biological processes, requiring deeper understanding. Here, using density functional theory and post-Hartree-Fock methods, we reveal two hydrogen bonding molecular orbitals crossing the hydrogen-bond’s O and H atoms in the water dimer. Energy decomposition analysis also shows a non-negligible contribution of the induction term. Our finding sheds light on the essential understanding of hydrogen bonding in ice, liquid water, functional materials and biological systems. PMID:26905305

  14. Molecular organization in liquid crystals: A comparative computational analysis

    International Nuclear Information System (INIS)

    A comparative computational analysis of molecular organization in four-nematogenic acids (nOCAC) having two, four, six, and eight carbon atoms in the alkyl chain is carried out with respect to translatory and orientational motions. The evaluation of the atomic charge and dipole moment at each atomic center is performed through the complete neglect differential overlap (CNDO/2) method. The Rayleigh-Schroedinger perturbation theory, along with the multicentered-multipole expansion method, is employed to evaluate the long-range interactions, while the '6-exp' potential function is assumed for short-range interactions. The total interaction-energy values obtained through these computations are used to calculate the probability of each configuration at the phase transition temperature via the Maxwell-Boltzmann formula. Further, the flexibility of various configurations is studied in terms of variation of probability due to small departures from the most probable configuration. A comparative picture of molecular parameters, such as the total energy, binding energy, and total dipole moment, is given. An attempt is made to explain the nematogenic behavior of these liquid crystals in terms of their relative order and, thereby, to develop a molecular model for the liquid crystallinity.

  15. Comparative Transcriptome Analysis Identifies Candidate Genes Related to Skin Color Differentiation in Red Tilapia.

    Science.gov (United States)

    Zhu, Wenbin; Wang, Lanmei; Dong, Zaijie; Chen, Xingting; Song, Feibiao; Liu, Nian; Yang, Hui; Fu, Jianjun

    2016-01-01

    Red tilapia is becoming more popular for aquaculture production in China in recent years. However, the pigmentation differentiation in genetic breeding is the main problem limiting its development of commercial red tilapia culture and the genetic basis of skin color variation is still unknown. In this study, we conducted Illumina sequencing of transcriptome on three color variety red tilapia. A total of 224,895,758 reads were generated, resulting in 160,762 assembled contigs that were used as reference contigs. The contigs of red tilapia transcriptome had hits in the range of 53.4% to 86.7% of the unique proteins of zebrafish, fugu, medaka, three-spined stickleback and tilapia. And 44,723 contigs containing 77,423 simple sequence repeats (SSRs) were identified, with 16,646 contigs containing more than one SSR. Three skin transcriptomes were compared pairwise and the results revealed that there were 148 common significantly differentially expressed unigenes and several key genes related to pigment synthesis, i.e. tyr, tyrp1, silv, sox10, slc24a5, cbs and slc7a11, were included. The results will facilitate understanding the molecular mechanisms of skin pigmentation differentiation in red tilapia and accelerate the molecular selection of the specific strain with consistent skin colors. PMID:27511178

  16. A Phylogenomic Census of Molecular Functions Identifies Modern Thermophilic Archaea as the Most Ancient Form of Cellular Life

    Directory of Open Access Journals (Sweden)

    Arshan Nasir

    2014-01-01

    Full Text Available The origins of diversified life remain mysterious despite considerable efforts devoted to untangling the roots of the universal tree of life. Here we reconstructed phylogenies that described the evolution of molecular functions and the evolution of species directly from a genomic census of gene ontology (GO definitions. We sampled 249 free-living genomes spanning organisms in the three superkingdoms of life, Archaea, Bacteria, and Eukarya, and used the abundance of GO terms as molecular characters to produce rooted phylogenetic trees. Results revealed an early thermophilic origin of Archaea that was followed by genome reduction events in microbial superkingdoms. Eukaryal genomes displayed extraordinary functional diversity and were enriched with hundreds of novel molecular activities not detected in the akaryotic microbial cells. Remarkably, the majority of these novel functions appeared quite late in evolution, synchronized with the diversification of the eukaryal superkingdom. The distribution of GO terms in superkingdoms confirms that Archaea appears to be the simplest and most ancient form of cellular life, while Eukarya is the most diverse and recent.

  17. A method for identifying compromised clients based on DNS traffic analysis

    DEFF Research Database (Denmark)

    Stevanovic, Matija; Pedersen, Jens Myrup; D’Alconzo, Alessandro;

    2016-01-01

    based on DNS traffic analysis. The proposed method identifies suspicious agile DNS mappings, i.e., mappings characterized by fast changing domain names or/and IP addresses, often used by malicious services. The approach discovers clients that have queried domains contained within identified suspicious...... domain-to-IP mappings, thus assisting in pinpointing potentially compromised clients within the network. The proposed approach targets compromised clients in large-scale operational networks. We have evaluated the proposed approach using an extensive set of DNS traffic traces from different operational......DNS is widely abused by Internet criminals in order to provide reliable communication within malicious network infrastructure as well as flexible and resilient hosting of malicious content. This paper presents a novel detection method that can be used for identifying potentially compromised clients...

  18. Genome-wide interaction-based association analysis identified multiple new susceptibility Loci for common diseases.

    Directory of Open Access Journals (Sweden)

    Yang Liu

    2011-03-01

    Full Text Available Genome-wide interaction-based association (GWIBA analysis has the potential to identify novel susceptibility loci. These interaction effects could be missed with the prevailing approaches in genome-wide association studies (GWAS. However, no convincing loci have been discovered exclusively from GWIBA methods, and the intensive computation involved is a major barrier for application. Here, we developed a fast, multi-thread/parallel program named "pair-wise interaction-based association mapping" (PIAM for exhaustive two-locus searches. With this program, we performed a complete GWIBA analysis on seven diseases with stringent control for false positives, and we validated the results for three of these diseases. We identified one pair-wise interaction between a previously identified locus, C1orf106, and one new locus, TEC, that was specific for Crohn's disease, with a Bonferroni corrected P < 0.05 (P = 0.039. This interaction was replicated with a pair of proxy linked loci (P = 0.013 on an independent dataset. Five other interactions had corrected P < 0.5. We identified the allelic effect of a locus close to SLC7A13 for coronary artery disease. This was replicated with a linked locus on an independent dataset (P = 1.09 × 10⁻⁷. Through a local validation analysis that evaluated association signals, rather than locus-based associations, we found that several other regions showed association/interaction signals with nominal P < 0.05. In conclusion, this study demonstrated that the GWIBA approach was successful for identifying novel loci, and the results provide new insights into the genetic architecture of common diseases. In addition, our PIAM program was capable of handling very large GWAS datasets that are likely to be produced in the future.

  19. Patent Network Analysis and Quadratic Assignment Procedures to Identify the Convergence of Robot Technologies

    Science.gov (United States)

    Lee, Woo Jin; Lee, Won Kyung

    2016-01-01

    Because of the remarkable developments in robotics in recent years, technological convergence has been active in this area. We focused on finding patterns of convergence within robot technology using network analysis of patents in both the USPTO and KIPO. To identify the variables that affect convergence, we used quadratic assignment procedures (QAP). From our analysis, we observed the patent network ecology related to convergence and found technologies that have great potential to converge with other robotics technologies. The results of our study are expected to contribute to setting up convergence based R&D policies for robotics, which can lead new innovation. PMID:27764196

  20. Identifying barriers to patient acceptance of active surveillance: content analysis of online patient communications.

    Directory of Open Access Journals (Sweden)

    Mark V Mishra

    Full Text Available OBJECTIVES: Qualitative research aimed at identifying patient acceptance of active surveillance (AS has been identified as a public health research priority. The primary objective of this study was to determine if analysis of a large-sample of anonymous internet conversations (ICs could be utilized to identify unmet public needs regarding AS. METHODS: English-language ICs regarding prostate cancer (PC treatment with AS from 2002-12 were identified using a novel internet search methodology. Web spiders were developed to mine, aggregate, and analyze content from the world-wide-web for ICs centered on AS. Collection of ICs was not restricted to any specific geographic region of origin. NLP was used to evaluate content and perform a sentiment analysis. Conversations were scored as positive, negative, or neutral. A sentiment index (SI was subsequently calculated according to the following formula to compare temporal trends in public sentiment towards AS: [(# Positive IC/#Total IC-(#Negative IC/#Total IC x 100]. RESULTS: A total of 464 ICs were identified. Sentiment increased from -13 to +2 over the study period. The increase sentiment has been driven by increased patient emphasis on quality-of-life factors and endorsement of AS by national medical organizations. Unmet needs identified in these ICs include: a gap between quantitative data regarding long-term outcomes with AS vs. conventional treatments, desire for treatment information from an unbiased specialist, and absence of public role models managed with AS. CONCLUSIONS: This study demonstrates the potential utility of online patient communications to provide insight into patient preferences and decision-making. Based on our findings, we recommend that multidisciplinary clinics consider including an unbiased specialist to present treatment options and that future decision tools for AS include quantitative data regarding outcomes after AS.

  1. Emergent team roles in organizational meetings: Identifying communication patterns via cluster analysis.

    OpenAIRE

    Lehmann-Willenbrock, N.K.; Beck, S.J.; Kauffeld, S.

    2016-01-01

    Previous team role taxonomies have largely relied on self-report data, focused on functional roles, and described individual predispositions or personality traits. Instead, this study takes a communicative approach and proposes that team roles are produced, shaped, and sustained in communicative behaviors. To identify team roles communicatively, 59 regular organizational meetings were videotaped and analyzed. Cluster analysis revealed five emergent roles: the solution seeker, the problem anal...

  2. Network analysis identifies protein clusters of functional importance in juvenile idiopathic arthritis

    OpenAIRE

    Stevens, Adam; Meyer, Stefan; Hanson, Daniel; Clayton, Peter; Donn, Rachelle

    2014-01-01

    Introduction Our objective was to utilise network analysis to identify protein clusters of greatest potential functional relevance in the pathogenesis of oligoarticular and rheumatoid factor negative (RF-ve) polyarticular juvenile idiopathic arthritis (JIA). Methods JIA genetic association data were used to build an interactome network model in BioGRID 3.2.99. The top 10% of this protein:protein JIA Interactome was used to generate a minimal essential network (MEN). Reactome FI Cytoscape 2.83...

  3. Identifying Gender-Preferred Communication Styles within Online Cancer Communities: A Retrospective, Longitudinal Analysis

    OpenAIRE

    Durant, Kathleen T.; McCray, Alexa T.; Charles Safran

    2012-01-01

    BACKGROUND: The goal of this research is to determine if different gender-preferred social styles can be observed within the user interactions at an online cancer community. To achieve this goal, we identify and measure variables that pertain to each gender-specific social style. METHODS AND FINDINGS: We perform social network and statistical analysis on the communication flow of 8,388 members at six different cancer forums over eight years. Kruskal-Wallis tests were conducted to measure the ...

  4. Identifying patterns in treatment response profiles in acute bipolar mania: a cluster analysis approach

    OpenAIRE

    Houston John P; Lipkovich Ilya A; Ahl Jonna

    2008-01-01

    Abstract Background Patients with acute mania respond differentially to treatment and, in many cases, fail to obtain or sustain symptom remission. The objective of this exploratory analysis was to characterize response in bipolar disorder by identifying groups of patients with similar manic symptom response profiles. Methods Patients (n = 222) were selected from a randomized, double-blind study of treatment with olanzapine or divalproex in bipolar I disorder, manic or mixed episode, with or w...

  5. Hot spot analysis applied to identify ecosystem services potential in Lithuania

    Science.gov (United States)

    Pereira, Paulo; Depellegrin, Daniel; Misiune, Ieva

    2016-04-01

    Hot spot analysis are very useful to identify areas with similar characteristics. This is important for a sustainable use of the territory, since we can identify areas that need to be protected, or restored. This is a great advantage in terms of land use planning and management, since we can allocate resources, reduce the economical costs and do a better intervention in the landscape. Ecosystem services (ES) are different according land use. Since landscape is very heterogeneous, it is of major importance understand their spatial pattern and where are located the areas that provide better ES and the others that provide less services. The objective of this work is to use hot-spot analysis to identify areas with the most valuable ES in Lithuania. CORINE land-cover (CLC) of 2006 was used as the main spatial information. This classification uses a grid of 100 m resolution and extracted a total of 31 land use types. ES ranking was carried out based on expert knowledge. They were asked to evaluate the ES potential of each different CLC from 0 (no potential) to 5 (very high potential). Hot spot analysis were evaluated using the Getis-ord test, which identifies cluster analysis available in ArcGIS toolbox. This tool identifies areas with significantly high low values and significant high values at a p level of 0.05. In this work we used hot spot analysis to assess the distribution of providing, regulating cultural and total (sum of the previous 3) ES. The Z value calculated from Getis-ord was used to statistical analysis to access the clusters of providing, regulating cultural and total ES. ES with high Z value show that they have a high number of cluster areas with high potential of ES. The results showed that the Z-score was significantly different among services (Kruskal Wallis ANOVA =834. 607, pareas that showed high and low significant regulating and cultural ES clusters are similar. The spatial distribution of these clusters is very high, which may be attributed to

  6. Molecular activation analysis for organo-halogen contaminants in yogurt

    International Nuclear Information System (INIS)

    The concentrations of total halogen (TX), extractable organo-halogen (EOX), extractable persistent organo-halogen (EPOX), organo-chlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) in 18 different yogurt specimens of 14 brands from Beijing, Tianjin, Shanghai, Guangzhou and Shijiazhuang were determined by epithermal neutron activation analysis (ENAA), molecular activation analysis (MAA) and GC-Mass Spectrometry (GC-MS), respectively. The results indicated that the halogen in yogurt mainly existed as inorganic species and non-extractable organo-halogen compounds. About 1/3 to 1/4 of EOX was EPOX. Further, EOCl and EPOCl were the main organo-halogen species in yogurt. The average concentration of the unknown organo-chlorine was 96% of the EPOCl. HCHs and DDTs were still the main contaminants of OCPs in the yogurt of interest. Also, PCB202, PCB103 and PCB208 were the main contaminants of PCBs. (authors)

  7. Identifying Innovative Interventions to Promote Healthy Eating Using Consumption-Oriented Food Supply Chain Analysis.

    Science.gov (United States)

    Hawkes, Corinna

    2009-07-01

    The mapping and analysis of supply chains is a technique increasingly used to address problems in the food system. Yet such supply chain management has not yet been applied as a means of encouraging healthier diets. Moreover, most policies recommended to promote healthy eating focus on the consumer end of the chain. This article proposes a consumption-oriented food supply chain analysis to identify the changes needed in the food supply chain to create a healthier food environment, measured in terms of food availability, prices, and marketing. Along with established forms of supply chain analysis, the method is informed by a historical overview of how food supply chains have changed over time. The method posits that the actors and actions in the chain are affected by organizational, financial, technological, and policy incentives and disincentives, which can in turn be levered for change. It presents a preliminary example of the supply of Coca-Cola beverages into school vending machines and identifies further potential applications. These include fruit and vegetable supply chains, local food chains, supply chains for health-promoting versions of food products, and identifying financial incentives in supply chains for healthier eating. PMID:23144674

  8. Integrative analysis of a cross-loci regulation network identifies App as a gene regulating insulin secretion from pancreatic islets.

    Directory of Open Access Journals (Sweden)

    Zhidong Tu

    Full Text Available Complex diseases result from molecular changes induced by multiple genetic factors and the environment. To derive a systems view of how genetic loci interact in the context of tissue-specific molecular networks, we constructed an F2 intercross comprised of >500 mice from diabetes-resistant (B6 and diabetes-susceptible (BTBR mouse strains made genetically obese by the Leptin(ob/ob mutation (Lep(ob. High-density genotypes, diabetes-related clinical traits, and whole-transcriptome expression profiling in five tissues (white adipose, liver, pancreatic islets, hypothalamus, and gastrocnemius muscle were determined for all mice. We performed an integrative analysis to investigate the inter-relationship among genetic factors, expression traits, and plasma insulin, a hallmark diabetes trait. Among five tissues under study, there are extensive protein-protein interactions between genes responding to different loci in adipose and pancreatic islets that potentially jointly participated in the regulation of plasma insulin. We developed a novel ranking scheme based on cross-loci protein-protein network topology and gene expression to assess each gene's potential to regulate plasma insulin. Unique candidate genes were identified in adipose tissue and islets. In islets, the Alzheimer's gene App was identified as a top candidate regulator. Islets from 17-week-old, but not 10-week-old, App knockout mice showed increased insulin secretion in response to glucose or a membrane-permeant cAMP analog, in agreement with the predictions of the network model. Our result provides a novel hypothesis on the mechanism for the connection between two aging-related diseases: Alzheimer's disease and type 2 diabetes.

  9. Effective Boolean dynamics analysis to identify functionally important genes in large-scale signaling networks.

    Science.gov (United States)

    Trinh, Hung-Cuong; Kwon, Yung-Keun

    2015-11-01

    Efficiently identifying functionally important genes in order to understand the minimal requirements of normal cellular development is challenging. To this end, a variety of structural measures have been proposed and their effectiveness has been investigated in recent literature; however, few studies have shown the effectiveness of dynamics-based measures. This led us to investigate a dynamic measure to identify functionally important genes, and the effectiveness of which was verified through application on two large-scale human signaling networks. We specifically consider Boolean sensitivity-based dynamics against an update-rule perturbation (BSU) as a dynamic measure. Through investigations on two large-scale human signaling networks, we found that genes with relatively high BSU values show slower evolutionary rate and higher proportions of essential genes and drug targets than other genes. Gene-ontology analysis showed clear differences between the former and latter groups of genes. Furthermore, we compare the identification accuracies of essential genes and drug targets via BSU and five well-known structural measures. Although BSU did not always show the best performance, it effectively identified the putative set of genes, which is significantly different from the results obtained via the structural measures. Most interestingly, BSU showed the highest synergy effect in identifying the functionally important genes in conjunction with other measures. Our results imply that Boolean-sensitive dynamics can be used as a measure to effectively identify functionally important genes in signaling networks.

  10. An ab initio molecular dynamics analysis of lignin as a potential antioxidant for hydrocarbons.

    Science.gov (United States)

    Pan, Tongyan; Cheng, Cheng

    2015-11-01

    Lignins are complex phenolic polymers with limited industrial uses. To identify new applications of lignins, this study aims to evaluate the conifer alcohol lignin as a potential antioxidant for hydrocarbons, using the petroleum asphalt as an example. Using the ab initio molecular dynamics (AIMD) method, the evaluation is accomplished by tracking the generation of critical species in a lignin-asphalt mixture under a simulated oxidative condition. The generation of new species was detected using nuclear magnetic resonance and four analytical methods including density of states analysis, highest occupied molecular orbital and lowest unoccupied molecular orbital analyses, bonding and energy level analysis, and electrostatic potential energy analysis. Results of the analyses show that the chemical radicals of carbon, nitrogen and sulfur generated in the oxidation process could enhance the agglomeration and/or decomposition tendency of asphalt. The effectiveness of lignins as an antioxidant depends on their chemical compositions. Lignins with a HOMO-LUMO gap larger than the HOMO-LUMO gap of the hydrocarbon system to be protected, such as the conifer alcohol lignin to protect petroleum asphalt as was studied in this work, do not demonstrate beneficial anti-oxidation capacity. Lignins, however, may be effective oxidants for hydrocarbon systems with a larger HOMO-LUMO gap. In addition, lignins may contain more polar sites than the hydrocarbons to be protected; thus the lignins' hydrophobicity and compatibility with the host hydrocarbons need to be well evaluated. The developed AIMD model provides a useful tool for developing antioxidants for generic hydrocarbons. PMID:26562413

  11. Exome analysis of two limb-girdle muscular dystrophy families: mutations identified and challenges encountered.

    Directory of Open Access Journals (Sweden)

    Kristin K McDonald

    Full Text Available The molecular diagnosis of muscle disorders is challenging: genetic heterogeneity (>100 causal genes for skeletal and cardiac muscle disease precludes exhaustive clinical testing, prioritizing sequencing of specific genes is difficult due to the similarity of clinical presentation, and the number of variants returned through exome sequencing can make the identification of the disease-causing variant difficult. We have filtered variants found through exome sequencing by prioritizing variants in genes known to be involved in muscle disease while examining the quality and depth of coverage of those genes. We ascertained two families with autosomal dominant limb-girdle muscular dystrophy of unknown etiology. To identify the causal mutations in these families, we performed exome sequencing on five affected individuals using the Agilent SureSelect Human All Exon 50 Mb kit and the Illumina HiSeq 2000 (2×100 bp. We identified causative mutations in desmin (IVS3+3A>G and filamin C (p.W2710X, and augmented the phenotype data for individuals with muscular dystrophy due to these mutations. We also discuss challenges encountered due to depth of coverage variability at specific sites and the annotation of a functionally proven splice site variant as an intronic variant.

  12. [Clinical and molecular genetic analysis of hereditary optic neuropathies].

    Science.gov (United States)

    Avetisov, S É; Sheremet, N L; Vorob'eva, O K; Eliseeva, É G; Chukhrova, A L; Loginova, A N; Khanakova, N A; Poliakov, A V

    2013-01-01

    DNA samples of 50 patients with optic neuropathy (ON) associated with congenital cataract were studied to find 3 major mt-DNA mutations (m.11778G>A, m.3460G>A, m.14484T>C), mutations in "hot" regions of OPA 1 gene (exons 8, 14, 15, 16, 18, 27, 28) and in the entire coding sequence of OPA3 gene for molecular genetic confirmation of diagnosis of hereditary Leber and autosomal dominant ON. Primary mutations of mtDNA responsible for hereditary Leber ON were found in 16 patients (32%). Pathogenic mutations of OPAl gene (c.869G>A and c. 2850delT) were identified in 2 patients (4%), these mutations were not found in the literature. OPA3 gene mutations were not revealed.

  13. Genetic variation of space flight carried rice and mutant analysis by AFLP molecular marker

    International Nuclear Information System (INIS)

    Rice seeds were carried by 'Shenzhou No.3' space shuttle, a mutant with golden chaff, stem and leaf was selected and named Golden 1 after the seeds returned to the earth. Except the golden color, other traits of Golden 1 are no obviously different with its original material H9808. Genetic analysis identified that color variation was control by a pair of recessive gene. The DNA fragments of the mutant were compared with its parent by AFLP molecular markers. Five specific bands were found through a serial selection. (authors)

  14. Efficient behavior of photosynthetic organelles via Pareto optimality, identifiability, and sensitivity analysis.

    Science.gov (United States)

    Carapezza, Giovanni; Umeton, Renato; Costanza, Jole; Angione, Claudio; Stracquadanio, Giovanni; Papini, Alessio; Lió, Pietro; Nicosia, Giuseppe

    2013-05-17

    In this work, we develop methodologies for analyzing and cross comparing metabolic models. We investigate three important metabolic networks to discuss the complexity of biological organization of organisms, modeling, and system properties. In particular, we analyze these metabolic networks because of their biotechnological and basic science importance: the photosynthetic carbon metabolism in a general leaf, the Rhodobacter spheroides bacterium, and the Chlamydomonas reinhardtii alga. We adopt single- and multi-objective optimization algorithms to maximize the CO 2 uptake rate and the production of metabolites of industrial interest or for ecological purposes. We focus both on the level of genes (e.g., finding genetic manipulations to increase the production of one or more metabolites) and on finding concentration enzymes for improving the CO 2 consumption. We find that R. spheroides is able to absorb an amount of CO 2 until 57.452 mmol h (-1) gDW (-1) , while C. reinhardtii obtains a maximum of 6.7331. We report that the Pareto front analysis proves extremely useful to compare different organisms, as well as providing the possibility to investigate them with the same framework. By using the sensitivity and robustness analysis, our framework identifies the most sensitive and fragile components of the biological systems we take into account, allowing us to compare their models. We adopt the identifiability analysis to detect functional relations among enzymes; we observe that RuBisCO, GAPDH, and FBPase belong to the same functional group, as suggested also by the sensitivity analysis.

  15. Identifying Enclosed Chemical Reaction and Dynamics at the Molecular Level Using Shell-Isolated Miniaturized Plasmonic Liquid Marble.

    Science.gov (United States)

    Han, Xuemei; Lee, Hiang Kwee; Lee, Yih Hong; Hao, Wei; Liu, Yejing; Phang, In Yee; Li, Shuzhou; Ling, Xing Yi

    2016-04-21

    Current microscale tracking of chemical kinetics is limited to destructive ex situ methods. Here we utilize Ag nanocube-based plasmonic liquid marble (PLM) microreactor for in situ molecular-level identification of reaction dynamics. We exploit the ultrasensitive surface-enhanced Raman scattering (SERS) capability imparted by the plasmonic shell to unravel the mechanism and kinetics of aryl-diazonium surface grafting reaction in situ, using just a 2-μL reaction droplet. This reaction is a robust approach to generate covalently functionalized metallic surfaces, yet its kinetics remain unknown to date. Experiments and simulations jointly uncover a two-step sequential grafting process. An initial Langmuir chemisorption of sulfonicbenzene diazonium (dSB) salt onto Ag surfaces forms an intermediate sulfonicbenzene monolayer (Ag-SB), followed by subsequent autocatalytic multilayer growth of Ag-SB3. Kinetic rate constants reveal 19-fold faster chemisorption than multilayer growth. Our ability to precisely decipher molecular-level reaction dynamics creates opportunities to develop more efficient processes in synthetic chemistry and nanotechnology. PMID:27050645

  16. Protein functional links in Trypanosoma brucei, identified by gene fusion analysis

    Directory of Open Access Journals (Sweden)

    Trimpalis Philip

    2011-07-01

    Full Text Available Abstract Background Domain or gene fusion analysis is a bioinformatics method for detecting gene fusions in one organism by comparing its genome to that of other organisms. The occurrence of gene fusions suggests that the two original genes that participated in the fusion are functionally linked, i.e. their gene products interact either as part of a multi-subunit protein complex, or in a metabolic pathway. Gene fusion analysis has been used to identify protein functional links in prokaryotes as well as in eukaryotic model organisms, such as yeast and Drosophila. Results In this study we have extended this approach to include a number of recently sequenced protists, four of which are pathogenic, to identify fusion linked proteins in Trypanosoma brucei, the causative agent of African sleeping sickness. We have also examined the evolution of the gene fusion events identified, to determine whether they can be attributed to fusion or fission, by looking at the conservation of the fused genes and of the individual component genes across the major eukaryotic and prokaryotic lineages. We find relatively limited occurrence of gene fusions/fissions within the protist lineages examined. Our results point to two trypanosome-specific gene fissions, which have recently been experimentally confirmed, one fusion involving proteins involved in the same metabolic pathway, as well as two novel putative functional links between fusion-linked protein pairs. Conclusions This is the first study of protein functional links in T. brucei identified by gene fusion analysis. We have used strict thresholds and only discuss results which are highly likely to be genuine and which either have already been or can be experimentally verified. We discuss the possible impact of the identification of these novel putative protein-protein interactions, to the development of new trypanosome therapeutic drugs.

  17. [Molecular genetic bases of adaptation processes and approaches to their analysis].

    Science.gov (United States)

    Salmenkova, E A

    2013-01-01

    Great interest in studying the molecular genetic bases of the adaptation processes is explained by their importance in understanding evolutionary changes, in the development ofintraspecific and interspecific genetic diversity, and in the creation of approaches and programs for maintaining and restoring the population. The article examines the sources and conditions for generating adaptive genetic variability and contribution of neutral and adaptive genetic variability to the population structure of the species; methods for identifying the adaptive genetic variability on the genome level are also described. Considerable attention is paid to the potential of new technologies of genome analysis, including next-generation sequencing and some accompanying methods. In conclusion, the important role of the joint use of genomics and proteomics approaches in understanding the molecular genetic bases of adaptation is emphasized.

  18. Molecular Shape Analysis-Guided Virtual Screening Platform for Adenosine Kinase Inhibitors

    Science.gov (United States)

    Bhutoria, Savita; Das, Ballari; Ghoshal, Nanda

    2016-01-01

    We propose a new application of molecular shape descriptors in hierarchical selection during virtual screening (VS). Here, a structure-based pharmacophore and docking-guided VS protocol have been evolved to identify inhibitors against adenosine kinase (AK). The knowledge gained on the shape requirements has been extrapolated in classifying active and inactive molecules against this target. This classification enabled us to pick the appropriate ligand conformation in the binding site. We have suggested a set of hierarchical filters for VS, from a simple molecular shape analysis (MSA) descriptor-based recursive models to docking scores. This approach permits a systematic study to understand the importance of spatial requirements and limitations for inhibitors against AK. Finally, the guidelines on how to select compounds for AK to achieve success have been highlighted. The utility of this approach has been suggested by giving an example of database screening for plausible active compounds. PMID:27478367

  19. Molecular Shape Analysis-Guided Virtual Screening Platform for Adenosine Kinase Inhibitors.

    Science.gov (United States)

    Bhutoria, Savita; Das, Ballari; Ghoshal, Nanda

    2016-01-01

    We propose a new application of molecular shape descriptors in hierarchical selection during virtual screening (VS). Here, a structure-based pharmacophore and docking-guided VS protocol have been evolved to identify inhibitors against adenosine kinase (AK). The knowledge gained on the shape requirements has been extrapolated in classifying active and inactive molecules against this target. This classification enabled us to pick the appropriate ligand conformation in the binding site. We have suggested a set of hierarchical filters for VS, from a simple molecular shape analysis (MSA) descriptor-based recursive models to docking scores. This approach permits a systematic study to understand the importance of spatial requirements and limitations for inhibitors against AK. Finally, the guidelines on how to select compounds for AK to achieve success have been highlighted. The utility of this approach has been suggested by giving an example of database screening for plausible active compounds. PMID:27478367

  20. Proteomic analysis of exosomes from nasopharyngeal carcinoma cell identifies intercellular transfer of angiogenic proteins.

    Science.gov (United States)

    Chan, Yuk-Kit; Zhang, Huoming; Liu, Pei; Tsao, Sai-Wah; Lung, Maria Li; Mak, Nai-Ki; Ngok-Shun Wong, Ricky; Ying-Kit Yue, Patrick

    2015-10-15

    Exosomes, a group of secreted extracellular nanovesicles containing genetic materials and signaling molecules, play a critical role in intercellular communication. During tumorigenesis, exosomes have been demonstrated to promote tumor angiogenesis and metastasis while their biological functions in nasopharyngeal carcinoma (NPC) are poorly understood. In this study, we focused on the role of NPC-derived exosomes on angiogenesis. Exosomes derived from the NPC C666-1 cells and immortalized nasopharyngeal epithelial cells (NP69 and NP460) were isolated using ultracentrifugation. The molecular profile and biophysical characteristics of exosomes were verified by Western blotting, sucrose density gradient and electron microscopy. We showed that the C666-1 exosomes (10 and 20 μg/ml) could significantly increase the tubulogenesis, migration and invasion of human umbilical vein endothelial cells (HUVECs) in a dose-dependent manner. Subsequently, an iTRAQ-based quantitative proteomics was used to identify the differentially expressed proteins in C666-1 exosomes. Among the 640 identified proteins, 51 and 89 proteins were considered as up- and down-regulated (≥ 1.5-fold variations) in C666-1 exosomes compared to the normal counterparts, respectively. As expected, pro-angiogenic proteins including intercellular adhesion molecule-1 (ICAM-1) and CD44 variant isoform 5 (CD44v5) are among the up-regulated proteins, whereas angio-suppressive protein, thrombospondin-1 (TSP-1) was down-regulated in C666-1 exosomes. Further confocal microscopic study and Western blotting clearly demonstrated that the alteration of ICAM-1 and TSP-1 expressions in recipient HUVECs are due to internalization of exosomes. Taken together, these data strongly indicated the critical roles of identified angiogenic proteins in the involvement of exosomes-induced angiogenesis, which could potentially be developed as therapeutic targets in future.

  1. Proteomic analysis of exosomes from nasopharyngeal carcinoma cell identifies intercellular transfer of angiogenic proteins

    KAUST Repository

    Chan, Yuk-kit

    2015-04-01

    Exosomes, a group of secreted extracellular nanovesicles containing genetic materials and signaling molecules, play a critical role in intercellular communication. During tumorigenesis, exosomes have been demonstrated to promote tumor angiogenesis and metastasis while their biological functions in nasopharyngeal carcinoma (NPC) are poorly understood. In this study, we focused on the role of NPC-derived exosomes on angiogenesis. Exosomes derived from the NPC C666-1 cells and immortalized nasopharyngeal epithelial cells (NP69 and NP460) were isolated using ultracentrifugation. The molecular profile and biophysical characteristics of exosomes were verified by Western blotting, sucrose density gradient, and electron microscopy. We showed that the C666-1 exosomes (10 and 20 μg/ml) could significantly increase the tubulogenesis, migration and invasion of human umbilical vein endothelial cells (HUVECs) in a dose-dependent manner. Subsequently, an iTRAQ-based quantitative proteomics was used to identify the differentially expressed proteins in C666-1 exosomes. Among the 640 identified proteins, 51 and 89 proteins were considered as up- and down-regulated (≥ 1.5-fold variations) in C666-1 exosomes compared to the normal counterparts, respectively. As expected, pro-angiogenic proteins including intercellular adhesion molecule-1 (ICAM-1) and CD44 variant isoform 5 (CD44v5) are among the up-regulated proteins, whereas angio-suppressive protein, thrombospondin-1 (TSP-1) was down-regulated in C666-1 exosomes. Further confocal microscopic study and Western blotting clearly demonstrated that the alteration of ICAM-1, and TSP-1 expressions in recipient HUVECs are due to internalization of exosomes. Taken together, these data strongly indicated the critical roles of identified angiogenic proteins in the involvement of exosomes-induced angiogenesis, which could potentially be developed as therapeutic targets in future. This article is protected by copyright. All rights reserved.

  2. Identifying type 1 diabetes candidate genes by DNA microarray analysis of islet-specific CD4+ T cells

    Directory of Open Access Journals (Sweden)

    Gregory J. Berry

    2015-09-01

    Full Text Available Type 1 diabetes (T1D is a T cell-mediated autoimmune disease resulting from the destruction of insulin-producing pancreatic beta cells and is fatal unless treated with insulin. During the last four decades, multiple insulin-dependent diabetes (Idd susceptibility/resistance loci that regulate T1D development have been identified in humans and non-obese diabetic (NOD mice, an established animal model for T1D. However, the exact mechanisms by which these loci confer diabetes risk and the identity of the causative genes remain largely elusive. To identify genes and molecular mechanisms that control the function of diabetogenic T cells, we conducted DNA microarray analysis in islet-specific CD4+ T cells from BDC2.5 TCR transgenic NOD mice that contain the Idd9 locus from T1D-susceptible NOD mice or T1D-resistant C57BL/10 mice. Here we describe in detail the contents and analyses for these gene expression data associated with our previous study [1]. Gene expression data are available at the Gene Expression Omnibus (GEO repository from the National Center for Biotechnology Information (accession number GSE64674.

  3. NCI-Molecular Analysis for Therapy Choice (NCI-MATCH) Trial

    Science.gov (United States)

    NCI's gateway for information about the NCI-Molecular Analysis for Therapy Choice (NCI-MATCH) trial, in which patients with advanced cancer are assigned to treatment arms based on the molecular profiles of their disease.

  4. An Integrative Transcriptomic Analysis for Identifying Novel Target Genes Corresponding to Severity Spectrum in Spinal Muscular Atrophy.

    Science.gov (United States)

    Yang, Chung-Wei; Chen, Chien-Lin; Chou, Wei-Chun; Lin, Ho-Chen; Jong, Yuh-Jyh; Tsai, Li-Kai; Chuang, Chun-Yu

    2016-01-01

    Spinal muscular atrophy (SMA) is an inherited neuromuscular disease resulting from a recessive mutation in the SMN1 gene. This disease affects multiple organ systems with varying degrees of severity. Exploration of the molecular pathological changes occurring in different cell types in SMA is crucial for developing new therapies. This study collected 39 human microarray datasets from ArrayExpress and GEO databases to build an integrative transcriptomic analysis for recognizing novel SMA targets. The transcriptomic analysis was conducted through combining weighted correlation network analysis (WGCNA) for gene module detection, gene set enrichment analysis (GSEA) for functional categorization and filtration, and Cytoscape (visual interaction gene network analysis) for target gene identification. Seven novel target genes (Bmp4, Serpine1, Gata6, Ptgs2, Bcl2, IL6 and Cntn1) of SMA were revealed, and are all known in the regulation of TNFα for controlling neural, cardiac and bone development. Sequentially, the differentially expressed patterns of these 7 target genes in mouse tissues (e.g., spinal cord, heart, muscles and bone) were validated in SMA mice of different severities (pre-symptomatic, mildly symptomatic, and severely symptomatic). In severely symptomatic SMA mice, TNFα was up-regulated with attenuation of Bmp4 and increase of Serpine1 and Gata6 (a pathway in neural and cardiac development), but not in pre-symptomatic and mildly symptomatic SMA mice. The severely symptomatic SMA mice also had the elevated levels of Ptgs2 and Bcl2 (a pathway in skeletal development) as well as IL6 and Cntn1 (a pathway in nervous system development). Thus, the 7 genes identified in this study might serve as potential target genes for future investigations of disease pathogenesis and SMA therapy. PMID:27331400

  5. An Integrative Transcriptomic Analysis for Identifying Novel Target Genes Corresponding to Severity Spectrum in Spinal Muscular Atrophy.

    Directory of Open Access Journals (Sweden)

    Chung-Wei Yang

    Full Text Available Spinal muscular atrophy (SMA is an inherited neuromuscular disease resulting from a recessive mutation in the SMN1 gene. This disease affects multiple organ systems with varying degrees of severity. Exploration of the molecular pathological changes occurring in different cell types in SMA is crucial for developing new therapies. This study collected 39 human microarray datasets from ArrayExpress and GEO databases to build an integrative transcriptomic analysis for recognizing novel SMA targets. The transcriptomic analysis was conducted through combining weighted correlation network analysis (WGCNA for gene module detection, gene set enrichment analysis (GSEA for functional categorization and filtration, and Cytoscape (visual interaction gene network analysis for target gene identification. Seven novel target genes (Bmp4, Serpine1, Gata6, Ptgs2, Bcl2, IL6 and Cntn1 of SMA were revealed, and are all known in the regulation of TNFα for controlling neural, cardiac and bone development. Sequentially, the differentially expressed patterns of these 7 target genes in mouse tissues (e.g., spinal cord, heart, muscles and bone were validated in SMA mice of different severities (pre-symptomatic, mildly symptomatic, and severely symptomatic. In severely symptomatic SMA mice, TNFα was up-regulated with attenuation of Bmp4 and increase of Serpine1 and Gata6 (a pathway in neural and cardiac development, but not in pre-symptomatic and mildly symptomatic SMA mice. The severely symptomatic SMA mice also had the elevated levels of Ptgs2 and Bcl2 (a pathway in skeletal development as well as IL6 and Cntn1 (a pathway in nervous system development. Thus, the 7 genes identified in this study might serve as potential target genes for future investigations of disease pathogenesis and SMA therapy.

  6. Candidate Genes Involved in the Biosynthesis of Triterpenoid Saponins in Platycodon grandiflorum Identified by Transcriptome Analysis

    Science.gov (United States)

    Ma, Chun-Hua; Gao, Zheng-Jie; Zhang, Jia-Jin; Zhang, Wei; Shao, Jian-Hui; Hai, Mei-Rong; Chen, Jun-Wen; Yang, Sheng-Chao; Zhang, Guang-Hui

    2016-01-01

    Background: Platycodon grandiflorum is the only species in the genus Platycodon of the family Campanulaceae, which has been traditionally used as a medicinal plant for its lung-heat-clearing, antitussive, and expectorant properties in China, Japanese, and Korean. Oleanane-type triterpenoid saponins were the main chemical components of P. grandiflorum and platycodin D was the abundant and main bioactive component, but little is known about their biosynthesis in plants. Hence, P. grandiflorum is an ideal medicinal plant for studying the biosynthesis of Oleanane-type saponins. In addition, the genomic information of this important herbal plant is unavailable. Principal findings: A total of 58,580,566 clean reads were obtained, which were assembled into 34,053 unigenes, with an average length of 936 bp and N50 of 1,661 bp by analyzing the transcriptome data of P. grandiflorum. Among these 34,053 unigenes, 22,409 unigenes (65.80%) were annotated based on the information available from public databases, including Nr, NCBI, Swiss-Prot, KOG, and KEGG. Furthermore, 21 candidate cytochrome P450 genes and 17 candidate UDP-glycosyltransferase genes most likely involved in triterpenoid saponins biosynthesis pathway were discovered from the transcriptome sequencing of P. grandiflorum. In addition, 10,626 SSRs were identified based on the transcriptome data, which would provide abundant candidates of molecular markers for genetic diversity and genetic map for this medicinal plant. Conclusion: The genomic data obtained from P. grandiflorum, especially the identification of putative genes involved in triterpenoid saponins biosynthesis pathway, will facilitate our understanding of the biosynthesis of triterpenoid saponins at molecular level. PMID:27242873

  7. Candidate genes involved in the biosynthesis of triterpenoid saponins in Platycodon grandiflorum identified by transcriptome analysis

    Directory of Open Access Journals (Sweden)

    Chunhua eMa

    2016-05-01

    Full Text Available Background: Platycodon grandiflorum is the only species in the genus Platycodon of the family Campanulaceae, which has been traditionally used as a medicinal plant for its lung-heat-clearing, antitussive, and expectorant properties in China, Japanese and Korean. Oleanane-type triterpenoid saponins were the main chemical components of P. grandiflorum and platycodin D was the abundant and main bioactive component, but little is known about their biosynthesis in plants. Hence, P. grandiflorum is an ideal medicinal plant for studying the biosynthesis of Oleanane-type saponins. In addition, the genomic information of this important herbal plant is unavailable.Principal Findings:A total of 58,580,566 clean reads were obtained, which were assembled into 34,053 unigenes, with an average length of 936 bp and N50 of 1,661 bp by analyzing the transcriptome data of P. grandiflorum. Among these 34,053 unigenes, 22,409 unigenes (65.80% were annotated based on the information available from public databases, including Nr, NCBI, Swiss-Prot, KOG and KEGG. Furthermore, 21 candidate cytochrome P450 genes and 17 candidate UDP-glycosyltransferase genes most likely involved in triterpenoid saponins biosynthesis pathway were discovered from the transcriptome sequencing of P. grandiflorum. In addition, 10,626 SSRs were identified based on the transcriptome data, which would provide abundant candidates of molecular markers for genetic diversity and genetic map for this medicinal plant.Conclusion:The genomic data obtained from P. grandiflorum, especially the identification of putative genes involved in triterpenoid saponins biosynthesis pathway, will facilitate our understanding of the biosynthesis of triterpenoid saponins at molecular level.

  8. Potential bacterial core species associated with digital dermatitis in cattle herds identified by molecular profiling of interdigital skin samples

    DEFF Research Database (Denmark)

    Weiss Nielsen, Martin; Strube, Mikael Lenz; Isbrand, Anastasia;

    2016-01-01

    Although treponemes are consistently identified in tissue from bovine digital dermatitis (DD) lesions, the definitive etiology of this debilitating polymicrobial disease is still unresolved. To study the microbiomes of 27 DD-infected and 10 healthy interdigital skin samples, we used a combination...

  9. Integrated Bioinformatics, Environmental Epidemiologic and Genomic Approaches to Identify Environmental and Molecular Links between Endometriosis and Breast Cancer

    OpenAIRE

    Deodutta Roy; Marisa Morgan; Changwon Yoo; Alok Deoraj; Sandhya Roy; Vijay Kumar Yadav; Mohannad Garoub; Hamza Assaggaf; Mayur Doke

    2015-01-01

    We present a combined environmental epidemiologic, genomic, and bioinformatics approach to identify: exposure of environmental chemicals with estrogenic activity; epidemiologic association between endocrine disrupting chemical (EDC) and health effects, such as, breast cancer or endometriosis; and gene-EDC interactions and disease associations. Human exposure measurement and modeling confirmed estrogenic activity of three selected class of environmental chemicals, polychlorinated biphenyls (PC...

  10. Identifying Sources and Transmission Routes of Norovirus Outbreaks : Molecular epidemiological methods as the basis for targeted prevention strategies

    NARCIS (Netherlands)

    F.H.A. Sukhrie (Faizel)

    2014-01-01

    markdownabstract__Abstract__ Norwalk virus, the prototype norovirus was first recognized as a cause of gastroenteritis in 1972 by means of electron microscopy (EM) on stool samples. Norwalk virus was identified by visualization of small round virus particles in stool samples from infected students

  11. Space-Time Analysis to Identify Areas at Risk of Mortality from Cardiovascular Disease

    Directory of Open Access Journals (Sweden)

    Poliany C. O. Rodrigues

    2015-01-01

    Full Text Available This study aimed at identifying areas that were at risk of mortality due to cardiovascular disease in residents aged 45 years or older of the cities of Cuiabá and Várzea Grande between 2009 and 2011. We conducted an ecological study of mortality rates related to cardiovascular disease. Mortality rates were calculated for each census tract by the Local Empirical Bayes estimator. High- and low-risk clusters were identified by retrospective space-time scans for each year using the Poisson probability model. We defined the year and month as the temporal analysis unit and the census tracts as the spatial analysis units adjusted by age and sex. The Mann-Whitney U test was used to compare the socioeconomic and environmental variables by risk classification. High-risk clusters showed higher income ratios than low-risk clusters, as did temperature range and atmospheric particulate matter. Low-risk clusters showed higher humidity than high-risk clusters. The Eastern region of Várzea Grande and the central region of Cuiabá were identified as areas at risk of mortality due to cardiovascular disease in individuals aged 45 years or older. High mortality risk was associated with socioeconomic and environmental factors. More high-risk clusters were observed at the end of the dry season.

  12. Design Analysis Rules to Identify Proper Noun from Bengali Sentence for Universal Networking language

    Directory of Open Access Journals (Sweden)

    Md. Syeful Islam

    2014-08-01

    Full Text Available Now-a-days hundreds of millions of people of almost all levels of education and attitudes from different country communicate with each other for different purposes and perform their jobs on internet or other communication medium using various languages. Not all people know all language; therefore it is very difficult to communicate or works on various languages. In this situation the computer scientist introduce various inter language translation program (Machine translation. UNL is such kind of inter language translation program. One of the major problem of UNL is identified a name from a sentence, which is relatively simple in English language, because such entities start with a capital letter. In Bangla we do not have concept of small or capital letters. Thus we find difficulties in understanding whether a word is a proper noun or not. Here we have proposed analysis rules to identify proper noun from a sentence and established post converter which translate the name entity from Bangla to UNL. The goal is to make possible Bangla sentence conversion to UNL and vice versa. UNL system prove that the theoretical analysis of our proposed system able to identify proper noun from Bangla sentence and produce relative Universal word for UNL.

  13. Whole Blood Transcriptomics Is Relevant to Identify Molecular Changes in Response to Genetic Selection for Feed Efficiency and Nutritional Status in the Pig.

    Directory of Open Access Journals (Sweden)

    Maëva Jégou

    Full Text Available The molecular mechanisms underlying feed efficiency need to be better understood to improve animal efficiency, a research priority to support a competitive and sustainable livestock production. This study was undertaken to determine whether pig blood transcriptome was affected by differences in feed efficiency and by ingested nutrients. Growing pigs from two lines divergently selected for residual feed intake (RFI and fed isoproteic and isocaloric diets contrasted in energy source and nutrients were considered. Between 74 and 132 days of age, pigs (n = 12 by diet and by line received a regular diet rich in cereals and low in fat (LF or a diet where cereals where partially substituted by lipids and fibers (HF. At the end of the feeding trial, the total number of white blood cells was not affected by the line or by the diet, whereas the red blood cell number was higher (P<0.001 in low RFI than in high RFI pigs. Analysis of the whole blood transcriptome using a porcine microarray reveals a higher number of probes differentially expressed (DE between RFI lines than between diets (2,154 versus 92 probes DE, P<0.01. This corresponds to 528 overexpressed genes and 477 underexpressed genes in low RFI pigs compared with high RFI pigs, respectively. Overexpressed genes were predominantly associated with translational elongation. Underexpressed genes were mainly involved in the immune response, regulation of inflammatory response, anti-apoptosis process, and cell organization. These findings suggest that selection for RFI has affected the immune status and defense mechanisms of pigs. Genes DE between diets were mainly related to the immune system and lipid metabolism. Altogether, this study demonstrates the usefulness of the blood transcriptome to identify the main biological processes affected by genetic selection and feeding strategies.

  14. Whole Blood Transcriptomics Is Relevant to Identify Molecular Changes in Response to Genetic Selection for Feed Efficiency and Nutritional Status in the Pig.

    Science.gov (United States)

    Jégou, Maëva; Gondret, Florence; Vincent, Annie; Tréfeu, Christine; Gilbert, Hélène; Louveau, Isabelle

    2016-01-01

    The molecular mechanisms underlying feed efficiency need to be better understood to improve animal efficiency, a research priority to support a competitive and sustainable livestock production. This study was undertaken to determine whether pig blood transcriptome was affected by differences in feed efficiency and by ingested nutrients. Growing pigs from two lines divergently selected for residual feed intake (RFI) and fed isoproteic and isocaloric diets contrasted in energy source and nutrients were considered. Between 74 and 132 days of age, pigs (n = 12 by diet and by line) received a regular diet rich in cereals and low in fat (LF) or a diet where cereals where partially substituted by lipids and fibers (HF). At the end of the feeding trial, the total number of white blood cells was not affected by the line or by the diet, whereas the red blood cell number was higher (PRFI than in high RFI pigs. Analysis of the whole blood transcriptome using a porcine microarray reveals a higher number of probes differentially expressed (DE) between RFI lines than between diets (2,154 versus 92 probes DE, PRFI pigs compared with high RFI pigs, respectively. Overexpressed genes were predominantly associated with translational elongation. Underexpressed genes were mainly involved in the immune response, regulation of inflammatory response, anti-apoptosis process, and cell organization. These findings suggest that selection for RFI has affected the immune status and defense mechanisms of pigs. Genes DE between diets were mainly related to the immune system and lipid metabolism. Altogether, this study demonstrates the usefulness of the blood transcriptome to identify the main biological processes affected by genetic selection and feeding strategies. PMID:26752050

  15. Natural history of chronic myelomonocytic leukemia: gene sequencing identifies multiple clonal molecular abnormalities associated with rapid progression to acute myeloid leukemia

    OpenAIRE

    Xiang, Zhifu; Kaur, Varinder; Aburiziq, Ibrahim K; Mehta, Paulette; Emanuel, Peter; Schichman, Steven A.

    2014-01-01

    Key Clinical Message Gene panel sequencing in a CMML patient without any detectable genetic abnormality by conventional genetic studies identified four concurrent somatic mutations in three genes. Gene panel mutation analysis is a rapidly emerging clinical tool to demonstrate the clonality in hematologic malignancies, and to identify the potential targets for therapy.

  16. Pharmacophore modeling and molecular dynamics simulation to identify the critical chemical features against human sirtuin 2 inhibitors

    Science.gov (United States)

    Sakkiah, Sugunadevi; Baek, Ayoung; Lee, Keun Woo

    2012-03-01

    Sirtuin 2 (SIRT2) is one of the emerging targets in chemotherapy field and mainly associated with many diseases such as cancer and Parkinson's. Hence, quantitative hypothesis was developed using Discovery Studio v2.5. Top ten resultant hypotheses were generated, among them Hypo1 was selected as a best hypothesis based on the statistical parameters like high cost difference (52), lowest RMS (0.71), and good correlation coefficient (0.96). Hypo1 has been validated by using well known methodologies such as Fischer's randomization method (95% confidence level), test set which has shown the correlation coefficient of 0.93 as well as the goodness of hit (0.65), and enrichment factor (8.80). All the above statistical validations confirm that the chemical features in Hypo1 (1 hydrogen bond acceptor, 1 hydrophobic, and 2 ring aromatic features) was able to inhibit the function of SIRT2. Hence, Hypo1 was used as a query in virtual screening to find a novel scaffolds by screening the various chemical databases. The screened molecules from the databases were checked for the ADMET as well as the drug-like properties. Due to the lack of SIRT2-ligand complex structure in PDB, molecular docking and molecular dynamics (MD) simulation was carried out to find the suitable orientation of ligand in the active site. The representative structure from MD simulations was used as a receptor to dock the molecules which passed the drug-like properties from the virtual screening. Finally, 29 compounds were selected as a potent candidate leads based on the interactions with the active site residues of SIRT2. Thus, the resultant pharmacophore can be used to discover and design the SIRT2 inhibitors with desired biological activity.

  17. A meta-analysis of 120 246 individuals identifies 18 new loci for fibrinogen concentration.

    Science.gov (United States)

    de Vries, Paul S; Chasman, Daniel I; Sabater-Lleal, Maria; Chen, Ming-Huei; Huffman, Jennifer E; Steri, Maristella; Tang, Weihong; Teumer, Alexander; Marioni, Riccardo E; Grossmann, Vera; Hottenga, Jouke J; Trompet, Stella; Müller-Nurasyid, Martina; Zhao, Jing Hua; Brody, Jennifer A; Kleber, Marcus E; Guo, Xiuqing; Wang, Jie Jin; Auer, Paul L; Attia, John R; Yanek, Lisa R; Ahluwalia, Tarunveer S; Lahti, Jari; Venturini, Cristina; Tanaka, Toshiko; Bielak, Lawrence F; Joshi, Peter K; Rocanin-Arjo, Ares; Kolcic, Ivana; Navarro, Pau; Rose, Lynda M; Oldmeadow, Christopher; Riess, Helene; Mazur, Johanna; Basu, Saonli; Goel, Anuj; Yang, Qiong; Ghanbari, Mohsen; Willemsen, Gonneke; Rumley, Ann; Fiorillo, Edoardo; de Craen, Anton J M; Grotevendt, Anne; Scott, Robert; Taylor, Kent D; Delgado, Graciela E; Yao, Jie; Kifley, Annette; Kooperberg, Charles; Qayyum, Rehan; Lopez, Lorna M; Berentzen, Tina L; Räikkönen, Katri; Mangino, Massimo; Bandinelli, Stefania; Peyser, Patricia A; Wild, Sarah; Trégouët, David-Alexandre; Wright, Alan F; Marten, Jonathan; Zemunik, Tatijana; Morrison, Alanna C; Sennblad, Bengt; Tofler, Geoffrey; de Maat, Moniek P M; de Geus, Eco J C; Lowe, Gordon D; Zoledziewska, Magdalena; Sattar, Naveed; Binder, Harald; Völker, Uwe; Waldenberger, Melanie; Khaw, Kay-Tee; Mcknight, Barbara; Huang, Jie; Jenny, Nancy S; Holliday, Elizabeth G; Qi, Lihong; Mcevoy, Mark G; Becker, Diane M; Starr, John M; Sarin, Antti-Pekka; Hysi, Pirro G; Hernandez, Dena G; Jhun, Min A; Campbell, Harry; Hamsten, Anders; Rivadeneira, Fernando; Mcardle, Wendy L; Slagboom, P Eline; Zeller, Tanja; Koenig, Wolfgang; Psaty, Bruce M; Haritunians, Talin; Liu, Jingmin; Palotie, Aarno; Uitterlinden, André G; Stott, David J; Hofman, Albert; Franco, Oscar H; Polasek, Ozren; Rudan, Igor; Morange, Pierre-Emmanuel; Wilson, James F; Kardia, Sharon L R; Ferrucci, Luigi; Spector, Tim D; Eriksson, Johan G; Hansen, Torben; Deary, Ian J; Becker, Lewis C; Scott, Rodney J; Mitchell, Paul; März, Winfried; Wareham, Nick J; Peters, Annette; Greinacher, Andreas; Wild, Philipp S; Jukema, J Wouter; Boomsma, Dorret I; Hayward, Caroline; Cucca, Francesco; Tracy, Russell; Watkins, Hugh; Reiner, Alex P; Folsom, Aaron R; Ridker, Paul M; O'Donnell, Christopher J; Smith, Nicholas L; Strachan, David P; Dehghan, Abbas

    2016-01-15

    Genome-wide association studies have previously identified 23 genetic loci associated with circulating fibrinogen concentration. These studies used HapMap imputation and did not examine the X-chromosome. 1000 Genomes imputation provides better coverage of uncommon variants, and includes indels. We conducted a genome-wide association analysis of 34 studies imputed to the 1000 Genomes Project reference panel and including ∼120 000 participants of European ancestry (95 806 participants with data on the X-chromosome). Approximately 10.7 million single-nucleotide polymorphisms and 1.2 million indels were examined. We identified 41 genome-wide significant fibrinogen loci; of which, 18 were newly identified. There were no genome-wide significant signals on the X-chromosome. The lead variants of five significant loci were indels. We further identified six additional independent signals, including three rare variants, at two previously characterized loci: FGB and IRF1. Together the 41 loci explain 3% of the variance in plasma fibrinogen concentration.

  18. The systematic functional analysis of plasmodium protein kinases identifies essential regulators of mosquito transmission

    KAUST Repository

    Tewari, Rita

    2010-10-21

    Although eukaryotic protein kinases (ePKs) contribute to many cellular processes, only three Plasmodium falciparum ePKs have thus far been identified as essential for parasite asexual blood stage development. To identify pathways essential for parasite transmission between their mammalian host and mosquito vector, we undertook a systematic functional analysis of ePKs in the genetically tractable rodent parasite Plasmodium berghei. Modeling domain signatures of conventional ePKs identified 66 putative Plasmodium ePKs. Kinomes are highly conserved between Plasmodium species. Using reverse genetics, we show that 23 ePKs are redundant for asexual erythrocytic parasite development in mice. Phenotyping mutants at four life cycle stages in Anopheles stephensi mosquitoes revealed functional clusters of kinases required for sexual development and sporogony. Roles for a putative SR protein kinase (SRPK) in microgamete formation, a conserved regulator of clathrin uncoating (GAK) in ookinete formation, and a likely regulator of energy metabolism (SNF1/KIN) in sporozoite development were identified. 2010 Elsevier Inc.

  19. Integrating Stakeholder Preferences and GIS-Based Multicriteria Analysis to Identify Forest Landscape Restoration Priorities

    Directory of Open Access Journals (Sweden)

    David Uribe

    2014-02-01

    Full Text Available A pressing question that arises during the planning of an ecological restoration process is: where to restore first? Answering this question is a complex task; it requires a multidimensional approach to consider economic constrains and the preferences of stakeholders. Being the problem of spatial nature, it may be explored effectively through Multicriteria Decision Analysis (MCDA performed in a Geographical Information System (GIS environment. The proposed approach is based on the definition and weighting of multiple criteria for evaluating land suitability. An MCDA-based methodology was used to identify priority areas for Forest Landscape Restoration in the Upper Mixtec region, Oaxaca (Mexico, one of the most degraded areas of Latin America. Socioeconomic and environmental criteria were selected and evaluated. The opinions of four different stakeholder groups were considered: general public, academic, Non-governmental organizations (NGOs and governmental officers. The preferences of these groups were spatially modeled to identify their priorities. The final result was a map that identifies the most preferable sites for restoration, where resources and efforts should be concentrated. MCDA proved to be a very useful tool in collective planning, when alternative sites have to be identified and prioritized to guide the restoration work.

  20. Unscented Kalman filter with parameter identifiability analysis for the estimation of multiple parameters in kinetic models

    Directory of Open Access Journals (Sweden)

    Baker Syed

    2011-01-01

    Full Text Available Abstract In systems biology, experimentally measured parameters are not always available, necessitating the use of computationally based parameter estimation. In order to rely on estimated parameters, it is critical to first determine which parameters can be estimated for a given model and measurement set. This is done with parameter identifiability analysis. A kinetic model of the sucrose accumulation in the sugar cane culm tissue developed by Rohwer et al. was taken as a test case model. What differentiates this approach is the integration of an orthogonal-based local identifiability method into the unscented Kalman filter (UKF, rather than using the more common observability-based method which has inherent limitations. It also introduces a variable step size based on the system uncertainty of the UKF during the sensitivity calculation. This method identified 10 out of 12 parameters as identifiable. These ten parameters were estimated using the UKF, which was run 97 times. Throughout the repetitions the UKF proved to be more consistent than the estimation algorithms used for comparison.

  1. A meta-analysis of 120 246 individuals identifies 18 new loci for fibrinogen concentration.

    Science.gov (United States)

    de Vries, Paul S; Chasman, Daniel I; Sabater-Lleal, Maria; Chen, Ming-Huei; Huffman, Jennifer E; Steri, Maristella; Tang, Weihong; Teumer, Alexander; Marioni, Riccardo E; Grossmann, Vera; Hottenga, Jouke J; Trompet, Stella; Müller-Nurasyid, Martina; Zhao, Jing Hua; Brody, Jennifer A; Kleber, Marcus E; Guo, Xiuqing; Wang, Jie Jin; Auer, Paul L; Attia, John R; Yanek, Lisa R; Ahluwalia, Tarunveer S; Lahti, Jari; Venturini, Cristina; Tanaka, Toshiko; Bielak, Lawrence F; Joshi, Peter K; Rocanin-Arjo, Ares; Kolcic, Ivana; Navarro, Pau; Rose, Lynda M; Oldmeadow, Christopher; Riess, Helene; Mazur, Johanna; Basu, Saonli; Goel, Anuj; Yang, Qiong; Ghanbari, Mohsen; Willemsen, Gonneke; Rumley, Ann; Fiorillo, Edoardo; de Craen, Anton J M; Grotevendt, Anne; Scott, Robert; Taylor, Kent D; Delgado, Graciela E; Yao, Jie; Kifley, Annette; Kooperberg, Charles; Qayyum, Rehan; Lopez, Lorna M; Berentzen, Tina L; Räikkönen, Katri; Mangino, Massimo; Bandinelli, Stefania; Peyser, Patricia A; Wild, Sarah; Trégouët, David-Alexandre; Wright, Alan F; Marten, Jonathan; Zemunik, Tatijana; Morrison, Alanna C; Sennblad, Bengt; Tofler, Geoffrey; de Maat, Moniek P M; de Geus, Eco J C; Lowe, Gordon D; Zoledziewska, Magdalena; Sattar, Naveed; Binder, Harald; Völker, Uwe; Waldenberger, Melanie; Khaw, Kay-Tee; Mcknight, Barbara; Huang, Jie; Jenny, Nancy S; Holliday, Elizabeth G; Qi, Lihong; Mcevoy, Mark G; Becker, Diane M; Starr, John M; Sarin, Antti-Pekka; Hysi, Pirro G; Hernandez, Dena G; Jhun, Min A; Campbell, Harry; Hamsten, Anders; Rivadeneira, Fernando; Mcardle, Wendy L; Slagboom, P Eline; Zeller, Tanja; Koenig, Wolfgang; Psaty, Bruce M; Haritunians, Talin; Liu, Jingmin; Palotie, Aarno; Uitterlinden, André G; Stott, David J; Hofman, Albert; Franco, Oscar H; Polasek, Ozren; Rudan, Igor; Morange, Pierre-Emmanuel; Wilson, James F; Kardia, Sharon L R; Ferrucci, Luigi; Spector, Tim D; Eriksson, Johan G; Hansen, Torben; Deary, Ian J; Becker, Lewis C; Scott, Rodney J; Mitchell, Paul; März, Winfried; Wareham, Nick J; Peters, Annette; Greinacher, Andreas; Wild, Philipp S; Jukema, J Wouter; Boomsma, Dorret I; Hayward, Caroline; Cucca, Francesco; Tracy, Russell; Watkins, Hugh; Reiner, Alex P; Folsom, Aaron R; Ridker, Paul M; O'Donnell, Christopher J; Smith, Nicholas L; Strachan, David P; Dehghan, Abbas

    2016-01-15

    Genome-wide association studies have previously identified 23 genetic loci associated with circulating fibrinogen concentration. These studies used HapMap imputation and did not examine the X-chromosome. 1000 Genomes imputation provides better coverage of uncommon variants, and includes indels. We conducted a genome-wide association analysis of 34 studies imputed to the 1000 Genomes Project reference panel and including ∼120 000 participants of European ancestry (95 806 participants with data on the X-chromosome). Approximately 10.7 million single-nucleotide polymorphisms and 1.2 million indels were examined. We identified 41 genome-wide significant fibrinogen loci; of which, 18 were newly identified. There were no genome-wide significant signals on the X-chromosome. The lead variants of five significant loci were indels. We further identified six additional independent signals, including three rare variants, at two previously characterized loci: FGB and IRF1. Together the 41 loci explain 3% of the variance in plasma fibrinogen concentration. PMID:26561523

  2. Identifying E-Business Model:A Value Chain-Based Analysis

    Institute of Scientific and Technical Information of China (English)

    ZENG Qingfeng; HUANG Lihua

    2004-01-01

    E-business will change the ways that all companies do business, and most traditional businesses will evolve from their current business model to a combination of place and space via e-business model To choose the proper e-business model becomes the important strategic concern for company to succeed The main objective of this paper is to investigate the analysis framework for identifying e-business model Based on the e-business process, from the value chain to the value net perspective. This paper provides a theoretical framework for identifying e-business models, and results in 11 e-business models. The strategic intend of every e-business model is discussed in the end of this paper. An enterprise e-business model design and implementation can be specified by the combination of one or more among 11 e-business models.

  3. Proteomic analysis of cell lines to identify the irinotecan resistance proteins

    Indian Academy of Sciences (India)

    Xing-Chen Peng; Feng-Ming Gong; Meng Wei; X I Chen; Y E Chen; K E Cheng; Feng Gao; Feng Xu; FENG Bi; Ji-Yan Liu

    2010-12-01

    Chemotherapeutic drug resistance is a frequent cause of treatment failure in colon cancer patients. Several mechanisms have been implicated in drug resistance. However, they are not sufficient to exhaustively account for this resistance emergence. In this study, two-dimensional gel electrophoresis (2-DE) and the PDQuest software analysis were applied to compare the differential expression of irinotecan-resistance-associated protein in human colon adenocarcinoma LoVo cells and irinotecan-resistant LoVo cells (LoVo/irinotecan). The differential protein dots were excised and analysed by ESI-Q-TOF mass spectrometry (MS). Fifteen proteins were identified, including eight proteins with decreased expression and seven proteins with increased expression. The identified known proteins included those that function in diverse biological processes such as cellular transcription, cell apoptosis, electron transport/redox regulation, cell proliferation/differentiation and retinol metabolism pathways. Identification of such proteins could allow improved understanding of the mechanisms leading to the acquisition of chemoresistance.

  4. Finite Element Creep-Fatigue Analysis of a Welded Furnace Roll for Identifying Failure Root Cause

    Science.gov (United States)

    Yang, Y. P.; Mohr, W. C.

    2015-11-01

    Creep-fatigue induced failures are often observed in engineering components operating under high temperature and cyclic loading. Understanding the creep-fatigue damage process and identifying failure root cause are very important for preventing such failures and improving the lifetime of engineering components. Finite element analyses including a heat transfer analysis and a creep-fatigue analysis were conducted to model the cyclic thermal and mechanical process of a furnace roll in a continuous hot-dip coating line. Typically, the roll has a short life, heat transfer analysis was conducted to predict the temperature history of the roll by modeling heat convection from hot air inside the furnace. The creep-fatigue analysis was performed by inputting the predicted temperature history and applying mechanical loads. The analysis results showed that the failure was resulted from a creep-fatigue mechanism rather than a creep mechanism. The difference of material properties between the filler metal and the base metal is the root cause for the roll failure, which induces higher creep strain and stress in the interface between the weld and the HAZ.

  5. Gene-network analysis identifies susceptibility genes related to glycobiology in autism.

    Directory of Open Access Journals (Sweden)

    Bert van der Zwaag

    Full Text Available The recent identification of copy-number variation in the human genome has opened up new avenues for the discovery of positional candidate genes underlying complex genetic disorders, especially in the field of psychiatric disease. One major challenge that remains is pinpointing the susceptibility genes in the multitude of disease-associated loci. This challenge may be tackled by reconstruction of functional gene-networks from the genes residing in these loci. We applied this approach to autism spectrum disorder (ASD, and identified the copy-number changes in the DNA of 105 ASD patients and 267 healthy individuals with Illumina Humanhap300 Beadchips. Subsequently, we used a human reconstructed gene-network, Prioritizer, to rank candidate genes in the segmental gains and losses in our autism cohort. This analysis highlighted several candidate genes already known to be mutated in cognitive and neuropsychiatric disorders, including RAI1, BRD1, and LARGE. In addition, the LARGE gene was part of a sub-network of seven genes functioning in glycobiology, present in seven copy-number changes specifically identified in autism patients with limited co-morbidity. Three of these seven copy-number changes were de novo in the patients. In autism patients with a complex phenotype and healthy controls no such sub-network was identified. An independent systematic analysis of 13 published autism susceptibility loci supports the involvement of genes related to glycobiology as we also identified the same or similar genes from those loci. Our findings suggest that the occurrence of genomic gains and losses of genes associated with glycobiology are important contributors to the development of ASD.

  6. Systematic enrichment analysis of gene expression profiling studies identifies consensus pathways implicated in colorectal cancer development

    Directory of Open Access Journals (Sweden)

    Jesús Lascorz

    2011-01-01

    Full Text Available Background: A large number of gene expression profiling (GEP studies on colorectal carcinogenesis have been performed but no reliable gene signature has been identified so far due to the lack of reproducibility in the reported genes. There is growing evidence that functionally related genes, rather than individual genes, contribute to the etiology of complex traits. We used, as a novel approach, pathway enrichment tools to define functionally related genes that are consistently up- or down-regulated in colorectal carcinogenesis. Materials and Methods: We started the analysis with 242 unique annotated genes that had been reported by any of three recent meta-analyses covering GEP studies on genes differentially expressed in carcinoma vs normal mucosa. Most of these genes (218, 91.9% had been reported in at least three GEP studies. These 242 genes were submitted to bioinformatic analysis using a total of nine tools to detect enrichment of Gene Ontology (GO categories or Kyoto Encyclopedia of Genes and Genomes (KEGG pathways. As a final consistency criterion the pathway categories had to be enriched by several tools to be taken into consideration. Results: Our pathway-based enrichment analysis identified the categories of ribosomal protein constituents, extracellular matrix receptor interaction, carbonic anhydrase isozymes, and a general category related to inflammation and cellular response as significantly and consistently overrepresented entities. Conclusions: We triaged the genes covered by the published GEP literature on colorectal carcinogenesis and subjected them to multiple enrichment tools in order to identify the consistently enriched gene categories. These turned out to have known functional relationships to cancer development and thus deserve further investigation.

  7. A sequence-based approach to identify reference genes for gene expression analysis

    Directory of Open Access Journals (Sweden)

    Chari Raj

    2010-08-01

    Full Text Available Abstract Background An important consideration when analyzing both microarray and quantitative PCR expression data is the selection of appropriate genes as endogenous controls or reference genes. This step is especially critical when identifying genes differentially expressed between datasets. Moreover, reference genes suitable in one context (e.g. lung cancer may not be suitable in another (e.g. breast cancer. Currently, the main approach to identify reference genes involves the mining of expression microarray data for highly expressed and relatively constant transcripts across a sample set. A caveat here is the requirement for transcript normalization prior to analysis, and measurements obtained are relative, not absolute. Alternatively, as sequencing-based technologies provide digital quantitative output, absolute quantification ensues, and reference gene identification becomes more accurate. Methods Serial analysis of gene expression (SAGE profiles of non-malignant and malignant lung samples were compared using a permutation test to identify the most stably expressed genes across all samples. Subsequently, the specificity of the reference genes was evaluated across multiple tissue types, their constancy of expression was assessed using quantitative RT-PCR (qPCR, and their impact on differential expression analysis of microarray data was evaluated. Results We show that (i conventional references genes such as ACTB and GAPDH are highly variable between cancerous and non-cancerous samples, (ii reference genes identified for lung cancer do not perform well for other cancer types (breast and brain, (iii reference genes identified through SAGE show low variability using qPCR in a different cohort of samples, and (iv normalization of a lung cancer gene expression microarray dataset with or without our reference genes, yields different results for differential gene expression and subsequent analyses. Specifically, key established pathways in lung

  8. Large-scale gene-centric meta-analysis across 32 studies identifies multiple lipid loci.

    Science.gov (United States)

    Asselbergs, Folkert W; Guo, Yiran; van Iperen, Erik P A; Sivapalaratnam, Suthesh; Tragante, Vinicius; Lanktree, Matthew B; Lange, Leslie A; Almoguera, Berta; Appelman, Yolande E; Barnard, John; Baumert, Jens; Beitelshees, Amber L; Bhangale, Tushar R; Chen, Yii-Der Ida; Gaunt, Tom R; Gong, Yan; Hopewell, Jemma C; Johnson, Toby; Kleber, Marcus E; Langaee, Taimour Y; Li, Mingyao; Li, Yun R; Liu, Kiang; McDonough, Caitrin W; Meijs, Matthijs F L; Middelberg, Rita P S; Musunuru, Kiran; Nelson, Christopher P; O'Connell, Jeffery R; Padmanabhan, Sandosh; Pankow, James S; Pankratz, Nathan; Rafelt, Suzanne; Rajagopalan, Ramakrishnan; Romaine, Simon P R; Schork, Nicholas J; Shaffer, Jonathan; Shen, Haiqing; Smith, Erin N; Tischfield, Sam E; van der Most, Peter J; van Vliet-Ostaptchouk, Jana V; Verweij, Niek; Volcik, Kelly A; Zhang, Li; Bailey, Kent R; Bailey, Kristian M; Bauer, Florianne; Boer, Jolanda M A; Braund, Peter S; Burt, Amber; Burton, Paul R; Buxbaum, Sarah G; Chen, Wei; Cooper-Dehoff, Rhonda M; Cupples, L Adrienne; deJong, Jonas S; Delles, Christian; Duggan, David; Fornage, Myriam; Furlong, Clement E; Glazer, Nicole; Gums, John G; Hastie, Claire; Holmes, Michael V; Illig, Thomas; Kirkland, Susan A; Kivimaki, Mika; Klein, Ronald; Klein, Barbara E; Kooperberg, Charles; Kottke-Marchant, Kandice; Kumari, Meena; LaCroix, Andrea Z; Mallela, Laya; Murugesan, Gurunathan; Ordovas, Jose; Ouwehand, Willem H; Post, Wendy S; Saxena, Richa; Scharnagl, Hubert; Schreiner, Pamela J; Shah, Tina; Shields, Denis C; Shimbo, Daichi; Srinivasan, Sathanur R; Stolk, Ronald P; Swerdlow, Daniel I; Taylor, Herman A; Topol, Eric J; Toskala, Elina; van Pelt, Joost L; van Setten, Jessica; Yusuf, Salim; Whittaker, John C; Zwinderman, A H; Anand, Sonia S; Balmforth, Anthony J; Berenson, Gerald S; Bezzina, Connie R; Boehm, Bernhard O; Boerwinkle, Eric; Casas, Juan P; Caulfield, Mark J; Clarke, Robert; Connell, John M; Cruickshanks, Karen J; Davidson, Karina W; Day, Ian N M; de Bakker, Paul I W; Doevendans, Pieter A; Dominiczak, Anna F; Hall, Alistair S; Hartman, Catharina A; Hengstenberg, Christian; Hillege, Hans L; Hofker, Marten H; Humphries, Steve E; Jarvik, Gail P; Johnson, Julie A; Kaess, Bernhard M; Kathiresan, Sekar; Koenig, Wolfgang; Lawlor, Debbie A; März, Winfried; Melander, Olle; Mitchell, Braxton D; Montgomery, Grant W; Munroe, Patricia B; Murray, Sarah S; Newhouse, Stephen J; Onland-Moret, N Charlotte; Poulter, Neil; Psaty, Bruce; Redline, Susan; Rich, Stephen S; Rotter, Jerome I; Schunkert, Heribert; Sever, Peter; Shuldiner, Alan R; Silverstein, Roy L; Stanton, Alice; Thorand, Barbara; Trip, Mieke D; Tsai, Michael Y; van der Harst, Pim; van der Schoot, Ellen; van der Schouw, Yvonne T; Verschuren, W M Monique; Watkins, Hugh; Wilde, Arthur A M; Wolffenbuttel, Bruce H R; Whitfield, John B; Hovingh, G Kees; Ballantyne, Christie M; Wijmenga, Cisca; Reilly, Muredach P; Martin, Nicholas G; Wilson, James G; Rader, Daniel J; Samani, Nilesh J; Reiner, Alex P; Hegele, Robert A; Kastelein, John J P; Hingorani, Aroon D; Talmud, Philippa J; Hakonarson, Hakon; Elbers, Clara C; Keating, Brendan J; Drenos, Fotios

    2012-11-01

    Genome-wide association studies (GWASs) have identified many SNPs underlying variations in plasma-lipid levels. We explore whether additional loci associated with plasma-lipid phenotypes, such as high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and triglycerides (TGs), can be identified by a dense gene-centric approach. Our meta-analysis of 32 studies in 66,240 individuals of European ancestry was based on the custom ∼50,000 SNP genotyping array (the ITMAT-Broad-CARe array) covering ∼2,000 candidate genes. SNP-lipid associations were replicated either in a cohort comprising an additional 24,736 samples or within the Global Lipid Genetic Consortium. We identified four, six, ten, and four unreported SNPs in established lipid genes for HDL-C, LDL-C, TC, and TGs, respectively. We also identified several lipid-related SNPs in previously unreported genes: DGAT2, HCAR2, GPIHBP1, PPARG, and FTO for HDL-C; SOCS3, APOH, SPTY2D1, BRCA2, and VLDLR for LDL-C; SOCS3, UGT1A1, BRCA2, UBE3B, FCGR2A, CHUK, and INSIG2 for TC; and SERPINF2, C4B, GCK, GATA4, INSR, and LPAL2 for TGs. The proportion of explained phenotypic variance in the subset of studies providing individual-level data was 9.9% for HDL-C, 9.5% for LDL-C, 10.3% for TC, and 8.0% for TGs. This large meta-analysis of lipid phenotypes with the use of a dense gene-centric approach identified multiple SNPs not previously described in established lipid genes and several previously unknown loci. The explained phenotypic variance from this approach was comparable to that from a meta-analysis of GWAS data, suggesting that a focused genotyping approach can further increase the understanding of heritability of plasma lipids. PMID:23063622

  9. Cluster analysis for identifying sub-groups and selecting potential discriminatory variables in human encephalitis

    Directory of Open Access Journals (Sweden)

    Crowcroft Natasha S

    2010-12-01

    Full Text Available Abstract Background Encephalitis is an acute clinical syndrome of the central nervous system (CNS, often associated with fatal outcome or permanent damage, including cognitive and behavioural impairment, affective disorders and epileptic seizures. Infection of the central nervous system is considered to be a major cause of encephalitis and more than 100 different pathogens have been recognized as causative agents. However, a large proportion of cases have unknown disease etiology. Methods We perform hierarchical cluster analysis on a multicenter England encephalitis data set with the aim of identifying sub-groups in human encephalitis. We use the simple matching similarity measure which is appropriate for binary data sets and performed variable selection using cluster heatmaps. We also use heatmaps to visually assess underlying patterns in the data, identify the main clinical and laboratory features and identify potential risk factors associated with encephalitis. Results Our results identified fever, personality and behavioural change, headache and lethargy as the main characteristics of encephalitis. Diagnostic variables such as brain scan and measurements from cerebrospinal fluids are also identified as main indicators of encephalitis. Our analysis revealed six major clusters in the England encephalitis data set. However, marked within-cluster heterogeneity is observed in some of the big clusters indicating possible sub-groups. Overall, the results show that patients are clustered according to symptom and diagnostic variables rather than causal agents. Exposure variables such as recent infection, sick person contact and animal contact have been identified as potential risk factors. Conclusions It is in general assumed and is a common practice to group encephalitis cases according to disease etiology. However, our results indicate that patients are clustered with respect to mainly symptom and diagnostic variables rather than causal agents

  10. Genetic diversity analysis of common beans based on molecular markers

    Directory of Open Access Journals (Sweden)

    Homar R. Gill-Langarica

    2011-01-01

    Full Text Available A core collection of the common bean (Phaseolus vulgaris L., representing genetic diversity in the entire Mexican holding, is kept at the INIFAP (Instituto Nacional de Investigaciones Forestales, Agricolas y Pecuarias, Mexico Germplasm Bank. After evaluation, the genetic structure of this collection (200 accessions was compared with that of landraces from the states of Oaxaca, Chiapas and Veracruz (10 genotypes from each, as well as a further 10 cultivars, by means of four amplified fragment length polymorphisms (AFLP +3/+3 primer combinations and seven simple sequence repeats (SSR loci, in order to define genetic diversity, variability and mutual relationships. Data underwent cluster (UPGMA and molecular variance (AMOVA analyses. AFLP analysis produced 530 bands (88.5% polymorphic while SSR primers amplified 174 alleles, all polymorphic (8.2 alleles per locus. AFLP indicated that the highest genetic diversity was to be found in ten commercial-seed classes from two major groups of accessions from Central Mexico and Chiapas, which seems to be an important center of diversity in the south. A third group included genotypes from Nueva Granada, Mesoamerica, Jalisco and Durango races. Here, SSR analysis indicated a reduced number of shared haplotypes among accessions, whereas the highest genetic components of AMOVA variation were found within accessions. Genetic diversity observed in the common-bean core collection represents an important sample of the total Phaseolus genetic variability at the main Germplasm Bank of INIFAP. Molecular marker strategies could contribute to a better understanding of the genetic structure of the core collection as well as to its improvement and validation.

  11. Genetic diversity analysis of common beans based on molecular markers.

    Science.gov (United States)

    Gill-Langarica, Homar R; Muruaga-Martínez, José S; Vargas-Vázquez, M L Patricia; Rosales-Serna, Rigoberto; Mayek-Pérez, Netzahualcoyotl

    2011-10-01

    A core collection of the common bean (Phaseolus vulgaris L.), representing genetic diversity in the entire Mexican holding, is kept at the INIFAP (Instituto Nacional de Investigaciones Forestales, Agricolas y Pecuarias, Mexico) Germplasm Bank. After evaluation, the genetic structure of this collection (200 accessions) was compared with that of landraces from the states of Oaxaca, Chiapas and Veracruz (10 genotypes from each), as well as a further 10 cultivars, by means of four amplified fragment length polymorphisms (AFLP) +3/+3 primer combinations and seven simple sequence repeats (SSR) loci, in order to define genetic diversity, variability and mutual relationships. Data underwent cluster (UPGMA) and molecular variance (AMOVA) analyses. AFLP analysis produced 530 bands (88.5% polymorphic) while SSR primers amplified 174 alleles, all polymorphic (8.2 alleles per locus). AFLP indicated that the highest genetic diversity was to be found in ten commercial-seed classes from two major groups of accessions from Central Mexico and Chiapas, which seems to be an important center of diversity in the south. A third group included genotypes from Nueva Granada, Mesoamerica, Jalisco and Durango races. Here, SSR analysis indicated a reduced number of shared haplotypes among accessions, whereas the highest genetic components of AMOVA variation were found within accessions. Genetic diversity observed in the common-bean core collection represents an important sample of the total Phaseolus genetic variability at the main Germplasm Bank of INIFAP. Molecular marker strategies could contribute to a better understanding of the genetic structure of the core collection as well as to its improvement and validation.

  12. Genetic diversity of popcorn genotypes using molecular analysis.

    Science.gov (United States)

    Resh, F S; Scapim, C A; Mangolin, C A; Machado, M F P S; do Amaral, A T; Ramos, H C C; Vivas, M

    2015-01-01

    In this study, we analyzed dominant molecular markers to estimate the genetic divergence of 26 popcorn genotypes and evaluate whether using various dissimilarity coefficients with these dominant markers influences the results of cluster analysis. Fifteen random amplification of polymorphic DNA primers produced 157 amplified fragments, of which 65 were monomorphic and 92 were polymorphic. To calculate the genetic distances among the 26 genotypes, the complements of the Jaccard, Dice, and Rogers and Tanimoto similarity coefficients were used. A matrix of Dij values (dissimilarity matrix) was constructed, from which the genetic distances among genotypes were represented in a more simplified manner as a dendrogram generated using the unweighted pair-group method with arithmetic average. Clusters determined by molecular analysis generally did not group material from the same parental origin together. The largest genetic distance was between varieties 17 (UNB-2) and 18 (PA-091). In the identification of genotypes with the smallest genetic distance, the 3 coefficients showed no agreement. The 3 dissimilarity coefficients showed no major differences among their grouping patterns because agreement in determining the genotypes with large, medium, and small genetic distances was high. The largest genetic distances were observed for the Rogers and Tanimoto dissimilarity coefficient (0.74), followed by the Jaccard coefficient (0.65) and the Dice coefficient (0.48). The 3 coefficients showed similar estimations for the cophenetic correlation coefficient. Correlations among the matrices generated using the 3 coefficients were positive and had high magnitudes, reflecting strong agreement among the results obtained using the 3 evaluated dissimilarity coefficients. PMID:26345916

  13. Use of Antibiotic Resistance Analysis To Identify Nonpoint Sources of Fecal Pollution

    OpenAIRE

    Wiggins, B A; Andrews, R. W.; Conway, R. A.; Corr, C. L.; Dobratz, E. J.; Dougherty, D. P.; Eppard, J. R.; Knupp, S. R.; Limjoco, M. C.; Mettenburg, J. M.; Rinehardt, J. M.; Sonsino, J.; Torrijos, R. L.; Zimmerman, M.E.

    1999-01-01

    A study was conducted to determine the reliability and repeatability of antibiotic resistance analysis as a method of identifying the sources of fecal pollution in surface water and groundwater. Four large sets of isolates of fecal streptococci (from 2,635 to 5,990 isolates per set) were obtained from 236 samples of human sewage and septage, cattle and poultry feces, and pristine waters. The patterns of resistance of the isolates to each of four concentrations of up to nine antibiotics were a...

  14. Differentially expressed genes in pancreatic ductal adenocarcinomas identified through serial analysis of gene expression

    DEFF Research Database (Denmark)

    Hustinx, Steven R; Cao, Dengfeng; Maitra, Anirban;

    2004-01-01

    Serial analysis of gene expression (SAGE) is a powerful tool for the discovery of novel tumor markers. The publicly available online SAGE libraries of normal and neoplastic tissues (http://www.ncbi.nlm.nih.gov/SAGE/) have recently been expanded; in addition, a more complete annotation of the human...... of this program. Novel differentially expressed genes in a cancer type can be identified by revisiting updated and expanded SAGE databases. TAGmapper should prove to be a powerful tool for the discovery of novel tumor markers through assignment of uncharacterized SAGE tags....

  15. Can molecular projected density of states (PDOS be systematically used in electronic conductance analysis?

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    Tonatiuh Rangel

    2015-06-01

    Full Text Available Using benzenediamine and benzenedithiol molecular junctions as benchmarks, we investigate the widespread analysis of the quantum transport conductance in terms of the projected density of states (PDOS onto molecular orbitals (MOs. We first consider two different methods for identifying the relevant MOs: (1 diagonalization of the Hamiltonian of the isolated molecule and (2 diagonalization of a submatrix of the junction Hamiltonian constructed by considering only basis elements localized on the molecule. We find that these two methods can lead to substantially different MOs and hence PDOS. Furthermore, within Method 1, the PDOS can differ depending on the isolated molecule chosen to represent the molecular junction (e.g., with or without dangling bonds; within Method 2, the PDOS depends on the chosen basis set. We show that these differences can be critical when the PDOS is used to provide a physical interpretation of the conductance (especially when its value is small, as it happens typically at zero bias. In this work, we propose a new approach in an attempt to reconcile the two traditional methods. Although some improvements were achieved, the main problems remain unsolved. Our results raise more general questions and doubts on a PDOS-based analysis of the conductance.

  16. Multifactor dimensionality reduction analysis identifies specific nucleotide patterns promoting genetic polymorphisms

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    Arehart Eric

    2009-03-01

    Full Text Available Abstract Background The fidelity of DNA replication serves as the nidus for both genetic evolution and genomic instability fostering disease. Single nucleotide polymorphisms (SNPs constitute greater than 80% of the genetic variation between individuals. A new theory regarding DNA replication fidelity has emerged in which selectivity is governed by base-pair geometry through interactions between the selected nucleotide, the complementary strand, and the polymerase active site. We hypothesize that specific nucleotide combinations in the flanking regions of SNP fragments are associated with mutation. Results We modeled the relationship between DNA sequence and observed polymorphisms using the novel multifactor dimensionality reduction (MDR approach. MDR was originally developed to detect synergistic interactions between multiple SNPs that are predictive of disease susceptibility. We initially assembled data from the Broad Institute as a pilot test for the hypothesis that flanking region patterns associate with mutagenesis (n = 2194. We then confirmed and expanded our inquiry with human SNPs within coding regions and their flanking sequences collected from the National Center for Biotechnology Information (NCBI database (n = 29967 and a control set of sequences (coding region not associated with SNP sites randomly selected from the NCBI database (n = 29967. We discovered seven flanking region pattern associations in the Broad dataset which reached a minimum significance level of p ≤ 0.05. Significant models (p Conclusion The present study represents the first use of this computational methodology for modeling nonlinear patterns in molecular genetics. MDR was able to identify distinct nucleotide patterning around sites of mutations dependent upon the observed nucleotide change. We discovered one flanking region set that included five nucleotides clustered around a specific type of SNP site. Based on the strongly associated patterns identified in

  17. RNA-seq analysis to identify novel roles of scleraxis during embryonic mouse heart valve remodeling.

    Directory of Open Access Journals (Sweden)

    Damien N Barnette

    Full Text Available Heart valve disease affects up to 30% of the population and has been shown to have origins during embryonic development. Valvulogenesis begins with formation of endocardial cushions in the atrioventricular canal and outflow tract regions. Subsequently, endocardial cushions remodel, elongate and progressively form mature valve structures composed of a highly organized connective tissue that provides the necessary biomechanical function throughout life. While endocardial cushion formation has been well studied, the processes required for valve remodeling are less well understood. The transcription factor Scleraxis (Scx is detected in mouse valves from E15.5 during initial stages of remodeling, and expression remains high until birth when formation of the highly organized mature structure is complete. Heart valves from Scx-/- mice are abnormally thick and develop fibrotic phenotypes similar to human disease by juvenile stages. These phenotypes begin around E15.5 and are associated with defects in connective tissue organization and valve interstitial cell differentiation. In order to understand the etiology of this phenotype, we analyzed the transcriptome of remodeling valves isolated from E15.5 Scx-/- embryos using RNA-seq. From this, we have identified a profile of protein and non-protein mRNAs that are dependent on Scx function and using bioinformatics we can predict the molecular functions and biological processes affected by these genes. These include processes and functions associated with gene regulation (methyltransferase activity, DNA binding, Notch signaling, vitamin A metabolism (retinoic acid biosynthesis and cellular development (cell morphology, cell assembly and organization. In addition, several mRNAs are affected by alternative splicing events in the absence of Scx, suggesting additional roles in post-transcriptional modification. In summary, our findings have identified transcriptome profiles from abnormal heart valves isolated

  18. Identification of HNPCC by Molecular Analysis of Colorectal and Endometrial Tumors

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    H. F. A. Vasen

    2004-01-01

    Full Text Available Hereditary nonpolyposis colorectal cancer (HNPCC, Lynch syndrome is a dominantly inherited syndrome characterized by the development of colorectal cancer, endometrial cancer and other cancers and the presence of microsatellite instability (MSI in tumors. The Bethesda guidelines have been proposed for the identification of families suspected of HNPCC that require further molecular analysis. We have evaluated the yield of MSI-analysis in a large series of Dutch families suspected of HNPCC. We also analysed whether the loss of mismatch repair (MMR protein detected by immunohistochemistry (IHC of colorectal cancer (CRC and endometrial cancer correlated with the presence of MSI and/or a MMR gene mutation. The results showed that the Bethesda criteria with a few modifications are appropriate to identify families eligible for genetic testing. In addition, we found that MSI and IHC-analysis of CRC using antibodies against MLH1, MSH2, MSH6 and PMS2 proteins are equally effective for identifying carriers of the known MMR gene defects. However, as long as the role of other putative MMR genes in hereditary CRC has not been elucidated, IHC-analysis cannot completely replace MSI. For this reason, we prefer MSI-analysis as first step in families suspected of HNPCC. On the other hand, in families fulfilling the revised Amsterdam criteria in which the probability of detecting a mutation is relatively high, we would recommend IHC as first diagnostic step because the result might predict the specific underlying MMR gene mutation. MSI or IHC-analysis of endometrial cancer alone was found to be less sensitive compared with these tests performed in colorectal cancer. Therefore, probably the best approach in the analysis of this cancer is to perform both techniques. The identification of HNPCC is important as it makes it possible to target effective preventative measures. Our studies showed that MSI and IHC analysis of colorectal and endometrial cancer, are reliable

  19. Integrative Functional Genomics Analysis of Sustained Polyploidy Phenotypes in Breast Cancer Cells Identifies an Oncogenic Profile for GINS2

    Directory of Open Access Journals (Sweden)

    Juha K. Rantala

    2010-11-01

    Full Text Available Aneuploidy is among the most obvious differences between normal and cancer cells. However, mechanisms contributing to development and maintenance of aneuploid cell growth are diverse and incompletely understood. Functional genomics analyses have shown that aneuploidy in cancer cells is correlated with diffuse gene expression signatures and aneuploidy can arise by a variety of mechanisms, including cytokinesis failures, DNA endoreplication, and possibly through polyploid intermediate states. To identify molecular processes contributing to development of aneuploidy, we used a cell spot microarray technique to identify genes inducing polyploidy and/or allowing maintenance of polyploid cell growth in breast cancer cells. Of 5760 human genes screened, 177 were found to induce severe DNA content alterations on prolonged transient silencing. Association with response to DNA damage stimulus and DNA repair was found to be the most enriched cellular processes among the candidate genes. Functional validation analysis of these genes highlighted GINS2 as the highest ranking candidate inducing polyploidy, accumulation of endogenous DNA damage, and impairing cell proliferation on inhibition. The cell growth inhibition and induction of polyploidy by suppression of GINS2 was verified in a panel of breast cancer cell lines. Bioinformatic analysis of published gene expression and DNA copy number studies of clinical breast tumors suggested GINS2 to be associated with the aggressive characteristics of a subgroup of breast cancers in vivo. In addition, nuclear GINS2 protein levels distinguished actively proliferating cancer cells suggesting potential use of GINS2 staining as a biomarker of cell proliferation as well as a potential therapeutic target.

  20. Identifying Chemistry Prospective Teachers' Difficulties Encountered in Practice of The Subject Area Textbook Analysis Course

    Directory of Open Access Journals (Sweden)

    Zeynep Bak Kibar

    2010-12-01

    Full Text Available Prospective teachers should already be aware of possible mistakes in the textbooks and have knowledge of textbooks selection procedure and criteria. These knowledge is tried to being gained to prospective teachers at the Subject Area Textbook Analysis Course. It is important to identify the difficulties they encountered and the skills they gained from the point of implementing effectively this lesson. To research these problems, a case study was realized with 38 student teachers from Department of Secondary Science and Mathematics Education Chemistry Teaching Program at the Karadeniz Technical University Faculty of Fatih Education. Results suggest that prospective teachers gained the knowledge of research, teaching life, writing report, and analyzing textbook. Also, it was determined that they had difficulties in group working, literature reviewing, report writing, analyzing textbook, and critical analysis.

  1. Towards a typology of business process management professionals: identifying patterns of competences through latent semantic analysis

    Science.gov (United States)

    Müller, Oliver; Schmiedel, Theresa; Gorbacheva, Elena; vom Brocke, Jan

    2016-01-01

    While researchers have analysed the organisational competences that are required for successful Business Process Management (BPM) initiatives, individual BPM competences have not yet been studied in detail. In this study, latent semantic analysis is used to examine a collection of 1507 BPM-related job advertisements in order to develop a typology of BPM professionals. This empirical analysis reveals distinct ideal types and profiles of BPM professionals on several levels of abstraction. A closer look at these ideal types and profiles confirms that BPM is a boundary-spanning field that requires interdisciplinary sets of competence that range from technical competences to business and systems competences. Based on the study's findings, it is posited that individual and organisational alignment with the identified ideal types and profiles is likely to result in high employability and organisational BPM success.

  2. Whole Genome Analysis of Injectional Anthrax Identifies Two Disease Clusters Spanning More Than 13 Years

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    Paul Keim

    2015-11-01

    Lay Person Interpretation: Injectional anthrax has been plaguing heroin drug users across Europe for more than 10 years. In order to better understand this outbreak, we assessed genomic relationships of all available injectional anthrax strains from four countries spanning a >12 year period. Very few differences were identified using genome-based analysis, but these differentiated the isolates into two distinct clusters. This strongly supports a hypothesis of at least two separate anthrax spore contamination events perhaps during the drug production processes. Identification of two events would not have been possible from standard epidemiological analysis. These comprehensive data will be invaluable for classifying future injectional anthrax isolates and for future geographic attribution.

  3. Quantitative assessment of in-solution digestion efficiency identifies optimal protocols for unbiased protein analysis

    DEFF Research Database (Denmark)

    Leon, Ileana R; Schwämmle, Veit; Jensen, Ole N;

    2013-01-01

    fractions. We evaluated nine trypsin-based digestion protocols, based on standard in-solution or on spin filter-aided digestion, including new optimized protocols. We investigated various reagents for protein solubilization and denaturation (dodecyl sulfate, deoxycholate, urea), several trypsin digestion...... conditions (buffer, RapiGest, deoxycholate, urea), and two methods for removal of detergents prior to analysis of peptides (acid precipitation or phase separation with ethyl acetate). Our data-independent quantitative LC-MS/MS workflow quantified over 3700 distinct peptides with 96% completeness between all...... protocols and replicates, with an average 40% protein sequence coverage and an average of 11 peptides identified per protein. Systematic quantitative and statistical analysis of physicochemical parameters demonstrated that deoxycholate-assisted in-solution digestion combined with phase transfer allows...

  4. Independent component analysis of high-resolution imaging data identifies distinct functional domains

    DEFF Research Database (Denmark)

    Reidl, Juergen; Starke, Jens; Omer, David;

    2007-01-01

    . Here we demonstrate that principal component analysis (PCA) followed by spatial independent component analysis (sICA), can be exploited to reduce the dimensionality of data sets recorded in the olfactory bulb and the somatosensory cortex of mice as well as the visual cortex of monkeys, without loosing...... the stimulus specific responses. Different neuronal populations are separated based on their stimulus specific time courses of activation. Both, spatial and temporal response characteristics can be objectively obtained, simultaneously. In the olfactory bulb, groups of glomeruli with different response...... latencies can be identified. This is shown for recordings of olfactory receptor neuron input measured with a calcium sensitive axon tracer and for network dynamics measured with the voltage sensitive dye RH 1838. In the somatosensory cortex, barrels responding to the stimulation of single whiskers can...

  5. Altered lipid metabolism in the aging kidney identified by three layered omic analysis.

    Science.gov (United States)

    Braun, Fabian; Rinschen, Markus M; Bartels, Valerie; Frommolt, Peter; Habermann, Bianca; Hoeijmakers, Jan H J; Schumacher, Björn; Dollé, Martijn E T; Müller, Roman-Ulrich; Benzing, Thomas; Schermer, Bernhard; Kurschat, Christine E

    2016-03-01

    Aging-associated diseases and their comorbidities affect the life of a constantly growing proportion of the population in developed countries. At the center of these comorbidities are changes of kidney structure and function as age-related chronic kidney disease predisposes to the development of cardiovascular diseases such as stroke, myocardial infarction or heart failure. To detect molecular mechanisms involved in kidney aging, we analyzed gene expression profiles of kidneys from adult and aged wild-type mice by transcriptomic, proteomic and targeted lipidomic methodologies. Interestingly, transcriptome and proteome analyses revealed differential expression of genes primarily involved in lipid metabolism and immune response. Additional lipidomic analyses uncovered significant age-related differences in the total amount of phosphatidylethanolamines, phosphatidylcholines and sphingomyelins as well as in subspecies of phosphatidylserines and ceramides with age. By integration of these datasets we identified Aldh1a1, a key enzyme in vitamin A metabolism specifically expressed in the medullary ascending limb, as one of the most prominent upregulated proteins in old kidneys. Moreover, ceramidase Asah1 was highly expressed in aged kidneys, consistent with a decrease in ceramide C16. In summary, our data suggest that changes in lipid metabolism are involved in the process of kidney aging and in the development of chronic kidney disease. PMID:26886165

  6. Analysis of micronuclei and microtubule arrangement to identify aneuploidy-inducing agents in cultured mammalian cells

    Energy Technology Data Exchange (ETDEWEB)

    Degrassi, F.; Pisano, C. [Centre di Genetica Evoluzionistica, Rome (Italy); Tanzarella, C.; Antoccia, A.; Battistoni, A. [Universita La Sapienza, Rome (Italy)

    1993-12-31

    The development of in vitro test methods to detect environmental agents that might induce aneuploidy is of crucial importance in genotoxicity testing. Chromosome numerical changes may arise from damage to various cell structures and activities such as spindle components or kinetochore proteins as well as from damage to the chromosomes. Therefore, the development of effective assays to identify chromosome misdistribution in mammalian cell cultures requires the contribution of different research areas such as cytogenetics, molecular biology and cell biology. Recently, we have been working at the development of an in vitro test for aneuploidy-inducing agents combining the micronucleus assay with the immunofluorescent staining of kinetochores in micronuclei (MN). The assay has been standardized by analyzing the induction of MN containing kinetochores (CREST-positive MN) after a number of agents with different mechanism of action. Subsequently, the optimization of the assay has been carried out by introducing cytochalasin-B (cyt-B) in the test protocol in order to score MN in cells that have undergone one cell cycle. Finally, with the aim of providing an understanding of the mechanisms responsible for the production of CREST-positive MN we have analyzed the cellular structures involved in mitotic division by using specific antibodies in immunofluorescence studies.

  7. [Subchromosomal microdeletion identified by molecular karyotyping using DNA microarrays (array CGH) in Rett syndrome girls negative for MECP2 gene mutations].

    Science.gov (United States)

    Vorsanova, S G; Iurov, I Iu; Voinova, V Iu; Kurinnaia, O S; Zelenova, M A; Demidova, I A; Ulas, E V; Iurov, Iu B

    2013-01-01

    Molecular karyotyping using DNA microarrays (array CGH) was applied for identification of subchromosomal microdeletions in a cohort of 12 girls with clinical features of RETT syndrome, but negative for MECP2 gene mutations. Recurrent microdeletions of MECP2 gene in chromosome X (locus Xq28) were identified in 5 girls of 12 studied. Probably RTT girls with subchromosomic microdeletions in Xq28 could represent a special subtype of the disease, which appears as clinically milder than the classic form of disease. In one case, an atypical form of RTT was associated with genomic abnormalities affecting CDKL5 gene and region critical for microdeletion Prader-Willi and Angelman syndromes (15q11.2). In addition, data are presented for the first time that genetic variation in regions 3p13, 3q27.1, and 1q21.1-1q21.2 could associate with RTT-like clinical manifestations. Without application of molecular karyotyping technology and bioinformatic method of assessing the pathogenic significance of genomic rearrangements these RTT-like girls negative for MECP2 gene mutations were considered as cases of idiopathic mental retardation associated with autism. It should be noted that absence of intragenic mutations in MECP2 gene is not sufficient criteria to reject the clinical diagnosis of RTT. To avoid errors in the genetic diagnosis of this genetically heterogeneous brain disease molecular cytogenetic studies using high resolution oligonucleotide array CGH (molecular karyotyping) are needed.

  8. Structural analysis of the genome of breast cancer cell line ZR-75-30 identifies twelve expressed fusion genes

    Directory of Open Access Journals (Sweden)

    Schulte Ina

    2012-12-01

    Full Text Available Abstract Background It has recently emerged that common epithelial cancers such as breast cancers have fusion genes like those in leukaemias. In a representative breast cancer cell line, ZR-75-30, we searched for fusion genes, by analysing genome rearrangements. Results We first analysed rearrangements of the ZR-75-30 genome, to around 10kb resolution, by molecular cytogenetic approaches, combining array painting and array CGH. We then compared this map with genomic junctions determined by paired-end sequencing. Most of the breakpoints found by array painting and array CGH were identified in the paired end sequencing—55% of the unamplified breakpoints and 97% of the amplified breakpoints (as these are represented by more sequence reads. From this analysis we identified 9 expressed fusion genes: APPBP2-PHF20L1, BCAS3-HOXB9, COL14A1-SKAP1, TAOK1-PCGF2, TIAM1-NRIP1, TIMM23-ARHGAP32, TRPS1-LASP1, USP32-CCDC49 and ZMYM4-OPRD1. We also determined the genomic junctions of a further three expressed fusion genes that had been described by others, BCAS3-ERBB2, DDX5-DEPDC6/DEPTOR and PLEC1-ENPP2. Of this total of 12 expressed fusion genes, 9 were in the coamplification. Due to the sensitivity of the technologies used, we estimate these 12 fusion genes to be around two-thirds of the true total. Many of the fusions seem likely to be driver mutations. For example, PHF20L1, BCAS3, TAOK1, PCGF2, and TRPS1 are fused in other breast cancers. HOXB9 and PHF20L1 are members of gene families that are fused in other neoplasms. Several of the other genes are relevant to cancer—in addition to ERBB2, SKAP1 is an adaptor for Src, DEPTOR regulates the mTOR pathway and NRIP1 is an estrogen-receptor coregulator. Conclusions This is the first structural analysis of a breast cancer genome that combines classical molecular cytogenetic approaches with sequencing. Paired-end sequencing was able to detect almost all breakpoints, where there was adequate read depth. It supports

  9. Hot spot analysis applied to identify ecosystem services potential in Lithuania

    Science.gov (United States)

    Pereira, Paulo; Depellegrin, Daniel; Misiune, Ieva

    2016-04-01

    Hot spot analysis are very useful to identify areas with similar characteristics. This is important for a sustainable use of the territory, since we can identify areas that need to be protected, or restored. This is a great advantage in terms of land use planning and management, since we can allocate resources, reduce the economical costs and do a better intervention in the landscape. Ecosystem services (ES) are different according land use. Since landscape is very heterogeneous, it is of major importance understand their spatial pattern and where are located the areas that provide better ES and the others that provide less services. The objective of this work is to use hot-spot analysis to identify areas with the most valuable ES in Lithuania. CORINE land-cover (CLC) of 2006 was used as the main spatial information. This classification uses a grid of 100 m resolution and extracted a total of 31 land use types. ES ranking was carried out based on expert knowledge. They were asked to evaluate the ES potential of each different CLC from 0 (no potential) to 5 (very high potential). Hot spot analysis were evaluated using the Getis-ord test, which identifies cluster analysis available in ArcGIS toolbox. This tool identifies areas with significantly high low values and significant high values at a p level of 0.05. In this work we used hot spot analysis to assess the distribution of providing, regulating cultural and total (sum of the previous 3) ES. The Z value calculated from Getis-ord was used to statistical analysis to access the clusters of providing, regulating cultural and total ES. ES with high Z value show that they have a high number of cluster areas with high potential of ES. The results showed that the Z-score was significantly different among services (Kruskal Wallis ANOVA =834. 607, p<0.001). The Z score of providing services (0.096±2.239) were significantly higher than the total (0.093±2.045), cultural (0.080±1.979) and regulating (0.076±1.961). These

  10. Comparative in silico analysis identifies bona fide MyoD binding sites within the Myocyte Stress 1 gene promoter

    Directory of Open Access Journals (Sweden)

    Imbalzano Anthony N

    2008-05-01

    Full Text Available Abstract Background Myocyte stress 1 (MS1 is a striated muscle actin binding protein required for the muscle specific activity of the evolutionary ancient myocardin related transcription factor (MRTF/serum response factor (SRF transcriptional pathway. To date, little is known about the molecular mechanisms that govern skeletal muscle specific expression of MS1. Such mechanisms are likely to play a major role in modulating SRF activity and therefore muscle determination, differentiation and regeneration. In this study we employed a comparative in silico analysis coupled with an experimental promoter characterisation to delineate these mechanisms. Results Analysis of MS1 expression in differentiating C2C12 muscle cells demonstrated a temporal differentiation dependent up-regulation in ms1 mRNA. An in silico comparative sequence analysis identified two conserved putative myogenic regulatory domains within the proximal 1.5 kbp of 5' upstream sequence. Co-transfecting C2C12 myoblasts with ms1 promoter/luciferase reporters and myogenic regulatory factor (MRF over-expression plasmids revealed specific sensitivity of the ms1 promoter to MyoD. Subsequent mutagenesis and EMSA analysis demonstrated specific targeting of MyoD at two distinct E-Boxes (E1 and E2 within identified evolutionary conserved regions (ECRs, α and β. Chromatin immunoprecipitation (ChIP analysis indicates that co-ordinated binding of MyoD at E-Boxes located within ECRs α and β correlates with the temporal induction in ms1 mRNA. Conclusion These findings suggest that the tissue specific and differentiation dependent up-regulation in ms1 mRNA is mediated by temporal binding of MyoD at distinct evolutionary conserved E-Boxes within the ms1 5' upstream sequence. We believe, through its activation of ms1, this is the first study to demonstrate a direct link between MyoD activity and SRF transcriptional signalling, with clear implications for the understanding of muscle determination

  11. Identifying New Drug Targets for Potent Phospholipase D Inhibitors: Combining Sequence Alignment, Molecular Docking, and Enzyme Activity/Binding Assays.

    Science.gov (United States)

    Djakpa, Helene; Kulkarni, Aditya; Barrows-Murphy, Scheneque; Miller, Greg; Zhou, Weihong; Cho, Hyejin; Török, Béla; Stieglitz, Kimberly

    2016-05-01

    Phospholipase D enzymes cleave phospholipid substrates generating choline and phosphatidic acid. Phospholipase D from Streptomyces chromofuscus is a non-HKD (histidine, lysine, and aspartic acid) phospholipase D as the enzyme is more similar to members of the diverse family of metallo-phosphodiesterase/phosphatase enzymes than phospholipase D enzymes with active site HKD repeats. A highly efficient library of phospholipase D inhibitors based on 1,3-disubstituted-4-amino-pyrazolopyrimidine core structure was utilized to evaluate the inhibition of purified S. chromofuscus phospholipase D. The molecules exhibited inhibition of phospholipase D activity (IC50 ) in the nanomolar range with monomeric substrate diC4 PC and micromolar range with phospholipid micelles and vesicles. Binding studies with vesicle substrate and phospholipase D strongly indicate that these inhibitors directly block enzyme vesicle binding. Following these compelling results as a starting point, sequence searches and alignments with S. chromofuscus phospholipase D have identified potential new drug targets. Using AutoDock, inhibitors were docked into the enzymes selected from sequence searches and alignments (when 3D co-ordinates were available) and results analyzed to develop next-generation inhibitors for new targets. In vitro enzyme activity assays with several human phosphatases demonstrated that the predictive protocol was accurate. The strategy of combining sequence comparison, docking, and high-throughput screening assays has helped to identify new drug targets and provided some insight into how to make potential inhibitors more specific to desired targets. PMID:26691755

  12. High-Throughput Platform for Identifying Molecular Factors Involved in Phenotypic Stabilization of Primary Human Hepatocytes In Vitro.

    Science.gov (United States)

    Shan, Jing; Logan, David J; Root, David E; Carpenter, Anne E; Bhatia, Sangeeta N

    2016-10-01

    Liver disease is a leading cause of morbidity worldwide and treatment options are limited, with organ transplantation being the only form of definitive management. Cell-based therapies have long held promise as alternatives to whole-organ transplantation but have been hindered by the rapid loss of liver-specific functions over a period of days in cultured hepatocytes. Hypothesis-driven studies have identified a handful of factors that modulate hepatocyte functions in vitro, but our understanding of the mechanisms involved remains incomplete. We thus report here the development of a high-throughput platform to enable systematic interrogation of liver biology in vitro. The platform is currently configured to enable genetic knockdown screens and includes an enzyme-linked immunosorbent assay-based functional assay to quantify albumin output as a surrogate marker for hepatocyte synthetic functions as well as an image-based viability assay that counts hepatocyte nuclei. Using this platform, we identified 12 gene products that may be important for hepatocyte viability and/or liver identity in vitro. These results represent important first steps in the elucidation of mechanisms instrumental to the phenotypic maintenance of hepatocytes in vitro, and we hope that the tools reported here will empower additional studies in various fields of liver research. PMID:27650791

  13. Molecular and Genetic Analysis of Hormone-Regulated Differential Cell Elongation in Arabidopsis

    Energy Technology Data Exchange (ETDEWEB)

    Ecker, Joseph R.

    2002-12-03

    The authors have utilized the response of Arabidopsis seedlings to the plant hormone ethylene to identify new genes involved in the regulation of ethylene biosynthesis, perception, signal transduction and differential cell growth. In building a genetic framework for the action of these genes, they developed a molecular model that has facilitated the understanding of the molecular requirements of ethylene for cell elongation processes. The ethylene response pathway in Arabidopsis appears to be primarily linear and is defined by the genes: ETR1, ETR2, ERS1, ERS2, EIN4, CTR1, EIN2, EIN3, EIN5 EIN6, and EIN. Downstream branches identified by the HLS1, EIR1, and AUX1 genes involve interactions with other hormonal (auxin) signals in the process of differential cell elongation in the hypocotyl hook. Cloning and characterization of HLS1 and three HLS1-LIKE genes in the laboratory has been supported under this award. HLS1 is required for differential elongation of cells in the hypocotyl and may act in the establishment of hormone gradients. Also during the award period, they have identified and begun preliminary characterization of two genes that genetically act upstream of the ethylene receptors. ETO1 and RAN1 encode negative regulators of ethylene biosynthesis and signaling respectively. Progress on the analysis of these genes along with HOOKLESS1 is described.

  14. Identifying Talent in Youth Sport: A Novel Methodology Using Higher-Dimensional Analysis.

    Directory of Open Access Journals (Sweden)

    Kevin Till

    Full Text Available Prediction of adult performance from early age talent identification in sport remains difficult. Talent identification research has generally been performed using univariate analysis, which ignores multivariate relationships. To address this issue, this study used a novel higher-dimensional model to orthogonalize multivariate anthropometric and fitness data from junior rugby league players, with the aim of differentiating future career attainment. Anthropometric and fitness data from 257 Under-15 rugby league players was collected. Players were grouped retrospectively according to their future career attainment (i.e., amateur, academy, professional. Players were blindly and randomly divided into an exploratory (n = 165 and validation dataset (n = 92. The exploratory dataset was used to develop and optimize a novel higher-dimensional model, which combined singular value decomposition (SVD with receiver operating characteristic analysis. Once optimized, the model was tested using the validation dataset. SVD analysis revealed 60 m sprint and agility 505 performance were the most influential characteristics in distinguishing future professional players from amateur and academy players. The exploratory dataset model was able to distinguish between future amateur and professional players with a high degree of accuracy (sensitivity = 85.7%, specificity = 71.1%; p<0.001, although it could not distinguish between future professional and academy players. The validation dataset model was able to distinguish future professionals from the rest with reasonable accuracy (sensitivity = 83.3%, specificity = 63.8%; p = 0.003. Through the use of SVD analysis it was possible to objectively identify criteria to distinguish future career attainment with a sensitivity over 80% using anthropometric and fitness data alone. As such, this suggests that SVD analysis may be a useful analysis tool for research and practice within talent identification.

  15. Identifying Talent in Youth Sport: A Novel Methodology Using Higher-Dimensional Analysis.

    Science.gov (United States)

    Till, Kevin; Jones, Ben L; Cobley, Stephen; Morley, David; O'Hara, John; Chapman, Chris; Cooke, Carlton; Beggs, Clive B

    2016-01-01

    Prediction of adult performance from early age talent identification in sport remains difficult. Talent identification research has generally been performed using univariate analysis, which ignores multivariate relationships. To address this issue, this study used a novel higher-dimensional model to orthogonalize multivariate anthropometric and fitness data from junior rugby league players, with the aim of differentiating future career attainment. Anthropometric and fitness data from 257 Under-15 rugby league players was collected. Players were grouped retrospectively according to their future career attainment (i.e., amateur, academy, professional). Players were blindly and randomly divided into an exploratory (n = 165) and validation dataset (n = 92). The exploratory dataset was used to develop and optimize a novel higher-dimensional model, which combined singular value decomposition (SVD) with receiver operating characteristic analysis. Once optimized, the model was tested using the validation dataset. SVD analysis revealed 60 m sprint and agility 505 performance were the most influential characteristics in distinguishing future professional players from amateur and academy players. The exploratory dataset model was able to distinguish between future amateur and professional players with a high degree of accuracy (sensitivity = 85.7%, specificity = 71.1%; p<0.001), although it could not distinguish between future professional and academy players. The validation dataset model was able to distinguish future professionals from the rest with reasonable accuracy (sensitivity = 83.3%, specificity = 63.8%; p = 0.003). Through the use of SVD analysis it was possible to objectively identify criteria to distinguish future career attainment with a sensitivity over 80% using anthropometric and fitness data alone. As such, this suggests that SVD analysis may be a useful analysis tool for research and practice within talent identification. PMID:27224653

  16. Identifying the oil price-macroeconomy relationship: An empirical mode decomposition analysis of US data

    International Nuclear Information System (INIS)

    This paper employs the empirical mode decomposition (EMD) method to filter cyclical components of US quarterly gross domestic product (GDP) and quarterly average oil price (West Texas Intermediate-WTI). The method is adaptive and applicable to non-linear and non-stationary data. A correlation analysis of the resulting components is performed and examined for insights into the relationship between oil and the economy. Several components of this relationship are identified. However, the principal one is that the medium-run component of the oil price has a negative relationship with the main cyclical component of the GDP. In addition, weak correlations suggesting a lagging, demand-driven component and a long-run component of the relationship were also identified. Comparisons of these findings with significant oil supply disruption and recession dates were supportive. The study identifies a number of lessons applicable to recent oil market events, including the eventuality of persistent oil price and economic decline following a long oil price run-up. In addition, it was found that oil market related exogenous events are associated with short- to medium-run price implications regardless of whether they lead to actual supply losses.

  17. Identifying the oil price-macroeconomy relationship. An empirical mode decomposition analysis of US data

    International Nuclear Information System (INIS)

    This paper employs the empirical mode decomposition (EMD) method to filter cyclical components of US quarterly gross domestic product (GDP) and quarterly average oil price (West Texas Intermediate - WTI). The method is adaptive and applicable to non-linear and non-stationary data. A correlation analysis of the resulting components is performed and examined for insights into the relationship between oil and the economy. Several components of this relationship are identified. However, the principal one is that the medium-run component of the oil price has a negative relationship with the main cyclical component of the GDP. In addition, weak correlations suggesting a lagging, demand-driven component and a long-run component of the relationship were also identified. Comparisons of these findings with significant oil supply disruption and recession dates were supportive. The study identifies a number of lessons applicable to recent oil market events, including the eventuality of persistent oil price and economic decline following a long oil price run-up. In addition, it was found that oil market related exogenous events are associated with short- to medium-run price implications regardless of whether they lead to actual supply losses. (author)

  18. Genome-wide association scan meta-analysis identifies three Loci influencing adiposity and fat distribution.

    Directory of Open Access Journals (Sweden)

    Cecilia M Lindgren

    2009-06-01

    Full Text Available To identify genetic loci influencing central obesity and fat distribution, we performed a meta-analysis of 16 genome-wide association studies (GWAS, N = 38,580 informative for adult waist circumference (WC and waist-hip ratio (WHR. We selected 26 SNPs for follow-up, for which the evidence of association with measures of central adiposity (WC and/or WHR was strong and disproportionate to that for overall adiposity or height. Follow-up studies in a maximum of 70,689 individuals identified two loci strongly associated with measures of central adiposity; these map near TFAP2B (WC, P = 1.9x10(-11 and MSRA (WC, P = 8.9x10(-9. A third locus, near LYPLAL1, was associated with WHR in women only (P = 2.6x10(-8. The variants near TFAP2B appear to influence central adiposity through an effect on overall obesity/fat-mass, whereas LYPLAL1 displays a strong female-only association with fat distribution. By focusing on anthropometric measures of central obesity and fat distribution, we have identified three loci implicated in the regulation of human adiposity.

  19. Computational EST database analysis identifies a novel member of the neuropoietic cytokine family.

    Science.gov (United States)

    Shi, Y; Wang, W; Yourey, P A; Gohari, S; Zukauskas, D; Zhang, J; Ruben, S; Alderson, R F

    1999-08-19

    A novel member of the neuropoietic cytokine family has been cloned and the protein expressed and characterized. In an effort to identify novel secreted proteins, an algorithm incorporating neural network algorithms was applied to a large EST database. A full-length clone was identified that is 1710 bp in length and has a single open reading frame of 225 amino acids. This new cytokine is most homologous to cardiotrophin-1, having a similarity and an identity of 46 and 29%, respectively, and therefore we have named it cardiotrophin-like cytokine (CLC). Northern hybridization analysis identified a 1.4-kb messenger RNA that is highly expressed in spleen and peripheral leukocytes. Purified recombinant CLC induced the activation of NFkappaB and SRE reporter constructs in the TF-1, U937, and M1 cell lines. Furthermore, the signal transduction pathway for CLC was characterized in the neuroblastoma cell line SK-N-MC and found to involve tyrosine phosphorylation of gp130 and STAT-1. PMID:10448081

  20. Multistep Molecular Dynamics Simulations Identify the Highly Cooperative Activity of Melittin in Recognizing and Stabilizing Membrane Pores.

    Science.gov (United States)

    Sun, Delin; Forsman, Jan; Woodward, Clifford E

    2015-09-01

    The prototypical antimicrobial peptide, melittin, is well-known for its ability to induce pores in zwitterionic model lipid membranes. However, the mechanism by which melittin accomplishes this is not fully understood. We have conducted all-atom and coarse-grained molecular dynamics simulations which suggest that melittin employs a highly cooperative mechanism for the induction of both small and large membrane pores. The process by which this peptide induces membrane pores appears to be driven by its affinity to membrane defects via its N-terminus region. In our simulations, a membrane defect was deliberately created through either lipid flip-flop or the reorientation of one adsorbed melittin peptide. In a cooperative response, other melittin molecules also inserted their N-termini into the created defect, thus lowering the overall free energy. The insertion of these peptide molecules ultimately allowed the defect to develop into a small transmembrane pore, with an estimated diameter of ∼1.5 nm and a lifetime of the order of tens of milliseconds. In the presence of a finite membrane tension, we show that this small pore can act as a nucleation site for the stochastic rupture of the lipid bilayer, so as to create a much larger pore. We found that a threshold membrane tension of 25 mN/m was needed to create a ruptured pore. Furthermore, by actively accumulating at its edge, adsorbed peptides are able to cooperatively stabilize this larger pore. The defect-mediated pore formation mechanism revealed in this work may also apply to other amphipathic membrane-active peptides. PMID:26267389

  1. Genome-wide association study meta-analysis identifies seven new rheumatoid arthritis risk loci

    Science.gov (United States)

    Stahl, Eli A.; Raychaudhuri, Soumya; Remmers, Elaine F.; Xie, Gang; Eyre, Stephen; Thomson, Brian P.; Li, Yonghong; Kurreeman, Fina A. S.; Zhernakova, Alexandra; Hinks, Anne; Guiducci, Candace; Chen, Robert; Alfredsson, Lars; Amos, Christopher I.; Ardlie, Kristin G.; Barton, Anne; Bowes, John; Brouwer, Elisabeth; Burtt, Noel P.; Catanese, Joseph J.; Coblyn, Jonathan; Coenen, Marieke JH; Costenbader, Karen H.; Criswell, Lindsey A.; Crusius, J. Bart A.; Cui, Jing; de Bakker, Paul I.W.; De Jager, Phillip L.; Ding, Bo; Emery, Paul; Flynn, Edward; Harrison, Pille; Hocking, Lynne J.; Huizinga, Tom W. J.; Kastner, Daniel L.; Ke, Xiayi; Lee, Annette T.; Liu, Xiangdong; Martin, Paul; Morgan, Ann W.; Padyukov, Leonid; Posthumus, Marcel D.; Radstake, Timothy RDJ; Reid, David M.; Seielstad, Mark; Seldin, Michael F.; Shadick, Nancy A.; Steer, Sophia; Tak, Paul P.; Thomson, Wendy; van der Helm-van Mil, Annette H. M.; van der Horst-Bruinsma, Irene E.; van der Schoot, C. Ellen; van Riel, Piet LCM; Weinblatt, Michael E.; Wilson, Anthony G.; Wolbink, Gert Jan; Wordsworth, Paul; Wijmenga, Cisca; Karlson, Elizabeth W.; Toes, Rene E. M.; de Vries, Niek; Begovich, Ann B.; Worthington, Jane; Siminovitch, Katherine A.; Gregersen, Peter K.; Klareskog, Lars; Plenge, Robert M.

    2014-01-01

    To identify novel genetic risk factors for rheumatoid arthritis (RA), we conducted a genome-wide association study (GWAS) meta-analysis of 5,539 autoantibody positive RA cases and 20,169 controls of European descent, followed by replication in an independent set of 6,768 RA cases and 8,806 controls. Of 34 SNPs selected for replication, 7 novel RA risk alleles were identified at genome-wide significance (P<5×10−8) in analysis of all 41,282 samples. The associated SNPs are near genes of known immune function, including IL6ST, SPRED2, RBPJ, CCR6, IRF5, and PXK. We also refined the risk alleles at two established RA risk loci (IL2RA and CCL21) and confirmed the association at AFF3. These new associations bring the total number of confirmed RA risk loci to 31 among individuals of European ancestry. An additional 11 SNPs replicated at P<0.05, many of which are validated autoimmune risk alleles, suggesting that most represent bona fide RA risk alleles. PMID:20453842

  2. Using FAME Analysis to Compare, Differentiate, and Identify Multiple Nematode Species

    Science.gov (United States)

    Sekora, Nicholas S.; Agudelo, Paula; van Santen, Edzard; McInroy, John A.

    2009-01-01

    We have adapted the Sherlock® Microbial Identification system for identification of plant parasitic nematodes based on their fatty acid profiles. Fatty acid profiles of 12 separate plant parasitic nematode species have been determined using this system. Additionally, separate profiles have been developed for Rotylenchulus reniformis and Meloidogyne incognita based on their host plant, four species and three races within the Meloidogyne genus, and three life stages of Heterodera glycines. Statistically, 85% of these profiles can be delimited from one another; the specific comparisons between the cyst and vermiform stages of H. glycines, M. hapla and M. arenaria, and M. arenaria and M. javanica cannot be segregated using canonical analysis. By incorporating each of these fatty acid profiles into the Sherlock® Analysis Software, 20 library entries were created. While there was some similarity among profiles, all entries correctly identified the proper organism to genus, species, race, life stage, and host at greater than 86% accuracy. The remaining 14% were correctly identified to genus, although species and race may not be correct due to the underlying variables of host or life stage. These results are promising and indicate that this library could be used for diagnostics labs to increase response time. PMID:22736811

  3. Root Source Analysis/ValuStream[Trade Mark] - A Methodology for Identifying and Managing Risks

    Science.gov (United States)

    Brown, Richard Lee

    2008-01-01

    Root Source Analysis (RoSA) is a systems engineering methodology that has been developed at NASA over the past five years. It is designed to reduce costs, schedule, and technical risks by systematically examining critical assumptions and the state of the knowledge needed to bring to fruition the products that satisfy mission-driven requirements, as defined for each element of the Work (or Product) Breakdown Structure (WBS or PBS). This methodology is sometimes referred to as the ValuStream method, as inherent in the process is the linking and prioritizing of uncertainties arising from knowledge shortfalls directly to the customer's mission driven requirements. RoSA and ValuStream are synonymous terms. RoSA is not simply an alternate or improved method for identifying risks. It represents a paradigm shift. The emphasis is placed on identifying very specific knowledge shortfalls and assumptions that are the root sources of the risk (the why), rather than on assessing the WBS product(s) themselves (the what). In so doing RoSA looks forward to anticipate, identify, and prioritize knowledge shortfalls and assumptions that are likely to create significant uncertainties/ risks (as compared to Root Cause Analysis, which is most often used to look back to discover what was not known, or was assumed, that caused the failure). Experience indicates that RoSA, with its primary focus on assumptions and the state of the underlying knowledge needed to define, design, build, verify, and operate the products, can identify critical risks that historically have been missed by the usual approaches (i.e., design review process and classical risk identification methods). Further, the methodology answers four critical questions for decision makers and risk managers: 1. What s been included? 2. What's been left out? 3. How has it been validated? 4. Has the real source of the uncertainty/ risk been identified, i.e., is the perceived problem the real problem? Users of the RoSA methodology

  4. Proteomic analysis identifies interleukin 11 regulated plasma membrane proteins in human endometrial epithelial cells in vitro

    Directory of Open Access Journals (Sweden)

    Stanton Peter G

    2011-05-01

    Full Text Available Abstract Background During the peri-implantation period, the embryo adheres to an adequately prepared or receptive endometrial surface epithelium. Abnormal embryo adhesion to the endometrium results in embryo implantation failure and infertility. Endometrial epithelial cell plasma membrane proteins critical in regulating adhesion may potentially be infertility biomarkers or targets for treating infertility. Interleukin (IL 11 regulates human endometrial epithelial cells (hEEC adhesion. Its production is abnormal in women with infertility. The objective of the study was to identify IL11 regulated plasma membrane proteins in hEEC in vitro using a proteomic approach. Methods Using a 2D-differential in-gel electrophoresis (DIGE electrophoresis combined with LCMS/MS mass spectrometry approach, we identified 20 unique plasma membrane proteins differentially regulated by IL11 in ECC-1 cells, a hEEC derived cell line. Two IL11 regulated proteins with known roles in cell adhesion, annexin A2 (ANXA2 and flotillin-1 (FLOT1, were validated by Western blot and immunocytochemistry in hEEC lines (ECC-1 and an additional cell line, Ishikawa and primary hEEC. Flotilin-1 was further validated by immunohistochemistry in human endometrium throughout the menstrual cycle (n = 6-8/cycle. Results 2D-DIGE analysis identified 4 spots that were significantly different between control and IL11 treated group. Of these 4 spots, there were 20 proteins that were identified with LCMS/MS. Two proteins; ANXA2 and FLOT1 were chosen for further analyses and have found to be significantly up-regulated following IL11 treatment. Western blot analysis showed a 2-fold and a 2.5-fold increase of ANXA2 in hEEC membrane fraction of ECC-1 and Ishikawa cells respectively. Similarly, a 1.8-fold and a 2.3/2.4-fold increase was also observed for FLOT1 in hEEC membrane fraction of ECC-1 and Ishikawa cells respectively. In vitro, IL11 induced stronger ANXA2 expression on cell surface of primary h

  5. Methylation Linear Discriminant Analysis (MLDA for identifying differentially methylated CpG islands

    Directory of Open Access Journals (Sweden)

    Vass J Keith

    2008-08-01

    Full Text Available Abstract Background Hypermethylation of promoter CpG islands is strongly correlated to transcriptional gene silencing and epigenetic maintenance of the silenced state. As well as its role in tumor development, CpG island methylation contributes to the acquisition of resistance to chemotherapy. Differential Methylation Hybridisation (DMH is one technique used for genome-wide DNA methylation analysis. The study of such microarray data sets should ideally account for the specific biological features of DNA methylation and the non-symmetrical distribution of the ratios of unmethylated and methylated sequences hybridised on the array. We have therefore developed a novel algorithm tailored to this type of data, Methylation Linear Discriminant Analysis (MLDA. Results MLDA was programmed in R (version 2.7.0 and the package is available at CRAN 1. This approach utilizes linear regression models of non-normalised hybridisation data to define methylation status. Log-transformed signal intensities of unmethylated controls on the microarray are used as a reference. The signal intensities of DNA samples digested with methylation sensitive restriction enzymes and mock digested are then transformed to the likelihood of a locus being methylated using this reference. We tested the ability of MLDA to identify loci differentially methylated as analysed by DMH between cisplatin sensitive and resistant ovarian cancer cell lines. MLDA identified 115 differentially methylated loci and 23 out of 26 of these loci have been independently validated by Methylation Specific PCR and/or bisulphite pyrosequencing. Conclusion MLDA has advantages for analyzing methylation data from CpG island microarrays, since there is a clear rational for the definition of methylation status, it uses DMH data without between-group normalisation and is less influenced by cross-hybridisation of loci. The MLDA algorithm successfully identified differentially methylated loci between two classes of

  6. Using EMMA and MIX analysis to assess mixing ratios and to identify hydrochemical reactions in groundwater.

    Science.gov (United States)

    Tubau, Isabel; Vàzquez-Suñé, Enric; Jurado, Anna; Carrera, Jesús

    2014-02-01

    This study presents a methodology using an end-member mixing analysis (EMMA) and MIX to compute mixing ratios and to identify hydrochemical reactions in groundwater. The methodology consists of (1) identifying the potential sources of recharge, (2) characterising recharge sources and mixed water samples using hydrogeochemistry, (3) selecting chemical species to be used in the analysis and (4) calculating mixing ratios and identification of hydrochemical reactions in groundwater. This approach has been applied in the Besòs River Delta area, where we have collected 51 groundwater samples and a long data register of the hydrogeochemistry of the Besòs River created by the Catalan Water Agency is also available. The EMMA performed in the Besòs River suggests that 3 end-members are required to explain its temporal variability, accounting for the species chloride, sulphate, sodium, bicarbonate, calcium, magnesium, potassium, ammonium, total nitrogen, and electrical conductivity. One river end-member is from the wet periods (W1), and two are from dry periods (D1 and D2). These end-members have been used to compute mixing ratios in groundwater samples because the Besòs River is considered the main recharge source for the aquifer. Overall, dry season end-members dominated over the wet season end-member, in a proportion of 4:1. Moreover, when departures from the mixing line exist, geochemical processes might be identified. Redox processes, carbonate dissolution/precipitation and ion exchange processes may occur in Besòs Delta aquifer. PMID:24246935

  7. Molecular analysis of endothelial progenitor cell (EPC subtypes reveals two distinct cell populations with different identities

    Directory of Open Access Journals (Sweden)

    Simpson David A

    2010-05-01

    Full Text Available Abstract Background The term endothelial progenitor cells (EPCs is currently used to refer to cell populations which are quite dissimilar in terms of biological properties. This study provides a detailed molecular fingerprint for two EPC subtypes: early EPCs (eEPCs and outgrowth endothelial cells (OECs. Methods Human blood-derived eEPCs and OECs were characterised by using genome-wide transcriptional profiling, 2D protein electrophoresis, and electron microscopy. Comparative analysis at the transcript and protein level included monocytes and mature endothelial cells as reference cell types. Results Our data show that eEPCs and OECs have strikingly different gene expression signatures. Many highly expressed transcripts in eEPCs are haematopoietic specific (RUNX1, WAS, LYN with links to immunity and inflammation (TLRs, CD14, HLAs, whereas many transcripts involved in vascular development and angiogenesis-related signalling pathways (Tie2, eNOS, Ephrins are highly expressed in OECs. Comparative analysis with monocytes and mature endothelial cells clusters eEPCs with monocytes, while OECs segment with endothelial cells. Similarly, proteomic analysis revealed that 90% of spots identified by 2-D gel analysis are common between OECs and endothelial cells while eEPCs share 77% with monocytes. In line with the expression pattern of caveolins and cadherins identified by microarray analysis, ultrastructural evaluation highlighted the presence of caveolae and adherens junctions only in OECs. Conclusions This study provides evidence that eEPCs are haematopoietic cells with a molecular phenotype linked to monocytes; whereas OECs exhibit commitment to the endothelial lineage. These findings indicate that OECs might be an attractive cell candidate for inducing therapeutic angiogenesis, while eEPC should be used with caution because of their monocytic nature.

  8. Platelet-Related Variants Identified by Exomechip Meta-analysis in 157,293 Individuals.

    Science.gov (United States)

    Eicher, John D; Chami, Nathalie; Kacprowski, Tim; Nomura, Akihiro; Chen, Ming-Huei; Yanek, Lisa R; Tajuddin, Salman M; Schick, Ursula M; Slater, Andrew J; Pankratz, Nathan; Polfus, Linda; Schurmann, Claudia; Giri, Ayush; Brody, Jennifer A; Lange, Leslie A; Manichaikul, Ani; Hill, W David; Pazoki, Raha; Elliot, Paul; Evangelou, Evangelos; Tzoulaki, Ioanna; Gao, He; Vergnaud, Anne-Claire; Mathias, Rasika A; Becker, Diane M; Becker, Lewis C; Burt, Amber; Crosslin, David R; Lyytikäinen, Leo-Pekka; Nikus, Kjell; Hernesniemi, Jussi; Kähönen, Mika; Raitoharju, Emma; Mononen, Nina; Raitakari, Olli T; Lehtimäki, Terho; Cushman, Mary; Zakai, Neil A; Nickerson, Deborah A; Raffield, Laura M; Quarells, Rakale; Willer, Cristen J; Peloso, Gina M; Abecasis, Goncalo R; Liu, Dajiang J; Deloukas, Panos; Samani, Nilesh J; Schunkert, Heribert; Erdmann, Jeanette; Fornage, Myriam; Richard, Melissa; Tardif, Jean-Claude; Rioux, John D; Dube, Marie-Pierre; de Denus, Simon; Lu, Yingchang; Bottinger, Erwin P; Loos, Ruth J F; Smith, Albert Vernon; Harris, Tamara B; Launer, Lenore J; Gudnason, Vilmundur; Velez Edwards, Digna R; Torstenson, Eric S; Liu, Yongmei; Tracy, Russell P; Rotter, Jerome I; Rich, Stephen S; Highland, Heather M; Boerwinkle, Eric; Li, Jin; Lange, Ethan; Wilson, James G; Mihailov, Evelin; Mägi, Reedik; Hirschhorn, Joel; Metspalu, Andres; Esko, Tõnu; Vacchi-Suzzi, Caterina; Nalls, Mike A; Zonderman, Alan B; Evans, Michele K; Engström, Gunnar; Orho-Melander, Marju; Melander, Olle; O'Donoghue, Michelle L; Waterworth, Dawn M; Wallentin, Lars; White, Harvey D; Floyd, James S; Bartz, Traci M; Rice, Kenneth M; Psaty, Bruce M; Starr, J M; Liewald, David C M; Hayward, Caroline; Deary, Ian J; Greinacher, Andreas; Völker, Uwe; Thiele, Thomas; Völzke, Henry; van Rooij, Frank J A; Uitterlinden, André G; Franco, Oscar H; Dehghan, Abbas; Edwards, Todd L; Ganesh, Santhi K; Kathiresan, Sekar; Faraday, Nauder; Auer, Paul L; Reiner, Alex P; Lettre, Guillaume; Johnson, Andrew D

    2016-07-01

    Platelet production, maintenance, and clearance are tightly controlled processes indicative of platelets' important roles in hemostasis and thrombosis. Platelets are common targets for primary and secondary prevention of several conditions. They are monitored clinically by complete blood counts, specifically with measurements of platelet count (PLT) and mean platelet volume (MPV). Identifying genetic effects on PLT and MPV can provide mechanistic insights into platelet biology and their role in disease. Therefore, we formed the Blood Cell Consortium (BCX) to perform a large-scale meta-analysis of Exomechip association results for PLT and MPV in 157,293 and 57,617 individuals, respectively. Using the low-frequency/rare coding variant-enriched Exomechip genotyping array, we sought to identify genetic variants associated with PLT and MPV. In addition to confirming 47 known PLT and 20 known MPV associations, we identified 32 PLT and 18 MPV associations not previously observed in the literature across the allele frequency spectrum, including rare large effect (FCER1A), low-frequency (IQGAP2, MAP1A, LY75), and common (ZMIZ2, SMG6, PEAR1, ARFGAP3/PACSIN2) variants. Several variants associated with PLT/MPV (PEAR1, MRVI1, PTGES3) were also associated with platelet reactivity. In concurrent BCX analyses, there was overlap of platelet-associated variants with red (MAP1A, TMPRSS6, ZMIZ2) and white (PEAR1, ZMIZ2, LY75) blood cell traits, suggesting common regulatory pathways with shared genetic architecture among these hematopoietic lineages. Our large-scale Exomechip analyses identified previously undocumented associations with platelet traits and further indicate that several complex quantitative hematological, lipid, and cardiovascular traits share genetic factors.

  9. Real-time analysis application for identifying bursty local areas related to emergency topics.

    Science.gov (United States)

    Sakai, Tatsuhiro; Tamura, Keiichi

    2015-01-01

    Since social media started getting more attention from users on the Internet, social media has been one of the most important information source in the world. Especially, with the increasing popularity of social media, data posted on social media sites are rapidly becoming collective intelligence, which is a term used to refer to new media that is displacing traditional media. In this paper, we focus on geotagged tweets on the Twitter site. These geotagged tweets are referred to as georeferenced documents because they include not only a short text message, but also the documents' posting time and location. Many researchers have been tackling the development of new data mining techniques for georeferenced documents to identify and analyze emergency topics, such as natural disasters, weather, diseases, and other incidents. In particular, the utilization of geotagged tweets to identify and analyze natural disasters has received much attention from administrative agencies recently because some case studies have achieved compelling results. In this paper, we propose a novel real-time analysis application for identifying bursty local areas related to emergency topics. The aim of our new application is to provide new platforms that can identify and analyze the localities of emergency topics. The proposed application is composed of three core computational intelligence techniques: the Naive Bayes classifier technique, the spatiotemporal clustering technique, and the burst detection technique. Moreover, we have implemented two types of application interface: a Web application interface and an android application interface. To evaluate the proposed application, we have implemented a real-time weather observation system embedded the proposed application. we used actual crawling geotagged tweets posted on the Twitter site. The weather observation system successfully detected bursty local areas related to observed emergency weather topics. PMID:25918679

  10. Transcriptomic analysis using olive varieties and breeding progenies identify candidate genes involved in plant architecture

    Directory of Open Access Journals (Sweden)

    Juan José eGonzález Plaza

    2016-03-01

    Full Text Available Plant architecture is a critical trait in fruit crops that can significantly influence yield, pruning, planting density and harvesting. Little is known about how plant architecture is genetically determined in olive, were most of the existing varieties are traditional with an architecture poorly suited for modern growing and harvesting systems. In the present study, we have carried out microarray analysis of meristematic tissue to compare expression profiles of olive varieties displaying differences in architecture, as well as seedlings from their cross pooled on the basis of their sharing architecture-related phenotypes. The microarray used, previously developed by our group has already been applied to identify candidates genes involved in regulating juvenile to adult transition in the shoot apex of seedlings. Varieties with distinct architecture phenotypes and individuals from segregating progenies displaying opposite architecture features were used to link phenotype to expression. Here, we identify 2,252 differentially expressed genes associated to differences in plant architecture. Microarray results were validated by quantitative RT-PCR carried out on genes with functional annotation likely related to plant architecture. Twelve of these genes were further analyzed in individual seedlings of the corresponding pool. We also examined Arabidopsis mutants in putative orthologs of these targeted candidate genes, finding altered architecture for most of them. This supports a functional conservation between species and potential biological relevance of the candidate genes identified. This study is the first to identify genes associated to plant architecture in olive, and the results obtained could be of great help in future programs aimed at selecting phenotypes adapted to modern cultivation practices in this species.

  11. Transcriptomic Analysis Using Olive Varieties and Breeding Progenies Identifies Candidate Genes Involved in Plant Architecture.

    Science.gov (United States)

    González-Plaza, Juan J; Ortiz-Martín, Inmaculada; Muñoz-Mérida, Antonio; García-López, Carmen; Sánchez-Sevilla, José F; Luque, Francisco; Trelles, Oswaldo; Bejarano, Eduardo R; De La Rosa, Raúl; Valpuesta, Victoriano; Beuzón, Carmen R

    2016-01-01

    Plant architecture is a critical trait in fruit crops that can significantly influence yield, pruning, planting density and harvesting. Little is known about how plant architecture is genetically determined in olive, were most of the existing varieties are traditional with an architecture poorly suited for modern growing and harvesting systems. In the present study, we have carried out microarray analysis of meristematic tissue to compare expression profiles of olive varieties displaying differences in architecture, as well as seedlings from their cross pooled on the basis of their sharing architecture-related phenotypes. The microarray used, previously developed by our group has already been applied to identify candidates genes involved in regulating juvenile to adult transition in the shoot apex of seedlings. Varieties with distinct architecture phenotypes and individuals from segregating progenies displaying opposite architecture features were used to link phenotype to expression. Here, we identify 2252 differentially expressed genes (DEGs) associated to differences in plant architecture. Microarray results were validated by quantitative RT-PCR carried out on genes with functional annotation likely related to plant architecture. Twelve of these genes were further analyzed in individual seedlings of the corresponding pool. We also examined Arabidopsis mutants in putative orthologs of these targeted candidate genes, finding altered architecture for most of them. This supports a functional conservation between species and potential biological relevance of the candidate genes identified. This study is the first to identify genes associated to plant architecture in olive, and the results obtained could be of great help in future programs aimed at selecting phenotypes adapted to modern cultivation practices in this species.

  12. Molecular characterization and association analysis of porcine PANE1 gene

    DEFF Research Database (Denmark)

    Huang, Honggang; Deng, Hong; Yang, Yiling;

    2010-01-01

    -polymerase chain reaction revealed that porcine PANE1 gene was differently expressed in seven diverse tissues, showed highest expression level in lymph node, but lowest in kidney. A single nucleotide polymorphism (SNP) (C>A) which can be digested by restriction enzyme BssHII was identified in intron 1 of porcine...... PANE1, allele frequencies determination in different pig breeds and association analysis were performed on this SNP BssHII by PCR-restriction fragment length polymorphism assay. Allele frequencies varied greatly among different pig breeds, and the association results indicated that piglet individuals...

  13. Co-expression Analysis Identifies CRC and AP1 the Regulator of Arabidopsis Fatty Acid Biosynthesis

    Institute of Scientific and Technical Information of China (English)

    Xinxin Han; Linlin Yin; Hongwei Xue

    2012-01-01

    Fatty acids (FAs) play crucial rules in signal transduction and plant development,however,the regulation of FA metabolism is still poorly understood.To study the relevant regulatory network,fifty-eight FA biosynthesis genes including de novo synthases,desaturases and elongases were selected as "guide genes" to construct the co-expression network.Calculation of the correlation between all Arabidopsis thaliana (L.) genes with each guide gene by Arabidopsis co-expression dating mining tools (ACT)identifies 797 candidate FA-correlated genes.Gene ontology (GO) analysis of these co-expressed genes showed they are tightly correlated to photosynthesis and carbohydrate metabolism,and function in many processes.Interestingly,63 transcription factors (TFs) were identified as candidate FA biosynthesis regulators and 8 TF families are enriched.Two TF genes,CRC and AP1,both correlating with 8 FA guide genes,were further characterized.Analyses of the ap1 and crc mutant showed the altered total FA composition of mature seeds.The contents of palmitoleic acid,stearic acid,arachidic acid and eicosadienoic acid are decreased,whereas that of oleic acid is increased in ap1 and crc seeds,which is consistent with the qRT-PCR analysis revealing the suppressed expression of the corresponding guide genes.In addition,yeast one-hybrid analysis and electrophoretic mobility shift assay (EMSA) revealed that CRC can bind to the promoter regions of KCS7 and KCS15,indicating that CRC may directly regulate FA biosynthesis.

  14. Identifying sleep apnea syndrome using heart rate and breathing effort variation analysis based on ballistocardiography.

    Science.gov (United States)

    Weichao Zhao; Hongbo Ni; Xingshe Zhou; Yalong Song; Tianben Wang

    2015-08-01

    Sleep apnea syndrome (SAS) is regarded as one of the most common sleep-related breathing disorders, which can severely affect sleep quality. Since SAS is usually accompanied with the cyclical heart rate variation (HRV), many studies have been conducted on heart rate (HR) to identify it at an earlier stage. While most related work mainly based on clinical devices or signals (e.g., polysomnography (PSG), electrocardiography (ECG)), in this paper we focus on the ballistocardiographic (BCG) signal which is obtained in a non-invasive way. Moreover, as the precision and reliability of BCG signal are not so good as PSG or ECG, we propose a fine-grained feature extraction and analysis approach in SAS recognition. Our analysis takes both the basic HRV features and the breathing effort variation into consideration during different sleep stages rather than the whole night. The breathing effort refers to the mechanical interaction between respiration and BCG signal when SAS events occur, which is independent from autonomous nervous system (ANS) modulations. Specifically, a novel method named STC-Min is presented to extract the breathing effort variation feature. The basic HRV features depict the ANS modulations on HR and Sample Entropy and Detrended Fluctuation Analysis are applied for the evaluations. All the extracted features along with personal factors are fed into the knowledge-based support vector machine (KSVM) classification model, and the prior knowledge is based on dataset distribution and domain knowledge. Experimental results on 42 subjects in 3 nights validate the effectiveness of the methods and features in identifying SAS (90.46% precision rate and 88.89% recall rate). PMID:26737303

  15. Subtle differences in molecular recognition between modified glycopeptide antibiotics and bacterial receptor peptides identified by electrospray ionization mass spectrometry

    DEFF Research Database (Denmark)

    Jørgensen, Thomas J. D.; Staroske, T; Roepstorff, P;

    1999-01-01

    showing that electrospray ionization mass spectrometry (ESI-MS) can be used in the rapid quantitative analysis of mixtures of vancomycin-group antibiotics and their bacterial cell-wall receptors allowing the identification of even subtle differences in binding constants. Differences in affinities...... are quantified for a mixture of vancomycin antibiotics (vancomycin, dechlorovancomycin and N-demethylvancomycin) and for a mixture of ristocetin A and its pseudoaglycone. Binding constants determined by ESI-MS were found to be in close agreement with those determined by more direct methods in aqueous solution....

  16. Molecular dynamics analysis on impact behavior of carbon nanotubes

    Energy Technology Data Exchange (ETDEWEB)

    Seifoori, Sajjad, E-mail: sajjad.seifoori@vru.ac.ir

    2015-01-30

    Graphical abstract: - Highlights: • We present an analytical solution of impact based on two degree of freedom model. • The accuracy is verified by Molecular dynamics simulations. • The effects of the small-size effects on the dynamic deflections are investigated. • The relative motion is also accounted that is due to local indentation. - Abstract: Dynamic analysis of impact of a nanoparticle on carbon nanotubes is investigated based on two degree of freedom model. The accuracy and stability of the present methods are verified by molecular dynamics (MD) simulations. The effect of different types of boundary condition on the maximum dynamic deflections is studied for zigzag and armchair SWCNTs with various aspect ratios (length/diameter). Besides, the influences of velocity of impactor on the dynamic deflections are studied. It is shown that the dynamic behavior on the armchair and zigzag single-walled carbon nanotubes are almost similar. Finally, by making use of the above MD simulation and theoretical results some insight has been obtained about the dynamic characteristics of the impact problems of nanobeam structures. Nonlocal Timoshenko beam models TBT2 should be employed for an accurate prediction of the dynamic deflection rather than nonlocal Euler–Bernoulli beam models EBT2 which ignores the effects of transverse shear deformation and rotary inertia that is especially significant for short beams. The results from nonlocal EBT2 and TBT2 models demonstrated good agreement with MD simulation. The EBT2 and TBT2 models also account for the relative motion between the nanoparticle and the nanobeam that is due to local indentation as can be seen in MD simulation.

  17. Molecular dynamics analysis on impact behavior of carbon nanotubes

    International Nuclear Information System (INIS)

    Graphical abstract: - Highlights: • We present an analytical solution of impact based on two degree of freedom model. • The accuracy is verified by Molecular dynamics simulations. • The effects of the small-size effects on the dynamic deflections are investigated. • The relative motion is also accounted that is due to local indentation. - Abstract: Dynamic analysis of impact of a nanoparticle on carbon nanotubes is investigated based on two degree of freedom model. The accuracy and stability of the present methods are verified by molecular dynamics (MD) simulations. The effect of different types of boundary condition on the maximum dynamic deflections is studied for zigzag and armchair SWCNTs with various aspect ratios (length/diameter). Besides, the influences of velocity of impactor on the dynamic deflections are studied. It is shown that the dynamic behavior on the armchair and zigzag single-walled carbon nanotubes are almost similar. Finally, by making use of the above MD simulation and theoretical results some insight has been obtained about the dynamic characteristics of the impact problems of nanobeam structures. Nonlocal Timoshenko beam models TBT2 should be employed for an accurate prediction of the dynamic deflection rather than nonlocal Euler–Bernoulli beam models EBT2 which ignores the effects of transverse shear deformation and rotary inertia that is especially significant for short beams. The results from nonlocal EBT2 and TBT2 models demonstrated good agreement with MD simulation. The EBT2 and TBT2 models also account for the relative motion between the nanoparticle and the nanobeam that is due to local indentation as can be seen in MD simulation

  18. Mathematical analysis of compressive/tensile molecular and nuclear structures

    Science.gov (United States)

    Wang, Dayu

    Mathematical analysis in chemistry is a fascinating and critical tool to explain experimental observations. In this dissertation, mathematical methods to present chemical bonding and other structures for many-particle systems are discussed at different levels (molecular, atomic, and nuclear). First, the tetrahedral geometry of single, double, or triple carbon-carbon bonds gives an unsatisfying demonstration of bond lengths, compared to experimental trends. To correct this, Platonic solids and Archimedean solids were evaluated as atoms in covalent carbon or nitrogen bond systems in order to find the best solids for geometric fitting. Pentagonal solids, e.g. the dodecahedron and icosidodecahedron, give the best fit with experimental bond lengths; an ideal pyramidal solid which models covalent bonds was also generated. Second, the macroscopic compression/tension architectural approach was applied to forces at the molecular level, considering atomic interactions as compressive (repulsive) and tensile (attractive) forces. Two particle interactions were considered, followed by a model of the dihydrogen molecule (H2; two protons and two electrons). Dihydrogen was evaluated as two different types of compression/tension structures: a coaxial spring model and a ring model. Using similar methods, covalent diatomic molecules (made up of C, N, O, or F) were evaluated. Finally, the compression/tension model was extended to the nuclear level, based on the observation that nuclei with certain numbers of protons/neutrons (magic numbers) have extra stability compared to other nucleon ratios. A hollow spherical model was developed that combines elements of the classic nuclear shell model and liquid drop model. Nuclear structure and the trend of the "island of stability" for the current and extended periodic table were studied.

  19. Gametogenesis in the Pacific oyster Crassostrea gigas: a microarrays-based analysis identifies sex and stage specific genes.

    Directory of Open Access Journals (Sweden)

    Nolwenn M Dheilly

    Full Text Available BACKGROUND: The Pacific oyster Crassostrea gigas (Mollusca, Lophotrochozoa is an alternative and irregular protandrous hermaphrodite: most individuals mature first as males and then change sex several times. Little is known about genetic and phenotypic basis of sex differentiation in oysters, and little more about the molecular pathways regulating reproduction. We have recently developed and validated a microarray containing 31,918 oligomers (Dheilly et al., 2011 representing the oyster transcriptome. The application of this microarray to the study of mollusk gametogenesis should provide a better understanding of the key factors involved in sex differentiation and the regulation of oyster reproduction. METHODOLOGY/PRINCIPAL FINDINGS: Gene expression was studied in gonads of oysters cultured over a yearly reproductive cycle. Principal component analysis and hierarchical clustering showed a significant divergence in gene expression patterns of males and females coinciding with the start of gonial mitosis. ANOVA analysis of the data revealed 2,482 genes differentially expressed during the course of males and/or females gametogenesis. The expression of 434 genes could be localized in either germ cells or somatic cells of the gonad by comparing the transcriptome of female gonads to the transcriptome of stripped oocytes and somatic tissues. Analysis of the annotated genes revealed conserved molecular mechanisms between mollusks and mammals: genes involved in chromatin condensation, DNA replication and repair, mitosis and meiosis regulation, transcription, translation and apoptosis were expressed in both male and female gonads. Most interestingly, early expressed male-specific genes included bindin and a dpy-30 homolog and female-specific genes included foxL2, nanos homolog 3, a pancreatic lipase related protein, cd63 and vitellogenin. Further functional analyses are now required in order to investigate their role in sex differentiation in oysters

  20. Aging-induced proteostatic changes in the rat hippocampus identify ARP3, NEB2 and BRAG2 as a molecular circuitry for cognitive impairment.

    Directory of Open Access Journals (Sweden)

    Philipp Ottis

    Full Text Available Disturbed proteostasis as a particular phenotype of the aging organism has been advanced in C. elegans experiments and is also conceived to underlie neurodegenerative diseases in humans. Here, we investigated whether particular changes in non-disease related proteostasis can be identified in the aged mammalian brain, and whether a particular signature of aberrant proteostasis is related to behavioral performance of learning and memory. Young (adult, n = 30 and aged (2 years, n = 50 Wistar rats were tested in the Morris Water Maze (MWM to distinguish superior and inferior performers. For both young and old rats, the best and worst performers in the MWM were selected and the insoluble proteome, termed aggregome, was purified from the hippocampus as evidence for aberrant proteostasis. Quantitative proteomics (iTRAQ was performed. The aged inferior performers were considered as a model for spontaneous, age-associated cognitive impairment. Whereas variability of the insoluble proteome increased with age, absolute changes in the levels of insoluble proteins were small compared to the findings in the whole C. elegans insoluble proteome. However, we identified proteins with aberrant proteostasis in aging. For the cognitively impaired rats, we identified a changed molecular circuitry of proteins selectively involved in F-actin remodeling, synapse building and long-term depression: actin related protein 3 (ARP3, neurabin II (NEB2 and IQ motif and SEC7 domain-containing protein 1 (BRAG2. We demonstrate that aberrant proteostasis is a specific phenotype of brain aging in mammals. We identify a distinct molecular circuitry where changes in proteostasis are characteristic for poor learning and memory performance in the wild type, aged rat. Our findings 1. establish the search for aberrant proteostasis as a successful strategy to identify neuronal dysfunction in deficient cognitive behavior, 2. reveal a previously unknown functional network of proteins (ARP3

  1. Co-expression network analysis identifies transcriptional modules in the mouse liver.

    Science.gov (United States)

    Liu, Wei; Ye, Hua

    2014-10-01

    The mouse liver transcriptome has been extensively studied but little is known about the global hepatic gene network of the mouse under normal physiological conditions. Understanding this will help reveal the transcriptional organization of the liver and elucidate its functional complexity. Here, weighted gene co-expression network analysis (WGCNA) was carried out to explore gene co-expression networks using large-scale microarray data from normal mouse livers. A total of 7,203 genes were parsed into 16 gene modules associated with protein catabolism, RNA processing, muscle contraction, transcriptional regulation, oxidation reduction, sterol biosynthesis, translation, fatty acid metabolism, immune response and others. The modules were organized into higher order co-expression groups. Hub genes in each module were found to be critical for module function. In sum, the analyses revealed the gene modular map of the mouse liver under normal physiological condition. These results provide a systems-level framework to help understand the complexity of the mouse liver at the molecular level, and should be beneficial in annotating uncharacterized genes. PMID:24816893

  2. Time-resolved Studies of IsdG Protein Identify Molecular Signposts along the Non-canonical Heme Oxygenase Pathway.

    Science.gov (United States)

    Streit, Bennett R; Kant, Ravi; Tokmina-Lukaszewska, Monika; Celis, Arianna I; Machovina, Melodie M; Skaar, Eric P; Bothner, Brian; DuBois, Jennifer L

    2016-01-01

    IsdGs are heme monooxygenases that break open the tetrapyrrole, releasing the iron, and thereby allowing bacteria expressing this protein to use heme as a nutritional iron source. Little is currently known about the mechanism by which IsdGs degrade heme, although the products differ from those generated by canonical heme oxygenases. A synthesis of time-resolved techniques, including in proteo mass spectrometry and conventional and stopped-flow UV/visible spectroscopy, was used in conjunction with analytical methods to define the reaction steps mediated by IsdG from Staphylococcus aureus and their time scales. An apparent meso-hydroxyheme (forming with k = 0.6 min(-1), pH 7.4, 10 mm ascorbate, 10 μm IsdG-heme, 22 °C) was identified as a likely common intermediate with the canonical heme oxygenases. Unlike heme oxygenases, this intermediate does not form with added H2O2 nor does it convert to verdoheme and CO. Rather, the next observable intermediates (k = 0.16 min(-1)) were a set of formyloxobilin isomers, similar to the mycobilin products of the IsdG homolog from Mycobacterium tuberculosis (MhuD). These converted in separate fast and slow phases to β-/δ-staphylobilin isomers and formaldehyde (CH2O). Controlled release of this unusual C1 product may support IsdG's dual role as both an oxygenase and a sensor of heme availability in S. aureus. PMID:26534961

  3. Genome-wide analysis of over 106 000 individuals identifies 9 neuroticism-associated loci.

    Science.gov (United States)

    Smith, D J; Escott-Price, V; Davies, G; Bailey, M E S; Colodro-Conde, L; Ward, J; Vedernikov, A; Marioni, R; Cullen, B; Lyall, D; Hagenaars, S P; Liewald, D C M; Luciano, M; Gale, C R; Ritchie, S J; Hayward, C; Nicholl, B; Bulik-Sullivan, B; Adams, M; Couvy-Duchesne, B; Graham, N; Mackay, D; Evans, J; Smith, B H; Porteous, D J; Medland, S E; Martin, N G; Holmans, P; McIntosh, A M; Pell, J P; Deary, I J; O'Donovan, M C

    2016-06-01

    Neuroticism is a personality trait of fundamental importance for psychological well-being and public health. It is strongly associated with major depressive disorder (MDD) and several other psychiatric conditions. Although neuroticism is heritable, attempts to identify the alleles involved in previous studies have been limited by relatively small sample sizes. Here we report a combined meta-analysis of genome-wide association study (GWAS) of neuroticism that includes 91 370 participants from the UK Biobank cohort, 6659 participants from the Generation Scotland: Scottish Family Health Study (GS:SFHS) and 8687 participants from a QIMR (Queensland Institute of Medical Research) Berghofer Medical Research Institute (QIMR) cohort. All participants were assessed using the same neuroticism instrument, the Eysenck Personality Questionnaire-Revised (EPQ-R-S) Short Form's Neuroticism scale. We found a single-nucleotide polymorphism-based heritability estimate for neuroticism of ∼15% (s.e.=0.7%). Meta-analysis identified nine novel loci associated with neuroticism. The strongest evidence for association was at a locus on chromosome 8 (P=1.5 × 10(-15)) spanning 4 Mb and containing at least 36 genes. Other associated loci included interesting candidate genes on chromosome 1 (GRIK3 (glutamate receptor ionotropic kainate 3)), chromosome 4 (KLHL2 (Kelch-like protein 2)), chromosome 17 (CRHR1 (corticotropin-releasing hormone receptor 1) and MAPT (microtubule-associated protein Tau)) and on chromosome 18 (CELF4 (CUGBP elav-like family member 4)). We found no evidence for genetic differences in the common allelic architecture of neuroticism by sex. By comparing our findings with those of the Psychiatric Genetics Consortia, we identified a strong genetic correlation between neuroticism and MDD and a less strong but significant genetic correlation with schizophrenia, although not with bipolar disorder. Polygenic risk scores derived from the primary UK Biobank sample captured

  4. Identifying typical patterns of vulnerability: A 5-step approach based on cluster analysis

    Science.gov (United States)

    Sietz, Diana; Lüdeke, Matthias; Kok, Marcel; Lucas, Paul; Carsten, Walther; Janssen, Peter

    2013-04-01

    Specific processes that shape the vulnerability of socio-ecological systems to climate, market and other stresses derive from diverse background conditions. Within the multitude of vulnerability-creating mechanisms, distinct processes recur in various regions inspiring research on typical patterns of vulnerability. The vulnerability patterns display typical combinations of the natural and socio-economic properties that shape a systems' vulnerability to particular stresses. Based on the identification of a limited number of vulnerability patterns, pattern analysis provides an efficient approach to improving our understanding of vulnerability and decision-making for vulnerability reduction. However, current pattern analyses often miss explicit descriptions of their methods and pay insufficient attention to the validity of their groupings. Therefore, the question arises as to how do we identify typical vulnerability patterns in order to enhance our understanding of a systems' vulnerability to stresses? A cluster-based pattern recognition applied at global and local levels is scrutinised with a focus on an applicable methodology and practicable insights. Taking the example of drylands, this presentation demonstrates the conditions necessary to identify typical vulnerability patterns. They are summarised in five methodological steps comprising the elicitation of relevant cause-effect hypotheses and the quantitative indication of mechanisms as well as an evaluation of robustness, a validation and a ranking of the identified patterns. Reflecting scale-dependent opportunities, a global study is able to support decision-making with insights into the up-scaling of interventions when available funds are limited. In contrast, local investigations encourage an outcome-based validation. This constitutes a crucial step in establishing the credibility of the patterns and hence their suitability for informing extension services and individual decisions. In this respect, working at

  5. Transcriptome analysis identifies genes involved in adventitious branches formation of Gracilaria lichenoides in vitro.

    Science.gov (United States)

    Wang, Wenlei; Li, Huanqin; Lin, Xiangzhi; Yang, Shanjun; Wang, Zhaokai; Fang, Baishan

    2015-12-11

    Tissue culture could solve the problems associated with Gracilaria cultivation, including the consistent supply of high-quality seed stock, strain improvement, and efficient mass culture of high-yielding commercial strains. However, STC lags behind that of higher plants because of the paucity of genomic information. Transcriptome analysis and the identification of potential unigenes involved in the formation and regeneration of callus or direct induction of ABs are essential. Herein, the CK, EWAB and NPA G. lichenoides transcriptomes were analyzed using the Illumina sequencing platform in first time. A total of 17,922,453,300 nucleotide clean bases were generated and assembled into 21,294 unigenes, providing a total gene space of 400,912,038 nucleotides with an average length of 1,883 and N 50 of 5,055 nucleotides and a G + C content of 52.02%. BLAST analysis resulted in the assignment of 13,724 (97.5%), 3,740 (26.6%), 9,934 (70.6%), 10,611 (75.4%), 9,490 (67.4%), and 7,773 (55.2%) unigenes were annotated to the NR, NT, Swiss-Prot, KEGG, COG, and GO databases, respectively, and the total of annotated unigenes was 14,070. A total of 17,099 transcripts were predicted to possess open reading frames, including 3,238 predicted and 13,861 blasted based on protein databases. In addition, 3,287 SSRs were detected in G.lichenoides, providing further support for genetic variation and marker-assisted selection in the future. Our results suggest that auxin polar transport, auxin signal transduction, crosstalk with other endogenous plant hormones and antioxidant systems, play important roles for ABs formation in G. lichenoides explants in vitro. The present findings will facilitate further studies on gene discovery and on the molecular mechanisms underlying the tissue culture of seaweed.

  6. Genome-wide meta-analysis identifies six novel loci associated with habitual coffee consumption.

    Science.gov (United States)

    Cornelis, M C; Byrne, E M; Esko, T; Nalls, M A; Ganna, A; Paynter, N; Monda, K L; Amin, N; Fischer, K; Renstrom, F; Ngwa, J S; Huikari, V; Cavadino, A; Nolte, I M; Teumer, A; Yu, K; Marques-Vidal, P; Rawal, R; Manichaikul, A; Wojczynski, M K; Vink, J M; Zhao, J H; Burlutsky, G; Lahti, J; Mikkilä, V; Lemaitre, R N; Eriksson, J; Musani, S K; Tanaka, T; Geller, F; Luan, J; Hui, J; Mägi, R; Dimitriou, M; Garcia, M E; Ho, W-K; Wright, M J; Rose, L M; Magnusson, P K E; Pedersen, N L; Couper, D; Oostra, B A; Hofman, A; Ikram, M A; Tiemeier, H W; Uitterlinden, A G; van Rooij, F J A; Barroso, I; Johansson, I; Xue, L; Kaakinen, M; Milani, L; Power, C; Snieder, H; Stolk, R P; Baumeister, S E; Biffar, R; Gu, F; Bastardot, F; Kutalik, Z; Jacobs, D R; Forouhi, N G; Mihailov, E; Lind, L; Lindgren, C; Michaëlsson, K; Morris, A; Jensen, M; Khaw, K-T; Luben, R N; Wang, J J; Männistö, S; Perälä, M-M; Kähönen, M; Lehtimäki, T; Viikari, J; Mozaffarian, D; Mukamal, K; Psaty, B M; Döring, A; Heath, A C; Montgomery, G W; Dahmen, N; Carithers, T; Tucker, K L; Ferrucci, L; Boyd, H A; Melbye, M; Treur, J L; Mellström, D; Hottenga, J J; Prokopenko, I; Tönjes, A; Deloukas, P; Kanoni, S; Lorentzon, M; Houston, D K; Liu, Y; Danesh, J; Rasheed, A; Mason, M A; Zonderman, A B; Franke, L; Kristal, B S; Karjalainen, J; Reed, D R; Westra, H-J; Evans, M K; Saleheen, D; Harris, T B; Dedoussis, G; Curhan, G; Stumvoll, M; Beilby, J; Pasquale, L R; Feenstra, B; Bandinelli, S; Ordovas, J M; Chan, A T; Peters, U; Ohlsson, C; Gieger, C; Martin, N G; Waldenberger, M; Siscovick, D S; Raitakari, O; Eriksson, J G; Mitchell, P; Hunter, D J; Kraft, P; Rimm, E B; Boomsma, D I; Borecki, I B; Loos, R J F; Wareham, N J; Vollenweider, P; Caporaso, N; Grabe, H J; Neuhouser, M L; Wolffenbuttel, B H R; Hu, F B; Hyppönen, E; Järvelin, M-R; Cupples, L A; Franks, P W; Ridker, P M; van Duijn, C M; Heiss, G; Metspalu, A; North, K E; Ingelsson, E; Nettleton, J A; van Dam, R M; Chasman, D I

    2015-05-01

    Coffee, a major dietary source of caffeine, is among the most widely consumed beverages in the world and has received considerable attention regarding health risks and benefits. We conducted a genome-wide (GW) meta-analysis of predominately regular-type coffee consumption (cups per day) among up to 91,462 coffee consumers of European ancestry with top single-nucleotide polymorphisms (SNPs) followed-up in ~30 062 and 7964 coffee consumers of European and African-American ancestry, respectively. Studies from both stages were combined in a trans-ethnic meta-analysis. Confirmed loci were examined for putative functional and biological relevance. Eight loci, including six novel loci, met GW significance (log10Bayes factor (BF)>5.64) with per-allele effect sizes of 0.03-0.14 cups per day. Six are located in or near genes potentially involved in pharmacokinetics (ABCG2, AHR, POR and CYP1A2) and pharmacodynamics (BDNF and SLC6A4) of caffeine. Two map to GCKR and MLXIPL genes related to metabolic traits but lacking known roles in coffee consumption. Enhancer and promoter histone marks populate the regions of many confirmed loci and several potential regulatory SNPs are highly correlated with the lead SNP of each. SNP alleles near GCKR, MLXIPL, BDNF and CYP1A2 that were associated with higher coffee consumption have previously been associated with smoking initiation, higher adiposity and fasting insulin and glucose but lower blood pressure and favorable lipid, inflammatory and liver enzyme profiles (P<5 × 10(-8)).Our genetic findings among European and African-American adults reinforce the role of caffeine in mediating habitual coffee consumption and may point to molecular mechanisms underlying inter-individual variability in pharmacological and health effects of coffee. PMID:25288136

  7. Diet of pumas (Puma concolor) in Sonora, Mexico, as determined by GPS kill sites and molecular identified scat, with comments on jaguar (Panthera onca) diet

    Science.gov (United States)

    Cassaigne, Ivonne; Medellin, Rodrigo A.; Thompson, Ron W.; Culver, Melanie; Ochoa, Alexander; Vargas, Karla; Childs, Jack L.; Sanderson, Jim; List, Rurik; Torres-Gomez, Armando

    2016-01-01

    We documented puma (Puma concolor) and jaguar (Panthera onca) prey consumption in northeastern Sonora, Mexico, by investigating global positioning system cluster sites (n = 220), and conducting molecular analyses of scat (n = 116) collected between 2011 and 2013. We used camera trap data (n = 8,976 camera days) to estimate relative abundances of pumas and jaguars. Deer (Odocoileus virginianus) was the most frequent prey for puma found at kill sites (67%) and identified from scat (74%), although based on relative numbers of prey consumed, deer represented 45% and lagomorphs 20% of the proportion of all individuals eaten. A variety of small prey (weighing Sonora.

  8. Genomic analysis and selected molecular pathways in rare cancers

    International Nuclear Information System (INIS)

    It is widely accepted that many cancers arise as a result of an acquired genomic instability and the subsequent evolution of tumor cells with variable patterns of selected and background aberrations. The presence and behaviors of distinct neoplastic cell populations within a patient's tumor may underlie multiple clinical phenotypes in cancers. A goal of many current cancer genome studies is the identification of recurring selected driver events that can be advanced for the development of personalized therapies. Unfortunately, in the majority of rare tumors, this type of analysis can be particularly challenging. Large series of specimens for analysis are simply not available, allowing recurring patterns to remain hidden. In this paper, we highlight the use of DNA content-based flow sorting to identify and isolate DNA-diploid and DNA-aneuploid populations from tumor biopsies as a strategy to comprehensively study the genomic composition and behaviors of individual cancers in a series of rare solid tumors: intrahepatic cholangiocarcinoma, anal carcinoma, adrenal leiomyosarcoma, and pancreatic neuroendocrine tumors. We propose that the identification of highly selected genomic events in distinct tumor populations within each tumor can identify candidate driver events that can facilitate the development of novel, personalized treatment strategies for patients with cancer. (paper)

  9. Transcriptome Analysis of Individual Stromal Cell Populations Identifies Stroma-Tumor Crosstalk in Mouse Lung Cancer Model

    Directory of Open Access Journals (Sweden)

    Hyejin Choi

    2015-02-01

    Full Text Available Emerging studies have begun to demonstrate that reprogrammed stromal cells play pivotal roles in tumor growth, metastasis, and resistance to therapy. However, the contribution of stromal cells to non-small-cell lung cancer (NSCLC has remained underexplored. We used an orthotopic model of Kras-driven NSCLC to systematically dissect the contribution of specific hematopoietic stromal cells in lung cancer. RNA deep-sequencing analysis of individually sorted myeloid lineage and tumor epithelial cells revealed cell-type-specific differentially regulated genes, indicative of activated stroma. We developed a computational model for crosstalk signaling discovery based on ligand-receptor interactions and downstream signaling networks and identified known and novel tumor-stroma paracrine and tumor autocrine crosstalk-signaling pathways in NSCLC. We provide cellular and molecular insights into components of the lung cancer microenvironment that contribute to carcinogenesis. This study has the potential for development of therapeutic strategies that target tumor-stroma interactions and may complement conventional anti-cancer treatments.

  10. Transcriptome analysis of individual stromal cell populations identifies stroma-tumor crosstalk in mouse lung cancer model.

    Science.gov (United States)

    Choi, Hyejin; Sheng, Jianting; Gao, Dingcheng; Li, Fuhai; Durrans, Anna; Ryu, Seongho; Lee, Sharrell B; Narula, Navneet; Rafii, Shahin; Elemento, Olivier; Altorki, Nasser K; Wong, Stephen T C; Mittal, Vivek

    2015-02-24

    Emerging studies have begun to demonstrate that reprogrammed stromal cells play pivotal roles in tumor growth, metastasis, and resistance to therapy. However, the contribution of stromal cells to non-small-cell lung cancer (NSCLC) has remained underexplored. We used an orthotopic model of Kras-driven NSCLC to systematically dissect the contribution of specific hematopoietic stromal cells in lung cancer. RNA deep-sequencing analysis of individually sorted myeloid lineage and tumor epithelial cells revealed cell-type-specific differentially regulated genes, indicative of activated stroma. We developed a computational model for crosstalk signaling discovery based on ligand-receptor interactions and downstream signaling networks and identified known and novel tumor-stroma paracrine and tumor autocrine crosstalk-signaling pathways in NSCLC. We provide cellular and molecular insights into components of the lung cancer microenvironment that contribute to carcinogenesis. This study has the potential for development of therapeutic strategies that target tumor-stroma interactions and may complement conventional anti-cancer treatments. PMID:25704820

  11. Genome-wide transcriptome analysis in the ovaries of two goats identifies differentially expressed genes related to fecundity.

    Science.gov (United States)

    Miao, Xiangyang; Luo, Qingmiao; Qin, Xiaoyu

    2016-05-10

    The goats are widely kept as livestock throughout the world. Two excellent domestic breeds in China, the Laiwu Black and Jining Grey goats, have different fecundities and prolificacies. Although the goat genome sequences have been resolved recently, little is known about the gene regulations at the transcriptional level in goat. To understand the molecular and genetic mechanisms related to the fecundities and prolificacies, we performed genome-wide sequencing of the mRNAs from two breeds of goat using the next-generation RNA-Seq technology and used functional annotation to identify pathways of interest. Digital gene expression analysis showed 338 genes were up-regulated in the Jining Grey goats and 404 were up-regulated in the Laiwu Black goats. Quantitative real-time PCR verified the reliability of the RNA-Seq data. This study suggests that multiple genes responsible for various biological functions and signaling pathways are differentially expressed in the two different goat breeds, and these genes might be involved in the regulation of goat fecundity and prolificacy. Taken together, our study provides insight into the transcriptional regulation in the ovaries of 2 species of goats that might serve as a key resource for understanding goat fecundity, prolificacy and genetic diversity between species. PMID:26851539

  12. VIBRATION ANALYSIS ON A COMPOSITE BEAM TO IDENTIFY DAMAGE AND DAMAGE SEVERITY USING FINITE ELEMENT METHOD

    Directory of Open Access Journals (Sweden)

    E.V.V.Ramanamurthy

    2011-07-01

    Full Text Available The objective of this paper is to develop a damage detection method in a composite cantilever beam with an edge crack has been studied using finite element method. A number of analytical, numerical andexperimental techniques are available for the study of damage identification in beams. Studies were carried out for three different types of analysis on a composite cantilever beam with an edge crack as damage. The material used in this analysis is glass-epoxy composite material. The finite element formulation was carried out in the analysis section of the package, known as ANSYS. The types of vibration analysis studied on a composite beam are Modal, Harmonic andTransient analysis. The crack is modeled such that the cantilever beam is replaced with two intact beams with the crack as additional boundary condition. Damage algorithms are used to identify and locate the damage. Damage index method is also used to find the severity of the damage. The results obtained from modal analysis were compared with the transient analysis results.The vibration-based damage detection methods are based on the fact that changes of physical properties (stiffness, mass and damping due to damage will manifest themselves as changes in the structural modal parameters (natural frequencies, mode shapes and modal damping. The task is then to monitor the selected indicators derived from modal parameters to distinguish between undamaged and damaged states. However, the quantitative changes of global modal parameters are not sufficiently sensitive to a local damage. The proposed approach, on the other hand, interprets the dynamic changes caused by damage in a different way. Although the basis for vibration-based damage detection appears intuitive, the implementation in real structures may encounter many significant challenges. The most fundamental issue is the fact that damage typically is a local phenomenon and may not dramatically influence the global dynamic response of a

  13. Automated local bright feature image analysis of nuclear proteindistribution identifies changes in tissue phenotype

    Energy Technology Data Exchange (ETDEWEB)

    Knowles, David; Sudar, Damir; Bator, Carol; Bissell, Mina

    2006-02-01

    The organization of nuclear proteins is linked to cell and tissue phenotypes. When cells arrest proliferation, undergo apoptosis, or differentiate, the distribution of nuclear proteins changes. Conversely, forced alteration of the distribution of nuclear proteins modifies cell phenotype. Immunostaining and fluorescence microscopy have been critical for such findings. However, there is an increasing need for quantitative analysis of nuclear protein distribution to decipher epigenetic relationships between nuclear structure and cell phenotype, and to unravel the mechanisms linking nuclear structure and function. We have developed imaging methods to quantify the distribution of fluorescently-stained nuclear protein NuMA in different mammary phenotypes obtained using three-dimensional cell culture. Automated image segmentation of DAPI-stained nuclei was generated to isolate thousands of nuclei from three-dimensional confocal images. Prominent features of fluorescently-stained NuMA were detected using a novel local bright feature analysis technique, and their normalized spatial density calculated as a function of the distance from the nuclear perimeter to its center. The results revealed marked changes in the distribution of the density of NuMA bright features as non-neoplastic cells underwent phenotypically normal acinar morphogenesis. In contrast, we did not detect any reorganization of NuMA during the formation of tumor nodules by malignant cells. Importantly, the analysis also discriminated proliferating non-neoplastic cells from proliferating malignant cells, suggesting that these imaging methods are capable of identifying alterations linked not only to the proliferation status but also to the malignant character of cells. We believe that this quantitative analysis will have additional applications for classifying normal and pathological tissues.

  14. Pathway Analysis Incorporating Protein-Protein Interaction Networks Identified Candidate Pathways for the Seven Common Diseases.

    Science.gov (United States)

    Lin, Peng-Lin; Yu, Ya-Wen; Chung, Ren-Hua

    2016-01-01

    Pathway analysis has become popular as a secondary analysis strategy for genome-wide association studies (GWAS). Most of the current pathway analysis methods aggregate signals from the main effects of single nucleotide polymorphisms (SNPs) in genes within a pathway without considering the effects of gene-gene interactions. However, gene-gene interactions can also have critical effects on complex diseases. Protein-protein interaction (PPI) networks have been used to define gene pairs for the gene-gene interaction tests. Incorporating the PPI information to define gene pairs for interaction tests within pathways can increase the power for pathway-based association tests. We propose a pathway association test, which aggregates the interaction signals in PPI networks within a pathway, for GWAS with case-control samples. Gene size is properly considered in the test so that genes do not contribute more to the test statistic simply due to their size. Simulation studies were performed to verify that the method is a valid test and can have more power than other pathway association tests in the presence of gene-gene interactions within a pathway under different scenarios. We applied the test to the Wellcome Trust Case Control Consortium GWAS datasets for seven common diseases. The most significant pathway is the chaperones modulate interferon signaling pathway for Crohn's disease (p-value = 0.0003). The pathway modulates interferon gamma, which induces the JAK/STAT pathway that is involved in Crohn's disease. Several other pathways that have functional implications for the seven diseases were also identified. The proposed test based on gene-gene interaction signals in PPI networks can be used as a complementary tool to the current existing pathway analysis methods focusing on main effects of genes. An efficient software implementing the method is freely available at http://puppi.sourceforge.net. PMID:27622767

  15. Shared Genetic Etiology between Type 2 Diabetes and Alzheimer's Disease Identified by Bioinformatics Analysis.

    Science.gov (United States)

    Gao, Lei; Cui, Zhen; Shen, Liang; Ji, Hong-Fang

    2015-01-01

    Type 2 diabetes (T2D) and Alzheimer's disease (AD) are two major health issues, and increasing evidence in recent years supports the close connection between these two diseases. The present study aimed to explore the shared genetic etiology underlying T2D and AD based on the available genome wide association studies (GWAS) data collected through August 2014. We performed bioinformatics analyses based on GWAS data of T2D and AD on single nucleotide polymorphisms (SNPs), gene, and pathway levels, respectively. Six SNPs (rs111789331, rs12721046, rs12721051, rs4420638, rs56131196, and rs66626994) were identified for the first time to be shared genetic factors between T2D and AD. Further functional enrichment analysis found lipid metabolism related pathways to be common between these two disorders. The findings may have important implications for future mechanistic and interventional studies for T2D and AD. PMID:26639962

  16. Identifying time measurement tampering in the traversal time and hop count analysis (TTHCA) wormhole detection algorithm.

    Science.gov (United States)

    Karlsson, Jonny; Dooley, Laurence S; Pulkkis, Göran

    2013-01-01

    Traversal time and hop count analysis (TTHCA) is a recent wormhole detection algorithm for mobile ad hoc networks (MANET) which provides enhanced detection performance against all wormhole attack variants and network types. TTHCA involves each node measuring the processing time of routing packets during the route discovery process and then delivering the measurements to the source node. In a participation mode (PM) wormhole where malicious nodes appear in the routing tables as legitimate nodes, the time measurements can potentially be altered so preventing TTHCA from successfully detecting the wormhole. This paper analyses the prevailing conditions for time tampering attacks to succeed for PM wormholes, before introducing an extension to the TTHCA detection algorithm called ∆T Vector which is designed to identify time tampering, while preserving low false positive rates. Simulation results confirm that the ∆T Vector extension is able to effectively detect time tampering attacks, thereby providing an important security enhancement to the TTHCA algorithm. PMID:23686143

  17. Identifying Time Measurement Tampering in the Traversal Time and Hop Count Analysis (TTHCA Wormhole Detection Algorithm

    Directory of Open Access Journals (Sweden)

    Jonny Karlsson

    2013-05-01

    Full Text Available Traversal time and hop count analysis (TTHCA is a recent wormhole detection algorithm for mobile ad hoc networks (MANET which provides enhanced detection performance against all wormhole attack variants and network types. TTHCA involves each node measuring the processing time of routing packets during the route discovery process and then delivering the measurements to the source node. In a participation mode (PM wormhole where malicious nodes appear in the routing tables as legitimate nodes, the time measurements can potentially be altered so preventing TTHCA from successfully detecting the wormhole. This paper analyses the prevailing conditions for time tampering attacks to succeed for PM wormholes, before introducing an extension to the TTHCA detection algorithm called ∆T Vector which is designed to identify time tampering, while preserving low false positive rates. Simulation results confirm that the ∆T Vector extension is able to effectively detect time tampering attacks, thereby providing an important security enhancement to the TTHCA algorithm.

  18. Confocal Raman data analysis enables identifying apoptosis of MCF-7 cells caused by anticancer drug paclitaxel

    Science.gov (United States)

    Salehi, Hamideh; Middendorp, Elodie; Panayotov, Ivan; Dutilleul, Pierre-Yves Collard; Vegh, Attila-Gergely; Ramakrishnan, Sathish; Gergely, Csilla; Cuisinier, Frederic

    2013-05-01

    Confocal Raman microscopy is a noninvasive, label-free imaging technique used to study apoptosis of live MCF-7 cells. The images are based on Raman spectra of cells components, and their apoptosis is monitored through diffusion of cytochrome c in cytoplasm. K-mean clustering is used to identify mitochondria in cells, and correlation analysis provides the cytochrome c distribution inside the cells. Our results demonstrate that incubation of cells for 3 h with 10 μM of paclitaxel does not induce apoptosis in MCF-7 cells. On the contrary, incubation for 30 min at a higher concentration (100 μM) of paclitaxel induces gradual release of the cytochrome c into the cytoplasm, indicating cell apoptosis via a caspase independent pathway.

  19. Identifying and Analysis of Scene Mining Methods Beased on Scenes Extracted Features

    CERN Document Server

    Jabari, Ashraf Sadat

    2012-01-01

    Scene mining is a subset of image mining in which scenes are classified to a distinct set of classes based on analysis of their content. In other word in scene mining, a label is given to visual content of scene, for example, mountain, beach. Scene mining is used in applications such as medicine, movie, information retrieval, computer vision, recognition of traffic scene. Reviewing of represented methods shows there are various methods in scene mining. Scene mining applications extension and existence of various scenes, make comparison of methods hard. Scene mining can be followed by identifying scene mining components and representing a framework to analyzing and evaluating methods. In this paper, at first, components of scene mining are introduced, then a framework based on extracted features of scene is represented to classify scene mining methods. Finally, these methods are analyzed and evaluated via a proposal framework.

  20. Molecular studies to identify the Fusarium species responsible for HT-2 and T-2 mycotoxins in UK oats.

    Science.gov (United States)

    Edwards, Simon G; Imathiu, Samuel M; Ray, Rumiana V; Back, Matthew; Hare, Martin C

    2012-05-15

    High levels of Fusarium mycotoxins HT-2 and T-2 have been detected in UK oats since surveys started in 2002. Fusarium langsethiae and the closely related species F. sporotrichioides have previously been associated with the contamination of cereals with type A trichothecenes HT-2 and T-2 in Nordic countries. Preliminary microbiological analysis of UK oat samples with high concentrations of HT-2 and T-2 detected and isolated F. langsethiae and F. poae but not the other type A trichothecene producing species F. sporotrichioides, F. sibiricum and F. armeniacum. Two hundred and forty oat flour samples with a known mycotoxin profile were selected from a previous four year study (2002-2005) to cover the full concentration range from below the limit of quantification (oat flour samples with known HT-2+T-2 content. Results showed a good regression (Poat grains. The results from this study provide strong evidence that F. langsethiae is the primary, if not sole, fungus responsible for high HT-2 and T-2 in UK oats.

  1. Using Principal Component Analysis to Identify Priority Neighbourhoods for Health Services Delivery by Ranking Socioeconomic Status

    Science.gov (United States)

    Friesen, Christine Elizabeth; Seliske, Patrick; Papadopoulos, Andrew

    2016-01-01

    Objectives. Socioeconomic status (SES) is a comprehensive indicator of health status and is useful in area-level health research and informing public health resource allocation. Principal component analysis (PCA) is a useful tool for developing SES indices to identify area-level disparities in SES within communities. While SES research in Canada has relied on census data, the voluntary nature of the 2011 National Household Survey challenges the validity of its data, especially income variables. This study sought to determine the appropriateness of replacing census income information with tax filer data in neighbourhood SES index development. Methods. Census and taxfiler data for Guelph, Ontario were retrieved for the years 2005, 2006, and 2011. Data were extracted for eleven income and non-income SES variables. PCA was employed to identify significant principal components from each dataset and weights of each contributing variable. Variable-specific factor scores were applied to standardized census and taxfiler data values to produce SES scores. Results. The substitution of taxfiler income variables for census income variables yielded SES score distributions and neighbourhood SES classifications that were similar to SES scores calculated using entirely census variables. Combining taxfiler income variables with census non-income variables also produced clearer SES level distinctions. Internal validation procedures indicated that utilizing multiple principal components produced clearer SES level distinctions than using only the first principal component. Conclusion. Identifying socioeconomic disparities between neighbourhoods is an important step in assessing the level of disadvantage of communities. The ability to replace census income information with taxfiler data to develop SES indices expands the versatility of public health research and planning in Canada, as more data sources can be explored. The apparent usefulness of PCA also contributes to the improvement

  2. Identifying the potential loss of monitoring wells using an uncertainty analysis.

    Science.gov (United States)

    Freedman, Vicky L; Waichler, Scott R; Cole, Charles R; Vermeul, Vince R; Bergeron, Marcel P

    2005-01-01

    From the mid-1940s through the 1980s, large volumes of waste water were discharged at the Hanford Site in southeastern Washington State, causing a large-scale rise (>20 m) in the water table. When waste water discharges ceased in 1988, ground water mounds began to dissipate. This caused a large number of wells to go dry and has made it difficult to monitor contaminant plume migration. To identify monitoring wells that will need replacement, a methodology has been developed using a first-order uncertainty analysis with UCODE, a nonlinear parameter estimation code. Using a three-dimensional, finite-element ground water flow code, key parameters were identified by calibrating to historical hydraulic head data. Results from the calibration period were then used to check model predictions by comparing monitoring wells' wet/dry status with field data. This status was analyzed using a methodology that incorporated the 0.3 cumulative probability derived from the confidence and prediction intervals. For comparison, a nonphysically based trend model was also used as a predictor of wells' wet/dry status. Although the numerical model outperformed the trend model, for both models, the central value of the intervals was a better predictor of a wet well status. The prediction interval, however, was more successful at identifying dry wells. Predictions made through the year 2048 indicated that 46% of the wells in the monitoring well network are likely to go dry in areas near the river and where the ground water mound is dissipating. PMID:16324012

  3. Predictors of Extubation Failure in Neurocritical Patients Identified by a Systematic Review and Meta-Analysis

    Science.gov (United States)

    Huang, Kaibin; Lin, Zhenzhou; Qiao, Weiguang; Pan, Suyue

    2014-01-01

    Background Prediction of extubation failure, particularly in neurocritical patients, is unique and controversial. We conducted a systematic review and meta-analysis to identify the risk factors for extubation failure in these patients. Methods A literature search of databases (MEDLINE, EMBASE, the Cochrane Library, and Web of Science) was performed up to August of 2013 to identify trials that evaluated extubation failure predictors. Included trials were either prospective or retrospective cohort studies. Results Nine studies involving 928 participants were included. The systematic review and meta-analysis revealed that the following were predictive for extubation failure: pneumonia, atelectasis, mechanical ventilation of >24 h, a low Glasgow Coma Scale score (7–9T) (OR = 4.96, 95% CI = 1.61–15.26, P = 0.005), the inability to follow commands (OR = 2.07, 95% CI = 1.15–3.71, P = 0.02), especially the command to close the eyes, thick secretion, and no intact gag reflex. Meanwhile, the following were not predictive for extubation failure: sex, secretion volume, coughing upon suctioning, and the inability to follow one command among showing two fingers, wiggling the toes, or coughing on command. Additionally, some traditional weaning parameters were shown to poorly predict extubation failure in neurocritical patients. Conclusions Besides pneumonia, atelectasis, and the duration of mechanical ventilation, other factors that should be taken into consideration in the prediction of extubation failure when neurocritical patients are weaned from tracheal intubation include neurologic abilities (Glasgow Coma Scale score and following commands), the secretion texture, and the presence of a gag reflex. PMID:25486091

  4. Deep Proteome Analysis Identifies Age-Related Processes in C. elegans.

    Science.gov (United States)

    Narayan, Vikram; Ly, Tony; Pourkarimi, Ehsan; Murillo, Alejandro Brenes; Gartner, Anton; Lamond, Angus I; Kenyon, Cynthia

    2016-08-01

    Effective network analysis of protein data requires high-quality proteomic datasets. Here, we report a near doubling in coverage of the C. elegans adult proteome, identifying >11,000 proteins in total with ∼9,400 proteins reproducibly detected in three biological replicates. Using quantitative mass spectrometry, we identify proteins whose abundances vary with age, revealing a concerted downregulation of proteins involved in specific metabolic pathways and upregulation of cellular stress responses with advancing age. Among these are ∼30 peroxisomal proteins, including the PRX-5/PEX5 import protein. Functional experiments confirm that protein import into the peroxisome is compromised in vivo in old animals. We also studied the behavior of the set of age-variant proteins in chronologically age-matched, long-lived daf-2 insulin/IGF-1-pathway mutants. Unexpectedly, the levels of many of these age-variant proteins did not scale with extended lifespan. This indicates that, despite their youthful appearance and extended lifespans, not all aspects of aging are reset in these long-lived mutants. PMID:27453442

  5. Principal components analysis based methodology to identify differentially expressed genes in time-course microarray data

    Directory of Open Access Journals (Sweden)

    Srinivasan Rajagopalan

    2008-06-01

    Full Text Available Abstract Background Time-course microarray experiments are being increasingly used to characterize dynamic biological processes. In these experiments, the goal is to identify genes differentially expressed in time-course data, measured between different biological conditions. These differentially expressed genes can reveal the changes in biological process due to the change in condition which is essential to understand differences in dynamics. Results In this paper, we propose a novel method for finding differentially expressed genes in time-course data and across biological conditions (say C1 and C2. We model the expression at C1 using Principal Component Analysis and represent the expression profile of each gene as a linear combination of the dominant Principal Components (PCs. Then the expression data from C2 is projected on the developed PCA model and scores are extracted. The difference between the scores is evaluated using a hypothesis test to quantify the significance of differential expression. We evaluate the proposed method to understand differences in two case studies (1 the heat shock response of wild-type and HSF1 knockout mice, and (2 cell-cycle between wild-type and Fkh1/Fkh2 knockout Yeast strains. Conclusion In both cases, the proposed method identified biologically significant genes.

  6. Perturbation-expression analysis identifies RUNX1 as a regulator of human mammary stem cell differentiation.

    Directory of Open Access Journals (Sweden)

    Ethan S Sokol

    2015-04-01

    Full Text Available The search for genes that regulate stem cell self-renewal and differentiation has been hindered by a paucity of markers that uniquely label stem cells and early progenitors. To circumvent this difficulty we have developed a method that identifies cell-state regulators without requiring any markers of differentiation, termed Perturbation-Expression Analysis of Cell States (PEACS. We have applied this marker-free approach to screen for transcription factors that regulate mammary stem cell differentiation in a 3D model of tissue morphogenesis and identified RUNX1 as a stem cell regulator. Inhibition of RUNX1 expanded bipotent stem cells and blocked their differentiation into ductal and lobular tissue rudiments. Reactivation of RUNX1 allowed exit from the bipotent state and subsequent differentiation and mammary morphogenesis. Collectively, our findings show that RUNX1 is required for mammary stem cells to exit a bipotent state, and provide a new method for discovering cell-state regulators when markers are not available.

  7. Comparative analysis of methods for identifying recurrent copy number alterations in cancer.

    Directory of Open Access Journals (Sweden)

    Xiguo Yuan

    Full Text Available Recurrent copy number alterations (CNAs play an important role in cancer genesis. While a number of computational methods have been proposed for identifying such CNAs, their relative merits remain largely unknown in practice since very few efforts have been focused on comparative analysis of the methods. To facilitate studies of recurrent CNA identification in cancer genome, it is imperative to conduct a comprehensive comparison of performance and limitations among existing methods. In this paper, six representative methods proposed in the latest six years are compared. These include one-stage and two-stage approaches, working with raw intensity ratio data and discretized data respectively. They are based on various techniques such as kernel regression, correlation matrix diagonal segmentation, semi-parametric permutation and cyclic permutation schemes. We explore multiple criteria including type I error rate, detection power, Receiver Operating Characteristics (ROC curve and the area under curve (AUC, and computational complexity, to evaluate performance of the methods under multiple simulation scenarios. We also characterize their abilities on applications to two real datasets obtained from cancers with lung adenocarcinoma and glioblastoma. This comparison study reveals general characteristics of the existing methods for identifying recurrent CNAs, and further provides new insights into their strengths and weaknesses. It is believed helpful to accelerate the development of novel and improved methods.

  8. Molecular network analysis of human microRNA targetome: from cancers to Alzheimer’s disease

    Directory of Open Access Journals (Sweden)

    Satoh Jun-ichi

    2012-10-01

    Full Text Available Abstract MicroRNAs (miRNAs, a class of endogenous small noncoding RNAs, mediate posttranscriptional regulation of protein-coding genes by binding chiefly to the 3’ untranslated region of target mRNAs, leading to translational inhibition, mRNA destabilization or degradation. A single miRNA concurrently downregulates hundreds of target mRNAs designated “targetome”, and thereby fine-tunes gene expression involved in diverse cellular functions, such as development, differentiation, proliferation, apoptosis and metabolism. Recently, we characterized the molecular network of the whole human miRNA targetome by using bioinformatics tools for analyzing molecular interactions on the comprehensive knowledgebase. We found that the miRNA targetome regulated by an individual miRNA generally constitutes the biological network of functionally-associated molecules in human cells, closely linked to pathological events involved in cancers and neurodegenerative diseases. We also identified a collaborative regulation of gene expression by transcription factors and miRNAs in cancer-associated miRNA targetome networks. This review focuses on the workflow of molecular network analysis of miRNA targetome in silico. We applied the workflow to two representative datasets, composed of miRNA expression profiling of adult T cell leukemia (ATL and Alzheimer’s disease (AD, retrieved from Gene Expression Omnibus (GEO repository. The results supported the view that miRNAs act as a central regulator of both oncogenesis and neurodegeneration.

  9. Comparative Transcriptome Analysis Identifies CCDC80 as a Novel Gene Associated with Pulmonary Arterial Hypertension

    Science.gov (United States)

    Sasagawa, Shota; Nishimura, Yuhei; Sawada, Hirofumi; Zhang, Erquan; Okabe, Shiko; Murakami, Soichiro; Ashikawa, Yoshifumi; Yuge, Mizuki; Kawaguchi, Koki; Kawase, Reiko; Mitani, Yoshihide; Maruyama, Kazuo; Tanaka, Toshio

    2016-01-01

    Pulmonary arterial hypertension (PAH) is a heterogeneous disorder associated with a progressive increase in pulmonary artery resistance and pressure. Although various therapies have been developed, the 5-year survival rate of PAH patients remains low. There is thus an important need to identify novel genes that are commonly dysregulated in PAH of various etiologies and could be used as biomarkers and/or therapeutic targets. In this study, we performed comparative transcriptome analysis of five mammalian PAH datasets downloaded from a public database. We identified 228 differentially expressed genes (DEGs) from a rat PAH model caused by inhibition of vascular endothelial growth factor receptor under hypoxic conditions, 379 DEGs from a mouse PAH model associated with systemic sclerosis, 850 DEGs from a mouse PAH model associated with schistosomiasis, 1598 DEGs from one cohort of human PAH patients, and 4260 DEGs from a second cohort of human PAH patients. Gene-by-gene comparison identified four genes that were differentially upregulated or downregulated in parallel in all five sets of DEGs. Expression of coiled-coil domain containing 80 (CCDC80) and anterior gradient two genes was significantly increased in the five datasets, whereas expression of SMAD family member six and granzyme A was significantly decreased. Weighted gene co-expression network analysis revealed a connection between CCDC80 and collagen type I alpha 1 (COL1A1) expression. To validate the function of CCDC80 in vivo, we knocked out ccdc80 in zebrafish using the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 system. In vivo imaging of zebrafish expressing a fluorescent protein in endothelial cells showed that ccdc80 deletion significantly increased the diameter of the ventral artery, a vessel supplying blood to the gills. We also demonstrated that expression of col1a1 and endothelin-1 mRNA was significantly decreased in the ccdc80-knockout zebrafish. Finally, we examined Ccdc

  10. Molecular analysis of mucopolysaccharidosis IVA: Common mutations and racial difference

    Energy Technology Data Exchange (ETDEWEB)

    Tomatsu, S.; Hori, T.; Nakashima, Y. [Gifu Univ. (Japan)] [and others

    1994-09-01

    Mucopolysaccharidosis IVA (MPS IVA) is an autosomal recessive disorder caused by a deficiency in N-acetylgalactosamine -6-sulfate sulfatase (GALNS). Studies on the molecular basis of MPS IVA have been facilitated following cloning of the full-length cDNA and genomic DNA. In this study we detected mutations from 20 Caucasian and 19 Japanese MPS IVA patients using SSCP system and compared mutations of Caucasian origin with those of Japanese origin. The results showed the presence of 16 various mutations (3 small, deletions, 2 nonsense and 11 missense mutations) for Caucasian patients and 15 (1 deletion, 1 large alteration and 13 missense mutations) for Japanese. Moreover, two common mutations existed; one is double gene deletion characteristic for Japanese (6 alleles; 15%) and the other is a point mutation (1113F A{yields}T transition) characteristic for Caucasian (9 alleles; 22.5%). And the clear genotype/phenotype relationship among 1342delCA, IVS1(-2), P151S, Q148X, R386C, I113F, Q473X, W220G, P151L, A291T, R90W, and P77R, for a severe type, G96B N204K and V138A for a milder type, was observed. Only R386 mutation was seen in both of the populations. Further, the precise DNA analysis for double gene deletion of a common double gene deletion has been performed by defining the breakpoints and the results showed that one deletion was caused by homologous recombination due to Alu repetitive sequences and the other was due to nonhomologous recombination of short direct repeat. Haplotype analysis for six alleles with double deletion were different, indicating the different origin of this mutation or the frequent recombination events before a mutational event. Thus the mutations in GALNS gene are very heterogeneous and the racial difference is characteristic.

  11. Molecular electrostatic potential analysis of non-covalent complexes

    Indian Academy of Sciences (India)

    PADINJARE VEETIL BIJINA; CHERUMUTTATHU H SURESH

    2016-10-01

    Ab initio MP4/Aug-cc-pvDZ//MP2/6-311++g(d,p) level interaction energy (Eint) and molecular electrostatic potential analysis (MESP) of a large variety of non-covalent intermolecular complexes, viz. tetrel, chalcogen, pnicogen, halogen, hydrogen, dihydrogen and lithium bonded complexes have been reported. The electronic changes associated with the non-covalent complex formation is monitored in terms of MESP minimum (Vmin) in the free and complexed states of the donor and acceptor molecules as well as in terms ofMESP at the donor and acceptor atoms (Vn) of the free monomers and complexes. The change in Vmin or Vn on the donor molecule (ΔVmin(D) or ΔVn(D)) during complex formation is proportional to its electron donating ability while such a change on the acceptor molecule (ΔVmin(A) or ΔVn(A)) is proportional to its electron accepting ability. Further, the quantities ΔΔVmin = ΔVmin(D) −ΔVmin(A) and ΔΔVn = ΔVn(D) −ΔVn(A) have shown strong linear correlations with Eint of the complex (Eint values fall in the range 0.7 to 46.2 kcal/mol for 54 complexes) and suggest that the intermolecular non-covalent interactions in a wide variety of systems can be monitored and assessed in terms of change in MESP due to complex formation in the gas phase. With the incorporation of solvent effect in the calculation, charged systems showed significant deviations from the linear correlation. The MESP based analysis proposes that the large variety of intermolecular non-covalent complexes considered in this study can be grouped under the general category of electron donor-acceptor (eDA) complexes

  12. Identifying patterns in treatment response profiles in acute bipolar mania: a cluster analysis approach

    Directory of Open Access Journals (Sweden)

    Houston John P

    2008-07-01

    Full Text Available Abstract Background Patients with acute mania respond differentially to treatment and, in many cases, fail to obtain or sustain symptom remission. The objective of this exploratory analysis was to characterize response in bipolar disorder by identifying groups of patients with similar manic symptom response profiles. Methods Patients (n = 222 were selected from a randomized, double-blind study of treatment with olanzapine or divalproex in bipolar I disorder, manic or mixed episode, with or without psychotic features. Hierarchical clustering based on Ward's distance was used to identify groups of patients based on Young-Mania Rating Scale (YMRS total scores at each of 5 assessments over 7 weeks. Logistic regression was used to identify baseline predictors for clusters of interest. Results Four distinct clusters of patients were identified: Cluster 1 (n = 64: patients did not maintain a response (YMRS total scores ≤ 12; Cluster 2 (n = 92: patients responded rapidly (within less than a week and response was maintained; Cluster 3 (n = 36: patients responded rapidly but relapsed soon afterwards (YMRS ≥ 15; Cluster 4 (n = 30: patients responded slowly (≥ 2 weeks and response was maintained. Predictive models using baseline variables found YMRS Item 10 (Appearance, and psychosis to be significant predictors for Clusters 1 and 4 vs. Clusters 2 and 3, but none of the baseline characteristics allowed discriminating between Clusters 1 vs. 4. Experiencing a mixed episode at baseline predicted membership in Clusters 2 and 3 vs. Clusters 1 and 4. Treatment with divalproex, larger number of previous manic episodes, lack of disruptive-aggressive behavior, and more prominent depressive symptoms at baseline were predictors for Cluster 3 vs. 2. Conclusion Distinct treatment response profiles can be predicted by clinical features at baseline. The presence of these features as potential risk factors for relapse in patients who have responded to treatment

  13. Network Analysis Identifies Mitochondrial Regulation of Epidermal Differentiation by MPZL3 and FDXR.

    Science.gov (United States)

    Bhaduri, Aparna; Ungewickell, Alexander; Boxer, Lisa D; Lopez-Pajares, Vanessa; Zarnegar, Brian J; Khavari, Paul A

    2015-11-23

    Current gene expression network approaches commonly focus on transcription factors (TFs), biasing network-based discovery efforts away from potentially important non-TF proteins. We developed proximity analysis, a network reconstruction method that uses topological constraints of scale-free, small-world biological networks to reconstruct relationships in eukaryotic systems, independent of subcellular localization. Proximity analysis identified MPZL3 as a highly connected hub that is strongly induced during epidermal differentiation. MPZL3 was essential for normal differentiation, acting downstream of p63, ZNF750, KLF4, and RCOR1, each of which bound near the MPZL3 gene and controlled its expression. MPZL3 protein localized to mitochondria, where it interacted with FDXR, which was itself also found to be essential for differentiation. Together, MPZL3 and FDXR increased reactive oxygen species (ROS) to drive epidermal differentiation. ROS-induced differentiation is dependent upon promotion of FDXR enzymatic activity by MPZL3. ROS induction by the MPZL3 and FDXR mitochondrial proteins is therefore essential for epidermal differentiation.

  14. Genome-wide meta-analysis identifies multiple novel associations and ethnic heterogeneity of psoriasis susceptibility.

    Science.gov (United States)

    Yin, Xianyong; Low, Hui Qi; Wang, Ling; Li, Yonghong; Ellinghaus, Eva; Han, Jiali; Estivill, Xavier; Sun, Liangdan; Zuo, Xianbo; Shen, Changbing; Zhu, Caihong; Zhang, Anping; Sanchez, Fabio; Padyukov, Leonid; Catanese, Joseph J; Krueger, Gerald G; Duffin, Kristina Callis; Mucha, Sören; Weichenthal, Michael; Weidinger, Stephan; Lieb, Wolfgang; Foo, Jia Nee; Li, Yi; Sim, Karseng; Liany, Herty; Irwan, Ishak; Teo, Yikying; Theng, Colin T S; Gupta, Rashmi; Bowcock, Anne; De Jager, Philip L; Qureshi, Abrar A; de Bakker, Paul I W; Seielstad, Mark; Liao, Wilson; Ståhle, Mona; Franke, Andre; Zhang, Xuejun; Liu, Jianjun

    2015-04-23

    Psoriasis is a common inflammatory skin disease with complex genetics and different degrees of prevalence across ethnic populations. Here we present the largest trans-ethnic genome-wide meta-analysis (GWMA) of psoriasis in 15,369 cases and 19,517 controls of Caucasian and Chinese ancestries. We identify four novel associations at LOC144817, COG6, RUNX1 and TP63, as well as three novel secondary associations within IFIH1 and IL12B. Fine-mapping analysis of MHC region demonstrates an important role for all three HLA class I genes and a complex and heterogeneous pattern of HLA associations between Caucasian and Chinese populations. Further, trans-ethnic comparison suggests population-specific effect or allelic heterogeneity for 11 loci. These population-specific effects contribute significantly to the ethnic diversity of psoriasis prevalence. This study not only provides novel biological insights into the involvement of immune and keratinocyte development mechanism, but also demonstrates a complex and heterogeneous genetic architecture of psoriasis susceptibility across ethnic populations.

  15. Transcriptome bioinformatic analysis identifies potential therapeutic mechanism of pentylenetetrazole in down syndrome

    Directory of Open Access Journals (Sweden)

    Sharma Abhay

    2010-10-01

    Full Text Available Abstract Background Pentylenetetrazole (PTZ has recently been found to ameliorate cognitive impairment in rodent models of Down syndrome (DS. The mechanism underlying PTZ's therapeutic effect in DS is however not clear. Microarray profiling has previously reported differential expression, both up- and down-regulation, of genes in DS. Given this, transcriptomic data related to PTZ treatment, if available, could be used to understand the drug's therapeutic mechanism in DS. No such mammalian data however exists. Nevertheless, a Drosophila model inspired by PTZ induced kindling plasticity in rodents has recently been described. Microarray profiling has shown PTZ's downregulatory effect on gene expression in the fly heads. Methods In a comparative transcriptomics approach, I have analyzed the available microarray data in order to identify potential therapeutic mechanism of PTZ in DS. In the analysis, summary data of up- and down-regulated genes reported in human DS studies and of down-regulated genes reported in the Drosophila model has been used. Results I find that transcriptomic correlate of chronic PTZ in Drosophila counteracts that of DS. Genes downregulated by PTZ significantly over-represent genes upregulated in DS and under-represent genes downregulated in DS. Further, the genes which are common in the downregulated and upregulated DS set show enrichment for MAP kinase pathway. Conclusion My analysis suggests that downregulation of MAP kinase pathway may mediate therapeutic effect of PTZ in DS. Existing evidence implicating MAP kinase pathway in DS supports this observation.

  16. Identifying differences in the experience of (in)authenticity: a latent class analysis approach.

    Science.gov (United States)

    Lenton, Alison P; Slabu, Letitia; Bruder, Martin; Sedikides, Constantine

    2014-01-01

    Generally, psychologists consider state authenticity - that is, the subjective sense of being one's true self - to be a unitary and unidimensional construct, such that (a) the phenomenological experience of authenticity is thought to be similar no matter its trigger, and (b) inauthenticity is thought to be simply the opposing pole (on the same underlying construct) of authenticity. Using latent class analysis, we put this conceptualization to a test. In order to avoid over-reliance on a Western conceptualization of authenticity, we used a cross-cultural sample (N = 543), comprising participants from Western, South-Asian, East-Asian, and South-East Asian cultures. Participants provided either a narrative in which the described when they felt most like being themselves or one in which they described when they felt least like being themselves. The analysis identified six distinct classes of experiences: two authenticity classes ("everyday" and "extraordinary"), three inauthenticity classes ("self-conscious," "deflated," and "extraordinary"), and a class representing convergence between authenticity and inauthenticity. The classes were phenomenologically distinct, especially with respect to negative affect, private and public self-consciousness, and self-esteem. Furthermore, relatively more interdependent cultures were less likely to report experiences of extraordinary (in)authenticity than relatively more independent cultures. Understanding the many facets of (in)authenticity may enable researchers to connect different findings and explain why the attainment of authenticity can be difficult.

  17. Functional analysis of TPM domain containing Rv2345 of Mycobacterium tuberculosis identifies its phosphatase activity.

    Science.gov (United States)

    Sinha, Avni; Eniyan, Kandasamy; Sinha, Swati; Lynn, Andrew Michael; Bajpai, Urmi

    2015-07-01

    Mycobacterium tuberculosis (Mtb) is the causal agent of tuberculosis, the second largest infectious disease. With the rise of multi-drug resistant strains of M. tuberculosis, serious challenge lies ahead of us in treating the disease. The availability of complete genome sequence of Mtb has improved the scope for identifying new proteins that would not only further our understanding of biology of the organism but could also serve to discover new drug targets. In this study, Rv2345, a hypothetical membrane protein of M. tuberculosis H37Rv, which is reported to be a putative ortholog of ZipA cell division protein has been assigned function through functional annotation using bioinformatics tools followed by experimental validation. Sequence analysis showed Rv2345 to have a TPM domain at its N-terminal region and predicted it to have phosphatase activity. The TPM domain containing region of Rv2345 was cloned and expressed using pET28a vector in Escherichia coli and purified by Nickel affinity chromatography. The purified TPM domain was tested in vitro and our results confirmed it to have phosphatase activity. The enzyme activity was first checked and optimized with pNPP as substrate, followed by using ATP, which was also found to be used as substrate by the purified protein. Hence sequence analysis followed by in vitro studies characterizes TPM domain of Rv2345 to contain phosphatase activity.

  18. Five endometrial cancer risk loci identified through genome-wide association analysis.

    Science.gov (United States)

    Cheng, Timothy H T; Thompson, Deborah J; O'Mara, Tracy A; Painter, Jodie N; Glubb, Dylan M; Flach, Susanne; Lewis, Annabelle; French, Juliet D; Freeman-Mills, Luke; Church, David; Gorman, Maggie; Martin, Lynn; Hodgson, Shirley; Webb, Penelope M; Attia, John; Holliday, Elizabeth G; McEvoy, Mark; Scott, Rodney J; Henders, Anjali K; Martin, Nicholas G; Montgomery, Grant W; Nyholt, Dale R; Ahmed, Shahana; Healey, Catherine S; Shah, Mitul; Dennis, Joe; Fasching, Peter A; Beckmann, Matthias W; Hein, Alexander; Ekici, Arif B; Hall, Per; Czene, Kamila; Darabi, Hatef; Li, Jingmei; Dörk, Thilo; Dürst, Matthias; Hillemanns, Peter; Runnebaum, Ingo; Amant, Frederic; Schrauwen, Stefanie; Zhao, Hui; Lambrechts, Diether; Depreeuw, Jeroen; Dowdy, Sean C; Goode, Ellen L; Fridley, Brooke L; Winham, Stacey J; Njølstad, Tormund S; Salvesen, Helga B; Trovik, Jone; Werner, Henrica M J; Ashton, Katie; Otton, Geoffrey; Proietto, Tony; Liu, Tao; Mints, Miriam; Tham, Emma; Li, Mulin Jun; Yip, Shun H; Wang, Junwen; Bolla, Manjeet K; Michailidou, Kyriaki; Wang, Qin; Tyrer, Jonathan P; Dunlop, Malcolm; Houlston, Richard; Palles, Claire; Hopper, John L; Peto, Julian; Swerdlow, Anthony J; Burwinkel, Barbara; Brenner, Hermann; Meindl, Alfons; Brauch, Hiltrud; Lindblom, Annika; Chang-Claude, Jenny; Couch, Fergus J; Giles, Graham G; Kristensen, Vessela N; Cox, Angela; Cunningham, Julie M; Pharoah, Paul D P; Dunning, Alison M; Edwards, Stacey L; Easton, Douglas F; Tomlinson, Ian; Spurdle, Amanda B

    2016-06-01

    We conducted a meta-analysis of three endometrial cancer genome-wide association studies (GWAS) and two follow-up phases totaling 7,737 endometrial cancer cases and 37,144 controls of European ancestry. Genome-wide imputation and meta-analysis identified five new risk loci of genome-wide significance at likely regulatory regions on chromosomes 13q22.1 (rs11841589, near KLF5), 6q22.31 (rs13328298, in LOC643623 and near HEY2 and NCOA7), 8q24.21 (rs4733613, telomeric to MYC), 15q15.1 (rs937213, in EIF2AK4, near BMF) and 14q32.33 (rs2498796, in AKT1, near SIVA1). We also found a second independent 8q24.21 signal (rs17232730). Functional studies of the 13q22.1 locus showed that rs9600103 (pairwise r(2) = 0.98 with rs11841589) is located in a region of active chromatin that interacts with the KLF5 promoter region. The rs9600103[T] allele that is protective in endometrial cancer suppressed gene expression in vitro, suggesting that regulation of the expression of KLF5, a gene linked to uterine development, is implicated in tumorigenesis. These findings provide enhanced insight into the genetic and biological basis of endometrial cancer. PMID:27135401

  19. Genomic, Epigenomic, and Transcriptomic Profiling towards Identifying Omics Features and Specific Biomarkers That Distinguish Uterine Leiomyosarcoma and Leiomyoma at Molecular Levels

    Science.gov (United States)

    Miyata, Tomoko; Sonoda, Kenzo; Tomikawa, Junko; Tayama, Chiharu; Okamura, Kohji; Maehara, Kayoko; Kobayashi, Hiroaki; Wake, Norio; Kato, Kiyoko; Hata, Kenichiro; Nakabayashi, Kazuhiko

    2015-01-01

    Uterine leiomyosarcoma (LMS) is the worst malignancy among the gynecologic cancers. Uterine leiomyoma (LM), a benign tumor of myometrial origin, is the most common among women of childbearing age. Because of their similar symptoms, it is difficult to preoperatively distinguish the two conditions only by ultrasound and pelvic MRI. While histopathological diagnosis is currently the main approach used to distinguish them postoperatively, unusual histologic variants of LM tend to be misdiagnosed as LMS. Therefore, development of molecular diagnosis as an alternative or confirmatory means will help to diagnose LMS more accurately. We adopted omics-based technologies to identify genome-wide features to distinguish LMS from LM and revealed that copy number, gene expression, and DNA methylation profiles successfully distinguished these tumors. LMS was found to possess features typically observed in malignant solid tumors, such as extensive chromosomal abnormalities, overexpression of cell cycle-related genes, hypomethylation spreading through large genomic regions, and frequent hypermethylation at the polycomb group target genes and protocadherin genes. We also identified candidate expression and DNA methylation markers, which will facilitate establishing postoperative molecular diagnostic tests based on conventional quantitative assays. Our results demonstrate the feasibility of establishing such tests and the possibility of developing preoperative and noninvasive methods. PMID:27057136

  20. Extensive temporal transcriptome and microRNA analyses identify molecular mechanisms underlying mitochondrial dysfunction induced by multi-walled carbon nanotubes in human lung cells.

    Science.gov (United States)

    Nymark, Penny; Wijshoff, Peter; Cavill, Rachel; van Herwijnen, Marcel; Coonen, Maarten L J; Claessen, Sandra; Catalán, Julia; Norppa, Hannu; Kleinjans, Jos C S; Briedé, Jacob J

    2015-01-01

    Understanding toxicity pathways of engineered nanomaterials (ENM) has recently been brought forward as a key step in twenty-first century ENM risk assessment. Molecular mechanisms linked to phenotypic end points is a step towards the development of toxicity tests based on key events, which may allow for grouping of ENM according to their modes of action. This study identified molecular mechanisms underlying mitochondrial dysfunction in human bronchial epithelial BEAS 2B cells following exposure to one of the most studied multi-walled carbon nanotubes (Mitsui MWCNT-7). Asbestos was used as a positive control and a non-carcinogenic glass wool material was included as a negative fibre control. Decreased mitochondrial membrane potential (MMP↓) was observed for MWCNTs at a biologically relevant dose (0.25 μg/cm(2)) and for asbestos at 2 μg/cm(2), but not for glass wool. Extensive temporal transcriptomic and microRNA expression analyses identified a 330-gene signature (including 26 genes with known mitochondrial function) related to MWCNT- and asbestos-induced MMP↓. Forty-nine of the MMP↓-associated genes showed highly similar expression patterns over time (six time points) and the majority was found to be regulated by two transcription factors strongly involved in mitochondrial homeostasis, APP and NRF1. In addition, four miRNAs were correlated with MMP↓ and one of them, miR-1275, was found to negatively correlate with a large part of the MMP↓-associated genes. Cellular processes such as gluconeogenesis, mitochondrial LC-fatty acid β-oxidation and spindle microtubule function were enriched among the MMP↓-associated genes and miRNAs. These results are expected to be useful in the identification of key events in ENM-related toxicity pathways for the development of molecular screening techniques.

  1. A meta-analysis to identify animal and management factors influencing gestating sow efficiency.

    Science.gov (United States)

    Douglas, S L; Szyszka, O; Stoddart, K; Edwards, S A; Kyriazakis, I

    2014-12-01

    A meta-analysis on the effects of management and animal-based factors on the reproductive efficiency of gestating sows can provide information on single-factor and interaction effects that may not have been detected in individual studies. This study analyzed the effects of such factors on the number of piglets born alive per litter (BA), piglet birth weight (BiW) and weaning weight (WW), and number of piglets born alive per kilogram of sow feed intake during gestation (BA/FI). A total of 51 papers and 7 data sources were identified for the meta-analysis, out of which 23 papers and 5 sets of production data were useable (a total of 121 treatments). The information gathered included the dependent variables as well as information regarding animal, management, and feed characteristics. While a number of factors were individually significant, the multivariate models identified significant effects only of 1) floor type (P=0.003), sow BW at the end of gestation (P=0.002), and housing (stalls vs. loose; P=0.004) on BA; as floor type and housing were confounded, they were included in 2 separate models. The BA was higher on solid (12.1) in comparison to partly slatted (11.4) and fully slatted floors (10.2); 2) sow gestation environment (P=0.017) and gestation feed allowance (P=0.046) on BiW, with BiW of pigs higher for sows kept outdoors rather than indoors (1.75 versus 1.49 kg); 3) parity number (P=0.003) and feed intake during gestation (P=0.017) on WW; in addition there was an interaction between parity number×feed ME and parity number×feed CP content of feed during gestation on WW, with the positive effects of feed ME and CP contents seen during early rather than later parities; and 4) floor type (P=0.019) and feed crude fiber (P=0.003) for BA/FI with a greater number for those kept on solid floors (5.11) versus partially and fully slatted floors (4.07 and 4.05). The meta-analysis confirmed the significant effect of several well-known factors on the efficiency of

  2. Family Wide Molecular Adaptations to Underground Life in African Mole-Rats Revealed by Phylogenomic Analysis.

    Science.gov (United States)

    Davies, Kalina T J; Bennett, Nigel C; Tsagkogeorga, Georgia; Rossiter, Stephen J; Faulkes, Christopher G

    2015-12-01

    During their evolutionary radiation, mammals have colonized diverse habitats. Arguably the subterranean niche is the most inhospitable of these, characterized by reduced oxygen, elevated carbon dioxide, absence of light, scarcity of food, and a substrate that is energetically costly to burrow through. Of all lineages to have transitioned to a subterranean niche, African mole-rats are one of the most successful. Much of their ecological success can be attributed to a diet of plant storage organs, which has allowed them to colonize climatically varied habitats across sub-Saharan Africa, and has probably contributed to the evolution of their diverse social systems. Yet despite their many remarkable phenotypic specializations, little is known about molecular adaptations underlying these traits. To address this, we sequenced the transcriptomes of seven mole-rat taxa, including three solitary species, and combined new sequences with existing genomic data sets. Alignments of more than 13,000 protein-coding genes encompassed, for the first time, all six genera and the full spectrum of ecological and social variation in the clade. We detected positive selection within the mole-rat clade and along ancestral branches in approximately 700 genes including loci associated with tumorigenesis, aging, morphological development, and sociality. By combining these results with gene ontology annotation and protein-protein networks, we identified several clusters of functionally related genes. This family wide analysis of molecular evolution in mole-rats has identified a suite of positively selected genes, deepening our understanding of the extreme phenotypic traits exhibited by this group.

  3. Transcriptome analysis of an apple (Malus × domestica) yellow fruit somatic mutation identifies a gene network module highly associated with anthocyanin and epigenetic regulation

    OpenAIRE

    El-Sharkawy, Islam; Liang, Dong; Xu, Kenong

    2015-01-01

    Using RNA-seq, this study analysed an apple (Malus×domestica) anthocyanin-deficient yellow-skin somatic mutant ‘Blondee’ (BLO) and its red-skin parent ‘Kidd’s D-8’ (KID), the original name of ‘Gala’, to understand the molecular mechanisms underlying the mutation. A total of 3299 differentially expressed genes (DEGs) were identified between BLO and KID at four developmental stages and/or between two adjacent stages within BLO and/or KID. A weighted gene co-expression network analysis (WGCNA) o...

  4. Potential biomarkers of fatigue identified by plasma metabolome analysis in rats.

    Science.gov (United States)

    Kume, Satoshi; Yamato, Masanori; Tamura, Yasuhisa; Jin, Guanghua; Nakano, Masayuki; Miyashige, Yukiharu; Eguchi, Asami; Ogata, Yoshiyuki; Goda, Nobuhito; Iwai, Kazuhiro; Yamano, Emi; Watanabe, Yasuyoshi; Soga, Tomoyoshi; Kataoka, Yosky

    2015-01-01

    In the present study, prior to the establishment of a method for the clinical diagnosis of chronic fatigue in humans, we validated the utility of plasma metabolomic analysis in a rat model of fatigue using capillary electrophoresis-mass spectrometry (CE-MS). In order to obtain a fatigued animal group, rats were placed in a cage filled with water to a height of 2.2 cm for 5 days. A food-restricted group, in which rats were limited to 10 g/d of food (around 50% of the control group), was also assessed. The food-restricted group exhibited weight reduction similar to that of the fatigued group. CE-MS measurements were performed to evaluate the profile of food intake-dependent metabolic changes, as well as the profile in fatigue loading, resulting in the identification of 48 metabolites in plasma. Multivariate analyses using hierarchical clustering and principal component analysis revealed that the plasma metabolome in the fatigued group showed clear differences from those in the control and food-restricted groups. In the fatigued group, we found distinctive changes in metabolites related to branched-chain amino acid metabolism, urea cycle, and proline metabolism. Specifically, the fatigued group exhibited significant increases in valine, leucine, isoleucine, and 2-oxoisopentanoate, and significant decreases in citrulline and hydroxyproline compared with the control and food-restricted groups. Plasma levels of total nitric oxide were increased in the fatigued group, indicating systemic oxidative stress. Further, plasma metabolites involved in the citrate cycle, such as cis-aconitate and isocitrate, were reduced in the fatigued group. The levels of ATP were significantly decreased in the liver and skeletal muscle, indicative of a deterioration in energy metabolism in these organs. Thus, this comprehensive metabolic analysis furthered our understanding of the pathophysiology of fatigue, and identified potential diagnostic biomarkers based on fatigue pathophysiology.

  5. Reproducibility and validity of dietary patterns identified using factor analysis among Chinese populations.

    Science.gov (United States)

    Hong, Xin; Ye, Qing; Wang, Zhiyong; Yang, Huafeng; Chen, Xupeng; Zhou, Hairong; Wang, Chenchen; Chu, Wenjie; Lai, Yichao; Sun, Liuyuan; Wang, Youfa; Xu, Fei

    2016-09-01

    In the present study, we evaluated the reproducibility and validity of dietary patterns among Chinese adult populations. A random subsample of 203 participants (aged 31-80 years) from a community-based nutrition and health survey was enrolled. An eighty-seven-item FFQ was administered twice (FFQ1 and FFQ2) 1 year apart; four 3 consecutive day, 24-h dietary recalls (24-HDR, as a reference method) were performed between the administrations of the two FFQ every 3 months. Dietary patterns from three separate dietary sources were derived using factor analysis based on twenty-eight predefined food groups. Comparisons between dietary pattern scores were made by using Pearson's or intraclass correlation coefficients (ICC), cross-classification analysis, weighted κ statistic and Bland-Altman plots; the four major dietary patterns identified from FFQ1, FFQ2 and 24-HDR were similar. Regarding reproducibility, ICC for z-scores between FFQ1 and FFQ2 were all >0·6 for dietary patterns. The 'animal and plant protein' pattern had the highest ICC of 0·870. For validity, the adjusted Pearson's correlation coefficients for dietary pattern z-scores between two FFQ and the mean of four 3 consecutive day 24-HDR ranged from 0·387 for the 'Chinese traditional' pattern to 0·838 for the 'animal and plant protein' pattern. More than 75 % of the participants were classified into the same or adjacent quartile, and <5 % were misclassified into opposite quartiles. The weighted κ ranged from 0·259 to 0·680. Bland-Altman plots indicated that no significant deviation was found between two dietary assessment methods. Our findings indicate a good reasonable reproducibility and a reasonable validity of dietary patterns derived by factor analysis in China. PMID:27405825

  6. Potential biomarkers of fatigue identified by plasma metabolome analysis in rats.

    Directory of Open Access Journals (Sweden)

    Satoshi Kume

    Full Text Available In the present study, prior to the establishment of a method for the clinical diagnosis of chronic fatigue in humans, we validated the utility of plasma metabolomic analysis in a rat model of fatigue using capillary electrophoresis-mass spectrometry (CE-MS. In order to obtain a fatigued animal group, rats were placed in a cage filled with water to a height of 2.2 cm for 5 days. A food-restricted group, in which rats were limited to 10 g/d of food (around 50% of the control group, was also assessed. The food-restricted group exhibited weight reduction similar to that of the fatigued group. CE-MS measurements were performed to evaluate the profile of food intake-dependent metabolic changes, as well as the profile in fatigue loading, resulting in the identification of 48 metabolites in plasma. Multivariate analyses using hierarchical clustering and principal component analysis revealed that the plasma metabolome in the fatigued group showed clear differences from those in the control and food-restricted groups. In the fatigued group, we found distinctive changes in metabolites related to branched-chain amino acid metabolism, urea cycle, and proline metabolism. Specifically, the fatigued group exhibited significant increases in valine, leucine, isoleucine, and 2-oxoisopentanoate, and significant decreases in citrulline and hydroxyproline compared with the control and food-restricted groups. Plasma levels of total nitric oxide were increased in the fatigued group, indicating systemic oxidative stress. Further, plasma metabolites involved in the citrate cycle, such as cis-aconitate and isocitrate, were reduced in the fatigued group. The levels of ATP were significantly decreased in the liver and skeletal muscle, indicative of a deterioration in energy metabolism in these organs. Thus, this comprehensive metabolic analysis furthered our understanding of the pathophysiology of fatigue, and identified potential diagnostic biomarkers based on fatigue

  7. Rat hepatocytes weighted gene co-expression network analysis identifies specific modules and hub genes related to liver regeneration after partial hepatectomy.

    Directory of Open Access Journals (Sweden)

    Yun Zhou

    Full Text Available The recovery of liver mass is mainly mediated by proliferation of hepatocytes after 2/3 partial hepatectomy (PH in rats. Studying the gene expression profiles of hepatocytes after 2/3 PH will be helpful to investigate the molecular mechanisms of liver regeneration (LR. We report here the first application of weighted gene co-expression network analysis (WGCNA to analyze the biological implications of gene expression changes associated with LR. WGCNA identifies 12 specific gene modules and some hub genes from hepatocytes genome-scale microarray data in rat LR. The results suggest that upregulated MCM5 may promote hepatocytes proliferation during LR; BCL3 may play an important role by activating or inhibiting NF-kB pathway; MAPK9 may play a permissible role in DNA replication by p38 MAPK inactivation in hepatocytes proliferation stage. Thus, WGCNA can provide novel insight into understanding the molecular mechanisms of LR.

  8. Transcriptome analysis identifies genes involved in ethanol response of Saccharomyces cerevisiae in Agave tequilana juice.

    Science.gov (United States)

    Ramirez-Córdova, Jesús; Drnevich, Jenny; Madrigal-Pulido, Jaime Alberto; Arrizon, Javier; Allen, Kirk; Martínez-Velázquez, Moisés; Alvarez-Maya, Ikuri

    2012-08-01

    During ethanol fermentation, yeast cells are exposed to stress due to the accumulation of ethanol, cell growth is altered and the output of the target product is reduced. For Agave beverages, like tequila, no reports have been published on the global gene expression under ethanol stress. In this work, we used microarray analysis to identify Saccharomyces cerevisiae genes involved in the ethanol response. Gene expression of a tequila yeast strain of S. cerevisiae (AR5) was explored by comparing global gene expression with that of laboratory strain S288C, both after ethanol exposure. Additionally, we used two different culture conditions, cells grown in Agave tequilana juice as a natural fermentation media or grown in yeast-extract peptone dextrose as artificial media. Of the 6368 S. cerevisiae genes in the microarray, 657 genes were identified that had different expression responses to ethanol stress due to strain and/or media. A cluster of 28 genes was found over-expressed specifically in the AR5 tequila strain that could be involved in the adaptation to tequila yeast fermentation, 14 of which are unknown such as yor343c, ylr162w, ygr182c, ymr265c, yer053c-a or ydr415c. These could be the most suitable genes for transforming tequila yeast to increase ethanol tolerance in the tequila fermentation process. Other genes involved in response to stress (RFC4, TSA1, MLH1, PAU3, RAD53) or transport (CYB2, TIP20, QCR9) were expressed in the same cluster. Unknown genes could be good candidates for the development of recombinant yeasts with ethanol tolerance for use in industrial tequila fermentation.

  9. Nonlinear analysis using Lyapunov exponents in breast thermograms to identify abnormal lesions

    Science.gov (United States)

    EtehadTavakol, M.; Ng, E. Y. K.; Lucas, C.; Sadri, S.; Ataei, M.

    2012-07-01

    Breast diseases are one of the major issues in women's health today. Early detection of breast cancer plays a significant role in reducing the mortality rate. Breast thermography is a potential early detection method which is non-invasive, non-radiating, passive, fast, painless, low cost, risk free with no contact with the body. By identifying and removing malignant tumors in early stages before they metastasize and spread to neighboring regions, cancer threats can be minimized. Cancer is often characterized as a chaotic, poorly regulated growth. Cancerous cells, tumors, and vasculature defy have irregular shapes which have potential to be described by a nonlinear dynamical system. Chaotic time series can provide the tools necessary to generate the procedures to evaluate the nonlinear system. Computing Lyapunov exponents is thus a powerful means of quantifying the degree of the chaos. In this paper, we present a novel approach using nonlinear chaotic dynamical system theory for estimating Lyapunov exponents in establishing possible difference between malignant and benign patterns. In order to develop the algorithm, the first hottest regions of breast thermal images are identified first, and then one dimensional scalar time series is obtained in terms of the distance between each subsequent boundary contour points and the center of the mass of the first hottest region. In the next step, the embedding dimension is estimated, and by time delay embedding method, the phase space is reconstructed. In the last step, the Lyapunov exponents are computed to analyze normality or abnormality of the lesions. Positive Lyapunov exponents indicates abnormality while negative Lyapunov exponents represent normality. The normalized errors show the algorithm is satisfactorily, and provide a measure of chaos. It is shown that nonlinear analysis of breast thermograms using Lyapunov exponents may potentially capable of improving reliability of thermography in breast tumor detection as

  10. Integrative Analysis of Genomics and Transcriptome Data to Identify Potential Functional Genes of BMDs in Females.

    Science.gov (United States)

    Chen, Yuan-Cheng; Guo, Yan-Fang; He, Hao; Lin, Xu; Wang, Xia-Fang; Zhou, Rou; Li, Wen-Ting; Pan, Dao-Yan; Shen, Jie; Deng, Hong-Wen

    2016-05-01

    Osteoporosis is known to be highly heritable. However, to date, the findings from more than 20 genome-wide association studies (GWASs) have explained less than 6% of genetic risks. Studies suggest that the missing heritability data may be because of joint effects among genes. To identify novel heritability for osteoporosis, we performed a system-level study on bone mineral density (BMD) by weighted gene coexpression network analysis (WGCNA), using the largest GWAS data set for BMD in the field, Genetic Factors for Osteoporosis Consortium (GEFOS-2), and a transcriptomic gene expression data set generated from transiliac bone biopsies in women. A weighted gene coexpression network was generated for 1574 genes with GWAS nominal evidence of association (p ≤ 0.05) based on dissimilarity measurement on the expression data. Twelve distinct gene modules were identified, and four modules showed nominally significant associations with BMD (p ≤ 0.05), but only one module, the yellow module, demonstrated a good correlation between module membership (MM) and gene significance (GS), suggesting that the yellow module serves an important biological role in bone regulation. Interestingly, through characterization of module content and topology, the yellow module was found to be significantly enriched with contractile fiber part (GO:044449), which is widely recognized as having a close relationship between muscle and bone. Furthermore, detailed submodule analyses of important candidate genes (HOMER1, SPTBN1) by all edges within the yellow module implied significant enrichment of functional connections between bone and cytoskeletal protein binding. Our study yielded novel information from system genetics analyses of GWAS data jointly with transcriptomic data. The findings highlighted a module and several genes in the model as playing important roles in the regulation of bone mass in females, which may yield novel insights into the genetic basis of osteoporosis. © 2016

  11. Large scale association analysis identifies three susceptibility loci for coronary artery disease.

    Directory of Open Access Journals (Sweden)

    Stephanie Saade

    Full Text Available Genome wide association studies (GWAS and their replications that have associated DNA variants with myocardial infarction (MI and/or coronary artery disease (CAD are predominantly based on populations of European or Eastern Asian descent. Replication of the most significantly associated polymorphisms in multiple populations with distinctive genetic backgrounds and lifestyles is crucial to the understanding of the pathophysiology of a multifactorial disease like CAD. We have used our Lebanese cohort to perform a replication study of nine previously identified CAD/MI susceptibility loci (LTA, CDKN2A-CDKN2B, CELSR2-PSRC1-SORT1, CXCL12, MTHFD1L, WDR12, PCSK9, SH2B3, and SLC22A3, and 88 genes in related phenotypes. The study was conducted on 2,002 patients with detailed demographic, clinical characteristics, and cardiac catheterization results. One marker, rs6922269, in MTHFD1L was significantly protective against MI (OR=0.68, p=0.0035, while the variant rs4977574 in CDKN2A-CDKN2B was significantly associated with MI (OR=1.33, p=0.0086. Associations were detected after adjustment for family history of CAD, gender, hypertension, hyperlipidemia, diabetes, and smoking. The parallel study of 88 previously published genes in related phenotypes encompassed 20,225 markers, three quarters of which with imputed genotypes The study was based on our genome-wide genotype data set, with imputation across the whole genome to HapMap II release 22 using HapMap CEU population as a reference. Analysis was conducted on both the genotyped and imputed variants in the 88 regions covering selected genes. This approach replicated HNRNPA3P1-CXCL12 association with CAD and identified new significant associations of CDKAL1, ST6GAL1, and PTPRD with CAD. Our study provides evidence for the importance of the multifactorial aspect of CAD/MI and describes genes predisposing to their etiology.

  12. Are sweep net sampling and pitfall trapping compatible with molecular analysis of predation?

    Science.gov (United States)

    Harwood, James D

    2008-08-01

    Molecular analysis of predation enables accurate and reliable elucidation of trophic linkages in complex food webs, but identifying the strength of such interactions can be subject to error. Currently two techniques dominate: monoclonal antibody-based enzyme-linked immunosorbent assay (ELISA) and polymerase chain reaction (PCR). Although the optimization and characterization of these systems ensures their sensitivity and specificity, predator collection protocols such as sweep-netting and vacuum sampling could overestimate feeding rates because of surface-level contamination, yielding positive reactivity or predation within the sampling device. Therefore, two sampling techniques (sweep-net sampling and hand collection) were compared within an alfalfa agroecosystem using a monoclonal antibody-based ELISA to test the hypothesis that cross-contamination is a source of error, i.e., significantly more predators (linyphiid spiders) would test positive for prey (Diptera) proteins. A concurrent study examining the viability of trapping predators into saline solution was also undertaken. No significant differences were found between the proportions of spiders screening positive for Diptera when collected by sweep-net versus hand collection, rejecting the hypothesis that sweep-netting predators for subsequent molecular gut content analysis overestimates predation frequency. ELISA was also capable of detecting prey proteins in predator guts from pitfall traps containing phosphate-buffered saline, indicating the suitability of this approach for the collection and analysis of epigeal predators. Although these results indicate that sweep netting and pitfall trapping into solution is appropriate in this predator-prey and ELISA analysis system, caution should be exercised with other interactions and PCR-based analysis. The likelihood for false-positive reactivity should therefore be considered on a case-by-case basis.

  13. Conformational flexibility of β-secretase:molecular dynamics simulation and essential dynamics analysis

    Institute of Scientific and Technical Information of China (English)

    Bing XIONG; Xiao-qin HUANG; Ling-ling SHEN; Jian-hua SHEN; Xiao-min LUO; Xu SHEN; Hua-liang JIANG; Kai-xian CHEN

    2004-01-01

    AIM: Based on the structural analysis to reveal the mechanism of ligand binding to β-secretase and the specificity of each binding sub-site. METHODS: Molecular dynamics was used to simulate on the ligand free β-secretase and ligand bound β-secretase. The trajectories were analyzed using the essential dynamics, and the significant conformational change was illustrated employing the DynDom program. RESULTS: The essential dynamics and DynDom analyses clearly showed that the β-secretase experienced a large conformational change upon the substrate or inhibitor binding. The flap structure adopted a swing motion, gradually covering the active site to facilitate the ligand binding process. Residues Ser86 and Ile87 served as the hinge point. Inhibitor-enzyme interaction analysis revealed that residues at P2, Pl, and P1' positions of the inhibitor were very important for the binding, and residues at P2' and P3' positions may be modified to improve the binding specificity. S3 subsite of the enzyme still had space to modify the inhibitors in increasing the binding affinity. CONCLUSION: The information presented here is valuable and could be used to identify small molecular inhibitors of β-secretase.

  14. Comprehensive Analysis of Low-Molecular-Weight Human Plasma Proteome Using Top-Down Mass Spectrometry.

    Science.gov (United States)

    Cheon, Dong Huey; Nam, Eun Ji; Park, Kyu Hyung; Woo, Se Joon; Lee, Hye Jin; Kim, Hee Cheol; Yang, Eun Gyeong; Lee, Cheolju; Lee, Ji Eun

    2016-01-01

    While human plasma serves as a great source for disease diagnosis, low-molecular-weight (LMW) proteome (mass spectrometry to analyze the LMW proteoforms present in four types of human plasma samples pooled from three healthy controls (HCs) without immunoaffinity depletion and with depletion of the top two, six, and seven high-abundance proteins. The LMW proteoforms were first fractionated based on molecular weight using gel-eluted liquid fraction entrapment electrophoresis (GELFrEE). Then, the GELFrEE fractions containing up to 30 kDa were subjected to nanocapillary-LC-MS/MS, and the high-resolution MS and MS/MS data were processed using ProSightPC 3.0. As a result, a total of 442 LMW proteins and cleaved products, including those with post-translational modifications and single amino acid variations, were identified. From additional comparative analysis of plasma samples without immunoaffinity depletion between HCs and colorectal cancer (CRC) patients via top-down approach, tens of LMW proteoforms, including platelet factor 4, were found to show >1.5-fold changes between the plasma samples of HCs and CRC patients, and six of the LMW proteins were verified by Western blot analysis.

  15. Application of high molecular weight DNA cloning in legume nodulation gene analysis

    International Nuclear Information System (INIS)

    High molecular weight (HMW) DNA was isolated from Glycine max (soybean) and the model legume Lotus japonicus for the purpose of legume genome analysis. The primary objectives were the gene regions that control nodulation, early plant-microbe interaction and cell division responses. HMW DNA was separated by pulse field gel electrophoresis (CHEF-PFGE) and analyzed with closely linked restriction fragment length polymorphism (RFLP) markers co-hybridized with clones, permitting estimation of the regional physical distances as they relate to recombination frequency. In the distal region of molecular linkage group H containing one of the genes controlling nodule number autoregulation and symbiotic nitrate tolerance (i.e. the nts gene), 1 cM was equivalent to less than 500 kb. Partially digested EcoRI soybean and L. japonicus HMW DNA were cloned into pYAC4. Stable yeast artificial chromosomes (YACs) carrying up to 960 kb DNA were generated. The average insert size was 200 kb. Hybridization with total genomic soybean DNA revealed YACs with different amounts of repeated DNA sequences. Mapping of the end clones demonstrated whether the YACs were chimeric. YACs of different complexity were used for chromosome identification using degenerate primer polymerase chain reaction and fluorescent in situ hybridization. This approach is a fast alternative to testing for YAC chimerism. Single arbitrary and structured mini-hairpin primers were used to amplify and DNA fingerprint the YACs, providing a means of identifying the additional markers needed for contig construction. HMW DNA was cloned into the F plasmid bacterial artificial chromosome (BAC) vector. The YACs and BACs were also constructed with DNA from the small genome/highly transformable legume L. japonicus. Mapping of the YAC and BAC clones with molecular markers will help to ascertain the degree of chimerism and stability in the different cloning systems. YACs, molecular markers and cDNA clones will be useful for chromosome

  16. Using End-Member Mixing Analysis to Identify Transport Pathways in Agricultural Watersheds

    Science.gov (United States)

    Essaid, H.

    2013-12-01

    Concentrations of naturally occurring solutes were monitored in six agricultural watersheds as part of the Agricultural Chemical Sources, Transport and Fate study of the U.S. Geological Survey National Water Quality Assessment Program. The watersheds, located in Indiana (IN), Iowa (IA), Maryland (MD), Nebraska (NE), Mississippi (MS) and Washington (WA), ranged in size from 5 to 1300 square kilometers, and agricultural land use accounted for 60 - 98% of the watershed area. Concentrations of chloride, calcium, magnesium, sodium, potassium, fluoride, sulfate and silica in stream water were analyzed using principal components analysis (PCA) to identify the dominant processes controlling stream water chemistry. Concentrations measured in wells, streambed piezometers, unsaturated zone lysimeters, overland flow, and tile drains were then used to project the chemistry of these flow compartments/components onto the stream chemistry PCA transformation. This facilitated the identification of end members explaining observed stream chemistry, and the source of the water for these end members. The majority of the variance in stream chemistry could be explained by the mixing of three end-members: 94% for Leary Weber Ditch, IN; 84% for South Fork Iowa River, IA; 91% for Morgan Creek, MD; 81% for Maple Creek, NE; 92% for Tommie Bayou, MS; and, 97% for DR2, WA. The chemistry of overland flow and tile drainage was also contained within the end member concentrations. The end members were generally represented by two groundwater components and a very low solute concentration component (precipitation or irrigation water) that diluted the groundwater signal. Generally, one groundwater component represented recently recharged water that resembled the concentration of water in the deepest unsaturated zone lysimeters, and the other groundwater component was representative of regional groundwater conditions. Compared to regional groundwater, the recent groundwater component had lower

  17. Network analysis of translocated Takahe populations to identify disease surveillance targets.

    Science.gov (United States)

    Grange, Zoë L; VAN Andel, Mary; French, Nigel P; Gartrell, Brett D

    2014-04-01

    Social network analysis is being increasingly used in epidemiology and disease modeling in humans, domestic animals, and wildlife. We investigated this tool in describing a translocation network (area that allows movement of animals between geographically isolated locations) used for the conservation of an endangered flightless rail, the Takahe (Porphyrio hochstetteri). We collated records of Takahe translocations within New Zealand and used social network principles to describe the connectivity of the translocation network. That is, networks were constructed and analyzed using adjacency matrices with values based on the tie weights between nodes. Five annual network matrices were created using the Takahe data set, each incremental year included records of previous years. Weights of movements between connected locations were assigned by the number of Takahe moved. We calculated the number of nodes (i(total)) and the number of ties (t(total)) between the nodes. To quantify the small-world character of the networks, we compared the real networks to random graphs of the equivalent size, weighting, and node strength. Descriptive analysis of cumulative annual Takahe movement networks involved determination of node-level characteristics, including centrality descriptors of relevance to disease modeling such as weighted measures of in degree (k(i)(in)), out degree (k(i)(out)), and betweenness (B(i)). Key players were assigned according to the highest node measure of k(i)(in), k(i)(out), and B(i) per network. Networks increased in size throughout the time frame considered. The network had some degree small-world characteristics. Nodes with the highest cumulative tie weights connecting them were the captive breeding center, the Murchison Mountains and 2 offshore islands. The key player fluctuated between the captive breeding center and the Murchison Mountains. The cumulative networks identified the captive breeding center every year as the hub of the network until the final

  18. Transcriptomic analysis to elucidate the molecular mechanisms that underlie feed efficiency in meat-type chickens.

    Science.gov (United States)

    Lee, Jeeyoung; Karnuah, Arthur B; Rekaya, Romdhane; Anthony, Nicholas B; Aggrey, Samuel E

    2015-10-01

    Feed efficiency phenotypes defined by genotypes or gene markers are unknown. To date, there are only limited studies on global gene expression profiling on feed efficiency. The objective of this study was to identify genes and pathways associated with residual feed intake (RFI) through transcriptional profiling of duodenum at two different ages in a chicken population divergently selected for low (LRFI) or high (HRFI) RFI. The global gene expression differences in LRFI and HRFI were assessed by the Affymetrix GeneChip(®) Chicken Genome Array and RT-PCR using duodenal tissue on days 35 and 42. The Ingenuity Pathway Analysis program was used to identify canonical and gene network pathways associated with RFI. A global view of gene expression differences between LRFI and HRFI suggest that RFI can be explained by differences in cell division, growth, proliferation and apoptosis, protein synthesis, lipid metabolism, and molecular transport of cellular molecules. Chickens selected for improved RFI achieve efficiency by reducing feed intake with a nominal or no change in weight gain by either up-regulating CD36, PPARα, HMGCS2, GCG or down-regulating PCSK2, CALB1, SAT1, and SGK1 genes within the lipid metabolism, small molecule biochemistry, molecular transport, cell death, and protein synthesis molecular and cellular functions. Chickens selected for reduced RFI via reduced feed intake with no change in weight gain achieve feed efficiency for growth by the up-regulation of genes that reduce appetite with increased cellular oxidative stress, prolonged cell cycle, DNA damage, and apoptosis in addition to increased oxidation of dietary fat and efficient fatty acids transported from the intestines. PMID:25782841

  19. Molecular Analysis of Endolithic Microbial Communities in Volcanic Glasses

    Science.gov (United States)

    di Meo, C. A.; Giovannoni, S.; Fisk, M.

    2002-12-01

    Terrestrial and marine volcanic glasses become mineralogically and chemically altered, and in many cases this alteration has been attributed to microbial activity. We have used molecular techniques to study the resident microbial communities from three different volcanic environments that may be responsible for this crustal alteration. Total microbial DNA was extracted from rhyolite glass of the 7 million year old Rattlesnake Tuff in eastern Oregon. The DNA was amplified using the polymerase chain reaction (PCR) with bacterial primers targeting the 16S rRNA gene. This 16S rDNA was cloned and screened with restriction fragment length polymorphism (RFLP). Out of 89 total clones screened, 46 belonged to 13 different clone families containing two or more members, while 43 clones were unique. Sequences of eight clones representing the most dominant clone families in the library were 92 to 97% similar to soil bacterial species. In a separate study, young pillow basalts (microbial life. Total DNA was extracted from the basalt glass and screened for the presence of both bacteria and archaea using the PCR. Repeated attempts with different primer sets yielded no bacterial genes, whereas archaeal genes were quite abundant. A genetic fingerprinting technique, terminal restriction fragment length polymorphism (T-RFLP), was used to compare the archaeal community compositions among the six different basalts. Filtered deep-sea water samples (~15 L) were examined in parallel to identify any overlap between rock- and seawater-associated archaea. The six rock community profiles were quite similar to each other, and the background water communities were also similar, respectively. Both the rock and water communities shared the same dominant peak. To identify the T-RFLP peaks corresponding to the individual members of the rock and seawater communities, clone libraries of the archaeal 16S rDNA for one basalt sample (Dive 3718) and its corresponding background water sample were

  20. The molecular turn in psychiatry: a philosophical analysis.

    Science.gov (United States)

    Rudnick, Abraham

    2002-06-01

    Biological psychiatry has been dominated by a psychopharmacologically-driven neurotransmitter dysfunction paradigm. The objective of this paper is to explore a reductionist assumption underlying this paradigm, and to suggest an improvement on it. The methods used are conceptual analysis with a comparative approach, particularly using illustrations from the history of both biological psychiatry and molecular biology. The results are that complete reduction to physicochemical explanations is not fruitful, at least in the initial stages of research in the medical and life sciences, and that an appropriate (non-reducible) integrative principle--addressing a property of the whole system under study--is required for each domain of research. This is illustrated in Pauling's use of a topological integrative principle for the discovery of the functioning of proteins and in Watson and Crick's use of the notion of a genetic code as an integrative principle for the discovery of the structure of genes. The neurotransmitter dysfunction paradigm addresses single molecules and their neural pathways, yet their interactions within the CNS as a whole seem most pertinent to mental disorders such as schizophrenia. The lack within biological psychiatry of an integrative principle addressing a property of the CNS as a whole may be responsible for the empirical failure of orthomolecular psychiatry, as well as for the central role that serendipity has played in the study of mental disorders, which is dominated by the neurotransmitter paradigm. The conclusion is that research in biological psychiatry may benefit from using, at least initially, some integrative principle(s) addressing a property of the CNS as a whole, such as connectionism or a hierarchical notion. PMID:12187435

  1. Molecular parentage analysis is essential in breeding Asian seabass.

    Directory of Open Access Journals (Sweden)

    Peng Liu

    Full Text Available In aquaculture species, maintaining pedigree information and genetic variation in each generation is essential, but very difficult. In this study, we used nine microsatellites to genotype 2,520 offspring from four independent full-factorial crosses (10 males × 10 females of Asian seabass to reconstruct pedigree and monitor the change of genetic variations. In all four crosses, over 96.8% of the offspring could be assigned to their parents, indicating the high power of the nine microsatellites for parentage assignment. This study revealed several interesting results: (1. In all four crosses, the contribution of parents to offspring was significantly uneven, and some dominant breeding fishes (i.e. brooders were found; (2. In two mass crosses where the brooders were carefully checked for reproductive status, a majority (≥ 90% of brooders contributed to offspring, whereas in another two crosses, where the brooders were randomly picked without checking reproductive status, only a few brooders (40.0-45.0% produced offspring; (3. Females had more problems in successful spawning compared to males; and (4. In the two crosses where a few brooders produced offspring, there was a substantial loss in allelic (24.1-34.3% and gene (20.5-25.7% diversities in offspring, while in the other two crosses, the majority of allelic (96.8-97.0% and gene diversities (94.8-97.1% were maintained. These observations suggest that a routine molecular parentage analysis is required to maintain both allelic and gene diversity in breeding Asian seabass.

  2. Automated Source Code Analysis to Identify and Remove Software Security Vulnerabilities: Case Studies on Java Programs

    Directory of Open Access Journals (Sweden)

    Natarajan Meghanathan

    2013-01-01

    Full Text Available The high-level contribution of this paper is to illustrate the development of generic solution strategies to remove software security vulnerabilities that could be identified using automated tools for source code analysis on software programs (developed in Java. We use the Source Code Analyzer and Audit Workbench automated tools, developed by HP Fortify Inc., for our testing purposes. We present case studies involving a file writer program embedded with features for password validation, and connection-oriented server socket programs to discover, analyze the impact and remove the following software security vulnerabilities: (i Hardcoded Password, (ii Empty Password Initialization, (iii Denial of Service, (iv System Information Leak, (v Unreleased Resource, (vi Path Manipulation, and (vii Resource Injection vulnerabilities. For each of these vulnerabilities, we describe the potential risks associated with leaving them unattended in a software program, and provide the solutions (including the code snippets in Java that can be incorporated to remove these vulnerabilities. The proposed solutions are very generic in nature, and can be suitably modified to correct any such vulnerabilities in software developed in any other programming language.

  3. Transcriptome Analysis Identifies the Dysregulation of Ultraviolet Target Genes in Human Skin Cancers

    Science.gov (United States)

    Shen, Yao; Kim, Arianna L.; Du, Rong; Liu, Liang

    2016-01-01

    Exposure to ultraviolet radiation (UVR) is a major risk factor for both melanoma and non-melanoma skin cancers. In addition to its mutagenic effect, UVR can also induce substantial transcriptional instability in skin cells affecting thousands of genes, including many cancer genes, suggesting that transcriptional instability may be another important etiological factor in skin photocarcinogenesis. In this study, we performed detailed transcriptomic profiling studies to characterize the kinetic changes in global gene expression in human keratinocytes exposed to different UVR conditions. We identified a subset of UV-responsive genes as UV signature genes (UVSGs) based on 1) conserved UV-responsiveness of this subset of genes among different keratinocyte lines; and 2) UV-induced persistent changes in their mRNA levels long after exposure. Interestingly, 11 of the UVSGs were shown to be critical to skin cancer cell proliferation and survival. Through computational Gene Set Enrichment Analysis, we demonstrated that a significant portion of the UVSGs were dysregulated in human skin squamous cell carcinomas, but not in other human malignancies. This highlights the potential and specificity of the UVSGs in clinical diagnosis of UV damage and stratification of skin cancer risk. PMID:27643989

  4. De Novo Transcriptome Analysis of Allium cepa L. (Onion Bulb to Identify Allergens and Epitopes.

    Directory of Open Access Journals (Sweden)

    Hemalatha Rajkumar

    Full Text Available Allium cepa (onion is a diploid plant with one of the largest nuclear genomes among all diploids. Onion is an example of an under-researched crop which has a complex heterozygous genome. There are no allergenic proteins and genomic data available for onions. This study was conducted to establish a transcriptome catalogue of onion bulb that will enable us to study onion related genes involved in medicinal use and allergies. Transcriptome dataset generated from onion bulb using the Illumina HiSeq 2000 technology showed a total of 99,074,309 high quality raw reads (~20 Gb. Based on sequence homology onion genes were categorized into 49 different functional groups. Most of the genes however, were classified under 'unknown' in all three gene ontology categories. Of the categorized genes, 61.2% showed metabolic functions followed by cellular components such as binding, cellular processes; catalytic activity and cell part. With BLASTx top hit analysis, a total of 2,511 homologous allergenic sequences were found, which had 37-100% similarity with 46 different types of allergens existing in the database. From the 46 contigs or allergens, 521 B-cell linear epitopes were identified using BepiPred linear epitope prediction tool. This is the first comprehensive insight into the transcriptome of onion bulb tissue using the NGS technology, which can be used to map IgE epitopes and prediction of structures and functions of various proteins.

  5. Antimicrobial susceptibility among clinical Nocardia species identified by multilocus sequence analysis.

    Science.gov (United States)

    McTaggart, Lisa R; Doucet, Jennifer; Witkowska, Maria; Richardson, Susan E

    2015-01-01

    Antimicrobial susceptibility patterns of 112 clinical isolates, 28 type strains, and 9 reference strains of Nocardia were determined using the Sensititre Rapmyco microdilution panel (Thermo Fisher, Inc.). Isolates were identified by highly discriminatory multilocus sequence analysis and were chosen to represent the diversity of species recovered from clinical specimens in Ontario, Canada. Susceptibility to the most commonly used drug, trimethoprim-sulfamethoxazole, was observed in 97% of isolates. Linezolid and amikacin were also highly effective; 100% and 99% of all isolates demonstrated a susceptible phenotype. For the remaining antimicrobials, resistance was species specific with isolates of Nocardia otitidiscaviarum, N. brasiliensis, N. abscessus complex, N. nova complex, N. transvalensis complex, N. farcinica, and N. cyriacigeorgica displaying the traditional characteristic drug pattern types. In addition, the antimicrobial susceptibility profiles of a variety of rarely encountered species isolated from clinical specimens are reported for the first time and were categorized into four additional drug pattern types. Finally, MICs for the control strains N. nova ATCC BAA-2227, N. asteroides ATCC 19247(T), and N. farcinica ATCC 23826 were robustly determined to demonstrate method reproducibility and suitability of the commercial Sensititre Rapmyco panel for antimicrobial susceptibility testing of Nocardia spp. isolated from clinical specimens. The reported values will facilitate quality control and standardization among laboratories. PMID:25348540

  6. RCAUSE – A ROOT CAUSE ANALYSIS MODEL TO IDENTIFY THE ROOT CAUSES OF SOFTWARE REENGINEERING PROBLEMS

    Directory of Open Access Journals (Sweden)

    Er. Anand Rajavat

    2011-01-01

    Full Text Available Organizations that wish to modernize their legacy systems, must adopt a financial viable evolution strategy to gratify the needs of modern business environment. There are various options available to modernize legacy system in to more contemporary system. Over the last few years’ legacy system reengineering has emerged as a popular system modernization technique. The reengineering generally focuses on the increased productivity and quality of the system. However many of these efforts are often less than successful because they only concentrate on symptoms of software reengineering risk without targeting root causes of those risk. A subjective assessment (diagnosis of software reengineering risk from different domain of legacy system is required to identify the root causes of those risks. The goal of this paper is to highlight root causes of software reengineering risk. We proposed a root cause analysis model RCause that classify root causes of software reengineering risk in to three distinctive but connected areas of interest i.e. system domain, managerial domain and technical domain. .

  7. Genome-Wide Pathway Analysis Identifies Genetic Pathways Associated with Psoriasis.

    Science.gov (United States)

    Aterido, Adrià; Julià, Antonio; Ferrándiz, Carlos; Puig, Lluís; Fonseca, Eduardo; Fernández-López, Emilia; Dauden, Esteban; Sánchez-Carazo, José Luís; López-Estebaranz, José Luís; Moreno-Ramírez, David; Vanaclocha, Francisco; Herrera, Enrique; de la Cueva, Pablo; Dand, Nick; Palau, Núria; Alonso, Arnald; López-Lasanta, María; Tortosa, Raül; García-Montero, Andrés; Codó, Laia; Gelpí, Josep Lluís; Bertranpetit, Jaume; Absher, Devin; Capon, Francesca; Myers, Richard M; Barker, Jonathan N; Marsal, Sara

    2016-03-01

    Psoriasis is a chronic inflammatory disease with a complex genetic architecture. To date, the psoriasis heritability is only partially explained. However, there is increasing evidence that the missing heritability in psoriasis could be explained by multiple genetic variants of low effect size from common genetic pathways. The objective of this study was to identify new genetic variation associated with psoriasis risk at the pathway level. We genotyped 598,258 single nucleotide polymorphisms in a discovery cohort of 2,281 case-control individuals from Spain. We performed a genome-wide pathway analysis using 1,053 reference biological pathways. A total of 14 genetic pathways (PFDR ≤ 2.55 × 10(-2)) were found to be significantly associated with psoriasis risk. Using an independent validation cohort of 7,353 individuals from the UK, a total of 6 genetic pathways were significantly replicated (PFDR ≤ 3.46 × 10(-2)). We found genetic pathways that had not been previously associated with psoriasis risk such as retinol metabolism (Pcombined = 1.84 × 10(-4)), the transport of inorganic ions and amino acids (Pcombined = 1.57 × 10(-7)), and post-translational protein modification (Pcombined = 1.57 × 10(-7)). In the latter pathway, MGAT5 showed a strong network centrality, and its association with psoriasis risk was further validated in an additional case-control cohort of 3,429 individuals (P psoriasis susceptibility. PMID:26743605

  8. LC-MS based Metabolomics Analysis to Identify Potential Allelochemicals in Wedelia trilobata

    Directory of Open Access Journals (Sweden)

    Kamalrul Azlan Azizan

    2016-05-01

    Full Text Available Wedelia trilobata is a noxious invasive weed that has been widely cultivated as a decorative and groundcover plant. The plant has been reported to contain diverse bioactive compounds with a broad spectrum of biological activities including allelochemicals. Allelochemicals contribute to allelopathy interactions that suppress the growth and development of nearby plants. Several studies have reported the allelopathic potential of W. trilobata and its negative effects to crop plants. However, relatively little is known about the allelochemicals’ composition and how allelochemicals contribute to the allelopathic behavior of this plant. In order to prove allelopathy, the identification of the causative allelochemicals is required. The identification of potential allelochemicals that serve as biomarkers could be useful for assessing allelopathy interactions. In this study, a liquid chromatography (LC based metabolomics approach was applied to find biomarkers with allelopathic effects from W. trilobata. Ethanol and water were used to extract metabolites from the leaves of W. trilobata and analyzed using liquid chromatography coupled with quadrupole high-resolution time of flight mass spectrometry (LC-QTOF-MS. Using multivariate statistical analysis (MVA, we identified eight Rt-m/z pairs as candidate marker compounds for assessing allelopathy interactions of W. trilobata. The results highlight the application of metabolomics for understanding of the role of allelochemicals in allelopathy interactions of W. trilobata .

  9. Urine metabolomic analysis identifies potential biomarkers and pathogenic pathways in kidney cancer.

    Science.gov (United States)

    Kim, Kyoungmi; Taylor, Sandra L; Ganti, Sheila; Guo, Lining; Osier, Michael V; Weiss, Robert H

    2011-05-01

    Kidney cancer is the seventh most common cancer in the Western world, its incidence is increasing, and it is frequently metastatic at presentation, at which stage patient survival statistics are grim. In addition, there are no useful biofluid markers for this disease, such that diagnosis is dependent on imaging techniques that are not generally used for screening. In the present study, we use metabolomics techniques to identify metabolites in kidney cancer patients' urine, which appear at different levels (when normalized to account for urine volume and concentration) from the same metabolites in nonkidney cancer patients. We found that quinolinate, 4-hydroxybenzoate, and gentisate are differentially expressed at a false discovery rate of 0.26, and these metabolites are involved in common pathways of specific amino acid and energetic metabolism, consistent with high tumor protein breakdown and utilization, and the Warburg effect. When added to four different (three kidney cancer-derived and one "normal") cell lines, several of the significantly altered metabolites, quinolinate, α-ketoglutarate, and gentisate, showed increased or unchanged cell proliferation that was cell line-dependent. Further evaluation of the global metabolomics analysis, as well as confirmation of the specific potential biomarkers using a larger sample size, will lead to new avenues of kidney cancer diagnosis and therapy. PMID:21348635

  10. Acute toxicity tests and meta-analysis identify gaps in tropical ecotoxicology for amphibians.

    Science.gov (United States)

    Ghose, Sonia L; Donnelly, Maureen A; Kerby, Jacob; Whitfield, Steven M

    2014-09-01

    Amphibian populations are declining worldwide, particularly in tropical regions where amphibian diversity is highest. Pollutants, including agricultural pesticides, have been identified as a potential contributor to decline, yet toxicological studies of tropical amphibians are very rare. The present study assesses toxic effects on amphibians of 10 commonly used commercial pesticides in tropical agriculture using 2 approaches. First, the authors conducted 8-d toxicity assays with formulations of each pesticide using individually reared red-eyed tree frog (Agalychnis callidryas) tadpoles. Second, they conducted a review of available data for the lethal concentration to kill 50% of test animals from the US Environmental Protection Agency's ECOTOX database to allow comparison with their findings. Lethal concentration estimates from the assays ranged over several orders of magnitude. The nematicides terbufos and ethoprophos and the fungicide chlorothalonil were very highly toxic, with evident effects within an order of magnitude of environmental concentrations. Acute toxicity assays and meta-analysis show that nematicides and fungicides are generally more toxic than herbicides yet receive far less research attention than less toxic herbicides. Given that the tropics have a high diversity of amphibians, the findings emphasize the need for research into the effects of commonly used pesticides in tropical countries and should help guide future ecotoxicological research in tropical regions.

  11. Patent analysis to identify shale gas development in China and the United States

    International Nuclear Information System (INIS)

    Shale gas has become an increasingly important form of hydrocarbon energy, and related technologies reflect the geographical characteristics of the countries where the gas is extracted and stored. The United States (U.S.) produces most of the world’s shale gas, while China has the world’s largest shale gas reserves. In this research, we focused on identifying the trends in shale-gas related technologies registered to the United States Patent and Trademark Office (USPTO) and to the State Intellectual Property Office of the People’s Republic of China (SIPO) respectively. To cluster shale-gas related technologies, we text-mined the abstracts of patent specifications. It was found that in the U.S., the key advanced technologies were related to hydraulic fracturing, horizontal drilling, and slick water areas, whereas China had a focus on proppants. The results of our study are expected to assist energy experts in designing energy policies related to technology importation. - Highlights: • We analyzed shale gas-related patent applications in the USPTO and SIPO. • We clustered shale gas patents by text mining patent abstract. • Differences were observed in shale gas technologies developed in the U.S. and China. • We proposed the policies of shale gas exploration and development based on patent analysis

  12. Systematic analysis of the PTEN 5' leader identifies a major AUU initiated proteoform.

    Science.gov (United States)

    Tzani, Ioanna; Ivanov, Ivaylo P; Andreev, Dmitri E; Dmitriev, Ruslan I; Dean, Kellie A; Baranov, Pavel V; Atkins, John F; Loughran, Gary

    2016-05-01

    Abundant evidence for translation within the 5' leaders of many human genes is rapidly emerging, especially, because of the advent of ribosome profiling. In most cases, it is believed that the act of translation rather than the encoded peptide is important. However, the wealth of available sequencing data in recent years allows phylogenetic detection of sequences within 5' leaders that have emerged under coding constraint and therefore allow for the prediction of functional 5' leader translation. Using this approach, we previously predicted a CUG-initiated, 173 amino acid N-terminal extension to the human tumour suppressor PTEN. Here, a systematic experimental analysis of translation events in the PTEN 5' leader identifies at least two additional non-AUG-initiated PTEN proteoforms that are expressed in most human cell lines tested. The most abundant extended PTEN proteoform initiates at a conserved AUU codon and extends the canonical AUG-initiated PTEN by 146 amino acids. All N-terminally extended PTEN proteoforms tested retain the ability to downregulate the PI3K pathway. We also provide evidence for the translation of two conserved AUG-initiated upstream open reading frames within the PTEN 5' leader that control the ratio of PTEN proteoforms.

  13. Genome-Wide Pathway Analysis Identifies Genetic Pathways Associated with Psoriasis.

    Science.gov (United States)

    Aterido, Adrià; Julià, Antonio; Ferrándiz, Carlos; Puig, Lluís; Fonseca, Eduardo; Fernández-López, Emilia; Dauden, Esteban; Sánchez-Carazo, José Luís; López-Estebaranz, José Luís; Moreno-Ramírez, David; Vanaclocha, Francisco; Herrera, Enrique; de la Cueva, Pablo; Dand, Nick; Palau, Núria; Alonso, Arnald; López-Lasanta, María; Tortosa, Raül; García-Montero, Andrés; Codó, Laia; Gelpí, Josep Lluís; Bertranpetit, Jaume; Absher, Devin; Capon, Francesca; Myers, Richard M; Barker, Jonathan N; Marsal, Sara

    2016-03-01

    Psoriasis is a chronic inflammatory disease with a complex genetic architecture. To date, the psoriasis heritability is only partially explained. However, there is increasing evidence that the missing heritability in psoriasis could be explained by multiple genetic variants of low effect size from common genetic pathways. The objective of this study was to identify new genetic variation associated with psoriasis risk at the pathway level. We genotyped 598,258 single nucleotide polymorphisms in a discovery cohort of 2,281 case-control individuals from Spain. We performed a genome-wide pathway analysis using 1,053 reference biological pathways. A total of 14 genetic pathways (PFDR ≤ 2.55 × 10(-2)) were found to be significantly associated with psoriasis risk. Using an independent validation cohort of 7,353 individuals from the UK, a total of 6 genetic pathways were significantly replicated (PFDR ≤ 3.46 × 10(-2)). We found genetic pathways that had not been previously associated with psoriasis risk such as retinol metabolism (Pcombined = 1.84 × 10(-4)), the transport of inorganic ions and amino acids (Pcombined = 1.57 × 10(-7)), and post-translational protein modification (Pcombined = 1.57 × 10(-7)). In the latter pathway, MGAT5 showed a strong network centrality, and its association with psoriasis risk was further validated in an additional case-control cohort of 3,429 individuals (P psoriasis susceptibility.

  14. Transcriptome Analysis Identifies the Dysregulation of Ultraviolet Target Genes in Human Skin Cancers.

    Science.gov (United States)

    Shen, Yao; Kim, Arianna L; Du, Rong; Liu, Liang

    2016-01-01

    Exposure to ultraviolet radiation (UVR) is a major risk factor for both melanoma and non-melanoma skin cancers. In addition to its mutagenic effect, UVR can also induce substantial transcriptional instability in skin cells affecting thousands of genes, including many cancer genes, suggesting that transcriptional instability may be another important etiological factor in skin photocarcinogenesis. In this study, we performed detailed transcriptomic profiling studies to characterize the kinetic changes in global gene expression in human keratinocytes exposed to different UVR conditions. We identified a subset of UV-responsive genes as UV signature genes (UVSGs) based on 1) conserved UV-responsiveness of this subset of genes among different keratinocyte lines; and 2) UV-induced persistent changes in their mRNA levels long after exposure. Interestingly, 11 of the UVSGs were shown to be critical to skin cancer cell proliferation and survival. Through computational Gene Set Enrichment Analysis, we demonstrated that a significant portion of the UVSGs were dysregulated in human skin squamous cell carcinomas, but not in other human malignancies. This highlights the potential and specificity of the UVSGs in clinical diagnosis of UV damage and stratification of skin cancer risk. PMID:27643989

  15. Expression Data Analysis to Identify Biomarkers Associated with Asthma in Children

    Directory of Open Access Journals (Sweden)

    Wen Xu

    2014-01-01

    Full Text Available Asthma is characterized by recurrent episodes of wheezing, shortness of breath, chest tightness, and coughing. It is usually caused by a combination of complex and incompletely understood environmental and genetic interactions. We obtained gene expression data with high-throughput screening and identified biomarkers of children's asthma using bioinformatics tools. Next, we explained the pathogenesis of children's asthma from the perspective of gene regulatory networks: DAVID was applied to perform Kyoto Encyclopedia of Genes and Genomes (KEGG pathway enriching analysis for the top 3000 pairs of relationships in differentially regulatory network. Finally, we found that HAND1, PTK1, NFKB1, ZIC3, STAT6, E2F1, PELP1, USF2, and CBFB may play important roles in children's asthma initiation. On account of regulatory impact factor (RIF score, HAND1, PTK7, and ZIC3 were the potential asthma-related factors. Our study provided some foundations of a strategy for biomarker discovery despite a poor understanding of the mechanisms underlying children's asthma.

  16. Whole exome analysis identifies frequent CNGA1 mutations in Japanese population with autosomal recessive retinitis pigmentosa.

    Directory of Open Access Journals (Sweden)

    Satoshi Katagiri

    Full Text Available OBJECTIVE: The purpose of this study was to investigate frequent disease-causing gene mutations in autosomal recessive retinitis pigmentosa (arRP in the Japanese population. METHODS: In total, 99 Japanese patients with non-syndromic and unrelated arRP or sporadic RP (spRP were recruited in this study and ophthalmic examinations were conducted for the diagnosis of RP. Among these patients, whole exome sequencing analysis of 30 RP patients and direct sequencing screening of all CNGA1 exons of the other 69 RP patients were performed. RESULTS: Whole exome sequencing of 30 arRP/spRP patients identified disease-causing gene mutations of CNGA1 (four patients, EYS (three patients and SAG (one patient in eight patients and potential disease-causing gene variants of USH2A (two patients, EYS (one patient, TULP1 (one patient and C2orf71 (one patient in five patients. Screening of an additional 69 arRP/spRP patients for the CNGA1 gene mutation revealed one patient with a homozygous mutation. CONCLUSIONS: This is the first identification of CNGA1 mutations in arRP Japanese patients. The frequency of CNGA1 gene mutation was 5.1% (5/99 patients. CNGA1 mutations are one of the most frequent arRP-causing mutations in Japanese patients.

  17. Global Gene-Expression Analysis to Identify Differentially Expressed Genes Critical for the Heat Stress Response in Brassica rapa.

    Directory of Open Access Journals (Sweden)

    Xiangshu Dong

    Full Text Available Genome-wide dissection of the heat stress response (HSR is necessary to overcome problems in crop production caused by global warming. To identify HSR genes, we profiled gene expression in two Chinese cabbage inbred lines with different thermotolerances, Chiifu and Kenshin. Many genes exhibited >2-fold changes in expression upon exposure to 0.5- 4 h at 45°C (high temperature, HT: 5.2% (2,142 genes in Chiifu and 3.7% (1,535 genes in Kenshin. The most enriched GO (Gene Ontology items included 'response to heat', 'response to reactive oxygen species (ROS', 'response to temperature stimulus', 'response to abiotic stimulus', and 'MAPKKK cascade'. In both lines, the genes most highly induced by HT encoded small heat shock proteins (Hsps and heat shock factor (Hsf-like proteins such as HsfB2A (Bra029292, whereas high-molecular weight Hsps were constitutively expressed. Other upstream HSR components were also up-regulated: ROS-scavenging genes like glutathione peroxidase 2 (BrGPX2, Bra022853, protein kinases, and phosphatases. Among heat stress (HS marker genes in Arabidopsis, only exportin 1A (XPO1A (Bra008580, Bra006382 can be applied to B. rapa for basal thermotolerance (BT and short-term acquired thermotolerance (SAT gene. CYP707A3 (Bra025083, Bra021965, which is involved in the dehydration response in Arabidopsis, was associated with membrane leakage in both lines following HS. Although many transcription factors (TF genes, including DREB2A (Bra005852, were involved in HS tolerance in both lines, Bra024224 (MYB41 and Bra021735 (a bZIP/AIR1 [Anthocyanin-Impaired-Response-1] were specific to Kenshin. Several candidate TFs involved in thermotolerance were confirmed as HSR genes by real-time PCR, and these assignments were further supported by promoter analysis. Although some of our findings are similar to those obtained using other plant species, clear differences in Brassica rapa reveal a distinct HSR in this species. Our data could also provide a

  18. Correlational analysis for identifying genes whose regulation contributes to chronic neuropathic pain

    Directory of Open Access Journals (Sweden)

    Wiesenfeld-Hallin Zsuzsanna

    2009-02-01

    Full Text Available Abstract Background Nerve injury-triggered hyperexcitability in primary sensory neurons is considered a major source of chronic neuropathic pain. The hyperexcitability, in turn, is thought to be related to transcriptional switching in afferent cell somata. Analysis using expression microarrays has revealed that many genes are regulated in the dorsal root ganglion (DRG following axotomy. But which contribute to pain phenotype versus other nerve injury-evoked processes such as nerve regeneration? Using the L5 spinal nerve ligation model of neuropathy we examined differential changes in gene expression in the L5 (and L4 DRGs in five mouse strains with contrasting susceptibility to neuropathic pain. We sought genes for which the degree of regulation correlates with strain-specific pain phenotype. Results In an initial experiment six candidate genes previously identified as important in pain physiology were selected for in situ hybridization to DRG sections. Among these, regulation of the Na+ channel α subunit Scn11a correlated with levels of spontaneous pain behavior, and regulation of the cool receptor Trpm8 correlated with heat hypersensibility. In a larger scale experiment, mRNA extracted from individual mouse DRGs was processed on Affymetrix whole-genome expression microarrays. Overall, 2552 ± 477 transcripts were significantly regulated in the axotomized L5DRG 3 days postoperatively. However, in only a small fraction of these was the degree of regulation correlated with pain behavior across strains. Very few genes in the "uninjured" L4DRG showed altered expression (24 ± 28. Conclusion Correlational analysis based on in situ hybridization provided evidence that differential regulation of Scn11a and Trpm8 contributes to across-strain variability in pain phenotype. This does not, of course, constitute evidence that the others are unrelated to pain. Correlational analysis based on microarray data yielded a larger "look-up table" of genes whose

  19. First genome analysis and molecular characterization of Chickpea chlorotic dwarf virus Egyptian isolate infecting squash.

    Science.gov (United States)

    Fahmy, Inas Farouk; Taha, Omnia; El-Ashry, Abdel Nasser

    2015-06-01

    This study aims to identifying and characterizing some molecular properties of geminiviruses co-infection in squash field crop cultivated in Egypt. Squash crops observed to be heavily infected with several insect vectors, also severe chlorosis and stunting was observed. Electron microscopic analysis has revealed geminate capsid particles which indicate the infection of Geminiviruses, especially SqLCV which represent an economic problem to squash filed crop in Egypt. We have investigated possible mixed infections with different plant viruses associated with chlorotic stunt diseases and or other genus groups of geminiviruses. The main objective of this study is to investigate the recombination events, possible recombinants and variants among these genera in the same family differing in vector transmission. This is the first report of the molecular characterization, phylogenetic analysis and putative recombination events of the full length genome of the Chickpea Chlorotic Dwarf Mastrevirus in Egypt. And the first report of co-infection with another begomovirus infecting squash plants. A full length clone of both viruses were isolated and characterized at the molecular level. The complete nucleotide sequence of DNA-A was determined (2,572 bp) and submitted to the genbank under accession no. KF692356. The isolate from Egypt has about 97.8 % homology with the Chickpea chlorotic dwarf virus (CpCDV) isolate from Syria DNA-A isolate FR687959, a 83.2 % homology with the Sudan isolate AM933134 and a 82.7 % homology with Pakistan isolate FR687960. To best of our knowledge this is the first report of complete genome of CpCDV that infect squash plants in Egypt and worldwide.

  20. Circulating tumor cells (CTCs) in breast cancer: a diagnostic tool for prognosis and molecular analysis

    Institute of Scientific and Technical Information of China (English)

    Xiaoshen Dong; R.Katherine Alpaugh; Massimo Cristofanilli

    2012-01-01

    Metastatic breast cancer (MBC) is characterized by a combination of tumor growth,proliferation and metastatic progression and is typically managed with palliative intent.The benefit of standard systemic therapies is relatively limited and the disease is considered incurable suggesting the need to investigate the biological drivers of the various phases of the metastatic process in order to improve the selection of molecularly driven therapies.The detection,enumeration and molecular analysis of circulating tumor cells (CTCs) provide an intriguing opportunity to advance this knowledge.CTCs enumerated by the Food and Drugs Administration-cleared CellSearchTM system are an independent prognostic factor of progression-free survival (PFS) and overall survival (OS) in MBC patients.Several published papers demonstrated the poor prognosis for MBC patients that presented basal CTC count ≥5 in 7.5 mL of blood.Therefore,the enumeration of CTCs during treatment for MBC provides a tool with the ability to predict progression of disease earlier than standard timing of anatomical assessment using conventional radiological tests.During the metastatic process cancer cells exhibit morphological and phenotypic plasticity undergoing epithelial-mesenchymal transition (EMT).This important phenomenon is associated with down regulation of epithelial marker (e.g.,EpCAM) with potential limitations in the applicability of current CTCs enrichment methods.Such observations translated in a number of investigations aimed at improving our capabilities to enumerate and perform molecular characterization of CTCs.Theoretically,the phenotypic analysis of CTCs can represent a "liquid" biopsy of breast tumor that is able to identify a new potential target against the metastatic disease and advance the development and monitoring of personalized therapies.

  1. Dengue virus. Fast Diagnosis of dengue virus by molecular analysis

    International Nuclear Information System (INIS)

    This article is about a regional project in the assurance and quality control of molecular diagnosis. It allows the identification of parasites genotypes that infect humans, particularly dengue that is a viral disease transmitted by mosquitoes

  2. Interactive analysis of systems biology molecular expression data

    OpenAIRE

    Prabhakar Sunil; Salt David E; Kane Michael D; Stephenson Alan; Ouyang Qi; Zhang Mingwu; Burgner John; Buck Charles; Zhang Xiang

    2008-01-01

    Abstract Background Systems biology aims to understand biological systems on a comprehensive scale, such that the components that make up the whole are connected to one another and work through dependent interactions. Molecular correlations and comparative studies of molecular expression are crucial to establishing interdependent connections in systems biology. The existing software packages provide limited data mining capability. The user must first generate visualization data with a preferr...

  3. Molecular Analysis of Bacterial Species Associated with Childhood Caries

    OpenAIRE

    Becker, Mitzi R.; Paster, Bruce J.; Leys, Eugene J.; Moeschberger, Melvin L.; Kenyon, Sarah G.; Galvin, Jamie L.; Boches, Susan K.; Dewhirst, Floyd E.; Griffen, Ann L.

    2002-01-01

    Although substantial epidemiologic evidence links Streptococcus mutans to caries, the pathobiology of caries may involve more complex communities of bacterial species. Molecular methods for bacterial identification and enumeration now make it possible to more precisely study the microbiota associated with dental caries. The purpose of this study was to compare the bacteria found in early childhood caries (ECC) to those found in caries-free children by using molecular identification methods. C...

  4. Molecular Analysis of the Microflora Associated with Dental Caries

    OpenAIRE

    Munson, M A; Banerjee, A.; Watson, T.F.; Wade, W. G.

    2004-01-01

    Molecular techniques have revealed many novel, presumed unculturable, taxa in oral infections. The aim of this study was to characterize the bacterial community of the middle and advancing front of carious dental lesions by cultural and molecular analyses. Samples were collected with a hand excavator from five teeth with carious lesions involving dentine. Samples were cultured on blood agar and Rogosa agar incubated in air plus 5% CO2 and on fastidious anaerobe agar anaerobically. DNA was als...

  5. Application of principal component analysis in protein unfolding: An all-atom molecular dynamics simulation study

    Science.gov (United States)

    Das, Atanu; Mukhopadhyay, Chaitali

    2007-10-01

    We have performed molecular dynamics (MD) simulation of the thermal denaturation of one protein and one peptide—ubiquitin and melittin. To identify the correlation in dynamics among various secondary structural fragments and also the individual contribution of different residues towards thermal unfolding, principal component analysis method was applied in order to give a new insight to protein dynamics by analyzing the contribution of coefficients of principal components. The cross-correlation matrix obtained from MD simulation trajectory provided important information regarding the anisotropy of backbone dynamics that leads to unfolding. Unfolding of ubiquitin was found to be a three-state process, while that of melittin, though smaller and mostly helical, is more complicated.