WorldWideScience

Sample records for factor analyses revealed

  1. Comparative analyses of developmental transcription factor repertoires in sponges reveal unexpected complexity of the earliest animals.

    Science.gov (United States)

    Fortunato, Sofia A V; Adamski, Marcin; Adamska, Maja

    2015-12-01

    Developmental transcription factors (DTFs) control development of animals by affecting expression of target genes, some of which are transcription factors themselves. In bilaterians and cnidarians, conserved DTFs are involved in homologous processes such as gastrulation or specification of neurons. The genome of Amphimedon queenslandica, the first sponge to be sequenced, revealed that only a fraction of these conserved DTF families are present in demosponges. This finding was in line with the view that morphological complexity in the animal lineage correlates with developmental toolkit complexity. However, as the phylum Porifera is very diverse, Amphimedon's genome may not be representative of all sponges. The recently sequenced genomes of calcareous sponges Sycon ciliatum and Leucosolenia complicata allowed investigations of DTFs in a sponge lineage evolutionarily distant from demosponges. Surprisingly, the phylogenetic analyses of identified DTFs revealed striking differences between the calcareous sponges and Amphimedon. As these differences appear to be a result of independent gene loss events in the two sponge lineages, the last common ancestor of sponges had to possess a much more diverse repertoire of DTFs than extant sponges. Developmental expression of sponge homologs of genes involved in specification of the Bilaterian endomesoderm and the neurosensory cells suggests that roles of many DTFs date back to the last common ancestor of all animals. Strikingly, even DTFs displaying apparent pan-metazoan conservation of sequence and function are not immune to being lost from individual species genomes. The quest for a comprehensive picture of the developmental toolkit in the last common metazoan ancestor is thus greatly benefitting from the increasing accessibility of sequencing, allowing comparisons of multiple genomes within each phylum.

  2. Proteomic analyses reveal distinct chromatin-associated and soluble transcription factor complexes.

    Science.gov (United States)

    Li, Xu; Wang, Wenqi; Wang, Jiadong; Malovannaya, Anna; Xi, Yuanxin; Li, Wei; Guerra, Rudy; Hawke, David H; Qin, Jun; Chen, Junjie

    2015-01-21

    The current knowledge on how transcription factors (TFs), the ultimate targets and executors of cellular signalling pathways, are regulated by protein-protein interactions remains limited. Here, we performed proteomics analyses of soluble and chromatin-associated complexes of 56 TFs, including the targets of many signalling pathways involved in development and cancer, and 37 members of the Forkhead box (FOX) TF family. Using tandem affinity purification followed by mass spectrometry (TAP/MS), we performed 214 purifications and identified 2,156 high-confident protein-protein interactions. We found that most TFs form very distinct protein complexes on and off chromatin. Using this data set, we categorized the transcription-related or unrelated regulators for general or specific TFs. Our study offers a valuable resource of protein-protein interaction networks for a large number of TFs and underscores the general principle that TFs form distinct location-specific protein complexes that are associated with the different regulation and diverse functions of these TFs.

  3. metagene Profiles Analyses Reveal Regulatory Element's Factor-Specific Recruitment Patterns.

    Science.gov (United States)

    Joly Beauparlant, Charles; Lamaze, Fabien C; Deschênes, Astrid; Samb, Rawane; Lemaçon, Audrey; Belleau, Pascal; Bilodeau, Steve; Droit, Arnaud

    2016-08-01

    ChIP-Sequencing (ChIP-Seq) provides a vast amount of information regarding the localization of proteins across the genome. The aggregation of ChIP-Seq enrichment signal in a metagene plot is an approach commonly used to summarize data complexity and to obtain a high level visual representation of the general occupancy pattern of a protein. Here we present the R package metagene, the graphical interface Imetagene and the companion package similaRpeak. Together, they provide a framework to integrate, summarize and compare the ChIP-Seq enrichment signal from complex experimental designs. Those packages identify and quantify similarities or dissimilarities in patterns between large numbers of ChIP-Seq profiles. We used metagene to investigate the differential occupancy of regulatory factors at noncoding regulatory regions (promoters and enhancers) in relation to transcriptional activity in GM12878 B-lymphocytes. The relationships between occupancy patterns and transcriptional activity suggest two different mechanisms of action for transcriptional control: i) a "gradient effect" where the regulatory factor occupancy levels follow transcription and ii) a "threshold effect" where the regulatory factor occupancy levels max out prior to reaching maximal transcription. metagene, Imetagene and similaRpeak are implemented in R under the Artistic license 2.0 and are available on Bioconductor.

  4. metagene Profiles Analyses Reveal Regulatory Element’s Factor-Specific Recruitment Patterns

    Science.gov (United States)

    Samb, Rawane; Lemaçon, Audrey; Bilodeau, Steve; Droit, Arnaud

    2016-01-01

    ChIP-Sequencing (ChIP-Seq) provides a vast amount of information regarding the localization of proteins across the genome. The aggregation of ChIP-Seq enrichment signal in a metagene plot is an approach commonly used to summarize data complexity and to obtain a high level visual representation of the general occupancy pattern of a protein. Here we present the R package metagene, the graphical interface Imetagene and the companion package similaRpeak. Together, they provide a framework to integrate, summarize and compare the ChIP-Seq enrichment signal from complex experimental designs. Those packages identify and quantify similarities or dissimilarities in patterns between large numbers of ChIP-Seq profiles. We used metagene to investigate the differential occupancy of regulatory factors at noncoding regulatory regions (promoters and enhancers) in relation to transcriptional activity in GM12878 B-lymphocytes. The relationships between occupancy patterns and transcriptional activity suggest two different mechanisms of action for transcriptional control: i) a “gradient effect” where the regulatory factor occupancy levels follow transcription and ii) a “threshold effect” where the regulatory factor occupancy levels max out prior to reaching maximal transcription. metagene, Imetagene and similaRpeak are implemented in R under the Artistic license 2.0 and are available on Bioconductor. PMID:27538250

  5. Expression and Protein Interaction Analyses Reveal Combinatorial Interactions of LBD Transcription Factors During Arabidopsis Pollen Development.

    Science.gov (United States)

    Kim, Mirim; Kim, Min-Jung; Pandey, Shashank; Kim, Jungmook

    2016-11-01

    LATERAL ORGAN BOUNDARIES DOMAIN (LBD) transcription factor gene family members play key roles in diverse aspects of plant development. LBD10 and LBD27 have been shown to be essential for pollen development in Arabidopsis thaliana. From the previous RNA sequencing (RNA-Seq) data set of Arabidopsis pollen, we identified the mRNAs of LBD22, LBD25 and LBD36 in addition to LBD10 and LBD27 in Arabidopsis pollen. Here we conducted expression and cellular analysis using GFP:GUS (green fluorescent protein:β-glucuronidase) reporter gene and subcellular localization assays using LBD:GFP fusion proteins expressed under the control of their own promoters in Arabidopsis. We found that these LBD proteins display spatially and temporally distinct and overlapping expression patterns during pollen development. Bimolecular fluorescence complementation and GST (glutathione S-transferase) pull-down assays demonstrated that protein-protein interactions occur among the LBDs exhibiting overlapping expression during pollen development. We further showed that LBD10, LBD22, LBD25, LBD27 and LBD36 interact with each other to form heterodimers, which are localized to the nucleus in Arabidopsis protoplasts. Taken together, these results suggest that combinatorial interactions among LBD proteins may be important for their function in pollen development in Arabidopsis.

  6. Microarray Analyses Reveal Marked Differences in Growth Factor and Receptor Expression Between 8-Cell Human Embryos and Pluripotent Stem Cells.

    Science.gov (United States)

    Vlismas, Antonis; Bletsa, Ritsa; Mavrogianni, Despina; Mamali, Georgina; Pergamali, Maria; Dinopoulou, Vasiliki; Partsinevelos, George; Drakakis, Peter; Loutradis, Dimitris; Kiessling, Ann A

    2016-01-15

    Previous microarray analyses of RNAs from 8-cell (8C) human embryos revealed a lack of cell cycle checkpoints and overexpression of core circadian oscillators and cell cycle drivers relative to pluripotent human stem cells [human embryonic stem cells/induced pluripotent stem (hES/iPS)] and fibroblasts, suggesting growth factor independence during early cleavage stages. To explore this possibility, we queried our combined microarray database for expression of 487 growth factors and receptors. Fifty-one gene elements were overdetected on the 8C arrays relative to hES/iPS cells, including 14 detected at least 80-fold higher, which annotated to multiple pathways: six cytokine family (CSF1R, IL2RG, IL3RA, IL4, IL17B, IL23R), four transforming growth factor beta (TGFB) family (BMP6, BMP15, GDF9, ENG), one fibroblast growth factor (FGF) family [FGF14(FH4)], one epidermal growth factor member (GAB1), plus CD36, and CLEC10A. 8C-specific gene elements were enriched (73%) for reported circadian-controlled genes in mouse tissues. High-level detection of CSF1R, ENG, IL23R, and IL3RA specifically on the 8C arrays suggests the embryo plays an active role in blocking immune rejection and is poised for trophectoderm development; robust detection of NRG1, GAB1, -2, GRB7, and FGF14(FHF4) indicates novel roles in early development in addition to their known roles in later development. Forty-four gene elements were underdetected on the 8C arrays, including 11 at least 80-fold under the pluripotent cells: two cytokines (IFITM1, TNFRSF8), five TGFBs (BMP7, LEFTY1, LEFTY2, TDGF1, TDGF3), two FGFs (FGF2, FGF receptor 1), plus ING5, and WNT6. The microarray detection patterns suggest that hES/iPS cells exhibit suppressed circadian competence, underexpression of early differentiation markers, and more robust expression of generic pluripotency genes, in keeping with an artificial state of continual uncommitted cell division. In contrast, gene expression patterns of the 8C embryo suggest that

  7. Microarray Analyses Reveal Marked Differences in Growth Factor and Receptor Expression Between 8-Cell Human Embryos and Pluripotent Stem Cells

    Science.gov (United States)

    Vlismas, Antonis; Bletsa, Ritsa; Mavrogianni, Despina; Mamali, Georgina; Pergamali, Maria; Dinopoulou, Vasiliki; Partsinevelos, George; Drakakis, Peter; Loutradis, Dimitris

    2016-01-01

    Previous microarray analyses of RNAs from 8-cell (8C) human embryos revealed a lack of cell cycle checkpoints and overexpression of core circadian oscillators and cell cycle drivers relative to pluripotent human stem cells [human embryonic stem cells/induced pluripotent stem (hES/iPS)] and fibroblasts, suggesting growth factor independence during early cleavage stages. To explore this possibility, we queried our combined microarray database for expression of 487 growth factors and receptors. Fifty-one gene elements were overdetected on the 8C arrays relative to hES/iPS cells, including 14 detected at least 80-fold higher, which annotated to multiple pathways: six cytokine family (CSF1R, IL2RG, IL3RA, IL4, IL17B, IL23R), four transforming growth factor beta (TGFB) family (BMP6, BMP15, GDF9, ENG), one fibroblast growth factor (FGF) family [FGF14(FH4)], one epidermal growth factor member (GAB1), plus CD36, and CLEC10A. 8C-specific gene elements were enriched (73%) for reported circadian-controlled genes in mouse tissues. High-level detection of CSF1R, ENG, IL23R, and IL3RA specifically on the 8C arrays suggests the embryo plays an active role in blocking immune rejection and is poised for trophectoderm development; robust detection of NRG1, GAB1, -2, GRB7, and FGF14(FHF4) indicates novel roles in early development in addition to their known roles in later development. Forty-four gene elements were underdetected on the 8C arrays, including 11 at least 80-fold under the pluripotent cells: two cytokines (IFITM1, TNFRSF8), five TGFBs (BMP7, LEFTY1, LEFTY2, TDGF1, TDGF3), two FGFs (FGF2, FGF receptor 1), plus ING5, and WNT6. The microarray detection patterns suggest that hES/iPS cells exhibit suppressed circadian competence, underexpression of early differentiation markers, and more robust expression of generic pluripotency genes, in keeping with an artificial state of continual uncommitted cell division. In contrast, gene expression patterns of the 8C embryo suggest that

  8. Analyses of genome architecture and gene expression reveal novel candidate virulence factors in the secretome of Phytophthora infestans

    Directory of Open Access Journals (Sweden)

    Cano Liliana M

    2010-11-01

    Full Text Available Abstract Background Phytophthora infestans is the most devastating pathogen of potato and a model organism for the oomycetes. It exhibits high evolutionary potential and rapidly adapts to host plants. The P. infestans genome experienced a repeat-driven expansion relative to the genomes of Phytophthora sojae and Phytophthora ramorum and shows a discontinuous distribution of gene density. Effector genes, such as members of the RXLR and Crinkler (CRN families, localize to expanded, repeat-rich and gene-sparse regions of the genome. This distinct genomic environment is thought to contribute to genome plasticity and host adaptation. Results We used in silico approaches to predict and describe the repertoire of P. infestans secreted proteins (the secretome. We defined the "plastic secretome" as a subset of the genome that (i encodes predicted secreted proteins, (ii is excluded from genome segments orthologous to the P. sojae and P. ramorum genomes and (iii is encoded by genes residing in gene sparse regions of P. infestans genome. Although including only ~3% of P. infestans genes, the plastic secretome contains ~62% of known effector genes and shows >2 fold enrichment in genes induced in planta. We highlight 19 plastic secretome genes induced in planta but distinct from previously described effectors. This list includes a trypsin-like serine protease, secreted oxidoreductases, small cysteine-rich proteins and repeat containing proteins that we propose to be novel candidate virulence factors. Conclusions This work revealed a remarkably diverse plastic secretome. It illustrates the value of combining genome architecture with comparative genomics to identify novel candidate virulence factors from pathogen genomes.

  9. Multiple independent analyses reveal only transcription factors as an enriched functional class associated with microRNAs

    Directory of Open Access Journals (Sweden)

    Croft Larry

    2012-07-01

    Full Text Available Abstract Background Transcription factors (TFs have long been known to be principally activators of transcription in eukaryotes and prokaryotes. The growing awareness of the ubiquity of microRNAs (miRNAs as suppressive regulators in eukaryotes, suggests the possibility of a mutual, preferential, self-regulatory connectivity between miRNAs and TFs. Here we investigate the connectivity from TFs and miRNAs to other genes and each other using text mining, TF promoter binding site and 6 different miRNA binding site prediction methods. Results In the first approach text mining of PubMed abstracts reveal statistically significant associations between miRNAs and both TFs and signal transduction gene classes. Secondly, prediction of miRNA targets in human and mouse 3’UTRs show enrichment only for TFs but not consistently across prediction methods for signal transduction or other gene classes. Furthermore, a random sample of 986 TarBase entries was scored for experimental evidence by manual inspection of the original papers, and enrichment for TFs was observed to increase with score. Low-scoring TarBase entries, where experimental evidence is anticorrelated miRNA:mRNA expression with predicted miRNA targets, appear not to select for real miRNA targets to any degree. Our manually validated text-mining results also suggests that miRNAs may be activated by more TFs than other classes of genes, as 7% of miRNA:TF co-occurrences in the literature were TFs activating miRNAs. This was confirmed when thirdly, we found enrichment for predicted, conserved TF binding sites in miRNA and TF genes compared to other gene classes. Conclusions We see enrichment of connections between miRNAs and TFs using several independent methods, suggestive of a network of mutual activating and suppressive regulation. We have also built regulatory networks (containing 2- and 3-loop motifs for mouse and human using predicted miRNA and TF binding sites and we have developed a web server

  10. Multiple independent analyses reveal only transcription factors as an enriched functional class associated with microRNAs

    DEFF Research Database (Denmark)

    Croft, Laurence J; Szklarczyk, Damian; Jensen, Lars J

    2012-01-01

    ABSTRACT: BACKGROUND: Transcription factors (TFs) have long been known to be principally activators of transcription in eukaryotes and prokaryotes. The growing awareness of the ubiquity of microRNAs (miRNAs) as suppressive regulators in eukaryotes, suggests the possibility of a mutual, preferential...

  11. The regulatory mechanism of fruit ripening revealed by analyses of direct targets of the tomato MADS-box transcription factor RIPENING INHIBITOR.

    Science.gov (United States)

    Fujisawa, Masaki; Ito, Yasuhiro

    2013-06-01

    The developmental process of ripening is unique to fleshy fruits and a key factor in fruit quality. The tomato (Solanum lycopersicum) MADS-box transcription factor RIPENING INHIBITOR (RIN), one of the earliest-acting ripening regulators, is required for broad aspects of ripening, including ethylene-dependent and -independent pathways. However, our knowledge of direct RIN target genes has been limited, considering the broad effects of RIN on ripening. In a recent work published in The Plant Cell, we identified 241 direct RIN target genes by chromatin immunoprecipitation coupled with DNA microarray (ChIP-chip) and transcriptome analysis. Functional classification of the targets revealed that RIN participates in the regulation of many biological processes including well-known ripening processes such as climacteric ethylene production and lycopene accumulation. In addition, we found that ethylene is required for the full expression of RIN and several RIN-targeting transcription factor genes at the ripening stage. Here, based on our recently published findings and additional data, we discuss the ripening processes regulated by RIN and the interplay between RIN and ethylene.

  12. Systematic two-hybrid and comparative proteomic analyses reveal novel yeast pre-mRNA splicing factors connected to Prp19.

    Directory of Open Access Journals (Sweden)

    Liping Ren

    Full Text Available Prp19 is the founding member of the NineTeen Complex, or NTC, which is a spliceosomal subcomplex essential for spliceosome activation. To define Prp19 connectivity and dynamic protein interactions within the spliceosome, we systematically queried the Saccharomyces cerevisiae proteome for Prp19 WD40 domain interaction partners by two-hybrid analysis. We report that in addition to S. cerevisiae Cwc2, the splicing factor Prp17 binds directly to the Prp19 WD40 domain in a 1:1 ratio. Prp17 binds simultaneously with Cwc2 indicating that it is part of the core NTC complex. We also find that the previously uncharacterized protein Urn1 (Dre4 in Schizosaccharomyces pombe directly interacts with Prp19, and that Dre4 is conditionally required for pre-mRNA splicing in S. pombe. S. pombe Dre4 and S. cerevisiae Urn1 co-purify U2, U5, and U6 snRNAs and multiple splicing factors, and dre4Δ and urn1Δ strains display numerous negative genetic interactions with known splicing mutants. The S. pombe Prp19-containing Dre4 complex co-purifies three previously uncharacterized proteins that participate in pre-mRNA splicing, likely before spliceosome activation. Our multi-faceted approach has revealed new low abundance splicing factors connected to NTC function, provides evidence for distinct Prp19 containing complexes, and underscores the role of the Prp19 WD40 domain as a splicing scaffold.

  13. Comparative transcriptome combined with morpho-physiological analyses revealed key factors for differential cadmium accumulation in two contrasting sweet sorghum genotypes.

    Science.gov (United States)

    Feng, Juanjuan; Jia, Weitao; Lv, Sulian; Bao, Hexigeduleng; Miao, Fangfang; Zhang, Xuan; Wang, Jinhui; Li, Jihong; Li, Dongsheng; Zhu, Cheng; Li, Shizhong; Li, Yinxin

    2017-07-13

    Cadmium (Cd) is a widespread soil contaminant threatening human health. As an ideal energy plant, sweet sorghum (Sorghum bicolor (L.) Moench) has great potential in phytoremediation of Cd-polluted soils, although the molecular mechanisms are largely unknown. In this study, key factors responsible for differential Cd accumulation between two contrasting sweet sorghum genotypes (high-Cd accumulation one H18, and low-Cd accumulation one L69) were investigated. H18 exhibited a much higher ability of Cd uptake and translocation than L69. Furthermore, Cd uptake through symplasmic pathway and Cd concentrations in xylem sap were both higher in H18 than those in L69. Root anatomy observation found the endodermal apoplasmic barriers were much stronger in L69, which may restrict the Cd loading into xylem. The molecular mechanisms underlying these morpho-physiological traits were further dissected by comparative transcriptome analysis. Many genes involved in cell wall modification and heavy metal transport were found to be Cd-responsive DEGs and/or DEGs between these two genotypes. KEGG pathway analysis found phenylpropanoid biosynthesis pathway was over-represented, indicating this pathway may play important roles in differential Cd accumulation between two genotypes. Based on these results, a schematic representation of main processes involved in differential Cd uptake and translocation in H18 and L69 is proposed, which suggests that higher Cd accumulation in H18 depends on a multilevel coordination of efficient Cd uptake and transport, including efficient root uptake and xylem loading, less root cell wall binding, and weaker endodermal apoplasmic barriers. © 2017 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

  14. Summary of the analyses for recovery factors

    Science.gov (United States)

    Verma, Mahendra K.

    2017-07-17

    IntroductionIn order to determine the hydrocarbon potential of oil reservoirs within the U.S. sedimentary basins for which the carbon dioxide enhanced oil recovery (CO2-EOR) process has been considered suitable, the CO2 Prophet model was chosen by the U.S. Geological Survey (USGS) to be the primary source for estimating recovery-factor values for individual reservoirs. The choice was made because of the model’s reliability and the ease with which it can be used to assess a large number of reservoirs. The other two approaches—the empirical decline curve analysis (DCA) method and a review of published literature on CO2-EOR projects—were deployed to verify the results of the CO2 Prophet model. This chapter discusses the results from CO2 Prophet (chapter B, by Emil D. Attanasi, this report) and compares them with results from decline curve analysis (chapter C, by Hossein Jahediesfanjani) and those reported in the literature for selected reservoirs with adequate data for analyses (chapter D, by Ricardo A. Olea).To estimate the technically recoverable hydrocarbon potential for oil reservoirs where CO2-EOR has been applied, two of the three approaches—CO2 Prophet modeling and DCA—do not include analysis of economic factors, while the third approach—review of published literature—implicitly includes economics. For selected reservoirs, DCA has provided estimates of the technically recoverable hydrocarbon volumes, which, in combination with calculated amounts of original oil in place (OOIP), helped establish incremental CO2-EOR recovery factors for individual reservoirs.The review of published technical papers and reports has provided substantial information on recovery factors for 70 CO2-EOR projects that are either commercially profitable or classified as pilot tests. When comparing the results, it is important to bear in mind the differences and limitations of these three approaches.

  15. (Capsicum annuum L.) genotypes revealed by AFLP analyses

    African Journals Online (AJOL)

    STORAGESEVER

    2009-09-15

    Sep 15, 2009 ... (26%) polymorphic AFLP markers out of total 215 DNA fragments from 4 primer pairs were used to define the genetic ... assisted selection and genome mapping. (Paran et al., ... of the consequences of breeding and selection for the production of ..... Comparative analyses of genetic diversities within tomato.

  16. Intron analyses reveal multiple calmodulin copies in Littorina.

    Science.gov (United States)

    Simpson, R J; Wilding, C S; Grahame, J

    2005-04-01

    Intron 3 and the flanking exons of the calmodulin gene have been amplified, cloned, and sequenced from 18 members of the gastropod genus Littorina. From the 48 sequences, at least five different gene copies have been identified and their functionality characterized using a strategy based upon the potential protein product predicted from flanking exon data. The functionality analyses suggest that four of the genes code for functional copies of calmodulin. All five copies have been identified across a wide range of littorinid species although not ubiquitously. Using this novel approach based on intron sequences, we have identified an unprecedented number of potential calmodulin copies in Littorina, exceeding that reported for any other invertebrate. This suggests a higher number of, and more ancient, gene duplications than previously detected in a single genus.

  17. Network analyses reveal novel aspects of ALS pathogenesis.

    Directory of Open Access Journals (Sweden)

    Mario Sanhueza

    2015-03-01

    Full Text Available Amyotrophic Lateral Sclerosis (ALS is a fatal neurodegenerative disease characterized by selective loss of motor neurons, muscle atrophy and paralysis. Mutations in the human VAMP-associated protein B (hVAPB cause a heterogeneous group of motor neuron diseases including ALS8. Despite extensive research, the molecular mechanisms underlying ALS pathogenesis remain largely unknown. Genetic screens for key interactors of hVAPB activity in the intact nervous system, however, represent a fundamental approach towards understanding the in vivo function of hVAPB and its role in ALS pathogenesis. Targeted expression of the disease-causing allele leads to neurodegeneration and progressive decline in motor performance when expressed in the adult Drosophila, eye or in its entire nervous system, respectively. By using these two phenotypic readouts, we carried out a systematic survey of the Drosophila genome to identify modifiers of hVAPB-induced neurotoxicity. Modifiers cluster in a diverse array of biological functions including processes and genes that have been previously linked to hVAPB function, such as proteolysis and vesicular trafficking. In addition to established mechanisms, the screen identified endocytic trafficking and genes controlling proliferation and apoptosis as potent modifiers of ALS8-mediated defects. Surprisingly, the list of modifiers was mostly enriched for proteins linked to lipid droplet biogenesis and dynamics. Computational analysis reveals that most modifiers can be linked into a complex network of interacting genes, and that the human genes homologous to the Drosophila modifiers can be assembled into an interacting network largely overlapping with that in flies. Identity markers of the endocytic process were also found to abnormally accumulate in ALS patients, further supporting the relevance of the fly data for human biology. Collectively, these results not only lead to a better understanding of hVAPB function but also point to

  18. Genome size analyses of Pucciniales reveal the largest fungal genomes

    Directory of Open Access Journals (Sweden)

    Silvia eTavares

    2014-08-01

    Full Text Available Rust fungi (Basidiomycota, Pucciniales are biotrophic plant pathogens which exhibit diverse complexities in their life cycles and host ranges. The completion of genome sequencing of a few rust fungi has revealed the occurrence of large genomes. Sequencing efforts for other rust fungi have been hampered by uncertainty concerning their genome sizes. Flow cytometry was recently applied to estimate the genome size of a few rust fungi, and confirmed the occurrence of large genomes in this order (averaging 151.5 Mbp, while the average for Basidiomycota was 49.9 Mbp and was 37.7 Mbp for all fungi. In this work, we have used an innovative and simple approach to simultaneously isolate nuclei from the rust and its host plant in order to estimate the genome size of 30 rust species by flow cytometry. Genome sizes varied over 10-fold, from 70 to 893 Mbp, with an average genome size value of 380.2 Mbp. Compared to the genome sizes of over 1,800 fungi, Gymnosporangium confusum possesses the largest fungal genome ever reported (893.2 Mbp. Moreover, even the smallest rust genome determined in this study is larger than the vast majority of fungal genomes (94 %. The average genome size of the Pucciniales is now of 305.5 Mbp, while the average Basidiomycota genome size has shifted to 70.4 Mbp and the average for all fungi reached 44.2 Mbp. Despite the fact that no correlation could be drawn between the genome sizes, the phylogenomics or the life cycle of rust fungi, it is interesting to note that rusts with Fabaceae hosts present genomes clearly larger than those with Poaceae hosts. Although this study comprises only a small fraction of the more than 7,000 rust species described, it seems already evident that the Pucciniales represent a group where genome size expansion could be a common characteristic. This is in sharp contrast to sister taxa, placing this order in a relevant position in fungal genomics research.

  19. Cross-culturally recurrent personality factors : Analyses of three factors

    NARCIS (Netherlands)

    De Raad, B; Peabody, D

    2005-01-01

    This study proceeds from an earlier one that examined the 'Big Five' factors (Peabody & De Raad, 2002). That study considered the substantive nature of five factors from six European psycholexical studies. The results supported Big Five Factor III (Conscientiousness), but Factors I (Extraversion) an

  20. Trends Analyses for Several Factors Affected by Tropical Cyclones

    Directory of Open Access Journals (Sweden)

    Md. T. Islam

    2011-01-01

    Full Text Available Problem statement: This study presents an analytical investigation for the trends of several factors such as number of death of peoples, damages of wealth, flood surge heights, wind speed and radius of the severe storm due to tropical cyclones in Bangladesh. Approach: The study is performed by conducting the field visits to cyclone site, collected data and information on damages and deaths of peoples during field visits, necessary data related to tropical cyclones obtained from available publications and news-study. The data since the period of the independence of Bangladesh (nearly 40 years are analyzed. Results: The analyses showed that the 17 major cyclones have been occurred since 1970. Among these 17 major cyclones, the 5 cyclones were tragically severe that killed over 400 thousand peoples. It is observed that the coast of the Bay of Bengal is particularly vulnerable to tropical cyclones. It is revealed that Bangladesh is more vulnerable to devastating cyclones in the recent years because the frequency of the severe cyclones has increased remarkably. Conclusion/Recommendation: The return period of the major cyclones was decreased drastically in recent years and the country, especially, the Bengal Bay is predominantly helpless during the cyclone seasons.

  1. Multi-tissue omics analyses reveal molecular regulatory networks for puberty in composite beef cattle.

    Science.gov (United States)

    Cánovas, Angela; Reverter, Antonio; DeAtley, Kasey L; Ashley, Ryan L; Colgrave, Michelle L; Fortes, Marina R S; Islas-Trejo, Alma; Lehnert, Sigrid; Porto-Neto, Laercio; Rincón, Gonzalo; Silver, Gail A; Snelling, Warren M; Medrano, Juan F; Thomas, Milton G

    2014-01-01

    Puberty is a complex physiological event by which animals mature into an adult capable of sexual reproduction. In order to enhance our understanding of the genes and regulatory pathways and networks involved in puberty, we characterized the transcriptome of five reproductive tissues (i.e. hypothalamus, pituitary gland, ovary, uterus, and endometrium) as well as tissues known to be relevant to growth and metabolism needed to achieve puberty (i.e., longissimus dorsi muscle, adipose, and liver). These tissues were collected from pre- and post-pubertal Brangus heifers (3/8 Brahman; Bos indicus x 5/8 Angus; Bos taurus) derived from a population of cattle used to identify quantitative trait loci associated with fertility traits (i.e., age of first observed corpus luteum (ACL), first service conception (FSC), and heifer pregnancy (HPG)). In order to exploit the power of complementary omics analyses, pre- and post-puberty co-expression gene networks were constructed by combining the results from genome-wide association studies (GWAS), RNA-Seq, and bovine transcription factors. Eight tissues among pre-pubertal and post-pubertal Brangus heifers revealed 1,515 differentially expressed and 943 tissue-specific genes within the 17,832 genes confirmed by RNA-Seq analysis. The hypothalamus experienced the most notable up-regulation of genes via puberty (i.e., 204 out of 275 genes). Combining the results of GWAS and RNA-Seq, we identified 25 loci containing a single nucleotide polymorphism (SNP) associated with ACL, FSC, and (or) HPG. Seventeen of these SNP were within a gene and 13 of the genes were expressed in uterus or endometrium. Multi-tissue omics analyses revealed 2,450 co-expressed genes relative to puberty. The pre-pubertal network had 372,861 connections whereas the post-pubertal network had 328,357 connections. A sub-network from this process revealed key transcriptional regulators (i.e., PITX2, FOXA1, DACH2, PROP1, SIX6, etc.). Results from these multi-tissue omics

  2. Multi-tissue omics analyses reveal molecular regulatory networks for puberty in composite beef cattle.

    Directory of Open Access Journals (Sweden)

    Angela Cánovas

    Full Text Available Puberty is a complex physiological event by which animals mature into an adult capable of sexual reproduction. In order to enhance our understanding of the genes and regulatory pathways and networks involved in puberty, we characterized the transcriptome of five reproductive tissues (i.e. hypothalamus, pituitary gland, ovary, uterus, and endometrium as well as tissues known to be relevant to growth and metabolism needed to achieve puberty (i.e., longissimus dorsi muscle, adipose, and liver. These tissues were collected from pre- and post-pubertal Brangus heifers (3/8 Brahman; Bos indicus x 5/8 Angus; Bos taurus derived from a population of cattle used to identify quantitative trait loci associated with fertility traits (i.e., age of first observed corpus luteum (ACL, first service conception (FSC, and heifer pregnancy (HPG. In order to exploit the power of complementary omics analyses, pre- and post-puberty co-expression gene networks were constructed by combining the results from genome-wide association studies (GWAS, RNA-Seq, and bovine transcription factors. Eight tissues among pre-pubertal and post-pubertal Brangus heifers revealed 1,515 differentially expressed and 943 tissue-specific genes within the 17,832 genes confirmed by RNA-Seq analysis. The hypothalamus experienced the most notable up-regulation of genes via puberty (i.e., 204 out of 275 genes. Combining the results of GWAS and RNA-Seq, we identified 25 loci containing a single nucleotide polymorphism (SNP associated with ACL, FSC, and (or HPG. Seventeen of these SNP were within a gene and 13 of the genes were expressed in uterus or endometrium. Multi-tissue omics analyses revealed 2,450 co-expressed genes relative to puberty. The pre-pubertal network had 372,861 connections whereas the post-pubertal network had 328,357 connections. A sub-network from this process revealed key transcriptional regulators (i.e., PITX2, FOXA1, DACH2, PROP1, SIX6, etc.. Results from these multi

  3. Comparative Genome Analyses of Vibrio anguillarum Strains Reveal a Link with Pathogenicity Traits

    Science.gov (United States)

    Castillo, Daniel; Alvise, Paul D.; Xu, Ruiqi; Zhang, Faxing; Middelboe, Mathias

    2017-01-01

    ABSTRACT Vibrio anguillarum is a marine bacterium that can cause vibriosis in many fish and shellfish species, leading to high mortalities and economic losses in aquaculture. Although putative virulence factors have been identified, the mechanism of pathogenesis of V. anguillarum is not fully understood. Here, we analyzed whole-genome sequences of a collection of V. anguillarum strains and compared them to virulence of the strains as determined in larval challenge assays. Previously identified virulence factors were globally distributed among the strains, with some genetic diversity. However, the pan-genome revealed that six out of nine high-virulence strains possessed a unique accessory genome that was attributed to pathogenic genomic islands, prophage-like elements, virulence factors, and a new set of gene clusters involved in biosynthesis, modification, and transport of polysaccharides. In contrast, V. anguillarum strains that were medium to nonvirulent had a high degree of genomic homogeneity. Finally, we found that a phylogeny based on the core genomes clustered the strains with moderate to no virulence, while six out of nine high-virulence strains represented phylogenetically separate clusters. Hence, we suggest a link between genotype and virulence characteristics of Vibrio anguillarum, which can be used to unravel the molecular evolution of V. anguillarum and can also be important from survey and diagnostic perspectives. IMPORTANCE Comparative genome analysis of strains of a pathogenic bacterial species can be a powerful tool to discover acquisition of mobile genetic elements related to virulence. Here, we compared 28 V. anguillarum strains that differed in virulence in fish larval models. By pan-genome analyses, we found that six of nine highly virulent strains had a unique core and accessory genome. In contrast, V. anguillarum strains that were medium to nonvirulent had low genomic diversity. Integration of genomic and phenotypic features provides

  4. A combination of transcriptome and methylation analyses reveals embryologically-relevant candidate genes in MRKH patients

    Directory of Open Access Journals (Sweden)

    Riess Olaf

    2011-05-01

    Full Text Available Abstract Background The Mayer-Rokitansky-Küster-Hauser (MRKH syndrome is present in at least 1 out of 4,500 female live births and is the second most common cause for primary amenorrhea. It is characterized by vaginal and uterine aplasia in an XX individual with normal secondary characteristics. It has long been considered a sporadic anomaly, but familial clustering occurs. Several candidate genes have been studied although no single factor has yet been identified. Cases of discordant monozygotic twins suggest that the involvement of epigenetic factors is more likely. Methods Differences in gene expression and methylation patterns of uterine tissue between eight MRKH patients and eight controls were identified using whole-genome microarray analyses. Results obtained by expression and methylation arrays were confirmed by qRT-PCR and pyrosequencing. Results We delineated 293 differentially expressed and 194 differentially methylated genes of which nine overlap in both groups. These nine genes are mainly embryologically relevant for the development of the female genital tract. Conclusion Our study used, for the first time, a combined whole-genome expression and methylation approach to reveal the etiology of the MRKH syndrome. The findings suggest that either deficient estrogen receptors or the ectopic expression of certain HOXA genes might lead to abnormal development of the female reproductive tract. In utero exposure to endocrine disruptors or abnormally high maternal hormone levels might cause ectopic expression or anterior transformation of HOXA genes. It is, however, also possible that different factors influence the anti-Mullerian hormone promoter activity during embryological development causing regression of the Müllerian ducts. Thus, our data stimulate new research directions to decipher the pathogenic basis of MRKH syndrome.

  5. Comparative Genome Analyses of Vibrio anguillarum Strains Reveal a Link with Pathogenicity Traits.

    Science.gov (United States)

    Castillo, Daniel; Alvise, Paul D; Xu, Ruiqi; Zhang, Faxing; Middelboe, Mathias; Gram, Lone

    2017-01-01

    Vibrio anguillarum is a marine bacterium that can cause vibriosis in many fish and shellfish species, leading to high mortalities and economic losses in aquaculture. Although putative virulence factors have been identified, the mechanism of pathogenesis of V. anguillarum is not fully understood. Here, we analyzed whole-genome sequences of a collection of V. anguillarum strains and compared them to virulence of the strains as determined in larval challenge assays. Previously identified virulence factors were globally distributed among the strains, with some genetic diversity. However, the pan-genome revealed that six out of nine high-virulence strains possessed a unique accessory genome that was attributed to pathogenic genomic islands, prophage-like elements, virulence factors, and a new set of gene clusters involved in biosynthesis, modification, and transport of polysaccharides. In contrast, V. anguillarum strains that were medium to nonvirulent had a high degree of genomic homogeneity. Finally, we found that a phylogeny based on the core genomes clustered the strains with moderate to no virulence, while six out of nine high-virulence strains represented phylogenetically separate clusters. Hence, we suggest a link between genotype and virulence characteristics of Vibrio anguillarum, which can be used to unravel the molecular evolution of V. anguillarum and can also be important from survey and diagnostic perspectives. IMPORTANCE Comparative genome analysis of strains of a pathogenic bacterial species can be a powerful tool to discover acquisition of mobile genetic elements related to virulence. Here, we compared 28 V. anguillarum strains that differed in virulence in fish larval models. By pan-genome analyses, we found that six of nine highly virulent strains had a unique core and accessory genome. In contrast, V. anguillarum strains that were medium to nonvirulent had low genomic diversity. Integration of genomic and phenotypic features provides insights

  6. Hierarchical structure of the Sicilian goats revealed by Bayesian analyses of microsatellite information.

    Science.gov (United States)

    Siwek, M; Finocchiaro, R; Curik, I; Portolano, B

    2011-02-01

    Genetic structure and relationship amongst the main goat populations in Sicily (Girgentana, Derivata di Siria, Maltese and Messinese) were analysed using information from 19 microsatellite markers genotyped on 173 individuals. A posterior Bayesian approach implemented in the program STRUCTURE revealed a hierarchical structure with two clusters at the first level (Girgentana vs. Messinese, Derivata di Siria and Maltese), explaining 4.8% of variation (amovaФ(ST) estimate). Seven clusters nested within these first two clusters (further differentiations of Girgentana, Derivata di Siria and Maltese), explaining 8.5% of variation (amovaФ(SC) estimate). The analyses and methods applied in this study indicate their power to detect subtle population structure.

  7. Design factors analyses of second-loop PRHRS

    Directory of Open Access Journals (Sweden)

    ZHANG Hongyan

    2017-05-01

    Full Text Available In order to study the operating characteristics of a second-loop Passive Residual Heat Removal System (PRHRS, the transient thermal analysis code RELAP5 is used to build simulation models of the main coolant system and second-loop PRHRS. Transient calculations and comparative analyses under station blackout accident and one-side feed water line break accident conditions are conducted for three critical design factors of the second-loop PRHRS:design capacity, emergency makeup tank and isolation valve opening speed. The impacts of the discussed design factors on the operating characteristics of the second-loop PRHRS are summarized based on calculations and analyses. The analysis results indicate that the system safety and cooling rate should be taken into consideration in designing PRHRS's capacity,and water injection from emergency makeup tank to steam generator can provide advantage to system cooling in the event of accident,and system startup performance can be improved by reducing the opening speed of isolation valve. The results can provide references for the design of the second-loop PRHRS in nuclear power plants.

  8. Trophic positioning of meiofauna revealed by stable isotopes and food web analyses.

    Science.gov (United States)

    Schmid-Araya, Jenny M; Schmid, Peter E; Tod, Steven P; Esteban, Genoveva F

    2016-11-01

    Despite important advances in the ecology of river food webs, the strength and nature of the connection between the meio- and macrofaunal components of the web are still debated. Some unresolved issues are the effects of the inclusion of meiofaunal links and their temporal variations on the overall river food web properties, and the significance of autochthonous and allochthonous material for these components. In the present study, we conducted analyses of gut content of macro- and meiofauna and stable isotope analyses of meiofauna to examine seasonal food webs of a chalk stream. The results of the gut content analyses, confirmed by the δ(13) C signatures, revealed a seasonal shift from a dependence on autochthonous (biofilm) to allochthonous food sources. Here, we demonstrate that aggregating basal or meiofaunal species into single categories affects key web properties such as web size, links, linkage density, and predator-prey ratios. More importantly, seasonal variation in attributes characterized the entire web and these changes persist regardless of taxonomic resolution. Furthermore, our analyses evidenced discrete variations in δ(15) N across the meiofauna community with a trophic structure that confirms gut content analyses, placing the meiofauna high in the food web. We, therefore, conclude that small-body-sized taxa can occur high in dynamic river food webs, questioning assumptions that trophic position increases with body size and that webs are static. © 2016 by the Ecological Society of America.

  9. Time-Series Analyses of Transcriptomes and Proteomes Reveal Molecular Networks Underlying Oil Accumulation in Canola

    Science.gov (United States)

    Wan, Huafang; Cui, Yixin; Ding, Yijuan; Mei, Jiaqin; Dong, Hongli; Zhang, Wenxin; Wu, Shiqi; Liang, Ying; Zhang, Chunyu; Li, Jiana; Xiong, Qing; Qian, Wei

    2017-01-01

    Understanding the regulation of lipid metabolism is vital for genetic engineering of canola (Brassica napus L.) to increase oil yield or modify oil composition. We conducted time-series analyses of transcriptomes and proteomes to uncover the molecular networks associated with oil accumulation and dynamic changes in these networks in canola. The expression levels of genes and proteins were measured at 2, 4, 6, and 8 weeks after pollination (WAP). Our results show that the biosynthesis of fatty acids is a dominant cellular process from 2 to 6 WAP, while the degradation mainly happens after 6 WAP. We found that genes in almost every node of fatty acid synthesis pathway were significantly up-regulated during oil accumulation. Moreover, significant expression changes of two genes, acetyl-CoA carboxylase and acyl-ACP desaturase, were detected on both transcriptomic and proteomic levels. We confirmed the temporal expression patterns revealed by the transcriptomic analyses using quantitative real-time PCR experiments. The gene set association analysis show that the biosynthesis of fatty acids and unsaturated fatty acids are the most significant biological processes from 2-4 WAP and 4-6 WAP, respectively, which is consistent with the results of time-series analyses. These results not only provide insight into the mechanisms underlying lipid metabolism, but also reveal novel candidate genes that are worth further investigation for their values in the genetic engineering of canola. PMID:28119706

  10. Metabolomic Analyses of Leishmania Reveal Multiple Species Differences and Large Differences in Amino Acid Metabolism.

    Directory of Open Access Journals (Sweden)

    Gareth D Westrop

    Full Text Available Comparative genomic analyses of Leishmania species have revealed relatively minor heterogeneity amongst recognised housekeeping genes and yet the species cause distinct infections and pathogenesis in their mammalian hosts. To gain greater information on the biochemical variation between species, and insights into possible metabolic mechanisms underpinning visceral and cutaneous leishmaniasis, we have undertaken in this study a comparative analysis of the metabolomes of promastigotes of L. donovani, L. major and L. mexicana. The analysis revealed 64 metabolites with confirmed identity differing 3-fold or more between the cell extracts of species, with 161 putatively identified metabolites differing similarly. Analysis of the media from cultures revealed an at least 3-fold difference in use or excretion of 43 metabolites of confirmed identity and 87 putatively identified metabolites that differed to a similar extent. Strikingly large differences were detected in their extent of amino acid use and metabolism, especially for tryptophan, aspartate, arginine and proline. Major pathways of tryptophan and arginine catabolism were shown to be to indole-3-lactate and arginic acid, respectively, which were excreted. The data presented provide clear evidence on the value of global metabolomic analyses in detecting species-specific metabolic features, thus application of this technology should be a major contributor to gaining greater understanding of how pathogens are adapted to infecting their hosts.

  11. Mitochondrial DNA analyses reveal low genetic diversity in Culex quinquefasciatus from residential areas in Malaysia.

    Science.gov (United States)

    Low, V L; Lim, P E; Chen, C D; Lim, Y A L; Tan, T K; Norma-Rashid, Y; Lee, H L; Sofian-Azirun, M

    2014-06-01

    The present study explored the intraspecific genetic diversity, dispersal patterns and phylogeographic relationships of Culex quinquefasciatus Say (Diptera: Culicidae) in Malaysia using reference data available in GenBank in order to reveal this species' phylogenetic relationships. A statistical parsimony network of 70 taxa aligned as 624 characters of the cytochrome c oxidase subunit I (COI) gene and 685 characters of the cytochrome c oxidase subunit II (COII) gene revealed three haplotypes (A1-A3) and four haplotypes (B1-B4), respectively. The concatenated sequences of both COI and COII genes with a total of 1309 characters revealed seven haplotypes (AB1-AB7). Analysis using tcs indicated that haplotype AB1 was the common ancestor and the most widespread haplotype in Malaysia. The genetic distance based on concatenated sequences of both COI and COII genes ranged from 0.00076 to 0.00229. Sequence alignment of Cx. quinquefasciatus from Malaysia and other countries revealed four haplotypes (AA1-AA4) by the COI gene and nine haplotypes (BB1-BB9) by the COII gene. Phylogenetic analyses demonstrated that Malaysian Cx. quinquefasciatus share the same genetic lineage as East African and Asian Cx. quinquefasciatus. This study has inferred the genetic lineages, dispersal patterns and hypothetical ancestral genotypes of Cx. quinquefasciatus.

  12. An Illumination Modeling System for Human Factors Analyses

    Science.gov (United States)

    Huynh, Thong; Maida, James C.; Bond, Robert L. (Technical Monitor)

    2002-01-01

    Seeing is critical to human performance. Lighting is critical for seeing. Therefore, lighting is critical to human performance. This is common sense, and here on earth, it is easily taken for granted. However, on orbit, because the sun will rise or set every 45 minutes on average, humans working in space must cope with extremely dynamic lighting conditions. Contrast conditions of harsh shadowing and glare is also severe. The prediction of lighting conditions for critical operations is essential. Crew training can factor lighting into the lesson plans when necessary. Mission planners can determine whether low-light video cameras are required or whether additional luminaires need to be flown. The optimization of the quantity and quality of light is needed because of the effects on crew safety, on electrical power and on equipment maintainability. To address all of these issues, an illumination modeling system has been developed by the Graphics Research and Analyses Facility (GRAF) and Lighting Environment Test Facility (LETF) in the Space Human Factors Laboratory at NASA Johnson Space Center. The system uses physically based ray tracing software (Radiance) developed at Lawrence Berkeley Laboratories, a human factors oriented geometric modeling system (PLAID) and an extensive database of humans and environments. Material reflectivity properties of major surfaces and critical surfaces are measured using a gonio-reflectometer. Luminaires (lights) are measured for beam spread distribution, color and intensity. Video camera performances are measured for color and light sensitivity. 3D geometric models of humans and the environment are combined with the material and light models to form a system capable of predicting lighting conditions and visibility conditions in space.

  13. [Analyses prognostic factors relevant to sudden sensorineural hearing loss].

    Science.gov (United States)

    Wang, Jun; Xiao, Shuifang; Zeng, Zhengang; Zhen, Zhen; Zhang, Xuexi; Lin, Feng; Dong, Mingmin; Lu, Wei; Qin, Zhaobing; Zuo, Bin; Bai, Xianfeng

    2015-06-01

    To investigate the prognostic factors relevant to sudden sensorineural hearing loss. The internationally accepted standardized clinical research methods, unified design, and unified program were adopted to conduct the prospective clinical multi-center study. The sudden deafness patients between 18 to 65 years old, with the course of this disorder less than two weeks, and without any medical treatments were collected, and then, divided into four types according to the hearing curve: type A, acute sensorineural hearing loss in low tone frequencies; type B, acute sensorineural hearing loss in high tone frequencies; type C, acute sensorineural hearing loss in all frequencies; and type D, total deafness. The factors, in terms of age, gender, type of initial audiogram, time delay before the first visit, and severity of hearing loss, were included in the analyses. A total of 1 024 cases with single side sudden deafness were collected in the study from 33 hospitals in China from August 2007 to October 2011, inclusive of for 492 males (48.05%) and 532 females (51.95%). The average age was (41.2 ± 12.8) years old. There were 553 cases (54.00%) in left ear, and 471 cases (46.00%) in right ear. The curative effects of different types were shown as follows: the type in low tone frequencies had the highest rate of 90.73%, the type in all frequencies was 82.59%; the type of total deafness was 70.29%; and the type in high tone frequencies had the lowest rate of 65.96%. It had significant difference of the effective rate between different types (χ(2) = 231.58, P = 0.000). Age, time delay before first visit, and severity of initial hearing loss were significantly correlated with hearing improvement. Initial audiogram of SSNHL might predict hearing recovery. The young in age and a short time delay before starting treatment are positive prognostic factors for hearing recovery in SSNHL. The initial severity of hearing loss is negative prognostic factor of hearing recovery.

  14. Coupled electrophysiological recording and single cell transcriptome analyses revealed molecular mechanisms underlying neuronal maturation

    Directory of Open Access Journals (Sweden)

    Xiaoying Chen

    2016-02-01

    Full Text Available ABSTRACT The mammalian brain is heterogeneous, containing billions of neurons and trillions of synapses forming various neural circuitries, through which sense, movement, thought, and emotion arise. The cellular heterogeneity of the brain has made it difficult to study the molecular logic of neural circuitry wiring, pruning, activation, and plasticity, until recently, transcriptome analyses with single cell resolution makes decoding of gene regulatory networks underlying aforementioned circuitry properties possible. Here we report success in performing both electrophysiological and whole-genome transcriptome analyses on single human neurons in culture. Using Weighted Gene Coexpression Network Analyses (WGCNA, we identified gene clusters highly correlated with neuronal maturation judged by electrophysiological characteristics. A tight link between neuronal maturation and genes involved in ubiquitination and mitochondrial function was revealed. Moreover, we identified a list of candidate genes, which could potentially serve as biomarkers for neuronal maturation. Coupled electrophysiological recording and single cell transcriptome analysis will serve as powerful tools in the future to unveil molecular logics for neural circuitry functions.

  15. Integrated Analyses Resolve Conflicts over Squamate Reptile Phylogeny and Reveal Unexpected Placements for Fossil Taxa

    Science.gov (United States)

    Reeder, Tod W.; Townsend, Ted M.; Mulcahy, Daniel G.; Noonan, Brice P.; Wood, Perry L.; Sites, Jack W.; Wiens, John J.

    2015-01-01

    Squamate reptiles (lizards and snakes) are a pivotal group whose relationships have become increasingly controversial. Squamates include >9000 species, making them the second largest group of terrestrial vertebrates. They are important medicinally and as model systems for ecological and evolutionary research. However, studies of squamate biology are hindered by uncertainty over their relationships, and some consider squamate phylogeny unresolved, given recent conflicts between molecular and morphological results. To resolve these conflicts, we expand existing morphological and molecular datasets for squamates (691 morphological characters and 46 genes, for 161 living and 49 fossil taxa, including a new set of 81 morphological characters and adding two genes from published studies) and perform integrated analyses. Our results resolve higher-level relationships as indicated by molecular analyses, and reveal hidden morphological support for the molecular hypothesis (but not vice-versa). Furthermore, we find that integrating molecular, morphological, and paleontological data leads to surprising placements for two major fossil clades (Mosasauria and Polyglyphanodontia). These results further demonstrate the importance of combining fossil and molecular information, and the potential problems of estimating the placement of fossil taxa from morphological data alone. Thus, our results caution against estimating fossil relationships without considering relevant molecular data, and against placing fossils into molecular trees (e.g. for dating analyses) without considering the possible impact of molecular data on their placement. PMID:25803280

  16. Integrated analyses resolve conflicts over squamate reptile phylogeny and reveal unexpected placements for fossil taxa.

    Science.gov (United States)

    Reeder, Tod W; Townsend, Ted M; Mulcahy, Daniel G; Noonan, Brice P; Wood, Perry L; Sites, Jack W; Wiens, John J

    2015-01-01

    Squamate reptiles (lizards and snakes) are a pivotal group whose relationships have become increasingly controversial. Squamates include >9000 species, making them the second largest group of terrestrial vertebrates. They are important medicinally and as model systems for ecological and evolutionary research. However, studies of squamate biology are hindered by uncertainty over their relationships, and some consider squamate phylogeny unresolved, given recent conflicts between molecular and morphological results. To resolve these conflicts, we expand existing morphological and molecular datasets for squamates (691 morphological characters and 46 genes, for 161 living and 49 fossil taxa, including a new set of 81 morphological characters and adding two genes from published studies) and perform integrated analyses. Our results resolve higher-level relationships as indicated by molecular analyses, and reveal hidden morphological support for the molecular hypothesis (but not vice-versa). Furthermore, we find that integrating molecular, morphological, and paleontological data leads to surprising placements for two major fossil clades (Mosasauria and Polyglyphanodontia). These results further demonstrate the importance of combining fossil and molecular information, and the potential problems of estimating the placement of fossil taxa from morphological data alone. Thus, our results caution against estimating fossil relationships without considering relevant molecular data, and against placing fossils into molecular trees (e.g. for dating analyses) without considering the possible impact of molecular data on their placement.

  17. Time series analyses reveal environmental and fisheries controls on Atlantic horse mackerel (Trachurus trachurus) catch rates

    Science.gov (United States)

    Leitão, Francisco

    2015-12-01

    Time-series models (Dynamic factorial analyses and; Min/max autocorrelation factor analysis) were used to explore the relative influences of environmental variables and fishing pressure of trawl, seine and artisanal fleets on catch rates on Trachurus trachurus in ICES IXa sub-divisions (IXaCN-North coast; IXa- CS-South coast; IXaS-Algarve, South coast, Algarve). Fishing effort influenced catch rates in all areas with a 2 year lag and fishing pressure for each area was related to specific fleet sectors effort. In IXaCN, winter upwelling (spawning peak) and both summer northerly wind and wind magnitude (outside of the spawning peak) were strongly correlated with catch rates. In IXaCS summer/autumn westerly winds were related with catch rates. Northerly winds in spring, upwelling and SST (winter and autumn) were related with catch rates in IXaS-Algarve. For species with a long spawning season such as horse mackerel, seasonal analyses at broad regional scales can detract from a better understanding of variability in short term sub-stock catch rates. Favorable environmental conditions, even during seasons with low spawning activity can positively affect catch rates. Ignoring the role of regional oceanographic features on the spatial distribution of the sub-stocks when analysing variability in catch rates can lead to poor inferences about the productivity of the populations.

  18. Genome-wide analyses reveal a role for peptide hormones in planarian germline development.

    Directory of Open Access Journals (Sweden)

    James J Collins

    Full Text Available Bioactive peptides (i.e., neuropeptides or peptide hormones represent the largest class of cell-cell signaling molecules in metazoans and are potent regulators of neural and physiological function. In vertebrates, peptide hormones play an integral role in endocrine signaling between the brain and the gonads that controls reproductive development, yet few of these molecules have been shown to influence reproductive development in invertebrates. Here, we define a role for peptide hormones in controlling reproductive physiology of the model flatworm, the planarian Schmidtea mediterranea. Based on our observation that defective neuropeptide processing results in defects in reproductive system development, we employed peptidomic and functional genomic approaches to characterize the planarian peptide hormone complement, identifying 51 prohormone genes and validating 142 peptides biochemically. Comprehensive in situ hybridization analyses of prohormone gene expression revealed the unanticipated complexity of the flatworm nervous system and identified a prohormone specifically expressed in the nervous system of sexually reproducing planarians. We show that this member of the neuropeptide Y superfamily is required for the maintenance of mature reproductive organs and differentiated germ cells in the testes. Additionally, comparative analyses of our biochemically validated prohormones with the genomes of the parasitic flatworms Schistosoma mansoni and Schistosoma japonicum identified new schistosome prohormones and validated half of all predicted peptide-encoding genes in these parasites. These studies describe the peptide hormone complement of a flatworm on a genome-wide scale and reveal a previously uncharacterized role for peptide hormones in flatworm reproduction. Furthermore, they suggest new opportunities for using planarians as free-living models for understanding the reproductive biology of flatworm parasites.

  19. Genomic and secretomic analyses reveal unique features of the lignocellulolytic enzyme system of Penicillium decumbens.

    Science.gov (United States)

    Liu, Guodong; Zhang, Lei; Wei, Xiaomin; Zou, Gen; Qin, Yuqi; Ma, Liang; Li, Jie; Zheng, Huajun; Wang, Shengyue; Wang, Chengshu; Xun, Luying; Zhao, Guo-Ping; Zhou, Zhihua; Qu, Yinbo

    2013-01-01

    Many Penicillium species could produce extracellular enzyme systems with good lignocellulose hydrolysis performance. However, these species and their enzyme systems are still poorly understood and explored due to the lacking of genetic information. Here, we present the genomic and secretomic analyses of Penicillium decumbens that has been used in industrial production of lignocellulolytic enzymes in China for more than fifteen years. Comparative genomics analysis with the phylogenetically most similar species Penicillium chrysogenum revealed that P. decumbens has evolved with more genes involved in plant cell wall degradation, but fewer genes in cellular metabolism and regulation. Compared with the widely used cellulase producer Trichoderma reesei, P. decumbens has a lignocellulolytic enzyme system with more diverse components, particularly for cellulose binding domain-containing proteins and hemicellulases. Further, proteomic analysis of secretomes revealed that P. decumbens produced significantly more lignocellulolytic enzymes in the medium with cellulose-wheat bran as the carbon source than with glucose. The results expand our knowledge on the genetic information of lignocellulolytic enzyme systems in Penicillium species, and will facilitate rational strain improvement for the production of highly efficient enzyme systems used in lignocellulose utilization from Penicillium species.

  20. Genomic and secretomic analyses reveal unique features of the lignocellulolytic enzyme system of Penicillium decumbens.

    Directory of Open Access Journals (Sweden)

    Guodong Liu

    Full Text Available Many Penicillium species could produce extracellular enzyme systems with good lignocellulose hydrolysis performance. However, these species and their enzyme systems are still poorly understood and explored due to the lacking of genetic information. Here, we present the genomic and secretomic analyses of Penicillium decumbens that has been used in industrial production of lignocellulolytic enzymes in China for more than fifteen years. Comparative genomics analysis with the phylogenetically most similar species Penicillium chrysogenum revealed that P. decumbens has evolved with more genes involved in plant cell wall degradation, but fewer genes in cellular metabolism and regulation. Compared with the widely used cellulase producer Trichoderma reesei, P. decumbens has a lignocellulolytic enzyme system with more diverse components, particularly for cellulose binding domain-containing proteins and hemicellulases. Further, proteomic analysis of secretomes revealed that P. decumbens produced significantly more lignocellulolytic enzymes in the medium with cellulose-wheat bran as the carbon source than with glucose. The results expand our knowledge on the genetic information of lignocellulolytic enzyme systems in Penicillium species, and will facilitate rational strain improvement for the production of highly efficient enzyme systems used in lignocellulose utilization from Penicillium species.

  1. Comparative sequence and genetic analyses of asparagus BACs reveal no microsynteny with onion or rice.

    Science.gov (United States)

    Jakse, Jernej; Telgmann, Alexa; Jung, Christian; Khar, Anil; Melgar, Sergio; Cheung, Foo; Town, Christopher D; Havey, Michael J

    2006-12-01

    The Poales (includes the grasses) and Asparagales [includes onion (Allium cepa L.) and asparagus (Asparagus officinalis L.)] are the two most economically important monocot orders. The Poales are a member of the commelinoid monocots, a group of orders sister to the Asparagales. Comparative genomic analyses have revealed a high degree of synteny among the grasses; however, it is not known if this synteny extends to other major monocot groups such as the Asparagales. Although we previously reported no evidence for synteny at the recombinational level between onion and rice, microsynteny may exist across shorter genomic regions in the grasses and Asparagales. We sequenced nine asparagus BACs to reveal physically linked genic-like sequences and determined their most similar positions in the onion and rice genomes. Four of the asparagus BACs were selected using molecular markers tightly linked to the sex-determining M locus on chromosome 5 of asparagus. These BACs possessed only two putative coding regions and had long tracts of degenerated retroviral elements and transposons. Five asparagus BACs were selected after hybridization of three onion cDNAs that mapped to three different onion chromosomes. Genic-like sequences that were physically linked on the cDNA-selected BACs or genetically linked on the M-linked BACs showed significant similarities (e < -20) to expressed sequences on different rice chromosomes, revealing no evidence for microsynteny between asparagus and rice across these regions. Genic-like sequences that were linked in asparagus were used to identify highly similar (e < -20) expressed sequence tags (ESTs) of onion. These onion ESTs mapped to different onion chromosomes and no relationship was observed between physical or genetic linkages in asparagus and genetic linkages in onion. These results further indicate that synteny among grass genomes does not extend to a sister order in the monocots and that asparagus may not be an appropriate smaller genome

  2. Comparative Genome Analyses of Vibrio anguillarum Strains Reveal a Link with Pathogenicity Traits

    DEFF Research Database (Denmark)

    Castillo, Daniel; D'Alvise, Paul; Xu, Ruiqi

    2017-01-01

    Vibrio anguillarum is a marine bacterium that can cause vibriosis in many fish and shellfish species, leading to high mortalities and economic losses in aquaculture. Although putative virulence factors have been identified, the mechanism of pathogenesis of V. anguillarum is not fully understood....... anguillarum strains that were medium to nonvirulent had a high degree of genomic homogeneity. Finally, we found that a phylogeny based on the core genomes clustered the strains with moderate to no virulence, while six out of nine high-virulence strains represented phylogenetically separate clusters. Hence, we suggest...... be a powerful tool to discover acquisition of mobile genetic elements related to virulence. Here, we compared 28 V. anguillarum strains that differed in virulence in fish larval models. By pan-genome analyses, we found that six of nine highly virulent strains had a unique core and accessory genome. In contrast...

  3. Comparative genome analyses of Serratia marcescens FS14 reveals its high antagonistic potential.

    Directory of Open Access Journals (Sweden)

    Pengpeng Li

    Full Text Available S. marcescens FS14 was isolated from an Atractylodes macrocephala Koidz plant that was infected by Fusarium oxysporum and showed symptoms of root rot. With the completion of the genome sequence of FS14, the first comprehensive comparative-genomic analysis of the Serratia genus was performed. Pan-genome and COG analyses showed that the majority of the conserved core genes are involved in basic cellular functions, while genomic factors such as prophages contribute considerably to genome diversity. Additionally, a Type I restriction-modification system, a Type III secretion system and tellurium resistance genes are found in only some Serratia species. Comparative analysis further identified that S. marcescens FS14 possesses multiple mechanisms for antagonism against other microorganisms, including the production of prodigiosin, bacteriocins, and multi-antibiotic resistant determinants as well as chitinases. The presence of two evolutionarily distinct Type VI secretion systems (T6SSs in FS14 may provide further competitive advantages for FS14 against other microbes. To our knowledge, this is the first report of comparative analysis on T6SSs in the genus, which identifies four types of T6SSs in Serratia spp.. Competition bioassays of FS14 against the vital plant pathogenic bacterium Ralstonia solanacearum and fungi Fusarium oxysporum and Sclerotinia sclerotiorum were performed to support our genomic analyses, in which FS14 demonstrated high antagonistic activities against both bacterial and fungal phytopathogens.

  4. Transcriptomic and metabolic analyses reveal salvage pathways in creatine-deficient AGAT(-/-) mice.

    Science.gov (United States)

    Stockebrand, Malte; Nejad, Ali Sasani; Neu, Axel; Kharbanda, Kusum K; Sauter, Kathrin; Schillemeit, Stefan; Isbrandt, Dirk; Choe, Chi-Un

    2016-08-01

    Skeletal muscles require energy either at constant low (e.g., standing and posture) or immediate high rates (e.g., exercise). To fulfill these requirements, myocytes utilize the phosphocreatine (PCr)/creatine (Cr) system as a fast energy buffer and shuttle. We have generated mice lacking L-arginine:glycine amidino transferase (AGAT), the first enzyme of creatine biosynthesis. These AGAT(-/-) (d/d) mice are devoid of the PCr/Cr system and reveal severely altered oxidative phosphorylation. In addition, they exhibit complete resistance to diet-induced obesity, which is associated with a chronic activation of AMP-activated protein kinase in muscle and white adipose tissue. The underlying metabolic rearrangements have not yet been further analyzed. Here, we performed gene expression analysis in skeletal muscle and a serum amino acid profile of d/d mice revealing transcriptomic and metabolic alterations in pyruvate and glucose pathways. Differential pyruvate tolerance tests demonstrated preferential conversion of pyruvate to alanine, which was supported by increased protein levels of enzymes involved in pyruvate and alanine metabolism. Pyruvate tolerance tests suggested severely impaired hepatic gluconeogenesis despite increased availability of pyruvate and alanine. Furthermore, enzymes of serine production and one-carbon metabolism were significantly up-regulated in d/d mice, indicating increased de novo formation of one-carbon units from carbohydrate metabolism linked to NAD(P)H production. Besides the well-established function of the PCr/Cr system in energy metabolism, our transcriptomic and metabolic analyses suggest that it plays a pivotal role in systemic one-carbon metabolism, oxidation/reduction, and biosynthetic processes. Therefore, the PCr/Cr system is not only an energy buffer and shuttle, but also a crucial component involved in numerous systemic metabolic processes.

  5. Concurrent growth rate and transcript analyses reveal essential gene stringency in Escherichia coli.

    Directory of Open Access Journals (Sweden)

    Shan Goh

    Full Text Available BACKGROUND: Genes essential for bacterial growth are of particular scientific interest. Many putative essential genes have been identified or predicted in several species, however, little is known about gene expression requirement stringency, which may be an important aspect of bacterial physiology and likely a determining factor in drug target development. METHODOLOGY/PRINCIPAL FINDINGS: Working from the premise that essential genes differ in absolute requirement for growth, we describe silencing of putative essential genes in E. coli to obtain a titration of declining growth rates and transcript levels by using antisense peptide nucleic acids (PNA and expressed antisense RNA. The relationship between mRNA decline and growth rate decline reflects the degree of essentiality, or stringency, of an essential gene, which is here defined by the minimum transcript level for a 50% reduction in growth rate (MTL(50. When applied to four growth essential genes, both RNA silencing methods resulted in MTL(50 values that reveal acpP as the most stringently required of the four genes examined, with ftsZ the next most stringently required. The established antibacterial targets murA and fabI were less stringently required. CONCLUSIONS: RNA silencing can reveal stringent requirements for gene expression with respect to growth. This method may be used to validate existing essential genes and to quantify drug target requirement.

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

    Directory of Open Access Journals (Sweden)

    Ari J S Ferreira

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

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

    KAUST Repository

    Ferreira, Ari J S

    2014-06-12

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

  8. Molecular analyses reveal high species diversity of trematodes in a sub-Arctic lake

    Science.gov (United States)

    Soldánová, Miroslava; Georgieva, Simona; Roháčováa, Jana; Knudsen, Rune; Kuhn, Jesper A.; Henriksen, Eirik H.; Siwertsson, Anna; Shaw, Jenny C.; Kuris, Armand M.; Amundsen, Per-Arne; Scholz, Tomáš; Lafferty, Kevin D.; Kostadinova, Aneta

    2017-01-01

    To identify trematode diversity and life-cycles in the sub-Arctic Lake Takvatn, Norway, we characterised 120 trematode isolates from mollusc first intermediate hosts, metacercariae from second intermediate host fishes and invertebrates, and adults from fish and invertebrate definitive hosts, using molecular techniques. Phylogenies based on nuclear and/or mtDNA revealed high species richness (24 species or species-level genetic lineages), and uncovered trematode diversity (16 putative new species) from five families typical in lake ecosystems (Allocreadiidae, Diplostomidae, Plagiorchiidae, Schistosomatidae and Strigeidae). Sampling potential invertebrate hosts allowed matching of sequence data for different stages, thus achieving molecular elucidation of trematode life-cycles and exploration of host-parasite interactions. Phylogenetic analyses also helped identify three major mollusc intermediate hosts (Radix balthica, Pisidium casertanum and Sphaerium sp.) in the lake. Our findings increase the known trematode diversity at the sub-Arctic Lake Takvatn, showing that digenean diversity is high in this otherwise depauperate sub-Arctic freshwater ecosystem, and indicating that sub-Arctic and Arctic ecosystems may be characterised by unique trematode assemblages.

  9. Transcriptome and biochemical analyses revealed a detailed proanthocyanidin biosynthesis pathway in brown cotton fiber.

    Directory of Open Access Journals (Sweden)

    Yue-Hua Xiao

    Full Text Available Brown cotton fiber is the major raw material for colored cotton industry. Previous studies have showed that the brown pigments in cotton fiber belong to proanthocyanidins (PAs. To clarify the details of PA biosynthesis pathway in brown cotton fiber, gene expression profiles in developing brown and white fibers were compared via digital gene expression profiling and qRT-PCR. Compared to white cotton fiber, all steps from phenylalanine to PA monomers (flavan-3-ols were significantly up-regulated in brown fiber. Liquid chromatography mass spectrometry analyses showed that most of free flavan-3-ols in brown fiber were in 2, 3-trans form (gallocatechin and catechin, and the main units of polymeric PAs were trihydroxylated on B ring. Consistent with monomeric composition, the transcript levels of flavonoid 3', 5'-hydroxylase and leucoanthocyanidin reductase in cotton fiber were much higher than their competing enzymes acting on the same substrates (dihydroflavonol 4-reductase and anthocyanidin synthase, respectively. Taken together, our data revealed a detailed PA biosynthesis pathway wholly activated in brown cotton fiber, and demonstrated that flavonoid 3', 5'-hydroxylase and leucoanthocyanidin reductase represented the primary flow of PA biosynthesis in cotton fiber.

  10. Skin barrier and contact allergy: Genetic risk factor analyses

    DEFF Research Database (Denmark)

    Ross-Hansen, Katrine

    2013-01-01

    by extracting epidermal proteins from human surgical waste samples and stratum corneum scrapings followed by binding studies using immobilized metal affinity chromatography. Results As suggested by Kaplan-Meier event history analyses, FLG null mutations lowered the age of onset of nickel dermatitis, when ear...

  11. Calibrating partial factors for Danish railway embankments using probabilistic analyses

    Institute of Scientific and Technical Information of China (English)

    Michael R. Lodahl; Kristian T.Brødbæk; Carsten S.Sørensen

    2014-01-01

    High costs are connected with upgrading railway embankments throughout Denmark using the partial factors for geotechnical design calibrated for general application. One way to reduce the costs is reliability-based calibration of the partial factors to a reasonable safety level taking into account the specific design situations and uncertainties relevant to railway embankments. A reliability-based design has been investigated, resulting in an optimal partial factor for the considered subsoil. With a stochastic soil model to simulate the undrained shear strength of soft soil deposits, the partial factor is calibrated using asymptotic sampling for the reliability assessment. The calibration shows that the partial factor can be reduced significantly compared to the value specified in the Danish National Annex to DS/EN 1997-1 (2007), Eurocode 7.

  12. Calibrating partial factors for Danish railway embankments using probabilistic analyses

    Directory of Open Access Journals (Sweden)

    Michael R. Lodahl

    2014-04-01

    Full Text Available High costs are connected with upgrading railway embankments throughout Denmark using the partial factors for geotechnical design calibrated for general application. One way to reduce the costs is reliability-based calibration of the partial factors to a reasonable safety level taking into account the specific design situations and uncertainties relevant to railway embankments. A reliability-based design has been investigated, resulting in an optimal partial factor for the considered subsoil. With a stochastic soil model to simulate the undrained shear strength of soft soil deposits, the partial factor is calibrated using asymptotic sampling for the reliability assessment. The calibration shows that the partial factor can be reduced significantly compared to the value specified in the Danish National Annex to DS/EN 1997-1 (2007, Eurocode 7.

  13. Genetic, molecular and functional analyses of complement factor I deficiency

    DEFF Research Database (Denmark)

    Nilsson, S.C.; Trouw, L.A.; Renault, N.;

    2009-01-01

    Complete deficiency of complement inhibitor factor I (FI) results in secondary complement deficiency due to uncontrolled spontaneous alternative pathway activation leading to susceptibility to infections. Current genetic examination of two patients with near complete FI deficiency and three...

  14. Multilocus Analyses Reveal Postglacial Demographic Shrinkage of Juniperus morrisonicola (Cupressaceae), a Dominant Alpine Species in Taiwan.

    Science.gov (United States)

    Huang, Chi-Chun; Hsu, Tsai-Wen; Wang, Hao-Ven; Liu, Zin-Huang; Chen, Yi-Yen; Chiu, Chi-Te; Huang, Chao-Li; Hung, Kuo-Hsiang; Chiang, Tzen-Yuh

    2016-01-01

    Postglacial climate changes alter geographical distributions and diversity of species. Such ongoing changes often force species to migrate along the latitude/altitude. Altitudinal gradients represent assemblage of environmental, especially climatic, variable factors that influence the plant distributions. Global warming that triggered upward migrations has therefore impacted the alpine plants on an island. In this study, we examined the genetic structure of Juniperus morrisonicola, a dominant alpine species in Taiwan, and inferred historical, demographic dynamics based on multilocus analyses. Lower levels of genetic diversity in north indicated that populations at higher latitudes were vulnerable to climate change, possibly related to historical alpine glaciers. Neither organellar DNA nor nuclear genes displayed geographical subdivisions, indicating that populations were likely interconnected before migrating upward to isolated mountain peaks, providing low possibilities of seed/pollen dispersal across mountain ranges. Bayesian skyline plots suggested steady population growth of J. morrisonicola followed by recent demographic contraction. In contrast, most lower-elevation plants experienced recent demographic expansion as a result of global warming. The endemic alpine conifer may have experienced dramatic climate changes over the alternation of glacial and interglacial periods, as indicated by a trend showing decreasing genetic diversity with the altitudinal gradient, plus a fact of upward migration.

  15. Kinetic analyses reveal multiple steps in forming TonB-FhuA complexes from Escherichia coli.

    Science.gov (United States)

    Khursigara, Cezar M; De Crescenzo, Gregory; Pawelek, Peter D; Coulton, James W

    2005-03-08

    FhuA, an outer membrane receptor of Escherichia coli, facilitates transport of hydroxamate siderophores and siderophore-antibiotic conjugates. The cytoplasmic membrane complex TonB-ExbB-ExbD provides energy for transport via the proton motive force. This energy is transduced by protein-protein interactions between TonB and FhuA, but the molecular determinants of these interactions remain uncharacterized. Our analyses of FhuA and two recombinant TonB species by surface plasmon resonance revealed that TonB undergoes a kinetically limiting rearrangement upon initial interaction with FhuA: an intermediate TonB-FhuA complex of 1:1 stoichiometry was detected. The intermediate then recruits a second TonB protein. Addition of ferricrocin, a FhuA-specific ligand, enhanced amounts of the 2:1 complex but was not essential for its formation. To assess the role of the cork domain of FhuA in forming a 2:1 TonB-FhuA complex, we tested a FhuA deletion (residues 21-128) for its ability to interact with TonB. Analytical ultracentrifugation demonstrated that deletion of this region of the cork domain resulted in a 1:1 complex. Furthermore, the high-affinity 2:1 complex requires the N-terminal region of TonB. Together these in vitro experiments establish that TonB-FhuA interactions require sequential steps of kinetically limiting rearrangements. Additionally, domains that contribute to complex formation were identified in TonB and in FhuA.

  16. DNA Sequence Analyses Reveal Abundant Diversity, Endemism and Evidence for Asian Origin of the Porcini Mushrooms

    Science.gov (United States)

    Feng, Bang; Xu, Jianping; Wu, Gang; Zeng, Nian-Kai; Li, Yan-Chun; Tolgor, Bau; Kost, Gerhard W.; Yang, Zhu L.

    2012-01-01

    The wild gourmet mushroom Boletus edulis and its close allies are of significant ecological and economic importance. They are found throughout the Northern Hemisphere, but despite their ubiquity there are still many unresolved issues with regard to the taxonomy, systematics and biogeography of this group of mushrooms. Most phylogenetic studies of Boletus so far have characterized samples from North America and Europe and little information is available on samples from other areas, including the ecologically and geographically diverse regions of China. Here we analyzed DNA sequence variation in three gene markers from samples of these mushrooms from across China and compared our findings with those from other representative regions. Our results revealed fifteen novel phylogenetic species (about one-third of the known species) and a newly identified lineage represented by Boletus sp. HKAS71346 from tropical Asia. The phylogenetic analyses support eastern Asia as the center of diversity for the porcini sensu stricto clade. Within this clade, B. edulis is the only known holarctic species. The majority of the other phylogenetic species are geographically restricted in their distributions. Furthermore, molecular dating and geological evidence suggest that this group of mushrooms originated during the Eocene in eastern Asia, followed by dispersal to and subsequent speciation in other parts of Asia, Europe, and the Americas from the middle Miocene through the early Pliocene. In contrast to the ancient dispersal of porcini in the strict sense in the Northern Hemisphere, the occurrence of B. reticulatus and B. edulis sensu lato in the Southern Hemisphere was probably due to recent human-mediated introductions. PMID:22629418

  17. Genome-wide transcriptome analyses of silicon metabolism in Phaeodactylum tricornutum reveal the multilevel regulation of silicic acid transporters.

    Directory of Open Access Journals (Sweden)

    Guillaume Sapriel

    Full Text Available BACKGROUND: Diatoms are largely responsible for production of biogenic silica in the global ocean. However, in surface seawater, Si(OH(4 can be a major limiting factor for diatom productivity. Analyzing at the global scale the genes networks involved in Si transport and metabolism is critical in order to elucidate Si biomineralization, and to understand diatoms contribution to biogeochemical cycles. METHODOLOGY/PRINCIPAL FINDINGS: Using whole genome expression analyses we evaluated the transcriptional response to Si availability for the model species Phaeodactylum tricornutum. Among the differentially regulated genes we found genes involved in glutamine-nitrogen pathways, encoding putative extracellular matrix components, or involved in iron regulation. Some of these compounds may be good candidates for intracellular intermediates involved in silicic acid storage and/or intracellular transport, which are very important processes that remain mysterious in diatoms. Expression analyses and localization studies gave the first picture of the spatial distribution of a silicic acid transporter in a diatom model species, and support the existence of transcriptional and post-transcriptional regulations. CONCLUSIONS/SIGNIFICANCE: Our global analyses revealed that about one fourth of the differentially expressed genes are organized in clusters, underlying a possible evolution of P. tricornutum genome, and perhaps other pennate diatoms, toward a better optimization of its response to variable environmental stimuli. High fitness and adaptation of diatoms to various Si levels in marine environments might arise in part by global regulations from gene (expression level to genomic (organization in clusters, dosage compensation by gene duplication, and by post-transcriptional regulation and spatial distribution of SIT proteins.

  18. Transcriptomic analyses reveal novel genes with sexually dimorphic expression in the zebrafish gonad and brain.

    Directory of Open Access Journals (Sweden)

    Rajini Sreenivasan

    Full Text Available BACKGROUND: Our knowledge on zebrafish reproduction is very limited. We generated a gonad-derived cDNA microarray from zebrafish and used it to analyze large-scale gene expression profiles in adult gonads and other organs. METHODOLOGY/PRINCIPAL FINDINGS: We have identified 116638 gonad-derived zebrafish expressed sequence tags (ESTs, 21% of which were isolated in our lab. Following in silico normalization, we constructed a gonad-derived microarray comprising 6370 unique, full-length cDNAs from differentiating and adult gonads. Labeled targets from adult gonad, brain, kidney and 'rest-of-body' from both sexes were hybridized onto the microarray. Our analyses revealed 1366, 881 and 656 differentially expressed transcripts (34.7% novel that showed highest expression in ovary, testis and both gonads respectively. Hierarchical clustering showed correlation of the two gonadal transcriptomes and their similarities to those of the brains. In addition, we have identified 276 genes showing sexually dimorphic expression both between the brains and between the gonads. By in situ hybridization, we showed that the gonadal transcripts with the strongest array signal intensities were germline-expressed. We found that five members of the GTP-binding septin gene family, from which only one member (septin 4 has previously been implicated in reproduction in mice, were all strongly expressed in the gonads. CONCLUSIONS/SIGNIFICANCE: We have generated a gonad-derived zebrafish cDNA microarray and demonstrated its usefulness in identifying genes with sexually dimorphic co-expression in both the gonads and the brains. We have also provided the first evidence of large-scale differential gene expression between female and male brains of a teleost. Our microarray would be useful for studying gonad development, differentiation and function not only in zebrafish but also in related teleosts via cross-species hybridizations. Since several genes have been shown to play similar

  19. Molecular genetic analyses of mating pheromones reveal intervariety mating or hybridization in Cryptococcus neoformans.

    Science.gov (United States)

    Chaturvedi, Vishnu; Fan, Jinjiang; Stein, Birgit; Behr, Melissa J; Samsonoff, William A; Wickes, Brian L; Chaturvedi, Sudha

    2002-09-01

    The sexual mating of the pathogenic yeast Cryptococcus neoformans is important for pathogenesis studies because the fungal virulence is linked to the alpha mating type (MAT(alpha)). We characterized C. neoformans mating pheromones (MF(alpha) 1 and MFa1) from 122 strains to understand intervariety hybridization or mating and intervariety virulence. MF(alpha) 1 in three C. neoformans varieties showed (a) specific nucleotide polymorphisms, (b) different copy numbers and chromosomal localizations, and (c) unique deduced amino acids in two geographic populations of C. neoformans var. gattii. MF(alpha) 1 of different varieties cross-hybridized in Southern hybridizations. Their phylogenetic analyses showed purifying selection (neutral evolution). These observations suggested that MAT(alpha) strains from any of the three C. neoformans varieties could mate or hybridize in nature with MATa strains of C. neoformans var. neoformans. A few serotype A/D diploid strains provided evidence for mating or hybridization, while a majority of A/D strains tested positive for haploid MF(alpha) 1 identical to that of C. neoformans var. grubii. MF(alpha) 1 sequence and copy numbers in diploids were identical to those of C. neoformans var. grubii, while their MFa1 sequences were identical to those of C. neoformans var. neoformans; thus, these strains were hybrids. The mice survival curves and histological lesions revealed A/D diploids to be highly pathogenic, with pathogenicity levels similar to that of the C. neoformans var. grubii type strain and unlike the low pathogenicity levels of C. neoformans var. neoformans strains. In contrast to MF(alpha) 1 in three varieties, MFa1 amplicons and hybridization signals could be obtained only from two C. neoformans var. neoformans reference strains and eight A/D diploids. This suggested that a yet undiscovered MFa pheromone(s) in C. neoformans var. gattii and C. neoformans var. grubii is unrelated to, highly divergent from, or rarer than that in C

  20. Big data analyses reveal patterns and drivers of the movements of southern elephant seals

    KAUST Repository

    Rodríguez, Jorge P.

    2017-03-02

    The growing number of large databases of animal tracking provides an opportunity for analyses of movement patterns at the scales of populations and even species. We used analytical approaches, developed to cope with

  1. Transcriptome and network analyses in Saccharomyces cerevisiae reveal that amphotericin B and lactoferrin synergy disrupt metal homeostasis and stress response

    Science.gov (United States)

    Pang, Chi Nam Ignatius; Lai, Yu-Wen; Campbell, Leona T.; Chen, Sharon C.-A.; Carter, Dee A.; Wilkins, Marc R.

    2017-01-01

    Invasive fungal infections are difficult to treat. The few available antifungal drugs have problems with toxicity or efficacy, and resistance is increasing. To overcome these challenges, existing therapies may be enhanced by synergistic combination with another agent. Previously, we found amphotericin B (AMB) and the iron chelator, lactoferrin (LF), were synergistic against a range of different fungal pathogens. This study investigates the mechanism of AMB-LF synergy, using RNA-seq and network analyses. AMB treatment resulted in increased expression of genes involved in iron homeostasis and ATP synthesis. Unexpectedly, AMB-LF treatment did not lead to increased expression of iron and zinc homeostasis genes. However, genes involved in adaptive response to zinc deficiency and oxidative stress had decreased expression. The clustering of co-expressed genes and network analysis revealed that many iron and zinc homeostasis genes are targets of transcription factors Aft1p and Zap1p. The aft1Δ and zap1Δ mutants were hypersensitive to AMB and H2O2, suggesting they are key regulators of the drug response. Mechanistically, AMB-LF synergy could involve AMB affecting the integrity of the cell wall and membrane, permitting LF to disrupt intracellular processes. We suggest that Zap1p- and Aft1p-binding molecules could be combined with existing antifungals to serve as synergistic treatments. PMID:28079179

  2. Metagenomics and in situ analyses reveal Propionivibrio spp. to be abundant GAO in biological wastewater treatment systems

    DEFF Research Database (Denmark)

    McIlroy, Simon Jon; Albertsen, Mads; Stokholm-Bjerregaard, Mikkel;

    to be present at equal levels. Metagenomics was employed to elucidate the identity and recover genomes from the abundant community members. Phylogenetic analyses revealed closely related “Ca. Accumulibacter” and Propionivibrio genera were co-dominant and were both targeted by the PAOmix probes. In situ staining...

  3. Integrative analyses reveal novel strategies in HPV11,-16 and-45 early infection

    DEFF Research Database (Denmark)

    Kaczkowski, Bogumil; Rossing, Maria; Andersen, Ditte;

    2012-01-01

    of genes not previously implicated in HPV biology, such as the PSG family and ANKRD1, and of genes implicated in the biology of other viruses, e. g. MX1, IFI44 and DDX60. Carcinogenesis-related genes, e. g. ABL2, MGLL and CYR61, were upregulated by high-risk HPV16 and -45. The integrative analysis revealed...

  4. Remote camera-trap methods and analyses reveal impacts of rangeland management on Namibian carnivore communities

    Science.gov (United States)

    Kauffman, M.J.; Sanjayan, M.; Lowenstein, J.; Nelson, A.; Jeo, R.M.; Crooks, K.R.

    2007-01-01

    Assessing the abundance and distribution of mammalian carnivores is vital for understanding their ecology and providing for their long-term conservation. Because of the difficulty of trapping and handling carnivores many studies have relied on abundance indices that may not accurately reflect real abundance and distribution patterns. We developed statistical analyses that detect spatial correlation in visitation data from combined scent station and camera-trap surveys, and we illustrate how to use such data to make inferences about changes in carnivore assemblages. As a case study we compared the carnivore communities of adjacent communal and freehold rangelands in central Namibia. We used an index of overdispersion to test for repeat visits to individual camera-trap scent stations and a bootstrap simulation to test for correlations in visits to camera neighbourhoods. After distilling our presence-absence data to the most defensible spatial scale, we assessed overall carnivore visitation using logistic regression. Our analyses confirmed the expected pattern of a depauparate fauna on the communal rangelands compared to the freehold rangelands. Additionally, the species that were not detected on communal sites were the larger-bodied carnivores. By modelling these rare visits as a Poisson process we illustrate a method of inferring whether or not such patterns are because of local extinction of species or are simply a result of low sample effort. Our Namibian case study indicates that these field methods and analyses can detect meaningful differences in the carnivore communities brought about by anthropogenic influences. ?? 2007 FFI.

  5. ObStruct: a method to objectively analyse factors driving population structure using Bayesian ancestry profiles.

    Directory of Open Access Journals (Sweden)

    Velimir Gayevskiy

    Full Text Available Bayesian inference methods are extensively used to detect the presence of population structure given genetic data. The primary output of software implementing these methods are ancestry profiles of sampled individuals. While these profiles robustly partition the data into subgroups, currently there is no objective method to determine whether the fixed factor of interest (e.g. geographic origin correlates with inferred subgroups or not, and if so, which populations are driving this correlation. We present ObStruct, a novel tool to objectively analyse the nature of structure revealed in Bayesian ancestry profiles using established statistical methods. ObStruct evaluates the extent of structural similarity between sampled and inferred populations, tests the significance of population differentiation, provides information on the contribution of sampled and inferred populations to the observed structure and crucially determines whether the predetermined factor of interest correlates with inferred population structure. Analyses of simulated and experimental data highlight ObStruct's ability to objectively assess the nature of structure in populations. We show the method is capable of capturing an increase in the level of structure with increasing time since divergence between simulated populations. Further, we applied the method to a highly structured dataset of 1,484 humans from seven continents and a less structured dataset of 179 Saccharomyces cerevisiae from three regions in New Zealand. Our results show that ObStruct provides an objective metric to classify the degree, drivers and significance of inferred structure, as well as providing novel insights into the relationships between sampled populations, and adds a final step to the pipeline for population structure analyses.

  6. Metagenomic analyses reveal no differences in genes involved in cellulose degradation under different tillage treatments.

    Science.gov (United States)

    de Vries, Maria; Schöler, Anne; Ertl, Julia; Xu, Zhuofei; Schloter, Michael

    2015-07-01

    Incorporation of plant litter is a frequent agricultural practice to increase nutrient availability in soil, and relies heavily on the activity of cellulose-degrading microorganisms. Here we address the question of how different tillage treatments affect soil microbial communities and their cellulose-degrading potential in a long-term agricultural experiment. To identify potential differences in microbial taxonomy and functionality, we generated six soil metagenomes of conventional (CT) and reduced (RT) tillage-treated topsoil samples, which differed in their potential extracellular cellulolytic activity as well as their microbial biomass. Taxonomic analysis of metagenomic data revealed few differences between RT and CT, and a dominance of Proteobacteria and Actinobacteria, whereas eukaryotic phyla were not prevalent. Prediction of cellulolytic enzymes revealed glycoside hydrolase families 1, 3 and 94, auxiliary activity family 8 and carbohydrate-binding module 2 as the most abundant in soil. These were annotated mainly to the phyla of Proteobacteria, Actinobacteria and Bacteroidetes. These results suggest that the observed higher cellulolytic activity in RT soils can be explained by a higher microbial biomass or changed expression levels but not by shifts in the soil microbiome. Overall, this study reveals the stability of soil microbial communities and cellulolytic gene composition under the investigated tillage treatments.

  7. Systems Analyses Reveal Shared and Diverse Attributes of Oct4 Regulation in Pluripotent Cells

    DEFF Research Database (Denmark)

    Ding, Li; Paszkowski-Rogacz, Maciej; Winzi, Maria;

    2015-01-01

    We combine a genome-scale RNAi screen in mouse epiblast stem cells (EpiSCs) with genetic interaction, protein localization, and "protein-level dependency" studies-a systematic technique that uncovers post-transcriptional regulation-to delineate the network of factors that control the expression...

  8. Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index

    NARCIS (Netherlands)

    Speliotes, Elizabeth K.; Willer, Cristen J.; Berndt, Sonja I.; Monda, Keri L.; Thorleifsson, Gudmar; Jackson, Anne U.; Allen, Hana Lango; Lindgren, Cecilia M.; Luan, Jian'an; Maegi, Reedik; Randall, Joshua C.; Vedantam, Sailaja; Winkler, Thomas W.; Qi, Lu; Workalemahu, Tsegaselassie; Heid, Iris M.; Steinthorsdottir, Valgerdur; Stringham, Heather M.; Weedon, Michael N.; Wheeler, Eleanor; Wood, Andrew R.; Ferreira, Teresa; Weyant, Robert J.; Segre, Ayellet V.; Estrada, Karol; Liang, Liming; Nemesh, James; Park, Ju-Hyun; Gustafsson, Stefan; Kilpelaenen, Tuomas O.; Yang, Jian; Bouatia-Naji, Nabila; Esko, Tonu; Feitosa, Mary F.; Kutalik, Zoltan; Mangino, Massimo; Raychaudhuri, Soumya; Scherag, Andre; Smith, Albert Vernon; Welch, Ryan; Zhao, Jing Hua; Aben, Katja K.; Absher, Devin M.; Amin, Najaf; Dixon, Anna L.; Fisher, Eva; Glazer, Nicole L.; Goddard, Michael E.; Heard-Costa, Nancy L.; Hoesel, Volker; Hottenga, Jouke-Jan; Johansson, Asa; Johnson, Toby; Ketkar, Shamika; Lamina, Claudia; Li, Shengxu; Moffatt, Miriam F.; Myers, Richard H.; Narisu, Narisu; Perry, John R. B.; Peters, Marjolein J.; Preuss, Michael; Ripatti, Samuli; Rivadeneira, Fernando; Sandholt, Camilla; Scott, Laura J.; Timpson, Nicholas J.; Tyrer, Jonathan P.; van Wingerden, Sophie; Watanabe, Richard M.; White, Charles C.; Wiklund, Fredrik; Barlassina, Christina; Chasman, Daniel I.; Cooper, Matthew N.; Jansson, John-Olov; Lawrence, Robert W.; Pellikka, Niina; Prokopenko, Inga; Shi, Jianxin; Thiering, Elisabeth; Alavere, Helene; Alibrandi, Maria T. S.; Almgren, Peter; Arnold, Alice M.; Aspelund, Thor; Atwood, Larry D.; Balkau, Beverley; Balmforth, Anthony J.; Bennett, Amanda J.; Ben-Shlomo, Yoav; Bergman, Richard N.; Bergmann, Sven; Biebermann, Heike; Blakemore, Alexandra I. F.; Boes, Tanja; Bonnycastle, Lori L.; Bornstein, Stefan R.; Brown, Morris J.; Buchanan, Thomas A.; Busonero, Fabio; Campbell, Harry; Cappuccio, Francesco P.; Cavalcanti-Proenca, Christine; Chen, Yii-Der Ida; Chen, Chih-Mei; Chines, Peter S.; Clarke, Robert; Coin, Lachlan; Connell, John; Day, Ian N. M.; den Heijer, Martin; Duan, Jubao; Ebrahim, Shah; Elliott, Paul; Elosua, Roberto; Eiriksdottir, Gudny; Erdos, Michael R.; Eriksson, Johan G.; Facheris, Maurizio F.; Felix, Stephan B.; Fischer-Posovszky, Pamela; Folsom, Aaron R.; Friedrich, Nele; Freimer, Nelson B.; Fu, Mao; Gaget, Stefan; Gejman, Pablo V.; Geus, Eco J. C.; Gieger, Christian; Gjesing, Anette P.; Goel, Anuj; Goyette, Philippe; Grallert, Harald; Graessler, Juergen; Greenawalt, Danielle M.; Groves, Christopher J.; Gudnason, Vilmundur; Guiducci, Candace; Hartikainen, Anna-Liisa; Hassanali, Neelam; Hall, Alistair S.; Havulinna, Aki S.; Hayward, Caroline; Heath, Andrew C.; Hengstenberg, Christian; Hicks, Andrew A.; Hinney, Anke; Hofman, Albert; Homuth, Georg; Hui, Jennie; Igl, Wilmar; Iribarren, Carlos; Isomaa, Bo; Jacobs, Kevin B.; Jarick, Ivonne; Jewell, Elizabeth; John, Ulrich; Jorgensen, Torben; Jousilahti, Pekka; Jula, Antti; Kaakinen, Marika; Kajantie, Eero; Kaplan, Lee M.; Kathiresan, Sekar; Kettunen, Johannes; Kinnunen, Leena; Knowles, Joshua W.; Kolcic, Ivana; Koenig, Inke R.; Koskinen, Seppo; Kovacs, Peter; Kuusisto, Johanna; Kraft, Peter; Kvaloy, Kirsti; Laitinen, Jaana; Lantieri, Olivier; Lanzani, Chiara; Launer, Lenore J.; Lecoeur, Cecile; Lehtimaeki, Terho; Lettre, Guillaume; Liu, Jianjun; Lokki, Marja-Liisa; Lorentzon, Mattias; Luben, Robert N.; Ludwig, Barbara; Manunta, Paolo; Marek, Diana; Marre, Michel; Martin, Nicholas G.; McArdle, Wendy L.; McCarthy, Anne; McKnight, Barbara; Meitinger, Thomas; Melander, Olle; Meyre, David; Midthjell, Kristian; Montgomery, Grant W.; Morken, Mario A.; Morris, Andrew P.; Mulic, Rosanda; Ngwa, Julius S.; Nelis, Mari; Neville, Matt J.; Nyholt, Dale R.; O'Donnell, Christopher J.; O'Rahilly, Stephen; Ong, Ken K.; Oostra, Ben; Pare, Guillaume; Parker, Alex N.; Perola, Markus; Pichler, Irene; Pietilaeinen, Kirsi H.; Platou, Carl G. P.; Polasek, Ozren; Pouta, Anneli; Rafelt, Suzanne; Raitakari, Olli; Rayner, Nigel W.; Ridderstrale, Martin; Rief, Winfried; Ruokonen, Aimo; Robertson, Neil R.; Rzehak, Peter; Salomaa, Veikko; Sanders, Alan R.; Sandhu, Manjinder S.; Sanna, Serena; Saramies, Jouko; Savolainen, Markku J.; Scherag, Susann; Schipf, Sabine; Schreiber, Stefan; Schunkert, Heribert; Silander, Kaisa; Sinisalo, Juha; Siscovick, David S.; Smit, Jan H.; Soranzo, Nicole; Sovio, Ulla; Stephens, Jonathan; Surakka, Ida; Swift, Amy J.; Tammesoo, Mari-Liis; Tardif, Jean-Claude; Teder-Laving, Maris; Teslovich, Tanya M.; Thompson, John R.; Thomson, Brian; Toenjes, Anke; Tuomi, Tiinamaija; van Meurs, Joyce B. J.; van Ommen, Gert-Jan; Vatin, Vincent; Viikari, Jorma; Visvikis-Siest, Sophie; Vitart, Veronique; Vogel, Carla I. G.; Voight, Benjamin F.; Waite, Lindsay L.; Wallaschofski, Henri; Walters, G. Bragi; Widen, Elisabeth; Wiegand, Susanna; Wild, Sarah H.; Willemsen, Gonneke; Witte, Daniel R.; Witteman, Jacqueline C.; Xu, Jianfeng; Zhang, Qunyuan; Zgaga, Lina; Ziegler, Andreas; Zitting, Paavo; Beilby, John P.; Farooqi, I. Sadaf; Hebebrand, Johannes; Huikuri, Heikki V.; James, Alan L.; Kaehoenen, Mika; Levinson, Douglas F.; Macciardi, Fabio; Nieminen, Markku S.; Ohlsson, Claes; Palmer, Lyle J.; Ridker, Paul M.; Stumvoll, Michael; Beckmann, Jacques S.; Boeing, Heiner; Boerwinkle, Eric; Boomsma, Dorret I.; Caulfield, Mark J.; Chanock, Stephen J.; Collins, Francis S.; Cupples, L. Adrienne; Smith, George Davey; Erdmann, Jeanette; Froguel, Philippe; Greonberg, Henrik; Gyllensten, Ulf; Hall, Per; Hansen, Torben; Harris, Tamara B.; Hattersley, Andrew T.; Hayes, Richard B.; Heinrich, Joachim; Hu, Frank B.; Hveem, Kristian; Illig, Thomas; Jarvelin, Marjo-Riitta; Kaprio, Jaakko; Karpe, Fredrik; Khaw, Kay-Tee; Kiemeney, Lambertus A.; Krude, Heiko; Laakso, Markku; Lawlor, Debbie A.; Metspalu, Andres; Munroe, Patricia B.; Ouwehand, Willem H.; Pedersen, Oluf; Penninx, Brenda W.; Peters, Annette; Pramstaller, Peter P.; Quertermous, Thomas; Reinehr, Thomas; Rissanen, Aila; Rudan, Igor; Samani, Nilesh J.; Schwarz, Peter E. H.; Shuldiner, Alan R.; Spector, Timothy D.; Tuomilehto, Jaakko; Uda, Manuela; Uitterlinden, Andre; Valle, Timo T.; Wabitsch, Martin; Waeber, Gerard; Wareham, Nicholas J.; Watkins, Hugh; Wilson, James F.; Wright, Alan F.; Zillikens, M. Carola; Chatterjee, Nilanjan; McCarroll, Steven A.; Purcell, Shaun; Schadt, Eric E.; Visscher, Peter M.; Assimes, Themistocles L.; Borecki, Ingrid B.; Deloukas, Panos; Fox, Caroline S.; Groop, Leif C.; Haritunians, Talin; Hunter, David J.; Kaplan, Robert C.; Mohlke, Karen L.; O'Connell, Jeffrey R.; Peltonen, Leena; Schlessinger, David; Strachan, David P.; van Duijn, Cornelia M.; Wichmann, H-Erich; Frayling, Timothy M.; Thorsteinsdottir, Unnur; Abecasis, Goncalo R.; Barroso, Ines; Boehnke, Michael; Stefansson, Kari; North, Kari E.; McCarthy, Mark I.; Hirschhorn, Joel N.; Ingelsson, Erik; Loos, Ruth J. F.

    2010-01-01

    Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and similar to 2.8 million SNPs in up to 123,865 individuals with targeted follow up of

  9. Comparative Genome Analyses of Vibrio anguillarum Strains Reveal a Link with Pathogenicity Traits

    DEFF Research Database (Denmark)

    Castillo, Daniel; D'Alvise, Paul; Xu, Ruiqi

    2017-01-01

    Vibrio anguillarum is a marine bacterium that can cause vibriosis in many fish and shellfish species, leading to high mortalities and economic losses in aquaculture. Although putative virulence factors have been identified, the mechanism of pathogenesis of V. anguillarum is not fully understood. ...

  10. Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index

    NARCIS (Netherlands)

    Speliotes, Elizabeth K.; Willer, Cristen J.; Berndt, Sonja I.; Monda, Keri L.; Thorleifsson, Gudmar; Jackson, Anne U.; Allen, Hana Lango; Lindgren, Cecilia M.; Luan, Jian'an; Maegi, Reedik; Randall, Joshua C.; Vedantam, Sailaja; Winkler, Thomas W.; Qi, Lu; Workalemahu, Tsegaselassie; Heid, Iris M.; Steinthorsdottir, Valgerdur; Stringham, Heather M.; Weedon, Michael N.; Wheeler, Eleanor; Wood, Andrew R.; Ferreira, Teresa; Weyant, Robert J.; Segre, Ayellet V.; Estrada, Karol; Liang, Liming; Nemesh, James; Park, Ju-Hyun; Gustafsson, Stefan; Kilpelaenen, Tuomas O.; Yang, Jian; Bouatia-Naji, Nabila; Esko, Tonu; Feitosa, Mary F.; Kutalik, Zoltan; Mangino, Massimo; Raychaudhuri, Soumya; Scherag, Andre; Smith, Albert Vernon; Welch, Ryan; Zhao, Jing Hua; Aben, Katja K.; Absher, Devin M.; Amin, Najaf; Dixon, Anna L.; Fisher, Eva; Glazer, Nicole L.; Goddard, Michael E.; Heard-Costa, Nancy L.; Hoesel, Volker; Hottenga, Jouke-Jan; Johansson, Asa; Johnson, Toby; Ketkar, Shamika; Lamina, Claudia; Li, Shengxu; Moffatt, Miriam F.; Myers, Richard H.; Narisu, Narisu; Perry, John R. B.; Peters, Marjolein J.; Preuss, Michael; Ripatti, Samuli; Rivadeneira, Fernando; Sandholt, Camilla; Scott, Laura J.; Timpson, Nicholas J.; Tyrer, Jonathan P.; van Wingerden, Sophie; Watanabe, Richard M.; White, Charles C.; Wiklund, Fredrik; Barlassina, Christina; Chasman, Daniel I.; Cooper, Matthew N.; Jansson, John-Olov; Lawrence, Robert W.; Pellikka, Niina; Prokopenko, Inga; Shi, Jianxin; Thiering, Elisabeth; Alavere, Helene; Alibrandi, Maria T. S.; Almgren, Peter; Arnold, Alice M.; Aspelund, Thor; Atwood, Larry D.; Balkau, Beverley; Balmforth, Anthony J.; Bennett, Amanda J.; Ben-Shlomo, Yoav; Bergman, Richard N.; Bergmann, Sven; Biebermann, Heike; Blakemore, Alexandra I. F.; Boes, Tanja; Bonnycastle, Lori L.; Bornstein, Stefan R.; Brown, Morris J.; Buchanan, Thomas A.; Busonero, Fabio; Campbell, Harry; Cappuccio, Francesco P.; Cavalcanti-Proenca, Christine; Chen, Yii-Der Ida; Chen, Chih-Mei; Chines, Peter S.; Clarke, Robert; Coin, Lachlan; Connell, John; Day, Ian N. M.; den Heijer, Martin; Duan, Jubao; Ebrahim, Shah; Elliott, Paul; Elosua, Roberto; Eiriksdottir, Gudny; Erdos, Michael R.; Eriksson, Johan G.; Facheris, Maurizio F.; Felix, Stephan B.; Fischer-Posovszky, Pamela; Folsom, Aaron R.; Friedrich, Nele; Freimer, Nelson B.; Fu, Mao; Gaget, Stefan; Gejman, Pablo V.; Geus, Eco J. C.; Gieger, Christian; Gjesing, Anette P.; Goel, Anuj; Goyette, Philippe; Grallert, Harald; Graessler, Juergen; Greenawalt, Danielle M.; Groves, Christopher J.; Gudnason, Vilmundur; Guiducci, Candace; Hartikainen, Anna-Liisa; Hassanali, Neelam; Hall, Alistair S.; Havulinna, Aki S.; Hayward, Caroline; Heath, Andrew C.; Hengstenberg, Christian; Hicks, Andrew A.; Hinney, Anke; Hofman, Albert; Homuth, Georg; Hui, Jennie; Igl, Wilmar; Iribarren, Carlos; Isomaa, Bo; Jacobs, Kevin B.; Jarick, Ivonne; Jewell, Elizabeth; John, Ulrich; Jorgensen, Torben; Jousilahti, Pekka; Jula, Antti; Kaakinen, Marika; Kajantie, Eero; Kaplan, Lee M.; Kathiresan, Sekar; Kettunen, Johannes; Kinnunen, Leena; Knowles, Joshua W.; Kolcic, Ivana; Koenig, Inke R.; Koskinen, Seppo; Kovacs, Peter; Kuusisto, Johanna; Kraft, Peter; Kvaloy, Kirsti; Laitinen, Jaana; Lantieri, Olivier; Lanzani, Chiara; Launer, Lenore J.; Lecoeur, Cecile; Lehtimaeki, Terho; Lettre, Guillaume; Liu, Jianjun; Lokki, Marja-Liisa; Lorentzon, Mattias; Luben, Robert N.; Ludwig, Barbara; Manunta, Paolo; Marek, Diana; Marre, Michel; Martin, Nicholas G.; McArdle, Wendy L.; McCarthy, Anne; McKnight, Barbara; Meitinger, Thomas; Melander, Olle; Meyre, David; Midthjell, Kristian; Montgomery, Grant W.; Morken, Mario A.; Morris, Andrew P.; Mulic, Rosanda; Ngwa, Julius S.; Nelis, Mari; Neville, Matt J.; Nyholt, Dale R.; O'Donnell, Christopher J.; O'Rahilly, Stephen; Ong, Ken K.; Oostra, Ben; Pare, Guillaume; Parker, Alex N.; Perola, Markus; Pichler, Irene; Pietilaeinen, Kirsi H.; Platou, Carl G. P.; Polasek, Ozren; Pouta, Anneli; Rafelt, Suzanne; Raitakari, Olli; Rayner, Nigel W.; Ridderstrale, Martin; Rief, Winfried; Ruokonen, Aimo; Robertson, Neil R.; Rzehak, Peter; Salomaa, Veikko; Sanders, Alan R.; Sandhu, Manjinder S.; Sanna, Serena; Saramies, Jouko; Savolainen, Markku J.; Scherag, Susann; Schipf, Sabine; Schreiber, Stefan; Schunkert, Heribert; Silander, Kaisa; Sinisalo, Juha; Siscovick, David S.; Smit, Jan H.; Soranzo, Nicole; Sovio, Ulla; Stephens, Jonathan; Surakka, Ida; Swift, Amy J.; Tammesoo, Mari-Liis; Tardif, Jean-Claude; Teder-Laving, Maris; Teslovich, Tanya M.; Thompson, John R.; Thomson, Brian; Toenjes, Anke; Tuomi, Tiinamaija; van Meurs, Joyce B. J.; van Ommen, Gert-Jan; Vatin, Vincent; Viikari, Jorma; Visvikis-Siest, Sophie; Vitart, Veronique; Vogel, Carla I. G.; Voight, Benjamin F.; Waite, Lindsay L.; Wallaschofski, Henri; Walters, G. Bragi; Widen, Elisabeth; Wiegand, Susanna; Wild, Sarah H.; Willemsen, Gonneke; Witte, Daniel R.; Witteman, Jacqueline C.; Xu, Jianfeng; Zhang, Qunyuan; Zgaga, Lina; Ziegler, Andreas; Zitting, Paavo; Beilby, John P.; Farooqi, I. Sadaf; Hebebrand, Johannes; Huikuri, Heikki V.; James, Alan L.; Kaehoenen, Mika; Levinson, Douglas F.; Macciardi, Fabio; Nieminen, Markku S.; Ohlsson, Claes; Palmer, Lyle J.; Ridker, Paul M.; Stumvoll, Michael; Beckmann, Jacques S.; Boeing, Heiner; Boerwinkle, Eric; Boomsma, Dorret I.; Caulfield, Mark J.; Chanock, Stephen J.; Collins, Francis S.; Cupples, L. Adrienne; Smith, George Davey; Erdmann, Jeanette; Froguel, Philippe; Greonberg, Henrik; Gyllensten, Ulf; Hall, Per; Hansen, Torben; Harris, Tamara B.; Hattersley, Andrew T.; Hayes, Richard B.; Heinrich, Joachim; Hu, Frank B.; Hveem, Kristian; Illig, Thomas; Jarvelin, Marjo-Riitta; Kaprio, Jaakko; Karpe, Fredrik; Khaw, Kay-Tee; Kiemeney, Lambertus A.; Krude, Heiko; Laakso, Markku; Lawlor, Debbie A.; Metspalu, Andres; Munroe, Patricia B.; Ouwehand, Willem H.; Pedersen, Oluf; Penninx, Brenda W.; Peters, Annette; Pramstaller, Peter P.; Quertermous, Thomas; Reinehr, Thomas; Rissanen, Aila; Rudan, Igor; Samani, Nilesh J.; Schwarz, Peter E. H.; Shuldiner, Alan R.; Spector, Timothy D.; Tuomilehto, Jaakko; Uda, Manuela; Uitterlinden, Andre; Valle, Timo T.; Wabitsch, Martin; Waeber, Gerard; Wareham, Nicholas J.; Watkins, Hugh; Wilson, James F.; Wright, Alan F.; Zillikens, M. Carola; Chatterjee, Nilanjan; McCarroll, Steven A.; Purcell, Shaun; Schadt, Eric E.; Visscher, Peter M.; Assimes, Themistocles L.; Borecki, Ingrid B.; Deloukas, Panos; Fox, Caroline S.; Groop, Leif C.; Haritunians, Talin; Hunter, David J.; Kaplan, Robert C.; Mohlke, Karen L.; O'Connell, Jeffrey R.; Peltonen, Leena; Schlessinger, David; Strachan, David P.; van Duijn, Cornelia M.; Wichmann, H-Erich; Frayling, Timothy M.; Thorsteinsdottir, Unnur; Abecasis, Goncalo R.; Barroso, Ines; Boehnke, Michael; Stefansson, Kari; North, Kari E.; McCarthy, Mark I.; Hirschhorn, Joel N.; Ingelsson, Erik; Loos, Ruth J. F.

    2010-01-01

    Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and similar to 2.8 million SNPs in up to 123,865 individuals with targeted follow up of

  11. Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index

    DEFF Research Database (Denmark)

    Speliotes, Elizabeth K; Willer, Cristen J; Berndt, Sonja I

    2010-01-01

    Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and ~ 2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SN...

  12. NFkappaB Selectivity of Estrogen Receptor Ligands Revealed By Comparative Crystallographic Analyses

    Energy Technology Data Exchange (ETDEWEB)

    Nettles, K.W.; Bruning, J.B.; Gil, G.; Nowak, J.; Sharma, S.K.; Hahm, J.B.; Kulp, K.; Hochberg, R.B.; Zhou, H.; Katzenellenbogen, J.A.; Katzenllenbogen, B.S.; Kim, Y.; Joachmiak, A.; Greene, G.L.

    2009-05-22

    Our understanding of how steroid hormones regulate physiological functions has been significantly advanced by structural biology approaches. However, progress has been hampered by misfolding of the ligand binding domains in heterologous expression systems and by conformational flexibility that interferes with crystallization. Here, we show that protein folding problems that are common to steroid hormone receptors are circumvented by mutations that stabilize well-characterized conformations of the receptor. We use this approach to present the structure of an apo steroid receptor that reveals a ligand-accessible channel allowing soaking of preformed crystals. Furthermore, crystallization of different pharmacological classes of compounds allowed us to define the structural basis of NF{kappa}B-selective signaling through the estrogen receptor, thus revealing a unique conformation of the receptor that allows selective suppression of inflammatory gene expression. The ability to crystallize many receptor-ligand complexes with distinct pharmacophores allows one to define structural features of signaling specificity that would not be apparent in a single structure.

  13. Phylogeographical analyses reveal global migration patterns of the barley scald pathogen Rhynchosporium secalis.

    Science.gov (United States)

    Zaffarano, Pascal L; McDonald, Bruce A; Linde, Celeste C

    2009-01-01

    A phylogeographical analysis of the scald pathogen Rhynchosporium secalis was conducted using nuclear DNA sequences from two neutral restriction fragment length polymorphism loci and the mating-type idiomorphs. Approximately 500 isolates sampled from more than 60 field populations from five continents were analysed to infer migration patterns and the demographic history of the fungus. Migration rates among continents were generally low, consistent with earlier reports of significant population subdivision among continents. Northern Europe was mainly a source population for global migration. We hypothesize that the pathogen only recently moved out of its centre of origin, resulting in founder populations that are reproductively isolated due to the contemporary absence of long-distance gene flow.

  14. Comparative Genomic and Phylogenomic Analyses Reveal a Conserved Core Genome Shared by Estuarine and Oceanic Cyanopodoviruses

    Science.gov (United States)

    Huang, Sijun; Zhang, Si; Jiao, Nianzhi; Chen, Feng

    2015-01-01

    Podoviruses are among the major viral groups that infect marine picocyanobacteria Prochlorococcus and Synechococcus. Here, we reported the genome sequences of five Synechococcus podoviruses isolated from the estuarine environment, and performed comparative genomic and phylogenomic analyses based on a total of 20 cyanopodovirus genomes. The genomes of all the known marine cyanopodoviruses are highly syntenic. A pan-genome of 349 clustered orthologous groups was determined, among which 15 were core genes. These core genes make up nearly half of each genome in length, reflecting the high level of genome conservation among this cyanophage type. The whole genome phylogenies based on concatenated core genes and gene content were highly consistent and confirmed the separation of two discrete marine cyanopodovirus clusters MPP-A and MPP-B. The genomes within cluster MPP-B grouped into subclusters mainly corresponding to Prochlorococcus or Synechococcus host types. Auxiliary metabolic genes tend to occur in a specific phylogenetic group of these cyanopodoviruses. All the MPP-B phages analyzed here encode the photosynthesis gene psbA, which are absent in all the MPP-A genomes thus far. Interestingly, all the MPP-B and two MPP-A Synechococcus podoviruses encode the thymidylate synthase gene thyX, while at the same genome locus all the MPP-B Prochlorococcus podoviruses encode the transaldolase gene talC. Both genes are hypothesized to have the potential to facilitate the biosynthesis of deoxynucleotide for phage replication. Inheritance of specific functional genes could be important to the evolution and ecological fitness of certain cyanophage genotypes. Our analyses demonstrate that cyanopodoviruses of estuarine and oceanic origins share a conserved core genome and suggest that accessory genes may be related to environmental adaptation. PMID:26569403

  15. Comparative Genomic and Phylogenomic Analyses Reveal a Conserved Core Genome Shared by Estuarine and Oceanic Cyanopodoviruses.

    Directory of Open Access Journals (Sweden)

    Sijun Huang

    Full Text Available Podoviruses are among the major viral groups that infect marine picocyanobacteria Prochlorococcus and Synechococcus. Here, we reported the genome sequences of five Synechococcus podoviruses isolated from the estuarine environment, and performed comparative genomic and phylogenomic analyses based on a total of 20 cyanopodovirus genomes. The genomes of all the known marine cyanopodoviruses are highly syntenic. A pan-genome of 349 clustered orthologous groups was determined, among which 15 were core genes. These core genes make up nearly half of each genome in length, reflecting the high level of genome conservation among this cyanophage type. The whole genome phylogenies based on concatenated core genes and gene content were highly consistent and confirmed the separation of two discrete marine cyanopodovirus clusters MPP-A and MPP-B. The genomes within cluster MPP-B grouped into subclusters mainly corresponding to Prochlorococcus or Synechococcus host types. Auxiliary metabolic genes tend to occur in a specific phylogenetic group of these cyanopodoviruses. All the MPP-B phages analyzed here encode the photosynthesis gene psbA, which are absent in all the MPP-A genomes thus far. Interestingly, all the MPP-B and two MPP-A Synechococcus podoviruses encode the thymidylate synthase gene thyX, while at the same genome locus all the MPP-B Prochlorococcus podoviruses encode the transaldolase gene talC. Both genes are hypothesized to have the potential to facilitate the biosynthesis of deoxynucleotide for phage replication. Inheritance of specific functional genes could be important to the evolution and ecological fitness of certain cyanophage genotypes. Our analyses demonstrate that cyanopodoviruses of estuarine and oceanic origins share a conserved core genome and suggest that accessory genes may be related to environmental adaptation.

  16. Genetic diversity among some canola cultivars as revealed by RAPD, SSR and AFLP analyses.

    Science.gov (United States)

    Moghaieb, Reda E A; Mohammed, Etr H K; Youssief, Sawsan S

    2014-08-01

    To assess the genetic diversity among four canola cultivars (namely, Serw-3, Serw-4, Misser L-16 and Semu 249), random amplified polymorphic DNA (RAPD), simple sequence repeat polymorphism (SSR) and amplified fragment length polymorphism (AFLP) analyses were performed. The data indicated that all of the three molecular markers gave different levels of polymorphism. A total of 118, 31 and 338 markers that show 61, 67.7 and 81 % polymorphism percentages were resulted from the RAPD, SSR and AFLP analyses, respectively. Based on the data obtained the three markers can be used to differentiate between the four canola cultivars. The genotype-specific markers were determined, 18 out of the 72 polymorphic RAPD markers generated were found to be genotype-specific (25 %). The highest number of RAPD specific markers was scored for Semu 249 (15 markers), while Serw-4 scored two markers. On the other hand, Serw-3 scored one marker. The cultivar Semu 249 scored the highest number of unique AFLP markers, giving 57 unique markers, followed by Misser L-16 which was characterized by 40 unique AFLP markers, then Serw-3 giving 31 unique markers. While Serw-4 was characterized by the lowest number producing 14 unique positive markers. The dendrogram built on the basis of combined data from RAPD, SSR and AFLP analysis represents the genetic distances among the four canola cultivars. Understanding the genetic variability among the current canola cultivars opens up a possibility for developing a molecular genetic map that will lead to the application of marker-assisted selection tools in genetic improvement of canola.

  17. Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index

    NARCIS (Netherlands)

    E.K. Speliotes (Elizabeth); C.J. Willer (Cristen); S.I. Berndt (Sonja); K.L. Monda (Keri); G. Thorleifsson (Gudmar); A.U. Jackson (Anne); H.L. Allen; C.M. Lindgren (Cecilia); J. Luan; R. Mägi (Reedik); J.C. Randall (Joshua); S. Vedantam (Sailaja); T.W. Winkler (Thomas); L. Qi (Lu); T. Workalemahu (Tsegaselassie); I.M. Heid (Iris); V. Steinthorsdottir (Valgerdur); H.M. Stringham (Heather); E. Wheeler (Eleanor); A.R. Wood (Andrew); T. Ferreira (Teresa); R.J. Weyant (Robert); A.V. Segrè (Ayellet); K. Eestrada (Karol); L. Liang (Liming); J. Nemesh (James); J.H. Park; S. Gustafsson (Stefan); T.O. Kilpeläinen (Tuomas); J. Yang (Joanna); N. Bouatia-Naji (Nabila); T. Eesko (Tõnu); M.F. Feitosa (Mary Furlan); Z. Kutalik (Zoltán); M. Mangino (Massimo); S. Raychaudhuri (Soumya); A. Scherag (Andre); A.V. Smith (Albert Vernon); R.P. Welch (Ryan); J.H. Zhao; K.K.H. Aben (Katja); D. Absher (Devin); N. Amin (Najaf); A.L. Dixon (Anna); E. Fisher (Eeva); N.L. Glazer (Nicole); M.E. Goddard (Michael); N.L. Heard-Costa (Nancy); V. Hoesel (Volker); J.J. Hottenga (Jouke Jan); A. Johansson (Åsa); T. Johnson (Toby); S. Ketkar (Shamika); C. Lamina (Claudia); S. Li (Shengxu); M.F. Moffatt (Miriam); R.H. Myers (Richard); N. Narisu (Narisu); J.R.B. Perry (John); M.J. Peters (Marjolein); M. Preuss (Michael); S. Ripatti (Samuli); F. Rivadeneira Ramirez (Fernando); C. Sandholt (Camilla); L.J. Scott (Laura); N. Timpson (Nicholas); J.P. Tyrer (Jonathan); S. van Wingerden (Sophie); C.C. White (Charles); F. Wiklund (Fredrik); C. Barlassina (Christina); D.I. Chasman (Daniel); M.N. Cooper (Matthew); J.O. Jansson; R.W. Lawrence (Robert); N. Pellikka (Niina); I. Prokopenko (Inga); J. Shi (Jianxin); E. Thiering (Eelisabeth); H. Alavere (Helene); M.T.S. Alibrandi (Maria); P. Almgren (Peter); A.M. Arnold (Alice); T. Aspelund (Thor); L.D. Atwood (Larry); B. Balkau (Beverley); A.J. Balmforth (Anthony); A.J. Bennett (Amanda); Y. Ben-Shlomo; R.N. Bergman (Richard); S.M. Bergmann (Sven); H. Biebermann (Heike); A.I.F. Blakemore (Alexandra); T. Boes (Tanja); L.L. Bonnycastle (Lori); S.R. Bornstein (Stefan); M.J. Brown (Morris); T.A. Buchanan (Thomas); F. Busonero; H. Campbell (Harry); F.P. Cappuccio (Francesco); C. Cavalcanti-Proença (Christine); Y.D.I. Chen (Yii-Der Ida); C.-M. Chen (Chih-Mei); P.S. Chines (Peter); R. Clarke; L. Coin (Lachlan); J. Connell (John); I.N.M. Day (Ian); M. den Heijer (Martin); J. Duan (Jubao); S. Eebrahim (Shah); P. Eelliott (Paul); R. Eelosua (Roberto); G. Eeiriksdottir (Gudny); M.R. Eerdos (Micheal); J.G. Eeriksson (Johan); M.F. Facheris (Maurizio); S.B. Felix (Stephan); P. Fischer-Posovszky (Pamela); A.R. Folsom (Aaron); N. Friedrich (Nele); N.B. Freimer (Nelson); M. Fu (Mao); S. Gaget (Stefan); P.V. Gejman (Pablo); E.J. Geus (Eeco); C. Gieger (Christian); A.P. Gjesing (Anette); A. Goel (Anuj); P. Goyette (Philippe); H. Grallert (Harald); J. Gräßler (Jürgen); D. Greenawalt (Danielle); C.J. Groves (Christopher); V. Gudnason (Vilmundur); C. Guiducci (Candace); A.L. Hartikainen; N. Hassanali (Neelam); A.S. Hall (Alistair); A.S. Havulinna (Aki); C. Hayward (Caroline); A.C. Heath (Andrew); C. Hengstenberg (Christian); A.A. Hicks (Andrew); A. Hinney (Anke); A. Hofman (Albert); G. Homuth (Georg); J. Hui (Jennie); W. Igl (Wilmar); C. Iribarren (Carlos); B. Isomaa (Bo); K.B. Jacobs (Kevin); I. Jarick (Ivonne); E. Jewell (Eelizabeth); U. John (Ulrich); T. Jørgensen (Torben); P. Jousilahti (Pekka); A. Jula (Antti); M. Kaakinen (Marika); E. Kajantie (Eero); R.C. Kaplan (Robert); S. Kathiresan (Sekar); J. Kettunen (Johannes); L. Kinnunen (Leena); J.W. Knowles (Joshua); I. Kolcic (Ivana); I.R. König (Inke); S. Koskinen (Seppo); P. Kovacs (Peter); J. Kusisto (Johanna); P. Kraft (Peter); K. Kvaløy (Kirsti); J. Laitinen (Jaana); O. Lantieri (Olivier); C. Lanzani (Chiara); L.J. Launer (Lenore); C. Lecoeur (Cécile); T. Lehtimäki (Terho); G. Lettre (Guillaume); J. Liu (Jianjun); M.L. Lokki; M. Lorentzon (Mattias); R.N. Luben (Robert); B. Ludwig (Barbara); P. Manunta (Paolo); D. Marek (Diana); M. Marre (Michel); N.G. Martin (Nicholas); W.L. McArdle (Wendy); M.I. McCarthy (Mark); B. McKnight (Barbara); T. Meitinger (Thomas); O. Melander (Olle); D. Meyre (David); K. Midthjell (Kristian); G.W. Montgomery (Grant); M.A. Morken (Mario); A.D. Morris (Andrew); R. Mulic (Rosanda); J.S. Ngwa; M. Nelis (Mari); M.J. Neville (Matthew); D.R. Nyholt (Dale); C.J. O'Ddonnell (Christopher); S. O'Rahilly (Stephen); K. Ong (Ken); B.A. Oostra (Ben); G. Paré (Guillaume); A.N. Parker (Alex); M. Perola (Markus); I. Pichler (Irene); K.H. Pietilainen (Kirsi Hannele); C.P. Platou (Carl); O. Polasek (Ozren); A. Pouta (Anneli); S. Rafelt (Suzanne); O. Raitakari (Olli); N.W. Rayner (Nigel William); M. Ridderstråle (Martin); W. Rief (Winfried); A. Ruokonen (Aimo); N.R. Robertson (Neil); P. Rzehak (Peter); V. Salomaa (Veikko); A.R. Sanders (Alan); M.S. Sandhu (Manjinder); S. Sanna (Serena); J. Saramies (Jouko); M.J. Savolainen (Markku); S. Schipf (Sabine); S. Schreiber (Stefan); H. Schunkert (Heribert); K. Silander (Kaisa); J. Sinisalo (Juha); D.S. Siscovick (David); J.H. Smit (Jan); N. Soranzo (Nicole); U. Sovio (Ulla); J. Stephens (Jonathan); I. Surakka (Ida); A.J. Swift (Amy); M.L. Tammesoo; J.-C. Tardif (Jean-Claude); M. Teder-Laving (Maris); T.M. Teslovich (Tanya); J.R. Thompson (John); B. Thomson (Brian); A. Tönjes (Anke); T. Tuomi (Tiinamaija); J.B.J. van Meurs (Joyce); G.J. van OMen; V. Vatin (Vincent); J. Viikari (Jorma); S. Visvikis-Siest (Sophie); V. Vitart (Veronique); C.I. Vogel (Carla); B.F. Voight (Benjamin); L. Waite (Lindsay); H. Wallaschofski (Henri); G.B. Walters (Bragi); E. Widen (Elisabeth); S. Wiegand (Susanna); S.H. Wild (Sarah); G.A.H.M. Willemsen (Gonneke); D.R. Witte (Deniel); J.C.M. Witteman (Jacqueline); J. Xu (Jianfeng); Q. Zhang (Qunyuan); L. Zgaga (Lina); A. Ziegler (Andreas); P. Zitting (Paavo); J.P. Beilby (John); I.S. FarOqi (Ssadaf); J. Hebebrand (Johannes); H.V. Huikuri (Heikki); A. James (Alan); M. Kähönen (Mika); D.F. Levinson (Douglas); F. MacCiardi (Fabio); M.S. Nieminen (Markku); C. Ohlsson (Claes); C. Palmer (Cameron); P.M. Ridker (Paul); M. Stumvoll (Michael); J.S. Beckmann (Jacques); H. Boeing (Heiner); E.A. Boerwinkle (Eric); D.I. Boomsma (Dorret); M. Caulfield (Mark); S.J. Chanock (Stephen); F.S. Collins (Francis); L.A. Cupples (Adrienne); J. Eerdmann (Jeanette); P. Frogue (Philippe); H. Grönberg (Henrik); U. Gyllensten (Ulf); T. Hansen (Torben); T.B. Harris (Tamara); A.T. Hattersley (Andrew); R.B. Hayes (Richard); J. Heinrich (Joachim); F.B. Hu (Frank); K. Hveem (Kristian); T. Illig (Thomas); M.R. Järvelin; J. Kaprio (Jaakko); F. Karpe (Fredrik); K-T. Khaw (Kay-Tee); L.A.L.M. Kiemeney (Bart); H. Krude; M. Laakso (Markku); D.A. Lawlor (Debbie); A. Metspalu (Andres); P. Munroe (Patricia); W.H. Ouwehand (Willem); O. Pedersen (Oluf); B.W.J.H. Penninx (Brenda); P.P. Pramstaller (Peter Paul); T. Quertermous (Thomas); T. Reinehr (Thomas); A. Rissanen (Aila); I. Rudan (Igor); N.J. Samani (Nilesh); P.E.H. Schwarz (Peter); A.R. Shuldiner (Alan); T.D. Spector (Timothy); J. Tuomilehto (Jaakko); M. Uda (Manuela); A.G. Uitterlinden (André); T.T. Valle (Timo); M. Wabitsch (Martin); G. Waeber (Gérard); N.J. Wareham (Nick); H. Watkins (Hugh); J.F. Wilson (James); A.F. Wright (Alan); M.C. Zillikens (Carola); N. ChatterjE (Nilanjan); S.A. McCarroll (Steve); S. Purcell (Shaun); E.E. Schadt (Eric); P.M. Visscher (Peter); T.L. Assimes (Themistocles); I.B. Borecki (Ingrid); P. Deloukas (Panagiotis); C.S. Fox (Caroline); L. Groop (Leif); T. Haritunians (Talin); D.J. Hunter (David); K.L. Mohlke (Karen); J.R. O'ConneL (Jeffrey); L. Peltonen (Leena Johanna); D. SchleSinger (David); D.P. Strachan (David); R.M. Watanabe (Richard); C.M. van Duijn (Cock); H.E. Wichmann (Heinz Erich); T.M. Frayling (Timothy); U. Thorsteinsdottir (Unnur); G.R. Abecasis (Gonçalo); M. Boehnke (Michael); K. StefanSon (Kari); K.E. North (Kari); M.I. McArthy (Mark); J.N. Hirschhorn (Joel); E. IngelSon (Erik); R.J.F. Loos (Ruth); M.N. Weedon (Michael)

    2010-01-01

    textabstractObesity is globaLy prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined aSociations betwEn body maS index and ĝ̂1/42.8 miLion SNPs in up to 123,865 individuals with targeted foLow up of

  18. Association analyses of 249,796 individuals reveal eighteen new loci associated with body mass index

    Science.gov (United States)

    Speliotes, Elizabeth K.; Willer, Cristen J.; Berndt, Sonja I.; Monda, Keri L.; Thorleifsson, Gudmar; Jackson, Anne U.; Allen, Hana Lango; Lindgren, Cecilia M.; Luan, Jian’an; Mägi, Reedik; Randall, Joshua C.; Vedantam, Sailaja; Winkler, Thomas W.; Qi, Lu; Workalemahu, Tsegaselassie; Heid, Iris M.; Steinthorsdottir, Valgerdur; Stringham, Heather M.; Weedon, Michael N.; Wheeler, Eleanor; Wood, Andrew R.; Ferreira, Teresa; Weyant, Robert J.; Segré, Ayellet V.; Estrada, Karol; Liang, Liming; Nemesh, James; Park, Ju-Hyun; Gustafsson, Stefan; Kilpeläinen, Tuomas O.; Yang, Jian; Bouatia-Naji, Nabila; Esko, Tõnu; Feitosa, Mary F.; Kutalik, Zoltán; Mangino, Massimo; Raychaudhuri, Soumya; Scherag, Andre; Smith, Albert Vernon; Welch, Ryan; Zhao, Jing Hua; Aben, Katja K.; Absher, Devin M.; Amin, Najaf; Dixon, Anna L.; Fisher, Eva; Glazer, Nicole L.; Goddard, Michael E.; Heard-Costa, Nancy L.; Hoesel, Volker; Hottenga, Jouke-Jan; Johansson, Åsa; Johnson, Toby; Ketkar, Shamika; Lamina, Claudia; Li, Shengxu; Moffatt, Miriam F.; Myers, Richard H.; Narisu, Narisu; Perry, John R.B.; Peters, Marjolein J.; Preuss, Michael; Ripatti, Samuli; Rivadeneira, Fernando; Sandholt, Camilla; Scott, Laura J.; Timpson, Nicholas J.; Tyrer, Jonathan P.; van Wingerden, Sophie; Watanabe, Richard M.; White, Charles C.; Wiklund, Fredrik; Barlassina, Christina; Chasman, Daniel I.; Cooper, Matthew N.; Jansson, John-Olov; Lawrence, Robert W.; Pellikka, Niina; Prokopenko, Inga; Shi, Jianxin; Thiering, Elisabeth; Alavere, Helene; Alibrandi, Maria T. S.; Almgren, Peter; Arnold, Alice M.; Aspelund, Thor; Atwood, Larry D.; Balkau, Beverley; Balmforth, Anthony J.; Bennett, Amanda J.; Ben-Shlomo, Yoav; Bergman, Richard N.; Bergmann, Sven; Biebermann, Heike; Blakemore, Alexandra I.F.; Boes, Tanja; Bonnycastle, Lori L.; Bornstein, Stefan R.; Brown, Morris J.; Buchanan, Thomas A.; Busonero, Fabio; Campbell, Harry; Cappuccio, Francesco P.; Cavalcanti-Proença, Christine; Chen, Yii-Der Ida; Chen, Chih-Mei; Chines, Peter S.; Clarke, Robert; Coin, Lachlan; Connell, John; Day, Ian N.M.; den Heijer, Martin; Duan, Jubao; Ebrahim, Shah; Elliott, Paul; Elosua, Roberto; Eiriksdottir, Gudny; Erdos, Michael R.; Eriksson, Johan G.; Facheris, Maurizio F.; Felix, Stephan B.; Fischer-Posovszky, Pamela; Folsom, Aaron R.; Friedrich, Nele; Freimer, Nelson B.; Fu, Mao; Gaget, Stefan; Gejman, Pablo V.; Geus, Eco J.C.; Gieger, Christian; Gjesing, Anette P.; Goel, Anuj; Goyette, Philippe; Grallert, Harald; Gräßler, Jürgen; Greenawalt, Danielle M.; Groves, Christopher J.; Gudnason, Vilmundur; Guiducci, Candace; Hartikainen, Anna-Liisa; Hassanali, Neelam; Hall, Alistair S.; Havulinna, Aki S.; Hayward, Caroline; Heath, Andrew C.; Hengstenberg, Christian; Hicks, Andrew A.; Hinney, Anke; Hofman, Albert; Homuth, Georg; Hui, Jennie; Igl, Wilmar; Iribarren, Carlos; Isomaa, Bo; Jacobs, Kevin B.; Jarick, Ivonne; Jewell, Elizabeth; John, Ulrich; Jørgensen, Torben; Jousilahti, Pekka; Jula, Antti; Kaakinen, Marika; Kajantie, Eero; Kaplan, Lee M.; Kathiresan, Sekar; Kettunen, Johannes; Kinnunen, Leena; Knowles, Joshua W.; Kolcic, Ivana; König, Inke R.; Koskinen, Seppo; Kovacs, Peter; Kuusisto, Johanna; Kraft, Peter; Kvaløy, Kirsti; Laitinen, Jaana; Lantieri, Olivier; Lanzani, Chiara; Launer, Lenore J.; Lecoeur, Cecile; Lehtimäki, Terho; Lettre, Guillaume; Liu, Jianjun; Lokki, Marja-Liisa; Lorentzon, Mattias; Luben, Robert N.; Ludwig, Barbara; Manunta, Paolo; Marek, Diana; Marre, Michel; Martin, Nicholas G.; McArdle, Wendy L.; McCarthy, Anne; McKnight, Barbara; Meitinger, Thomas; Melander, Olle; Meyre, David; Midthjell, Kristian; Montgomery, Grant W.; Morken, Mario A.; Morris, Andrew P.; Mulic, Rosanda; Ngwa, Julius S.; Nelis, Mari; Neville, Matt J.; Nyholt, Dale R.; O’Donnell, Christopher J.; O’Rahilly, Stephen; Ong, Ken K.; Oostra, Ben; Paré, Guillaume; Parker, Alex N.; Perola, Markus; Pichler, Irene; Pietiläinen, Kirsi H.; Platou, Carl G.P.; Polasek, Ozren; Pouta, Anneli; Rafelt, Suzanne; Raitakari, Olli; Rayner, Nigel W.; Ridderstråle, Martin; Rief, Winfried; Ruokonen, Aimo; Robertson, Neil R.; Rzehak, Peter; Salomaa, Veikko; Sanders, Alan R.; Sandhu, Manjinder S.; Sanna, Serena; Saramies, Jouko; Savolainen, Markku J.; Scherag, Susann; Schipf, Sabine; Schreiber, Stefan; Schunkert, Heribert; Silander, Kaisa; Sinisalo, Juha; Siscovick, David S.; Smit, Jan H.; Soranzo, Nicole; Sovio, Ulla; Stephens, Jonathan; Surakka, Ida; Swift, Amy J.; Tammesoo, Mari-Liis; Tardif, Jean-Claude; Teder-Laving, Maris; Teslovich, Tanya M.; Thompson, John R.; Thomson, Brian; Tönjes, Anke; Tuomi, Tiinamaija; van Meurs, Joyce B.J.; van Ommen, Gert-Jan; Vatin, Vincent; Viikari, Jorma; Visvikis-Siest, Sophie; Vitart, Veronique; Vogel, Carla I. G.; Voight, Benjamin F.; Waite, Lindsay L.; Wallaschofski, Henri; Walters, G. Bragi; Widen, Elisabeth; Wiegand, Susanna; Wild, Sarah H.; Willemsen, Gonneke; Witte, Daniel R.; Witteman, Jacqueline C.; Xu, Jianfeng; Zhang, Qunyuan; Zgaga, Lina; Ziegler, Andreas; Zitting, Paavo; Beilby, John P.; Farooqi, I. Sadaf; Hebebrand, Johannes; Huikuri, Heikki V.; James, Alan L.; Kähönen, Mika; Levinson, Douglas F.; Macciardi, Fabio; Nieminen, Markku S.; Ohlsson, Claes; Palmer, Lyle J.; Ridker, Paul M.; Stumvoll, Michael; Beckmann, Jacques S.; Boeing, Heiner; Boerwinkle, Eric; Boomsma, Dorret I.; Caulfield, Mark J.; Chanock, Stephen J.; Collins, Francis S.; Cupples, L. Adrienne; Smith, George Davey; Erdmann, Jeanette; Froguel, Philippe; Grönberg, Henrik; Gyllensten, Ulf; Hall, Per; Hansen, Torben; Harris, Tamara B.; Hattersley, Andrew T.; Hayes, Richard B.; Heinrich, Joachim; Hu, Frank B.; Hveem, Kristian; Illig, Thomas; Jarvelin, Marjo-Riitta; Kaprio, Jaakko; Karpe, Fredrik; Khaw, Kay-Tee; Kiemeney, Lambertus A.; Krude, Heiko; Laakso, Markku; Lawlor, Debbie A.; Metspalu, Andres; Munroe, Patricia B.; Ouwehand, Willem H.; Pedersen, Oluf; Penninx, Brenda W.; Peters, Annette; Pramstaller, Peter P.; Quertermous, Thomas; Reinehr, Thomas; Rissanen, Aila; Rudan, Igor; Samani, Nilesh J.; Schwarz, Peter E.H.; Shuldiner, Alan R.; Spector, Timothy D.; Tuomilehto, Jaakko; Uda, Manuela; Uitterlinden, André; Valle, Timo T.; Wabitsch, Martin; Waeber, Gérard; Wareham, Nicholas J.; Watkins, Hugh; Wilson, James F.; Wright, Alan F.; Zillikens, M. Carola; Chatterjee, Nilanjan; McCarroll, Steven A.; Purcell, Shaun; Schadt, Eric E.; Visscher, Peter M.; Assimes, Themistocles L.; Borecki, Ingrid B.; Deloukas, Panos; Fox, Caroline S.; Groop, Leif C.; Haritunians, Talin; Hunter, David J.; Kaplan, Robert C.; Mohlke, Karen L.; O’Connell, Jeffrey R.; Peltonen, Leena; Schlessinger, David; Strachan, David P.; van Duijn, Cornelia M.; Wichmann, H.-Erich; Frayling, Timothy M.; Thorsteinsdottir, Unnur; Abecasis, Gonçalo R.; Barroso, Inês; Boehnke, Michael; Stefansson, Kari; North, Kari E.; McCarthy, Mark I.; Hirschhorn, Joel N.; Ingelsson, Erik; Loos, Ruth J.F.

    2010-01-01

    Obesity is globally prevalent and highly heritable, but the underlying genetic factors remain largely elusive. To identify genetic loci for obesity-susceptibility, we examined associations between body mass index (BMI) and ~2.8 million SNPs in up to 123,865 individuals, with targeted follow-up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity-susceptibility loci and identified 18 new loci associated with BMI (Pbody weight regulation. PMID:20935630

  19. A Systematic Review of Studies Using the Brief COPE: Religious Coping in Factor Analyses

    Directory of Open Access Journals (Sweden)

    Christian U. Krägeloh

    2011-07-01

    Full Text Available Religion is generally recognized as a major resource for dealing with stressful events, but its relationship with secular coping strategies continues to be debated. The present article provides a systematic review of the way in which analyses of the sub-scale turning to religion of the widely used Brief COPE [1] instrument are presented in peer-reviewed research articles, in order to investigate how the wealth of data published using this instrument can inform how religious coping relates to other coping strategies. Of the 212 identified articles that included turning to religion in their analyses, 80 combined sub-scale scores to form higher-order coping factors, 38 of which based on exploratory factor analyses of their own datasets. When factor analyses had used individual items as indicators, religious coping was more likely to load together with maladaptive coping strategies, and more likely with adaptive coping strategies when analyses were conducted at sub-scale level. To a large extent, the variation in the results from exploratory factor analyses appears to be due to the diverse and often inappropriate factor analytic techniques used to determine the factor structure of the Brief COPE instrument. Reports from factor analyses of the Brief COPE therefore have very little value when trying to make general conclusions about the role of religious coping in relation to secular coping methods.

  20. Sequencing and analyses of all known human rhinovirus genomes reveal structure and evolution.

    Science.gov (United States)

    Palmenberg, Ann C; Spiro, David; Kuzmickas, Ryan; Wang, Shiliang; Djikeng, Appolinaire; Rathe, Jennifer A; Fraser-Liggett, Claire M; Liggett, Stephen B

    2009-04-03

    Infection by human rhinovirus (HRV) is a major cause of upper and lower respiratory tract disease worldwide and displays considerable phenotypic variation. We examined diversity by completing the genome sequences for all known serotypes (n = 99). Superimposition of capsid crystal structure and optimal-energy RNA configurations established alignments and phylogeny. These revealed conserved motifs; clade-specific diversity, including a potential newly identified species (HRV-D); mutations in field isolates; and recombination. In analogy with poliovirus, a hypervariable 5' untranslated region tract may affect virulence. A configuration consistent with nonscanning internal ribosome entry was found in all HRVs and may account for rapid translation. The data density from complete sequences of the reference HRVs provided high resolution for this degree of modeling and serves as a platform for full genome-based epidemiologic studies and antiviral or vaccine development.

  1. Dynamic changes in brewing yeast cells in culture revealed by statistical analyses of yeast morphological data.

    Science.gov (United States)

    Ohnuki, Shinsuke; Enomoto, Kenichi; Yoshimoto, Hiroyuki; Ohya, Yoshikazu

    2014-03-01

    The vitality of brewing yeasts has been used to monitor their physiological state during fermentation. To investigate the fermentation process, we used the image processing software, CalMorph, which generates morphological data on yeast mother cells and bud shape, nuclear shape and location, and actin distribution. We found that 248 parameters changed significantly during fermentation. Successive use of principal component analysis (PCA) revealed several important features of yeast, providing insight into the dynamic changes in the yeast population. First, PCA indicated that much of the observed variability in the experiment was summarized in just two components: a change with a peak and a change over time. Second, PCA indicated the independent and important morphological features responsible for dynamic changes: budding ratio, nucleus position, neck position, and actin organization. Thus, the large amount of data provided by imaging analysis can be used to monitor the fermentation processes involved in beer and bioethanol production.

  2. Intact-Brain Analyses Reveal Distinct Information Carried by SNc Dopamine Subcircuits.

    Science.gov (United States)

    Lerner, Talia N; Shilyansky, Carrie; Davidson, Thomas J; Evans, Kathryn E; Beier, Kevin T; Zalocusky, Kelly A; Crow, Ailey K; Malenka, Robert C; Luo, Liqun; Tomer, Raju; Deisseroth, Karl

    2015-07-30

    Recent progress in understanding the diversity of midbrain dopamine neurons has highlighted the importance--and the challenges--of defining mammalian neuronal cell types. Although neurons may be best categorized using inclusive criteria spanning biophysical properties, wiring of inputs, wiring of outputs, and activity during behavior, linking all of these measurements to cell types within the intact brains of living mammals has been difficult. Here, using an array of intact-brain circuit interrogation tools, including CLARITY, COLM, optogenetics, viral tracing, and fiber photometry, we explore the diversity of dopamine neurons within the substantia nigra pars compacta (SNc). We identify two parallel nigrostriatal dopamine neuron subpopulations differing in biophysical properties, input wiring, output wiring to dorsomedial striatum (DMS) versus dorsolateral striatum (DLS), and natural activity patterns during free behavior. Our results reveal independently operating nigrostriatal information streams, with implications for understanding the logic of dopaminergic feedback circuits and the diversity of mammalian neuronal cell types.

  3. Microbial Response to Soil Liming of Damaged Ecosystems Revealed by Pyrosequencing and Phospholipid Fatty Acid Analyses

    Science.gov (United States)

    Narendrula-Kotha, Ramya; Nkongolo, Kabwe K.

    2017-01-01

    Aims To assess the effects of dolomitic limestone applications on soil microbial communities’ dynamics and bacterial and fungal biomass, relative abundance, and diversity in metal reclaimed regions. Methods and Results The study was conducted in reclaimed mining sites and metal uncontaminated areas. The limestone applications were performed over 35 years ago. Total microbial biomass was determined by Phospholipid fatty acids. Bacterial and fungal relative abundance and diversity were assessed using 454 pyrosequencing. There was a significant increase of total microbial biomass in limed sites (342 ng/g) compared to unlimed areas (149 ng/g). Chao1 estimates followed the same trend. But the total number of OTUs (Operational Taxonomic Units) in limed (463 OTUs) and unlimed (473 OTUs) soil samples for bacteria were similar. For fungi, OTUs were 96 and 81 for limed and unlimed soil samples, respectively. Likewise, Simpson and Shannon diversity indices revealed no significant differences between limed and unlimed sites. Bacterial and fungal groups specific to either limed or unlimed sites were identified. Five major bacterial phyla including Actinobacteria, Acidobacteria, Chloroflexi, Firmicutes, and Proteobacteria were found. The latter was the most prevalent phylum in all the samples with a relative abundance of 50%. Bradyrhizobiaceae family with 12 genera including the nitrogen fixing Bradirhizobium genus was more abundant in limed sites compared to unlimed areas. For fungi, Ascomycota was the most predominant phylum in unlimed soils (46%) while Basidiomycota phylum represented 86% of all fungi in the limed areas. Conclusion Detailed analysis of the data revealed that although soil liming increases significantly the amount of microbial biomass, the level of species diversity remain statistically unchanged even though the microbial compositions of the damaged and restored sites are different. Significance and Impact of the study Soil liming still have a significant

  4. Cloning and comparative analyses of the zebrafish Ugt repertoire reveal its evolutionary diversity.

    Directory of Open Access Journals (Sweden)

    Haiyan Huang

    Full Text Available UDP-glucuronosyltransferases (Ugts are a supergene family of phase II drug-metabolizing enzymes that catalyze the conjugation of numerous hydrophobic small molecules with the UDP-glucuronic acid, converting them into hydrophilic molecules. Here, we report the identification and cloning of the complete zebrafish Ugt gene repertoire. We found that the zebrafish genome contains 45 Ugt genes that can be divided into three families: Ugt1, Ugt2, and Ugt5. Both Ugt1 and Ugt2 have two unlinked clusters: a and b. The Ugt1a, Ugt1b, Ugt2a, and Ugt2b clusters each contain variable and constant regions, similar to that of the protocadherin (Pcdh, immunoglobulin (Ig, and T-cell receptor (Tcr clusters. Cloning the full-length coding sequences confirmed that each of the variable exons is separately spliced to the set of constant exons within each zebrafish Ugt cluster. Comparative analyses showed that both a and b clusters of the zebrafish Ugt1 and Ugt2 genes have orthologs in other teleosts, suggesting that they may be resulted from the "fish-specific" whole-genome duplication event. The Ugt5 genes are a novel family of Ugt genes that exist in teleosts and amphibians. Their entire open reading frames are encoded by single large exons. The zebrafish Ugt1, Ugt2, and Ugt5 genes can generate additional transcript diversity through alternative splicing. Based on phylogenetic analyses, we propose that the ancestral tetrapod and teleost Ugt1 clusters contained multiple Ugt1 paralogs. After speciation, these ancestral Ugt1 clusters underwent lineage-specific gene loss and duplication. The ancestral vertebrate Ugt2 cluster also underwent lineage-specific duplication. The intronless Ugt5 open reading frames may be derived from retrotransposition followed by gene duplication. They have been expanded dramatically in teleosts and have become the most abundant Ugt family in these lineages. These findings have interesting implications regarding the molecular evolution of

  5. Physiological and transcriptomic analyses reveal a response mechanism to cold stress in Santalum album L. leaves

    Science.gov (United States)

    Zhang, Xinhua; Teixeira da Silva, Jaime A.; Niu, Meiyun; Li, Mingzhi; He, Chunmei; Zhao, Jinhui; Zeng, Songjun; Duan, Jun; Ma, Guohua

    2017-01-01

    Santalum album L. (Indian sandalwood) is an economically important plant species because of its ability to produce highly valued perfume oils. Little is known about the mechanisms by which S. album adapts to low temperatures. In this study, we obtained 100,445,724 raw reads by paired-end sequencing from S. album leaves. Physiological and transcriptomic changes in sandalwood seedlings exposed to 4 °C for 0–48 h were characterized. Cold stress induced the accumulation of malondialdehyde, proline and soluble carbohydrates, and increased the levels of antioxidants. A total of 4,424 differentially expressed genes were responsive to cold, including 3,075 cold-induced and 1,349 cold-repressed genes. When cold stress was prolonged, there was an increase in the expression of cold-responsive genes coding for transporters, responses to stimuli and stress, regulation of defense response, as well as genes related to signal transduction of all phytohormones. Candidate genes in the terpenoid biosynthetic pathway were identified, eight of which were significantly involved in the cold stress response. Gene expression analyses using qRT-PCR showed a peak in the accumulation of SaCBF2 to 4, 50-fold more than control leaves and roots following 12 h and 24 h of cold stress, respectively. The CBF-dependent pathway may play a crucial role in increasing cold tolerance. PMID:28169358

  6. Structural, Bioinformatic, and In Vivo Analyses of Two Treponema pallidum Lipoproteins Reveal a Unique TRAP Transporter

    Energy Technology Data Exchange (ETDEWEB)

    Deka, Ranjit K.; Brautigam, Chad A.; Goldberg, Martin; Schuck, Peter; Tomchick, Diana R.; Norgard, Michael V. (NIH); (UTSMC)

    2012-05-25

    Treponema pallidum, the bacterial agent of syphilis, is predicted to encode one tripartite ATP-independent periplasmic transporter (TRAP-T). TRAP-Ts typically employ a periplasmic substrate-binding protein (SBP) to deliver the cognate ligand to the transmembrane symporter. Herein, we demonstrate that the genes encoding the putative TRAP-T components from T. pallidum, tp0957 (the SBP), and tp0958 (the symporter), are in an operon with an uncharacterized third gene, tp0956. We determined the crystal structure of recombinant Tp0956; the protein is trimeric and perforated by a pore. Part of Tp0956 forms an assembly similar to those of 'tetratricopeptide repeat' (TPR) motifs. The crystal structure of recombinant Tp0957 was also determined; like the SBPs of other TRAP-Ts, there are two lobes separated by a cleft. In these other SBPs, the cleft binds a negatively charged ligand. However, the cleft of Tp0957 has a strikingly hydrophobic chemical composition, indicating that its ligand may be substantially different and likely hydrophobic. Analytical ultracentrifugation of the recombinant versions of Tp0956 and Tp0957 established that these proteins associate avidly. This unprecedented interaction was confirmed for the native molecules using in vivo cross-linking experiments. Finally, bioinformatic analyses suggested that this transporter exemplifies a new subfamily of TPATs (TPR-protein-associated TRAP-Ts) that require the action of a TPR-containing accessory protein for the periplasmic transport of a potentially hydrophobic ligand(s).

  7. Metabolomic and Functional Genomic Analyses Reveal Varietal Differences in Bioactive Compounds of Cooked Rice

    Science.gov (United States)

    Heuberger, Adam L.; Lewis, Matthew R.; Chen, Ming-Hsuan; Brick, Mark A.; Leach, Jan E.; Ryan, Elizabeth P.

    2010-01-01

    Emerging evidence supports that cooked rice (Oryza sativa L.) contains metabolites with biomedical activities, yet little is known about the genetic diversity that is responsible for metabolite variation and differences in health traits. Metabolites from ten diverse varieties of cooked rice were detected using ultra performance liquid chromatography coupled to mass spectrometry. A total of 3,097 compounds were detected, of which 25% differed among the ten varieties. Multivariate analyses of the metabolite profiles showed that the chemical diversity among the varieties cluster according to their defined subspecies classifications: indica, japonica, and aus. Metabolite-specific genetic diversity in rice was investigated by analyzing a collection of single nucleotide polymorphisms (SNPs) in genes from biochemical pathways of nutritional importance. Two classes of bioactive compounds, phenolics and vitamin E, contained nonsynonymous SNPs and SNPs in the 5′ and 3′ untranslated regions for genes in their biosynthesis pathways. Total phenolics and tocopherol concentrations were determined to examine the effect of the genetic diversity among the ten varieties. Per gram of cooked rice, total phenolics ranged from 113.7 to 392.6 µg (gallic acid equivalents), and total tocopherols ranged between 7.2 and 20.9 µg. The variation in the cooked rice metabolome and quantities of bioactive components supports that the SNP-based genetic diversity influenced nutritional components in rice, and that this approach may guide rice improvement strategies for plant and human health. PMID:20886119

  8. Evolutionary trajectories of snake genes and genomes revealed by comparative analyses of five-pacer viper

    Science.gov (United States)

    Yin, Wei; Wang, Zong-ji; Li, Qi-ye; Lian, Jin-ming; Zhou, Yang; Lu, Bing-zheng; Jin, Li-jun; Qiu, Peng-xin; Zhang, Pei; Zhu, Wen-bo; Wen, Bo; Huang, Yi-jun; Lin, Zhi-long; Qiu, Bi-tao; Su, Xing-wen; Yang, Huan-ming; Zhang, Guo-jie; Yan, Guang-mei; Zhou, Qi

    2016-01-01

    Snakes have numerous features distinctive from other tetrapods and a rich history of genome evolution that is still obscure. Here, we report the high-quality genome of the five-pacer viper, Deinagkistrodon acutus, and comparative analyses with other representative snake and lizard genomes. We map the evolutionary trajectories of transposable elements (TEs), developmental genes and sex chromosomes onto the snake phylogeny. TEs exhibit dynamic lineage-specific expansion, and many viper TEs show brain-specific gene expression along with their nearby genes. We detect signatures of adaptive evolution in olfactory, venom and thermal-sensing genes and also functional degeneration of genes associated with vision and hearing. Lineage-specific relaxation of functional constraints on respective Hox and Tbx limb-patterning genes supports fossil evidence for a successive loss of forelimbs then hindlimbs during snake evolution. Finally, we infer that the ZW sex chromosome pair had undergone at least three recombination suppression events in the ancestor of advanced snakes. These results altogether forge a framework for our deep understanding into snakes' history of molecular evolution. PMID:27708285

  9. Ancient origins of metazoan gonadotropin-releasing hormone and their receptors revealed by phylogenomic analyses.

    Science.gov (United States)

    Plachetzki, David C; Tsai, Pei-San; Kavanaugh, Scott I; Sower, Stacia A

    2016-08-01

    The discovery of genes related to gonadotropin-releasing hormones (GnRH) and their receptors from diverse species has driven important advances in comparative endocrinology. However, our view of the evolutionary histories and nomenclature of these gene families has become inconsistent as several different iterations of GnRH and receptor relationships have been proposed. Whole genome sequence data are now available for most of the major lineages of animals, and an exhaustive view of the phylogenies of GnRH and their receptors is now possible. In this paper, we leverage data from publically available whole genome sequences to present a new phylogenomic analysis of GnRH and GnRH receptors and the distant relatives of each across metazoan phylogeny. Our approach utilizes a phylogenomics pipeline that searches data from 36 whole genome sequences and conducts phylogenetic analyses of gene trees. We provide a comprehensive analysis of the major groupings of GnRH peptides, related hormones and their receptors and provide some suggestions for a new nomenclature. Our study provides a framework for understanding the functional diversification of this family of neuromodulatory peptides and their receptors.

  10. Kinetic features revealed by top-hat electrostatic analysers: numerical simulations and instrument response results

    Science.gov (United States)

    De Marco, Rossana; Marcucci, Maria Federica; Brienza, Daniele; Bruno, Roberto; Consolini, Giuseppe; Perrone, Denise; Valentini, Franceso; Servidio, Sergio; Stabile, Sara; Pezzi, Oreste; Sorriso-Valvo, Luca; Lavraud, Benoit; De Keyser, Johan; Retinò, Alessandro; Fazakerley, Andrew; Wicks, Robert; Vaivads, Andris; Salatti, Mario; Veltri, Pierliugi

    2017-04-01

    Turbulence Heating ObserveR (THOR) is the first mission devoted to study energization, acceleration and heating of turbulent space plasmas, and designed to perform field and particle measurements at kinetic scales in different near-Earth regions and in the solar wind. Solar Orbiter (SolO), together with Solar Probe Plus, will provide the first comprehensive remote and in situ measurements which are critical to establish the fundamental physical links between the Sun's dynamic atmosphere and the turbulent solar wind. The fundamental process of turbulent dissipation is mediated by physical mechanism that occur at a variety of temporal and spatial scales, and most efficiently at the kinetics scales. Hybrid Vlasov-Maxwell simulations of solar-wind turbulence show that kinetic effects manifest as particle beams, production of temperature anisotropies and ring-like modulations, preferential heating of heavy ions. We use a numerical code able to reproduce the response of a typical electrostatic analyzer of top-hat type starting from velocity distribution functions (VDFs) generated by Hybrid Vlasov-Maxwell (HVM) numerical simulations. Here, we show how optimized particle measurements by top-hat analysers can capture the kinetic features injected by turbulence in the VDFs.

  11. Molecular phylogeny and morphometric analyses reveal deep divergence between Amazonia and Atlantic Forest species of Dendrophryniscus.

    Science.gov (United States)

    Fouquet, Antoine; Recoder, Renato; Teixeira, Mauro; Cassimiro, José; Amaro, Renata Cecília; Camacho, Agustín; Damasceno, Roberta; Carnaval, Ana Carolina; Moritz, Craig; Rodrigues, Miguel Trefaut

    2012-03-01

    Dendrophryniscus is an early diverging clade of bufonids represented by few small-bodied species distributed in Amazonia and the Atlantic Forest. We used mitochondrial (414 bp of 12S, 575 bp of 16S genes) and nuclear DNA (785 bp of RAG-1) to investigate phylogenetic relationships and the timing of diversification within the genus. These molecular data were gathered from 23 specimens from 19 populations, including eight out of the 10 nominal species of the genus as well as Rhinella boulengeri. Analyses also included sequences of representatives of 18 other bufonid genera that were publically available. We also examined morphological characters to analyze differences within Dendrophryniscus. We found deep genetic divergence between an Amazonian and an Atlantic Forest clade, dating back to Eocene. Morphological data corroborate this distinction. We thus propose to assign the Amazonian species to a new genus, Amazonella. The species currently named R. boulengeri, which has been previously assigned to the genus Rhamphophryne, is shown to be closely related to Dendrophryniscus species. Our findings illustrate cryptic trends in bufonid morphological evolution, and point to a deep history of persistence and diversification within the Amazonian and Atlantic rainforests. We discuss our results in light of available paleoecological data and the biogeographic patterns observed in other similarly distributed groups.

  12. Phylogeographic and population genetic analyses reveal multiple species of Boa and independent origins of insular dwarfism.

    Science.gov (United States)

    Card, Daren C; Schield, Drew R; Adams, Richard H; Corbin, Andrew B; Perry, Blair W; Andrew, Audra L; Pasquesi, Giulia I M; Smith, Eric N; Jezkova, Tereza; Boback, Scott M; Booth, Warren; Castoe, Todd A

    2016-09-01

    Boa is a Neotropical genus of snakes historically recognized as monotypic despite its expansive distribution. The distinct morphological traits and color patterns exhibited by these snakes, together with the wide diversity of ecosystems they inhabit, collectively suggest that the genus may represent multiple species. Morphological variation within Boa also includes instances of dwarfism observed in multiple offshore island populations. Despite this substantial diversity, the systematics of the genus Boa has received little attention until very recently. In this study we examined the genetic structure and phylogenetic relationships of Boa populations using mitochondrial sequences and genome-wide SNP data obtained from RADseq. We analyzed these data at multiple geographic scales using a combination of phylogenetic inference (including coalescent-based species delimitation) and population genetic analyses. We identified extensive population structure across the range of the genus Boa and multiple lines of evidence for three widely-distributed clades roughly corresponding with the three primary land masses of the Western Hemisphere. We also find both mitochondrial and nuclear support for independent origins and parallel evolution of dwarfism on offshore island clusters in Belize and Cayos Cochinos Menor, Honduras. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Chemical analyses of wasp-associated streptomyces bacteria reveal a prolific potential for natural products discovery.

    Directory of Open Access Journals (Sweden)

    Michael Poulsen

    Full Text Available Identifying new sources for small molecule discovery is necessary to help mitigate the continuous emergence of antibiotic-resistance in pathogenic microbes. Recent studies indicate that one potentially rich source of novel natural products is Actinobacterial symbionts associated with social and solitary Hymenoptera. Here we test this possibility by examining two species of solitary mud dauber wasps, Sceliphron caementarium and Chalybion californicum. We performed enrichment isolations from 33 wasps and obtained more than 200 isolates of Streptomyces Actinobacteria. Chemical analyses of 15 of these isolates identified 11 distinct and structurally diverse secondary metabolites, including a novel polyunsaturated and polyoxygenated macrocyclic lactam, which we name sceliphrolactam. By pairing the 15 Streptomyces strains against a collection of fungi and bacteria, we document their antifungal and antibacterial activity. The prevalence and anti-microbial properties of Actinobacteria associated with these two solitary wasp species suggest the potential role of these Streptomyces as antibiotic-producing symbionts, potentially helping defend their wasp hosts from pathogenic microbes. Finding phylogenetically diverse and chemically prolific Actinobacteria from solitary wasps suggests that insect-associated Actinobacteria can provide a valuable source of novel natural products of pharmaceutical interest.

  14. Dimensionality of the Chinese Dyadic Adjustment Scale Based on Confirmatory Factor Analyses

    Science.gov (United States)

    Shek, Daniel T. L.; Cheung, C. K.

    2008-01-01

    Based on the responses of 1,501 Chinese married adults to the Chinese version of the Dyadic Adjustment Scale (C-DAS), confirmatory factor analyses showed that four factors were abstracted from the C-DAS (Dyadic Consensus, Dyadic Cohesion, Dyadic Satisfaction and Affectional Expression) and these four primary factors were subsumed under a…

  15. Comparative Systems Analyses Reveal Molecular Signatures of Clinically tested Vaccine Adjuvants.

    Science.gov (United States)

    Olafsdottir, Thorunn A; Lindqvist, Madelene; Nookaew, Intawat; Andersen, Peter; Maertzdorf, Jeroen; Persson, Josefine; Christensen, Dennis; Zhang, Yuan; Anderson, Jenna; Khoomrung, Sakda; Sen, Partho; Agger, Else Marie; Coler, Rhea; Carter, Darrick; Meinke, Andreas; Rappuoli, Rino; Kaufmann, Stefan H E; Reed, Steven G; Harandi, Ali M

    2016-12-13

    A better understanding of the mechanisms of action of human adjuvants could inform a rational development of next generation vaccines for human use. Here, we exploited a genome wide transcriptomics analysis combined with a systems biology approach to determine the molecular signatures induced by four clinically tested vaccine adjuvants, namely CAF01, IC31, GLA-SE and Alum in mice. We report signature molecules, pathways, gene modules and networks, which are shared by or otherwise exclusive to these clinical-grade adjuvants in whole blood and draining lymph nodes of mice. Intriguingly, co-expression analysis revealed blood gene modules highly enriched for molecules with documented roles in T follicular helper (TFH) and germinal center (GC) responses. We could show that all adjuvants enhanced, although with different magnitude and kinetics, TFH and GC B cell responses in draining lymph nodes. These results represent, to our knowledge, the first comparative systems analysis of clinically tested vaccine adjuvants that may provide new insights into the mechanisms of action of human adjuvants.

  16. Comparative Systems Analyses Reveal Molecular Signatures of Clinically tested Vaccine Adjuvants

    Science.gov (United States)

    Olafsdottir, Thorunn A.; Lindqvist, Madelene; Nookaew, Intawat; Andersen, Peter; Maertzdorf, Jeroen; Persson, Josefine; Christensen, Dennis; Zhang, Yuan; Anderson, Jenna; Khoomrung, Sakda; Sen, Partho; Agger, Else Marie; Coler, Rhea; Carter, Darrick; Meinke, Andreas; Rappuoli, Rino; Kaufmann, Stefan H. E.; Reed, Steven G.; Harandi, Ali M.

    2016-12-01

    A better understanding of the mechanisms of action of human adjuvants could inform a rational development of next generation vaccines for human use. Here, we exploited a genome wide transcriptomics analysis combined with a systems biology approach to determine the molecular signatures induced by four clinically tested vaccine adjuvants, namely CAF01, IC31, GLA-SE and Alum in mice. We report signature molecules, pathways, gene modules and networks, which are shared by or otherwise exclusive to these clinical-grade adjuvants in whole blood and draining lymph nodes of mice. Intriguingly, co-expression analysis revealed blood gene modules highly enriched for molecules with documented roles in T follicular helper (TFH) and germinal center (GC) responses. We could show that all adjuvants enhanced, although with different magnitude and kinetics, TFH and GC B cell responses in draining lymph nodes. These results represent, to our knowledge, the first comparative systems analysis of clinically tested vaccine adjuvants that may provide new insights into the mechanisms of action of human adjuvants.

  17. COMPARATIVE ANALYSES OF MORPHOLOGICAL CHARACTERS IN SPHAERODORIDAE AND ALLIES (ANNELIDA REVEALED BY AN INTEGRATIVE MICROSCOPICAL APPROACH

    Directory of Open Access Journals (Sweden)

    Conrad eHelm

    2015-01-01

    Full Text Available Sphaerodoridae is a group of benthic marine worms (Annelida characterized by the presence of spherical tubercles covering their whole surface. They are commonly considered as belonging to Phyllodocida although sistergroup relationships are still far from being understood. Primary homology assessment of their morphological features are lacking, hindering the appraisal of evolutionary relationships between taxa. Therefore, our detailed morphological investigation focuses on different Sphaerodoridae as well as on other members of Phyllodocida using an integrative approach combining scanning electron microscopy (SEM as well as immunohistochemistry with standard neuronal (anti-5-HT and muscular (phalloidin-rhodamine markers and subsequent CLSM analysis of whole mounts and sections. Furthermore, we provide histological (HES and light microscopical data to shed light on the structures and hypothetical function of sphaerodorid key morphological features. We provide fundamental details into the sphaerodorid morphology supporting a Phyllodocida ancestry of these enigmatic worms. However, the muscular arrangement and the presence of an axial muscular pharynx is similar to conditions observed in other members of the Errantia too. Furthermore, nervous system and muscle staining as well as SEM and histological observations of different types of tubercles indicate a homology of the so called microtubercles, present in the long-bodied sphaerodorids, to the dorsal cirri of other Errantia. The macrotubercles seem to represent a sphaerodorid autapomorphy based on our investigations. Therefore, our results allow comparisons concerning morphological patterns between Sphaerodoridae and other Phyllodocida and constitute a starting point for further comparative investigations to reveal the evolution of the remarkable Sphaerodoridae.

  18. Global terrestrial water storage connectivity revealed using complex climate network analyses

    Directory of Open Access Journals (Sweden)

    A. Y. Sun

    2015-04-01

    Full Text Available Terrestrial water storage (TWS exerts a key control in global water, energy, and biogeochemical cycles. Although certain causal relationships exist between precipitation and TWS, the latter also reflects impacts of anthropogenic activities. Thus, quantification of the spatial patterns of TWS will not only help to understand feedbacks between climate dynamics and hydrologic cycle, but also provide new model calibration constraints for improving the current land surface models. In this work, the connectivity of TWS is quantified using the climate network theory, which has received broad attention in the climate modeling community in recent years. Complex networks of TWS anomalies are built using two global TWS datasets, a remote-sensing product that is obtained from the Gravity Recovery and Climate Experiment (GRACE satellite mission, and a model-generated dataset from the global land data assimilation system's NOAH model (GLDAS-NOAH. Both datasets have 1 ° × 1 ° resolutions and cover most global land areas except for permafrost regions. TWS networks are built by first quantifying pairwise correlation among all valid TWS anomaly time series, and then applying a statistical cutoff threshold to retain only the most important features in the network. Basinwise network connectivity maps are used to illuminate connectivity of individual river basins with other regions. The constructed network degree centrality maps show TWS hotspots around the globe and the patterns are consistent with recent GRACE studies. Parallel analyses of networks constructed using the two datasets indicate that the GLDAS-NOAH model captures many of the spatial patterns shown by GRACE, although significant discrepancies exist in some regions. Thus, our results provide important insights for constraining land surface models, especially in data sparse regions.

  19. Phylogenomic analyses reveal convergent patterns of adaptive evolution in elephant and human ancestries.

    Science.gov (United States)

    Goodman, Morris; Sterner, Kirstin N; Islam, Munirul; Uddin, Monica; Sherwood, Chet C; Hof, Patrick R; Hou, Zhuo-Cheng; Lipovich, Leonard; Jia, Hui; Grossman, Lawrence I; Wildman, Derek E

    2009-12-08

    Specific sets of brain-expressed genes, such as aerobic energy metabolism genes, evolved adaptively in the ancestry of humans and may have evolved adaptively in the ancestry of other large-brained mammals. The recent addition of genomes from two afrotherians (elephant and tenrec) to the expanding set of publically available sequenced mammalian genomes provided an opportunity to test this hypothesis. Elephants resemble humans by having large brains and long life spans; tenrecs, in contrast, have small brains and short life spans. Thus, we investigated whether the phylogenomic patterns of adaptive evolution are more similar between elephant and human than between either elephant and tenrec lineages or human and mouse lineages, and whether aerobic energy metabolism genes are especially well represented in the elephant and human patterns. Our analyses encompassed approximately 6,000 genes in each of these lineages with each gene yielding extensive coding sequence matches in interordinal comparisons. Each gene's nonsynonymous and synonymous nucleotide substitution rates and dN/dS ratios were determined. Then, from gene ontology information on genes with the higher dN/dS ratios, we identified the more prevalent sets of genes that belong to specific functional categories and that evolved adaptively. Elephant and human lineages showed much slower nucleotide substitution rates than tenrec and mouse lineages but more adaptively evolved genes. In correlation with absolute brain size and brain oxygen consumption being largest in elephants and next largest in humans, adaptively evolved aerobic energy metabolism genes were most evident in the elephant lineage and next most evident in the human lineage.

  20. DEEP DIVISION IN THE CHLOROPHYCEAE (CHLOROPHYTA) REVEALED BY CHLOROPLAST PHYLOGENOMIC ANALYSES(1).

    Science.gov (United States)

    Turmel, Monique; Brouard, Jean-Simon; Gagnon, Cédric; Otis, Christian; Lemieux, Claude

    2008-06-01

    The Chlorophyceae (sensu Mattox and Stewart) is a morphologically diverse class of the Chlorophyta displaying biflagellate and quadriflagellate motile cells with varying configurations of the flagellar apparatus. Phylogenetic analyses of 18S rDNA data and combined 18S and 26S rDNA data from a broad range of chlorophycean taxa uncovered five major monophyletic groups (Chlamydomonadales, Sphaeropleales, Oedogoniales, Chaetophorales, and Chaetopeltidales) but could not resolve their branching order. To gain insight into the interrelationships of these groups, we analyzed multiple genes encoded by the chloroplast genomes of Chlamydomonas reinhardtii P. A. Dang. and Chlamydomonas moewusii Gerloff (Chlamydomonadales), Scenedesmus obliquus (Turpin) Kütz. (Sphaeropleales), Oedogonium cardiacum Wittr. (Oedogoniales), Stigeoclonium helveticum Vischer (Chaetophorales), and Floydiella terrestris (Groover et Hofstetter) Friedl et O'Kelly (Chaetopeltidales). The C. moewusii, Oedogonium, and Floydiella chloroplast DNAs were partly sequenced using a random strategy. Trees were reconstructed from nucleotide and amino acid data sets derived from 44 protein-coding genes of 11 chlorophytes and nine streptophytes as well as from 57 protein-coding genes of the six chlorophycean taxa. All best trees identified two robustly supported major lineages within the Chlorophyceae: a clade uniting the Chlamydomonadales and Sphaeropleales, and a clade uniting the Oedogoniales, Chaetophorales, and Chaetopeltidales (OCC clade). This dichotomy is independently supported by molecular signatures in chloroplast genes, such as insertions/deletions and the distribution of trans-spliced group II introns. Within the OCC clade, the sister relationship observed for the Chaetophorales and Chaetopeltidales is also strengthened by independent data. Character state reconstruction of basal body orientation allowed us to refine hypotheses regarding the evolution of the flagellar apparatus.

  1. Comparative genome analyses reveal distinct structure in the saltwater crocodile MHC.

    Science.gov (United States)

    Jaratlerdsiri, Weerachai; Deakin, Janine; Godinez, Ricardo M; Shan, Xueyan; Peterson, Daniel G; Marthey, Sylvain; Lyons, Eric; McCarthy, Fiona M; Isberg, Sally R; Higgins, Damien P; Chong, Amanda Y; John, John St; Glenn, Travis C; Ray, David A; Gongora, Jaime

    2014-01-01

    The major histocompatibility complex (MHC) is a dynamic genome region with an essential role in the adaptive immunity of vertebrates, especially antigen presentation. The MHC is generally divided into subregions (classes I, II and III) containing genes of similar function across species, but with different gene number and organisation. Crocodylia (crocodilians) are widely distributed and represent an evolutionary distinct group among higher vertebrates, but the genomic organisation of MHC within this lineage has been largely unexplored. Here, we studied the MHC region of the saltwater crocodile (Crocodylus porosus) and compared it with that of other taxa. We characterised genomic clusters encompassing MHC class I and class II genes in the saltwater crocodile based on sequencing of bacterial artificial chromosomes. Six gene clusters spanning ∼452 kb were identified to contain nine MHC class I genes, six MHC class II genes, three TAP genes, and a TRIM gene. These MHC class I and class II genes were in separate scaffold regions and were greater in length (2-6 times longer) than their counterparts in well-studied fowl B loci, suggesting that the compaction of avian MHC occurred after the crocodilian-avian split. Comparative analyses between the saltwater crocodile MHC and that from the alligator and gharial showed large syntenic areas (>80% identity) with similar gene order. Comparisons with other vertebrates showed that the saltwater crocodile had MHC class I genes located along with TAP, consistent with birds studied. Linkage between MHC class I and TRIM39 observed in the saltwater crocodile resembled MHC in eutherians compared, but absent in avian MHC, suggesting that the saltwater crocodile MHC appears to have gene organisation intermediate between these two lineages. These observations suggest that the structure of the saltwater crocodile MHC, and other crocodilians, can help determine the MHC that was present in the ancestors of archosaurs.

  2. Comparative genome analyses reveal distinct structure in the saltwater crocodile MHC.

    Directory of Open Access Journals (Sweden)

    Weerachai Jaratlerdsiri

    Full Text Available The major histocompatibility complex (MHC is a dynamic genome region with an essential role in the adaptive immunity of vertebrates, especially antigen presentation. The MHC is generally divided into subregions (classes I, II and III containing genes of similar function across species, but with different gene number and organisation. Crocodylia (crocodilians are widely distributed and represent an evolutionary distinct group among higher vertebrates, but the genomic organisation of MHC within this lineage has been largely unexplored. Here, we studied the MHC region of the saltwater crocodile (Crocodylus porosus and compared it with that of other taxa. We characterised genomic clusters encompassing MHC class I and class II genes in the saltwater crocodile based on sequencing of bacterial artificial chromosomes. Six gene clusters spanning ∼452 kb were identified to contain nine MHC class I genes, six MHC class II genes, three TAP genes, and a TRIM gene. These MHC class I and class II genes were in separate scaffold regions and were greater in length (2-6 times longer than their counterparts in well-studied fowl B loci, suggesting that the compaction of avian MHC occurred after the crocodilian-avian split. Comparative analyses between the saltwater crocodile MHC and that from the alligator and gharial showed large syntenic areas (>80% identity with similar gene order. Comparisons with other vertebrates showed that the saltwater crocodile had MHC class I genes located along with TAP, consistent with birds studied. Linkage between MHC class I and TRIM39 observed in the saltwater crocodile resembled MHC in eutherians compared, but absent in avian MHC, suggesting that the saltwater crocodile MHC appears to have gene organisation intermediate between these two lineages. These observations suggest that the structure of the saltwater crocodile MHC, and other crocodilians, can help determine the MHC that was present in the ancestors of archosaurs.

  3. Comparative analyses of reproductive structures in harvestmen (opiliones) reveal multiple transitions from courtship to precopulatory antagonism.

    Science.gov (United States)

    Burns, Mercedes M; Hedin, Marshal; Shultz, Jeffrey W

    2013-01-01

    Explaining the rapid, species-specific diversification of reproductive structures and behaviors is a long-standing goal of evolutionary biology, with recent research tending to attribute reproductive phenotypes to the evolutionary mechanisms of female mate choice or intersexual conflict. Progress in understanding these and other possible mechanisms depends, in part, on reconstructing the direction, frequency and relative timing of phenotypic evolution of male and female structures in species-rich clades. Here we examine evolution of reproductive structures in the leiobunine harvestmen or "daddy long-legs" of eastern North America, a monophyletic group that includes species in which males court females using nuptial gifts and other species that are equipped for apparent precopulatory antagonism (i.e., males with long, hardened penes and females with sclerotized pregenital barriers). We used parsimony- and Bayesian likelihood-based analyses to reconstruct character evolution in categorical reproductive traits and found that losses of ancestral gift-bearing penile sacs are strongly associated with gains of female pregenital barriers. In most cases, both events occur on the same internal branch of the phylogeny. These coevolutionary changes occurred at least four times, resulting in clade-specific designs in the penis and pregenital barrier. The discovery of convergent origins and/or enhancements of apparent precopulatory antagonism among closely related species offers an unusual opportunity to investigate how major changes in reproductive morphology have occurred. We propose new hypotheses that attribute these enhancements to changes in ecology or life history that reduce the duration of breeding seasons, an association that is consistent with female choice, sexual conflict, and/or an alternative evolutionary mechanism.

  4. Comparative analyses of reproductive structures in harvestmen (opiliones reveal multiple transitions from courtship to precopulatory antagonism.

    Directory of Open Access Journals (Sweden)

    Mercedes M Burns

    Full Text Available Explaining the rapid, species-specific diversification of reproductive structures and behaviors is a long-standing goal of evolutionary biology, with recent research tending to attribute reproductive phenotypes to the evolutionary mechanisms of female mate choice or intersexual conflict. Progress in understanding these and other possible mechanisms depends, in part, on reconstructing the direction, frequency and relative timing of phenotypic evolution of male and female structures in species-rich clades. Here we examine evolution of reproductive structures in the leiobunine harvestmen or "daddy long-legs" of eastern North America, a monophyletic group that includes species in which males court females using nuptial gifts and other species that are equipped for apparent precopulatory antagonism (i.e., males with long, hardened penes and females with sclerotized pregenital barriers. We used parsimony- and Bayesian likelihood-based analyses to reconstruct character evolution in categorical reproductive traits and found that losses of ancestral gift-bearing penile sacs are strongly associated with gains of female pregenital barriers. In most cases, both events occur on the same internal branch of the phylogeny. These coevolutionary changes occurred at least four times, resulting in clade-specific designs in the penis and pregenital barrier. The discovery of convergent origins and/or enhancements of apparent precopulatory antagonism among closely related species offers an unusual opportunity to investigate how major changes in reproductive morphology have occurred. We propose new hypotheses that attribute these enhancements to changes in ecology or life history that reduce the duration of breeding seasons, an association that is consistent with female choice, sexual conflict, and/or an alternative evolutionary mechanism.

  5. Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index.

    Science.gov (United States)

    Speliotes, Elizabeth K; Willer, Cristen J; Berndt, Sonja I; Monda, Keri L; Thorleifsson, Gudmar; Jackson, Anne U; Lango Allen, Hana; Lindgren, Cecilia M; Luan, Jian'an; Mägi, Reedik; Randall, Joshua C; Vedantam, Sailaja; Winkler, Thomas W; Qi, Lu; Workalemahu, Tsegaselassie; Heid, Iris M; Steinthorsdottir, Valgerdur; Stringham, Heather M; Weedon, Michael N; Wheeler, Eleanor; Wood, Andrew R; Ferreira, Teresa; Weyant, Robert J; Segrè, Ayellet V; Estrada, Karol; Liang, Liming; Nemesh, James; Park, Ju-Hyun; Gustafsson, Stefan; Kilpeläinen, Tuomas O; Yang, Jian; Bouatia-Naji, Nabila; Esko, Tõnu; Feitosa, Mary F; Kutalik, Zoltán; Mangino, Massimo; Raychaudhuri, Soumya; Scherag, Andre; Smith, Albert Vernon; Welch, Ryan; Zhao, Jing Hua; Aben, Katja K; Absher, Devin M; Amin, Najaf; Dixon, Anna L; Fisher, Eva; Glazer, Nicole L; Goddard, Michael E; Heard-Costa, Nancy L; Hoesel, Volker; Hottenga, Jouke-Jan; Johansson, Asa; Johnson, Toby; Ketkar, Shamika; Lamina, Claudia; Li, Shengxu; Moffatt, Miriam F; Myers, Richard H; Narisu, Narisu; Perry, John R B; Peters, Marjolein J; Preuss, Michael; Ripatti, Samuli; Rivadeneira, Fernando; Sandholt, Camilla; Scott, Laura J; Timpson, Nicholas J; Tyrer, Jonathan P; van Wingerden, Sophie; Watanabe, Richard M; White, Charles C; Wiklund, Fredrik; Barlassina, Christina; Chasman, Daniel I; Cooper, Matthew N; Jansson, John-Olov; Lawrence, Robert W; Pellikka, Niina; Prokopenko, Inga; Shi, Jianxin; Thiering, Elisabeth; Alavere, Helene; Alibrandi, Maria T S; Almgren, Peter; Arnold, Alice M; Aspelund, Thor; Atwood, Larry D; Balkau, Beverley; Balmforth, Anthony J; Bennett, Amanda J; Ben-Shlomo, Yoav; Bergman, Richard N; Bergmann, Sven; Biebermann, Heike; Blakemore, Alexandra I F; Boes, Tanja; Bonnycastle, Lori L; Bornstein, Stefan R; Brown, Morris J; Buchanan, Thomas A; Busonero, Fabio; Campbell, Harry; Cappuccio, Francesco P; Cavalcanti-Proença, Christine; Chen, Yii-Der Ida; Chen, Chih-Mei; Chines, Peter S; Clarke, Robert; Coin, Lachlan; Connell, John; Day, Ian N M; den Heijer, Martin; Duan, Jubao; Ebrahim, Shah; Elliott, Paul; Elosua, Roberto; Eiriksdottir, Gudny; Erdos, Michael R; Eriksson, Johan G; Facheris, Maurizio F; Felix, Stephan B; Fischer-Posovszky, Pamela; Folsom, Aaron R; Friedrich, Nele; Freimer, Nelson B; Fu, Mao; Gaget, Stefan; Gejman, Pablo V; Geus, Eco J C; Gieger, Christian; Gjesing, Anette P; Goel, Anuj; Goyette, Philippe; Grallert, Harald; Grässler, Jürgen; Greenawalt, Danielle M; Groves, Christopher J; Gudnason, Vilmundur; Guiducci, Candace; Hartikainen, Anna-Liisa; Hassanali, Neelam; Hall, Alistair S; Havulinna, Aki S; Hayward, Caroline; Heath, Andrew C; Hengstenberg, Christian; Hicks, Andrew A; Hinney, Anke; Hofman, Albert; Homuth, Georg; Hui, Jennie; Igl, Wilmar; Iribarren, Carlos; Isomaa, Bo; Jacobs, Kevin B; Jarick, Ivonne; Jewell, Elizabeth; John, Ulrich; Jørgensen, Torben; Jousilahti, Pekka; Jula, Antti; Kaakinen, Marika; Kajantie, Eero; Kaplan, Lee M; Kathiresan, Sekar; Kettunen, Johannes; Kinnunen, Leena; Knowles, Joshua W; Kolcic, Ivana; König, Inke R; Koskinen, Seppo; Kovacs, Peter; Kuusisto, Johanna; Kraft, Peter; Kvaløy, Kirsti; Laitinen, Jaana; Lantieri, Olivier; Lanzani, Chiara; Launer, Lenore J; Lecoeur, Cecile; Lehtimäki, Terho; Lettre, Guillaume; Liu, Jianjun; Lokki, Marja-Liisa; Lorentzon, Mattias; Luben, Robert N; Ludwig, Barbara; Manunta, Paolo; Marek, Diana; Marre, Michel; Martin, Nicholas G; McArdle, Wendy L; McCarthy, Anne; McKnight, Barbara; Meitinger, Thomas; Melander, Olle; Meyre, David; Midthjell, Kristian; Montgomery, Grant W; Morken, Mario A; Morris, Andrew P; Mulic, Rosanda; Ngwa, Julius S; Nelis, Mari; Neville, Matt J; Nyholt, Dale R; O'Donnell, Christopher J; O'Rahilly, Stephen; Ong, Ken K; Oostra, Ben; Paré, Guillaume; Parker, Alex N; Perola, Markus; Pichler, Irene; Pietiläinen, Kirsi H; Platou, Carl G P; Polasek, Ozren; Pouta, Anneli; Rafelt, Suzanne; Raitakari, Olli; Rayner, Nigel W; Ridderstråle, Martin; Rief, Winfried; Ruokonen, Aimo; Robertson, Neil R; Rzehak, Peter; Salomaa, Veikko; Sanders, Alan R; Sandhu, Manjinder S; Sanna, Serena; Saramies, Jouko; Savolainen, Markku J; Scherag, Susann; Schipf, Sabine; Schreiber, Stefan; Schunkert, Heribert; Silander, Kaisa; Sinisalo, Juha; Siscovick, David S; Smit, Jan H; Soranzo, Nicole; Sovio, Ulla; Stephens, Jonathan; Surakka, Ida; Swift, Amy J; Tammesoo, Mari-Liis; Tardif, Jean-Claude; Teder-Laving, Maris; Teslovich, Tanya M; Thompson, John R; Thomson, Brian; Tönjes, Anke; Tuomi, Tiinamaija; van Meurs, Joyce B J; van Ommen, Gert-Jan; Vatin, Vincent; Viikari, Jorma; Visvikis-Siest, Sophie

    2010-11-01

    Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and ∼ 2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 × 10⁻⁸), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation.

  6. Lineage-specific evolution of the vertebrate Otopetrin gene family revealed by comparative genomic analyses

    Directory of Open Access Journals (Sweden)

    Ryan Joseph F

    2011-01-01

    Full Text Available Abstract Background Mutations in the Otopetrin 1 gene (Otop1 in mice and fish produce an unusual bilateral vestibular pathology that involves the absence of otoconia without hearing impairment. The encoded protein, Otop1, is the only functionally characterized member of the Otopetrin Domain Protein (ODP family; the extended sequence and structural preservation of ODP proteins in metazoans suggest a conserved functional role. Here, we use the tools of sequence- and cytogenetic-based comparative genomics to study the Otop1 and the Otop2-Otop3 genes and to establish their genomic context in 25 vertebrates. We extend our evolutionary study to include the gene mutated in Usher syndrome (USH subtype 1G (Ush1g, both because of the head-to-tail clustering of Ush1g with Otop2 and because Otop1 and Ush1g mutations result in inner ear phenotypes. Results We established that OTOP1 is the boundary gene of an inversion polymorphism on human chromosome 4p16 that originated in the common human-chimpanzee lineage more than 6 million years ago. Other lineage-specific evolutionary events included a three-fold expansion of the Otop genes in Xenopus tropicalis and of Ush1g in teleostei fish. The tight physical linkage between Otop2 and Ush1g is conserved in all vertebrates. To further understand the functional organization of the Ushg1-Otop2 locus, we deduced a putative map of binding sites for CCCTC-binding factor (CTCF, a mammalian insulator transcription factor, from genome-wide chromatin immunoprecipitation-sequencing (ChIP-seq data in mouse and human embryonic stem (ES cells combined with detection of CTCF-binding motifs. Conclusions The results presented here clarify the evolutionary history of the vertebrate Otop and Ush1g families, and establish a framework for studying the possible interaction(s of Ush1g and Otop in developmental pathways.

  7. Proteomic and Physiological Analyses Reveal Detoxification and Antioxidation Induced by Cd Stress in Kandelia candel Roots

    Institute of Scientific and Technical Information of China (English)

    Zhaoxia Weng; Lingxia Wang; Fanglin Tan; Li Huang; Jianhong Xing; Shipin Chen; Chilien Cheng

    2012-01-01

    The heavy metal Cadmium (Cd),added to the water bodies through weathering of rocks and human activities,constitutes one of the major environmental pollutants toxic to plants.This study examines the proteome changes in roots of actively growing Kandelia candel (L.) Druce when challenged with Cd.This mangrove-like species proliferates in estuaries and bays and is a potential choice for phytoremediation of Cd.A total of 53 proteins were up-or down-regulated following a short-term Cd treatment.The identities of the differentially expressed proteins were determined by MALDI-TOF/TOF.Approximately half of the up-regulated proteins are involved in oxidative response,including antioxidant enzymes,enzymes required for glutathione biosynthesis,enzymes in TCA and PPP cycles for generating ATP,NADH and NADPH.These results support the prediction that a prompt antioxidative response is necessary for the reduction of the oxidative stress caused by Cd and set the stage for further investigating of Cd up-regulated proteins in Kandelia candel.In summary,this investigation of global proteomic changes in K.candel roots reveals a complex cellular network affected by Cd stress.The network covers a broad range of metabolic processes,including protein synthesis,antioxidative/detoxifying reactions,energy generation,and metabolites production against Cd stress.Particularly important,our results support the predicted key roles of glutathione biosynthesis,ascorbate-glutathione cycle and antioxidative defense system in Cd detoxification in K.candel roots.This understanding is necessary for developing the woody plant K.candel for phytoremediation of Cd and other heavy metals and may be critical for maintaining health mangrove ecology.

  8. Hemoglobin analyses in the Netherlands reveal more than 80 different variants including six novel ones.

    Science.gov (United States)

    van Zwieten, Rob; Veldthuis, Martijn; Delzenne, Barend; Berghuis, Jeffrey; Groen, Joke; Ait Ichou, Fatima; Clifford, Els; Harteveld, Cornelis L; Stroobants, An K

    2014-01-01

    More than 20,000 blood samples of individuals living in The Netherlands and suspected of hemolytic anemia or diabetes were analyzed by high resolution cation exchange high performance liquid chromatography (HPLC). Besides common disease-related hemoglobins (Hbs), rare variants were also detected. The variant Hbs were retrospectively analyzed by capillary zone electrophoresis (CZE) and by isoelectric focusing (IEF). For unambiguous identification, the globin genes were sequenced. Most of the 80 Hb variants detected by initial screening on HPLC were also separated by capillary electrophoresis (CE), but a few variants were only detectable with one of these methods. Some variants were unstable, had thalassemic properties or increased oxygen affinity, and some interfered with Hb A2 measurement, detection of sickle cell Hb or Hb A1c quantification. Two of the six novel variants, Hb Enschede (HBA2: c.308G  > A, p.Ser103Asn) and Hb Weesp (HBA1: c.301C > T, p.Leu101Phe), had no clinical consequences. In contrast, two others appeared clinically significant: Hb Ede (HBB: c.53A > T, p.Lys18Met) caused thalassemia and Hb Waterland (HBB: c.428C > T, pAla143Val) was related to mild polycytemia. Hb A2-Venlo (HBD: c.193G > A, p.Gly65Ser) and Hb A2-Rotterdam (HBD: c.38A > C, p.Asn13Thr) interfered with Hb A2 quantification. This survey shows that HPLC analysis followed by globin gene sequencing of rare variants is an effective method to reveal Hb variants.

  9. Landscape genetic analyses reveal fine-scale effects of forest fragmentation in an insular tropical bird.

    Science.gov (United States)

    Khimoun, Aurélie; Peterman, William; Eraud, Cyril; Faivre, Bruno; Navarro, Nicolas; Garnier, Stéphane

    2017-07-20

    Within the framework of landscape genetics, resistance surface modelling is particularly relevant to explicitly test competing hypotheses about landscape effects on gene flow. To investigate how fragmentation of tropical forest affects population connectivity in a forest specialist bird species, we optimized resistance surfaces without a priori specification, using least-cost (LCP) or resistance (IBR) distances. We implemented a two-step procedure in order (i) to objectively define the landscape thematic resolution (level of detail in classification scheme to describe landscape variables) and spatial extent (area within the landscape boundaries) and then (ii) to test the relative role of several landscape features (elevation, roads, land cover) in genetic differentiation in the Plumbeous Warbler (Setophaga plumbea). We detected a small-scale reduction of gene flow mainly driven by land cover, with a negative impact of the nonforest matrix on landscape functional connectivity. However, matrix components did not equally constrain gene flow, as their conductivity increased with increasing structural similarity with forest habitat: urban areas and meadows had the highest resistance values whereas agricultural areas had intermediate resistance values. Our results revealed a higher performance of IBR compared to LCP in explaining gene flow, reflecting suboptimal movements across this human-modified landscape, challenging the common use of LCP to design habitat corridors and advocating for a broader use of circuit theory modelling. Finally, our results emphasize the need for an objective definition of landscape scales (landscape extent and thematic resolution) and highlight potential pitfalls associated with parameterization of resistance surfaces. © 2017 John Wiley & Sons Ltd.

  10. Risk Factor Analyses for the Return of Spontaneous Circulation in the Asphyxiation Cardiac Arrest Porcine Model

    Directory of Open Access Journals (Sweden)

    Cai-Jun Wu

    2015-01-01

    Full Text Available Background: Animal models of asphyxiation cardiac arrest (ACA are frequently used in basic research to mirror the clinical course of cardiac arrest (CA. The rates of the return of spontaneous circulation (ROSC in ACA animal models are lower than those from studies that have utilized ventricular fibrillation (VF animal models. The purpose of this study was to characterize the factors associated with the ROSC in the ACA porcine model. Methods: Forty-eight healthy miniature pigs underwent endotracheal tube clamping to induce CA. Once induced, CA was maintained untreated for a period of 8 min. Two minutes following the initiation of cardiopulmonary resuscitation (CPR, defibrillation was attempted until ROSC was achieved or the animal died. To assess the factors associated with ROSC in this CA model, logistic regression analyses were performed to analyze gender, the time of preparation, the amplitude spectrum area (AMSA from the beginning of CPR and the pH at the beginning of CPR. A receiver-operating characteristic (ROC curve was used to evaluate the predictive value of AMSA for ROSC. Results: ROSC was only 52.1% successful in this ACA porcine model. The multivariate logistic regression analyses revealed that ROSC significantly depended on the time of preparation, AMSA at the beginning of CPR and pH at the beginning of CPR. The area under the ROC curve in for AMSA at the beginning of CPR was 0.878 successful in predicting ROSC (95% confidence intervals: 0.773∼0.983, and the optimum cut-off value was 15.62 (specificity 95.7% and sensitivity 80.0%. Conclusions: The time of preparation, AMSA and the pH at the beginning of CPR were associated with ROSC in this ACA porcine model. AMSA also predicted the likelihood of ROSC in this ACA animal model.

  11. Interactome analyses of Salmonella pathogenicity islands reveal SicA indispensable for virulence.

    Science.gov (United States)

    Lahiri, Chandrajit; Pawar, Shrikant; Sabarinathan, Radhakrishnan; Ashraf, Md Izhar; Chand, Yamini; Chakravortty, Dipshikha

    2014-12-21

    Serovars of Salmonella enterica, namely Typhi and Typhimurium, reportedly, are the bacterial pathogens causing systemic infections like gastroenteritis and typhoid fever. To elucidate the role and importance in such infection, the proteins of the Type III secretion system of Salmonella pathogenicity islands and two component signal transduction systems, have been mainly focused. However, the most indispensable of these virulent ones and their hierarchical role has not yet been studied extensively. We have adopted a theoretical approach to build an interactome comprising the proteins from the Salmonella pathogeneicity islands (SPI) and two component signal transduction systems. This interactome was then analyzed by using network parameters like centrality and k-core measures. An initial step to capture the fingerprint of the core network resulted in a set of proteins which are involved in the process of invasion and colonization, thereby becoming more important in the process of infection. These proteins pertained to the Inv, Org, Prg, Sip, Spa, Ssa and Sse operons along with chaperone protein SicA. Amongst them, SicA was figured out to be the most indispensable protein from different network parametric analyses. Subsequently, the gene expression levels of all these theoretically identified important proteins were confirmed by microarray data analysis. Finally, we have proposed a hierarchy of the proteins involved in the total infection process. This theoretical approach is the first of its kind to figure out potential virulence determinants encoded by SPI for therapeutic targets for enteric infection. A set of responsible virulent proteins was identified and the expression level of their genes was validated by using independent, published microarray data. The result was a targeted set of proteins that could serve as sensitive predictors and form the foundation for a series of trials in the wet-lab setting. Understanding these regulatory and virulent proteins would

  12. Gene expression analyses reveal metabolic specifications in acute O2 -sensing chemoreceptor cells.

    Science.gov (United States)

    Gao, Lin; Bonilla-Henao, Victoria; García-Flores, Paula; Arias-Mayenco, Ignacio; Ortega-Sáenz, Patricia; López-Barneo, José

    2017-07-17

    Glomus cells in the carotid body (CB) and chromaffin cells in the adrenal medulla (AM) are essential for reflex cardiorespiratory adaptation to hypoxia. However, the mechanisms whereby these cells detect changes in O2 tension are poorly understood. The metabolic properties of acute O2 -sensing cells have been investigated by comparing the transcriptomes of CB and AM cells, which are O2 -sensitive, with superior cervical ganglion neurons, which are practically O2 -insensitive. In O2 -sensitive cells, we found a characteristic prolyl hydroxylase 3 down-regulation and hypoxia inducible factor 2α up-regulation, as well as overexpression of genes coding for three atypical mitochondrial electron transport subunits and pyruvate carboxylase, an enzyme that replenishes tricarboxylic acid cycle intermediates. In agreement with this observation, the inhibition of succinate dehydrogenase impairs CB acute O2 sensing. The responsiveness of peripheral chemoreceptor cells to acute hypoxia depends on a 'signature metabolic profile'. Acute O2 sensing is a fundamental property of cells in the peripheral chemoreceptors, e.g. glomus cells in the carotid body (CB) and chromaffin cells in the adrenal medulla (AM), and is necessary for adaptation to hypoxia. These cells contain O2 -sensitive ion channels, which mediate membrane depolarization and transmitter release upon exposure to hypoxia. However, the mechanisms underlying the detection of changes in O2 tension by cells are still poorly understood. Recently, we suggested that CB glomus cells have specific metabolic features that favour the accumulation of reduced quinone and the production of mitochondrial NADH and reactive oxygen species during hypoxia. These signals alter membrane ion channel activity. To investigate the metabolic profile characteristic of acute O2 -sensing cells, we used adult mice to compare the transcriptomes of three cell types derived from common sympathoadrenal progenitors, but exhibiting variable

  13. Phylogenomic analyses reveal the diversity of laccase-coding genes in Fonsecaea genomes

    Science.gov (United States)

    Feng, Peiying; Weiss, Vinicius Almir; Vicente, Vania Aparecida; Stielow, J. Benjamin; de Hoog, Sybren

    2017-01-01

    The genus Fonsecaea comprises black yeast-like fungi of clinical relevance, including etiologic agents of chromoblastomycosis and cerebral phaeohyphomycosis. Presence of melanin and assimilation of monoaromatic hydrocarbons and alkylbenzenes have been proposed as virulence factors. Multicopper oxidase (MCO) is a family of enzymes including laccases, ferroxidases and ascorbate oxidases which are able to catalyze the oxidation of various aromatic organic compounds with the reduction of molecular oxygen to water. Additionally, laccases are required for the production of fungal melanins, a cell-wall black pigment recognized as a key polymer for pathogenicity and extremotolerance in black yeast-like fungi. Although the activity of laccase enzymes has previously been reported in many wood-rotting fungi, the diversity of laccase genes in Fonsecaea has not yet been assessed. In this study, we identified and characterized laccase-coding genes and determined their genomic location in five clinical and environmental Fonsecaea species. The identification of laccases sensu stricto will provide insights into carbon acquisition strategies as well as melanin production in Fonsecaea. PMID:28187150

  14. Comparative analyses reveal discrepancies among results of commonly used methods for Anopheles gambiaemolecular form identification

    Directory of Open Access Journals (Sweden)

    Pinto João

    2011-08-01

    Full Text Available Abstract Background Anopheles gambiae M and S molecular forms, the major malaria vectors in the Afro-tropical region, are ongoing a process of ecological diversification and adaptive lineage splitting, which is affecting malaria transmission and vector control strategies in West Africa. These two incipient species are defined on the basis of single nucleotide differences in the IGS and ITS regions of multicopy rDNA located on the X-chromosome. A number of PCR and PCR-RFLP approaches based on form-specific SNPs in the IGS region are used for M and S identification. Moreover, a PCR-method to detect the M-specific insertion of a short interspersed transposable element (SINE200 has recently been introduced as an alternative identification approach. However, a large-scale comparative analysis of four widely used PCR or PCR-RFLP genotyping methods for M and S identification was never carried out to evaluate whether they could be used interchangeably, as commonly assumed. Results The genotyping of more than 400 A. gambiae specimens from nine African countries, and the sequencing of the IGS-amplicon of 115 of them, highlighted discrepancies among results obtained by the different approaches due to different kinds of biases, which may result in an overestimation of MS putative hybrids, as follows: i incorrect match of M and S specific primers used in the allele specific-PCR approach; ii presence of polymorphisms in the recognition sequence of restriction enzymes used in the PCR-RFLP approaches; iii incomplete cleavage during the restriction reactions; iv presence of different copy numbers of M and S-specific IGS-arrays in single individuals in areas of secondary contact between the two forms. Conclusions The results reveal that the PCR and PCR-RFLP approaches most commonly utilized to identify A. gambiae M and S forms are not fully interchangeable as usually assumed, and highlight limits of the actual definition of the two molecular forms, which might

  15. Lysine acetylation stoichiometry and proteomics analyses reveal pathways regulated by sirtuin 1 in human cells.

    Science.gov (United States)

    Gil, Jeovanis; Ramírez-Torres, Alberto; Chiappe, Diego; Luna-Peñaloza, Juan; Fernandez-Reyes, Francis C; Arcos-Encarnación, Bolivar; Contreras, Sandra; Encarnación-Guevara, Sergio

    2017-09-11

    Lysine acetylation is a widespread posttranslational modification (PTM) affecting many biological pathways. Recent studies indicate that acetylated lysine residues mainly exhibit low acetylation occupancy, but challenges in sample preparation and analysis make it difficult to confidently assign these numbers, limiting understanding of their biological significance. Here, we tested three common sample preparation methods to determine their suitability for assessing acetylation stoichiometry in three human cell lines, identifying the acetylation occupancy in more than 1,300 proteins from each cell line. The stoichiometric analysis in combination with quantitative proteomics also enabled us to explore their functional roles. We found that higher abundance of the deacetylase sirtuin 1 (SIRT1) correlated with lower acetylation occupancy and lower levels of ribosomal proteins including those involved in ribosome biogenesis and rRNA processing. Treatment with the SIRT1 inhibitor EX-527 confirmed SIRT1's role in the regulation of pre-rRNA synthesis and processing. Specifically, proteins involved in pre-rRNA transcription, including subunits of the Pol 1 and SL1 complexes and the RNA polymerase I specific transcription initiation factor RRN3 were up-regulated after SIRT1 inhibition. Moreover, many protein effectors and regulators of pre-rRNA processing needed for rRNA maturation were also up-regulated after EX-527 treatment, with the outcome that pre-rRNA and 28S rRNA levels also increased. More generally, we found that SIRT1 inhibition down-regulates metabolic pathways including glycolysis and pyruvate metabolism. Together, these results provide the largest dataset thus far of lysine acetylation stoichiometry (available via ProteomeXchange with identifier PXD005903) and set the stage for further biological investigations of this central PTM. Copyright © 2017, The American Society for Biochemistry and Molecular Biology.

  16. Metagenome analyses of corroded concrete wastewater pipe biofilms reveal a complex microbial system

    Directory of Open Access Journals (Sweden)

    Gomez-Alvarez Vicente

    2012-06-01

    Full Text Available Abstract Background Concrete corrosion of wastewater collection systems is a significant cause of deterioration and premature collapse. Failure to adequately address the deteriorating infrastructure networks threatens our environment, public health, and safety. Analysis of whole-metagenome pyrosequencing data and 16S rRNA gene clone libraries was used to determine microbial composition and functional genes associated with biomass harvested from crown (top and invert (bottom sections of a corroded wastewater pipe. Results Taxonomic and functional analysis demonstrated that approximately 90% of the total diversity was associated with the phyla Actinobacteria, Bacteroidetes, Firmicutes and Proteobacteria. The top (TP and bottom pipe (BP communities were different in composition, with some of the differences attributed to the abundance of sulfide-oxidizing and sulfate-reducing bacteria. Additionally, human fecal bacteria were more abundant in the BP communities. Among the functional categories, proteins involved in sulfur and nitrogen metabolism showed the most significant differences between biofilms. There was also an enrichment of genes associated with heavy metal resistance, virulence (protein secretion systems and stress response in the TP biofilm, while a higher number of genes related to motility and chemotaxis were identified in the BP biofilm. Both biofilms contain a high number of genes associated with resistance to antibiotics and toxic compounds subsystems. Conclusions The function potential of wastewater biofilms was highly diverse with level of COG diversity similar to that described for soil. On the basis of the metagenomic data, some factors that may contribute to niche differentiation were pH, aerobic conditions and availability of substrate, such as nitrogen and sulfur. The results from this study will help us better understand the genetic network and functional capability of microbial members of wastewater concrete biofilms.

  17. Comparative transcriptome analyses reveal a special glucosinolate metabolism mechanism in Brassica alboglabra sprouts

    Directory of Open Access Journals (Sweden)

    Rongfang Guo

    2016-10-01

    Full Text Available Brassica sprouts contain abundant phytochemicals, especially glucosinolates (GSs. Various methods have been used to enhance GS content in sprouts. However, the molecular basis of GS metabolism in sprouts remains an open question. Here we employed RNA-seq analysis to compare the transcriptomes of high-GS (JL-08 and low-GS (JL-09 Brassica alboglabra sprouts. Paired-end Illumina RNA-seq reads were generated and mapped to the B. oleracea reference genome. The differentially expressed genes were analyzed between JL-08 and JL-09. Among these, 1,477 genes were up-regulated and 1,239 down-regulated in JL-09 compared with JL-08. Enrichment analysis of these differentially expressed genes showed that the GS biosynthesis had the smallest enrichment factor and the highest Q value of all metabolic pathways in Kyoto Encyclopedia of Genes and Genomes database, indicating the main metabolic difference between JL-08 and JL-09 is the GS biosynthetic pathway. Thirty-seven genes of the sequenced data were annotated as putatively involved in GS biosynthesis, degradation and regulation, of which 11 were differentially expressed in JL-08 and JL-09. The expression level of GS degradation enzyme myrosinase in high-GS JL-08 was lower compared with low-GS JL-09. Surprisingly, in high-GS JL-08, the expression levels of GS biosynthesis genes were also lower than those in low-GS JL-09. As the GS contents in sprouts are determined by dynamic equilibrium of seed stored GS mobilization, de novo synthesis, degradation, and extra transport, the result of this study leads us to suggest that efforts to increase GS content should focus on either raising GS content in seeds or decreasing myrosinase activity, rather than improving the expression level of GS biosynthesis genes in sprouts.

  18. Replicated landscape genetic and network analyses reveal wide variation in functional connectivity for American pikas.

    Science.gov (United States)

    Castillo, Jessica A; Epps, Clinton W; Jeffress, Mackenzie R; Ray, Chris; Rodhouse, Thomas J; Schwalm, Donelle

    2016-09-01

    Landscape connectivity is essential for maintaining viable populations, particularly for species restricted to fragmented habitats or naturally arrayed in metapopulations and facing rapid climate change. The importance of assessing both structural connectivity (physical distribution of favorable habitat patches) and functional connectivity (how species move among habitat patches) for managing such species is well understood. However, the degree to which functional connectivity for a species varies among landscapes, and the resulting implications for conservation, have rarely been assessed. We used a landscape genetics approach to evaluate resistance to gene flow and, thus, to determine how landscape and climate-related variables influence gene flow for American pikas (Ochotona princeps) in eight federally managed sites in the western United States. We used empirically derived, individual-based landscape resistance models in conjunction with predictive occupancy models to generate patch-based network models describing functional landscape connectivity. Metareplication across landscapes enabled identification of limiting factors for dispersal that would not otherwise have been apparent. Despite the cool microclimates characteristic of pika habitat, south-facing aspects consistently represented higher resistance to movement, supporting the previous hypothesis that exposure to relatively high temperatures may limit dispersal in American pikas. We found that other barriers to dispersal included areas with a high degree of topographic relief, such as cliffs and ravines, as well as streams and distances greater than 1-4 km depending on the site. Using the empirically derived network models of habitat patch connectivity, we identified habitat patches that were likely disproportionately important for maintaining functional connectivity, areas in which habitat appeared fragmented, and locations that could be targeted for management actions to improve functional connectivity

  19. Assessing an organizational culture instrument based on the Competing Values Framework: Exploratory and confirmatory factor analyses

    Directory of Open Access Journals (Sweden)

    Mohr David C

    2007-04-01

    Full Text Available Abstract Background The Competing Values Framework (CVF has been widely used in health services research to assess organizational culture as a predictor of quality improvement implementation, employee and patient satisfaction, and team functioning, among other outcomes. CVF instruments generally are presented as well-validated with reliable aggregated subscales. However, only one study in the health sector has been conducted for the express purpose of validation, and that study population was limited to hospital managers from a single geographic locale. Methods We used exploratory and confirmatory factor analyses to examine the underlying structure of data from a CVF instrument. We analyzed cross-sectional data from a work environment survey conducted in the Veterans Health Administration (VHA. The study population comprised all staff in non-supervisory positions. The survey included 14 items adapted from a popular CVF instrument, which measures organizational culture according to four subscales: hierarchical, entrepreneurial, team, and rational. Results Data from 71,776 non-supervisory employees (approximate response rate 51% from 168 VHA facilities were used in this analysis. Internal consistency of the subscales was moderate to strong (α = 0.68 to 0.85. However, the entrepreneurial, team, and rational subscales had higher correlations across subscales than within, indicating poor divergent properties. Exploratory factor analysis revealed two factors, comprising the ten items from the entrepreneurial, team, and rational subscales loading on the first factor, and two items from the hierarchical subscale loading on the second factor, along with one item from the rational subscale that cross-loaded on both factors. Results from confirmatory factor analysis suggested that the two-subscale solution provides a more parsimonious fit to the data as compared to the original four-subscale model. Conclusion This study suggests that there may be problems

  20. Functional assays and metagenomic analyses reveals differences between the microbial communities inhabiting the soil horizons of a Norway spruce plantation.

    Directory of Open Access Journals (Sweden)

    Stéphane Uroz

    Full Text Available In temperate ecosystems, acidic forest soils are among the most nutrient-poor terrestrial environments. In this context, the long-term differentiation of the forest soils into horizons may impact the assembly and the functions of the soil microbial communities. To gain a more comprehensive understanding of the ecology and functional potentials of these microbial communities, a suite of analyses including comparative metagenomics was applied on independent soil samples from a spruce plantation (Breuil-Chenue, France. The objectives were to assess whether the decreasing nutrient bioavailability and pH variations that naturally occurs between the organic and mineral horizons affects the soil microbial functional biodiversity. The 14 Gbp of pyrosequencing and Illumina sequences generated in this study revealed complex microbial communities dominated by bacteria. Detailed analyses showed that the organic soil horizon was significantly enriched in sequences related to Bacteria, Chordata, Arthropoda and Ascomycota. On the contrary the mineral horizon was significantly enriched in sequences related to Archaea. Our analyses also highlighted that the microbial communities inhabiting the two soil horizons differed significantly in their functional potentials according to functional assays and MG-RAST analyses, suggesting a functional specialisation of these microbial communities. Consistent with this specialisation, our shotgun metagenomic approach revealed a significant increase in the relative abundance of sequences related glycoside hydrolases in the organic horizon compared to the mineral horizon that was significantly enriched in glycoside transferases. This functional stratification according to the soil horizon was also confirmed by a significant correlation between the functional assays performed in this study and the functional metagenomic analyses. Together, our results suggest that the soil stratification and particularly the soil resource

  1. Single-Cell Analyses of ESCs Reveal Alternative Pluripotent Cell States and Molecular Mechanisms that Control Self-Renewal

    Directory of Open Access Journals (Sweden)

    Dmitri Papatsenko

    2015-08-01

    Full Text Available Analyses of gene expression in single mouse embryonic stem cells (mESCs cultured in serum and LIF revealed the presence of two distinct cell subpopulations with individual gene expression signatures. Comparisons with published data revealed that cells in the first subpopulation are phenotypically similar to cells isolated from the inner cell mass (ICM. In contrast, cells in the second subpopulation appear to be more mature. Pluripotency Gene Regulatory Network (PGRN reconstruction based on single-cell data and published data suggested antagonistic roles for Oct4 and Nanog in the maintenance of pluripotency states. Integrated analyses of published genomic binding (ChIP data strongly supported this observation. Certain target genes alternatively regulated by OCT4 and NANOG, such as Sall4 and Zscan10, feed back into the top hierarchical regulator Oct4. Analyses of such incoherent feedforward loops with feedback (iFFL-FB suggest a dynamic model for the maintenance of mESC pluripotency and self-renewal.

  2. Fossil-based comparative analyses reveal ancient marine ancestry erased by extinction in ray-finned fishes.

    Science.gov (United States)

    Betancur-R, Ricardo; Ortí, Guillermo; Pyron, Robert Alexander

    2015-05-01

    The marine-freshwater boundary is a major biodiversity gradient and few groups have colonised both systems successfully. Fishes have transitioned between habitats repeatedly, diversifying in rivers, lakes and oceans over evolutionary time. However, their history of habitat colonisation and diversification is unclear based on available fossil and phylogenetic data. We estimate ancestral habitats and diversification and transition rates using a large-scale phylogeny of extant fish taxa and one containing a massive number of extinct species. Extant-only phylogenetic analyses indicate freshwater ancestry, but inclusion of fossils reveal strong evidence of marine ancestry in lineages now restricted to freshwaters. Diversification and colonisation dynamics vary asymmetrically between habitats, as marine lineages colonise and flourish in rivers more frequently than the reverse. Our study highlights the importance of including fossils in comparative analyses, showing that freshwaters have played a role as refuges for ancient fish lineages, a signal erased by extinction in extant-only phylogenies.

  3. Latent physiological factors of complex human diseases revealed by independent component analysis of clinarrays

    Directory of Open Access Journals (Sweden)

    Chen David P

    2010-10-01

    Full Text Available Abstract Background Diagnosis and treatment of patients in the clinical setting is often driven by known symptomatic factors that distinguish one particular condition from another. Treatment based on noticeable symptoms, however, is limited to the types of clinical biomarkers collected, and is prone to overlooking dysfunctions in physiological factors not easily evident to medical practitioners. We used a vector-based representation of patient clinical biomarkers, or clinarrays, to search for latent physiological factors that underlie human diseases directly from clinical laboratory data. Knowledge of these factors could be used to improve assessment of disease severity and help to refine strategies for diagnosis and monitoring disease progression. Results Applying Independent Component Analysis on clinarrays built from patient laboratory measurements revealed both known and novel concomitant physiological factors for asthma, types 1 and 2 diabetes, cystic fibrosis, and Duchenne muscular dystrophy. Serum sodium was found to be the most significant factor for both type 1 and type 2 diabetes, and was also significant in asthma. TSH3, a measure of thyroid function, and blood urea nitrogen, indicative of kidney function, were factors unique to type 1 diabetes respective to type 2 diabetes. Platelet count was significant across all the diseases analyzed. Conclusions The results demonstrate that large-scale analyses of clinical biomarkers using unsupervised methods can offer novel insights into the pathophysiological basis of human disease, and suggest novel clinical utility of established laboratory measurements.

  4. A new technique for analysing interacting factors affecting biodiversity patterns: crossed-DPCoA.

    Science.gov (United States)

    Pavoine, Sandrine; Blondel, Jacques; Dufour, Anne B; Gasc, Amandine; Bonsall, Michael B

    2013-01-01

    We developed an approach for analysing the effects of two crossed factors A and B on the functional, taxonomic or phylogenetic composition of communities. The methodology, known as crossed-DPCoA, defines a space where species, communities and the levels of the two factors are organised as a set of points. In this space, the Euclidean distance between two species-specific points is a measure of the (functional, taxonomic or phylogenetic) dissimilarity. The communities are positioned at the centroid of their constitutive species; and the levels of two factors at the centroid of the communities associated with them. We develop two versions for crossed-DPCoA, the first one moves the levels of factor B to the centre of the space and analyses the axes of highest variance in the coordinates of the levels of factor A. It is related to previous ordination approaches such as partial canonical correspondence analysis and partial non-symmetrical correspondence analysis. The second version projects all points on the orthogonal complement of the space generated by the principal axes of factor B. This second version should be preferred when there is an a priori suspicion that factor A and B are associated. We apply the two versions of crossed-DPCoA to analyse the phylogenetic composition of Central European and Mediterranean bird communities. Applying crossed-DPCoA on bird communities supports the hypothesis that allopatric speciation processes during the Quaternary occurred in open and patchily distributed landscapes, while the lack of geographic barriers to dispersal among forest habitats may explain the homogeneity of forest bird communities over the whole western Palaearctic. Generalizing several ordination analyses commonly used in ecology, crossed-DPCoA provides an approach for analysing the effects of crossed factors on functional, taxonomic and phylogenetic diversity, environmental and geographic structure of species niches, and more broadly the role of genetics on

  5. A new technique for analysing interacting factors affecting biodiversity patterns: crossed-DPCoA.

    Directory of Open Access Journals (Sweden)

    Sandrine Pavoine

    Full Text Available We developed an approach for analysing the effects of two crossed factors A and B on the functional, taxonomic or phylogenetic composition of communities. The methodology, known as crossed-DPCoA, defines a space where species, communities and the levels of the two factors are organised as a set of points. In this space, the Euclidean distance between two species-specific points is a measure of the (functional, taxonomic or phylogenetic dissimilarity. The communities are positioned at the centroid of their constitutive species; and the levels of two factors at the centroid of the communities associated with them. We develop two versions for crossed-DPCoA, the first one moves the levels of factor B to the centre of the space and analyses the axes of highest variance in the coordinates of the levels of factor A. It is related to previous ordination approaches such as partial canonical correspondence analysis and partial non-symmetrical correspondence analysis. The second version projects all points on the orthogonal complement of the space generated by the principal axes of factor B. This second version should be preferred when there is an a priori suspicion that factor A and B are associated. We apply the two versions of crossed-DPCoA to analyse the phylogenetic composition of Central European and Mediterranean bird communities. Applying crossed-DPCoA on bird communities supports the hypothesis that allopatric speciation processes during the Quaternary occurred in open and patchily distributed landscapes, while the lack of geographic barriers to dispersal among forest habitats may explain the homogeneity of forest bird communities over the whole western Palaearctic. Generalizing several ordination analyses commonly used in ecology, crossed-DPCoA provides an approach for analysing the effects of crossed factors on functional, taxonomic and phylogenetic diversity, environmental and geographic structure of species niches, and more broadly the role of

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

    Science.gov (United States)

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

    2015-04-03

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

  7. Analyses of transcriptome sequences reveal multiple ancient large-scale duplication events in the ancestor of Sphagnopsida (Bryophyta).

    Science.gov (United States)

    Devos, Nicolas; Szövényi, Péter; Weston, David J; Rothfels, Carl J; Johnson, Matthew G; Shaw, A Jonathan

    2016-07-01

    The goal of this research was to investigate whether there has been a whole-genome duplication (WGD) in the ancestry of Sphagnum (peatmoss) or the class Sphagnopsida, and to determine if the timing of any such duplication(s) and patterns of paralog retention could help explain the rapid radiation and current ecological dominance of peatmosses. RNA sequencing (RNA-seq) data were generated for nine taxa in Sphagnopsida (Bryophyta). Analyses of frequency plots for synonymous substitutions per synonymous site (Ks ) between paralogous gene pairs and reconciliation of 578 gene trees were conducted to assess evidence of large-scale or genome-wide duplication events in each transcriptome. Both Ks frequency plots and gene tree-based analyses indicate multiple duplication events in the history of the Sphagnopsida. The most recent WGD event predates divergence of Sphagnum from the two other genera of Sphagnopsida. Duplicate retention is highly variable across species, which might be best explained by local adaptation. Our analyses indicate that the last WGD could have been an important factor underlying the diversification of peatmosses and facilitated their rise to ecological dominance in peatlands. The timing of the duplication events and their significance in the evolutionary history of peat mosses are discussed.

  8. Analyses on the tectonic thermal evolution and influence factors in the deep-water Qiongdongnan Basin

    Institute of Scientific and Technical Information of China (English)

    WANG Zhenfeng; SHI Xiaobin; YANG Jun; HUANG Baojia; SUN Zhen; WANG Yahui; JIANG Haiyan; YU Chuanhai; YANG Xiaoqiu

    2014-01-01

    To reveal the tectonic thermal evolution and influence factors on the present heat flow distribution, based on 154 heat flow data, the present heat flow distribution features of the main tectonic units are first analyzed in detail, then the tectonic thermal evolution histories of 20 profiles are reestablished crossing the main deep-water sags with a structural, thermal and sedimentary coupled numerical model. On the basis of the present geothermal features, the Qiongdongnan Basin could be divided into three regions: the northern shelf and upper slope region with a heat flow of 50–70 mW/m2, most of the central depression zone of 70–85 mW/m2, and a NE trending high heat flow zone of 85–105 mW/m2 lying in the eastern basin. Numerical modeling shows that during the syn-rift phase, the heat flow increases generally with time, and is higher in basement high area than in its adjacent sags. At the end of the syn-rift phase, the heat flow in the deep-water sags was in a range of 60–85 mW/m2, while in the basement high area, it was in a range of 75–100 mW/m2. During the post-rift phase, the heat flow decreased gradually, and tended to be more uniform in the basement highs and sags. However, an extensive magmatism, which equivalently happened at around 5 Ma, has greatly increased the heat flow values, and the relict heat still contributes about 10–25 mW/m2to the present surface heat flow in the central depression zone and the southern uplift zone. Further analyses suggested that the present high heat flow in the deep-water Qiongdongnan Basin is a combined result of the thermal anomaly in the upper mantle, highly thinning of the lithosphere, and the recent extensive magma-tism. Other secondary factors might have affected the heat flow distribution features in some local regions. These factors include basement and seafloor topography, sediment heat generation, thermal blanketing, local magmatic injecting and hydrothermal activities related to faulting and

  9. Comparative Genomic Analyses of the Human NPHP1 Locus Reveal Complex Genomic Architecture and Its Regional Evolution in Primates.

    Directory of Open Access Journals (Sweden)

    Bo Yuan

    2015-12-01

    Full Text Available Many loci in the human genome harbor complex genomic structures that can result in susceptibility to genomic rearrangements leading to various genomic disorders. Nephronophthisis 1 (NPHP1, MIM# 256100 is an autosomal recessive disorder that can be caused by defects of NPHP1; the gene maps within the human 2q13 region where low copy repeats (LCRs are abundant. Loss of function of NPHP1 is responsible for approximately 85% of the NPHP1 cases-about 80% of such individuals carry a large recurrent homozygous NPHP1 deletion that occurs via nonallelic homologous recombination (NAHR between two flanking directly oriented ~45 kb LCRs. Published data revealed a non-pathogenic inversion polymorphism involving the NPHP1 gene flanked by two inverted ~358 kb LCRs. Using optical mapping and array-comparative genomic hybridization, we identified three potential novel structural variant (SV haplotypes at the NPHP1 locus that may protect a haploid genome from the NPHP1 deletion. Inter-species comparative genomic analyses among primate genomes revealed massive genomic changes during evolution. The aggregated data suggest that dynamic genomic rearrangements occurred historically within the NPHP1 locus and generated SV haplotypes observed in the human population today, which may confer differential susceptibility to genomic instability and the NPHP1 deletion within a personal genome. Our study documents diverse SV haplotypes at a complex LCR-laden human genomic region. Comparative analyses provide a model for how this complex region arose during primate evolution, and studies among humans suggest that intra-species polymorphism may potentially modulate an individual's susceptibility to acquiring disease-associated alleles.

  10. Phylogeographic analyses of submesophotic snappers Etelis coruscans and Etelis "marshi" (family Lutjanidae reveal concordant genetic structure across the Hawaiian Archipelago.

    Directory of Open Access Journals (Sweden)

    Kimberly R Andrews

    Full Text Available The Hawaiian Archipelago has become a natural laboratory for understanding genetic connectivity in marine organisms as a result of the large number of population genetics studies that have been conducted across this island chain for a wide taxonomic range of organisms. However, population genetic studies have been conducted for only two species occurring in the mesophotic or submesophotic zones (30+m in this archipelago. To gain a greater understanding of genetic connectivity in these deepwater habitats, we investigated the genetic structure of two submesophotic fish species (occurring ∼200-360 m in this archipelago. We surveyed 16 locations across the archipelago for submesophotic snappers Etelis coruscans (N = 787 and E. "marshi" (formerly E. carbunculus; N = 770 with 436-490 bp of mtDNA cytochrome b and 10-11 microsatellite loci. Phylogeographic analyses reveal no geographic structuring of mtDNA lineages and recent coalescence times that are typical of shallow reef fauna. Population genetic analyses reveal no overall structure across most of the archipelago, a pattern also typical of dispersive shallow fishes. However some sites in the mid-archipelago (Raita Bank to French Frigate Shoals had significant population differentiation. This pattern of no structure between ends of the Hawaiian range, and significant structure in the middle, was previously observed in a submesophotic snapper (Pristipomoides filamentosus and a submesophotic grouper (Hyporthodus quernus. Three of these four species also have elevated genetic diversity in the mid-archipelago. Biophysical larval dispersal models from previous studies indicate that this elevated diversity may result from larval supplement from Johnston Atoll, ∼800 km southwest of Hawaii. In this case the boundaries of stocks for fishery management cannot be defined simply in terms of geography, and fishery management in Hawaii may need to incorporate external larval supply into management

  11. Comparative analyses of lipidomes and transcriptomes reveal a concerted action of multiple defensive systems against photooxidative stress in Haematococcus pluvialis.

    Science.gov (United States)

    Gwak, Yunho; Hwang, Yong-sic; Wang, Baobei; Kim, Minju; Jeong, Jooyeon; Lee, Choul-Gyun; Hu, Qiang; Han, Danxiang; Jin, EonSeon

    2014-08-01

    Haematococcus pluvialis cells predominantly remain in the macrozooid stage under favourable environmental conditions but are rapidly differentiated into haematocysts upon exposure to various environmental stresses. Haematocysts are characterized by massive accumulations of astaxanthin sequestered in cytosolic oil globules. Lipidomic analyses revealed that synthesis of the storage lipid triacylglycerol (TAG) was substantially stimulated under high irradiance. Simultaneously, remodelling of membrane glycerolipids occurred as a result of dramatic reductions in chloroplast membrane glycolipids but remained unchanged or declined slightly in extraplastidic membrane glycerolipids. De novo assembly of transcriptomes revealed the genomic and metabolic features of this unsequenced microalga. Comparative transcriptomic analysis showed that so-called resting cells (haematocysts) may be more active than fast-growing vegetative cells (macrozooids) regarding metabolic pathways and functions. Comparative transcriptomic analyses of astaxanthin biosynthesis suggested that the non-mevalonate pathway mediated the synthesis of isopentenyl diphosphate, as the majority of genes involved in subsequent astaxanthin biosynthesis were substantially up-regulated under high irradiance, with the genes encoding phytoene synthase, phytoene desaturase, and β-carotene hydroxylase identified as the most prominent regulatory components. Accumulation of TAG under high irradiance was attributed to moderate up-regulation of de novo fatty acid biosynthesis at the gene level as well as to moderate elevation of the TAG assembly pathways. Additionally, inferred from transcriptomic differentiation, an increase in reactive oxygen species (ROS) scavenging activity, a decrease in ROS production, and the relaxation of over-reduction of the photosynthetic electron transport chain will work together to protect against photooxidative stress in H. pluvialis under high irradiance. © The Author 2014. Published by

  12. The Chinese Family Assessment Instrument (C-FAI): Hierarchical Confirmatory Factor Analyses and Factorial Invariance

    Science.gov (United States)

    Shek, Daniel T. L.; Ma, Cecilia M. S.

    2010-01-01

    Objective: This paper examines the dimensionality and factorial invariance of the Chinese Family Assessment Instrument (C-FAI) using multigroup confirmatory factor analyses (MCFAs). Method: A total of 3,649 students responded to the C-FAI in a community survey. Results: Results showed that there are five dimensions of the C-FAI (communication,…

  13. Classification of L2 Vocabulary Learning Strategies: Evidence from Exploratory and Confirmatory Factor Analyses

    Science.gov (United States)

    Zhang, Bo; Li, Changyu

    2011-01-01

    This research presents a classification theory for the L2 vocabulary learning strategies. Based on the exploratory and confirmatory factor analyses of strategies that adult Chinese English learners used, this theory identifies six categories, four of which are related to the cognitive process in lexical acquisition and the other two are…

  14. Dimensionality of the Chinese Positive Youth Development Scale: Confirmatory Factor Analyses

    Science.gov (United States)

    Shek, Daniel T. L.; Ma, Cecilia M. S.

    2010-01-01

    This paper examines the dimensionality and factorial invariance of the Chinese Positive Youth Development Scale (CPYDS) using multigroup confirmatory factor analyses (MCFA). Secondary 1 students (N = 5,649) responded to the CPYDS in the context of a positive youth development program. Results showed that there are 15 basic dimensions of the CPYDS…

  15. Structural analyses of Legionella LepB reveal a new GAP fold that catalytically mimics eukaryotic RasGAP

    Institute of Scientific and Technical Information of China (English)

    Qin Yu; Liyan Hu; Qing Yao; Yongqun Zhu; Na Dong; Da-Cheng Wang; Feng Shao

    2013-01-01

    Rab GTPases are emerging targets of diverse bacterial pathogens.Here,we perform biochemical and structural analyses of LepB,a Rab GTPase-activating protein (GAP) effector from Legionellapneumophila.We map LepB GAP domain to residues 313-618 and show that the GAP domain is Rab1 specific with a catalytic activity higher than the canonical eukaryotic TBC GAP and the newly identified VirA/EspG family of bacterial RabGAP effectors.Exhaustive mutation analyses identify Arg444 as the arginine finger,but no catalytically essential glutamine residues.Crystal structures of LepB313-618 alone and the GAP domain of Legionella drancourtii LepB in complex with Rab1-GDP-AIF3 support the catalytic role of Arg444,and also further reveal a 3D architecture and a GTPase-binding mode distinct from all known GAPs.Glu449,structurally equivalent to TBC RabGAP glutamine finger in apo-LepB,undergoes a drastic movement upon Rab1 binding,which induces Rab1 Gin70 side-chain flipping towards GDP-AIF3 through a strong ionic interaction.This conformationally rearranged Gln70 acts as the catalytic cis-glutamine,therefore uncovering an unexpected RasGAP-like catalytic mechanism for LepB.Our studies highlight an extraordinary structural and catalytic diversity of RabGAPs,particularly those from bacterial pathogens.

  16. Phenotypic factor analysis of psychopathology reveals a new body-related transdiagnostic factor.

    Science.gov (United States)

    Pezzoli, Patrizia; Antfolk, Jan; Santtila, Pekka

    2017-01-01

    Comorbidity challenges the notion of mental disorders as discrete categories. An increasing body of literature shows that symptoms cut across traditional diagnostic boundaries and interact in shaping the latent structure of psychopathology. Using exploratory and confirmatory factor analysis, we reveal the latent sources of covariation among nine measures of psychopathological functioning in a population-based sample of 13024 Finnish twins and their siblings. By implementing unidimensional, multidimensional, second-order, and bifactor models, we illustrate the relationships between observed variables, specific, and general latent factors. We also provide the first investigation to date of measurement invariance of the bifactor model of psychopathology across gender and age groups. Our main result is the identification of a distinct "Body" factor, alongside the previously identified Internalizing and Externalizing factors. We also report relevant cross-disorder associations, especially between body-related psychopathology and trait anger, as well as substantial sex and age differences in observed and latent means. The findings expand the meta-structure of psychopathology, with implications for empirical and clinical practice, and demonstrate shared mechanisms underlying attitudes towards nutrition, self-image, sexuality and anger, with gender- and age-specific features.

  17. Genome-Wide Association and Transcriptome Analyses Reveal Candidate Genes Underlying Yield-determining Traits in Brassica napus

    Science.gov (United States)

    Lu, Kun; Peng, Liu; Zhang, Chao; Lu, Junhua; Yang, Bo; Xiao, Zhongchun; Liang, Ying; Xu, Xingfu; Qu, Cunmin; Zhang, Kai; Liu, Liezhao; Zhu, Qinlong; Fu, Minglian; Yuan, Xiaoyan; Li, Jiana

    2017-01-01

    Yield is one of the most important yet complex crop traits. To improve our understanding of the genetic basis of yield establishment, and to identify candidate genes responsible for yield improvement in Brassica napus, we performed genome-wide association studies (GWAS) for seven yield-determining traits [main inflorescence pod number (MIPN), branch pod number (BPN), pod number per plant (PNP), seed number per pod (SPP), thousand seed weight, main inflorescence yield (MIY), and branch yield], using data from 520 diverse B. napus accessions from two different yield environments. In total, we detected 128 significant single nucleotide polymorphisms (SNPs), 93 of which were revealed as novel by integrative analysis. A combination of GWAS and transcriptome sequencing on 21 haplotype blocks from samples pooled by four extremely high-yielding or low-yielding accessions revealed the differential expression of 14 crucial candiate genes (such as Bna.MYB83, Bna.SPL5, and Bna.ROP3) associated with multiple traits or containing multiple SNPs associated with the same trait. Functional annotation and expression pattern analyses further demonstrated that these 14 candiate genes might be important in developmental processes and biomass accumulation, thus affecting the yield establishment of B. napus. These results provide valuable information for understanding the genetic mechanisms underlying the establishment of high yield in B. napus, and lay the foundation for developing high-yielding B. napus varieties. PMID:28261256

  18. Gene expression profiling and phenotype analyses of S. cerevisiae in response to changing copper reveals six genes with new roles in copper and iron metabolism.

    Science.gov (United States)

    van Bakel, Harm; Strengman, Eric; Wijmenga, Cisca; Holstege, Frank C P

    2005-08-11

    Exhaustive microarray time course analyses of Saccharomyces cerevisiae during copper starvation and copper excess reveal new aspects of metal-induced gene regulation. Aside from identifying targets of established copper- and iron-responsive transcription factors, we find that genes encoding mitochondrial proteins are downregulated and that copper-independent iron transport genes are preferentially upregulated, both during prolonged copper deprivation. The experiments also suggest the presence of a small regulatory iron pool that links copper and iron responses. One hundred twenty-eight genes with putative roles in metal metabolism were further investigated by several systematic phenotype screens. Of the novel phenotypes uncovered, hsp12-Delta and arn1-Delta display increased sensitivity to copper, cyc1-Delta and crr1-Delta show resistance to high copper, vma13-Delta exhibits increased sensitivity to iron deprivation, and pep12-Delta results in reduced growth in high copper and low iron. Besides revealing new components of eukaryotic metal trafficking pathways, the results underscore the previously determined intimate links between iron and copper metabolism and mitochondrial and vacuolar function in metal trafficking. The analyses further suggest that copper starvation can specifically lead to downregulation of respiratory function to preserve iron and copper for other cellular processes.

  19. Structural analyses of Avocado sunblotch viroid reveal differences in the folding of plus and minus RNA strands.

    Science.gov (United States)

    Delan-Forino, Clémentine; Deforges, Jules; Benard, Lionel; Sargueil, Bruno; Maurel, Marie-Christine; Torchet, Claire

    2014-01-29

    Viroids are small pathogenic circular single-stranded RNAs, present in two complementary sequences, named plus and minus, in infected plant cells. A high degree of complementarities between different regions of the RNAs allows them to adopt complex structures. Since viroids are naked non-coding RNAs, interactions with host factors appear to be closely related to their structural and catalytic characteristics. Avocado sunblotch viroid (ASBVd), a member of the family Avsunviroidae, replicates via a symmetric RNA-dependant rolling-circle process, involving self-cleavage via hammerhead ribozymes. Consequently, it is assumed that ASBVd plus and minus strands adopt similar structures. Moreover, by computer analyses, a quasi-rod-like secondary structure has been predicted. Nevertheless, secondary and tertiary structures of both polarities of ASBVd remain unsolved. In this study, we analyzed the characteristic of each strand of ASBVd through biophysical analyses. We report that ASBVd transcripts of plus and minus polarities exhibit differences in electrophoretic mobility under native conditions and in thermal denaturation profiles. Subsequently, the secondary structures of plus and minus polarities of ASBVd were probed using the RNA-selective 2'-hydroxyl acylation analyzed by primer extension (SHAPE) method. The models obtained show that both polarities fold into different structures. Moreover, our results suggest the existence of a kissing-loop interaction within the minus strand that may play a role in in vivo viroid life cycle.

  20. Structural Analyses of Avocado sunblotch viroid Reveal Differences in the Folding of Plus and Minus RNA Strands

    Science.gov (United States)

    Delan-Forino, Clémentine; Deforges, Jules; Benard, Lionel; Sargueil, Bruno; Maurel, Marie-Christine; Torchet, Claire

    2014-01-01

    Viroids are small pathogenic circular single-stranded RNAs, present in two complementary sequences, named plus and minus, in infected plant cells. A high degree of complementarities between different regions of the RNAs allows them to adopt complex structures. Since viroids are naked non-coding RNAs, interactions with host factors appear to be closely related to their structural and catalytic characteristics. Avocado sunblotch viroid (ASBVd), a member of the family Avsunviroidae, replicates via a symmetric RNA-dependant rolling-circle process, involving self-cleavage via hammerhead ribozymes. Consequently, it is assumed that ASBVd plus and minus strands adopt similar structures. Moreover, by computer analyses, a quasi-rod-like secondary structure has been predicted. Nevertheless, secondary and tertiary structures of both polarities of ASBVd remain unsolved. In this study, we analyzed the characteristic of each strand of ASBVd through biophysical analyses. We report that ASBVd transcripts of plus and minus polarities exhibit differences in electrophoretic mobility under native conditions and in thermal denaturation profiles. Subsequently, the secondary structures of plus and minus polarities of ASBVd were probed using the RNA-selective 2'-hydroxyl acylation analyzed by primer extension (SHAPE) method. The models obtained show that both polarities fold into different structures. Moreover, our results suggest the existence of a kissing-loop interaction within the minus strand that may play a role in in vivo viroid life cycle. PMID:24481250

  1. Structural Analyses of Avocado sunblotch viroid Reveal Differences in the Folding of Plus and Minus RNA Strands

    Directory of Open Access Journals (Sweden)

    Clémentine Delan-Forino

    2014-01-01

    Full Text Available Viroids are small pathogenic circular single-stranded RNAs, present in two complementary sequences, named plus and minus, in infected plant cells. A high degree of complementarities between different regions of the RNAs allows them to adopt complex structures. Since viroids are naked non-coding RNAs, interactions with host factors appear to be closely related to their structural and catalytic characteristics. Avocado sunblotch viroid (ASBVd, a member of the family Avsunviroidae, replicates via a symmetric RNA-dependant rolling-circle process, involving self-cleavage via hammerhead ribozymes. Consequently, it is assumed that ASBVd plus and minus strands adopt similar structures. Moreover, by computer analyses, a quasi-rod-like secondary structure has been predicted. Nevertheless, secondary and tertiary structures of both polarities of ASBVd remain unsolved. In this study, we analyzed the characteristic of each strand of ASBVd through biophysical analyses. We report that ASBVd transcripts of plus and minus polarities exhibit differences in electrophoretic mobility under native conditions and in thermal denaturation profiles. Subsequently, the secondary structures of plus and minus polarities of ASBVd were probed using the RNA-selective 2'-hydroxyl acylation analyzed by primer extension (SHAPE method. The models obtained show that both polarities fold into different structures. Moreover, our results suggest the existence of a kissing-loop interaction within the minus strand that may play a role in in vivo viroid life cycle.

  2. Proteomic Analyses Reveal the Mechanism of Dunaliella salina Ds-26-16 Gene Enhancing Salt Tolerance in Escherichia coli.

    Directory of Open Access Journals (Sweden)

    Yanlong Wang

    Full Text Available We previously screened the novel gene Ds-26-16 from a 4 M salt-stressed Dunaliella salina cDNA library and discovered that this gene conferred salt tolerance to broad-spectrum organisms, including E. coli (Escherichia coli, Haematococcus pluvialis and tobacco. To determine the mechanism of this gene conferring salt tolerance, we studied the proteome of E. coli overexpressing the full-length cDNA of Ds-26-16 using the iTRAQ (isobaric tags for relative and absolute quantification approach. A total of 1,610 proteins were identified, which comprised 39.4% of the whole proteome. Of the 559 differential proteins, 259 were up-regulated and 300 were down-regulated. GO (gene ontology and KEGG (Kyoto encyclopedia of genes and genomes enrichment analyses identified 202 major proteins, including those involved in amino acid and organic acid metabolism, energy metabolism, carbon metabolism, ROS (reactive oxygen species scavenging, membrane proteins and ABC (ATP binding cassette transporters, and peptidoglycan synthesis, as well as 5 up-regulated transcription factors. Our iTRAQ data suggest that Ds-26-16 up-regulates the transcription factors in E. coli to enhance salt resistance through osmotic balance, energy metabolism, and oxidative stress protection. Changes in the proteome were also observed in E. coli overexpressing the ORF (open reading frame of Ds-26-16. Furthermore, pH, nitric oxide and glycerol content analyses indicated that Ds-26-16 overexpression increases nitric oxide content but has no effect on glycerol content, thus confirming that enhanced nitric oxide synthesis via lower intercellular pH was one of the mechanisms by which Ds-26-16 confers salt tolerance to E. coli.

  3. Phylogenetic and morphologic analyses of a coastal fish reveals a marine biogeographic break of terrestrial origin in the southern Caribbean.

    Directory of Open Access Journals (Sweden)

    Ricardo Betancur-R

    Full Text Available BACKGROUND: Marine allopatric speciation involves interplay between intrinsic organismal properties and extrinsic factors. However, the relative contribution of each depends on the taxon under study and its geographic context. Utilizing sea catfishes in the Cathorops mapale species group, this study tests the hypothesis that both reproductive strategies conferring limited dispersal opportunities and an apparent geomorphologic barrier in the Southern Caribbean have promoted speciation in this group from a little studied area of the world. METHODOLOGY/PRINCIPAL FINDINGS: Mitochondrial gene sequences were obtained from representatives of the Cathorops mapale species group across its distributional range from Colombia to Venezuela. Morphometric and meristic analyses were also done to assess morphologic variation. Along a approximately 2000 km transect, two major lineages, Cathorops sp. and C. mapale, were identified by levels of genetic differentiation, phylogenetic reconstructions, and morphological analyses. The lineages are separated by approximately 150 km at the Santa Marta Massif (SMM in Colombia. The northward displacement of the SMM into the Caribbean in the early Pleistocene altered the geomorphology of the continental margin, ultimately disrupting the natural habitat of C. mapale. The estimated approximately 0.86 my divergence of the lineages from a common ancestor coincides with the timing of the SMM displacement at approximately 0.78 my. MAIN CONCLUSIONS/SIGNIFICANCE: Results presented here support the hypothesis that organismal properties as well as extrinsic factors lead to diversification of the Cathorops mapale group along the northern coast of South America. While a lack of pelagic larval stages and ecological specialization are forces impacting this process, the identification of the SMM as contributing to allopatric speciation in marine organisms adds to the list of recognized barriers in the Caribbean. Comparative examination of

  4. Phylogenetic and Morphologic Analyses of a Coastal Fish Reveals a Marine Biogeographic Break of Terrestrial Origin in the Southern Caribbean

    Science.gov (United States)

    Betancur-R, Ricardo; Acero P., Arturo; Duque-Caro, Hermann; Santos, Scott R.

    2010-01-01

    Background Marine allopatric speciation involves interplay between intrinsic organismal properties and extrinsic factors. However, the relative contribution of each depends on the taxon under study and its geographic context. Utilizing sea catfishes in the Cathorops mapale species group, this study tests the hypothesis that both reproductive strategies conferring limited dispersal opportunities and an apparent geomorphologic barrier in the Southern Caribbean have promoted speciation in this group from a little studied area of the world. Methodology/Principal Findings Mitochondrial gene sequences were obtained from representatives of the Cathorops mapale species group across its distributional range from Colombia to Venezuela. Morphometric and meristic analyses were also done to assess morphologic variation. Along a ∼2000 km transect, two major lineages, Cathorops sp. and C. mapale, were identified by levels of genetic differentiation, phylogenetic reconstructions, and morphological analyses. The lineages are separated by ∼150 km at the Santa Marta Massif (SMM) in Colombia. The northward displacement of the SMM into the Caribbean in the early Pleistocene altered the geomorphology of the continental margin, ultimately disrupting the natural habitat of C. mapale. The estimated ∼0.86 my divergence of the lineages from a common ancestor coincides with the timing of the SMM displacement at ∼0.78 my. Main Conclusions/Significance Results presented here support the hypothesis that organismal properties as well as extrinsic factors lead to diversification of the Cathorops mapale group along the northern coast of South America. While a lack of pelagic larval stages and ecological specialization are forces impacting this process, the identification of the SMM as contributing to allopatric speciation in marine organisms adds to the list of recognized barriers in the Caribbean. Comparative examination of additional Southern Caribbean taxa, particularly those with

  5. Transcriptome sequencing and genome-wide association analyses reveal lysosomal function and actin cytoskeleton remodeling in schizophrenia and bipolar disorder.

    Science.gov (United States)

    Zhao, Z; Xu, J; Chen, J; Kim, S; Reimers, M; Bacanu, S-A; Yu, H; Liu, C; Sun, J; Wang, Q; Jia, P; Xu, F; Zhang, Y; Kendler, K S; Peng, Z; Chen, X

    2015-05-01

    Schizophrenia (SCZ) and bipolar disorder (BPD) are severe mental disorders with high heritability. Clinicians have long noticed the similarities of clinic symptoms between these disorders. In recent years, accumulating evidence indicates some shared genetic liabilities. However, what is shared remains elusive. In this study, we conducted whole transcriptome analysis of post-mortem brain tissues (cingulate cortex) from SCZ, BPD and control subjects, and identified differentially expressed genes in these disorders. We found 105 and 153 genes differentially expressed in SCZ and BPD, respectively. By comparing the t-test scores, we found that many of the genes differentially expressed in SCZ and BPD are concordant in their expression level (q⩽0.01, 53 genes; q⩽0.05, 213 genes; q⩽0.1, 885 genes). Using genome-wide association data from the Psychiatric Genomics Consortium, we found that these differentially and concordantly expressed genes were enriched in association signals for both SCZ (Pgenes show concordant expression and association for both SCZ and BPD. Pathway analyses of these genes indicated that they are involved in the lysosome, Fc gamma receptor-mediated phagocytosis, regulation of actin cytoskeleton pathways, along with several cancer pathways. Functional analyses of these genes revealed an interconnected pathway network centered on lysosomal function and the regulation of actin cytoskeleton. These pathways and their interacting network were principally confirmed by an independent transcriptome sequencing data set of the hippocampus. Dysregulation of lysosomal function and cytoskeleton remodeling has direct impacts on endocytosis, phagocytosis, exocytosis, vesicle trafficking, neuronal maturation and migration, neurite outgrowth and synaptic density and plasticity, and different aspects of these processes have been implicated in SCZ and BPD.

  6. Exploratory Metabolomic Analyses Reveal Compounds Correlated with Lutein Concentration in Frontal Cortex, Hippocampus, and Occipital Cortex of Human Infant Brain.

    Directory of Open Access Journals (Sweden)

    Jacqueline C Lieblein-Boff

    Full Text Available Lutein is a dietary carotenoid well known for its role as an antioxidant in the macula, and recent reports implicate a role for lutein in cognitive function. Lutein is the dominant carotenoid in both pediatric and geriatric brain tissue. In addition, cognitive function in older adults correlated with macular and postmortem brain lutein concentrations. Furthermore, lutein was found to preferentially accumulate in the infant brain in comparison to other carotenoids that are predominant in diet. While lutein is consistently related to cognitive function, the mechanisms by which lutein may influence cognition are not clear. In an effort to identify potential mechanisms through which lutein might influence neurodevelopment, an exploratory study relating metabolite signatures and lutein was completed. Post-mortem metabolomic analyses were performed on human infant brain tissues in three regions important for learning and memory: the frontal cortex, hippocampus, and occipital cortex. Metabolomic profiles were compared to lutein concentration, and correlations were identified and reported here. A total of 1276 correlations were carried out across all brain regions. Of 427 metabolites analyzed, 257 were metabolites of known identity. Unidentified metabolite correlations (510 were excluded. In addition, moderate correlations with xenobiotic relationships (2 or those driven by single outliers (3 were excluded from further study. Lutein concentrations correlated with lipid pathway metabolites, energy pathway metabolites, brain osmolytes, amino acid neurotransmitters, and the antioxidant homocarnosine. These correlations were often brain region-specific. Revealing relationships between lutein and metabolic pathways may help identify potential candidates on which to complete further analyses and may shed light on important roles of lutein in the human brain during development.

  7. Multilocus assignment analyses reveal multiple units and rare migration events in the recently expanded yellow-eyed penguin (Megadyptes antipodes).

    Science.gov (United States)

    Boessenkool, Sanne; Star, Bastiaan; Waters, Jonathan M; Seddon, Philip J

    2009-06-01

    The identification of demographically independent populations and the recognition of management units have been greatly facilitated by the continuing advances in genetic tools. Managements units now play a key role in short-term conservation management programmes of declining species, but their importance in expanding populations receives comparatively little attention. The endangered yellow-eyed penguin (Megadyptes antipodes) expanded its range from the subantarctic to New Zealand's South Island a few hundred years ago and this new population now represents almost half of the species' total census size. This dramatic expansion attests to M. antipodes' high dispersal abilities and suggests the species is likely to constitute a single demographic population. Here we test this hypothesis of panmixia by investigating genetic differentiation and levels of gene flow among penguin breeding areas using 12 autosomal microsatellite loci along with mitochondrial control region sequence analyses for 350 individuals. Contrary to our hypothesis, however, the analyses reveal two genetically and geographically distinct assemblages: South Island vs. subantarctic populations. Using assignment tests, we recognize just two first-generation migrants between these populations (corresponding to a migration rate of < 2%), indicating that ongoing levels of long-distance migration are low. Furthermore, the South Island population has low genetic variability compared to the subantarctic population. These results suggest that the South Island population was founded by only a small number of individuals, and that subsequent levels of gene flow have remained low. The demographic independence of the two populations warrants their designation as distinct management units and conservation efforts should be adjusted accordingly to protect both populations.

  8. Stimulatory effect of Echinacea purpurea extract on the trafficking activity of mouse dendritic cells: revealed by genomic and proteomic analyses.

    Science.gov (United States)

    Yin, Shu-Yi; Wang, Wen-Hsin; Wang, Bi-Xue; Aravindaram, Kandan; Hwang, Pei-Ing; Wu, Han-Ming; Yang, Ning-Sun

    2010-11-01

    Several Echinacea species have been used as nutraceuticals or botanical drugs for "immunostimulation", but scientific evidence supporting their therapeutic use is still controversial. In this study, a phytocompound mixture extracted from the butanol fraction (BF) of a stem and leaf (S+L) extract of E. purpurea ([BF/S+L/Ep]) containing stringently defined bioactive phytocompounds was obtained using standardized and published procedures. The transcriptomic and proteomic effects of this phytoextract on mouse bone marrow-derived dendritic cells (BMDCs) were analyzed using primary cultures. Treatment of BMDCs with [BF/S+L/Ep] did not significantly influence the phenotypic maturation activity of dendritic cells (DCs). Affymetrix DNA microarray and bioinformatics analyses of genes differentially expressed in DCs treated with [BF/S+L/Ep] for 4 or 12 h revealed that the majority of responsive genes were related to cell adhesion or motility (Cdh10, Itga6, Cdh1, Gja1 and Mmp8), or were chemokines (Cxcl2, Cxcl7) or signaling molecules (Nrxn1, Pkce and Acss1). TRANSPATH database analyses of gene expression and related signaling pathways in treated-DCs predicted the JNK, PP2C-α, AKT, ERK1/2 or MAPKAPK pathways as the putative targets of [BF/S+L/Ep]. In parallel, proteomic analysis showed that the expressions of metabolic-, cytoskeleton- or NF-κB signaling-related proteins were regulated by treatment with [BF/S+L/Ep]. In vitro flow cytometry analysis of chemotaxis-related receptors and in vivo cell trafficking assay further showed that DCs treated with [BF/S+L/Ep] were able to migrate more effectively to peripheral lymph node and spleen tissues than DCs treated as control groups. Results from this study suggest that [BF/S+L/Ep] modulates DC mobility and related cellular physiology in the mouse immune system. Moreover, the signaling networks and molecules highlighted here are potential targets for nutritional or clinical application of Echinacea or other candidate medicinal

  9. Comparative proteomic and physiological analyses reveal the protective effect of exogenous calcium on the germinating soybean response to salt stress.

    Science.gov (United States)

    Yin, Yongqi; Yang, Runqiang; Han, Yongbin; Gu, Zhenxin

    2015-01-15

    suppressed under salt stress condition. According to previous studies, exogenous calcium counters the harmful effect of salt stress and increases the biomass and GABA content of germinating soybeans. Nevertheless, the precise molecular mechanism underlying the role of calcium in resistance to salt stress is still unknown. This paper is the first study employing comparative proteomic and physiological analyses to reveal the protective effect of exogenous calcium in the germinating soybean response to salt stress. Our study links the biological events with proteomic information and provides detailed peptide information on all identified proteins. The functions of those significantly changed proteins are also analyzed. The physiological and comparative proteomic analyses revealed the putative molecular mechanism of exogenous calcium treatment induced salt stress responses. The findings from this paper are beneficial to high GABA-rich germinating soybean biomass. Additionally, these findings also might be applicable to the genetic engineering of soybean plants to improve stress tolerance.

  10. Whole-genome analyses reveals the animal origin of a rotavirus G4P[6] detected in a child with severe diarrhea.

    Science.gov (United States)

    Martinez, Magaly; Galeano, Maria E; Akopov, Asmik; Palacios, Ruth; Russomando, Graciela; Kirkness, Ewen F; Parra, Gabriel I

    2014-10-01

    Group A rotaviruses are a major cause of severe gastroenteritis in children worldwide. Currently, two rotavirus vaccines are being used in vaccination programs, and one of the factors involved in lower vaccine efficacy is the mismatch among the circulating strains and the vaccine strains. Thus, the emergence of animal strains in the human population could affect the efficacy of vaccination programs. Here we report the presence of a G4P[6] strain in a Paraguayan child presenting acute gastroenteritis in 2009. Genomic analyses revealed that the strain presents a porcine-like genome (G4-P[6]-I1-R1-C1-M1-A8-N1-T7-E1-H1), suggesting a direct animal-to-human transmission. Continuous surveillance of rotaviruses in humans and animals will help us to better understand rotavirus epidemiology and evolution.

  11. Round Robin Analyses on Stress Intensity Factors of Inner Surface Cracks in Welded Stainless Steel Pipes

    Directory of Open Access Journals (Sweden)

    Chang-Gi Han

    2016-12-01

    Full Text Available Austenitic stainless steels (ASSs are widely used for nuclear pipes as they exhibit a good combination of mechanical properties and corrosion resistance. However, high tensile residual stresses may occur in ASS welds because postweld heat treatment is not generally conducted in order to avoid sensitization, which causes a stress corrosion crack. In this study, round robin analyses on stress intensity factors (SIFs were carried out to examine the appropriateness of structural integrity assessment methods for ASS pipe welds with two types of circumferential cracks. Typical stress profiles were generated from finite element analyses by considering residual stresses and normal operating conditions. Then, SIFs of cracked ASS pipes were determined by analytical equations represented in fitness-for-service assessment codes as well as reference finite element analyses. The discrepancies of estimated SIFs among round robin participants were confirmed due to different assessment procedures and relevant considerations, as well as the mistakes of participants. The effects of uncertainty factors on SIFs were deducted from sensitivity analyses and, based on the similarity and conservatism compared with detailed finite element analysis results, the R6 code, taking into account the applied internal pressure and combination of stress components, was recommended as the optimum procedure for SIF estimation.

  12. Allosteric Inhibition of Macrophage Migration Inhibitory Factor Revealed by Ibudilast

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Y.; Crichlow, G; Vermeire, J; Leng, L; Du, X; Hodsdon, M; Bucala, R; Cappello, M; Gross, M; et al.

    2010-01-01

    AV411 (ibudilast; 3-isobutyryl-2-isopropylpyrazolo-[1,5-a]pyridine) is an antiinflammatory drug that was initially developed for the treatment of bronchial asthma but which also has been used for cerebrovascular and ocular indications. It is a nonselective inhibitor of various phosphodiesterases (PDEs) and has varied antiinflammatory activity. More recently, AV411 has been studied as a possible therapeutic for the treatment of neuropathic pain and opioid withdrawal through its actions on glial cells. As described herein, the PDE inhibitor AV411 and its PDE-inhibition-compromised analog AV1013 inhibit the catalytic and chemotactic functions of the proinflammatory protein, macrophage migration inhibitory factor (MIF). Enzymatic analysis indicates that these compounds are noncompetitive inhibitors of the p-hydroxyphenylpyruvate (HPP) tautomerase activity of MIF and an allosteric binding site of AV411 and AV1013 is detected by NMR. The allosteric inhibition mechanism is further elucidated by X-ray crystallography based on the MIF/AV1013 binary and MIF/AV1013/HPP ternary complexes. In addition, our antibody experiments directed against MIF receptors indicate that CXCR2 is the major receptor for MIF-mediated chemotaxis of peripheral blood mononuclear cells.

  13. Demographic and random amplified polymorphic DNA analyses reveal high levels of genetic diversity in a clonal violet.

    Science.gov (United States)

    Auge, H; Neuffer, B; Erlinghagen, F; Grupe, R; Brandl, R

    2001-07-01

    We performed demographic and molecular investigations on woodland populations of the clonal herb Viola riviniana in central Germany. We investigated the pattern of seedling recruitment, the amount of genotypic (clonal) variation and the partitioning of genetic variation among and within populations. Our demographic study was carried out in six violet populations of different ages and habitat conditions. It revealed that repeated seedling recruitment takes place in all of these populations, and that clonal propagation is accompanied by high ramet mortality. Our molecular investigations were performed on a subset of three of these six violet populations. Random amplified polymorphic DNA analyses using six primers yielded 45 scorable bands that were used to identify multilocus genotypes, i.e. putative clones. Consistent with our demographic results and independent of population age, we found a large genotypic diversity with a mean proportion of distinguishable genotypes of 0.93 and a mean Simpson's diversity index of 0.99. Using AMOVA we found a strong genetic differentiation among these violet populations with a PhiST value of 0.41. We suggest that a high selfing rate, limited gene flow due to short seed dispersal distances and drift due to founder effects are responsible for this pattern. Although Viola riviniana is a clonal plant, traits associated with sexual reproduction rather than clonality per se are moulding the pattern of genetic variation in this species.

  14. Pronounced genetic differentiation and recent secondary contact in the mangrove tree Lumnitzera racemosa revealed by population genomic analyses

    Science.gov (United States)

    Li, Jianfang; Yang, Yuchen; Chen, Qipian; Fang, Lu; He, Ziwen; Guo, Wuxia; Qiao, Sitan; Wang, Zhengzhen; Guo, Miaomiao; Zhong, Cairong; Zhou, Renchao; Shi, Suhua

    2016-01-01

    Systematically investigating the impacts of Pleistocene sea-level fluctuations on mangrove plants may provide a better understanding of their demographic history and useful information for their conservation. Therefore, we conducted population genomic analyses of 88 nuclear genes to explore the population dynamics of a mangrove tree Lumnitzera racemosa across the Indo-West Pacific region. Our results revealed pronounced genetic differentiation in this species between the populations from the Indian Ocean and the Pacific Ocean, which may be attributable to the long-term isolation between the western and eastern coasts of the Malay Peninsula during sea-level drops in the Pleistocene glacial periods. The mixing of haplotypes from the two highly divergent groups was identified in a Cambodian population at almost all 88 nuclear genes, suggesting genetic admixture of the two lineages at the boundary region. Similar genetic admixture was also found in other populations from Southeast Asia based on the Bayesian clustering analysis of six nuclear genes, which suggests extensive and recent secondary contact of the two divergent lineages in Southeast Asia. Computer simulations indicated substantial migration from the Indian Ocean towards the South China Sea, which likely results in the genetic admixture in Southeast Asia. PMID:27380895

  15. Genetic Diversity of Marine Anaerobic Ammonium-Oxidizing Bacteria as Revealed by Genomic and Proteomic Analyses of 'Candidatus Scalindua japonica'.

    Science.gov (United States)

    Oshiki, Mamoru; Mizuto, Keisuke; Kimura, Zenichiro; Kindaichi, Tomonori; Satoh, Hisashi; Okabe, Satoshi

    2017-09-11

    Anaerobic ammonium-oxidizing (anammox) bacteria affiliated with the genus 'Candidatus Scalindua' are responsible for significant nitrogen loss in oceans, and thus their ecophysiology is of great interest. Here, we enriched a marine anammox bacterium, 'Ca. S. japonica' from a Hiroshima bay sediment in Japan, and comparative genomic and proteomic analyses of 'Ca. S. japonica' were conducted. Sequence of the 4.81-Mb genome containing 4,019 coding regions of genes (CDSs) composed of 47 contigs was determined. In the proteome, 1,762 out of 4,019 CDSs in the 'Ca. S. japonica' genome were detected. Based on the genomic and proteomic data, the core anammox process and carbon fixation of 'Ca. S. japonica' were further investigated. Additionally, the present study provides the first detailed insights into the genetic background responsible for iron acquisition and menaquinone biosynthesis in anammox bacterial cells. Comparative analysis of the 'Ca. Scalindua' genomes revealed that the 1,502 genes found in the 'Ca. S. japonica' genome were not present in the 'Ca. S. profunda' and 'Ca. S. rubra' genomes, showing a high genomic diversity. This result may reflect a high phylogenetic diversity of the genus 'Ca. Scalindua'. This article is protected by copyright. All rights reserved. © 2017 Society for Applied Microbiology and John Wiley & Sons Ltd.

  16. Post-genomic analyses of fungal lignocellulosic biomass degradation reveal the unexpected potential of the plant pathogen Ustilago maydis

    Directory of Open Access Journals (Sweden)

    Couturier Marie

    2012-02-01

    Full Text Available Abstract Background Filamentous fungi are potent biomass degraders due to their ability to thrive in ligno(hemicellulose-rich environments. During the last decade, fungal genome sequencing initiatives have yielded abundant information on the genes that are putatively involved in lignocellulose degradation. At present, additional experimental studies are essential to provide insights into the fungal secreted enzymatic pools involved in lignocellulose degradation. Results In this study, we performed a wide analysis of 20 filamentous fungi for which genomic data are available to investigate their biomass-hydrolysis potential. A comparison of fungal genomes and secretomes using enzyme activity profiling revealed discrepancies in carbohydrate active enzymes (CAZymes sets dedicated to plant cell wall. Investigation of the contribution made by each secretome to the saccharification of wheat straw demonstrated that most of them individually supplemented the industrial Trichoderma reesei CL847 enzymatic cocktail. Unexpectedly, the most striking effect was obtained with the phytopathogen Ustilago maydis that improved the release of total sugars by 57% and of glucose by 22%. Proteomic analyses of the best-performing secretomes indicated a specific enzymatic mechanism of U. maydis that is likely to involve oxido-reductases and hemicellulases. Conclusion This study provides insight into the lignocellulose-degradation mechanisms by filamentous fungi and allows for the identification of a number of enzymes that are potentially useful to further improve the industrial lignocellulose bioconversion process.

  17. Complete genome sequence and transcriptomics analyses reveal pigment biosynthesis and regulatory mechanisms in an industrial strain, Monascus purpureus YY-1.

    Science.gov (United States)

    Yang, Yue; Liu, Bin; Du, Xinjun; Li, Ping; Liang, Bin; Cheng, Xiaozhen; Du, Liangcheng; Huang, Di; Wang, Lei; Wang, Shuo

    2015-02-09

    Monascus has been used to produce natural colorants and food supplements for more than one thousand years, and approximately more than one billion people eat Monascus-fermented products during their daily life. In this study, using next-generation sequencing and optical mapping approaches, a 24.1-Mb complete genome of an industrial strain, Monascus purpureus YY-1, was obtained. This genome consists of eight chromosomes and 7,491 genes. Phylogenetic analysis at the genome level provides convincing evidence for the evolutionary position of M. purpureus. We provide the first comprehensive prediction of the biosynthetic pathway for Monascus pigment. Comparative genomic analyses show that the genome of M. purpureus is 13.6-40% smaller than those of closely related filamentous fungi and has undergone significant gene losses, most of which likely occurred during its specialized adaptation to starch-based foods. Comparative transcriptome analysis reveals that carbon starvation stress, resulting from the use of relatively low-quality carbon sources, contributes to the high yield of pigments by repressing central carbon metabolism and augmenting the acetyl-CoA pool. Our work provides important insights into the evolution of this economically important fungus and lays a foundation for future genetic manipulation and engineering of this strain.

  18. NMR spectroscopic and bioinformatic analyses of the LTBP1 C-terminus reveal a highly dynamic domain organisation.

    Directory of Open Access Journals (Sweden)

    Ian B Robertson

    Full Text Available Proteins from the LTBP/fibrillin family perform key structural and functional roles in connective tissues. LTBP1 forms the large latent complex with TGFβ and its propeptide LAP, and sequesters the latent growth factor to the extracellular matrix. Bioinformatics studies suggest the main structural features of the LTBP1 C-terminus are conserved through evolution. NMR studies were carried out on three overlapping C-terminal fragments of LTBP1, comprising four domains with characterised homologues, cbEGF14, TB3, EGF3 and cbEGF15, and three regions with no homology to known structures. The NMR data reveal that the four domains adopt canonical folds, but largely lack the interdomain interactions observed with homologous fibrillin domains; the exception is the EGF3-cbEGF15 domain pair which has a well-defined interdomain interface. (15N relaxation studies further demonstrate that the three interdomain regions act as flexible linkers, allowing a wide range of motion between the well-structured domains. This work is consistent with the LTBP1 C-terminus adopting a flexible "knotted rope" structure, which may facilitate cell matrix interactions, and the accessibility to proteases or other factors that could contribute to TGFβ activation.

  19. Novel evolutionary lineages revealed in the Chaetothyriales (fungi based on multigene phylogenetic analyses and comparison of its secondary structure.

    Directory of Open Access Journals (Sweden)

    Martina Réblová

    Full Text Available Cyphellophora and Phialophora (Chaetothyriales, Pezizomycota comprise species known from skin infections of humans and animals and from a variety of environmental sources. These fungi were studied based on the comparison of cultural and morphological features and phylogenetic analyses of five nuclear loci, i.e., internal transcribed spacer rDNA operon (ITS, large and small subunit nuclear ribosomal DNA (nuc28S rDNA, nuc18S rDNA, β-tubulin, DNA replication licensing factor (mcm7 and second largest subunit of RNA polymerase II (rpb2. Phylogenetic results were supported by comparative analysis of ITS1 and ITS2 secondary structure of representatives of the Chaetothyriales and the identification of substitutions among the taxa analyzed. Base pairs with non-conserved, co-evolving nucleotides that maintain base pairing in the RNA transcript and unique evolutionary motifs in the ITS2 that characterize whole clades or individual taxa were mapped on predicted secondary structure models. Morphological characteristics, structural data and phylogenetic analyses of three datasets, i.e., ITS, ITS-β-tubulin and 28S-18S-rpb2-mcm7, define a robust clade containing eight species of Cyphellophora (including the type and six species of Phialophora. These taxa are now accommodated in the Cyphellophoraceae, a novel evolutionary lineage within the Chaetothyriales. Cyphellophora is emended and expanded to encompass species with both septate and nonseptate conidia formed on discrete, intercalary, terminal or lateral phialides. Six new combinations in Cyphellophora are proposed and a dichotomous key to species accepted in the genus is provided. Cyphellophora eugeniae and C. hylomeconis, which grouped in the Chaetothyriaceae, represent another novel lineage and are introduced as the type species of separate genera.

  20. Analyses of the contributing factors associated with foodborne outbreaks in school settings (2000-2010).

    Science.gov (United States)

    Venuto, Margaret; Garcia, Kristin

    2015-03-01

    State-reported school foodborne outbreaks account for about 3.8% (n = 464) of all outbreaks and 8.2% (n = 20,667) of all illnesses reported to the Centers for Disease Control and Prevention's Foodborne Disease Outbreak Surveillance System. Of 464 school foodborne outbreaks, 122 (26%) outbreaks, 7,603 illnesses, and 301 reported food safety errors met the criteria for inclusion in the analyses. The purpose of the authors' study was to examine the role of contributing factors in school foodborne outbreaks. Contamination factors accounted for the greatest proportion (49.2%) of outbreaks involving some level of food handling interaction by a school food service worker, followed by proliferation (34.9%) and survival factors (15.9%). Over 56% of all illnesses were associated with norovirus and food service worker practices. The results of these analyses highlight the importance of effective food safety education programs that focus on the role of contributing factors and prevention of foodborne disease from food safety errors.

  1. Stimulatory effect of Echinacea purpurea extract on the trafficking activity of mouse dendritic cells: revealed by genomic and proteomic analyses

    Directory of Open Access Journals (Sweden)

    Wang Bi-Xue

    2010-11-01

    Full Text Available Abstract Background Several Echinacea species have been used as nutraceuticals or botanical drugs for "immunostimulation", but scientific evidence supporting their therapeutic use is still controversial. In this study, a phytocompound mixture extracted from the butanol fraction (BF of a stem and leaf (S+L extract of E. purpurea ([BF/S+L/Ep] containing stringently defined bioactive phytocompounds was obtained using standardized and published procedures. The transcriptomic and proteomic effects of this phytoextract on mouse bone marrow-derived dendritic cells (BMDCs were analyzed using primary cultures. Results Treatment of BMDCs with [BF/S+L/Ep] did not significantly influence the phenotypic maturation activity of dendritic cells (DCs. Affymetrix DNA microarray and bioinformatics analyses of genes differentially expressed in DCs treated with [BF/S+L/Ep] for 4 or 12 h revealed that the majority of responsive genes were related to cell adhesion or motility (Cdh10, Itga6, Cdh1, Gja1 and Mmp8, or were chemokines (Cxcl2, Cxcl7 or signaling molecules (Nrxn1, Pkce and Acss1. TRANSPATH database analyses of gene expression and related signaling pathways in treated-DCs predicted the JNK, PP2C-α, AKT, ERK1/2 or MAPKAPK pathways as the putative targets of [BF/S+L/Ep]. In parallel, proteomic analysis showed that the expressions of metabolic-, cytoskeleton- or NF-κB signaling-related proteins were regulated by treatment with [BF/S+L/Ep]. In vitro flow cytometry analysis of chemotaxis-related receptors and in vivo cell trafficking assay further showed that DCs treated with [BF/S+L/Ep] were able to migrate more effectively to peripheral lymph node and spleen tissues than DCs treated as control groups. Conclusion Results from this study suggest that [BF/S+L/Ep] modulates DC mobility and related cellular physiology in the mouse immune system. Moreover, the signaling networks and molecules highlighted here are potential targets for nutritional or clinical

  2. Transcriptome and proteomic analyses reveal multiple differences associated with chloroplast development in the spaceflight-induced wheat albino mutant mta.

    Science.gov (United States)

    Shi, Kui; Gu, Jiayu; Guo, Huijun; Zhao, Linshu; Xie, Yongdun; Xiong, Hongchun; Li, Junhui; Zhao, Shirong; Song, Xiyun; Liu, Luxiang

    2017-01-01

    Chloroplast development is an integral part of plant survival and growth, and occurs in parallel with chlorophyll biosynthesis. However, little is known about the mechanisms underlying chloroplast development in hexaploid wheat. Here, we obtained a spaceflight-induced wheat albino mutant mta. Chloroplast ultra-structural observation showed that chloroplasts of mta exhibit abnormal morphology and distribution compared to wild type. Photosynthetic pigments content was also significantly decreased in mta. Transcriptome and chloroplast proteome profiling of mta and wild type were done to identify differentially expressed genes (DEGs) and proteins (DEPs), respectively. In total 4,588 DEGs including 1,980 up- and 2,608 down-regulated, and 48 chloroplast DEPs including 15 up- and 33 down-regulated were identified in mta. Classification of DEGs revealed that most were involved in chloroplast development, chlorophyll biosynthesis, or photosynthesis. Besides, transcription factors such as PIF3, GLK and MYB which might participate in those pathways were also identified. The correlation analysis between DEGs and DEPs revealed that the transcript-to-protein in abundance was functioned into photosynthesis and chloroplast relevant groups. Real time qPCR analysis validated that the expression level of genes encoding photosynthetic proteins was significantly decreased in mta. Together, our results suggest that the molecular mechanism for albino leaf color formation in mta is a thoroughly regulated and complicated process. The combined analysis of transcriptome and proteome afford comprehensive information for further research on chloroplast development mechanism in wheat. And spaceflight provides a potential means for mutagenesis in crop breeding.

  3. Comparative analyses reveal potential uses of Brachypodium distachyon as a model for cold stress responses in temperate grasses

    Directory of Open Access Journals (Sweden)

    Li Chuan

    2012-05-01

    Full Text Available Abstract Background Little is known about the potential of Brachypodium distachyon as a model for low temperature stress responses in Pooideae. The ice recrystallization inhibition protein (IRIP genes, fructosyltransferase (FST genes, and many C-repeat binding factor (CBF genes are Pooideae specific and important in low temperature responses. Here we used comparative analyses to study conservation and evolution of these gene families in B. distachyon to better understand its potential as a model species for agriculturally important temperate grasses. Results Brachypodium distachyon contains cold responsive IRIP genes which have evolved through Brachypodium specific gene family expansions. A large cold responsive CBF3 subfamily was identified in B. distachyon, while CBF4 homologs are absent from the genome. No B. distachyon FST gene homologs encode typical core Pooideae FST-motifs and low temperature induced fructan accumulation was dramatically different in B. distachyon compared to core Pooideae species. Conclusions We conclude that B. distachyon can serve as an interesting model for specific molecular mechanisms involved in low temperature responses in core Pooideae species. However, the evolutionary history of key genes involved in low temperature responses has been different in Brachypodium and core Pooideae species. These differences limit the use of B. distachyon as a model for holistic studies relevant for agricultural core Pooideae species.

  4. Distinct signal transduction pathways downstream of the (PRR revealed by microarray and ChIP-chip analyses.

    Directory of Open Access Journals (Sweden)

    Daniela Zaade

    Full Text Available The (prorenin receptor ((PRR signaling is involved in different pathophysiologies ranging from cardiorenal end-organ damage via diabetic retinopathy to tumorigenesis. We have previously shown that the transcription factor promyelocytic leukemia zinc finger (PLZF is an adaptor protein of the (PRR. Furthermore, recent publications suggest that major functions of the (PRR are mediated ligand-independently by its transmembrane and intracellular part, which acts as an accessory protein of V-ATPases. The transcriptome and recruitmentome downstream of the V-ATPase function and PLZF in the context of the (PRR are currently unknown. Therefore, we performed a set of microarray and chromatin-immunoprecipitation (ChIP-chip experiments using siRNA against the (PRR, stable overexpression of PLZF, the PLZF translocation inhibitor genistein and the specific V-ATPase inhibitor bafilomycin to dissect transcriptional pathways downstream of the (PRR. We were able to identify distinct and overlapping genetic signatures as well as novel real-time PCR-validated target genes of the different molecular functions of the (PRR. Moreover, bioinformatic analyses of our data confirm the role of (PRŔs signal transduction pathways in cardiovascular disease and tumorigenesis.

  5. Combined genomic and structural analyses of a cultured magnetotactic bacterium reveals its niche adaptation to a dynamic environment

    Directory of Open Access Journals (Sweden)

    Ana Carolina Vieira Araujo

    2016-10-01

    Full Text Available Abstract Background Magnetotactic bacteria (MTB are a unique group of prokaryotes that have a potentially high impact on global geochemical cycling of significant primary elements because of their metabolic plasticity and the ability to biomineralize iron-rich magnetic particles called magnetosomes. Understanding the genetic composition of the few cultivated MTB along with the unique morphological features of this group of bacteria may provide an important framework for discerning their potential biogeochemical roles in natural environments. Results Genomic and ultrastructural analyses were combined to characterize the cultivated magnetotactic coccus Magnetofaba australis strain IT-1. Cells of this species synthesize a single chain of elongated, cuboctahedral magnetite (Fe3O4 magnetosomes that cause them to align along magnetic field lines while they swim being propelled by two bundles of flagella at velocities up to 300 μm s−1. High-speed microscopy imaging showed the cells move in a straight line rather than in the helical trajectory described for other magnetotactic cocci. Specific genes within the genome of Mf. australis strain IT-1 suggest the strain is capable of nitrogen fixation, sulfur reduction and oxidation, synthesis of intracellular polyphosphate granules and transporting iron with low and high affinity. Mf. australis strain IT-1 and Magnetococcus marinus strain MC-1 are closely related phylogenetically although similarity values between their homologous proteins are not very high. Conclusion Mf. australis strain IT-1 inhabits a constantly changing environment and its complete genome sequence reveals a great metabolic plasticity to deal with these changes. Aside from its chemoautotrophic and chemoheterotrophic metabolism, genomic data indicate the cells are capable of nitrogen fixation, possess high and low affinity iron transporters, and might be capable of reducing and oxidizing a number of sulfur compounds. The relatively

  6. Phylogenetic analyses of eurotiomycetous endophytes reveal their close affinities to Chaetothyriales, Eurotiales, and a new order - Phaeomoniellales.

    Science.gov (United States)

    Chen, Ko-Hsuan; Miadlikowska, Jolanta; Molnár, Katalin; Arnold, A Elizabeth; U'Ren, Jana M; Gaya, Ester; Gueidan, Cécile; Lutzoni, François

    2015-04-01

    Symbiotic fungi living in plants as endophytes, and in lichens as endolichenic fungi, cause no apparent symptoms to their hosts. They are ubiquitous, ecologically important, hyperdiverse, and represent a rich source of secondary compounds for new pharmaceutical and biocontrol products. Due in part to the lack of visible reproductive structures and other distinctive phenotypic traits for many species, the diversity and phylogenetic affiliations of these cryptic fungi are often poorly known. The goal of this study was to determine the phylogenetic placement of representative endophytes within the Eurotiomycetes (Pezizomycotina, Ascomycota), one of the most diverse and evolutionarily dynamic fungal classes, and to use that information to infer processes of macroevolution in trophic modes. Sequences of a single locus marker spanning the nuclear ribosomal internal transcribed spacer region (nrITS) and 600 base pairs at the 5' end of the nuclear ribosomal large subunit (nrLSU) were obtained from previous studies of >6000 endophytic and endolichenic fungi from diverse biogeographic locations and hosts. We conducted phylum-wide phylogenetic searches using this marker to determine which fungal strains belonged to Eurotiomycetes and the results were used as the basis for a class-wide, seven-locus phylogenetic study focusing on endophytic and endolichenic Eurotiomycetes. Our cumulative supermatrix-based analyses revealed that representative endophytes within Eurotiomycetes are distributed in three main clades: Eurotiales, Chaetothyriales and Phaeomoniellales ord. nov., a clade that had not yet been described formally. This new order, described herein, is sister to the clade including Verrucariales and Chaetothyriales. It appears to consist mainly of endophytes and plant pathogens. Morphological characters of endophytic Phaeomoniellales resemble those of the pathogenic genus Phaeomoniella. This study highlights the capacity of endophytic and endolichenic fungi to expand our

  7. Genome and phylogenetic analyses of Trypanosoma evansi reveal extensive similarity to T. brucei and multiple independent origins for dyskinetoplasty.

    Science.gov (United States)

    Carnes, Jason; Anupama, Atashi; Balmer, Oliver; Jackson, Andrew; Lewis, Michael; Brown, Rob; Cestari, Igor; Desquesnes, Marc; Gendrin, Claire; Hertz-Fowler, Christiane; Imamura, Hideo; Ivens, Alasdair; Kořený, Luděk; Lai, De-Hua; MacLeod, Annette; McDermott, Suzanne M; Merritt, Chris; Monnerat, Severine; Moon, Wonjong; Myler, Peter; Phan, Isabelle; Ramasamy, Gowthaman; Sivam, Dhileep; Lun, Zhao-Rong; Lukeš, Julius; Stuart, Ken; Schnaufer, Achim

    2015-01-01

    Two key biological features distinguish Trypanosoma evansi from the T. brucei group: independence from the tsetse fly as obligatory vector, and independence from the need for functional mitochondrial DNA (kinetoplast or kDNA). In an effort to better understand the molecular causes and consequences of these differences, we sequenced the genome of an akinetoplastic T. evansi strain from China and compared it to the T. b. brucei reference strain. The annotated T. evansi genome shows extensive similarity to the reference, with 94.9% of the predicted T. b. brucei coding sequences (CDS) having an ortholog in T. evansi, and 94.6% of the non-repetitive orthologs having a nucleotide identity of 95% or greater. Interestingly, several procyclin-associated genes (PAGs) were disrupted or not found in this T. evansi strain, suggesting a selective loss of function in the absence of the insect life-cycle stage. Surprisingly, orthologous sequences were found in T. evansi for all 978 nuclear CDS predicted to represent the mitochondrial proteome in T. brucei, although a small number of these may have lost functionality. Consistent with previous results, the F1FO-ATP synthase γ subunit was found to have an A281 deletion, which is involved in generation of a mitochondrial membrane potential in the absence of kDNA. Candidates for CDS that are absent from the reference genome were identified in supplementary de novo assemblies of T. evansi reads. Phylogenetic analyses show that the sequenced strain belongs to a dominant group of clonal T. evansi strains with worldwide distribution that also includes isolates classified as T. equiperdum. At least three other types of T. evansi or T. equiperdum have emerged independently. Overall, the elucidation of the T. evansi genome sequence reveals extensive similarity of T. brucei and supports the contention that T. evansi should be classified as a subspecies of T. brucei.

  8. Molecular analyses reveal two geographic and genetic lineages for tapeworms, Taenia solium and Taenia saginata, from Ecuador using mitochondrial DNA.

    Science.gov (United States)

    Solano, Danilo; Navarro, Juan Carlos; León-Reyes, Antonio; Benítez-Ortiz, Washington; Rodríguez-Hidalgo, Richar

    2016-12-01

    Tapeworms Taenia solium and Taenia saginata are the causative agents of taeniasis/cysticercosis. These are diseases with high medical and veterinary importance due to their impact on public health and rural economy in tropical countries. The re-emergence of T. solium as a result of human migration, the economic burden affecting livestock industry, and the large variability of symptoms in several human cysticercosis, encourage studies on genetic diversity, and the identification of these parasites with molecular phylogenetic tools. Samples collected from the Ecuadorian provinces: Loja, Guayas, Manabí, Tungurahua (South), and Imbabura, Pichincha (North) from 2000 to 2012 were performed under Maximum Parsimony analyses and haplotype networks using partial sequences of mitochondrial DNA, cytochrome oxidase subunit I (COI) and NADH subunit I (NDI), from Genbank and own sequences of Taenia solium and Taenia saginata from Ecuador. Both species have shown reciprocal monophyly, which confirms its molecular taxonomic identity. The COI and NDI genes results suggest phylogenetic structure for both parasite species from south and north of Ecuador. In T. solium, both genes gene revealed greater geographic structure, whereas in T. saginata, the variability for both genes was low. In conclusion, COI haplotype networks of T. solium suggest two geographical events in the introduction of this species in Ecuador (African and Asian lineages) and occurring sympatric, probably through the most common routes of maritime trade between the XV-XIX centuries. Moreover, the evidence of two NDI geographical lineages in T. solium from the north (province of Imbabura) and the south (province of Loja) of Ecuador derivate from a common Indian ancestor open new approaches for studies on genetic populations and eco-epidemiology.

  9. Iron homeostasis in Arabidopsis thaliana: transcriptomic analyses reveal novel FIT-regulated genes, iron deficiency marker genes and functional gene networks.

    Science.gov (United States)

    Mai, Hans-Jörg; Pateyron, Stéphanie; Bauer, Petra

    2016-10-03

    FIT (FER-LIKE IRON DEFICIENCY-INDUCED TRANSCRIPTION FACTOR) is the central regulator of iron uptake in Arabidopsis thaliana roots. We performed transcriptome analyses of six day-old seedlings and roots of six week-old plants using wild type, a fit knock-out mutant and a FIT over-expression line grown under iron-sufficient or iron-deficient conditions. We compared genes regulated in a FIT-dependent manner depending on the developmental stage of the plants. We assembled a high likelihood dataset which we used to perform co-expression and functional analysis of the most stably iron deficiency-induced genes. 448 genes were found FIT-regulated. Out of these, 34 genes were robustly FIT-regulated in root and seedling samples and included 13 novel FIT-dependent genes. Three hundred thirty-one genes showed differential regulation in response to the presence and absence of FIT only in the root samples, while this was the case for 83 genes in the seedling samples. We assembled a virtual dataset of iron-regulated genes based on a total of 14 transcriptomic analyses of iron-deficient and iron-sufficient wild-type plants to pinpoint the best marker genes for iron deficiency and analyzed this dataset in depth. Co-expression analysis of this dataset revealed 13 distinct regulons part of which predominantly contained functionally related genes. We could enlarge the list of FIT-dependent genes and discriminate between genes that are robustly FIT-regulated in roots and seedlings or only in one of those. FIT-regulated genes were mostly induced, few of them were repressed by FIT. With the analysis of a virtual dataset we could filter out and pinpoint new candidates among the most reliable marker genes for iron deficiency. Moreover, co-expression and functional analysis of this virtual dataset revealed iron deficiency-induced and functionally distinct regulons.

  10. A forward genetic screen reveals essential and non-essential RNAi factors in Paramecium tetraurelia.

    Science.gov (United States)

    Marker, Simone; Carradec, Quentin; Tanty, Véronique; Arnaiz, Olivier; Meyer, Eric

    2014-06-01

    In most eukaryotes, small RNA-mediated gene silencing pathways form complex interacting networks. In the ciliate Paramecium tetraurelia, at least two RNA interference (RNAi) mechanisms coexist, involving distinct but overlapping sets of protein factors and producing different types of short interfering RNAs (siRNAs). One is specifically triggered by high-copy transgenes, and the other by feeding cells with double-stranded RNA (dsRNA)-producing bacteria. In this study, we designed a forward genetic screen for mutants deficient in dsRNA-induced silencing, and a powerful method to identify the relevant mutations by whole-genome sequencing. We present a set of 47 mutant alleles for five genes, revealing two previously unknown RNAi factors: a novel Paramecium-specific protein (Pds1) and a Cid1-like nucleotidyl transferase. Analyses of allelic diversity distinguish non-essential and essential genes and suggest that the screen is saturated for non-essential, single-copy genes. We show that non-essential genes are specifically involved in dsRNA-induced RNAi while essential ones are also involved in transgene-induced RNAi. One of the latter, the RNA-dependent RNA polymerase RDR2, is further shown to be required for all known types of siRNAs, as well as for sexual reproduction. These results open the way for the dissection of the genetic complexity, interconnection, mechanisms and natural functions of RNAi pathways in P. tetraurelia.

  11. Factor analyses of an Adult Epilepsy Self-Management Measurement Instrument (AESMMI).

    Science.gov (United States)

    Escoffery, Cam; Bamps, Yvan; LaFrance, W Curt; Stoll, Shelley; Shegog, Ross; Buelow, Janice; Shafer, Patricia; Thompson, Nancy J; McGee, Robin E; Hatfield, Katherine

    2015-09-01

    The purpose of this study was to test the psychometric properties of an enhanced Adult Epilepsy Self-Management Measurement Instrument (AESMMI). An instrument of 113 items, covering 10 a priori self-management domains, was generated through a multiphase process, based on a review of the literature, validated epilepsy and other chronic condition self-management scales and expert input. Reliability and exploratory factor analyses were conducted on data collected from 422 adults with epilepsy. The instrument was reduced to 65 items, converging on 11 factors: Health-care Communication, Coping, Treatment Management, Seizure Tracking, Social Support, Seizure Response, Wellness, Medication Adherence, Safety, Stress Management, and Proactivity. Exploratory factors supported the construct validity for 6 a priori domains, albeit with significant changes in the retained items or in their scope and 3 new factors. One a priori domain was split in 2 subscales pertaining to treatment. The configuration of the 11 factors provides additional insight into epilepsy self-management behaviors. Internal consistency reliability of the 65-item instrument was high (α=.935). Correlations with independent measures of health status, quality of life, depression, seizure severity, and life impact of epilepsy further validated the instrument. This instrument shows potential for use in research and clinical settings and for assessing intervention outcomes and self-management behaviors in adults with epilepsy.

  12. Integrative genomics analyses reveal molecularly distinct subgroups of B-cell chronic lymphocytic leukemia patients with 13q14 deletion.

    Science.gov (United States)

    Mosca, Laura; Fabris, Sonia; Lionetti, Marta; Todoerti, Katia; Agnelli, Luca; Morabito, Fortunato; Cutrona, Giovanna; Andronache, Adrian; Matis, Serena; Ferrari, Francesco; Gentile, Massimo; Spriano, Mauro; Callea, Vincenzo; Festini, Gianluca; Molica, Stefano; Deliliers, Giorgio Lambertenghi; Bicciato, Silvio; Ferrarini, Manlio; Neri, Antonino

    2010-12-01

    Chromosome 13q14 deletion occurs in a substantial number of chronic lymphocytic leukemia (CLL) patients and it is believed to play a pathogenetic role. The exact mechanisms involved in this lesion have not yet been fully elucidated because of its heterogeneity and the imprecise knowledge of the implicated genes. This study was addressed to further contribute to the molecular definition of this lesion in CLL. We applied single-nucleotide polymorphism (SNP)-array technology and gene expression profiling data to investigate the 13q14 deletion occurring in a panel of 100 untreated, early-stage (Binet A) patients representative of the major genetics, molecular, and biological features of the disease. Concordantly with FISH analysis, SNP arrays identified 44 patients with del(13)(q14) including 11 cases with a biallelic deletion. The shorter monoallelic deletion was 635-kb long. The loss of the miR-15a/16-1 cluster occurred in all del(13)(q14) cases except in 2 patients with a monoallelic deletion, who retained both copies. MiR-15a/16 expression was significantly downregulated only in patients with the biallelic loss of the miRNA cluster compared to 13q normal cases. Finally, the natural grouping of SNP profiles by nonnegative matrix factorization algorithm showed that patients could be classified into 2 separate clusters, mainly characterized by short/biallelic versus wide/monoallelic 13q14 deletions. Supervised analyses of expression data showed that specific transcriptional profiles are correlated with these 2 genomic subgroups. Overall, our data highlight the presence of 2 distinct molecular types of 13q14 deletions, which may be of clinical relevance in CLL. ©2010 AACR.

  13. CREB3 subfamily transcription factors are not created equal: Recent insights from global analyses and animal models

    Directory of Open Access Journals (Sweden)

    Chan Chi-Ping

    2011-02-01

    Full Text Available Abstract The CREB3 subfamily of membrane-bound bZIP transcription factors has five members in mammals known as CREB3 and CREB3L1-L4. One current model suggests that CREB3 subfamily transcription factors are similar to ATF6 in regulated intramembrane proteolysis and transcriptional activation. Particularly, they were all thought to be proteolytically activated in response to endoplasmic reticulum (ER stress to stimulate genes that are involved in unfolded protein response (UPR. Although the physiological inducers of their proteolytic activation remain to be identified, recent findings from microarray analyses, RNAi screens and gene knockouts not only demonstrated their critical roles in regulating development, metabolism, secretion, survival and tumorigenesis, but also revealed cell type-specific patterns in the activation of their target genes. Members of the CREB3 subfamily show differential activity despite their structural similarity. The spectrum of their biological function expands beyond ER stress and UPR. Further analyses are required to elucidate the mechanism of their proteolytic activation and the molecular basis of their target recognition.

  14. Exploratory and confirmatory factor analyses of the pervasive developmental disorders rating scale for young children with autistic disorder.

    Science.gov (United States)

    Eaves, Ronald C; Williams, Thomas O

    2006-03-01

    In this study, the authors examined the construct validity of the Pervasive Developmental Disorder Rating Scale (PDDRS; R. C. Eaves, 1993), which is a screening instrument used to identify individuals with autistic disorder and other pervasive developmental disorders. The PDDRS is purported to measure 3 factors--arousal, affect, and cognition-that collectively make up the construct of autism. Using scores from 199 children (aged 1-6 years) diagnosed with autistic disorder, the authors submitted data to exploratory and confirmatory factor analyses. In the 1st series of analyses, the authors analyzed a user-specified 3-factor solution using principal axis factor analysis with a promax rotation to evaluate the assertion of a correlated 3-factor structure. Next, the authors analyzed 1-factor and 2-factor solutions to determine if they provided a better factor structure for the data. In the 2nd series, the authors conducted confirmatory factor analyses, which compared the theorized hierarchical 2nd-order factor model with 5 plausible competing models. The results of the exploratory analyses supported the 3-factor solution. With the confirmatory analyses, the 2nd-order factor model provided the best fit for the data. The exploratory and confirmatory analyses supported the theoretical assumptions undergirding the development of the PDDRS. The authors discuss theoretical implications, practical implications, and areas for further research.

  15. Stable isotope analyses reveal the importance of seagrass beds as feeding areas for juvenile Myrophic punctatus in Florida

    Science.gov (United States)

    The feeding habits and habitats of the speckled worm eel Myrophis punctatus were studied on the mangrove edge of the Indian River Lagoon (Florida) using stomach contents and stable isotope analyses of carbon (δ13C) and nitrogen (δ15N). Stomach dietary analyses identified four tax...

  16. Integrated transcriptional profiling and genomic analyses reveal RPN2 and HMGB1 as promising biomarkers in colorectal cancer.

    Science.gov (United States)

    Zhang, Jialing; Yan, Bin; Späth, Stephan Stanislaw; Qun, Hu; Cornelius, Shaleeka; Guan, Daogang; Shao, Jiaofang; Hagiwara, Koichi; Van Waes, Carter; Chen, Zhong; Su, Xiulan; Bi, Yongyi

    2015-01-01

    Colorectal cancer (CRC) is a heterogeneous disease that is associated with a gradual accumulation of genetic and epigenetic alterations. Among all CRC stages, stage II tumors are highly heterogeneous with a high relapse rate in about 20-25 % of stage II CRC patients following surgery. Thus, a comprehensive analysis of gene signatures to identify aggressive and metastatic phenotypes in stage II CRC is desired for a more accurate disease classification and outcome prediction. By utilizing a Cancer Array, containing 440 oncogenes and tumor suppressors to profile mRNA expression, we identified a larger number of differentially expressed genes in poorly differentiated stage II colorectal adenocarcinoma tissues, compared to their matched normal tissues. Ontology and Ingenuity Pathway Analysis (IPA) indicated that these genes are involved in functional mechanisms associated with several transcription factors. Genomic alterations of these genes were also investigated through The Cancer Genome Atlas (TCGA) database, utilizing 195 published CRC specimens. The percentage of genomic alterations in these genes was ranked based on their mRNA expression, copy number variations and mutations. This data was further combined with published microarray studies from a large set of CRC tumors classified based on prognostic features. This led to the identification of eight candidate genes including RPN2, HMGB1, AARS, IGFBP3, STAT1, HYOU1, NQO1 and PEA15 that were associated with the progressive phenotype. In particular, RPN2 and HMGB1 displayed a higher genomic alteration frequency in CRC, compared to eight other major solid cancers. Immunohistochemistry was performed on additional 78 stage I-IV CRC samples, where RPN2 protein immunostaining exhibited a significant association with stage III/IV tumors, distant metastasis, and poor differentiation, indicating that RPN2 expression is associated with poor prognosis. Further, our study revealed significant transcriptional regulatory

  17. A model for analysing factors which may influence quality management procedures in higher education

    Directory of Open Access Journals (Sweden)

    Cătălin MAICAN

    2015-12-01

    Full Text Available In all universities, the Office for Quality Assurance defines the procedure for assessing the performance of the teaching staff, with a view to establishing students’ perception as regards the teachers’ activity from the point of view of the quality of the teaching process, of the relationship with the students and of the assistance provided for learning. The present paper aims at creating a combined model for evaluation, based on Data Mining statistical methods: starting from the findings revealed by the evaluations teachers performed to students, using the cluster analysis and the discriminant analysis, we identified the subjects which produced significant differences between students’ grades, subjects which were subsequently subjected to an evaluation by students. The results of these analyses allowed the formulation of certain measures for enhancing the quality of the evaluation process.

  18. Comparative Genomic, MicroRNA, and Tissue Analyses Reveal Subtle Differences between Non-Diabetic and Diabetic Foot Skin.

    Science.gov (United States)

    Ramirez, Horacio A; Liang, Liang; Pastar, Irena; Rosa, Ashley M; Stojadinovic, Olivera; Zwick, Thomas G; Kirsner, Robert S; Maione, Anna G; Garlick, Jonathan A; Tomic-Canic, Marjana

    2015-01-01

    Diabetes Mellitus (DM) is a chronic, severe disease rapidly increasing in incidence and prevalence and is associated with numerous complications. Patients with DM are at high risk of developing diabetic foot ulcers (DFU) that often lead to lower limb amputations, long term disability, and a shortened lifespan. Despite this, the effects of DM on human foot skin biology are largely unknown. Thus, the focus of this study was to determine whether DM changes foot skin biology predisposing it for healing impairment and development of DFU. Foot skin samples were collected from 20 patients receiving corrective foot surgery and, using a combination of multiple molecular and cellular approaches, we performed comparative analyses of non-ulcerated non-neuropathic diabetic foot skin (DFS) and healthy non-diabetic foot skin (NFS). MicroRNA (miR) profiling of laser captured epidermis and primary dermal fibroblasts from both DFS and NFS samples identified 5 miRs de-regulated in the epidermis of DFS though none reached statistical significance. MiR-31-5p and miR-31-3p were most profoundly induced. Although none were significantly regulated in diabetic fibroblasts, miR-29c-3p showed a trend of up-regulation, which was confirmed by qPCR in a prospective set of 20 skin samples. Gene expression profiling of full thickness biopsies identified 36 de-regulated genes in DFS (>2 fold-change, unadjusted p-value ≤ 0.05). Of this group, three out of seven tested genes were confirmed by qPCR: SERPINB3 was up-regulated whereas OR2A4 and LGR5 were down-regulated in DFS. However no morphological differences in histology, collagen deposition, and number of blood vessels or lymphocytes were found. No difference in proliferative capacity was observed by quantification of Ki67 positive cells in epidermis. These findings suggest DM causes only subtle changes to foot skin. Since morphology, mRNA and miR levels were not affected in a major way, additional factors, such as neuropathy, vascular

  19. Comparative Genomic, MicroRNA, and Tissue Analyses Reveal Subtle Differences between Non-Diabetic and Diabetic Foot Skin.

    Directory of Open Access Journals (Sweden)

    Horacio A Ramirez

    Full Text Available Diabetes Mellitus (DM is a chronic, severe disease rapidly increasing in incidence and prevalence and is associated with numerous complications. Patients with DM are at high risk of developing diabetic foot ulcers (DFU that often lead to lower limb amputations, long term disability, and a shortened lifespan. Despite this, the effects of DM on human foot skin biology are largely unknown. Thus, the focus of this study was to determine whether DM changes foot skin biology predisposing it for healing impairment and development of DFU. Foot skin samples were collected from 20 patients receiving corrective foot surgery and, using a combination of multiple molecular and cellular approaches, we performed comparative analyses of non-ulcerated non-neuropathic diabetic foot skin (DFS and healthy non-diabetic foot skin (NFS. MicroRNA (miR profiling of laser captured epidermis and primary dermal fibroblasts from both DFS and NFS samples identified 5 miRs de-regulated in the epidermis of DFS though none reached statistical significance. MiR-31-5p and miR-31-3p were most profoundly induced. Although none were significantly regulated in diabetic fibroblasts, miR-29c-3p showed a trend of up-regulation, which was confirmed by qPCR in a prospective set of 20 skin samples. Gene expression profiling of full thickness biopsies identified 36 de-regulated genes in DFS (>2 fold-change, unadjusted p-value ≤ 0.05. Of this group, three out of seven tested genes were confirmed by qPCR: SERPINB3 was up-regulated whereas OR2A4 and LGR5 were down-regulated in DFS. However no morphological differences in histology, collagen deposition, and number of blood vessels or lymphocytes were found. No difference in proliferative capacity was observed by quantification of Ki67 positive cells in epidermis. These findings suggest DM causes only subtle changes to foot skin. Since morphology, mRNA and miR levels were not affected in a major way, additional factors, such as neuropathy

  20. Medulloblastoma in China: clinicopathologic analyses of SHH, WNT, and non-SHH/WNT molecular subgroups reveal different therapeutic responses to adjuvant chemotherapy.

    Science.gov (United States)

    Zhang, Zhen-Yu; Xu, Jian; Ren, Yong; Li, Kay Ka-Wai; Ng, Ho-Keung; Mao, Ying; Zhong, Ping; Yao, Yu; Zhou, Liang-Fu

    2014-01-01

    Medulloblastoma (MB) is one of the most common primary central nervous system tumors in children. Data is lacking of a large cohort of medulloblastoma patients in China. Also, our knowledge on the sensitivity of different molecular subgroups of MB to adjuvant radiation therapy (RT) or chemotherapy (CHT) is still limited. The authors performed a retrospective study of 173 medulloblastoma patients treated at two institutions from 2002 to 2011. Formalin-fixed paraffin embedded (FFPE) tissues were available in all the cases and sections were stained to classify histological and molecular subgroups. Univariate and multivariate analyses were used to investigate prognostic factors. Of 173 patients, there were 118 children and 55 adults, 112 males and 61 females. Estimated 5-year overall survival (OS) rates for all patients, children and adults were 52%, 48% and 63%, respectively. After multivariate analysis, postoperative primary radiation therapy (RT) and chemotherapy (CHT) were revealed as favorable prognostic factors influencing OS and EFS. Postoperative primary chemotherapy (CHT) was found significantly improving the survival of children (pSHH and Non-SHH/WNT subtypes) given postoperative adjuvant therapies. Postoperative primary RT was found to be a strong prognostic factor influencing the survival in all histological and molecular subgroups (pSHH subgroup (OS p = 0.020, EFS p = 0.049) and WNT subgroup (OS p = 0.003, EFS p = 0.016) but not in desmoplastic/nodular medulloblastoma (DMB) (OS p = 0.361, EFS p = 0.834) and Non-SHH/WNT subgroup (OS p = 0.127, EFS p = 0.055). Our study showed postoperative primary CHT significantly influence the survival of CMB, SHH subgroup and WNT subgroup but not in DMB and Non-SHH/WNT subgroup of MB.

  1. Transcriptome and membrane fatty acid analyses reveal different strategies for responding to permeating and non-permeating solutes in the bacterium Sphingomonas wittichii

    Directory of Open Access Journals (Sweden)

    Johnson David R

    2011-11-01

    Full Text Available Abstract Background Sphingomonas wittichii strain RW1 can completely oxidize dibenzo-p-dioxins and dibenzofurans, which are persistent contaminants of soils and sediments. For successful application in soil bioremediation systems, strain RW1 must cope with fluctuations in water availability, or water potential. Thus far, however, little is known about the adaptive strategies used by Sphingomonas bacteria to respond to changes in water potential. To improve our understanding, strain RW1 was perturbed with either the cell-permeating solute sodium chloride or the non-permeating solute polyethylene glycol with a molecular weight of 8000 (PEG8000. These solutes are assumed to simulate the solute and matric components of the total water potential, respectively. The responses to these perturbations were then assessed and compared using a combination of growth assays, transcriptome profiling, and membrane fatty acid analyses. Results Under conditions producing a similar decrease in water potential but without effect on growth rate, there was only a limited shared response to perturbation with sodium chloride or PEG8000. This shared response included the increased expression of genes involved with trehalose and exopolysaccharide biosynthesis and the reduced expression of genes involved with flagella biosynthesis. Mostly, the responses to perturbation with sodium chloride or PEG8000 were very different. Only sodium chloride triggered the increased expression of two ECF-type RNA polymerase sigma factors and the differential expression of many genes involved with outer membrane and amino acid metabolism. In contrast, only PEG8000 triggered the increased expression of a heat shock-type RNA polymerase sigma factor along with many genes involved with protein turnover and repair. Membrane fatty acid analyses further corroborated these differences. The degree of saturation of membrane fatty acids increased after perturbation with sodium chloride but had the

  2. Unitary Root Music and Unitary Music with Real-Valued Rank Revealing Triangular Factorization

    Science.gov (United States)

    2010-06-01

    AFRL-RY-WP-TP-2010-1213 UNITARY ROOT MUSIC AND UNITARY MUSIC WITH REAL-VALUED RANK REVEALING TRIANGULAR FACTORIZATION (Postprint) Nizar...DATES COVERED (From - To) June 2010 Journal Article Postprint 08 September 2006 – 31 August 2009 4. TITLE AND SUBTITLE UNITARY ROOT MUSIC AND...UNITARY MUSIC WITH REAL-VALUED RANK REVEALING TRIANGULAR FACTORIZATION (Postprint) 5a. CONTRACT NUMBER 5b. GRANT NUMBER FA8650-05-D-1912-0007 5c

  3. Phylogeny, Functional Annotation, and Protein Interaction Network Analyses of the Xenopus tropicalis Basic Helix-Loop-Helix Transcription Factors

    Directory of Open Access Journals (Sweden)

    Wuyi Liu

    2013-01-01

    Full Text Available The previous survey identified 70 basic helix-loop-helix (bHLH proteins, but it was proved to be incomplete, and the functional information and regulatory networks of frog bHLH transcription factors were not fully known. Therefore, we conducted an updated genome-wide survey in the Xenopus tropicalis genome project databases and identified 105 bHLH sequences. Among the retrieved 105 sequences, phylogenetic analyses revealed that 103 bHLH proteins belonged to 43 families or subfamilies with 46, 26, 11, 3, 15, and 4 members in the corresponding supergroups. Next, gene ontology (GO enrichment analyses showed 65 significant GO annotations of biological processes and molecular functions and KEGG pathways counted in frequency. To explore the functional pathways, regulatory gene networks, and/or related gene groups coding for Xenopus tropicalis bHLH proteins, the identified bHLH genes were put into the databases KOBAS and STRING to get the signaling information of pathways and protein interaction networks according to available public databases and known protein interactions. From the genome annotation and pathway analysis using KOBAS, we identified 16 pathways in the Xenopus tropicalis genome. From the STRING interaction analysis, 68 hub proteins were identified, and many hub proteins created a tight network or a functional module within the protein families.

  4. High overlap of CNVs and selection signatures revealed by varLD analyses of taurine and zebu cattle

    Science.gov (United States)

    Selection Signatures (SS) assessed through analysis of genomic data are being widely studied to discover population specific regions selected via artificial or natural selection. Different methodologies have been proposed for these analyses, each having specific limitations as to the age of the sele...

  5. Single-cell expression analyses during cellular reprogramming reveal an early stochastic and a late hierarchic phase

    NARCIS (Netherlands)

    Buganim, Y.; Faddah, D.A.; Cheng, A.W.; Itskovich, E.; Markoulaki, S.; Ganz, K.; Klemm, S.L.; van Oudenaarden, A.; Jaenisch, R.

    2012-01-01

    During cellular reprogramming, only a small fraction of cells become induced pluripotent stem cells (iPSCs). Previous analyses of gene expression during reprogramming were based on populations of cells, impeding single-cell level identification of reprogramming events. We utilized two gene

  6. Genome-wide transcriptomic and proteomic analyses of bollworm-infested developing cotton bolls revealed the genes and pathways involved in the insect pest defence mechanism.

    Science.gov (United States)

    Kumar, Saravanan; Kanakachari, Mogilicherla; Gurusamy, Dhandapani; Kumar, Krishan; Narayanasamy, Prabhakaran; Kethireddy Venkata, Padmalatha; Solanke, Amolkumar; Gamanagatti, Savita; Hiremath, Vamadevaiah; Katageri, Ishwarappa S; Leelavathi, Sadhu; Kumar, Polumetla Ananda; Reddy, Vanga Siva

    2016-06-01

    Cotton bollworm, Helicoverpa armigera, is a major insect pest that feeds on cotton bolls causing extensive damage leading to crop and productivity loss. In spite of such a major impact, cotton plant response to bollworm infection is yet to be witnessed. In this context, we have studied the genome-wide response of cotton bolls infested with bollworm using transcriptomic and proteomic approaches. Further, we have validated this data using semi-quantitative real-time PCR. Comparative analyses have revealed that 39% of the transcriptome and 35% of the proteome were differentially regulated during bollworm infestation. Around 36% of significantly regulated transcripts and 45% of differentially expressed proteins were found to be involved in signalling followed by redox regulation. Further analysis showed that defence-related stress hormones and their lipid precursors, transcription factors, signalling molecules, etc. were stimulated, whereas the growth-related counterparts were suppressed during bollworm infestation. Around 26% of the significantly up-regulated proteins were defence molecules, while >50% of the significantly down-regulated were related to photosynthesis and growth. Interestingly, the biosynthesis genes for synergistically regulated jasmonate, ethylene and suppressors of the antagonistic factor salicylate were found to be up-regulated, suggesting a choice among stress-responsive phytohormone regulation. Manual curation of the enzymes and TFs highlighted the components of retrograde signalling pathways. Our data suggest that a selective regulatory mechanism directs the reallocation of metabolic resources favouring defence over growth under bollworm infestation and these insights could be exploited to develop bollworm-resistant cotton varieties.

  7. Structural and Kinetic Analyses of Macrophage Migration Inhibitory Factor Active Site Interactions

    Energy Technology Data Exchange (ETDEWEB)

    Crichlow, G.; Lubetsky, J; Leng, L; Bucala, R; Lolis, E

    2009-01-01

    Macrophage migration inhibitory factor (MIF) is a secreted protein expressed in numerous cell types that counters the antiinflammatory effects of glucocorticoids and has been implicated in sepsis, cancer, and certain autoimmune diseases. Interestingly, the structure of MIF contains a catalytic site resembling the tautomerase/isomerase sites of microbial enzymes. While bona fide physiological substrates remain unknown, model substrates have been identified. Selected compounds that bind in the tautomerase active site also inhibit biological functions of MIF. It had previously been shown that the acetaminophen metabolite, N-acetyl-p-benzoquinone imine (NAPQI), covalently binds to the active site of MIF. In this study, kinetic data indicate that NAPQI inhibits MIF both covalently and noncovalently. The structure of MIF cocrystallized with NAPQI reveals that the NAPQI has undergone a chemical alteration forming an acetaminophen dimer (bi-APAP) and binds noncovalently to MIF at the mouth of the active site. We also find that the commonly used protease inhibitor, phenylmethylsulfonyl fluoride (PMSF), forms a covalent complex with MIF and inhibits the tautomerase activity. Crystallographic analysis reveals the formation of a stable, novel covalent bond for PMSF between the catalytic nitrogen of the N-terminal proline and the sulfur of PMSF with complete, well-defined electron density in all three active sites of the MIF homotrimer. Conclusions are drawn from the structures of these two MIF-inhibitor complexes regarding the design of novel compounds that may provide more potent reversible and irreversible inhibition of MIF.

  8. Extensive expansion of A1 family aspartic proteinases in fungi revealed by evolutionary analyses of 107 complete eukaryotic proteomes

    NARCIS (Netherlands)

    Revuelta, M.V.; Kan, van J.A.L.; Kay, J.; Have, ten A.

    2014-01-01

    The A1 family of eukaryotic aspartic proteinases (APs) forms one of the 16 AP families. Although one of the best characterized families, the recent increase in genome sequence data has revealed many fungal AP homologs with novel sequence characteristics. This study was performed to explore the funga

  9. Parsimony and Model-Based Analyses of Indels in Avian Nuclear Genes Reveal Congruent and Incongruent Phylogenetic Signals

    Directory of Open Access Journals (Sweden)

    Frederick H. Sheldon

    2013-03-01

    Full Text Available Insertion/deletion (indel mutations, which are represented by gaps in multiple sequence alignments, have been used to examine phylogenetic hypotheses for some time. However, most analyses combine gap data with the nucleotide sequences in which they are embedded, probably because most phylogenetic datasets include few gap characters. Here, we report analyses of 12,030 gap characters from an alignment of avian nuclear genes using maximum parsimony (MP and a simple maximum likelihood (ML framework. Both trees were similar, and they exhibited almost all of the strongly supported relationships in the nucleotide tree, although neither gap tree supported many relationships that have proven difficult to recover in previous studies. Moreover, independent lines of evidence typically corroborated the nucleotide topology instead of the gap topology when they disagreed, although the number of conflicting nodes with high bootstrap support was limited. Filtering to remove short indels did not substantially reduce homoplasy or reduce conflict. Combined analyses of nucleotides and gaps resulted in the nucleotide topology, but with increased support, suggesting that gap data may prove most useful when analyzed in combination with nucleotide substitutions.

  10. Medulloblastoma in China: clinicopathologic analyses of SHH, WNT, and non-SHH/WNT molecular subgroups reveal different therapeutic responses to adjuvant chemotherapy.

    Directory of Open Access Journals (Sweden)

    Zhen-Yu Zhang

    Full Text Available Medulloblastoma (MB is one of the most common primary central nervous system tumors in children. Data is lacking of a large cohort of medulloblastoma patients in China. Also, our knowledge on the sensitivity of different molecular subgroups of MB to adjuvant radiation therapy (RT or chemotherapy (CHT is still limited. The authors performed a retrospective study of 173 medulloblastoma patients treated at two institutions from 2002 to 2011. Formalin-fixed paraffin embedded (FFPE tissues were available in all the cases and sections were stained to classify histological and molecular subgroups. Univariate and multivariate analyses were used to investigate prognostic factors. Of 173 patients, there were 118 children and 55 adults, 112 males and 61 females. Estimated 5-year overall survival (OS rates for all patients, children and adults were 52%, 48% and 63%, respectively. After multivariate analysis, postoperative primary radiation therapy (RT and chemotherapy (CHT were revealed as favorable prognostic factors influencing OS and EFS. Postoperative primary chemotherapy (CHT was found significantly improving the survival of children (p<0.001 while it was not a significant prognostic factor for adult patients. Moreover, patients in WNT subtype had better OS (p = 0.028 than others (SHH and Non-SHH/WNT subtypes given postoperative adjuvant therapies. Postoperative primary RT was found to be a strong prognostic factor influencing the survival in all histological and molecular subgroups (p<0.001. Postoperative primary CHT was found significantly to influence the survival of classic medulloblastoma (CMB (OS p<0.001, EFS p<0.001, SHH subgroup (OS p = 0.020, EFS p = 0.049 and WNT subgroup (OS p = 0.003, EFS p = 0.016 but not in desmoplastic/nodular medulloblastoma (DMB (OS p = 0.361, EFS p = 0.834 and Non-SHH/WNT subgroup (OS p = 0.127, EFS p = 0.055. Our study showed postoperative primary CHT significantly influence the

  11. Genome-wide classification and evolutionary and expression analyses of citrus MYB transcription factor families in sweet orange.

    Directory of Open Access Journals (Sweden)

    Xiao-Jin Hou

    Full Text Available MYB family genes are widely distributed in plants and comprise one of the largest transcription factors involved in various developmental processes and defense responses of plants. To date, few MYB genes and little expression profiling have been reported for citrus. Here, we describe and classify 177 members of the sweet orange MYB gene (CsMYB family in terms of their genomic gene structures and similarity to their putative Arabidopsis orthologs. According to these analyses, these CsMYBs were categorized into four groups (4R-MYB, 3R-MYB, 2R-MYB and 1R-MYB. Gene structure analysis revealed that 1R-MYB genes possess relatively more introns as compared with 2R-MYB genes. Investigation of their chromosomal localizations revealed that these CsMYBs are distributed across nine chromosomes. Sweet orange includes a relatively small number of MYB genes compared with the 198 members in Arabidopsis, presumably due to a paralog reduction related to repetitive sequence insertion into promoter and non-coding transcribed region of the genes. Comparative studies of CsMYBs and Arabidopsis showed that CsMYBs had fewer gene duplication events. Expression analysis revealed that the MYB gene family has a wide expression profile in sweet orange development and plays important roles in development and stress responses. In addition, 337 new putative microsatellites with flanking sequences sufficient for primer design were also identified from the 177 CsMYBs. These results provide a useful reference for the selection of candidate MYB genes for cloning and further functional analysis forcitrus.

  12. Genome-wide classification and evolutionary and expression analyses of citrus MYB transcription factor families in sweet orange.

    Science.gov (United States)

    Hou, Xiao-Jin; Li, Si-Bei; Liu, Sheng-Rui; Hu, Chun-Gen; Zhang, Jin-Zhi

    2014-01-01

    MYB family genes are widely distributed in plants and comprise one of the largest transcription factors involved in various developmental processes and defense responses of plants. To date, few MYB genes and little expression profiling have been reported for citrus. Here, we describe and classify 177 members of the sweet orange MYB gene (CsMYB) family in terms of their genomic gene structures and similarity to their putative Arabidopsis orthologs. According to these analyses, these CsMYBs were categorized into four groups (4R-MYB, 3R-MYB, 2R-MYB and 1R-MYB). Gene structure analysis revealed that 1R-MYB genes possess relatively more introns as compared with 2R-MYB genes. Investigation of their chromosomal localizations revealed that these CsMYBs are distributed across nine chromosomes. Sweet orange includes a relatively small number of MYB genes compared with the 198 members in Arabidopsis, presumably due to a paralog reduction related to repetitive sequence insertion into promoter and non-coding transcribed region of the genes. Comparative studies of CsMYBs and Arabidopsis showed that CsMYBs had fewer gene duplication events. Expression analysis revealed that the MYB gene family has a wide expression profile in sweet orange development and plays important roles in development and stress responses. In addition, 337 new putative microsatellites with flanking sequences sufficient for primer design were also identified from the 177 CsMYBs. These results provide a useful reference for the selection of candidate MYB genes for cloning and further functional analysis forcitrus.

  13. Ancient DNA Analyses Reveal Contrasting Phylogeographic Patterns amongst Kiwi (Apteryx spp.) and a Recently Extinct Lineage of Spotted Kiwi

    OpenAIRE

    Shepherd, Lara D; Worthy, Trevor H.; Tennyson, Alan J. D.; R Paul Scofield; Ramstad, Kristina M.; Lambert, David M.

    2012-01-01

    The little spotted kiwi (Apteryx owenii) is a flightless ratite formerly found throughout New Zealand but now greatly reduced in distribution. Previous phylogeographic studies of the related brown kiwi (A. mantelli, A. rowi and A. australis), with which little spotted kiwi was once sympatric, revealed extremely high levels of genetic structuring, with mitochondrial DNA haplotypes often restricted to populations. We surveyed genetic variation throughout the present and pre-human range of littl...

  14. Air Force Officer Qualifying Test Form T: Initial Item-, Test-, Factor-,and Composite-Level Analyses

    Science.gov (United States)

    2016-12-01

    AFRL-RH-WP-TR-2016-0093 AIR FORCE OFFICER QUALIFYING TEST FORM T: INITIAL ITEM-, TEST -, FACTOR-, AND COMPOSITE-LEVEL ANALYSES...July 2016 – 28 Nov 2016 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER FA8650-11-C-6158 Air Force Officer Qualifying Test Form T...Initial Item-, Test -, Factor-, and Composite-Level Analyses 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 62202F 6. AUTHOR(S) 5d. PROJECT

  15. Genome-wide analyses of Epstein-Barr virus reveal conserved RNA structures and a novel stable intronic sequence RNA

    OpenAIRE

    2013-01-01

    Background Epstein-Barr virus (EBV) is a human herpesvirus implicated in cancer and autoimmune disorders. Little is known concerning the roles of RNA structure in this important human pathogen. This study provides the first comprehensive genome-wide survey of RNA and RNA structure in EBV. Results Novel EBV RNAs and RNA structures were identified by computational modeling and RNA-Seq analyses of EBV. Scans of the genomic sequences of four EBV strains (EBV-1, EBV-2, GD1, and GD2) and of the clo...

  16. An assessment of recently published gene expression data analyses: reporting experimental design and statistical factors

    Directory of Open Access Journals (Sweden)

    Azuaje Francisco

    2006-06-01

    Full Text Available Abstract Background The analysis of large-scale gene expression data is a fundamental approach to functional genomics and the identification of potential drug targets. Results derived from such studies cannot be trusted unless they are adequately designed and reported. The purpose of this study is to assess current practices on the reporting of experimental design and statistical analyses in gene expression-based studies. Methods We reviewed hundreds of MEDLINE-indexed papers involving gene expression data analysis, which were published between 2003 and 2005. These papers were examined on the basis of their reporting of several factors, such as sample size, statistical power and software availability. Results Among the examined papers, we concentrated on 293 papers consisting of applications and new methodologies. These papers did not report approaches to sample size and statistical power estimation. Explicit statements on data transformation and descriptions of the normalisation techniques applied prior to data analyses (e.g. classification were not reported in 57 (37.5% and 104 (68.4% of the methodology papers respectively. With regard to papers presenting biomedical-relevant applications, 41(29.1 % of these papers did not report on data normalisation and 83 (58.9% did not describe the normalisation technique applied. Clustering-based analysis, the t-test and ANOVA represent the most widely applied techniques in microarray data analysis. But remarkably, only 5 (3.5% of the application papers included statements or references to assumption about variance homogeneity for the application of the t-test and ANOVA. There is still a need to promote the reporting of software packages applied or their availability. Conclusion Recently-published gene expression data analysis studies may lack key information required for properly assessing their design quality and potential impact. There is a need for more rigorous reporting of important experimental

  17. Comparative sequence analyses of genome and transcriptome reveal novel transcripts and variants in the Asian elephant Elephas maximus

    Indian Academy of Sciences (India)

    Puli Chandramouli Reddy; Ishani Sinha; Ashwin Kelkar; Farhat Habib; Saurabh J Pradhan; Raman Sukumar; Sanjeev Galande

    2015-12-01

    The Asian elephant Elephas maximus and the African elephant Loxodonta africana that diverged 5-7 million years ago exhibit differences in their physiology, behaviour and morphology. A comparative genomics approach would be useful and necessary for evolutionary and functional genetic studies of elephants. We performed sequencing of E. maximus and map to L. africana at ∼ 15X coverage. Through comparative sequence analyses, we have identified Asian elephant specific homozygous, non-synonymous single nucleotide variants (SNVs) that map to 1514 protein coding genes, many of which are involved in olfaction. We also present the first report of a high-coverage transcriptome sequence in E. maximus from peripheral blood lymphocytes. We have identified 103 novel protein coding transcripts and 66-long non-coding (Inc)RNAs. We also report the presence of 181 protein domains unique to elephants when compared to other Afrotheria species. Each of these findings can be further investigated to gain a better understanding of functional differences unique to elephant species, as well as those unique to elephantids in comparison with other mammals. This work therefore provides a valuable resource to explore the immense research potential of comparative analyses of transcriptome and genome sequences in the Asian elephant.

  18. Differential MicroRNA Analyses of Burkholderia pseudomallei- and Francisella tularensis-Exposed hPBMCs Reveal Potential Biomarkers

    Science.gov (United States)

    Herrera-Galeano, J. Enrique; Frey, Kenneth G.; Schully, Kevin L.; Luu, Truong V.; Pesce, John; Mokashi, Vishwesh P.; Keane-Myers, Andrea M.; Bishop-Lilly, Kimberly A.

    2017-01-01

    Increasing evidence that microRNAs (miRNAs) play important roles in the immune response against infectious agents suggests that miRNA might be exploitable as signatures of exposure to specific infectious agents. In order to identify potential early miRNA biomarkers of bacterial infections, human peripheral blood mononuclear cells (hPBMCs) were exposed to two select agents, Burkholderia pseudomallei K96243 and Francisella tularensis SHU S4, as well as to the nonpathogenic control Escherichia coli DH5α. RNA samples were harvested at three early time points, 30, 60, and 120 minutes postexposure, then sequenced. RNAseq analyses identified 87 miRNAs to be differentially expressed (DE) in a linear fashion. Of these, 31 miRNAs were tested using the miScript miRNA qPCR assay. Through RNAseq identification and qPCR validation, we identified differentially expressed miRNA species that may be involved in the early response to bacterial infections. Based upon its upregulation at early time points postexposure in two different individuals, hsa-mir-30c-5p is a miRNA species that could be studied further as a potential biomarker for exposure to these gram-negative intracellular pathogens. Gene ontology functional analyses demonstrated that programmed cell death is the first ranking biological process associated with miRNAs that are upregulated in F. tularensis-exposed hPBMCs. PMID:28791299

  19. Comparative sequence analyses of genome and transcriptome reveal novel transcripts and variants in the Asian elephant Elephas maximus.

    Science.gov (United States)

    Reddy, Puli Chandramouli; Sinha, Ishani; Kelkar, Ashwin; Habib, Farhat; Pradhan, Saurabh J; Sukumar, Raman; Galande, Sanjeev

    2015-12-01

    The Asian elephant Elephas maximus and the African elephant Loxodonta africana that diverged 5-7 million years ago exhibit differences in their physiology, behaviour and morphology. A comparative genomics approach would be useful and necessary for evolutionary and functional genetic studies of elephants. We performed sequencing of E. maximus and map to L. africana at ~15X coverage. Through comparative sequence analyses, we have identified Asian elephant specific homozygous, non-synonymous single nucleotide variants (SNVs) that map to 1514 protein coding genes, many of which are involved in olfaction. We also present the first report of a high-coverage transcriptome sequence in E. maximus from peripheral blood lymphocytes. We have identified 103 novel protein coding transcripts and 66-long non-coding (lnc)RNAs. We also report the presence of 181 protein domains unique to elephants when compared to other Afrotheria species. Each of these findings can be further investigated to gain a better understanding of functional differences unique to elephant species, as well as those unique to elephantids in comparison with other mammals. This work therefore provides a valuable resource to explore the immense research potential of comparative analyses of transcriptome and genome sequences in the Asian elephant.

  20. Genomic Analyses Reveal Demographic History and Temperate Adaptation of the Newly Discovered Honey Bee Subspecies Apis mellifera sinisxinyuan n. ssp.

    Science.gov (United States)

    Chen, Chao; Liu, Zhiguang; Pan, Qi; Chen, Xiao; Wang, Huihua; Guo, Haikun; Liu, Shidong; Lu, Hongfeng; Tian, Shilin; Li, Ruiqiang; Shi, Wei

    2016-05-01

    Studying the genetic signatures of climate-driven selection can produce insights into local adaptation and the potential impacts of climate change on populations. The honey bee (Apis mellifera) is an interesting species to study local adaptation because it originated in tropical/subtropical climatic regions and subsequently spread into temperate regions. However, little is known about the genetic basis of its adaptation to temperate climates. Here, we resequenced the whole genomes of ten individual bees from a newly discovered population in temperate China and downloaded resequenced data from 35 individuals from other populations. We found that the new population is an undescribed subspecies in the M-lineage of A. mellifera (Apis mellifera sinisxinyuan). Analyses of population history show that long-term global temperature has strongly influenced the demographic history of A. m. sinisxinyuan and its divergence from other subspecies. Further analyses comparing temperate and tropical populations identified several candidate genes related to fat body and the Hippo signaling pathway that are potentially involved in adaptation to temperate climates. Our results provide insights into the demographic history of the newly discovered A. m. sinisxinyuan, as well as the genetic basis of adaptation of A. mellifera to temperate climates at the genomic level. These findings will facilitate the selective breeding of A. mellifera to improve the survival of overwintering colonies.

  1. Genome-wide association and longitudinal analyses reveal genetic loci linking pubertal height growth, pubertal timing and childhood adiposity

    NARCIS (Netherlands)

    Cousminer, Diana L.; Berry, Diane J.; Timpson, Nicholas J.; Ang, Wei; Thiering, Elisabeth; Byrne, Enda M.; Taal, H. Rob; Huikari, Ville; Bradfield, Jonathan P.; Kerkhof, Marjan; Groen-Blokhuis, Maria M.; Kreiner-Moller, Eskil; Marinelli, Marcella; Holst, Claus; Leinonen, Jaakko T.; Perry, John R. B.; Surakka, Ida; Pietilainen, Olli; Kettunen, Johannes; Anttila, Verneri; Kaakinen, Marika; Sovio, Ulla; Pouta, Anneli; Das, Shikta; Lagou, Vasiliki; Power, Chris; Prokopenko, Inga; Evans, David M.; Kemp, John P.; St Pourcain, Beate; Ring, Susan; Palotie, Aarno; Kajantie, Eero; Osmond, Clive; Lehtimaki, Terho; Viikari, Jorma S.; Kahonen, Mika; Warrington, Nicole M.; Lye, Stephen J.; Palmer, Lyle J.; Tiesler, Carla M. T.; Flexeder, Claudia; Montgomery, Grant W.; Medland, Sarah E.; Hofman, Albert; Hakonarson, Hakon; Guxens, Monica; Bartels, Meike; Salomaa, Veikko; Murabito, Joanne M.; Kaprio, Jaakko; Sorensen, Thorkild I. A.; Ballester, Ferran; Bisgaard, Hans; Boomsma, Dorret I.; Koppelman, Gerard H.; Grant, Struan F. A.; Jaddoe, Vincent W. V.; Martin, Nicholas G.; Heinrich, Joachim; Pennell, Craig E.; Raitakari, Olli T.; Eriksson, Johan G.; Smith, George Davey; Hypponen, Elina; Jarvelin, Marjo-Riitta; McCarthy, Mark I.; Ripatti, Samuli; Widen, Elisabeth

    2013-01-01

    The pubertal height growth spurt is a distinctive feature of childhood growth reflecting both the central onset of puberty and local growth factors. Although little is known about the underlying genetics, growth variability during puberty correlates with adult risks for hormone-dependent cancer and

  2. Analysing physical fitness and biomechanical factors that determine tennis serve performance

    Directory of Open Access Journals (Sweden)

    Ertuğrul Gelen

    2009-11-01

    Full Text Available Normal 0 21 false false false TR X-NONE X-NONE MicrosoftInternetExplorer4 The purpose of the study is to analyse the fitness and the biomechanical factors which determine the velocity of the ball during serve in tennis (VBTS. The subjects of the study were fifteen male tournament level tennis player between the ages of sixteen and twenty five (18,8 ± 2,70 age/year. The physical fitness measurement of the study were; length, body weight, skinfold, diameter, circumference and length of the body, body composition, isometric handgrip strength, vertical jump, upper extremity range of motion (ROM and isokinetic strength. The angular velocity of racket head, racket handhold, middle finger, wrist, elbow, shoulder and hip joints on three axis during serve shoot were used for the biomechanical measurement.  The relationship between VBTS with physical fitness and biomechanical factors were measured with Pearson Correlation. The analysis showed that there was significant positive relation between VBTS and length, negative relation with mesomorphy; positive relation between ROM of shoulder dominant internal and external rotation, trunk hyper-extension, left lateral flexion and right rotation, negative relation in dominant wrist flexion, positive relation between isokinetic strength characteristics such as shoulder and elbow extension, shoulder internal and external rotation, wrist flexion, handgrip isometric strength, also in biomechanical measures, positive relation between in Y axis elbow, wrist, finger and head of the racket. As a result, fitness and biomechanical parameters that are intensively used in tennis determine VBTS. We think trainers may speed up VBTS by improved parameters and accelerated training programmes.

  3. Multivariate analyses reveal a new assemblage of diverse and small archosauriforms (Reptilia, Diapsida) from the Upper Triassic of India

    Science.gov (United States)

    Shafi Bhat, Mohd; Ray, Sanghamitra; Mohan Datta, Pradipendra

    2017-04-01

    The study is based on a large collection of vertebrate microfossils collected from the Upper Triassic Tiki Formation of the Rewa Gondwana basin of India, which is a mud-dominated fluvial succession. About 8600 kg of mudrocks from the Tiki Formation were screen washed to yield 1865 vertebrate microfossils, of which 67% are isolated teeth. Of these, there are about 450 well-preserved teeth, which are leaf-shaped, slightly recurved and have subtriangular crowns with expanded and asymmetric bases, and distinct denticles both on the posterior or anterior carinae. The morphology of these teeth suggests that these belong to Archosauriformes (Heckert, 2004; Irmis et al., 2007). Since the teeth were found isolated, without being associated with any other skeletal elements, it is not possible to ascertain their taxonomic position up to the generic and species level. However, based on their distinct dental attributes, twelve morphotypes are identified, of which five show similarity with the teeth of the basal saurischian dinosaurs. Principal Component and Canonical Variate analyses (PCA and CVA) are performed on these isolated teeth to evaluate the differentiation of the specimens based on the variance of their variables and to assess the consistency of identification by qualitative and quantitative methods (Hammer and Harper, 2006). PCA and CVA are applied to the variance-covariance matrix of the logarithmically transformed variables, the latter including six measured dimensions characterizing the different crown proportions. Since the first three principal components (PCs) account for more than 98% of the total variance, PC4 is discarded. Principal component scores are plotted on PC 1 and PC 2, and PC 2 and PC 3 to show the scatter of the archosauriform teeth examined. Although distinct clustering of specimens belonging to the different morphotypes is seen, there is considerable overlapping as represented by the convex hull polygons. The quantitative analyses show that many

  4. Concept of ground facilities and the analyses of the factors for cost estimation

    Energy Technology Data Exchange (ETDEWEB)

    Lee, J. Y.; Choi, H. J.; Choi, J. W.; Kim, S. K.; Cho, D. K

    2007-09-15

    The geologic disposal of spent fuels generated from the nuclear power plants is the only way to protect the human beings and the surrounding environments present and future. The direct disposal of the spent fuels from the nuclear power plants is considered, and a Korean Reference HLW disposal System(KRS) suitable for our representative geological conditions have been developed. In this study, the concept of the spent fuel encapsulation process as a key of the above ground facilities for deep geological disposal was established. To do this, the design requirements, such as the functions and the spent fuel accumulations, were reviewed. Also, the design principles and the bases were established. Based on the requirements and the bases, the encapsulation process of the spent fuel from receiving spent fuel of nuclear power plants to transferring canister into the underground repository was established. Simulation for the above-ground facility in graphic circumstances through KRS design concept and disposal scenarios for spent nuclear fuel showed that an appropriate process was performed based on facility design concept and required for more improvement on construction facility by actual demonstration test. And, based on the concept of the above ground facilities for the Korean Reference HLW disposal System, the analyses of the factors for the cost estimation was carried out.

  5. Physiological and proteomic analyses of leaves from the halophyte Tangut Nitraria reveals diverse response pathways critical for high salinity tolerance

    Directory of Open Access Journals (Sweden)

    Tielong eCheng

    2015-02-01

    Full Text Available Soil salinization poses a serious threat to the environment and agricultural productivity worldwide. Studies on the physiological and molecular mechanisms of salinity tolerance in halophytic plants provide valuable information to enhance their salt tolerance. Tangut Nitraria is a widely distributed halophyte in saline–alkali soil in the northern areas of China. In this study, we used a proteomic approach to investigate the molecular pathways of the high salt tolerance of T. Nitraria. We analyzed the changes in biomass, photosynthesis, and redox-related enzyme activities in T. Nitraria leaves from plant seedlings treated with high salt concentration. Comparative proteomic analysis of the leaves revealed that the expression of 71 proteins was significantly altered after salinity treatments of T. Nitraria. These salinity-responsive proteins were mainly involved in photosynthesis, redox homeostasis, stress/defense, carbohydrate and energy metabolism, protein metabolism, signal transduction, and membrane transport. Results showed that the reduction of photosynthesis under salt stress was attributed to the down-regulation of the enzymes and proteins involved in the light reaction and Calvin cycle. Protein–protein interaction analysis revealed that the proteins involved in redox homeostasis, photosynthesis, and energy metabolism constructed two types of response networks to high salt stress. T. Nitraria plants developed diverse mechanisms for scavenging reactive oxygen species in their leaves to cope with stress induced by high salinity. This study provides important information regarding the salt tolerance of the halophyte T. Nitraria.

  6. Combined DNA and lipid analyses of sediments reveal changes in Holocene haptophyte and diatom populations in an Antarctic lake

    Science.gov (United States)

    Coolen, Marco J. L.; Muyzer, Gerard; Rijpstra, W. Irene C.; Schouten, Stefan; Volkman, John K.; Sinninghe Damsté, Jaap S.

    2004-06-01

    Preserved ribosomal DNA of planktonic phototrophic algae was recovered from Holocene anoxic sediments of Ace Lake (Antarctica), and the ancient community members were identified based on comparative sequence analysis. The similar concentration profiles of DNA of haptophytes and their traditional lipid biomarkers (alkenones and alkenoates) revealed that fossil rDNA also served as quantitative biomarkers in this environment. The DNA data clearly revealed the presence of six novel phylotypes related to known alkenone and alkenoate-biosynthesizing haptophytes with Isochrysis galbana UIO 102 as their closest relative. The relative abundance of these phylotypes changed as the lake chemistry, particularly salinity, evolved over time. Changes in the alkenone distributions reflect these population changes rather than a physiological response to salinity by a single haptophyte. Using this novel paleo-ecological approach of combining data from lipid biomarkers and preserved DNA, we showed that the post-glacial development of Ace Lake from freshwater basin to marine inlet and the present-day lacustrine saline system caused major qualitative and quantitative changes in the biodiversity of the planktonic populations over time.

  7. Whole genome analyses of a well-differentiated liposarcoma reveals novel SYT1 and DDR2 rearrangements.

    Science.gov (United States)

    Egan, Jan B; Barrett, Michael T; Champion, Mia D; Middha, Sumit; Lenkiewicz, Elizabeth; Evers, Lisa; Francis, Princy; Schmidt, Jessica; Shi, Chang-Xin; Van Wier, Scott; Badar, Sandra; Ahmann, Gregory; Kortuem, K Martin; Boczek, Nicole J; Fonseca, Rafael; Craig, David W; Carpten, John D; Borad, Mitesh J; Stewart, A Keith

    2014-01-01

    Liposarcoma is the most common soft tissue sarcoma, but little is known about the genomic basis of this disease. Given the low cell content of this tumor type, we utilized flow cytometry to isolate the diploid normal and aneuploid tumor populations from a well-differentiated liposarcoma prior to array comparative genomic hybridization and whole genome sequencing. This work revealed massive highly focal amplifications throughout the aneuploid tumor genome including MDM2, a gene that has previously been found to be amplified in well-differentiated liposarcoma. Structural analysis revealed massive rearrangement of chromosome 12 and 11 gene fusions, some of which may be part of double minute chromosomes commonly present in well-differentiated liposarcoma. We identified a hotspot of genomic instability localized to a region of chromosome 12 that includes a highly conserved, putative L1 retrotransposon element, LOC100507498 which resides within a gene cluster (NAV3, SYT1, PAWR) where 6 of the 11 fusion events occurred. Interestingly, a potential gene fusion was also identified in amplified DDR2, which is a potential therapeutic target of kinase inhibitors such as dastinib, that are not routinely used in the treatment of patients with liposarcoma. Furthermore, 7 somatic, damaging single nucleotide variants have also been identified, including D125N in the PTPRQ protein. In conclusion, this work is the first to report the entire genome of a well-differentiated liposarcoma with novel chromosomal rearrangements associated with amplification of therapeutically targetable genes such as MDM2 and DDR2.

  8. Whole genome analyses of a well-differentiated liposarcoma reveals novel SYT1 and DDR2 rearrangements.

    Directory of Open Access Journals (Sweden)

    Jan B Egan

    Full Text Available Liposarcoma is the most common soft tissue sarcoma, but little is known about the genomic basis of this disease. Given the low cell content of this tumor type, we utilized flow cytometry to isolate the diploid normal and aneuploid tumor populations from a well-differentiated liposarcoma prior to array comparative genomic hybridization and whole genome sequencing. This work revealed massive highly focal amplifications throughout the aneuploid tumor genome including MDM2, a gene that has previously been found to be amplified in well-differentiated liposarcoma. Structural analysis revealed massive rearrangement of chromosome 12 and 11 gene fusions, some of which may be part of double minute chromosomes commonly present in well-differentiated liposarcoma. We identified a hotspot of genomic instability localized to a region of chromosome 12 that includes a highly conserved, putative L1 retrotransposon element, LOC100507498 which resides within a gene cluster (NAV3, SYT1, PAWR where 6 of the 11 fusion events occurred. Interestingly, a potential gene fusion was also identified in amplified DDR2, which is a potential therapeutic target of kinase inhibitors such as dastinib, that are not routinely used in the treatment of patients with liposarcoma. Furthermore, 7 somatic, damaging single nucleotide variants have also been identified, including D125N in the PTPRQ protein. In conclusion, this work is the first to report the entire genome of a well-differentiated liposarcoma with novel chromosomal rearrangements associated with amplification of therapeutically targetable genes such as MDM2 and DDR2.

  9. Integrative genomic analyses reveal an androgen-driven somatic alteration landscape in early-onset prostate cancer

    DEFF Research Database (Denmark)

    Weischenfeldt, Joachim; Simon, Ronald; Feuerbach, Lars;

    2013-01-01

    comparative assessments with seven elderly-onset PCA genomes. Remarkable age-related differences in structural rearrangement (SR) formation became evident, suggesting distinct disease pathomechanisms. Whereas EO-PCAs harbored a prevalence of balanced SRs, with a specific abundance of androgen-regulated ETS......Early-onset prostate cancer (EO-PCA) represents the earliest clinical manifestation of prostate cancer. To compare the genomic alteration landscapes of EO-PCA with "classical" (elderly-onset) PCA, we performed deep sequencing-based genomics analyses in 11 tumors diagnosed at young age, and pursued...... gene fusions including TMPRSS2:ERG, elderly-onset PCAs displayed primarily non-androgen-associated SRs. Data from a validation cohort of > 10,000 patients showed age-dependent androgen receptor levels and a prevalence of SRs affecting androgen-regulated genes, further substantiating the activity...

  10. Dynamic regulation of GDP binding to G proteins revealed by magnetic field-dependent NMR relaxation analyses.

    Science.gov (United States)

    Toyama, Yuki; Kano, Hanaho; Mase, Yoko; Yokogawa, Mariko; Osawa, Masanori; Shimada, Ichio

    2017-02-22

    Heterotrimeric guanine-nucleotide-binding proteins (G proteins) serve as molecular switches in signalling pathways, by coupling the activation of cell surface receptors to intracellular responses. Mutations in the G protein α-subunit (Gα) that accelerate guanosine diphosphate (GDP) dissociation cause hyperactivation of the downstream effector proteins, leading to oncogenesis. However, the structural mechanism of the accelerated GDP dissociation has remained unclear. Here, we use magnetic field-dependent nuclear magnetic resonance relaxation analyses to investigate the structural and dynamic properties of GDP bound Gα on a microsecond timescale. We show that Gα rapidly exchanges between a ground-state conformation, which tightly binds to GDP and an excited conformation with reduced GDP affinity. The oncogenic D150N mutation accelerates GDP dissociation by shifting the equilibrium towards the excited conformation.

  11. Dynamic regulation of GDP binding to G proteins revealed by magnetic field-dependent NMR relaxation analyses

    Science.gov (United States)

    Toyama, Yuki; Kano, Hanaho; Mase, Yoko; Yokogawa, Mariko; Osawa, Masanori; Shimada, Ichio

    2017-01-01

    Heterotrimeric guanine-nucleotide-binding proteins (G proteins) serve as molecular switches in signalling pathways, by coupling the activation of cell surface receptors to intracellular responses. Mutations in the G protein α-subunit (Gα) that accelerate guanosine diphosphate (GDP) dissociation cause hyperactivation of the downstream effector proteins, leading to oncogenesis. However, the structural mechanism of the accelerated GDP dissociation has remained unclear. Here, we use magnetic field-dependent nuclear magnetic resonance relaxation analyses to investigate the structural and dynamic properties of GDP bound Gα on a microsecond timescale. We show that Gα rapidly exchanges between a ground-state conformation, which tightly binds to GDP and an excited conformation with reduced GDP affinity. The oncogenic D150N mutation accelerates GDP dissociation by shifting the equilibrium towards the excited conformation. PMID:28223697

  12. Proteome and Computational Analyses Reveal New Insights into the Mechanisms of Hepatitis C Virus Mediated Liver Disease Post-Transplantation

    Science.gov (United States)

    Diamond, Deborah L.; Krasnoselsky, Alexei L.; Burnum, Kristin E.; Monroe, Matthew E.; Webb-Robertson, Bobbie-Jo; McDermott, Jason E.; Yeh, Matthew M.; Dzib, Jose Felipe Golib; Susnow, Nathan; Strom, Susan; Proll, Sean C.; Belisle, Sarah E.; Purdy, David E.; Rasmussen, Angela L.; Walters, Kathie-Anne; Jacobs, Jon M.; Gritsenko, Marina A.; Camp, David G.; Bhattacharya, Renuka; Perkins, James D.; Carithers, Robert L.; Liou, Iris W.; Larson, Anne M.; Benecke, Arndt; Waters, Katrina M.; Smith, Richard D.; Katze, Michael G.

    2012-01-01

    Liver transplant tissues offer the unique opportunity to model the longitudinal protein abundance changes occurring during hepatitis C virus (HCV)-associated liver disease progression in vivo. In this study, our goal was to identify molecular signatures, and potential key regulatory proteins, representative of the processes influencing early progression to fibrosis. We performed global protein profiling analyses on 24 liver biopsy specimens obtained from 15 HCV+ liver transplant recipients at 6 and/or 12 months post-transplantation. Differentially regulated proteins associated with early progression to fibrosis were identified by analysis of the area under the receiver operating characteristic curve (AUC). Analysis of serum metabolites was performed on samples obtained from an independent cohort of 60 HCV+ liver transplant patients. Computational modeling approaches were applied to identify potential key regulatory proteins of liver fibrogenesis. Among 4,324 proteins identified, 250 exhibited significant differential regulation in patients with rapidly progressive fibrosis. Patients with rapid fibrosis progression exhibited enrichment in differentially regulated proteins associated with various immune, hepatoprotective, and fibrogenic processes. The observed increase in pro-inflammatory activity and impairment in anti-oxidant defenses suggests that patients who develop significant liver injury experience elevated oxidative stresses. This was supported by an independent study demonstrating the altered abundance of oxidative stress associated serum metabolites in patients who develop severe liver injury. Computational modeling approaches further highlight a potentially important link between HCV-associated oxidative stress and epigenetic regulatory mechanisms impacting on liver fibrogenesis. In conclusion, our proteome and metabolome analyses provide new insights into the role for increased oxidative stress in the rapid fibrosis progression observed in HCV+ liver

  13. Comparative genomic analyses reveal a lack of a substantial signature of host adaptation in Rhodococcus equi ('Prescottella equi').

    Science.gov (United States)

    Sangal, Vartul; Jones, Amanda L; Goodfellow, Michael; Sutcliffe, Iain C; Hoskisson, Paul A

    2014-08-01

    Rhodococcus equi ('Prescottella equi') is a pathogenic actinomycete primarily infecting horses but has emerged as an opportunistic human pathogen. We have sequenced the genome of the type strain of this species, R. equi strain C7(T) , and compared the genome with that of another foal isolate 103S and of a human isolate ATCC 33707. The R. equi strains are closely related to each other and yet distantly related to other rhodococci and Nocardia brasiliensis. The comparison of gene contents among R. equi strains revealed minor differences that could be associated with host adaptation from foals to humans, including the presence of a paa operon in the human isolate, which is potentially involved in pathogenesis. © 2013 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

  14. Trophic structure of mesopelagic fishes in the Gulf of Mexico revealed by gut content and stable isotope analyses

    Science.gov (United States)

    McClain-Counts, Jennifer P.; Demopoulos, Amanda W.J.; Ross, Steve W.

    2017-01-01

    Mesopelagic fishes represent an important component of the marine food web due to their global distributions, high abundances and ability to transport organic material throughout a large part of the water column. This study combined stable isotope (SIAs) and gut content analyses (GCAs) to characterize the trophic structure of mesopelagic fishes in the North-Central Gulf of Mexico. Additionally, this study examined whether mesopelagic fishes utilized chemosynthetic energy from cold seeps. Specimens were collected (9–25 August 2007) over three deep (>1,000 m) cold seeps at discrete depths (surface to 1,503 m) over the diurnal cycle. GCA classified 31 species (five families) of mesopelagic fishes into five feeding guilds: piscivores, large crustacean consumers, copepod consumers, generalists and mixed zooplanktivores. However, these guilds were less clearly defined based on stable isotope mixing model (MixSIAR) results, suggesting diets may be more mixed over longer time periods (weeks–months) and across co-occurring species. Copepods were likely important for the majority of mesopelagic fishes, consistent with GCA (this study) and previous literature. MixSIAR results also identified non-crustacean prey items, including salps and pteropods, as potentially important prey items for mesopelagic fishes, including those fishes not analysed in GCA (Sternoptyx spp. and Melamphaidae). Salps and other soft-bodied species are often missed in GCAs. Mesopelagic fishes had δ13C results consistent with particulate organic matter serving as the baseline organic carbon source, fueling up to three trophic levels. Fishes that undergo diel vertical migration were depleted in 15N relative to weak migrators, consistent with depth-specific isotope trends in sources and consumers, and assimilation of 15N-depleted organic matter in surface waters. Linear correlations between fish size and δ15N values suggested ontogenetic changes in fish diets for several species. While there was

  15. Genetic introgression and hybridization in Antillean freshwater turtles (Trachemys) revealed by coalescent analyses of mitochondrial and cloned nuclear markers.

    Science.gov (United States)

    Parham, James F; Papenfuss, Theodore J; Dijk, Peter Paul van; Wilson, Byron S; Marte, Cristian; Schettino, Lourdes Rodriguez; Brian Simison, W

    2013-04-01

    Determining whether a conflict between gene trees and species trees represents incomplete lineage sorting (ILS) or hybridization involving native and/or invasive species has implications for reconstructing evolutionary relationships and guiding conservation decisions. Among vertebrates, turtles represent an exceptional case for exploring these issues because of the propensity for even distantly related lineages to hybridize. In this study we investigate a group of freshwater turtles (Trachemys) from a part of its range (the Greater Antilles) where it is purported to have undergone reticulation events from both natural and anthropogenic processes. We sequenced mtDNA for 83 samples, sequenced three nuDNA markers for 45 samples, and cloned 29 polymorphic sequences, to identify species boundaries, hybridization, and intergrade zones for Antillean Trachemys and nearby mainland populations. Initial coalescent analyses of phased nuclear alleles (using (*)BEAST) recovered a Bayesian species tree that strongly conflicted with the mtDNA phylogeny and traditional taxonomy, and appeared to be confounded by hybridization. Therefore, we undertook exploratory phylogenetic analyses of mismatched alleles from the "coestimated" gene trees (Heled and Drummond, 2010) in order to identify potential hybrid origins. The geography, morphology, and sampling context of most samples with potential introgressed alleles suggest hybridization over ILS. We identify contact zones between different species on Jamaica (T. decussata × T. terrapen), on Hispaniola (T. decorata × T. stejnegeri), and in Central America (T. emolli × T. venusta). We are unable to determine whether the distribution of T. decussata on Jamaica is natural or the result of prehistoric introduction by Native Americans. This uncertainty means that the conservation status of the Jamaican T. decussata populations and contact zone with T. terrapen are unresolved. Human-mediated dispersal events were more conclusively implicated

  16. Population dynamics and genetic changes of Picea abies in the South Carpathians revealed by pollen and ancient DNA analyses

    Directory of Open Access Journals (Sweden)

    Braun Mihály

    2011-03-01

    Full Text Available Abstract Background Studies on allele length polymorphism designate several glacial refugia for Norway spruce (Picea abies in the South Carpathian Mountains, but infer only limited expansion from these refugia after the last glaciation. To better understand the genetic dynamics of a South Carpathian spruce lineage, we compared ancient DNA from 10,700 and 11,000-year-old spruce pollen and macrofossils retrieved from Holocene lake sediment in the Retezat Mountains with DNA extracted from extant material from the same site. We used eight primer pairs that amplified short and variable regions of the spruce cpDNA. In addition, from the same lake sediment we obtained a 15,000-years-long pollen accumulation rate (PAR record for spruce that helped us to infer changes in population size at this site. Results We obtained successful amplifications for Norway spruce from 17 out of 462 pollen grains tested, while the macrofossil material provided 22 DNA sequences. Two fossil sequences were found to be unique to the ancient material. Population genetic statistics showed higher genetic diversity in the ancient individuals compared to the extant ones. Similarly, statistically significant Ks and Kst values showed a considerable level of differentiation between extant and ancient populations at the same loci. Lateglacial and Holocene PAR values suggested that population size of the ancient population was small, in the range of 1/10 or 1/5 of the extant population. PAR analysis also detected two periods of rapid population growths (from ca. 11,100 and 3900 calibrated years before present (cal yr BP and three bottlenecks (around 9180, 7200 and 2200 cal yr BP, likely triggered by climatic change and human impact. Conclusion Our results suggest that the paternal lineages observed today in the Retezat Mountains persisted at this site at least since the early Holocene. Combination of the results from the genetic and the PAR analyses furthermore suggests that the higher

  17. Multilocus sequence analyses reveal extensive diversity and multiple origins of fluconazole resistance in Candida tropicalis from tropical China

    Science.gov (United States)

    Wu, Jin-Yan; Guo, Hong; Wang, Hua-Min; Yi, Guo-Hui; Zhou, Li-Min; He, Xiao-Wen; Zhang, Ying; Xu, Jianping

    2017-01-01

    Candida tropicalis is among the most prevalent human pathogenic yeast species, second only to C. albicans in certain geographic regions such as East Asia and Brazil. However, compared to C. albicans, relatively little is known about the patterns of genetic variation in C. tropicalis. This study analyzed the genetic diversity and relationships among isolates of C. tropicalis from the southern Chinese island of Hainan. A total of 116 isolates were obtained from seven geographic regions located across the Island. For each isolate, a total of 2677 bp from six gene loci were sequenced and 79 (2.96%) polymorphic nucleotide sites were found in our sample. Comparisons with strains reported from other parts of the world identified significant novel diversities in Hainan, including an average of six novel sequences (with a range 1 to 14) per locus and 80 novel diploid sequence types. Most of the genetic variation was found within individual strains and there was abundant evidence for gene flow among the seven geographic locations within Hainan. Interestingly, our analyses identified no significant correlation between the diploid sequence types at the six loci and fluconazole susceptibility, consistent with multiple origins of fluconazole resistance in the Hainan population of C. tropicalis. PMID:28186162

  18. Analyses of Dynein Heavy Chain Mutations Reveal Complex Interactions Between Dynein Motor Domains and Cellular Dynein Functions

    Science.gov (United States)

    Sivagurunathan, Senthilkumar; Schnittker, Robert R.; Razafsky, David S.; Nandini, Swaran; Plamann, Michael D.; King, Stephen J.

    2012-01-01

    Cytoplasmic dynein transports cargoes for a variety of crucial cellular functions. However, since dynein is essential in most eukaryotic organisms, the in-depth study of the cellular function of dynein via genetic analysis of dynein mutations has not been practical. Here, we identify and characterize 34 different dynein heavy chain mutations using a genetic screen of the ascomycete fungus Neurospora crassa, in which dynein is nonessential. Interestingly, our studies show that these mutations segregate into five different classes based on the in vivo localization of the mutated dynein motors. Furthermore, we have determined that the different classes of dynein mutations alter vesicle trafficking, microtubule organization, and nuclear distribution in distinct ways and require dynactin to different extents. In addition, biochemical analyses of dynein from one mutant strain show a strong correlation between its in vitro biochemical properties and the aberrant intracellular function of that altered dynein. When the mutations were mapped to the published dynein crystal structure, we found that the three-dimensional structural locations of the heavy chain mutations were linked to particular classes of altered dynein functions observed in cells. Together, our data indicate that the five classes of dynein mutations represent the entrapment of dynein at five separate points in the dynein mechanochemical and transport cycles. We have developed N. crassa as a model system where we can dissect the complexities of dynein structure, function, and interaction with other proteins with genetic, biochemical, and cell biological studies. PMID:22649085

  19. Large-scale phylogenomic analyses reveal that two enigmatic protist lineages, telonemia and centroheliozoa, are related to photosynthetic chromalveolates.

    Science.gov (United States)

    Burki, Fabien; Inagaki, Yuji; Bråte, Jon; Archibald, John M; Keeling, Patrick J; Cavalier-Smith, Thomas; Sakaguchi, Miako; Hashimoto, Tetsuo; Horak, Ales; Kumar, Surendra; Klaveness, Dag; Jakobsen, Kjetill S; Pawlowski, Jan; Shalchian-Tabrizi, Kamran

    2009-07-27

    Understanding the early evolution and diversification of eukaryotes relies on a fully resolved phylogenetic tree. In recent years, most eukaryotic diversity has been assigned to six putative supergroups, but the evolutionary origin of a few major "orphan" lineages remains elusive. Two ecologically important orphan groups are the heterotrophic Telonemia and Centroheliozoa. Telonemids have been proposed to be related to the photosynthetic cryptomonads or stramenopiles and centrohelids to haptophytes, but molecular phylogenies have failed to provide strong support for any phylogenetic hypothesis. Here, we investigate the origins of Telonema subtilis (a telonemid) and Raphidiophrys contractilis (a centrohelid) by large-scale 454 pyrosequencing of cDNA libraries and including new genomic data from two cryptomonads (Guillardia theta and Plagioselmis nannoplanctica) and a haptophyte (Imantonia rotunda). We demonstrate that 454 sequencing of cDNA libraries is a powerful and fast method of sampling a high proportion of protist genes, which can yield ample information for phylogenomic studies. Our phylogenetic analyses of 127 genes from 72 species indicate that telonemids and centrohelids are members of an emerging major group of eukaryotes also comprising cryptomonads and haptophytes. Furthermore, this group is possibly closely related to the SAR clade comprising stramenopiles (heterokonts), alveolates, and Rhizaria. Our results link two additional heterotrophic lineages to the predominantly photosynthetic chromalveolate supergroup, providing a new framework for interpreting the evolution of eukaryotic cell structures and the diversification of plastids.

  20. Patterns of juvenile habitat use by the spider crab Maja brachydactyla as revealed by stable isotope analyses

    Directory of Open Access Journals (Sweden)

    Juan Freire

    2009-03-01

    Full Text Available Patterns of habitat use by spider crab juveniles, Maja brachydactyla, from two geographic areas on the NW coast of the Iberian Peninsula were studied through the analysis of carbon and nitrogen stable isotope relations in muscle and hepatopancreas. Main potential preys of spider crab juveniles in rocky and sandy habitats and different organic matter sources in coastal food webs were also analysed. Isotopic ratios showed no difference between rocky and sandy habitats. The use of carapace colour and epibiosis as an indicator of habitat use was not supported by our data. These results suggest that movements between the two habitats are much more frequent than suggested in previous studies. In the coastal food web, two main trophic compartments were identified according to their organic matter source: one based on plankton and seaweeds (rocky habitats, and one based on sedimentary particulate organic matter (sandy bottoms. By means of the model of Phillips and Gregg (2003, it was found that juveniles of Maja brachydactyla from both habitats consumed approximately two thirds of the preys in rocky habitats and one third in sedimentary habitats. The results indicate that in exposed environments large juveniles spend most of the time on sedimentary bottoms, where they find more refuge, moving frequently to nearby rocky substrates to feed.

  1. Genomic and Phenotypic Analyses Reveal the Emergence of an Atypical Salmonella enterica Serovar Senftenberg Variant in China

    KAUST Repository

    Abd El Ghany, Moataz

    2016-05-25

    Human infections with Salmonella enterica subspecies enterica serovar Senftenberg are often associated with exposure to poultry flocks, farm environments, or contaminated food. The recent emergence of multidrug-resistant isolates has raised public health concerns. In this study, comparative genomics and phenotypic analysis were used to characterize 14 Salmonella Senftenberg clinical isolates recovered from multiple outbreaks in Shenzhen and Shanghai, China, between 2002 and 2011. Single-nucleotide polymorphism analyses identified two phylogenetically distinct clades of S. Senftenberg, designated SC1 and SC2, harboring variations in Salmonella pathogenicity island 1 (SPI-1) and SPI-2 and exhibiting distinct biochemical and phenotypic signatures. Although the two variants shared the same serotype, the SC2 isolates of sequence type 14 (ST14) harbored intact SPI-1 and -2 and hence were characterized by possessing efficient invasion capabilities. In contrast, the SC1 isolates had structural deletion patterns in both SPI-1 and -2 that correlated with an impaired capacity to invade cultured human cells and also the year of their isolation. These atypical SC1 isolates also lacked the capacity to produce hydrogen sulfide. These findings highlight the emergence of atypical Salmonella Senftenberg variants in China and provide genetic validation that variants lacking SPI-1 and regions of SPI-2, which leads to impaired invasion capacity, can still cause clinical disease. These data have identified an emerging public health concern and highlight the need to strengthen surveillance to detect the prevalence and transmission of nontyphoidal Salmonella species.

  2. Metagenomic analyses reveal the involvement of syntrophic consortia in methanol/electricity conversion in microbial fuel cells.

    Directory of Open Access Journals (Sweden)

    Ayaka Yamamuro

    Full Text Available Methanol is widely used in industrial processes, and as such, is discharged in large quantities in wastewater. Microbial fuel cells (MFCs have the potential to recover electric energy from organic pollutants in wastewater; however, the use of MFCs to generate electricity from methanol has not been reported. In the present study, we developed single-chamber MFCs that generated electricity from methanol at the maximum power density of 220 mW m(-2 (based on the projected area of the anode. In order to reveal how microbes generate electricity from methanol, pyrosequencing of 16S rRNA-gene amplicons and Illumina shotgun sequencing of metagenome were conducted. The pyrosequencing detected in abundance Dysgonomonas, Sporomusa, and Desulfovibrio in the electrolyte and anode and cathode biofilms, while Geobacter was detected only in the anode biofilm. Based on known physiological properties of these bacteria, it is considered that Sporomusa converts methanol into acetate, which is then utilized by Geobacter to generate electricity. This speculation is supported by results of shotgun metagenomics of the anode-biofilm microbes, which reconstructed relevant catabolic pathways in these bacteria. These results suggest that methanol is anaerobically catabolized by syntrophic bacterial consortia with electrodes as electron acceptors.

  3. Physiological and transcriptomic analyses reveal mechanistic insight into the adaption of marine Bacillus subtilis C01 to alumina nanoparticles.

    Science.gov (United States)

    Mu, Dashuai; Yu, Xiuxia; Xu, Zhenxing; Du, Zongjun; Chen, Guanjun

    2016-07-21

    An increasing number of studies have investigated the effects of nanoparticles (NPs) on microbial systems; however, few existing reports have focused on the defense mechanisms of bacteria against NPs. Whether secondary metabolism biosynthesis is a response to NP stress and contributes to the adaption of bacteria to NPs is unclear. Here, a significant induction in the surfactin production and biofilm formation were detected by adding Al2O3 NPs to the B. subtilis fermentation broth. Physiological analysis showed that Al2O3 NP stress could also affect the cell and colony morphogenesis and inhibit the motility and sporulation. Exogenously adding commercial surfactin restored the swarming motility. Additionally, a suite of toxicity assays analyzing membrane damage, cellular ROS generation, electron transport activity and membrane potential was used to determine the molecular mechanisms of toxicity of Al2O3 NPs. Furthermore, whole transcriptomic analysis was used to elucidate the mechanisms of B. subtilis adaption to Al2O3 NPs. These results revealed several mechanisms by which marine B. subtilis C01 adapt to Al2O3 NPs. Additionally, this study broadens the applications of nanomaterials and describes the important effects on secondary metabolism and multicellularity regulation by using Al2O3 NPs or other nano-products.

  4. Distinct and shared functions of ALS-associated proteins TDP-43, FUS and TAF15 revealed by multisystem analyses.

    Science.gov (United States)

    Kapeli, Katannya; Pratt, Gabriel A; Vu, Anthony Q; Hutt, Kasey R; Martinez, Fernando J; Sundararaman, Balaji; Batra, Ranjan; Freese, Peter; Lambert, Nicole J; Huelga, Stephanie C; Chun, Seung J; Liang, Tiffany Y; Chang, Jeremy; Donohue, John P; Shiue, Lily; Zhang, Jiayu; Zhu, Haining; Cambi, Franca; Kasarskis, Edward; Hoon, Shawn; Ares, Manuel; Burge, Christopher B; Ravits, John; Rigo, Frank; Yeo, Gene W

    2016-07-05

    The RNA-binding protein (RBP) TAF15 is implicated in amyotrophic lateral sclerosis (ALS). To compare TAF15 function to that of two ALS-associated RBPs, FUS and TDP-43, we integrate CLIP-seq and RNA Bind-N-Seq technologies, and show that TAF15 binds to ∼4,900 RNAs enriched for GGUA motifs in adult mouse brains. TAF15 and FUS exhibit similar binding patterns in introns, are enriched in 3' untranslated regions and alter genes distinct from TDP-43. However, unlike FUS and TDP-43, TAF15 has a minimal role in alternative splicing. In human neural progenitors, TAF15 and FUS affect turnover of their RNA targets. In human stem cell-derived motor neurons, the RNA profile associated with concomitant loss of both TAF15 and FUS resembles that observed in the presence of the ALS-associated mutation FUS R521G, but contrasts with late-stage sporadic ALS patients. Taken together, our findings reveal convergent and divergent roles for FUS, TAF15 and TDP-43 in RNA metabolism.

  5. Metagenomic analyses reveal the involvement of syntrophic consortia in methanol/electricity conversion in microbial fuel cells.

    Science.gov (United States)

    Yamamuro, Ayaka; Kouzuma, Atsushi; Abe, Takashi; Watanabe, Kazuya

    2014-01-01

    Methanol is widely used in industrial processes, and as such, is discharged in large quantities in wastewater. Microbial fuel cells (MFCs) have the potential to recover electric energy from organic pollutants in wastewater; however, the use of MFCs to generate electricity from methanol has not been reported. In the present study, we developed single-chamber MFCs that generated electricity from methanol at the maximum power density of 220 mW m(-2) (based on the projected area of the anode). In order to reveal how microbes generate electricity from methanol, pyrosequencing of 16S rRNA-gene amplicons and Illumina shotgun sequencing of metagenome were conducted. The pyrosequencing detected in abundance Dysgonomonas, Sporomusa, and Desulfovibrio in the electrolyte and anode and cathode biofilms, while Geobacter was detected only in the anode biofilm. Based on known physiological properties of these bacteria, it is considered that Sporomusa converts methanol into acetate, which is then utilized by Geobacter to generate electricity. This speculation is supported by results of shotgun metagenomics of the anode-biofilm microbes, which reconstructed relevant catabolic pathways in these bacteria. These results suggest that methanol is anaerobically catabolized by syntrophic bacterial consortia with electrodes as electron acceptors.

  6. Functional analyses of a flavonol synthase - like gene from Camellia nitidissima reveal its roles in flavonoid metabolism during floral pigmentation

    Indian Academy of Sciences (India)

    Xing-Wen Zhou; Zheng-Qi Fan; Yue Chen; Yu-Lin Zhu; Ji-Yuan Li; Heng-Fu Yin

    2013-09-01

    The flavonoids metabolic pathway plays central roles in floral coloration, in which anthocyanins and flavonols are derived from common precursors, dihydroflavonols. Flavonol synthase (FLS) catalyses dihydroflavonols into flavonols, which presents a key branch of anthocyanins biosynthesis. The yellow flower of Camellia nitidissima Chi. is a unique feature within the genus Camellia, which makes it a precious resource for breeding yellow camellia varieties. In this work, we characterized the secondary metabolites of pigments during floral development of C. nitidissima and revealed that accumulation of flavonols correlates with floral coloration. We first isolated CnFLS1 and showed that it is a FLS of C. nitidissima by gene family analysis. Second, expression analysis during floral development and different floral organs indicated that the expression level of CnFLS1 was regulated by developmental cues, which was in agreement with the accumulating pattern of flavonols. Furthermore, over-expression of CnFLS1 in Nicotiana tabacum altered floral colour into white or light yellow, and metabolic analysis showed significant increasing of flavonols and reducing of anthocyanins in transgenic plants. Our work suggested CnFLS1 plays critical roles in yellow colour pigmentation and is potentially a key point of genetic engineering toward colour modification in Camellia.

  7. Microbial analyses of traditional Italian salami reveal microorganisms transfer from the natural casing to the meat matrix.

    Science.gov (United States)

    Pisacane, Vincenza; Callegari, Maria Luisa; Puglisi, Edoardo; Dallolio, Giuliano; Rebecchi, Annalisa

    2015-08-17

    In this study the bacterial biodiversity, during the maturation process of traditional sausages (Salame Mantovano), produced with two different kinds of casing (hog middle or "Crespone" and hog bung or "Gentile"), was investigated by means of culture-dependent and -independent methods. In order to assess the natural variability linked to the type of casing used in production, the ingredients, as well as ripening conditions, were identical in both productions. The aim of the study was to understand the contribution of casing microflora during sausage ripening by identifying the dominant species and strains. The bacterial ecology of casings and salami at different ripening stages, as determined by plating, revealed higher staphylococci and enterococci counts for Gentile casing and for the entire ripening period of the salami studied. After molecular identification of 219 Lactobacilli and 225 cocci gram positive catalase positive (GPCP) isolates, the species most frequently isolated were Lactobacillus sakei, Lactobacillus curvatus, Staphylococcus xylosus, and Staphylococcus saprophyticus. Some L. sakei and S. saprophyticus strains, coming from casing, were also found in the salami at different times of ripening. A richer biodiversity was only detected at the beginning of maturation. We also report the first detection, by PCR-DGGE method, of Arcobacter marinus and Brochothrix thermosphacta species in casings and Kokuria salsicia in fresh sausage. Results suggesting that casing can be an important source of bacteria during natural fermentation when starter cultures are not used.

  8. Ancient DNA analyses reveal contrasting phylogeographic patterns amongst kiwi (Apteryx spp. and a recently extinct lineage of spotted kiwi.

    Directory of Open Access Journals (Sweden)

    Lara D Shepherd

    Full Text Available The little spotted kiwi (Apteryx owenii is a flightless ratite formerly found throughout New Zealand but now greatly reduced in distribution. Previous phylogeographic studies of the related brown kiwi (A. mantelli, A. rowi and A. australis, with which little spotted kiwi was once sympatric, revealed extremely high levels of genetic structuring, with mitochondrial DNA haplotypes often restricted to populations. We surveyed genetic variation throughout the present and pre-human range of little spotted kiwi by obtaining mitochondrial DNA sequences from contemporary and ancient samples. Little spotted kiwi and great spotted kiwi (A. haastii formed a monophyletic clade sister to brown kiwi. Ancient samples of little spotted kiwi from the northern North Island, where it is now extinct, formed a lineage that was distinct from remaining little spotted kiwi and great spotted kiwi lineages, potentially indicating unrecognized taxonomic diversity. Overall, little spotted kiwi exhibited much lower levels of genetic diversity and structuring than brown kiwi, particularly through the South Island. Our results also indicate that little spotted kiwi (or at least hybrids involving this species survived on the South Island mainland until more recently than previously thought.

  9. Vitamin E analyses in seeds reveal a dominant presence of tocotrienols over tocopherols in the Arecaceae family.

    Science.gov (United States)

    Siles, Laura; Cela, Jana; Munné-Bosch, Sergi

    2013-11-01

    Tocopherols are thought to prevent oxidative damage during seed quiescence and dormancy in all angiosperms. However, several monocot species accumulate tocotrienols in seeds and their role remains elusive. Here, we aimed to unravel the distribution of tocopherols and tocotrienols in seeds of the Arecaceae family, to examine possible trends of vitamin E accumulation within different clades of the same family. We examined the tocopherol and tocotrienol content in seeds of 84 species. Furthermore, we evaluated the vitamin E composition of the seed coat, endosperm and embryo of seeds from 6 species, to determine possible tissue-specific functions of particular vitamin E forms. While seeds of 98.8% (83 out of 84) of the species accumulated tocotrienols, only 58.3% (49 out of 84) accumulated tocopherols. The presence of tocopherols did not follow a clear evolutionary trend, and appeared randomly in some clades only. In addition, the tissue-specific location of vitamin E in seeds revealed that the embryo contains mostly α-tocopherol (in seed tocopherol-accumulating species) or α-tocotrienol (in seed tocopherol-deficient species). However, some species such as Socratea exorrhiza mostly accumulate β-tocotrienol, and Parajubaea torallyi accumulates a mixture of tocopherols and tocotrienols in the embryo. This suggests that tocotrienols can play a similar protective role to that exerted by tocopherols in seeds, at least in some species of the Arecaceae family. We conclude that tocotrienol, rather than tocopherol, accumulation is a conserved trait in seeds of the Arecaceae family.

  10. Proteomic Analyses Reveal that Sky1 Modulates Apoptosis and Mitophagy in Saccharomyces cerevisiae Cells Exposed to Cisplatin

    Directory of Open Access Journals (Sweden)

    Silvia Rodríguez-Lombardero

    2014-07-01

    Full Text Available Sky1 is the only member of the SR (Serine–Arginine protein kinase family in Saccharomyces cerevisiae. When yeast cells are treated with the anti-cancer drug cisplatin, Sky1 kinase activity is necessary to produce the cytotoxic effect. In this study, proteome changes in response to this drug and/or SKY1 deletion have been evaluated in order to understand the role of Sky1 in the response of yeast cells to cisplatin. Results reveal differential expression of proteins previously related to the oxidative stress response, DNA damage, apoptosis and mitophagy. With these precedents, the role of Sky1 in apoptosis, necrosis and mitophagy has been evaluated by flow-cytometry, fluorescence microscopy, biosensors and fluorescence techniques. After cisplatin treatment, an apoptotic-like process diminishes in the ∆sky1 strain in comparison to the wild-type. The treatment does not affect mitophagy in the wild-type strain, while an increase is observed in the ∆sky1 strain. The increased resistance to cisplatin observed in the ∆sky1 strain may be attributable to a decrease of apoptosis and an increase of mitophagy.

  11. Culture-Independent Analyses Reveal Novel Anaerolineaceae as Abundant Primary Fermenters in Anaerobic Digesters Treating Waste Activated Sludge

    Directory of Open Access Journals (Sweden)

    Simon J. McIlroy

    2017-06-01

    Full Text Available Anaerobic digestion for biogas production is reliant on the tightly coupled synergistic activities of complex microbial consortia. Members of the uncultured A6 phylotype, within the phylum Chloroflexi, are among the most abundant genus-level-taxa of mesophilic anaerobic digester systems treating primary and surplus sludge from wastewater treatment plants, yet are known only by their 16S rRNA gene sequence. This study applied metagenomics to obtain a complete circular genome (2.57 Mbp from a representative of the A6 taxon. Preliminary annotation of the genome indicates these organisms to be anaerobic chemoorganoheterotrophs with a fermentative metabolism. Given their observed abundance, they are likely important primary fermenters in digester systems. Application of fluorescence in situ hybridisation probes designed in this study revealed their morphology to be short filaments present within the flocs. The A6 were sometimes co-located with the filamentous Archaea Methanosaeta spp. suggesting potential undetermined synergistic relationships. Based on its genome sequence and morphology we propose the species name Brevefilum fermentans gen. nov. sp. nov.

  12. Ancient DNA analyses reveal contrasting phylogeographic patterns amongst kiwi (Apteryx spp.) and a recently extinct lineage of spotted kiwi.

    Science.gov (United States)

    Shepherd, Lara D; Worthy, Trevor H; Tennyson, Alan J D; Scofield, R Paul; Ramstad, Kristina M; Lambert, David M

    2012-01-01

    The little spotted kiwi (Apteryx owenii) is a flightless ratite formerly found throughout New Zealand but now greatly reduced in distribution. Previous phylogeographic studies of the related brown kiwi (A. mantelli, A. rowi and A. australis), with which little spotted kiwi was once sympatric, revealed extremely high levels of genetic structuring, with mitochondrial DNA haplotypes often restricted to populations. We surveyed genetic variation throughout the present and pre-human range of little spotted kiwi by obtaining mitochondrial DNA sequences from contemporary and ancient samples. Little spotted kiwi and great spotted kiwi (A. haastii) formed a monophyletic clade sister to brown kiwi. Ancient samples of little spotted kiwi from the northern North Island, where it is now extinct, formed a lineage that was distinct from remaining little spotted kiwi and great spotted kiwi lineages, potentially indicating unrecognized taxonomic diversity. Overall, little spotted kiwi exhibited much lower levels of genetic diversity and structuring than brown kiwi, particularly through the South Island. Our results also indicate that little spotted kiwi (or at least hybrids involving this species) survived on the South Island mainland until more recently than previously thought.

  13. Cytogenetic analyses of Azadirachtin reveal absence of genotoxicity but marked antiproliferative effects in human lymphocytes and CHO cells in vitro.

    Science.gov (United States)

    Mosesso, Pasquale; Bohm, Lothar; Pepe, Gaetano; Fiore, Mario; Carpinelli, Alice; Gäde, Gerd; Nagini, Siddavaram; Ottavianelli, Alessandro; Degrassi, Francesca

    2012-09-18

    In this work we have examined the genotoxic potential of the bioinsecticide Azadirachtin A (AZA) and its influence on cell proliferation on human lymphocytes and Chinese Hamster ovary (CHO) cells. AZA genotoxicity was assessed by the analysis of chromosomal aberrations and sister chromatid exchanges (SCEs) in the absence and presence of rat liver S9 metabolism. Primary DNA damage was also investigated by means of the comet assay. The results obtained clearly indicate that AZA is not genotoxic in mammalian cells. On the other hand, AZA proved to interfere with cell cycle progression as shown by modulation of frequencies of first (M1) and second division (M2) metaphases detected by 5-Bromo-2'-deoxyuridine labeling. Accumulation of M1 metaphases were more pronounced in human lymphocytes. In the transformed CHO cell line, however, significant increases of multinucleated interphases and polyploid cells were observed at long treatment time. At higher dose-levels, the incidence of polyploidy was close to 100%. Identification of spindle structure and number of centrosomes by fluorescent immunostaining with α- and γ-tubulin antibodies revealed aberrant mitoses exhibiting multipolar spindles with several centrosomal signals. These findings suggest that AZA can act either through a stabilizing activity of microtubules or by inhibition of Aurora A, since both mechanisms are able to generate genetically unstable polyploid cells with multipolar spindles and multinucleated interphases. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  14. RNA-Seq Analyses for Two Silkworm Strains Reveals Insight into Their Susceptibility and Resistance to Beauveria bassiana Infection.

    Science.gov (United States)

    Xing, Dongxu; Yang, Qiong; Jiang, Liang; Li, Qingrong; Xiao, Yang; Ye, Mingqiang; Xia, Qingyou

    2017-02-10

    The silkworm Bombyx mori is an economically important species. White muscardine caused by Beauveria bassiana is the main fungal disease in sericulture, and understanding the silkworm responses to B. bassiana infection is of particular interest. Herein, we investigated the molecular mechanisms underlying these responses in two silkworm strains Haoyue (HY, sensitive to B. bassiana) and Kang 8 (K8, resistant to B. bassiana) using an RNA-seq approach. For each strain, three biological replicates for immersion treatment, two replicates for injection treatment and three untreated controls were collected to generate 16 libraries for sequencing. Differentially expressed genes (DEGs) between treated samples and untreated controls, and between the two silkworm strains, were identified. DEGs and the enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of the two strains exhibited an obvious difference. Several genes encoding cuticle proteins, serine proteinase inhibitors (SPI) and antimicrobial peptides (AMP) and the drug metabolism pathway involved in toxin detoxification were considered to be related to the resistance of K8 to B. bassiana. These results revealed insight into the resistance and susceptibility of two silkworm strains against B. bassiana infection and provided a roadmap for silkworm molecular breeding to enhance its resistance to B. bassiana.

  15. Phylogenetic analyses of nitrogen-fixing cyanobacteria from the Baltic Sea reveal sequence anomalies in the phycocyanin operon.

    Science.gov (United States)

    Janson, Sven; Granéli, Edna

    2002-07-01

    The examination of molecular phylogenies of cyanobacteria and other micro-organisms is increasing dramatically. The use of a single locus in these studies leaves the resulting phylogenies unconfirmed. In this study, the partial sequences of two loci containing segments of protein-encoding genes, the hetR and the phycocyanin locus (PC-IGS), were examined. Laboratory strains and natural populations of the heterocyst-forming cyanobacteria Anabaena, Aphanizomenon and Nodularia from the Baltic Sea were used, in total 41 sequences were determined and their phylogenies were analysed with maximum-likelihood methods. The hetR phylogenies suggested that the planktonic Aphanizomenon and Nodularia each comprise one species, while there were numerous Anabaena species present in the Baltic Sea. In the case of Nodularia, the PC-IGS phylogenies were incongruent with this and suggested that several lineages of Nodularia plankton species existed. In the hetR phylogeny, the floating and nodularin-producing strains of Nodularia were grouped together. For both the hetR and PC-IGS loci of cultured species of Nodularia their molecular phylogeny did not correspond well with the affiliation suggested by morphology. In sequences derived from species of Anabaena and Aphanizomenon the PC-IGS and hetR phylogenies were congruent, suggesting that Aphanizomenon sp. from the Baltic Sea is genetically distinct from both Aphanizomenon flos-aquae from lakes and Aphanizomenon sp. TR183 from the Baltic Sea. In both Nodularia and Anabaena/Aphanizomenon, the PC-IGS sequences showed a significant degree of either recombination events or selection, while none was detected within the hetR sequences. This is the first study comprising the phylogenies of multiple loci from all heterocystous cyanobacteria from the Baltic Sea and shows that earlier results using the PC-IGS locus should be interpreted cautiously in the absence of a confirmation using a second locus.

  16. Deconvolution analyses with tent functions reveal delayed and long-sustained increases of BOLD signals with acupuncture stimulation.

    Science.gov (United States)

    Murase, Tomokazu; Umeda, Masahiro; Fukunaga, Masaki; Tanaka, Chuzo; Higuchi, Toshihiro

    2013-01-01

    We used deconvolution analysis to examine temporal changes in brain activity after acupuncture stimulation and assess brain responses without expected reference functions. We also examined temporal changes in brain activity after sham acupuncture (noninsertive) and scrubbing stimulation. We divided 26 healthy right-handed adults into a group of 13 who received real acupuncture with manual manipulation and a group of 13 who received both tactical stimulations. Functional magnetic resonance imaging (fMRI) sequences consisted of four 15-s stimulation blocks (ON) interspersed between one 30-s and four 45-s rest blocks (OFF) for a total scanning time of 270 s. We analyzed data by using Statistical Parametric Mapping 8 (SPM8), MarsBaR, and Analysis of Functional NeuroImages (AFNI) software. For statistical analysis, we used 3dDeconvolve, part of the AFNI package, to extract the impulse response functions (IRFs) of the fMRI signals on a voxel-wise basis, and we tested the time courses of the extracted IRFs for the stimulations. We found stimulus-specific impulse responses of blood oxygen level-dependent (BOLD) signals in various brain regions. We observed significantly delayed and long-sustained increases of BOLD signals in several brain regions following real acupuncture compared to sham acupuncture and palm scrubbing, which we attribute to peripheral nocireceptors, flare responses, and processing of the central nervous system. Acupuncture stimulation induced continued activity that was stronger than activity after the other stimulations. We used tent function deconvolution to process fMRI data for acupuncture stimulation and found delayed increasing and delayed decreasing changes in BOLD signal in the somatosensory areas and areas related to pain perception. Deconvolution analyses with tent functions are expected to be useful in extracting complicated and associated brain activity that is delayed and sustained for a long period after various stimulations.

  17. RAPD and internal transcribed spacer sequence analyses reveal Zea nicaraguensis as a section Luxuriantes species close to Zea luxurians.

    Science.gov (United States)

    Wang, Pei; Lu, Yanli; Zheng, Mingmin; Rong, Tingzhao; Tang, Qilin

    2011-04-15

    Genetic relationship of a newly discovered teosinte from Nicaragua, Zea nicaraguensis with waterlogging tolerance, was determined based on randomly amplified polymorphic DNA (RAPD) markers and the internal transcribed spacer (ITS) sequences of nuclear ribosomal DNA using 14 accessions from Zea species. RAPD analysis showed that a total of 5,303 fragments were produced by 136 random decamer primers, of which 84.86% bands were polymorphic. RAPD-based UPGMA analysis demonstrated that the genus Zea can be divided into section Luxuriantes including Zea diploperennis, Zea luxurians, Zea perennis and Zea nicaraguensis, and section Zea including Zea mays ssp. mexicana, Zea mays ssp. parviglumis, Zea mays ssp. huehuetenangensis and Zea mays ssp. mays. ITS sequence analysis showed the lengths of the entire ITS region of the 14 taxa in Zea varied from 597 to 605 bp. The average GC content was 67.8%. In addition to the insertion/deletions, 78 variable sites were recorded in the total ITS region with 47 in ITS1, 5 in 5.8S, and 26 in ITS2. Sequences of these taxa were analyzed with neighbor-joining (NJ) and maximum parsimony (MP) methods to construct the phylogenetic trees, selecting Tripsacum dactyloides L. as the outgroup. The phylogenetic relationships of Zea species inferred from the ITS sequences are highly concordant with the RAPD evidence that resolved two major subgenus clades. Both RAPD and ITS sequence analyses indicate that Zea nicaraguensis is more closely related to Zea luxurians than the other teosintes and cultivated maize, which should be regarded as a section Luxuriantes species.

  18. RAPD and internal transcribed spacer sequence analyses reveal Zea nicaraguensis as a section Luxuriantes species close to Zea luxurians.

    Directory of Open Access Journals (Sweden)

    Pei Wang

    Full Text Available Genetic relationship of a newly discovered teosinte from Nicaragua, Zea nicaraguensis with waterlogging tolerance, was determined based on randomly amplified polymorphic DNA (RAPD markers and the internal transcribed spacer (ITS sequences of nuclear ribosomal DNA using 14 accessions from Zea species. RAPD analysis showed that a total of 5,303 fragments were produced by 136 random decamer primers, of which 84.86% bands were polymorphic. RAPD-based UPGMA analysis demonstrated that the genus Zea can be divided into section Luxuriantes including Zea diploperennis, Zea luxurians, Zea perennis and Zea nicaraguensis, and section Zea including Zea mays ssp. mexicana, Zea mays ssp. parviglumis, Zea mays ssp. huehuetenangensis and Zea mays ssp. mays. ITS sequence analysis showed the lengths of the entire ITS region of the 14 taxa in Zea varied from 597 to 605 bp. The average GC content was 67.8%. In addition to the insertion/deletions, 78 variable sites were recorded in the total ITS region with 47 in ITS1, 5 in 5.8S, and 26 in ITS2. Sequences of these taxa were analyzed with neighbor-joining (NJ and maximum parsimony (MP methods to construct the phylogenetic trees, selecting Tripsacum dactyloides L. as the outgroup. The phylogenetic relationships of Zea species inferred from the ITS sequences are highly concordant with the RAPD evidence that resolved two major subgenus clades. Both RAPD and ITS sequence analyses indicate that Zea nicaraguensis is more closely related to Zea luxurians than the other teosintes and cultivated maize, which should be regarded as a section Luxuriantes species.

  19. A systematic review of cost-effectiveness analyses of complex wound interventions reveals optimal treatments for specific wound types.

    Science.gov (United States)

    Tricco, Andrea C; Cogo, Elise; Isaranuwatchai, Wanrudee; Khan, Paul A; Sanmugalingham, Geetha; Antony, Jesmin; Hoch, Jeffrey S; Straus, Sharon E

    2015-04-22

    Complex wounds present a substantial economic burden on healthcare systems, costing billions of dollars annually in North America alone. The prevalence of complex wounds is a significant patient and societal healthcare concern and cost-effective wound care management remains unclear. This article summarizes the cost-effectiveness of interventions for complex wound care through a systematic review of the evidence base. We searched multiple databases (MEDLINE, EMBASE, Cochrane Library) for cost-effectiveness studies that examined adults treated for complex wounds. Two reviewers independently screened the literature, abstracted data from full-text articles, and assessed methodological quality using the Drummond 10-item methodological quality tool. Incremental cost-effectiveness ratios were reported, or, if not reported, calculated and converted to United States Dollars for the year 2013. Overall, 59 cost-effectiveness analyses were included; 71% (42 out of 59) of the included studies scored 8 or more points on the Drummond 10-item checklist tool. Based on these, 22 interventions were found to be more effective and less costly (i.e., dominant) compared to the study comparators: 9 for diabetic ulcers, 8 for venous ulcers, 3 for pressure ulcers, 1 for mixed venous and venous/arterial ulcers, and 1 for mixed complex wound types. Our results can be used by decision-makers in maximizing the deployment of clinically effective and resource efficient wound care interventions. Our analysis also highlights specific treatments that are not cost-effective, thereby indicating areas of resource savings. Please see related article: http://dx.doi.org/10.1186/s12916-015-0288-5.

  20. Analytical pyrolysis and stable isotope analyses reveal past environmental changes in coralloid speleothems from Easter Island (Chile).

    Science.gov (United States)

    Miller, Ana Z; De la Rosa, José M; Jiménez-Morillo, Nicasio T; Pereira, Manuel F C; González-Pérez, José A; Calaforra, José M; Saiz-Jimenez, Cesareo

    2016-08-26

    This study comprises an innovative approach based on the combination of chromatography (analytical pyrolysis and pyrolysis compound-specific isotope analysis (Py-CSIA)), light stable isotopes, microscopy and mineralogy analyses to characterize the internal layering of coralloid speleothems from the Ana Heva lava tube in Easter Island (Chile). This multidisciplinary proxy showed that the speleothems consist of banded siliceous materials of low crystallinity with different mineralogical compositions and a significant contribution of organic carbon. Opal-A constitutes the outermost grey layer of the coralloids, whereas calcite and amorphous Mg hydrate silicate are the major components of the inner whitish and honey-brown layers, respectively. The differences found in the mineralogical, elemental, molecular and isotopic composition of these distinct coloured layers are related to environmental changes during speleothem development. Stable isotopes and analytical pyrolysis suggested alterations in the water regime, pointing to wetter conditions during the formation of the Ca-rich layer and a possible increase in the amount of water dripping into the cave. The trend observed for δ(15)N values suggested an increase in the average temperature over time, which is consistent with the so-called climate warming during the Holocene. The pyrolysis compound-specific isotope analysis of each speleothem layer showed a similar trend with the bulk δ(13)C values pointing to the appropriateness of direct Py-CSIA in paleoenvironmental studies. The δ(13)C values for n-alkanes reinforced the occurrence of a drastic environmental change, indicating that the outermost Opal layer was developed under drier and more arid environmental conditions.

  1. The functional potential of high Arctic permafrost revealed by metagenomic sequencing, qPCR and microarray analyses.

    Science.gov (United States)

    Yergeau, Etienne; Hogues, Hervé; Whyte, Lyle G; Greer, Charles W

    2010-09-01

    The fate of the carbon stocked in permafrost following global warming and permafrost thaw is of major concern in view of the potential for increased CH(4) and CO(2) emissions from these soils. Complex carbon compound degradation and greenhouse gas emissions are due to soil microbial communities, but no comprehensive study has yet addressed their composition and functional potential in permafrost. Here, a 2-m deep permafrost sample and its overlying active layer soil were subjected to metagenomic sequencing, quantitative PCR (qPCR) and microarray analyses. The active layer soil and the 2-m permafrost microbial community structures were very similar, with Actinobacteria being the dominant phylum. The two samples also possessed a highly similar spectrum of functional genes, especially when compared with other already published metagenomes. Key genes related to methane generation, methane oxidation and organic matter degradation were highly diverse for both samples in the metagenomic libraries and some (for example, pmoA) showed relatively high abundance in qPCR assays. Genes related to nitrogen fixation and ammonia oxidation, which could have important roles following climatic change in these nitrogen-limited environments, showed low diversity but high abundance. The 2-m permafrost showed lower abundance and diversity for all the assessed genes and taxa. Experimental biases were also evaluated using qPCR and showed that the whole-community genome amplification technique used caused representational biases in the metagenomic libraries by increasing the abundance of Bacteroidetes and decreasing the abundance of Actinobacteria. This study describes for the first time the detailed functional potential of permafrost-affected soils.

  2. Correlation analyses revealed global microRNA-mRNA expression associations in human peripheral blood mononuclear cells.

    Science.gov (United States)

    Wang, Lan; Zhu, Jiang; Deng, Fei-Yan; Wu, Long-Fei; Mo, Xing-Bo; Zhu, Xiao-Wei; Xia, Wei; Xie, Fang-Fei; He, Pei; Bing, Peng-Fei; Qiu, Ying-Hua; Lin, Xiang; Lu, Xin; Zhang, Lei; Yi, Neng-Jun; Zhang, Yong-Hong; Lei, Shu-Feng

    2017-09-06

    MicroRNAs (miRNAs) can regulate gene expression through binding to complementary sites in the 3'-untranslated regions of target mRNAs, which will lead to existence of correlation in expression between miRNA and mRNA. However, the miRNA-mRNA correlation patterns are complex and remain largely unclear yet. To establish the global correlation patterns in human peripheral blood mononuclear cells (PBMCs), multiple miRNA-mRNA correlation analyses and expression quantitative trait locus (eQTL) analysis were conducted in this study. We predicted and achieved 861 miRNA-mRNA pairs (65 miRNAs, 412 mRNAs) using multiple bioinformatics programs, and found global negative miRNA-mRNA correlations in PBMC from all 46 study subjects. Among the 861 pairs of correlations, 19.5% were significant (P correlation network was complex and highlighted key miRNAs/genes in PBMC. Some miRNAs, such as hsa-miR-29a, hsa-miR-148a, regulate a cluster of target genes. Some genes, e.g., TNRC6A, are regulated by multiple miRNAs. The identified genes tend to be enriched in molecular functions of DNA and RNA binding, and biological processes such as protein transport, regulation of translation and chromatin modification. The results provided a global view of the miRNA-mRNA expression correlation profile in human PBMCs, which would facilitate in-depth investigation of biological functions of key miRNAs/mRNAs and better understanding of the pathogenesis underlying PBMC-related diseases.

  3. Multiple correlation analyses revealed complex relationship between DNA methylation and mRNA expression in human peripheral blood mononuclear cells.

    Science.gov (United States)

    Xie, Fang-Fei; Deng, Fei-Yan; Wu, Long-Fei; Mo, Xing-Bo; Zhu, Hong; Wu, Jian; Guo, Yu-Fan; Zeng, Ke-Qin; Wang, Ming-Jun; Zhu, Xiao-Wei; Xia, Wei; Wang, Lan; He, Pei; Bing, Peng-Fei; Lu, Xin; Zhang, Yong-Hong; Lei, Shu-Feng

    2017-07-22

    DNA methylation is an important regulator on the mRNA expression. However, a genome-wide correlation pattern between DNA methylation and mRNA expression in human peripheral blood mononuclear cells (PBMCs) is largely unknown. The comprehensive relationship between mRNA and DNA methylation was explored by using four types of correlation analyses and a genome-wide methylation-mRNA expression quantitative trait locus (eQTL) analysis in PBMCs in 46 unrelated female subjects. An enrichment analysis was performed to detect biological function for the detected genes. Single pair correlation coefficient (r T1) between methylation level and mRNA is moderate (-0.63-0.62) in intensity, and the negative and positive correlations are nearly equal in quantity. Correlation analysis on each gene (T4) found 60.1% genes showed correlations between mRNA and gene-based methylation at P correlation (R T4 > 0.8). Methylation sites have regulation effects on mRNA expression in eQTL analysis, with more often observations in region of transcription start site (TSS). The genes under significant methylation regulation both in correlation analysis and eQTL analysis tend to cluster to the categories (e.g., transcription, translation, regulation of transcription) that are essential for maintaining the basic life activities of cells. Our findings indicated that DNA methylation has predictive regulation effect on mRNA with a very complex pattern in PBMCs. The results increased our understanding on correlation of methylation and mRNA and also provided useful clues for future epigenetic studies in exploring biological and disease-related regulatory mechanisms in PBMC.

  4. Combining quantitative trait loci and heterogeneous microarray data analyses reveals putative candidate pathways affecting mastitis in cattle.

    Science.gov (United States)

    Lewandowska-Sabat, A M; Günther, J; Seyfert, H M; Olsaker, I

    2012-12-01

    Mastitis is a frequent disease and considerable problem for the global dairy industry. Identification of solutions leading to the development of new control strategies is therefore of high importance. In this study, we have integrated genomic data from genome-wide association mapping in cattle with transcriptomic data from microarray studies of several mastitis pathogens and host species in vitro and in vivo. To identify significant candidate pathways directly and indirectly involved in the immune response to mastitis, ingenuity pathway analysis (ipa) and database for annotation, visualization and integrated discovery bioinformatic (david) were applied. Several candidate pathways were found. Of great interest are IL-17 and IL-8 signalling pathways, responsible for the recruitment and migration of inflammatory cells into tissue during inflammation and infection. These results may emphasize further functional studies for identification of factors contributing to resistance to mastitis pathogens in cattle.

  5. Spliced leader-based analyses reveal the effects of polycyclic aromatic hydrocarbons on gene expression in the copepod Pseudodiaptomus poplesia.

    Science.gov (United States)

    Zhuang, Yunyun; Yang, Feifei; Xu, Donghui; Chen, Hongju; Zhang, Huan; Liu, Guangxing

    2017-02-01

    Polycyclic aromatic hydrocarbons (PAHs) are a group of toxic and carcinogenic pollutants that can adversely affect the development, growth and reproduction of marine organisms including copepods. However, knowledge on the molecular mechanisms regulating the response to PAH exposure in marine planktonic copepods is limited. In this study, we investigated the survival and gene expression of the calanoid copepod Pseudodiaptomus poplesia upon exposure to two PAHs, 1, 2-dimethylnaphthalene (1, 2-NAPH) and pyrene. Acute toxicity responses resulted in 96-h LC50 of 788.98μgL(-1) and 54.68μgL(-1) for 1, 2-NAPH and pyrene, respectively. Using the recently discovered copepod spliced leader as a primer, we constructed full-length cDNA libraries from copepods exposed to sublethal concentrations and revealed 289 unique genes of diverse functions, including stress response genes and novel genes previously undocumented for this species. Eighty-three gene families were specifically expressed in PAH exposure libraries. We further analyzed the expression of seven target genes by reverse transcription-quantitative PCR in a time-course test with three sublethal concentrations. These target genes have primary roles in detoxification, oxidative defense, and signal transduction, and include different forms of glutathione S-transferase (GST), glutathione peroxidases (GPX), peroxiredoxin (PRDX), methylmalonate-semialdehyde dehydrogenase (MSDH) and ras-related C3 botulinum toxin substrate (RAC1). Expression stability of seven candidate reference genes were evaluated and the two most stable ones (RPL15 and RPS20 for 1, 2-NAPH exposure, RPL15 and EF1D for pyrene exposure) were used to normalize the expression levels of the target genes. Significant upregulation was detected in GST-T, GST-DE, GPX4, PRDX6 and RAC1 upon 1, 2-NAPH exposure, and GST-DE and MSDH upon pyrene exposure. These results indicated that the oxidative stress was induced and that signal transduction might be affected by PAH

  6. Pathway Network Analyses for Autism Reveal Multisystem Involvement, Major Overlaps with Other Diseases and Convergence upon MAPK and Calcium Signaling.

    Science.gov (United States)

    Wen, Ya; Alshikho, Mohamad J; Herbert, Martha R

    2016-01-01

    We used established databases in standard ways to systematically characterize gene ontologies, pathways and functional linkages in the large set of genes now associated with autism spectrum disorders (ASDs). These conditions are particularly challenging--they lack clear pathognomonic biological markers, they involve great heterogeneity across multiple levels (genes, systemic biological and brain characteristics, and nuances of behavioral manifestations)-and yet everyone with this diagnosis meets the same defining behavioral criteria. Using the human gene list from Simons Foundation Autism Research Initiative (SFARI) we performed gene set enrichment analysis with the Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway Database, and then derived a pathway network from pathway-pathway functional interactions again in reference to KEGG. Through identifying the GO (Gene Ontology) groups in which SFARI genes were enriched, mapping the coherence between pathways and GO groups, and ranking the relative strengths of representation of pathway network components, we 1) identified 10 disease-associated and 30 function-associated pathways 2) revealed calcium signaling pathway and neuroactive ligand-receptor interaction as the most enriched, statistically significant pathways from the enrichment analysis, 3) showed calcium signaling pathways and MAPK signaling pathway to be interactive hubs with other pathways and also to be involved with pervasively present biological processes, 4) found convergent indications that the process "calcium-PRC (protein kinase C)-Ras-Raf-MAPK/ERK" is likely a major contributor to ASD pathophysiology, and 5) noted that perturbations associated with KEGG's category of environmental information processing were common. These findings support the idea that ASD-associated genes may contribute not only to core features of ASD themselves but also to vulnerability to other chronic and systemic problems potentially including cancer, metabolic conditions

  7. Bacterial Communities in Women with Bacterial Vaginosis: High Resolution Phylogenetic Analyses Reveal Relationships of Microbiota to Clinical Criteria

    Science.gov (United States)

    Srinivasan, Sujatha; Hoffman, Noah G.; Morgan, Martin T.; Matsen, Frederick A.; Fiedler, Tina L.; Hall, Robert W.; Ross, Frederick J.; McCoy, Connor O.; Bumgarner, Roger; Marrazzo, Jeanne M.; Fredricks, David N.

    2012-01-01

    Background Bacterial vaginosis (BV) is a common condition that is associated with numerous adverse health outcomes and is characterized by poorly understood changes in the vaginal microbiota. We sought to describe the composition and diversity of the vaginal bacterial biota in women with BV using deep sequencing of the 16S rRNA gene coupled with species-level taxonomic identification. We investigated the associations between the presence of individual bacterial species and clinical diagnostic characteristics of BV. Methodology/Principal Findings Broad-range 16S rRNA gene PCR and pyrosequencing were performed on vaginal swabs from 220 women with and without BV. BV was assessed by Amsel’s clinical criteria and confirmed by Gram stain. Taxonomic classification was performed using phylogenetic placement tools that assigned 99% of query sequence reads to the species level. Women with BV had heterogeneous vaginal bacterial communities that were usually not dominated by a single taxon. In the absence of BV, vaginal bacterial communities were dominated by either Lactobacillus crispatus or Lactobacillus iners. Leptotrichia amnionii and Eggerthella sp. were the only two BV-associated bacteria (BVABs) significantly associated with each of the four Amsel’s criteria. Co-occurrence analysis revealed the presence of several sub-groups of BVABs suggesting metabolic co-dependencies. Greater abundance of several BVABs was observed in Black women without BV. Conclusions/Significance The human vaginal bacterial biota is heterogeneous and marked by greater species richness and diversity in women with BV; no species is universally present. Different bacterial species have different associations with the four clinical criteria, which may account for discrepancies often observed between Amsel and Nugent (Gram stain) diagnostic criteria. Several BVABs exhibited race-dependent prevalence when analyzed in separate groups by BV status which may contribute to increased incidence of BV in

  8. Inverse relationship between chitobiase and transglycosylation activities of chitinase-D from Serratia proteamaculans revealed by mutational and biophysical analyses

    Science.gov (United States)

    Madhuprakash, Jogi; Bobbili, Kishore Babu; Moerschbacher, Bruno M.; Singh, Tej Pal; Swamy, Musti J.; Podile, Appa Rao

    2015-01-01

    Serratia proteamaculans chitinase-D (SpChiD) has a unique combination of hydrolytic and transglycosylation (TG) activities. The TG activity of SpChiD can be used for large-scale production of chito-oligosaccharides (CHOS). The multiple activities (hydrolytic and/or chitobiase activities and TG) of SpChiD appear to be strongly influenced by the substrate-binding cleft. Here, we report the unique property of SpChiD substrate-binding cleft, wherein, the residues Tyr28, Val35 and Thr36 control chitobiase activity and the residues Trp160 and Trp290 are crucial for TG activity. Mutants with reduced (V35G and T36G/F) or no (SpChiDΔ30–42 and Y28A) chitobiase activity produced higher amounts of the quantifiable even-chain TG product with degree of polymerization (DP)-6, indicating that the chitobiase and TG activities are inversely related. In addition to its unprecedented catalytic properties, unlike other chitinases, the single modular SpChiD showed dual unfolding transitions. Ligand-induced thermal stability studies with the catalytically inactive mutant of SpChiD (E153A) showed that the transition temperature increased upon binding of CHOS with DP2–6. Isothermal titration calorimetry experiments revealed the exceptionally high binding affinities for E153A to CHOS with DP2–6. These observations strongly support that the architecture of SpChiD substrate-binding cleft adopted to control chitobiase and TG activities, in addition to usual chitinase-mediated hydrolysis. PMID:26493546

  9. Comparative analyses of six solanaceous transcriptomes reveal a high degree of sequence conservation and species-specific transcripts

    Directory of Open Access Journals (Sweden)

    Ouyang Shu

    2005-09-01

    Full Text Available Abstract Background The Solanaceae is a family of closely related species with diverse phenotypes that have been exploited for agronomic purposes. Previous studies involving a small number of genes suggested sequence conservation across the Solanaceae. The availability of large collections of Expressed Sequence Tags (ESTs for the Solanaceae now provides the opportunity to assess sequence conservation and divergence on a genomic scale. Results All available ESTs and Expressed Transcripts (ETs, 449,224 sequences for six Solanaceae species (potato, tomato, pepper, petunia, tobacco and Nicotiana benthamiana, were clustered and assembled into gene indices. Examination of gene ontologies revealed that the transcripts within the gene indices encode a similar suite of biological processes. Although the ESTs and ETs were derived from a variety of tissues, 55–81% of the sequences had significant similarity at the nucleotide level with sequences among the six species. Putative orthologs could be identified for 28–58% of the sequences. This high degree of sequence conservation was supported by expression profiling using heterologous hybridizations to potato cDNA arrays that showed similar expression patterns in mature leaves for all six solanaceous species. 16–19% of the transcripts within the six Solanaceae gene indices did not have matches among Solanaceae, Arabidopsis, rice or 21 other plant gene indices. Conclusion Results from this genome scale analysis confirmed a high level of sequence conservation at the nucleotide level of the coding sequence among Solanaceae. Additionally, the results indicated that part of the Solanaceae transcriptome is likely to be unique for each species.

  10. Genomic expression analyses reveal lysosomal, innate immunity proteins, as disease correlates in murine models of a lysosomal storage disorder.

    Directory of Open Access Journals (Sweden)

    Md Suhail Alam

    Full Text Available Niemann-Pick Type C (NPC disease is a rare, genetic, lysosomal disorder with progressive neurodegeneration. Poor understanding of the pathophysiology and a lack of blood-based diagnostic markers are major hurdles in the treatment and management of NPC and several additional, neurological lysosomal disorders. To identify disease severity correlates, we undertook whole genome expression profiling of sentinel organs, brain, liver, and spleen of Balb/c Npc1(-/- mice relative to Npc1(+/- at an asymptomatic stage, as well as early- and late-symptomatic stages. Unexpectedly, we found prominent up regulation of innate immunity genes with age-dependent change in their expression, in all three organs. We shortlisted a set of 12 secretory genes whose expression steadily increased with age in both brain and liver, as potential plasma correlates of neurological and/or liver disease. Ten were innate immune genes with eight ascribed to lysosomes. Several are known to be elevated in diseased organs of murine models of other lysosomal diseases including Gaucher's disease, Sandhoff disease and MPSIIIB. We validated the top candidate lysozyme, in the plasma of Npc1(-/- as well as Balb/c Npc1(nmf164 mice (bearing a point mutation closer to human disease mutants and show its reduction in response to an emerging therapeutic. We further established elevation of innate immunity in Npc1(-/- mice through multiple functional assays including inhibition of bacterial infection as well as cellular analysis and immunohistochemistry. These data revealed neutrophil elevation in the Npc1(-/- spleen and liver (where large foci were detected proximal to damaged tissue. Together our results yield a set of lysosomal, secretory innate immunity genes that have potential to be developed as pan or specific plasma markers for neurological diseases associated with lysosomal storage and where diagnosis is a major problem. Further, the accumulation of neutrophils in diseased organs

  11. Benzaldehyde is a precursor of phenylpropylamino alkaloids as revealed by targeted metabolic profiling and comparative biochemical analyses in Ephedra spp.

    Science.gov (United States)

    Krizevski, Raz; Bar, Einat; Shalit, O R; Levy, Asaf; Hagel, Jillian M; Kilpatrick, Korey; Marsolais, Frédéric; Facchini, Peter J; Ben-Shabat, Shimon; Sitrit, Yaron; Lewinsohn, Efraim

    2012-09-01

    Ephedrine and pseudoephedrine are phenylpropylamino alkaloids widely used in modern medicine. Some Ephedra species such as E. sinica Stapf (Ephedraceae), a widely used Chinese medicinal plant (Chinese name: Ma Huang), accumulate ephedrine alkaloids as active constituents. Other Ephedra species, such as E. foeminea Forssk. (syn. E. campylopoda C.A. Mey) lack ephedrine alkaloids and their postulated metabolic precursors 1-phenylpropane-1,2-dione and (S)-cathinone. Solid-phase microextraction analysis of freshly picked young E. sinica and E. foeminea stems revealed the presence of increased benzaldehyde levels in E. foeminea, whereas 1-phenylpropane-1,2-dione was detected only in E. sinica. Soluble protein preparations from E. sinica and E. foeminea stems catalyzed the conversion of benzaldehyde and pyruvate to (R)-phenylacetylcarbinol, (S)-phenylacetylcarbinol, (R)-2-hydroxypropiophenone (S)-2-hydroxypropiophenone and 1-phenylpropane-1,2-dione. The activity, termed benzaldehyde carboxyligase (BCL) required the presence of magnesium and thiamine pyrophosphate and was 40 times higher in E. sinica as compared to E. foeminea. The distribution patterns of BCL activity in E. sinica tissues correlates well with the distribution pattern of the ephedrine alkaloids. (S)-Cathinone reductase enzymatic activities generating (1R,2S)-norephedrine and (1S,1R)-norephedrine were significantly higher in E. sinica relative to the levels displayed by E. foeminea. Surprisingly, (1R,2S)-norephedrine N-methyltransferase activity which is a downstream enzyme in ephedrine biosynthesis was significantly higher in E. foeminea than in E. sinica. Our studies further support that benzaldehyde is the metabolic precursor to phenylpropylamino alkaloids in E. sinica.

  12. Integration of deep transcriptome and proteome analyses reveals the components of alkaloid metabolism in opium poppy cell cultures

    Directory of Open Access Journals (Sweden)

    Schriemer David C

    2010-11-01

    Full Text Available Abstract Background Papaver somniferum (opium poppy is the source for several pharmaceutical benzylisoquinoline alkaloids including morphine, the codeine and sanguinarine. In response to treatment with a fungal elicitor, the biosynthesis and accumulation of sanguinarine is induced along with other plant defense responses in opium poppy cell cultures. The transcriptional induction of alkaloid metabolism in cultured cells provides an opportunity to identify components of this process via the integration of deep transcriptome and proteome databases generated using next-generation technologies. Results A cDNA library was prepared for opium poppy cell cultures treated with a fungal elicitor for 10 h. Using 454 GS-FLX Titanium pyrosequencing, 427,369 expressed sequence tags (ESTs with an average length of 462 bp were generated. Assembly of these sequences yielded 93,723 unigenes, of which 23,753 were assigned Gene Ontology annotations. Transcripts encoding all known sanguinarine biosynthetic enzymes were identified in the EST database, 5 of which were represented among the 50 most abundant transcripts. Liquid chromatography-tandem mass spectrometry (LC-MS/MS of total protein extracts from cell cultures treated with a fungal elicitor for 50 h facilitated the identification of 1,004 proteins. Proteins were fractionated by one-dimensional SDS-PAGE and digested with trypsin prior to LC-MS/MS analysis. Query of an opium poppy-specific EST database substantially enhanced peptide identification. Eight out of 10 known sanguinarine biosynthetic enzymes and many relevant primary metabolic enzymes were represented in the peptide database. Conclusions The integration of deep transcriptome and proteome analyses provides an effective platform to catalogue the components of secondary metabolism, and to identify genes encoding uncharacterized enzymes. The establishment of corresponding transcript and protein databases generated by next-generation technologies in a

  13. Comparative analyses of vertebrate posterior HoxD clusters reveal atypical cluster architecture in the caecilian Typhlonectes natans

    Directory of Open Access Journals (Sweden)

    Amemiya Chris T

    2010-11-01

    Full Text Available Abstract Background The posterior genes of the HoxD cluster play a crucial role in the patterning of the tetrapod limb. This region is under the control of a global, long-range enhancer that is present in all vertebrates. Variation in limb types, as is the case in amphibians, can probably not only be attributed to variation in Hox genes, but is likely to be the product of differences in gene regulation. With a collection of vertebrate genome sequences available today, we used a comparative genomics approach to study the posterior HoxD cluster of amphibians. A frog and a caecilian were included in the study to compare coding sequences as well as to determine the gain and loss of putative regulatory sequences. Results We sequenced the posterior end of the HoxD cluster of a caecilian and performed comparative analyses of this region using HoxD clusters of other vertebrates. We determined the presence of conserved non-coding sequences and traced gains and losses of these footprints during vertebrate evolution, with particular focus on amphibians. We found that the caecilian HoxD cluster is almost three times larger than its mammalian counterpart. This enlargement is accompanied with the loss of one gene and the accumulation of repeats in that area. A similar phenomenon was observed in the coelacanth, where a different gene was lost and expansion of the area where the gene was lost has occurred. At least one phylogenetic footprint present in all vertebrates was lost in amphibians. This conserved region is a known regulatory element and functions as a boundary element in neural tissue to prevent expression of Hoxd genes. Conclusion The posterior part of the HoxD cluster of Typhlonectes natans is among the largest known today. The loss of Hoxd-12 and the expansion of the intergenic region may exert an influence on the limb enhancer, by having to bypass a distance seven times that of regular HoxD clusters. Whether or not there is a correlation with the

  14. Genome-wide analyses reveal lineage specific contributions of positive selection and recombination to the evolution of Listeria monocytogenes

    Directory of Open Access Journals (Sweden)

    Sun Qi

    2008-08-01

    Full Text Available Abstract Background The genus Listeria includes two closely related pathogenic and non-pathogenic species, L. monocytogenes and L. innocua. L. monocytogenes is an opportunistic human foodborne and animal pathogen that includes two common lineages. While lineage I is more commonly found among human listeriosis cases, lineage II appears to be overrepresented among isolates from foods and environmental sources. This study used the genome sequences for one L. innocua strain and four L. monocytogenes strains representing lineages I and II, to characterize the contributions of positive selection and recombination to the evolution of the L. innocua/L. monocytogenes core genome. Results Among the 2267 genes in the L. monocytogenes/L. innocua core genome, 1097 genes showed evidence for recombination and 36 genes showed evidence for positive selection. Positive selection was strongly associated with recombination. Specifically, 29 of the 36 genes under positive selection also showed evidence for recombination. Recombination was more common among isolates in lineage II than lineage I; this trend was confirmed by sequencing five genes in a larger isolate set. Positive selection was more abundant in the ancestral branch of lineage II (20 genes as compared to the ancestral branch of lineage I (9 genes. Additional genes under positive selection were identified in the branch separating the two species; for this branch, genes in the role category "Cell wall and membrane biogenesis" were significantly more likely to have evidence for positive selection. Positive selection of three genes was confirmed in a larger isolate set, which also revealed occurrence of multiple premature stop codons in one positively selected gene involved in flagellar motility (flaR. Conclusion While recombination and positive selection both contribute to evolution of L. monocytogenes, the relative contributions of these evolutionary forces seem to differ by L. monocytogenes lineages and

  15. "Contrasting patterns of selection at Pinus pinaster Ait. Drought stress candidate genes as revealed by genetic differentiation analyses".

    Science.gov (United States)

    Eveno, Emmanuelle; Collada, Carmen; Guevara, M Angeles; Léger, Valérie; Soto, Alvaro; Díaz, Luis; Léger, Patrick; González-Martínez, Santiago C; Cervera, M Teresa; Plomion, Christophe; Garnier-Géré, Pauline H

    2008-02-01

    The importance of natural selection for shaping adaptive trait differentiation among natural populations of allogamous tree species has long been recognized. Determining the molecular basis of local adaptation remains largely unresolved, and the respective roles of selection and demography in shaping population structure are actively debated. Using a multilocus scan that aims to detect outliers from simulated neutral expectations, we analyzed patterns of nucleotide diversity and genetic differentiation at 11 polymorphic candidate genes for drought stress tolerance in phenotypically contrasted Pinus pinaster Ait. populations across its geographical range. We compared 3 coalescent-based methods: 2 frequentist-like, including 1 approach specifically developed for biallelic single nucleotide polymorphisms (SNPs) here and 1 Bayesian. Five genes showed outlier patterns that were robust across methods at the haplotype level for 2 of them. Two genes presented higher F(ST) values than expected (PR-AGP4 and erd3), suggesting that they could have been affected by the action of diversifying selection among populations. In contrast, 3 genes presented lower F(ST) values than expected (dhn-1, dhn2, and lp3-1), which could represent signatures of homogenizing selection among populations. A smaller proportion of outliers were detected at the SNP level suggesting the potential functional significance of particular combinations of sites in drought-response candidate genes. The Bayesian method appeared robust to low sample sizes, flexible to assumptions regarding migration rates, and powerful for detecting selection at the haplotype level, but the frequentist-like method adapted to SNPs was more efficient for the identification of outlier SNPs showing low differentiation. Population-specific effects estimated in the Bayesian method also revealed populations with lower immigration rates, which could have led to favorable situations for local adaptation. Outlier patterns are discussed

  16. Gene expression analyses implicate an alternative splicing program in regulating contractile gene expression and serum response factor activity in mice.

    Directory of Open Access Journals (Sweden)

    Twishasri Dasgupta

    Full Text Available Members of the CUG-BP, Elav-like family (CELF regulate alternative splicing in the heart. In MHC-CELFΔ transgenic mice, CELF splicing activity is inhibited postnatally in heart muscle via expression of a nuclear dominant negative CELF protein under an α-myosin heavy chain promoter. MHC-CELFΔ mice develop dilated cardiomyopathy characterized by alternative splicing defects, enlarged hearts, and severe contractile dysfunction. In this study, gene expression profiles in the hearts of wild type, high- and low-expressing lines of MHC-CELFΔ mice were compared using microarrays. Gene ontology and pathway analyses identified contraction and calcium signaling as the most affected processes. Network analysis revealed that the serum response factor (SRF network is highly affected. Downstream targets of SRF were up-regulated in MHC-CELFΔ mice compared to the wild type, suggesting an increase in SRF activity. Although SRF levels remained unchanged, known inhibitors of SRF activity were down-regulated. Conversely, we found that these inhibitors are up-regulated and downstream SRF targets are down-regulated in the hearts of MCKCUG-BP1 mice, which mildly over-express CELF1 in heart and skeletal muscle. This suggests that changes in SRF activity are a consequence of changes in CELF-mediated regulation rather than a secondary result of compensatory pathways in heart failure. In MHC-CELFΔ males, where the phenotype is only partially penetrant, both alternative splicing changes and down-regulation of inhibitors of SRF correlate with the development of cardiomyopathy. Together, these results strongly support a role for CELF-mediated alternative splicing in the regulation of contractile gene expression, achieved in part through modulating the activity of SRF, a key cardiac transcription factor.

  17. Are semantic and phonological fluency based on the same or distinct sets of cognitive processes? Insights from factor analyses in healthy adults and stroke patients.

    Science.gov (United States)

    Schmidt, Charlotte S M; Schumacher, Lena V; Römer, Pia; Leonhart, Rainer; Beume, Lena; Martin, Markus; Dressing, Andrea; Weiller, Cornelius; Kaller, Christoph P

    2017-05-01

    Verbal fluency for semantic categories and phonological letters is frequently applied to studies of language and executive functions. Despite its popularity, it is still debated whether measures of semantic and phonological fluency reflect the same or distinct sets of cognitive processes. Word generation in the two task variants is believed to involve different types of search processes. Findings from the lesion and neuroimaging literature further suggest a stronger reliance of phonological and semantic fluency on frontal and temporal brain areas, respectively. This evidence for differential cognitive and neural contributions is, however, strongly challenged by findings from factor analyses, which have consistently yielded only one explanatory factor. As all previous factor-analytical approaches were based on very small item sets, this apparent discrepancy may be due to methodological limitations. In this study, we therefore applied a German version of the verbal fluency task with 8 semantic (i.e. categories) and 8 phonological items (i.e. letters). An exploratory factor analysis with oblique rotation in N=69 healthy young adults indeed revealed a two-factor solution with markedly different loadings for semantic and phonological items. This pattern was corroborated by a confirmatory factor analysis in a sample of N=174 stroke patients. As results from both samples also revealed a substantial portion of common variance between the semantic and phonological factor, the present data further demonstrate that semantic and phonological verbal fluency are based on clearly distinct but also on shared sets of cognitive processes. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Multicenter quality assessment of 16S ribosomal DNA-sequencing for microbiome analyses reveals high inter-center variability.

    Science.gov (United States)

    Hiergeist, Andreas; Reischl, Udo; Gessner, Andrè

    2016-08-01

    The composition of human as well as animal microbiota has increasingly gained in interest since metabolites and structural components of endogenous microorganisms fundamentally influence all aspects of host physiology. Since many of the bacteria are still unculturable, molecular techniques such as high-throughput sequencing have dramatically increased our knowledge of microbial communities. The majority of microbiome studies published thus far are based on bacterial 16S ribosomal RNA (rRNA) gene sequencing, so that they can, at least in principle, be compared to determine the role of the microbiome composition for host metabolism and physiology, developmental processes, as well as different diseases. However, differences in DNA preparation and purification, 16S rDNA PCR amplification, sequencing procedures and platforms, as well as bioinformatic analysis and quality control measures may strongly affect the microbiome composition results obtained in different laboratories. To systematically evaluate the comparability of results and identify the most influential methodological factors affecting these differences, identical human stool sample replicates spiked with quantified marker bacteria, and their subsequent DNA sequences were analyzed by nine different centers in an external quality assessment (EQA). While high intra-center reproducibility was observed in repetitive tests, significant inter-center differences of reported microbiota composition were obtained. All steps of the complex analysis workflow significantly influenced microbiome profiles, but the magnitude of variation caused by PCR primers for 16S rDNA amplification was clearly the largest. In order to advance microbiome research to a more standardized and routine medical diagnostic procedure, it is essential to establish uniform standard operating procedures throughout laboratories and to initiate regular proficiency testing.

  19. High resolution genome wide binding event finding and motif discovery reveals transcription factor spatial binding constraints.

    Directory of Open Access Journals (Sweden)

    Yuchun Guo

    Full Text Available An essential component of genome function is the syntax of genomic regulatory elements that determine how diverse transcription factors interact to orchestrate a program of regulatory control. A precise characterization of in vivo spacing constraints between key transcription factors would reveal key aspects of this genomic regulatory language. To discover novel transcription factor spatial binding constraints in vivo, we developed a new integrative computational method, genome wide event finding and motif discovery (GEM. GEM resolves ChIP data into explanatory motifs and binding events at high spatial resolution by linking binding event discovery and motif discovery with positional priors in the context of a generative probabilistic model of ChIP data and genome sequence. GEM analysis of 63 transcription factors in 214 ENCODE human ChIP-Seq experiments recovers more known factor motifs than other contemporary methods, and discovers six new motifs for factors with unknown binding specificity. GEM's adaptive learning of binding-event read distributions allows it to further improve upon previous methods for processing ChIP-Seq and ChIP-exo data to yield unsurpassed spatial resolution and discovery of closely spaced binding events of the same factor. In a systematic analysis of in vivo sequence-specific transcription factor binding using GEM, we have found hundreds of spatial binding constraints between factors. GEM found 37 examples of factor binding constraints in mouse ES cells, including strong distance-specific constraints between Klf4 and other key regulatory factors. In human ENCODE data, GEM found 390 examples of spatially constrained pair-wise binding, including such novel pairs as c-Fos:c-Jun/USF1, CTCF/Egr1, and HNF4A/FOXA1. The discovery of new factor-factor spatial constraints in ChIP data is significant because it proposes testable models for regulatory factor interactions that will help elucidate genome function and the

  20. High resolution genome wide binding event finding and motif discovery reveals transcription factor spatial binding constraints.

    Science.gov (United States)

    Guo, Yuchun; Mahony, Shaun; Gifford, David K

    2012-01-01

    An essential component of genome function is the syntax of genomic regulatory elements that determine how diverse transcription factors interact to orchestrate a program of regulatory control. A precise characterization of in vivo spacing constraints between key transcription factors would reveal key aspects of this genomic regulatory language. To discover novel transcription factor spatial binding constraints in vivo, we developed a new integrative computational method, genome wide event finding and motif discovery (GEM). GEM resolves ChIP data into explanatory motifs and binding events at high spatial resolution by linking binding event discovery and motif discovery with positional priors in the context of a generative probabilistic model of ChIP data and genome sequence. GEM analysis of 63 transcription factors in 214 ENCODE human ChIP-Seq experiments recovers more known factor motifs than other contemporary methods, and discovers six new motifs for factors with unknown binding specificity. GEM's adaptive learning of binding-event read distributions allows it to further improve upon previous methods for processing ChIP-Seq and ChIP-exo data to yield unsurpassed spatial resolution and discovery of closely spaced binding events of the same factor. In a systematic analysis of in vivo sequence-specific transcription factor binding using GEM, we have found hundreds of spatial binding constraints between factors. GEM found 37 examples of factor binding constraints in mouse ES cells, including strong distance-specific constraints between Klf4 and other key regulatory factors. In human ENCODE data, GEM found 390 examples of spatially constrained pair-wise binding, including such novel pairs as c-Fos:c-Jun/USF1, CTCF/Egr1, and HNF4A/FOXA1. The discovery of new factor-factor spatial constraints in ChIP data is significant because it proposes testable models for regulatory factor interactions that will help elucidate genome function and the implementation of combinatorial

  1. Development of a Body Image Concern Scale using both exploratory and confirmatory factor analyses in Chinese university students

    Directory of Open Access Journals (Sweden)

    He W

    2017-05-01

    Full Text Available Wenxin He, Qiming Zheng, Yutian Ji, Chanchan Shen, Qisha Zhu, Wei Wang Department of Clinical Psychology and Psychiatry, School of Public Health, Zhejiang University College of Medicine, Hangzhou, People’s Republic of China Background: The body dysmorphic disorder is prevalent in general population and in psychiatric, dermatological, and plastic-surgery patients, but there lacks a structure-validated, comprehensive self-report measure of body image concerns, which is established through both exploratory and confirmatory factor analyses. Methods: We have composed a 34-item matrix targeting the body image concerns and trialed it in 328 male and 365 female Chinese university students. Answers to the matrix dealt with treatments including exploratory factor analyses, reserve of qualified items, and confirmatory factor analyses of latent structures. Results: Six latent factors, namely the Social Avoidance, Appearance Dissatisfaction, Preoccupation with Reassurance, Perceived Distress/Discrimination, Defect Hiding, and Embarrassment in Public, were identified. The factors and their respective items have composed a 24-item questionnaire named as the Body Image Concern Scale. Each factor earned a satisfactory internal reliability, and the intercorrelations between these factors were in a median level. Women scored significantly higher than men did on the Appearance Dissatisfaction, Preoccupation with Reassurance, and Defect Hiding. Conclusion: The Body Image Concern Scale has displayed its structure validation and gender preponderance in Chinese university students. Keywords: body dysmorphic disorder, body image, factor analysis, questionnaire development

  2. Quality assessment and factor analysis of systematic reviews and meta-analyses of endoscopic ultrasound diagnosis.

    Directory of Open Access Journals (Sweden)

    Danlu Liu

    Full Text Available Comprehensive monitoring of the quality of systematic reviews (SRs and meta-analyses (MAs of endoscopic ultrasound (EUS requires complete and accurate reporting and methodology.To assess the reporting and methodological quality of SRs/MAs on EUS diagnosis and to explore the potential factors influencing articles' quality.The quality of the reporting and methodology was evaluated in relation to the adherence of papers to the PRISMA checklist and the AMSTAR quality scale. The total scores for every criterion and for every article on the two standards were calculated. Data were evaluated and analyzed using SPSS17.0 and RevMan 5.1 in terms of publication time, category of reviews, category of journals, and funding resource.A total of 72 SRs/MAs was included, but no Cochrane Systematic Reviews (CSRs were obtained. The number of SRs/MAs ranged from 1 in 1998 to 15 in 2013; 88.1% used the QUADAS tool; the average overall scores by PRISMA statement and AMSTAR tool were 19.9 and 5.4, respectively. Scores on some items showed substantial improvement after publication of PRISMA and AMSTAR. However, no reviews followed the criterion of protocol and registration, and only 11.1% of articles fulfilled the criterion of literature search. SRs/MAs from the Science Citation Index (SCI were of better quality than non-SCI studies. Funding resource made no difference to quality. Regression analysis showed that time of publication and inclusion in the SCI were significantly correlated with total scores on the two standards.The reporting and methodological quality of SRs/MAs on EUS diagnosis has improved measurably since PRISMA and AMSTAR checklists released. It is hoped that CSR in this field will be produced. Literature searching and protocol criteria, as well as QUADAS-2 tool need to be addressed more in the future. Time of publication and SCI relate more to the overall quality of SRs/MAs than does funding resource.

  3. Exploratory and Confirmatory Factor Analyses of the WISC-IV with Gifted Students

    Science.gov (United States)

    Rowe, Ellen W.; Dandridge, Jessica; Pawlush, Alexandra; Thompson, Dawna F.; Ferrier, David E.

    2014-01-01

    These 2 studies investigated the factor structure of the Wechsler Intelligence Scale for Children-4th edition (WISC-IV; Wechsler, 2003a) with exploratory factor analysis (EFA; Study 1) and confirmatory factor analysis (CFA; Study 2) among 2 independent samples of gifted students. The EFA sample consisted of 225 children who were referred for a…

  4. Investigation of the factor structure of the Wechsler Adult Intelligence Scale--Fourth Edition (WAIS-IV): exploratory and higher order factor analyses.

    Science.gov (United States)

    Canivez, Gary L; Watkins, Marley W

    2010-12-01

    The present study examined the factor structure of the Wechsler Adult Intelligence Scale--Fourth Edition (WAIS-IV; D. Wechsler, 2008a) standardization sample using exploratory factor analysis, multiple factor extraction criteria, and higher order exploratory factor analysis (J. Schmid & J. M. Leiman, 1957) not included in the WAIS-IV Technical and Interpretation Manual (D. Wechsler, 2008b). Results indicated that the WAIS-IV subtests were properly associated with the theoretically proposed first-order factors, but all but one factor-extraction criterion recommended extraction of one or two factors. Hierarchical exploratory analyses with the Schmid and Leiman procedure found that the second-order g factor accounted for large portions of total and common variance, whereas the four first-order factors accounted for small portions of total and common variance. It was concluded that the WAIS-IV provides strong measurement of general intelligence, and clinical interpretation should be primarily at that level.

  5. Genetic Analyses and Simulations of Larval Dispersal Reveal Distinct Populations and Directional Connectivity across the Range of the Hawaiian Grouper (Epinephelus quernus

    Directory of Open Access Journals (Sweden)

    Malia Ana J. Rivera

    2011-01-01

    Full Text Available Integration of ecological and genetic data to study patterns of biological connectivity can aid in ecosystem-based management. Here we investigated connectivity of the Hawaiian grouper Epinephelus quernus, a species of management concern within the Main Hawaiian Islands (MHI, by comparing genetic analyses with simulated larval dispersal patterns across the species range in the Hawaiian Archipelago and Johnston Atoll. Larval simulations revealed higher dispersal from the MHI to the Northwestern Hawaiian Islands (NWHI than in the opposite direction and evidence for a dispersal corridor between Johnston and the middle of the Hawaiian Archipelago. Genetic analyses using mitochondrial DNA (mtDNA control region sequences and microsatellites revealed relatively high connectivity across the Hawaiian Archipelago, with the exception of genetically distinct populations and higher mtDNA diversity in the mid-Archipelago. These analyses support the preservation of the mid-archipelago as a source of genetic diversity and a region of connectivity with locations outside the Hawaiian Archipelago. Additionally, our evidence for directional dispersal away from the MHI lends caution to any management decisions that would rely on the NWHI replenishing depleted MHI stocks.

  6. Impact of cardiovascular risk factors on medical expenditure: evidence from epidemiological studies analysing data on health checkups and medical insurance.

    Science.gov (United States)

    Nakamura, Koshi

    2014-01-01

    Concerns have increasingly been raised about the medical economic burden in Japan, of which approximately 20% is attributable to cardiovascular disease, including coronary heart disease and stroke. Because the management of risk factors is essential for the prevention of cardiovascular disease, it is important to understand the relationship between cardiovascular risk factors and medical expenditure in the Japanese population. However, only a few Japanese epidemiological studies analysing data on health checkups and medical insurance have provided evidence on this topic. Patients with cardiovascular risk factors, including obesity, hypertension, and diabetes, may incur medical expenditures through treatment of the risk factors themselves and through procedures for associated diseases that usually require hospitalization and sometimes result in death. Untreated risk factors may cause medical expenditure surges, mainly due to long-term hospitalization, more often than risk factors preventively treated by medication. On an individual patient level, medical expenditures increase with the number of concomitant cardiovascular risk factors. For single risk factors, personal medical expenditure may increase with the severity of that factor. However, on a population level, the medical economic burden attributable to cardiovascular risk factors results largely from a single, particularly prevalent risk factor, especially from mildly-to-moderately abnormal levels of the factor. Therefore, cardiovascular risk factors require management on the basis of both a cost-effective strategy of treating high-risk patients and a population strategy for reducing both the ill health and medical economic burdens that result from cardiovascular disease.

  7. Substrate recognition by complement convertases revealed in the C5-cobra venom factor complex

    DEFF Research Database (Denmark)

    Laursen, Nick Stub; Andersen, Kasper Røjkjær; Braren, Ingke

    2011-01-01

    with a protease subunit (Bb or C2a). We determined the crystal structures of the C3b homologue cobra venom factor (CVF) in complex with C5, and in complex with C5 and the inhibitor SSL7 at 4.3 Å resolution. The structures reveal a parallel two-point attachment between C5 and CVF, where the presence of SSL7 only...

  8. Comparative "-omics" in Mycoplasma pneumoniae Clinical Isolates Reveals Key Virulence Factors.

    Directory of Open Access Journals (Sweden)

    Maria Lluch-Senar

    Full Text Available The human respiratory tract pathogen M. pneumoniae is one of the best characterized minimal bacterium. Until now, two main groups of clinical isolates of this bacterium have been described (types 1 and 2, differing in the sequence of the P1 adhesin gene. Here, we have sequenced the genomes of 23 clinical isolates of M. pneumoniae. Studying SNPs, non-synonymous mutations, indels and genome rearrangements of these 23 strains and 4 previously sequenced ones, has revealed new subclasses in the two main groups, some of them being associated with the country of isolation. Integrative analysis of in vitro gene essentiality and mutation rates enabled the identification of several putative virulence factors and antigenic proteins; revealing recombination machinery, glycerol metabolism and peroxide production as possible factors in the genetics and physiology of these pathogenic strains. Additionally, the transcriptomes and proteomes of two representative strains, one from each of the two main groups, have been characterized to evaluate the impact of mutations on RNA and proteins levels. This study has revealed that type 2 strains show higher expression levels of CARDS toxin, a protein recently shown to be one of the major factors of inflammation. Thus, we propose that type 2 strains could be more toxigenic than type 1 strains of M. pneumoniae.

  9. Factors for analysing and improving performance of R&D in Malaysian universities

    NARCIS (Netherlands)

    Ramli, Mohammad Shakir; de Boer, S.J.; de Bruijn, E.J.

    2004-01-01

    This paper presents a model for analysing and improving performance of R&D in Malaysian universities. There are various general models for R&D analysis, but none is specific for improving the performance of R&D in Malaysian universities. This research attempts to fill a gap in the body of knowledge

  10. Quantitative Analyses in a Multivariate Study of Language Attrition: The Impact of Extralinguistic Factors

    Science.gov (United States)

    Schmid, Monika S.; Dusseldorp, Elise

    2010-01-01

    Most linguistic processes--acquisition, change, deterioration--take place in and are determined by a complex and multifactorial web of language internal and language external influences. This implies that the impact of each individual factor can only be determined on the basis of a careful consideration of its interplay with all other factors. The…

  11. Global deprivation of brain-derived neurotrophic factor in the CNS reveals an area-specific requirement for dendritic growth.

    Science.gov (United States)

    Rauskolb, Stefanie; Zagrebelsky, Marta; Dreznjak, Anita; Deogracias, Rubén; Matsumoto, Tomoya; Wiese, Stefan; Erne, Beat; Sendtner, Michael; Schaeren-Wiemers, Nicole; Korte, Martin; Barde, Yves-Alain

    2010-02-03

    Although brain-derived neurotrophic factor (BDNF) is linked with an increasing number of conditions causing brain dysfunction, its role in the postnatal CNS has remained difficult to assess. This is because the bdnf-null mutation causes the death of the animals before BDNF levels have reached adult levels. In addition, the anterograde axonal transport of BDNF complicates the interpretation of area-specific gene deletion. The present study describes the generation of a new conditional mouse mutant essentially lacking BDNF throughout the CNS. It shows that BDNF is not essential for prolonged postnatal survival, but that the behavior of such mutant animals is markedly altered. It also reveals that BDNF is not a major survival factor for most CNS neurons and for myelination of their axons. However, it is required for the postnatal growth of the striatum, and single-cell analyses revealed a marked decreased in dendritic complexity and spine density. In contrast, BDNF is dispensable for the growth of the hippocampus and only minimal changes were observed in the dendrites of CA1 pyramidal neurons in mutant animals. Spine density remained unchanged, whereas the proportion of the mushroom-type spine was moderately decreased. In line with these in vivo observations, we found that BDNF markedly promotes the growth of cultured striatal neurons and of their dendrites, but not of those of hippocampal neurons, suggesting that the differential responsiveness to BDNF is part of a neuron-intrinsic program.

  12. A multi-scale model of hepcidin promoter regulation reveals factors controlling systemic iron homeostasis.

    Directory of Open Access Journals (Sweden)

    Guillem Casanovas

    2014-01-01

    Full Text Available Systemic iron homeostasis involves a negative feedback circuit in which the expression level of the peptide hormone hepcidin depends on and controls the iron blood levels. Hepcidin expression is regulated by the BMP6/SMAD and IL6/STAT signaling cascades. Deregulation of either pathway causes iron-related diseases such as hemochromatosis or anemia of inflammation. We quantitatively analyzed how BMP6 and IL6 control hepcidin expression. Transcription factor (TF phosphorylation and reporter gene expression were measured under co-stimulation conditions, and the promoter was perturbed by mutagenesis. Using mathematical modeling, we systematically analyzed potential mechanisms of cooperative and competitive promoter regulation by the transcription factors, and experimentally validated the model predictions. Our results reveal that hepcidin cross-regulation primarily occurs by combinatorial transcription factor binding to the promoter, whereas signaling crosstalk is insignificant. We find that the presence of two BMP-responsive elements enhances the steepness of the promoter response towards the iron-sensing BMP signaling axis, which promotes iron homeostasis in vivo. IL6 co-stimulation reduces the promoter sensitivity towards the BMP signal, because the SMAD and STAT transcription factors compete for recruiting RNA polymerase to the transcription start site. This may explain why inflammatory signals disturb iron homeostasis in anemia of inflammation. Taken together, our results reveal why the iron homeostasis circuit is sensitive to perturbations implicated in disease.

  13. Who will volunteer? Analysing individual and structural factors of volunteering in Swiss sports clubs.

    Science.gov (United States)

    Schlesinger, Torsten; Nagel, Siegfried

    2013-01-01

    This article analyses the conditions influencing volunteering in sports clubs. It focuses not only on individual characteristics of volunteers but also on the corresponding structural conditions of sports clubs. It proposes a model of voluntary work in sports clubs based on economic behaviour theory. The influences of both the individual and context levels on the decision to engage in voluntary work are estimated in different multilevel models. Results of these multilevel analyses indicate that volunteering is not just an outcome of individual characteristics such as lower workloads, higher income, children belonging to the sports club, longer club memberships, or a strong commitment to the club. It is also influenced by club-specific structural conditions; volunteering is more probable in rural sports clubs whereas growth-oriented goals in clubs have a destabilising effect.

  14. Analyses of in vivo interactions between transcription factors and the archaeal RNA polymerase.

    Science.gov (United States)

    Walker, Julie E; Santangelo, Thomas J

    2015-09-15

    Transcription factors regulate the activities of RNA polymerase (RNAP) at each stage of the transcription cycle. Many basal transcription factors with common ancestry are employed in eukaryotic and archaeal systems that directly bind to RNAP and influence intramolecular movements of RNAP and modulate DNA or RNA interactions. We describe and employ a flexible methodology to directly probe and quantify the binding of transcription factors to RNAP in vivo. We demonstrate that binding of the conserved and essential archaeal transcription factor TFE to the archaeal RNAP is directed, in part, by interactions with the RpoE subunit of RNAP. As the surfaces involved are conserved in many eukaryotic and archaeal systems, the identified TFE-RNAP interactions are likely conserved in archaeal-eukaryal systems and represent an important point of contact that can influence the efficiency of transcription initiation.

  15. Mitochondrial dysfunction, oxidative stress and apoptosis revealed by proteomic and transcriptomic analyses of the striata in two mouse models of Parkinson’s disease

    Energy Technology Data Exchange (ETDEWEB)

    Chin, Mark H.; Qian, Weijun; Wang, Haixing; Petyuk, Vladislav A.; Bloom, Joshua S.; Sforza, Daniel M.; Lacan, Goran; Liu, Dahai; Khan, Arshad H.; Cantor, Rita M.; Bigelow, Diana J.; Melega, William P.; Camp, David G.; Smith, Richard D.; Smith, Desmond J.

    2008-02-10

    The molecular mechanisms underlying the changes in the nigrostriatal pathway in Parkinson disease (PD) are not completely understood. Here we use mass spectrometry and microarrays to study the proteomic and transcriptomic changes in the striatum of two mouse models of PD, induced by the distinct neurotoxins 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and methamphetamine (METH). Proteomic analyses resulted in the identification and relative quantification of 912 proteins with two or more unique peptides and 85 proteins with significant abundance changes following neurotoxin treatment. Similarly, microarray analyses revealed 181 genes with significant changes in mRNA following neurotoxin treatment. The combined protein and gene list provides a clearer picture of the potential mechanisms underlying neurodegeneration observed in PD. Functional analysis of this combined list revealed a number of significant categories, including mitochondrial dysfunction, oxidative stress response and apoptosis. Additionally, codon usage and miRNAs may play an important role in translational control in the striatum. These results constitute one of the largest datasets integrating protein and transcript changes for these neurotoxin models with many similar endpoint phenotypes but distinct mechanisms.

  16. Complete genomic sequence analyses of the first group A giraffe rotavirus reveals close evolutionary relationship with rotaviruses infecting other members of the Artiodactyla.

    Science.gov (United States)

    O'Shea, Helen; Mulherin, Emily; Matthijnssens, Jelle; McCusker, Matthew P; Collins, P J; Cashman, Olivia; Gunn, Lynda; Beltman, Marijke E; Fanning, Séamus

    2014-05-14

    Group A Rotaviruses (RVA) have been established as significant contributory agents of acute gastroenteritis in young children and many animal species. In 2008, we described the first RVA strain detected in a giraffe calf (RVA/Giraffe-wt/IRL/GirRV/2008/G10P[11]), presenting with acute diarrhoea. Molecular characterisation of the VP7 and VP4 genes revealed the bovine-like genotypes G10 and P[11], respectively. To further investigate the origin of this giraffe RVA strain, the 9 remaining gene segments were sequenced and analysed, revealing the following genotype constellation: G10-P[11]-I2-R2-C2-M2-A3-N2-T6-E2-H3. This genotype constellation is very similar to RVA strains isolated from cattle or other members of the artiodactyls. Phylogenetic analyses confirmed the close relationship between GirRV and RVA strains with a bovine-like genotype constellation detected from several host species, including humans. These results suggest that RVA strain GirRV was the result of an interspecies transmission from a bovine host to the giraffe calf. However, we cannot rule out completely that this bovine-like RVA genotype constellation may be enzootic in giraffes. Future RVA surveillance in giraffes may answer this intriguing question.

  17. Lessons for public health campaigns from analysing commercial food marketing success factors: a case study

    Directory of Open Access Journals (Sweden)

    Aschemann-Witzel Jessica

    2012-02-01

    Full Text Available Abstract Background Commercial food marketing has considerably shaped consumer food choice behaviour. Meanwhile, public health campaigns for healthier eating have had limited impact to date. Social marketing suggests that successful commercial food marketing campaigns can provide useful lessons for public sector activities. The aim of the present study was to empirically identify food marketing success factors that, using the social marketing approach, could help improve public health campaigns to promote healthy eating. Methods In this case-study analysis, 27 recent and successful commercial food and beverage marketing cases were purposively sampled from different European countries. The cases involved different consumer target groups, product categories, company sizes and marketing techniques. The analysis focused on cases of relatively healthy food types, and nutrition and health-related aspects in the communication related to the food. Visual as well as written material was gathered, complemented by semi-structured interviews with 12 food market trend experts and 19 representatives of food companies and advertising agencies. Success factors were identified by a group of experts who reached consensus through discussion structured by a card sorting method. Results Six clusters of success factors emerged from the analysis and were labelled as "data and knowledge", "emotions", "endorsement", "media", "community" and "why and how". Each cluster subsumes two or three success factors and is illustrated by examples. In total, 16 factors were identified. It is argued that the factors "nutritional evidence", "trend awareness", "vertical endorsement", "simple naturalness" and "common values" are of particular importance in the communication of health with regard to food. Conclusions The present study identified critical factors for the success of commercial food marketing campaigns related to the issue of nutrition and health, which are possibly

  18. Lessons for public health campaigns from analysing commercial food marketing success factors: a case study.

    Science.gov (United States)

    Aschemann-Witzel, Jessica; Perez-Cueto, Federico J A; Niedzwiedzka, Barbara; Verbeke, Wim; Bech-Larsen, Tino

    2012-02-21

    Commercial food marketing has considerably shaped consumer food choice behaviour. Meanwhile, public health campaigns for healthier eating have had limited impact to date. Social marketing suggests that successful commercial food marketing campaigns can provide useful lessons for public sector activities. The aim of the present study was to empirically identify food marketing success factors that, using the social marketing approach, could help improve public health campaigns to promote healthy eating. In this case-study analysis, 27 recent and successful commercial food and beverage marketing cases were purposively sampled from different European countries. The cases involved different consumer target groups, product categories, company sizes and marketing techniques. The analysis focused on cases of relatively healthy food types, and nutrition and health-related aspects in the communication related to the food. Visual as well as written material was gathered, complemented by semi-structured interviews with 12 food market trend experts and 19 representatives of food companies and advertising agencies. Success factors were identified by a group of experts who reached consensus through discussion structured by a card sorting method. Six clusters of success factors emerged from the analysis and were labelled as "data and knowledge", "emotions", "endorsement", "media", "community" and "why and how". Each cluster subsumes two or three success factors and is illustrated by examples. In total, 16 factors were identified. It is argued that the factors "nutritional evidence", "trend awareness", "vertical endorsement", "simple naturalness" and "common values" are of particular importance in the communication of health with regard to food. The present study identified critical factors for the success of commercial food marketing campaigns related to the issue of nutrition and health, which are possibly transferable to the public health sector. Whether or not a particular

  19. Lessons for public health campaigns from analysing commercial food marketing success factors: a case study

    Science.gov (United States)

    2012-01-01

    Background Commercial food marketing has considerably shaped consumer food choice behaviour. Meanwhile, public health campaigns for healthier eating have had limited impact to date. Social marketing suggests that successful commercial food marketing campaigns can provide useful lessons for public sector activities. The aim of the present study was to empirically identify food marketing success factors that, using the social marketing approach, could help improve public health campaigns to promote healthy eating. Methods In this case-study analysis, 27 recent and successful commercial food and beverage marketing cases were purposively sampled from different European countries. The cases involved different consumer target groups, product categories, company sizes and marketing techniques. The analysis focused on cases of relatively healthy food types, and nutrition and health-related aspects in the communication related to the food. Visual as well as written material was gathered, complemented by semi-structured interviews with 12 food market trend experts and 19 representatives of food companies and advertising agencies. Success factors were identified by a group of experts who reached consensus through discussion structured by a card sorting method. Results Six clusters of success factors emerged from the analysis and were labelled as "data and knowledge", "emotions", "endorsement", "media", "community" and "why and how". Each cluster subsumes two or three success factors and is illustrated by examples. In total, 16 factors were identified. It is argued that the factors "nutritional evidence", "trend awareness", "vertical endorsement", "simple naturalness" and "common values" are of particular importance in the communication of health with regard to food. Conclusions The present study identified critical factors for the success of commercial food marketing campaigns related to the issue of nutrition and health, which are possibly transferable to the public health

  20. Integrated in silico Analyses of Regulatory and Metabolic Networks of Synechococcus sp. PCC 7002 Reveal Relationships between Gene Centrality and Essentiality

    Directory of Open Access Journals (Sweden)

    Hyun-Seob Song

    2015-03-01

    Full Text Available Cyanobacteria dynamically relay environmental inputs to intracellular adaptations through a coordinated adjustment of photosynthetic efficiency and carbon processing rates. The output of such adaptations is reflected through changes in transcriptional patterns and metabolic flux distributions that ultimately define growth strategy. To address interrelationships between metabolism and regulation, we performed integrative analyses of metabolic and gene co-expression networks in a model cyanobacterium, Synechococcus sp. PCC 7002. Centrality analyses using the gene co-expression network identified a set of key genes, which were defined here as “topologically important.” Parallel in silico gene knock-out simulations, using the genome-scale metabolic network, classified what we termed as “functionally important” genes, deletion of which affected growth or metabolism. A strong positive correlation was observed between topologically and functionally important genes. Functionally important genes exhibited variable levels of topological centrality; however, the majority of topologically central genes were found to be functionally essential for growth. Subsequent functional enrichment analysis revealed that both functionally and topologically important genes in Synechococcus sp. PCC 7002 are predominantly associated with translation and energy metabolism, two cellular processes critical for growth. This research demonstrates how synergistic network-level analyses can be used for reconciliation of metabolic and gene expression data to uncover fundamental biological principles.

  1. A quantitative method to analyse an open-ended questionnaire: A case study about the Boltzmann Factor

    Science.gov (United States)

    Rosario Battaglia, Onofrio; Di Paola, Benedetto

    2016-05-01

    This paper describes a quantitative method to analyse an open-ended questionnaire. Student responses to a specially designed written questionnaire are quantitatively analysed by not hierarchical clustering called k -means method. Through this we can characterise behaviour students with respect their expertise to formulate explanations for phenomena or processes and/or use a given model in the different context. The physics topic is about the Boltzmann Factor, which allows the students to have a unifying view of different phenomena in different contexts.

  2. Personality Assessment Through Internet: Factor Analyses By Age Group Of The Zka Personality Questionnaire

    Directory of Open Access Journals (Sweden)

    Angel Blanch

    2013-12-01

    Full Text Available This study evaluated the psychometric properties of an on-line version of the Zuckerman-Kuhlman-Aluja Personality Questionnaire (ZKA-PQ by sex and age. The questionnaire was responded by 1598 people, 474 males and 1124 females, with a mean age of 32.57 (SD = 11.72. Males and females differed in their responses to all personality dimensions evaluated by this instrument, in a similar way as that reported in past research. In addition, younger people scored higher in the Aggressiveness factor, especially concerning the Physical Aggression facet, whereas older people scored higher in the Activity factor. Besides, younger people scored higher in the Neuroticism and the Sensation Seeking factors, even though there were no age differences in the Extraversion factor. The ZKA-PQ five-factor structure was clear and yielded high congruence coefficients with the original Spanish validation sample. Altogether, the findings support the validity of the online version of this instrument. The ZKAPQ online version is therefore helpful in both, basic and applied research settings about human personality and individual differences.

  3. A Systematic Analysis of Factors Localized to Damaged Chromatin Reveals PARP-Dependent Recruitment of Transcription Factors

    Directory of Open Access Journals (Sweden)

    Lior Izhar

    2015-06-01

    Full Text Available Localization to sites of DNA damage is a hallmark of DNA damage response (DDR proteins. To identify DDR factors, we screened epitope-tagged proteins for localization to sites of chromatin damaged by UV laser microirradiation and found >120 proteins that localize to damaged chromatin. These include the BAF tumor suppressor complex and the amyotrophic lateral sclerosis (ALS candidate protein TAF15. TAF15 contains multiple domains that bind damaged chromatin in a poly-(ADP-ribose polymerase (PARP-dependent manner, suggesting a possible role as glue that tethers multiple PAR chains together. Many positives were transcription factors; > 70% of randomly tested transcription factors localized to sites of DNA damage, and of these, ∼90% were PARP dependent for localization. Mutational analyses showed that localization to damaged chromatin is DNA-binding-domain dependent. By examining Hoechst staining patterns at damage sites, we see evidence of chromatin decompaction that is PARP dependent. We propose that PARP-regulated chromatin remodeling at sites of damage allows transient accessibility of DNA-binding proteins.

  4. Statistical Analyses of Scatterplots to Identify Important Factors in Large-Scale Simulations

    Energy Technology Data Exchange (ETDEWEB)

    Kleijnen, J.P.C.; Helton, J.C.

    1999-04-01

    The robustness of procedures for identifying patterns in scatterplots generated in Monte Carlo sensitivity analyses is investigated. These procedures are based on attempts to detect increasingly complex patterns in the scatterplots under consideration and involve the identification of (1) linear relationships with correlation coefficients, (2) monotonic relationships with rank correlation coefficients, (3) trends in central tendency as defined by means, medians and the Kruskal-Wallis statistic, (4) trends in variability as defined by variances and interquartile ranges, and (5) deviations from randomness as defined by the chi-square statistic. The following two topics related to the robustness of these procedures are considered for a sequence of example analyses with a large model for two-phase fluid flow: the presence of Type I and Type II errors, and the stability of results obtained with independent Latin hypercube samples. Observations from analysis include: (1) Type I errors are unavoidable, (2) Type II errors can occur when inappropriate analysis procedures are used, (3) physical explanations should always be sought for why statistical procedures identify variables as being important, and (4) the identification of important variables tends to be stable for independent Latin hypercube samples.

  5. Prospective Analyses of Childhood Factors and Antisocial Behavior for Students with High-Incidence Disabilities

    Science.gov (United States)

    Chen, Chin-Chih; Symons, Frank J.; Reynolds, Arthur J.

    2011-01-01

    This prospective longitudinal study investigated the association between childhood factors (individual, family, and school characteristics) and later antisocial behavior (official juvenile delinquency and adult crime) for students identified with high-incidence disabilities (i.e., learning disabilities, emotional disturbance). The sample consisted…

  6. Structural, functional, and genetic analyses of the actinobacterial transcription factor RbpA.

    Science.gov (United States)

    Hubin, Elizabeth A; Tabib-Salazar, Aline; Humphrey, Laurence J; Flack, Joshua E; Olinares, Paul Dominic B; Darst, Seth A; Campbell, Elizabeth A; Paget, Mark S

    2015-06-01

    Gene expression is highly regulated at the step of transcription initiation, and transcription activators play a critical role in this process. RbpA, an actinobacterial transcription activator that is essential in Mycobacterium tuberculosis (Mtb), binds selectively to group 1 and certain group 2 σ-factors. To delineate the molecular mechanism of RbpA, we show that the Mtb RbpA σ-interacting domain (SID) and basic linker are sufficient for transcription activation. We also present the crystal structure of the Mtb RbpA-SID in complex with domain 2 of the housekeeping σ-factor, σ(A). The structure explains the basis of σ-selectivity by RbpA, showing that RbpA interacts with conserved regions of σ(A) as well as the nonconserved region (NCR), which is present only in housekeeping σ-factors. Thus, the structure is the first, to our knowledge, to show a protein interacting with the NCR of a σ-factor. We confirm the basis of selectivity and the observed interactions using mutagenesis and functional studies. In addition, the structure allows for a model of the RbpA-SID in the context of a transcription initiation complex. Unexpectedly, the structural modeling suggests that RbpA contacts the promoter DNA, and we present in vivo and in vitro studies supporting this finding. Our combined data lead to a better understanding of the mechanism of RbpA function as a transcription activator.

  7. Mutational analyses of epidermal growth factor receptor and downstream pathways in adrenocortical carcinoma

    NARCIS (Netherlands)

    Hermsen, I.G.; Haak, H.R.; Krijger, R.R. de; Kerkhofs, T.M.; Feelders, R.A.; Herder, W.W. de; Wilmink, H.; Smit, J.W.A.; Gelderblom, H.; Miranda, N.F. de; Eijk, R. van; Wezel, T. van; Morreau, H.

    2013-01-01

    BACKGROUND: Adrenocortical carcinoma (ACC) is a rare disease with a poor prognosis and limited therapeutic options. Mitotane is considered the standard first-line therapy with only 30% of the patients showing objective tumour response. Defining predictive factors for response is therefore of clinica

  8. Cluster and factor analyses using water quality data in the Sapkyo reservoir watershed

    Energy Technology Data Exchange (ETDEWEB)

    Rim, Chang-Soo [Chungwoon University, Hongsung(Korea); Shin, Jae-Ki [Inje University, Kimhae(Korea)

    2002-04-30

    The monthly water quality data measured at 19 stations located in the Sapkyo reservoir watershed were clustered into 2 to 7 clusters and factor analysis was conducted to characterize the water quality, using the information obtained from cluster analysis. The result of cluster analysis shows that Sapkyo reservoir and each stream (Sapkyo stream, Muhan stream and Kokkyo stream) in Sapkyo reservoir watershed have their own water quality characteristics. The result of water quality analysis indicates that the concentration of suspended solids from Sapkyo reservoir is much higher than those of other streams, and which is probably because of increment of phytoplankton biomass with rich nutrient flowing into Sapkyo reservoir from the upper stream of watershed. Furthermore, the concentrations of biochemical oxygen demand and chemical oxygen demand were 3.5 to 4.8 times and 1.7 to 2.5 times those of other streams, respectively. The overall water quality of Sapkyo reservoir watershed was considered to exceed eutrophic condition. Based on factor analysis, the water quality characteristics of Sapkyo stream and Muhan stream were closely related with farm land and residence. The water quality of Kokkyo stream was influenced by superabundant organic matter flowing from Chonan city and district wastewater treatment plant located in the upper stream of Kokkyo stream. The water quality factor influencing Sapkyo reservoir was closely related with water quality factors of other three streams. (author). 20 refs., 6 tabs., 3 figs.

  9. Meta-analyses of Big Six Interests and Big Five Personality Factors.

    Science.gov (United States)

    Larson, Lisa M.; Rottinghaus, Patrick J.; Borgen, Fred H.

    2002-01-01

    Meta-analysis of 24 samples demonstrated overlap between Holland's vocational interest domains (measured by Self Directed Search, Strong Interest Inventory, and Vocational Preference Inventory) and Big Five personality factors (measured by Revised NEO Personalty Inventory). The link is stronger for five interest-personality pairs:…

  10. Quantitative analyses in a multivariate study of language attrition : the impact of extralinguistic factors

    NARCIS (Netherlands)

    Schmid, Monika S.; Dusseldorp, Elise

    2010-01-01

    Most linguistic processes - acquisition, change, deterioration - take place in and are determined by a complex and multifactorial web of language internal and language external influences. This implies that the impact of each individual factor can only be determined on the basis of a careful conside

  11. Quantitative analyses in a multivariate study of language attrition: The impact of extralinguistic factors

    NARCIS (Netherlands)

    Schmid, M.S.; Dusseldorp, E.

    2010-01-01

    Most linguistic processes - acquisition, change, deterioration - take place in and are determined by a complex and multifactorial web of language internal and language external influences. This implies that the impact of each individual factor can only be determined on the basis of a careful conside

  12. Factors related to age at natural menopause: longitudinal analyses from SWAN.

    Science.gov (United States)

    Gold, Ellen B; Crawford, Sybil L; Avis, Nancy E; Crandall, Carolyn J; Matthews, Karen A; Waetjen, L Elaine; Lee, Jennifer S; Thurston, Rebecca; Vuga, Marike; Harlow, Siobán D

    2013-07-01

    Early age at the natural final menstrual period (FMP) or menopause has been associated with numerous health outcomes and might be a marker of future ill health. However, potentially modifiable factors affecting age at menopause have not been examined longitudinally in large, diverse populations. The Study of Women's Health Across the Nation (SWAN) followed 3,302 initially premenopausal and early perimenopausal women from 7 US sites and 5 racial/ethnic groups, using annual data (1996-2007) and Cox proportional hazards models to assess the relation of time-invariant and time-varying sociodemographic, lifestyle, and health factors to age at natural FMP. Median age at the FMP was 52.54 years (n = 1,483 observed natural FMPs). Controlling for sociodemographic, lifestyle, and health factors, we found that racial/ethnic groups did not differ in age at the FMP. Higher educational level, prior oral contraceptive use, and higher weight at baseline, as well as being employed, not smoking, consuming alcohol, having less physical activity, and having better self-rated health over follow-up, were significantly associated with later age at the FMP. These results suggest that age at the natural FMP reflects a complex interrelation of health and socioeconomic factors, which could partially explain the relation of late age at FMP to reduced morbidity and mortality.

  13. Comparative Factor Analyses of the Personal Attributes Questionnaire and the Bem Sex-Role Inventory.

    Science.gov (United States)

    Antill, John K.; Cunningham, John D.

    1982-01-01

    Compared the Personal Attributes Questionnaire (PAQ) and the Bem Sex Role Inventory (BSRI) as measures of androgyny. Results showed that femininty (Concern for Others) and masculinity (Dominance) accounted for most of the variance, but for PAQ, clusters of male- and female-valued items (i.e., Extroversion and Insecurity) formed subsidiary factors.…

  14. Demographic, socioeconomic, and behavioral factors affecting patterns of tooth decay in the permanent dentition: principal components and factor analyses.

    Science.gov (United States)

    Shaffer, John R; Polk, Deborah E; Feingold, Eleanor; Wang, Xiaojing; Cuenco, Karen T; Weeks, Daniel E; DeSensi, Rebecca S; Weyant, Robert J; Crout, Richard; McNeil, Daniel W; Marazita, Mary L

    2013-08-01

    Dental caries of the permanent dentition is a multifactorial disease resulting from the complex interplay of endogenous and environmental risk factors. The disease is not easily quantitated due to the innumerable possible combinations of carious lesions across individual tooth surfaces of the permanent dentition. Global measures of decay, such as the DMFS index (which was developed for surveillance applications), may not be optimal for studying the epidemiology of dental caries because they ignore the distinct patterns of decay across the dentition. We hypothesize that specific risk factors may manifest their effects on specific tooth surfaces leading to patterns of decay that can be identified and studied. In this study, we utilized two statistical methods of extracting patterns of decay from surface-level caries data to create novel phenotypes with which to study the risk factors affecting dental caries. Intra-oral dental examinations were performed on 1068 participants aged 18-75 years to assess dental caries. The 128 tooth surfaces of the permanent dentition were scored as carious or not and used as input for principal components analysis (PCA) and factor analysis (FA), two methods of identifying underlying patterns without a priori knowledge of the patterns. Demographic (age, sex, birth year, race/ethnicity, and educational attainment), anthropometric (height, body mass index, waist circumference), endogenous (saliva flow), and environmental (tooth brushing frequency, home water source, and home water fluoride) risk factors were tested for association with the caries patterns identified by PCA and FA, as well as DMFS, for comparison. The ten strongest patterns (i.e. those that explain the most variation in the data set) extracted by PCA and FA were considered. The three strongest patterns identified by PCA reflected (i) global extent of decay (i.e. comparable to DMFS index), (ii) pit and fissure surface caries and (iii) smooth surface caries, respectively. The

  15. Integrated transcript and genome analyses reveal NKX2-1 and MEF2C as potential oncogenes in T cell acute lymphoblastic leukemia.

    Science.gov (United States)

    Homminga, Irene; Pieters, Rob; Langerak, Anton W; de Rooi, Johan J; Stubbs, Andrew; Verstegen, Monique; Vuerhard, Maartje; Buijs-Gladdines, Jessica; Kooi, Clarissa; Klous, Petra; van Vlierberghe, Pieter; Ferrando, Adolfo A; Cayuela, Jean Michel; Verhaaf, Brenda; Beverloo, H Berna; Horstmann, Martin; de Haas, Valerie; Wiekmeijer, Anna-Sophia; Pike-Overzet, Karin; Staal, Frank J T; de Laat, Wouter; Soulier, Jean; Sigaux, Francois; Meijerink, Jules P P

    2011-04-12

    To identify oncogenic pathways in T cell acute lymphoblastic leukemia (T-ALL), we combined expression profiling of 117 pediatric patient samples and detailed molecular-cytogenetic analyses including the Chromosome Conformation Capture on Chip (4C) method. Two T-ALL subtypes were identified that lacked rearrangements of known oncogenes. One subtype associated with cortical arrest, expression of cell cycle genes, and ectopic NKX2-1 or NKX2-2 expression for which rearrangements were identified. The second subtype associated with immature T cell development and high expression of the MEF2C transcription factor as consequence of rearrangements of MEF2C, transcription factors that target MEF2C, or MEF2C-associated cofactors. We propose NKX2-1, NKX2-2, and MEF2C as T-ALL oncogenes that are activated by various rearrangements.

  16. Analysing the correlations of long-term seasonal water quality parameters, suspended solids and total dissolved solids in a shallow reservoir with meteorological factors.

    Science.gov (United States)

    Zhang, Chen; Zhang, Wenna; Huang, Yixuan; Gao, Xueping

    2017-03-01

    To explore the correlations among water quality parameters, suspended solids (SS) and total dissolved solids (TDS) with meteorological factors in a shallow reservoir in China, the long-term variations of water quality were considered. A non-parametric regression method, generalized additive models (GAM), was used to analyse the correlations among eleven physicochemical and biological parameters as well as three meteorological factors (wind speed, rainfall and solar radiation) which we collected from 2000 to 2011. The results indicate that the three meteorological factors may have positive effects on SS. Moreover, statistically significant correlations between many water quality parameters and SS or TDS were exhibited seasonally. The correlations between electrical conductivity (EC) and SS were opposite to correlations between EC and TDS. This finding reveals that TDS have a positive impact on EC, while EC negatively affects SS. The results indicated that many parameters, such as total nitrogen, total phosphorus, biological oxygen demand (BOD) and chemical oxygen demand (COD), were related to SS due to the adsorption of SS. Moreover, both positive and negative correlations between COD and TDS were observed in this freshwater reservoir. The positive correlation between chlorophyll a and SS suggested that the change of SS concentration in autumn was caused by the growth of algae. Meanwhile, significant correlations between SS and meteorological factors were also observed, indicating that meteorological factors had effects on SS dynamics. This study provides useful information regarding the correlations among water quality parameters, SS and TDS with meteorological factors in a freshwater reservoir.

  17. Analysing risk factors for urinary tract infection based on automated monitoring of hospital-acquired infection.

    Science.gov (United States)

    Redder, J D; Leth, R A; Møller, J K

    2016-04-01

    Urinary tract infections account for as much as one-third of all nosocomial infections. The aim of this study was to examine previously reported characteristics of patients with hospital-acquired urinary tract infections (HA-UTI) using an automated infection monitoring system (Hospital-Acquired Infection Registry: HAIR). A matched case-control study was conducted to investigate the association of risk factors with HA-UTI. Patients with HA-UTI more frequently had indwelling urinary catheters or a disease in the genitourinary or nervous system than the controls. Automated hospital-acquired infection monitoring enables documentation of key risk factors to better evaluate infection control interventions in general or for selected groups of patients.

  18. Heritable patterns of tooth decay in the permanent dentition: principal components and factor analyses.

    Science.gov (United States)

    Shaffer, John R; Feingold, Eleanor; Wang, Xiaojing; Tcuenco, Karen T; Weeks, Daniel E; DeSensi, Rebecca S; Polk, Deborah E; Wendell, Steve; Weyant, Robert J; Crout, Richard; McNeil, Daniel W; Marazita, Mary L

    2012-03-09

    Dental caries is the result of a complex interplay among environmental, behavioral, and genetic factors, with distinct patterns of decay likely due to specific etiologies. Therefore, global measures of decay, such as the DMFS index, may not be optimal for identifying risk factors that manifest as specific decay patterns, especially if the risk factors such as genetic susceptibility loci have small individual effects. We used two methods to extract patterns of decay from surface-level caries data in order to generate novel phenotypes with which to explore the genetic regulation of caries. The 128 tooth surfaces of the permanent dentition were scored as carious or not by intra-oral examination for 1,068 participants aged 18 to 75 years from 664 biological families. Principal components analysis (PCA) and factor analysis (FA), two methods of identifying underlying patterns without a priori surface classifications, were applied to our data. The three strongest caries patterns identified by PCA recaptured variation represented by DMFS index (correlation, r = 0.97), pit and fissure surface caries (r = 0.95), and smooth surface caries (r = 0.89). However, together, these three patterns explained only 37% of the variability in the data, indicating that a priori caries measures are insufficient for fully quantifying caries variation. In comparison, the first pattern identified by FA was strongly correlated with pit and fissure surface caries (r = 0.81), but other identified patterns, including a second pattern representing caries of the maxillary incisors, were not representative of any previously defined caries indices. Some patterns identified by PCA and FA were heritable (h(2) = 30-65%, p = 0.043-0.006), whereas other patterns were not, indicating both genetic and non-genetic etiologies of individual decay patterns. This study demonstrates the use of decay patterns as novel phenotypes to assist in understanding the multifactorial nature of dental caries.

  19. Analysing a Numerical Calculation Adequacy of the Recovery Factor for Various Problem Statement Options

    Directory of Open Access Journals (Sweden)

    A. D. Kliukvin

    2016-01-01

    Full Text Available The paper studies a recovery temperature distribution in a turbulent boundary layer of the compressible gas in a rectangular heat-insulated channel in supersonic flow mode using the numerical methods of gas dynamics. The software package ANSYS Fluent was used for calculation.In the numerical simulation were used SST and k-epsilon turbulence models with two types of thermal boundary conditions on the channel wall: the standard adiabatic condition, provided by the software package, as well as the user boundary condition (UDF based on the empirical dependence of the recovery factor in a turbulent boundary layer on the Prandtl number of the medium.A data analysis showed that an application of the standard boundary condition of a heatinsulated wall, in some cases, results in recovery factor values on the wall, corresponding to the laminar rather than turbulent boundary layer.For all options of the numerical model under consideration was found a non-zero value of the heat flow to the adiabatic wall. In the case of setting the user boundary conditions, this fact is due to the approximate nature of the dependence of the recovery factor on the Prandtl number.For standard boundary condition of an adiabatic wall the most likely explanation for this result is a feature of the numerical solution scheme, according to which, to set the zero heat flow, is used a number of ghost cells, which can lead to the heat pattern distortion in the computational domain in the vicinity of the wall.Correction of boundary conditions using an empirical relationship for the recovery factor enabled us to reduce the heat flows and have a better approximation of the adiabatic boundary condition.Thus, it follows from the data obtained that the calculation of heat exchange in a turbulent boundary layer by means of ANSYS Fluent software physically yet does not provide the adequate results, and for its update at the moment the third party experimental data are required.

  20. Systematic review and meta-analyses of risk factors for childhood overweight identifiable during infancy

    OpenAIRE

    2012-01-01

    Objective To determine risk factors for childhood overweight that can be identified during the first year of life to facilitate early identification and targeted intervention. Design Systematic review and meta-analysis. Search strategy Electronic database search of MEDLINE, EMBASE, PubMed and CAB Abstracts. Eligibility criteria Prospective observational studies following up children from birth for at least 2 years. Results Thirty prospective studies were identified. Significant and strong ind...

  1. Heritable patterns of tooth decay in the permanent dentition: principal components and factor analyses

    Directory of Open Access Journals (Sweden)

    Shaffer John R

    2012-03-01

    Full Text Available Abstract Background Dental caries is the result of a complex interplay among environmental, behavioral, and genetic factors, with distinct patterns of decay likely due to specific etiologies. Therefore, global measures of decay, such as the DMFS index, may not be optimal for identifying risk factors that manifest as specific decay patterns, especially if the risk factors such as genetic susceptibility loci have small individual effects. We used two methods to extract patterns of decay from surface-level caries data in order to generate novel phenotypes with which to explore the genetic regulation of caries. Methods The 128 tooth surfaces of the permanent dentition were scored as carious or not by intra-oral examination for 1,068 participants aged 18 to 75 years from 664 biological families. Principal components analysis (PCA and factor analysis (FA, two methods of identifying underlying patterns without a priori surface classifications, were applied to our data. Results The three strongest caries patterns identified by PCA recaptured variation represented by DMFS index (correlation, r = 0.97, pit and fissure surface caries (r = 0.95, and smooth surface caries (r = 0.89. However, together, these three patterns explained only 37% of the variability in the data, indicating that a priori caries measures are insufficient for fully quantifying caries variation. In comparison, the first pattern identified by FA was strongly correlated with pit and fissure surface caries (r = 0.81, but other identified patterns, including a second pattern representing caries of the maxillary incisors, were not representative of any previously defined caries indices. Some patterns identified by PCA and FA were heritable (h2 = 30-65%, p = 0.043-0.006, whereas other patterns were not, indicating both genetic and non-genetic etiologies of individual decay patterns. Conclusions This study demonstrates the use of decay patterns as novel phenotypes to assist in understanding

  2. Multicollinearity in prognostic factor analyses using the EORTC QLQ-C30: identification and impact on model selection.

    Science.gov (United States)

    Van Steen, Kristel; Curran, Desmond; Kramer, Jocelyn; Molenberghs, Geert; Van Vreckem, Ann; Bottomley, Andrew; Sylvester, Richard

    2002-12-30

    Clinical and quality of life (QL) variables from an EORTC clinical trial of first line chemotherapy in advanced breast cancer were used in a prognostic factor analysis of survival and response to chemotherapy. For response, different final multivariate models were obtained from forward and backward selection methods, suggesting a disconcerting instability. Quality of life was measured using the EORTC QLQ-C30 questionnaire completed by patients. Subscales on the questionnaire are known to be highly correlated, and therefore it was hypothesized that multicollinearity contributed to model instability. A correlation matrix indicated that global QL was highly correlated with 7 out of 11 variables. In a first attempt to explore multicollinearity, we used global QL as dependent variable in a regression model with other QL subscales as predictors. Afterwards, standard diagnostic tests for multicollinearity were performed. An exploratory principal components analysis and factor analysis of the QL subscales identified at most three important components and indicated that inclusion of global QL made minimal difference to the loadings on each component, suggesting that it is redundant in the model. In a second approach, we advocate a bootstrap technique to assess the stability of the models. Based on these analyses and since global QL exacerbates problems of multicollinearity, we therefore recommend that global QL be excluded from prognostic factor analyses using the QLQ-C30. The prognostic factor analysis was rerun without global QL in the model, and selected the same significant prognostic factors as before.

  3. Complexity of CNC transcription factors as revealed by gene targeting of the Nrf3 locus.

    Science.gov (United States)

    Derjuga, Anna; Gourley, Tania S; Holm, Teresa M; Heng, Henry H Q; Shivdasani, Ramesh A; Ahmed, Rafi; Andrews, Nancy C; Blank, Volker

    2004-04-01

    Cap'n'collar (CNC) family basic leucine zipper transcription factors play crucial roles in the regulation of mammalian gene expression and development. To determine the in vivo function of the CNC protein Nrf3 (NF-E2-related factor 3), we generated mice deficient in this transcription factor. We performed targeted disruption of two Nrf3 exons coding for CNC homology, basic DNA-binding, and leucine zipper dimerization domains. Nrf3 null mice developed normally and revealed no obvious phenotypic differences compared to wild-type animals. Nrf3(-/-) mice were fertile, and gross anatomy as well as behavior appeared normal. The mice showed normal age progression and did not show any apparent additional phenotype during their life span. We observed no differences in various blood parameters and chemistry values. We infected wild-type and Nrf3(-/-) mice with acute lymphocytic choriomeningitis virus and found no differences in these animals with respect to their number of virus-specific CD8 and CD4 T cells as well as their B-lymphocyte response. To determine whether the mild phenotype of Nrf3 null animals is due to functional redundancy, we generated mice deficient in multiple CNC factors. Contrary to our expectations, an absence of Nrf3 does not seem to cause additional lethality in compound Nrf3(-/-)/Nrf2(-/-) and Nrf3(-/-)/p45(-/-) mice. We hypothesize that the role of Nrf3 in vivo may become apparent only after appropriate challenge to the mice.

  4. Analyses of mode filling factor of a laser end-pumped by a LD with high-order transverse modes

    Science.gov (United States)

    Han, Juhong; Wang, You; An, Guofei; Rong, Kepeng; Yu, Hang; Wang, Shunyan; Zhang, Wei; Cai, He; Xue, Liangping; Wang, Hongyuan; Zhou, Jie

    2017-05-01

    Although the concept of the mode filling factor (also named as "mode-matching efficiency") has been well discussed decades before, the concept of so-called overlap coefficient is often confused by the laser technicians because there are several different formulae for various engineering purposes. Furthermore, the LD-pumped configurations have become the mainstream of solid-state lasers since their compact size, high optical-to-optical efficiency, low heat generation, etc. As the beam quality of LDs are usually very unsatisfactory, it is necessary to investigate how the mode filling factor of a laser system is affected by a high-powered LD pump source. In this paper, theoretical analyses of an end-pumped laser are carried out based on the normalized overlap coefficient formalism. The study provides a convenient tool to describe the intrinsically complex issue of mode interaction corresponding to a laser and an end-pumped source. The mode filling factor has been studied for many cases in which the pump mode and the laser mode have been considered together in the calculation based on analyses of the rate equations. The results should be applied for analyses of any other types of lasers with the similar optical geometry.

  5. Genome-wide mapping of transcription factor binding reveals developmental process integration and a fresh look at evolutionary dynamics.

    Science.gov (United States)

    Yant, Levi

    2012-02-01

    How does evolution forge adaptive responses? Are many changes required or few? Just how complex are the transcriptional networks that control development? Diverse questions like these are being newly addressed by next-generation sequencing-based techniques. Facilitating a mechanistic understanding, these approaches reveal the direct in vivo interactions between transcription factors and their physical targets, combined with genome-scale readouts to comprehensively map adaptive gene regulatory networks (GRNs). Here I focus on pioneering work from the last 3 years that has leveraged these data to investigate diverse aspects of GRN circuitry controlling the reproductive transition in plants. These approaches have revealed surprising new functions for long-investigated key players in developmental programs and laid bare the basis for pleiotropy in many others, suggesting widespread process integration at the transcriptional level. Evolutionary questions begged by the recent deluge of GRN mapping data are being assessed anew, both by emerging work outside Arabidopsis thaliana and novel analyses within. These studies have swiftly exposed the distinctive power and adaptability of genome-wide GRN mapping and illustrate that this unique data type holds tremendous promise for plant biology.

  6. Phylogeographic Analyses of Submesophotic Snappers Etelis coruscans and Etelis “marshi” (Family Lutjanidae) Reveal Concordant Genetic Structure across the Hawaiian Archipelago

    Science.gov (United States)

    Andrews, Kimberly R.; Moriwake, Virginia N.; Wilcox, Christie; Grau, E. Gordon; Kelley, Christopher; Pyle, Richard L.; Bowen, Brian W.

    2014-01-01

    The Hawaiian Archipelago has become a natural laboratory for understanding genetic connectivity in marine organisms as a result of the large number of population genetics studies that have been conducted across this island chain for a wide taxonomic range of organisms. However, population genetic studies have been conducted for only two species occurring in the mesophotic or submesophotic zones (30+m) in this archipelago. To gain a greater understanding of genetic connectivity in these deepwater habitats, we investigated the genetic structure of two submesophotic fish species (occurring ∼200–360 m) in this archipelago. We surveyed 16 locations across the archipelago for submesophotic snappers Etelis coruscans (N = 787) and E. “marshi” (formerly E. carbunculus; N = 770) with 436–490 bp of mtDNA cytochrome b and 10–11 microsatellite loci. Phylogeographic analyses reveal no geographic structuring of mtDNA lineages and recent coalescence times that are typical of shallow reef fauna. Population genetic analyses reveal no overall structure across most of the archipelago, a pattern also typical of dispersive shallow fishes. However some sites in the mid-archipelago (Raita Bank to French Frigate Shoals) had significant population differentiation. This pattern of no structure between ends of the Hawaiian range, and significant structure in the middle, was previously observed in a submesophotic snapper (Pristipomoides filamentosus) and a submesophotic grouper (Hyporthodus quernus). Three of these four species also have elevated genetic diversity in the mid-archipelago. Biophysical larval dispersal models from previous studies indicate that this elevated diversity may result from larval supplement from Johnston Atoll, ∼800 km southwest of Hawaii. In this case the boundaries of stocks for fishery management cannot be defined simply in terms of geography, and fishery management in Hawaii may need to incorporate external larval supply into management plans

  7. Complete mitochondrial genome sequences of three bats species and whole genome mitochondrial analyses reveal patterns of codon bias and lend support to a basal split in Chiroptera.

    Science.gov (United States)

    Meganathan, P R; Pagan, Heidi J T; McCulloch, Eve S; Stevens, Richard D; Ray, David A

    2012-01-15

    Order Chiroptera is a unique group of mammals whose members have attained self-powered flight as their main mode of locomotion. Much speculation persists regarding bat evolution; however, lack of sufficient molecular data hampers evolutionary and conservation studies. Of ~1200 species, complete mitochondrial genome sequences are available for only eleven. Additional sequences should be generated if we are to resolve many questions concerning these fascinating mammals. Herein, we describe the complete mitochondrial genomes of three bats: Corynorhinus rafinesquii, Lasiurus borealis and Artibeus lituratus. We also compare the currently available mitochondrial genomes and analyze codon usage in Chiroptera. C. rafinesquii, L. borealis and A. lituratus mitochondrial genomes are 16438 bp, 17048 bp and 16709 bp, respectively. Genome organization and gene arrangements are similar to other bats. Phylogenetic analyses using complete mitochondrial genome sequences support previously established phylogenetic relationships and suggest utility in future studies focusing on the evolutionary aspects of these species. Comprehensive analyses of available bat mitochondrial genomes reveal distinct nucleotide patterns and synonymous codon preferences corresponding to different chiropteran families. These patterns suggest that mutational and selection forces are acting to different extents within Chiroptera and shape their mitochondrial genomes.

  8. Genus-Wide Comparative Genome Analyses of Colletotrichum Species Reveal Specific Gene Family Losses and Gains during Adaptation to Specific Infection Lifestyles.

    Science.gov (United States)

    Gan, Pamela; Narusaka, Mari; Kumakura, Naoyoshi; Tsushima, Ayako; Takano, Yoshitaka; Narusaka, Yoshihiro; Shirasu, Ken

    2016-05-22

    Members from Colletotrichum genus adopt a diverse range of lifestyles during infection of plants and represent a group of agriculturally devastating pathogens. In this study, we present the draft genome of Colletotrichum incanum from the spaethianum clade of Colletotrichum and the comparative analyses with five other Colletotrichum species from distinct lineages. We show that the C. incanum strain, originally isolated from Japanese daikon radish, is able to infect both eudicot plants, such as certain ecotypes of the eudicot Arabidopsis, and monocot plants, such as lily. Being closely related to Colletotrichum species both in the graminicola clade, whose members are restricted strictly to monocot hosts, and to the destructivum clade, whose members are mostly associated with dicot infections, C. incanum provides an interesting model system for comparative genomics to study how fungal pathogens adapt to monocot and dicot hosts. Genus-wide comparative genome analyses reveal that Colletotrichum species have tailored profiles of their carbohydrate-degrading enzymes according to their infection lifestyles. In addition, we show evidence that positive selection acting on secreted and nuclear localized proteins that are highly conserved may be important in adaptation to specific hosts or ecological niches. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  9. Linear and nonlinear analyses of multi-channel mechanomyographic recordings reveal heterogeneous activation of wrist extensors in presence of delayed onset muscle soreness.

    Science.gov (United States)

    Madeleine, Pascal; Hansen, Ernst A; Samani, Afshin

    2014-12-01

    In this study, we applied multi-channel mechanomyographic (MMG) recordings in combination with linear and nonlinear analyses to investigate muscular and musculotendinous effects of high intensity eccentric exercise. Twelve accelerometers arranged in a 3 × 4 matrix over the dominant elbow muscles were used to detect MMG activity in 12 healthy participants. Delayed onset muscle soreness was induced by repetitive high intensity eccentric contractions of the wrist extensor muscles. Average rectified values (ARV) as well as percentage of recurrence (%REC) and percentage of determinism (%DET) extracted from recurrence quantification analysis were computed from data obtained during static-dynamic contractions performed before exercise, immediately after exercise, and in presence of muscle soreness. A linear mixed model was used for the statistical analysis. The ARV, %REC, and %DET maps revealed heterogeneous MMG activity over the wrist extensor muscles before, immediately after, and in presence of muscle soreness (P<0.01). The ARVs were higher while the %REC and %DET were lower in presence of muscle soreness compared with before exercise (P<0.05). The study provides new key information on linear and nonlinear analyses of multi-channel MMG recordings of the wrist extensor muscles following eccentric exercise that results in muscle soreness. Recurrence quantification analysis can be suggested as a tool for detection of MMG changes in presence of muscle soreness.

  10. The genetic diversity of genus Bacillus and the related genera revealed by 16S rRNA gene sequences and ardra analyses isolated from geothermal regions of turkey

    Directory of Open Access Journals (Sweden)

    Arzu Coleri Cihan

    2012-03-01

    Full Text Available Previously isolated 115 endospore-forming bacilli were basically grouped according to their temperature requirements for growth: the thermophiles (74%, the facultative thermophiles (14% and the mesophiles (12%. These isolates were taken into 16S rRNA gene sequence analyses, and they were clustered among the 7 genera: Anoxybacillus, Aeribacillus, Bacillus, Brevibacillus, Geobacillus, Paenibacillus, and Thermoactinomycetes. Of these bacilli, only the thirty two isolates belonging to genera Bacillus (16, Brevibacillus (13, Paenibacillus (1 and Thermoactinomycetes (2 were selected and presented in this paper. The comparative sequence analyses revealed that the similarity values were ranged as 91.4-100 %, 91.8- 99.2 %, 92.6- 99.8 % and 90.7 - 99.8 % between the isolates and the related type strains from these four genera, respectively. Twenty nine of them were found to be related with the validly published type strains. The most abundant species was B. thermoruber with 9 isolates followed by B. pumilus (6, B. lichenformis (3, B. subtilis (3, B. agri (3, B. smithii (2, T. vulgaris (2 and finally P. barengoltzii (1. In addition, isolates of A391a, B51a and D295 were proposed as novel species as their 16S rRNA gene sequences displayed similarities ≤ 97% to their closely related type strains. The AluI-, HaeIII- and TaqI-ARDRA results were in congruence with the 16S rRNA gene sequence analyses. The ARDRA results allowed us to differentiate these isolates, and their discriminative restriction fragments were able to be determined. Some of their phenotypic characters and their amylase, chitinase and protease production were also studied and biotechnologically valuable enzyme producing isolates were introduced in order to use in further studies.

  11. Deciphering the cryptic genome: genome-wide analyses of the rice pathogen Fusarium fujikuroi reveal complex regulation of secondary metabolism and novel metabolites.

    Directory of Open Access Journals (Sweden)

    Philipp Wiemann

    Full Text Available The fungus Fusarium fujikuroi causes "bakanae" disease of rice due to its ability to produce gibberellins (GAs, but it is also known for producing harmful mycotoxins. However, the genetic capacity for the whole arsenal of natural compounds and their role in the fungus' interaction with rice remained unknown. Here, we present a high-quality genome sequence of F. fujikuroi that was assembled into 12 scaffolds corresponding to the 12 chromosomes described for the fungus. We used the genome sequence along with ChIP-seq, transcriptome, proteome, and HPLC-FTMS-based metabolome analyses to identify the potential secondary metabolite biosynthetic gene clusters and to examine their regulation in response to nitrogen availability and plant signals. The results indicate that expression of most but not all gene clusters correlate with proteome and ChIP-seq data. Comparison of the F. fujikuroi genome to those of six other fusaria revealed that only a small number of gene clusters are conserved among these species, thus providing new insights into the divergence of secondary metabolism in the genus Fusarium. Noteworthy, GA biosynthetic genes are present in some related species, but GA biosynthesis is limited to F. fujikuroi, suggesting that this provides a selective advantage during infection of the preferred host plant rice. Among the genome sequences analyzed, one cluster that includes a polyketide synthase gene (PKS19 and another that includes a non-ribosomal peptide synthetase gene (NRPS31 are unique to F. fujikuroi. The metabolites derived from these clusters were identified by HPLC-FTMS-based analyses of engineered F. fujikuroi strains overexpressing cluster genes. In planta expression studies suggest a specific role for the PKS19-derived product during rice infection. Thus, our results indicate that combined comparative genomics and genome-wide experimental analyses identified novel genes and secondary metabolites that contribute to the evolutionary

  12. Deciphering the Cryptic Genome: Genome-wide Analyses of the Rice Pathogen Fusarium fujikuroi Reveal Complex Regulation of Secondary Metabolism and Novel Metabolites

    Science.gov (United States)

    Studt, Lena; Niehaus, Eva-Maria; Espino, Jose J.; Huß, Kathleen; Michielse, Caroline B.; Albermann, Sabine; Wagner, Dominik; Bergner, Sonja V.; Connolly, Lanelle R.; Fischer, Andreas; Reuter, Gunter; Kleigrewe, Karin; Bald, Till; Wingfield, Brenda D.; Ophir, Ron; Freeman, Stanley; Hippler, Michael; Smith, Kristina M.; Brown, Daren W.; Proctor, Robert H.; Münsterkötter, Martin; Freitag, Michael; Humpf, Hans-Ulrich; Güldener, Ulrich; Tudzynski, Bettina

    2013-01-01

    The fungus Fusarium fujikuroi causes “bakanae” disease of rice due to its ability to produce gibberellins (GAs), but it is also known for producing harmful mycotoxins. However, the genetic capacity for the whole arsenal of natural compounds and their role in the fungus' interaction with rice remained unknown. Here, we present a high-quality genome sequence of F. fujikuroi that was assembled into 12 scaffolds corresponding to the 12 chromosomes described for the fungus. We used the genome sequence along with ChIP-seq, transcriptome, proteome, and HPLC-FTMS-based metabolome analyses to identify the potential secondary metabolite biosynthetic gene clusters and to examine their regulation in response to nitrogen availability and plant signals. The results indicate that expression of most but not all gene clusters correlate with proteome and ChIP-seq data. Comparison of the F. fujikuroi genome to those of six other fusaria revealed that only a small number of gene clusters are conserved among these species, thus providing new insights into the divergence of secondary metabolism in the genus Fusarium. Noteworthy, GA biosynthetic genes are present in some related species, but GA biosynthesis is limited to F. fujikuroi, suggesting that this provides a selective advantage during infection of the preferred host plant rice. Among the genome sequences analyzed, one cluster that includes a polyketide synthase gene (PKS19) and another that includes a non-ribosomal peptide synthetase gene (NRPS31) are unique to F. fujikuroi. The metabolites derived from these clusters were identified by HPLC-FTMS-based analyses of engineered F. fujikuroi strains overexpressing cluster genes. In planta expression studies suggest a specific role for the PKS19-derived product during rice infection. Thus, our results indicate that combined comparative genomics and genome-wide experimental analyses identified novel genes and secondary metabolites that contribute to the evolutionary success of F

  13. Proteomic analyses of human cytomegalovirus strain AD169 derivatives reveal highly conserved patterns of viral and cellular proteins in infected fibroblasts.

    Science.gov (United States)

    Reyda, Sabine; Büscher, Nicole; Tenzer, Stefan; Plachter, Bodo

    2014-01-07

    Human cytomegalovirus (HCMV) particle morphogenesis in infected cells is an orchestrated process that eventually results in the release of enveloped virions. Proteomic analysis has been employed to reveal the complexity in the protein composition of these extracellular particles. Only limited information is however available regarding the proteome of infected cells preceding the release of HCMV virions. We used quantitative mass spectrometry to address the pattern of viral and cellular proteins in cells, infected with derivatives of the AD169 laboratory strain. Our analyses revealed a remarkable conservation in the patterns of viral and of abundant cellular proteins in cells, infected for 2 hours, 2 days, or 4 days. Most viral proteins increased in abundance as the infection progressed over time. Of the proteins that were reliably detectable by mass spectrometry, only IE1 (pUL123), pTRS1, and pIRS1 were downregulated at 4 days after infection. In addition, little variation of viral proteins in the virions of the different viruses was detectable, independent of the expression of the major tegument protein pp65. Taken together these data suggest that there is little variation in the expression program of viral and cellular proteins in cells infected with related HCMVs, resulting in a conserved pattern of viral proteins ultimately associated with extracellular virions.

  14. Spatial genetic analyses reveal cryptic population structure and migration patterns in a continuously harvested grey wolf (Canis lupus population in north-eastern Europe.

    Directory of Open Access Journals (Sweden)

    Maris Hindrikson

    Full Text Available Spatial genetics is a relatively new field in wildlife and conservation biology that is becoming an essential tool for unravelling the complexities of animal population processes, and for designing effective strategies for conservation and management. Conceptual and methodological developments in this field are therefore critical. Here we present two novel methodological approaches that further the analytical possibilities of STRUCTURE and DResD. Using these approaches we analyse structure and migrations in a grey wolf (Canislupus population in north-eastern Europe. We genotyped 16 microsatellite loci in 166 individuals sampled from the wolf population in Estonia and Latvia that has been under strong and continuous hunting pressure for decades. Our analysis demonstrated that this relatively small wolf population is represented by four genetic groups. We also used a novel methodological approach that uses linear interpolation to statistically test the spatial separation of genetic groups. The new method, which is capable of using program STRUCTURE output, can be applied widely in population genetics to reveal both core areas and areas of low significance for genetic groups. We also used a recently developed spatially explicit individual-based method DResD, and applied it for the first time to microsatellite data, revealing a migration corridor and barriers, and several contact zones.

  15. Lessons for public health campaigns from analysing commercial food marketing success factors

    DEFF Research Database (Denmark)

    Aschemann-Witzel, Jessica; JA Perez-Cueto, Federico; Niedzwiedzka, Barbara

    2012-01-01

    Background: Commercial food marketing has considerably shaped consumer food choice behaviour. Meanwhile, public health campaigns for healthier eating have had limited impact to date. Social marketing suggests that successful commercial food marketing campaigns can provide useful lessons for public...... sector activities. The aim of the present study was to empirically identify food marketing success factors that, using the social marketing approach, could help improve public health campaigns to promote healthy eating. Methods: In this case-study analysis, 27 recent and successful commercial food...... and beverage marketing cases were purposively sampled from different European countries. The cases involved different consumer target groups, product categories, company sizes and marketing techniques. The analysis focused on cases of relatively healthy food types, and nutrition and health-related aspects...

  16. Kernel principal component and maximum autocorrelation factor analyses for change detection

    DEFF Research Database (Denmark)

    Nielsen, Allan Aasbjerg; Canty, Morton John

    2009-01-01

    in Nevada acquired on successive passes of the Landsat-5 satellite in August-September 1991. The six-band images (the thermal band is omitted) with 1,000 by 1,000 28.5 m pixels were first processed with the iteratively re-weighted MAD (IR-MAD) algorithm in order to discriminate change. Then the MAD image......Principal component analysis (PCA) has often been used to detect change over time in remotely sensed images. A commonly used technique consists of finding the projections along the eigenvectors for data consisting of pair-wise (perhaps generalized) differences between corresponding spectral bands...... covering the same geographical region acquired at two different time points. In this paper kernel versions of the principal component and maximum autocorrelation factor (MAF) transformations are used to carry out the analysis. An example is based on bi-temporal Landsat-5 TM imagery over irrigation fields...

  17. Regulation of Nucleosome Architecture and Factor Binding Revealed by Nuclease Footprinting of the ESC Genome.

    Science.gov (United States)

    Hainer, Sarah J; Fazzio, Thomas G

    2015-10-06

    Functional interactions between gene regulatory factors and chromatin architecture have been difficult to directly assess. Here, we use micrococcal nuclease (MNase) footprinting to probe the functions of two chromatin-remodeling complexes. By simultaneously quantifying alterations in small MNase footprints over the binding sites of 30 regulatory factors in mouse embryonic stem cells (ESCs), we provide evidence that esBAF and Mbd3/NuRD modulate the binding of several regulatory proteins. In addition, we find that nucleosome occupancy is reduced at specific loci in favor of subnucleosomes upon depletion of esBAF, including sites of histone H2A.Z localization. Consistent with these data, we demonstrate that esBAF is required for normal H2A.Z localization in ESCs, suggesting esBAF either stabilizes H2A.Z-containing nucleosomes or promotes subnucleosome to nucleosome conversion by facilitating H2A.Z deposition. Therefore, integrative examination of MNase footprints reveals insights into nucleosome dynamics and functional interactions between chromatin structure and key gene-regulatory factors.

  18. Regulation of Nucleosome Architecture and Factor Binding Revealed by Nuclease Footprinting of the ESC Genome

    Directory of Open Access Journals (Sweden)

    Sarah J. Hainer

    2015-10-01

    Full Text Available Functional interactions between gene regulatory factors and chromatin architecture have been difficult to directly assess. Here, we use micrococcal nuclease (MNase footprinting to probe the functions of two chromatin-remodeling complexes. By simultaneously quantifying alterations in small MNase footprints over the binding sites of 30 regulatory factors in mouse embryonic stem cells (ESCs, we provide evidence that esBAF and Mbd3/NuRD modulate the binding of several regulatory proteins. In addition, we find that nucleosome occupancy is reduced at specific loci in favor of subnucleosomes upon depletion of esBAF, including sites of histone H2A.Z localization. Consistent with these data, we demonstrate that esBAF is required for normal H2A.Z localization in ESCs, suggesting esBAF either stabilizes H2A.Z-containing nucleosomes or promotes subnucleosome to nucleosome conversion by facilitating H2A.Z deposition. Therefore, integrative examination of MNase footprints reveals insights into nucleosome dynamics and functional interactions between chromatin structure and key gene-regulatory factors.

  19. Disease Model of GATA4 Mutation Reveals Transcription Factor Cooperativity in Human Cardiogenesis.

    Science.gov (United States)

    Ang, Yen-Sin; Rivas, Renee N; Ribeiro, Alexandre J S; Srivas, Rohith; Rivera, Janell; Stone, Nicole R; Pratt, Karishma; Mohamed, Tamer M A; Fu, Ji-Dong; Spencer, C Ian; Tippens, Nathaniel D; Li, Molong; Narasimha, Anil; Radzinsky, Ethan; Moon-Grady, Anita J; Yu, Haiyuan; Pruitt, Beth L; Snyder, Michael P; Srivastava, Deepak

    2016-12-15

    Mutation of highly conserved residues in transcription factors may affect protein-protein or protein-DNA interactions, leading to gene network dysregulation and human disease. Human mutations in GATA4, a cardiogenic transcription factor, cause cardiac septal defects and cardiomyopathy. Here, iPS-derived cardiomyocytes from subjects with a heterozygous GATA4-G296S missense mutation showed impaired contractility, calcium handling, and metabolic activity. In human cardiomyocytes, GATA4 broadly co-occupied cardiac enhancers with TBX5, another transcription factor that causes septal defects when mutated. The GATA4-G296S mutation disrupted TBX5 recruitment, particularly to cardiac super-enhancers, concomitant with dysregulation of genes related to the phenotypic abnormalities, including cardiac septation. Conversely, the GATA4-G296S mutation led to failure of GATA4 and TBX5-mediated repression at non-cardiac genes and enhanced open chromatin states at endothelial/endocardial promoters. These results reveal how disease-causing missense mutations can disrupt transcriptional cooperativity, leading to aberrant chromatin states and cellular dysfunction, including those related to morphogenetic defects. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Meta and pooled analyses of FGFR4 Gly388Arg polymorphism as a cancer prognostic factor.

    Science.gov (United States)

    Frullanti, Elisa; Berking, Carola; Harbeck, Nadia; Jézéquel, Pascal; Haugen, Aage; Mawrin, Christian; Parise, Orlando; Sasaki, Hidefumi; Tsuchiya, Norihiko; Dragani, Tommaso A

    2011-07-01

    Fibroblast growth factor receptor 4 (FGFR4) contains a Gly388Arg functional polymorphism (rs351855) that has shown contrasting results in association studies. In this study, we assessed the association between the FGFR4 Gly388Arg polymorphism and cancer prognosis. Meta-analysis and pooled analysis of 6817 and 2537 cancer cases, respectively, were carried out by nodal status and overall survival. The study included the following types of cancer: brain, breast, colorectal, head and neck, larynx, lung, melanoma, prostate, sarcomas. A statistically significant association between the Arg388Arg genotype and nodal involvement was found in the meta-analysis (odds ratio=1.33, 95% confidence interval 1.01-1.74). In the pooled analysis, the Arg388 allele carriers showed an increased hazard of poor overall survival compared with homozygous carriers of the common Gly388 allele, even after adjusting for nodal status (hazard ratio=1.21, 95% confidence interval 1.05-1.40). These results provide evidence of a role for the FGFR4 Gly388Arg polymorphism in modulating patients' outcome in different types of cancer, thus offering to clinicians a new marker to predict predisposition to poor survival in cancer patients.

  1. Expression and functional analyses of Krüppel-like factor 3 in chicken adipose tissue.

    Science.gov (United States)

    Zhang, Zhi-Wei; Wu, Chun-Yan; Li, Hui; Wang, Ning

    2014-01-01

    Studies in mammalian species showed that Krüppel-like factor 3 (KLF3) regulated adipose tissue development. However, it was not reported in chicken. In the current study, we found that during the growth and development of abdominal fat tissue, chicken KLF3 (Gallus gallus KLF3, gKLF3) was consecutively expressed, and its transcripts were higher at 7 weeks of age and lower at 10 weeks of age in lean broilers than in fat broilers. In addition, gKLF3 overexpression suppressed chicken CCAAT/enhancer binding protein alpha (C/EBPα), fatty acid binding protein 4 (FABP4), fatty acid synthase (FASN), and lipoprotein lipase (LPL) promoter activities, but increased chicken peroxisome proliferator-activated receptor gamma (PPARγ) promoter activity. Additionally, point mutagenesis analysis showed that the substitution of Asp by Gly within the Pro-Val-Asp-Leu-Thr (PVDLT) motif of gKLF3 significantly reduced the ability of gKLF3 to regulate the promoter activities of FABP4, FASN, LPL, C/EBPα, and PPARγ.

  2. High glycemic index diet as a risk factor for depression: analyses from the Women's Health Initiative.

    Science.gov (United States)

    Gangwisch, James E; Hale, Lauren; Garcia, Lorena; Malaspina, Dolores; Opler, Mark G; Payne, Martha E; Rossom, Rebecca C; Lane, Dorothy

    2015-08-01

    The consumption of sweetened beverages, refined foods, and pastries has been shown to be associated with an increased risk of depression in longitudinal studies. However, any influence that refined carbohydrates has on mood could be commensurate with their proportion in the overall diet; studies are therefore needed that measure overall intakes of carbohydrate and sugar, glycemic index (GI), and glycemic load. We hypothesized that higher dietary GI and glycemic load would be associated with greater odds of the prevalence and incidence of depression. This was a prospective cohort study to investigate the relations between dietary GI, glycemic load, and other carbohydrate measures (added sugars, total sugars, glucose, sucrose, lactose, fructose, starch, carbohydrate) and depression in postmenopausal women who participated in the Women's Health Initiative Observational Study at baseline between 1994 and 1998 (n = 87,618) and at the 3-y follow-up (n = 69,954). We found a progressively higher dietary GI to be associated with increasing odds of incident depression in fully adjusted models (OR for the fifth compared with first quintile: 1.22; 95% CI: 1.09, 1.37), with the trend being statistically significant (P = 0.0032). Progressively higher consumption of dietary added sugars was also associated with increasing odds of incident depression (OR for the fifth compared with first quintile: 1.23; 95% CI: 1.07, 1.41; P-trend = 0.0029). Higher consumption of lactose, fiber, nonjuice fruit, and vegetables was significantly associated with lower odds of incident depression, and nonwhole/refined grain consumption was associated with increased odds of depression. The results from this study suggest that high-GI diets could be a risk factor for depression in postmenopausal women. Randomized trials should be undertaken to examine the question of whether diets rich in low-GI foods could serve as treatments and primary preventive measures for depression in postmenopausal women.

  3. Comparative genomic and functional analyses: unearthing the diversity and specificity of nematicidal factors in Pseudomonas putida strain 1A00316

    Science.gov (United States)

    Guo, Jing; Jing, Xueping; Peng, Wen-Lei; Nie, Qiyu; Zhai, Yile; Shao, Zongze; Zheng, Longyu; Cai, Minmin; Li, Guangyu; Zuo, Huaiyu; Zhang, Zhitao; Wang, Rui-Ru; Huang, Dian; Cheng, Wanli; Yu, Ziniu; Chen, Ling-Ling; Zhang, Jibin

    2016-01-01

    We isolated Pseudomonas putida (P. putida) strain 1A00316 from Antarctica. This bacterium has a high efficiency against Meloidogyne incognita (M. incognita) in vitro and under greenhouse conditions. The complete genome of P. putida 1A00316 was sequenced using PacBio single molecule real-time (SMRT) technology. A comparative genomic analysis of 16 Pseudomonas strains revealed that although P. putida 1A00316 belonged to P. putida, it was phenotypically more similar to nematicidal Pseudomonas fluorescens (P. fluorescens) strains. We characterized the diversity and specificity of nematicidal factors in P. putida 1A00316 with comparative genomics and functional analysis, and found that P. putida 1A00316 has diverse nematicidal factors including protein alkaline metalloproteinase AprA and two secondary metabolites, hydrogen cyanide and cyclo-(l-isoleucyl-l-proline). We show for the first time that cyclo-(l-isoleucyl-l-proline) exhibit nematicidal activity in P. putida. Interestingly, our study had not detected common nematicidal factors such as 2,4-diacetylphloroglucinol (2,4-DAPG) and pyrrolnitrin in P. putida 1A00316. The results of the present study reveal the diversity and specificity of nematicidal factors in P. putida strain 1A00316. PMID:27384076

  4. Confirmatory factor analyses of the full and short versions of the Marlowe-Crowne Social Desirability Scale.

    Science.gov (United States)

    Loo, R; Thorpe, K

    2000-10-01

    Over the years, researchers have developed various short versions of the Marlowe-Crowne Social Desirability Scale (D. P. Crowne & D. Marlowe, 1960). The authors used confirmatory factor analyses (J. L. Arbuckle, 1997) as well as item and scale analyses to evaluate the adequacy of the full version and various short versions. Overall, the results from 232 Canadian undergraduates showed (a) that all the short versions in the present study are a significant improvement in fit over the 33-item full scale and (b) that W. M. Reynolds's (1982) Forms A and B are the best fitting short versions. No gender differences were found for the full scale or any of the short versions. The results show that the full scale could be improved psychometrically and that the psychometrically sound short versions should be available because they require less administration time than the full scale.

  5. Systematic Selection of Key Logistic Regression Variables for Risk Prediction Analyses: A Five-Factor Maximum Model.

    Science.gov (United States)

    Hewett, Timothy E; Webster, Kate E; Hurd, Wendy J

    2017-08-16

    The evolution of clinical practice and medical technology has yielded an increasing number of clinical measures and tests to assess a patient's progression and return to sport readiness after injury. The plethora of available tests may be burdensome to clinicians in the absence of evidence that demonstrates the utility of a given measurement. Thus, there is a critical need to identify a discrete number of metrics to capture during clinical assessment to effectively and concisely guide patient care. The data sources included Pubmed and PMC Pubmed Central articles on the topic. Therefore, we present a systematic approach to injury risk analyses and how this concept may be used in algorithms for risk analyses for primary anterior cruciate ligament (ACL) injury in healthy athletes and patients after ACL reconstruction. In this article, we present the five-factor maximum model, which states that in any predictive model, a maximum of 5 variables will contribute in a meaningful manner to any risk factor analysis. We demonstrate how this model already exists for prevention of primary ACL injury, how this model may guide development of the second ACL injury risk analysis, and how the five-factor maximum model may be applied across the injury spectrum for development of the injury risk analysis.

  6. Endogenous Purification Reveals GREB1 as a Key Estrogen Receptor Regulatory Factor

    Directory of Open Access Journals (Sweden)

    Hisham Mohammed

    2013-02-01

    Full Text Available Estrogen receptor-α (ER is the driving transcription factor in most breast cancers, and its associated proteins can influence drug response, but direct methods for identifying interacting proteins have been limited. We purified endogenous ER using an approach termed RIME (rapid immunoprecipitation mass spectrometry of endogenous proteins and discovered the interactome under agonist- and antagonist-liganded conditions in breast cancer cells, revealing transcriptional networks in breast cancer. The most estrogen-enriched ER interactor is GREB1, a potential clinical biomarker with no known function. GREB1 is shown to be a chromatin-bound ER coactivator and is essential for ER-mediated transcription, because it stabilizes interactions between ER and additional cofactors. We show a GREB1-ER interaction in three xenograft tumors, and using a directed protein-protein approach, we find GREB1-ER interactions in half of ER+ primary breast cancers. This finding is supported by histological expression of GREB1, which shows that GREB1 is expressed in half of ER+ cancers, and predicts good clinical outcome. These findings reveal an unexpected role for GREB1 as an estrogen-specific ER cofactor that is expressed in drug-sensitive contexts.

  7. A Papillary Thyroid Microcarcinoma Revealed by a Single Bone Lesion with No Poor Prognostic Factors

    Directory of Open Access Journals (Sweden)

    Yann Godbert

    2013-01-01

    Full Text Available Objectives. Thyroid carcinomas incidence, in particular papillary variants, is increasing. These cancers are generally considered to have excellent prognosis, and papillary microcarcinomas are usually noninvasive. Many prognostic histopathology factors have been described to guide therapeutic decisions. Most patients are treated with total thyroidectomy without radioiodine treatment or partial surgery. Case Summary. A 65-year-old man with no significant medical history presented with pain in the left chest wall that had been present for several months. A computed tomography (CT found a large tissue mass of 4 cm responsible for lysis of the middle arch of the 4th rib on the left. It was a single lesion, highly hypermetabolic on the 18-FDG PET/CT. The histology analysis of the biopsy and surgical specimen favored an adenocarcinoma with immunostaining positive for TTF1 and thyroglobulin (Tg. The total thyroidectomy carried out subsequently revealed a 4 mm papillary microcarcinoma with vesicular architecture of the right lobe, well delimited and distant from the capsule without vascular embolisms. After two radioiodine treatments, the patient is in complete clinical, biological, and radiological remission. Conclusion. This extremely rare case of a singular bone metastasis revealing a papillary thyroid microcarcinoma illustrates the necessity of further research to better characterize the forms of papillary thyroid microcarcinomas with potentially poor prognosis.

  8. Analyses of expressed sequence tags in Neurospora reveal rapid evolution of genes associated with the early stages of sexual reproduction in fungi

    Directory of Open Access Journals (Sweden)

    Nygren Kristiina

    2012-11-01

    Full Text Available Abstract Background The broadly accepted pattern of rapid evolution of reproductive genes is primarily based on studies of animal systems, although several examples of rapidly evolving genes involved in reproduction are found in diverse additional taxa. In fungi, genes involved in mate recognition have been found to evolve rapidly. However, the examples are too few to draw conclusions on a genome scale. Results In this study, we performed microarray hybridizations between RNA from sexual and vegetative tissues of two strains of the heterothallic (self-sterile filamentous ascomycete Neurospora intermedia, to identify a set of sex-associated genes in this species. We aligned Expressed Sequence Tags (ESTs from sexual and vegetative tissue of N. intermedia to orthologs from three closely related species: N. crassa, N. discreta and N. tetrasperma. The resulting four-species alignments provided a dataset for molecular evolutionary analyses. Our results confirm a general pattern of rapid evolution of fungal sex-associated genes, compared to control genes with constitutive expression or a high relative expression during vegetative growth. Among the rapidly evolving sex-associated genes, we identified candidates that could be of importance for mating or fruiting-body development. Analyses of five of these candidate genes from additional species of heterothallic Neurospora revealed that three of them evolve under positive selection. Conclusions Taken together, our study represents a novel finding of a genome-wide pattern of rapid evolution of sex-associated genes in the fungal kingdom, and provides a list of candidate genes important for reproductive isolation in Neurospora.

  9. RNA-Sequencing Analysis Reveals a Regulatory Role for Transcription Factor Fezf2 in the Mature Motor Cortex

    Directory of Open Access Journals (Sweden)

    Alison J. Clare

    2017-09-01

    Full Text Available Forebrain embryonic zinc finger (Fezf2 encodes a transcription factor essential for the specification of layer 5 projection neurons (PNs in the developing cerebral cortex. As with many developmental transcription factors, Fezf2 continues to be expressed into adulthood, suggesting it remains crucial to the maintenance of neuronal phenotypes. Despite the continued expression, a function has yet to be explored for Fezf2 in the PNs of the developed cortex. Here, we investigated the role of Fezf2 in mature neurons, using lentiviral-mediated delivery of a shRNA to conditionally knockdown the expression of Fezf2 in the mouse primary motor cortex (M1. RNA-sequencing analysis of Fezf2-reduced M1 revealed significant changes to the transcriptome, identifying a regulatory role for Fezf2 in the mature M1. Kyoto Encyclopedia Genes and Genomes (KEGG pathway analyses of Fezf2-regulated genes indicated a role in neuronal signaling and plasticity, with significant enrichment of neuroactive ligand-receptor interaction, cell adhesion molecules and calcium signaling pathways. Gene Ontology analysis supported a functional role for Fezf2-regulated genes in neuronal transmission and additionally indicated an importance in the regulation of behavior. Using the mammalian phenotype ontology database, we identified a significant overrepresentation of Fezf2-regulated genes associated with specific behavior phenotypes, including associative learning, social interaction, locomotor activation and hyperactivity. These roles were distinct from that of Fezf2-regulated genes identified in development, indicating a dynamic transition in Fezf2 function. Together our findings demonstrate a regulatory role for Fezf2 in the mature brain, with Fezf2-regulated genes having functional roles in sustaining normal neuronal and behavioral phenotypes. These results support the hypothesis that developmental transcription factors are important for maintaining neuron transcriptomes and that

  10. Tomato GOLDEN2-LIKE transcription factors reveal molecular gradients that function during fruit development and ripening.

    Science.gov (United States)

    Nguyen, Cuong V; Vrebalov, Julia T; Gapper, Nigel E; Zheng, Yi; Zhong, Silin; Fei, Zhangjun; Giovannoni, James J

    2014-02-01

    Fruit ripening is the summation of changes rendering fleshy fruit tissues attractive and palatable to seed dispersing organisms. For example, sugar content is influenced by plastid numbers and photosynthetic activity in unripe fruit and later by starch and sugar catabolism during ripening. Tomato fruit are sinks of photosynthate, yet unripe green fruit contribute significantly to the sugars that ultimately accumulate in the ripe fruit. Plastid numbers and chlorophyll content are influenced by numerous environmental and genetic factors and are positively correlated with photosynthesis and photosynthate accumulation. GOLDEN2-LIKE (GLK) transcription factors regulate plastid and chlorophyll levels. Tomato (Solanum lycopersicum), like most plants, contains two GLKs (i.e., GLK1 and GLK2/UNIFORM). Mutant and transgene analysis demonstrated that these genes encode functionally similar peptides, though differential expression renders GLK1 more important in leaves, while GLK2 is predominant in fruit. A latitudinal gradient of GLK2 expression influences the typical uneven coloration of green and ripe wild-type fruit. Transcriptome profiling revealed a broader fruit gene expression gradient throughout development. The gradient influenced general ripening activities beyond plastid development and was consistent with the easily observed yet poorly studied ripening gradient present in tomato and many fleshy fruits.

  11. The structure of the TFIIH p34 subunit reveals a von Willebrand factor A like fold.

    Directory of Open Access Journals (Sweden)

    Dominik R Schmitt

    Full Text Available RNA polymerase II dependent transcription and nucleotide excision repair are mediated by a multifaceted interplay of subunits within the general transcription factor II H (TFIIH. A better understanding of the molecular structure of TFIIH is the key to unravel the mechanism of action of this versatile protein complex within these vital cellular processes. The importance of this complex becomes further evident in the context of severe diseases like xeroderma pigmentosum, Cockayne's syndrome and trichothiodystrophy, that arise from single point mutations in TFIIH subunits. Here we describe the structure of the p34 subunit of the TFIIH complex from the eukaryotic thermophilic fungus Chaetomium thermophilum. The structure revealed that p34 contains a von Willebrand Factor A (vWA like domain, a fold which is generally known to be involved in protein-protein interactions. Within TFIIH p34 strongly interacts with p44, a positive regulator of the helicase XPD. Putative protein-protein interfaces are analyzed and possible binding sites for the p34-p44 interaction suggested.

  12. Mars Organic Matter Revealed by the Detection of Organo-chlorinated Molecules from Pyro-GCMS Analyses of Yellowknife Bay Mudstone

    Science.gov (United States)

    Szopa, C.; Freissinet, C.; Glavin, D. P.; Buch, A.; Coll, P. J.; Cabane, M.; Millan, M.; Belmahadi, I.; Navarro-Gonzalez, R.; Steele, A.; Summons, R. E.; Eigenbrode, J. L.; Mahaffy, P. R.

    2015-12-01

    Mudstones collected on the Yellowknife Bay site in Gale crater by the Curiosity rover, were analyzed with the Sample Analysis at Mars (SAM) chemical laboratory with the aim (among others) to detect and identify organic molecules in the Martian reglith [1]. The pyrolysis (to 900°C)-gas chromatography-mass spectrometry (Pyro-GCMS) analytical mode was systematically used to reach that goal. It revealed the existence of complex interactions between compounds present in the soil sample (e.g. oxychlorines [2]) and internal components of the SAM experiment (e.g. derivatization reactant) resulting in signals complex to interpret [3]. By comparing these results with those obtained for the other Mars samples analysed with SAM, and by carefully identifying, from laboratory work, the possible SAM internal contributions to the organic molecules detected [4], chlorobenzene has already been identified as mainly originating from organics present in the mudstone [5]. Since this discovery, we did additional studies of the chromatograms that reveal the presence of dichlorobenzene originating from an organic source endogenous to the sample. Even if the exact original source of these organic molecules cannot be strictly identified, the detection of several chlorinated aromatic molecules suggests the presence of a significant amount of aromatized materials which are in an oxidized state involving oxygen in the mudstone. We present here the corresponding results and the implication it can have on the origin of these organic materials References: [1] Mahaffy, P. et al. (2012) Space Sci Rev, 170, 401-478. [2] Glavin, D. et al. (2013), JGR. [3] Ming D. et al. (2013), Science 32, 64, [4] Miller K. et al. (In press), JGR, [5] Freissinet et al., (2015), JGR Pla. 120, 495.

  13. Comparative live-cell imaging analyses of SPA-2, BUD-6 and BNI-1 in Neurospora crassa reveal novel features of the filamentous fungal polarisome.

    Directory of Open Access Journals (Sweden)

    Alexander Lichius

    Full Text Available A key multiprotein complex involved in regulating the actin cytoskeleton and secretory machinery required for polarized growth in fungi, is the polarisome. Recognized core constituents in budding yeast are the proteins Spa2, Pea2, Aip3/Bud6, and the key effector Bni1. Multicellular fungi display a more complex polarized morphogenesis than yeasts, suggesting that the filamentous fungal polarisome might fulfill additional functions. In this study, we compared the subcellular organization and dynamics of the putative polarisome components BUD-6 and BNI-1 with those of the bona fide polarisome marker SPA-2 at various developmental stages of Neurospora crassa. All three proteins exhibited a yeast-like polarisome configuration during polarized germ tube growth, cell fusion, septal pore plugging and tip repolarization. However, the localization patterns of all three proteins showed spatiotemporally distinct characteristics during the establishment of new polar axes, septum formation and cytokinesis, and maintained hyphal tip growth. Most notably, in vegetative hyphal tips BUD-6 accumulated as a subapical cloud excluded from the Spitzenkörper (Spk, whereas BNI-1 and SPA-2 partially colocalized with the Spk and the tip apex. Novel roles during septal plugging and cytokinesis, connected to the reinitiation of tip growth upon physical injury and conidial maturation, were identified for BUD-6 and BNI-1, respectively. Phenotypic analyses of gene deletion mutants revealed additional functions for BUD-6 and BNI-1 in cell fusion regulation, and the maintenance of Spk integrity. Considered together, our findings reveal novel polarisome-independent functions of BUD-6 and BNI-1 in Neurospora, but also suggest that all three proteins cooperate at plugged septal pores, and their complex arrangement within the apical dome of mature hypha might represent a novel aspect of filamentous fungal polarisome architecture.

  14. Vertical Distribution of Bacterial Communities in the Indian Ocean as Revealed by Analyses of 16S rRNA and nasA Genes.

    Science.gov (United States)

    Jiang, Xuexia; Jiao, Nianzhi

    2016-09-01

    Bacteria play an important role in the marine biogeochemical cycles. However, research on the bacterial community structure of the Indian Ocean is scarce, particularly within the vertical dimension. In this study, we investigated the bacterial diversity of the pelagic, mesopelagic and bathypelagic zones of the southwestern Indian Ocean (50.46°E, 37.71°S). The clone libraries constructed by 16S rRNA gene sequence revealed that most phylotypes retrieved from the Indian Ocean were highly divergent from those retrieved from other oceans. Vertical differences were observed based on the analysis of natural bacterial community populations derived from the 16S rRNA gene sequences. Based on the analysis of the nasA gene sequences from GenBank database, a pair of general primers was developed and used to amplify the bacterial nitrate-assimilating populations. Environmental factors play an important role in mediating the bacterial communities in the Indian Ocean revealed by canonical correlation analysis.

  15. Phylogenetic analyses of the subgenus Mollienesia (Poecilia, Poeciliidae, Teleostei) reveal taxonomic inconsistencies, cryptic biodiversity, and spatio-temporal aspects of diversification in Middle America.

    Science.gov (United States)

    Palacios, Maura; Voelker, Gary; Arias Rodriguez, Lenin; Mateos, Mariana; Tobler, Michael

    2016-10-01

    The subgenus Mollienesia is a diverse group of freshwater fishes, including species that have served as important models across multiple biological disciplines. Nonetheless, the taxonomic history of this group has been conflictive and convoluted, in part because the evolutionary relationships have not been rigorously resolved. We conducted a comprehensive molecular phylogenetic analysis of the subgenus Mollienesia to identify taxonomic discrepancies and potentially identify undescribed species, estimate ancestral areas of origin and estimate dates of divergence, as well as explore biogeographical patterns. Our findings confirm the presence of three main clades composed of the P. latipinna, P. sphenops, and P. mexicana species complexes. Unlike previously hypothesized morphology-based analyses, species found on the Caribbean Islands are not part of Mollienesia, but are more closely related to species of the subgenus Limia. Our study also revealed several taxonomic inconsistencies and distinct lineages in the P. mexicana species complex that may represent undescribed species. The diversity in the subgenus Mollienesia is a result of dynamic geologic activity leading to vicariant events, dispersal across geologic blocks, and ecological speciation.

  16. Mechanisms for the adverse effects of late gestational increases in maternal cortisol on the heart revealed by transcriptomic analyses of the fetal septum.

    Science.gov (United States)

    Richards, Elaine M; Wood, Charles E; Rabaglino, Maria Belen; Antolic, Andrew; Keller-Wood, Maureen

    2014-08-01

    We have previously shown in sheep that 10 days of modest chronic increase in maternal cortisol resulting from maternal infusion of cortisol (1 mg/kg/day) caused fetal heart enlargement and Purkinje cell apoptosis. In subsequent studies we extended the cortisol infusion to term, finding a dramatic incidence of stillbirth in the pregnancies with chronically increased cortisol. To investigate effects of maternal cortisol on the heart, we performed transcriptomic analyses on the septa using ovine microarrays and Webgestalt and Cytoscape programs for pathway inference. Analyses of the transcriptomic effects of maternal cortisol infusion for 10 days (130 day cortisol vs 130 day control), or ∼25 days (140 day cortisol vs 140 day control) and of normal maturation (140 day control vs 130 day control) were performed. Gene ontology terms related to immune function and cytokine actions were significantly overrepresented as genes altered by both cortisol and maturation in the septa. After 10 days of cortisol, growth factor and muscle cell apoptosis pathways were significantly overrepresented, consistent with our previous histologic findings. In the term fetuses (∼25 days of cortisol) nutrient pathways were significantly overrepresented, consistent with altered metabolism and reduced mitochondria. Analysis of mitochondrial number by mitochondrial DNA expression confirmed a significant decrease in mitochondria. The metabolic pathways modeled as altered by cortisol treatment to term were different from those modeled during maturation of the heart to term, and thus changes in gene expression in these metabolic pathways may be indicative of the fetal heart pathophysiologies seen in pregnancies complicated by stillbirth, including gestational diabetes, Cushing's disease and chronic stress.

  17. Directed random walks and constraint programming reveal active pathways in hepatocyte growth factor signaling.

    Science.gov (United States)

    Kittas, Aristotelis; Delobelle, Aurélien; Schmitt, Sabrina; Breuhahn, Kai; Guziolowski, Carito; Grabe, Niels

    2016-01-01

    An effective means to analyze mRNA expression data is to take advantage of established knowledge from pathway databases, using methods such as pathway-enrichment analyses. However, pathway databases are not case-specific and expression data could be used to infer gene-regulation patterns in the context of specific pathways. In addition, canonical pathways may not always describe the signaling mechanisms properly, because interactions can frequently occur between genes in different pathways. Relatively few methods have been proposed to date for generating and analyzing such networks, preserving the causality between gene interactions and reasoning over the qualitative logic of regulatory effects. We present an algorithm (MCWalk) integrated with a logic programming approach, to discover subgraphs in large-scale signaling networks by random walks in a fully automated pipeline. As an exemplary application, we uncover the signal transduction mechanisms in a gene interaction network describing hepatocyte growth factor-stimulated cell migration and proliferation from gene-expression measured with microarray and RT-qPCR using in-house perturbation experiments in a keratinocyte-fibroblast co-culture. The resulting subgraphs illustrate possible associations of hepatocyte growth factor receptor c-Met nodes, differentially expressed genes and cellular states. Using perturbation experiments and Answer Set programming, we are able to select those which are more consistent with the experimental data. We discover key regulator nodes by measuring the frequency with which they are traversed when connecting signaling between receptors and significantly regulated genes and predict their expression-shift consistently with the measured data. The Java implementation of MCWalk is publicly available under the MIT license at: https://bitbucket.org/akittas/biosubg.

  18. Exploratory and Higher-Order Factor Analyses of the Wechsler Adult Intelligence Scale-Fourth Edition (WAIS-IV) Adolescent Subsample

    Science.gov (United States)

    Canivez, Gary L.; Watkins, Marley W.

    2010-01-01

    The factor structure of the Wechsler Adult Intelligence Scale-Fourth Edition (WAIS-IV; Wechsler, 2008a) with the adolescent participants (ages 16-19 years; N = 400) in the standardization sample was assessed using exploratory factor analysis, multiple factor extraction criteria, and higher-order exploratory factor analyses. Results from…

  19. Exploratory and Higher-Order Factor Analyses of the Wechsler Adult Intelligence Scale-Fourth Edition (WAIS-IV) Adolescent Subsample

    Science.gov (United States)

    Canivez, Gary L.; Watkins, Marley W.

    2010-01-01

    The factor structure of the Wechsler Adult Intelligence Scale-Fourth Edition (WAIS-IV; Wechsler, 2008a) with the adolescent participants (ages 16-19 years; N = 400) in the standardization sample was assessed using exploratory factor analysis, multiple factor extraction criteria, and higher-order exploratory factor analyses. Results from…

  20. Phylogeographic Analyses Reveal a Crucial Role of Xinjiang in HIV-1 CRF07_BC and HCV 3a Transmissions in Asia

    Science.gov (United States)

    Liu, Jun; Zhang, Chiyu

    2011-01-01

    Background China faces an increasing prevalence of two HIV-1 circulating recombinant forms (CRFs) 07_BC and 08_BC. Both CRFs_BC were previously demonstrated to originate in Yunnan and spread to Liaoning from Yunnan via injection drug use (IDU) in China. Supposing it is true, we are unable to answer why only CRF07_BC, rather than both CRFs_BC together, was transmitted to Xinjiang. Methodology/Principal Findings We investigated the phylogeography of CRF07_BC and CRF08_BC using multiple HIV-1 genomic regions with Bayesian phylogeography method. Phylogenetic reconstructions showed that all CRF07_BC sequences were divided into two clades, Yunnan and Xinjiang, and all strains from other regions of mainland China clustered within the Xinjiang clade. Significant geographic diffusion links of Xinjiang with other regions (including Liaoning, Beijing, Jiangsu and Guangdong) were supported by Bayes factor tests. The temporal dynamics analyses showed that CRF07_BC spread from Xinjiang to Liaoning in 1996.10, and to Jiangsu in 2000.9. The analyses of CRF08_BC not only confirmed the previous conclusion on temporal and spatial dynamics of CRF08_BC, but also indicated that the CRF08_BC strains from Guangdong and Shanghai originated from Yunnan. The analyses of HCV 3a showed that it was introduced into Xinjiang in the early 1980s, and spread from Xinjiang to Yunnan in 1990.10 and to Jiangsu in 1999.2, and further from Yunnan to Guangxi in 1995.3. The temporal and spatial dynamics of HCV 3a were similar to some extent to that of HIV-1 CRF07_BC and/or CRF08_BC, suggesting a possible association in migration patterns between HCV and HIV-1 through IDU. In addition, HCV 3a spread from Xinjiang to Pakistan, implying a drug trafficking route linking them. Conclusions/Significance Xinjiang, as the most important transfer station for drug trafficking from Golden Crescent to other regions of China, plays a very crucial role in the transmission of viruses (e.g., HIV-1 and HCV) through IDU in

  1. Helmet Use Amongst Equestrians: Harnessing Social and Attitudinal Factors Revealed in Online Forums

    Science.gov (United States)

    Haigh, Laura; Thompson, Kirrilly

    2015-01-01

    Simple Summary Epidemiological research details a high rate of horse-related injury, despite technical countermeasures being widely available and largely affordable. Whilst barriers to engaging in preventative behavior such as helmet-use have been identified, less attention has been given to enabling factors. These factors could contribute to the design of more effective injury prevention interventions. To identify barriers as well as enablers in an Australian context, we explored how riders discussed helmet use amongst one another in an online setting. Our analysis revealed that social relations heavily influenced safety behavior. In particular, we identified three attitudes that affected helmet use: “I Can Control Risk”, “It Does Not Feel Right” and “Accidents Happen”. Abstract Equestrian activities pose significant head injury risks to participants. Yet, helmet use is not mandatory in Australia outside of selected competitions. Awareness of technical countermeasures and the dangers of equestrian activities has not resulted in widespread adoption of simple precautionary behaviors like helmet use. Until the use of helmets whilst riding horses is legislated in Australia, there is an urgent need to improve voluntary use. To design effective injury prevention interventions, the factors affecting helmet use must first be understood. To add to current understandings of these factors, we examined the ways horse riders discussed helmet use by analyzing 103 posts on two helmet use related threads from two different Australian equestrian forums. We found evidence of social influence on helmet use behaviors as well as three attitudes that contributed towards stated helmet use that we termed: “I Can Control Risk”, “It Does Not Feel Right” and “Accidents Happen”. Whilst we confirm barriers identified in previous literature, we also identify their ability to support helmet use. This suggests challenging but potentially useful complexity in the

  2. Transcriptome analysis of sexually dimorphic Chinese white wax scale insects reveals key differences in developmental programs and transcription factor expression.

    Science.gov (United States)

    Yang, Pu; Chen, Xiao-Ming; Liu, Wei-Wei; Feng, Ying; Sun, Tao

    2015-01-01

    The Chinese white wax scale insect, Ericerus pela, represents one of the most dramatic examples of sexual dimorphism in any insect species. In this study, we showed that although E. pela males display complete metamorphosis similar to holometabolous insects, the species forms the sister group to Acyrthosiphon pisum and cluster with hemimetabolous insects. The gene expression profile and Gene Ontology (GO) analyses revealed that the two sexes engaged in distinct developmental programs. In particular, female development appeared to prioritize the expression of genes related to cellular, metabolic, and developmental processes and to anatomical structure formation in nymphs. By contrast, male nymphal development is characterized by the significant down-regulation of genes involved in chitin, the respiratory system, and neurons. The wing and appendage morphogenesis, anatomical and tissue structure morphogenesis programs activated after male nymphal development. Transcription factors (that convey juvenile hormone or ecdysone signals, and Hox genes) and DNA methyltransferase were also differentially expressed between females and males. These results may indicate the roles that these differentially expressed genes play in regulating sexual dimorphism through orchestrating complex genetic programs. This differential expression was particularly prominent for processes linked to female development and wing development in males.

  3. Oogonial biometry and phylogenetic analyses of the Pythium vexans species group from woody agricultural hosts in South Africa reveal distinct groups within this taxon.

    Science.gov (United States)

    Spies, Christoffel F J; Mazzola, Mark; Botha, Wilhelm J; Van Der Rijst, Marieta; Mostert, Lizel; Mcleod, Adéle

    2011-02-01

    Pythium vexans fits into the internal transcribed spacer (ITS) clade K sensu Lévesque & De Cock (2004). Within clade K, P. vexans forms a distinct clade containing two enigmatic species, Pythium indigoferae and Pythium cucurbitacearum of which no ex-type strains are available. In South Africa, as well as in other regions of the world, P. vexans isolates are known to be heterogeneous in their ITS sequences and may consist of more than one species. This study aimed to investigate the diversity of South African P. vexans isolates, mainly from grapevines, but also citrus and apple using (i) phylogenetic analyses of the ITS, cytochrome c oxidase (cox) I, cox II, and β-tubulin regions and (ii) seven biometric oogonial parameters. Each of the phylogenies clustered P. vexans isolates into a single well-supported clade, distinct from other clade K species. The β-tubulin region was phylogenetically uninformative regarding the P. vexans group. The ITS phylogeny and combined cox I and II phylogenies, although each revealing several P. vexans subclades, were incongruent. One of the most striking incongruences was the presence of one cox subclade that contained two distinct ITS subclades (Ib and IV). Three groups (A-C) were subjectively identified among South African P. vexans isolates using (i) phylogenetic clades (ITS and cox), (ii) univariate analysis of oogonial diameters, and (iii) multivariate analyses of biometric oogonial parameters. Group A is considered to be P. vexans s. str. since it contained the P. vexans CBS reference strain from Van der Plaats-Niterink (1981). This group had significantly smaller oogonial diameters than group B and C isolates. Group B contained the isolates from ITS subclades Ib and IV, which formed a single cox subclade. The ITS subclade IV isolates were all sexually sterile or produced mainly abortive oospores, as opposed to the sexually fertile subclade Ib isolates, and may thus represent a distinct assemblage within group B. Although ITS

  4. ChIP-seq and in vivo transcriptome analyses of the Aspergillus fumigatus SREBP SrbA reveals a new regulator of the fungal hypoxia response and virulence.

    Directory of Open Access Journals (Sweden)

    Dawoon Chung

    2014-11-01

    Full Text Available The Aspergillus fumigatus sterol regulatory element binding protein (SREBP SrbA belongs to the basic Helix-Loop-Helix (bHLH family of transcription factors and is crucial for antifungal drug resistance and virulence. The latter phenotype is especially striking, as loss of SrbA results in complete loss of virulence in murine models of invasive pulmonary aspergillosis (IPA. How fungal SREBPs mediate fungal virulence is unknown, though it has been suggested that lack of growth in hypoxic conditions accounts for the attenuated virulence. To further understand the role of SrbA in fungal infection site pathobiology, chromatin immunoprecipitation followed by massively parallel DNA sequencing (ChIP-seq was used to identify genes under direct SrbA transcriptional regulation in hypoxia. These results confirmed the direct regulation of ergosterol biosynthesis and iron uptake by SrbA in hypoxia and revealed new roles for SrbA in nitrate assimilation and heme biosynthesis. Moreover, functional characterization of an SrbA target gene with sequence similarity to SrbA identified a new transcriptional regulator of the fungal hypoxia response and virulence, SrbB. SrbB co-regulates genes involved in heme biosynthesis and demethylation of C4-sterols with SrbA in hypoxic conditions. However, SrbB also has regulatory functions independent of SrbA including regulation of carbohydrate metabolism. Loss of SrbB markedly attenuates A. fumigatus virulence, and loss of both SREBPs further reduces in vivo fungal growth. These data suggest that both A. fumigatus SREBPs are critical for hypoxia adaptation and virulence and reveal new insights into SREBPs' complex role in infection site adaptation and fungal virulence.

  5. Genome-wide analysis of the Dof transcription factor gene family reveals soybean-specific duplicable and functional characteristics.

    Directory of Open Access Journals (Sweden)

    Yong Guo

    Full Text Available The Dof domain protein family is a classic plant-specific zinc-finger transcription factor family involved in a variety of biological processes. There is great diversity in the number of Dof genes in different plants. However, there are only very limited reports on the characterization of Dof transcription factors in soybean (Glycine max. In the present study, 78 putative Dof genes were identified from the whole-genome sequence of soybean. The predicted GmDof genes were non-randomly distributed within and across 19 out of 20 chromosomes and 97.4% (38 pairs were preferentially retained duplicate paralogous genes located in duplicated regions of the genome. Soybean-specific segmental duplications contributed significantly to the expansion of the soybean Dof gene family. These Dof proteins were phylogenetically clustered into nine distinct subgroups among which the gene structure and motif compositions were considerably conserved. Comparative phylogenetic analysis of these Dof proteins revealed four major groups, similar to those reported for Arabidopsis and rice. Most of the GmDofs showed specific expression patterns based on RNA-seq data analyses. The expression patterns of some duplicate genes were partially redundant while others showed functional diversity, suggesting the occurrence of sub-functionalization during subsequent evolution. Comprehensive expression profile analysis also provided insights into the soybean-specific functional divergence among members of the Dof gene family. Cis-regulatory element analysis of these GmDof genes suggested diverse functions associated with different processes. Taken together, our results provide useful information for the functional characterization of soybean Dof genes by combining phylogenetic analysis with global gene-expression profiling.

  6. Genetic characterization of the HrpL regulon of the fire blight pathogen Erwinia amylovora reveals novel virulence factors.

    Science.gov (United States)

    McNally, R Ryan; Toth, Ian K; Cock, Peter J A; Pritchard, Leighton; Hedley, Pete E; Morris, Jenny A; Zhao, Youfu; Sundin, George W

    2012-02-01

    The bacterial pathogen Erwinia amylovora is the causal agent of fire blight, an economically significant disease of apple and pear. Disease initiation by E. amylovora requires the translocation of effector proteins into host cells via the hypersensitive response and pathogenicity (hrp) type III secretion system (T3SS). The alternative sigma factor HrpL positively regulates the transcription of structural and translocated components of the T3SS via hrp promoter elements. To characterize genome-wide HrpL-dependent gene expression in E. amylovora Ea1189, wild-type and Ea1189ΔhrpL strains were cultured in hrp-inducing minimal medium, and total RNA was compared using a custom microarray designed to represent the annotated genes of E. amylovora ATCC 49946. The results revealed 24 genes differentially regulated in Ea1189ΔhrpL relative to Ea1189 with fold-change expression ratios greater than 1.5; of these, 19 genes exhibited decreased transcript abundance and five genes showed increased transcript abundance relative to Ea1189. To expand our understanding of the HrpL regulon and to elucidate direct versus indirect HrpL-mediated effects on gene expression, the genome of E. amylovora ATCC 49946 was examined in silico using a hidden Markov model assembled from known Erwinia spp. hrp promoters. This technique identified 15 putative type III novel hrp promoters, seven of which were validated with quantitative polymerase chain reaction based on expression analyses. It was found that HrpL-regulated genes encode all known components of the hrp T3SS, as well as five putative type III effectors. Eight genes displayed apparent indirect HrpL regulation, suggesting that the HrpL regulon is connected to downstream signalling networks. The construction of deletion mutants of three novel HrpL-regulated genes resulted in the identification of additional virulence factors as well as mutants displaying abnormal motility and biofilm phenotypes.

  7. A quorum-sensing factor in vegetative Dictyostelium discoideum cells revealed by quantitative migration analysis.

    Directory of Open Access Journals (Sweden)

    Laurent Golé

    Full Text Available BACKGROUND: Many cells communicate through the production of diffusible signaling molecules that accumulate and once a critical concentration has been reached, can activate or repress a number of target genes in a process termed quorum sensing (QS. In the social amoeba Dictyostelium discoideum, QS plays an important role during development. However little is known about its effect on cell migration especially in the growth phase. METHODS AND FINDINGS: To investigate the role of cell density on cell migration in the growth phase, we use multisite timelapse microscopy and automated cell tracking. This analysis reveals a high heterogeneity within a given cell population, and the necessity to use large data sets to draw reliable conclusions on cell motion. In average, motion is persistent for short periods of time (t ≤ 5 min, but normal diffusive behavior is recovered over longer time periods. The persistence times are positively correlated with the migrated distances. Interestingly, the migrated distance decreases as well with cell density. The adaptation of cell migration to cell density highlights the role of a secreted quorum sensing factor (QSF on cell migration. Using a simple model describing the balance between the rate of QSF generation and the rate of QSF dilution, we were able to gather all experimental results into a single master curve, showing a sharp cell transition between high and low motile behaviors with increasing QSF. CONCLUSION: This study unambiguously demonstrates the central role played by QSF on amoeboid motion in the growth phase.

  8. Structures of ribosome-bound initiation factor 2 reveal the mechanism of subunit association

    Science.gov (United States)

    Sprink, Thiemo; Ramrath, David J. F.; Yamamoto, Hiroshi; Yamamoto, Kaori; Loerke, Justus; Ismer, Jochen; Hildebrand, Peter W.; Scheerer, Patrick; Bürger, Jörg; Mielke, Thorsten; Spahn, Christian M. T.

    2016-01-01

    Throughout the four phases of protein biosynthesis—initiation, elongation, termination, and recycling—the ribosome is controlled and regulated by at least one specified translational guanosine triphosphatase (trGTPase). Although the structural basis for trGTPase interaction with the ribosome has been solved for the last three steps of translation, the high-resolution structure for the key initiation trGTPase, initiation factor 2 (IF2), complexed with the ribosome, remains elusive. We determine the structure of IF2 complexed with a nonhydrolyzable guanosine triphosphate analog and initiator fMet-tRNAiMet in the context of the Escherichia coli ribosome to 3.7-Å resolution using cryo-electron microscopy. The structural analysis reveals previously unseen intrinsic conformational modes of the 70S initiation complex, establishing the mutual interplay of IF2 and initator transfer RNA (tRNA) with the ribsosome and providing the structural foundation for a mechanistic understanding of the final steps of translation initiation. PMID:26973877

  9. Genetic Structuration, Demography and Evolutionary History of Mycobacterium tuberculosis LAM9 Sublineage in the Americas as Two Distinct Subpopulations Revealed by Bayesian Analyses.

    Science.gov (United States)

    Reynaud, Yann; Millet, Julie; Rastogi, Nalin

    2015-01-01

    Tuberculosis (TB) remains broadly present in the Americas despite intense global efforts for its control and elimination. Starting from a large dataset comprising spoligotyping (n = 21183 isolates) and 12-loci MIRU-VNTRs data (n = 4022 isolates) from a total of 31 countries of the Americas (data extracted from the SITVIT2 database), this study aimed to get an overview of lineages circulating in the Americas. A total of 17119 (80.8%) strains belonged to the Euro-American lineage 4, among which the most predominant genotypic family belonged to the Latin American and Mediterranean (LAM) lineage (n = 6386, 30.1% of strains). By combining classical phylogenetic analyses and Bayesian approaches, this study revealed for the first time a clear genetic structuration of LAM9 sublineage into two subpopulations named LAM9C1 and LAM9C2, with distinct genetic characteristics. LAM9C1 was predominant in Chile, Colombia and USA, while LAM9C2 was predominant in Brazil, Dominican Republic, Guadeloupe and French Guiana. Globally, LAM9C2 was characterized by higher allelic richness as compared to LAM9C1 isolates. Moreover, LAM9C2 sublineage appeared to expand close to twenty times more than LAM9C1 and showed older traces of expansion. Interestingly, a significant proportion of LAM9C2 isolates presented typical signature of ancestral LAM-RDRio MIRU-VNTR type (224226153321). Further studies based on Whole Genome Sequencing of LAM strains will provide the needed resolution to decipher the biogeographical structure and evolutionary history of this successful family.

  10. Ancient DNA analyses of early archaeological sites in New Zealand reveal extreme exploitation of moa (Aves: Dinornithiformes) at all life stages

    Science.gov (United States)

    Oskam, Charlotte L.; Allentoft, Morten E.; Walter, Richard; Scofield, R. Paul; Haile, James; Holdaway, Richard N.; Bunce, Michael; Jacomb, Chris

    2012-10-01

    The human colonisation of New Zealand in the late thirteenth century AD led to catastrophic impacts on the local biota and is among the most compelling examples of human over-exploitation of native fauna, including megafauna. Nearly half of the species in New Zealand' s pre-human avifauna are now extinct, including all nine species of large, flightless moa (Aves: Dinornithiformes). The abundance of moa in early archaeological sites demonstrates the significance of these megaherbivores in the diet of the first New Zealanders. Combining moa assemblage data, based on DNA identification of eggshell and bone, with morphological identification of bone (literature and museum catalogued specimens), we present the most comprehensive audit of moa to date from several significant 13th-15th century AD archaeological deposits across the east coast of the South Island. Mitochondrial DNA (mtDNA) was amplified from 251 of 323 (78%) eggshell fragments and 22 of 27 (88%) bone samples, and the analyses revealed the presence of four moa species: Anomalopteryx didiformis; Dinornis robustus; Emeus crassus and Euryapteryx curtus. The mtDNA, along with polymorphic microsatellite markers, enabled an estimate of the minimum number of individual eggs consumed at each site. Remarkably, in one deposit over 50 individual eggs were identified - a number that likely represents a considerable proportion of the total reproductive output of moa in the area and emphasises that human predation of all life stages of moa was intense. Molecular sexing was conducted on bones (n = 11). Contrary to previous ancient DNA studies from natural sites that consistently report an excess of female moa, we observed an excess of males (2.7:1), suggestive that males were preferential targets. This could be related to different behaviour between the two highly size-dimorphic sexes in moa. Lastly, we investigated the moa species from recovered skeletal and eggshell remains from seven Wairau Bar burials, and identified

  11. Physiological and proteomics analyses reveal the mechanism of Eichhornia crassipes tolerance to high-concentration cadmium stress compared with Pistia stratiotes.

    Directory of Open Access Journals (Sweden)

    Xiong Li

    Full Text Available Cadmium (Cd pollution is an environmental problem worldwide. Phytoremediation is a convenient method of removing Cd from both soil and water, but its efficiency is still low, especially in aquatic environments. Scientists have been trying to improve the ability of plants to absorb and accumulate Cd based on interactions between plants and Cd, especially the mechanism by which plants resist Cd. Eichhornia crassipes and Pistia stratiotes are aquatic plants commonly used in the phytoremediation of heavy metals. In the present study, we conducted physiological and biochemical analyses to compare the resistance of these two species to Cd stress at 100 mg/L. E. crassipes showed stronger resistance and was therefore used for subsequent comparative proteomics to explore the potential mechanism of E. crassipes tolerance to Cd stress at the protein level. The expression patterns of proteins in different functional categories revealed that the physiological activities and metabolic processes of E. crassipes were affected by exposure to Cd stress. However, when some proteins related to these processes were negatively inhibited, some analogous proteins were induced to compensate for the corresponding functions. As a result, E. crassipes could maintain more stable physiological parameters than P. stratiotes. Many stress-resistance substances and proteins, such as proline and heat shock proteins (HSPs and post translational modifications, were found to be involved in the protection and repair of functional proteins. In addition, antioxidant enzymes played important roles in ROS detoxification. These findings will facilitate further understanding of the potential mechanism of plant response to Cd stress at the protein level.

  12. Genetic Structuration, Demography and Evolutionary History of Mycobacterium tuberculosis LAM9 Sublineage in the Americas as Two Distinct Subpopulations Revealed by Bayesian Analyses.

    Directory of Open Access Journals (Sweden)

    Yann Reynaud

    Full Text Available Tuberculosis (TB remains broadly present in the Americas despite intense global efforts for its control and elimination. Starting from a large dataset comprising spoligotyping (n = 21183 isolates and 12-loci MIRU-VNTRs data (n = 4022 isolates from a total of 31 countries of the Americas (data extracted from the SITVIT2 database, this study aimed to get an overview of lineages circulating in the Americas. A total of 17119 (80.8% strains belonged to the Euro-American lineage 4, among which the most predominant genotypic family belonged to the Latin American and Mediterranean (LAM lineage (n = 6386, 30.1% of strains. By combining classical phylogenetic analyses and Bayesian approaches, this study revealed for the first time a clear genetic structuration of LAM9 sublineage into two subpopulations named LAM9C1 and LAM9C2, with distinct genetic characteristics. LAM9C1 was predominant in Chile, Colombia and USA, while LAM9C2 was predominant in Brazil, Dominican Republic, Guadeloupe and French Guiana. Globally, LAM9C2 was characterized by higher allelic richness as compared to LAM9C1 isolates. Moreover, LAM9C2 sublineage appeared to expand close to twenty times more than LAM9C1 and showed older traces of expansion. Interestingly, a significant proportion of LAM9C2 isolates presented typical signature of ancestral LAM-RDRio MIRU-VNTR type (224226153321. Further studies based on Whole Genome Sequencing of LAM strains will provide the needed resolution to decipher the biogeographical structure and evolutionary history of this successful family.

  13. Genes for the Major Structural Components of Thermotogales Species' Togas Revealed by Proteomic and Evolutionary Analyses of OmpA and OmpB Homologs

    Energy Technology Data Exchange (ETDEWEB)

    Petrus, Amanda K. [Univ. of Connecticut, Storrs, CT (United States); Swithers, Kristen S. [Univ. of Connecticut, Storrs, CT (United States); Ranjit, Chaman R. [Univ. of Connecticut, Storrs, CT (United States); Wu, Si [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Brewer, Heather M. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Gogarten, J. Peter [Univ. of Connecticut, Storrs, CT (United States); Pasa-Tolic, Ljiljana [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Noll, Kenneth M. [Univ. of Connecticut, Storrs, CT (United States)

    2012-06-29

    The unifying structural characteristic of members of the bacterial order Thermotogales is an unusual cell envelope that includes a loose-fitting sheath around each cell, often called a toga. Only two toga-associated structural proteins have been identified in Thermotoga maritima: the anchor protein OmpA1 (previously termed Ompα) and the porin OmpB (previously termed Ompβ). The gene encoding OmpA (ompA1) was assigned in the genome sequence to TM0477, but because no peptide sequence was available for OmpB, its gene (ompB) was not annotated. Here we identify the ompB gene as TM0476, determined by LC/MS/MS analysis of the native OmpB protein purified from T. maritima cells. The purified OmpB had β-sheet secondary structure as determined by circular dichroism. Analysis of the sequence of ompB product shows it has porin characteristics including a carboxy terminus anchoring motif and a porin-specific amino acid composition. Orthologs of ompB were found in the genomes of some, but not all, Thermotogales. Those without orthologs have putative analogs. Phylogenetic analyses of OmpA1 revealed that each species of the Thermotogales has one to three OmpA homologs. T. maritima has two OmpA homologs, encoded by ompA1(TM0477) and ompA2 (TM1729), both of which were found in the toga protein-enriched cell extracts. These annotations of the genes encoding toga structural proteins will guide future examinations of the structure and function of this unusual lineage-defining cell sheath.

  14. Genetic diversity within the genus Francisella as revealed by comparative analyses of the genomes of two North American isolates from environmental sources

    Directory of Open Access Journals (Sweden)

    Siddaramappa Shivakumara

    2012-08-01

    Full Text Available Abstract Background Francisella tularensis is an intracellular pathogen that causes tularemia in humans and the public health importance of this bacterium has been well documented in recent history. Francisella philomiragia, a distant relative of F. tularensis, is thought to constitute an environmental lineage along with Francisella novicida. Nevertheless, both F. philomiragia and F. novicida have been associated with human disease, primarily in immune-compromised individuals. To understand the genetic relationships and evolutionary contexts among different lineages within the genus Francisella, the genome of Francisella spp. strain TX07-7308 was sequenced and compared to the genomes of F. philomiragia strains ATCC 25017 and 25015, F. novicida strain U112, and F. tularensis strain Schu S4. Results The size of strain ATCC 25017 chromosome was 2,045,775 bp and contained 1,983 protein-coding genes. The size of strain TX07-7308 chromosome was 2,035,931 bp and contained 1,980 protein-coding genes. Pairwise BLAST comparisons indicated that strains TX07-7308 and ATCC 25017 contained 1,700 protein coding genes in common. NUCmer analyses revealed that the chromosomes of strains TX07-7308 and ATCC 25017 were mostly collinear except for a few gaps, translocations, and/or inversions. Using the genome sequence data and comparative analyses with other members of the genus Francisella (e.g., F. novicida strain U112 and F. tularensis strain Schu S4, several strain-specific genes were identified. Strains TX07-7308 and ATCC 25017 contained an operon with six open reading frames encoding proteins related to enzymes involved in thiamine biosynthesis that was absent in F. novicida strain U112 and F. tularensis strain Schu S4. Strain ATCC 25017 contained an operon putatively involved in lactose metabolism that was absent in strain TX07-7308, F. novicida strain U112, and F. tularensis strain Schu S4. In contrast, strain TX07-7308 contained an operon putatively

  15. Analysing the causes of chronic cough: relation to diesel exhaust, ozone, nitrogen oxides, sulphur oxides and other environmental factors

    Directory of Open Access Journals (Sweden)

    Wagner Ulrich

    2006-05-01

    Full Text Available Abstract Air pollution remains a leading cause of many respiratory diseases including chronic cough. Although episodes of incidental, dramatic air pollution are relatively rare, current levels of exposure of pollutants in industrialized and developing countries such as total articles, diesel exhaust particles and common cigarette smoke may be responsible for the development of chronic cough both in children and adults. The present study analyses the effects of common environmental factors as potential causes of chronic cough. Different PubMed-based researches were performed that related the term cough to various environmental factors. There is some evidence that chronic inhalation of diesel can lead to the development of cough. For long-term exposure to nitrogen dioxide (NO2, children were found to exhibit increased incidences of chronic cough and decreased lung function parameters. Although a number of studies did not show that outdoor pollution directly causes the development of asthma, they have demonstrated that high levels pollutants and their interaction with sunlight produce ozone (O3 and that repeated exposure to it can lead to chronic cough. In summary, next to the well-known air pollutants which also include particulate matter and sulphur dioxide, a number of other indoor and outdoor pollutants have been demonstrated to cause chronic cough and therefore, environmental factors have to be taken into account as potential initiators of both adult and pediatric chronic cough.

  16. Expression profiling and Ingenuity biological function analyses of interleukin-6- versus nerve growth factor-stimulated PC12 cells

    Directory of Open Access Journals (Sweden)

    Dimitriades-Schmutz Beatrice

    2009-02-01

    Full Text Available Abstract Background The major goal of the study was to compare the genetic programs utilized by the neuropoietic cytokine Interleukin-6 (IL-6 and the neurotrophin (NT Nerve Growth Factor (NGF for neuronal differentiation. Results The designer cytokine Hyper-IL-6 in which IL-6 is covalently linked to its soluble receptor s-IL-6R as well as NGF were used to stimulate PC12 cells for 24 hours. Changes in gene expression levels were monitored using Affymetrix GeneChip technology. We found different expression for 130 genes in IL-6- and 102 genes in NGF-treated PC12 cells as compared to unstimulated controls. The gene set shared by both stimuli comprises only 16 genes. A key step is upregulation of growth factors and functionally related external molecules known to play important roles in neuronal differentiation. In particular, IL-6 enhances gene expression of regenerating islet-derived 3 alpha (REG3A; 1084-fold, regenerating islet-derived 3 beta (REG3B/PAPI; 672-fold, growth differentiation factor 15 (GDF15; 80-fold, platelet-derived growth factor alpha (PDGFA; 69-fold, growth hormone releasing hormone (GHRH; 30-fold, adenylate cyclase activating polypeptide (PACAP; 20-fold and hepatocyte growth factor (HGF; 5-fold. NGF recruits GDF15 (131-fold, transforming growth factor beta 1 (TGFB1; 101-fold and brain-derived neurotrophic factor (BDNF; 89-fold. Both stimuli activate growth-associated protein 43 (GAP-43 indicating that PC12 cells undergo substantial neuronal differentiation. Moreover, IL-6 activates the transcription factors retinoic acid receptor alpha (RARA; 20-fold and early growth response 1 (Egr1/Zif268; 3-fold known to play key roles in neuronal differentiation. Ingenuity biological function analysis revealed that completely different repertoires of molecules are recruited to exert the same biological functions in neuronal differentiation. Major sub-categories include cellular growth and differentiation, cell migration, chemotaxis, cell

  17. Factor VIII/V C-domain swaps reveal discrete C-domain roles in factor VIII function and intracellular trafficking.

    Science.gov (United States)

    Ebberink, Eduard H T M; Bouwens, Eveline A M; Bloem, Esther; Boon-Spijker, Mariëtte; van den Biggelaar, Maartje; Voorberg, Jan; Meijer, Alexander B; Mertens, Koen

    2017-04-01

    Factor VIII C-domains are believed to have specific functions in cofactor activity and in interactions with von Willebrand factor. We have previously shown that factor VIII is co-targeted with von Willebrand factor to the Weibel-Palade bodies in blood outgrowth endothelial cells, even when factor VIII carries mutations in the light chain that are associated with defective von Willebrand factor binding. In this study, we addressed the contribution of individual factor VIII C-domains in intracellular targeting, von Willebrand factor binding and cofactor activity by factor VIII/V C-domain swapping. Blood outgrowth endothelial cells were transduced with lentivirus encoding factor V, factor VIII or YFP-tagged C-domain chimeras, and examined by confocal microscopy. The same chimeras were produced in HEK293-cells for in vitro characterization and chemical foot-printing by mass spectrometry. In contrast to factor VIII, factor V did not target to Weibel-Palade bodies. The chimeras showed reduced Weibel-Palade body targeting, suggesting that this requires the factor VIII C1-C2 region. The factor VIII/V-C1 chimera did not bind von Willebrand factor and had reduced affinity for activated factor IX, whereas the factor VIII/V-C2 chimera showed a minor reduction in von Willebrand factor binding and normal interaction with activated factor IX. This suggests that mainly the C1-domain carries factor VIII-specific features in assembly with von Willebrand factor and activated factor IX. Foot-printing analysis of the chimeras revealed increased exposure of lysine residues in the A1/C2- and C1/C2-domain interface, suggesting increased C2-domain mobility and disruption of the natural C-domain tandem pair orientation. Apparently, this affects intracellular trafficking, but not extracellular function. Copyright© Ferrata Storti Foundation.

  18. Glycan structure of Gc Protein-derived Macrophage Activating Factor as revealed by mass spectrometry.

    Science.gov (United States)

    Borges, Chad R; Rehder, Douglas S

    2016-09-15

    Disagreement exists regarding the O-glycan structure attached to human vitamin D binding protein (DBP). Previously reported evidence indicated that the O-glycan of the Gc1S allele product is the linear core 1 NeuNAc-Gal-GalNAc-Thr trisaccharide. Here, glycan structural evidence is provided from glycan linkage analysis and over 30 serial glycosidase-digestion experiments which were followed by analysis of the intact protein by electrospray ionization mass spectrometry (ESI-MS). Results demonstrate that the O-glycan from the Gc1F protein is the same linear trisaccharide found on the Gc1S protein and that the hexose residue is galactose. In addition, the putative anti-cancer derivative of DBP known as Gc Protein-derived Macrophage Activating Factor (GcMAF, which is formed by the combined action of β-galactosidase and neuraminidase upon DBP) was analyzed intact by ESI-MS, revealing that the activating E. coli β-galactosidase cleaves nothing from the protein-leaving the glycan structure of active GcMAF as a Gal-GalNAc-Thr disaccharide, regardless of the order in which β-galactosidase and neuraminidase are applied. Moreover, glycosidase digestion results show that α-N-Acetylgalactosamindase (nagalase) lacks endoglycosidic function and only cleaves the DBP O-glycan once it has been trimmed down to a GalNAc-Thr monosaccharide-precluding the possibility of this enzyme removing the O-glycan trisaccharide from cancer-patient DBP in vivo.

  19. Functional biogeography of ocean microbes revealed through non-negative matrix factorization.

    Directory of Open Access Journals (Sweden)

    Xingpeng Jiang

    Full Text Available The direct "metagenomic" sequencing of genomic material from complex assemblages of bacteria, archaea, viruses and microeukaryotes has yielded new insights into the structure of microbial communities. For example, analysis of metagenomic data has revealed the existence of previously unknown microbial taxa whose spatial distributions are limited by environmental conditions, ecological competition, and dispersal mechanisms. However, differences in genotypes that might lead biologists to designate two microbes as taxonomically distinct need not necessarily imply differences in ecological function. Hence, there is a growing need for large-scale analysis of the distribution of microbial function across habitats. Here, we present a framework for investigating the biogeography of microbial function by analyzing the distribution of protein families inferred from environmental sequence data across a global collection of sites. We map over 6,000,000 protein sequences from unassembled reads from the Global Ocean Survey dataset to [Formula: see text] protein families, generating a protein family relative abundance matrix that describes the distribution of each protein family across sites. We then use non-negative matrix factorization (NMF to approximate these protein family profiles as linear combinations of a small number of ecological components. Each component has a characteristic functional profile and site profile. Our approach identifies common functional signatures within several of the components. We use our method as a filter to estimate functional distance between sites, and find that an NMF-filtered measure of functional distance is more strongly correlated with environmental distance than a comparable PCA-filtered measure. We also find that functional distance is more strongly correlated with environmental distance than with geographic distance, in agreement with prior studies. We identify similar protein functions in several components and

  20. An Allosteric Pathway Revealed in the Ribosome Binding Stress Factor BipA

    Energy Technology Data Exchange (ETDEWEB)

    Makanji, H.; deLivron, M; Robinson, V

    2009-01-01

    BipA is a highly conserved prokaryotic GTPase that functions as a master regulator of stress and virulence processes in bacteria. It is a member of the translational factor family of GTPases along with EF-G, IF-2 and LepA. Structural and biochemical data suggest that ribosome binding specificity for each member of this family lies in an effector domain. As with other bacterial GTPases, the ribosome binding and GTPase activities of this protein are tightly coupled. However, the mechanism by which this occurs is still unknown. A series of experiments have been designed to probe structural features of the protein to see if we can pinpoint specific areas of BipA, perhaps even individual residues, which are important to its association with the ribosome. Included in the list are the C-terminal effector domain of the protein, which is distinct to the BipA family of proteins, and amino acid residues in the switch I and II regions of the G domain. Using sucrose density gradients, we have shown that the C-terminal domain is required in order for BipA to bind to the ribosome. Moreover, deletion of this domain increases the GTP hydrolysis rates of the protein, likely through relief of inhibitory contacts. Additional evidence has revealed an allosteric connection between the conformationally flexible switch II region and the C-terminal domain of BipA. Site directed mutagenesis, sucrose gradients and malachite green assays are being used to elucidate the details of this coupling.

  1. Koala retrovirus genotyping analyses reveal a low prevalence of KoRV-A in Victorian koalas and an association with clinical disease.

    Science.gov (United States)

    Legione, Alistair R; Patterson, Jade L S; Whiteley, Pam; Firestone, Simon M; Curnick, Megan; Bodley, Kate; Lynch, Michael; Gilkerson, James R; Sansom, Fiona M; Devlin, Joanne M

    2017-02-01

    Koala retrovirus (KoRV) is undergoing endogenization into the genome of koalas in Australia, providing an opportunity to assess the effect of retrovirus infection on the health of a population. The prevalence of KoRV in north-eastern Australia (Queensland and New South Wales) is 100 %, whereas previous preliminary investigations in south-eastern Australia (Victoria) suggested KoRV is present at a lower prevalence, although the values have varied widely. Here, we describe a large study of free-ranging koalas in Victoria to estimate the prevalence of KoRV and assess the clinical significance of KoRV infection in wild koalas. Blood or spleen samples from 648 koalas where tested for KoRV provirus, and subsequently genotyped, using PCRs to detect the pol and env genes respectively. Clinical data was also recorded where possible and analysed in comparison to infection status. The prevalence of KoRV was 24.7 % (160/648). KoRV-A was detected in 141/160 cases, but KoRV-B, a genotype associated with neoplasia in captive koalas, was not detected. The genotype in 19 cases could not be determined. Genomic differences between KoRV in Victoria and type strains may have impacted genotyping. Factors associated with KoRV infection, based on multivariable analysis, were low body condition score, region sampled, and 'wet bottom' (a staining of the fur around the rump associated with chronic urinary incontinence). Koalas with wet bottom were nearly twice as likely to have KoRV provirus detected than those without wet bottom (odds ratio=1.90, 95 % confidence interval 1.21, 2.98). Our findings have important implications for the conservation of this iconic species, particularly regarding translocation potential of Victorian koalas.

  2. The Anxiety Sensitivity Index--Revised: Confirmatory Factor Analyses, Structural Invariance in Caucasian and African American Samples, and Score Reliability and Validity

    Science.gov (United States)

    Arnau, Randolph C.; Broman-Fulks, Joshua J.; Green, Bradley A.; Berman, Mitchell E.

    2009-01-01

    The most commonly used measure of anxiety sensitivity is the 36-item Anxiety Sensitivity Index--Revised (ASI-R). Exploratory factor analyses have produced several different factors structures for the ASI-R, but an acceptable fit using confirmatory factor analytic approaches has only been found for a 21-item version of the instrument. We evaluated…

  3. The Anxiety Sensitivity Index--Revised: Confirmatory Factor Analyses, Structural Invariance in Caucasian and African American Samples, and Score Reliability and Validity

    Science.gov (United States)

    Arnau, Randolph C.; Broman-Fulks, Joshua J.; Green, Bradley A.; Berman, Mitchell E.

    2009-01-01

    The most commonly used measure of anxiety sensitivity is the 36-item Anxiety Sensitivity Index--Revised (ASI-R). Exploratory factor analyses have produced several different factors structures for the ASI-R, but an acceptable fit using confirmatory factor analytic approaches has only been found for a 21-item version of the instrument. We evaluated…

  4. Gender-Specific Analyses of the Prevalence and Factors Associated with Substance Use and Misuse among Bosniak Adolescents

    Directory of Open Access Journals (Sweden)

    Natasa Zenic

    2015-06-01

    Full Text Available Ethnicity and religion are known to be important factors associated with substance use and misuse (SUM. Ethnic Bosniaks, Muslims by religion, are the third largest ethnic group in the territory of the former Yugoslavia, but no study has examined SUM patterns among them. The aim of this study was to explore the prevalence of SUM and to examine scholastic-, familial- and sport-factors associated with SUM in adolescent Bosniaks from Bosnia-and-Herzegovina. The sample comprised 970 17-to-18-year-old adolescents (48% boys. Testing was performed using an previously validated questionnaire investigating socio-demographic-factors, scholastic-variables, and sport-factors, cigarette smoking, alcohol drinking, simultaneous smoking and drinking (multiple SUM, and the consumption of other drugs. The 30% of boys and 32% of girls smoke (OR = 1.13; 95% CI = 0.86–1.49, 41% of boys and 27% of girls are defined as harmful alcohol drinkers (OR = 1.94; 95% CI = 1.48–2.54, multiple SUM is prevalent in 17% of boys and 15% of girls (OR = 1.11; 95% CI = 0.79–1.56, while the consumption of other drugs, including sedatives, is higher in girls (6% and 15% for boys and girls, respectively; OR = 2.98; 95% CI = 1.89–4.70. Scholastic achievement is negatively associated with SUM. SUM is more prevalent in those girls who report higher income, and boys who report a worse familial financial situation. The study revealed more negative than positive associations between sport participation and SUM, especially among girls. Results can help public health authorities to develop more effective prevention campaign against SUM in adolescence.

  5. Stable isotope analyses reveal the importance of seagrass beds as feeding areas for juvenile Myrophis punctatus (Angulliformes: Ophichthidae) inthe coastal waters of Florida

    Science.gov (United States)

    The feeding habits and habitats of the speckled worm eel Myrophis punctatus were studied on the mangrove edge of the Indian River Lagoon (Florida) using stomach contents and stable isotope analyses of carbon (δ13C) and nitrogen (δ15N). Stomach dietary analyses identified four tax...

  6. Proteomic analyses reveal the key roles of BrlA and AbaA in biogenesis of gliotoxin in Aspergillus fumigatus

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Kwang-Soo, E-mail: shinks@dju.kr [Division of Life Science, Daejeon University, Daejeon, 300-716 (Korea, Republic of); Kim, Young Hwan [Biomedical Omics Team, Korea Basic Science Institute (KBSI), Ohcang, 368-883 (Korea, Republic of); Graduate School of Analytical Science and Technology, Chungnam National University, Daejeon, 305-764 (Korea, Republic of); Department of Bio-Analytical Science, University of Science and Technology, Daejeon, 305-333 (Korea, Republic of); Yu, Jae-Hyuk, E-mail: jyu1@wisc.edu [Departments of Bacteriology and Genetics, The University of Wisconsin–Madison, Madison, WI, 53706 (United States)

    2015-07-31

    The opportunistic human pathogenic fungus Aspergillus fumigatus primarily reproduces by forming a large number of asexual spores (conidia). Sequential activation of the central regulators BrlA, AbaA and WetA is necessary for the fungus to undergo asexual development. In this study, to address the presumed roles of these key developmental regulators during proliferation of the fungus, we analyzed and compared the proteomes of vegetative cells of wild type (WT) and individual mutant strains. Approximately 1300 protein spots were detectable from 2-D electrophoresis gels. Among these, 13 proteins exhibiting significantly altered accumulation levels were further identified by ESI-MS/MS. Markedly, we found that the GliM and GliT proteins associated with gliotoxin (GT) biosynthesis and self-protection of the fungus from GT were significantly down-regulated in the ΔabaA and ΔbrlA mutants. Moreover, mRNA levels of other GT biosynthetic genes including gliM, gliP, gliT, and gliZ were significantly reduced in both mutant strains, and no and low levels of GT were detectable in the ΔbrlA and ΔabaA mutant strains, respectively. As GliT is required for the protection of the fungus from GT, growth of the ΔbrlA mutant with reduced levels of GliT was severely impaired by exogenous GT. Our studies demonstrate that AbaA and BrlA positively regulate expression of the GT biosynthetic gene cluster in actively growing vegetative cells, and likely bridge morphological and chemical development during the life-cycle of A. fumigatus. - Highlights: • Proteome analyses of WT and mutants reveal 13 differentially expressed proteins. • The GliT and GliM proteins are significantly down-regulated by ΔabaA and ΔbrlA. • Expression of other gliotoxin biosynthetic genes is lowered by ΔabaA and ΔbrlA. • Growth of ΔbrlA strain lacking GliT is completely inhibited by exogenous gliotoxin. • BrlA and AbaA play key roles in biogenesis of gliotoxin in Aspergillus fumigatus.

  7. Genes for the major structural components of Thermotogales species' togas revealed by proteomic and evolutionary analyses of OmpA and OmpB homologs.

    Directory of Open Access Journals (Sweden)

    Amanda K Petrus

    Full Text Available The unifying structural characteristic of members of the bacterial order Thermotogales is their toga, an unusual cell envelope that includes a loose-fitting sheath around each cell. Only two toga-associated structural proteins have been purified and characterized in Thermotoga maritima: the anchor protein OmpA1 (or Ompα and the porin OmpB (or Ompβ. The gene encoding OmpA1 (ompA1 was cloned and sequenced and later assigned to TM0477 in the genome sequence, but because no peptide sequence was available for OmpB, its gene (ompB was not annotated. We identified six porin candidates in the genome sequence of T. maritima. Of these candidates, only one, encoded by TM0476, has all the characteristics reported for OmpB and characteristics expected of a porin including predominant β-sheet structure, a carboxy terminus porin anchoring motif, and a porin-specific amino acid composition. We highly enriched a toga fraction of cells for OmpB by sucrose gradient centrifugation and hydroxyapatite chromatography and analyzed it by LC/MS/MS. We found that the only porin candidate that it contained was the TM0476 product. This cell fraction also had β-sheet character as determined by circular dichroism, consistent with its enrichment for OmpB. We conclude that TM0476 encodes OmpB. A phylogenetic analysis of OmpB found orthologs encoded in syntenic locations in the genomes of all but two Thermotogales species. Those without orthologs have putative isofunctional genes in their place. Phylogenetic analyses of OmpA1 revealed that each species of the Thermotogales has one or two OmpA homologs. T. maritima has two OmpA homologs, encoded by ompA1 (TM0477 and ompA2 (TM1729, both of which were found in the toga protein-enriched cell extracts. These annotations of the genes encoding toga structural proteins will guide future examinations of the structure and function of this unusual lineage-defining cell sheath.

  8. Genes for the Major Structural Components of Thermotogales Species’ Togas Revealed by Proteomic and Evolutionary Analyses of OmpA and OmpB Homologs

    Energy Technology Data Exchange (ETDEWEB)

    Petrus, Amanda K.; Swithers, Kristen S.; Ranjit, Chaman R.; Wu, Si; Brewer, Heather M.; Gogarten, J Peter; Pasa-Tolic, Ljiljana; Noll, Kenneth M.

    2012-06-29

    The unifying structural characteristic of members of the bacterial order Thermotogales is their toga, an unusual cell envelope that includes a loose-fitting sheath around each cell. Only two toga-associated structural proteins have been purified and characterized in Thermotoga maritima: the anchor protein OmpA1 (or Ompa) and the porin OmpB (or Ompb). The gene encoding OmpA1 (ompA1) was cloned and sequenced and later assigned to TM0477 in the genome sequence, but because no peptide sequence was available for OmpB, its gene (ompB) was not annotated. We identified six porin candidates in the genome sequence of T. maritima. Of these candidates, only one, encoded by TM0476, has all the characteristics reported for OmpB and characteristics expected of a porin including predominant b-sheet structure, a carboxy terminus porin anchoring motif, and a porin-specific amino acid composition. We highly enriched a toga fraction of cells for OmpB by sucrose gradient centrifugation and hydroxyapatite chromatography and analyzed it by LC/MS/MS. We found that the only porin candidate that it contained was the TM0476 product. This cell fraction also had b-sheet character as determined by circular dichroism, consistent with its enrichment for OmpB. We conclude that TM0476 encodes OmpB. A phylogenetic analysis of OmpB found orthologs encoded in syntenic locations in the genomes of all but two Thermotogales species. Those without orthologs have putative isofunctional genes in their place. Phylogenetic analyses of OmpA1 revealed that each species of the Thermotogales has one or two OmpA homologs. T. maritima has two OmpA homologs, encoded by ompA1 (TM0477) and ompA2 (TM1729), both of which were found in the toga protein-enriched cell extracts. These annotations of the genes encoding toga structural proteins will guide future examinations of the structure and function of this unusual lineage-defining cell sheath.

  9. Genes for the Major Structural Components of Thermotogales Species’ Togas Revealed by Proteomic and Evolutionary Analyses of OmpA and OmpB Homologs

    Science.gov (United States)

    Petrus, Amanda K.; Swithers, Kristen S.; Ranjit, Chaman; Wu, Si; Brewer, Heather M.; Gogarten, J. Peter; Pasa-Tolic, Ljiljana; Noll, Kenneth M.

    2012-01-01

    The unifying structural characteristic of members of the bacterial order Thermotogales is their toga, an unusual cell envelope that includes a loose-fitting sheath around each cell. Only two toga-associated structural proteins have been purified and characterized in Thermotoga maritima: the anchor protein OmpA1 (or Ompα) and the porin OmpB (or Ompβ). The gene encoding OmpA1 (ompA1) was cloned and sequenced and later assigned to TM0477 in the genome sequence, but because no peptide sequence was available for OmpB, its gene (ompB) was not annotated. We identified six porin candidates in the genome sequence of T. maritima. Of these candidates, only one, encoded by TM0476, has all the characteristics reported for OmpB and characteristics expected of a porin including predominant β-sheet structure, a carboxy terminus porin anchoring motif, and a porin-specific amino acid composition. We highly enriched a toga fraction of cells for OmpB by sucrose gradient centrifugation and hydroxyapatite chromatography and analyzed it by LC/MS/MS. We found that the only porin candidate that it contained was the TM0476 product. This cell fraction also had β-sheet character as determined by circular dichroism, consistent with its enrichment for OmpB. We conclude that TM0476 encodes OmpB. A phylogenetic analysis of OmpB found orthologs encoded in syntenic locations in the genomes of all but two Thermotogales species. Those without orthologs have putative isofunctional genes in their place. Phylogenetic analyses of OmpA1 revealed that each species of the Thermotogales has one or two OmpA homologs. T. maritima has two OmpA homologs, encoded by ompA1 (TM0477) and ompA2 (TM1729), both of which were found in the toga protein-enriched cell extracts. These annotations of the genes encoding toga structural proteins will guide future examinations of the structure and function of this unusual lineage-defining cell sheath. PMID:22768259

  10. Functional genomic analyses of two morphologically distinct classes of Drosophila sensory neurons: post-mitotic roles of transcription factors in dendritic patterning.

    Directory of Open Access Journals (Sweden)

    Eswar Prasad R Iyer

    Full Text Available BACKGROUND: Neurons are one of the most structurally and functionally diverse cell types found in nature, owing in large part to their unique class specific dendritic architectures. Dendrites, being highly specialized in receiving and processing neuronal signals, play a key role in the formation of functional neural circuits. Hence, in order to understand the emergence and assembly of a complex nervous system, it is critical to understand the molecular mechanisms that direct class specific dendritogenesis. METHODOLOGY/PRINCIPAL FINDINGS: We have used the Drosophila dendritic arborization (da neurons to gain systems-level insight into dendritogenesis by a comparative study of the morphologically distinct Class-I (C-I and Class-IV (C-IV da neurons. We have used a combination of cell-type specific transcriptional expression profiling coupled to a targeted and systematic in vivo RNAi functional validation screen. Our comparative transcriptomic analyses have revealed a large number of differentially enriched/depleted gene-sets between C-I and C-IV neurons, including a broad range of molecular factors and biological processes such as proteolytic and metabolic pathways. Further, using this data, we have identified and validated the role of 37 transcription factors in regulating class specific dendrite development using in vivo class-specific RNAi knockdowns followed by rigorous and quantitative neurometric analysis. CONCLUSIONS/SIGNIFICANCE: This study reports the first global gene-expression profiles from purified Drosophila C-I and C-IV da neurons. We also report the first large-scale semi-automated reconstruction of over 4,900 da neurons, which were used to quantitatively validate the RNAi screen phenotypes. Overall, these analyses shed global and unbiased novel insights into the molecular differences that underlie the morphological diversity of distinct neuronal cell-types. Furthermore, our class-specific gene expression datasets should prove a

  11. Global transcriptional profiling reveals Streptococcus agalactiae genes controlled by the MtaR transcription factor

    Directory of Open Access Journals (Sweden)

    Cvek Urska

    2008-12-01

    Full Text Available Abstract Background Streptococcus agalactiae (group B Streptococcus; GBS is a significant bacterial pathogen of neonates and an emerging pathogen of adults. Though transcriptional regulators are abundantly encoded on the GBS genome, their role in GBS pathogenesis is poorly understood. The mtaR gene encodes a putative LysR-type transcriptional regulator that is critical for the full virulence of GBS. Previous studies have shown that an mtaR- mutant transports methionine at reduced rates and grows poorly in normal human plasma not supplemented with methionine. The decreased virulence of the mtaR mutant was correlated with a methionine transport defect; however, no MtaR-regulated genes were identified. Results Microarray analysis of wild-type GBS and an mtaR mutant revealed differential expression of 12 genes, including 1 upregulated and 11 downregulated genes in the mtaR mutant. Among the downregulated genes, we identified a cluster of cotranscribed genes encoding a putative methionine transporter (metQ1NP and peptidase (pdsM. The expression of four genes potentially involved in arginine transport (artPQ and arginine biosynthesis (argGH was downregulated and these genes localized to two transcriptional units. The virulence factor cspA, which encodes an extracellular protease, was downregulated. Additionally, the SAN_1255 locus, which putatively encodes a protein displaying similarity to plasminogen activators, was downregulated. Conclusion To our knowledge, this is the first study to describe the global influence of MtaR on GBS gene expression. This study implicates the metQ1NP genes as encoding the MtaR-regulated methionine transporter, which may provide a mechanistic explanation for the methionine-dependent growth defect of the mtaR mutant. In addition to modulating the expression of genes involved in metabolism and amino acid transport, inactivation of mtaR affected the expression of other GBS genes implicated in pathogenesis. These findings

  12. Identification of colonic fibroblast secretomes reveals secretory factors regulating colon cancer cell proliferation.

    Science.gov (United States)

    Chen, Sun-Xia; Xu, Xiao-En; Wang, Xiao-Qing; Cui, Shu-Jian; Xu, Lei-Lei; Jiang, Ying-Hua; Zhang, Yang; Yan, Hai-Bo; Zhang, Qian; Qiao, Jie; Yang, Peng-Yuan; Liu, Feng

    2014-10-14

    Stromal microenvironment influences tumor cell proliferation and migration. Fibroblasts represent the most abundant stromal constituents. Here, we established two pairs of normal fibroblast (NF) and cancer-associated fibroblast (CAF) cultures from colorectal adenocarcinoma tissues and the normal counterparts. The NFs and CAFs were stained positive for typical fibroblast markers and inhibited colon cancer (CC) cell proliferation in in vitro cocultures and in xenograft mouse models. The fibroblast conditioned media were analyzed using LC-MS and 227 proteins were identified at a false discovery rate of 1.3%, including 131 putative secretory and 20 plasma membrane proteins. These proteins were enriched for functional categories of extracellular matrix, adhesion, cell motion, inflammatory response, redox homeostasis and peptidase inhibitor. Secreted protein acidic and rich in cysteine, transgelin, follistatin-related protein 1 (FSTL1) and decorin was abundant in the fibroblast secretome as confirmed by Western blot. Silencing of FSTL1 and transgelin in colonic fibroblast cell line CCD-18Co induced an accelerated proliferation of CC cells in cocultures. Exogenous FSTL1 attenuates CC cell proliferation in a negative fashion. FSTL1 was upregulated in CC patient plasma and cancerous tissues but had no implication in prognosis. Our results provided novel insights into the molecular signatures and modulatory role of CC associated fibroblasts. In this study, a label-free LC-MS was performed to analyze the secretomes of two paired primary fibroblasts, which were isolated from fresh surgical specimen of colorectal adenocarcinoma and adjacent normal colonic tissues and exhibited negative modulatory activity for colon cancer cell growth in in vitro cocultures and in vivo xenograph mouse models. Follistatin-related protein 1 was further revealed to be one of the stroma-derived factors of potential suppression role for colon cancer cell proliferation. Our results provide novel

  13. Molecular analyses reveal an abundant diversity of ticks and rickettsial agents associated with wild birds in two regions of primary Brazilian Atlantic Rainforest.

    Science.gov (United States)

    Luz, Hermes Ribeiro; Faccini, João Luiz Horacio; McIntosh, Douglas

    2017-06-01

    Brazilian wild birds are recognized as frequent and important hosts for immature stages of more than half of the 32 recognized species of Amblyomma ticks recorded in that country. Several species of Amblyomma harbor rickettsial agents, including members of the spotted fever group (SFG). Most studies on this topic relied primarily on morphological characterization and reported large portions of the collected ticks at the genus rather than species level. Clearly, this factor may have contributed to an underestimation of tick diversity and distribution and makes comparisons between studies difficult. The current investigation combined morphological and molecular analyses to assess the diversity of ticks and rickettsial agents associated with wild birds, captured in two regions of native Atlantic rainforest, in the state of Rio de Janeiro, Brazil. A total of 910 birds were captured, representing two orders, 34 families and 106 species, among which 93 specimens (10.2%), were parasitized by 138 immature ticks (60 larvae and 78 nymphs), representing 10 recognized species of the genus Amblyomma; together with two reasonably well classified haplotypes (Amblyomma sp. haplotype Nazaré and Amblyomma sp. strain USNTC 6792). Amplification by PCR and sequencing of rickettsial genes (htrA, gltA, ompA and ompB), demonstrated the presence of Rickettsia DNA in 48 (34%) of the ticks. Specifically, Rickettsia bellii was detected in a single larva and a single nymph of A. aureolatum; R. amblyomatis was found in 16 of 37 A. longirostre and was recorded for the first time in three nymphs of A. calcaratum; R. rhipicephali was detected in 9 (47%) of 19 Amblyomma sp. haplotype Nazaré ticks. The remaining ticks were infected with genetic variants of R. parkeri, namely strain ApPR in 12 A. parkeri and seven Amblyomma sp. haplotype Nazaré ticks, with the strain NOD found in two specimens of A. nodosum. Interestingly, a single larvae of A. ovale was shown to be infected with the emerging

  14. Genome-Wide Association between Transcription Factor Expression and Chromatin Accessibility Reveals Regulators of Chromatin Accessibility

    Science.gov (United States)

    Rueedi, Rico

    2017-01-01

    To better understand genome regulation, it is important to uncover the role of transcription factors in the process of chromatin structure establishment and maintenance. Here we present a data-driven approach to systematically characterise transcription factors that are relevant for this process. Our method uses a linear mixed modelling approach to combine datasets of transcription factor binding motif enrichments in open chromatin and gene expression across the same set of cell lines. Applying this approach to the ENCODE dataset, we confirm already known and imply numerous novel transcription factors that play a role in the establishment or maintenance of open chromatin. In particular, our approach rediscovers many factors that have been annotated as pioneer factors. PMID:28118358

  15. Evidence of a right-shift factor affecting infant hand-use preferences from 7 to 11 months of age as revealed by latent class analysis.

    Science.gov (United States)

    Michel, George F; Sheu, Ching-Fan; Brumley, Michele R

    2002-01-01

    Infant hand-use preferences for apprehending objects were assessed three times at 7, 9, and 11 months of age for 154 infants (79 males) using a reliable and valid procedure. Two classification procedures (differing in Type I classification error rates) were used to identify an infant's preference (right, left, no preference) at each age, and these data were examined using two- and three-group latent class analysis models. These analyses revealed the importance of using a handedness classification procedure with low Type I error rates and evidence of a right-shift factor similar to that expressed in child and adult handedness. Thus, infant hand-use preferences for apprehending objects are likely a developmental precursor of adult handedness. The relation of the right-shift factor to increased susceptibility to social influences during development and the evolution of human abilities also is discussed.

  16. Empirical Bayes factor analyses of quantitative trait loci for gestation length in Iberian × Meishan F2 sows.

    Science.gov (United States)

    Casellas, J; Varona, L; Muñoz, G; Ramírez, O; Barragán, C; Tomás, A; Martínez-Giner, M; Ovilo, C; Sánchez, A; Noguera, J L; Rodríguez, M C

    2008-02-01

    The aim of this study was to investigate chromosomal regions affecting gestation length in sows. An experimental F2 cross between Iberian and Meishan pig breeds was used for this purpose and we genotyped 119 markers covering the 18 porcine autosomal chromosomes. Within this context, we have developed a new empirical Bayes factor (BF) approach to compare between nested models, with and without the quantitative trait loci (QTL) effect, and after including the location of the QTL as an unknown parameter in the model. This empirical BF can be easily calculated from the output of a Markov chain Monte Carlo sampling by averaging conditional densities at the null QTL effects. Linkage analyses were performed in each chromosome using an animal model to account for infinitesimal genetic effects. Initially, three QTL were detected at chromosomes 6, 8 and 11 although, after correcting for multiple testing, only the additive QTL located in cM 110 of chromosome 8 remained. For this QTL, the allelic effect of substitution of the Iberian allele increased gestation length in 0.521 days, with a highest posterior density region at 95% ranged between 0.121 and 0.972 days. Although future studies are necessary to confirm if detected QTL is relevant and segregating in commercial pig populations, a hot-spot on the genetic regulation of gestation length in pigs seems to be located in chromosome 8.

  17. Malignancy risk of anti-tumor necrosis factor alpha blockers: an overview of systematic reviews and meta-analyses.

    Science.gov (United States)

    Chen, Yuehong; Sun, Jianhong; Yang, Yuan; Huang, Yupeng; Liu, Gang

    2016-01-01

    The objective of the study is to systematically review the malignancy risk of anti-tumor necrosis factor alpha (anti-TNFα) agents. Databases of PubMed Medline, OVID EMBASE, and Cochrane Library were searched to identify published systematic reviews and meta-analyses of randomized control trials, observational studies, and case series that evaluated malignancy risk of anti-TNFα blockers. Search time duration was restricted from January 1st, 2000 to July 16th, 2015. Overview Quality Assessment Questionnaires were used to assess the quality of included reviews. Two methodology trained reviewers separately and repeatedly screened searched studies according to study selection criteria, collected data, and assessed quality. Totally, 42 reviews proved eligible with only one Cochrane review. Anti-TNFα antagonists were extensively used to treat various diseases; nevertheless, malignancy risks were most commonly described in patients with rheumatoid arthritis (RA) and inflammatory bowel disease (IBD). In RA patients, no increased risks of breast cancer, lymphoma, and non-melanoma skin cancer were found, but if the use of anti-TNFα agents was associated with elevated risk of overall malignancy was still uncertainty. In IBD patients, the use of anti-TNFα inhibitors was not connected with enhanced risk of overall cancer. No increased cancer risk was found in other disease conditions. Twenty-nine reviews were rated as good quality, 12 as moderate, and one as poor. There are no sufficient evidences to draw the conclusion that anti-TNFα blockers have relationship with increased malignancy risk.

  18. Hopping of a processivity factor on DNA revealed by single-molecule assays of diffusion

    NARCIS (Netherlands)

    Komazin-Meredith, Gloria; Mirchev, Rossen; Golan, David E.; Oijen, Antoine M. van; Coen, Donald M.; Richardson, Charles C.

    2008-01-01

    Many DNA-interacting proteins diffuse on DNA to perform their biochemical functions. Processivity factors diffuse on DNA to permit unimpeded elongation by their associated DNA polymerases, but little is known regarding their rates and mechanisms of diffusion. The processivity factor of herpes simple

  19. Parallel phylogenetic analyses using the N, G or Nv gene from a fixed group of VHSV isolates reveal the same overall genetic typing

    DEFF Research Database (Denmark)

    Einer-Jensen, Katja; Ahrens, Peter; Lorenzen, Niels

    2005-01-01

    Different genetic regions representing the viral phospho-(P), nucleocapsid-(N) or glyco-protein (G) gene have been used for phylogenetic studies of viral haemorrhagic septicaemia virus (VHSV). Since these analyses were performed on different virus isolates using various genomic regions, it has been...

  20. Integrated transcript and genome analyses reveal NKX2-1 and MEF2C as potential oncogenes in T cell acute lymphoblastic leukemia

    NARCIS (Netherlands)

    Homminga, I.; Pieters, R.; Langerak, A.W.; de Rooi, J.J.; Stubbs, A.; Verstegen, M.; Vuerhard, M.; Buijs-Gladdines, J.; Kooi, C.; Klous, P.; van Vlierberghe, P.; Ferrando, A.A.; Cayuela, J.M.; Verhaaf, B.; Beverloo, H.B.; Horstmann, M.; de Haas, V.; Wiekmeijer, A.S.; Pike-Overzet, K.; Staal, F.J.; de Laat, W.; Soulier, J.; Sigaux, F.; Meijerink, J.P.

    2011-01-01

    To identify oncogenic pathways in T cell acute lymphoblastic leukemia (T-ALL), we combined expression profiling of 117 pediatric patient samples and detailed molecular-cytogenetic analyses including the Chromosome Conformation Capture on Chip (4C) method. Two T-ALL subtypes were identified that lack

  1. RNA-Seq transcriptomics and pathway analyses reveal potential regulatory genes and molecular mechanisms in high- and low-residual feed intake in Nordic dairy cattle

    DEFF Research Database (Denmark)

    Salleh, M. S.; Mazzoni, G.; Höglund, J. K.

    2017-01-01

    genes and biomarkers was derived for their potential inclusion in breeding programmes to improve FE. The bovine RNA-Seq gene expression data from the liver was analysed to identify DEGs and, subsequently, identify the molecular mechanisms, pathways and possible candidate biomarkers of feed efficiency...

  2. Analyses of wrky18 wrky40 plants reveal critical roles of SA/EDS1 signaling and indole-glucosinolate biosynthesis for Golovinomyces orontii resistance and a loss-of resistance towards Pseudomonas syringae pv. tomato AvrRPS4.

    Science.gov (United States)

    Schön, Moritz; Töller, Armin; Diezel, Celia; Roth, Charlotte; Westphal, Lore; Wiermer, Marcel; Somssich, Imre E

    2013-07-01

    Simultaneous mutation of two WRKY-type transcription factors, WRKY18 and WRKY40, renders otherwise susceptible wild-type Arabidopsis plants resistant towards the biotrophic powdery mildew fungus Golovinomyces orontii. Resistance in wrky18 wrky40 double mutant plants is accompanied by massive transcriptional reprogramming, imbalance in salicylic acid (SA) and jasmonic acid (JA) signaling, altered ENHANCED DISEASE SUSCEPTIBILITY1 (EDS1) expression, and accumulation of the phytoalexin camalexin. Genetic analyses identified SA biosynthesis and EDS1 signaling as well as biosynthesis of the indole-glucosinolate 4MI3G as essential components required for loss-of-WRKY18 WRKY40-mediated resistance towards G. orontii. The analysis of wrky18 wrky40 pad3 mutant plants impaired in camalexin biosynthesis revealed an uncoupling of pre- from postinvasive resistance against G. orontii. Comprehensive infection studies demonstrated the specificity of wrky18 wrky40-mediated G. orontii resistance. Interestingly, WRKY18 and WRKY40 act as positive regulators in effector-triggered immunity, as the wrky18 wrky40 double mutant was found to be strongly susceptible towards the bacterial pathogen Pseudomonas syringae DC3000 expressing the effector AvrRPS4 but not against other tested Pseudomonas strains. We hypothesize that G. orontii depends on the function of WRKY18 and WRKY40 to successfully infect Arabidopsis wild-type plants while, in the interaction with P. syringae AvrRPS4, they are required to mediate effector-triggered immunity.

  3. Analyses of Evolutionary Characteristics of the Hemagglutinin-Esterase Gene of Influenza C Virus during a Period of 68 Years Reveals Evolutionary Patterns Different from Influenza A and B Viruses

    Directory of Open Access Journals (Sweden)

    Yuki Furuse

    2016-11-01

    Full Text Available Infections with the influenza C virus causing respiratory symptoms are common, particularly among children. Since isolation and detection of the virus are rarely performed, compared with influenza A and B viruses, the small number of available sequences of the virus makes it difficult to analyze its evolutionary dynamics. Recently, we reported the full genome sequence of 102 strains of the virus. Here, we exploited the data to elucidate the evolutionary characteristics and phylodynamics of the virus compared with influenza A and B viruses. Along with our data, we obtained public sequence data of the hemagglutinin-esterase gene of the virus; the dataset consists of 218 unique sequences of the virus collected from 14 countries between 1947 and 2014. Informatics analyses revealed that (1 multiple lineages have been circulating globally; (2 there have been weak and infrequent selective bottlenecks; (3 the evolutionary rate is low because of weak positive selection and a low capability to induce mutations; and (4 there is no significant positive selection although a few mutations affecting its antigenicity have been induced. The unique evolutionary dynamics of the influenza C virus must be shaped by multiple factors, including virological, immunological, and epidemiological characteristics.

  4. Analyses of Evolutionary Characteristics of the Hemagglutinin-Esterase Gene of Influenza C Virus during a Period of 68 Years Reveals Evolutionary Patterns Different from Influenza A and B Viruses.

    Science.gov (United States)

    Furuse, Yuki; Matsuzaki, Yoko; Nishimura, Hidekazu; Oshitani, Hitoshi

    2016-11-26

    Infections with the influenza C virus causing respiratory symptoms are common, particularly among children. Since isolation and detection of the virus are rarely performed, compared with influenza A and B viruses, the small number of available sequences of the virus makes it difficult to analyze its evolutionary dynamics. Recently, we reported the full genome sequence of 102 strains of the virus. Here, we exploited the data to elucidate the evolutionary characteristics and phylodynamics of the virus compared with influenza A and B viruses. Along with our data, we obtained public sequence data of the hemagglutinin-esterase gene of the virus; the dataset consists of 218 unique sequences of the virus collected from 14 countries between 1947 and 2014. Informatics analyses revealed that (1) multiple lineages have been circulating globally; (2) there have been weak and infrequent selective bottlenecks; (3) the evolutionary rate is low because of weak positive selection and a low capability to induce mutations; and (4) there is no significant positive selection although a few mutations affecting its antigenicity have been induced. The unique evolutionary dynamics of the influenza C virus must be shaped by multiple factors, including virological, immunological, and epidemiological characteristics.

  5. Revealing the Differences Between Free and Complexed Enzyme Mechanisms and Factors Contributing to Cell Wall Recalcitrance

    Energy Technology Data Exchange (ETDEWEB)

    Resch, Michael G.; Donohoe, Byron; Ciesielski, Peter; Nill, Jennifer; McKinney, Kellene; Mittal, Ashutosh; Katahira, Rui; Himmel, Michael; Biddy, Mary; Beckham, Gregg; Decker, Steve

    2014-09-08

    Enzymatic depolymerization of polysaccharides is a key step in the production of fuels and chemicals from lignocellulosic biomass, and discovery of synergistic biomass-degrading enzyme paradigms will enable improved conversion processes. Historically, revealing insights into enzymatic saccharification mechanisms on plant cell walls has been hindered by uncharacterized substrates and low resolution.

  6. Long-Term Data Reveal Rate and Risk Factors for Subsequent Surgeries Following Initial ACL Reconstruction

    Science.gov (United States)

    ... and Risk Factors for Subsequent Surgeries Following Initial ACL Reconstruction Nearly one-fifth of patients who undergo ... surgery to reconstruct a torn anterior cruciate ligament (ACL) eventually need to have additional surgery on the ...

  7. Misexpression Screen in Drosophila melanogaster Aiming to Reveal Novel Factors Involved in Formation of Body Parts

    OpenAIRE

    Grieder, N.; Charlafti, I.; Kloter, U.; Jaeckle, H.; Schaefer, U.; Gehring, W

    2007-01-01

    To identify novel factors that lead a fly imaginal disc to adopt its developmental fate, we carried out a modular dominant misexpression screen in imaginal discs. We have identified two factors that appear to change the fate of the respective body structure and appear to lead to the transformation of a body part. In one mutant line, notum tissue, normally derived from wing imaginal tissue, formed close to the site of the sternopleural bristles, which are leg disc derivatives. In the other lin...

  8. Analysis of Cryptococcus neoformans sexual development reveals rewiring of the pheromone-response network by a change in transcription factor identity.

    Science.gov (United States)

    Kruzel, Emilia K; Giles, Steven S; Hull, Christina M

    2012-06-01

    The fundamental mechanisms that control eukaryotic development include extensive regulation at the level of transcription. Gene regulatory networks, composed of transcription factors, their binding sites in DNA, and their target genes, are responsible for executing transcriptional programs. While divergence of these control networks drives species-specific gene expression that contributes to biological diversity, little is known about the mechanisms by which these networks evolve. To investigate how network evolution has occurred in fungi, we used a combination of microarray expression profiling, cis-element identification, and transcription-factor characterization during sexual development of the human fungal pathogen Cryptococcus neoformans. We first defined the major gene expression changes that occur over time throughout sexual development. Through subsequent bioinformatic and molecular genetic analyses, we identified and functionally characterized the C. neoformans pheromone-response element (PRE). We then discovered that transcriptional activation via the PRE requires direct binding of the high-mobility transcription factor Mat2, which we conclude functions as the elusive C. neoformans pheromone-response factor. This function of Mat2 distinguishes the mechanism of regulation through the PRE of C. neoformans from all other fungal systems studied to date and reveals species-specific adaptations of a fungal transcription factor that defies predictions on the basis of sequence alone. Overall, our findings reveal that pheromone-response network rewiring has occurred at the level of transcription factor identity, despite the strong conservation of upstream and downstream components, and serve as a model for how selection pressures act differently on signaling vs. gene regulatory components during eukaryotic evolution.

  9. Sustainability Efficiency Factor: Measuring Sustainability in Advanced Energy Systems through Exergy, Exergoeconomic, Life Cycle, and Economic Analyses

    Science.gov (United States)

    Boldon, Lauren

    (NHES) reference case studies to (1) introduce sustainability metrics, such as life cycle assessment, (2) demonstrate the methods behind exergy and exergoeconomic analyses, (3) provide an economic analysis of the potential for SMR development from first-of-a-kind (FOAK) to nth-of-a-kind (NOAK), thereby illustrating possible cost reductions and deployment flexibility for SMRs over large conventional nuclear reactors, (4) assess the competitive potential for incorporation of storage and hydrogen production in NHES and in regulated and deregulated electricity markets, (5) compare an SMR-hydrogen production plant to a natural gas steam methane reforming plant using the SEF, and (6) identify and review the social considerations which would support future nuclear development domestically and abroad, such as public and political/regulatory needs and challenges. The Global Warming Potential (GWP) for the SMR (300 MWth)-wind (60 MWe)-high temperature steam electrolysis (200 tons Hydrogen per day) system was calculated as approximately 874 g CO2-equivalent as part of the life cycle assessment. This is 92.6% less than the GWP estimated for steam methane reforming production of hydrogen by Spath and Mann. The unit exergetic and exergoeconomic costs were determined for each flow within the NHES system as part of the exergy/exergoeconomic cost analyses. The unit exergetic cost is lower for components yielding more meaningful work like the one exiting the SMR with a unit exergetic cost of 1.075 MW/MW. In comparison, the flow exiting the turbine has a very high unit exergetic cost of 15.31, as most of the useful work was already removed through the turning of the generator/compressor shaft. In a similar manner, the high unit exergoeconomic cost of 12.45/MW*sec is observed for the return flow to the reactors, because there is very little exergy present. The first and second law efficiencies and the exergoeconomic factors were also determined over several cases. For the first or base SMR

  10. The Development of Protein Microarrays and Their Applications in DNA-Protein and Protein-Protein Interaction Analyses of Arabidopsis Transcription Factors

    Institute of Scientific and Technical Information of China (English)

    Wei Gong; Kun He; Mike Covington; S.R Dinesh-Kumar; Michael Snyder; Stacey L.Harmer; Yu-Xian Zhu; Xing Wang Deng

    2008-01-01

    We used our collection of Arabidopsis transcription factor (TF) ORFeome clones to constructprotein microarrays containing as many as 802 TF proteins. These protein microarrays were used for both protein-DNA and proteinprotein interaction analyses. For protein-DNA interaction studies, we examined AP2/ERF family TFs and their cognate cis-elements. By careful comparison of the DNA-binding specificity of 13 TFs on the protein microarray with previous non-microarray data, we showed that protein microarrays provide an efficient and high throughput tool for genome-wide analysis of TF-DNA interactions. This microarray protein-DNA interaction analysis allowed us to derive a comprehensive view of DNA-binding profiles of AP2/ERF family proteins in Arabidopsis. It also revealed four TFs that bound the EE (evening element) and had the expected phased gene expression under clock-regulation, thus providing a basis for further functional analysis of their roles in clock regulation of gene expression. We also developed procedures for detecting protein interactions using this TF protein microarray and discovered four novel partners that interact with HY5, which can be validated by yeast two-hybrid assays. Thus, plant TF protein microarrays offer an attractive high-throughput alternative to traditional techniques for TF functional characterization on a global scale.

  11. The development of protein microarrays and their applications in DNA-protein and protein-protein interaction analyses of Arabidopsis transcription factors.

    Science.gov (United States)

    Gong, Wei; He, Kun; Covington, Mike; Dinesh-Kumar, S P; Snyder, Michael; Harmer, Stacey L; Zhu, Yu-Xian; Deng, Xing Wang

    2008-01-01

    We used our collection of Arabidopsis transcription factor (TF) ORFeome clones to construct protein microarrays containing as many as 802 TF proteins. These protein microarrays were used for both protein-DNA and protein-protein interaction analyses. For protein-DNA interaction studies, we examined AP2/ERF family TFs and their cognate cis-elements. By careful comparison of the DNA-binding specificity of 13 TFs on the protein microarray with previous non-microarray data, we showed that protein microarrays provide an efficient and high throughput tool for genome-wide analysis of TF-DNA interactions. This microarray protein-DNA interaction analysis allowed us to derive a comprehensive view of DNA-binding profiles of AP2/ERF family proteins in Arabidopsis. It also revealed four TFs that bound the EE (evening element) and had the expected phased gene expression under clock-regulation, thus providing a basis for further functional analysis of their roles in clock regulation of gene expression. We also developed procedures for detecting protein interactions using this TF protein microarray and discovered four novel partners that interact with HY5, which can be validated by yeast two-hybrid assays. Thus, plant TF protein microarrays offer an attractive high-throughput alternative to traditional techniques for TF functional characterization on a global scale.

  12. Rembrandt and/ or studio, Saul and David, c.1655: revealing the curtain using cross-section analyses and X-ray fluorescence imaging

    NARCIS (Netherlands)

    Noble, P.; van Loon, A.; Alfeld, M.; Janssens, K.; Dik, J.

    2012-01-01

    Recent technical investigation of a late Rembrandt painting - Saul and David, c.1655 - from the collection of the Mauritshuis in The Hague has revealed important new information regarding the picture’s condition and original appearance. As already known, at some point in the past, the two figures we

  13. Rembrandt and/ or studio, Saul and David, c.1655: revealing the curtain using cross-section analyses and X-ray fluorescence imaging

    NARCIS (Netherlands)

    Noble, P.; van Loon, A.; Alfeld, M.; Janssens, K.; Dik, J.

    2012-01-01

    Recent technical investigation of a late Rembrandt painting - Saul and David, c.1655 - from the collection of the Mauritshuis in The Hague has revealed important new information regarding the picture’s condition and original appearance. As already known, at some point in the past, the two figures

  14. Genetic and epigenetic factors affecting meiosis induction in eukaryotes revealed in paramecium research.

    Science.gov (United States)

    Prajer, Małgorzata

    2008-01-01

    This review presents studies of the induction of meiosis undertaken on the ciliate Paramecium, a unicellular model eukaryotic organism. Meiosis in Paramecium, preceding the process of fertilization, appears in starved cells after passing a defined number of divisions (cell generations), starting from the last fertilization. Investigations were performed on clones of cells entering autogamy, a self-fertilization process. Genetic as well as epigenetic factors, i.e. endo- and exogenous factors, affecting the induction ofmeiosis and changing the duration of the interautogamous interval (IAI), were analyzed. The results show that: (1) Meiosis induction is controlled genetically by the somatic macronucleus. However, besides the nuclear factors, the cytoplasmic protein immaturin also affects this process (Haga & Hiwatashi 1981); (2) Epigenetic factors, such as non-genetically disturbed cytoskeleton structures and changes in the cell architecture observed in doublet Paramecium cells, exert internal mechanical stress (Ingber 2003), which constitutes the endogenous impulse accelerating meiosis; (3) Mild osmotic stress, acting as an exogenous factor, can initiate the specific MAP kinases signaling pathway resulting in earlier meiosis induction, as in other unicellular eukaryotes (Seet & Pawson 2004).

  15. Comparative "-omics" in mycoplasma pneumoniae clinical isolates reveals key virulence factors

    OpenAIRE

    Maria Lluch-Senar; Luca Cozzuto; Jaime Cano; Javier Delgado; Verónica Llórens-Rico; Sabine Pereyre; Cécile Bebear; Luis Serrano

    2015-01-01

    The human respiratory tract pathogen M. pneumoniae is one of the best characterized minimal bacterium. Until now, two main groups of clinical isolates of this bacterium have been described (types 1 and 2), differing in the sequence of the P1 adhesin gene. Here, we have sequenced the genomes of 23 clinical isolates of M. pneumoniae. Studying SNPs, non-synonymous mutations, indels and genome rearrangements of these 23 strains and 4 previously sequenced ones, has revealed new subclasses in the t...

  16. Misexpression screen in Drosophila melanogaster aiming to reveal novel factors involved in formation of body parts.

    Science.gov (United States)

    Grieder, Nicole C; Charlafti, Ilias; Kloter, Urs; Jäckle, Herbert; Schäfer, Ulrich; Gehring, Walter J

    2007-04-01

    To identify novel factors that lead a fly imaginal disc to adopt its developmental fate, we carried out a modular dominant misexpression screen in imaginal discs. We have identified two factors that appear to change the fate of the respective body structure and appear to lead to the transformation of a body part. In one mutant line, notum tissue, normally derived from wing imaginal tissue, formed close to the site of the sternopleural bristles, which are leg disc derivatives. In the other line, the arista is transformed into a tubular structure, resembling an abnormal leg. We found that ectopic expression of abrupt was responsible for this potential transformation of the arista.

  17. Identification of a GCC transcription factor responding to fruit colour change events in citrus through the transcriptomic analyses of two mutants

    Directory of Open Access Journals (Sweden)

    Cercós Manuel

    2010-12-01

    Full Text Available Abstract Background External ripening in Citrus fruits is morphologically characterized by a colour shift from green to orange due to the degradation of chlorophylls and the accumulation of carotenoid pigments. Although numerous genes coding for enzymes involved in such biochemical pathways have been identified, the molecular control of this process has been scarcely studied. In this work we used the Citrus clementina mutants 39B3 and 39E7, showing delayed colour break, to isolate genes potentially related to the regulation of peel ripening and its physiological or biochemical effects. Results Pigment analyses revealed different profiles of carotenoid and chlorophyll modification in 39B3 and 39E7 mutants. Flavedo from 39B3 fruits showed an overall delay in carotenoid accumulation and chlorophyll degradation, while the flavedo of 39E7 was devoid of the apocarotenoid β-citraurin among other carotenoid alterations. A Citrus microarray containing about 20,000 cDNA fragments was used to identify genes that were differentially expressed during colour change in the flavedo of 39B3 and 39E7 mutants respect to the parental variety. The results highlighted 73 and 90 genes that were respectively up- and down-regulated in both mutants. CcGCC1 gene, coding for a GCC type transcriptional factor, was found to be down-regulated. CcGCC1 expression was strongly induced at the onset of colour change in the flavedo of parental clementine fruit. Moreover, treatment of fruits with gibberellins, a retardant of external ripening, delayed both colour break and CcGCC1 overexpression. Conclusions In this work, the citrus fruit ripening mutants 39B3 and 39E7 have been characterized at the phenotypic, biochemical and transcriptomic level. A defective synthesis of the apocarotenoid β-citraurin has been proposed to cause the yellowish colour of fully ripe 39E7 flavedo. The analyses of the mutant transcriptomes revealed that colour change during peel ripening was strongly

  18. Comparative analyses of factors determining soil erosion rates based on network of Mediterranean monitored catchments for the innovative, adaptive and resilient agriculture of the future

    Science.gov (United States)

    Smetanová, Anna; Le Bissonnais, Yves; Raclot, Damien; Perdo Nunes, João; Licciardello, Feliciana; Mathys, Nicolle; Latron, Jérôme; Rodríguez Caballero, Emilio; Le Bouteiller, Caroline; Klotz, Sébastien; Mekki, Insaf; Gallart, Francesc; Solé Benet, Albert; Pérez Gallego, Nuria; Andrieux, Patrick; Jantzi, Hugo; Moussa, Roger; Planchon, Olivier; Marisa Santos, Juliana

    2015-04-01

    In order to project the soil erosion response to climate change in the fragile Mediterranean region it is inevitable to understand its existing patterns. Soil erosion monitoring on a catchment scale enables to analyse temporal and spatial variability of soil erosion and sediment delivery, while the integrating study of different catchments is often undertaken to depicther the general patterns. In this study, eight small catchments (with area up to 1,32 km2), representative for the western part of the Mediterranean region (according to climate, bedrock, soils and main type of land use) were compared. These catchments, grouped in the R-OS Med Network were situated in France (3), Spain (2), Portugal (1), Italy (1) and Tunisia (1). The average precipitation ranged between 236 to 1303 mm·a-1 and mean annual sediment yield varied 7.5 to 6900 Mg·km-2·a-1. The complex databes was based on more than 120 years of hydrological and sediment data, with series between 3 and 29 years long. The variability of sediment data was described on annual and monthly basis. The relationship between the sediment yield and more than 35 factors influencing the sediment yield including the characteristics of climate, topography, rainfall, runoff, land use, vegetation and soil cover, connectivity and dominant geomorphic processes, was studied. The preliminary results confirmed the differences in rainfall, runoff and sediment response, and revealed both the similarities and differences in soil erosion responses of the catchments. They are further dependent on the variability of factors themselves, with important contribution of the state of soil properties, vegetation cover and land use. Anna Smetanová has received the support of the European Union, in the framework of the Marie-Curie FP7 COFUND People Programme, through the award of an AgreenSkills' fellowship (under grant agreement n° 267196)

  19. Genetic sharing with cardiovascular disease risk factors and diabetes reveals novel bone mineral density loci

    NARCIS (Netherlands)

    S. Reppe (Sjur); Y. Wang (Yunpeng); W.K. Thompson (Wesley K.); L.K. McEvoy (Linda K.); N.J. Schork (Nicholas); V. Zuber (Verena); M. Leblanc (Marissa); F. Bettella (Francesco); I.G. Mills (Ian G.); R.S. Desikan (Rahul S.); S. Djurovic (Srdjan); K.M. Gautvik (Kaare); A.M. Dale (Anders); O.A. Andreassen (Ole A.); K. Estrada Gil (Karol); U. Styrkarsdottir (Unnur); E. Evangelou (Evangelos); Y.-H. Hsu (Yi-Hsiang); E.L. Duncan (Emma); E.E. Ntzani (Evangelia); L. Oei (Ling); O.M.E. Albagha (Omar M.); N. Amin (Najaf); J.P. Kemp (John); D.L. Koller (Daniel); G. Li (Guo); C.-T. Liu (Ching-Ti); R.L. Minster (Ryan); A. Moayyeri (Alireza); L. Vandenput (Liesbeth); D. Willner (Dana); S.-M. Xiao (Su-Mei); L.M. Yerges-Armstrong (Laura); H.-F. Zheng (Hou-Feng); N. Alonso (Nerea); J. Eriksson (Joel); C.M. Kammerer (Candace); S. Kaptoge (Stephen); P.J. Leo (Paul); G. Thorleifsson (Gudmar); S.G. Wilson (Scott); J.F. Wilson (James F); V. Aalto (Ville); M. Alen (Markku); A.K. Aragaki (Aaron); T. Aspelund (Thor); J.R. Center (Jacqueline); Z. Dailiana (Zoe); C. Duggan; M. Garcia (Melissa); N. Garcia-Giralt (Natàlia); S. Giroux (Sylvie); G. Hallmans (Göran); L.J. Hocking (Lynne); L.B. Husted (Lise Bjerre); K. Jameson (Karen); R. Khusainova (Rita); G.S. Kim (Ghi Su); C. Kooperberg (Charles); T. Koromila (Theodora); M. Kruk (Marcin); M. Laaksonen (Marika); A.Z. Lacroix (Andrea Z.); S.H. Lee (Seung Hun); P.C. Leung (Ping C.); J.R. Lewis (Joshua); L. Masi (Laura); S. Mencej-Bedrac (Simona); T.V. Nguyen (Tuan); X. Nogues (Xavier); M.S. Patel (Millan); J. Prezelj (Janez); L.M. Rose (Lynda); S. Scollen (Serena); K. Siggeirsdottir (Kristin); G.D. Smith; O. Svensson (Olle); S. Trompet (Stella); O. Trummer (Olivia); N.M. van Schoor (Natasja); J. Woo (Jean); K. Zhu (Kun); S. Balcells (Susana); M.L. Brandi; B.M. Buckley (Brendan M.); S. Cheng (Sulin); C. Christiansen; C. Cooper (Charles); G.V. Dedoussis (George); I. Ford (Ian); M. Frost (Morten); D. Goltzman (David); J. González-Macías (Jesús); M. Kähönen (Mika); M. Karlsson (Magnus); E.K. Khusnutdinova (Elza); J.-M. Koh (Jung-Min); P. Kollia (Panagoula); B.L. Langdahl (Bente); W.D. Leslie (William D.); P. Lips (Paul); O. Ljunggren (Östen); R. Lorenc (Roman); J. Marc (Janja); D. Mellström (Dan); B. Obermayer-Pietsch (Barbara); D. Olmos (David); U. Pettersson-Kymmer (Ulrika); D.M. Reid (David); J.A. Riancho (José); P.M. Ridker (Paul); M.F. Rousseau (Francois); P.E. Slagboom (Eline); N.L.S. Tang (Nelson L.S.); R. Urreizti (Roser); W. Van Hul (Wim); J. Viikari (Jorma); M.T. Zarrabeitia (María); Y.S. Aulchenko (Yurii); M.C. Castaño Betancourt (Martha); E. Grundberg (Elin); L. Herrera (Lizbeth); T. Ingvarsson (Torvaldur); H. Johannsdottir (Hrefna); T. Kwan (Tony); R. Li (Rui); R.N. Luben (Robert); M.C. Medina-Gomez (Carolina); S.T. Palsson (Stefan Th); J.I. Rotter (Jerome I.); G. Sigurdsson (Gunnar); J.B.J. van Meurs (Joyce); D.J. Verlaan (Dominique); F.M. Williams (Frances); A.R. Wood (Andrew); Y. Zhou (Yanhua); T. Pastinen (Tomi); S. Raychaudhuri (Soumya); J.A. Cauley (Jane); D.I. Chasman (Daniel); G.R. Clark (Graeme); S.R. Cummings (Steven R.); P. Danoy (Patrick); E.M. Dennison (Elaine); R. Eastell (Richard); J.A. Eisman (John); V. Gudnason (Vilmundur); A. Hofman (Albert); R.D. Jackson (Rebecca); G. Jones (Graeme); J.W. Jukema (Jan Wouter); K.T. Khaw; T. Lehtimäki (Terho); Y. Liu (Yongmei); M. Lorentzon (Mattias); E. McCloskey (Eugene); B.D. Mitchell (Braxton); K. Nandakumar (Kannabiran); G.C. Nicholson (Geoffrey); B.A. Oostra (Ben); M. Peacock (Munro); H.A.P. Pols (Huibert A. P.); R.L. Prince (Richard); O. Raitakari (Olli); I.R. Reid (Ian); J. Robbins (John); P.N. Sambrook (Philip); P.C. Sham (Pak Chung); A.R. Shuldiner (Alan); F.A. Tylavsky (Frances); C.M. van Duijn (Cock); N.J. Wareham (Nicholas J.); L.A. Cupples (Adrienne); M.J. Econs (Michael); D.M. Evans (David); T.B. Harris (Tamara B.); A.W.C. Kung (Annie Wai Chee); B.M. Psaty (Bruce); J. Reeve (Jonathan); T.D. Spector (Timothy); E.A. Streeten (Elizabeth); M.C. Zillikens (Carola); U. Thorsteinsdottir (Unnur); C. Ohlsson (Claes); D. Karasik (David); J.B. Richards (J. Brent); M.A. Brown (Matthew); J-A. Zwart (John-Anker); A.G. Uitterlinden (André); S.H. Ralston (Stuart); J.P.A. Ioannidis (John P.A.); D.P. Kiel (Douglas P.); F. Rivadeneira Ramirez (Fernando)

    2015-01-01

    textabstractBone Mineral Density (BMD) is a highly heritable trait, but genome-wide association studies have identified few genetic risk factors. Epidemiological studies suggest associations between BMD and several traits and diseases, but the nature of the suggestive comorbidity is still unknown. W

  20. RNA Sequencing Analysis Reveals Transcriptomic Variations in Tobacco (Nicotiana tabacum Leaves Affected by Climate, Soil, and Tillage Factors

    Directory of Open Access Journals (Sweden)

    Bo Lei

    2014-04-01

    Full Text Available The growth and development of plants are sensitive to their surroundings. Although numerous studies have analyzed plant transcriptomic variation, few have quantified the effect of combinations of factors or identified factor-specific effects. In this study, we performed RNA sequencing (RNA-seq analysis on tobacco leaves derived from 10 treatment combinations of three groups of ecological factors, i.e., climate factors (CFs, soil factors (SFs, and tillage factors (TFs. We detected 4980, 2916, and 1605 differentially expressed genes (DEGs that were affected by CFs, SFs, and TFs, which included 2703, 768, and 507 specific and 703 common DEGs (simultaneously regulated by CFs, SFs, and TFs, respectively. GO and KEGG enrichment analyses showed that genes involved in abiotic stress responses and secondary metabolic pathways were overrepresented in the common and CF-specific DEGs. In addition, we noted enrichment in CF-specific DEGs related to the circadian rhythm, SF-specific DEGs involved in mineral nutrient absorption and transport, and SF- and TF-specific DEGs associated with photosynthesis. Based on these results, we propose a model that explains how plants adapt to various ecological factors at the transcriptomic level. Additionally, the identified DEGs lay the foundation for future investigations of stress resistance, circadian rhythm and photosynthesis in tobacco.

  1. Classification and regression tree (CART analyses of genomic signatures reveal sets of tetramers that discriminate temperature optima of archaea and bacteria

    Directory of Open Access Journals (Sweden)

    Betsey Dexter Dyer

    2008-01-01

    Full Text Available Classification and regression tree (CART analysis was applied to genome-wide tetranucleotide frequencies (genomic signatures of 195 archaea and bacteria. Although genomic signatures have typically been used to classify evolutionary divergence, in this study, convergent evolution was the focus. Temperature optima for most of the organisms examined could be distinguished by CART analyses of tetranucleotide frequencies. This suggests that pervasive (nonlinear qualities of genomes may reflect certain environmental conditions (such as temperature in which those genomes evolved. The predominant use of GAGA and AGGA as the discriminating tetramers in CART models suggests that purine-loading and codon biases of thermophiles may explain some of the results.

  2. A multi-group confirmatory factor analyses of the LupusPRO between southern California and Filipino samples of patients with systemic lupus erythematosus.

    Science.gov (United States)

    Azizoddin, D R; Olmstead, R; Cost, C; Jolly, M; Ayeroff, J; Racaza, G; Sumner, L A; Ormseth, S; Weisman, M; Nicassio, P M

    2017-08-01

    Introduction Systemic lupus erythematosus (SLE) leads to a range of biopsychosocial health outcomes through an unpredictable and complex disease path. The LupusPRO is a comprehensive, self-report measure developed specifically for populations with SLE, which assesses both health-related quality of life and non-health related quality of life. Given its increasingly widespread use, additional research is needed to evaluate the psychometric integrity of the LupusPRO across diverse populations. The objectives of this study were to evaluate the performance of the LupusPRO in two divergent patient samples and the model fit between both samples. Methods Two diverse samples with SLE included 136 patients from an ethnically-diverse, urban region in southern California and 100 from an ethnically-homogenous, rural region in Manila, Philippines. All patients met the ACR classification criteria for SLE. Confirmatory factor analysis (CFAs) were conducted in each sample separately and combined to provide evidence of the factorial integrity of the 12 subscales in the LupusPRO. Results Demographic analyses indicated significant differences in age, disease activity and duration, education, income, insurance, and medication use between groups. Results of the separate CFAs indicated moderate fit to the data for the hypothesized 12-factor model for both the Manila and southern California groups, respectively [χ(2) (794) = 1283.32, p factor structures of the LupusPRO in the southern California and Manila groups were constrained to be equal between the two groups, findings revealed that the factor structures of measured variables fit the two groups reasonably well [χ(2 ) (1697) = 2950.413, df = 1697, p model fit improved significantly [χ(2) (15) = 147.165, p < 0.000]. Conclusions This research provides significant support for the subscale structure of the LupusPRO in two disparate cultural samples of SLE patients. Despite significant sociodemographic and

  3. Transcription closed and open complex dynamics studies reveal balance between genetic determinants and co-factors.

    Science.gov (United States)

    Sala, Adrien; Shoaib, Muhammad; Anufrieva, Olga; Mutharasu, Gnanavel; Jahan Hoque, Rawnak; Yli-Harja, Olli; Kandhavelu, Meenakshisundaram

    2015-05-19

    In E. coli, promoter closed and open complexes are key steps in transcription initiation, where magnesium-dependent RNA polymerase catalyzes RNA synthesis. However, the exact mechanism of initiation remains to be fully elucidated. Here, using single mRNA detection and dual reporter studies, we show that increased intracellular magnesium concentration affects Plac initiation complex formation resulting in a highly dynamic process over the cell growth phases. Mg2+ regulates transcription transition, which modulates bimodality of mRNA distribution in the exponential phase. We reveal that Mg2+ regulates the size and frequency of the mRNA burst by changing the open complex duration. Moreover, increasing magnesium concentration leads to higher intrinsic and extrinsic noise in the exponential phase. RNAP-Mg2+ interaction simulation reveals critical movements creating a shorter contact distance between aspartic acid residues and Nucleotide Triphosphate residues and increasing electrostatic charges in the active site. Our findings provide unique biophysical insights into the balanced mechanism of genetic determinants and magnesium ion in transcription initiation regulation during cell growth.

  4. Virus genomes reveal factors that spread and sustained the Ebola epidemic

    DEFF Research Database (Denmark)

    Dudas, Gytis; Carvalho, Luiz Max; Bedford, Trevor

    2017-01-01

    The 2013-2016 West African epidemic caused by the Ebola virus was of unprecedented magnitude, duration and impact. Here we reconstruct the dispersal, proliferation and decline of Ebola virus throughout the region by analysing 1,610 Ebola virus genomes, which represent over 5% of the known cases. We...... test the association of geography, climate and demography with viral movement among administrative regions, inferring a classic 'gravity' model, with intense dispersal between larger and closer populations. Despite attenuation of international dispersal after border closures, cross-border transmission...... had already sown the seeds for an international epidemic, rendering these measures ineffective at curbing the epidemic. We address why the epidemic did not spread into neighbouring countries, showing that these countries were susceptible to substantial outbreaks but at lower risk of introductions...

  5. Bacterial diversity in a finished compost and vermicompost: differences revealed by cultivation-independent analyses of PCR-amplified 16S rRNA genes.

    Science.gov (United States)

    Fracchia, Letizia; Dohrmann, Anja B; Martinotti, Maria Giovanna; Tebbe, Christoph C

    2006-08-01

    Bacterial communities are important catalysts in the production of composts. Here, it was analysed whether the diversity of bacteria in finished composts is stable and specific for the production process. Single-strand conformation polymorphism (SSCP) based on polymerase chain reaction amplified partial 16S rRNA genes was used to profile and analyse bacterial communities found in total DNA extracted from finished composts. Different batches of compost samples stored over a period of 12 years and a 1-year-old vermicompost were compared to each other. According to digital image analysis, clear differences could be detected between the profiles from compost and vermicompost. Differences between three different periods of compost storage and between replicate vermicompost windrows were only minor. A total of 41 different 16S rRNA genes were identified from the SSCP profiles by DNA sequencing, with the vast majority related to yet-uncultivated bacteria. Sequences retrieved from compost mainly belonged to the phyla Actinobacteria and Firmicutes. In contrast, vermicompost was dominated by bacteria related to uncultured Chloroflexi, Acidobacteria, Bacteroidetes and Gemmatimonadetes. The differences were underscored with specific gene probes and Southern blot hybridizations. The results confirmed that different substrates and composting processes selected for specific bacterial communities in the finished products. The specificity and consistency of the bacterial communities inhabiting the compost materials suggest that cultivation-independent bacterial community analysis is a potentially useful indicator to characterize the quality of finished composts in regard to production processes and effects of storage conditions.

  6. Biochemical and full genome sequence analyses of clinical Vibrio cholerae isolates in Mexico reveals the presence of novel V. cholerae strains.

    Science.gov (United States)

    Díaz-Quiñonez, José Alberto; Hernández-Monroy, Irma; Montes-Colima, Norma Angélica; Moreno-Pérez, María Asunción; Galicia-Nicolás, Adriana Guadalupe; López-Martínez, Irma; Ruiz-Matus, Cuitláhuac; Kuri-Morales, Pablo; Ortíz-Alcántara, Joanna María; Garcés-Ayala, Fabiola; Ramírez-González, José Ernesto

    2016-05-01

    The first week of September 2013, the National Epidemiological Surveillance System identified two cases of cholera in Mexico City. The cultures of both samples were confirmed as Vibrio cholerae serogroup O1, serotype Ogawa, biotype El Tor. Initial analyses by PFGE and by PCR-amplification of the virulence genes, suggested that both strains were similar, but different from those previously reported in Mexico. The following week, four more cases were identified in a community in the state of Hidalgo, located 121 km northeast of Mexico City. Thereafter a cholera outbreak started in the region of La Huasteca. Genomic analyses of the four strains obtained in this study confirmed the presence of Pathogenicity Islands VPI-1 and -2, VSP-1 and -2, and of the integrative element SXT. The genomic structure of the 4 isolates was similar to that of V. cholerae strain 2010 EL-1786, identified during the epidemic in Haiti in 2010. Copyright © 2016 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  7. Comparative Proteomic, Physiological, Morphological, and Biochemical Analyses Reveal the Characteristics of the Diploid Spermatozoa of Allotetraploid Hybrids of Red Crucian Carp (Carassius auratus) and Common Carp (Cyprinus carpio).

    Science.gov (United States)

    Duan, Wei; Xu, Kang; Hu, Fangzhou; Zhang, Yi; Wen, Ming; Wang, Jing; Tao, Min; Luo, Kaikun; Zhao, Rurong; Qin, Qinbo; Zhang, Chun; Liu, Jinhui; Liu, Yun; Liu, Shaojun

    2016-02-01

    The generation of diploid spermatozoa is essential for the continuity of tetraploid lineages. The DNA content of diploid spermatozoa from allotetraploid hybrids of red crucian carp and common carp was nearly twice as great as that of haploid spermatozoa from common carp, and the durations of rapid and slow progressive motility were longer. We performed comparative proteomic analyses to measure variations in protein composition between diploid and haploid spermatozoa. Using two-dimensional electrophoresis followed by liquid chromatography tandem mass spectrometry, 21 protein spots that changed in abundance were analyzed. As the common carp and the allotetraploid hybrids are not fully sequenced organisms, we identified proteins by Mascot searching against the National Center for Biotechnology Information non-redundant (NR) protein database for the zebrafish (Danio rerio), and verified them against predicted homologous proteins derived from transcriptomes of the testis. Twenty protein spots were identified successfully, belonging to four gene ontogeny categories: cytoskeleton, energy metabolism, the ubiquitin-proteasome system, and other functions, indicating that these might be associated with the variation in diploid spermatozoa. This categorization of variations in protein composition in diploid spermatozoa will provide new perspectives on male polyploidy. Moreover, our approach indicates that transcriptome data are useful for proteomic analyses in organisms lacking full protein sequences.

  8. Stress analyses coupled with damage laws to determine biomechanical risk factors for deep tissue injury during sitting.

    Science.gov (United States)

    Linder-Ganz, Eran; Gefen, Amit

    2009-01-01

    Deep tissue injury (DTI) is a potentially life-threatening form of pressure ulcer that onsets in muscle tissue overlying bony prominences and progresses unnoticeably to more superficial tissues. To minimize DTI, the efficacy of wheelchair cushions should be evaluated not only based on their performance in redistributing interface pressures but also according to their effects on stress concentrations in deep tissues, particularly muscles. However, a standard bioengineering approach for such analyses is missing in literature. The goals of this study were to develop an algorithm to couple finite element (FE) modeling of the buttocks with an injury threshold for skeletal muscle and with a damage-stiffening law for injured muscle tissue, from previous animal experiments, to predict DTI onset and progression for different patient anatomies and wheelchair cushions. The algorithm was also employed for identifying intrinsic (anatomical) biomechanical risk factors for DTI onset. A set of three-dimensional FE models of seated human buttocks was developed, representing different severities of pathoanatomical changes observed in chronically sitting patients: muscle atrophy and "flattening" of the ischial tuberosity (IT). These models were then tested with cushions of different stiffnesses representing products available on the market and semirigid supports. Outcome measures were the percentage of damaged muscle tissue volumes after 90 min and 110 min of simulated continuous immobilized sitting as well as muscle injury rates post-60 min, -90 min, and -110 min of continuous sitting. Damaged muscle volumes grew exponentially with the level of muscle atrophy. For example, simulation of a subject with 70% muscle atrophy sitting on a soft cushion showed damage to 33% of the muscle volume after 90 min of immobilized sitting, whereas a comparable simulation with a nonatrophied muscle yielded only 0.4% damaged tissue volume. The rates of DTI progression also increased substantially with

  9. A Case-Control Study and Meta-Analysis Reveal BDNF Val66Met Is a Possible Risk Factor for PTSD

    Directory of Open Access Journals (Sweden)

    Dagmar Bruenig

    2016-01-01

    Full Text Available Posttraumatic stress disorder (PTSD is a debilitating condition that develops in some people after exposure to a traumatic event. Brain-derived neurotrophic factor (BDNF is highly expressed in the mammalian brain and is thought to be involved in learning and memory processes. A nonsynonymous polymorphism in the BDNF gene, rs6265 (Val66Met, has been hypothesised to be associated with PTSD. Association studies examining the Val66Met polymorphism and PTSD have been inconclusive, likely due to the variability in type of trauma exposure analysed. Vietnam veterans (n=257 screened for PTSD and controlled for trauma exposure were genotyped for BDNF Val66Met. The association was not significant so we incorporated our data into a meta-analysis to obtain greater statistical power. A comprehensive search of more than 1237 articles revealed eight additional studies suitable for meta-analysis (n=3625. A random-effects meta-analysis observed a potential protective factor of the Val/Val genotype. After removing two studies with violation of Hardy-Weinberg equilibrium, findings for the Val/Val genotype reached significance. Subgroup analyses confirmed a trend for this finding. Limitations of some studies that inform this meta-analysis include poorly screened controls and a lack of examination of population stratification. Effectively designed studies should inform this line of research in the future.

  10. Structural and biochemical analyses reveal insights into covalent flavinylation of the Escherichia coli Complex II homolog quinol:fumarate reductase

    Energy Technology Data Exchange (ETDEWEB)

    Starbird, C.A.; Maklashina, Elena; Sharma, Pankaj; Qualls-Histed, Susan; Cecchini, Gary; Iverson, T.M. (VA); (UCSF); (Vanderbilt)

    2017-06-14

    The Escherichia coli Complex II homolog quinol:fumarate reductase (QFR, FrdABCD) catalyzes the interconversion of fumarate and succinate at a covalently attached FAD within the FrdA subunit. The SdhE assembly factor enhances covalent flavinylation of Complex II homologs, but the mechanisms underlying the covalent attachment of FAD remain to be fully elucidated. Here, we explored the mechanisms of covalent flavinylation of the E. coli QFR FrdA subunit. Using a ΔsdhE E. coli strain, we show that the requirement for the assembly factor depends on the cellular redox environment. We next identified residues important for the covalent attachment and selected the FrdAE245 residue, which contributes to proton shuttling during fumarate reduction, for detailed biophysical and structural characterization. We found that QFR complexes containing FrdAE245Q have a structure similar to that of the WT flavoprotein, but lack detectable substrate binding and turnover. In the context of the isolated FrdA subunit, the anticipated assembly intermediate during covalent flavinylation, FrdAE245 variants had stability similar to that of WT FrdA, contained noncovalent FAD, and displayed a reduced capacity to interact with SdhE. However, small-angle X-ray scattering (SAXS) analysis of WT FrdA cross-linked to SdhE suggested that the FrdAE245 residue is unlikely to contribute directly to the FrdA-SdhE protein-protein interface. We also found that no auxiliary factor is absolutely required for flavinylation, indicating that the covalent flavinylation is autocatalytic. We propose that multiple factors, including the SdhE assembly factor and bound dicarboxylates, stimulate covalent flavinylation by preorganizing the active site to stabilize the quinone-methide intermediate.

  11. Multivariable analysis of clinical influence factors on liver enhancement of Gd-EOB-DTPA-enhanced 3T MRI; Multivariable Analyse klinischer Einflussfaktoren auf die Signalintensitaet bei Gd-EOB-DTPA 3T-MRT der Leber

    Energy Technology Data Exchange (ETDEWEB)

    Verloh, N.; Haimerl, M.; Stroszczynski, C.; Fellner, C.; Wiggermann, P. [University Hospital Regensburg (Germany). Dept. of Radiology; Zeman, F. [University Hospital Regensburg (Germany). Center for Clinical Trials; Teufel, A. [University Hospital Regensburg (Germany). Dept. of Gastroenterology; Lang, S. [University Hospital Regensburg (Germany). Dept. of Surgery

    2015-01-15

    The purpose of this study was to identify clinical factors influencing Gd-EOB-DTPA liver uptake in patients with healthy liver parenchyma. A total of 124 patients underwent contrast-enhanced MRI with a hepatocyte-specific contrast agent at 3T. T1-weighted volume interpolated breath-hold examination (VIBE) sequences with fat suppression were acquired before and 20 minutes after contrast injection. The relative enhancement (RE) between plain and contrast-enhanced signal intensity was calculated. Simple and multiple linear regression analyses were performed to evaluate clinical factors influencing the relative enhancement. Patients were subdivided into three groups according to their relative liver enhancement (HRE, RE ≥ 100 %; MRE, 100 % > RE > 50 %; NRE, RE ≤ 50 %) and were analyzed according to the relevant risk factors. Simple regression analyses revealed patient age, transaminases (AST, ALT, GGT), liver, spleen and delta-liver volume (the difference between the volumetrically measured liver volume and the estimated liver volume based on body weight) as significant factors influencing relative enhancement. In the multiple analysis the transaminase AST, spleen and delta liver volume remained significant factors influencing relative enhancement. Delta liver volume showed a significant difference between all analyzed groups. Liver enhancement in the hepatobiliary phase depends on a variety of factors. Body weight-adapted administration of Gd-EOB-DTPA may lead to inadequate liver enhancement after 20 minutes especially when the actual liver volume differs from the expected volume.

  12. The Effect of Pleistocene Climate Fluctuations on Distribution of European Abalone (Haliotis tuberculata), Revealed by Combined Mitochondrial and Nuclear Marker Analyses.

    Science.gov (United States)

    Roussel, Valérie; Van Wormhoudt, Alain

    2017-04-01

    The genetic differentiation among the populations of the European abalone Haliotis tuberculata was investigated using different markers to better understand the evolutionary history and exchanges between populations. Three markers were used: mitochondrial cytochrome oxidase I (COI), the sperm lysin nuclear gene, and eight nuclear microsatellites. These markers present different characteristics concerning mutation rate and inheritance, which provided complementary information about abalone history and gene diversity. Genetic diversity and relationships among subspecies were calculated from a sample of approximately 500 individuals, collected from 17 different locations in the north-eastern Atlantic Ocean, Macaronesia, and Mediterranean Sea. COI marker was used to explore the phylogeny of the species with a network analysis and two phylogenetic methods. The analysis revealed 18 major haplotypes grouped into two distinct clades with a pairwise sequence divergence up to 3.5 %. These clades do not correspond to subspecies but revealed many contacts along Atlantic coast during the Pleistocene interglaciations. The sperm lysin gene analysis separated two different subtaxa: one associated to Macaronesian islands, and the other to all other populations. Moreover, a small population of the northern subtaxon was isolated in the Adriatic Sea-probably before the separation of the two lineages-and evolved independently. Microsatellites were analyzed by different genetics methods, including the Bayesian clustering method and migration patterns analysis. It revealed genetically distinct microsatellite patterns among populations from Mediterranean Sea, Brittany and Normandy, Morocco, and Canary and Balearic islands. Gene flow is asymmetric among the regions; the Azores and the Canary Islands are particularly isolated and have low effective population sizes. Our results support the hypothesis that climate changes since the Pleistocene glaciations have played a major role in the

  13. Revealing the Differences Between Free and Complexed Enzyme Mechanisms and Factors Contributing to Cell Wall Recalcitrance

    Energy Technology Data Exchange (ETDEWEB)

    Resch, M.

    2014-09-08

    Enzymatic depolymerization of polysaccharides is a key step in the production of fuels and chemicals from lignocellulosic biomass, and discovery of synergistic biomass-degrading enzyme paradigms will enable improved conversion processes. Historically, revealing insights into enzymatic saccharification mechanisms on plant cell walls has been hindered by uncharacterized substrates and low resolution imaging techniques. Also, translating findings between model substrates to intact biomass is critical for evaluating enzyme performance. Here we employ a fungal free enzyme cocktail, a complexed cellulosomal system, and a combination of the two to investigate saccharification mechanisms on cellulose I, II and III along with corn stover from Clean Fractionation (CF), which is an Organosolv pretreatment. The insoluble Cellulose Enriched Fraction (CEF) from CF contains mainly cellulose with minor amounts of residual hemicellulose and lignin, the amount of which depends on the CF pretreatment severity. Enzymatic digestions at both low and high-solids loadings demonstrate that CF reduces the amount of enzyme required to depolymerize polysaccharides relative to deacetylated, dilute acid pretreated corn stover. Transmission and scanning electron microscopy of the biomass provides evidence for the different mechanisms of enzymatic deconstruction between free and complexed enzyme systems, and reveals the basis for the synergistic relationship between the two enzyme paradigms on a process-relevant substrate for the first time. These results also demonstrate that the presence of lignin, rather than cellulose morphology, is more detrimental to cellulosome action than to free cellulases. As enzyme costs are a major economic driver for biorefineries, this study provides key inputs for the evaluation of CF as a pretreatment method for biomass conversion.

  14. Yeast genetic analysis reveals the involvement of chromatin reassembly factors in repressing HIV-1 basal transcription.

    Directory of Open Access Journals (Sweden)

    Manuela Vanti

    2009-01-01

    Full Text Available Rebound of HIV viremia after interruption of anti-retroviral therapy is due to the small population of CD4+ T cells that remain latently infected. HIV-1 transcription is the main process controlling post-integration latency. Regulation of HIV-1 transcription takes place at both initiation and elongation levels. Pausing of RNA polymerase II at the 5' end of HIV-1 transcribed region (5'HIV-TR, which is immediately downstream of the transcription start site, plays an important role in the regulation of viral expression. The activation of HIV-1 transcription correlates with the rearrangement of a positioned nucleosome located at this region. These two facts suggest that the 5'HIV-TR contributes to inhibit basal transcription of those HIV-1 proviruses that remain latently inactive. However, little is known about the cell elements mediating the repressive role of the 5'HIV-TR. We performed a genetic analysis of this phenomenon in Saccharomyces cerevisiae after reconstructing a minimal HIV-1 transcriptional system in this yeast. Unexpectedly, we found that the critical role played by the 5'HIV-TR in maintaining low levels of basal transcription in yeast is mediated by FACT, Spt6, and Chd1, proteins so far associated with chromatin assembly and disassembly during ongoing transcription. We confirmed that this group of factors plays a role in HIV-1 postintegration latency in human cells by depleting the corresponding human orthologs with shRNAs, both in HIV latently infected cell populations and in particular single-integration clones, including a latent clone with a provirus integrated in a highly transcribed gene. Our results indicate that chromatin reassembly factors participate in the establishment of the equilibrium between activation and repression of HIV-1 when it integrates into the human genome, and they open the possibility of considering these factors as therapeutic targets of HIV-1 latency.

  15. Comparative Genomic Analyses of Multiple Pseudomonas Strains Infecting Corylus avellana Trees Reveal the Occurrence of Two Genetic Clusters with Both Common and Distinctive Virulence and Fitness Traits.

    Directory of Open Access Journals (Sweden)

    Simone Marcelletti

    Full Text Available The European hazelnut (Corylus avellana is threatened in Europe by several pseudomonads which cause symptoms ranging from twig dieback to tree death. A comparison of the draft genomes of nine Pseudomonas strains isolated from symptomatic C. avellana trees was performed to identify common and distinctive genomic traits. The thorough assessment of genetic relationships among the strains revealed two clearly distinct clusters: P. avellanae and P. syringae. The latter including the pathovars avellanae, coryli and syringae. Between these two clusters, no recombination event was found. A genomic island of approximately 20 kb, containing the hrp/hrc type III secretion system gene cluster, was found to be present without any genomic difference in all nine pseudomonads. The type III secretion system effector repertoires were remarkably different in the two groups, with P. avellanae showing a higher number of effectors. Homologue genes of the antimetabolite mangotoxin and ice nucleation activity clusters were found solely in all P. syringae pathovar strains, whereas the siderophore yersiniabactin was only present in P. avellanae. All nine strains have genes coding for pectic enzymes and sucrose metabolism. By contrast, they do not have genes coding for indolacetic acid and anti-insect toxin. Collectively, this study reveals that genomically different Pseudomonas can converge on the same host plant by suppressing the host defence mechanisms with the use of different virulence weapons. The integration into their genomes of a horizontally acquired genomic island could play a fundamental role in their evolution, perhaps giving them the ability to exploit new ecological niches.

  16. Biochemical and genome sequence analyses of Megasphaera sp. strain DISK18 from dental plaque of a healthy individual reveals commensal lifestyle

    Science.gov (United States)

    Nallabelli, Nayudu; Patil, Prashant P.; Pal, Vijay Kumar; Singh, Namrata; Jain, Ashish; Patil, Prabhu B.; Grover, Vishakha; Korpole, Suresh

    2016-01-01

    Much of the work in periodontal microbiology in recent years has focused on identifying and understanding periodontal pathogens. As the majority of oral microbes have not yet been isolated in pure form, it is essential to understand the phenotypic characteristics of microbes to decipher their role in oral environment. In this study, strain DISK18 was isolated from gingival sulcus and identified as a Megasphaera species. Although metagenomics studies revealed Megasphaera species as a major group within the oral habitat, they have never been isolated in cultivable form to date. Therefore, we have characterized the DISK18 strain to better understand its role in the periodontal ecosystem. Strain Megasphaera sp. DISK18 displayed the ability to adhere and self-aggregate, which are essential requisite features for inhabiting and persisting in oral cavity. It also coaggregated with other pioneer oral colonizers like Streptococcus and Lactobacillus species but not with Veillonella. This behaviour points towards its role in the ecologic succession of a multispecies biofilm as an early colonizer. The absence of virulence determining genes as observed in whole genome sequence analysis coupled with an inability to degrade collagen reveals that Megasphaera sp. strain DISK18 is likely not a pathogenic species and emphasizes its commensal lifestyle. PMID:27651180

  17. Phylogenetic analyses of Norovirus strains detected in Uruguay reveal the circulation of the novel GII.P7/GII.6 recombinant variant.

    Science.gov (United States)

    Fajardo, Álvaro; Tort, Fernando López; Victoria, Matías; Fumian, Tulio M; Miagostovich, Marize P; Leite, José Paulo G; Cristina, Juan; Colina, Rodney

    2014-12-01

    Noroviruses (NoV) are one of the major etiological agent of acute gastroenteritis (AGE) outbreaks worldwide. Distinct NoV genotypes have been associated with different transmission patterns and disease severity in humans. Therefore, it is important to identify genetically different NoV genotypes circulating in a particular region. However, genotyping has become a challenge due to recombination events occurring mainly nearby ORF1/ORF2 junction of NoV genome, leading to distinct genotypes with polymerase and capsid regions derived from parenteral strains. Taking this into account, ORF1/ORF2 sequences were obtained from NoV strains collected from patients with AGE in Uruguay. This study reveals in silico evidences of recombination events taking place in four out of six strains analyzed for which its polymerase gene and its capsid region correspond to GII.P7 and to GII.6 genotype, respectively. These results also reveal the circulation of a GII.P7/GII.6 recombinant variant in the natural populations of NoV strains in the northwestern region of Uruguay. As far as we know this is the first report about the circulation of a NoV GII.P7/GII.6 recombinant variant in the Americas.

  18. Comprehensive transcriptional and functional analyses of melatonin synthesis genes in cassava reveal their novel role in hypersensitive-like cell death

    Science.gov (United States)

    Wei, Yunxie; Hu, Wei; Wang, Qiannan; Liu, Wei; Wu, Chunjie; Zeng, Hongqiu; Yan, Yu; Li, Xiaolin; He, Chaozu; Shi, Haitao

    2016-01-01

    Melatonin is a widely known hormone in animals. Since melatonin was discovered in plants, more and more studies highlight its involvement in a wide range of physiological processes including plant development and stress responses. Many advances have been made in the terms of melatonin-mediated abiotic stress resistance and innate immunity in plants, focusing on model plants such as rice and Arabidopsis. In this study, 7 melatonin synthesis genes were systematically analyzed in cassava. Quantitative real-time PCR showed that all these genes were commonly regulated by melatonin, flg22, Xanthomonas axonopodis pv manihotis (Xam) and hydrogen peroxide (H2O2). Transient expression in Nicotiana benthamiana revealed the subcellular locations and possible roles of these melatonin synthesis genes. Notably, we highlight novel roles of these genes in hypersensitive-like cell death, as confirmed by the results of several physiological parameters. Moreover, transient expression of these genes had significant effects on the transcripts of reactive oxygen species (ROS) accumulation and defense-related genes, and triggered the burst of callose depositions and papillae-associated plant defense, indicating the possible role of them in plant innate immunity. Taken together, this study reveals the comprehensive transcripts and putative roles of melatonin synthesis genes as well as melatonin in immune responses in cassava. PMID:27739451

  19. Lethal factor VII deficiency due to novel mutations in the F7 promoter: functional analysis reveals disruption of HNF4 binding site.

    Science.gov (United States)

    Giansily-Blaizot, Muriel; Lopez, Estelle; Viart, Victoria; Chafa, Ouerdia; Tapon-Bretaudière, Jacqueline; Claustres, Mireille; Taulan, Magali

    2012-08-01

    Hereditary factor VII (FVII) deficiency is a rare autosomal recessive disorder. Deleterious mutations that prevent the synthesis of any amount of functional FVII have been associated with life-threatening haemorrhage in neonates. Here we report two infants, of Maghrebian origin, who suffered a fatal spontaneous cerebral haemorrhage. Investigation of the molecular basis for their severe FVII deficiency revealed novel mutations in a homozygous state within the F7 gene promoter: a single nucleotide substitution (c.-65G>C) and a 2bp deletion (c.-60_-59delTT). To determine whether these promoter variants were responsible for the FVII deficiency, computer-assisted sequence analyses were performed. The data predicted a disrupted binding of both HNF4 and COUP-TF transcription factors with each variant. Concordantly, experimental results revealed an altered HNF4-induced transactivation in the promoter mutated variants. The execution of functional tests is critical to ensuring a complete understanding of the effect of any promoter mutant on FVII deficiency. Only then can an accurate molecular diagnosis be made and further genetic counselling and prenatal diagnosis be offered.

  20. Host-dependent differences in resource use associated with Anilocra spp. parasitism in two coral reef fishes, as revealed by stable carbon and nitrogen isotope analyses

    Science.gov (United States)

    Welicky, Rachel; Demopoulos, Amanda W. J.; Sikkel, Paul C.

    2017-01-01

    The role of parasites in trophic ecology is poorly understood in marine ecosystems. Stable isotope analyses (SIA) have been widely used in studies of trophic ecology, but have rarely been applied to study the role of parasites. Considering that some parasites are associated with altered host foraging patterns, SIA can help elucidate whether parasitism influences host trophic interactions. French grunt (Haemulon flavolineatum), an abundant Caribbean coral reef fish, contributes greatly to trophic connectivity. They typically depart the reef at dusk, feed overnight in seagrass beds, and return to the reef at dawn. The large parasitic isopod Anilocra haemuli commonly infects French grunt, and infected fish are less likely to complete their diel migration, and are in poorer condition than uninfected conspecifics. Brown chromis (Chromis multilineata) are diurnally feeding planktivores and infection by Anilocra chromis does not influence host condition. To determine if Anilocra infection influences host diet and foraging locality, we conducted stable carbon and nitrogen isotope analyses on scale, muscle, heart and gill tissues of infected and uninfected French grunt and brown chromis. We determined that all French grunt had δ13C values representative of seagrass habitats, but infected French grunt were significantly enriched in 13C and 15N compared to uninfected conspecifics. This suggests that compared to uninfected conspecifics, infected French grunt forage in seagrass, but on isotopically enriched prey, and/or are in poorer condition, which can elevate δ13C and δ15N values. For brown chromis, infection did not significantly influence any δ13C and δ15N values; hence they all foraged in the same environment and on similar prey. This is the first study to use SIA to examine differences in resource use by Caribbean coral reef fishes associated with parasitism and to evaluate how closely related parasites might have host-dependent effects on host trophic ecology.

  1. Combined analyses of the ITS loci and the corresponding 16S rRNA genes reveal high micro- and macrodiversity of SAR11 populations in the Red Sea.

    KAUST Repository

    Ngugi, David

    2012-11-20

    Bacteria belonging to the SAR11 clade are among the most abundant prokaryotes in the pelagic zone of the ocean. 16S rRNA gene-based analyses indicate that they constitute up to 60% of the bacterioplankton community in the surface waters of the Red Sea. This extremely oligotrophic water body is further characterized by an epipelagic zone, which has a temperature above 24 °C throughout the year, and a remarkable uniform temperature (~22 °C) and salinity (~41 psu) from the mixed layer (~200 m) to the bottom at over 2000 m depth. Despite these conditions that set it apart from other marine environments, the microbiology of this ecosystem is still vastly understudied. Prompted by the limited phylogenetic resolution of the 16S rRNA gene, we extended our previous study by sequencing the internal transcribed spacer (ITS) region of SAR11 in different depths of the Red Sea\\'s water column together with the respective 16S fragment. The overall diversity captured by the ITS loci was ten times higher than that of the corresponding 16S rRNA genes. Moreover, species estimates based on the ITS showed a highly diverse population of SAR11 in the mixed layer that became diminished in deep isothermal waters, which was in contrast to results of the related 16S rRNA genes. While the 16S rRNA gene-based sequences clustered into three phylogenetic subgroups, the related ITS fragments fell into several phylotypes that showed clear depth-dependent shifts in relative abundances. Blast-based analyses not only documented the observed vertical partitioning and universal co-occurrence of specific phylotypes in five other distinct oceanic provinces, but also highlighted the influence of ecosystem-specific traits (e.g., temperature, nutrient availability, and concentration of dissolved oxygen) on the population dynamics of this ubiquitous marine bacterium.

  2. Combined analyses of the ITS loci and the corresponding 16S rRNA genes reveal high micro- and macrodiversity of SAR11 populations in the Red Sea.

    Directory of Open Access Journals (Sweden)

    David Kamanda Ngugi

    Full Text Available Bacteria belonging to the SAR11 clade are among the most abundant prokaryotes in the pelagic zone of the ocean. 16S rRNA gene-based analyses indicate that they constitute up to 60% of the bacterioplankton community in the surface waters of the Red Sea. This extremely oligotrophic water body is further characterized by an epipelagic zone, which has a temperature above 24 °C throughout the year, and a remarkable uniform temperature (~22 °C and salinity (~41 psu from the mixed layer (~200 m to the bottom at over 2000 m depth. Despite these conditions that set it apart from other marine environments, the microbiology of this ecosystem is still vastly understudied. Prompted by the limited phylogenetic resolution of the 16S rRNA gene, we extended our previous study by sequencing the internal transcribed spacer (ITS region of SAR11 in different depths of the Red Sea's water column together with the respective 16S fragment. The overall diversity captured by the ITS loci was ten times higher than that of the corresponding 16S rRNA genes. Moreover, species estimates based on the ITS showed a highly diverse population of SAR11 in the mixed layer that became diminished in deep isothermal waters, which was in contrast to results of the related 16S rRNA genes. While the 16S rRNA gene-based sequences clustered into three phylogenetic subgroups, the related ITS fragments fell into several phylotypes that showed clear depth-dependent shifts in relative abundances. Blast-based analyses not only documented the observed vertical partitioning and universal co-occurrence of specific phylotypes in five other distinct oceanic provinces, but also highlighted the influence of ecosystem-specific traits (e.g., temperature, nutrient availability, and concentration of dissolved oxygen on the population dynamics of this ubiquitous marine bacterium.

  3. RNA-Seq transcriptomics and pathway analyses reveal potential regulatory genes and molecular mechanisms in high- and low-residual feed intake in Nordic dairy cattle.

    Science.gov (United States)

    Salleh, M S; Mazzoni, G; Höglund, J K; Olijhoek, D W; Lund, P; Løvendahl, P; Kadarmideen, H N

    2017-03-24

    The selective breeding of cattle with high-feed efficiencies (FE) is an important goal of beef and dairy cattle producers. Global gene expression patterns in relevant tissues can be used to study the functions of genes that are potentially involved in regulating FE. In the present study, high-throughput RNA sequencing data of liver biopsies from 19 dairy cows were used to identify differentially expressed genes (DEGs) between high- and low-FE groups of cows (based on Residual Feed Intake or RFI). Subsequently, a profile of the pathways connecting the DEGs to FE was generated, and a list of candidate genes and biomarkers was derived for their potential inclusion in breeding programmes to improve FE. The bovine RNA-Seq gene expression data from the liver was analysed to identify DEGs and, subsequently, identify the molecular mechanisms, pathways and possible candidate biomarkers of feed efficiency. On average, 57 million reads (short reads or short mRNA sequences genes showed interaction effects in the Jersey cows. The analyses showed that DEGs act through certain pathways to affect or regulate FE, including steroid hormone biosynthesis, retinol metabolism, starch and sucrose metabolism, ether lipid metabolism, arachidonic acid metabolism and drug metabolism cytochrome P450. We used RNA-Seq-based liver transcriptomic profiling of high- and low-RFI dairy cows in two breeds and identified significantly DEGs, their molecular mechanisms, their interactions with other genes and functional enrichments of different molecular pathways. The DEGs that were identified were the CYP's and GIMAP genes for the Holstein and Jersey cows, respectively, which are related to the primary immunodeficiency pathway and play a major role in feed utilization and the metabolism of lipids, sugars and proteins.

  4. Mycorrhiza analyses in New Zealand truffières reveal frequent but variable persistence of Tuber melanosporum in co-existence with other truffle species.

    Science.gov (United States)

    Guerin-Laguette, Alexis; Cummings, Nicholas; Hesom-Williams, Nina; Butler, Ruth; Wang, Yun

    2013-02-01

    This study compiles the results from an examination of mycorrhizae on root samples from Tuber melanosporum truffières in New Zealand. Samples were taken over 5 years from 328 trees in 43 truffières established with nursery-inoculated trees. Mycorrhizae were analysed using a combination of morphological and molecular techniques, focusing on the identification of Tuber species. Results show that 49% of the trees, and nearly 90% of the truffières, retained T. melanosporum mycorrhizae up to 21 years after planting. Tuber mycorrhizae with spiky cystidia were found on 26.9% of the tested trees: Tuber brumale (5.5%), Tuber maculatum (10.7%), and unidentified Tuber species (10.7%), and were detected in 67% of the truffières tested. T. brumale was found in 28% and T. maculatum in 35% of the truffières. In 56% of the truffières, T. melanosporum was found to occur with spiky Tuber species. The existence of T. brumale and T. maculatum in the same truffière was recorded only once. Forty-four percent of trees examined had Scleroderma-like (SCL) mycorrhizae and 50% of trees hosted other ectomycorrhizal species (OE). For all categories of mycorrhizal species examined, the variation between truffières was greater than variation within each truffière. Overall results indicate that Corylus avellana tends to be more receptive to mycorrhizae of Tuber species than Quercus robur but is not necessarily more productive. In productive truffières, Q. robur appears to host SCL mycorrhizae more often than C. avellana. This is the first study of its scale to analyse the mycorrhizal species associated with T. melanosporum truffières in the Southern Hemisphere.

  5. In Vitro Functional Analyses of Infrequent Nucleotide Variants in the Lactase Enhancer Reveal Different Molecular Routes to Increased Lactase Promoter Activity and Lactase Persistence

    Science.gov (United States)

    Liebert, Anke; Jones, Bryony L.; Danielsen, Erik Thomas; Olsen, Anders Krüger; Troelsen, Jesper T.

    2016-01-01

    Summary The genetic trait that allows intestinal lactase to persist into adulthood in some 35% of humans worldwide operates at the level of transcription, the effect being caused by cis‐acting nucleotide changes upstream of the lactase gene (LCT). A single nucleotide substitution, ‐13910 C>T, the first causal variant to be identified, accounts for lactase persistence over most of Europe. Located in a region shown to have enhancer function in vitro, it causes increased activity of the LCT promoter in Caco‐2 cells, and altered transcription factor binding. Three other variants in close proximity, ‐13907 C>G, ‐13915 T>C and ‐14010 G>C, were later shown to behave in a similar manner. Here, we study four further candidate functional variants. Two, ‐14009 T>G and ‐14011 C>T, adjacent to the well‐studied ‐14010 G>C variant, also have a clear effect on promoter activity upregulation as assessed by transfection assays, but notably are involved in different molecular interactions. The results for the two other variants (‐14028 T>C, ‐13779 G>C) were suggestive of function, ‐14028*C showing a clear change in transcription factor binding, but no obvious effect in transfections, while ‐13779*G showed greater effect in transfections but less on transcription factor binding. Each of the four variants arose on independent haplotypic backgrounds with different geographic distribution. PMID:27714771

  6. Helmet Use Amongst Equestrians: Harnessing Social and Attitudinal Factors Revealed in Online Forums

    Directory of Open Access Journals (Sweden)

    Laura Haigh

    2015-07-01

    Full Text Available Equestrian activities pose significant head injury risks to participants. Yet, helmet use is not mandatory