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Sample records for analysis reveals global

  1. Revealing the underlying drivers of disaster risk: a global analysis

    NASA Astrophysics Data System (ADS)

    Peduzzi, Pascal

    2017-04-01

    Disasters events are perfect examples of compound events. Disaster risk lies at the intersection of several independent components such as hazard, exposure and vulnerability. Understanding the weight of each component requires extensive standardisation. Here, I show how footprints of past disastrous events were generated using GIS modelling techniques and used for extracting population and economic exposures based on distribution models. Using past event losses, it was possible to identify and quantify a wide range of socio-politico-economic drivers associated with human vulnerability. The analysis was applied to about nine thousand individual past disastrous events covering earthquakes, floods and tropical cyclones. Using a multiple regression analysis on these individual events it was possible to quantify each risk component and assess how vulnerability is influenced by various hazard intensities. The results show that hazard intensity, exposure, poverty, governance as well as other underlying factors (e.g. remoteness) can explain the magnitude of past disasters. Analysis was also performed to highlight the role of future trends in population and climate change and how this may impacts exposure to tropical cyclones in the future. GIS models combined with statistical multiple regression analysis provided a powerful methodology to identify, quantify and model disaster risk taking into account its various components. The same methodology can be applied to various types of risk at local to global scale. This method was applied and developed for the Global Risk Analysis of the Global Assessment Report on Disaster Risk Reduction (GAR). It was first applied on mortality risk in GAR 2009 and GAR 2011. New models ranging from global assets exposure and global flood hazard models were also recently developed to improve the resolution of the risk analysis and applied through CAPRA software to provide probabilistic economic risk assessments such as Average Annual Losses (AAL

  2. Global Analysis of Perovskite Photophysics Reveals Importance of Geminate Pathways

    SciTech Connect

    Manger, Lydia H.; Rowley, Matthew B.; Fu, Yongping; Foote, Alexander K.; Rea, Morgan T.; Wood, Sharla L.; Jin, Song; Wright, John C.; Goldsmith, Randall H.

    2016-12-20

    Hybrid organic-inorganic perovskites demonstrate desirable photophysical behaviors and promising applications from efficient photovoltaics to lasing, but the fundamental nature of excited state species is still under debate. We also collected time-resolved photoluminescence of single-crystal nanoplates of methylammonium lead iodide perovskite (MAPbI3), with excitation over a range of fluences and repetition rates, to provide a more complete photophysical picture. A fundamentally different way of simulating the photophysics is developed that relies on unnormalized decays, global analysis over a large array of conditions, and inclusion of steady-state behavior; these details are critical to capturing observed behaviors. These additional constraints require inclusion of spatially-correlated pairs, along with free carriers and traps, demonstrating the importance of our comprehensive analysis. Modeling geminate and non-geminate pathways shows geminate processes are dominant at high carrier densities and early times. This combination of data and simulation provides a detailed picture of perovskite photophysics across multiple excitation regimes that was not previously available.

  3. Global Analysis of Perovskite Photophysics Reveals Importance of Geminate Pathways

    DOE PAGES

    Manger, Lydia H.; Rowley, Matthew B.; Fu, Yongping; ...

    2016-12-20

    Hybrid organic-inorganic perovskites demonstrate desirable photophysical behaviors and promising applications from efficient photovoltaics to lasing, but the fundamental nature of excited state species is still under debate. We also collected time-resolved photoluminescence of single-crystal nanoplates of methylammonium lead iodide perovskite (MAPbI3), with excitation over a range of fluences and repetition rates, to provide a more complete photophysical picture. A fundamentally different way of simulating the photophysics is developed that relies on unnormalized decays, global analysis over a large array of conditions, and inclusion of steady-state behavior; these details are critical to capturing observed behaviors. These additional constraints require inclusion ofmore » spatially-correlated pairs, along with free carriers and traps, demonstrating the importance of our comprehensive analysis. Modeling geminate and non-geminate pathways shows geminate processes are dominant at high carrier densities and early times. This combination of data and simulation provides a detailed picture of perovskite photophysics across multiple excitation regimes that was not previously available.« less

  4. Global Analysis of ATM Polymorphism Reveals Significant Functional Constraint

    PubMed Central

    Thorstenson, Yvonne R.; Shen, Peidong; Tusher, Virginia G.; Wayne, Tierney L.; Davis, Ronald W.; Chu, Gilbert; Oefner, Peter J.

    2001-01-01

    ATM, the gene that is mutated in ataxia-telangiectasia, is associated with cerebellar degeneration, abnormal proliferation of small blood vessels, and cancer. These clinically important manifestations have stimulated interest in defining the sequence variation in the ATM gene. Therefore, we undertook a comprehensive survey of sequence variation in ATM in diverse human populations. The protein-encoding exons of the gene (9,168 bp) and the adjacent intron and untranslated sequences (14,661 bp) were analyzed in 93 individuals from seven major human populations. In addition, the coding sequence was analyzed in one chimpanzee, one gorilla, one orangutan, and one Old World monkey. In human ATM, 88 variant sites were discovered by denaturing high-performance liquid chromatography, which is 96%–100% sensitive for detection of DNA sequence variation. ATM was compared to 14 other autosomal genes for nucleotide diversity. The noncoding regions of ATM had diversity values comparable to other genes, but the coding regions had very low diversity, especially in the last 29% of the protein sequence. A test of the neutral evolution hypothesis, through use of the Hudson/Kreitman/Aguadé statistic, revealed that this region of the human ATM gene was significantly constrained relative to that of the orangutan, the Old World monkey, and the mouse, but not relative to that of the chimpanzee or the gorilla. ATM displayed extensive linkage disequilibrium, consistent with suppression of meiotic recombination at this locus. Seven haplotypes were defined. Two haplotypes accounted for 82% of all chromosomes analyzed in all major populations; two others carrying the same D126E missense polymorphism accounted for 33% of chromosomes in Africa but were never observed outside of Africa. The high frequency of this polymorphism may be due either to a population expansion within Africa or to selective pressure. PMID:11443540

  5. Global RNA Half-Life Analysis in Escherichia coli Reveals Positional Patterns of Transcript Degradation

    PubMed Central

    Selinger, Douglas W.; Saxena, Rini Mukherjee; Cheung, Kevin J.; Church, George M.; Rosenow, Carsten

    2003-01-01

    Subgenic-resolution oligonucleotide microarrays were used to study global RNA degradation in wild-type Escherichia coli MG1655. RNA chemical half-lives were measured for 1036 open reading frames (ORFs) and for 329 known and predicted operons. The half-life of total mRNA was 6.8 min under the conditions tested. We also observed significant relationships between gene functional assignments and transcript stability. Unexpectedly, transcription of a single operon (tdcABCDEFG) was relatively rifampicin-insensitive and showed significant increases 2.5 min after rifampicin addition. This supports a novel mechanism of transcription for the tdc operon, whose promoter lacks any recognizable ς binding sites. Probe by probe analysis of all known and predicted operons showed that the 5′ ends of operons degrade, on average, more quickly than the rest of the transcript, with stability increasing in a 3′ direction, supporting and further generalizing the current model of a net 5′ to 3′ directionality of degradation. Hierarchical clustering analysis of operon degradation patterns revealed that this pattern predominates but is not exclusive. We found a weak but highly significant correlation between the degradation of adjacent operon regions, suggesting that stability is determined by a combination of local and operon-wide stability determinants. The 16 ORF dcw gene cluster, which has a complex promoter structure and a partially characterized degradation pattern, was studied at high resolution, allowing a detailed and integrated description of its abundance and degradation. We discuss the application of subgenic resolution DNA microarray analysis to study global mechanisms of RNA transcription and processing. PMID:12566399

  6. Global transcriptomic analysis of Cyanothece 51142 reveals robust diurnal oscillation of central metabolic processes.

    PubMed

    Stöckel, Jana; Welsh, Eric A; Liberton, Michelle; Kunnvakkam, Rangesh; Aurora, Rajeev; Pakrasi, Himadri B

    2008-04-22

    Cyanobacteria are photosynthetic organisms and are the only prokaryotes known to have a circadian lifestyle. Unicellular diazotrophic cyanobacteria such as Cyanothece sp. ATCC 51142 produce oxygen and can also fix atmospheric nitrogen, a process exquisitely sensitive to oxygen. To accommodate such antagonistic processes, the intracellular environment of Cyanothece oscillates between aerobic and anaerobic conditions during a day-night cycle. This is accomplished by temporal separation of the two processes: photosynthesis during the day and nitrogen fixation at night. Although previous studies have examined periodic changes in transcript levels for a limited number of genes in Cyanothece and other unicellular diazotrophic cyanobacteria, a comprehensive study of transcriptional activity in a nitrogen-fixing cyanobacterium is necessary to understand the impact of the temporal separation of photosynthesis and nitrogen fixation on global gene regulation and cellular metabolism. We have examined the expression patterns of nearly 5,000 genes in Cyanothece 51142 during two consecutive diurnal periods. Our analysis showed that approximately 30% of these genes exhibited robust oscillating expression profiles. Interestingly, this set included genes for almost all central metabolic processes in Cyanothece 51142. A transcriptional network of all genes with significantly oscillating transcript levels revealed that the majority of genes encoding enzymes in numerous individual biochemical pathways, such as glycolysis, oxidative pentose phosphate pathway, and glycogen metabolism, were coregulated and maximally expressed at distinct phases during the diurnal cycle. These studies provide a comprehensive picture of how a physiologically relevant diurnal light-dark cycle influences the metabolism in a photosynthetic bacterium.

  7. Quantitative analysis of proteome and lipidome dynamics reveals functional regulation of global lipid metabolism.

    PubMed

    Casanovas, Albert; Sprenger, Richard R; Tarasov, Kirill; Ruckerbauer, David E; Hannibal-Bach, Hans Kristian; Zanghellini, Jürgen; Jensen, Ole N; Ejsing, Christer S

    2015-03-19

    Elucidating how and to what extent lipid metabolism is remodeled under changing conditions is essential for understanding cellular physiology. Here, we analyzed proteome and lipidome dynamics to investigate how regulation of lipid metabolism at the global scale supports remodeling of cellular architecture and processes during physiological adaptations in yeast. Our results reveal that activation of cardiolipin synthesis and remodeling supports mitochondrial biogenesis in the transition from fermentative to respiratory metabolism, that down-regulation of de novo sterol synthesis machinery prompts differential turnover of lipid droplet-associated triacylglycerols and sterol esters during respiratory growth, that sphingolipid metabolism is regulated in a previously unrecognized growth stage-specific manner, and that endogenous synthesis of unsaturated fatty acids constitutes an in vivo upstream activator of peroxisomal biogenesis, via the heterodimeric Oaf1/Pip2 transcription factor. Our work demonstrates the pivotal role of lipid metabolism in adaptive processes and provides a resource to investigate its regulation at the cellular level.

  8. Risk analysis reveals global hotspots for marine debris ingestion by sea turtles.

    PubMed

    Schuyler, Qamar A; Wilcox, Chris; Townsend, Kathy A; Wedemeyer-Strombel, Kathryn R; Balazs, George; van Sebille, Erik; Hardesty, Britta Denise

    2016-02-01

    Plastic marine debris pollution is rapidly becoming one of the critical environmental concerns facing wildlife in the 21st century. Here we present a risk analysis for plastic ingestion by sea turtles on a global scale. We combined global marine plastic distributions based on ocean drifter data with sea turtle habitat maps to predict exposure levels to plastic pollution. Empirical data from necropsies of deceased animals were then utilised to assess the consequence of exposure to plastics. We modelled the risk (probability of debris ingestion) by incorporating exposure to debris and consequence of exposure, and included life history stage, species of sea turtle and date of stranding observation as possible additional explanatory factors. Life history stage is the best predictor of debris ingestion, but the best-fit model also incorporates encounter rates within a limited distance from stranding location, marine debris predictions specific to the date of the stranding study and turtle species. There is no difference in ingestion rates between stranded turtles vs. those caught as bycatch from fishing activity, suggesting that stranded animals are not a biased representation of debris ingestion rates in the background population. Oceanic life-stage sea turtles are at the highest risk of debris ingestion, and olive ridley turtles are the most at-risk species. The regions of highest risk to global sea turtle populations are off of the east coasts of the USA, Australia and South Africa; the east Indian Ocean, and Southeast Asia. Model results can be used to predict the number of sea turtles globally at risk of debris ingestion. Based on currently available data, initial calculations indicate that up to 52% of sea turtles may have ingested debris.

  9. Risk Analysis Reveals Global Hotspots for Marine Debris Ingestion by Sea Turtles

    NASA Astrophysics Data System (ADS)

    Schuyler, Q. A.; Wilcox, C.; Townsend, K.; Wedemeyer-Strombel, K.; Balazs, G.; van Sebille, E.; Hardesty, B. D.

    2016-02-01

    Plastic marine debris pollution is rapidly becoming one of the critical environmental concerns facing wildlife in the 21st century. Here we present a risk analysis for plastic ingestion by sea turtles on a global scale. We combined global marine plastic distributions based on ocean drifter data with sea turtle habitat maps to predict exposure levels to plastic pollution. Empirical data from necropsies of deceased animals were then utilised to assess the consequence of exposure to plastics. We modelled the risk (probability of debris ingestion) by incorporating exposure to debris and consequence of exposure, and included life history stage, species of sea turtle, and date of stranding observation as possible additional explanatory factors. Life history stage is the best predictor of debris ingestion, but the best-fit model also incorporates encounter rates within a limited distance from stranding location, marine debris predictions specific to the date of the stranding study, and turtle species. There was no difference in ingestion rates between stranded turtles vs. those caught as bycatch from fishing activity, suggesting that stranded animals are not a biased representation of debris ingestion rates in the background population. Oceanic life-stage sea turtles are at the highest risk of debris ingestion, and olive ridley turtles are the most at-risk species. The regions of highest risk to global sea turtle populations are off of the east coasts of the USA, Australia, and South Africa; the east Indian Ocean, and Southeast Asia. Model results can be used to predict the number of sea turtles globally at risk of debris ingestion. Based on currently available data, initial calculations indicate that up to 52% of sea turtles may have ingested debris.

  10. Global Analysis of Truncated RNA Ends Reveals New Insights into Ribosome Stalling in Plants[OPEN

    PubMed Central

    Lee, Wen‐Chi; Chou, Hsiao‐Chun; Chen, Ai‐Ping; Chou, Shu‐Jen

    2016-01-01

    High-throughput approaches for profiling the 5′ ends of RNA degradation intermediates on a genome-wide scale are frequently applied to analyze and validate cleavage sites guided by microRNAs (miRNAs). However, the complexity of the RNA degradome other than miRNA targets is currently largely uncharacterized, and this limits the application of RNA degradome studies. We conducted a global analysis of 5′-truncated mRNA ends that mapped to coding sequences (CDSs) of Arabidopsis thaliana, rice (Oryza sativa), and soybean (Glycine max). Based on this analysis, we provide multiple lines of evidence to show that the plant RNA degradome contains in vivo ribosome-protected mRNA fragments. We observed a 3-nucleotide periodicity in the position of free 5′ RNA ends and a bias toward the translational frame. By examining conserved peptide upstream open reading frames (uORFs) of Arabidopsis and rice, we found a predominance of 5′ termini of RNA degradation intermediates that were separated by a length equal to a ribosome-protected mRNA fragment. Through the analysis of RNA degradome data, we discovered uORFs and CDS regions potentially associated with stacked ribosomes in Arabidopsis. Furthermore, our analysis of RNA degradome data suggested that the binding of Arabidopsis ARGONAUTE7 to a noncleavable target site of miR390 might directly hinder ribosome movement. This work demonstrates an alternative use of RNA degradome data in the study of ribosome stalling. PMID:27742800

  11. Global meta-analysis reveals low consistency of biodiversity congruence relationships.

    PubMed

    Westgate, Martin J; Barton, Philip S; Lane, Peter W; Lindenmayer, David B

    2014-05-21

    Knowledge of the number and distribution of species is fundamental to biodiversity conservation efforts, but this information is lacking for the majority of species on earth. Consequently, subsets of taxa are often used as proxies for biodiversity; but this assumes that different taxa display congruent distribution patterns. Here we use a global meta-analysis to show that studies of cross-taxon congruence rarely give consistent results. Instead, species richness congruence is highest at extreme spatial scales and close to the equator, while congruence in species composition is highest at large extents and grain sizes. Studies display highest variance in cross-taxon congruence when conducted in areas with dissimilar areal extents (for species richness) or latitudes (for species composition). These results undermine the assumption that a subset of taxa can be representative of biodiversity. Therefore, researchers whose goal is to prioritize locations or actions for conservation should use data from a range of taxa.

  12. Global analysis of gene expression in pulmonary fibrosis reveals distinct programs regulating lung inflammation and fibrosis

    NASA Astrophysics Data System (ADS)

    Kaminski, Naftali; Allard, John D.; Pittet, Jean F.; Zuo, Fengrong; Griffiths, Mark J. D.; Morris, David; Huang, Xiaozhu; Sheppard, Dean; Heller, Renu A.

    2000-02-01

    The molecular mechanisms of pulmonary fibrosis are poorly understood. We have used oligonucleotide arrays to analyze the gene expression programs that underlie pulmonary fibrosis in response to bleomycin, a drug that causes lung inflammation and fibrosis, in two strains of susceptible mice (129 and C57BL/6). We then compared the gene expression patterns in these mice with 129 mice carrying a null mutation in the epithelial-restricted integrin 6 subunit (6/-), which develop inflammation but are protected from pulmonary fibrosis. Cluster analysis identified two distinct groups of genes involved in the inflammatory and fibrotic responses. Analysis of gene expression at multiple time points after bleomycin administration revealed sequential induction of subsets of genes that characterize each response. The availability of this comprehensive data set should accelerate the development of more effective strategies for intervention at the various stages in the development of fibrotic diseases of the lungs and other organs.

  13. Global analysis of SUMO chain function reveals multiple roles in chromatin regulation

    PubMed Central

    Srikumar, Tharan; Lewicki, Megan C.; Costanzo, Michael; Tkach, Johnny M.; van Bakel, Harm; Tsui, Kyle; Johnson, Erica S.; Brown, Grant W.; Andrews, Brenda J.; Boone, Charles; Giaever, Guri; Nislow, Corey

    2013-01-01

    Like ubiquitin, the small ubiquitin-related modifier (SUMO) proteins can form oligomeric “chains,” but the biological functions of these superstructures are not well understood. Here, we created mutant yeast strains unable to synthesize SUMO chains (smt3allR) and subjected them to high-content microscopic screening, synthetic genetic array (SGA) analysis, and high-density transcript profiling to perform the first global analysis of SUMO chain function. This comprehensive assessment identified 144 proteins with altered localization or intensity in smt3allR cells, 149 synthetic genetic interactions, and 225 mRNA transcripts (primarily consisting of stress- and nutrient-response genes) that displayed a >1.5-fold increase in expression levels. This information-rich resource strongly implicates SUMO chains in the regulation of chromatin. Indeed, using several different approaches, we demonstrate that SUMO chains are required for the maintenance of normal higher-order chromatin structure and transcriptional repression of environmental stress response genes in budding yeast. PMID:23547032

  14. Global analysis of SUMO chain function reveals multiple roles in chromatin regulation.

    PubMed

    Srikumar, Tharan; Lewicki, Megan C; Costanzo, Michael; Tkach, Johnny M; van Bakel, Harm; Tsui, Kyle; Johnson, Erica S; Brown, Grant W; Andrews, Brenda J; Boone, Charles; Giaever, Guri; Nislow, Corey; Raught, Brian

    2013-04-01

    Like ubiquitin, the small ubiquitin-related modifier (SUMO) proteins can form oligomeric "chains," but the biological functions of these superstructures are not well understood. Here, we created mutant yeast strains unable to synthesize SUMO chains (smt3(allR)) and subjected them to high-content microscopic screening, synthetic genetic array (SGA) analysis, and high-density transcript profiling to perform the first global analysis of SUMO chain function. This comprehensive assessment identified 144 proteins with altered localization or intensity in smt3(allR) cells, 149 synthetic genetic interactions, and 225 mRNA transcripts (primarily consisting of stress- and nutrient-response genes) that displayed a >1.5-fold increase in expression levels. This information-rich resource strongly implicates SUMO chains in the regulation of chromatin. Indeed, using several different approaches, we demonstrate that SUMO chains are required for the maintenance of normal higher-order chromatin structure and transcriptional repression of environmental stress response genes in budding yeast.

  15. Global transcriptomic analysis of Cyanothece 51142 reveals robust diurnal oscillation of central metabolic processes

    SciTech Connect

    Stockel, Jana; Welsh, Eric A.; Liberton, Michelle L.; Kunnavakkam, Rangesh V.; Aurora, Rajeev; Pakrasi, Himadri B.

    2008-04-22

    Cyanobacteria are oxygenic photosynthetic organisms, and the only prokaryotes known to have a circadian cycle. Unicellular diazotrophic cyanobacteria such as Cyanothece 51142 can fix atmospheric nitrogen, a process exquisitely sensitive to oxygen. Thus, the intracellular environment of Cyanothece oscillates between aerobic and anaerobic conditions during a day-night cycle. This is accomplished by temporal separation of two processes: photosynthesis during the day, and nitrogen fixation at night. While previous studies have examined periodic changes transcript levels for a limited number of genes in Cyanothece and other unicellular diazotrophic cyanobacteria, a comprehensive study of transcriptional activity in a nitrogen-fixing cyanobacterium is necessary to understand the impact of the temporal separation of photosynthesis and nitrogen fixation on global gene regulation and cellular metabolism. We have examined the expression patterns of nearly 5000 genes in Cyanothece 51142 during two consecutive diurnal periods. We found that ~30% of these genes exhibited robust oscillating expression profiles. Interestingly, this set included genes for almost all central metabolic processes in Cyanothece. A transcriptional network of all genes with significantly oscillating transcript levels revealed that the majority of genes in numerous individual pathways, such as glycolysis, pentose phosphate pathway and glycogen metabolism, were co-regulated and maximally expressed at distinct phases during the diurnal cycle. Our analyses suggest that the demands of nitrogen fixation greatly influence major metabolic activities inside Cyanothece cells and thus drive various cellular activities. These studies provide a comprehensive picture of how a physiologically relevant diurnal light-dark cycle influences the metabolism in a photosynthetic bacterium

  16. Global analysis of asymmetric RNA enrichment in oocytes reveals low conservation between closely related Xenopus species

    PubMed Central

    Claußen, Maike; Lingner, Thomas; Pommerenke, Claudia; Opitz, Lennart; Salinas, Gabriela; Pieler, Tomas

    2015-01-01

    RNAs that localize to the vegetal cortex during Xenopus laevis oogenesis have been reported to function in germ layer patterning, axis determination, and development of the primordial germ cells. Here we report on the genome-wide, comparative analysis of differentially localizing RNAs in Xenopus laevis and Xenopus tropicalis oocytes, revealing a surprisingly weak degree of conservation in respect to the identity of animally as well as vegetally enriched transcripts in these closely related species. Heterologous RNA injections and protein binding studies indicate that the different RNA localization patterns in these two species are due to gain/loss of cis-acting localization signals rather than to differences in the RNA-localizing machinery. PMID:26337391

  17. Phylum-specific environmental DNA analysis reveals remarkably high global biodiversity of Cercozoa (Protozoa).

    PubMed

    Bass, David; Cavalier-Smith, Thomas

    2004-11-01

    This study presents the first 18S rRNA multi-library environmental PCR survey of a single protozoan phylum, Cercozoa Cavalier-Smith 1998, from a range of different habitats. Phylogenetic analysis reveals at least nine novel clades within the phylum, several possibly at the level of order or above. Further experiments are described to ascertain the true ecological and geographical distributions of some clades that might be inferred from the tree to be restricted in either or both ways. These results suggest that the diversity of cercozoan taxa may run into thousands of lineages, making it comparable in diversity to the largest better-characterized protozoan phyla, e.g. Ciliophora (ciliates and suctorians) and Foraminifera. New sequences of cultured Spongomonas, Metromonas and Metopion are also presented. In the light of these additions, and the increased taxon sampling from the environmental libraries, some revisions of cercozoan classification are made: the transfer of Spongomonadea from Reticulofilosa to Monadofilosa; the removal of Metopiida from Sarcomonadea; and the creation of the new order Metromonadida, currently containing the single genus Metromonas. Although Metromonas groups with weak to moderate support with Chlorarachnea, it is here placed in superclass Monadofilosa, to which it is morphologically more similar.

  18. Global analysis of transcriptionally engaged yeast RNA polymerase III reveals extended tRNA transcripts

    PubMed Central

    Turowski, Tomasz W.; Leśniewska, Ewa; Delan-Forino, Clementine; Sayou, Camille; Boguta, Magdalena; Tollervey, David

    2016-01-01

    RNA polymerase III (RNAPIII) synthesizes a range of highly abundant small stable RNAs, principally pre-tRNAs. Here we report the genome-wide analysis of nascent transcripts attached to RNAPIII under permissive and restrictive growth conditions. This revealed strikingly uneven polymerase distributions across transcription units, generally with a predominant 5′ peak. This peak was higher for more heavily transcribed genes, suggesting that initiation site clearance is rate-limiting during RNAPIII transcription. Down-regulation of RNAPIII transcription under stress conditions was found to be uneven; a subset of tRNA genes showed low response to nutrient shift or loss of the major transcription regulator Maf1, suggesting potential “housekeeping” roles. Many tRNA genes were found to generate long, 3′-extended forms due to read-through of the canonical poly(U) terminators. The degree of read-through was anti-correlated with the density of U-residues in the nascent tRNA, and multiple, functional terminators can be located far downstream. The steady-state levels of 3′-extended pre-tRNA transcripts are low, apparently due to targeting by the nuclear surveillance machinery, especially the RNA binding protein Nab2, cofactors for the nuclear exosome, and the 5′-exonuclease Rat1. PMID:27206856

  19. Global Phospholipidomics Analysis Reveals Selective Pulmonary Peroxidation Profiles Upon Inhalation of Single Walled Carbon Nanotubes

    PubMed Central

    Tyurina, Yulia Y.; Kisin, Elena R.; Murray, Ashley; Tyurin, Vladimir A.; Kapralova, Valentina I.; Sparvero, Louis J.; Amoscato, Andrew A.; Samhan-Arias, Alejandro K.; Swedin, Linda; Lahesmaa, Riitta; Fadeel, Bengt; Shvedova, Anna A.; Kagan, Valerian E.

    2011-01-01

    It is commonly believed that nanomaterials cause non-specific oxidative damage. Our mass spectrometry-based oxidative lipidomics analysis of all major phospholipid classes revealed highly selective patterns of pulmonary peroxidation after inhalation exposure of mice to single-walled carbon nanotubes. No oxidized molecular species were found in two most abundant phospholipid classes – phosphatidylcholine and phosphatidylethanolamine. Peroxidation products were identified in three relatively minor classes of anionic phospholipids, cardiolipin, phosphatidylserine and phosphatidylinositol whereby oxygenation of polyunsaturated fatty acid residues also showed unusual substrate specificity. This non-random peroxidation coincided with the accumulation of apoptotic cells in the lung. A similar selective phospholipid peroxidation profile was detected upon incubation of a mixture of total lung lipids with H2O2/cytochrome c known to catalyze cardiolipin and phosphatidylserine peroxidation in apoptotic cells. The characterized specific phospholipid peroxidation signaling pathways indicate new approaches to the development of mitochondria targeted regulators of cardiolipin peroxidation to protect against deleterious effects of pro-apoptotic effects of single-walled carbon nanotubes in the lung. PMID:21800898

  20. Global transcriptional analysis reveals surface remodeling of Anaplasma marginale in the tick vector

    PubMed Central

    2014-01-01

    Background Pathogens dependent upon vectors for transmission to new hosts undergo environment specific changes in gene transcription dependent on whether they are replicating in the vector or the mammalian host. Differential gene transcription, especially of potential vaccine candidates, is of interest in Anaplasma marginale, the tick-borne causative agent of bovine anaplasmosis. Methods RNA-seq technology allowed a comprehensive analysis of the transcriptional status of A. marginale genes in two conditions: bovine host blood and tick derived cell culture, a model for the tick vector. Quantitative PCR was used to assess transcription of a set of genes in A. marginale infected tick midguts and salivary glands at two time points during the transmission cycle. Results Genes belonging to fourteen pathways or component groups were found to be differentially transcribed in A. marginale in the bovine host versus the tick vector. One of the most significantly altered groups was composed of surface proteins. Of the 56 genes included in the surface protein group, eight were up regulated and 26 were down regulated. The down regulated surface protein encoding genes include several that are well studied due to their immunogenicity and function. Quantitative PCR of a set of genes demonstrated that transcription in tick cell culture most closely approximates transcription in salivary glands of recently infected ticks. Conclusions The ISE6 tick cell culture line is an acceptable model for early infection in tick salivary glands, and reveals disproportionate down regulation of surface protein genes in the tick. Transcriptional profiling in other cell lines may help us simulate additional microenvironments. Understanding vector-specific alteration of gene transcription, especially of surface protein encoding genes, may aid in the development of vaccines or transmission blocking therapies. PMID:24751137

  1. Global Transcriptome Analysis Reveals That Poly(ADP-Ribose) Polymerase 1 Regulates Gene Expression through EZH2.

    PubMed

    Martin, Kayla A; Cesaroni, Matteo; Denny, Michael F; Lupey, Lena N; Tempera, Italo

    2015-12-01

    Posttranslational modifications, such as poly(ADP-ribosyl)ation (PARylation), regulate chromatin-modifying enzymes, ultimately affecting gene expression. This study explores the role of poly(ADP-ribose) polymerase (PARP) on global gene expression in a lymphoblastoid B cell line. We found that inhibition of PARP catalytic activity with olaparib resulted in global gene deregulation, affecting approximately 11% of the genes expressed. Gene ontology analysis revealed that PARP could exert these effects through transcription factors and chromatin-remodeling enzymes, including the polycomb repressive complex 2 (PRC2) member EZH2. EZH2 mediates the trimethylation of histone H3 at lysine 27 (H3K27me3), a modification associated with chromatin compaction and gene silencing. Both pharmacological inhibition of PARP and knockdown of PARP1 induced the expression of EZH2, which resulted in increased global H3K27me3. Chromatin immunoprecipitation confirmed that PARP1 inhibition led to H3K27me3 deposition at EZH2 target genes, which resulted in gene silencing. Moreover, increased EZH2 expression is attributed to the loss of the occupancy of the transcription repressor E2F4 at the EZH2 promoter following PARP inhibition. Together, these data show that PARP plays an important role in global gene regulation and identifies for the first time a direct role of PARP1 in regulating the expression and function of EZH2. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  2. Global Phosphoproteomic Analysis Reveals the Involvement of Phosphorylation in Aflatoxins Biosynthesis in the Pathogenic Fungus Aspergillus flavus

    PubMed Central

    Ren, Silin; Yang, Mingkun; Li, Yu; Zhang, Feng; Chen, Zhuo; Zhang, Jia; Yang, Guang; Yue, Yuewei; Li, Siting; Ge, Feng; Wang, Shihua

    2016-01-01

    Aspergillus flavus is a pathogenic fungus that produces toxic and carcinogenic aflatoxins and is the causative agent of aflatoxicosis. A growing body of evidence indicates that reversible phosphorylation plays important roles in regulating diverse functions in this pathogen. However, only a few phosphoproteins of this fungus have been identified, which hampers our understanding of the roles of phosphorylation in A. flavus. So we performed a global and site-specific phosphoproteomic analysis of A. flavus. A total of 598 high-confidence phosphorylation sites were identified in 283 phosphoproteins. The identified phosphoproteins were involved in various biological processes, including signal transduction and aflatoxins biosynthesis. Five identified phosphoproteins associated with MAPK signal transduction and aflatoxins biosynthesis were validated by immunoblotting using phospho-specific antibodies. Further functional studies revealed that phosphorylation of the MAP kinase kinase kinase Ste11 affected aflatoxins biosynthesis in A. flavus. Our data represent the results of the first global survey of protein phosphorylation in A. flavus and reveal previously unappreciated roles for phosphorylation in the regulation of aflatoxins production. The generated dataset can serve as an important resource for the functional analysis of protein phosphorylation in A. flavus and facilitate the elucidation of phosphorylated signaling networks in this pathogen. PMID:27667718

  3. Global meta-analysis reveals no net change in local-scale plant biodiversity over time

    PubMed Central

    Vellend, Mark; Baeten, Lander; Myers-Smith, Isla H.; Elmendorf, Sarah C.; Beauséjour, Robin; Brown, Carissa D.; De Frenne, Pieter; Verheyen, Kris; Wipf, Sonja

    2013-01-01

    Global biodiversity is in decline. This is of concern for aesthetic and ethical reasons, but possibly also for practical reasons, as suggested by experimental studies, mostly with plants, showing that biodiversity reductions in small study plots can lead to compromised ecosystem function. However, inferring that ecosystem functions will decline due to biodiversity loss in the real world rests on the untested assumption that such loss is actually occurring at these small scales in nature. Using a global database of 168 published studies and >16,000 nonexperimental, local-scale vegetation plots, we show that mean temporal change in species diversity over periods of 5–261 y is not different from zero, with increases at least as likely as declines over time. Sites influenced primarily by plant species’ invasions showed a tendency for declines in species richness, whereas sites undergoing postdisturbance succession showed increases in richness over time. Other distinctions among studies had little influence on temporal richness trends. Although maximizing diversity is likely important for maintaining ecosystem function in intensely managed systems such as restored grasslands or tree plantations, the clear lack of any general tendency for plant biodiversity to decline at small scales in nature directly contradicts the key assumption linking experimental results to ecosystem function as a motivation for biodiversity conservation in nature. How often real world changes in the diversity and composition of plant communities at the local scale cause ecosystem function to deteriorate, or actually to improve, remains unknown and is in critical need of further study. PMID:24167259

  4. Global meta-analysis reveals no net change in local-scale plant biodiversity over time.

    PubMed

    Vellend, Mark; Baeten, Lander; Myers-Smith, Isla H; Elmendorf, Sarah C; Beauséjour, Robin; Brown, Carissa D; De Frenne, Pieter; Verheyen, Kris; Wipf, Sonja

    2013-11-26

    Global biodiversity is in decline. This is of concern for aesthetic and ethical reasons, but possibly also for practical reasons, as suggested by experimental studies, mostly with plants, showing that biodiversity reductions in small study plots can lead to compromised ecosystem function. However, inferring that ecosystem functions will decline due to biodiversity loss in the real world rests on the untested assumption that such loss is actually occurring at these small scales in nature. Using a global database of 168 published studies and >16,000 nonexperimental, local-scale vegetation plots, we show that mean temporal change in species diversity over periods of 5-261 y is not different from zero, with increases at least as likely as declines over time. Sites influenced primarily by plant species' invasions showed a tendency for declines in species richness, whereas sites undergoing postdisturbance succession showed increases in richness over time. Other distinctions among studies had little influence on temporal richness trends. Although maximizing diversity is likely important for maintaining ecosystem function in intensely managed systems such as restored grasslands or tree plantations, the clear lack of any general tendency for plant biodiversity to decline at small scales in nature directly contradicts the key assumption linking experimental results to ecosystem function as a motivation for biodiversity conservation in nature. How often real world changes in the diversity and composition of plant communities at the local scale cause ecosystem function to deteriorate, or actually to improve, remains unknown and is in critical need of further study.

  5. HGDP and HapMap Analysis by Ancestry Mapper Reveals Local and Global Population Relationships

    PubMed Central

    Magalhães, Tiago R.; Casey, Jillian P.; Conroy, Judith; Regan, Regina; Fitzpatrick, Darren J.; Shah, Naisha; Sobral, João; Ennis, Sean

    2012-01-01

    Knowledge of human origins, migrations, and expansions is greatly enhanced by the availability of large datasets of genetic information from different populations and by the development of bioinformatic tools used to analyze the data. We present Ancestry Mapper, which we believe improves on existing methods, for the assignment of genetic ancestry to an individual and to study the relationships between local and global populations. The principle function of the method, named Ancestry Mapper, is to give each individual analyzed a genetic identifier, made up of just 51 genetic coordinates, that corresponds to its relationship to the HGDP reference population. As a consequence, the Ancestry Mapper Id (AMid) has intrinsic biological meaning and provides a tool to measure similarity between world populations. We applied Ancestry Mapper to a dataset comprised of the HGDP and HapMap data. The results show distinctions at the continental level, while simultaneously giving details at the population level. We clustered AMids of HGDP/HapMap and observe a recapitulation of human migrations: for a small number of clusters, individuals are grouped according to continental origins; for a larger number of clusters, regional and population distinctions are evident. Calculating distances between AMids allows us to infer ancestry. The number of coordinates is expandable, increasing the power of Ancestry Mapper. An R package called Ancestry Mapper is available to apply this method to any high density genomic data set. PMID:23189146

  6. HGDP and HapMap analysis by Ancestry Mapper reveals local and global population relationships.

    PubMed

    Magalhães, Tiago R; Casey, Jillian P; Conroy, Judith; Regan, Regina; Fitzpatrick, Darren J; Shah, Naisha; Sobral, João; Ennis, Sean

    2012-01-01

    Knowledge of human origins, migrations, and expansions is greatly enhanced by the availability of large datasets of genetic information from different populations and by the development of bioinformatic tools used to analyze the data. We present Ancestry Mapper, which we believe improves on existing methods, for the assignment of genetic ancestry to an individual and to study the relationships between local and global populations. The principle function of the method, named Ancestry Mapper, is to give each individual analyzed a genetic identifier, made up of just 51 genetic coordinates, that corresponds to its relationship to the HGDP reference population. As a consequence, the Ancestry Mapper Id (AMid) has intrinsic biological meaning and provides a tool to measure similarity between world populations. We applied Ancestry Mapper to a dataset comprised of the HGDP and HapMap data. The results show distinctions at the continental level, while simultaneously giving details at the population level. We clustered AMids of HGDP/HapMap and observe a recapitulation of human migrations: for a small number of clusters, individuals are grouped according to continental origins; for a larger number of clusters, regional and population distinctions are evident. Calculating distances between AMids allows us to infer ancestry. The number of coordinates is expandable, increasing the power of Ancestry Mapper. An R package called Ancestry Mapper is available to apply this method to any high density genomic data set.

  7. Global analysis of the glycoproteome in Saccharomyces cerevisiae reveals new roles for protein glycosylation in eukaryotes

    PubMed Central

    Kung, Li A; Tao, Sheng-Ce; Qian, Jiang; Smith, Michael G; Snyder, Michael; Zhu, Heng

    2009-01-01

    To further understand the roles of protein glycosylation in eukaryotes, we globally identified glycan-containing proteins in yeast. A fluorescent lectin binding assay was developed and used to screen protein microarrays containing over 5000 proteins purified from yeast. A total of 534 yeast proteins were identified that bound either Concanavalin A (ConA) or Wheat-Germ Agglutinin (WGA); 406 of them were novel. Among the novel glycoproteins, 45 were validated by mobility shift upon treatment with EndoH and PNGase F, thereby extending the number of validated yeast glycoproteins to 350. In addition to many components of the secretory pathway, we identified other types of proteins, such as transcription factors and mitochondrial proteins. To further explore the role of glycosylation in mitochondrial function, the localization of four mitochondrial proteins was examined in the presence and absence of tunicamycin, an inhibitor of N-linked protein glycosylation. For two proteins, localization to the mitochondria is diminished upon tunicamycin treatment, indicating that protein glycosylation is important for protein function. Overall, our studies greatly extend our understanding of protein glycosylation in eukaryotes through the cataloguing of glycoproteins, and describe a novel role for protein glycosylation in mitochondrial protein function and localization. PMID:19756047

  8. Quantitative proteomic analysis reveals a simple strategy of global resource allocation in bacteria.

    PubMed

    Hui, Sheng; Silverman, Josh M; Chen, Stephen S; Erickson, David W; Basan, Markus; Wang, Jilong; Hwa, Terence; Williamson, James R

    2015-02-12

    A central aim of cell biology was to understand the strategy of gene expression in response to the environment. Here, we study gene expression response to metabolic challenges in exponentially growing Escherichia coli using mass spectrometry. Despite enormous complexity in the details of the underlying regulatory network, we find that the proteome partitions into several coarse-grained sectors, with each sector's total mass abundance exhibiting positive or negative linear relations with the growth rate. The growth rate-dependent components of the proteome fractions comprise about half of the proteome by mass, and their mutual dependencies can be characterized by a simple flux model involving only two effective parameters. The success and apparent generality of this model arises from tight coordination between proteome partition and metabolism, suggesting a principle for resource allocation in proteome economy of the cell. This strategy of global gene regulation should serve as a basis for future studies on gene expression and constructing synthetic biological circuits. Coarse graining may be an effective approach to derive predictive phenomenological models for other 'omics' studies.

  9. Quantitative proteomic analysis reveals a simple strategy of global resource allocation in bacteria

    PubMed Central

    Hui, Sheng; Silverman, Josh M; Chen, Stephen S; Erickson, David W; Basan, Markus; Wang, Jilong; Hwa, Terence; Williamson, James R

    2015-01-01

    A central aim of cell biology was to understand the strategy of gene expression in response to the environment. Here, we study gene expression response to metabolic challenges in exponentially growing Escherichia coli using mass spectrometry. Despite enormous complexity in the details of the underlying regulatory network, we find that the proteome partitions into several coarse-grained sectors, with each sector's total mass abundance exhibiting positive or negative linear relations with the growth rate. The growth rate-dependent components of the proteome fractions comprise about half of the proteome by mass, and their mutual dependencies can be characterized by a simple flux model involving only two effective parameters. The success and apparent generality of this model arises from tight coordination between proteome partition and metabolism, suggesting a principle for resource allocation in proteome economy of the cell. This strategy of global gene regulation should serve as a basis for future studies on gene expression and constructing synthetic biological circuits. Coarse graining may be an effective approach to derive predictive phenomenological models for other ‘omics’ studies. PMID:25678603

  10. A global analysis of bird plumage patterns reveals no association between habitat and camouflage.

    PubMed

    Somveille, Marius; Marshall, Kate L A; Gluckman, Thanh-Lan

    2016-01-01

    Evidence suggests that animal patterns (motifs) function in camouflage. Irregular mottled patterns can facilitate concealment when stationary in cluttered habitats, whereas regular patterns typically prevent capture during movement in open habitats. Bird plumage patterns have predominantly converged on just four types-mottled (irregular), scales, bars and spots (regular)-and habitat could be driving convergent evolution in avian patterning. Based on sensory ecology, we therefore predict that irregular patterns would be associated with visually noisy closed habitats and that regular patterns would be associated with open habitats. Regular patterns have also been shown to function in communication for sexually competing males to stand-out and attract females, so we predict that male breeding plumage patterns evolved in both open and closed habitats. Here, taking phylogenetic relatedness into account, we investigate ecological selection for bird plumage patterns across the class Aves. We surveyed plumage patterns in 80% of all avian species worldwide. Of these, 2,756 bird species have regular and irregular plumage patterns as well as habitat information. In this subset, we tested whether adult breeding/non-breeding plumages in each sex, and juvenile plumages, were associated with the habitat types found within the species' geographical distributions. We found no evidence for an association between habitat and plumage patterns across the world's birds and little phylogenetic signal. We also found that species with regular and irregular plumage patterns were distributed randomly across the world's eco-regions without being affected by habitat type. These results indicate that at the global spatial and taxonomic scale, habitat does not predict convergent evolution in bird plumage patterns, contrary to the camouflage hypothesis.

  11. A global analysis of bird plumage patterns reveals no association between habitat and camouflage

    PubMed Central

    Marshall, Kate L.A.; Gluckman, Thanh-Lan

    2016-01-01

    Evidence suggests that animal patterns (motifs) function in camouflage. Irregular mottled patterns can facilitate concealment when stationary in cluttered habitats, whereas regular patterns typically prevent capture during movement in open habitats. Bird plumage patterns have predominantly converged on just four types—mottled (irregular), scales, bars and spots (regular)—and habitat could be driving convergent evolution in avian patterning. Based on sensory ecology, we therefore predict that irregular patterns would be associated with visually noisy closed habitats and that regular patterns would be associated with open habitats. Regular patterns have also been shown to function in communication for sexually competing males to stand-out and attract females, so we predict that male breeding plumage patterns evolved in both open and closed habitats. Here, taking phylogenetic relatedness into account, we investigate ecological selection for bird plumage patterns across the class Aves. We surveyed plumage patterns in 80% of all avian species worldwide. Of these, 2,756 bird species have regular and irregular plumage patterns as well as habitat information. In this subset, we tested whether adult breeding/non-breeding plumages in each sex, and juvenile plumages, were associated with the habitat types found within the species’ geographical distributions. We found no evidence for an association between habitat and plumage patterns across the world’s birds and little phylogenetic signal. We also found that species with regular and irregular plumage patterns were distributed randomly across the world’s eco-regions without being affected by habitat type. These results indicate that at the global spatial and taxonomic scale, habitat does not predict convergent evolution in bird plumage patterns, contrary to the camouflage hypothesis. PMID:27867762

  12. Global genome splicing analysis reveals an increased number of alternatively spliced genes with aging.

    PubMed

    Rodríguez, Sofía A; Grochová, Diana; McKenna, Tomás; Borate, Bhavesh; Trivedi, Niraj S; Erdos, Michael R; Eriksson, Maria

    2016-04-01

    Alternative splicing (AS) is a key regulatory mechanism for the development of different tissues; however, not much is known about changes to alternative splicing during aging. Splicing events may become more frequent and widespread genome-wide as tissues age and the splicing machinery stringency decreases. Using skin, skeletal muscle, bone, thymus, and white adipose tissue from wild-type C57BL6/J male mice (4 and 18 months old), we examined the effect of age on splicing by AS analysis of the differential exon usage of the genome. The results identified a considerable number of AS genes in skeletal muscle, thymus, bone, and white adipose tissue between the different age groups (ranging from 27 to 246 AS genes corresponding to 0.3-3.2% of the total number of genes analyzed). For skin, skeletal muscle, and bone, we included a later age group (28 months old) that showed that the number of alternatively spliced genes increased with age in all three tissues (P < 0.01). Analysis of alternatively spliced genes across all tissues by gene ontology and pathway analysis identified 158 genes involved in RNA processing. Additional analysis of AS in a mouse model for the premature aging disease Hutchinson-Gilford progeria syndrome was performed. The results show that expression of the mutant protein, progerin, is associated with an impaired developmental splicing. As progerin accumulates, the number of genes with AS increases compared to in wild-type skin. Our results indicate the existence of a mechanism for increased AS during aging in several tissues, emphasizing that AS has a more important role in the aging process than previously known.

  13. Global Dynamics of the Advanced Light Source Revealed through Experimental Frequency Map Analysis

    NASA Astrophysics Data System (ADS)

    Robin, D.; Steier, C.; Laskar, J.; Nadolski, L.

    2000-07-01

    Frequency map analysis was first used for the dynamical study of numerical simulations of physical systems (solar system, galaxies, particle accelerators). Here it is applied directly to the experimental results obtained at the Advanced Light Source. For the first time, the network of coupling resonances is clearly visible in an experiment, in a similar way as in the numerical simulation. Excellent agreement between numerical and experimental results leads us to propose this technique as a tool for improving numerical models and actual behavior of particle accelerators. Moreover, it provides a model-independent diagnostic for the evaluation of the dynamical properties of the beam.

  14. Global analysis of fission yeast mating genes reveals new autophagy factors.

    PubMed

    Sun, Ling-Ling; Li, Ming; Suo, Fang; Liu, Xiao-Man; Shen, En-Zhi; Yang, Bing; Dong, Meng-Qiu; He, Wan-Zhong; Du, Li-Lin

    2013-01-01

    Macroautophagy (autophagy) is crucial for cell survival during starvation and plays important roles in animal development and human diseases. Molecular understanding of autophagy has mainly come from the budding yeast Saccharomyces cerevisiae, and it remains unclear to what extent the mechanisms are the same in other organisms. Here, through screening the mating phenotype of a genome-wide deletion collection of the fission yeast Schizosaccharomyces pombe, we obtained a comprehensive catalog of autophagy genes in this highly tractable organism, including genes encoding three heretofore unidentified core Atg proteins, Atg10, Atg14, and Atg16, and two novel factors, Ctl1 and Fsc1. We systematically examined the subcellular localization of fission yeast autophagy factors for the first time and characterized the phenotypes of their mutants, thereby uncovering both similarities and differences between the two yeasts. Unlike budding yeast, all three Atg18/WIPI proteins in fission yeast are essential for autophagy, and we found that they play different roles, with Atg18a uniquely required for the targeting of the Atg12-Atg5·Atg16 complex. Our investigation of the two novel factors revealed unforeseen autophagy mechanisms. The choline transporter-like protein Ctl1 interacts with Atg9 and is required for autophagosome formation. The fasciclin domain protein Fsc1 localizes to the vacuole membrane and is required for autophagosome-vacuole fusion but not other vacuolar fusion events. Our study sheds new light on the evolutionary diversity of the autophagy machinery and establishes the fission yeast as a useful model for dissecting the mechanisms of autophagy.

  15. Global Analysis of Fission Yeast Mating Genes Reveals New Autophagy Factors

    PubMed Central

    Sun, Ling-Ling; Shen, En-Zhi; Yang, Bing; Dong, Meng-Qiu; He, Wan-Zhong; Du, Li-Lin

    2013-01-01

    Macroautophagy (autophagy) is crucial for cell survival during starvation and plays important roles in animal development and human diseases. Molecular understanding of autophagy has mainly come from the budding yeast Saccharomyces cerevisiae, and it remains unclear to what extent the mechanisms are the same in other organisms. Here, through screening the mating phenotype of a genome-wide deletion collection of the fission yeast Schizosaccharomyces pombe, we obtained a comprehensive catalog of autophagy genes in this highly tractable organism, including genes encoding three heretofore unidentified core Atg proteins, Atg10, Atg14, and Atg16, and two novel factors, Ctl1 and Fsc1. We systematically examined the subcellular localization of fission yeast autophagy factors for the first time and characterized the phenotypes of their mutants, thereby uncovering both similarities and differences between the two yeasts. Unlike budding yeast, all three Atg18/WIPI proteins in fission yeast are essential for autophagy, and we found that they play different roles, with Atg18a uniquely required for the targeting of the Atg12–Atg5·Atg16 complex. Our investigation of the two novel factors revealed unforeseen autophagy mechanisms. The choline transporter-like protein Ctl1 interacts with Atg9 and is required for autophagosome formation. The fasciclin domain protein Fsc1 localizes to the vacuole membrane and is required for autophagosome-vacuole fusion but not other vacuolar fusion events. Our study sheds new light on the evolutionary diversity of the autophagy machinery and establishes the fission yeast as a useful model for dissecting the mechanisms of autophagy. PMID:23950735

  16. Global Analysis of CPEBs Reveals Sequential and Non-Redundant Functions in Mitotic Cell Cycle

    PubMed Central

    Giangarrà, Valeria; Igea, Ana; Castellazzi, Chiara Lara; Bava, Felice-Alessio; Mendez, Raul

    2015-01-01

    CPEB (Cytoplasmic Polyadenylation Element Binding) proteins are a family of four RNA-binding proteins that regulate the translation of maternal mRNAs controlling meiotic cell cycle progression. But CPEBs are not limited to the transcriptionally silent germline; they are also expressed, in various combinations, in somatic cells, yet their role in regulation of mitosis-related gene expression is largely unknown. Deregulation of CPEB1 and CPEB4 have been linked to tumor development. However, a systematic analysis addressing their requirements for the temporal regulation of mitotic gene expression has yet to be performed. This study addresses the requirements of each of the four CPEBs for mitotic phase transitions, with a particular focus on cytoplasmic polyadenylation and translational regulation. We demonstrate that CPEB3 is the only member dispensable for mitotic cell division, whereas the other three members, CPEB1, 2, and 4, are essential to successful mitotic cell division. Thus, CPEB1 is required for prophase entry, CPEB2 for metaphase and CPEB4 for cytokinesis. These three CPEBs have sequential non-redundant functions that promote the phase-specific polyadenylation and translational activation of CPE-regulated transcripts in the mitotic cell cycle. PMID:26398195

  17. Neonatal Salivary Analysis Reveals Global Developmental Gene Expression Changes in the Premature Infant

    PubMed Central

    Maron, Jill L.; Johnson, Kirby L.; Rocke, David M.; Cohen, Michael G.; Liley, Albert J.; Bianchi, Diana W.

    2010-01-01

    Background: There is an important need to develop noninvasive biomarkers to detect disease in premature neonates. Our objective was to determine if salivary genomic analysis provides novel information about neonatal developmental gene expression. Methods: Saliva (50-200 μL) was prospectively collected from five premature infants at five time points: before, starting, and advancing enteral nutrition, at introduction of oral feeds, and at advanced oral feeds. Salivary RNA was extracted, amplified, and hybridized onto whole genomic microarrays. Results: Bioinformatic analyses identified 9,286 gene transcripts that showed statistically significant gene expression changes across subjects over time. Of these, 3,522 (37.9%) genes were down-regulated and 5,764 (62.1%) genes were up-regulated. Gene expression changes were highly associated with developmental pathways. Statistically significantly down-regulated expression was seen in embryonic development, connective tissue development and function, hematological system development and function, and survival of the organism (10−14 < p <10−3). Conversely, genes associated with behavior, nervous system development, tissue development, organ development, and digestive system development were statistically significantly up-regulated (10−11 < p < 10−2). Discussion: Comparative genomic salivary analyses provide robust, comprehensive, real-time information regarding nearly all organs and tissues in the developing preterm infant. This innovative and noninvasive technique represents a new approach for monitoring health, disease, and development in this vulnerable patient population. By comparing these data in healthy infants to those who develop medical complications, we expect to identify new biomarkers that will ultimately improve newborn care. PMID:19959617

  18. Global Phylogeography with Mixed-Marker Analysis Reveals Male-Mediated Dispersal in the Endangered Scalloped Hammerhead Shark (Sphyrna lewini)

    PubMed Central

    Daly-Engel, Toby S.; Seraphin, Kanesa D.; Holland, Kim N.; Coffey, John P.; Nance, Holly A.; Toonen, Robert J.; Bowen, Brian W.

    2012-01-01

    Background The scalloped hammerhead shark, Sphyrna lewini, is a large endangered predator with a circumglobal distribution, observed in the open ocean but linked ontogenetically to coastal embayments for parturition and juvenile development. A previous survey of maternal (mtDNA) markers demonstrated strong genetic partitioning overall (global ΦST = 0.749) and significant population separations across oceans and between discontinuous continental coastlines. Methodology/Principal Findings We surveyed the same global range with increased sample coverage (N = 403) and 13 microsatellite loci to assess the male contribution to dispersal and population structure. Biparentally inherited microsatellites reveal low or absent genetic structure across ocean basins and global genetic differentiation (FST = 0.035) over an order of magnitude lower than the corresponding measures for maternal mtDNA lineages (ΦST = 0.749). Nuclear allelic richness and heterozygosity are high throughout the Indo-Pacific, while genetic structure is low. In contrast, allelic diversity is low while population structure is higher for populations at the ends of the range in the West Atlantic and East Pacific. Conclusions/Significance These data are consistent with the proposed Indo-Pacific center of origin for S. lewini, and indicate that females are philopatric or adhere to coastal habitats while males facilitate gene flow across oceanic expanses. This study includes the largest sampling effort and the most molecular loci ever used to survey the complete range of a large oceanic predator, and findings emphasize the importance of incorporating mixed-marker analysis into stock assessments of threatened and endangered shark species. PMID:22253848

  19. Global phylogeography with mixed-marker analysis reveals male-mediated dispersal in the endangered scalloped hammerhead shark (Sphyrna lewini).

    PubMed

    Daly-Engel, Toby S; Seraphin, Kanesa D; Holland, Kim N; Coffey, John P; Nance, Holly A; Toonen, Robert J; Bowen, Brian W

    2012-01-01

    The scalloped hammerhead shark, Sphyrna lewini, is a large endangered predator with a circumglobal distribution, observed in the open ocean but linked ontogenetically to coastal embayments for parturition and juvenile development. A previous survey of maternal (mtDNA) markers demonstrated strong genetic partitioning overall (global Φ(ST) = 0.749) and significant population separations across oceans and between discontinuous continental coastlines. We surveyed the same global range with increased sample coverage (N = 403) and 13 microsatellite loci to assess the male contribution to dispersal and population structure. Biparentally inherited microsatellites reveal low or absent genetic structure across ocean basins and global genetic differentiation (F(ST) = 0.035) over an order of magnitude lower than the corresponding measures for maternal mtDNA lineages (Φ(ST) = 0.749). Nuclear allelic richness and heterozygosity are high throughout the Indo-Pacific, while genetic structure is low. In contrast, allelic diversity is low while population structure is higher for populations at the ends of the range in the West Atlantic and East Pacific. These data are consistent with the proposed Indo-Pacific center of origin for S. lewini, and indicate that females are philopatric or adhere to coastal habitats while males facilitate gene flow across oceanic expanses. This study includes the largest sampling effort and the most molecular loci ever used to survey the complete range of a large oceanic predator, and findings emphasize the importance of incorporating mixed-marker analysis into stock assessments of threatened and endangered shark species.

  20. Global proteomic analysis of Chelidonium majus and Corydalis cava (Papaveraceae) extracts revealed similar defense-related protein compositions.

    PubMed

    Nawrot, Robert; Zauber, Henrik; Schulze, Waltraud X

    2014-04-01

    Chelidonium majus and Corydalis cava are phylogenetically closely related (Papaveraceae family). The medicinal and pharmaceutical interest in these plants is based on their synthesis of pharmaceutically important compounds, such as alkaloids, flavonoids, phenolic acids and proteins. C. majus shoot and C. cava tuber extracts have been used in traditional folk medicine to treat many diseases, such as fungal, bacterial and viral infections, liver disorders, fever, post-traumatic, colic, abdominal and menstrual pains and even cancer. This study attempts to perform a global comparative proteomic analysis of pharmacologically important extracts from these two closely related unsequenced plant species to gain insights into the protein basis of these plant organs and to compare their common and specific proteomic compositions. We used a shotgun proteomic approach combined with label-free protein quantitation according to the exponentially modified protein abundance index (emPAI). In total, a mean number of 228 protein identification results were recorded in C. cava tuber extracts and about 1240 in C. majus shoot extracts. Comparative analysis revealed a similar stress and defense-related protein composition of pharmacologically active plant species and showed the presence of different pathogenesis-related and low molecular inducible antimicrobial peptides. These findings could form the basis for further elucidation of the mechanism of the strong pharmacological activities of these medicinal plant extracts. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. Global aspects of pacC regulation of pathogenicity genes in Colletotrichum gloeosporioides as revealed by transcriptome analysis.

    PubMed

    Alkan, Noam; Meng, Xiangchun; Friedlander, Gilgi; Reuveni, Eli; Sukno, Serenella; Sherman, Amir; Thon, Michael; Fluhr, Robert; Prusky, Dov

    2013-11-01

    Colletotrichum gloeosporioides alkalinizes its surroundings during colonization of host tissue. The transcription factor pacC is a regulator of pH-controlled genes and is essential for successful colonization. We present here the sequence assembly of the Colletotrichum fruit pathogen and use it to explore the global regulation of pathogenicity by ambient pH. The assembled genome size was 54 Mb, encoding 18,456 genes. Transcriptomes of the wild type and ΔpacC mutant were established by RNA-seq and explored for their global pH-dependent gene regulation. The analysis showed that pacC upregulates 478 genes and downregulates 483 genes, comprising 5% of the fungal genome, including transporters, antioxidants, and cell-wall-degrading enzymes. Interestingly, gene families with similar functionality are both up- and downregulated by pacC. Global analysis of secreted genes showed significant pacC activation of degradative enzymes at alkaline pH and during fruit infection. Select genes from alkalizing-type pathogen C. gloeosporioides and from acidifying-type pathogen Sclerotinia sclerotiorum were verified by quantitative reverse-transcription polymerase chain reaction analysis at different pH values. Knock out of several pacC-activated genes confirmed their involvement in pathogenic colonization of alkalinized surroundings. The results suggest a global regulation by pacC of key pathogenicity genes during pH change in alkalinizing and acidifying pathogens.

  2. Global Transcriptional Analysis Reveals Unique and Shared Responses in Arabidopsis thaliana Exposed to Combined Drought and Pathogen Stress

    PubMed Central

    Gupta, Aarti; Sarkar, Ananda K.; Senthil-Kumar, Muthappa

    2016-01-01

    With frequent fluctuations in global climate, plants are exposed to co-occurring drought and pathogen infection and this combination adversely affects plant survival. In the past, some studies indicated that morpho-physiological responses of plants to the combined stress are different from the individual stressed plants. However, interaction of drought stressed plants with pathogen has not been widely studied at molecular level. Such studies are important to understand the defense pathways that operate as part of combined stress tolerance mechanism. In this study, Arabidopsis thaliana was exposed to individual drought stress, Pseudomonas syringae pv tomato DC3000 (Pst DC3000) infection and their combination. Using Affymetrix WT gene 1.0 ST array, global transcriptome profiling of leaves under individual drought stress and pathogen infection was compared with their combination. The results obtained from pathway mapping (KAAS and MAPMAN) demonstrated the modulation in defense pathways in A. thaliana under drought and host pathogen Pst DC3000 infection. Further, our study revealed “tailored” responses under combined stress and the time of occurrence of each stress during their concurrence has shown differences in transcriptome profile. Our results from microarray and RT-qPCR revealed regulation of 20 novel genes uniquely during the stress interaction. This study indicates that plants exposed to concurrent drought and pathogen stress experience a new state of stress. Thus, under frequently changing climatic conditions, time of occurrence of each stress in the interaction defines the plant responses and should thus be studied explicitly. PMID:27252712

  3. Analysis of global gene expression in Brachypodium distachyon reveals extensive network plasticity in response to abiotic stress.

    PubMed

    Priest, Henry D; Fox, Samuel E; Rowley, Erik R; Murray, Jessica R; Michael, Todd P; Mockler, Todd C

    2014-01-01

    Brachypodium distachyon is a close relative of many important cereal crops. Abiotic stress tolerance has a significant impact on productivity of agriculturally important food and feedstock crops. Analysis of the transcriptome of Brachypodium after chilling, high-salinity, drought, and heat stresses revealed diverse differential expression of many transcripts. Weighted Gene Co-Expression Network Analysis revealed 22 distinct gene modules with specific profiles of expression under each stress. Promoter analysis implicated short DNA sequences directly upstream of module members in the regulation of 21 of 22 modules. Functional analysis of module members revealed enrichment in functional terms for 10 of 22 network modules. Analysis of condition-specific correlations between differentially expressed gene pairs revealed extensive plasticity in the expression relationships of gene pairs. Photosynthesis, cell cycle, and cell wall expression modules were down-regulated by all abiotic stresses. Modules which were up-regulated by each abiotic stress fell into diverse and unique gene ontology GO categories. This study provides genomics resources and improves our understanding of abiotic stress responses of Brachypodium.

  4. Comparative transcriptome analysis reveals a global insight into molecular processes regulating citrate accumulation in sweet orange (Citrus sinensis).

    PubMed

    Lu, Xiaopeng; Cao, Xiongjun; Li, Feifei; Li, Jing; Xiong, Jiang; Long, Guiyou; Cao, Shangyin; Xie, Shenxi

    2016-12-01

    Citrate, the predominant organic acid in citrus, determines the taste of these fruits. However, little is known about the synergic molecular processes regulating citrate accumulation. Using 'Dahongtiancheng' (Citrus sinensis) and 'Bingtangcheng' (C. sinensis) with significant difference in citrate, the objectives of this study were to understand the global mechanisms of high-citrate accumulation in sweet orange. 'Dahongtiancheng' and 'Bingtangcheng' exhibit significantly different patterns in citrate accumulation throughout fruit development, with the largest differences observed at 50-70 days after full bloom (DAFB). Comparative transcriptome profiling was performed for the endocarps of both cultivars at 50 and 70 DAFB. Over 34.5 million clean reads per library were successfully mapped to the reference database and 670-2630 differentially expressed genes (DEGs) were found in four libraries. Among the genes, five transcription factors were ascertained to be the candidates regulating citrate accumulation. Functional assignments of the DEGs indicated that photosynthesis, the citrate cycle and amino acid metabolism were significantly altered in 'Dahongtiancheng'. Physiological and molecular analyses suggested that high photosynthetic efficiency and partial impairment of citrate catabolism were crucial for the high-citrate trait, and amino acid biosynthesis was one of the important directions for citrate flux. The results reveal a global insight into the gene expression changes in a high-citrate compared with a low-citrate sweet orange. High accumulating efficiency and impaired degradation of citrate may be associated with the high-citrate trait of 'Dahongtiancheng'. Findings in this study increase understanding of the molecular processes regulating citrate accumulation in sweet orange. © 2016 Scandinavian Plant Physiology Society.

  5. Revealing global regulatory perturbations across human cancers

    PubMed Central

    Goodarzi, Hani; Elemento, Olivier; Tavazoie, Saeed

    2010-01-01

    Summary The discovery of pathways and regulatory networks whose perturbation contributes to neoplastic transformation remains a fundamental challenge for cancer biology. We show that such pathway perturbations, and the cis-regulatory elements through which they operate, can be efficiently extracted from global gene-expression profiles. Our approach utilizes information-theoretic analysis of expression levels, pathways, and genomic sequences. Analysis across a diverse set of human cancers reveals the majority of previously known cancer pathways. Through de novo motif discovery we associate these pathways with transcription-factor binding sites and miRNA targets, including those of E2F, NF-Y, p53, and let-7. Follow-up experiments confirmed that these predictions correspond to functional in vivo regulatory interactions. Strikingly, the majority of the perturbations, associated with putative cis-regulatory elements, fall outside of known cancer pathways. Our study provides a systems-level dissection of regulatory perturbations in cancer—an essential component of a rational strategy for therapeutic intervention and drug-target discovery. PMID:20005852

  6. Are Proteins Just Coiled Cords? Local and Global Analysis of Contact Maps Reveals the Backbone-Dependent Nature of Proteins.

    PubMed

    Santoni, Daniele; Paci, Paola; Di Paola, Luisa; Giuliani, Alessandro

    2016-01-01

    In this work, we present an extensive analysis of protein contact network topology applied to a wide data set. We extended the concept of degree distribution to graphlets, describing local connectivity patterns. We compared results to those derived from artificial networks of the same size (number of nodes), reproducing the average degree of each protein network. The artificial networks resemble the coiling of immaterial cords and we tried to understand if they could catch the protein structure topology upon the sole constraint of backbone (cord). We found a surprisingly similar pattern for local topological descriptors (graphlets distribution) while real proteins and cords differ at large extent in the global topological invariant average shortest path that presumably catches the systemic nature of protein and the non negligible encumbrance of backbone (residues steric hindrance). We demonstrated average shortest path to link polymer length and physical size of the molecule, and its minimization plays the role of `target function` of folding process.

  7. Systems-level analysis of age-related macular degeneration reveals global biomarkers and phenotype-specific functional networks

    PubMed Central

    2012-01-01

    Background Age-related macular degeneration (AMD) is a leading cause of blindness that affects the central region of the retinal pigmented epithelium (RPE), choroid, and neural retina. Initially characterized by an accumulation of sub-RPE deposits, AMD leads to progressive retinal degeneration, and in advanced cases, irreversible vision loss. Although genetic analysis, animal models, and cell culture systems have yielded important insights into AMD, the molecular pathways underlying AMD's onset and progression remain poorly delineated. We sought to better understand the molecular underpinnings of this devastating disease by performing the first comparative transcriptome analysis of AMD and normal human donor eyes. Methods RPE-choroid and retina tissue samples were obtained from a common cohort of 31 normal, 26 AMD, and 11 potential pre-AMD human donor eyes. Transcriptome profiles were generated for macular and extramacular regions, and statistical and bioinformatic methods were employed to identify disease-associated gene signatures and functionally enriched protein association networks. Selected genes of high significance were validated using an independent donor cohort. Results We identified over 50 annotated genes enriched in cell-mediated immune responses that are globally over-expressed in RPE-choroid AMD phenotypes. Using a machine learning model and a second donor cohort, we show that the top 20 global genes are predictive of AMD clinical diagnosis. We also discovered functionally enriched gene sets in the RPE-choroid that delineate the advanced AMD phenotypes, neovascular AMD and geographic atrophy. Moreover, we identified a graded increase of transcript levels in the retina related to wound response, complement cascade, and neurogenesis that strongly correlates with decreased levels of phototransduction transcripts and increased AMD severity. Based on our findings, we assembled protein-protein interactomes that highlight functional networks likely to be

  8. Promoter analysis reveals globally differential regulation of human long non-coding RNA and protein-coding genes

    SciTech Connect

    Alam, Tanvir; Medvedeva, Yulia A.; Jia, Hui; Brown, James B.; Lipovich, Leonard; Bajic, Vladimir B.; Mantovani, Roberto

    2014-10-02

    Transcriptional regulation of protein-coding genes is increasingly well-understood on a global scale, yet no comparable information exists for long non-coding RNA (lncRNA) genes, which were recently recognized to be as numerous as protein-coding genes in mammalian genomes. We performed a genome-wide comparative analysis of the promoters of human lncRNA and protein-coding genes, finding global differences in specific genetic and epigenetic features relevant to transcriptional regulation. These two groups of genes are hence subject to separate transcriptional regulatory programs, including distinct transcription factor (TF) proteins that significantly favor lncRNA, rather than coding-gene, promoters. We report a specific signature of promoter-proximal transcriptional regulation of lncRNA genes, including several distinct transcription factor binding sites (TFBS). Experimental DNase I hypersensitive site profiles are consistent with active configurations of these lncRNA TFBS sets in diverse human cell types. TFBS ChIP-seq datasets confirm the binding events that we predicted using computational approaches for a subset of factors. For several TFs known to be directly regulated by lncRNAs, we find that their putative TFBSs are enriched at lncRNA promoters, suggesting that the TFs and the lncRNAs may participate in a bidirectional feedback loop regulatory network. Accordingly, cells may be able to modulate lncRNA expression levels independently of mRNA levels via distinct regulatory pathways. Our results also raise the possibility that, given the historical reliance on protein-coding gene catalogs to define the chromatin states of active promoters, a revision of these chromatin signature profiles to incorporate expressed lncRNA genes is warranted in the future.

  9. Promoter analysis reveals globally differential regulation of human long non-coding RNA and protein-coding genes

    DOE PAGES

    Alam, Tanvir; Medvedeva, Yulia A.; Jia, Hui; ...

    2014-10-02

    Transcriptional regulation of protein-coding genes is increasingly well-understood on a global scale, yet no comparable information exists for long non-coding RNA (lncRNA) genes, which were recently recognized to be as numerous as protein-coding genes in mammalian genomes. We performed a genome-wide comparative analysis of the promoters of human lncRNA and protein-coding genes, finding global differences in specific genetic and epigenetic features relevant to transcriptional regulation. These two groups of genes are hence subject to separate transcriptional regulatory programs, including distinct transcription factor (TF) proteins that significantly favor lncRNA, rather than coding-gene, promoters. We report a specific signature of promoter-proximal transcriptionalmore » regulation of lncRNA genes, including several distinct transcription factor binding sites (TFBS). Experimental DNase I hypersensitive site profiles are consistent with active configurations of these lncRNA TFBS sets in diverse human cell types. TFBS ChIP-seq datasets confirm the binding events that we predicted using computational approaches for a subset of factors. For several TFs known to be directly regulated by lncRNAs, we find that their putative TFBSs are enriched at lncRNA promoters, suggesting that the TFs and the lncRNAs may participate in a bidirectional feedback loop regulatory network. Accordingly, cells may be able to modulate lncRNA expression levels independently of mRNA levels via distinct regulatory pathways. Our results also raise the possibility that, given the historical reliance on protein-coding gene catalogs to define the chromatin states of active promoters, a revision of these chromatin signature profiles to incorporate expressed lncRNA genes is warranted in the future.« less

  10. Promoter analysis reveals globally differential regulation of human long non-coding RNA and protein-coding genes.

    PubMed

    Alam, Tanvir; Medvedeva, Yulia A; Jia, Hui; Brown, James B; Lipovich, Leonard; Bajic, Vladimir B

    2014-01-01

    Transcriptional regulation of protein-coding genes is increasingly well-understood on a global scale, yet no comparable information exists for long non-coding RNA (lncRNA) genes, which were recently recognized to be as numerous as protein-coding genes in mammalian genomes. We performed a genome-wide comparative analysis of the promoters of human lncRNA and protein-coding genes, finding global differences in specific genetic and epigenetic features relevant to transcriptional regulation. These two groups of genes are hence subject to separate transcriptional regulatory programs, including distinct transcription factor (TF) proteins that significantly favor lncRNA, rather than coding-gene, promoters. We report a specific signature of promoter-proximal transcriptional regulation of lncRNA genes, including several distinct transcription factor binding sites (TFBS). Experimental DNase I hypersensitive site profiles are consistent with active configurations of these lncRNA TFBS sets in diverse human cell types. TFBS ChIP-seq datasets confirm the binding events that we predicted using computational approaches for a subset of factors. For several TFs known to be directly regulated by lncRNAs, we find that their putative TFBSs are enriched at lncRNA promoters, suggesting that the TFs and the lncRNAs may participate in a bidirectional feedback loop regulatory network. Accordingly, cells may be able to modulate lncRNA expression levels independently of mRNA levels via distinct regulatory pathways. Our results also raise the possibility that, given the historical reliance on protein-coding gene catalogs to define the chromatin states of active promoters, a revision of these chromatin signature profiles to incorporate expressed lncRNA genes is warranted in the future.

  11. Global analysis of the root hair morphogenesis transcriptome reveals new candidate genes involved in root hair formation in barley.

    PubMed

    Kwasniewski, Miroslaw; Janiak, Agnieszka; Mueller-Roeber, Bernd; Szarejko, Iwona

    2010-09-01

    Root hairs are long tubular outgrowths of specialized root epidermal cells that play an important role in plant nutrition and water uptake. They are also an important model in studies of higher plant cell differentiation. In contrast to the model dicot Arabidopsis thaliana, currently very little is known about the genetic and molecular basis of root hair formation in monocots, including major cereals. To elucidate candidate genes controlling this developmental process in barley, we took advantage of the recently established Affymetrix GeneChip Barley1 Genome Array to carry out global transcriptome analyses of hairless and root hair primordia-forming roots of two barely mutant lines. Expression profiling of the root-hairless mutant rhl1.a and its wild type parent variety 'Karat' revealed 10 genes potentially involved in the early step of root hair formation in barley. Differential expression of all identified genes was confirmed by quantitative reverse transcription-polymerase chain reaction. The genes identified encode proteins associated with the cell wall and membranes, including one gene for xyloglucan endotransglycosylase, three for peroxidase enzymes and five for arabinogalactan protein, extensin, leucine-rich-repeat protein, phosphatidylinositol phosphatidylcholine transfer protein and a RhoGTPase GDP dissociation inhibitor, respectively. The molecular function of one gene is unknown at present. The expression levels of these genes were strongly reduced in roots of the root-hairless mutant rhl1.a compared to the parent variety, while expression of all 10 genes was similar in another mutant, i.e. rhp1.b, that has lost its ability to develop full root hairs but still forms hairs blocked at the primordium stage, and its wild type relative. This clearly indicates that the new genes identified are involved in the initiation of root hair morphogenesis in barley. Copyright 2010 Elsevier GmbH. All rights reserved.

  12. Rules of RNA specificity of hnRNP A1 revealed by global and quantitative analysis of its affinity distribution

    PubMed Central

    Jain, Niyati; Lin, Hsuan-Chun; Morgan, Christopher E.; Harris, Michael E.; Tolbert, Blanton S.

    2017-01-01

    Heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) is a multipurpose RNA-binding protein (RBP) involved in normal and pathological RNA metabolism. Transcriptome-wide mapping and in vitro evolution identify consensus hnRNP A1 binding motifs; however, such data do not reveal how surrounding RNA sequence and structural context modulate affinity. We determined the affinity of hnRNP A1 for all possible sequence variants (n = 16,384) of the HIV exon splicing silencer 3 (ESS3) 7-nt apical loop. Analysis of the affinity distribution identifies the optimal motif 5′-YAG-3′ and shows how its copy number, position in the loop, and loop structure modulate affinity. For a subset of ESS3 variants, we show that specificity is determined by association rate constants and that variants lacking the minimal sequence motif bind competitively with consensus RNA. Thus, the results reveal general rules of specificity of hnRNP A1 and provide a quantitative framework for understanding how it discriminates between alternative competing RNA ligands in vivo. PMID:28193894

  13. Rules of RNA specificity of hnRNP A1 revealed by global and quantitative analysis of its affinity distribution.

    PubMed

    Jain, Niyati; Lin, Hsuan-Chun; Morgan, Christopher E; Harris, Michael E; Tolbert, Blanton S

    2017-02-28

    Heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) is a multipurpose RNA-binding protein (RBP) involved in normal and pathological RNA metabolism. Transcriptome-wide mapping and in vitro evolution identify consensus hnRNP A1 binding motifs; however, such data do not reveal how surrounding RNA sequence and structural context modulate affinity. We determined the affinity of hnRNP A1 for all possible sequence variants (n = 16,384) of the HIV exon splicing silencer 3 (ESS3) 7-nt apical loop. Analysis of the affinity distribution identifies the optimal motif 5'-YAG-3' and shows how its copy number, position in the loop, and loop structure modulate affinity. For a subset of ESS3 variants, we show that specificity is determined by association rate constants and that variants lacking the minimal sequence motif bind competitively with consensus RNA. Thus, the results reveal general rules of specificity of hnRNP A1 and provide a quantitative framework for understanding how it discriminates between alternative competing RNA ligands in vivo.

  14. Global analysis of the sugarcane microtranscriptome reveals a unique composition of small RNAs associated with axillary bud outgrowth

    PubMed Central

    Ortiz-Morea, Fausto A.; Vicentini, Renato; Silva, Geraldo F.F.; Silva, Eder M.; Carrer, Helaine; Rodrigues, Ana P.; Nogueira, Fabio T.S.

    2013-01-01

    Axillary bud outgrowth determines shoot architecture and is under the control of endogenous hormones and a fine-tuned gene-expression network, which probably includes small RNAs (sRNAs). Although it is well known that sRNAs act broadly in plant development, our understanding about their roles in vegetative bud outgrowth remains limited. Moreover, the expression profiles of microRNAs (miRNAs) and their targets within axillary buds are largely unknown. Here, we employed sRNA next-generation sequencing as well as computational and gene-expression analysis to identify and quantify sRNAs and their targets in vegetative axillary buds of the biofuel crop sugarcane (Saccharum spp.). Computational analysis allowed the identification of 26 conserved miRNA families and two putative novel miRNAs, as well as a number of trans-acting small interfering RNAs. sRNAs associated with transposable elements and protein-encoding genes were similarly represented in both inactive and developing bud libraries. Conversely, sequencing and quantitative reverse transcription-PCR results revealed that specific miRNAs were differentially expressed in developing buds, and some correlated negatively with the expression of their targets at specific stages of axillary bud development. For instance, the expression patterns of miR159 and its target GAMYB suggested that they may play roles in regulating abscisic acid-signalling pathways during sugarcane bud outgrowth. Our work reveals, for the first time, differences in the composition and expression profiles of diverse sRNAs and targets between inactive and developing vegetative buds that, together with the endogenous balance of specific hormones, may be important in regulating axillary bud outgrowth. PMID:23564956

  15. Global fit analysis of glucose binding curves reveals a minimal model for kinetic cooperativity in human glucokinase.

    PubMed

    Larion, Mioara; Miller, Brian G

    2010-10-19

    Human pancreatic glucokinase is a monomeric enzyme that displays kinetic cooperativity, a feature that facilitates enzyme-mediated regulation of blood glucose levels in the body. Two theoretical models have been proposed to describe the non-Michaelis-Menten behavior of human glucokinase. The mnemonic mechanism postulates the existence of one thermodynamically favored enzyme conformation in the absence of glucose, whereas the ligand-induced slow transition model (LIST) requires a preexisting equilibrium between two enzyme species that interconvert with a rate constant slower than turnover. To investigate whether either of these mechanisms is sufficient to describe glucokinase cooperativity, a transient-state kinetic analysis of glucose binding to the enzyme was undertaken. A complex, time-dependent change in enzyme intrinsic fluorescence was observed upon exposure to glucose, which is best described by an analytical solution comprised of the sum of four exponential terms. Transient-state glucose binding experiments conducted in the presence of increasing glycerol concentrations demonstrate that three of the observed rate constants decrease with increasing viscosity. Global fit analyses of experimental glucose binding curves are consistent with a kinetic model that is an extension of the LIST mechanism with a total of four glucose-bound binary complexes. The kinetic model presented herein suggests that glucokinase samples multiple conformations in the absence of ligand and that this conformational heterogeneity persists even after the enzyme associates with glucose.

  16. Energy transfer pathways in light-harvesting complexes of purple bacteria as revealed by global kinetic analysis of two-dimensional transient spectra.

    PubMed

    Ostroumov, Evgeny E; Mulvaney, Rachel M; Anna, Jessica M; Cogdell, Richard J; Scholes, Gregory D

    2013-09-26

    Excited state dynamics in LH2 complexes of two purple bacterial species were studied by broad-band two-dimensional electronic spectroscopy. The optical response was measured in the 500-600 nm spectral region on the 0-400 fs time scale. Global target analysis of two-dimensional (2D) transient spectra revealed the main energy transfer pathways between carotenoid S2, 1Bu(-) and S1 states and bacteriochlorophyll Qx state. Global analysis ascertained the evolutionary and vibration-associated spectra, which also indicated the presence of a higher-lying vibrational level in the carotenoid S1 state. The estimation of the spectral overlap between the 1Bu(-) state and the Qx state indicated a significant contribution of the 1Bu(-) state to the overall S2-to-Qx excitation energy transfer.

  17. Global geno-proteomic analysis reveals cross-continental sequence conservation and druggable sites among influenza virus polymerases.

    PubMed

    Babar, Mustafeez Mujtaba; Zaidi, Najam-us-Sahar Sadaf; Tahir, Muhammad

    2014-12-01

    Influenza virus is one of the major causes of mortality and morbidity associated with respiratory diseases. The high rate of mutation in the viral proteome provides it with the ability to survive in a variety of host species. This property helps it in maintaining and developing its pathogenicity, transmission and drug resistance. Alternate drug targets, particularly the internal proteins, can potentially be exploited for addressing the resistance issues. In the current analysis, the degree of conservation of influenza virus polymerases has been studied as one of the essential elements for establishing its candidature as a potential target of antiviral therapy. We analyzed more than 130,000 nucleotide and amino acid sequences by classifying them on the basis of continental presence of host organisms. Computational analyses including genetic polymorphism study, mutation pattern determination, molecular evolution and geophylogenetic analysis were performed to establish the high degree of conservation among the sequences. These studies lead to establishing the polymerases, in particular PB1, as highly conserved proteins. Moreover, we mapped the conservation percentage on the tertiary structures of proteins to identify the conserved, druggable sites. The research study, hence, revealed that the influenza virus polymerases are highly conserved (95-99%) proteins with a very slow mutation rate. Potential drug binding sites on various polymerases have also been reported. A scheme for drug target candidate development that can be employed to rapidly mutating proteins has been presented. Moreover, the research output can help in designing new therapeutic molecules against the identified targets.

  18. A global transcriptional analysis of Megalobrama amblycephala revealing the molecular determinants of diet-induced hepatic steatosis.

    PubMed

    Zhang, Dingdong; Lu, Kangle; Jiang, Guangzhen; Liu, Wenbin; Dong, Zaijie; Tian, Hongyan; Li, Xiangfei

    2015-10-10

    Blunt snout bream (Megalobrama amblycephala), a prevalent species in China's intensive polyculture systems, is highly susceptible to hepatic steatosis, resulting in considerable losses to the fish farming industry. Due to a lack of genomic resources, the molecular mechanisms of lipid metabolism in M. amblycephala are poorly understood. Here, a hepatic cDNA library was generated from equal amounts of mRNAs isolated from M. amblycephala fed normal-fat and high-fat diets. Sequencing of this library using the Illumina/Solexa platform produced approximately 51.87 million clean reads, which were assembled into 48,439 unigenes with an average length of 596 bp and an N50 value of 800 bp. These unigenes were searched against the nucleotide (NT), non-redundant (NR), Swiss-Prot, Cluster of Orthologous Groups (COG), and Kyoto Encyclopedia of Genes and Genome (KEGG) databases using the BLASTn or BLASTx algorithms (E-value ≤ 10(-5)). A total of 8602 unigenes and 22,155 unigenes were functionally classified into 25 COG categories and 259 KEGG pathways, respectively. Furthermore, 22,072 unigenes were grouped into 62 sub-categories belonging to three main Gene Ontology (GO) terms. Using a digital gene expression analysis and the M. amblycephala transcriptome as a reference, 477 genes (134 up-regulated and 343 down-regulated) were identified as differentially expressed in fish fed a high-fat diet versus a normal-fat diet. KEGG and GO functional enrichment analyses of the differentially expressed unigenes were performed and 12 candidate genes related to lipid metabolism were identified. This study provides a global survey of hepatic transcriptome profiles and identifies candidate genes that may be related to lipid metabolism in M. amblycephala. These findings will facilitate further investigations of the mechanisms underlying hepatic steatosis in M. amblycephala.

  19. Global Gene Expression and Focused Knockout Analysis Reveals Genes Associated with Fungal Fruiting Body Development in Neurospora crassa

    PubMed Central

    Wang, Zheng; Lopez-Giraldez, Francesc; Lehr, Nina; Farré, Marta; Common, Ralph; Trail, Frances

    2014-01-01

    Fungi can serve as highly tractable models for understanding genetic basis of sexual development in multicellular organisms. Applying a reverse-genetic approach to advance such a model, we used random and multitargeted primers to assay gene expression across perithecial development in Neurospora crassa. We found that functionally unclassified proteins accounted for most upregulated genes, whereas downregulated genes were enriched for diverse functions. Moreover, genes associated with developmental traits exhibited stage-specific peaks of expression. Expression increased significantly across sexual development for mating type gene mat a-1 and for mat A-1 specific pheromone precursor ccg-4. In addition, expression of a gene encoding a protein similar to zinc finger, stc1, was highly upregulated early in perithecial development, and a strain with a knockout of this gene exhibited arrest at the same developmental stage. A similar expression pattern was observed for genes in RNA silencing and signaling pathways, and strains with knockouts of these genes were also arrested at stages of perithecial development that paralleled their peak in expression. The observed stage specificity allowed us to correlate expression upregulation and developmental progression and to identify regulators of sexual development. Bayesian networks inferred from our expression data revealed previously known and new putative interactions between RNA silencing genes and pathways. Overall, our analysis provides a fine-scale transcriptomic landscape and novel inferences regarding the control of the multistage development process of sexual crossing and fruiting body development in N. crassa. PMID:24243796

  20. Global Gene Expression Analysis Reveals Crosstalk between Response Mechanisms to Cold and Drought Stresses in Cassava Seedlings.

    PubMed

    Li, Shuxia; Yu, Xiang; Cheng, Zhihao; Yu, Xiaoling; Ruan, Mengbin; Li, Wenbin; Peng, Ming

    2017-01-01

    Abiotic stress negatively impacts cassava (Manihot esculenta) growth and yield. Several molecular mechanisms of plant response to cold and drought have been identified and described in the literature, however, little is known about the crosstalk of the responses of cassava to these two stresses. To elucidate this question, transcriptome analysis of cassava seedlings under cold or PEG-simulated drought stress treatment was performed. Our results showed that 6103 and 7462 transcripts were significantly regulated by cold and drought stress, respectively. Gene Ontology annotation revealed that the abscisic and jasmonic acid signaling pathways shared between the two stresses responses. We further identified 2434 common differentially expressed genes (DEGs), including 1130 up-regulated and 841 down-regulated DEGs by the two stresses. These co-induced or co-suppressed genes are grouped as stress signal perception and transduction, transcription factors (TFs), metabolism as well as transport facilitation according to the function annotation. Furthermore, a large proportion of well characterized protein kinases, TF families and ubiquitin proteasome system related genes, such as RLKs, MAPKs, AP2/ERFBPs, WRKYs, MYBs, E2 enzymes and E3 ligases, including three complexes of interacting proteins were shown as key points of crosstalk between cold and drought stress signaling transduction pathways in a hierarchical manner. Our research provides valuable information and new insights for genetically improving the tolerance of crops to multiple abiotic stresses.

  1. Global Gene Expression Analysis Reveals Crosstalk between Response Mechanisms to Cold and Drought Stresses in Cassava Seedlings

    PubMed Central

    Li, Shuxia; Yu, Xiang; Cheng, Zhihao; Yu, Xiaoling; Ruan, Mengbin; Li, Wenbin; Peng, Ming

    2017-01-01

    Abiotic stress negatively impacts cassava (Manihot esculenta) growth and yield. Several molecular mechanisms of plant response to cold and drought have been identified and described in the literature, however, little is known about the crosstalk of the responses of cassava to these two stresses. To elucidate this question, transcriptome analysis of cassava seedlings under cold or PEG-simulated drought stress treatment was performed. Our results showed that 6103 and 7462 transcripts were significantly regulated by cold and drought stress, respectively. Gene Ontology annotation revealed that the abscisic and jasmonic acid signaling pathways shared between the two stresses responses. We further identified 2434 common differentially expressed genes (DEGs), including 1130 up-regulated and 841 down-regulated DEGs by the two stresses. These co-induced or co-suppressed genes are grouped as stress signal perception and transduction, transcription factors (TFs), metabolism as well as transport facilitation according to the function annotation. Furthermore, a large proportion of well characterized protein kinases, TF families and ubiquitin proteasome system related genes, such as RLKs, MAPKs, AP2/ERFBPs, WRKYs, MYBs, E2 enzymes and E3 ligases, including three complexes of interacting proteins were shown as key points of crosstalk between cold and drought stress signaling transduction pathways in a hierarchical manner. Our research provides valuable information and new insights for genetically improving the tolerance of crops to multiple abiotic stresses. PMID:28769962

  2. Global mRNA decay analysis at single nucleotide resolution reveals segmental and positional degradation patterns in a Gram-positive bacterium

    PubMed Central

    2012-01-01

    Background Recent years have shown a marked increase in the use of next-generation sequencing technologies for quantification of gene expression (RNA sequencing, RNA-Seq). The expression level of a gene is a function of both its rate of transcription and RNA decay, and the influence of mRNA decay rates on gene expression in genome-wide studies of Gram-positive bacteria is under-investigated. Results In this work, we employed RNA-Seq in a genome-wide determination of mRNA half-lives in the Gram-positive bacterium Bacillus cereus. By utilizing a newly developed normalization protocol, RNA-Seq was used successfully to determine global mRNA decay rates at the single nucleotide level. The analysis revealed positional degradation patterns, with mRNAs being degraded from both ends of the molecule, indicating that both 5' to 3' and 3' to 5' directions of RNA decay are present in B. cereus. Other operons showed segmental degradation patterns where specific ORFs within polycistrons were degraded at variable rates, underlining the importance of RNA processing in gene regulation. We determined the half-lives for more than 2,700 ORFs in B. cereus ATCC 10987, ranging from less than one minute to more than fifteen minutes, and showed that mRNA decay rate correlates globally with mRNA expression level, GC content, and functional class of the ORF. Conclusions To our knowledge, this study presents the first global analysis of mRNA decay in a bacterium at single nucleotide resolution. We provide a proof of principle for using RNA-Seq in bacterial mRNA decay analysis, revealing RNA processing patterns at the single nucleotide level. PMID:22537947

  3. A global analysis of the impacts of urbanization on bird and plant diversity reveals key anthropogenic drivers.

    PubMed

    Aronson, Myla F J; La Sorte, Frank A; Nilon, Charles H; Katti, Madhusudan; Goddard, Mark A; Lepczyk, Christopher A; Warren, Paige S; Williams, Nicholas S G; Cilliers, Sarel; Clarkson, Bruce; Dobbs, Cynnamon; Dolan, Rebecca; Hedblom, Marcus; Klotz, Stefan; Kooijmans, Jip Louwe; Kühn, Ingolf; Macgregor-Fors, Ian; McDonnell, Mark; Mörtberg, Ulla; Pysek, Petr; Siebert, Stefan; Sushinsky, Jessica; Werner, Peter; Winter, Marten

    2014-04-07

    Urbanization contributes to the loss of the world's biodiversity and the homogenization of its biota. However, comparative studies of urban biodiversity leading to robust generalities of the status and drivers of biodiversity in cities at the global scale are lacking. Here, we compiled the largest global dataset to date of two diverse taxa in cities: birds (54 cities) and plants (110 cities). We found that the majority of urban bird and plant species are native in the world's cities. Few plants and birds are cosmopolitan, the most common being Columba livia and Poa annua. The density of bird and plant species (the number of species per km(2)) has declined substantially: only 8% of native bird and 25% of native plant species are currently present compared with estimates of non-urban density of species. The current density of species in cities and the loss in density of species was best explained by anthropogenic features (landcover, city age) rather than by non-anthropogenic factors (geography, climate, topography). As urbanization continues to expand, efforts directed towards the conservation of intact vegetation within urban landscapes could support higher concentrations of both bird and plant species. Despite declines in the density of species, cities still retain endemic native species, thus providing opportunities for regional and global biodiversity conservation, restoration and education.

  4. A global analysis of the impacts of urbanization on bird and plant diversity reveals key anthropogenic drivers

    PubMed Central

    Aronson, Myla F. J.; La Sorte, Frank A.; Nilon, Charles H.; Katti, Madhusudan; Goddard, Mark A.; Lepczyk, Christopher A.; Warren, Paige S.; Williams, Nicholas S. G.; Cilliers, Sarel; Clarkson, Bruce; Dobbs, Cynnamon; Dolan, Rebecca; Hedblom, Marcus; Klotz, Stefan; Kooijmans, Jip Louwe; Kühn, Ingolf; MacGregor-Fors, Ian; McDonnell, Mark; Mörtberg, Ulla; Pyšek, Petr; Siebert, Stefan; Sushinsky, Jessica; Werner, Peter; Winter, Marten

    2014-01-01

    Urbanization contributes to the loss of the world's biodiversity and the homogenization of its biota. However, comparative studies of urban biodiversity leading to robust generalities of the status and drivers of biodiversity in cities at the global scale are lacking. Here, we compiled the largest global dataset to date of two diverse taxa in cities: birds (54 cities) and plants (110 cities). We found that the majority of urban bird and plant species are native in the world's cities. Few plants and birds are cosmopolitan, the most common being Columba livia and Poa annua. The density of bird and plant species (the number of species per km2) has declined substantially: only 8% of native bird and 25% of native plant species are currently present compared with estimates of non-urban density of species. The current density of species in cities and the loss in density of species was best explained by anthropogenic features (landcover, city age) rather than by non-anthropogenic factors (geography, climate, topography). As urbanization continues to expand, efforts directed towards the conservation of intact vegetation within urban landscapes could support higher concentrations of both bird and plant species. Despite declines in the density of species, cities still retain endemic native species, thus providing opportunities for regional and global biodiversity conservation, restoration and education. PMID:24523278

  5. Trends in Selenium Utilization in Marine Microbial World Revealed through the Analysis of the Global Ocean Sampling (GOS) Project

    PubMed Central

    Zhang, Yan; Gladyshev, Vadim N.

    2008-01-01

    Selenium is an important trace element that occurs in proteins in the form of selenocysteine (Sec) and in tRNAs in the form of selenouridine. Recent large-scale metagenomics projects provide an opportunity for understanding global trends in trace element utilization. Herein, we characterized the selenoproteome of the microbial marine community derived from the Global Ocean Sampling (GOS) expedition. More than 3,600 selenoprotein gene sequences belonging to 58 protein families were detected, including sequences representing 7 newly identified selenoprotein families, such as homologs of ferredoxin–thioredoxin reductase and serine protease. In addition, a new eukaryotic selenoprotein family, thiol reductase GILT, was identified. Most GOS selenoprotein families originated from Cys-containing thiol oxidoreductases. In both Pacific and Atlantic microbial communities, SelW-like and SelD were the most widespread selenoproteins. Geographic location had little influence on Sec utilization as measured by selenoprotein variety and the number of selenoprotein genes detected; however, both higher temperature and marine (as opposed to freshwater and other aquatic) environment were associated with increased use of this amino acid. Selenoproteins were also detected with preference for either environment. We identified novel fusion forms of several selenoproteins that highlight redox activities of these proteins. Almost half of Cys-containing SelDs were fused with NADH dehydrogenase, whereas such SelD forms were rare in terrestrial organisms. The selenouridine utilization trait was also analyzed and showed an independent evolutionary relationship with Sec utilization. Overall, our study provides insights into global trends in microbial selenium utilization in marine environments. PMID:18551170

  6. Global Phylogenomic Analysis of Nonencapsulated Streptococcus pneumoniae Reveals a Deep-Branching Classic Lineage That Is Distinct from Multiple Sporadic Lineages

    PubMed Central

    Hilty, Markus; Wüthrich, Daniel; Salter, Susannah J.; Engel, Hansjürg; Campbell, Samuel; Sá-Leão, Raquel; de Lencastre, Hermínia; Hermans, Peter; Sadowy, Ewa; Turner, Paul; Chewapreecha, Claire; Diggle, Mathew; Pluschke, Gerd; McGee, Lesley; Köseoğlu Eser, Özgen; Low, Donald E.; Smith-Vaughan, Heidi; Endimiani, Andrea; Küffer, Marianne; Dupasquier, Mélanie; Beaudoing, Emmanuel; Weber, Johann; Bruggmann, Rémy; Hanage, William P.; Parkhill, Julian; Hathaway, Lucy J.; Mühlemann, Kathrin; Bentley, Stephen D.

    2014-01-01

    The surrounding capsule of Streptococcus pneumoniae has been identified as a major virulence factor and is targeted by pneumococcal conjugate vaccines (PCV). However, nonencapsulated S. pneumoniae (non-Ec-Sp) have also been isolated globally, mainly in carriage studies. It is unknown if non-Ec-Sp evolve sporadically, if they have high antibiotic nonsusceptiblity rates and a unique, specific gene content. Here, whole-genome sequencing of 131 non-Ec-Sp isolates sourced from 17 different locations around the world was performed. Results revealed a deep-branching classic lineage that is distinct from multiple sporadic lineages. The sporadic lineages clustered with a previously sequenced, global collection of encapsulated S. pneumoniae (Ec-Sp) isolates while the classic lineage is comprised mainly of the frequently identified multilocus sequences types (STs) ST344 (n = 39) and ST448 (n = 40). All ST344 and nine ST448 isolates had high nonsusceptiblity rates to β-lactams and other antimicrobials. Analysis of the accessory genome reveals that the classic non-Ec-Sp contained an increased number of mobile elements, than Ec-Sp and sporadic non-Ec-Sp. Performing adherence assays to human epithelial cells for selected classic and sporadic non-Ec-Sp revealed that the presence of a integrative conjugative element (ICE) results in increased adherence to human epithelial cells (P = 0.005). In contrast, sporadic non-Ec-Sp lacking the ICE had greater growth in vitro possibly resulting in improved fitness. In conclusion, non-Ec-Sp isolates from the classic lineage have evolved separately. They have spread globally, are well adapted to nasopharyngeal carriage and are able to coexist with Ec-Sp. Due to continued use of PCV, non-Ec-Sp may become more prevalent. PMID:25480686

  7. Global gene transcriptome analysis in vaccinated cattle revealed a dominant role of IL-22 for protection against bovine tuberculosis.

    PubMed

    Bhuju, Sabin; Aranday-Cortes, Elihu; Villarreal-Ramos, Bernardo; Xing, Zhou; Singh, Mahavir; Vordermeier, H Martin

    2012-12-01

    Bovine tuberculosis (bTB) is a chronic disease of cattle caused by Mycobacterium bovis, a member of the Mycobacterium tuberculosis complex group of bacteria. Vaccination of cattle might offer a long-term solution for controlling the disease and priority has been given to the development of a cattle vaccine against bTB. Identification of biomarkers in tuberculosis research remains elusive and the goal is to identify host correlates of protection. We hypothesized that by studying global gene expression we could identify in vitro predictors of protection that could help to facilitate vaccine development. Calves were vaccinated with BCG or with a heterologous BCG prime adenovirally vectored subunit boosting protocol. Protective efficacy was determined after M. bovis challenge. RNA was prepared from PPD-stimulated PBMC prepared from vaccinated-protected, vaccinated-unprotected and unvaccinated control cattle prior to M. bovis challenge and global gene expression determined by RNA-seq. 668 genes were differentially expressed in vaccinated-protected cattle compared with vaccinated-unprotected and unvaccinated control cattle. Cytokine-cytokine receptor interaction was the most significant pathway related to this dataset with IL-22 expression identified as the dominant surrogate of protection besides INF-γ. Finally, the expression of these candidate genes identified by RNA-seq was evaluated by RT-qPCR in an independent set of PBMC samples from BCG vaccinated and unvaccinated calves. This experiment confirmed the importance of IL-22 as predictor of vaccine efficacy.

  8. Global-scale computational analysis of genomic sequences reveals the recombination pattern and coevolution dynamics of cereal-infecting geminiviruses.

    PubMed

    Wu, Beilei; Shang, Xiaonan; Schubert, Jörg; Habekuß, Antje; Elena, Santiago F; Wang, Xifeng

    2015-01-30

    Genetic diversity and recombination patterns were evaluated for 229 isolates of Wheat dwarf virus (WDV), which are important cereal-infecting geminiviruses. Recombination hot spots were concentrated at the boundary of the genes encoding for the replication protein (Rep), the coat protein (cp) and the movement protein (mp), as well as inside Rep and cp and in the short intergenic regions (SIR). Phylogenomic analyses confirmed that the global population of WDV clustered into two groups according to their specific host: wheat and barley, and the crucial regions for the division of two groups were mp and the large intergenic regions (LIR). The computationally inferred pattern of coevolution between amino acid residues and the predicted 3D structure for the viral proteins provided further differences among the strains or species at the genome and protein level. Pervasive interaction between Rep and Rep A proteins in WDV-wheat-specific group reflected their important and complex function in the replication and transcription of WDV. Furthermore, significant predicted interactions between CP and Rep and CP and Rep A proteins in the WDV-wheat-specific group are thought to be crucial for successful encapsidation and movement of the virus during infection.

  9. A global analysis of transcription reveals two modes of Spt4/5 recruitment to archaeal RNA polymerase.

    PubMed

    Smollett, Katherine; Blombach, Fabian; Reichelt, Robert; Thomm, Michael; Werner, Finn

    2017-03-01

    The archaeal transcription apparatus is closely related to the eukaryotic RNA polymerase (RNAP) II system, while archaeal genomes are more similar to bacteria with densely packed genes organized in operons. This makes understanding transcription in archaea vital, both in terms of molecular mechanisms and evolution. Very little is known about how archaeal cells orchestrate transcription on a systems level. We have characterized the genome-wide occupancy of the Methanocaldococcus jannaschii transcription machinery and its transcriptome. Our data reveal how the TATA and BRE promoter elements facilitate recruitment of the essential initiation factors TATA-binding protein and transcription factor B, respectively, which in turn are responsible for the loading of RNAP into the transcription units. The occupancies of RNAP and Spt4/5 strongly correlate with each other and with RNA levels. Our results show that Spt4/5 is a general elongation factor in archaea as its presence on all genes matches RNAP. Spt4/5 is recruited proximal to the transcription start site on the majority of transcription units, while on a subset of genes, including rRNA and CRISPR loci, Spt4/5 is recruited to the transcription elongation complex during early elongation within 500 base pairs of the transcription start site and akin to its bacterial homologue NusG.

  10. Transcriptome meta-analysis reveals common differential and global gene expression profiles in cystic fibrosis and other respiratory disorders and identifies CFTR regulators.

    PubMed

    Clarke, Luka A; Botelho, Hugo M; Sousa, Lisete; Falcao, Andre O; Amaral, Margarida D

    2015-11-01

    A meta-analysis of 13 independent microarray data sets was performed and gene expression profiles from cystic fibrosis (CF), similar disorders (COPD: chronic obstructive pulmonary disease, IPF: idiopathic pulmonary fibrosis, asthma), environmental conditions (smoking, epithelial injury), related cellular processes (epithelial differentiation/regeneration), and non-respiratory "control" conditions (schizophrenia, dieting), were compared. Similarity among differentially expressed (DE) gene lists was assessed using a permutation test, and a clustergram was constructed, identifying common gene markers. Global gene expression values were standardized using a novel approach, revealing that similarities between independent data sets run deeper than shared DE genes. Correlation of gene expression values identified putative gene regulators of the CF transmembrane conductance regulator (CFTR) gene, of potential therapeutic significance. Our study provides a novel perspective on CF epithelial gene expression in the context of other lung disorders and conditions, and highlights the contribution of differentiation/EMT and injury to gene signatures of respiratory disease.

  11. Global Transcriptome Analysis Reveals Distinct Aluminum-Tolerance Pathways in the Al-Accumulating Species Hydrangea macrophylla and Marker Identification

    PubMed Central

    Chen, Haixia; Lu, Changping; Jiang, Hui; Peng, Jinhui

    2015-01-01

    Hydrangea (Hydrangea macrophylla) is a well known Al-accumulating plant, showing a high level of aluminum (Al) tolerance and accumulation. Although the physiological mechanisms for detoxification of Al and the roles of Al in blue hydrangea sepals have been reported, the molecular mechanisms of Al tolerance and accumulation are poorly understood in hydrangea. In this study, we conducted a genome-wide transcriptome analysis of Al-response genes in the roots and leaves of hydrangea by RNA sequencing (RNA-seq). The assembly of hydrangea transcriptome provides a rich source for gene identification and mining molecular markers, including single nucleotide polymorphism (SNP) and simple sequence repeat (SSR). A total of 401,215 transcripts with an average length of 810.77bp were assembled, generating 256,127 unigenes. After annotation, 4,287 genes in the roots and 730 genes in the leaves were up-regulated by Al exposure, while 236 genes in the roots and 719 genes in the leaves were down-regulated, respectively. Many transporters, including MATE and ABC families, were involved in the process of Al-citrate complex transporting from the roots in hydrangea. A plasma membrane Al uptake transporter, Nramp aluminum transporter was up-regulated in roots and leaves under Al stress, indicating it may play an important role in Al tolerance by reducing the level of toxic Al. Although the exact roles of these candidate genes remain to be examined, these results provide a platform for further functional analysis of the process of detoxification of Al in hydrangea. PMID:26660093

  12. Global Transcriptome Analysis Reveals Acclimation-Primed Processes Involved in the Acquisition of Desiccation Tolerance in Boea hygrometrica.

    PubMed

    Zhu, Yan; Wang, Bo; Phillips, Jonathan; Zhang, Zhen-Nan; Du, Hong; Xu, Tao; Huang, Lian-Cheng; Zhang, Xiao-Fei; Xu, Guang-Hui; Li, Wen-Long; Wang, Zhi; Wang, Ling; Liu, Yong-Xiu; Deng, Xin

    2015-07-01

    Boea hygrometrica resurrection plants require a period of acclimation by slow soil-drying in order to survive a subsequent period of rapid desiccation. The molecular basis of this observation was investigated by comparing gene expression profiles under different degrees of water deprivation. Transcripts were clustered according to the expression profiles in plants that were air-dried (rapid desiccation), soil-dried (gradual desiccation), rehydrated (acclimated) and air-dried after acclimation. Although phenotypically indistinguishable, it was shown by principal component analysis that the gene expression profiles in rehydrated, acclimated plants resemble those of desiccated plants more closely than those of hydrated acclimated plants. Enrichment analysis based on gene ontology was performed to deconvolute the processes that accompanied desiccation tolerance. Transcripts associated with autophagy and α-tocopherol accumulation were found to be activated in both air-dried, acclimated plants and soil-dried non-acclimated plants. Furthermore, transcripts associated with biosynthesis of ascorbic acid, cell wall catabolism, chaperone-assisted protein folding, respiration and macromolecule catabolism were activated and maintained during soil-drying and rehydration. Based on these findings, we hypothesize that activation of these processes leads to the establishment of an optimal physiological and cellular state that enables tolerance during rapid air-drying. Our study provides a novel insight into the transcriptional regulation of critical priming responses to enable survival following rapid dehydration in B. hygrometrica. © The Author 2015. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  13. Global transcriptional analysis of Burkholderia pseudomallei high and low biofilm producers reveals insights into biofilm production and virulence.

    PubMed

    Chin, Chui-Yoke; Hara, Yuka; Ghazali, Ahmad-Kamal; Yap, Soon-Joo; Kong, Cin; Wong, Yee-Chin; Rozali, Naufal; Koh, Seng-Fook; Hoh, Chee-Choong; Puthucheary, Savithri D; Nathan, Sheila

    2015-06-20

    Chronic bacterial infections occur as a result of the infecting pathogen's ability to live within a biofilm, hence escaping the detrimental effects of antibiotics and the immune defense system. Burkholderia pseudomallei, a gram-negative facultative pathogen, is distinctive in its ability to survive within phagocytic and non-phagocytic cells, to persist in vivo for many years and subsequently leading to relapse as well as the development of chronic disease. The capacity to persist has been attributed to the pathogen's ability to form biofilm. However, the underlying biology of B. pseudomallei biofilm development remains unresolved. We utilised RNA-Sequencing to identify genes that contribute to B. pseudomallei biofilm phenotype. Transcriptome analysis of a high and low biofilm producer identified 563 differentially regulated genes, implying that expression of ~9.5% of the total B. pseudomallei gene content was altered during biofilm formation. Genes involved in surface-associated motility, surface composition and cell wall biogenesis were over-expressed and probably play a role in the initial attachment of biofilms. Up-regulation of genes related to two component signal transduction systems and a denitrification enzyme pathway suggest that the B. pseudomallei high biofilm producer is able to sense the surrounding environmental conditions and regulate the production of extracellular polymeric substance matrix, a hallmark of microbial biofilm formation. The transcriptome profile described here provides the first comprehensive view of genes that contribute to the biofilm phenotype in B. pseudomallei.

  14. Differentiation State-Specific Mitochondrial Dynamic Regulatory Networks Are Revealed by Global Transcriptional Analysis of the Developing Chicken Lens

    PubMed Central

    Chauss, Daniel; Basu, Subhasree; Rajakaruna, Suren; Ma, Zhiwei; Gau, Victoria; Anastas, Sara; Brennan, Lisa A.; Hejtmancik, J. Fielding; Menko, A. Sue; Kantorow, Marc

    2014-01-01

    The mature eye lens contains a surface layer of epithelial cells called the lens epithelium that requires a functional mitochondrial population to maintain the homeostasis and transparency of the entire lens. The lens epithelium overlies a core of terminally differentiated fiber cells that must degrade their mitochondria to achieve lens transparency. These distinct mitochondrial populations make the lens a useful model system to identify those genes that regulate the balance between mitochondrial homeostasis and elimination. Here we used an RNA sequencing and bioinformatics approach to identify the transcript levels of all genes expressed by distinct regions of the lens epithelium and maturing fiber cells of the embryonic Gallus gallus (chicken) lens. Our analysis detected more than 15,000 unique transcripts expressed by the embryonic chicken lens. Of these, more than 3000 transcripts exhibited significant differences in expression between lens epithelial cells and fiber cells. Multiple transcripts coding for separate mitochondrial homeostatic and degradation mechanisms were identified to exhibit preferred patterns of expression in lens epithelial cells that require mitochondria relative to lens fiber cells that require mitochondrial elimination. These included differences in the expression levels of metabolic (DUT, PDK1, SNPH), autophagy (ATG3, ATG4B, BECN1, FYCO1, WIPI1), and mitophagy (BNIP3L/NIX, BNIP3, PARK2, p62/SQSTM1) transcripts between lens epithelial cells and lens fiber cells. These data provide a comprehensive window into all genes transcribed by the lens and those mitochondrial regulatory and degradation pathways that function to maintain mitochondrial populations in the lens epithelium and to eliminate mitochondria in maturing lens fiber cells. PMID:24928582

  15. Global transcriptional responses of denitrifying bacteria to functionalized single-walled carbon nanotubes revealed by weighted gene-coexpression network analysis.

    PubMed

    Zheng, Xiong; Su, Yinglong; Chen, Yinguang; Huang, Haining; Shen, Qiuting

    2017-09-24

    Functionalized single-walled carbon nanotubes (f-SWNTs) are widely used in many fields due to the unique structure and the excellent properties. Although these nanomaterials have been reported to enable to cause negative effects on denitrifying bacteria once they enter the environment, the toxic behaviors and regulatory mechanisms of f-SWNTs to denitrification remain unclear. In this study, the denitrification performance of a model denitrifier exposed to pristine and functionalized SWNTs was investigated, and the global transcriptional responses were comprehensively explored by RNA-seq and weighted gene-coexpression network analysis (WGCNA). Although both hydroxyl SWNTs (SWNTs-OH) and carboxyl SWNTs (SWNTs-COOH) showed inhibitory effects on bacterial denitrification, the former more severely inhibited denitrification than the latter. Transcriptional profiles showed that compared with SWNTs-COOH, SWNTs-OH much more strongly influenced the expressions of the key genes related to signal transduction, substance transport, electron transfer and transcriptional regulation. Functional analysis further indicated that the genes associated with substrate transport, carbon source metabolism and electron transfer underwent dramatic down-regulation. Using WGCNA, 12 gene modules were established corresponding to various types of carbon nanotubes, and eigengene adjacency analysis revealed the key gene modules related to denitrification performance under different conditions. Hub gene network analysis revealed the key regulatory factors of bacterial denitrification induced by f-SWNTs. The results suggested that f-SWNTs modulated the key genes responsible for the glycerolipid/free fatty acid (GL/FFA) cycle, and thus disturb processes associated with denitrification, including signaling process, energy homeostasis, intracellular redox balance and transportation. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Comparative Genome Analysis and Global Phylogeny of the Toxin Variant Clostridium difficile PCR Ribotype 017 Reveals the Evolution of Two Independent Sublineages.

    PubMed

    Cairns, M D; Preston, M D; Hall, C L; Gerding, D N; Hawkey, P M; Kato, H; Kim, H; Kuijper, E J; Lawley, T D; Pituch, H; Reid, S; Kullin, B; Riley, T V; Solomon, K; Tsai, P J; Weese, J S; Stabler, R A; Wren, B W

    2017-03-01

    The diarrheal pathogen Clostridium difficile consists of at least six distinct evolutionary lineages. The RT017 lineage is anomalous, as strains only express toxin B, compared to strains from other lineages that produce toxins A and B and, occasionally, binary toxin. Historically, RT017 initially was reported in Asia but now has been reported worldwide. We used whole-genome sequencing and phylogenetic analysis to investigate the patterns of global spread and population structure of 277 RT017 isolates from animal and human origins from six continents, isolated between 1990 and 2013. We reveal two distinct evenly split sublineages (SL1 and SL2) of C. difficile RT017 that contain multiple independent clonal expansions. All 24 animal isolates were contained within SL1 along with human isolates, suggesting potential transmission between animals and humans. Genetic analyses revealed an overrepresentation of antibiotic resistance genes. Phylogeographic analyses show a North American origin for RT017, as has been found for the recently emerged epidemic RT027 lineage. Despite having only one toxin, RT017 strains have evolved in parallel from at least two independent sources and can readily transmit between continents. Copyright © 2017 Cairns et al.

  17. Comparative Genome Analysis and Global Phylogeny of the Toxin Variant Clostridium difficile PCR Ribotype 017 Reveals the Evolution of Two Independent Sublineages

    PubMed Central

    Cairns, M. D.; Preston, M. D.; Hall, C. L.; Gerding, D. N.; Hawkey, P. M.; Kato, H.; Kim, H.; Kuijper, E. J.; Lawley, T. D.; Pituch, H.; Reid, S.; Kullin, B.; Riley, T. V.; Solomon, K.; Tsai, P. J.; Weese, J. S.

    2016-01-01

    ABSTRACT The diarrheal pathogen Clostridium difficile consists of at least six distinct evolutionary lineages. The RT017 lineage is anomalous, as strains only express toxin B, compared to strains from other lineages that produce toxins A and B and, occasionally, binary toxin. Historically, RT017 initially was reported in Asia but now has been reported worldwide. We used whole-genome sequencing and phylogenetic analysis to investigate the patterns of global spread and population structure of 277 RT017 isolates from animal and human origins from six continents, isolated between 1990 and 2013. We reveal two distinct evenly split sublineages (SL1 and SL2) of C. difficile RT017 that contain multiple independent clonal expansions. All 24 animal isolates were contained within SL1 along with human isolates, suggesting potential transmission between animals and humans. Genetic analyses revealed an overrepresentation of antibiotic resistance genes. Phylogeographic analyses show a North American origin for RT017, as has been found for the recently emerged epidemic RT027 lineage. Despite having only one toxin, RT017 strains have evolved in parallel from at least two independent sources and can readily transmit between continents. PMID:28031436

  18. Global gene expression analysis reveals pathway differences between teratogenic and non-teratogenic exposure concentrations of bisphenol A and 17β-estradiol in embryonic zebrafish

    PubMed Central

    Saili, Katerine S.; Tilton, Susan C.; Waters, Katrina M.; Tanguay, Robert L.

    2013-01-01

    Transient developmental exposure to 0.1 μM bisphenol A (BPA) results in larval zebrafish hyperactivity and learning impairments in the adult, while exposure to 80 μM BPA results in teratogenic responses, including craniofacial abnormalities and edema. The mode of action underlying these effects is unclear. We used global gene expression analysis to identify candidate genes and signaling pathways that mediate BPA’s developmental toxicity in zebrafish. Exposure concentrations were selected and anchored to the positive control, 17β-estradiol (E2), based on previously determined behavioral or teratogenic phenotypes. Functional analysis of differentially expressed genes revealed distinct expression profiles at 24 hours post fertilization for 0.1 versus 80 μM BPA and 0.1 versus 15 μM E2 exposure, identification of prothrombin activation as a top canonical pathway impacted by both 0.1 μM BPA and 0.1 μM E2 exposure, and suppressed expression of several genes involved in nervous system development and function following 0.1 μM BPAexposure. PMID:23557687

  19. Switch of sensitivity dynamics revealed with DyGloSA toolbox for dynamical global sensitivity analysis as an early warning for system's critical transition.

    PubMed

    Baumuratova, Tatiana; Dobre, Simona; Bastogne, Thierry; Sauter, Thomas

    2013-01-01

    Systems with bifurcations may experience abrupt irreversible and often unwanted shifts in their performance, called critical transitions. For many systems like climate, economy, ecosystems it is highly desirable to identify indicators serving as early warnings of such regime shifts. Several statistical measures were recently proposed as early warnings of critical transitions including increased variance, autocorrelation and skewness of experimental or model-generated data. The lack of automatized tool for model-based prediction of critical transitions led to designing DyGloSA - a MATLAB toolbox for dynamical global parameter sensitivity analysis (GPSA) of ordinary differential equations models. We suggest that the switch in dynamics of parameter sensitivities revealed by our toolbox is an early warning that a system is approaching a critical transition. We illustrate the efficiency of our toolbox by analyzing several models with bifurcations and predicting the time periods when systems can still avoid going to a critical transition by manipulating certain parameter values, which is not detectable with the existing SA techniques. DyGloSA is based on the SBToolbox2 and contains functions, which compute dynamically the global sensitivity indices of the system by applying four main GPSA methods: eFAST, Sobol's ANOVA, PRCC and WALS. It includes parallelized versions of the functions enabling significant reduction of the computational time (up to 12 times). DyGloSA is freely available as a set of MATLAB scripts at http://bio.uni.lu/systems_biology/software/dyglosa. It requires installation of MATLAB (versions R2008b or later) and the Systems Biology Toolbox2 available at www.sbtoolbox2.org. DyGloSA can be run on Windows and Linux systems, -32 and -64 bits.

  20. Switch of Sensitivity Dynamics Revealed with DyGloSA Toolbox for Dynamical Global Sensitivity Analysis as an Early Warning for System's Critical Transition

    PubMed Central

    Baumuratova, Tatiana; Dobre, Simona; Bastogne, Thierry; Sauter, Thomas

    2013-01-01

    Systems with bifurcations may experience abrupt irreversible and often unwanted shifts in their performance, called critical transitions. For many systems like climate, economy, ecosystems it is highly desirable to identify indicators serving as early warnings of such regime shifts. Several statistical measures were recently proposed as early warnings of critical transitions including increased variance, autocorrelation and skewness of experimental or model-generated data. The lack of automatized tool for model-based prediction of critical transitions led to designing DyGloSA – a MATLAB toolbox for dynamical global parameter sensitivity analysis (GPSA) of ordinary differential equations models. We suggest that the switch in dynamics of parameter sensitivities revealed by our toolbox is an early warning that a system is approaching a critical transition. We illustrate the efficiency of our toolbox by analyzing several models with bifurcations and predicting the time periods when systems can still avoid going to a critical transition by manipulating certain parameter values, which is not detectable with the existing SA techniques. DyGloSA is based on the SBToolbox2 and contains functions, which compute dynamically the global sensitivity indices of the system by applying four main GPSA methods: eFAST, Sobol's ANOVA, PRCC and WALS. It includes parallelized versions of the functions enabling significant reduction of the computational time (up to 12 times). DyGloSA is freely available as a set of MATLAB scripts at http://bio.uni.lu/systems_biology/software/dyglosa. It requires installation of MATLAB (versions R2008b or later) and the Systems Biology Toolbox2 available at www.sbtoolbox2.org. DyGloSA can be run on Windows and Linux systems, -32 and -64 bits. PMID:24367574

  1. Comparative 16S rRNA Analysis of Lake Bacterioplankton Reveals Globally Distributed Phylogenetic Clusters Including an Abundant Group of Actinobacteria

    PubMed Central

    Glöckner, Frank Oliver; Zaichikov, Evgeny; Belkova, Natalia; Denissova, Ludmilla; Pernthaler, Jakob; Pernthaler, Annelie; Amann, Rudolf

    2000-01-01

    In a search for cosmopolitan phylogenetic clusters of freshwater bacteria, we recovered a total of 190 full and partial 16S ribosomal DNA (rDNA) sequences from three different lakes (Lake Gossenköllesee, Austria; Lake Fuchskuhle, Germany; and Lake Baikal, Russia). The phylogenetic comparison with the currently available rDNA data set showed that our sequences fall into 16 clusters, which otherwise include bacterial rDNA sequences of primarily freshwater and soil, but not marine, origin. Six of the clusters were affiliated with the α, four were affiliated with the β, and one was affiliated with the γ subclass of the Proteobacteria; four were affiliated with the Cytophaga-Flavobacterium-Bacteroides group; and one was affiliated with the class Actinobacteria (formerly known as the high-G+C gram-positive bacteria). The latter cluster (hgcI) is monophyletic and so far includes only sequences directly retrieved from aquatic environments. Fluorescence in situ hybridization (FISH) with probes specific for the hgcI cluster showed abundances of up to 1.7 × 105 cells ml−1 in Lake Gossenköllesee, with strong seasonal fluctuations, and high abundances in the two other lakes investigated. Cell size measurements revealed that Actinobacteria in Lake Gossenköllesee can account for up to 63% of the bacterioplankton biomass. A combination of phylogenetic analysis and FISH was used to reveal 16 globally distributed sequence clusters and to confirm the broad distribution, abundance, and high biomass of members of the class Actinobacteria in freshwater ecosystems. PMID:11055963

  2. Global gene expression and Ingenuity biological functions analysis on PCB 153 and 138 induced human PBMC in vitro reveals differential mode(s) of action in developing toxicities

    PubMed Central

    Ghosh, Somiranjan; Zang, Shizhu; Mitra, Partha S.; Ghimbovschi, Svetlana; Hoffman, Eric P.; Dutta, Sisir K.

    2011-01-01

    Several reports have indicated that low level of polychlorinated biphenyl (PCB) exposure can adversely affect a multitude of physiological disorders and diseases in in vitro, in vivo, and as reported in epidemiological studies. This investigation is focused on the possible contribution of two most prevalent PCB congeners in vitro in developing toxicities. We used PCB 138 and 153 at the human equivalence level as model agents to test their specificity. We chose a global approach using oligonucleotide microarray technology to investigate modulated gene expression for biological effects, upon exposure of PCBs, followed by Ingenuity Pathway Analysis (IPA), to understand the underlying consequence in developing disease and disorders. We performed in vitro studies with human peripheral blood mononuclear cells (PBMC), where PBMC cells were exposed to respective PCBs for 48 hrs. Overall, our observation on gene expression indicated that PCB produces a unique signature affecting different pathways, specific for each congener. While analyzing these data through IPA, the prominent and interesting disease and disorders were Neurological disease, Cancer, Cardiovascular disease, respiratory disease, as well as endocrine system disorders Genetic disorders, and reproductive system disease. They showed strong resemblances with in vitro, in vivo, and in the epidemiological studies. A distinct difference was observed in renal and urological diseases, organisimal injury and abnormalities, dental disease, ophthalmic disease, and psychological disorders, which are only revealed by PCB 138 exposure, but not in PCB 153. The present study emphasizes the challenges of global gene expression in vitro and was correlated with the results of exposed human population. The microarray results give a molecular mechanistic insight and functional effects, following PCB exposure. The extent of changes in genes related to several possible mode(s) of action highlights the changes in cellular functions

  3. Global Gene-expression Analysis of the Response of Salmonella Enteritidis to Egg White Exposure Reveals Multiple Egg White-imposed Stress Responses

    PubMed Central

    Baron, Florence; Bonnassie, Sylvie; Alabdeh, Mariah; Cochet, Marie-Françoise; Nau, Françoise; Guérin-Dubiard, Catherine; Gautier, Michel; Andrews, Simon C.; Jan, Sophie

    2017-01-01

    Chicken egg white protects the embryo from bacterial invaders by presenting an assortment of antagonistic activities that combine together to both kill and inhibit growth. The key features of the egg white anti-bacterial system are iron restriction, high pH, antibacterial peptides and proteins, and viscosity. Salmonella enterica serovar Enteritidis is the major pathogen responsible for egg-borne infection in humans, which is partly explained by its exceptional capacity for survival under the harsh conditions encountered within egg white. However, at temperatures up to 42°C, egg white exerts a much stronger bactericidal effect on S. Enteritidis than at lower temperatures, although the mechanism of egg white-induced killing is only partly understood. Here, for the first time, the impact of exposure of S. Enteritidis to egg white under bactericidal conditions (45°C) is explored by global-expression analysis. A large-scale (18.7% of genome) shift in transcription is revealed suggesting major changes in specific aspects of S. Enteritidis physiology: induction of egg white related stress-responses (envelope damage, exposure to heat and alkalinity, and translation shutdown); shift in energy metabolism from respiration to fermentation; and enhanced micronutrient provision (due to iron and biotin restriction). Little evidence of DNA damage or redox stress was obtained. Instead, data are consistent with envelope damage resulting in cell death by lysis. A surprise was the high degree of induction of hexonate/hexuronate utilization genes, despite no evidence indicating the presence of these substrates in egg white. PMID:28553268

  4. Global and System-Specific Resting-State fMRI Fluctuations Are Uncorrelated: Principal Component Analysis Reveals Anti-Correlated Networks

    PubMed Central

    Carbonell, Felix; Bellec, Pierre

    2011-01-01

    Abstract The influence of the global average signal (GAS) on functional-magnetic resonance imaging (fMRI)–based resting-state functional connectivity is a matter of ongoing debate. The global average fluctuations increase the correlation between functional systems beyond the correlation that reflects their specific functional connectivity. Hence, removal of the GAS is a common practice for facilitating the observation of network-specific functional connectivity. This strategy relies on the implicit assumption of a linear-additive model according to which global fluctuations, irrespective of their origin, and network-specific fluctuations are super-positioned. However, removal of the GAS introduces spurious negative correlations between functional systems, bringing into question the validity of previous findings of negative correlations between fluctuations in the default-mode and the task-positive networks. Here we present an alternative method for estimating global fluctuations, immune to the complications associated with the GAS. Principal components analysis was applied to resting-state fMRI time-series. A global-signal effect estimator was defined as the principal component (PC) that correlated best with the GAS. The mean correlation coefficient between our proposed PC-based global effect estimator and the GAS was 0.97±0.05, demonstrating that our estimator successfully approximated the GAS. In 66 out of 68 runs, the PC that showed the highest correlation with the GAS was the first PC. Since PCs are orthogonal, our method provides an estimator of the global fluctuations, which is uncorrelated to the remaining, network-specific fluctuations. Moreover, unlike the regression of the GAS, the regression of the PC-based global effect estimator does not introduce spurious anti-correlations beyond the decrease in seed-based correlation values allowed by the assumed additive model. After regressing this PC-based estimator out of the original time-series, we observed

  5. 450K-array analysis of chronic lymphocytic leukemia cells reveals global DNA methylation to be relatively stable over time and similar in resting and proliferative compartments.

    PubMed

    Cahill, N; Bergh, A-C; Kanduri, M; Göransson-Kultima, H; Mansouri, L; Isaksson, A; Ryan, F; Smedby, K E; Juliusson, G; Sundström, C; Rosén, A; Rosenquist, R

    2013-01-01

    In chronic lymphocytic leukemia (CLL), the microenvironment influences gene expression patterns; however, knowledge is limited regarding the extent to which methylation changes with time and exposure to specific microenvironments. Using high-resolution 450K arrays, we provide the most comprehensive DNA methylation study of CLL to date, analyzing paired diagnostic/follow-up samples from IGHV-mutated/untreated and IGHV-unmutated/treated patients (n=36) and patient-matched peripheral blood and lymph node samples (n=20). On an unprecedented scale, we revealed 2239 differentially methylated CpG sites between IGHV-mutated and unmutated patients, with the majority of sites positioned outside annotated CpG islands. Intriguingly, CLL prognostic genes (for example, CLLU1, LPL, ZAP70 and NOTCH1), epigenetic regulator (for example, HDAC9, HDAC4 and DNMT3B), B-cell signaling (for example, IBTK) and numerous TGF-β and NF-κB/TNF pathway genes were alternatively methylated between subgroups. Contrary, DNA methylation over time was deemed rather stable with few recurrent changes noted within subgroups. Although a larger number of non-recurrent changes were identified among IGHV-unmutated relative to mutated cases over time, these equated to a low global change. Similarly, few changes were identified between compartment cases. Altogether, we reveal CLL subgroups to display unique methylation profiles and unveil methylation as relatively stable over time and similar within different CLL compartments, implying aberrant methylation as an early leukemogenic event.

  6. Primary Charge Separation in the Photosystem II Reaction Center Revealed by a Global Analysis of the Two-dimensional Electronic Spectra.

    PubMed

    Duan, Hong-Guang; Prokhorenko, Valentyn I; Wientjes, Emilie; Croce, Roberta; Thorwart, Michael; Miller, R J Dwayne

    2017-09-27

    The transfer of electronic charge in the reaction center of Photosystem II is one of the key building blocks of the conversion of sunlight energy into chemical energy within the cascade of the photosynthetic reactions. Since the charge transfer dynamics is mixed with the energy transfer dynamics, an effective tool for the direct resolution of charge separation in the reaction center is still missing. Here, we use experimental two-dimensional optical photon echo spectroscopy in combination with the theoretical calculation to resolve its signature. A global fitting analysis allows us to clearly and directly identify a decay pathway associated to the primary charge separation. In particular, it can be distinguished from regular energy transfer and occurs on a time scale of 1.5 ps under ambient conditions. This technique provides a general tool to identify charge separation signatures from the energy transport in two-dimensional optical spectroscopy.

  7. Altered proteostasis in aging and heat shock response in C. elegans revealed by analysis of the global and de novo synthesized proteome.

    PubMed

    Liang, Vanessa; Ullrich, Milena; Lam, Hong; Chew, Yee Lian; Banister, Samuel; Song, Xiaomin; Zaw, Thiri; Kassiou, Michael; Götz, Jürgen; Nicholas, Hannah R

    2014-09-01

    Protein misfolding and aggregation as a consequence of impaired protein homeostasis (proteostasis) not only characterizes numerous age-related diseases but also the aging process itself. Functionally related to the aging process are, among others, ribosomal proteins, suggesting an intimate link between proteostasis and aging. We determined by iTRAQ quantitative proteomic analysis in C. elegans how the proteome changes with age and in response to heat shock. Levels of ribosomal proteins and mitochondrial chaperones were decreased in aged animals, supporting the notion that proteostasis is altered during aging. Mitochondrial enzymes of the tricarboxylic acid cycle and the electron transport chain were also reduced, consistent with an age-associated energy impairment. Moreover, we observed an age-associated decline in the heat shock response. In order to determine how protein synthesis is altered in aging and in response to heat shock, we complemented our global analysis by determining the de novo proteome. For that, we established a novel method that enables both the visualization and identification of de novo synthesized proteins, by incorporating the non-canonical methionine analogue, azidohomoalanine (AHA), into the nascent polypeptides, followed by reacting the azide group of AHA by 'click chemistry' with an alkyne-labeled tag. Our analysis of AHA-tagged peptides demonstrated that the decreased abundance of, for example, ribosomal proteins in aged animals is not solely due to degradation but also reflects a relative decrease in their synthesis. Interestingly, although the net rate of protein synthesis is reduced in aged animals, our analyses indicate that the synthesis of certain proteins such as the vitellogenins increases with age.

  8. Global Transcriptional Analysis Reveals the Complex Relationship between Tea Quality, Leaf Senescence and the Responses to Cold-Drought Combined Stress in Camellia sinensis

    PubMed Central

    Zheng, Chao; Wang, Yu; Ding, Zhaotang; Zhao, Lei

    2016-01-01

    In field conditions, especially in arid and semi-arid areas, tea plants are often simultaneously exposed to various abiotic stresses such as cold and drought, which have profound effects on leaf senescence process and tea quality. However, most studies of gene expression in stress responses focus on a single inciting agent, and the confounding effect of multiple stresses on crop quality and leaf senescence remain unearthed. Here, global transcriptome profiles of tea leaves under separately cold and drought stress were compared with their combination using RNA-Seq technology. This revealed that tea plants shared a large overlap in unigenes displayed “similar” (26%) expression pattern and avoid antagonistic responses (lowest level of “prioritized” mode: 0%) to exhibit very congruent responses to co-occurring cold and drought stress; 31.5% differential expressed genes and 38% of the transcriptome changes in response to combined stresses were unpredictable from cold or drought single-case studies. We also identified 319 candidate genes for enhancing plant resistance to combined stress. We then investigated the combined effect of cold and drought on tea quality and leaf senescence. Our results showed that drought-induced leaf senescence were severely delayed by (i) modulation of a number of senescence-associated genes and cold responsive genes, (ii) enhancement of antioxidant capacity, (iii) attenuation of lipid degradation, (iv) maintenance of cell wall and photosynthetic system, (v) alteration of senescence-induced sugar effect/sensitivity, as well as (vi) regulation of secondary metabolism pathways that significantly influence the quality of tea during combined stress. Therefore, care should be taken when utilizing a set of stresses to try and maximize leaf longevity and tea quality. PMID:28018394

  9. The use of global transcriptional analysis to reveal the biological and cellular events involved in distinct development phases of Trichophyton rubrum conidial germination

    PubMed Central

    Liu, Tao; Zhang, Qian; Wang, Lingling; Yu, Lu; Leng, Wenchuan; Yang, Jian; Chen, Lihong; Peng, Junping; Ma, Li; Dong, Jie; Xu, Xingye; Xue, Ying; Zhu, Yafang; Zhang, Wenliang; Yang, Li; Li, Weijun; Sun, Lilian; Wan, Zhe; Ding, Guohui; Yu, Fudong; Tu, Kang; Qian, Ziliang; Li, Ruoyu; Shen, Yan; Li, Yixue; Jin, Qi

    2007-01-01

    Background Conidia are considered to be the primary cause of infections by Trichophyton rubrum. Results We have developed a cDNA microarray containing 10250 ESTs to monitor the transcriptional strategy of conidial germination. A total of 1561 genes that had their expression levels specially altered in the process were obtained and hierarchically clustered with respect to their expression profiles. By functional analysis, we provided a global view of an important biological system related to conidial germination, including characterization of the pattern of gene expression at sequential developmental phases, and changes of gene expression profiles corresponding to morphological transitions. We matched the EST sequences to GO terms in the Saccharomyces Genome Database (SGD). A number of homologues of Saccharomyces cerevisiae genes related to signalling pathways and some important cellular processes were found to be involved in T. rubrum germination. These genes and signalling pathways may play roles in distinct steps, such as activating conidial germination, maintenance of isotropic growth, establishment of cell polarity and morphological transitions. Conclusion Our results may provide insights into molecular mechanisms of conidial germination at the cell level, and may enhance our understanding of regulation of gene expression related to the morphological construction of T. rubrum. PMID:17428342

  10. Global transcriptome and chromatin occupancy analysis reveal the short isoform of GATA1 is deficient for erythroid specification and gene expression

    PubMed Central

    Chlon, Timothy M.; McNulty, Maureen; Goldenson, Benjamin; Rosinski, Alexander; Crispino, John D.

    2015-01-01

    GATA1 is a master transcriptional regulator of the differentiation of several related myeloid blood cell types, including erythrocytes and megakaryocytes. Germ-line mutations that cause loss of full length GATA1, but allow for expression of the short isoform (GATA1s), are associated with defective erythropoiesis in a subset of patients with Diamond Blackfan Anemia. Despite extensive studies of GATA1s in megakaryopoiesis, the mechanism by which GATA1s fails to support normal erythropoiesis is not understood. In this study, we used global gene expression and chromatin occupancy analysis to compare the transcriptional activity of GATA1s to GATA1. We discovered that compared to GATA1, GATA1s is less able to activate the erythroid gene expression program and terminal differentiation in cells with dual erythroid-megakaryocytic differentiation potential. Moreover, we found that GATA1s bound to many of its erythroid-specific target genes less efficiently than full length GATA1. These results suggest that the impaired ability of GATA1s to promote erythropoiesis in DBA may be caused by failure to occupy erythroid-specific gene regulatory elements. PMID:25682601

  11. Global transcriptome and chromatin occupancy analysis reveal the short isoform of GATA1 is deficient for erythroid specification and gene expression.

    PubMed

    Chlon, Timothy M; McNulty, Maureen; Goldenson, Benjamin; Rosinski, Alexander; Crispino, John D

    2015-05-01

    GATA1 is a master transcriptional regulator of the differentiation of several related myeloid blood cell types, including erythrocytes and megakaryocytes. Germ-line mutations that cause loss of full length GATA1, but allow for expression of the short isoform (GATA1s), are associated with defective erythropoiesis in a subset of patients with Diamond Blackfan Anemia. Despite extensive studies of GATA1s in megakaryopoiesis, the mechanism by which GATA1s fails to support normal erythropoiesis is not understood. In this study, we used global gene expression and chromatin occupancy analysis to compare the transcriptional activity of GATA1s to GATA1. We discovered that compared to GATA1, GATA1s is less able to activate the erythroid gene expression program and terminal differentiation in cells with dual erythroid-megakaryocytic differentiation potential. Moreover, we found that GATA1s bound to many of its erythroid-specific target genes less efficiently than full length GATA1. These results suggest that the impaired ability of GATA1s to promote erythropoiesis in DBA may be caused by failure to occupy erythroid-specific gene regulatory elements. Copyright© Ferrata Storti Foundation.

  12. Transcriptome analysis of an mvp mutant reveals important changes in global gene expression and a role for methyl jasmonate in vernalization and flowering in wheat

    PubMed Central

    Diallo, Amadou Oury; Agharbaoui, Zahra; Sarhan, Fathey

    2014-01-01

    The einkorn wheat mutant mvp-1 (maintained vegetative phase 1) has a non-flowering phenotype caused by deletions including, but not limited to, the genes CYS, PHYC, and VRN1. However, the impact of these deletions on global gene expression is still unknown. Transcriptome analysis showed that these deletions caused the upregulation of several pathogenesis-related (PR) and jasmonate-responsive genes. These results suggest that jasmonates may be involved in flowering and vernalization in wheat. To test this hypothesis, jasmonic acid (JA) and methyl jasmonate (MeJA) content in mvp and wild-type plants was measured. The content of JA was comparable in all plants, whereas the content of MeJA was higher by more than 6-fold in mvp plants. The accumulation of MeJA was also observed in vernalization-sensitive hexaploid winter wheat during cold exposure. This accumulation declined rapidly once plants were deacclimated under floral-inductive growth conditions. This suggests that MeJA may have a role in floral transition. To confirm this result, we treated vernalization-insensitive spring wheat with MeJA. The treatment delayed flowering with significant downregulation of both TaVRN1 and TaFT1 genes. These data suggest a role for MeJA in modulating vernalization and flowering time in wheat. PMID:24683181

  13. Metabolic flux ratio analysis and multi-objective optimization revealed a globally conserved and coordinated metabolic response of E. coli to paraquat-induced oxidative stress.

    PubMed

    Shen, Tie; Rui, Bin; Zhou, Hong; Zhang, Ximing; Yi, Yin; Wen, Han; Zheng, Haoran; Wu, Jihui; Shi, Yunyu

    2013-01-27

    The ability of a microorganism to adapt to changes in the environment, such as in nutrient or oxygen availability, is essential for its competitive fitness and survival. The cellular objective and the strategy of the metabolic response to an extreme environment are therefore of tremendous interest and, thus, have been increasingly explored. However, the cellular objective of the complex regulatory structure of the metabolic changes has not yet been fully elucidated and more details regarding the quantitative behaviour of the metabolic flux redistribution are required to understand the systems-wide biological significance of this response. In this study, the intracellular metabolic flux ratios involved in the central carbon metabolism were determined by fractional (13)C-labeling and metabolic flux ratio analysis (MetaFoR) of the wild-type E. coli strain JM101 at an oxidative environment in a chemostat. We observed a significant increase in the flux through phosphoenolpyruvate carboxykinase (PEPCK), phosphoenolpyruvate carboxylase (PEPC), malic enzyme (MEZ) and serine hydroxymethyltransferase (SHMT). We applied an ε-constraint based multi-objective optimization to investigate the trade-off relationships between the biomass yield and the generation of reductive power using the in silico iJR904 genome-scale model of E. coli K-12. The theoretical metabolic redistribution supports that the trans-hydrogenase pathway should not play a direct role in the defence mounted by E. coli against oxidative stress. The agreement between the measured ratio and the theoretical redistribution established the significance of NADPH synthesis as the goal of the metabolic reprogramming that occurs in response to oxidative stress. Our work presents a framework that combines metabolic flux ratio analysis and multi-objective optimization to investigate the metabolic trade-offs that occur under varied environmental conditions. Our results led to the proposal that the metabolic response of E

  14. Global Analysis of the Transcriptional Response of Whitefly to Tomato Yellow Leaf Curl China Virus Reveals the Relationship of Coevolved Adaptations▿ †

    PubMed Central

    Luan, Jun-Bo; Li, Jun-Min; Varela, Nélia; Wang, Yong-Liang; Li, Fang-Fang; Bao, Yan-Yuan; Zhang, Chuan-Xi; Liu, Shu-Sheng; Wang, Xiao-Wei

    2011-01-01

    The begomoviruses are the largest and most economically important group of plant viruses transmitted exclusively by the whitefly Bemisia tabaci in a circulative, persistent manner. The circulation of the viruses within the insect vectors involves complex interactions between virus and vector components; however, the molecular mechanisms of these interactions remain largely unknown. Here we investigated the transcriptional response of the invasive B. tabaci Middle East-Asia Minor 1 species to Tomato yellow leaf curl China virus (TYLCCNV) using Illumina sequencing technology. Results showed that 1,606 genes involved in 157 biochemical pathways were differentially expressed in the viruliferous whiteflies. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that TYLCCNV can perturb the cell cycle and primary metabolism in the whitefly, which explains the negative effect of this virus on the longevity and fecundity of B. tabaci. Our data also demonstrated that TYLCCNV can activate whitefly immune responses, such as autophagy and antimicrobial peptide production, which might lead to a gradual decrease of viral particles within the body of the viruliferous whitefly. Furthermore, PCR results showed that TYLCCNV can invade the ovary and fat body tissues of the whitefly, and Lysotracker and Western blot analyses revealed that the invasion of TYLCCNV induced autophagy in both the ovary and fat body tissues. Surprisingly, TYLCCNV also suppressed the whitefly immune responses by downregulating the expression of genes involved in Toll-like signaling and mitogen-activated protein kinase (MAPK) pathways. Taken together, these results reveal the relationship of coevolved adaptations between begomoviruses and whiteflies and will provide a road map for future investigations into the complex interactions between plant viruses and their insect vectors. PMID:21270146

  15. Global analysis of the transcriptional response of whitefly to tomato yellow leaf curl China virus reveals the relationship of coevolved adaptations.

    PubMed

    Luan, Jun-Bo; Li, Jun-Min; Varela, Nélia; Wang, Yong-Liang; Li, Fang-Fang; Bao, Yan-Yuan; Zhang, Chuan-Xi; Liu, Shu-Sheng; Wang, Xiao-Wei

    2011-04-01

    The begomoviruses are the largest and most economically important group of plant viruses transmitted exclusively by the whitefly Bemisia tabaci in a circulative, persistent manner. The circulation of the viruses within the insect vectors involves complex interactions between virus and vector components; however, the molecular mechanisms of these interactions remain largely unknown. Here we investigated the transcriptional response of the invasive B. tabaci Middle East-Asia Minor 1 species to Tomato yellow leaf curl China virus (TYLCCNV) using Illumina sequencing technology. Results showed that 1,606 genes involved in 157 biochemical pathways were differentially expressed in the viruliferous whiteflies. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that TYLCCNV can perturb the cell cycle and primary metabolism in the whitefly, which explains the negative effect of this virus on the longevity and fecundity of B. tabaci. Our data also demonstrated that TYLCCNV can activate whitefly immune responses, such as autophagy and antimicrobial peptide production, which might lead to a gradual decrease of viral particles within the body of the viruliferous whitefly. Furthermore, PCR results showed that TYLCCNV can invade the ovary and fat body tissues of the whitefly, and Lysotracker and Western blot analyses revealed that the invasion of TYLCCNV induced autophagy in both the ovary and fat body tissues. Surprisingly, TYLCCNV also suppressed the whitefly immune responses by downregulating the expression of genes involved in Toll-like signaling and mitogen-activated protein kinase (MAPK) pathways. Taken together, these results reveal the relationship of coevolved adaptations between begomoviruses and whiteflies and will provide a road map for future investigations into the complex interactions between plant viruses and their insect vectors.

  16. Global Analysis of DNA Methylation Variation in Adipose Tissue from Twins Reveals Links to Disease-Associated Variants in Distal Regulatory Elements

    PubMed Central

    Grundberg, Elin; Meduri, Eshwar; Sandling, Johanna K.; Hedman, Åsa K.; Keildson, Sarah; Buil, Alfonso; Busche, Stephan; Yuan, Wei; Nisbet, James; Sekowska, Magdalena; Wilk, Alicja; Barrett, Amy; Small, Kerrin S.; Ge, Bing; Caron, Maxime; Shin, So-Youn; Ahmadi, Kourosh R.; Ainali, Chrysanthi; Barrett, Amy; Bataille, Veronique; Bell, Jordana T.; Buil, Alfonso; Deloukas, Panos; Dermitzakis, Emmanouil T.; Dimas, Antigone S.; Durbin, Richard; Glass, Daniel; Grundberg, Elin; Hassanali, Neelam; Hedman, Åsa K.; Ingle, Catherine; Knowles, David; Krestyaninova, Maria; Lindgren, Cecilia M.; Lowe, Christopher E.; McCarthy, Mark I.; Meduri, Eshwar; di Meglio, Paola; Min, Josine L.; Montgomery, Stephen B.; Nestle, Frank O.; Nica, Alexandra C.; Nisbet, James; O’Rahilly, Stephen; Parts, Leopold; Potter, Simon; Sandling, Johanna; Sekowska, Magdalena; Shin, So-Youn; Small, Kerrin S.; Soranzo, Nicole; Spector, Tim D.; Surdulescu, Gabriela; Travers, Mary E.; Tsaprouni, Loukia; Tsoka, Sophia; Wilk, Alicja; Yang, Tsun-Po; Zondervan, Krina T.; Lathrop, Mark; Dermitzakis, Emmanouil T.; McCarthy, Mark I.; Spector, Timothy D.; Bell, Jordana T.; Deloukas, Panos

    2013-01-01

    Epigenetic modifications such as DNA methylation play a key role in gene regulation and disease susceptibility. However, little is known about the genome-wide frequency, localization, and function of methylation variation and how it is regulated by genetic and environmental factors. We utilized the Multiple Tissue Human Expression Resource (MuTHER) and generated Illumina 450K adipose methylome data from 648 twins. We found that individual CpGs had low variance and that variability was suppressed in promoters. We noted that DNA methylation variation was highly heritable (h2median = 0.34) and that shared environmental effects correlated with metabolic phenotype-associated CpGs. Analysis of methylation quantitative-trait loci (metQTL) revealed that 28% of CpGs were associated with nearby SNPs, and when overlapping them with adipose expression quantitative-trait loci (eQTL) from the same individuals, we found that 6% of the loci played a role in regulating both gene expression and DNA methylation. These associations were bidirectional, but there were pronounced negative associations for promoter CpGs. Integration of metQTL with adipose reference epigenomes and disease associations revealed significant enrichment of metQTL overlapping metabolic-trait or disease loci in enhancers (the strongest effects were for high-density lipoprotein cholesterol and body mass index [BMI]). We followed up with the BMI SNP rs713586, a cg01884057 metQTL that overlaps an enhancer upstream of ADCY3, and used bisulphite sequencing to refine this region. Our results showed widespread population invariability yet sequence dependence on adipose DNA methylation but that incorporating maps of regulatory elements aid in linking CpG variation to gene regulation and disease risk in a tissue-dependent manner. PMID:24183450

  17. Global gene expression analysis of very small embryonic-like stem cells reveals that the Ezh2-dependent bivalent domain mechanism contributes to their pluripotent state.

    PubMed

    Shin, Dong-Myung; Liu, Rui; Wu, Wan; Waigel, Sabine J; Zacharias, Wolfgang; Ratajczak, Mariusz Z; Kucia, Magda

    2012-07-01

    Recently, we identified a population of Oct4(+)Sca-1(+)Lin(-)CD45(-) very small embryonic-like stem cells (VSELs) in murine and human adult tissues. VSELs can differentiate in vitro into cells from all 3 germ layers and in vivo tissue-committed stem cells. Open chromatin structure of core pluripotency transcription factors (TFs) supports the pluripotent state of VSELs. However, it has been difficult to determine how primitive VSELs maintain pluripotency, owing to their limited number in adult tissues. Here, we demonstrate by genome-wide gene-expression analysis with a small number of highly purified murine bone marrow-derived VSELs that Oct4(+) VSELs (i) express a similar, yet nonidentical, transcriptome as embryonic stem cells (ESCs), (ii) highly express cell cycle checkpoint genes, (iii) express at a low level genes involved in protein turnover and mitogenic pathways, and (iv) highly express enhancer of zeste drosophila homolog 2 (Ezh2), a polycomb group protein. Furthermore, as a result of high expression of Ezh2, VSELs, like ESCs, exhibit bivalently modified nucleosomes (trimethylated H3K27 and H3K4) at promoters of important homeodomain-containing developmental TFs, thus preventing premature activation of the lineage-committing factors. Notably, spontaneous or RNA interference-enforced downregulation of Ezh2 during VSEL differentiation removes the bivalent domain (BD) structure, which leads to de-repression of several BD-regulated genes. Therefore, we suggest that Oct4(+) VSELs, like other pluripotent stem cells, maintain their pluripotent state through an Ezh2-dependent BD-mediated epigenetic mechanism. Furthermore, our global survey of VSEL gene expression signature would not only advance our understanding of biological process for their pluripotency, differentiation, and quiescence but should also help to develop better protocols for ex vivo expansion of VSELs.

  18. Analyses Reveal Record-Shattering Global Warm Temperatures in 2015

    NASA Image and Video Library

    2017-09-28

    2015 was the warmest year since modern record-keeping began in 1880, according to a new analysis by NASA’s Goddard Institute for Space Studies. The record-breaking year continues a long-term warming trend — 15 of the 16 warmest years on record have now occurred since 2001. Credits: Scientific Visualization Studio/Goddard Space Flight Center Details: Earth’s 2015 surface temperatures were the warmest since modern record keeping began in 1880, according to independent analyses by NASA and the National Oceanic and Atmospheric Administration (NOAA). Globally-averaged temperatures in 2015 shattered the previous mark set in 2014 by 0.23 degrees Fahrenheit (0.13 Celsius). Only once before, in 1998, has the new record been greater than the old record by this much. The 2015 temperatures continue a long-term warming trend, according to analyses by scientists at NASA’s Goddard Institute for Space Studies (GISS) in New York (GISTEMP). NOAA scientists agreed with the finding that 2015 was the warmest year on record based on separate, independent analyses of the data. Because weather station locations and measurements change over time, there is some uncertainty in the individual values in the GISTEMP index. Taking this into account, NASA analysis estimates 2015 was the warmest year with 94 percent certainty. Read more: www.nasa.gov/press-release/nasa-noaa-analyses-reveal-reco... NASA image use policy. NASA Goddard Space Flight Center enables NASA’s mission through four scientific endeavors: Earth Science, Heliophysics, Solar System Exploration, and Astrophysics. Goddard plays a leading role in NASA’s accomplishments by contributing compelling scientific knowledge to advance the Agency’s mission. Follow us on Twitter Like us on Facebook Find us on Instagram

  19. Large scale analysis of co-existing post-translational modifications in histone tails reveals global fine structure of cross-talk.

    PubMed

    Schwämmle, Veit; Aspalter, Claudia-Maria; Sidoli, Simone; Jensen, Ole N

    2014-07-01

    Mass spectrometry (MS) is a powerful analytical method for the identification and quantification of co-existing post-translational modifications in histone proteins. One of the most important challenges in current chromatin biology is to characterize the relationships between co-existing histone marks, the order and hierarchy of their deposition, and their distinct biological functions. We developed the database CrossTalkDB to organize observed and reported co-existing histone marks as revealed by MS experiments of histone proteins and their derived peptides. Statistical assessment revealed sample-specific patterns for the co-frequency of histone post-translational modifications. We implemented a new method to identify positive and negative interplay between pairs of methylation and acetylation marks in proteins. Many of the detected features were conserved between different cell types or exist across species, thereby revealing general rules for cross-talk between histone marks. The observed features are in accordance with previously reported examples of cross-talk. We observed novel types of interplay among acetylated residues, revealing positive cross-talk between nearby acetylated sites but negative cross-talk for distant ones, and for discrete methylation states at Lys-9, Lys-27, and Lys-36 of histone H3, suggesting a more differentiated functional role of methylation beyond the general expectation of enhanced activity at higher methylation states.

  20. Satellite-detected fluorescence reveals global physiology of ocean phytoplankton

    NASA Astrophysics Data System (ADS)

    Behrenfeld, M. J.; Westberry, T. K.; Boss, E. S.; O'Malley, R. T.; Siegel, D. A.; Wiggert, J. D.; Franz, B. A.; McClain, C. R.; Feldman, G. C.; Doney, S. C.; Moore, J. K.; Dall'Olmo, G.; Milligan, A. J.; Lima, I.; Mahowald, N.

    2009-05-01

    Phytoplankton photosynthesis links global ocean biology and climate-driven fluctuations in the physical environment. These interactions are largely expressed through changes in phytoplankton physiology, but physiological status has proven extremely challenging to characterize globally. Phytoplankton fluorescence does provide a rich source of physiological information long exploited in laboratory and field studies, and is now observed from space. Here we evaluate the physiological underpinnings of global variations in satellite-based phytoplankton chlorophyll fluorescence. The three dominant factors influencing fluorescence distributions are chlorophyll concentration, pigment packaging effects on light absorption, and light-dependent energy-quenching processes. After accounting for these three factors, resultant global distributions of quenching-corrected fluorescence quantum yields reveal a striking consistency with anticipated patterns of iron availability. High fluorescence quantum yields are typically found in low iron waters, while low quantum yields dominate regions where other environmental factors are most limiting to phytoplankton growth. Specific properties of photosynthetic membranes are discussed that provide a mechanistic view linking iron stress to satellite-detected fluorescence. Our results present satellite-based fluorescence as a valuable tool for evaluating nutrient stress predictions in ocean ecosystem models and give the first synoptic observational evidence that iron plays an important role in seasonal phytoplankton dynamics of the Indian Ocean. Satellite fluorescence may also provide a path for monitoring climate-phytoplankton physiology interactions and improving descriptions of phytoplankton light use efficiencies in ocean productivity models.

  1. GRID-seq reveals the global RNA-chromatin interactome.

    PubMed

    Li, Xiao; Zhou, Bing; Chen, Liang; Gou, Lan-Tao; Li, Hairi; Fu, Xiang-Dong

    2017-09-18

    Higher eukaryotic genomes are bound by a large number of coding and non-coding RNAs, but approaches to comprehensively map the identity and binding sites of these RNAs are lacking. Here we report a method to capture in situ global RNA interactions with DNA by deep sequencing (GRID-seq), which enables the comprehensive identification of the entire repertoire of chromatin-interacting RNAs and their respective binding sites. In human, mouse, and Drosophila cells, we detected a large set of tissue-specific coding and non-coding RNAs that are bound to active promoters and enhancers, especially super-enhancers. Assuming that most mRNA-chromatin interactions indicate the physical proximity of a promoter and an enhancer, we constructed a three-dimensional global connectivity map of promoters and enhancers, revealing transcription-activity-linked genomic interactions in the nucleus.

  2. Comparative transcriptomic analysis reveals the oncogenic fusion protein PAX3-FOXO1 globally alters mRNA and miRNA to enhance myoblast invasion

    PubMed Central

    Loupe, J M; Miller, P J; Bonner, B P; Maggi, E C; Vijayaraghavan, J; Crabtree, J S; Taylor, C M; Zabaleta, J; Hollenbach, A D

    2016-01-01

    Rhabdomyosarcoma, one of the most common childhood sarcomas, is comprised of two main subtypes, embryonal and alveolar (ARMS). ARMS, the more aggressive subtype, is primarily characterized by the t(2;13)(p35;p14) chromosomal translocation, which fuses two transcription factors, PAX3 and FOXO1 to generate the oncogenic fusion protein PAX3-FOXO1. Patients with PAX3-FOXO1-postitive tumors have a poor prognosis, in part due to the enhanced local invasive capacity of these cells, which leads to the increased metastatic potential for this tumor. Despite this knowledge, little is known about the role that the oncogenic fusion protein has in this increased invasive potential. In this report we use large-scale comparative transcriptomic analyses in physiologically relevant primary myoblasts to demonstrate that the presence of PAX3-FOXO1 is sufficient to alter the expression of 70 mRNA and 27 miRNA in a manner predicted to promote cellular invasion. In contrast the expression of PAX3 alters 60 mRNA and 23 miRNA in a manner predicted to inhibit invasion. We demonstrate that these alterations in mRNA and miRNA translate into changes in the invasive potential of primary myoblasts with PAX3-FOXO1 increasing invasion nearly 2-fold while PAX3 decreases invasion nearly 4-fold. Taken together, these results allow us to build off of previous reports and develop a more expansive molecular model by which the presence of PAX3-FOXO1 alters global gene regulatory networks to enhance the local invasiveness of cells. Further, the global nature of our observed changes highlights the fact that instead of focusing on a single-gene target, we must develop multi-faceted treatment regimens targeting multiple genes of a single oncogenic phenotype or multiple genes that target different oncogenic phenotypes for tumor progression. PMID:27454080

  3. USE OF TRANSCRIPTIONAL COUPLING AND KEGG PATHWAY ANALYSIS OF GLOBAL GENE EXPRESSION TO REVEAL TRANSCRIPTIONAL CHANGES BETWEEN STATIONARY- AND LOG-PHASE SALMONELLA TYPHIMURIUM LT2

    EPA Science Inventory

    DNA microarray analysis is plagued by a lack of data reproducibility and by limits to the detectability of transcripts by hybridization. To mitigate these limitations, we employed transcriptional coupling within the S. typhimurium genome. This genome has 2664 transcriptionally co...

  4. USE OF TRANSCRIPTIONAL COUPLING AND KEGG PATHWAY ANALYSIS OF GLOBAL GENE EXPRESSION TO REVEAL TRANSCRIPTIONAL CHANGES BETWEEN STATIONARY- AND LOG-PHASE SALMONELLA TYPHIMURIUM LT2

    EPA Science Inventory

    DNA microarray analysis is plagued by a lack of data reproducibility and by limits to the detectability of transcripts by hybridization. To mitigate these limitations, we employed transcriptional coupling within the S. typhimurium genome. This genome has 2664 transcriptionally co...

  5. Highly expressed amino acid biosynthesis genes revealed by global gene expression analysis of Salmonella enterica serovar Enteritidis during growth in whole egg are not essential for this growth.

    PubMed

    Jakočiūnė, Džiuginta; Herrero-Fresno, Ana; Jelsbak, Lotte; Olsen, John Elmerdahl

    2016-05-02

    Salmonella enterica serovar Enteritidis (S. Enteritidis) is the most common cause of egg borne salmonellosis in many parts of the world. This study analyzed gene expression of this bacterium during growth in whole egg, and whether highly expressed genes were essential for the growth. High quality RNA was extracted from S. Enteritidis using a modified RNA-extraction protocol. Global gene expression during growth in whole egg was compared to growth in LB-medium using DNA array method. Twenty-six genes were significantly upregulated during growth in egg; these belonged to amino acid biosynthesis, di/oligopeptide transport system, biotin synthesis, ferrous iron transport system, and type III secretion system. Significant downregulation of 15 genes related to formate hydrogenlyase (FHL) and trehalose metabolism was observed. The results suggested that S. Enteritidis is starved for amino-acids, biotin and iron when growing in egg. However, site specific mutation of amino acid biosynthesis genes asnA (17.3 fold upregulated), asnB (18.6 fold upregulated), asnA/asnB and, serA (12.0 fold upregulated) and gdhA (3.7 fold upregulated), did not result in growth attenuation, suggesting that biosynthesis using the enzymes encoded from these genes may represent the first choice for S. Enteritidis when growing in egg, but when absent, the bacterium could use alternative ways to obtain the amino acids.

  6. Global isotope metabolomics reveals adaptive strategies for nitrogen assimilation

    DOE PAGES

    Kurczy, Michael E.; Forsberg, Erica M.; Thorgersen, Michael P.; ...

    2016-04-05

    Nitrogen cycling is a microbial metabolic process essential for global ecological/agricultural balance. To investigate the link between the well-established ammonium and the alternative nitrate assimilation metabolic pathways, global isotope metabolomics was employed to examine three nitrate reducing bacteria using 15NO3 as a nitrogen source. In contrast to a control (Pseudomonas stutzeri RCH2), the results show that two of the isolates from Oak Ridge, Tennessee (Pseudomonas N2A2 and N2E2) utilize nitrate and ammonia for assimilation concurrently with differential labeling observed across multiple classes of metabolites including amino acids and nucleotides. The data reveal that the N2A2 and N2E2 strains conserve nitrogen-containingmore » metabolites, indicating that the nitrate assimilation pathway is a conservation mechanism for the assimilation of nitrogen. Co-utilization of nitrate and ammonia is likely an adaption to manage higher levels of nitrite since the denitrification pathways utilized by the N2A2 and N2E2 strains from the Oak Ridge site are predisposed to the accumulation of the toxic nitrite. In conclusion, the use of global isotope metabolomics allowed for this adaptive strategy to be investigated, which would otherwise not have been possible to decipher.« less

  7. Global isotope metabolomics reveals adaptive strategies for nitrogen assimilation

    SciTech Connect

    Kurczy, Michael E.; Forsberg, Erica M.; Thorgersen, Michael P.; Poole, Farris L.; Benton, H. Paul; Ivanisevic, Julijana; Tran, Minerva L.; Wall, Judy D.; Elias, Dwayne A.; Adams, Michael W. W.; Siuzdak, Gary

    2016-04-05

    Nitrogen cycling is a microbial metabolic process essential for global ecological/agricultural balance. To investigate the link between the well-established ammonium and the alternative nitrate assimilation metabolic pathways, global isotope metabolomics was employed to examine three nitrate reducing bacteria using 15NO3 as a nitrogen source. In contrast to a control (Pseudomonas stutzeri RCH2), the results show that two of the isolates from Oak Ridge, Tennessee (Pseudomonas N2A2 and N2E2) utilize nitrate and ammonia for assimilation concurrently with differential labeling observed across multiple classes of metabolites including amino acids and nucleotides. The data reveal that the N2A2 and N2E2 strains conserve nitrogen-containing metabolites, indicating that the nitrate assimilation pathway is a conservation mechanism for the assimilation of nitrogen. Co-utilization of nitrate and ammonia is likely an adaption to manage higher levels of nitrite since the denitrification pathways utilized by the N2A2 and N2E2 strains from the Oak Ridge site are predisposed to the accumulation of the toxic nitrite. In conclusion, the use of global isotope metabolomics allowed for this adaptive strategy to be investigated, which would otherwise not have been possible to decipher.

  8. Global Isotope Metabolomics Reveals Adaptive Strategies for Nitrogen Assimilation.

    PubMed

    Kurczy, Michael E; Forsberg, Erica M; Thorgersen, Michael P; Poole, Farris L; Benton, H Paul; Ivanisevic, Julijana; Tran, Minerva L; Wall, Judy D; Elias, Dwayne A; Adams, Michael W W; Siuzdak, Gary

    2016-06-17

    Nitrogen cycling is a microbial metabolic process essential for global ecological/agricultural balance. To investigate the link between the well-established ammonium and the alternative nitrate assimilation metabolic pathways, global isotope metabolomics was employed to examine three nitrate reducing bacteria using (15)NO3 as a nitrogen source. In contrast to a control (Pseudomonas stutzeri RCH2), the results show that two of the isolates from Oak Ridge, Tennessee (Pseudomonas N2A2 and N2E2) utilize nitrate and ammonia for assimilation concurrently with differential labeling observed across multiple classes of metabolites including amino acids and nucleotides. The data reveal that the N2A2 and N2E2 strains conserve nitrogen-containing metabolites, indicating that the nitrate assimilation pathway is a conservation mechanism for the assimilation of nitrogen. Co-utilization of nitrate and ammonia is likely an adaption to manage higher levels of nitrite since the denitrification pathways utilized by the N2A2 and N2E2 strains from the Oak Ridge site are predisposed to the accumulation of the toxic nitrite. The use of global isotope metabolomics allowed for this adaptive strategy to be investigated, which would otherwise not have been possible to decipher.

  9. Global transcriptome analysis reveals extensive gene remodeling, alternative splicing and differential transcription profiles in non-seed vascular plant Selaginella moellendorffii.

    PubMed

    Zhu, Yan; Chen, Longxian; Zhang, Chengjun; Hao, Pei; Jing, Xinyun; Li, Xuan

    2017-01-25

    Selaginella moellendorffii, a lycophyte, is a model plant to study the early evolution and development of vascular plants. As the first and only sequenced lycophyte to date, the genome of S. moellendorffii revealed many conserved genes and pathways, as well as specialized genes different from flowering plants. Despite the progress made, little is known about long noncoding RNAs (lncRNA) and the alternative splicing (AS) of coding genes in S. moellendorffii. Its coding gene models have not been fully validated with transcriptome data. Furthermore, it remains important to understand whether the regulatory mechanisms similar to flowering plants are used, and how they operate in a non-seed primitive vascular plant. RNA-sequencing (RNA-seq) was performed for three S. moellendorffii tissues, root, stem, and leaf, by constructing strand-specific RNA-seq libraries from RNA purified using RiboMinus isolation protocol. A total of 176 million reads (44 Gbp) were obtained from three tissue types, and were mapped to S. moellendorffii genome. By comparing with 22,285 existing gene models of S. moellendorffii, we identified 7930 high-confidence novel coding genes (a 35.6% increase), and for the first time reported 4422 lncRNAs in a lycophyte. Further, we refined 2461 (11.0%) of existing gene models, and identified 11,030 AS events (for 5957 coding genes) revealed for the first time for lycophytes. Tissue-specific gene expression with functional implication was analyzed, and 1031, 554, and 269 coding genes, and 174, 39, and 17 lncRNAs were identified in root, stem, and leaf tissues, respectively. The expression of critical genes for vascular development stages, i.e. formation of provascular cells, xylem specification and differentiation, and phloem specification and differentiation, was compared in S. moellendorffii tissues, indicating a less complex regulatory mechanism in lycophytes than in flowering plants. The results were further strengthened by the evolutionary trend of

  10. Global transcription analysis of Krebs tricarboxylic acid cycle mutants reveals an alternating pattern of gene expression and effects on hypoxic and oxidative genes.

    PubMed

    McCammon, Mark T; Epstein, Charles B; Przybyla-Zawislak, Beata; McAlister-Henn, Lee; Butow, Ronald A

    2003-03-01

    To understand the many roles of the Krebs tricarboxylic acid (TCA) cycle in cell function, we used DNA microarrays to examine gene expression in response to TCA cycle dysfunction. mRNA was analyzed from yeast strains harboring defects in each of 15 genes that encode subunits of the eight TCA cycle enzymes. The expression of >400 genes changed at least threefold in response to TCA cycle dysfunction. Many genes displayed a common response to TCA cycle dysfunction indicative of a shift away from oxidative metabolism. Another set of genes displayed a pairwise, alternating pattern of expression in response to contiguous TCA cycle enzyme defects: expression was elevated in aconitase and isocitrate dehydrogenase mutants, diminished in alpha-ketoglutarate dehydrogenase and succinyl-CoA ligase mutants, elevated again in succinate dehydrogenase and fumarase mutants, and diminished again in malate dehydrogenase and citrate synthase mutants. This pattern correlated with previously defined TCA cycle growth-enhancing mutations and suggested a novel metabolic signaling pathway monitoring TCA cycle function. Expression of hypoxic/anaerobic genes was elevated in alpha-ketoglutarate dehydrogenase mutants, whereas expression of oxidative genes was diminished, consistent with a heme signaling defect caused by inadequate levels of the heme precursor, succinyl-CoA. These studies have revealed extensive responses to changes in TCA cycle function and have uncovered new and unexpected metabolic networks that are wired into the TCA cycle.

  11. Global Oct4 target gene analysis reveals novel downstream PTEN and TNC genes required for drug-resistance and metastasis in lung cancer

    PubMed Central

    Tang, Yen-An; Chen, Chi-Hsin; Sun, H. Sunny; Cheng, Chun-Pei; Tseng, Vincent S.; Hsu, Han-Shui; Su, Wu-Chou; Lai, Wu-Wei; Wang, Yi-Ching

    2015-01-01

    Overexpression of Oct4, a stemness gene encoding a transcription factor, has been reported in several cancers. However, the mechanism by which Oct4 directs transcriptional program that leads to somatic cancer progression remains unclear. In this study, we provide mechanistic insight into Oct4-driven transcriptional network promoting drug-resistance and metastasis in lung cancer cell, animal and clinical studies. Through an integrative approach combining our Oct4 chromatin-immunoprecipitation sequencing and ENCODE datasets, we identified the genome-wide binding regions of Oct4 in lung cancer at promoter and enhancer of numerous genes involved in critical pathways which promote tumorigenesis. Notably, PTEN and TNC were previously undefined targets of Oct4. In addition, novel Oct4-binding motifs were found to overlap with DNA elements for Sp1 transcription factor. We provided evidence that Oct4 suppressed PTEN in an Sp1-dependent manner by recruitment of HDAC1/2, leading to activation of AKT signaling and drug-resistance. In contrast, Oct4 transactivated TNC independent of Sp1 and resulted in cancer metastasis. Clinically, lung cancer patients with Oct4 high, PTEN low and TNC high expression profile significantly correlated with poor disease-free survival. Our study reveals a critical Oct4-driven transcriptional program that promotes lung cancer progression, illustrating the therapeutic potential of targeting Oc4 transcriptionally regulated genes. PMID:25609695

  12. Global analysis of human duplicated genes reveals the relative importance of whole-genome duplicates originated in the early vertebrate evolution.

    PubMed

    Acharya, Debarun; Ghosh, Tapash C

    2016-01-22

    Gene duplication is a genetic mutation that creates functionally redundant gene copies that are initially relieved from selective pressures and may adapt themselves to new functions with time. The levels of gene duplication may vary from small-scale duplication (SSD) to whole genome duplication (WGD). Studies with yeast revealed ample differences between these duplicates: Yeast WGD pairs were functionally more similar, less divergent in subcellular localization and contained a lesser proportion of essential genes. In this study, we explored the differences in evolutionary genomic properties of human SSD and WGD genes, with the identifiable human duplicates coming from the two rounds of whole genome duplication occurred early in vertebrate evolution. We observed that these two groups of duplicates were also dissimilar in terms of their evolutionary and genomic properties. But interestingly, this is not like the same observed in yeast. The human WGDs were found to be functionally less similar, diverge more in subcellular level and contain a higher proportion of essential genes than the SSDs, all of which are opposite from yeast. Additionally, we explored that human WGDs were more divergent in their gene expression profile, have higher multifunctionality and are more often associated with disease, and are evolutionarily more conserved than human SSDs. Our study suggests that human WGD duplicates are more divergent and entails the adaptation of WGDs to novel and important functions that consequently lead to their evolutionary conservation in the course of evolution.

  13. Global Considerations in Hierarchical Clustering Reveal Meaningful Patterns in Data

    PubMed Central

    Varshavsky, Roy; Horn, David; Linial, Michal

    2008-01-01

    Background A hierarchy, characterized by tree-like relationships, is a natural method of organizing data in various domains. When considering an unsupervised machine learning routine, such as clustering, a bottom-up hierarchical (BU, agglomerative) algorithm is used as a default and is often the only method applied. Methodology/Principal Findings We show that hierarchical clustering that involve global considerations, such as top-down (TD, divisive), or glocal (global-local) algorithms are better suited to reveal meaningful patterns in the data. This is demonstrated, by testing the correspondence between the results of several algorithms (TD, glocal and BU) and the correct annotations provided by experts. The correspondence was tested in multiple domains including gene expression experiments, stock trade records and functional protein families. The performance of each of the algorithms is evaluated by statistical criteria that are assigned to clusters (nodes of the hierarchy tree) based on expert-labeled data. Whereas TD algorithms perform better on global patterns, BU algorithms perform well and are advantageous when finer granularity of the data is sought. In addition, a novel TD algorithm that is based on genuine density of the data points is presented and is shown to outperform other divisive and agglomerative methods. Application of the algorithm to more than 500 protein sequences belonging to ion-channels illustrates the potential of the method for inferring overlooked functional annotations. ClustTree, a graphical Matlab toolbox for applying various hierarchical clustering algorithms and testing their quality is made available. Conclusions Although currently rarely used, global approaches, in particular, TD or glocal algorithms, should be considered in the exploratory process of clustering. In general, applying unsupervised clustering methods can leverage the quality of manually-created mapping of proteins families. As demonstrated, it can also provide

  14. Global Analysis of the Fungal Microbiome in Cystic Fibrosis Patients Reveals Loss of Function of the Transcriptional Repressor Nrg1 as a Mechanism of Pathogen Adaptation

    PubMed Central

    Kim, Sang Hu; Clark, Shawn T.; Surendra, Anuradha; Copeland, Julia K.; Wang, Pauline W.; Ammar, Ron; Collins, Cathy; Tullis, D. Elizabeth; Nislow, Corey; Hwang, David M.; Guttman, David S.; Cowen, Leah E.

    2015-01-01

    The microbiome shapes diverse facets of human biology and disease, with the importance of fungi only beginning to be appreciated. Microbial communities infiltrate diverse anatomical sites as with the respiratory tract of healthy humans and those with diseases such as cystic fibrosis, where chronic colonization and infection lead to clinical decline. Although fungi are frequently recovered from cystic fibrosis patient sputum samples and have been associated with deterioration of lung function, understanding of species and population dynamics remains in its infancy. Here, we coupled high-throughput sequencing of the ribosomal RNA internal transcribed spacer 1 (ITS1) with phenotypic and genotypic analyses of fungi from 89 sputum samples from 28 cystic fibrosis patients. Fungal communities defined by sequencing were concordant with those defined by culture-based analyses of 1,603 isolates from the same samples. Different patients harbored distinct fungal communities. There were detectable trends, however, including colonization with Candida and Aspergillus species, which was not perturbed by clinical exacerbation or treatment. We identified considerable inter- and intra-species phenotypic variation in traits important for host adaptation, including antifungal drug resistance and morphogenesis. While variation in drug resistance was largely between species, striking variation in morphogenesis emerged within Candida species. Filamentation was uncoupled from inducing cues in 28 Candida isolates recovered from six patients. The filamentous isolates were resistant to the filamentation-repressive effects of Pseudomonas aeruginosa, implicating inter-kingdom interactions as the selective force. Genome sequencing revealed that all but one of the filamentous isolates harbored mutations in the transcriptional repressor NRG1; such mutations were necessary and sufficient for the filamentous phenotype. Six independent nrg1 mutations arose in Candida isolates from different patients

  15. Global Analysis of the Fungal Microbiome in Cystic Fibrosis Patients Reveals Loss of Function of the Transcriptional Repressor Nrg1 as a Mechanism of Pathogen Adaptation.

    PubMed

    Kim, Sang Hu; Clark, Shawn T; Surendra, Anuradha; Copeland, Julia K; Wang, Pauline W; Ammar, Ron; Collins, Cathy; Tullis, D Elizabeth; Nislow, Corey; Hwang, David M; Guttman, David S; Cowen, Leah E

    2015-11-01

    The microbiome shapes diverse facets of human biology and disease, with the importance of fungi only beginning to be appreciated. Microbial communities infiltrate diverse anatomical sites as with the respiratory tract of healthy humans and those with diseases such as cystic fibrosis, where chronic colonization and infection lead to clinical decline. Although fungi are frequently recovered from cystic fibrosis patient sputum samples and have been associated with deterioration of lung function, understanding of species and population dynamics remains in its infancy. Here, we coupled high-throughput sequencing of the ribosomal RNA internal transcribed spacer 1 (ITS1) with phenotypic and genotypic analyses of fungi from 89 sputum samples from 28 cystic fibrosis patients. Fungal communities defined by sequencing were concordant with those defined by culture-based analyses of 1,603 isolates from the same samples. Different patients harbored distinct fungal communities. There were detectable trends, however, including colonization with Candida and Aspergillus species, which was not perturbed by clinical exacerbation or treatment. We identified considerable inter- and intra-species phenotypic variation in traits important for host adaptation, including antifungal drug resistance and morphogenesis. While variation in drug resistance was largely between species, striking variation in morphogenesis emerged within Candida species. Filamentation was uncoupled from inducing cues in 28 Candida isolates recovered from six patients. The filamentous isolates were resistant to the filamentation-repressive effects of Pseudomonas aeruginosa, implicating inter-kingdom interactions as the selective force. Genome sequencing revealed that all but one of the filamentous isolates harbored mutations in the transcriptional repressor NRG1; such mutations were necessary and sufficient for the filamentous phenotype. Six independent nrg1 mutations arose in Candida isolates from different patients

  16. Global Genome Comparative Analysis Reveals Insights of Resistome and Life-Style Adaptation of Pseudomonas putida Strain T2-2 in Oral Cavity

    PubMed Central

    How, Kah Yan; Yin, Wai-Fong; Chan, Kok-Gan

    2014-01-01

    Most Pseudomonas putida strains are environmental microorganisms exhibiting a wide range of metabolic capability but certain strains have been reported as rare opportunistic pathogens and some emerged as multidrug resistant P. putida. This study aimed to assess the drug resistance profile of, via whole genome analysis, P. putida strain T2-2 isolated from oral cavity. At the same time, we also compared the nonenvironmental strain with environmentally isolated P. putida. In silico comparative genome analysis with available reference strains of P. putida shows that T2-2 has lesser gene counts on carbohydrate and aromatic compounds metabolisms, which suggested its little versatility. The detection of its edd gene also suggested T2-2's catabolism of glucose via ED pathway instead of EMP pathway. On the other hand, its drug resistance profile was observed via in silico gene prediction and most of the genes found were in agreement with drug-susceptibility testing in laboratory by automated VITEK 2. In addition, the finding of putative genes of multidrug resistance efflux pump and ATP-binding cassette transporters in this strain suggests a multidrug resistant phenotype. In summary, it is believed that multiple metabolic characteristics and drug resistance in P. putida strain T2-2 helped in its survival in human oral cavity. PMID:25436236

  17. A yield-associated gene TaCWI, in wheat: its function, selection and evolution in global breeding revealed by haplotype analysis.

    PubMed

    Jiang, Yanmiao; Jiang, Qiyan; Hao, Chenyang; Hou, Jian; Wang, Lanfen; Zhang, Hongna; Zhang, Suna; Chen, Xinhong; Zhang, Xueyong

    2015-01-01

    Wheat anther-specific invertase genes were haplotyped in wheat. Strong allelic selection occurred during wheat polyploidization, domestication and breeding because of their association with yield traits. Plant invertase hydrolyzes sucrose into glucose and fructose. Cell wall invertase (CWI), one of the three types of invertase, is essential for plant development. Based on isolated TaCWI genes from chromosomes 4A, 5B and 5D, two SNPs were detected in the promoter region of TaCWI-4A, and four SNPs and two Indels were present in the TaCWI-5D gene. No polymorphism was detected in TaCWI-5B coding or promoter regions. CAPS markers caps4A and caps5D were developed to discriminate haplotypes of TaCWI-4A and TaCWI-5D. Marker/trait association analysis indicated that Hap-5D-C at TaCWI-5D was significantly associated with higher thousand kernel weight (TKW) in 348 Chinese modern cultivars grown in multiple environments. Geographic distributions and changes over time of favored haplotypes showed that Hap-5D-C was the most frequent haplotype in modern cultivars and was strongly positively selected in six major wheat production regions worldwide. However, selection for haplotypes at TaCWI-4A was not so evident, possibly due to balancing effects of the two haplotypes on TKW and grain number per spike (GN). In rainfed production regions, Hap-4A-C was favored because it brought more seeds, but in well irrigated conditions, Hap-4A-T was favored in modern breeding because of higher TKW. Evolutionary analysis among wheat and its relatives showed that genetic diversity of TaCWI genes on chromosomes 4A and 5D declined dramatically in progression from the diploid level to modern polyploid cultivars. There was strong allelic selection during polyploidization, domestication and breeding.

  18. Global and Targeted Lipid Analysis of Gemmata obscuriglobus Reveals the Presence of Lipopolysaccharide, a Signature of the Classical Gram-Negative Outer Membrane

    PubMed Central

    Mahat, Rajendra; Seebart, Corrine

    2015-01-01

    ABSTRACT Planctomycete bacteria possess many unusual cellular properties, contributing to a cell plan long considered to be unique among the bacteria. However, data from recent studies are more consistent with a modified Gram-negative cell plan. A key feature of the Gram-negative plan is the presence of an outer membrane (OM), for which lipopolysaccharide (LPS) is a signature molecule. Despite genomic evidence for an OM in planctomycetes, no biochemical verification has been reported. We attempted to detect and characterize LPS in the planctomycete Gemmata obscuriglobus. We obtained direct evidence for LPS and lipid A using electrophoresis and differential staining. Gas chromatography-mass spectrometry (GC-MS) compositional analysis of LPS extracts identified eight different 3-hydroxy fatty acids (3-HOFAs), 2-keto 3-deoxy-d-manno-octulosonic acid (Kdo), glucosamine, and hexose and heptose sugars, a chemical profile unique to Gram-negative LPS. Combined with molecular/structural information collected from matrix-assisted laser desorption ionization–time of flight (MALDI-TOF) MS analysis of putative intact lipid A, these data led us to propose a heterogeneous hexa-acylated lipid A structure (multiple-lipid A species). We also confirmed previous reports of G. obscuriglobus whole-cell fatty acid (FA) and sterol compositions and detected a novel polyunsaturated FA (PUFA). Our confirmation of LPS, and by implication an OM, in G. obscuriglobus raises the possibility that other planctomycetes possess an OM. The pursuit of this question, together with studies of the structural connections between planctomycete LPS and peptidoglycans, will shed more light on what appears to be a planctomycete variation on the Gram-negative cell plan. IMPORTANCE Bacterial species are classified as Gram positive or negative based on their cell envelope structure. For 25 years, the envelope of planctomycete bacteria has been considered a unique exception, as it lacks peptidoglycan and an

  19. Quantitative analysis of tissue deformation dynamics reveals three characteristic growth modes and globally aligned anisotropic tissue deformation during chick limb development.

    PubMed

    Morishita, Yoshihiro; Kuroiwa, Atsushi; Suzuki, Takayuki

    2015-05-01

    Tissue-level characterization of deformation dynamics is crucial for understanding organ morphogenetic mechanisms, especially the interhierarchical links among molecular activities, cellular behaviors and tissue/organ morphogenetic processes. Limb development is a well-studied topic in vertebrate organogenesis. Nevertheless, there is still little understanding of tissue-level deformation relative to molecular and cellular dynamics. This is mainly because live recording of detailed cell behaviors in whole tissues is technically difficult. To overcome this limitation, by applying a recently developed Bayesian approach, we here constructed tissue deformation maps for chick limb development with high precision, based on snapshot lineage tracing using dye injection. The precision of the constructed maps was validated with a clear statistical criterion. From the geometrical analysis of the map, we identified three characteristic tissue growth modes in the limb and showed that they are consistent with local growth factor activity and cell cycle length. In particular, we report that SHH signaling activity changes dynamically with developmental stage and strongly correlates with the dynamic shift in the tissue growth mode. We also found anisotropic tissue deformation along the proximal-distal axis. Morphogenetic simulation and experimental studies suggested that this directional tissue elongation, and not local growth, has the greatest impact on limb shaping. This result was supported by the novel finding that anisotropic tissue elongation along the proximal-distal axis occurs independently of cell proliferation. Our study marks a pivotal point for multi-scale system understanding in vertebrate development. © 2015. Published by The Company of Biologists Ltd.

  20. Global analysis of physical and functional RNA targets of hnRNP L reveals distinct sequence and epigenetic features of repressed and enhanced exons

    PubMed Central

    Cole, Brian S.; Tapescu, Iulia; Allon, Samuel J.; Mallory, Michael J.; Qiu, Jinsong; Lake, Robert J.; Fan, Hua-Ying; Fu, Xiang-Dong; Lynch, Kristen W.

    2015-01-01

    HnRNP L is a ubiquitous splicing-regulatory protein that is critical for the development and function of mammalian T cells. Previous work has identified a few targets of hnRNP L-dependent alternative splicing in T cells and has described transcriptome-wide association of hnRNP L with RNA. However, a comprehensive analysis of the impact of hnRNP L on mRNA expression remains lacking. Here we use next-generation sequencing to identify transcriptome changes upon depletion of hnRNP L in a model T-cell line. We demonstrate that hnRNP L primarily regulates cassette-type alternative splicing, with minimal impact of hnRNP L depletion on transcript abundance, intron retention, or other modes of alternative splicing. Strikingly, we find that binding of hnRNP L within or flanking an exon largely correlates with exon repression by hnRNP L. In contrast, exons that are enhanced by hnRNP L generally lack proximal hnRNP L binding. Notably, these hnRNP L-enhanced exons share sequence and context features that correlate with poor nucleosome positioning, suggesting that hnRNP may enhance inclusion of a subset of exons via a cotranscriptional or epigenetic mechanism. Our data demonstrate that hnRNP L controls inclusion of a broad spectrum of alternative cassette exons in T cells and suggest both direct RNA regulation as well as indirect mechanisms sensitive to the epigenetic landscape. PMID:26437669

  1. Computational methods for global/local analysis

    NASA Technical Reports Server (NTRS)

    Ransom, Jonathan B.; Mccleary, Susan L.; Aminpour, Mohammad A.; Knight, Norman F., Jr.

    1992-01-01

    Computational methods for global/local analysis of structures which include both uncoupled and coupled methods are described. In addition, global/local analysis methodology for automatic refinement of incompatible global and local finite element models is developed. Representative structural analysis problems are presented to demonstrate the global/local analysis methods.

  2. Global Geometric Affinity for Revealing High Fidelity Protein Interaction Network

    PubMed Central

    Fang, Yi; Benjamin, William; Sun, Mengtian; Ramani, Karthik

    2011-01-01

    Protein-protein interaction (PPI) network analysis presents an essential role in understanding the functional relationship among proteins in a living biological system. Despite the success of current approaches for understanding the PPI network, the large fraction of missing and spurious PPIs and a low coverage of complete PPI network are the sources of major concern. In this paper, based on the diffusion process, we propose a new concept of global geometric affinity and an accompanying computational scheme to filter the uncertain PPIs, namely, reduce the spurious PPIs and recover the missing PPIs in the network. The main concept defines a diffusion process in which all proteins simultaneously participate to define a similarity metric (global geometric affinity (GGA)) to robustly reflect the internal connectivity among proteins. The robustness of the GGA is attributed to propagating the local connectivity to a global representation of similarity among proteins in a diffusion process. The propagation process is extremely fast as only simple matrix products are required in this computation process and thus our method is geared toward applications in high-throughput PPI networks. Furthermore, we proposed two new approaches that determine the optimal geometric scale of the PPI network and the optimal threshold for assigning the PPI from the GGA matrix. Our approach is tested with three protein-protein interaction networks and performs well with significant random noises of deletions and insertions in true PPIs. Our approach has the potential to benefit biological experiments, to better characterize network data sets, and to drive new discoveries. PMID:21559288

  3. Global phylogenetic structure of the hyperdiverse ant genus Pheidole reveals the repeated evolution of macroecological patterns

    PubMed Central

    Economo, Evan P.; Klimov, Pavel; Sarnat, Eli M.; Guénard, Benoit; Weiser, Michael D.; Lecroq, Beatrice; Knowles, L. Lacey

    2015-01-01

    Adaptive radiations are of particular interest owing to what they reveal about the ecological and evolutionary regulation of biodiversity. This applies to localized island radiations such as Darwin's finches, and also to rapid radiations occurring on a global scale. Here we analyse the macroevolution and macroecology of Pheidole, a famously hyperdiverse and ecologically dominant ant genus. We generate and analyse four novel datasets: (i) a robust global phylogeny including 285 Pheidole species, (ii) a global database on regional Pheidole richness in 365 political areas summarizing over 97 000 individual records from more than 6500 studies, (iii) a global database of Pheidole richness from 3796 local communities and (iv) a database of Pheidole body sizes across species. Analysis of the potential climate drivers of richness revealed that the patterns are statistically very similar across different biogeographic regions, with both regional and local richness associated with the same coefficients of temperature and precipitation. This similarity occurs even though phylogenetic analysis shows that Pheidole reached dominance in communities through serial localized radiations into different biomes within different continents and islands. Pheidole body size distributions have likewise converged across geographical regions. We propose these cases of convergence indicate that the global radiation of Pheidole is structured by deterministic factors regulating diversification and diversity. PMID:25429013

  4. Global Population Genetic Structure of Caenorhabditis remanei Reveals Incipient Speciation

    PubMed Central

    Dey, Alivia; Jeon, Yong; Wang, Guo-Xiu; Cutter, Asher D.

    2012-01-01

    Mating system transitions dramatically alter the evolutionary trajectories of genomes that can be revealed by contrasts of species with disparate modes of reproduction. For such transitions in Caenorhabditis nematodes, some major causes of genome variation in selfing species have been discerned. And yet, we have only limited understanding of species-wide population genetic processes for their outcrossing relatives, which represent the reproductive state of the progenitors of selfing species. Multilocus–multipopulation sequence polymorphism data provide a powerful means to uncover the historical demography and evolutionary processes that shape genomes. Here we survey nucleotide polymorphism across the X chromosome for three populations of the outcrossing nematode Caenorhabditis remanei and demonstrate its divergence from a fourth population describing a closely related new species from China, C. sp. 23. We find high genetic variation globally and within each local population sample. Despite geographic barriers and moderate genetic differentiation between Europe and North America, considerable gene flow connects C. remanei populations. We discovered C. sp. 23 while investigating C. remanei, observing strong genetic differentiation characteristic of reproductive isolation that was confirmed by substantial F2 hybrid breakdown in interspecific crosses. That C. sp. 23 represents a distinct biological species provides a cautionary example of how standard practice can fail for mating tests of species identity in this group. This species pair permits full application of divergence population genetic methods to obligately outcrossing species of Caenorhabditis and also presents a new focus for interrogation of the genetics and evolution of speciation with the Caenorhabditis model system. PMID:22649079

  5. Analyses Reveal Record-Shattering Global Warm Temperatures in 2015

    NASA Image and Video Library

    2016-01-20

    2015 was the warmest year since modern record-keeping began in 1880, according to a new analysis by NASA’s Goddard Institute for Space Studies. The record-breaking year continues a long-term warming trend — 15 of the 16 warmest years on record have now occurred since 2001. Credits: Scientific Visualization Studio/Goddard Space Flight Center Details: Earth’s 2015 surface temperatures were the warmest since modern record keeping began in 1880, according to independent analyses by NASA and the National Oceanic and Atmospheric Administration (NOAA). Globally-averaged temperatures in 2015 shattered the previous mark set in 2014 by 0.23 degrees Fahrenheit (0.13 Celsius). Only once before, in 1998, has the new record been greater than the old record by this much. The 2015 temperatures continue a long-term warming trend, according to analyses by scientists at NASA’s Goddard Institute for Space Studies (GISS) in New York (GISTEMP). NOAA scientists agreed with the finding that 2015 was the warmest year on record based on separate, independent analyses of the data. Because weather station locations and measurements change over time, there is some uncertainty in the individual values in the GISTEMP index. Taking this into account, NASA analysis estimates 2015 was the warmest year with 94 percent certainty.

  6. A global analysis of island pyrogeography

    NASA Astrophysics Data System (ADS)

    Trauernicht, C.; Murphy, B. P.

    2014-12-01

    Islands have provided insight into the ecological role of fire worldwide through research on the positive feedbacks between fire and nonnative grasses, particularly in the Hawaiian Islands. However, the global extent and frequency of fire on islands as an ecological disturbance has received little attention, possibly because 'natural fires' on islands are typically limited to infrequent dry lightning strikes and isolated volcanic events. But because most contemporary fires on islands are anthropogenic, islands provide ideal systems with which to understand the linkages between socio-economic development, shifting fire regimes, and ecological change. Here we use the density of satellite-derived (MODIS) active fire detections for the years 2000-2014 and global data sets of vegetation, climate, population density, and road development to examine the drivers of fire activity on islands at the global scale, and compare these results to existing pyrogeographic models derived from continental data sets. We also use the Hawaiian Islands as a case study to understand the extent to which novel fire regimes can pervade island ecosystems. The global analysis indicates that fire is a frequent disturbance across islands worldwide, strongly affected by human activities, indicating people can more readily override climatic drivers than on continental land masses. The extent of fire activity derived from local records in the Hawaiian Islands reveals that our global analysis likely underestimates the prevalence of fire among island systems and that the combined effects of human activity and invasion by nonnative grasses can create conditions for frequent and relatively large-scale fires. Understanding the extent of these novel fire regimes, and mitigating their impacts, is critical to reducing the current and rapid degradation of native island ecosystems worldwide.

  7. Network analysis of global influenza spread.

    PubMed

    Chan, Joseph; Holmes, Antony; Rabadan, Raul

    2010-11-18

    Although vaccines pose the best means of preventing influenza infection, strain selection and optimal implementation remain difficult due to antigenic drift and a lack of understanding global spread. Detecting viral movement by sequence analysis is complicated by skewed geographic and seasonal distributions in viral isolates. We propose a probabilistic method that accounts for sampling bias through spatiotemporal clustering and modeling regional and seasonal transmission as a binomial process. Analysis of H3N2 not only confirmed East-Southeast Asia as a source of new seasonal variants, but also increased the resolution of observed transmission to a country level. H1N1 data revealed similar viral spread from the tropics. Network analysis suggested China and Hong Kong as the origins of new seasonal H3N2 strains and the United States as a region where increased vaccination would maximally disrupt global spread of the virus. These techniques provide a promising methodology for the analysis of any seasonal virus, as well as for the continued surveillance of influenza.

  8. Water balance of global aquifers revealed by groundwater footprint.

    PubMed

    Gleeson, Tom; Wada, Yoshihide; Bierkens, Marc F P; van Beek, Ludovicus P H

    2012-08-09

    Groundwater is a life-sustaining resource that supplies water to billions of people, plays a central part in irrigated agriculture and influences the health of many ecosystems. Most assessments of global water resources have focused on surface water, but unsustainable depletion of groundwater has recently been documented on both regional and global scales. It remains unclear how the rate of global groundwater depletion compares to the rate of natural renewal and the supply needed to support ecosystems. Here we define the groundwater footprint (the area required to sustain groundwater use and groundwater-dependent ecosystem services) and show that humans are overexploiting groundwater in many large aquifers that are critical to agriculture, especially in Asia and North America. We estimate that the size of the global groundwater footprint is currently about 3.5 times the actual area of aquifers and that about 1.7 billion people live in areas where groundwater resources and/or groundwater-dependent ecosystems are under threat. That said, 80 per cent of aquifers have a groundwater footprint that is less than their area, meaning that the net global value is driven by a few heavily overexploited aquifers. The groundwater footprint is the first tool suitable for consistently evaluating the use, renewal and ecosystem requirements of groundwater at an aquifer scale. It can be combined with the water footprint and virtual water calculations, and be used to assess the potential for increasing agricultural yields with renewable groundwaterref. The method could be modified to evaluate other resources with renewal rates that are slow and spatially heterogeneous, such as fisheries, forestry or soil.

  9. Global transport of Asian dust revealed by NASA/CALIPSO and a global aerosol transport model

    NASA Astrophysics Data System (ADS)

    Eguchi, K.; Yumimoto, K.; Uno, I.; Takemura, T.

    2009-12-01

    Trans-Pacific transport of mineral dust and air pollutants originating from Asia to North America is well known. Eguchi et al. (2009, ACP) pointed out that the Taklimakan Desert supplies mineral dust for upper troposphere and can play an important role in intercontinental-scale dust transport. Asian dust is also detected from ice cores on Greenland and French Alps. The effects of Asian dust on cloud systems and the associated radiative forcing can extend over the Northern Hemisphere. In this study, we report the detailed structure of Asian dust during the global transport using integrated analysis of observations by CALIOP on-boarded NASA/CALIPSO satellite and a glocal aerosol transport model. We used the CALIOP Level 1B data products (ver. 2.01), containing the total attenuated backscatter coefficients at 532/1064 nm and the volume depolarization ratio at 532 nm. Dust extinction coefficients are then derived from the Fernald’s inversion method by setting the lidar ratio to S1=50 sr. As for a global aerosol transport model, we used the Spectral Radiation Transport Model for the Aerosol Species (SPRINTARS; Takemura et al., 2005, JGR). We performed a sensitivity experiment that aims at an analysis specified for a single dust event originating from the Taklimakan. The simulation was performed over May 2007. A sever dust storm occurred on 8-9 May 2007 in Taklimakan Desert. Dust cloud emitted during this dust storm is uplifted to altitude of 8-10 km and starts the travel of full circuit around the globe. It has a meridional width of 100-200 km. About one tenth of the original uplifted dust mass (8.1 Gg) is encircling the globe taking about 2 weeks. Because of its high transport height, the dust cloud almost unaffected by wet removal so that the decay of its concentration level is small. Over the western North Pacific of 2nd circuit, the dust cloud pulls down to the lower troposphere by anticyclonic down draft, and finally it settles on North Pacific because of wet

  10. New features of global climatology revealed by satellite-derived oceanic rainfall maps

    NASA Technical Reports Server (NTRS)

    Rao, M. S. V.; Theon, J. S.

    1977-01-01

    Quantitative rainfall maps over the oceanic areas of the globe were derived from the Nimbus 5 Electrically Scanning Microwave Radiometer (ESMR) data. Analysis of satellite derived oceanic rainfall maps reveal certain distinctive characteristics of global patterns for the years 1973-74. The main ones are (1) the forking of the Intertropical Convergence Zone in the Pacific, (2) a previously unrecognized rain area in the South Atlantic, (3) the bimodal behavior of rainbelts in the Indian Ocean and (4) the large interannual variability in oceanic rainfall. These features are discussed.

  11. Cool seafloor hydrothermal springs reveal global geochemical fluxes

    NASA Astrophysics Data System (ADS)

    Wheat, C. Geoffrey; Fisher, Andrew T.; McManus, James; Hulme, Samuel M.; Orcutt, Beth N.

    2017-10-01

    We present geochemical data from the first samples of spring fluids from Dorado Outcrop, a basaltic edifice on 23 M.y. old seafloor of the Cocos Plate, eastern Pacific Ocean. These samples were collected from the discharge of a cool hydrothermal system (CHS) on a ridge flank, where typical reaction temperatures in the volcanic crust are low (2-20 °C) and fluid residence times are short. Ridge-flank hydrothermal systems extract 25% of Earth's lithospheric heat, with a global discharge rate equivalent to that of Earth's river discharge to the ocean; CHSs comprise a significant fraction of this global flow. Upper crustal temperatures around Dorado Outcrop are ∼15 °C, the calculated residence time is <3 y, and the composition of discharging fluids is only slightly altered from bottom seawater. Many of the major ions concentrations in spring fluids are indistinguishable from those of bottom seawater; however, concentrations of Rb, Mo, V, U, Mg, phosphate, Si and Li are different. Applying these observed differences to calculated global CHS fluxes results in chemical fluxes for these ions that are ≥15% of riverine fluxes. Fluxes of K and B also may be significant, but better analytical resolution is required to confirm this result. Spring fluids also have ∼50% less dissolved oxygen (DO) than bottom seawater. Calculations of an analytical model suggest that the loss of DO occurs primarily (>80%) within the upper basaltic crust by biotic and/or abiotic consumption. This calculation demonstrates that permeable pathways within the upper crust can support oxic water-rock interactions for millions of years.

  12. Space flight alters bacterial gene expression and virulence and reveals a role for global regulator Hfq

    PubMed Central

    Wilson, J. W.; Ott, C. M.; zu Bentrup, K. Höner; Ramamurthy, R.; Quick, L.; Porwollik, S.; Cheng, P.; McClelland, M.; Tsaprailis, G.; Radabaugh, T.; Hunt, A.; Fernandez, D.; Richter, E.; Shah, M.; Kilcoyne, M.; Joshi, L.; Nelman-Gonzalez, M.; Hing, S.; Parra, M.; Dumars, P.; Norwood, K.; Bober, R.; Devich, J.; Ruggles, A.; Goulart, C.; Rupert, M.; Stodieck, L.; Stafford, P.; Catella, L.; Schurr, M. J.; Buchanan, K.; Morici, L.; McCracken, J.; Allen, P.; Baker-Coleman, C.; Hammond, T.; Vogel, J.; Nelson, R.; Pierson, D. L.; Stefanyshyn-Piper, H. M.; Nickerson, C. A.

    2007-01-01

    A comprehensive analysis of both the molecular genetic and phenotypic responses of any organism to the space flight environment has never been accomplished because of significant technological and logistical hurdles. Moreover, the effects of space flight on microbial pathogenicity and associated infectious disease risks have not been studied. The bacterial pathogen Salmonella typhimurium was grown aboard Space Shuttle mission STS-115 and compared with identical ground control cultures. Global microarray and proteomic analyses revealed that 167 transcripts and 73 proteins changed expression with the conserved RNA-binding protein Hfq identified as a likely global regulator involved in the response to this environment. Hfq involvement was confirmed with a ground-based microgravity culture model. Space flight samples exhibited enhanced virulence in a murine infection model and extracellular matrix accumulation consistent with a biofilm. Strategies to target Hfq and related regulators could potentially decrease infectious disease risks during space flight missions and provide novel therapeutic options on Earth. PMID:17901201

  13. Spaceflight Alters Bacterial Gene Expression and Virulence and Reveals Role for Global Regulator Hfq

    NASA Technical Reports Server (NTRS)

    Wilson, J. W.; Ott, C. M.; zuBentrup, K. Honer; Ramamurthy R.; Quick, L.; Porwollik, S.; Cheng, P.; McClellan, M.; Tsaprailis, G.; Radabaugh, T.; hide

    2007-01-01

    A comprehensive analysis of both the molecular genetic and phenotypic responses of any organism to the spaceflight environment has never been accomplished due to significant technological and logistical hurdles. Moreover, the effects of spaceflight on microbial pathogenicity and associated infectious disease risks have not been studied. The bacterial pathogen Salmonella typhimurium was grown aboard Space Shuttle mission STS-115 and compared to identical ground control cultures. Global microarray and proteomic analyses revealed 167 transcripts and 73 proteins changed expression with the conserved RNA-binding protein Hfq identified as a likely global regulator involved in the response to this environment. Hfq involvement was confirmed with a ground based microgravity culture model. Spaceflight samples exhibited enhanced virulence in a murine infection model and extracellular matrix accumulation consistent with a biofilm. Strategies to target Hfq and related regulators could potentially decrease infectious disease risks during spaceflight missions and provide novel therapeutic options on Earth.

  14. Space flight alters bacterial gene expression and virulence and reveals a role for global regulator Hfq.

    PubMed

    Wilson, J W; Ott, C M; Höner zu Bentrup, K; Ramamurthy, R; Quick, L; Porwollik, S; Cheng, P; McClelland, M; Tsaprailis, G; Radabaugh, T; Hunt, A; Fernandez, D; Richter, E; Shah, M; Kilcoyne, M; Joshi, L; Nelman-Gonzalez, M; Hing, S; Parra, M; Dumars, P; Norwood, K; Bober, R; Devich, J; Ruggles, A; Goulart, C; Rupert, M; Stodieck, L; Stafford, P; Catella, L; Schurr, M J; Buchanan, K; Morici, L; McCracken, J; Allen, P; Baker-Coleman, C; Hammond, T; Vogel, J; Nelson, R; Pierson, D L; Stefanyshyn-Piper, H M; Nickerson, C A

    2007-10-09

    A comprehensive analysis of both the molecular genetic and phenotypic responses of any organism to the space flight environment has never been accomplished because of significant technological and logistical hurdles. Moreover, the effects of space flight on microbial pathogenicity and associated infectious disease risks have not been studied. The bacterial pathogen Salmonella typhimurium was grown aboard Space Shuttle mission STS-115 and compared with identical ground control cultures. Global microarray and proteomic analyses revealed that 167 transcripts and 73 proteins changed expression with the conserved RNA-binding protein Hfq identified as a likely global regulator involved in the response to this environment. Hfq involvement was confirmed with a ground-based microgravity culture model. Space flight samples exhibited enhanced virulence in a murine infection model and extracellular matrix accumulation consistent with a biofilm. Strategies to target Hfq and related regulators could potentially decrease infectious disease risks during space flight missions and provide novel therapeutic options on Earth.

  15. Global response of M-I coulping revealed by AMPERE

    NASA Astrophysics Data System (ADS)

    Waters, C. L.; Anderson, B. J.; Korth, H.

    2014-12-01

    The Active Magnetosphere and Planetary Electrodynamics Response Experiment (AMPERE) provides one of the few in-situ datasets that allows studies of global properties of magnetosphere-ionosphere (M-I) interactions. The characterisation of the Birkeland currents, sensed by the Iridium constellation of satellites for both hemispheres simultaneously, is possible particularly for storm-time events. Other data sets (e.g. HF radar) that provide large spatial coverage may also be combined with AMPERE data in order to understand hemisphere differences in power input. In this presentation, we focus on the ability of AMPERE data to provide details of M-I coupling in both hemispheres simultaneously. The presentation will be illustrated using examples showing comparisons from north and south hemisphere Birkeland current configurations and Poynting flux.

  16. Global phosphoproteomic profiling reveals perturbed signaling in a mouse model of dilated cardiomyopathy

    PubMed Central

    Kuzmanov, Uros; Guo, Hongbo; Buchsbaum, Diana; Cosme, Jake; Abbasi, Cynthia; Isserlin, Ruth; Sharma, Parveen; Gramolini, Anthony O.; Emili, Andrew

    2016-01-01

    Phospholamban (PLN) plays a central role in Ca2+ homeostasis in cardiac myocytes through regulation of the sarco(endo)plasmic reticulum Ca2+-ATPase 2A (SERCA2A) Ca2+ pump. An inherited mutation converting arginine residue 9 in PLN to cysteine (R9C) results in dilated cardiomyopathy (DCM) in humans and transgenic mice, but the downstream signaling defects leading to decompensation and heart failure are poorly understood. Here we used precision mass spectrometry to study the global phosphorylation dynamics of 1,887 cardiac phosphoproteins in early affected heart tissue in a transgenic R9C mouse model of DCM compared with wild-type littermates. Dysregulated phosphorylation sites were quantified after affinity capture and identification of 3,908 phosphopeptides from fractionated whole-heart homogenates. Global statistical enrichment analysis of the differential phosphoprotein patterns revealed selective perturbation of signaling pathways regulating cardiovascular activity in early stages of DCM. Strikingly, dysregulated signaling through the Notch-1 receptor, recently linked to cardiomyogenesis and embryonic cardiac stem cell development and differentiation but never directly implicated in DCM before, was a prominently perturbed pathway. We verified alterations in Notch-1 downstream components in early symptomatic R9C transgenic mouse cardiomyocytes compared with wild type by immunoblot analysis and confocal immunofluorescence microscopy. These data reveal unexpected connections between stress-regulated cell signaling networks, specific protein kinases, and downstream effectors essential for proper cardiac function. PMID:27742792

  17. Global phosphoproteomic profiling reveals perturbed signaling in a mouse model of dilated cardiomyopathy.

    PubMed

    Kuzmanov, Uros; Guo, Hongbo; Buchsbaum, Diana; Cosme, Jake; Abbasi, Cynthia; Isserlin, Ruth; Sharma, Parveen; Gramolini, Anthony O; Emili, Andrew

    2016-11-01

    Phospholamban (PLN) plays a central role in Ca(2+) homeostasis in cardiac myocytes through regulation of the sarco(endo)plasmic reticulum Ca(2+)-ATPase 2A (SERCA2A) Ca(2+) pump. An inherited mutation converting arginine residue 9 in PLN to cysteine (R9C) results in dilated cardiomyopathy (DCM) in humans and transgenic mice, but the downstream signaling defects leading to decompensation and heart failure are poorly understood. Here we used precision mass spectrometry to study the global phosphorylation dynamics of 1,887 cardiac phosphoproteins in early affected heart tissue in a transgenic R9C mouse model of DCM compared with wild-type littermates. Dysregulated phosphorylation sites were quantified after affinity capture and identification of 3,908 phosphopeptides from fractionated whole-heart homogenates. Global statistical enrichment analysis of the differential phosphoprotein patterns revealed selective perturbation of signaling pathways regulating cardiovascular activity in early stages of DCM. Strikingly, dysregulated signaling through the Notch-1 receptor, recently linked to cardiomyogenesis and embryonic cardiac stem cell development and differentiation but never directly implicated in DCM before, was a prominently perturbed pathway. We verified alterations in Notch-1 downstream components in early symptomatic R9C transgenic mouse cardiomyocytes compared with wild type by immunoblot analysis and confocal immunofluorescence microscopy. These data reveal unexpected connections between stress-regulated cell signaling networks, specific protein kinases, and downstream effectors essential for proper cardiac function.

  18. Global resilience analysis of water distribution systems.

    PubMed

    Diao, Kegong; Sweetapple, Chris; Farmani, Raziyeh; Fu, Guangtao; Ward, Sarah; Butler, David

    2016-12-01

    Evaluating and enhancing resilience in water infrastructure is a crucial step towards more sustainable urban water management. As a prerequisite to enhancing resilience, a detailed understanding is required of the inherent resilience of the underlying system. Differing from traditional risk analysis, here we propose a global resilience analysis (GRA) approach that shifts the objective from analysing multiple and unknown threats to analysing the more identifiable and measurable system responses to extreme conditions, i.e. potential failure modes. GRA aims to evaluate a system's resilience to a possible failure mode regardless of the causal threat(s) (known or unknown, external or internal). The method is applied to test the resilience of four water distribution systems (WDSs) with various features to three typical failure modes (pipe failure, excess demand, and substance intrusion). The study reveals GRA provides an overview of a water system's resilience to various failure modes. For each failure mode, it identifies the range of corresponding failure impacts and reveals extreme scenarios (e.g. the complete loss of water supply with only 5% pipe failure, or still meeting 80% of demand despite over 70% of pipes failing). GRA also reveals that increased resilience to one failure mode may decrease resilience to another and increasing system capacity may delay the system's recovery in some situations. It is also shown that selecting an appropriate level of detail for hydraulic models is of great importance in resilience analysis. The method can be used as a comprehensive diagnostic framework to evaluate a range of interventions for improving system resilience in future studies.

  19. Revealing Student Teacher's Thinking through Dilemma Analysis

    ERIC Educational Resources Information Center

    Talanquer, Vicente; Tomanek, Debra; Novodvorsky, Ingrid

    2007-01-01

    We explore the potential of dilemma analysis as an assessment tool to reveal student teachers' thinking and concerns about their practice. For this purpose we analyze the dilemma analyses completed by 22 student teachers enrolled in our science teacher preparation program over a period of four semesters. Student teachers' dilemmas fall into two…

  20. Global hormone profiling of murine placenta reveals Secretin expression

    PubMed Central

    Knox, K.; Leuenberger, D.; Penn, A.A.; Baker, J.C.

    2013-01-01

    Objective To elucidate and categorize the murine placental hormones expressed across gestation, including the expression of hormones with previously undescribed roles. Study design Expression levels of all genes with known or predicted hormone activity expressed in two separate tissues, the placenta and maternal decidua, were assessed across a timecourse spanning the full lifetime of the placenta. Novel expression patterns were confirmed by in situ hybridization and protein level measurements. Results A combination of temporal and spatial information defines five groups that can accurately predict the patterns of uncharacterized hormones. Our analysis identified Secretin, a novel placental hormone that is expressed specifically by the trophoblast at levels many times greater than in any other tissue. Conclusions The characteristics of Secretin fit the paradigm of known placental hormones and suggest that it may play an important role during pregnancy. PMID:21944867

  1. SILAC for global phosphoproteomic analysis.

    PubMed

    Pimienta, Genaro; Chaerkady, Raghothama; Pandey, Akhilesh

    2009-01-01

    Establishing the phosphorylation pattern of proteins in a comprehensive fashion is an important goal of a majority of cell signaling projects. Phosphoproteomic strategies should be designed in such a manner as to identify sites of phosphorylation as well as to provide quantitative information about the extent of phosphorylation at the sites. In this chapter, we describe an experimental strategy that outlines such an approach using stable isotope labeling with amino acids in cell culture (SILAC) coupled to LC-MS/MS. We highlight the importance of quantitative strategies in signal transduction as a platform for a systematic and global elucidation of biological processes.

  2. Revealing Student Teachers' Thinking through Dilemma Analysis

    NASA Astrophysics Data System (ADS)

    Talanquer, Vicente; Tomanek, Debra; Novodvorsky, Ingrid

    2007-06-01

    We explore the potential of dilemma analysis as an assessment tool to reveal student teachers’ thinking and concerns about their practice. For this purpose we analyze the dilemma analyses completed by 22 student teachers enrolled in our science teacher preparation program over a period of four semesters. Student teachers’ dilemmas fall into two main groups: dilemmas about student performance and dilemmas associated with instructional decisions. These dilemmas reveal a variety of concerns that student teachers have about their work. In particular, concerns about lack of student motivation and its consequences on performance and instruction play a central role in student teachers’ thinking. The recognition of common patterns of thought in our student teacher thinking has made us reflect on and re-evaluate important components of the curriculum in our science teacher preparation program.

  3. Sensitivity analysis, optimization, and global critical points

    SciTech Connect

    Cacuci, D.G. )

    1989-11-01

    The title of this paper suggests that sensitivity analysis, optimization, and the search for critical points in phase-space are somehow related; the existence of such a kinship has been undoubtedly felt by many of the nuclear engineering practitioners of optimization and/or sensitivity analysis. However, a unified framework for displaying this relationship has so far been lacking, especially in a global setting. The objective of this paper is to present such a global and unified framework and to suggest, within this framework, a new direction for future developments for both sensitivity analysis and optimization of the large nonlinear systems encountered in practical problems.

  4. Global analysis of photosynthesis transcriptional regulatory networks.

    PubMed

    Imam, Saheed; Noguera, Daniel R; Donohue, Timothy J

    2014-12-01

    Photosynthesis is a crucial biological process that depends on the interplay of many components. This work analyzed the gene targets for 4 transcription factors: FnrL, PrrA, CrpK and MppG (RSP_2888), which are known or predicted to control photosynthesis in Rhodobacter sphaeroides. Chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) identified 52 operons under direct control of FnrL, illustrating its regulatory role in photosynthesis, iron homeostasis, nitrogen metabolism and regulation of sRNA synthesis. Using global gene expression analysis combined with ChIP-seq, we mapped the regulons of PrrA, CrpK and MppG. PrrA regulates ∼34 operons encoding mainly photosynthesis and electron transport functions, while CrpK, a previously uncharacterized Crp-family protein, regulates genes involved in photosynthesis and maintenance of iron homeostasis. Furthermore, CrpK and FnrL share similar DNA binding determinants, possibly explaining our observation of the ability of CrpK to partially compensate for the growth defects of a ΔFnrL mutant. We show that the Rrf2 family protein, MppG, plays an important role in photopigment biosynthesis, as part of an incoherent feed-forward loop with PrrA. Our results reveal a previously unrealized, high degree of combinatorial regulation of photosynthetic genes and significant cross-talk between their transcriptional regulators, while illustrating previously unidentified links between photosynthesis and the maintenance of iron homeostasis.

  5. Global Profiling of Protein Lysine Malonylation in Escherichia coli Reveals Its Role in Energy Metabolism.

    PubMed

    Qian, Lili; Nie, Litong; Chen, Ming; Liu, Ping; Zhu, Jun; Zhai, Linhui; Tao, Sheng-Ce; Cheng, Zhongyi; Zhao, Yingming; Tan, Minjia

    2016-06-03

    Protein lysine malonylation is a recently identified post-translational modification (PTM), which is evolutionarily conserved from bacteria to mammals. Although analysis of lysine malonylome in mammalians suggested that this modification was related to energy metabolism, the substrates and biological roles of malonylation in prokaryotes are still poorly understood. In this study, we performed qualitative and quantitative analyses to globally identify lysine malonylation substrates in Escherichia coli. We identified 1745 malonylation sites in 594 proteins in E. coli, representing the first and largest malonylome data set in prokaryotes up to date. Bioinformatic analyses showed that lysine malonylation was significantly enriched in protein translation, energy metabolism pathways and fatty acid biosynthesis, implying the potential roles of protein malonylation in bacterial physiology. Quantitative proteomics by fatty acid synthase inhibition in both auxotrophic and prototrophic E. coli strains revealed that lysine malonylation is closely associated with E. coli fatty acid metabolism. Protein structural analysis and mutagenesis experiment suggested malonylation could impact enzymatic activity of citrate synthase, a key enzyme in citric acid (TCA) cycle. Further comparative analysis among lysine malonylome, succinylome and acetylome data showed that these three modifications could participate in some similar enriched metabolism pathways, but they could also possibly play distinct roles such as in fatty acid synthesis. These data expanded our knowledge of lysine malonylation in prokaryotes, providing a resource for functional study of lysine malonylation in bacteria.

  6. Global multi-level analysis of the 'scientific food web'.

    PubMed

    Mazloumian, Amin; Helbing, Dirk; Lozano, Sergi; Light, Robert P; Börner, Katy

    2013-01-01

    We introduce a network-based index analyzing excess scientific production and consumption to perform a comprehensive global analysis of scholarly knowledge production and diffusion on the level of continents, countries, and cities. Compared to measures of scientific production and consumption such as number of publications or citation rates, our network-based citation analysis offers a more differentiated picture of the 'ecosystem of science'. Quantifying knowledge flows between 2000 and 2009, we identify global sources and sinks of knowledge production. Our knowledge flow index reveals, where ideas are born and consumed, thereby defining a global 'scientific food web'. While Asia is quickly catching up in terms of publications and citation rates, we find that its dependence on knowledge consumption has further increased.

  7. Global Analysis of Photosynthesis Transcriptional Regulatory Networks

    PubMed Central

    Imam, Saheed; Noguera, Daniel R.; Donohue, Timothy J.

    2014-01-01

    Photosynthesis is a crucial biological process that depends on the interplay of many components. This work analyzed the gene targets for 4 transcription factors: FnrL, PrrA, CrpK and MppG (RSP_2888), which are known or predicted to control photosynthesis in Rhodobacter sphaeroides. Chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) identified 52 operons under direct control of FnrL, illustrating its regulatory role in photosynthesis, iron homeostasis, nitrogen metabolism and regulation of sRNA synthesis. Using global gene expression analysis combined with ChIP-seq, we mapped the regulons of PrrA, CrpK and MppG. PrrA regulates ∼34 operons encoding mainly photosynthesis and electron transport functions, while CrpK, a previously uncharacterized Crp-family protein, regulates genes involved in photosynthesis and maintenance of iron homeostasis. Furthermore, CrpK and FnrL share similar DNA binding determinants, possibly explaining our observation of the ability of CrpK to partially compensate for the growth defects of a ΔFnrL mutant. We show that the Rrf2 family protein, MppG, plays an important role in photopigment biosynthesis, as part of an incoherent feed-forward loop with PrrA. Our results reveal a previously unrealized, high degree of combinatorial regulation of photosynthetic genes and significant cross-talk between their transcriptional regulators, while illustrating previously unidentified links between photosynthesis and the maintenance of iron homeostasis. PMID:25503406

  8. High-speed panoramic light-sheet microscopy reveals global endodermal cell dynamics

    PubMed Central

    Schmid, Benjamin; Shah, Gopi; Scherf, Nico; Weber, Michael; Thierbach, Konstantin; Campos, Citlali Pérez; Roeder, Ingo; Aanstad, Pia; Huisken, Jan

    2013-01-01

    The ever-increasing speed and resolution of modern microscopes make the storage and post-processing of images challenging and prevent thorough statistical analyses in developmental biology. Here, instead of deploying massive storage and computing power, we exploit the spherical geometry of zebrafish embryos by computing a radial maximum intensity projection in real time with a 240-fold reduction in data rate. In our four-lens selective plane illumination microscope (SPIM) setup the development of multiple embryos is recorded in parallel and a map of all labelled cells is obtained for each embryo in <10 s. In these panoramic projections, cell segmentation and flow analysis reveal characteristic migration patterns and global tissue remodelling in the early endoderm. Merging data from many samples uncover stereotypic patterns that are fundamental to endoderm development in every embryo. We demonstrate that processing and compressing raw image data in real time is not only efficient but indispensable for image-based systems biology. PMID:23884240

  9. Integrative annotation of human large intergenic noncoding RNAs reveals global properties and specific subclasses

    PubMed Central

    Cabili, Moran N.; Trapnell, Cole; Goff, Loyal; Koziol, Magdalena; Tazon-Vega, Barbara; Regev, Aviv; Rinn, John L.

    2011-01-01

    Large intergenic noncoding RNAs (lincRNAs) are emerging as key regulators of diverse cellular processes. Determining the function of individual lincRNAs remains a challenge. Recent advances in RNA sequencing (RNA-seq) and computational methods allow for an unprecedented analysis of such transcripts. Here, we present an integrative approach to define a reference catalog of >8000 human lincRNAs. Our catalog unifies previously existing annotation sources with transcripts we assembled from RNA-seq data collected from ∼4 billion RNA-seq reads across 24 tissues and cell types. We characterize each lincRNA by a panorama of >30 properties, including sequence, structural, transcriptional, and orthology features. We found that lincRNA expression is strikingly tissue-specific compared with coding genes, and that lincRNAs are typically coexpressed with their neighboring genes, albeit to an extent similar to that of pairs of neighboring protein-coding genes. We distinguish an additional subset of transcripts that have high evolutionary conservation but may include short ORFs and may serve as either lincRNAs or small peptides. Our integrated, comprehensive, yet conservative reference catalog of human lincRNAs reveals the global properties of lincRNAs and will facilitate experimental studies and further functional classification of these genes. PMID:21890647

  10. Population Genetic Analysis Reveals a High Genetic Diversity in the Brazilian Cryptococcus gattii VGII Population and Shifts the Global Origin from the Amazon Rainforest to the Semi-arid Desert in the Northeast of Brazil.

    PubMed

    Souto, Ana C P; Bonfietti, Lucas X; Ferreira-Paim, Kennio; Trilles, Luciana; Martins, Marilena; Ribeiro-Alves, Marcelo; Pham, Cau D; Martins, Liline; Dos Santos, Wallace; Chang, Marilene; Brito-Santos, Fabio; Santos, Dayane C S; Fortes, Silvana; Lockhart, Shawn R; Wanke, Bodo; Melhem, Márcia S C; Lazéra, Márcia S; Meyer, Wieland

    2016-08-01

    Cryptococcus neoformans and Cryptococcus gattii are responsible globally for almost one million cryptococcosis cases yearly, mostly in immunocompromised patients, such as those living with HIV. Infections due to C. gattii have mainly been described in tropical and subtropical regions, but its adaptation to temperate regions was crucial in the species evolution and highlighted the importance of this pathogenic yeast in the context of disease. Cryptococcus gattii molecular type VGII has come to the forefront in connection with an on-going emergence in the Pacific North West of North America. Taking into account that previous work pointed towards South America as an origin of this species, the present work aimed to assess the genetic diversity within the Brazilian C. gattii VGII population in order to gain new insights into its origin and global dispersal from the South American continent using the ISHAM consensus MLST typing scheme. Our results corroborate the finding that the Brazilian C. gattii VGII population is highly diverse. The diversity is likely due to recombination generated from sexual reproduction, as evidenced by the presence of both mating types in clinical and environmental samples. The data presented herein strongly supports the emergence of highly virulent strains from ancestors in the Northern regions of Brazil, Amazonia and the Northeast. Numerous genotypes represent a link between Brazil and other parts of the world reinforcing South America as the most likely origin of the C. gattii VGII subtypes and their subsequent global spread, including their dispersal into North America, where they caused a major emergence.

  11. Population Genetic Analysis Reveals a High Genetic Diversity in the Brazilian Cryptococcus gattii VGII Population and Shifts the Global Origin from the Amazon Rainforest to the Semi-arid Desert in the Northeast of Brazil

    PubMed Central

    Ferreira-Paim, Kennio; Trilles, Luciana; Martins, Marilena; Ribeiro-Alves, Marcelo; Pham, Cau D.; Martins, Liline; dos Santos, Wallace; Chang, Marilene; Brito-Santos, Fabio; Santos, Dayane C. S.; Fortes, Silvana; Lockhart, Shawn R.; Wanke, Bodo; Melhem, Márcia S. C.; Lazéra, Márcia S.; Meyer, Wieland

    2016-01-01

    Cryptococcus neoformans and Cryptococcus gattii are responsible globally for almost one million cryptococcosis cases yearly, mostly in immunocompromised patients, such as those living with HIV. Infections due to C. gattii have mainly been described in tropical and subtropical regions, but its adaptation to temperate regions was crucial in the species evolution and highlighted the importance of this pathogenic yeast in the context of disease. Cryptococcus gattii molecular type VGII has come to the forefront in connection with an on-going emergence in the Pacific North West of North America. Taking into account that previous work pointed towards South America as an origin of this species, the present work aimed to assess the genetic diversity within the Brazilian C. gattii VGII population in order to gain new insights into its origin and global dispersal from the South American continent using the ISHAM consensus MLST typing scheme. Our results corroborate the finding that the Brazilian C. gattii VGII population is highly diverse. The diversity is likely due to recombination generated from sexual reproduction, as evidenced by the presence of both mating types in clinical and environmental samples. The data presented herein strongly supports the emergence of highly virulent strains from ancestors in the Northern regions of Brazil, Amazonia and the Northeast. Numerous genotypes represent a link between Brazil and other parts of the world reinforcing South America as the most likely origin of the C. gattii VGII subtypes and their subsequent global spread, including their dispersal into North America, where they caused a major emergence. PMID:27529479

  12. Variational global analysis of satellite temperature soundings

    NASA Technical Reports Server (NTRS)

    Halem, M.; Kalnay, E.

    1983-01-01

    A variational spherical harmonic analysis is developed for the production of global geopotential height and geostropic wind fields from the TIROS-N spacecraft's temperature sounding profiles. This scheme is based on Tykhonov's (1964) regularization method, and the smoothing parameter is determined by cross validation. The scheme is noted to be stable and computationally efficient, and it does not depend on a priori information. Its applications to three-dimensional temperature retrievals and to four-dimensional spectral analyses are illustrated.

  13. The global analysis of DEER data.

    PubMed

    Brandon, Suzanne; Beth, Albert H; Hustedt, Eric J

    2012-05-01

    Double Electron-Electron Resonance (DEER) has emerged as a powerful technique for measuring long range distances and distance distributions between paramagnetic centers in biomolecules. This information can then be used to characterize functionally relevant structural and dynamic properties of biological molecules and their macromolecular assemblies. Approaches have been developed for analyzing experimental data from standard four-pulse DEER experiments to extract distance distributions. However, these methods typically use an a priori baseline correction to account for background signals. In the current work an approach is described for direct fitting of the DEER signal using a model for the distance distribution which permits a rigorous error analysis of the fitting parameters. Moreover, this approach does not require a priori background correction of the experimental data and can take into account excluded volume effects on the background signal when necessary. The global analysis of multiple DEER data sets is also demonstrated. Global analysis has the potential to provide new capabilities for extracting distance distributions and additional structural parameters in a wide range of studies.

  14. The global analysis of DEER data

    NASA Astrophysics Data System (ADS)

    Brandon, Suzanne; Beth, Albert H.; Hustedt, Eric J.

    2012-05-01

    Double Electron-Electron Resonance (DEER) has emerged as a powerful technique for measuring long range distances and distance distributions between paramagnetic centers in biomolecules. This information can then be used to characterize functionally relevant structural and dynamic properties of biological molecules and their macromolecular assemblies. Approaches have been developed for analyzing experimental data from standard four-pulse DEER experiments to extract distance distributions. However, these methods typically use an a priori baseline correction to account for background signals. In the current work an approach is described for direct fitting of the DEER signal using a model for the distance distribution which permits a rigorous error analysis of the fitting parameters. Moreover, this approach does not require a priori background correction of the experimental data and can take into account excluded volume effects on the background signal when necessary. The global analysis of multiple DEER data sets is also demonstrated. Global analysis has the potential to provide new capabilities for extracting distance distributions and additional structural parameters in a wide range of studies.

  15. A global analysis of neutrino oscillations

    NASA Astrophysics Data System (ADS)

    Fogli, G. L.; Lisi, E.; Marrone, A.; Montanino, D.; Palazzo, A.; Rotunno, A. M.

    2013-02-01

    We present a global analysis of neutrino oscillation data, including high-precision measurements of the neutrino mixing angle θ13 at reactor experiments, which have confirmed previous indications in favor of θ13>0. Recent data presented at this Conference are also included. We focus on the correlations between θ13 and the mixing angle θ23, as well as between θ13 and the neutrino CP-violation phase δ. We find interesting indications for θ23<π/4 and possible hints for δ˜π, with no significant difference between normal and inverted mass hierarchy.

  16. Global molecular phylogeography reveals persistent Arctic circumpolar isolation in a marine planktonic protist.

    PubMed

    Darling, Kate F; Kucera, Michal; Wade, Christopher M

    2007-03-20

    The high-latitude planktonic foraminifera have proved to be particularly useful model organisms for the study of global patterns of vicariance and gene flow in the oceans. Such studies demonstrate that gene flow can occur over enormous distances in the pelagic marine environment leading to cosmopolitanism but also that there are ecological and geographical barriers to gene flow producing biogeographic structure. Here, we have undertaken a comprehensive global study of genetic diversity within a marine protist species, the high-latitude planktonic foraminiferan Neogloboquadrina pachyderma. We present extensive new data sets from the North Pacific and Arctic Oceans that, in combination with our earlier data from the North Atlantic and Southern Oceans, allow us to determine the global phylogeography of this species. The new genetic data reveal a pattern of Arctic circumpolar isolation and bipolar asymmetry between the Atlantic and Pacific Oceans. We show that the ancestry of North Pacific N. pachyderma is relatively recent. It lies within the upwelling systems and subpolar waters of the Southern Hemisphere and remarkably not within the neighboring Arctic Ocean. Instead, the Arctic Ocean population forms a genetic continuum with the North Atlantic population, which became isolated from the southern populations much earlier, after the onset of Northern hemisphere glaciation. Data from the planktonic foraminiferal morphospecies Globigerina bulloides is also introduced to highlight the isolation and endemism found within the subpolar North Pacific gyre. These data provide perspective for interpretation and discussion of global gene flow and speciation patterns in the plankton.

  17. Global Proteomics Analysis of Protein Lysine Methylation.

    PubMed

    Cao, Xing-Jun; Garcia, Benjamin A

    2016-11-01

    Lysine methylation is a common protein post-translational modification dynamically mediated by protein lysine methyltransferases (PKMTs) and protein lysine demethylases (PKDMs). Beyond histone proteins, lysine methylation on non-histone proteins plays a substantial role in a variety of functions in cells and is closely associated with diseases such as cancer. A large body of evidence indicates that the dysregulation of some PKMTs leads to tumorigenesis via their non-histone substrates. However, most studies on other PKMTs have made slow progress owing to the lack of approaches for extensive screening of lysine methylation sites. However, recently, there has been a series of publications to perform large-scale analysis of protein lysine methylation. In this unit, we introduce a protocol for the global analysis of protein lysine methylation in cells by means of immunoaffinity enrichment and mass spectrometry. © 2016 by John Wiley & Sons, Inc. Copyright © 2016 John Wiley & Sons, Inc.

  18. Global Proteomics Analysis of Protein Lysine Methylation

    PubMed Central

    Cao, Xing-Jun; Garcia, Benjamin A.

    2017-01-01

    Lysine methylation is a common protein post-translational modification dynamically mediated by protein lysine methyltransferases (PKMTs) and demethylases (PKDMs). Beyond histone proteins, lysine methylation on non-histone proteins play substantial roles in a variety of functions in cells, and is closely associated with diseases such as cancer. A large body of evidence indicates that the dysregulation of some PKMTs lead to tumorigenesis via their non-histone substrates. However, more studies on other PKMTs have made slow progress owing to the lack of the approaches for extensive screening of lysine methylation sites. Recently a series of publications to perform large-scale analysis of protein lysine methylation have emerged. In this unit, we introduce a protocol for the global analysis of protein lysine methylation in cells by means of immunoaffinity enrichment and mass spectrometry. PMID:27801517

  19. On computational schemes for global-local stress analysis

    NASA Technical Reports Server (NTRS)

    Reddy, J. N.

    1989-01-01

    An overview is given of global-local stress analysis methods and associated difficulties and recommendations for future research. The phrase global-local analysis is understood to be an analysis in which some parts of the domain or structure are identified, for reasons of accurate determination of stresses and displacements or for more refined analysis than in the remaining parts. The parts of refined analysis are termed local and the remaining parts are called global. Typically local regions are small in size compared to global regions, while the computational effort can be larger in local regions than in global regions.

  20. Tsunamis: Global Exposure and Local Risk Analysis

    NASA Astrophysics Data System (ADS)

    Harbitz, C. B.; Løvholt, F.; Glimsdal, S.; Horspool, N.; Griffin, J.; Davies, G.; Frauenfelder, R.

    2014-12-01

    The 2004 Indian Ocean tsunami led to a better understanding of the likelihood of tsunami occurrence and potential tsunami inundation, and the Hyogo Framework for Action (HFA) was one direct result of this event. The United Nations International Strategy for Disaster Risk Reduction (UN-ISDR) adopted HFA in January 2005 in order to reduce disaster risk. As an instrument to compare the risk due to different natural hazards, an integrated worldwide study was implemented and published in several Global Assessment Reports (GAR) by UN-ISDR. The results of the global earthquake induced tsunami hazard and exposure analysis for a return period of 500 years are presented. Both deterministic and probabilistic methods (PTHA) are used. The resulting hazard levels for both methods are compared quantitatively for selected areas. The comparison demonstrates that the analysis is rather rough, which is expected for a study aiming at average trends on a country level across the globe. It is shown that populous Asian countries account for the largest absolute number of people living in tsunami prone areas, more than 50% of the total exposed people live in Japan. Smaller nations like Macao and the Maldives are among the most exposed by population count. Exposed nuclear power plants are limited to Japan, China, India, Taiwan, and USA. On the contrary, a local tsunami vulnerability and risk analysis applies information on population, building types, infrastructure, inundation, flow depth for a certain tsunami scenario with a corresponding return period combined with empirical data on tsunami damages and mortality. Results and validation of a GIS tsunami vulnerability and risk assessment model are presented. The GIS model is adapted for optimal use of data available for each study. Finally, the importance of including landslide sources in the tsunami analysis is also discussed.

  1. Quantitative interactome analysis reveals a chemoresistant edgotype

    PubMed Central

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

    2015-01-01

    Chemoresistance is a common mode of therapy failure for many cancers. Tumours develop resistance to chemotherapeutics through a variety of mechanisms, with proteins serving pivotal roles. Changes in protein conformations and interactions affect the cellular response to environmental conditions contributing to the development of new phenotypes. The ability to understand how protein interaction networks adapt to yield new function or alter phenotype is limited by the inability to determine structural and protein interaction changes on a proteomic scale. Here, chemical crosslinking and mass spectrometry were employed to quantify changes in protein structures and interactions in multidrug-resistant human carcinoma cells. Quantitative analysis of the largest crosslinking-derived, protein interaction network comprising 1,391 crosslinked peptides allows for ‘edgotype' analysis in a cell model of chemoresistance. We detect consistent changes to protein interactions and structures, including those involving cytokeratins, topoisomerase-2-alpha, and post-translationally modified histones, which correlate with a chemoresistant phenotype. PMID:26235782

  2. A global analysis of soil acidification caused by nitrogen addition

    NASA Astrophysics Data System (ADS)

    Tian, Dashuan; Niu, Shuli

    2015-02-01

    Nitrogen (N) deposition-induced soil acidification has become a global problem. However, the response patterns of soil acidification to N addition and the underlying mechanisms remain far from clear. Here, we conducted a meta-analysis of 106 studies to reveal global patterns of soil acidification in responses to N addition. We found that N addition significantly reduced soil pH by 0.26 on average globally. However, the responses of soil pH varied with ecosystem types, N addition rate, N fertilization forms, and experimental durations. Soil pH decreased most in grassland, whereas boreal forest was not observed a decrease to N addition in soil acidification. Soil pH decreased linearly with N addition rates. Addition of urea and NH4NO3 contributed more to soil acidification than NH4-form fertilizer. When experimental duration was longer than 20 years, N addition effects on soil acidification diminished. Environmental factors such as initial soil pH, soil carbon and nitrogen content, precipitation, and temperature all influenced the responses of soil pH. Base cations of Ca2+, Mg2+ and K+ were critical important in buffering against N-induced soil acidification at the early stage. However, N addition has shifted global soils into the Al3+ buffering phase. Overall, this study indicates that acidification in global soils is very sensitive to N deposition, which is greatly modified by biotic and abiotic factors. Global soils are now at a buffering transition from base cations (Ca2+, Mg2+ and K+) to non-base cations (Mn2+ and Al3+). This calls our attention to care about the limitation of base cations and the toxic impact of non-base cations for terrestrial ecosystems with N deposition.

  3. Global in Time Analysis and Sensitivity Analysis for the Reduced NS- α Model of Incompressible Flow

    NASA Astrophysics Data System (ADS)

    Rebholz, Leo; Zerfas, Camille; Zhao, Kun

    2017-09-01

    We provide a detailed global in time analysis, and sensitivity analysis and testing, for the recently proposed (by the authors) reduced NS- α model. We extend the known analysis of the model to the global in time case by proving it is globally well-posed, and also prove some new results for its long time treatment of energy. We also derive PDE system that describes the sensitivity of the model with respect to the filtering radius parameter, and prove it is well-posed. An efficient numerical scheme for the sensitivity system is then proposed and analyzed, and proven to be stable and optimally accurate. Finally, two physically meaningful test problems are simulated: channel flow past a cylinder (including lift and drag calculations) and turbulent channel flow with {Re_{τ}=590}. The numerical results reveal that sensitivity is created near boundaries, and thus this is where the choice of the filtering radius is most critical.

  4. Microbial mediation of biogeochemical cycles revealed by simulation of global changes with soil transplant and cropping

    PubMed Central

    Zhao, Mengxin; Xue, Kai; Wang, Feng; Liu, Shanshan; Bai, Shijie; Sun, Bo; Zhou, Jizhong; Yang, Yunfeng

    2014-01-01

    Despite microbes' key roles in driving biogeochemical cycles, the mechanism of microbe-mediated feedbacks to global changes remains elusive. Recently, soil transplant has been successfully established as a proxy to simulate climate changes, as the current trend of global warming coherently causes range shifts toward higher latitudes. Four years after southward soil transplant over large transects in China, we found that microbial functional diversity was increased, in addition to concurrent changes in microbial biomass, soil nutrient content and functional processes involved in the nitrogen cycle. However, soil transplant effects could be overridden by maize cropping, which was attributed to a negative interaction. Strikingly, abundances of nitrogen and carbon cycle genes were increased by these field experiments simulating global change, coinciding with higher soil nitrification potential and carbon dioxide (CO2) efflux. Further investigation revealed strong correlations between carbon cycle genes and CO2 efflux in bare soil but not cropped soil, and between nitrogen cycle genes and nitrification. These findings suggest that changes of soil carbon and nitrogen cycles by soil transplant and cropping were predictable by measuring microbial functional potentials, contributing to a better mechanistic understanding of these soil functional processes and suggesting a potential to incorporate microbial communities in greenhouse gas emission modeling. PMID:24694714

  5. Microbial mediation of biogeochemical cycles revealed by simulation of global changes with soil transplant and cropping.

    PubMed

    Zhao, Mengxin; Xue, Kai; Wang, Feng; Liu, Shanshan; Bai, Shijie; Sun, Bo; Zhou, Jizhong; Yang, Yunfeng

    2014-10-01

    Despite microbes' key roles in driving biogeochemical cycles, the mechanism of microbe-mediated feedbacks to global changes remains elusive. Recently, soil transplant has been successfully established as a proxy to simulate climate changes, as the current trend of global warming coherently causes range shifts toward higher latitudes. Four years after southward soil transplant over large transects in China, we found that microbial functional diversity was increased, in addition to concurrent changes in microbial biomass, soil nutrient content and functional processes involved in the nitrogen cycle. However, soil transplant effects could be overridden by maize cropping, which was attributed to a negative interaction. Strikingly, abundances of nitrogen and carbon cycle genes were increased by these field experiments simulating global change, coinciding with higher soil nitrification potential and carbon dioxide (CO2) efflux. Further investigation revealed strong correlations between carbon cycle genes and CO2 efflux in bare soil but not cropped soil, and between nitrogen cycle genes and nitrification. These findings suggest that changes of soil carbon and nitrogen cycles by soil transplant and cropping were predictable by measuring microbial functional potentials, contributing to a better mechanistic understanding of these soil functional processes and suggesting a potential to incorporate microbial communities in greenhouse gas emission modeling.

  6. The Tara Oceans voyage reveals global diversity and distribution patterns of marine planktonic ciliates

    PubMed Central

    Gimmler, Anna; Korn, Ralf; de Vargas, Colomban; Audic, Stéphane; Stoeck, Thorsten

    2016-01-01

    Illumina reads of the SSU-rDNA-V9 region obtained from the circumglobal Tara Oceans expedition allow the investigation of protistan plankton diversity patterns on a global scale. We analyzed 6,137,350 V9-amplicons from ocean surface waters and the deep chlorophyll maximum, which were taxonomically assigned to the phylum Ciliophora. For open ocean samples global planktonic ciliate diversity is relatively low (ca. 1,300 observed and predicted ciliate OTUs). We found that 17% of all detected ciliate OTUs occurred in all oceanic regions under study. On average, local ciliate OTU richness represented 27% of the global ciliate OTU richness, indicating that a large proportion of ciliates is widely distributed. Yet, more than half of these OTUs shared <90% sequence similarity with reference sequences of described ciliates. While alpha-diversity measures (richness and exp(Shannon H)) are hardly affected by contemporary environmental conditions, species (OTU) turnover and community similarity (β-diversity) across taxonomic groups showed strong correlation to environmental parameters. Logistic regression models predicted significant correlations between the occurrence of specific ciliate genera and individual nutrients, the oceanic carbonate system and temperature. Planktonic ciliates displayed distinct vertical distributions relative to chlorophyll a. In contrast, the Tara Oceans dataset did not reveal any evidence that latitude is structuring ciliate communities. PMID:27633177

  7. Deep sequencing reveals a global reprogramming of lncRNA transcriptome during EMT.

    PubMed

    Liao, Jian-You; Wu, Jue; Wang, Yan-Jie; He, Jie-Hua; Deng, Wei-Xi; Hu, KaiShun; Zhang, Yu-Chan; Zhang, Yin; Yan, Haiyan; Wang, Dan-Lan; Liu, Qiang; Zeng, Mu-Sheng; Phillip Koeffler, H; Song, Erwei; Yin, Dong

    2017-10-01

    Several studies have shown that long non-coding RNAs (lncRNAs) may play an essential role in Epithelial-Mesenchymal Transition (EMT), which is an important step in tumor metastasis; however, little is known about the global change of lncRNA transcriptome during EMT. To investigate how lncRNA transcriptome alterations contribute to EMT progression regulation, we deep-sequenced the whole-transcriptome of MCF10A as the cells underwent TGF-β-induced EMT. Deep-sequencing results showed that the long RNA transcriptome of MCF10A had undergone global changes as early as 8h after treatment with TGF-β. The expression of 3403 known and novel lncRNAs, and 570 known and novel circRNAs were altered during EMT. To identify the key lncRNA-regulator, we constructed the co-expression network and found all junction nodes in the network are lncRNAs. One junction node, RP6-65G23.5, was further verified as a key regulator of EMT. Intriguingly, we identified 216 clusters containing lncRNAs which were located in "gene desert" regions. The expressions of all lncRNAs in these clusters changed concurrently during EMT, strongly suggesting that these clusters might play important roles in EMT. Our study reveals a global reprogramming of lncRNAs transcriptome during EMT and provides clues for the future study of the molecular mechanism of EMT. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Global absolute quantification reveals tight regulation of protein expression in single Xenopus eggs.

    PubMed

    Smits, Arne H; Lindeboom, Rik G H; Perino, Matteo; van Heeringen, Simon J; Veenstra, Gert Jan C; Vermeulen, Michiel

    2014-09-01

    While recent developments in genomic sequencing technology have enabled comprehensive transcriptome analyses of single cells, single cell proteomics has thus far been restricted to targeted studies. Here, we perform global absolute protein quantification of fertilized Xenopus laevis eggs using mass spectrometry-based proteomics, quantifying over 5800 proteins in the largest single cell proteome characterized to date. Absolute protein amounts in single eggs are highly consistent, thus indicating a tight regulation of global protein abundance. Protein copy numbers in single eggs range from tens of thousands to ten trillion copies per cell. Comparison between the single-cell proteome and transcriptome reveal poor expression correlation. Finally, we identify 439 proteins that significantly change in abundance during early embryogenesis. Downregulated proteins include ribosomal proteins and upregulated proteins include basal transcription factors, among others. Many of these proteins do not show regulation at the transcript level. Altogether, our data reveal that the transcriptome is a poor indicator of the proteome and that protein levels are tightly controlled in X. laevis eggs.

  9. Global absolute quantification reveals tight regulation of protein expression in single Xenopus eggs

    PubMed Central

    Smits, Arne H.; Lindeboom, Rik G.H.; Perino, Matteo; van Heeringen, Simon J.; Veenstra, Gert Jan C.; Vermeulen, Michiel

    2014-01-01

    While recent developments in genomic sequencing technology have enabled comprehensive transcriptome analyses of single cells, single cell proteomics has thus far been restricted to targeted studies. Here, we perform global absolute protein quantification of fertilized Xenopus laevis eggs using mass spectrometry-based proteomics, quantifying over 5800 proteins in the largest single cell proteome characterized to date. Absolute protein amounts in single eggs are highly consistent, thus indicating a tight regulation of global protein abundance. Protein copy numbers in single eggs range from tens of thousands to ten trillion copies per cell. Comparison between the single-cell proteome and transcriptome reveal poor expression correlation. Finally, we identify 439 proteins that significantly change in abundance during early embryogenesis. Downregulated proteins include ribosomal proteins and upregulated proteins include basal transcription factors, among others. Many of these proteins do not show regulation at the transcript level. Altogether, our data reveal that the transcriptome is a poor indicator of the proteome and that protein levels are tightly controlled in X. laevis eggs. PMID:25056316

  10. Identification of lncRNA-associated competing triplets reveals global patterns and prognostic markers for cancer

    PubMed Central

    Wang, Peng; Ning, Shangwei; Zhang, Yunpeng; Li, Ronghong; Ye, Jingrun; Zhao, Zuxianglan; Zhi, Hui; Wang, Tingting; Guo, Zheng; Li, Xia

    2015-01-01

    Recent studies have suggested that long non-coding RNAs (lncRNAs) can interact with microRNAs (miRNAs) and indirectly regulate miRNA targets though competing interactions. However, the molecular mechanisms underlying these interactions are still largely unknown. In this study, these lncRNA–miRNA–gene interactions were defined as lncRNA-associated competing triplets (LncACTs), and an integrated pipeline was developed to identify lncACTs that are active in cancer. Competing lncRNAs had sponge features distinct from non-competing lncRNAs. In the lncACT cross-talk network, disease-associated lncRNAs, miRNAs and coding-genes showed specific topological patterns indicative of their competence and control of communication within the network. The construction of global competing activity profiles revealed that lncACTs had high activity specific to cancers. Analyses of clustered lncACTs revealed that they were enriched in various cancer-related biological processes. Based on the global cross-talk network and cluster analyses, nine cancer-specific sub-networks were constructed. H19- and BRCA1/2-associated lncACTs were able to discriminate between two groups of patients with different clinical outcomes. Disease-associated lncACTs also showed variable competing patterns across normal and cancer patient samples. In summary, this study uncovered and systematically characterized global properties of human lncACTs that may have prognostic value for predicting clinical outcome in cancer patients. PMID:25800746

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

    NASA Astrophysics Data System (ADS)

    Sun, A. Y.; Chen, J.; Donges, J.

    2015-07-01

    Terrestrial water storage (TWS) exerts a key control in global water, energy, and biogeochemical cycles. Although certain causal relationship exists between precipitation and TWS, the latter quantity 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 the hydrologic cycle, but also provide new insights and model calibration constraints for improving the current land surface models. This work is the first attempt to quantify the spatial connectivity of TWS using the complex 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 data sets, a remote sensing product that is obtained from the Gravity Recovery and Climate Experiment (GRACE) satellite mission, and a model-generated data set from the global land data assimilation system's NOAH model (GLDAS-NOAH). Both data sets have 1° × 1° grid 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 cutoff threshold derived from the edge-density function 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 the TWS anomaly hotspots around the globe and the patterns are consistent with recent GRACE studies. Parallel analyses of networks constructed using the two data sets reveal 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 further measures for constraining the current land surface models, especially in data sparse regions.

  12. Electric dipole moments: A global analysis

    NASA Astrophysics Data System (ADS)

    Chupp, Timothy; Ramsey-Musolf, Michael

    2015-03-01

    We perform a global analysis of searches for the permanent electric dipole moments (EDMs) of the neutron, neutral atoms, and molecules in terms of six leptonic, semileptonic, and nonleptonic interactions involving photons, electrons, pions, and nucleons. By translating the results into fundamental charge-conjugation-parity symmetry (CP) violating effective interactions through dimension six involving standard model particles, we obtain rough lower bounds on the scale of beyond the standard model CP-violating interactions ranging from 1.5 TeV for the electron EDM to 1300 TeV for the nuclear spin-independent electron-quark interaction. We show that planned future measurements involving systems or combinations of systems with complementary sensitivities to the low-energy parameters may extend the mass reach by an order of magnitude or more.

  13. Global analysis of population growth and river water quality

    NASA Astrophysics Data System (ADS)

    Wen, Yingrong; Schoups, Gerrit; van de Giesen, Nick

    2014-05-01

    Human-related pressures on river water quality are a concern of global proportions.. However, little is known about the more specific impact of increasing population on river water quality and how it provides a vital environmental reference for water management. Combining global gridded data on population and river discharge with digitized river networks, we conduct numerical simulations to demonstrate the direct impact of population growth on river water quality. Our model traces the transport, dilution, and degradation of anthropogenic organic matter (BOD) emissions into rivers. Spanning the period from the early 20th century to the present, our analysis indicates that the pressure on downstream river networks markedly increased since the population explosion starting in 1950, especially in developing countries. The ratio of population to river discharge reveals the link between impact severity and dilution capacity. In addition, a denser population is found to be correlated with higher impact severity. Consideration of direct population influences on global river water quality becomes limited as society develops and should be studied as a fundamental reference for human-related river water management. Keywords: Population growth, River water quality, Space-time analysis, Human activities, Water Management

  14. Global gene expression profiles reveal significant nuclear reprogramming by the blastocyst stage after cloning.

    PubMed

    Smith, Sadie L; Everts, Robin E; Tian, X Cindy; Du, Fuliang; Sung, Li-Ying; Rodriguez-Zas, Sandra L; Jeong, Byeong-Seon; Renard, Jean-Paul; Lewin, Harris A; Yang, Xiangzhong

    2005-12-06

    Nuclear transfer (NT) has potential applications in agriculture and biomedicine, but the technology is hindered by low efficiency. Global gene expression analysis of clones is important for the comprehensive study of nuclear reprogramming. Here, we compared global gene expression profiles of individual bovine NT blastocysts with their somatic donor cells and fertilized control embryos using cDNA microarray technology. The NT embryos' gene expression profiles were drastically different from those of their donor cells and closely resembled those of the naturally fertilized embryos. Our findings demonstrate that the NT embryos have undergone significant nuclear reprogramming by the blastocyst stage; however, problems may occur during redifferentiation for tissue genesis and organogenesis, and small reprogramming errors may be magnified downstream in development.

  15. Analysis of Globalization, the Planet and Education

    ERIC Educational Resources Information Center

    Tsegay, Samson Maekele

    2016-01-01

    Thorough the framework of theories analyzing globalization and education, this paper focuses on the intersection among globalization, the environment and education. This paper critically analyzes how globalization could affect environmental devastation, and explore the role of pedagogies that could foster planetary citizenship by exposing…

  16. Global Proteomics Reveal An Atypical Strategy for Carbon/Nitrogen Assimilation by a Cyanobacterium Under Diverse Environmental Perturbations

    SciTech Connect

    Wegener, Kimberly M.; Singh, Abhay K.; Jacobs, Jon M.; Elvitigala, Thanura R.; Welsh, Eric A.; Keren, Nir S.; Gritsenko, Marina A.; Ghosh, Bijoy K.; Camp, David G.; Smith, Richard D.; Pakrasi, Himadri B.

    2010-12-01

    Cyanobacteria, the only prokaryotes capable of oxygenic photosynthesis, are present in diverse ecological niches and play crucial roles in global carbon and nitrogen cycles. To proliferate in nature, cyanobacteria utilize a host of stress responses to accommodate periodic changes in environmental conditions. A detailed knowledge of the composition of, as well as the dynamic changes in, the proteome is necessary to gain fundamental insights into such stress responses. Toward this goal, we have performed a largescale proteomic analysis of the widely studied model cyanobacterium Synechocystis sp. PCC 6803 under 33 different environmental conditions. The resulting high-quality dataset consists of 22,318 unique peptides corresponding to 1,955 proteins, a coverage of 53% of the predicted proteome. Quantitative determination of protein abundances has led to the identification of 1,198 differentially regulated proteins. Notably, our analysis revealed that a common stress response under various environmental perturbations, irrespective of amplitude and duration, is the activation of atypical pathways for the acquisition of carbon and nitrogen from urea and arginine. In particular, arginine is catabolized via putrescine to produce succinate and glutamate, sources of carbon and nitrogen, respectively. This study provides the most comprehensive functional and quantitative analysis of the Synechocystis proteome to date, and shows that a significant stress response of cyanobacteria involves an uncommon mode of acquisition of carbon and nitrogen. Oxygenic phototrophic prokaryotes, the progenitors of the chloroplast, are crucial to global oxygen production and worldwide carbon and nitrogen cycles. These microalgae are robust organisms capable carbon neutral biofuel production. Synechocystis sp. PCC 6803 has historically been a model cyanobacterium for photosynthetic research and is emerging as a promising biofuel platform. Cellular responses are severely modified by environmental

  17. Global analysis of the immune response

    NASA Astrophysics Data System (ADS)

    Ribeiro, Leonardo C.; Dickman, Ronald; Bernardes, Américo T.

    2008-10-01

    The immune system may be seen as a complex system, characterized using tools developed in the study of such systems, for example, surface roughness and its associated Hurst exponent. We analyze densitometric (Panama blot) profiles of immune reactivity, to classify individuals into groups with similar roughness statistics. We focus on a population of individuals living in a region in which malaria endemic, as well as a control group from a disease-free region. Our analysis groups individuals according to the presence, or absence, of malaria symptoms and number of malaria manifestations. Applied to the Panama blot data, our method proves more effective at discriminating between groups than principal-components analysis or super-paramagnetic clustering. Our findings provide evidence that some phenomena observed in the immune system can be only understood from a global point of view. We observe similar tendencies between experimental immune profiles and those of artificial profiles, obtained from an immune network model. The statistical entropy of the experimental profiles is found to exhibit variations similar to those observed in the Hurst exponent.

  18. Global phylogeography of marine Synechococcus and Prochlorococcus reveals a distinct partitioning of lineages among oceanic biomes.

    PubMed

    Zwirglmaier, Katrin; Jardillier, Ludwig; Ostrowski, Martin; Mazard, Sophie; Garczarek, Laurence; Vaulot, Daniel; Not, Fabrice; Massana, Ramon; Ulloa, Osvaldo; Scanlan, Dave J

    2008-01-01

    Marine cyanobacteria of the genera Prochlorococcus and Synechococcus are important contributors to global primary production occupying a key position at the base of marine food webs. The genetically diverse nature of each genus is likely an important reason for their successful colonization of vast tracts of the world's oceans, a feature that has led to detailed analysis of the distribution of these genetic lineages at the local and ocean basin scale. Here, we extend these analyses to the global dimension, using new data from cruises in the Pacific, Indian and Arctic Oceans in combination with data from previous studies in the Atlantic Ocean, Arabian Sea, Red Sea and a circumnavigation of the southern hemisphere to form a data set which comprises most of the world's major ocean systems. We show that the distribution patterns of Prochlorococcus and Synechococcus lineages are remarkably similar in different ocean systems with comparable environmental conditions, but producing a strikingly different 'signature' in the four major ocean domains or biomes (the Polar Domain, Coastal Boundary Domain, Trade Winds Domain and Westerly Winds Domain). This clearly reiterates the idea of spatial partitioning of individual cyanobacterial lineages, but at the global scale.

  19. Digital epidemiology reveals global childhood disease seasonality and the effects of immunization

    PubMed Central

    2016-01-01

    Public health surveillance systems are important for tracking disease dynamics. In recent years, social and real-time digital data sources have provided new means of studying disease transmission. Such affordable and accessible data have the potential to offer new insights into disease epidemiology at national and international scales. We used the extensive information repository Google Trends to examine the digital epidemiology of a common childhood disease, chicken pox, caused by varicella zoster virus (VZV), over an 11-y period. We (i) report robust seasonal information-seeking behavior for chicken pox using Google data from 36 countries, (ii) validate Google data using clinical chicken pox cases, (iii) demonstrate that Google data can be used to identify recurrent seasonal outbreaks and forecast their magnitude and seasonal timing, and (iv) reveal that VZV immunization significantly dampened seasonal cycles in information-seeking behavior. Our findings provide strong evidence that VZV transmission is seasonal and that seasonal peaks show remarkable latitudinal variation. We attribute the dampened seasonal cycles in chicken pox information-seeking behavior to VZV vaccine-induced reduction of seasonal transmission. These data and the methodological approaches provide a way to track the global burden of childhood disease and illustrate population-level effects of immunization. The global latitudinal patterns in outbreak seasonality could direct future studies of environmental and physiological drivers of disease transmission. PMID:27247405

  20. Digital epidemiology reveals global childhood disease seasonality and the effects of immunization.

    PubMed

    Bakker, Kevin M; Martinez-Bakker, Micaela Elvira; Helm, Barbara; Stevenson, Tyler J

    2016-06-14

    Public health surveillance systems are important for tracking disease dynamics. In recent years, social and real-time digital data sources have provided new means of studying disease transmission. Such affordable and accessible data have the potential to offer new insights into disease epidemiology at national and international scales. We used the extensive information repository Google Trends to examine the digital epidemiology of a common childhood disease, chicken pox, caused by varicella zoster virus (VZV), over an 11-y period. We (i) report robust seasonal information-seeking behavior for chicken pox using Google data from 36 countries, (ii) validate Google data using clinical chicken pox cases, (iii) demonstrate that Google data can be used to identify recurrent seasonal outbreaks and forecast their magnitude and seasonal timing, and (iv) reveal that VZV immunization significantly dampened seasonal cycles in information-seeking behavior. Our findings provide strong evidence that VZV transmission is seasonal and that seasonal peaks show remarkable latitudinal variation. We attribute the dampened seasonal cycles in chicken pox information-seeking behavior to VZV vaccine-induced reduction of seasonal transmission. These data and the methodological approaches provide a way to track the global burden of childhood disease and illustrate population-level effects of immunization. The global latitudinal patterns in outbreak seasonality could direct future studies of environmental and physiological drivers of disease transmission.

  1. Phylogenomics of Brazilian epidemic isolates of Mycobacterium abscessus subsp. bolletii reveals relationships of global outbreak strains

    PubMed Central

    Davidson, Rebecca M.; Hasan, Nabeeh A.; de Moura, Vinicius Calado Nogueira; Duarte, Rafael Silva; Jackson, Mary; Strong, Michael

    2013-01-01

    Rapidly growing, non-tuberculous mycobacteria (NTM) in the Mycobacterium abscessus (MAB) species are emerging pathogens that cause various diseases including skin and respiratory infections. The species has undergone recent taxonomic nomenclature refinement, and is currently recognized as two subspecies, M. abscessus subsp. abscessus (MAB-A) and M. abscessus subsp. bolletii (MAB-B). The recently reported outbreaks of MAB-B in surgical patients in Brazil from 2004 to 2009 and in cystic fibrosis patients in the United Kingdom (UK) in 2006 to 2012 underscore the need to investigate the genetic diversity of clinical MAB strains. To this end, we sequenced the genomes of two Brazilian MAB-B epidemic isolates (CRM-0019 and CRM-0020) derived from an outbreak of skin infections in Rio de Janeiro, two unrelated MAB strains from patients with pulmonary infections in the United States (US) (NJH8 and NJH11) and one type MAB-B strain (CCUG 48898) and compared them to 25 publically available genomes of globally diverse MAB strains. Genome-wide analyses of 27,598 core genome single nucleotide polymorphisms (SNPs) revealed that the two Brazilian derived CRM strains are nearly indistinguishable from one another and are more closely related to UK outbreak isolates infecting CF patients than to strains from the US, Malaysia or France. Comparative genomic analyses of six closely related outbreak strains revealed geographic-specific large-scale insertion/deletion variation that corresponds to bacteriophage insertions and recombination hotspots. Our study integrates new genome sequence data with existing genomic information to explore the global diversity of infectious M. abscessus isolates and to compare clinically relevant outbreak strains from different continents. PMID:24055961

  2. Global stability analysis of electrified jets

    NASA Astrophysics Data System (ADS)

    Rivero-Rodriguez, Javier; Pérez-Saborid, Miguel

    2014-11-01

    Electrospinning is a common process used to produce micro and nano polymeric fibers. In this technique, the whipping mode of a very thin electrified jet generated in an electrospray device is nhanced in order to increase its elongation. In this work, we use a theoretical Eulerian model that describes the kinematics and dynamics of the midline of the jet, its radius and convective velocity. The model equations result from balances of mass, linear and angular momentum applied to any differential slice of the jet together with constitutive laws for viscous forces and moments, as well as appropriate expressions for capillary and electrical forces. As a first step towards computing the complete nonlinear, transient dynamics of the electrified jet, we have performed a global stability analysis of the forementioned equations and compared the results with experimental data obtained by Guillaume et al. [2011] and Guerrero-Millán et al. [2014]. The support of the Ministry of Science and Innovation of Spain (Project DPI 2010-20450-C03-02) is acknowledged.

  3. Determinants for global cargo analysis tools

    NASA Astrophysics Data System (ADS)

    Wilmoth, M.; Kay, W.; Sessions, C.; Hancock, M.

    2007-04-01

    The purpose of Global TRADER (GT) is not only to gather and query supply-chain transactional data for facts but also to analyze that data for hidden knowledge for the purpose of useful and meaningful pattern prediction. The application of advanced analytics provides benefits beyond simple information retrieval from GT, including computer-aided detection of useful patterns and associations. Knowledge discovery, offering a breadth and depth of analysis unattainable by manual processes, involves three components: repository structures, analytical engines, and user tools and reports. For a large and complex domain like supply-chains, there are many stages to developing the most advanced analytic capabilities; however, significant benefits accrue as components are incrementally added. These benefits include detecting emerging patterns; identifying new patterns; fusing data; creating models that can learn and predict behavior; and identifying new features for future tools. The GT Analyst Toolset was designed to overcome a variety of constraints, including lack of third party data, partial data loads, non-cleansed data (non-disambiguation of parties, misspellings, transpositions, etc.), and varying levels of analyst experience and expertise. The end result was a set of analytical tools that are flexible, extensible, tunable, and able to support a wide range of analyst demands.

  4. Stability of fundamental couplings: A global analysis

    NASA Astrophysics Data System (ADS)

    Martins, C. J. A. P.; Pinho, A. M. M.

    2017-01-01

    Astrophysical tests of the stability of fundamental couplings are becoming an increasingly important probe of new physics. Motivated by the recent availability of new and stronger constraints we update previous works testing the consistency of measurements of the fine-structure constant α and the proton-to-electron mass ratio μ =mp/me (mostly obtained in the optical/ultraviolet) with combined measurements of α , μ and the proton gyromagnetic ratio gp (mostly in the radio band). We carry out a global analysis of all available data, including the 293 archival measurements of Webb et al. and 66 more recent dedicated measurements, and constraining both time and spatial variations. While nominally the full data sets show a slight statistical preference for variations of α and μ (at up to two standard deviations), we also find several inconsistencies between different subsets, likely due to hidden systematics and implying that these statistical preferences need to be taken with caution. The statistical evidence for a spatial dipole in the values of α is found at the 2.3 sigma level. Forthcoming studies with facilities such as ALMA and ESPRESSO should clarify these issues.

  5. A pathway analysis of global aerosol processes

    NASA Astrophysics Data System (ADS)

    Schutgens, N. A. J.; Stier, P.

    2014-06-01

    We present a detailed budget of the changes in atmospheric aerosol mass and numbers due to various processes: emission, nucleation, coagulation, H2SO4 condensation and in-cloud production, ageing and deposition. The budget is created from monthly-averaged tracer tendencies calculated by the global aerosol model ECHAM5.5-HAM2 and allows us to investigate process contributions at various length- and time-scales. As a result, we show in unprecedented detail what processes drive the evolution of aerosol. In particular, we show that the processes that affect aerosol masses are quite different from those affecting aerosol numbers. Condensation of H2SO4 gas onto pre-existing particles is an important process, dominating the growth of small particles in the nucleation mode to the Aitken mode and the ageing of hydrophobic matter. Together with in-cloud production of H2SO4, it significantly contributes to (and often dominates) the mass burden (and hence composition) of the hydrophilic Aitken and accumulation mode particles. Particle growth itself is the leading source of number densities in the hydrophilic Aitken and accumulation modes, with their hydrophobic counterparts contributing (even locally) relatively little. As expected, the coarse mode is dominated by primary emissions and mostly decoupled from the smaller modes. Our analysis also suggests that coagulation serves mainly as a loss process for number densities and that, relative to other processes, it is a rather unimportant contributor to composition changes of aerosol. The analysis is extended with sensitivity studies where the impact of a lower model resolution or pre-industrial emissions is shown to be small. We discuss the use of the current budget for model simplification, prioritisation of model improvements, identification of potential structural model errors and model evaluation against observations.

  6. A pathway analysis of global aerosol processes

    NASA Astrophysics Data System (ADS)

    Schutgens, N. A. J.; Stier, P.

    2014-11-01

    We present a detailed budget of the changes in atmospheric aerosol mass and numbers due to various processes: emission (including instant condensation of soluble biogenic emissions), nucleation, coagulation, H2SO4 condensation and in-cloud production, aging and deposition. The budget is created from monthly averaged tracer tendencies calculated by the global aerosol model ECHAM5.5-HAM2 and allows us to investigate process contributions at various length-scales and timescales. As a result, we show in unprecedented detail what processes drive the evolution of aerosol. In particular, we show that the processes that affect aerosol masses are quite different from those that affect aerosol numbers. Condensation of H2SO4 gas onto pre-existing particles is an important process, dominating the growth of small particles in the nucleation mode to the Aitken mode and the aging of hydrophobic matter. Together with in-cloud production of H2SO4, it significantly contributes to (and often dominates) the mass burden (and hence composition) of the hydrophilic Aitken and accumulation mode particles. Particle growth itself is the leading source of number densities in the hydrophilic Aitken and accumulation modes, with their hydrophobic counterparts contributing (even locally) relatively little. As expected, the coarse mode is dominated by primary emissions and mostly decoupled from the smaller modes. Our analysis also suggests that coagulation serves mainly as a loss process for number densities and that, relative to other processes, it is a rather unimportant contributor to composition changes of aerosol. The analysis is extended with sensitivity studies where the impact of a lower model resolution or pre-industrial emissions is shown to be small. We discuss the use of the current budget for model simplification, prioritization of model improvements, identification of potential structural model errors and model evaluation against observations.

  7. Economic Analysis and Assumptions in Global Education.

    ERIC Educational Resources Information Center

    Miller, Steven L.

    Economic educators recognize the importance of a global perspective, at least in part because the international sector has become more important over the past few decades. The application of economic principles calls into question some assumptions that appear to be common among members of the global education movement. That these assumptions might…

  8. Changing carbon cycle: a global analysis

    SciTech Connect

    Trabalka, J.R.; Reichle, D.E.

    1986-01-01

    An attempt is made to examine current knowledge about the fluxes, sources, and sinks in the global carbon cycle, as well as our ability to predict changes in atmospheric CO/sub 2/ concentration resulting from anthropogenic influences. The reader will find authoritative discussions of: past and expected releases of CO/sub 2/ from fossil fuels; the historical record and implications of atmospheric CO/sub 2/ increases; isotopic and geological records of past carbon cycle processes; the role of the oceans in the global carbon cycle; the influence of the world biosphere on changes in atmospheric CO/sub 2/ levels; and, evidence linking the components of the global carbon cycle.

  9. Global metagenomic survey reveals a new bacterial candidate phylum in geothermal springs.

    PubMed

    Eloe-Fadrosh, Emiley A; Paez-Espino, David; Jarett, Jessica; Dunfield, Peter F; Hedlund, Brian P; Dekas, Anne E; Grasby, Stephen E; Brady, Allyson L; Dong, Hailiang; Briggs, Brandon R; Li, Wen-Jun; Goudeau, Danielle; Malmstrom, Rex; Pati, Amrita; Pett-Ridge, Jennifer; Rubin, Edward M; Woyke, Tanja; Kyrpides, Nikos C; Ivanova, Natalia N

    2016-01-27

    Analysis of the increasing wealth of metagenomic data collected from diverse environments can lead to the discovery of novel branches on the tree of life. Here we analyse 5.2 Tb of metagenomic data collected globally to discover a novel bacterial phylum ('Candidatus Kryptonia') found exclusively in high-temperature pH-neutral geothermal springs. This lineage had remained hidden as a taxonomic 'blind spot' because of mismatches in the primers commonly used for ribosomal gene surveys. Genome reconstruction from metagenomic data combined with single-cell genomics results in several high-quality genomes representing four genera from the new phylum. Metabolic reconstruction indicates a heterotrophic lifestyle with conspicuous nutritional deficiencies, suggesting the need for metabolic complementarity with other microbes. Co-occurrence patterns identifies a number of putative partners, including an uncultured Armatimonadetes lineage. The discovery of Kryptonia within previously studied geothermal springs underscores the importance of globally sampled metagenomic data in detection of microbial novelty, and highlights the extraordinary diversity of microbial life still awaiting discovery.

  10. Global metagenomic survey reveals a new bacterial candidate phylum in geothermal springs

    PubMed Central

    Eloe-Fadrosh, Emiley A.; Paez-Espino, David; Jarett, Jessica; Dunfield, Peter F.; Hedlund, Brian P.; Dekas, Anne E.; Grasby, Stephen E.; Brady, Allyson L.; Dong, Hailiang; Briggs, Brandon R.; Li, Wen-Jun; Goudeau, Danielle; Malmstrom, Rex; Pati, Amrita; Pett-Ridge, Jennifer; Rubin, Edward M.; Woyke, Tanja; Kyrpides, Nikos C.; Ivanova, Natalia N.

    2016-01-01

    Analysis of the increasing wealth of metagenomic data collected from diverse environments can lead to the discovery of novel branches on the tree of life. Here we analyse 5.2 Tb of metagenomic data collected globally to discover a novel bacterial phylum (‘Candidatus Kryptonia') found exclusively in high-temperature pH-neutral geothermal springs. This lineage had remained hidden as a taxonomic ‘blind spot' because of mismatches in the primers commonly used for ribosomal gene surveys. Genome reconstruction from metagenomic data combined with single-cell genomics results in several high-quality genomes representing four genera from the new phylum. Metabolic reconstruction indicates a heterotrophic lifestyle with conspicuous nutritional deficiencies, suggesting the need for metabolic complementarity with other microbes. Co-occurrence patterns identifies a number of putative partners, including an uncultured Armatimonadetes lineage. The discovery of Kryptonia within previously studied geothermal springs underscores the importance of globally sampled metagenomic data in detection of microbial novelty, and highlights the extraordinary diversity of microbial life still awaiting discovery. PMID:26814032

  11. Global metagenomic survey reveals a new bacterial candidate phylum in geothermal springs

    SciTech Connect

    Eloe-Fadrosh, Emiley A.; Paez-Espino, David; Jarett, Jessica; Dunfield, Peter F.; Hedlund, Brian P.; Dekas, Anne E.; Grasby, Stephen E.; Brady, Allyson L.; Dong, Hailiang; Briggs, Brandon R.; Li, Wen -Jun; Goudeau, Danielle; Malmstrom, Rex; Pati, Amrita; Pett-Ridge, Jennifer; Rubin, Edward M.; Woyke, Tanja; Kyrpides, Nikos C.; Ivanova, Natalia N.

    2016-01-27

    Analysis of the increasing wealth of metagenomic data collected from diverse environments can lead to the discovery of novel branches on the tree of life. Here we analyse 5.2 Tb of metagenomic data collected globally to discover a novel bacterial phylum ('Candidatus Kryptonia') found exclusively in higherature pH-neutral geothermal springs. This lineage had remained hidden as a taxonomic 'blind spot' because of mismatches in the primers commonly used for ribosomal gene surveys. Genome reconstruction from metagenomic data combined with single-cell genomics results in several high-quality genomes representing four genera from the new phylum. Metabolic reconstruction indicates a heterotrophic lifestyle with conspicuous nutritional deficiencies, suggesting the need for metabolic complementarity with other microbes. Co-occurrence patterns identifies a number of putative partners, including an uncultured Armatimonadetes lineage. The discovery of Kryptonia within previously studied geothermal springs underscores the importance of globally sampled metagenomic data in detection of microbial novelty, and highlights the extraordinary diversity of microbial life still awaiting discovery.

  12. Global metagenomic survey reveals a new bacterial candidate phylum in geothermal springs

    DOE PAGES

    Eloe-Fadrosh, Emiley A.; Paez-Espino, David; Jarett, Jessica; ...

    2016-01-27

    Analysis of the increasing wealth of metagenomic data collected from diverse environments can lead to the discovery of novel branches on the tree of life. Here we analyse 5.2 Tb of metagenomic data collected globally to discover a novel bacterial phylum ('Candidatus Kryptonia') found exclusively in higherature pH-neutral geothermal springs. This lineage had remained hidden as a taxonomic 'blind spot' because of mismatches in the primers commonly used for ribosomal gene surveys. Genome reconstruction from metagenomic data combined with single-cell genomics results in several high-quality genomes representing four genera from the new phylum. Metabolic reconstruction indicates a heterotrophic lifestyle withmore » conspicuous nutritional deficiencies, suggesting the need for metabolic complementarity with other microbes. Co-occurrence patterns identifies a number of putative partners, including an uncultured Armatimonadetes lineage. The discovery of Kryptonia within previously studied geothermal springs underscores the importance of globally sampled metagenomic data in detection of microbial novelty, and highlights the extraordinary diversity of microbial life still awaiting discovery.« less

  13. Global sensitivity analysis in wind energy assessment

    NASA Astrophysics Data System (ADS)

    Tsvetkova, O.; Ouarda, T. B.

    2012-12-01

    Wind energy is one of the most promising renewable energy sources. Nevertheless, it is not yet a common source of energy, although there is enough wind potential to supply world's energy demand. One of the most prominent obstacles on the way of employing wind energy is the uncertainty associated with wind energy assessment. Global sensitivity analysis (SA) studies how the variation of input parameters in an abstract model effects the variation of the variable of interest or the output variable. It also provides ways to calculate explicit measures of importance of input variables (first order and total effect sensitivity indices) in regard to influence on the variation of the output variable. Two methods of determining the above mentioned indices were applied and compared: the brute force method and the best practice estimation procedure In this study a methodology for conducting global SA of wind energy assessment at a planning stage is proposed. Three sampling strategies which are a part of SA procedure were compared: sampling based on Sobol' sequences (SBSS), Latin hypercube sampling (LHS) and pseudo-random sampling (PRS). A case study of Masdar City, a showcase of sustainable living in the UAE, is used to exemplify application of the proposed methodology. Sources of uncertainty in wind energy assessment are very diverse. In the case study the following were identified as uncertain input parameters: the Weibull shape parameter, the Weibull scale parameter, availability of a wind turbine, lifetime of a turbine, air density, electrical losses, blade losses, ineffective time losses. Ineffective time losses are defined as losses during the time when the actual wind speed is lower than the cut-in speed or higher than the cut-out speed. The output variable in the case study is the lifetime energy production. Most influential factors for lifetime energy production are identified with the ranking of the total effect sensitivity indices. The results of the present

  14. Global Nanotribology Research Output (1996–2010): A Scientometric Analysis

    PubMed Central

    Elango, Bakthavachalam; Rajendran, Periyaswamy; Bornmann, Lutz

    2013-01-01

    This study aims to assess the nanotribology research output at global level using scientometric tools. The SCOPUS database was used to retrieve records related to the nanotribology research for the period 1996–2010. Publications were counted on a fractional basis. The level of collaboration and its citation impact were examined. The performance of the most productive countries, institutes and most preferred journals is assessed. Various visualization tools such as the Sci2 tool and Ucinet were employed. The USA ranked top in terms of number of publications, citations per paper and h-index, while Switzerland published a higher percentage of international collaborative papers. The most productive institution was Tsinghua University followed by Ohio State University and Lanzhou Institute of Chemical Physics, CAS. The most preferred journals were Tribology Letters, Wear and Journal of Japanese Society of Tribologists. The result of author keywords analysis reveals that Molecular Dynamics, MEMS, Hard Disk and Diamond like Carbon are major research topics. PMID:24339900

  15. Global richness patterns of venomous snakes reveal contrasting influences of ecology and history in two different clades.

    PubMed

    Terribile, Levi Carina; Olalla-Tárraga, Miguel Angel; Morales-Castilla, Ignacio; Rueda, Marta; Vidanes, Rosa M; Rodríguez, Miguel Angel; Diniz-Filho, José Alexandre Felizola

    2009-03-01

    Recent studies addressing broad-scale species richness gradients have proposed two main primary drivers: contemporary climate and evolutionary processes (differential balance between speciation and extinction). Here, we analyze the global richness patterns of two venomous snake clades, Viperidae and Elapidae. We used ordinary least squares multiple regression (OLS) and partial regression analysis to investigate to what extent actual evapotranspiration (AET; summarizing current environmental conditions) and biogeographical regions (representing evolutionary effects) were associated with species richness. For viperids, AET explained 45.6% of the variance in richness whereas the effect of this variable for elapids was almost null (0.5%). On the other hand, biogeographic regions were the best predictors of elapid richness (56.5%), against its relatively small effect (25.9%) in viperid richness. Partial regressions also revealed similar patterns for independent effects of climate and history in both clades. However, the independent historical effect in Elapidae decreased from 45.2 to 17.8% when we excluded Australia from the analyses, indicating that the strong historical effect that had emerged for the global richness pattern was reflecting the historical process of elapid radiation into Australia. Even after excluding Australia, the historical signal in elapid richness in the rest of the globe was still significant and much higher than that observed in viperid richness at a global scale (2.7% after controlling for AET effects). Differences in the evolutionary age of these two clades can be invoked to explain these contrasting results, in that viperids probably had more time for diversification, generating richness responses to environmental gradients, whereas the pattern of distribution of elapid richness can be more directly interpreted in an evolutionary context. Moreover, these results show the importance of starting to adopt deconstructive approaches to species

  16. Genome and metagenome enabled analyses reveal new insight into the global biogeography and potential urea utilization in marine Thaumarchaeota.

    NASA Astrophysics Data System (ADS)

    Ahlgren, N.; Parada, A. E.; Fuhrman, J. A.

    2016-02-01

    Marine Thaumarchaea are an abundant, important group of marine microbial communities as they fix carbon, oxidize ammonium, and thus contribute to key N and C cycles in the oceans. From an enrichment culture, we have sequenced the complete genome of a new Thaumarchaeota strain, SPOT01. Analysis of this genome and other Thaumarchaeal genomes contributes new insight into its role in N cycling and clarifies the broader biogeography of marine Thaumarchaeal genera. Phylogenomics of Thaumarchaeota genomes reveal coherent separation into clusters roughly equivalent to the genus level, and SPOT01 represents a new genus of marine Thaumarchaea. Competitive fragment recruitment of globally distributed metagenomes from TARA, Ocean Sampling Day, and those generated from a station off California shows that the SPOT01 genus is often the most abundant genus, especially where total Thaumarchaea are most abundant in the overall community. The SPOT01 genome contains urease genes allowing it to use an alternative form of N. Genomic and metagenomic analysis also reveal that among planktonic genomes and populations, the urease genes in general are more frequently found in members of the SPOT01 genus and another genus dominant in deep waters, thus we predict these two genera contribute most significantly to urea utilization among marine Thaumarchaea. Recruitment also revealed broader biogeographic and ecological patterns of the putative genera. The SPOT01 genus was most abundant at colder temperatures (<16 C), reflective of its dominance at subpolar to polar latitudes (>45 degrees). The genus containing Nitrosopumilus maritimus had the highest temperature range, and the genus containing Candidatus Nitrosopelagicus brevis was typically most abundant at intermediate temperatures and intermediate latitudes ( 35-45 degrees). Together these genome and metagenome enabled analyses provide significant new insight into the ecology and biogeochemical contributions of marine archaea.

  17. Nitrosopumilus maritimus genome reveals unique mechanisms for nitrification and autotrophy in globally distributed marine crenarchaea.

    PubMed

    Walker, C B; de la Torre, J R; Klotz, M G; Urakawa, H; Pinel, N; Arp, D J; Brochier-Armanet, C; Chain, P S G; Chan, P P; Gollabgir, A; Hemp, J; Hügler, M; Karr, E A; Könneke, M; Shin, M; Lawton, T J; Lowe, T; Martens-Habbena, W; Sayavedra-Soto, L A; Lang, D; Sievert, S M; Rosenzweig, A C; Manning, G; Stahl, D A

    2010-05-11

    Ammonia-oxidizing archaea are ubiquitous in marine and terrestrial environments and now thought to be significant contributors to carbon and nitrogen cycling. The isolation of Candidatus "Nitrosopumilus maritimus" strain SCM1 provided the opportunity for linking its chemolithotrophic physiology with a genomic inventory of the globally distributed archaea. Here we report the 1,645,259-bp closed genome of strain SCM1, revealing highly copper-dependent systems for ammonia oxidation and electron transport that are distinctly different from known ammonia-oxidizing bacteria. Consistent with in situ isotopic studies of marine archaea, the genome sequence indicates N. maritimus grows autotrophically using a variant of the 3-hydroxypropionate/4-hydroxybutryrate pathway for carbon assimilation, while maintaining limited capacity for assimilation of organic carbon. This unique instance of archaeal biosynthesis of the osmoprotectant ectoine and an unprecedented enrichment of multicopper oxidases, thioredoxin-like proteins, and transcriptional regulators points to an organism responsive to environmental cues and adapted to handling reactive copper and nitrogen species that likely derive from its distinctive biochemistry. The conservation of N. maritimus gene content and organization within marine metagenomes indicates that the unique physiology of these specialized oligophiles may play a significant role in the biogeochemical cycles of carbon and nitrogen.

  18. Nitrosopumilus maritimus genome reveals unique mechanisms for nitrification and autotrophy in globally distributed marine crenarchaea

    PubMed Central

    Walker, C. B.; de la Torre, J. R.; Klotz, M. G.; Urakawa, H.; Pinel, N.; Arp, D. J.; Brochier-Armanet, C.; Chain, P. S. G.; Chan, P. P.; Gollabgir, A.; Hemp, J.; Hügler, M.; Karr, E. A.; Könneke, M.; Lawton, T. J.; Lowe, T.; Martens-Habbena, W.; Sayavedra-Soto, L. A.; Lang, D.; Sievert, S. M.; Rosenzweig, A. C.; Manning, G.; Stahl, D. A.

    2010-01-01

    Ammonia-oxidizing archaea are ubiquitous in marine and terrestrial environments and now thought to be significant contributors to carbon and nitrogen cycling. The isolation of Candidatus “Nitrosopumilus maritimus” strain SCM1 provided the opportunity for linking its chemolithotrophic physiology with a genomic inventory of the globally distributed archaea. Here we report the 1,645,259-bp closed genome of strain SCM1, revealing highly copper-dependent systems for ammonia oxidation and electron transport that are distinctly different from known ammonia-oxidizing bacteria. Consistent with in situ isotopic studies of marine archaea, the genome sequence indicates N. maritimus grows autotrophically using a variant of the 3-hydroxypropionate/4-hydroxybutryrate pathway for carbon assimilation, while maintaining limited capacity for assimilation of organic carbon. This unique instance of archaeal biosynthesis of the osmoprotectant ectoine and an unprecedented enrichment of multicopper oxidases, thioredoxin-like proteins, and transcriptional regulators points to an organism responsive to environmental cues and adapted to handling reactive copper and nitrogen species that likely derive from its distinctive biochemistry. The conservation of N. maritimus gene content and organization within marine metagenomes indicates that the unique physiology of these specialized oligophiles may play a significant role in the biogeochemical cycles of carbon and nitrogen. PMID:20421470

  19. Rapid regional perturbations to the recent global geomagnetic decay revealed by a new Hawaiian record

    PubMed Central

    de Groot, L. V.; Biggin, A. J.; Dekkers, M. J.; Langereis, C. G.; Herrero-Bervera, E.

    2013-01-01

    The dominant dipolar component of the Earth’s magnetic field has been steadily weakening for at least the last 170 years. Prior to these direct measurements, archaeomagnetic records show short periods of significantly elevated geomagnetic intensity. These striking phenomena are not captured by current field models and their relationship to the recent dipole decay is highly unclear. Here we apply a novel multi-method archaeomagnetic approach to produce a new high-quality record of geomagnetic intensity variations for Hawaii, a crucial locality in the central Pacific. It reveals a short period of high intensity occurring ~1,000 years ago, qualitatively similar to behaviour observed 200 years earlier in Europe and 500 years later in Mesoamerica. We combine these records with one from Japan to produce a coherent picture that includes the dipole decaying steadily over the last millennium. Strong, regional, short-term intensity perturbations are superimposed on this global trend; their asynchronicity necessitates a highly non-dipolar nature. PMID:24177390

  20. Rapid regional perturbations to the recent global geomagnetic decay revealed by a new Hawaiian record

    NASA Astrophysics Data System (ADS)

    de Groot, L. V.; Biggin, A. J.; Dekkers, M. J.; Langereis, C. G.; Herrero-Bervera, E.

    2013-10-01

    The dominant dipolar component of the Earth’s magnetic field has been steadily weakening for at least the last 170 years. Prior to these direct measurements, archaeomagnetic records show short periods of significantly elevated geomagnetic intensity. These striking phenomena are not captured by current field models and their relationship to the recent dipole decay is highly unclear. Here we apply a novel multi-method archaeomagnetic approach to produce a new high-quality record of geomagnetic intensity variations for Hawaii, a crucial locality in the central Pacific. It reveals a short period of high intensity occurring ~1,000 years ago, qualitatively similar to behaviour observed 200 years earlier in Europe and 500 years later in Mesoamerica. We combine these records with one from Japan to produce a coherent picture that includes the dipole decaying steadily over the last millennium. Strong, regional, short-term intensity perturbations are superimposed on this global trend; their asynchronicity necessitates a highly non-dipolar nature.

  1. Splicing Functions and Global Dependency on Fission Yeast Slu7 Reveal Diversity in Spliceosome Assembly

    PubMed Central

    Banerjee, Shataparna; Khandelia, Piyush; Melangath, Geetha; Bashir, Samirul; Nagampalli, Vijaykrishna

    2013-01-01

    The multiple short introns in Schizosaccharomyces pombe genes with degenerate cis sequences and atypically positioned polypyrimidine tracts make an interesting model to investigate canonical and alternative roles for conserved splicing factors. Here we report functions and interactions of the S. pombe slu7+ (spslu7+) gene product, known from Saccharomyces cerevisiae and human in vitro reactions to assemble into spliceosomes after the first catalytic reaction and to dictate 3′ splice site choice during the second reaction. By using a missense mutant of this essential S. pombe factor, we detected a range of global splicing derangements that were validated in assays for the splicing status of diverse candidate introns. We ascribe widespread, intron-specific SpSlu7 functions and have deduced several features, including the branch nucleotide-to-3′ splice site distance, intron length, and the impact of its A/U content at the 5′ end on the intron's dependence on SpSlu7. The data imply dynamic substrate-splicing factor relationships in multiintron transcripts. Interestingly, the unexpected early splicing arrest in spslu7-2 revealed a role before catalysis. We detected a salt-stable association with U5 snRNP and observed genetic interactions with spprp1+, a homolog of human U5-102k factor. These observations together point to an altered recruitment and dependence on SpSlu7, suggesting its role in facilitating transitions that promote catalysis, and highlight the diversity in spliceosome assembly. PMID:23754748

  2. Graph-theoretical model of global human interactome reveals enhanced long-range communicability in cancer networks

    PubMed Central

    Gladilin, Evgeny

    2017-01-01

    Malignant transformation is known to involve substantial rearrangement of the molecular genetic landscape of the cell. A common approach to analysis of these alterations is a reductionist one and consists of finding a compact set of differentially expressed genes or associated signaling pathways. However, due to intrinsic tumor heterogeneity and tissue specificity, biomarkers defined by a small number of genes/pathways exhibit substantial variability. As an alternative to compact differential signatures, global features of genetic cell machinery are conceivable. Global network descriptors suggested in previous works are, however, known to potentially be biased by overrepresentation of interactions between frequently studied genes-proteins. Here, we construct a cellular network of 74538 directional and differential gene expression weighted protein-protein and gene regulatory interactions, and perform graph-theoretical analysis of global human interactome using a novel, degree-independent feature—the normalized total communicability (NTC). We apply this framework to assess differences in total information flow between different cancer (BRCA/COAD/GBM) and non-cancer interactomes. Our experimental results reveal that different cancer interactomes are characterized by significant enhancement of long-range NTC, which arises from circulation of information flow within robustly organized gene subnetworks. Although enhancement of NTC emerges in different cancer types from different genomic profiles, we identified a subset of 90 common genes that are related to elevated NTC in all studied tumors. Our ontological analysis shows that these genes are associated with enhanced cell division, DNA replication, stress response, and other cellular functions and processes typically upregulated in cancer. We conclude that enhancement of long-range NTC manifested in the correlated activity of genes whose tight coordination is required for survival and proliferation of all tumor cells

  3. Is globalization healthy: a statistical indicator analysis of the impacts of globalization on health

    PubMed Central

    2010-01-01

    It is clear that globalization is something more than a purely economic phenomenon manifesting itself on a global scale. Among the visible manifestations of globalization are the greater international movement of goods and services, financial capital, information and people. In addition, there are technological developments, more transboundary cultural exchanges, facilitated by the freer trade of more differentiated products as well as by tourism and immigration, changes in the political landscape and ecological consequences. In this paper, we link the Maastricht Globalization Index with health indicators to analyse if more globalized countries are doing better in terms of infant mortality rate, under-five mortality rate, and adult mortality rate. The results indicate a positive association between a high level of globalization and low mortality rates. In view of the arguments that globalization provides winners and losers, and might be seen as a disequalizing process, we should perhaps be careful in interpreting the observed positive association as simple evidence that globalization is mostly good for our health. It is our hope that a further analysis of health impacts of globalization may help in adjusting and optimising the process of globalization on every level in the direction of a sustainable and healthy development for all. PMID:20849605

  4. Is globalization healthy: a statistical indicator analysis of the impacts of globalization on health.

    PubMed

    Martens, Pim; Akin, Su-Mia; Maud, Huynen; Mohsin, Raza

    2010-09-17

    It is clear that globalization is something more than a purely economic phenomenon manifesting itself on a global scale. Among the visible manifestations of globalization are the greater international movement of goods and services, financial capital, information and people. In addition, there are technological developments, more transboundary cultural exchanges, facilitated by the freer trade of more differentiated products as well as by tourism and immigration, changes in the political landscape and ecological consequences. In this paper, we link the Maastricht Globalization Index with health indicators to analyse if more globalized countries are doing better in terms of infant mortality rate, under-five mortality rate, and adult mortality rate. The results indicate a positive association between a high level of globalization and low mortality rates. In view of the arguments that globalization provides winners and losers, and might be seen as a disequalizing process, we should perhaps be careful in interpreting the observed positive association as simple evidence that globalization is mostly good for our health. It is our hope that a further analysis of health impacts of globalization may help in adjusting and optimising the process of globalization on every level in the direction of a sustainable and healthy development for all.

  5. Seasonal cycle of volume transport through Kerama Gap revealed by a 20-year global HYbrid Coordinate Ocean Model reanalysis

    DTIC Science & Technology

    2015-11-10

    cycle of volume transport through Kerama Gap revealed by a 20-year global HYbrid Coordinate Ocean Model reanalysis Zhitao Yua,b,∗, E. Joseph Metzgerb...Island − a part of Ryukyu Islands Arc) is investigated using a 20-year global HYbrid Coordinate Ocean Model (HYCOM) reanalysis with the Navy Coupled...Gordon et al., 2014) and hen enters the East China Sea (ECS) through the East Taiwan Channel ETC) between Taiwan and Ishigaki Island; it carries warm

  6. An Analysis of Solar Global Activity

    NASA Astrophysics Data System (ADS)

    Mouradian, Zadig

    2013-02-01

    This article proposes a unified observational model of solar activity based on sunspot number and the solar global activity in the rotation of the structures, both per 11-year cycle. The rotation rates show a variation of a half-century period and the same period is also associated to the sunspot amplitude variation. The global solar rotation interweaves with the observed global organisation of solar activity. An important role for this assembly is played by the Grand Cycle formed by the merging of five sunspot cycles: a forgotten discovery by R. Wolf. On the basis of these elements, the nature of the Dalton Minimum, the Maunder Minimum, the Gleissberg Cycle, and the Grand Minima are presented.

  7. Global Human Settlement Analysis for Disaster Risk Reduction

    NASA Astrophysics Data System (ADS)

    Pesaresi, M.; Ehrlich, D.; Ferri, S.; Florczyk, A.; Freire, S.; Haag, F.; Halkia, M.; Julea, A. M.; Kemper, T.; Soille, P.

    2015-04-01

    The Global Human Settlement Layer (GHSL) is supported by the European Commission, Joint Research Center (JRC) in the frame of his institutional research activities. Scope of GHSL is developing, testing and applying the technologies and analysis methods integrated in the JRC Global Human Settlement analysis platform for applications in support to global disaster risk reduction initiatives (DRR) and regional analysis in the frame of the European Cohesion policy. GHSL analysis platform uses geo-spatial data, primarily remotely sensed and population. GHSL also cooperates with the Group on Earth Observation on SB-04-Global Urban Observation and Information, and various international partners andWorld Bank and United Nations agencies. Some preliminary results integrating global human settlement information extracted from Landsat data records of the last 40 years and population data are presented.

  8. Core Microbial Functional Activities in Ocean Environments Revealed by Global Metagenomic Profiling Analyses

    PubMed Central

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

    2014-01-01

    Metagenomics-based functional profiling analysis is an effective means of gaining deeper insight into the composition of marine microbial populations and developing a better understanding of the interplay between the functional genome content of microbial communities and abiotic factors. Here we present a comprehensive analysis of 24 datasets covering surface and depth-related environments at 11 sites around the world's oceans. The complete datasets comprises approximately 12 million sequences, totaling 5,358 Mb. Based on profiling patterns of Clusters of Orthologous Groups (COGs) of proteins, a core set of reference photic and aphotic depth-related COGs, and a collection of COGs that are associated with extreme oxygen limitation were defined. Their inferred functions were utilized as indicators to characterize the distribution of light- and oxygen-related biological activities in marine environments. The results reveal that, while light level in the water column is a major determinant of phenotypic adaptation in marine microorganisms, oxygen concentration in the aphotic zone has a significant impact only in extremely hypoxic waters. Phylogenetic profiling of the reference photic/aphotic gene sets revealed a greater variety of source organisms in the aphotic zone, although the majority of individual photic and aphotic depth-related COGs are assigned to the same taxa across the different sites. This increase in phylogenetic and functional diversity of the core aphotic related COGs most probably reflects selection for the utilization of a broad range of alternate energy sources in the absence of light. PMID:24921648

  9. Global metabolomics reveals potential urinary biomarkers of esophageal squamous cell carcinoma for diagnosis and staging

    NASA Astrophysics Data System (ADS)

    Xu, Jing; Chen, Yanhua; Zhang, Ruiping; He, Jiuming; Song, Yongmei; Wang, Jingbo; Wang, Huiqing; Wang, Luhua; Zhan, Qimin; Abliz, Zeper

    2016-10-01

    We performed a metabolomics study using liquid chromatography-mass spectrometry (LC-MS) combined with multivariate data analysis (MVDA) to discriminate global urine profiles in urine samples from esophageal squamous cell carcinoma (ESCC) patients and healthy controls (NC). Our work evaluated the feasibility of employing urine metabolomics for the diagnosis and staging of ESCC. The satisfactory classification between the healthy controls and ESCC patients was obtained using the MVDA model, and obvious classification of early-stage and advanced-stage patients was also observed. The results suggest that the combination of LC-MS analysis and MVDA may have potential applications for ESCC diagnosis and staging. We then conducted LC-MS/MS experiments to identify the potential biomarkers with large contributions to the discrimination. A total of 83 potential diagnostic biomarkers for ESCC were screened out, and 19 potential biomarkers were identified; the variations between the differences in staging using these potential biomarkers were further analyzed. These biomarkers may not be unique to ESCCs, but instead result from any malignant disease. To further elucidate the pathophysiology of ESCC, we studied related metabolic pathways and found that ESCC is associated with perturbations of fatty acid β-oxidation and the metabolism of amino acids, purines, and pyrimidines.

  10. Global seismic data reveal little water in the mantle transition zone

    NASA Astrophysics Data System (ADS)

    Houser, C.

    2016-08-01

    Knowledge of the Earth's present water content is necessary to constrain the amount of water and other volatiles the Earth acquired during its formation and the amount that is cycled back into the interior from the surface. This study compares 410 and 660 km discontinuity depth with shear wave tomography within the mantle transition zone to identify regions with seismic signals consistent with water. The depth of the 410 and 660 km discontinuities is determined from a large updated dataset of SS-S410S and SS-S660S differential travel times, known as SS precursors. The discontinuity depths measured from binning and stacking the SS precursor data are then compared to the shear velocity model HMSL-S06 in the transition zone. Mapping all the possible combinations, very few locations match the predictions from mineral physics for the effects of water on discontinuity depth and shear velocity. The predictions, although not yet measured at actual transition zone temperatures and pressures, are a shallow 410 km discontinuity, a deep 660 km discontinuity, and a slow shear velocity. Only 8% of the bins with high-quality data are consistent with these predictions, and the calculated average water content within these bins is around 0.6 wt.%. A few isolated locations have patterns of velocity/topography that are consistent with water, while there are large regional-scale patterns consistent with cold/hot temperature anomalies. Combining this global analysis of long period seismic data and the current mineral physics predictions for water in transition zone minerals, I find that the mantle transition zone is generally dry, containing less than one Earth ocean of water. Although subduction zones could be locally hydrated, the combined discontinuity and velocity data show no evidence that wadsleyite or ringwoodite have been globally hydrated by subduction or initial Earth conditions.

  11. Multiple-stage ambiguity in motion perception reveals global computation of local motion directions.

    PubMed

    Rider, Andrew T; Nishida, Shin'ya; Johnston, Alan

    2016-12-01

    The motion of a 1D image feature, such as a line, seen through a small aperture, or the small receptive field of a neural motion sensor, is underconstrained, and it is not possible to derive the true motion direction from a single local measurement. This is referred to as the aperture problem. How the visual system solves the aperture problem is a fundamental question in visual motion research. In the estimation of motion vectors through integration of ambiguous local motion measurements at different positions, conventional theories assume that the object motion is a rigid translation, with motion signals sharing a common motion vector within the spatial region over which the aperture problem is solved. However, this strategy fails for global rotation. Here we show that the human visual system can estimate global rotation directly through spatial pooling of locally ambiguous measurements, without an intervening step that computes local motion vectors. We designed a novel ambiguous global flow stimulus, which is globally as well as locally ambiguous. The global ambiguity implies that the stimulus is simultaneously consistent with both a global rigid translation and an infinite number of global rigid rotations. By the standard view, the motion should always be seen as a global translation, but it appears to shift from translation to rotation as observers shift fixation. This finding indicates that the visual system can estimate local vectors using a global rotation constraint, and suggests that local motion ambiguity may not be resolved until consistencies with multiple global motion patterns are assessed.

  12. Toward Global Content Analysis and Media Criticism.

    ERIC Educational Resources Information Center

    Nordenstreng, Kaarle

    1995-01-01

    Presents the background, rationale, and implementation prospects for an international system of monitoring media coverage of global problems such as peace and war, human rights, and the environment. Outlines the monitoring project carried out in January 1995 concerning the representation and portrayal of women in news media. (SR)

  13. Global Proteome Analysis of Leptospira interrogans

    USDA-ARS?s Scientific Manuscript database

    Comparative global proteome analyses were performed on Leptospira interrogans serovar Copenhageni grown under conventional in vitro conditions and those mimicking in vivo conditions (iron limitation and serum presence). Proteomic analyses were conducted using iTRAQ and LC-ESI-tandem mass spectrometr...

  14. Toward Global Content Analysis and Media Criticism.

    ERIC Educational Resources Information Center

    Nordenstreng, Kaarle

    1995-01-01

    Presents the background, rationale, and implementation prospects for an international system of monitoring media coverage of global problems such as peace and war, human rights, and the environment. Outlines the monitoring project carried out in January 1995 concerning the representation and portrayal of women in news media. (SR)

  15. Global Population Genetic Analysis of Aspergillus fumigatus

    PubMed Central

    Ashu, Eta Ebasi; Hagen, Ferry; Chowdhary, Anuradha

    2017-01-01

    ABSTRACT Aspergillus fumigatus is a ubiquitous opportunistic fungal pathogen capable of causing invasive aspergillosis, a globally distributed disease with a mortality rate of up to 90% in high-risk populations. Effective control and prevention of this disease require a thorough understanding of its epidemiology. However, despite significant efforts, the global molecular epidemiology of A. fumigatus remains poorly understood. In this study, we analyzed 2,026 A. fumigatus isolates from 13 countries in four continents using nine highly polymorphic microsatellite markers. Genetic cluster analyses suggest that our global sample of A. fumigatus isolates belonged to eight genetic clusters, with seven of the eight clusters showing broad geographic distributions. We found common signatures of sexual recombination within individual genetic clusters and clear evidence of hybridization between several clusters. Limited but statistically significant genetic differentiations were found among geographic and ecological populations. However, there was abundant evidence for gene flow at the local, regional, and global scales. Interestingly, the triazole-susceptible and triazole-resistant populations showed different population structures, consistent with antifungal drug pressure playing a significant role in local adaptation. Our results suggest that global populations of A. fumigatus are shaped by historical differentiation, contemporary gene flow, sexual reproduction, and the localized antifungal drug selection that is driving clonal expansion of genotypes resistant to multiple triazole drugs. IMPORTANCE The genetic diversity and geographic structure of the human fungal pathogen A. fumigatus have been the subject of many studies. However, most previous studies had relatively limited sample ranges and sizes and/or used genetic markers with low-level polymorphisms. In this paper, we characterize a global collection of strains of A. fumigatus using a panel of 9 highly

  16. Global analysis of duality maps in quantum field theory

    SciTech Connect

    Restuccia, A.

    1997-03-15

    A global analysis of duality transformations is presented. Global constraints are introduced in order to have the correct structure of the configuration spaces. This global structure is completely determined from the quantum equivalence of dual actions. Applications to S-dual actions and to T duality of string theories and D-branes are briefly discussed. It is shown that a new topological term in the dual open string actions is required.

  17. Global functions in global-local finite-element analysis of localized stresses in prismatic structures

    NASA Technical Reports Server (NTRS)

    Dong, Stanley B.

    1989-01-01

    An important consideration in the global local finite-element method (GLFEM) is the availability of global functions for the given problem. The role and mathematical requirements of these global functions in a GLFEM analysis of localized stress states in prismatic structures are discussed. A method is described for determining these global functions. Underlying this method are theorems due to Toupin and Knowles on strain energy decay rates, which are related to a quantitative expression of Saint-Venant's principle. It is mentioned that a mathematically complete set of global functions can be generated, so that any arbitrary interface condition between the finite element and global subregions can be represented. Convergence to the true behavior can be achieved with increasing global functions and finite-element degrees of freedom. Specific attention is devoted to mathematically two-dimensional and three-dimensional prismatic structures. Comments are offered on the GLFEM analysis of NASA flat panel with a discontinuous stiffener. Methods for determining global functions for other effects are also indicated, such as steady-state dynamics and bodies under initial stress.

  18. Global analysis of translation termination in E. coli.

    PubMed

    Baggett, Natalie E; Zhang, Yan; Gross, Carol A

    2017-03-01

    Terminating protein translation accurately and efficiently is critical for both protein fidelity and ribosome recycling for continued translation. The three bacterial release factors (RFs) play key roles: RF1 and 2 recognize stop codons and terminate translation; and RF3 promotes disassociation of bound release factors. Probing release factors mutations with reporter constructs containing programmed frameshifting sequences or premature stop codons had revealed a propensity for readthrough or frameshifting at these specific sites, but their effects on translation genome-wide have not been examined. We performed ribosome profiling on a set of isogenic strains with well-characterized release factor mutations to determine how they alter translation globally. Consistent with their known defects, strains with increasingly severe release factor defects exhibit increasingly severe accumulation of ribosomes over stop codons, indicative of an increased duration of the termination/release phase of translation. Release factor mutant strains also exhibit increased occupancy in the region following the stop codon at a significant number of genes. Our global analysis revealed that, as expected, translation termination is generally efficient and accurate, but that at a significant number of genes (≥ 50) the ribosome signature after the stop codon is suggestive of translation past the stop codon. Even native E. coli K-12 exhibits the ribosome signature suggestive of protein extension, especially at UGA codons, which rely exclusively on the reduced function RF2 variant of the K-12 strain for termination. Deletion of RF3 increases the severity of the defect. We unambiguously demonstrate readthrough and frameshifting protein extensions and their further accumulation in mutant strains for a few select cases. In addition to enhancing recoding, ribosome accumulation over stop codons disrupts attenuation control of biosynthetic operons, and may alter expression of some overlapping genes

  19. Global analysis of translation termination in E. coli

    PubMed Central

    Baggett, Natalie E.

    2017-01-01

    Terminating protein translation accurately and efficiently is critical for both protein fidelity and ribosome recycling for continued translation. The three bacterial release factors (RFs) play key roles: RF1 and 2 recognize stop codons and terminate translation; and RF3 promotes disassociation of bound release factors. Probing release factors mutations with reporter constructs containing programmed frameshifting sequences or premature stop codons had revealed a propensity for readthrough or frameshifting at these specific sites, but their effects on translation genome-wide have not been examined. We performed ribosome profiling on a set of isogenic strains with well-characterized release factor mutations to determine how they alter translation globally. Consistent with their known defects, strains with increasingly severe release factor defects exhibit increasingly severe accumulation of ribosomes over stop codons, indicative of an increased duration of the termination/release phase of translation. Release factor mutant strains also exhibit increased occupancy in the region following the stop codon at a significant number of genes. Our global analysis revealed that, as expected, translation termination is generally efficient and accurate, but that at a significant number of genes (≥ 50) the ribosome signature after the stop codon is suggestive of translation past the stop codon. Even native E. coli K-12 exhibits the ribosome signature suggestive of protein extension, especially at UGA codons, which rely exclusively on the reduced function RF2 variant of the K-12 strain for termination. Deletion of RF3 increases the severity of the defect. We unambiguously demonstrate readthrough and frameshifting protein extensions and their further accumulation in mutant strains for a few select cases. In addition to enhancing recoding, ribosome accumulation over stop codons disrupts attenuation control of biosynthetic operons, and may alter expression of some overlapping genes

  20. Global phylogeography of Dengue type 1 and 2 viruses reveals the role of India.

    PubMed

    Walimbe, Atul M; Lotankar, Mrunalini; Cecilia, D; Cherian, Sarah S

    2014-03-01

    Patterns in virus dispersal and epidemiology of viral diseases can be revealed by phylogeographic studies. Currently knowledge about phylogeography of Dengue virus (DENV) Types 1 and 2 is limited. We carried out the phylogeographic analyses for DENV-1 and DENV-2, by the Bayesian Markov Chain Monte Carlo (MCMC) approach, with emphasis on Indian isolates in relation to the global evolutionary dynamics of the viruses. More than 250 E-gene sequences of each virus, available in GenBank, were used for the analyses. The study was focused on understanding the most likely geographical origin for the major genotypes and sub-lineages of DENV-1/DENV-2 and also the possible pathways in the dispersal of the virus. The results showed that for DENV-1, Southeast Asia was the most likely geographical origin and India was determined to be the ancestral location of the Cosmopolitan genotype circulating in India, Sri Lanka, West and East Africa, Caribbean region, East and Southeast Asia. For DENV-2, the ancestral source could not be precisely inferred. Further, in spite of the earliest isolate from Trinidad-1953 of the American genotype, it was depicted that India may have been the probable ancestor of this genotype. India was also determined to be the ancestral location of a subgroup of the Cosmopolitan genotype. It was noted that DENV-1 and DENV-2 were introduced into India during 1940s and 1910s respectively. Subsequently, dispersal of both the viruses between India and different regions including West, East and Central Africa, Southeast and East Asia and Caribbean was inferred. Overall, the current study provides insight into the spatial as well as temporal dynamics of dengue virus serotypes 1 and 2. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. Global Phosphoproteome Profiling Reveals Unanticipated Networks Responsive to Cisplatin Treatment of Embryonic Stem Cells ▿ †

    PubMed Central

    Pines, Alex; Kelstrup, Christian D.; Vrouwe, Mischa G.; Puigvert, Jordi C.; Typas, Dimitris; Misovic, Branislav; de Groot, Anton; von Stechow, Louise; van de Water, Bob; Danen, Erik H. J.; Vrieling, Harry; Mullenders, Leon H. F.; Olsen, Jesper V.

    2011-01-01

    Cellular responses to DNA-damaging agents involve the activation of various DNA damage signaling and transduction pathways. Using quantitative and high-resolution tandem mass spectrometry, we determined global changes in protein level and phosphorylation site profiles following treatment of SILAC (stable isotope labeling by amino acids in cell culture)-labeled murine embryonic stem cells with the anticancer drug cisplatin. Network and pathway analyses indicated that processes related to the DNA damage response and cytoskeleton organization were significantly affected. Although the ATM (ataxia telangiectasia mutated) and ATR (ATM and Rad3-related) consensus sequence (S/T-Q motif) was significantly overrepresented among hyperphosphorylated peptides, about half of the >2-fold-upregulated phosphorylation sites based on the consensus sequence were not direct substrates of ATM and ATR. Eleven protein kinases mainly belonging to the mitogen-activated protein kinase (MAPK) family were identified as being regulated in their kinase domain activation loop. The biological importance of three of these kinases (cyclin-dependent kinase 7 [CDK7], Plk1, and KPCD1) in the protection against cisplatin-induced cytotoxicity was demonstrated by small interfering RNA (siRNA)-mediated knockdown. Our results indicate that the cellular response to cisplatin involves a variety of kinases and phosphatases not only acting in the nucleus but also regulating cytoplasmic targets, resulting in extensive cytoskeletal rearrangements. Integration of transcriptomic and proteomic data revealed a poor correlation between changes in the relative levels of transcripts and their corresponding proteins, but a large overlap in affected pathways at the levels of mRNA, protein, and phosphoprotein. This study provides an integrated view of pathways activated by genotoxic stress and deciphers kinases that play a pivotal role in regulating cellular processes other than the DNA damage response. PMID:22006019

  2. Developmental Control of Stress Stimulons in Streptomyces coelicolor Revealed by Statistical Analyses of Global Gene Expression Patterns

    PubMed Central

    Vohradsky, J.; Li, X.-M.; Dale, G.; Folcher, M.; Nguyen, L.; Viollier, P. H.; Thompson, C. J.

    2000-01-01

    Stress-induced regulatory networks coordinated with a procaryotic developmental program were revealed by two-dimensional gel analyses of global gene expression. Four developmental stages were identified by their distinctive protein synthesis patterns using principal component analysis. Statistical analyses focused on five stress stimulons (induced by heat, cold, salt, ethanol, or antibiotic shock) and their synthesis during development. Unlike other bacteria, for which various stresses induce expression of similar sets of protein spots, in Streptomyces coelicolor heat, salt, and ethanol stimulons were composed of independent sets of proteins. This suggested independent control by different physiological stress signals and their corresponding regulatory systems. These stress proteins were also under developmental control. Cluster analysis of stress protein synthesis profiles identified 10 different developmental patterns or “synexpression groups.” Proteins induced by cold, heat, or salt shock were enriched in three developmental synexpression groups. In addition, certain proteins belonging to the heat and salt shock stimulons were coregulated during development. Thus, stress regulatory systems controlling these stimulons were implicated as integral parts of the developmental program. This correlation suggested that thermal shock and salt shock stress response regulatory systems either allow the cell to adapt to stresses associated with development or directly control the developmental program. PMID:10940043

  3. Phaeobacter gallaeciensis genomes from globally opposite locations reveal high similarity of adaptation to surface life

    PubMed Central

    Thole, Sebastian; Kalhoefer, Daniela; Voget, Sonja; Berger, Martine; Engelhardt, Tim; Liesegang, Heiko; Wollherr, Antje; Kjelleberg, Staffan; Daniel, Rolf; Simon, Meinhard; Thomas, Torsten; Brinkhoff, Thorsten

    2012-01-01

    Phaeobacter gallaeciensis, a member of the abundant marine Roseobacter clade, is known to be an effective colonizer of biotic and abiotic marine surfaces. Production of the antibiotic tropodithietic acid (TDA) makes P. gallaeciensis a strong antagonist of many bacteria, including fish and mollusc pathogens. In addition to TDA, several other secondary metabolites are produced, allowing the mutualistic bacterium to also act as an opportunistic pathogen. Here we provide the manually annotated genome sequences of the P. gallaeciensis strains DSM 17395 and 2.10, isolated at the Atlantic coast of north western Spain and near Sydney, Australia, respectively. Despite their isolation sites from the two different hemispheres, the genome comparison demonstrated a surprisingly high level of synteny (only 3% nucleotide dissimilarity and 88% and 93% shared genes). Minor differences in the genomes result from horizontal gene transfer and phage infection. Comparison of the P. gallaeciensis genomes with those of other roseobacters revealed unique genomic traits, including the production of iron-scavenging siderophores. Experiments supported the predicted capacity of both strains to grow on various algal osmolytes. Transposon mutagenesis was used to expand the current knowledge on the TDA biosynthesis pathway in strain DSM 17395. This first comparative genomic analysis of finished genomes of two closely related strains belonging to one species of the Roseobacter clade revealed features that provide competitive advantages and facilitate surface attachment and interaction with eukaryotic hosts. PMID:22717884

  4. Global Analysis of Aerosol Properties Above Clouds

    NASA Technical Reports Server (NTRS)

    Waquet, F.; Peers, F.; Ducos, F.; Goloub, P.; Platnick, S. E.; Riedi, J.; Tanre, D.; Thieuleux, F.

    2013-01-01

    The seasonal and spatial varability of Aerosol Above Cloud (AAC) properties are derived from passive satellite data for the year 2008. A significant amount of aerosols are transported above liquid water clouds on the global scale. For particles in the fine mode (i.e., radius smaller than 0.3 m), including both clear sky and AAC retrievals increases the global mean aerosol optical thickness by 25(+/- 6%). The two main regions with man-made AAC are the tropical Southeast Atlantic, for biomass burning aerosols, and the North Pacific, mainly for pollutants. Man-made AAC are also detected over the Arctic during the spring. Mineral dust particles are detected above clouds within the so-called dust belt region (5-40 N). AAC may cause a warming effect and bias the retrieval of the cloud properties. This study will then help to better quantify the impacts of aerosols on clouds and climate.

  5. Change in global temperature: A statistical analysis

    SciTech Connect

    Richards, G.R. )

    1993-03-01

    This paper investigates several issues relating to global climatic change using statistical techniques that impose minimal restrictions on the data. The main findings are as follows: (1) The global temperature increase since the last century is a systematic development. (2) Short-term variations in temperature do not have long-lasting effects on the final realizations of the series over time, stochastic perturbations dissipate and temperature reverts to trend. (3) Multivariate tests for causality demonstrate that atmospheric CO[sub 2] is a significant forcing factor. The implied change in temperature with respect to a doubling of atmospheric CO[sub 2] lies in a range of 2.17[degrees] to 2.57[degrees]C, with a mean value of 2.34[degrees]C. The contributions of solar irradiance and volcanic loading are much smaller. (4) In a multivariate system, shocks to forcing factors generate stochastic cycles in temperature comparable to the results from unforced simulations of climatological models. (5) Extrapolation of regression equations predict changes in global temperature that are marginally lower than the results from climatological simulation models.

  6. Global chromatin profiling reveals NSD2 mutations in pediatric acute lymphoblastic leukemia

    PubMed Central

    Jaffe, Jacob D; Wang, Yan; Chan, Ho Man; Zhang, Jinghui; Huether, Robert; Kryukov, Gregory V; Bhang, Hyo-eun C; Taylor, Jordan E; Hu, Min; Englund, Nathan P; Yan, Feng; Wang, Zhaofu; McDonald, E Robert; Wei, Lei; Ma, Jing; Easton, John; Yu, Zhengtian; deBeaumount, Rosalie; Gibaja, Veronica; Venkatesan, Kavitha; Schlegel, Robert; Sellers, William R; Keen, Nicholas; Liu, Jun; Caponigro, Giordano; Barretina, Jordi; Cooke, Vesselina G; Mullighan, Charles; Carr, Steven A; Downing, James R; Garraway, Levi A; Stegmeier, Frank

    2014-01-01

    Epigenetic dysregulation is an emerging hallmark of cancers. We developed a high-information-content mass spectrometry approach to profile global histone modifications in human cancers. When applied to 115 lines from the Cancer Cell Line Encyclopedia1, this approach identified distinct molecular chromatin signatures. One signature was characterized by increased histone 3 lysine 36 (H3K36) dimethylation, exhibited by several lines harboring translocations in NSD2, which encodes a methyltransferase. A previously unknown NSD2 p.Glu1099Lys (p.E1099K) variant was identified in nontranslocated acute lymphoblastic leukemia (ALL) cell lines sharing this signature. Ectopic expression of the variant induced a chromatin signature characteristic of NSD2 hyperactivation and promoted transformation. NSD2 knockdown selectively inhibited the proliferation of NSD2-mutant lines and impaired the in vivo growth of an NSD2-mutant ALL xenograft. Sequencing analysis of >1,000 pediatric cancer genomes identified the NSD2 p.E1099K alteration in 14% of t(12;21) ETV6-RUNX1–containing ALLs. These findings identify NSD2 as a potential therapeutic target for pediatric ALL and provide a general framework for the functional annotation of cancer epigenomes. PMID:24076604

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

    PubMed

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

    2005-03-01

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

  8. "Competing Conceptions of Globalization" Revisited: Relocating the Tension between World-Systems Analysis and Globalization Analysis

    ERIC Educational Resources Information Center

    Clayton, Thomas

    2004-01-01

    In recent years, many scholars have become fascinated by a contemporary, multidimensional process that has come to be known as "globalization." Globalization originally described economic developments at the world level. More specifically, scholars invoked the concept in reference to the process of global economic integration and the seemingly…

  9. "Competing Conceptions of Globalization" Revisited: Relocating the Tension between World-Systems Analysis and Globalization Analysis

    ERIC Educational Resources Information Center

    Clayton, Thomas

    2004-01-01

    In recent years, many scholars have become fascinated by a contemporary, multidimensional process that has come to be known as "globalization." Globalization originally described economic developments at the world level. More specifically, scholars invoked the concept in reference to the process of global economic integration and the seemingly…

  10. Global Hawk: Root Cause Analysis of Projected Unit Cost Growth

    DTIC Science & Technology

    2011-05-01

    2009 (WSARA). This report describes our task analysis and findings. The Global Hawk Program Global Hawk is a family of high -altitude, high -endurance...Document (CDD) • Cost Analysis Requirements Description (CARD) • Test and Evaluation Master Plan ( TEMP ) • Acquisition Program Baseline (APB...fixed content and completion criteria as defined by the new CDD, CARD, TEMP , and ASR. The four increments shown in the table above reflect the

  11. Analysis of Global Properties of Shapes

    DTIC Science & Technology

    2010-06-01

    shown in Figure 3.9. The images in Figure 3.9b show dis- crete segmentations of a kangaroo produced by a randomized hierarchical clustering algorithm...it lies on a segment boundary. We believe that this continuous function reveals more information about the part structure of the kangaroo than does

  12. Crystallographic and electron microscopic analyses of a bacterial phytochrome reveal local and global rearrangements during photoconversion.

    PubMed

    Burgie, E Sethe; Wang, Tong; Bussell, Adam N; Walker, Joseph M; Li, Huilin; Vierstra, Richard D

    2014-08-29

    Phytochromes are multidomain photoswitches that drive light perception in plants and microorganisms by coupling photoreversible isomerization of their bilin chromophore to various signaling cascades. How changes in bilin conformation affect output by these photoreceptors remains poorly resolved and might include several species-specific routes. Here, we present detailed three-dimensional models of the photosensing module and a picture of an entire dimeric photoreceptor through structural analysis of the Deinococcus radiodurans phytochrome BphP assembled with biliverdin (BV). A 1.16-Å resolution crystal structure of the bilin-binding pocket in the dark-adapted red light-absorbing state illuminated the intricate network of bilin/protein/water interactions and confirmed the protonation and ZZZssa conformation of BV. Structural and spectroscopic comparisons with the photochemically compromised D207A mutant revealed that substitutions of Asp-207 allow inclusion of cyclic porphyrins in addition to BV. A crystal structure of the entire photosensing module showed a head-to-head, twisted dimeric arrangement with bowed helical spines and a hairpin protrusion connecting the cGMP phosphodiesterase/adenylyl cyclase/FhlA (GAF) and phytochrome-specific (PHY) domains. A key conserved hairpin feature is its anti-parallel, two β-strand stem, which we show by mutagenesis to be critical for BphP photochemistry. Comparisons of single particle electron microscopic images of the full-length BphP dimer in the red light-absorbing state and the photoactivated far-red light-absorbing state revealed a large scale reorientation of the PHY domain relative to the GAF domain, which alters the position of the downstream histidine kinase output module. Together, our data support a toggle model whereby bilin photoisomerization alters GAF/PHY domain interactions through conformational modification of the hairpin, which regulates signaling by impacting the relationship between sister output modules

  13. Global Gene Expression Analysis for the Assessment of Nanobiomaterials.

    PubMed

    Hanagata, Nobutaka

    2015-01-01

    Using global gene expression analysis, the effects of biomaterials and nanomaterials can be analyzed at the genetic level. Even though information obtained from global gene expression analysis can be useful for the evaluation and design of biomaterials and nanomaterials, its use for these purposes is not widespread. This is due to the difficulties involved in data analysis. Because the expression data of about 20,000 genes can be obtained at once with global gene expression analysis, the data must be analyzed using bioinformatics. A method of bioinformatic analysis called gene ontology can estimate the kinds of changes on cell functions caused by genes whose expression level is changed by biomaterials and nanomaterials. Also, by applying a statistical analysis technique called hierarchical clustering to global gene expression data between a variety of biomaterials, the effects of the properties of materials on cell functions can be estimated. In this chapter, these theories of analysis and examples of applications to nanomaterials and biomaterials are described. Furthermore, global microRNA analysis, a method that has gained attention in recent years, and its application to nanomaterials are introduced.

  14. Analysis and visualization of global magnetospheric processes

    SciTech Connect

    Winske, D.; Mozer, F.S.; Roth, I.

    1998-12-31

    This is the final report of a three-year, Laboratory Directed Research and Development (LDRD) project at Los Alamos National Laboratory (LANL). The purpose of this project is to develop new computational and visualization tools to analyze particle dynamics in the Earth`s magnetosphere. These tools allow the construction of a global picture of particle fluxes, which requires only a small number of in situ spacecraft measurements as input parameters. The methods developed in this project have led to a better understanding of particle dynamics in the Earth`s magnetotail in the presence of turbulent wave fields. They have also been used to demonstrate how large electromagnetic pulses in the solar wind can interact with the magnetosphere to increase the population of energetic particles and even form new radiation belts.

  15. Polyandry in nature: a global analysis.

    PubMed

    Taylor, Michelle L; Price, Tom A R; Wedell, Nina

    2014-07-01

    A popular notion in sexual selection is that females are polyandrous and their offspring are commonly sired by more than a single male. We now have large-scale evidence from natural populations to be able to verify this assumption. Although we concur that polyandry is a generally common and ubiquitous phenomenon, we emphasise that it remains variable. In particular, the persistence of single paternity, both within and between populations, requires more careful consideration. We also explore an intriguing relation of polyandry with latitude. Several recent large-scale analyses of the relations between key population fitness variables, such as heterozygosity, effective population size (Ne), and inbreeding coefficients, make it possible to examine the global effects of polyandry on population fitness for the first time. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  16. National health expenditures: a global analysis.

    PubMed

    Murray, C J; Govindaraj, R; Musgrove, P

    1994-01-01

    As part of the background research to the World development report 1993: investing in health, an effort was made to estimate public, private and total expenditures on health for all countries of the world. Estimates could be found for public spending for most countries, but for private expenditure in many fewer countries. Regressions were used to predict the missing values of regional and global estimates. These econometric exercises were also used to relate expenditure to measures of health status. In 1990 the world spent an estimated US$ 1.7 trillion (1.7 x 10(12) on health, or $1.9 trillion (1.9 x 10(12)) in dollars adjusted for higher purchasing power in poorer countries. This amount was about 60% public and 40% private in origin. However, as incomes rise, public health expenditure tends to displace private spending and to account for the increasing share of incomes devoted to health.

  17. Water Grabbing analysis at global scale

    NASA Astrophysics Data System (ADS)

    Rulli, M.; Saviori, A.; D'Odorico, P.

    2012-12-01

    "Land grabbing" is the acquisition of agricultural land by foreign governments and corporations, a phenomenon that has greatly intensified over the last few years as a result of the increase in food prices and biofuel demand. Land grabbing is inherently associated with an appropriation of freshwater resources that has never been investigated before. Here we provide a global assessment of the total grabbed land and water resources. Using process-based agro-hydrological models we estimate the rates of freshwater grabbing worldwide. We find that this phenomenon is occurring at alarming rates in all continents except Antarctica. The per capita volume of grabbed water often exceeds the water requirements for a balanced diet and would be sufficient to abate malnourishment in the grabbed countries. High rates of water grabbing are often associated with deforestation and the increase in water withdrawals for irrigation.

  18. National health expenditures: a global analysis.

    PubMed Central

    Murray, C. J.; Govindaraj, R.; Musgrove, P.

    1994-01-01

    As part of the background research to the World development report 1993: investing in health, an effort was made to estimate public, private and total expenditures on health for all countries of the world. Estimates could be found for public spending for most countries, but for private expenditure in many fewer countries. Regressions were used to predict the missing values of regional and global estimates. These econometric exercises were also used to relate expenditure to measures of health status. In 1990 the world spent an estimated US$ 1.7 trillion (1.7 x 10(12) on health, or $1.9 trillion (1.9 x 10(12)) in dollars adjusted for higher purchasing power in poorer countries. This amount was about 60% public and 40% private in origin. However, as incomes rise, public health expenditure tends to displace private spending and to account for the increasing share of incomes devoted to health. PMID:7923542

  19. Mode of Anisotropy Reveals Global Diffusion Alterations in Attention-Deficit/Hyperactivity Disorder

    PubMed Central

    Yoncheva, Yuliya N.; Somandepalli, Krishna; Reiss, Philip T.; Kelly, Clare; Di Martino, Adriana; Lazar, Mariana; Zhou, Juan; Milham, Michael P.; Castellanos, F. Xavier

    2016-01-01

    Objective Diffusion tensor imaging (DTI) can identify structural connectivity alterations in attention-deficit/hyperactivity disorder (ADHD). Most ADHD DTI studies have concentrated on regional differences in fractional anisotropy (FA) despite its limited sensitivity to complex white matter architecture and increasing evidence of global brain differences in ADHD. Here, we examine multiple DTI metrics in separate samples of children and adults with and without ADHD with a principal focus on global between-group differences. Method Two samples: adults with ADHD (n = 42) and without (n = 65) and children with ADHD (n = 82) and without (n = 80) were separately group matched for age, sex, and head motion. Five DTI metrics (FA, axial diffusivity, radial diffusivity, mean diffusivity, and mode of anisotropy) were analyzed via tract-based spatial statistics. Group analyses tested for diagnostic differences at the global (averaged across the entire white matter skeleton) and regional level for each metric. Results Robust global group differences in diffusion indices were found in adults, with the largest effect size for mode of anisotropy (MA; Cohen’s d = 1.45). Global MA also differed significantly between groups in the pediatric sample (d = 0.68). In both samples, global MA increased classification accuracy compared to the model with clinical Conners’ ADHD ratings alone. Regional diagnostic differences did not survive familywise correction for multiple comparisons. Conclusion Global DTI metrics, particularly the mode of anisotropy, which is sensitive to crossing fibers, capture connectivity abnormalities in ADHD across both pediatric and adult samples. These findings highlight potential diffuse white matter microarchitecture differences in ADHD. PMID:26802781

  20. FUNGAL SYMBIONTS. Global assessment of arbuscular mycorrhizal fungus diversity reveals very low endemism.

    PubMed

    Davison, J; Moora, M; Öpik, M; Adholeya, A; Ainsaar, L; Bâ, A; Burla, S; Diedhiou, A G; Hiiesalu, I; Jairus, T; Johnson, N C; Kane, A; Koorem, K; Kochar, M; Ndiaye, C; Pärtel, M; Reier, Ü; Saks, Ü; Singh, R; Vasar, M; Zobel, M

    2015-08-28

    The global biogeography of microorganisms remains largely unknown, in contrast to the well-studied diversity patterns of macroorganisms. We used arbuscular mycorrhizal (AM) fungus DNA from 1014 plant-root samples collected worldwide to determine the global distribution of these plant symbionts. We found that AM fungal communities reflected local environmental conditions and the spatial distance between sites. However, despite AM fungi apparently possessing limited dispersal ability, we found 93% of taxa on multiple continents and 34% on all six continents surveyed. This contrasts with the high spatial turnover of other fungal taxa and with the endemism displayed by plants at the global scale. We suggest that the biogeography of AM fungi is driven by unexpectedly efficient dispersal, probably via both abiotic and biotic vectors, including humans.

  1. Global kinetic analysis of seeded BSA aggregation.

    PubMed

    Sahin, Ziya; Demir, Yusuf Kemal; Kayser, Veysel

    2016-04-30

    Accelerated aggregation studies were conducted around the melting temperature (Tm) to elucidate the kinetics of seeded BSA aggregation. Aggregation was tracked by SEC-HPLC and intrinsic fluorescence spectroscopy. Time evolution of monomer, dimer and soluble aggregate concentrations were globally analysed to reliably deduce mechanistic details pertinent to the process. Results showed that BSA aggregated irreversibly through both sequential monomer addition and aggregate-aggregate interactions. Sequential monomer addition proceeded only via non-native monomers, starting to occur only by 1-2°C below the Tm. Aggregate-aggregate interactions were the dominant mechanism below the Tm due to an initial presence of small aggregates that acted as seeds. Aggregate-aggregate interactions were significant also above the Tm, particularly at later stages of aggregation when sequential monomer addition seemed to cease, leading in some cases to insoluble aggregate formation. The adherence (or non-thereof) of the mechanisms to Arrhenius kinetics were discussed alongside possible implications of seeding for biopharmaceutical shelf-life and spectroscopic data interpretation, the latter of which was found to often be overlooked in BSA aggregation studies. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Invoking Thomas Kuhn: What Citation Analysis Reveals about Science Education

    NASA Astrophysics Data System (ADS)

    Loving, Cathleen C.; Cobern, William W.

    This paper analyzes how Thomas Kuhn's writings are used by others, especially science education researchers. Previous research in citation analysis is used to frame questions related to who cites Kuhn, in what manner and why. Research questions first focus on the variety of disciplines invoking Kuhn and to what extent Structure of Scientific Revolutions (SSR) is cited. The Web of Science database provides material from 1982 for this analysis. The science education literature is analyzed using back issues from 1985 of the Journal of Research in Science Teaching and Science Education. An article analysis reveals trends in terms of what Kuhnian ideas are most frequently invoked. Results indicate a wide array of disciplines from beekeeping to law cite Kuhn - especially generic citations to SSR. The science education journal analysis reveals pervasive use of the term paradigm, although use is quite varied. The two areas of research in science education most impacted by Kuhn appear to be conceptual change theory and constructivist epistemologies. Additional uses of Kuhn are discussed. The degree to which Kuhn is invoked in ways supporting the theoretical framework of citation analysis, whether his work is misappropriated, and the impact of Kuhn are discussed.

  3. Exposure to ionizing radiation reveals global dose- and time-dependent changes in the urinary metabolome of rat

    PubMed Central

    Mak, Tytus D.; Tyburski, John B.; Krausz, Kristopher W.; Kalinich, John F.; Gonzalez, Frank J.; Fornace, Albert J.

    2014-01-01

    The potential for exposures to ionizing radiation has increased in recent years. Although advances have been made, understanding the global metabolic response as a function of both dose and exposure time is challenging considering the complexity of the responses. Herein we report our findings on the dose- and time-dependency of the urinary response to ionizing radiation in the male rat using radiation metabolomics. Urine samples were collected from adult male rats, exposed to 0.5 to 10 Gy γ–radiation, both before from 6 to 72 h following exposures. Samples were analyzed by liquid chromatography coupled with time-of-flight mass spectrometry, and deconvoluted mass chromatographic data were initially analyzed by principal component analysis. However, the breadth and complexity of the data necessitated the development of a novel approach to summarizing biofluid constituents after exposure, called Visual Analysis of Metabolomics Package (VAMP). VAMP revealed clear urine metabolite profile differences to as little as 0.5 Gy after 6 h exposure. Via VAMP, it was discovered that the response to radiation exposure found in rat urine is characterized by an overall net down-regulation of ion excretion with only a modest number of ions excreted in excess over pre-exposure levels. Our results show both similarities and differences with the published mouse urine response and a dose- and time-dependent net decrease in urine ion excretion associated with radiation exposure. These findings mark an important step in the development of minimally invasive radiation biodosimetry. VAMP should have general applicability in metabolomics to visualize overall differences and trends in many sample sets. PMID:26557048

  4. Global/local stress analysis of composite panels

    NASA Technical Reports Server (NTRS)

    Ransom, Jonathan B.; Knight, Norman F., Jr.

    1989-01-01

    A method for performing a global/local stress analysis is described, and its capabilities are demonstrated. The method employs spline interpolation functions which satisfy the linear plate bending equation to determine displacements and rotations from a global model which are used as boundary conditions for the local model. Then, the local model is analyzed independent of the global model of the structure. This approach can be used to determine local, detailed stress states for specific structural regions using independent, refined local models which exploit information from less-refined global models. The method presented is not restricted to having a priori knowledge of the location of the regions requiring local detailed stress analysis. This approach also reduces the computational effort necessary to obtain the detailed stress state. Criteria for applying the method are developed. The effectiveness of the method is demonstrated using a classical stress concentration problem and a graphite-epoxy blade-stiffened panel with a discontinuous stiffener.

  5. Global analysis of urban surface water supply vulnerability

    NASA Astrophysics Data System (ADS)

    Padowski, Julie C.; Gorelick, Steven M.

    2014-10-01

    This study presents a global analysis of urban water supply vulnerability in 71 surface-water supplied cities, with populations exceeding 750 000 and lacking source water diversity. Vulnerability represents the failure of an urban supply-basin to simultaneously meet demands from human, environmental and agricultural users. We assess a baseline (2010) condition and a future scenario (2040) that considers increased demand from urban population growth and projected agricultural demand. We do not account for climate change, which can potentially exacerbate or reduce urban supply vulnerability. In 2010, 35% of large cities are vulnerable as they compete with agricultural users. By 2040, without additional measures 45% of cities are vulnerable due to increased agricultural and urban demands. Of the vulnerable cities in 2040, the majority are river-supplied with mean flows so low (1200 liters per person per day, l/p/d) that the cities experience ‘chronic water scarcity’ (1370 l/p/d). Reservoirs supply the majority of cities facing individual future threats, revealing that constructed storage potentially provides tenuous water security. In 2040, of the 32 vulnerable cities, 14 would reduce their vulnerability via reallocating water by reducing environmental flows, and 16 would similarly benefit by transferring water from irrigated agriculture. Approximately half remain vulnerable under either potential remedy.

  6. Global Analysis of Protein Expression of Inner Ear Hair Cells.

    PubMed

    Hickox, Ann E; Wong, Ann C Y; Pak, Kwang; Strojny, Chelsee; Ramirez, Miguel; Yates, John R; Ryan, Allen F; Savas, Jeffrey N

    2017-02-01

    The mammalian inner ear (IE) subserves auditory and vestibular sensations via highly specialized cells and proteins. Sensory receptor hair cells (HCs) are necessary for transducing mechanical inputs and stimulating sensory neurons by using a host of known and as yet unknown protein machinery. To understand the protein composition of these unique postmitotic cells, in which irreversible protein degradation or damage can lead to impaired hearing and balance, we analyzed IE samples by tandem mass spectrometry to generate an unbiased, shotgun-proteomics view of protein identities and abundances. By using Pou4f3/eGFP-transgenic mice in which HCs express GFP driven by Pou4f3, we FACS purified a population of HCs to analyze and compare the HC proteome with other IE subproteomes from sensory epithelia and whole IE. We show that the mammalian HC proteome comprises hundreds of uniquely or highly expressed proteins. Our global proteomic analysis of purified HCs extends the existing HC transcriptome, revealing previously undetected gene products and isoform-specific protein expression. Comparison of our proteomic data with mouse and human databases of genetic auditory/vestibular impairments confirms the critical role of the HC proteome for normal IE function, providing a cell-specific pool of candidates for novel, important HC genes. Several proteins identified exclusively in HCs by proteomics and verified by immunohistochemistry map to human genetic deafness loci, potentially representing new deafness genes.

  7. Global Methods for Image Motion Analysis

    DTIC Science & Technology

    1992-10-01

    including the time for reviewing instructions , searching existing data sources, gathering and maintaining the data needed, and completing and reviewing...thanks go to Pankaj who inspired me in research , to Prasad from whom I have learned so much, and to Ronie and Laureen, the memories of whose company...of images to determine egomotion and to extract information from the scene. Research in motion analysis has been focussed on the problems of

  8. Interaction network analysis revealed biomarkers in myocardial infarction.

    PubMed

    Zhang, Tong; Zhao, Li-Li; Zhang, Zhuo-Ran; Fu, Pei-De; Su, Zhen-Dong; Qi, Li-Chun; Li, Xue-Qi; Dong, Yu-Mei

    2014-08-01

    Myocardial infarction (MI) is a serious heart disease. The cardiac cells of patients with MI will die due to lack of blood for a long time. In this study, we aimed to find new targets for MI diagnosis and therapy. We downloaded GSE22229 including 12 blood samples from healthy persons and GSE29111 from Gene Expression Omnibus including 36 blood samples from MI patients. Then we identified differentially expressed genes (DEGs) in patients with MI compared to normal controls with p value < 0.05 and |logFC| > 1. Furthermore, interaction network and sub-network of these of these DEGs were constructed by NetBox. Linker genes were screened in the Global Network database. The degree of linker genes were calculated by igraph package in R language. Gene ontology and kyoto encyclopedia of genes and genomes pathway analysis were performed for DEGs and network modules. A total of 246 DEGs were identified in MI, which were enriched in the immune response. In the interaction network, LCK, CD247, CD3D, FYN, HLA-DRA, IL2, CD8A CD3E, CD4, CD3G had high degree, among which CD3E, CD4, CD3G were DEGs while others were linker genes screened from Global Network database. Genes in the sub-network were also enriched in the immune response pathway. The genes with high degree may be biomarkers for MI diagnosis and therapy.

  9. Proto-Pacific OAE2 osmium isotope records revealed: global correlation and basin dynamics

    NASA Astrophysics Data System (ADS)

    Du Vivier, A.; Selby, D. S.; Takashima, R.; Condon, D. J.; Nishi, H.

    2013-12-01

    Globally the marine realm across the Cenomanian-Turonian boundary interval records the oceanic anoxic event (OAE) 2. This event has been studied using several geochemical proxies at several sites from the proto-Atlantic. In contrast, there are limited studies from the proto-Pacific. We present initial osmium isotope stratigraphy (Osi) from two proto-Pacific sites: the Yezo Group (YG) section, Hokkaido, Japan, and the Great Valley Sequence (GVS), California, USA; to evaluate the Os seawater chemistry of the proto-Pacific with that of the proto-Atlantic. For the YG section the Osi prior to OAE2 are moderately radiogenic and heterogeneous. Synchronous with OAE2 onset the Osi abruptly become unradiogenic and remain homogenous before showing a gradual return to more radiogenic Osi throughout the middle to late OAE2. The Osi profile from the YG is analogous to the record from the Portland #1 core of the Western Interior Seaway (WIS). In contrast, the Osi profile from the GVS is disparate to the YG profile and those of several proto-Atlantic locations. The Osi for the GVS oscillate from radiogenic to unradiogenic values across the OAE2. We suggest the Osi of the GVS was influenced interchangeably by both unradiogenic and radiogenic Os; where radiogenic Osi is associated with weathered evolved continental rocks and unradiogenic Osi is derived from a submarine hydrothermal input associated with the Caribbean Large Igneous Province (CLIP). All proto-Atlantic sections show a synchronous correlation between Osi and δ13Corg excursions. However, this is not the case for the YG. As such we infer that the OAE2 excursion has been misidentified in the δ13Cwood analysis for the YG and thus the onset is ~24 m higher in the section. In order to further facilitate correlation we identified a number of zircon bearing tuff horizons throughout the YG for U-Pb ID-TIMS zircon geochronology. The Osi data and U-Pb age(s) combined, improves the correlation and the identification of the OAE2

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

    NASA Astrophysics Data System (ADS)

    Sun, A. Y.; Chen, J.; Donges, J.

    2015-04-01

    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.

  11. Dynamic analysis of global copper flows. Global stocks, postconsumer material flows, recycling indicators, and uncertainty evaluation.

    PubMed

    Glöser, Simon; Soulier, Marcel; Tercero Espinoza, Luis A

    2013-06-18

    We present a dynamic model of global copper stocks and flows which allows a detailed analysis of recycling efficiencies, copper stocks in use, and dissipated and landfilled copper. The model is based on historical mining and refined copper production data (1910-2010) enhanced by a unique data set of recent global semifinished goods production and copper end-use sectors provided by the copper industry. To enable the consistency of the simulated copper life cycle in terms of a closed mass balance, particularly the matching of recycled metal flows to reported historical annual production data, a method was developed to estimate the yearly global collection rates of end-of-life (postconsumer) scrap. Based on this method, we provide estimates of 8 different recycling indicators over time. The main indicator for the efficiency of global copper recycling from end-of-life (EoL) scrap--the EoL recycling rate--was estimated to be 45% on average, ± 5% (one standard deviation) due to uncertainty and variability over time in the period 2000-2010. As uncertainties of specific input data--mainly concerning assumptions on end-use lifetimes and their distribution--are high, a sensitivity analysis with regard to the effect of uncertainties in the input data on the calculated recycling indicators was performed. The sensitivity analysis included a stochastic (Monte Carlo) uncertainty evaluation with 10(5) simulation runs.

  12. Contemporary evolution of plant reproductive strategies under global change is revealed by stored seeds.

    PubMed

    Thomann, M; Imbert, E; Engstrand, R C; Cheptou, P-O

    2015-04-01

    Global change is expected to impose new selection pressures on natural populations. Phenotypic responses, such as earlier phenology in response to climate warming, have been repeatedly observed in the field. The recent pollinator decline is also expected to change selection on reproductive traits in flowering plants. However, it remains unclear whether short-term adaptation of plant reproductive strategies occurs in response to global change. In this study, we report the evolution of some important reproductive traits of the annual self-incompatible weed Centaurea cyanus. In a common garden experiment, we germinated stored seeds, sampled 18 years apart from the same location, in a region where warmer springs and indices of pollinator decline have been reported. Compared to the ancestral population (1992), our results showed that plants of the descendant population (2010) flowered earlier and also produced larger capitula with longer receptivity and a larger floral display. QST -FST comparisons indicated that natural selection has likely contributed to the evolution of some of the traits investigated. Lower FST within temporal samples than among spatial samples further suggests a limited role of gene flow from neighbouring populations. We therefore propose that trait shifts could partly be due to adaptation to global change. © 2015 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2015 European Society For Evolutionary Biology.

  13. Recurrence quantification analysis of global stock markets

    NASA Astrophysics Data System (ADS)

    Bastos, João A.; Caiado, Jorge

    2011-04-01

    This study investigates the presence of deterministic dependencies in international stock markets using recurrence plots and recurrence quantification analysis (RQA). The results are based on a large set of free float-adjusted market capitalization stock indices, covering a period of 15 years. The statistical tests suggest that the dynamics of stock prices in emerging markets is characterized by higher values of RQA measures when compared to their developed counterparts. The behavior of stock markets during critical financial events, such as the burst of the technology bubble, the Asian currency crisis, and the recent subprime mortgage crisis, is analyzed by performing RQA in sliding windows. It is shown that during these events stock markets exhibit a distinctive behavior that is characterized by temporary decreases in the fraction of recurrence points contained in diagonal and vertical structures.

  14. Global/local finite element analysis of composite materials

    NASA Technical Reports Server (NTRS)

    Griffin, O. Hayden, Jr.; Vidussoni, M. A.

    1988-01-01

    The motivation for performing global/local finite element analysis in composite materials is described. An example of such an analysis of a composite plate with a central circular hole is presented. Deformed finite element grids and interlaminar normal stress distributions are presented to aid understanding of the plate response. Such distribution at the plate edge is shown to be basically unaffected, although transverse displacements of the edge were slightly different from an analysis of a similar plate with no hole.

  15. Uncertainty analysis and global sensitivity analysis of techno-economic assessments for biodiesel production.

    PubMed

    Tang, Zhang-Chun; Zhenzhou, Lu; Zhiwen, Liu; Ningcong, Xiao

    2015-01-01

    There are various uncertain parameters in the techno-economic assessments (TEAs) of biodiesel production, including capital cost, interest rate, feedstock price, maintenance rate, biodiesel conversion efficiency, glycerol price and operating cost. However, fewer studies focus on the influence of these parameters on TEAs. This paper investigated the effects of these parameters on the life cycle cost (LCC) and the unit cost (UC) in the TEAs of biodiesel production. The results show that LCC and UC exhibit variations when involving uncertain parameters. Based on the uncertainty analysis, three global sensitivity analysis (GSA) methods are utilized to quantify the contribution of an individual uncertain parameter to LCC and UC. The GSA results reveal that the feedstock price and the interest rate produce considerable effects on the TEAs. These results can provide a useful guide for entrepreneurs when they plan plants. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. Global analysis of heat shock response in Desulfovibrio vulgaris Hildenborough.

    SciTech Connect

    Arkin, A. P.; Wall, J. D.; Hazen, T. C.; He, Z.; Zhou, J.; Huang, K. H.; Gaucher, Sara P.; He, Q.; Hadi, Masood Z.; Chhabra, Swapnil R.; Alm, Eric J.; Singh, A. K.

    2005-08-01

    Desulfovibrio vulgaris Hildenborough belongs to a class of sulfate-reducing bacteria (SRB) and is found ubiquitously in nature. Given the importance of SRB-mediated reduction for bioremediation of metal ion contaminants, ongoing research on D. vulgaris has been in the direction of elucidating regulatory mechanisms for this organism under a variety of stress conditions. This work presents a global view of this organism's response to elevated growth temperature using whole-cell transcriptomics and proteomics tools. Transcriptional response (1.7-fold change or greater; Z {ge} 1.5) ranged from 1,135 genes at 15 min to 1,463 genes at 120 min for a temperature up-shift of 13 C from a growth temperature of 37 C for this organism and suggested both direct and indirect modes of heat sensing. Clusters of orthologous group categories that were significantly affected included posttranslational modifications; protein turnover and chaperones (up-regulated); energy production and conversion (down-regulated), nucleotide transport, metabolism (down-regulated), and translation; ribosomal structure; and biogenesis (down-regulated). Analysis of the genome sequence revealed the presence of features of both negative and positive regulation which included the CIRCE element and promoter sequences corresponding to the alternate sigma factors {sigma}{sup 32} and {sigma}{sup 54}. While mechanisms of heat shock control for some genes appeared to coincide with those established for Escherichia coli and Bacillus subtilis, the presence of unique control schemes for several other genes was also evident. Analysis of protein expression levels using differential in-gel electrophoresis suggested good agreement with transcriptional profiles of several heat shock proteins, including DnaK (DVU0811), HtpG (DVU2643), HtrA (DVU1468), and AhpC (DVU2247). The proteomics study also suggested the possibility of posttranslational modifications in the chaperones DnaK, AhpC, GroES (DVU1977), and GroEL (DVU1976

  17. Global Analysis of Heat Shock Response in Desulfovibrio vulgaris Hildenborough.

    SciTech Connect

    Chhabra, S.R.; He, Q.; Huang, K.H.; Gaucher, S.P.; Alm, E.J.; He,Z.; Hadi, M.Z.; Hazen, T.C.; Wall, J.D.; Zhou, J.; Arkin, A.P.; Singh, A.K.

    2005-09-16

    Desulfovibrio vulgaris Hildenborough belongs to a class ofsulfate-reducing bacteria (SRB) and is found ubiquitously in nature.Given the importance of SRB-mediated reduction for bioremediation ofmetal ion contaminants, ongoing research on D. vulgaris has been in thedirection of elucidating regulatory mechanisms for this organism under avariety of stress conditions. This work presents a global view of thisorganism's response to elevated growth temperature using whole-celltranscriptomics and proteomics tools. Transcriptional response (1.7-foldchange or greater; Z>1.5) ranged from 1,135 genes at 15 min to 1,463genes at 120 min for a temperature up-shift of 13oC from a growthtemperature of 37oC for this organism and suggested both direct andindirect modes of heat sensing. Clusters of orthologous group categoriesthat were significantly affected included posttranslationalmodifications; protein turnover and chaperones (up-regulated); energyproduction and conversion (down-regulated), nucleotide transport,metabolism (down-regulated), and translation; ribosomal structure; andbiogenesis (down-regulated). Analysis of the genome sequence revealed thepresence of features of both negative and positive regulation whichincluded the CIRCE element and promoter sequences corresponding to thealternate sigma factors ?32 and ?54. While mechanisms of heat shockcontrol for some genes appeared to coincide with those established forEscherichia coli and Bacillus subtilis, the presence of unique controlschemes for several other genes was also evident. Analysis of proteinexpression levels using differential in-gel electrophoresis suggestedgood agreement with transcriptional profiles of several heat shockproteins, including DnaK (DVU0811), HtpG (DVU2643), HtrA (DVU1468), andAhpC (DVU2247). The proteomics study also suggested the possibility ofposttranslational modifications in the chaperones DnaK, AhpC, GroES(DVU1977), and GroEL (DVU1976) and also several periplasmic ABCtransporters.

  18. Optimizing human activity patterns using global sensitivity analysis

    PubMed Central

    Hickmann, Kyle S.; Mniszewski, Susan M.; Del Valle, Sara Y.; Hyman, James M.

    2014-01-01

    Implementing realistic activity patterns for a population is crucial for modeling, for example, disease spread, supply and demand, and disaster response. Using the dynamic activity simulation engine, DASim, we generate schedules for a population that capture regular (e.g., working, eating, and sleeping) and irregular activities (e.g., shopping or going to the doctor). We use the sample entropy (SampEn) statistic to quantify a schedule’s regularity for a population. We show how to tune an activity’s regularity by adjusting SampEn, thereby making it possible to realistically design activities when creating a schedule. The tuning process sets up a computationally intractable high-dimensional optimization problem. To reduce the computational demand, we use Bayesian Gaussian process regression to compute global sensitivity indices and identify the parameters that have the greatest effect on the variance of SampEn. We use the harmony search (HS) global optimization algorithm to locate global optima. Our results show that HS combined with global sensitivity analysis can efficiently tune the SampEn statistic with few search iterations. We demonstrate how global sensitivity analysis can guide statistical emulation and global optimization algorithms to efficiently tune activities and generate realistic activity patterns. Though our tuning methods are applied to dynamic activity schedule generation, they are general and represent a significant step in the direction of automated tuning and optimization of high-dimensional computer simulations. PMID:25580080

  19. Optimizing human activity patterns using global sensitivity analysis

    SciTech Connect

    Fairchild, Geoffrey; Hickmann, Kyle S.; Mniszewski, Susan M.; Del Valle, Sara Y.; Hyman, James M.

    2013-12-10

    Implementing realistic activity patterns for a population is crucial for modeling, for example, disease spread, supply and demand, and disaster response. Using the dynamic activity simulation engine, DASim, we generate schedules for a population that capture regular (e.g., working, eating, and sleeping) and irregular activities (e.g., shopping or going to the doctor). We use the sample entropy (SampEn) statistic to quantify a schedule’s regularity for a population. We show how to tune an activity’s regularity by adjusting SampEn, thereby making it possible to realistically design activities when creating a schedule. The tuning process sets up a computationally intractable high-dimensional optimization problem. To reduce the computational demand, we use Bayesian Gaussian process regression to compute global sensitivity indices and identify the parameters that have the greatest effect on the variance of SampEn. Here we use the harmony search (HS) global optimization algorithm to locate global optima. Our results show that HS combined with global sensitivity analysis can efficiently tune the SampEn statistic with few search iterations. We demonstrate how global sensitivity analysis can guide statistical emulation and global optimization algorithms to efficiently tune activities and generate realistic activity patterns. Finally, though our tuning methods are applied to dynamic activity schedule generation, they are general and represent a significant step in the direction of automated tuning and optimization of high-dimensional computer simulations.

  20. Optimizing human activity patterns using global sensitivity analysis

    DOE PAGES

    Fairchild, Geoffrey; Hickmann, Kyle S.; Mniszewski, Susan M.; ...

    2013-12-10

    Implementing realistic activity patterns for a population is crucial for modeling, for example, disease spread, supply and demand, and disaster response. Using the dynamic activity simulation engine, DASim, we generate schedules for a population that capture regular (e.g., working, eating, and sleeping) and irregular activities (e.g., shopping or going to the doctor). We use the sample entropy (SampEn) statistic to quantify a schedule’s regularity for a population. We show how to tune an activity’s regularity by adjusting SampEn, thereby making it possible to realistically design activities when creating a schedule. The tuning process sets up a computationally intractable high-dimensional optimizationmore » problem. To reduce the computational demand, we use Bayesian Gaussian process regression to compute global sensitivity indices and identify the parameters that have the greatest effect on the variance of SampEn. Here we use the harmony search (HS) global optimization algorithm to locate global optima. Our results show that HS combined with global sensitivity analysis can efficiently tune the SampEn statistic with few search iterations. We demonstrate how global sensitivity analysis can guide statistical emulation and global optimization algorithms to efficiently tune activities and generate realistic activity patterns. Finally, though our tuning methods are applied to dynamic activity schedule generation, they are general and represent a significant step in the direction of automated tuning and optimization of high-dimensional computer simulations.« less

  1. Optimizing human activity patterns using global sensitivity analysis.

    PubMed

    Fairchild, Geoffrey; Hickmann, Kyle S; Mniszewski, Susan M; Del Valle, Sara Y; Hyman, James M

    2014-12-01

    Implementing realistic activity patterns for a population is crucial for modeling, for example, disease spread, supply and demand, and disaster response. Using the dynamic activity simulation engine, DASim, we generate schedules for a population that capture regular (e.g., working, eating, and sleeping) and irregular activities (e.g., shopping or going to the doctor). We use the sample entropy (SampEn) statistic to quantify a schedule's regularity for a population. We show how to tune an activity's regularity by adjusting SampEn, thereby making it possible to realistically design activities when creating a schedule. The tuning process sets up a computationally intractable high-dimensional optimization problem. To reduce the computational demand, we use Bayesian Gaussian process regression to compute global sensitivity indices and identify the parameters that have the greatest effect on the variance of SampEn. We use the harmony search (HS) global optimization algorithm to locate global optima. Our results show that HS combined with global sensitivity analysis can efficiently tune the SampEn statistic with few search iterations. We demonstrate how global sensitivity analysis can guide statistical emulation and global optimization algorithms to efficiently tune activities and generate realistic activity patterns. Though our tuning methods are applied to dynamic activity schedule generation, they are general and represent a significant step in the direction of automated tuning and optimization of high-dimensional computer simulations.

  2. Breastfeeding policy: a globally comparative analysis

    PubMed Central

    Raub, Amy; Earle, Alison

    2013-01-01

    Abstract Objective To explore the extent to which national policies guaranteeing breastfeeding breaks to working women may facilitate breastfeeding. Methods An analysis was conducted of the number of countries that guarantee breastfeeding breaks, the daily number of hours guaranteed, and the duration of guarantees. To obtain current, detailed information on national policies, original legislation as well as secondary sources on 182 of the 193 Member States of the United Nations were examined. Regression analyses were conducted to test the association between national policy and rates of exclusive breastfeeding while controlling for national income level, level of urbanization, female percentage of the labour force and female literacy rate. Findings Breastfeeding breaks with pay are guaranteed in 130 countries (71%) and unpaid breaks are guaranteed in seven (4%). No policy on breastfeeding breaks exists in 45 countries (25%). In multivariate models, the guarantee of paid breastfeeding breaks for at least 6 months was associated with an increase of 8.86 percentage points in the rate of exclusive breastfeeding (P < 0.05). Conclusion A greater percentage of women practise exclusive breastfeeding in countries where laws guarantee breastfeeding breaks at work. If these findings are confirmed in longitudinal studies, health outcomes could be improved by passing legislation on breastfeeding breaks in countries that do not yet ensure the right to breastfeed. PMID:24052676

  3. Evolutionary trace of G protein-coupled receptors reveals clusters of residues that determine global and class-specific functions.

    PubMed

    Madabushi, Srinivasan; Gross, Alecia K; Philippi, Anne; Meng, Elaine C; Wensel, Theodore G; Lichtarge, Olivier

    2004-02-27

    G protein-coupled receptor (GPCR) activation mediated by ligand-induced structural reorganization of its helices is poorly understood. To determine the universal elements of this conformational switch, we used evolutionary tracing (ET) to identify residue positions commonly important in diverse GPCRs. When mapped onto the rhodopsin structure, these trace residues cluster into a network of contacts from the retinal binding site to the G protein-coupling loops. Their roles in a generic transduction mechanism were verified by 211 of 239 published mutations that caused functional defects. When grouped according to the nature of the defects, these residues sub-divided into three striking sub-clusters: a trigger region, where mutations mostly affect ligand binding, a coupling region near the cytoplasmic interface to the G protein, where mutations affect G protein activation, and a linking core in between where mutations cause constitutive activity and other defects. Differential ET analysis of the opsin family revealed an additional set of opsin-specific residues, several of which form part of the retinal binding pocket, and are known to cause functional defects upon mutation. To test the predictive power of ET, we introduced novel mutations in bovine rhodopsin at a globally important position, Leu-79, and at an opsin-specific position, Trp-175. Both were functionally critical, causing constitutive G protein activation of the mutants and rapid loss of regeneration after photobleaching. These results define in GPCRs a canonical signal transduction mechanism where ligand binding induces conformational changes propagated through adjacent trigger, linking core, and coupling regions.

  4. A multiyear, global gridded fossil fuel CO2 emission data product: Evaluation and analysis of results

    NASA Astrophysics Data System (ADS)

    Asefi-Najafabady, S.; Rayner, P. J.; Gurney, K. R.; McRobert, A.; Song, Y.; Coltin, K.; Huang, J.; Elvidge, C.; Baugh, K.

    2014-09-01

    High-resolution, global quantification of fossil fuel CO2 emissions is emerging as a critical need in carbon cycle science and climate policy. We build upon a previously developed fossil fuel data assimilation system (FFDAS) for estimating global high-resolution fossil fuel CO2 emissions. We have improved the underlying observationally based data sources, expanded the approach through treatment of separate emitting sectors including a new pointwise database of global power plants, and extended the results to cover a 1997 to 2010 time series at a spatial resolution of 0.1°. Long-term trend analysis of the resulting global emissions shows subnational spatial structure in large active economies such as the United States, China, and India. These three countries, in particular, show different long-term trends and exploration of the trends in nighttime lights, and population reveal a decoupling of population and emissions at the subnational level. Analysis of shorter-term variations reveals the impact of the 2008-2009 global financial crisis with widespread negative emission anomalies across the U.S. and Europe. We have used a center of mass (CM) calculation as a compact metric to express the time evolution of spatial patterns in fossil fuel CO2 emissions. The global emission CM has moved toward the east and somewhat south between 1997 and 2010, driven by the increase in emissions in China and South Asia over this time period. Analysis at the level of individual countries reveals per capita CO2 emission migration in both Russia and India. The per capita emission CM holds potential as a way to succinctly analyze subnational shifts in carbon intensity over time. Uncertainties are generally lower than the previous version of FFDAS due mainly to an improved nightlight data set.

  5. SEDPHAT – a platform for global ITC analysis and global multi-method analysis of molecular interactions

    PubMed Central

    Zhao, Huaying; Piszczek, Grzegorz; Schuck, Peter

    2014-01-01

    Isothermal titration calorimetry experiments can provide significantly more detailed information about molecular interactions when combined in global analysis. For example, global analysis can improve the precision of binding affinity and enthalpy, and of possible linkage parameters, even for simple bimolecular interactions, and greatly facilitate the study of multi-site and multi-component systems with competition or cooperativity. A pre-requisite for global analysis is the departure from the traditional binding model, including an ‘n’-value describing unphysical, non-integral numbers of sites. Instead, concentration correction factors can be introduced to account for either errors in the concentration determination or for the presence of inactive fractions of material. SEDPHAT is a computer program that embeds these ideas and provides a graphical user interface for the seamless combination of biophysical experiments to be globally modeled with a large number of different binding models. It offers statistical tools for the rigorous determination of parameter errors, correlations, as well as advanced statistical functions for global ITC (gITC) and global multi-method analysis (GMMA). SEDPHAT will also take full advantage of error bars of individual titration data points determined with the unbiased integration software NITPIC. The present communication reviews principles and strategies of global analysis for ITC and its extension to GMMA in SEDPHAT. We will also introduce a new graphical tool for aiding experimental design by surveying the concentration space and generating simulated data sets, which can be subsequently statistically examined for their information content. This procedure can replace the ‘c’-value as an experimental design parameter, which ceases to be helpful for multi-site systems and in the context of gITC. PMID:25477226

  6. SEDPHAT--a platform for global ITC analysis and global multi-method analysis of molecular interactions.

    PubMed

    Zhao, Huaying; Piszczek, Grzegorz; Schuck, Peter

    2015-04-01

    Isothermal titration calorimetry experiments can provide significantly more detailed information about molecular interactions when combined in global analysis. For example, global analysis can improve the precision of binding affinity and enthalpy, and of possible linkage parameters, even for simple bimolecular interactions, and greatly facilitate the study of multi-site and multi-component systems with competition or cooperativity. A pre-requisite for global analysis is the departure from the traditional binding model, including an 'n'-value describing unphysical, non-integral numbers of sites. Instead, concentration correction factors can be introduced to account for either errors in the concentration determination or for the presence of inactive fractions of material. SEDPHAT is a computer program that embeds these ideas and provides a graphical user interface for the seamless combination of biophysical experiments to be globally modeled with a large number of different binding models. It offers statistical tools for the rigorous determination of parameter errors, correlations, as well as advanced statistical functions for global ITC (gITC) and global multi-method analysis (GMMA). SEDPHAT will also take full advantage of error bars of individual titration data points determined with the unbiased integration software NITPIC. The present communication reviews principles and strategies of global analysis for ITC and its extension to GMMA in SEDPHAT. We will also introduce a new graphical tool for aiding experimental design by surveying the concentration space and generating simulated data sets, which can be subsequently statistically examined for their information content. This procedure can replace the 'c'-value as an experimental design parameter, which ceases to be helpful for multi-site systems and in the context of gITC.

  7. Multifaceted diversity-area relationships reveal global hotspots of mammalian species, trait and lineage diversity

    PubMed Central

    Mazel, Florent; Guilhaumon, François; Mouquet, Nicolas; Devictor, Vincent; Gravel, Dominique; Renaud, Julien; Cianciaruso, Marcus Vinicius; Loyola, Rafael Dias; Diniz-Filho, José Alexandre Felizola; Mouillot, David; Thuiller, Wilfried

    2014-01-01

    Aim To define biome-scale hotspots of phylogenetic and functional mammalian biodiversity (PD and FD, respectively) and compare them to ‘classical’ hotspots based on species richness (SR) only. Location Global Methods SR, PD & FD were computed for 782 terrestrial ecoregions using distribution ranges of 4616 mammalian species. We used a set of comprehensive diversity indices unified by a recent framework that incorporates the species relative coverage in each ecoregion. We build large-scale multifaceted diversity-area relationships to rank ecoregions according to their levels of biodiversity while accounting for the effect of area on each diversity facet. Finally we defined hotspots as the top-ranked ecoregions. Results While ignoring species relative coverage led to a relative good congruence between biome top ranked SR, PD and FD hotspots, ecoregions harboring a rich and abundantly represented evolutionary history and functional diversity did not match with top ranked ecoregions defined by species richness. More importantly PD and FD hotspots showed important spatial mismatches. We also found that FD and PD generally reached their maximum values faster than species richness as a function of area. Main conclusions The fact that PD/FD reach faster their maximal value than SR may suggest that the two former facets might be less vulnerable to habitat loss than the latter. While this point is expected, it is the first time that it is quantified at global scale and should have important consequences in conservation. Incorporating species relative coverage into the delineation of multifaceted hotspots of diversity lead to weak congruence between SR, PD and FD hotspots. This means that maximizing species number may fail at preserving those nodes (in the phylogenetic or functional tree) that are relatively abundant in the ecoregion. As a consequence it may be of prime importance to adopt a multifaceted biodiversity perspective to inform conservation strategies at global

  8. Dual African Origins of Global Aedes aegypti s.l. Populations Revealed by Mitochondrial DNA

    PubMed Central

    Moore, Michelle; Sylla, Massamba; Goss, Laura; Burugu, Marion Warigia; Sang, Rosemary; Kamau, Luna W.; Kenya, Eucharia Unoma; Bosio, Chris; Munoz, Maria de Lourdes; Sharakova, Maria; Black, William Cormack

    2013-01-01

    Background Aedes aegypti is the primary global vector to humans of yellow fever and dengue flaviviruses. Over the past 50 years, many population genetic studies have documented large genetic differences among global populations of this species. These studies initially used morphological polymorphisms, followed later by allozymes, and most recently various molecular genetic markers including microsatellites and mitochondrial markers. In particular, since 2000, fourteen publications and four unpublished datasets have used sequence data from the NADH dehydrogenase subunit 4 mitochondrial gene to compare Ae. aegypti collections and collectively 95 unique mtDNA haplotypes have been found. Phylogenetic analyses in these many studies consistently resolved two clades but no comprehensive study of mtDNA haplotypes have been made in Africa, the continent in which the species originated. Methods and Findings ND4 haplotypes were sequenced in 426 Ae. aegypti s.l. from Senegal, West Africa and Kenya, East Africa. In Senegal 15 and in Kenya 7 new haplotypes were discovered. When added to the 95 published haplotypes and including 6 African Aedes species as outgroups, phylogenetic analyses showed that all but one Senegal haplotype occurred in a basal clade while most East African haplotypes occurred in a second clade arising from the basal clade. Globally distributed haplotypes occurred in both clades demonstrating that populations outside Africa consist of mixtures of mosquitoes from both clades. Conclusions Populations of Ae. aegypti outside Africa consist of mosquitoes arising from one of two ancestral clades. One clade is basal and primarily associated with West Africa while the second arises from the first and contains primarily mosquitoes from East Africa PMID:23638196

  9. Global gene expression profiling reveals similarities and differences among mouse pluripotent stem cells of different origins and strains

    PubMed Central

    Sharova, Lioudmila V.; Sharov, Alexei A.; Piao, Yulan; Shaik, Nabeebi; Sullivan, Terry; Stewart, Colin L.; Hogan, Brigid L.M.; Ko, Minoru S.H.

    2007-01-01

    Pluripotent stem cell lines with similar phenotypes can be derived from both blastocysts (embryonic stem cells, ESC) and primordial germ cells (embryonic germ cells, EGC). Here, we present a compendium DNA microarray analysis of multiple mouse ESCs and EGCs from different genetic backgrounds (strains 129 and C57BL/6) cultured under standard conditions and in differentiation-promoting conditions by the withdrawal of Leukemia Inhibitory Factor (LIF) or treatment with retinoic acid (RA). All pluripotent cell lines showed similar gene expression patterns, which separated them clearly from other tissue stem cells with lower developmental potency. Differences between pluripotent lines derived from different sources (ESC vs. EGC) were smaller than differences between lines derived from different mouse strains (129 vs. C57BL/6). Even in the differentiation-promoting conditions, these pluripotent cells showed the same general trends of gene expression changes regardless of their origin and genetic background. These data indicate that ESCs and EGCs are indistinguishable based on global gene expression patterns alone. On the other hand, a detailed comparison between a group of ESC lines and a group of EGC lines identified 20 signature genes whose average expression levels were consistently higher in ESC lines, and 84 signature genes whose average expression levels were consistently higher in EGC lines, irrespective of mouse strains. Similar analysis identified 250 signature genes whose average expression levels were consistently higher in a group of 129 cell lines, and 337 signature genes whose average expression levels were consistently higher in a group of C57BL/6 cell lines. Although none of the genes was exclusively expressed in either ESCs versus EGCs or 129 versus C57BL/6, in combination these signature genes provide a reliable separation and identification of each cell type. Differentiation-promoting conditions also revealed some minor differences between the cell

  10. Integrating abundance and functional traits reveals new global hotspots of fish diversity.

    PubMed

    Stuart-Smith, Rick D; Bates, Amanda E; Lefcheck, Jonathan S; Duffy, J Emmett; Baker, Susan C; Thomson, Russell J; Stuart-Smith, Jemina F; Hill, Nicole A; Kininmonth, Stuart J; Airoldi, Laura; Becerro, Mikel A; Campbell, Stuart J; Dawson, Terence P; Navarrete, Sergio A; Soler, German A; Strain, Elisabeth M A; Willis, Trevor J; Edgar, Graham J

    2013-09-26

    Species richness has dominated our view of global biodiversity patterns for centuries. The dominance of this paradigm is reflected in the focus by ecologists and conservation managers on richness and associated occurrence-based measures for understanding drivers of broad-scale diversity patterns and as a biological basis for management. However, this is changing rapidly, as it is now recognized that not only the number of species but the species present, their phenotypes and the number of individuals of each species are critical in determining the nature and strength of the relationships between species diversity and a range of ecological functions (such as biomass production and nutrient cycling). Integrating these measures should provide a more relevant representation of global biodiversity patterns in terms of ecological functions than that provided by simple species counts. Here we provide comparisons of a traditional global biodiversity distribution measure based on richness with metrics that incorporate species abundances and functional traits. We use data from standardized quantitative surveys of 2,473 marine reef fish species at 1,844 sites, spanning 133 degrees of latitude from all ocean basins, to identify new diversity hotspots in some temperate regions and the tropical eastern Pacific Ocean. These relate to high diversity of functional traits amongst individuals in the community (calculated using Rao's Q), and differ from previously reported patterns in functional diversity and richness for terrestrial animals, which emphasize species-rich tropical regions only. There is a global trend for greater evenness in the number of individuals of each species, across the reef fish species observed at sites ('community evenness'), at higher latitudes. This contributes to the distribution of functional diversity hotspots and contrasts with well-known latitudinal gradients in richness. Our findings suggest that the contribution of species diversity to a range of

  11. Global Spectrum of Copy Number Variations Reveals Genome Organizational Plasticity and Proposes New Migration Routes

    PubMed Central

    Veerappa, Avinash M.; Manjegowda, Dinesh S.; Ramachandra, Nallur B.

    2015-01-01

    Global spectrum of CNVs is required to catalog variations to provide a high-resolution on the dynamics of genome-organization and human migration. In this study, we performed genome-wide genotyping using high-resolution arrays and identified 44,109 CNVs from 1,715 genomes across 12 populations. The study unraveled the force of independent evolutionary dynamics on genome-organizational plasticity across populations. We demonstrated the use of CNV tool to study human migration and identified a second major settlement establishing new migration routes in addition to existing ones. PMID:25909454

  12. Mathematical Analysis of Biomolecular Network Reveals Connections Between Diseases

    NASA Astrophysics Data System (ADS)

    Wang, Guanyu

    2012-02-01

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

  13. Global Analysis of Protein Expression of Inner Ear Hair Cells

    PubMed Central

    Wong, Ann C.Y.; Pak, Kwang; Strojny, Chelsee; Ramirez, Miguel

    2017-01-01

    The mammalian inner ear (IE) subserves auditory and vestibular sensations via highly specialized cells and proteins. Sensory receptor hair cells (HCs) are necessary for transducing mechanical inputs and stimulating sensory neurons by using a host of known and as yet unknown protein machinery. To understand the protein composition of these unique postmitotic cells, in which irreversible protein degradation or damage can lead to impaired hearing and balance, we analyzed IE samples by tandem mass spectrometry to generate an unbiased, shotgun-proteomics view of protein identities and abundances. By using Pou4f3/eGFP-transgenic mice in which HCs express GFP driven by Pou4f3, we FACS purified a population of HCs to analyze and compare the HC proteome with other IE subproteomes from sensory epithelia and whole IE. We show that the mammalian HC proteome comprises hundreds of uniquely or highly expressed proteins. Our global proteomic analysis of purified HCs extends the existing HC transcriptome, revealing previously undetected gene products and isoform-specific protein expression. Comparison of our proteomic data with mouse and human databases of genetic auditory/vestibular impairments confirms the critical role of the HC proteome for normal IE function, providing a cell-specific pool of candidates for novel, important HC genes. Several proteins identified exclusively in HCs by proteomics and verified by immunohistochemistry map to human genetic deafness loci, potentially representing new deafness genes. SIGNIFICANCE STATEMENT Hearing and balance rely on specialized sensory hair cells (HCs) in the inner ear (IE) to convey information about sound, acceleration, and orientation to the brain. Genetically and environmentally induced perturbations to HC proteins can result in deafness and severe imbalance. We used transgenic mice with GFP-expressing HCs, coupled with FACS sorting and tandem mass spectrometry, to define the most complete HC and IE proteome to date. We show that

  14. A global optimization approach to multi-polarity sentiment analysis.

    PubMed

    Li, Xinmiao; Li, Jing; Wu, Yukeng

    2015-01-01

    Following the rapid development of social media, sentiment analysis has become an important social media mining technique. The performance of automatic sentiment analysis primarily depends on feature selection and sentiment classification. While information gain (IG) and support vector machines (SVM) are two important techniques, few studies have optimized both approaches in sentiment analysis. The effectiveness of applying a global optimization approach to sentiment analysis remains unclear. We propose a global optimization-based sentiment analysis (PSOGO-Senti) approach to improve sentiment analysis with IG for feature selection and SVM as the learning engine. The PSOGO-Senti approach utilizes a particle swarm optimization algorithm to obtain a global optimal combination of feature dimensions and parameters in the SVM. We evaluate the PSOGO-Senti model on two datasets from different fields. The experimental results showed that the PSOGO-Senti model can improve binary and multi-polarity Chinese sentiment analysis. We compared the optimal feature subset selected by PSOGO-Senti with the features in the sentiment dictionary. The results of this comparison indicated that PSOGO-Senti can effectively remove redundant and noisy features and can select a domain-specific feature subset with a higher-explanatory power for a particular sentiment analysis task. The experimental results showed that the PSOGO-Senti approach is effective and robust for sentiment analysis tasks in different domains. By comparing the improvements of two-polarity, three-polarity and five-polarity sentiment analysis results, we found that the five-polarity sentiment analysis delivered the largest improvement. The improvement of the two-polarity sentiment analysis was the smallest. We conclude that the PSOGO-Senti achieves higher improvement for a more complicated sentiment analysis task. We also compared the results of PSOGO-Senti with those of the genetic algorithm (GA) and grid search method. From

  15. Global metagenomic survey reveals a new bacterial candidate phylum in geothermal springs

    SciTech Connect

    Eloe-Fadrosh, Emiley A.; Paez-Espino, David; Jarett, Jessica; Dunfield, Peter F.; Hedlund, Brian P.; Dekas, Anne E.; Grasby, Stephen E.; Brady, Allyson L.; Dong, Hailiang; Briggs, Brandon R.; Li, Wen-Jun; Goudeau, Danielle; Malmstrom, Rex; Pati, Amrita; Pett-Ridge, Jennifer; Rubin, Edward M.; Woyke, Tanja; Kyrpides, Nikos C.; Ivanova, Natalia N.

    2016-01-27

    We analyse the increasing wealth of metagenomic data collected from diverse environments can lead to the discovery of novel branches on the tree of life. Here we analyse 5.2 Tb of metagenomic data collected globally to discover a novel bacterial phylum (‘Candidatus Kryptonia’) found exclusively in high-temperature pH-neutral geothermal springs. This lineage had remained hidden as a taxonomic ‘blind spot’ because of mismatches in the primers commonly used for ribosomal gene surveys. Genome reconstruction from metagenomic data combined with single-cell genomics results in several high-quality genomes representing four genera from the new phylum. Metabolic reconstruction indicates a heterotrophic lifestyle with conspicuous nutritional deficiencies, suggesting the need for metabolic complementarity with other microbes. Co-occurrence patterns identifies a number of putative partners, including an uncultured Armatimonadetes lineage. The discovery of Kryptonia within previously studied geothermal springs underscores the importance of globally sampled metagenomic data in detection of microbial novelty, and highlights the extraordinary diversity of microbial life still awaiting discovery.

  16. A global synthesis reveals biodiversity loss as a major driver of ecosystem change.

    PubMed

    Hooper, David U; Adair, E Carol; Cardinale, Bradley J; Byrnes, Jarrett E K; Hungate, Bruce A; Matulich, Kristin L; Gonzalez, Andrew; Duffy, J Emmett; Gamfeldt, Lars; O'Connor, Mary I

    2012-05-02

    Evidence is mounting that extinctions are altering key processes important to the productivity and sustainability of Earth's ecosystems. Further species loss will accelerate change in ecosystem processes, but it is unclear how these effects compare to the direct effects of other forms of environmental change that are both driving diversity loss and altering ecosystem function. Here we use a suite of meta-analyses of published data to show that the effects of species loss on productivity and decomposition--two processes important in all ecosystems--are of comparable magnitude to the effects of many other global environmental changes. In experiments, intermediate levels of species loss (21-40%) reduced plant production by 5-10%, comparable to previously documented effects of ultraviolet radiation and climate warming. Higher levels of extinction (41-60%) had effects rivalling those of ozone, acidification, elevated CO(2) and nutrient pollution. At intermediate levels, species loss generally had equal or greater effects on decomposition than did elevated CO(2) and nitrogen addition. The identity of species lost also had a large effect on changes in productivity and decomposition, generating a wide range of plausible outcomes for extinction. Despite the need for more studies on interactive effects of diversity loss and environmental changes, our analyses clearly show that the ecosystem consequences of local species loss are as quantitatively significant as the direct effects of several global change stressors that have mobilized major international concern and remediation efforts.

  17. Global metagenomic survey reveals a new bacterial candidate phylum in geothermal springs

    DOE PAGES

    Eloe-Fadrosh, Emiley A.; Paez-Espino, David; Jarett, Jessica; ...

    2016-01-27

    We analyse the increasing wealth of metagenomic data collected from diverse environments can lead to the discovery of novel branches on the tree of life. Here we analyse 5.2 Tb of metagenomic data collected globally to discover a novel bacterial phylum (‘Candidatus Kryptonia’) found exclusively in high-temperature pH-neutral geothermal springs. This lineage had remained hidden as a taxonomic ‘blind spot’ because of mismatches in the primers commonly used for ribosomal gene surveys. Genome reconstruction from metagenomic data combined with single-cell genomics results in several high-quality genomes representing four genera from the new phylum. Metabolic reconstruction indicates a heterotrophic lifestyle withmore » conspicuous nutritional deficiencies, suggesting the need for metabolic complementarity with other microbes. Co-occurrence patterns identifies a number of putative partners, including an uncultured Armatimonadetes lineage. The discovery of Kryptonia within previously studied geothermal springs underscores the importance of globally sampled metagenomic data in detection of microbial novelty, and highlights the extraordinary diversity of microbial life still awaiting discovery.« less

  18. Can global navigation satellite system signals reveal the ecological attributes of forests?

    NASA Astrophysics Data System (ADS)

    Liu, Jingbin; Hyyppä, Juha; Yu, Xiaowei; Jaakkola, Anttoni; Liang, Xinlian; Kaartinen, Harri; Kukko, Antero; Zhu, Lingli; Wang, Yunsheng; Hyyppä, Hannu

    2016-08-01

    Forests have important impacts on the global carbon cycle and climate, and they are also related to a wide range of industrial sectors. Currently, one of the biggest challenges in forestry research is effectively and accurately measuring and monitoring forest variables, as the exploitation potential of forest inventory products largely depends on the accuracy of estimates and on the cost of data collection. A low-cost crowdsourcing solution is needed for forest inventory to collect forest variables. Here, we propose global navigation satellite system (GNSS) signals as a novel type of observables for predicting forest attributes and show the feasibility of utilizing GNSS signals for estimating important attributes of forest plots, including mean tree height, mean diameter at breast height, basal area, stem volume and tree biomass. The prediction accuracies of the proposed technique were better in boreal forest conditions than those of the conventional techniques of 2D remote sensing. More importantly, this technique provides a novel, cost-effective way of collecting large-scale forest measurements in the crowdsourcing context. This technique can be applied by, for example, harvesters or persons hiking or working in forests because GNSS devices are widely used, and the field operation of this technique is simple and does not require professional forestry skills.

  19. In situ imaging reveals the biomass of giant protists in the global ocean.

    PubMed

    Biard, Tristan; Stemmann, Lars; Picheral, Marc; Mayot, Nicolas; Vandromme, Pieter; Hauss, Helena; Gorsky, Gabriel; Guidi, Lionel; Kiko, Rainer; Not, Fabrice

    2016-04-28

    Planktonic organisms play crucial roles in oceanic food webs and global biogeochemical cycles. Most of our knowledge about the ecological impact of large zooplankton stems from research on abundant and robust crustaceans, and in particular copepods. A number of the other organisms that comprise planktonic communities are fragile, and therefore hard to sample and quantify, meaning that their abundances and effects on oceanic ecosystems are poorly understood. Here, using data from a worldwide in situ imaging survey of plankton larger than 600 μm, we show that a substantial part of the biomass of this size fraction consists of giant protists belonging to the Rhizaria, a super-group of mostly fragile unicellular marine organisms that includes the taxa Phaeodaria and Radiolaria (for example, orders Collodaria and Acantharia). Globally, we estimate that rhizarians in the top 200 m of world oceans represent a standing stock of 0.089 Pg carbon, equivalent to 5.2% of the total oceanic biota carbon reservoir. In the vast oligotrophic intertropical open oceans, rhizarian biomass is estimated to be equivalent to that of all other mesozooplankton (plankton in the size range 0.2-20 mm). The photosymbiotic association of many rhizarians with microalgae may be an important factor in explaining their distribution. The previously overlooked importance of these giant protists across the widest ecosystem on the planet changes our understanding of marine planktonic ecosystems.

  20. Global Multi-Level Analysis of the ‘Scientific Food Web'

    NASA Astrophysics Data System (ADS)

    Mazloumian, Amin; Helbing, Dirk; Lozano, Sergi; Light, Robert P.; Börner, Katy

    2013-01-01

    We introduce a network-based index analyzing excess scientific production and consumption to perform a comprehensive global analysis of scholarly knowledge production and diffusion on the level of continents, countries, and cities. Compared to measures of scientific production and consumption such as number of publications or citation rates, our network-based citation analysis offers a more differentiated picture of the `ecosystem of science'. Quantifying knowledge flows between 2000 and 2009, we identify global sources and sinks of knowledge production. Our knowledge flow index reveals, where ideas are born and consumed, thereby defining a global `scientific food web'. While Asia is quickly catching up in terms of publications and citation rates, we find that its dependence on knowledge consumption has further increased.

  1. Global Multi-Level Analysis of the ‘Scientific Food Web'

    PubMed Central

    Mazloumian, Amin; Helbing, Dirk; Lozano, Sergi; Light, Robert P.; Börner, Katy

    2013-01-01

    We introduce a network-based index analyzing excess scientific production and consumption to perform a comprehensive global analysis of scholarly knowledge production and diffusion on the level of continents, countries, and cities. Compared to measures of scientific production and consumption such as number of publications or citation rates, our network-based citation analysis offers a more differentiated picture of the ‘ecosystem of science’. Quantifying knowledge flows between 2000 and 2009, we identify global sources and sinks of knowledge production. Our knowledge flow index reveals, where ideas are born and consumed, thereby defining a global ‘scientific food web’. While Asia is quickly catching up in terms of publications and citation rates, we find that its dependence on knowledge consumption has further increased. PMID:23378902

  2. Characteristics of the tomato chromoplast revealed by proteomic analysis.

    PubMed

    Barsan, Cristina; Sanchez-Bel, Paloma; Rombaldi, Cesar; Egea, Isabel; Rossignol, Michel; Kuntz, Marcel; Zouine, Mohamed; Latché, Alain; Bouzayen, Mondher; Pech, Jean-Claude

    2010-05-01

    Chromoplasts are non-photosynthetic specialized plastids that are important in ripening tomato fruit (Solanum lycopersicum) since, among other functions, they are the site of accumulation of coloured compounds. Analysis of the proteome of red fruit chromoplasts revealed the presence of 988 proteins corresponding to 802 Arabidopsis unigenes, among which 209 had not been listed so far in plastidial databanks. These data revealed several features of the chromoplast. Proteins of lipid metabolism and trafficking were well represented, including all the proteins of the lipoxygenase pathway required for the synthesis of lipid-derived aroma volatiles. Proteins involved in starch synthesis co-existed with several starch-degrading proteins and starch excess proteins. Chromoplasts lacked proteins of the chlorophyll biosynthesis branch and contained proteins involved in chlorophyll degradation. None of the proteins involved in the thylakoid transport machinery were discovered. Surprisingly, chromoplasts contain the entire set of Calvin cycle proteins including Rubisco, as well as the oxidative pentose phosphate pathway (OxPPP). The present proteomic analysis, combined with available physiological data, provides new insights into the metabolic characteristics of the tomato chromoplast and enriches our knowledge of non-photosynthetic plastids.

  3. Genomic analysis of regulatory network dynamics reveals large topological changes

    NASA Astrophysics Data System (ADS)

    Luscombe, Nicholas M.; Madan Babu, M.; Yu, Haiyuan; Snyder, Michael; Teichmann, Sarah A.; Gerstein, Mark

    2004-09-01

    Network analysis has been applied widely, providing a unifying language to describe disparate systems ranging from social interactions to power grids. It has recently been used in molecular biology, but so far the resulting networks have only been analysed statically. Here we present the dynamics of a biological network on a genomic scale, by integrating transcriptional regulatory information and gene-expression data for multiple conditions in Saccharomyces cerevisiae. We develop an approach for the statistical analysis of network dynamics, called SANDY, combining well-known global topological measures, local motifs and newly derived statistics. We uncover large changes in underlying network architecture that are unexpected given current viewpoints and random simulations. In response to diverse stimuli, transcription factors alter their interactions to varying degrees, thereby rewiring the network. A few transcription factors serve as permanent hubs, but most act transiently only during certain conditions. By studying sub-network structures, we show that environmental responses facilitate fast signal propagation (for example, with short regulatory cascades), whereas the cell cycle and sporulation direct temporal progression through multiple stages (for example, with highly inter-connected transcription factors). Indeed, to drive the latter processes forward, phase-specific transcription factors inter-regulate serially, and ubiquitously active transcription factors layer above them in a two-tiered hierarchy. We anticipate that many of the concepts presented here-particularly the large-scale topological changes and hub transience-will apply to other biological networks, including complex sub-systems in higher eukaryotes.

  4. Proteogenomic analysis reveals exosomes are more oncogenic than ectosomes

    PubMed Central

    Liem, Michael; Fonseka, Pamali; Atukorala, Ishara; Ozcitti, Cemil; Mechler, Adam; Adda, Christopher G.; Ang, Ching-Seng; Mathivanan, Suresh

    2015-01-01

    Extracellular vesicles (EVs) include the exosomes (30-100 nm) that are produced through the endocytic pathway via the multivesicular bodies and the ectosomes (100-1000 nm) that are released through the budding of the plasma membrane. Despite the differences in the mode of biogenesis and size, reliable markers that can distinguish between exosomes and ectosomes are non-existent. Moreover, the precise functional differences between exosomes and ectosomes remains poorly characterised. Here, using label-free quantitative proteomics, we highlight proteins that could be exploited as markers to discriminate between exosomes and ectosomes. For the first time, a global proteogenomics analysis unveiled the secretion of mutant proteins that are implicated in cancer progression through tumor-derived EVs. Follow up integrated bioinformatics analysis highlighted the enrichment of oncogenic cargo in exosomes and ectosomes. Interestingly, exosomes induced significant cell proliferation and migration in recipient cells compared to ectosomes confirming the oncogenic nature of exosomes. These findings ascertain that cancer cells facilitate oncogenesis by the secretion of mutant and oncoproteins into the tumor microenvironment via exosomes and ectosomes. The integrative proteogenomics approach utilized in this study has the potential to identify disease biomarker candidates which can be later assayed in liquid biopsies obtained from cancer patients. PMID:25944692

  5. Proteogenomic analysis reveals exosomes are more oncogenic than ectosomes.

    PubMed

    Keerthikumar, Shivakumar; Gangoda, Lahiru; Liem, Michael; Fonseka, Pamali; Atukorala, Ishara; Ozcitti, Cemil; Mechler, Adam; Adda, Christopher G; Ang, Ching-Seng; Mathivanan, Suresh

    2015-06-20

    Extracellular vesicles (EVs) include the exosomes (30-100 nm) that are produced through the endocytic pathway via the multivesicular bodies and the ectosomes (100-1000 nm) that are released through the budding of the plasma membrane. Despite the differences in the mode of biogenesis and size, reliable markers that can distinguish between exosomes and ectosomes are non-existent. Moreover, the precise functional differences between exosomes and ectosomes remains poorly characterised. Here, using label-free quantitative proteomics, we highlight proteins that could be exploited as markers to discriminate between exosomes and ectosomes. For the first time, a global proteogenomics analysis unveiled the secretion of mutant proteins that are implicated in cancer progression through tumor-derived EVs. Follow up integrated bioinformatics analysis highlighted the enrichment of oncogenic cargo in exosomes and ectosomes. Interestingly, exosomes induced significant cell proliferation and migration in recipient cells compared to ectosomes confirming the oncogenic nature of exosomes. These findings ascertain that cancer cells facilitate oncogenesis by the secretion of mutant and oncoproteins into the tumor microenvironment via exosomes and ectosomes. The integrative proteogenomics approach utilized in this study has the potential to identify disease biomarker candidates which can be later assayed in liquid biopsies obtained from cancer patients.

  6. Genomic analysis of regulatory network dynamics reveals large topological changes.

    PubMed

    Luscombe, Nicholas M; Babu, M Madan; Yu, Haiyuan; Snyder, Michael; Teichmann, Sarah A; Gerstein, Mark

    2004-09-16

    Network analysis has been applied widely, providing a unifying language to describe disparate systems ranging from social interactions to power grids. It has recently been used in molecular biology, but so far the resulting networks have only been analysed statically. Here we present the dynamics of a biological network on a genomic scale, by integrating transcriptional regulatory information and gene-expression data for multiple conditions in Saccharomyces cerevisiae. We develop an approach for the statistical analysis of network dynamics, called SANDY, combining well-known global topological measures, local motifs and newly derived statistics. We uncover large changes in underlying network architecture that are unexpected given current viewpoints and random simulations. In response to diverse stimuli, transcription factors alter their interactions to varying degrees, thereby rewiring the network. A few transcription factors serve as permanent hubs, but most act transiently only during certain conditions. By studying sub-network structures, we show that environmental responses facilitate fast signal propagation (for example, with short regulatory cascades), whereas the cell cycle and sporulation direct temporal progression through multiple stages (for example, with highly inter-connected transcription factors). Indeed, to drive the latter processes forward, phase-specific transcription factors inter-regulate serially, and ubiquitously active transcription factors layer above them in a two-tiered hierarchy. We anticipate that many of the concepts presented here--particularly the large-scale topological changes and hub transience--will apply to other biological networks, including complex sub-systems in higher eukaryotes.

  7. Geometric morphometric analysis reveals sexual dimorphism in the distal femur.

    PubMed

    Cavaignac, Etienne; Savall, Frederic; Faruch, Marie; Reina, Nicolas; Chiron, Philippe; Telmon, Norbert

    2016-02-01

    An individual's sex can be determined by the shape of their distal femur. The goal of this study was to show that differences in distal femur shape related to sexual dimorphism could be identified, visualized, and quantified using 3D geometric morphometric analysis. Geometric morphometric analysis was carried out on CT scans of the distal femur of 256 subjects living in the south of France. Ten landmarks were defined on 3D reconstructions of the distal femur. Both traditional metric and geometric morphometric analyses were carried out on these bone reconstructions; these analyses identified trends in bone shape in sex-based subgroups. Sex-related differences in shape were statistically significant. The subject's sex was correctly assigned in 77.3% of cases using geometric morphometric analysis. This study has shown that geometric morphometric analysis of the distal femur is feasible and has revealed sexual dimorphism differences in this bone segment. This reliable, accurate method could be used for virtual autopsy and be used to perform diachronic and interethnic comparisons. Moreover, this study provides updated morphometric data for a modern population in the south of France. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  8. Global land cover mapping: a review and uncertainty analysis

    USGS Publications Warehouse

    Congalton, Russell G.; Gu, Jianyu; Yadav, Kamini; Thenkabail, Prasad S.; Ozdogan, Mutlu

    2014-01-01

    Given the advances in remotely sensed imagery and associated technologies, several global land cover maps have been produced in recent times including IGBP DISCover, UMD Land Cover, Global Land Cover 2000 and GlobCover 2009. However, the utility of these maps for specific applications has often been hampered due to considerable amounts of uncertainties and inconsistencies. A thorough review of these global land cover projects including evaluating the sources of error and uncertainty is prudent and enlightening. Therefore, this paper describes our work in which we compared, summarized and conducted an uncertainty analysis of the four global land cover mapping projects using an error budget approach. The results showed that the classification scheme and the validation methodology had the highest error contribution and implementation priority. A comparison of the classification schemes showed that there are many inconsistencies between the definitions of the map classes. This is especially true for the mixed type classes for which thresholds vary for the attributes/discriminators used in the classification process. Examination of these four global mapping projects provided quite a few important lessons for the future global mapping projects including the need for clear and uniform definitions of the classification scheme and an efficient, practical, and valid design of the accuracy assessment.

  9. Ecological network analysis on global virtual water trade.

    PubMed

    Yang, Zhifeng; Mao, Xufeng; Zhao, Xu; Chen, Bin

    2012-02-07

    Global water interdependencies are likely to increase with growing virtual water trade. To address the issues of the indirect effects of water trade through the global economic circulation, we use ecological network analysis (ENA) to shed insight into the complicated system interactions. A global model of virtual water flow among agriculture and livestock production trade in 1995-1999 is also built as the basis for network analysis. Control analysis is used to identify the quantitative control or dependency relations. The utility analysis provides more indicators for describing the mutual relationship between two regions/countries by imitating the interactions in the ecosystem and distinguishes the beneficiary and the contributor of virtual water trade system. Results show control and utility relations can well depict the mutual relation in trade system, and direct observable relations differ from integral ones with indirect interactions considered. This paper offers a new way to depict the interrelations between trade components and can serve as a meaningful start as we continue to use ENA in providing more valuable implications for freshwater study on a global scale.

  10. Global Analysis of Horizontal Gene Transfer in Fusarium verticillioides

    USDA-ARS?s Scientific Manuscript database

    The co-occurrence of microbes within plants and other specialized niches may facilitate horizontal gene transfer (HGT) affecting host-pathogen interactions. We recently identified fungal-to-fungal HGTs involving metabolic gene clusters. For a global analysis of HGTs in the maize pathogen Fusarium ve...

  11. Global and Local Sensitivity Analysis Methods for a Physical System

    ERIC Educational Resources Information Center

    Morio, Jerome

    2011-01-01

    Sensitivity analysis is the study of how the different input variations of a mathematical model influence the variability of its output. In this paper, we review the principle of global and local sensitivity analyses of a complex black-box system. A simulated case of application is given at the end of this paper to compare both approaches.…

  12. Globalization and International Student Mobility: A Network Analysis

    ERIC Educational Resources Information Center

    Shields, Robin

    2013-01-01

    This article analyzes changes to the network of international student mobility in higher education over a 10-year period (1999-2008). International student flows have increased rapidly, exceeding 3 million in 2009, and extensive data on mobility provide unique insight into global educational processes. The analysis is informed by three theoretical…

  13. Global and Local Sensitivity Analysis Methods for a Physical System

    ERIC Educational Resources Information Center

    Morio, Jerome

    2011-01-01

    Sensitivity analysis is the study of how the different input variations of a mathematical model influence the variability of its output. In this paper, we review the principle of global and local sensitivity analyses of a complex black-box system. A simulated case of application is given at the end of this paper to compare both approaches.…

  14. Global/local finite element analysis for textile composites

    NASA Technical Reports Server (NTRS)

    Woo, Kyeongsik; Whitcomb, John

    1993-01-01

    Conventional analysis of textile composites is impractical because of the complex microstructure. Global/local methodology combined with special macro elements is proposed herein as a practical alternative. Initial tests showed dramatic reductions in the computational effort with only small loss in accuracy.

  15. Global/local finite element analysis for textile composites

    SciTech Connect

    Woo, K.; Whitcomb, J.

    1993-01-01

    Conventional analysis of textile composites is impractical because of the complex microstructure. Global/local methodology combined with special macro elements is proposed herein as a practical alternative. Initial tests showed dramatic reductions in the computational effort with only small loss in accuracy. 9 refs.

  16. Globalization and International Student Mobility: A Network Analysis

    ERIC Educational Resources Information Center

    Shields, Robin

    2013-01-01

    This article analyzes changes to the network of international student mobility in higher education over a 10-year period (1999-2008). International student flows have increased rapidly, exceeding 3 million in 2009, and extensive data on mobility provide unique insight into global educational processes. The analysis is informed by three theoretical…

  17. Global Analysis of Helicity PDFs: past - present - future

    SciTech Connect

    de Florian, D.; Stratmann, M.; Sassot, R.; Vogelsang, W.

    2011-04-11

    We discuss the current status of the DSSV global analysis of helicity-dependent parton densities. A comparison with recent semi-inclusive DIS data from COMPASS is presented, and constraints on the polarized strangeness density are examined in some detail.

  18. The Wmo Global Atmosphere Watch Programme: Global Framework for Atmospheric Composition Observations and Analysis

    NASA Astrophysics Data System (ADS)

    Tarasova, O. A.; Jalkanen, L.

    2010-12-01

    The WMO Global Atmosphere Watch (GAW) Programme is the only existing long-term international global programme providing an international coordinated framework for observations and analysis of the chemical composition of the atmosphere. GAW is a partnership involving contributors from about 80 countries. It includes a coordinated global network of observing stations along with supporting facilities (Central Facilities) and expert groups (Scientific Advisory Groups, SAGs and Expert Teams, ETs). Currently GAW coordinates activities and data from 27 Global Stations and a substantial number of Regional and Contributing Stations. Station information is available through the GAW Station Information System GAWSIS (http://gaw.empa.ch/gawsis/). There are six key groups of variables which are addressed by the GAW Programme, namely: ozone, reactive gases, greenhouse gases, aerosols, UV radiation and precipitation chemistry. GAW works to implement integrated observations unifying measurements from different platforms (ground based in situ and remote, balloons, aircraft and satellite) supported by modeling activities. GAW provides data for ozone assessments, Greenhouse Gas Bulletins, Ozone Bulletins and precipitation chemistry assessments published on a regular basis and for early warnings of changes in the chemical composition and related physical characteristics of the atmosphere. To ensure that observations can be used for global assessments, the GAW Programme has developed a Quality Assurance system. Five types of Central Facilities dedicated to the six groups of measurement variables are operated by WMO Members and form the basis of quality assurance and data archiving for the GAW global monitoring network. They include Central Calibration Laboratories (CCLs) that host primary standards (PS), Quality Assurance/Science Activity Centres (QA/SACs), World Calibration Centers (WCCs), Regional Calibration Centers (RCCs), and World Data Centers (WDCs) with responsibility for

  19. Global Survey of Cell Death Mechanisms Reveals Metabolic Regulation of Ferroptosis

    PubMed Central

    Shimada, Kenichi; Skouta, Rachid; Kaplan, Anna; Yang, Wan Seok; Hayano, Miki; Dixon, Scott J.; Brown, Lewis M.; Valenzuela, Carlos A.; Wolpaw, Adam J.

    2016-01-01

    Apoptosis is known as programmed cell death. Some non-apoptotic cell death is increasingly recognized as genetically controlled, or ‘regulated’. However, the full extent and diversity of these alternative cell death mechanisms remains uncharted. Here, we surveyed the landscape of pharmacologically-accessible cell death mechanisms. Of 56 caspase-independent lethal compounds, modulatory profiling revealed ten inducing three types of regulated non-apoptotic cell death. Lead optimization of one of the ten resulted in the discovery of FIN56, a specific inducer of ferroptosis. Ferroptosis occurs when the lipid repair enzyme GPX4 is inhibited. We found that FIN56 promotes degradation of GPX4. We performed chemoproteomics to reveal that FIN56 also binds to and activates squalene synthase, an enzyme involved in the cholesterol synthesis, in a manner independent of GPX4 degradation. These discoveries reveal that dysregulation of lipid metabolism is associated with ferroptosis. This systematic approach is a means to discover and characterize novel cell death phenotypes. PMID:27159577

  20. Catch reconstructions reveal that global marine fisheries catches are higher than reported and declining.

    PubMed

    Pauly, Daniel; Zeller, Dirk

    2016-01-19

    Fisheries data assembled by the Food and Agriculture Organization (FAO) suggest that global marine fisheries catches increased to 86 million tonnes in 1996, then slightly declined. Here, using a decade-long multinational 'catch reconstruction' project covering the Exclusive Economic Zones of the world's maritime countries and the High Seas from 1950 to 2010, and accounting for all fisheries, we identify catch trajectories differing considerably from the national data submitted to the FAO. We suggest that catch actually peaked at 130 million tonnes, and has been declining much more strongly since. This decline in reconstructed catches reflects declines in industrial catches and to a smaller extent declining discards, despite industrial fishing having expanded from industrialized countries to the waters of developing countries. The differing trajectories documented here suggest a need for improved monitoring of all fisheries, including often neglected small-scale fisheries, and illegal and other problematic fisheries, as well as discarded bycatch.

  1. Scenarios of global agricultural biomass harvest reveal conflicts and trade-offs for bioenergy with CCS

    NASA Astrophysics Data System (ADS)

    Powell, Tom; Lenton, Tim

    2013-04-01

    We assess the quantitative potential for future land management to help rebalance the global carbon cycle by actively removing carbon dioxide (CO2) from the atmosphere with simultaneous bio-energy offsets of CO2 emissions, whilst meeting global food demand, preserving natural ecosystems and minimising CO2 emissions from land use change. Four alternative future scenarios are considered out to 2050 with different combinations of high or low technology food production and high or low meat diets. Natural ecosystems are protected except when additional land is necessary to fulfil the dietary demands of the global population. Dedicated bio-energy crops can only be grown on land that is already under management but is no longer needed for food production. We find that there is only room for dedicated bio-energy crops if there is a marked increase in the efficiency of food production (sustained annual yield growth of 1%, shifts towards more efficient animals like pigs and poultry, and increased recycling of wastes and residues). If there is also a return to lower meat diets, biomass energy with carbon storage (BECS) as CO2 and biochar could remove up to 4.0 Pg C per year in 2050. With the current trend to higher meat diets there is only room for limited expansion of bio-energy crops after 2035 and instead BECS must be based largely on biomass residues, removing up to 1.5 Pg C per year in. A high-meat, low-efficiency future would be a catastrophe for natural ecosystems (and thus for the humans that depend on their services) with around 8.5 Gha under cultivation in 2050. When included in a simple earth system model with a technological mitigation CO2 emission baseline these produce atmospheric CO2 concentrations of ~ 450-525ppm in 2050. In addition we assess the potential for future biodiversity loss under the scenarios due to three interacting factors; energy withdrawal from ecosystems due to biomass harvest, habitat loss due to land-use change, and climate change

  2. Catch reconstructions reveal that global marine fisheries catches are higher than reported and declining

    PubMed Central

    Pauly, Daniel; Zeller, Dirk

    2016-01-01

    Fisheries data assembled by the Food and Agriculture Organization (FAO) suggest that global marine fisheries catches increased to 86 million tonnes in 1996, then slightly declined. Here, using a decade-long multinational ‘catch reconstruction' project covering the Exclusive Economic Zones of the world's maritime countries and the High Seas from 1950 to 2010, and accounting for all fisheries, we identify catch trajectories differing considerably from the national data submitted to the FAO. We suggest that catch actually peaked at 130 million tonnes, and has been declining much more strongly since. This decline in reconstructed catches reflects declines in industrial catches and to a smaller extent declining discards, despite industrial fishing having expanded from industrialized countries to the waters of developing countries. The differing trajectories documented here suggest a need for improved monitoring of all fisheries, including often neglected small-scale fisheries, and illegal and other problematic fisheries, as well as discarded bycatch. PMID:26784963

  3. [(18)F]DPA-714 PET Imaging Reveals Global Neuroinflammation in Zika Virus-Infected Mice.

    PubMed

    Kuszpit, Kyle; Hollidge, Bradley S; Zeng, Xiankun; Stafford, Robert G; Daye, Sharon; Zhang, Xiang; Basuli, Falguni; Golden, Joseph W; Swenson, Rolf E; Smith, Darci R; Bocan, Thomas M

    2017-09-12

    The association of Zika virus (ZIKV) infection and development of neurological sequelae require a better understanding of the pathogenic mechanisms causing severe disease. The purpose of this study was to evaluate the ability and sensitivity of positron emission tomography (PET) imaging using [(18)F]DPA-714, a translocator protein (TSPO) 18 kDa radioligand, to detect and quantify neuroinflammation in ZIKV-infected mice. We assessed ZIKV-induced pathogenesis in wild-type C57BL/6 mice administered an antibody to inhibit type I interferon (IFN) signaling. [(18)F]DPA-714 PET imaging was performed on days 3, 6, and 10 post-infection (PI), and tissues were subsequently processed for histological evaluation, quantification of microgliosis, and detection of viral RNA by in situ hybridization (ISH). In susceptible ZIKV-infected mice, viral titers in the brain increased from days 3 to 10 PI. Over this span, these mice showed a two- to sixfold increase in global brain neuroinflammation using [(18)F]DPA-714 PET imaging despite limited, regional detection of viral RNA. No measurable increase in ionized calcium binding adaptor molecule 1 (Iba-1) expression was noted at day 3 PI; however, there was a modest increase at day 6 PI and an approximately significant fourfold increase in Iba-1 expression at day 10 PI in the susceptible ZIKV-infected group relative to controls. The results of the current study demonstrate that global neuroinflammation plays a significant role in the progression of ZIKV infection and that [(18)F]DPA-714 PET imaging is a sensitive tool relative to histology for the detection of neuroinflammation. [(18)F]DPA-714 PET imaging may be useful in dynamically characterizing the pathology associated with neurotropic viruses and the evaluation of therapeutics being developed for treatment of infectious diseases.

  4. Serum global metabolomics profiling reveals profound metabolic impairments in patients with MPS IIIA and MPS IIIB.

    PubMed

    Fu, Haiyan; Meadows, Aaron S; Pineda, Ricardo J; Mohney, Robert P; Stirdivant, Steve; McCarty, Douglas M

    2017-04-05

    The monogenic defects in specific lysosomal enzymes in mucopolysaccharidosis (MPS) III lead to lysosomal storage of glycosaminoglycans and complex CNS and somatic pathology, for which the detailed mechanisms remain unclear. In this study, serum samples from patients with MPS IIIA (age 2-9 yr) and MPS IIIB (2-13 yr) and healthy controls (age 2-9 yr) were assayed by global metabolomics profiling of 658 metabolites using mass spectrometry. Significant alterations were detected in 423 metabolites in all MPS III patients, of which 366 (86.5%) decreased and 57 (13.5%) increased. Similar profiles were observed when analyzing data from MPS IIIA and MPS IIIB samples separately, with only limited age variations in 36 metabolites. The observed metabolic disturbances in MPS III patients involve virtually all major pathways of amino acid (101/150), peptide (17/21), carbohydrate (19/23), lipid (221/325), nucleotide (15/25), energy (8/9), vitamins and co-factors (8/21), and xenobiotics (34/84) metabolism. Notably, detected serum metabolite decreases involved all key amino acids, all major neurotransmitter pathways, and broad neuroprotective compounds. The elevated metabolites are predominantly lipid derivatives, and also include cysteine metabolites and a fibrinogen peptide fragment, consistent with the status of oxidative stress and inflammation in MPS III. This study demonstrates that the lysosomal glycosaminoglycans storage triggers profound metabolic disturbances in patients with MPS III disorders, leading to severe functional depression of virtually all metabolic pathways, which emerge early during the disease progression. Serum global metabolomics profiling may provide an important and minimally invasive tool for better understanding the disease mechanisms and identification of potential biomarkers for MPS III.

  5. Atom-by-atom analysis of global downhill protein folding

    NASA Astrophysics Data System (ADS)

    Sadqi, Mourad; Fushman, David; Muñoz, Victor

    2006-07-01

    Protein folding is an inherently complex process involving coordination of the intricate networks of weak interactions that stabilize native three-dimensional structures. In the conventional paradigm, simple protein structures are assumed to fold in an all-or-none process that is inaccessible to experiment. Existing experimental methods therefore probe folding mechanisms indirectly. A widely used approach interprets changes in protein stability and/or folding kinetics, induced by engineered mutations, in terms of the structure of the native protein. In addition to limitations in connecting energetics with structure, mutational methods have significant experimental uncertainties and are unable to map complex networks of interactions. In contrast, analytical theory predicts small barriers to folding and the possibility of downhill folding. These theoretical predictions have been confirmed experimentally in recent years, including the observation of global downhill folding. However, a key remaining question is whether downhill folding can indeed lead to the high-resolution analysis of protein folding processes. Here we show, with the use of nuclear magnetic resonance (NMR), that the downhill protein BBL from Escherichia coli unfolds atom by atom starting from a defined three-dimensional structure. Thermal unfolding data on 158 backbone and side-chain protons out of a total of 204 provide a detailed view of the structural events during folding. This view confirms the statistical nature of folding, and exposes the interplay between hydrogen bonding, hydrophobic forces, backbone conformation and side-chain entropy. From the data we also obtain a map of the interaction network in this protein, which reveals the source of folding cooperativity. Our approach can be extended to other proteins with marginal barriers (less than 3RT), providing a new tool for the study of protein folding.

  6. Global Genomic Analysis of Pseudomonas savastanoi pv. savastanoi Plasmids▿ †

    PubMed Central

    Pérez-Martínez, Isabel; Zhao, Youfu; Murillo, Jesús; Sundin, George W.; Ramos, Cayo

    2008-01-01

    Pseudomonas savastanoi pv. savastanoi strains harbor native plasmids belonging to the pPT23A plasmid family (PFPs) which are detected in all pathovars of the related species Pseudomonas syringae examined and contribute to the ecological and pathogenic fitness of their host. However, there is a general lack of information about the gene content of P. savastanoi pv. savastanoi plasmids and their role in the interaction of this pathogen with olive plants. We designed a DNA macroarray containing 135 plasmid-borne P. syringae genes to conduct a global genetic analysis of 32 plasmids obtained from 10 P. savastanoi pv. savastanoi strains. Hybridization results revealed that the number of PFPs per strain varied from one to four. Additionally, most strains contained at least one plasmid (designated non-PFP) that did not hybridize to the repA gene of pPT23A. Only three PFPs contained genes involved in the biosynthesis of the virulence factor indole-3-acetic acid (iaaM, iaaH, and iaaL). In contrast, ptz, a gene involved in the biosynthesis of cytokinins, was found in five PFPs and one non-PFP. Genes encoding a type IV secretion system (T4SS), type IVA, were found in both PFPs and non-PFPs; however, type IVB genes were found only on PFPs. Nine plasmids encoded both T4SSs, whereas seven other plasmids carried none of these genes. Most PFPs and non-PFPs hybridized to at least one putative type III secretion system effector gene and to a variety of additional genes encoding known P. syringae virulence factors and one or more insertion sequence transposase genes. These results indicate that non-PFPs may contribute to the virulence and fitness of the P. savastanoi pv. savastanoi host. The overall gene content of P. savastanoi pv. savastanoi plasmids, with their repeated information, mosaic arrangement, and insertion sequences, suggests a possible role in adaptation to a changing environment. PMID:17993520

  7. Spatial and temporal variation of total electron content as revealed by principal component analysis

    NASA Astrophysics Data System (ADS)

    Talaat, Elsayed R.; Zhu, Xun

    2016-11-01

    Eleven years of global total electron content (TEC) data derived from the assimilated thermosphere-ionosphere electrodynamics general circulation model are analyzed using empirical orthogonal function (EOF) decomposition and the corresponding principal component analysis (PCA) technique. For the daily averaged TEC field, the first EOF explains more than 89 % and the first four EOFs explain more than 98 % of the total variance of the TEC field, indicating an effective data compression and clear separation of different physical processes. The effectiveness of the PCA technique for TEC is nearly insensitive to the horizontal resolution and the length of the data records. When the PCA is applied to global TEC including local-time variations, the rich spatial and temporal variations of field can be represented by the first three EOFs that explain 88 % of the total variance. The spectral analysis of the time series of the EOF coefficients reveals how different mechanisms such as solar flux variation, change in the orbital declination, nonlinear mode coupling and geomagnetic activity are separated and expressed in different EOFs. This work demonstrates the usefulness of using the PCA technique to assimilate and monitor the global TEC field.

  8. Genomic analysis of primordial dwarfism reveals novel disease genes.

    PubMed

    Shaheen, Ranad; Faqeih, Eissa; Ansari, Shinu; Abdel-Salam, Ghada; Al-Hassnan, Zuhair N; Al-Shidi, Tarfa; Alomar, Rana; Sogaty, Sameera; Alkuraya, Fowzan S

    2014-02-01

    Primordial dwarfism (PD) is a disease in which severely impaired fetal growth persists throughout postnatal development and results in stunted adult size. The condition is highly heterogeneous clinically, but the use of certain phenotypic aspects such as head circumference and facial appearance has proven helpful in defining clinical subgroups. In this study, we present the results of clinical and genomic characterization of 16 new patients in whom a broad definition of PD was used (e.g., 3M syndrome was included). We report a novel PD syndrome with distinct facies in two unrelated patients, each with a different homozygous truncating mutation in CRIPT. Our analysis also reveals, in addition to mutations in known PD disease genes, the first instance of biallelic truncating BRCA2 mutation causing PD with normal bone marrow analysis. In addition, we have identified a novel locus for Seckel syndrome based on a consanguineous multiplex family and identified a homozygous truncating mutation in DNA2 as the likely cause. An additional novel PD disease candidate gene XRCC4 was identified by autozygome/exome analysis, and the knockout mouse phenotype is highly compatible with PD. Thus, we add a number of novel genes to the growing list of PD-linked genes, including one which we show to be linked to a novel PD syndrome with a distinct facial appearance. PD is extremely heterogeneous genetically and clinically, and genomic tools are often required to reach a molecular diagnosis.

  9. Genomic analysis of primordial dwarfism reveals novel disease genes

    PubMed Central

    Shaheen, Ranad; Faqeih, Eissa; Ansari, Shinu; Abdel-Salam, Ghada; Al-Hassnan, Zuhair N.; Al-Shidi, Tarfa; Alomar, Rana; Sogaty, Sameera; Alkuraya, Fowzan S.

    2014-01-01

    Primordial dwarfism (PD) is a disease in which severely impaired fetal growth persists throughout postnatal development and results in stunted adult size. The condition is highly heterogeneous clinically, but the use of certain phenotypic aspects such as head circumference and facial appearance has proven helpful in defining clinical subgroups. In this study, we present the results of clinical and genomic characterization of 16 new patients in whom a broad definition of PD was used (e.g., 3M syndrome was included). We report a novel PD syndrome with distinct facies in two unrelated patients, each with a different homozygous truncating mutation in CRIPT. Our analysis also reveals, in addition to mutations in known PD disease genes, the first instance of biallelic truncating BRCA2 mutation causing PD with normal bone marrow analysis. In addition, we have identified a novel locus for Seckel syndrome based on a consanguineous multiplex family and identified a homozygous truncating mutation in DNA2 as the likely cause. An additional novel PD disease candidate gene XRCC4 was identified by autozygome/exome analysis, and the knockout mouse phenotype is highly compatible with PD. Thus, we add a number of novel genes to the growing list of PD-linked genes, including one which we show to be linked to a novel PD syndrome with a distinct facial appearance. PD is extremely heterogeneous genetically and clinically, and genomic tools are often required to reach a molecular diagnosis. PMID:24389050

  10. The Global Challenge of Antimicrobial Resistance: Insights from Economic Analysis

    PubMed Central

    Eggleston, Karen; Zhang, Ruifang; Zeckhauser, Richard J.

    2010-01-01

    The prevalence of antimicrobial resistance (AR) limits the therapeutic options for treatment of infections, and increases the social benefit from disease prevention. Like an environmental resource, antimicrobials require stewardship. The effectiveness of an antimicrobial agent is a global public good. We argue for greater use of economic analysis as an input to policy discussion about AR, including for understanding the incentives underlying health behaviors that spawn AR, and to supplement other methods of tracing the evolution of AR internationally. We also discuss integrating antimicrobial stewardship into global health governance. PMID:20948953

  11. Whole genome resequencing reveals diagnostic markers for investigating global migration and hybridization between minke whale species.

    PubMed

    Malde, Ketil; Seliussen, Bjørghild B; Quintela, María; Dahle, Geir; Besnier, Francois; Skaug, Hans J; Øien, Nils; Solvang, Hiroko K; Haug, Tore; Skern-Mauritzen, Rasmus; Kanda, Naohisa; Pastene, Luis A; Jonassen, Inge; Glover, Kevin A

    2017-01-13

    In the marine environment, where there are few absolute physical barriers, contemporary contact between previously isolated species can occur across great distances, and in some cases, may be inter-oceanic. An example of this can be seen in the minke whale species complex. Antarctic minke whales are genetically and morphologically distinct from the common minke found in the north Atlantic and Pacific oceans, and the two species are estimated to have been isolated from each other for 5 million years or more. Recent atypical migrations from the southern to the northern hemisphere have been documented and fertile hybrids and back-crossed individuals between both species have also been identified. However, it is not known whether this represents a contemporary event, potentially driven by ecosystem changes in the Antarctic, or a sporadic occurrence happening over an evolutionary time-scale. We successfully used whole genome resequencing to identify a panel of diagnostic SNPs which now enable us address this evolutionary question. A large number of SNPs displaying fixed or nearly fixed allele frequency differences among the minke whale species were identified from the sequence data. Five panels of putatively diagnostic markers were established on a genotyping platform for validation of allele frequencies; two panels (26 and 24 SNPs) separating the two species of minke whale, and three panels (22, 23, and 24 SNPs) differentiating the three subspecies of common minke whale. The panels were validated against a set of reference samples, demonstrating the ability to accurately identify back-crossed whales up to three generations. This work has resulted in the development of a panel of novel diagnostic genetic markers to address inter-oceanic and global contact among the genetically isolated minke whale species and sub-species. These markers, including a globally relevant genetic reference data set for this species complex, are now openly available for researchers interested

  12. Cross-species global proteomics reveals conserved and unique processes in Phytophthora sojae and P. ramorum

    SciTech Connect

    Savidor, Alon; Donahoo, Ryan S; Hurtado-Gonzales, Oscar; Land, Miriam L; Shah, Manesh B; Lamour, Kurt H; McDonald, W Hayes

    2008-08-01

    Phytophthora ramorum and Phytophthora sojae are destructive plant pathogens. Phytophthora sojae has a narrow host range whereas P. ramorum has a wide host range. A global proteomic comparison of the vegetative (mycelium) and infective (germinating-cyst) life-stages of P. sojae and P. ramorum was conducted to identify candidate proteins involved in host range, early infection and vegetative growth. Sixty-two candidates for early infection, 26 candidates for vegetative growth, and numerous proteins that may be involved in defining host specificity were identified. In addition, common life stage proteomic trends between the organisms were observed. In mycelia, proteins involved in transport and metabolism of amino acids, carbohydrates and other small molecules were up-regulated. In the germinating cysts, up-regulated proteins associated with lipid transport and metabolism, cytoskeleton and protein synthesis were observed. It appears that the germinating cyst catabolizes lipid reserves through the -oxidation pathway to drive the extensive protein synthesis necessary to produce the germ tube and initiate infection. Once inside the host, the pathogen switches to vegetative growth, where energy is derived from glycolysis and utilized for synthesis of amino acids and other molecules that assist survival in the plant tissue.

  13. Global biogeography of the ectomycorrhizal /sebacina lineage (Fungi, Sebacinales) as revealed from comparative phylogenetic analyses.

    PubMed

    Tedersoo, Leho; Bahram, Mohammad; Ryberg, Martin; Otsing, Eveli; Kõljalg, Urmas; Abarenkov, Kessy

    2014-08-01

    Compared with plants and animals, large-scale biogeographic patterns of microbes including fungi are poorly understood. By the use of a comparative phylogenetic approach and ancestral state reconstructions, we addressed the global biogeography, rate of evolution and evolutionary origin of the widely distributed ectomycorrhizal (EcM) /sebacina lineage that forms a large proportion of the Sebacinales order. We downloaded all publicly available internal transcribed spacer (ITS) sequences and metadata and supplemented sequence information from three genes to construct dated phylogenies and test biogeographic hypotheses. The /sebacina lineage evolved 45-57 Myr ago that groups it with relatively young EcM taxa in other studies. The most parsimonious origin for /sebacina is inferred to be North American temperate coniferous forests. Among biogeographic traits, region and biome exhibited stronger phylogenetic signal than host family. Consistent with the resource availability (environmental energy) hypothesis, the ITS region is evolving at a faster rate in tropical than nontropical regions. Most biogeographic regions exhibited substantial phylogenetic clustering suggesting a strong impact of dispersal limitation over a large geographic scale. In northern Holarctic regions, however, phylogenetic distances and phylogenetic grouping of isolates indicate multiple recent dispersal events. © 2014 John Wiley & Sons Ltd.

  14. Anthropogenic osmium in rain and snow reveals global-scale atmospheric contamination.

    PubMed

    Chen, Cynthia; Sedwick, Peter N; Sharma, Mukul

    2009-05-12

    Osmium is one of the rarer elements in seawater, with typical concentration of approximately 10 x 10(-15) g g(-1) (5.3 x 10(-14) mol kg(-1)). The osmium isotope composition ((187)Os/(188)Os ratio) of deep oceans is 1.05, reflecting a balance between inputs from continental crust (approximately 1.3) and mantle/cosmic dust (approximately 0.13). Here, we show that the (187)Os/(188)Os ratios measured in rain and snow collected around the world range from 0.16 to 0.48, much lower than expected (>1), but similar to the isotope composition of ores (approximately 0.2) that are processed to extract platinum and other metals to be used primarily in automobile catalytic converters. Present-day surface seawater has a lower (187)Os/(188)Os ratio (approximately 0.95) than deep waters, suggesting that human activities have altered the isotope composition of the world's oceans and impacted the global geochemical cycle of osmium. The contamination of the surface ocean is particularly remarkable given that osmium has few industrial uses. The pollution may increase with growing demand for platinum-based catalysts.

  15. Anthropogenic osmium in rain and snow reveals global-scale atmospheric contamination

    PubMed Central

    Chen, Cynthia; Sedwick, Peter N.; Sharma, Mukul

    2009-01-01

    Osmium is one of the rarer elements in seawater, with typical concentration of ≈10 × 10−15 g g−1 (5.3 × 10−14 mol kg−1). The osmium isotope composition (187Os/188Os ratio) of deep oceans is 1.05, reflecting a balance between inputs from continental crust (≈1.3) and mantle/cosmic dust (≈0.13). Here, we show that the 187Os/188Os ratios measured in rain and snow collected around the world range from 0.16 to 0.48, much lower than expected (>1), but similar to the isotope composition of ores (≈0.2) that are processed to extract platinum and other metals to be used primarily in automobile catalytic converters. Present-day surface seawater has a lower 187Os/188Os ratio (≈0.95) than deep waters, suggesting that human activities have altered the isotope composition of the world's oceans and impacted the global geochemical cycle of osmium. The contamination of the surface ocean is particularly remarkable given that osmium has few industrial uses. The pollution may increase with growing demand for platinum-based catalysts. PMID:19416862

  16. Global Metabolomics Reveals the Metabolic Dysfunction in Ox-LDL Induced Macrophage-Derived Foam Cells

    PubMed Central

    Xu, Wenjuan; Wei, Ziyi; Dong, Jiaojiao; Duan, Feipeng; Chen, Kuikui; Chen, Chang; Liu, Jie; Yang, Xiaowei; Chen, Lianming; Xiao, Hongbin; Liu, An

    2017-01-01

    Atherosclerosis (AS) is a chronic disorder of large arteries that is a major risk factors of high morbidity and mortality. Oxidative modification LDL is one of the important contributors to atherogenesis. Macrophages take up ox-LDL and convert into foam cells, which is the hallmark of AS. To advance the understanding of the metabolic perturbation involved in ox-LDL induced macrophage-derived foam cells and discover the potential biomarkers of early AS, a global metabolomics approach was applied based on UHPLC-QTOF/MS. Multivariate statistical analyses identified five metabolites (25-azacholesterol, anandamide, glycocholate, oleoyl ethanolamide, and 3-oxo-4, 6-choladienoate) for distinguishing foamy macrophages from controls. Among the six main metabolic pathways, the unsaturated fatty acid, especially arachidonic acid metabolism, contributed importantly to early AS. A new biomarker, anandamide (AEA), whose synthesis and metabolism in macrophages are disturbed by overloaded ox-LDL, results in metabolic obstruction. This study is the first to investigate the metabolic disturbance in macrophage-derived foam cells induced by ox-LDL and screen potential biomarkers and metabolic pathways associated with early AS. Our findings provide a new insight in the underlying pathophysiological mechanisms and also help to identify novel targets for the intervention of AS. PMID:28912717

  17. Quantitative Proteomics of Sleep-Deprived Mouse Brains Reveals Global Changes in Mitochondrial Proteins

    PubMed Central

    Li, Tie-Mei; Zhang, Ju-en; Lin, Rui; Chen, She; Luo, Minmin; Dong, Meng-Qiu

    2016-01-01

    Sleep is a ubiquitous, tightly regulated, and evolutionarily conserved behavior observed in almost all animals. Prolonged sleep deprivation can be fatal, indicating that sleep is a physiological necessity. However, little is known about its core function. To gain insight into this mystery, we used advanced quantitative proteomics technology to survey the global changes in brain protein abundance. Aiming to gain a comprehensive profile, our proteomics workflow included filter-aided sample preparation (FASP), which increased the coverage of membrane proteins; tandem mass tag (TMT) labeling, for relative quantitation; and high resolution, high mass accuracy, high throughput mass spectrometry (MS). In total, we obtained the relative abundance ratios of 9888 proteins encoded by 6070 genes. Interestingly, we observed significant enrichment for mitochondrial proteins among the differentially expressed proteins. This finding suggests that sleep deprivation strongly affects signaling pathways that govern either energy metabolism or responses to mitochondrial stress. Additionally, the differentially-expressed proteins are enriched in pathways implicated in age-dependent neurodegenerative diseases, including Parkinson’s, Huntington’s, and Alzheimer’s, hinting at possible connections between sleep loss, mitochondrial stress, and neurodegeneration. PMID:27684481

  18. Multi-edge gene set networks reveal novel insights into global relationships between biological themes.

    PubMed

    Parikh, Jignesh R; Xia, Yu; Marto, Jarrod A

    2012-01-01

    Curated gene sets from databases such as KEGG Pathway and Gene Ontology are often used to systematically organize lists of genes or proteins derived from high-throughput data. However, the information content inherent to some relationships between the interrogated gene sets, such as pathway crosstalk, is often underutilized. A gene set network, where nodes representing individual gene sets such as KEGG pathways are connected to indicate a functional dependency, is well suited to visualize and analyze global gene set relationships. Here we introduce a novel gene set network construction algorithm that integrates gene lists derived from high-throughput experiments with curated gene sets to construct co-enrichment gene set networks. Along with previously described co-membership and linkage algorithms, we apply the co-enrichment algorithm to eight gene set collections to construct integrated multi-evidence gene set networks with multiple edge types connecting gene sets. We demonstrate the utility of approach through examples of novel gene set networks such as the chromosome map co-differential expression gene set network. A total of twenty-four gene set networks are exposed via a web tool called MetaNet, where context-specific multi-edge gene set networks are constructed from enriched gene sets within user-defined gene lists. MetaNet is freely available at http://blaispathways.dfci.harvard.edu/metanet/.

  19. The world as the new local clinic: a critical analysis of three discourses of global medical competency.

    PubMed

    Martimianakis, Maria Athina Tina; Hafferty, Frederic W

    2013-06-01

    The effects of globalization on health are the focus of administrators, educators, policy makers and researchers as they work to consider how best to train and regulate health professionals to practice in a globalized world. This study explores what happens to constructs such as medical competence when the context of medical practice is discursively expanded to include the whole world. An archive of texts was assembled (1970-2011) totaling 1100 items and analyzed using a governmentality approach. Texts were included that articulated rationales for pursuing global education activities, and/or that implicitly or explicitly took a position on medical competencies in relation to practicing medicine in international or culturally diverse contexts, or in dealing with health issues as global concerns. The analysis revealed three distinct visions, representative of a primarily western mentality, for preparing physicians to practice in a globalized world: the universal global physician, the culturally versed global physician and the global physician advocate. Each has its own epistemological relationship to globalization and is supported by an evidence base. All three discourses are active and productive, sometimes within the same context. However, the discourse of the universal global physician is currently the most established. The challenge to policy makers and educators in evolving regulatory frameworks and curricula that are current and relevant necessitates a better understanding of the socio-political effects of globalization on medical education, and the ethical, political, cultural and scientific issues underlying efforts to prepare students to practice competently in a globalized world.

  20. Deep sequencing reveals global patterns of mRNA recruitment during translation initiation

    PubMed Central

    Gao, Rong; Yu, Kai; Nie, Jukui; Lian, Tengfei; Jin, Jianshi; Liljas, Anders; Su, Xiao-Dong

    2016-01-01

    In this work, we developed a method to systematically study the sequence preference of mRNAs during translation initiation. Traditionally, the dynamic process of translation initiation has been studied at the single molecule level with limited sequencing possibility. Using deep sequencing techniques, we identified the sequence preference at different stages of the initiation complexes. Our results provide a comprehensive and dynamic view of the initiation elements in the translation initiation region (TIR), including the S1 binding sequence, the Shine-Dalgarno (SD)/anti-SD interaction and the second codon, at the equilibrium of different initiation complexes. Moreover, our experiments reveal the conformational changes and regional dynamics throughout the dynamic process of mRNA recruitment. PMID:27460773

  1. Stability investigations of airfoil flow by global analysis

    NASA Technical Reports Server (NTRS)

    Morzynski, Marek; Thiele, Frank

    1992-01-01

    As the result of global, non-parallel flow stability analysis the single value of the disturbance growth-rate and respective frequency is obtained. This complex value characterizes the stability of the whole flow configuration and is not referred to any particular flow pattern. The global analysis assures that all the flow elements (wake, boundary and shear layer) are taken into account. The physical phenomena connected with the wake instability are properly reproduced by the global analysis. This enhances the investigations of instability of any 2-D flows, including ones in which the boundary layer instability effects are known to be of dominating importance. Assuming fully 2-D disturbance form, the global linear stability problem is formulated. The system of partial differential equations is solved for the eigenvalues and eigenvectors. The equations, written in the pure stream function formulation, are discretized via FDM using a curvilinear coordinate system. The complex eigenvalues and corresponding eigenvectors are evaluated by an iterative method. The investigations performed for various Reynolds numbers emphasize that the wake instability develops into the Karman vortex street. This phenomenon is shown to be connected with the first mode obtained from the non-parallel flow stability analysis. The higher modes are reflecting different physical phenomena as for example Tollmien-Schlichting waves, originating in the boundary layer and having the tendency to emerge as instabilities for the growing Reynolds number. The investigations are carried out for a circular cylinder, oblong ellipsis and airfoil. It is shown that the onset of the wake instability, the waves in the boundary layer, the shear layer instability are different solutions of the same eigenvalue problem, formulated using the non-parallel theory. The analysis offers large potential possibilities as the generalization of methods used till now for the stability analysis.

  2. Low-frequency variability of the global sea surface height revealed by satellite altimetry

    NASA Technical Reports Server (NTRS)

    Fu, Lee-Lueng

    2004-01-01

    The focus of the paper is the variability of the North Atlantic Ocean. Large-scale low-frequency variability of the North Atlantic has recently been studied based on model simulations, as well as analysis of altimetry data in conjuction with in-situ data. These studies have suggested significant interannual to decadal changes in the North Atlantic in the 1990's.

  3. The current system east of the Ryukyu Islands as revealed by a global ocean reanalysis

    NASA Astrophysics Data System (ADS)

    Thoppil, Prasad G.; Metzger, E. Joseph; Hurlburt, Harley E.; Smedstad, Ole Martin; Ichikawa, Hiroshi

    2016-02-01

    The structure and variability of the Ryukyu Current System (RCS), which forms the western boundary current along the eastern slope of the Ryukyu Islands, are studied using results from a 32-layer, 1/12.5° global HYbrid Coordinate Ocean Model (HYCOM) and Navy Coupled Ocean Data Assimilation (NCODA) reanalysis for the period 1993-2012. It is confirmed that the reanalysis realistically reproduces salient features of the observed currents at three sections southeast of Miyakojima, Okinawa and Amami-Ohshima. The mean velocity sections show well-developed subsurface velocity maxima between 700 and 900 m. The current core southeast of Amami-Ohshima shows year-to-year variations with cyclonic (anticyclonic) circulation east of Amami-Ohshima generating weak (strong) velocity cores. Interaction of the RCS with an anticyclonic eddy often produces a two-core velocity structure, with a surface core in the upper 300 m and a deeper core near 700-900 m. The horizontal structure of the RCS at 15 m depth shows a well-developed northeastward current northeast of Okinawa, which is partly fed by the southwestward extension of the anticyclonic recirculation gyre. The RCS forms a continuous northeastward current from Miyakojima to Amami-Ohshima below 500 m with shoreward intensification. The circulation at 2000 m shows a seasonal flow reversal, which is northeastward from December to June and southwestward from August to October with July and November being the transition months. The volume transports across these three sections have respective mean values of 0.6, 6.2 and 12.4 Sv (1 Sv ≡ 106 m3 s-1) and standard deviations of 10.2, 7.1 and 11.3 Sv. They have dominant seasonal variations with the maximum in winter and spring and the minimum in summer. The interannual variation of the transport anomaly, which co-varies with the RCS core, results from westward propagating mesoscale eddies arriving from the Pacific interior.

  4. The current system east of the Ryukyu Islands as revealed by a global ocean reanalysis

    NASA Astrophysics Data System (ADS)

    Thoppil, P. G.; Metzger, E. J.; Hurlburt, H. E.; Smedstad, O. M.; Ichikawa, H.

    2016-02-01

    The structure and variability of the Ryukyu Current System (RCS), which forms the western boundary current along the eastern slope of the Ryukyu Islands, are studied using results from a 32-layer, 1/12.5° global HYbrid Coordinate Ocean Model (HYCOM) reanalysis for the period 1993-2012. The reanalysis realistically reproduces salient features of the velocity observations at three locations southeast of Miyakojima, Okinawa and Amami-Oshima. The mean velocity across the three sections shows a well-developed subsurface RCS core between 700 and 900 m. The current core southeast of Amami-Oshima shows year-to-year variations with cyclonic (anticyclonic) circulation east of Amami-Oshima generating weak (strong) velocity cores. RCS interactions with anticyclonic eddies often produce a two-core velocity structure, with a surface core in the upper 300 m and a deeper core near 700-900 m. The horizontal structure of the RCS at 15 m depth shows a well-developed northeastward current northeast of Okinawa, which is partly fed by the southwestward extension of the anticyclonic recirculation gyre. The RCS forms a continuous northeastward current from Miyakojima to Amami-Oshima below 500 m with shoreward intensification. A quasi-steady southwestward current is present below 2000 m with its origin at 30°N, triggered by a cyclonic eddy. The volume transports across these three sections have respectively the mean values of 0.6, 6.2 and 12.4 Sv (Sv = 106 m3 s-1) and standard deviations of 10.2, 7.1 and 11.3 Sv. They have dominant seasonal variations with the maximum in winter and spring and minimum in summer. On interannual time scales the transport anomaly, which co-varies with the RCS core, results from the westward propagating mesoscale eddies from the east.

  5. Metabolite profiling of Phycomyces blakesleeanus carotene mutants reveals global changes across intermediary metabolism.

    PubMed

    Alcalde, Eugenio; Fraser, Paul David

    2016-11-01

    The filamentous fungus Phycomyces blakesleeanus provides a renewable biosource of industrial high-value compounds such as carotenes, other isoprenoids (ubiquinone and sterols), organic acids and fatty acids. Several Phycomyces mutants involved in the formation of β-carotene are available. For example, the carA mutants have a leaky mutation in the phytoene synthase and produce significantly lower amounts of carotenes, while the carB and carR mutants produce phytoene and lycopene, respectively, due to a null mutation in the genes encoding the phytoene dehydrogenase and lycopene cyclase, respectively. The carS mutants are mutated in the gene encoding the oxygenase responsible for the conversion of β-carotene into apocarotenoids and, as a result, β-carotene accumulates. In order to ascertain further the biochemical changes arising in these potential industrial strains, a metabolite profiling workflow was implemented for Phycomyces. GC-MS and ultra-performance liquid chromatography-photodiode array platforms enabled the identification of over 100 metabolites in 11 carA, carB, carR and carS mutant strains and their wild-type comparator. All mutant strains possessed decreased TCA cycle intermediates, galactose, alanine and ribitol, while dodecanol and valine showed a general increase. As predicted, other terpenoid levels were affected in the carB, carR and carS mutants but not in the carA mutants. The global changes across intermediary metabolism of the mutants suggest that complex metabolic networks exist between intermediary and secondary metabolism or that other mutations beyond the carotene pathway may exist in these mutants. These data show the utility of the methodology in metabolically phenotyping Phycomyces strains with potential industrial exploitation.

  6. Comparative analysis reveals the underlying mechanism of vertebrate seasonal reproduction.

    PubMed

    Ikegami, Keisuke; Yoshimura, Takashi

    2016-02-01

    Animals utilize photoperiodic changes as a calendar to regulate seasonal reproduction. Birds have highly sophisticated photoperiodic mechanisms and functional genomics analysis in quail uncovered the signal transduction pathway regulating avian seasonal reproduction. Birds detect light with deep brain photoreceptors. Long day (LD) stimulus induces secretion of thyroid-stimulating hormone (TSH) from the pars tuberalis (PT) of the pituitary gland. PT-derived TSH locally activates thyroid hormone (TH) in the hypothalamus, which induces gonadotropin-releasing hormone (GnRH) and hence gonadotropin secretion. However, during winter, low temperatures increase serum TH for adaptive thermogenesis, which accelerates germ cell apoptosis by activating the genes involved in metamorphosis. Therefore, TH has a dual role in the regulation of seasonal reproduction. Studies using TSH receptor knockout mice confirmed the involvement of PT-derived TSH in mammalian seasonal reproduction. In addition, studies in mice revealed that the tissue-specific glycosylation of TSH diversifies its function in the circulation to avoid crosstalk. In contrast to birds and mammals, one of the molecular machineries necessary for the seasonal reproduction of fish are localized in the saccus vasculosus from the photoreceptor to the neuroendocrine output. Thus, comparative analysis is a powerful tool to uncover the universality and diversity of fundamental properties in various organisms.

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

    PubMed Central

    Díaz-Pascual, Francisco; Ortíz-Severín, Javiera; Varas, Macarena A.; Allende, Miguel L.; Chávez, Francisco P.

    2017-01-01

    demonstrated the suitability of zebrafish embryos as a model for in vivo host-pathogen based proteomic studies in P. aeruginosa. Our global proteomic profiling identifies novel molecular signatures that give systematic insight into zebrafish-Pseudomonas interaction. PMID:28791256

  8. Lattice Boltzmann methods for global linear instability analysis

    NASA Astrophysics Data System (ADS)

    Pérez, José Miguel; Aguilar, Alfonso; Theofilis, Vassilis

    2016-11-01

    Modal global linear instability analysis is performed using, for the first time ever, the lattice Boltzmann method (LBM) to analyze incompressible flows with two and three inhomogeneous spatial directions. Four linearization models have been implemented in order to recover the linearized Navier-Stokes equations in the incompressible limit. Two of those models employ the single relaxation time and have been proposed previously in the literature as linearization of the collision operator of the lattice Boltzmann equation. Two additional models are derived herein for the first time by linearizing the local equilibrium probability distribution function. Instability analysis results are obtained in three benchmark problems, two in closed geometries and one in open flow, namely the square and cubic lid-driven cavity flow and flow in the wake of the circular cylinder. Comparisons with results delivered by classic spectral element methods verify the accuracy of the proposed new methodologies and point potential limitations particular to the LBM approach. The known issue of appearance of numerical instabilities when the SRT model is used in direct numerical simulations employing the LBM is shown to be reflected in a spurious global eigenmode when the SRT model is used in the instability analysis. Although this mode is absent in the multiple relaxation times model, other spurious instabilities can also arise and are documented herein. Areas of potential improvements in order to make the proposed methodology competitive with established approaches for global instability analysis are discussed.

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

    PubMed Central

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

    2015-01-01

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

  10. Global analysis of cloud field coverage and radiative properties, using morphological methods and MODIS observations

    NASA Astrophysics Data System (ADS)

    Bar-Or, R. Z.; Altaratz, O.; Koren, I.

    2011-01-01

    The recently recognized continuous transition zone between detectable clouds and cloud-free atmosphere ("the twilight zone") is affected by undetectable clouds and humidified aerosol. In this study, we suggest to distinguish cloud fields (including the detectable clouds and the surrounding twilight zone) from cloud-free areas, which are not affected by clouds. For this classification, a robust and simple-to-implement cloud field masking algorithm which uses only the spatial distribution of clouds, is presented in detail. A global analysis, estimating Earth's cloud field coverage (50° S-50° N) for 28 July 2008, using the Moderate Resolution Imaging Spectroradiometer (MODIS) data, finds that while the declared cloud fraction is 51%, the global cloud field coverage reaches 88%. The results reveal the low likelihood for finding a cloud-free pixel and suggest that this likelihood may decrease as the pixel size becomes larger. A global latitudinal analysis of cloud fields finds that unlike oceans, which are more uniformly covered by cloud fields, land areas located under the subsidence zones of the Hadley cell (the desert belts), contain proper areas for investigating cloud-free atmosphere as there is 40-80% probability to detect clear sky over them. Usually these golden-pixels, with higher likelihood to be free of clouds, are over deserts. Independent global statistical analysis, using MODIS aerosol and cloud products, reveals a sharp exponential decay of the global mean aerosol optical depth (AOD) as a function of the distance from the nearest detectable cloud, both above ocean and land. Similar statistical analysis finds an exponential growth of mean aerosol fine-mode fraction (FMF) over oceans when the distance from the nearest cloud increases. A 30 km scale break clearly appears in several analyses here, suggesting this is a typical natural scale of cloud fields. This work shows different microphysical and optical properties of cloud fields, urging to separately

  11. Global analysis of cloud field coverage and radiative properties, using morphological methods and MODIS observations

    NASA Astrophysics Data System (ADS)

    Bar-Or, R. Z.; Altaratz, O.; Koren, I.

    2010-08-01

    The recently recognized continuous transition zone between detectable clouds and cloud-free atmosphere ("the twilight zone") is affected by undetectable clouds and humidified aerosol. In this study, we suggest to distinguish cloud fields (including the detectable clouds and the surrounding twilight zone) from cloud-free areas, which are not affected by clouds. For this classification, a robust and simple-to-implement cloud field masking algorithm which uses only the spatial distribution of clouds, is presented in detail. A global analysis, estimating Earth's cloud field coverage (50° S-50° N) for 28 July 2008, using the Moderate Resolution Imaging Spectroradiometer (MODIS) data, finds that while the declared cloud fraction is 51%, the global cloud field coverage reaches 88%. The results reveal the low likelihood for finding a cloud free pixel and suggest that this likelihood may decrease as the pixel size becomes larger. A global latitudinal analysis of cloud fields finds that unlike oceans, which are more uniformly covered by cloud fields, land areas located under the subsidence zones of the Hadley cell (the desert belts), contain proper areas for investigating cloud free atmosphere as there is 40-80% probability to detect clear sky over them. Usually these golden-pixels, with higher likelihood to be free of clouds, are over deserts. Independent global statistical analysis, using MODIS aerosol and cloud products, reveals a sharp exponential decay of the global mean aerosol optical depth (AOD) as a function of the distance from the nearest detectable cloud, both above ocean and land. Similar statistical analysis finds an exponential growth of mean aerosol fine-mode fraction (FMF) over Oceans when the distance from the nearest cloud increases. A 30 km scale break clearly appears in several analyses here, suggesting this is a typical natural scale of cloud fields. This work shows different microphysical and optical properties of cloud fields, urging to separately

  12. Global Mapping of the Inc-Human Interactome Reveals that Retromer Restricts Chlamydia Infection.

    PubMed

    Mirrashidi, Kathleen M; Elwell, Cherilyn A; Verschueren, Erik; Johnson, Jeffrey R; Frando, Andrew; Von Dollen, John; Rosenberg, Oren; Gulbahce, Natali; Jang, Gwendolyn; Johnson, Tasha; Jäger, Stefanie; Gopalakrishnan, Anusha M; Sherry, Jessica; Dunn, Joe Dan; Olive, Andrew; Penn, Bennett; Shales, Michael; Cox, Jeffery S; Starnbach, Michael N; Derre, Isabelle; Valdivia, Raphael; Krogan, Nevan J; Engel, Joanne

    2015-07-08

    Chlamydia trachomatis is a leading cause of genital and ocular infections for which no vaccine exists. Upon entry into host cells, C. trachomatis resides within a membrane-bound compartment—the inclusion—and secretes inclusion membrane proteins (Incs) that are thought to modulate the host-bacterium interface. To expand our understanding of Inc function(s), we subjected putative C. trachomatis Incs to affinity purification-mass spectroscopy (AP-MS). We identified Inc-human interactions for 38/58 Incs with enrichment in host processes consistent with Chlamydia's intracellular life cycle. There is significant overlap between Inc targets and viral proteins, suggesting common pathogenic mechanisms among obligate intracellular microbes. IncE binds to sorting nexins (SNXs) 5/6, components of the retromer, which relocalizes SNX5/6 to the inclusion membrane and augments inclusion membrane tubulation. Depletion of retromer components enhances progeny production, revealing that retromer restricts Chlamydia infection. This study demonstrates the value of proteomics in unveiling host-pathogen interactions in genetically challenging microbes.

  13. Frequency analysis of nonlinear oscillations via the global error minimization

    NASA Astrophysics Data System (ADS)

    Kalami Yazdi, M.; Hosseini Tehrani, P.

    2016-06-01

    The capacity and effectiveness of a modified variational approach, namely global error minimization (GEM) is illustrated in this study. For this purpose, the free oscillations of a rod rocking on a cylindrical surface and the Duffing-harmonic oscillator are treated. In order to validate and exhibit the merit of the method, the obtained result is compared with both of the exact frequency and the outcome of other well-known analytical methods. The corollary reveals that the first order approximation leads to an acceptable relative error, specially for large initial conditions. The procedure can be promisingly exerted to the conservative nonlinear problems.

  14. A global overview of drought and heat-induced tree mortality reveals emerging climate change risks for forests

    USGS Publications Warehouse

    Allen, C.D.; Macalady, A.K.; Chenchouni, H.; Bachelet, D.; McDowell, N.; Vennetier, M.; Kitzberger, T.; Rigling, A.; Breshears, D.D.; Hogg, E.H.(T.); Gonzalez, P.; Fensham, R.; Zhang, Z.; Castro, J.; Demidova, N.; Lim, J.-H.; Allard, G.; Running, S.W.; Semerci, A.; Cobb, N.

    2010-01-01

    Greenhouse gas emissions have significantly altered global climate, and will continue to do so in the future. Increases in the frequency, duration, and/or severity of drought and heat stress associated with climate change could fundamentally alter the composition, structure, and biogeography of forests in many regions. Of particular concern are potential increases in tree mortality associated with climate-induced physiological stress and interactions with other climate-mediated processes such as insect outbreaks and wildfire. Despite this risk, existing projections of tree mortality are based on models that lack functionally realistic mortality mechanisms, and there has been no attempt to track observations of climate-driven tree mortality globally. Here we present the first global assessment of recent tree mortality attributed to drought and heat stress. Although episodic mortality occurs in the absence of climate change, studies compiled here suggest that at least some of the world's forested ecosystems already may be responding to climate change and raise concern that forests may become increasingly vulnerable to higher background tree mortality rates and die-off in response to future warming and drought, even in environments that are not normally considered water-limited. This further suggests risks to ecosystem services, including the loss of sequestered forest carbon and associated atmospheric feedbacks. Our review also identifies key information gaps and scientific uncertainties that currently hinder our ability to predict tree mortality in response to climate change and emphasizes the need for a globally coordinated observation system. Overall, our review reveals the potential for amplified tree mortality due to drought and heat in forests worldwide.

  15. Genomic analysis reveals distinct mechanisms and functional classes of SOX10-regulated genes in melanocytes

    PubMed Central

    Fufa, Temesgen D.; Harris, Melissa L.; Watkins-Chow, Dawn E.; Levy, Denise; Gorkin, David U.; Gildea, Derek E.; Song, Lingyun; Safi, Alexias; Crawford, Gregory E.; Sviderskaya, Elena V.; Bennett, Dorothy C.; Mccallion, Andrew S.; Loftus, Stacie K.; Pavan, William J.

    2015-01-01

    SOX10 is required for melanocyte development and maintenance, and has been linked to melanoma initiation and progression. However, the molecular mechanisms by which SOX10 guides the appropriate gene expression programs necessary to promote the melanocyte lineage are not fully understood. Here we employ genetic and epigenomic analysis approaches to uncover novel genomic targets and previously unappreciated molecular roles of SOX10 in melanocytes. Through global analysis of SOX10-binding sites and epigenetic characteristics of chromatin states, we uncover an extensive catalog of SOX10 targets genome-wide. Our findings reveal that SOX10 predominantly engages ‘open’ chromatin regions and binds to distal regulatory elements, including novel and previously known melanocyte enhancers. Integrated chromatin occupancy and transcriptome analysis suggest a role for SOX10 in both transcriptional activation and repression to regulate functionally distinct classes of genes. We demonstrate that distinct epigenetic signatures and cis-regulatory sequence motifs predicted to bind putative co-regulatory transcription factors define SOX10-activated and SOX10-repressed target genes. Collectively, these findings uncover a central role of SOX10 as a global regulator of gene expression in the melanocyte lineage by targeting diverse regulatory pathways. PMID:26206884

  16. Genetic diversity and relationship of global faba bean (Vicia faba L.) germplasm revealed by ISSR markers.

    PubMed

    Wang, Hai-Fei; Zong, Xu-Xiao; Guan, Jian-Ping; Yang, Tao; Sun, Xue-Lian; Ma, Yu; Redden, Robert

    2012-03-01

    Genetic diversity and relationships of 802 faba bean (Vicia faba L.) landraces and varieties from different geographical locations of China and abroad were examined using ISSR markers. A total of 212 repeatable amplified bands were generated with 11 ISSR primers, of which 209 were polymorphic. Accessions from North China showed highest genetic diversity, while accessions from central China showed low level of diversity. Chinese spring faba bean germplasm was clearly separated from Chinese winter faba bean, based on principal component analysis and UPGMA clustering analysis. Winter accessions from Zhejiang (East China), Jiangxi (East China), Sichuan (Southwest China) and Guizhou (Southwest China) were quite distinct to that from other provinces in China. Great differentiation between Chinese accessions and those from rest of the world was shown with a UPGMA dendrogram. AMOVA analyses demonstrated large variation and differentiation within and among groups of accessions from China. As a continental geographic group, accessions from Europe were genetically closer to those from North Africa. Based on ISSR data, grouping results of accessions from Asia, Europe and Africa were obviously associated with their geographical origin. The overall results indicated that the genetic relationship of faba bean germplasm was closely associated with their geographical origin and their ecological habit.

  17. Conformational diversity analysis reveals three functional mechanisms in proteins

    PubMed Central

    Fornasari, María Silvina

    2017-01-01

    Protein motions are a key feature to understand biological function. Recently, a large-scale analysis of protein conformational diversity showed a positively skewed distribution with a peak at 0.5 Å C-alpha root-mean-square-deviation (RMSD). To understand this distribution in terms of structure-function relationships, we studied a well curated and large dataset of ~5,000 proteins with experimentally determined conformational diversity. We searched for global behaviour patterns studying how structure-based features change among the available conformer population for each protein. This procedure allowed us to describe the RMSD distribution in terms of three main protein classes sharing given properties. The largest of these protein subsets (~60%), which we call “rigid” (average RMSD = 0.83 Å), has no disordered regions, shows low conformational diversity, the largest tunnels and smaller and buried cavities. The two additional subsets contain disordered regions, but with differential sequence composition and behaviour. Partially disordered proteins have on average 67% of their conformers with disordered regions, average RMSD = 1.1 Å, the highest number of hinges and the longest disordered regions. In contrast, malleable proteins have on average only 25% of disordered conformers and average RMSD = 1.3 Å, flexible cavities affected in size by the presence of disordered regions and show the highest diversity of cognate ligands. Proteins in each set are mostly non-homologous to each other, share no given fold class, nor functional similarity but do share features derived from their conformer population. These shared features could represent conformational mechanisms related with biological functions. PMID:28192432

  18. A Global Optimization Approach to Multi-Polarity Sentiment Analysis

    PubMed Central

    Li, Xinmiao; Li, Jing; Wu, Yukeng

    2015-01-01

    Following the rapid development of social media, sentiment analysis has become an important social media mining technique. The performance of automatic sentiment analysis primarily depends on feature selection and sentiment classification. While information gain (IG) and support vector machines (SVM) are two important techniques, few studies have optimized both approaches in sentiment analysis. The effectiveness of applying a global optimization approach to sentiment analysis remains unclear. We propose a global optimization-based sentiment analysis (PSOGO-Senti) approach to improve sentiment analysis with IG for feature selection and SVM as the learning engine. The PSOGO-Senti approach utilizes a particle swarm optimization algorithm to obtain a global optimal combination of feature dimensions and parameters in the SVM. We evaluate the PSOGO-Senti model on two datasets from different fields. The experimental results showed that the PSOGO-Senti model can improve binary and multi-polarity Chinese sentiment analysis. We compared the optimal feature subset selected by PSOGO-Senti with the features in the sentiment dictionary. The results of this comparison indicated that PSOGO-Senti can effectively remove redundant and noisy features and can select a domain-specific feature subset with a higher-explanatory power for a particular sentiment analysis task. The experimental results showed that the PSOGO-Senti approach is effective and robust for sentiment analysis tasks in different domains. By comparing the improvements of two-polarity, three-polarity and five-polarity sentiment analysis results, we found that the five-polarity sentiment analysis delivered the largest improvement. The improvement of the two-polarity sentiment analysis was the smallest. We conclude that the PSOGO-Senti achieves higher improvement for a more complicated sentiment analysis task. We also compared the results of PSOGO-Senti with those of the genetic algorithm (GA) and grid search method. From

  19. Global Geometric Morphometric Analyses of the Human Pelvis Reveal Substantial Neutral Population History Effects, Even across Sexes

    PubMed Central

    Betti, Lia; von Cramon-Taubadel, Noreen; Manica, Andrea; Lycett, Stephen J.

    2013-01-01

    Recent applications of population genetic models to human craniodental traits have revealed a strong neutral component to patterns of global variation. However, little work has been undertaken to determine whether neutral processes might also be influencing the postcranium, perhaps due to substantial evidence for selection and plastic environmental responses in these regions. Recent work has provided evidence for neutral effects in the pelvis, but has been limited in regard to shape data (small numbers of linear measurements) and restricted only to males. Here, we use geometric morphometric methods to examine population variation in the human os coxae (pelvic bone) in both males and females. Neutrality is examined via apportionment of variance patterns and fit to an Out-of-Africa serial founder effect model, which is known to structure neutral genetic patterns. Moreover, we compare males and females directly, and the true versus false pelvis, in order to examine potential obstetrical effects. Our results indicate evidence for substantial neutral population history effects on pelvic shape variation. They also reveal evidence for the effect of obstetrical constraints, but these affect males and females to equivalent extents. Our results do not deny an important role for selection in regard to specific aspects of human pelvic variation, especially in terms of features associated with body size and proportions. However, our analyses demonstrate that at a global level, the shape of the os coxae reveals substantial evidence for neutral variation. Our analyses thus indicate that population variation in the human pelvis might be used to address important questions concerning population history, just as the human cranium has done. PMID:23409086

  20. A Comparative Analysis of Global Cropping Systems Models and Maps

    NASA Astrophysics Data System (ADS)

    Anderson, W. B.; You, L.; Wood, S.; Wood-Sichra, U.; Wu, W.

    2013-12-01

    Agricultural practices have dramatically altered the land cover of the Earth, but the spatial extent and intensity of these practices is often difficult to catalogue. Cropland accounts for nearly 15 million km2 of the Earth's land cover - amounting to 12% of the Earth's ice-free land surface - yet information on the distribution and performance of specific crops is often available only through national or sub-national statistics. While remote sensing products offer spatially disaggregated information, those currently available on a global scale are ill-suited for many applications due to the limited separation of crop types within the area classified as cropland. Recently, however, there have been multiple independent efforts to incorporate the detailed information available from statistical surveys with supplemental spatial information to produce a spatially explicit global dataset specific to individual cropss for the year 2000. While these datasets provide analysts and decision makers with improved information on global cropping systems, the final global cropping maps differ from one another substantially. This study aims to explore and quantify systematic similarities and differences between four major global cropping systems products: the monthly irrigated and rainfed crop areas around the year 2000 (MIRAC2000) dataset, the spatial production allocation model (SPAM), the global agro-ecological zone (GAEZ) dataset, and the dataset developed by Monfreda et al., 2008. The analysis explores not only the final cropping systems maps but also the interdependencies of each product, methodological differences and modeling assumptions, which will provide users with information vital for discerning between datasets in selecting a product appropriate for each intended application.

  1. The Global Financial Crisis: Analysis and Policy Implications

    DTIC Science & Technology

    2010-02-04

    Buy American’ Clause,” Spiegel Online International, February 3, 2009, Internet edition. The Global Financial Crisis: Analysis and Policy...China Railway Materials closed deals to buy stakes in FerrAus and United Minerals, two miners of iron ore in Australia, while China Guangdong Nuclear...companies get primary access low priced raw materials from domestic producers, non-Chinese companies must buy the products in the open market, where

  2. Global Transcriptional Response of Human Liver Cells to Ethanol Stress of Different Strength Reveals Hormetic Behavior.

    PubMed

    Schmidt-Heck, Wolfgang; Wönne, Eva C; Hiller, Thomas; Menzel, Uwe; Koczan, Dirk; Damm, Georg; Seehofer, Daniel; Knöspel, Fanny; Freyer, Nora; Guthke, Reinhard; Dooley, Steven; Zeilinger, Katrin

    2017-05-01

    The liver is the major site for alcohol metabolism in the body and therefore the primary target organ for ethanol (EtOH)-induced toxicity. In this study, we investigated the in vitro response of human liver cells to different EtOH concentrations in a perfused bioartificial liver device that mimics the complex architecture of the natural organ. Primary human liver cells were cultured in the bioartificial liver device and treated for 24 hours with medium containing 150 mM (low), 300 mM (medium), or 600 mM (high) EtOH, while a control culture was kept untreated. Gene expression patterns for each EtOH concentration were monitored using Affymetrix Human Gene 1.0 ST Gene chips. Scaled expression profiles of differentially expressed genes (DEGs) were clustered using Fuzzy c-means algorithm. In addition, functional classification methods, KEGG pathway mapping and also a machine learning approach (Random Forest) were utilized. A number of 966 (150 mM EtOH), 1,334 (300 mM EtOH), or 4,132 (600 mM EtOH) genes were found to be differentially expressed. Dose-response relationships of the identified clusters of co-expressed genes showed a monotonic, threshold, or nonmonotonic (hormetic) behavior. Functional classification of DEGs revealed that low or medium EtOH concentrations operate adaptation processes, while alterations observed for the high EtOH concentration reflect the response to cellular damage. The genes displaying a hormetic response were functionally characterized by overrepresented "cellular ketone metabolism" and "carboxylic acid metabolism." Altered expression of the genes BAHD1 and H3F3B was identified as sufficient to classify the samples according to the applied EtOH doses. Different pathways of metabolic and epigenetic regulation are affected by EtOH exposition and partly undergo hormetic regulation in the bioartificial liver device. Gene expression changes observed at high EtOH concentrations reflect in some aspects the situation of alcoholic hepatitis

  3. GLOBAL ANALYSIS OF KOI-977: SPECTROSCOPY, ASTEROSEISMOLOGY, AND PHASE-CURVE ANALYSIS

    SciTech Connect

    Hirano, Teruyuki; Sato, Bun'ei; Kobayashi, Atsushi; Masuda, Kento; Benomar, Othman; Takeda, Yoichi; Omiya, Masashi; Harakawa, Hiroki

    2015-01-20

    We present a global analysis of KOI-977, one of the planet host candidates detected by Kepler. The Kepler Input Catalog (KIC) reports that KOI-977 is a red giant, for which few close-in planets have been discovered. Our global analysis involves spectroscopic and asteroseismic determinations of stellar parameters (e.g., mass and radius) and radial velocity (RV) measurements. Our analyses reveal that KOI-977 is indeed a red giant, possibly in the red clump, but its estimated radius (≳ 20 R {sub ☉} = 0.093 AU) is much larger than KOI-977.01's orbital distance (∼0.027 AU) estimated from its period (P {sub orb} ∼ 1.35 days) and host star's mass. RV measurements show a small variation, which also contradicts the amplitude of ellipsoidal variations seen in the light curve folded with KOI-977.01's period. Therefore, we conclude that KOI-977.01 is a false positive, meaning that the red giant, for which we measured the radius and RVs, is different from the object that produces the transit-like signal (i.e., an eclipsing binary). On the basis of this assumption, we also perform a light curve analysis including the modeling of transits/eclipses and phase-curve variations, adopting various values for the dilution factor D, which is defined as the flux ratio between the red giant and eclipsing binary. Fitting the whole folded light curve as well as individual transits in the short cadence data simultaneously, we find that the estimated mass and radius ratios of the eclipsing binary are consistent with those of a solar-type star and a late-type star (e.g., an M dwarf) for D ≳ 20.

  4. Statistical modelling reveals demography and time are the main contributing factors in global sperm count changes between 1938 and 1996.

    PubMed

    Bahadur, G; Ling, K L; Katz, M

    1996-12-01

    Declining sperm count reports have caused enormous concern to both the scientific community and to society. We reproduced the linear regression analysis and the quadratic model analysis using the 50 year sperm count data published in Carlsen's report and found that neither model adequately described the data. The reported decline in sperm count could be due to observational bias and overinterpretation of linear regression. In fact only 36% of the total variability in sperm count was explained by the linear model and 42% by the quadratic model. The linear model was no longer valid when three new European reports on sperm counts were included in the analysis. The quadratic model, however, suggested an upward trend of sperm count after 1975 (R2 = 0.48, P < 0.0001). Factors other than the 'passage of time' may have contributed to the initial decline of sperm count. An immediate candidate was demography. Our analysis showed that sperm counts in USA were significantly higher in 1938-1956 compared with those in 1957-1974 and 1975-1988, but not in the European or Asian/African/South American countries. The variability of the USA sperm count (1938-1988) explained by the linear and quadratic models was found to be 71 and 70% respectively. The quadratic model importantly indicated that the sperm count in USA decreases asymptotically towards a limiting value and global sperm counts could be increasing since 1970. The non-uniform nature of the global sperm count change suggested that local variations in pollution, diet but not global warming were important determinants of reproductive health.

  5. Global Metabolomic Profiling Reveals an Association of Metal Fume Exposure and Plasma Unsaturated Fatty Acids

    PubMed Central

    Chang, Chiung-yu; Fan, Tianteng; Su, Li; Chen, Feng; Christiani, David C.

    2013-01-01

    Background Welding-associated air pollutants negatively affect the health of exposed workers; however, their molecular mechanisms in causing disease remain largely unclear. Few studies have systematically investigated the systemic toxic effects of welding fumes on humans. Objectives To explore the effects of welding fumes on the plasma metabolome, and to identify biomarkers for risk assessment of welding fume exposure. Methods The two-stage, self-controlled exploratory study included 11 boilermakers from a 2011 discovery panel and 8 boilermakers from a 2012 validation panel. Plasma samples were collected pre- and post-welding fume exposure and analyzed by chromatography/mass spectrometry. Results Eicosapentaenoic or docosapentaenoic acid metabolic changes post-welding were significantly associated with particulate (PM2.5) exposure (p<0.05). The combined analysis by linear mixed-effects model showed that exposure was associated with a statistically significant decline in metabolite change of eicosapentaenoic acid [(95% CI) = −0.013(−0.022∼−0.004); p = 0.005], docosapentaenoic acid n3 [(95% CI) = −0.010(−0.018∼−0.002); p = 0.017], and docosapentaenoic acid n6 [(95% CI) = −0.007(−0.013∼−0.001); p = 0.021]. Pathway analysis identified an association of the unsaturated fatty acid pathway with exposure (pStudy−2011 = 0.025; pStudy−2012 = 0.021; pCombined = 0.009). The functional network built by these fatty acids and their interactive genes contained significant enrichment of genes associated with various diseases, including neoplasms, cardiovascular diseases, and lipid metabolism disorders. Conclusions High-dose exposure of metal welding fumes decreases unsaturated fatty acids with an exposure-response relationship. This alteration in fatty acids is a potential biological mediator and biomarker for exposure-related health disorders. PMID:24143234

  6. Point-of-gaze analysis reveals visual search strategies

    NASA Astrophysics Data System (ADS)

    Rajashekar, Umesh; Cormack, Lawrence K.; Bovik, Alan C.

    2004-06-01

    Seemingly complex tasks like visual search can be analyzed using a cognition-free, bottom-up framework. We sought to reveal strategies used by observers in visual search tasks using accurate eye tracking and image analysis at point of gaze. Observers were instructed to search for simple geometric targets embedded in 1/f noise. By analyzing the stimulus at the point of gaze using the classification image (CI) paradigm, we discovered CI templates that indeed resembled the target. No such structure emerged for a random-searcher. We demonstrate, qualitatively and quantitatively, that these CI templates are useful in predicting stimulus regions that draw human fixations in search tasks. Filtering a 1/f noise stimulus with a CI results in a 'fixation prediction map'. A qualitative evaluation of the prediction was obtained by overlaying k-means clusters of observers' fixations on the prediction map. The fixations clustered around the local maxima in the prediction map. To obtain a quantitative comparison, we computed the Kullback-Leibler distance between the recorded fixations and the prediction. Using random-searcher CIs in Monte Carlo simulations, a distribution of this distance was obtained. The z-scores for the human CIs and the original target were -9.70 and -9.37 respectively indicating that even in noisy stimuli, observers deploy their fixations efficiently to likely targets rather than casting them randomly hoping to fortuitously find the target.

  7. Dynamical analysis reveals individuality of locomotion in goldfish.

    PubMed

    Neumeister, H; Cellucci, C J; Rapp, P E; Korn, H; Faber, D S

    2004-02-01

    Goldfish swimming was analysed quantitatively to determine if it exhibits distinctive individual spatio-temporal patterns. Due to the inherent variability in fish locomotion, this hypothesis was tested using five nonlinear measures, complemented by mean velocity. A library was constructed of 75 trajectories, each of 5 min duration, acquired from five fish swimming in a constant and relatively homogeneous environment. Three nonlinear measures, the 'characteristic fractal dimension' and 'Richardson dimension', both quantifying the degree to which a trajectory departs from a straight line, and 'relative dispersion', characterizing the variance as a function of the duration, have coefficients of variation less than 7%, in contrast to mean velocity (30%). A discriminant analysis, or classification system, based on all six measures revealed that trajectories are indeed highly individualistic, with the probability that any two trajectories generated from different fish are equivalent being less than 1%. That is, the combination of these measures allows a given trajectory to be assigned to its source with a high degree of confidence. The Richardson dimension and the 'Hurst exponent', which quantifies persistence, were the most effective measures.

  8. [Global Atmospheric Chemistry/Transport Modeling and Data-Analysis

    NASA Technical Reports Server (NTRS)

    Prinn, Ronald G.

    1999-01-01

    This grant supported a global atmospheric chemistry/transport modeling and data- analysis project devoted to: (a) development, testing, and refining of inverse methods for determining regional and global transient source and sink strengths for trace gases; (b) utilization of these inverse methods which use either the Model for Atmospheric Chemistry and Transport (MATCH) which is based on analyzed observed winds or back- trajectories calculated from these same winds for determining regional and global source and sink strengths for long-lived trace gases important in ozone depletion and the greenhouse effect; (c) determination of global (and perhaps regional) average hydroxyl radical concentrations using inverse methods with multiple "titrating" gases; and (d) computation of the lifetimes and spatially resolved destruction rates of trace gases using 3D models. Important ultimate goals included determination of regional source strengths of important biogenic/anthropogenic trace gases and also of halocarbons restricted by the Montreal Protocol and its follow-on agreements, and hydrohalocarbons now used as alternatives to the above restricted halocarbons.

  9. GLobal Ocean Data Analysis Project (GLODAP): Data and Analyses

    DOE Data Explorer

    Sabine, C. L.; Key, R. M.; Feely, R. A.; Bullister, J. L.; Millero, F. J.; Wanninkhof, R.; Peng, T. H.; Kozyr, A.

    The GLobal Ocean Data Analysis Project (GLODAP) is a cooperative effort to coordinate global synthesis projects funded through NOAA, DOE, and NSF as part of the Joint Global Ocean Flux Study - Synthesis and Modeling Project (JGOFS-SMP). Cruises conducted as part of the World Ocean Circulation Experiment (WOCE), JGOFS, and the NOAA Ocean-Atmosphere Exchange Study (OACES) over the decade of the 1990s have created an important oceanographic database for the scientific community investigating carbon cycling in the oceans. The unified data help to determine the global distributions of both natural and anthropogenic inorganic carbon, including radiocarbon. These estimates provide an important benchmark against which future observational studies will be compared. They also provide tools for the direct evaluation of numerical ocean carbon models. GLODAP information available through CDIAC includes gridded and bottle data, a live server, an interactive atlas that provides access to data plots, and other tools for viewing and interacting with the data. [from http://cdiac.esd.ornl.gov/oceans/glodap/Glopintrod.htm](Specialized Interface)

  10. An interactive system for analysis of global cloud imagery

    NASA Technical Reports Server (NTRS)

    Woodberry, Karen; Tanaka, Ken; Hendon, Harry; Salby, Murry

    1991-01-01

    Synoptic images of the global cloud pattern composited from six contemporaneous satellites provide an unprecedented view of the global cloud field. Having horizontal resolution of about 0.5 deg and temporal resolution of 3 h, the global cloud imagery (GCI) resolves most of the variability of organized convection, including several harmonics of the diurnal cycle. Although the GCI has these attractive features, the dense and 3D nature of that data make it a formidable volume of information to treat in a practical and efficient manner. An interactive image-analysis system (IAS) has been developed to investigate the space-time variability of global cloud behavior. In the IAS, data, hardware, and software are integrated into a single system providing a variety of space-time covariance analyses in a menu-driven format. Owing to its customized architecture and certain homogeneous properties of the GCI, the IAS calculates such quantities effectively. Many covariance statistics are derived from 3D data with interactive speed, allowing the user to interrogate the archive iteratively in a single session. The 3D nature of those analyses and the speed with which they are performed distinguish the IAS from conventional image processing of 2D data.

  11. Global sensitivity analysis in stochastic simulators of uncertain reaction networks.

    PubMed

    Navarro Jimenez, M; Le Maître, O P; Knio, O M

    2016-12-28

    Stochastic models of chemical systems are often subjected to uncertainties in kinetic parameters in addition to the inherent random nature of their dynamics. Uncertainty quantification in such systems is generally achieved by means of sensitivity analyses in which one characterizes the variability with the uncertain kinetic parameters of the first statistical moments of model predictions. In this work, we propose an original global sensitivity analysis method where the parametric and inherent variability sources are both treated through Sobol's decomposition of the variance into contributions from arbitrary subset of uncertain parameters and stochastic reaction channels. The conceptual development only assumes that the inherent and parametric sources are independent, and considers the Poisson processes in the random-time-change representation of the state dynamics as the fundamental objects governing the inherent stochasticity. A sampling algorithm is proposed to perform the global sensitivity analysis, and to estimate the partial variances and sensitivity indices characterizing the importance of the various sources of variability and their interactions. The birth-death and Schlögl models are used to illustrate both the implementation of the algorithm and the richness of the proposed analysis method. The output of the proposed sensitivity analysis is also contrasted with a local derivative-based sensitivity analysis method classically used for this type of systems.

  12. A global ocean carbon climatology: Results from Global Data Analysis Project (GLODAP)

    SciTech Connect

    Key, Robert; Kozyr, Alexander; Sabine, Chris; Lee, K.; Wanninkhof, R.; Bullister, J.L.; Feely, R. A.; Millero, F. J.; Mordy, C.; Peng, T.-H.

    2004-01-01

    During the 1990s, ocean sampling expeditions were carried out as part of the World Ocean Circulation Experiment (WOCE), the Joint Global Ocean Flux Study (JGOFS), and the Ocean Atmosphere Carbon Exchange Study (OACES). Subsequently, a group of U.S. scientists synthesized the data into easily usable and readily available products. This collaboration is known as the Global Ocean Data Analysis Project (GLODAP). Results were merged into a common format data set, segregated by ocean. For comparison purposes, each ocean data set includes a small number of high-quality historical cruises. The data were subjected to rigorous quality control procedures to eliminate systematic data measurement biases. The calibrated 1990s data were used to estimate anthropogenic CO{sub 2}, potential alkalinity, CFC watermass ages, CFC partial pressure, bomb-produced radiocarbon, and natural radiocarbon. These quantities were merged into the measured data files. The data were used to produce objectively gridded property maps at a 1{sup o} resolution on 33 depth surfaces chosen to match existing climatologies for temperature, salinity, oxygen, and nutrients. The mapped fields are interpreted as an annual mean distribution in spite of the inaccuracy in that assumption. Both the calibrated data and the gridded products are available from the Carbon Dioxide Information Analysis Center. Here we describe the important details of the data treatment and the mapping procedure, and present summary quantities and integrals for the various parameters.

  13. Metatranscriptomic Analysis of Groundwater Reveals an Active Anammox Bacterial Population

    NASA Astrophysics Data System (ADS)

    Jewell, T. N. M.; Karaoz, U.; Thomas, B. C.; Banfield, J. F.; Brodie, E.; Williams, K. H.; Beller, H. R.

    2014-12-01

    Groundwater is a major natural resource, yet little is known about the contribution of microbial anaerobic ammonium oxidation (anammox) activity to subsurface nitrogen cycling. During anammox, energy is generated as ammonium is oxidized under anaerobic conditions to dinitrogen gas, using nitrite as the final electron acceptor. This process is a global sink for fixed nitrogen. Only a narrow range of monophyletic bacteria within the Planctomycetes carries out anammox, and the full extent of their metabolism, and subsequent impact on nitrogen cycling and microbial community structure, is still unknown. Here, we employ a metatranscriptomic analysis on enriched mRNA to identify the abundance and activity of a population of anammox bacteria within an aquifer at Rifle, CO. Planktonic biomass was collected over a two-month period after injection of up to 1.5 mM nitrate. Illumina-generated sequences were mapped to a phylogenetically binned Rifle metagenome database. We identified transcripts for genes with high protein sequence identities (81-98%) to those of anammox strain KSU-1 and to two of the five anammox bacteria genera, Brocadia and Kuenenia, suggesting an active, if not diverse, anammox population. Many of the most abundant anammox transcripts mapped to a single scaffold, indicative of a single dominant anammox species. Transcripts of the genes necessary for the anammox pathway were present, including an ammonium transporter (amtB), nitrite/formate transporter, nitrite reductase (nirK), and hydrazine oxidoreductase (hzoB). The form of nitrite reductase encoded by anammox is species-dependent, and we only identified nirK, with no evidence of anammox nirS. In addition to the anammox pathway we saw evidence of the anammox bacterial dissimilatory nitrate reduction to ammonium pathway (narH, putative nrfA, and nrfB), which provides an alternate means of generating substrates for anammox from nitrate, rather than relying on an external pool. Transcripts for hydroxylamine

  14. Global health initiative investments and health systems strengthening: a content analysis of global fund investments

    PubMed Central

    2013-01-01

    Background Millions of dollars are invested annually under the umbrella of national health systems strengthening. Global health initiatives provide funding for low- and middle-income countries through disease-oriented programmes while maintaining that the interventions simultaneously strengthen systems. However, it is as yet unclear which, and to what extent, system-level interventions are being funded by these initiatives, nor is it clear how much funding they allocate to disease-specific activities – through conventional ‘vertical-programming’ approach. Such funding can be channelled to one or more of the health system building blocks while targeting disease(s) or explicitly to system-wide activities. Methods We operationalized the World Health Organization health system framework of the six building blocks to conduct a detailed assessment of Global Fund health system investments. Our application of this framework framework provides a comprehensive quantification of system-level interventions. We applied this systematically to a random subset of 52 of the 139 grants funded in Round 8 of the Global Fund to Fight AIDS, Tuberculosis and Malaria (totalling approximately US$1 billion). Results According to the analysis, 37% (US$ 362 million) of the Global Fund Round 8 funding was allocated to health systems strengthening. Of that, 38% (US$ 139 million) was for generic system-level interventions, rather than disease-specific system support. Around 82% of health systems strengthening funding (US$ 296 million) was allocated to service delivery, human resources, and medicines & technology, and within each of these to two to three interventions. Governance, financing, and information building blocks received relatively low funding. Conclusions This study shows that a substantial portion of Global Fund’s Round 8 funds was devoted to health systems strengthening. Dramatic skewing among the health system building blocks suggests opportunities for more balanced

  15. Global trend analysis of the MODIS drought severity index

    NASA Astrophysics Data System (ADS)

    Orvos, P. I.; Homonnai, V.; Várai, A.; Bozóki, Z.; Jánosi, I. M.

    2015-10-01

    Recently, Mu et al. (2013) compiled an open access database of a remotely sensed global drought severity index (DSI) based on MODIS (Moderate Resolution Imaging Spectroradiometer) satellite measurements covering a continuous period of 12 years. The highest spatial resolution is 0.05° × 0.05° in the geographic band between 60° S and 80° N latitudes (more than 4.9 million locations over land). Here we present a global trend analysis of these satellite-based DSI time series in order to identify geographic locations where either positive or negative trends are statistically significant. Our main result is that 17.34 % of land areas exhibit significant trends of drying or wetting, and these sites constitute geographically connected regions. Since a DSI value conveys local characterization at a given site, we argue that usual field significance tests cannot provide more information about the observations than the presented analysis. The relatively short period of 12 years hinders linking the trends to global climate change; however, we think that the observations might be related to slow (decadal) modes of natural climate variability or anthropogenic impacts.

  16. Polyadenylated mRNA staining reveals distinct neuronal phenotypes following endothelin 1, focal brain ischemia, and global brain ischemia/ reperfusion

    PubMed Central

    Jamison, Jill T.; Lewis, Monique K.; Kreipke, Christian W.; Rafols, Jose A.; DeGracia, Donald J.

    2011-01-01

    Objectives Most work on ischemia-induced neuronal death has revolved around the relative contributions of necrosis and apoptosis, but this work has not accounted for the role of ischemia-induced stress responses. An expanded view recognizes a competition between ischemia-induced damage mechanisms and stress responses in the genesis of ischemia-induced neuronal death. An important marker of post-ischemic stress responses is inhibition of neuronal protein synthesis, a morphological correlate of which is the compartmentalization of mRNA away from ribosomes in the form of cytoplasmic mRNA granules. Methods Here we assessed the generality of this mRNA granule response following either 10 or 15 minutes global brain ischemia and 1 hour reperfusion, 4 hours focal cerebral ischemia alone, and endothelin 1 intraventricular injection. Results Both global and focal ischemia led to prominent neuronal cytoplasmic mRNA granule formation in layer II cortical neurons. In addition, we report here new post-ischemic cellular phenotypes characterized by the loss of nuclear polyadenylated mRNA staining in cortical neurons following endothelin 1 treatment and 15 minutes global ischemia. Both mRNA granulation and loss of nuclear mRNAs occurred in non-shrunken post-ischemic neurons. Discussion Where cytoplasmic mRNA granules generally appear to mark a protective response in surviving cells, loss of nuclear mRNAs may mark cellular damage leading to cell atrophy/death. Hence, staining for total mRNA may reveal facets of the competition between stress responses and damage mechanisms at early stages in post-ischemic neurons. PMID:21499502

  17. Analysis of the transcriptional differences between indigenous and invasive whiteflies reveals possible mechanisms of whitefly invasion.

    PubMed

    Wang, Yong-Liang; Wang, Yu-Jun; Luan, Jun-Bo; Yan, Gen-Hong; Liu, Shu-Sheng; Wang, Xiao-Wei

    2013-01-01

    The whitefly Bemisa tabaci is a species complex of more than 31 cryptic species which include some of the most destructive invasive pests of crops worldwide. Among them, Middle East-Asia Minor 1 (MEAM1) and Mediterranean have invaded many countries and displaced the native whitefly species. The successful invasion of the two species is largely due to their wide range of host plants, high resistance to insecticides and remarkable tolerance to environmental stresses. However, the molecular differences between invasive and indigenous whiteflies remain largely unknown. Here the global transcriptional difference between the two invasive whitefly species (MEAM1, MED) and one indigenous whitefly species (Asia II 3) were analyzed using the Illumina sequencing. Our analysis indicated that 2,422 genes between MEAM1 and MED; 3,073 genes between MEAM1 and Asia II 3; and 3,644 genes between MED and Asia II 3 were differentially expressed. Gene Ontology enrichment analysis revealed that the differently expressed genes between the invasive and indigenous whiteflies were significantly enriched in the term of 'oxidoreductase activity'. Pathway enrichment analysis showed that carbohydrate, amino acid and glycerolipid metabolisms were more active in MEAM1 and MED than in Asia II 3, which may contribute to their differences in biological characteristics. Our analysis also illustrated that the majority of genes involved in 'drug metabolic pathway' were expressed at a higher level in MEAM1 and MED than in Asia II 3. Taken together, these results revealed that the genes related to basic metabolism and detoxification were expressed at an elevated level in the invasive whiteflies, which might be responsible for their higher resistance to insecticides and environmental stresses. The extensive comparison of MEAM1, MED and Asia II 3 gene expression may serve as an invaluable resource for revealing the molecular mechanisms underlying their biological differences and the whitefly invasion.

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

    PubMed

    Forgacs, David; Wallen, Rick L; Dobson, Lauren K; Derr, James N

    2016-01-01

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

  19. Mitochondrial Genome Analysis Reveals Historical Lineages in Yellowstone Bison

    PubMed Central

    Derr, James N.

    2016-01-01

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

  20. Quantitative flux analysis reveals folate-dependent NADPH production

    NASA Astrophysics Data System (ADS)

    Fan, Jing; Ye, Jiangbin; Kamphorst, Jurre J.; Shlomi, Tomer; Thompson, Craig B.; Rabinowitz, Joshua D.

    2014-06-01

    ATP is the dominant energy source in animals for mechanical and electrical work (for example, muscle contraction or neuronal firing). For chemical work, there is an equally important role for NADPH, which powers redox defence and reductive biosynthesis. The most direct route to produce NADPH from glucose is the oxidative pentose phosphate pathway, with malic enzyme sometimes also important. Although the relative contribution of glycolysis and oxidative phosphorylation to ATP production has been extensively analysed, similar analysis of NADPH metabolism has been lacking. Here we demonstrate the ability to directly track, by liquid chromatography-mass spectrometry, the passage of deuterium from labelled substrates into NADPH, and combine this approach with carbon labelling and mathematical modelling to measure NADPH fluxes. In proliferating cells, the largest contributor to cytosolic NADPH is the oxidative pentose phosphate pathway. Surprisingly, a nearly comparable contribution comes from serine-driven one-carbon metabolism, in which oxidation of methylene tetrahydrofolate to 10-formyl-tetrahydrofolate is coupled to reduction of NADP+ to NADPH. Moreover, tracing of mitochondrial one-carbon metabolism revealed complete oxidation of 10-formyl-tetrahydrofolate to make NADPH. As folate metabolism has not previously been considered an NADPH producer, confirmation of its functional significance was undertaken through knockdown of methylenetetrahydrofolate dehydrogenase (MTHFD) genes. Depletion of either the cytosolic or mitochondrial MTHFD isozyme resulted in decreased cellular NADPH/NADP+ and reduced/oxidized glutathione ratios (GSH/GSSG) and increased cell sensitivity to oxidative stress. Thus, although the importance of folate metabolism for proliferating cells has been long recognized and attributed to its function of producing one-carbon units for nucleic acid synthesis, another crucial function of this pathway is generating reducing power.

  1. Isotope analysis reveals foraging area dichotomy for atlantic leatherback turtles.

    PubMed

    Caut, Stéphane; Fossette, Sabrina; Guirlet, Elodie; Angulo, Elena; Das, Krishna; Girondot, Marc; Georges, Jean-Yves

    2008-03-26

    The leatherback turtle (Dermochelys coriacea) has undergone a dramatic decline over the last 25 years, and this is believed to be primarily the result of mortality associated with fisheries bycatch followed by egg and nesting female harvest. Atlantic leatherback turtles undertake long migrations across ocean basins from subtropical and tropical nesting beaches to productive frontal areas. Migration between two nesting seasons can last 2 or 3 years, a time period termed the remigration interval (RI). Recent satellite transmitter data revealed that Atlantic leatherbacks follow two major dispersion patterns after nesting season, through the North Gulf Stream area or more eastward across the North Equatorial Current. However, information on the whole RI is lacking, precluding the accurate identification of feeding areas where conservation measures may need to be applied. Using stable isotopes as dietary tracers we determined the characteristics of feeding grounds of leatherback females nesting in French Guiana. During migration, 3-year RI females differed from 2-year RI females in their isotope values, implying differences in their choice of feeding habitats (offshore vs. more coastal) and foraging latitude (North Atlantic vs. West African coasts, respectively). Egg-yolk and blood isotope values are correlated in nesting females, indicating that egg analysis is a useful tool for assessing isotope values in these turtles, including adults when not available. Our results complement previous data on turtle movements during the first year following the nesting season, integrating the diet consumed during the year before nesting. We suggest that the French Guiana leatherback population segregates into two distinct isotopic groupings, and highlight the urgent need to determine the feeding habitats of the turtle in the Atlantic in order to protect this species from incidental take by commercial fisheries. Our results also emphasize the use of eggs, a less-invasive sampling

  2. Differential transcriptomic analysis reveals hidden light response in Streptomyces lividans.

    PubMed

    Koepff, Joachim; Morschett, Holger; Busche, Tobias; Winkler, Anika; Kalinowski, Jörn; Wiechert, Wolfgang; Oldiges, Marco

    2017-09-27

    Recently, a comprehensive screening workflow for the filamentous bacterium Streptomyces lividans, a highly performant source for pharmaceutically active agents was introduced. This framework used parallelized cultivation in microtiter plates to efficiently accelerate early upstream process development. Focusing on growth performance, cultivation was successfully scaled-up to 1 liter stirred tank reactors. However, metabolic adaptation was observed on the transcriptomic level as among others, several genes incorporated in light response were up-regulated during bioreactor cultivation. Despite it was assumed that this was attributed to the fact that reactor cultivations were carried out in glass vessels exposed to daylight and artificial room light, this setup did not allow distinguishing exclusively between light and other effects. Upon that, the present study directly investigates the influence of light by defined illumination of microtiter plate cultures. Almost identical growth performance was observed for cultures grown in the dark or with illumination. Transcriptomics revealed the up-regulation of seven genes of which 6 have previously been described to be relevant for carotenoid synthesis and its regulation. These pigments are effective quenchers of reactive oxygen species. The seventh transcript coded for a photo-lyase incorporated in UV-damage repair of DNA further confirming induced light response. However, this was fully compensated by metabolic adaptation on the transcriptomic level and overall process performance was maintained. Consequently, environmental conditions need extremely careful control and evaluation during in-depth omics analysis of bioprocesses. Otherwise metabolic adaptation induced by such issues can easily be misinterpreted, especially during studies addressing cultivation system comparisons. This article is protected by copyright. All rights reserved. © 2017 American Institute of Chemical Engineers.

  3. Isotope Analysis Reveals Foraging Area Dichotomy for Atlantic Leatherback Turtles

    PubMed Central

    Angulo, Elena; Das, Krishna; Girondot, Marc

    2008-01-01

    Background The leatherback turtle (Dermochelys coriacea) has undergone a dramatic decline over the last 25 years, and this is believed to be primarily the result of mortality associated with fisheries bycatch followed by egg and nesting female harvest. Atlantic leatherback turtles undertake long migrations across ocean basins from subtropical and tropical nesting beaches to productive frontal areas. Migration between two nesting seasons can last 2 or 3 years, a time period termed the remigration interval (RI). Recent satellite transmitter data revealed that Atlantic leatherbacks follow two major dispersion patterns after nesting season, through the North Gulf Stream area or more eastward across the North Equatorial Current. However, information on the whole RI is lacking, precluding the accurate identification of feeding areas where conservation measures may need to be applied. Methodology/Principal Findings Using stable isotopes as dietary tracers we determined the characteristics of feeding grounds of leatherback females nesting in French Guiana. During migration, 3-year RI females differed from 2-year RI females in their isotope values, implying differences in their choice of feeding habitats (offshore vs. more coastal) and foraging latitude (North Atlantic vs. West African coasts, respectively). Egg-yolk and blood isotope values are correlated in nesting females, indicating that egg analysis is a useful tool for assessing isotope values in these turtles, including adults when not available. Conclusions/Significance Our results complement previous data on turtle movements during the first year following the nesting season, integrating the diet consumed during the year before nesting. We suggest that the French Guiana leatherback population segregates into two distinct isotopic groupings, and highlight the urgent need to determine the feeding habitats of the turtle in the Atlantic in order to protect this species from incidental take by commercial fisheries. Our

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

    PubMed

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

    2013-09-01

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

  5. Microarray Analysis Reveals Novel Features of the Muscle Aging Process in Men and Women

    PubMed Central

    2013-01-01

    To develop a global view of muscle transcriptional differences between older men and women and sex-specific aging, we obtained muscle biopsies from the biceps brachii of young and older men and women and profiled the whole-genome gene expression using microarray. A logistic regression-based method in combination with an intensity-based Bayesian moderated t test was used to identify significant sex- and aging-related gene functional groups. Our analysis revealed extensive sex differences in the muscle transcriptome of older individuals and different patterns of transcriptional changes with aging in men and women. In older women, we observed a coordinated transcriptional upregulation of immune activation, extracellular matrix remodeling, and lipids storage; and a downregulation of mitochondrial biogenesis and function and muscle regeneration. The effect of aging results in sexual dimorphic alterations in the skeletal muscle transcriptome, which may modify the risk for developing musculoskeletal and metabolic diseases in men and women. PMID:23418191

  6. Global Sensitivity Analysis of Environmental Models: Convergence, Robustness and Validation

    NASA Astrophysics Data System (ADS)

    Sarrazin, Fanny; Pianosi, Francesca; Khorashadi Zadeh, Farkhondeh; Van Griensven, Ann; Wagener, Thorsten

    2015-04-01

    Global Sensitivity Analysis aims to characterize the impact that variations in model input factors (e.g. the parameters) have on the model output (e.g. simulated streamflow). In sampling-based Global Sensitivity Analysis, the sample size has to be chosen carefully in order to obtain reliable sensitivity estimates while spending computational resources efficiently. Furthermore, insensitive parameters are typically identified through the definition of a screening threshold: the theoretical value of their sensitivity index is zero but in a sampling-base framework they regularly take non-zero values. There is little guidance available for these two steps in environmental modelling though. The objective of the present study is to support modellers in making appropriate choices, regarding both sample size and screening threshold, so that a robust sensitivity analysis can be implemented. We performed sensitivity analysis for the parameters of three hydrological models with increasing level of complexity (Hymod, HBV and SWAT), and tested three widely used sensitivity analysis methods (Elementary Effect Test or method of Morris, Regional Sensitivity Analysis, and Variance-Based Sensitivity Analysis). We defined criteria based on a bootstrap approach to assess three different types of convergence: the convergence of the value of the sensitivity indices, of the ranking (the ordering among the parameters) and of the screening (the identification of the insensitive parameters). We investigated the screening threshold through the definition of a validation procedure. The results showed that full convergence of the value of the sensitivity indices is not necessarily needed to rank or to screen the model input factors. Furthermore, typical values of the sample sizes that are reported in the literature can be well below the sample sizes that actually ensure convergence of ranking and screening.

  7. Omics approaches on fresh-cut lettuce reveal global molecular responses to sodium hypochlorite and peracetic acid treatment.

    PubMed

    Daddiego, Loretta; Bianco, Linda; Capodicasa, Cristina; Carbone, Fabrizio; Dalmastri, Claudia; Daroda, Lorenza; Del Fiore, Antonella; De Rossi, Patrizia; Di Carli, Mariasole; Donini, Marcello; Lopez, Loredana; Mengoni, Alessio; Paganin, Patrizia; Perrotta, Gaetano; Bevivino, Annamaria

    2017-07-04

    Lettuce is a leafy vegetable that is extensively commercialized as a ready-to-eat product because of its widespread use in human nutrition as salad. It is well known that washing treatments can severely affect the quality and shelf-life of ready-to-eat vegetables. The study presented here evaluated the effect of two washing procedures on fresh-cut lettuce during storage. An omics approach was applied to reveal global changes at molecular level induced by peracetic acid washing in comparison with sodium hypochlorite treatment. Microbiological analyses were also performed to quantify total bacterial abundance and composition. The study revealed wide metabolic alterations induced by the two sanitizers. In particular, transcriptomic and proteomic analyses pointed out a number of transcripts and proteins differentially accumulated in response to peracetic acid washing, mainly occurring on the first day of storage. In parallel, different microbiota composition and significant reduction in total bacterial load following washing were also observed. The results provide useful information for the fresh-cut industry to select an appropriate washing procedure preserving fresh-like attributes as much as possible during storage of the end product. Molecular evidence indicated peracetic acid to be a valid alternative to sodium hypochlorite as sanitizer solution. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  8. A global census of continental rift activity since 250 Ma reveals a missing element of the deep carbon cycle

    NASA Astrophysics Data System (ADS)

    Brune, Sascha; Williams, Simon; Müller, Dietmar

    2017-04-01

    The deep carbon cycle connects CO2 concentrations within the atmosphere to the vast carbon reservoir in Earth's mantle: subducted lithosphere carries carbon into the mantle, while extensional plate boundaries and arc volcanoes release it back to Earth's surface. The length of plate boundaries thereby exerts first-order control on global CO2 fluxes on geological time scales. Here we provide a global census of rift length from the Triassic to present day, combining a new plate reconstruction analysis technique with data from the geological rift record. We find that the most extensive rift phase during the fragmentation of Pangea occurred in the Jurassic/Early Cretaceous with extension along the South Atlantic (9700 km) and North Atlantic rifts (9100 km), within East Gondwana (8500 km), the failed African rift systems (4900 km), and between Australia and Antarctica (3700 km). The combined extent of these and other rift systems amounts to more than 50.000 km of simultaneously active continental rifts. During the Late Cretaceous, in the aftermath of this massive rift episode, the global rift length dropped by 60% to 20.000 km. We further show that a second pronounced rift episode starts in the Eocene with global rift lengths of up to 30.000 km. It is well-accepted that volcanoes at plate boundaries release large amounts of CO2 from the Earth's interior. Recent work, however, highlights the importance of deep-cutting faults and diffuse degassing on CO2 emissions in the East African Rift, which appear to be comparable to CO2 release rates at mid-ocean ridges worldwide. Upscaling measured CO2 fluxes from East Africa to all concurrently active global rift zones with due caution, we compute the first-order history of cumulative rift-related CO2 degassing rates for the last 250 Myr. We demonstrate that rift-related CO2 release in the Early Cretaceous may have reached 400% of present-day rates. In first-order agreement with paleo-atmospheric CO2 concentrations from proxy

  9. Drivers of wetland conversion: a global meta-analysis.

    PubMed

    van Asselen, Sanneke; Verburg, Peter H; Vermaat, Jan E; Janse, Jan H

    2013-01-01

    Meta-analysis of case studies has become an important tool for synthesizing case study findings in land change. Meta-analyses of deforestation, urbanization, desertification and change in shifting cultivation systems have been published. This present study adds to this literature, with an analysis of the proximate causes and underlying forces of wetland conversion at a global scale using two complementary approaches of systematic review. Firstly, a meta-analysis of 105 case-study papers describing wetland conversion was performed, showing that different combinations of multiple-factor proximate causes, and underlying forces, drive wetland conversion. Agricultural development has been the main proximate cause of wetland conversion, and economic growth and population density are the most frequently identified underlying forces. Secondly, to add a more quantitative component to the study, a logistic meta-regression analysis was performed to estimate the likelihood of wetland conversion worldwide, using globally-consistent biophysical and socioeconomic location factor maps. Significant factors explaining wetland conversion, in order of importance, are market influence, total wetland area (lower conversion probability), mean annual temperature and cropland or built-up area. The regression analyses results support the outcomes of the meta-analysis of the processes of conversion mentioned in the individual case studies. In other meta-analyses of land change, similar factors (e.g., agricultural development, population growth, market/economic factors) are also identified as important causes of various types of land change (e.g., deforestation, desertification). Meta-analysis helps to identify commonalities across the various local case studies and identify which variables may lead to individual cases to behave differently. The meta-regression provides maps indicating the likelihood of wetland conversion worldwide based on the location factors that have determined historic

  10. Drivers of Wetland Conversion: a Global Meta-Analysis

    PubMed Central

    van Asselen, Sanneke; Verburg, Peter H.; Vermaat, Jan E.; Janse, Jan H.

    2013-01-01

    Meta-analysis of case studies has become an important tool for synthesizing case study findings in land change. Meta-analyses of deforestation, urbanization, desertification and change in shifting cultivation systems have been published. This present study adds to this literature, with an analysis of the proximate causes and underlying forces of wetland conversion at a global scale using two complementary approaches of systematic review. Firstly, a meta-analysis of 105 case-study papers describing wetland conversion was performed, showing that different combinations of multiple-factor proximate causes, and underlying forces, drive wetland conversion. Agricultural development has been the main proximate cause of wetland conversion, and economic growth and population density are the most frequently identified underlying forces. Secondly, to add a more quantitative component to the study, a logistic meta-regression analysis was performed to estimate the likelihood of wetland conversion worldwide, using globally-consistent biophysical and socioeconomic location factor maps. Significant factors explaining wetland conversion, in order of importance, are market influence, total wetland area (lower conversion probability), mean annual temperature and cropland or built-up area. The regression analyses results support the outcomes of the meta-analysis of the processes of conversion mentioned in the individual case studies. In other meta-analyses of land change, similar factors (e.g., agricultural development, population growth, market/economic factors) are also identified as important causes of various types of land change (e.g., deforestation, desertification). Meta-analysis helps to identify commonalities across the various local case studies and identify which variables may lead to individual cases to behave differently. The meta-regression provides maps indicating the likelihood of wetland conversion worldwide based on the location factors that have determined historic

  11. Phenotypic Analysis Reveals that the 2010 Haiti Cholera Epidemic Is Linked to a Hypervirulent Strain

    PubMed Central

    Jones, Christopher J.; Wong, Jennifer; Queen, Jessica; Agarwal, Shivani; Yildiz, Fitnat H.

    2016-01-01

    Vibrio cholerae O1 El Tor strains have been responsible for pandemic cholera since 1961. These strains have evolved over time, spreading globally in three separate waves. Wave 3 is caused by altered El Tor (AET) variant strains, which include the strain with the signature ctxB7 allele that was introduced in 2010 into Haiti, where it caused a devastating epidemic. In this study, we used phenotypic analysis to compare an early isolate from the Haiti epidemic to wave 1 El Tor isolates commonly used for research. It is demonstrated that the Haiti isolate has increased production of cholera toxin (CT) and hemolysin, increased motility, and a reduced ability to form biofilms. This strain also outcompetes common wave 1 El Tor isolates for colonization of infant mice, indicating that it has increased virulence. Monitoring of CT production and motility in additional wave 3 isolates revealed that this phenotypic variation likely evolved over time rather than in a single genetic event. Analysis of available whole-genome sequences and phylogenetic analyses suggested that increased virulence arose from positive selection for mutations found in known and putative regulatory genes, including hns and vieA, diguanylate cyclase genes, and genes belonging to the lysR and gntR regulatory families. Overall, the studies presented here revealed that V. cholerae virulence potential can evolve and that the currently prevalent wave 3 AET strains are both phenotypically distinct from and more virulent than many El Tor isolates. PMID:27297393

  12. Isotopic ratio outlier analysis global metabolomics of Caenorhabditis elegans.

    PubMed

    Stupp, Gregory S; Clendinen, Chaevien S; Ajredini, Ramadan; Szewc, Mark A; Garrett, Timothy; Menger, Robert F; Yost, Richard A; Beecher, Chris; Edison, Arthur S

    2013-12-17

    We demonstrate the global metabolic analysis of Caenorhabditis elegans stress responses using a mass-spectrometry-based technique called isotopic ratio outlier analysis (IROA). In an IROA protocol, control and experimental samples are isotopically labeled with 95 and 5% (13)C, and the two sample populations are mixed together for uniform extraction, sample preparation, and LC-MS analysis. This labeling strategy provides several advantages over conventional approaches: (1) compounds arising from biosynthesis are easily distinguished from artifacts, (2) errors from sample extraction and preparation are minimized because the control and experiment are combined into a single sample, (3) measurement of both the molecular weight and the exact number of carbon atoms in each molecule provides extremely accurate molecular formulas, and (4) relative concentrations of all metabolites are easily determined. A heat-shock perturbation was conducted on C. elegans to demonstrate this approach. We identified many compounds that significantly changed upon heat shock, including several from the purine metabolism pathway. The metabolomic response information by IROA may be interpreted in the context of a wealth of genetic and proteomic information available for C. elegans . Furthermore, the IROA protocol can be applied to any organism that can be isotopically labeled, making it a powerful new tool in a global metabolomics pipeline.

  13. A proteomic strategy for global analysis of plant protein complexes.

    PubMed

    Aryal, Uma K; Xiong, Yi; McBride, Zachary; Kihara, Daisuke; Xie, Jun; Hall, Mark C; Szymanski, Daniel B

    2014-10-01

    Global analyses of protein complex assembly, composition, and location are needed to fully understand how cells coordinate diverse metabolic, mechanical, and developmental activities. The most common methods for proteome-wide analysis of protein complexes rely on affinity purification-mass spectrometry or yeast two-hybrid approaches. These methods are time consuming and are not suitable for many plant species that are refractory to transformation or genome-wide cloning of open reading frames. Here, we describe the proof of concept for a method allowing simultaneous global analysis of endogenous protein complexes that begins with intact leaves and combines chromatographic separation of extracts from subcellular fractions with quantitative label-free protein abundance profiling by liquid chromatography-coupled mass spectrometry. Applying this approach to the crude cytosolic fraction of Arabidopsis thaliana leaves using size exclusion chromatography, we identified hundreds of cytosolic proteins that appeared to exist as components of stable protein complexes. The reliability of the method was validated by protein immunoblot analysis and comparisons with published size exclusion chromatography data and the masses of known complexes. The method can be implemented with appropriate instrumentation, is applicable to any biological system, and has the potential to be further developed to characterize the composition of protein complexes and measure the dynamics of protein complex localization and assembly under different conditions.

  14. Isotopic Ratio Outlier Analysis Global Metabolomics of Caenorhabditis elegans

    PubMed Central

    Szewc, Mark A.; Garrett, Timothy; Menger, Robert F.; Yost, Richard A.; Beecher, Chris; Edison, Arthur S.

    2014-01-01

    We demonstrate the global metabolic analysis of Caenorhabditis elegans stress responses using a mass spectrometry-based technique called Isotopic Ratio Outlier Analysis (IROA). In an IROA protocol, control and experimental samples are isotopically labeled with 95% and 5% 13C, and the two sample populations are mixed together for uniform extraction, sample preparation, and LC-MS analysis. This labeling strategy provides several advantages over conventional approaches: 1) compounds arising from biosynthesis are easily distinguished from artifacts, 2) errors from sample extraction and preparation are minimized because the control and experiment are combined into a single sample, 3) measurement of both the molecular weight and the exact number of carbon atoms in each molecule provides extremely accurate molecular formulae, and 4) relative concentrations of all metabolites are easily determined. A heat shock perturbation was conducted on C. elegans to demonstrate this approach. We identified many compounds that significantly changed upon heat shock, including several from the purine metabolism pathway, which we use to demonstrate the approach. The metabolomic response information by IROA may be interpreted in the context of a wealth of genetic and proteomic information available for C. elegans. Furthermore, the IROA protocol can be applied to any organism that can be isotopically labeled, making it a powerful new tool in a global metabolomics pipeline. PMID:24274725

  15. A Systemic Analysis of Transcriptomic and Epigenomic Data To Reveal Regulation Patterns for Complex Disease

    PubMed Central

    Xu, Chao; Zhang, Ji-Gang; Lin, Dongdong; Zhang, Lan; Shen, Hui; Deng, Hong-Wen

    2017-01-01

    Integrating diverse genomics data can provide a global view of the complex biological processes related to the human complex diseases. Although substantial efforts have been made to integrate different omics data, there are at least three challenges for multi-omics integration methods: (i) How to simultaneously consider the effects of various genomic factors, since these factors jointly influence the phenotypes; (ii) How to effectively incorporate the information from publicly accessible databases and omics datasets to fully capture the interactions among (epi)genomic factors from diverse omics data; and (iii) Until present, the combination of more than two omics datasets has been poorly explored. Current integration approaches are not sufficient to address all of these challenges together. We proposed a novel integrative analysis framework by incorporating sparse model, multivariate analysis, Gaussian graphical model, and network analysis to address these three challenges simultaneously. Based on this strategy, we performed a systemic analysis for glioblastoma multiforme (GBM) integrating genome-wide gene expression, DNA methylation, and miRNA expression data. We identified three regulatory modules of genomic factors associated with GBM survival time and revealed a global regulatory pattern for GBM by combining the three modules, with respect to the common regulatory factors. Our method can not only identify disease-associated dysregulated genomic factors from different omics, but more importantly, it can incorporate the information from publicly accessible databases and omics datasets to infer a comprehensive interaction map of all these dysregulated genomic factors. Our work represents an innovative approach to enhance our understanding of molecular genomic mechanisms underlying human complex diseases. PMID:28500050

  16. A Systemic Analysis of Transcriptomic and Epigenomic Data To Reveal Regulation Patterns for Complex Disease.

    PubMed

    Xu, Chao; Zhang, Ji-Gang; Lin, Dongdong; Zhang, Lan; Shen, Hui; Deng, Hong-Wen

    2017-07-05

    Integrating diverse genomics data can provide a global view of the complex biological processes related to the human complex diseases. Although substantial efforts have been made to integrate different omics data, there are at least three challenges for multi-omics integration methods: (i) How to simultaneously consider the effects of various genomic factors, since these factors jointly influence the phenotypes; (ii) How to effectively incorporate the information from publicly accessible databases and omics datasets to fully capture the interactions among (epi)genomic factors from diverse omics data; and (iii) Until present, the combination of more than two omics datasets has been poorly explored. Current integration approaches are not sufficient to address all of these challenges together. We proposed a novel integrative analysis framework by incorporating sparse model, multivariate analysis, Gaussian graphical model, and network analysis to address these three challenges simultaneously. Based on this strategy, we performed a systemic analysis for glioblastoma multiforme (GBM) integrating genome-wide gene expression, DNA methylation, and miRNA expression data. We identified three regulatory modules of genomic factors associated with GBM survival time and revealed a global regulatory pattern for GBM by combining the three modules, with respect to the common regulatory factors. Our method can not only identify disease-associated dysregulated genomic factors from different omics, but more importantly, it can incorporate the information from publicly accessible databases and omics datasets to infer a comprehensive interaction map of all these dysregulated genomic factors. Our work represents an innovative approach to enhance our understanding of molecular genomic mechanisms underlying human complex diseases. Copyright © 2017 Xu et al.

  17. Exploratory spatial data analysis of global MODIS active fire data

    NASA Astrophysics Data System (ADS)

    Oom, D.; Pereira, J. M. C.

    2013-04-01

    We performed an exploratory spatial data analysis (ESDA) of autocorrelation patterns in the NASA MODIS MCD14ML Collection 5 active fire dataset, for the period 2001-2009, at the global scale. The dataset was screened, resulting in an annual rate of false alarms and non-vegetation fires ranging from a minimum of 3.1% in 2003 to a maximum of 4.4% in 2001. Hot bare soils and gas flares were the major sources of false alarms and non-vegetation fires. The data were aggregated at 0.5° resolution for the global and local spatial autocorrelation Fire counts were found to be positively correlated up to distances of around 200 km, and negatively for larger distances. A value of 0.80 (p = 0.001, α = 0.05) for Moran's I indicates strong spatial autocorrelation between fires at global scale, with 60% of all cells displaying significant positive or negative spatial correlation. Different types of spatial autocorrelation were mapped and regression diagnostics allowed for the identification of spatial outlier cells, with fire counts much higher or lower than expected, considering their spatial context.

  18. Consensus Diversity Plots: a global diversity analysis of chemical libraries.

    PubMed

    González-Medina, Mariana; Prieto-Martínez, Fernando D; Owen, John R; Medina-Franco, José L

    2016-01-01

    Measuring the structural diversity of compound databases is relevant in drug discovery and many other areas of chemistry. Since molecular diversity depends on molecular representation, comprehensive chemoinformatic analysis of the diversity of libraries uses multiple criteria. For instance, the diversity of the molecular libraries is typically evaluated employing molecular scaffolds, structural fingerprints, and physicochemical properties. However, the assessment with each criterion is analyzed independently and it is not straightforward to provide an evaluation of the "global diversity". Herein the Consensus Diversity Plot (CDP) is proposed as a novel method to represent in low dimensions the diversity of chemical libraries considering simultaneously multiple molecular representations. We illustrate the application of CDPs to classify eight compound data sets and two subsets with different sizes and compositions using molecular scaffolds, structural fingerprints, and physicochemical properties. CDPs are general data mining tools that represent in two-dimensions the global diversity of compound data sets using multiple metrics. These plots can be constructed using single or combined measures of diversity. An online version of the CDPs is freely available at: https://consensusdiversityplots-difacquim-unam.shinyapps.io/RscriptsCDPlots/.Graphical AbstractConsensus Diversity Plot is a novel data mining tool that represents in two-dimensions the global diversity of compound data sets using multiple metrics.

  19. Revealing the Eruptive History of Volcanoes from Massive Cross-Correlation of Seismic Signal at Global Scale

    NASA Astrophysics Data System (ADS)

    Dupont, A.; Gaillard, P.; Grenouille, A.; Bui-Quang, P.; Guilhem, A.; Bobrov, D.; Kitov, I. O.; Rozhkov, M.

    2015-12-01

    We propose here a massive cross-correlation technique applied to seismic events located around volcanoes and recorded at teleseismic distance. Multichannel cross-correlations are performed between 2002 to 2012 using seismic templates occurring at the time of moderate to large volcanic eruptions. The volcanic periods are reported from the Global Volcanism Program database while the waveform data are obtained from the Comprehensive Nuclear-Test-Ban Treaty Organization (CTBTO). The temporal distribution of new seismic events, built from the association of teleseismic detections reveals acceleration patterns, which are highly correlated to the past eruptive activities. These newly detected events are relocated using Bayesian approach and leads to preliminary interpretation of the volcanic plumbing system. Two examples are presented. First, the large 2008 eruption (Volcanic Explosivity Index, VEI4) of Kasatochi (Aleutian Islands, 52.10°N/175.31°W) is used to demonstrate that only few seismic templates (~3) help to reveal the time scale of the eruption. Results are compared to hydroacoustic signal, which is highly correlated to the distribution of new seismic events prior and during eruption. We also show that after the peaked seismic activity (i.e., ~ 100 seismic events in 1 hour) the infrasound signal starts and signs the volcanic plume activity. The second case example reveals with success seven past volcanic eruptions of lower magnitude (VEI1 to VEI2) of the Karangetang volcano (Siau Island in Indonesia, 2.46°N/125.24°E). We show the potential of this method to detect volcanic eruptions in isolated areas. This is of special interest especially when there is no volcano observatory to monitor the volcanic activity, or when the last eruptive period is unknown.

  20. Indian plant germplasm on the global platter: an analysis.

    PubMed

    Jacob, Sherry R; Tyagi, Vandana; Agrawal, Anuradha; Chakrabarty, Shyamal K; Tyagi, Rishi K

    2015-01-01

    , about 50% of the Indian-origin accessions deposited in SGSV are traditional varieties or landraces with defined traits which form the backbone of any crop gene pool. This paper is also attempting to correlate the global data on Indian-origin germplasm with the national germplasm export profile. The analysis from this paper is discussed with the perspective of possible implications in the access and benefit sharing regime of both the International Treaty on Plant Genetic Resources for Food and Agriculture and the newly enforced Nagoya Protocol under the Convention on Biological Diversity.

  1. Indian Plant Germplasm on the Global Platter: An Analysis

    PubMed Central

    Jacob, Sherry R.; Tyagi, Vandana; Agrawal, Anuradha; Chakrabarty, Shyamal K.; Tyagi, Rishi K.

    2015-01-01

    , about 50% of the Indian-origin accessions deposited in SGSV are traditional varieties or landraces with defined traits which form the backbone of any crop gene pool. This paper is also attempting to correlate the global data on Indian-origin germplasm with the national germplasm export profile. The analysis from this paper is discussed with the perspective of possible implications in the access and benefit sharing regime of both the International Treaty on Plant Genetic Resources for Food and Agriculture and the newly enforced Nagoya Protocol under the Convention on Biological Diversity. PMID:25974270

  2. Global analysis of frequency modulation experiments in a vortex oscillator

    NASA Astrophysics Data System (ADS)

    Martin, S. Y.; Thirion, C.; Hoarau, C.; Baraduc, C.; Diény, B.

    2016-02-01

    Frequency modulation is performed on a vortex oscillator at various modulation frequencies and powers. A global analysis of the whole set of data is proposed, so that all experimental curves are described with the same four parameters. Three of these parameters describe the dependence of the instantaneous frequency with modulating current. This dependence appears significantly different from the frequency-current dependence observed in a quasi-static experiment. The discrepancy is ascribed to the different time scales involved, compared to the relaxation time of the vortex oscillator.

  3. A Meta-Analysis of Global Urban Land Expansion

    PubMed Central

    Seto, Karen C.; Fragkias, Michail; Güneralp, Burak; Reilly, Michael K.

    2011-01-01

    The conversion of Earth's land surface to urban uses is one of the most irreversible human impacts on the global biosphere. It drives the loss of farmland, affects local climate, fragments habitats, and threatens biodiversity. Here we present a meta-analysis of 326 studies that have used remotely sensed images to map urban land conversion. We report a worldwide observed increase in urban land area of 58,000 km2 from 1970 to 2000. India, China, and Africa have experienced the highest rates of urban land expansion, and the largest change in total urban extent has occurred in North America. Across all regions and for all three decades, urban land expansion rates are higher than or equal to urban population growth rates, suggesting that urban growth is becoming more expansive than compact. Annual growth in GDP per capita drives approximately half of the observed urban land expansion in China but only moderately affects urban expansion in India and Africa, where urban land expansion is driven more by urban population growth. In high income countries, rates of urban land expansion are slower and increasingly related to GDP growth. However, in North America, population growth contributes more to urban expansion than it does in Europe. Much of the observed variation in urban expansion was not captured by either population, GDP, or other variables in the model. This suggests that contemporary urban expansion is related to a variety of factors difficult to observe comprehensively at the global level, including international capital flows, the informal economy, land use policy, and generalized transport costs. Using the results from the global model, we develop forecasts for new urban land cover using SRES Scenarios. Our results show that by 2030, global urban land cover will increase between 430,000 km2 and 12,568,000 km2, with an estimate of 1,527,000 km2 more likely. PMID:21876770

  4. Gene expression analysis of endometrium reveals progesterone resistance and candidate susceptibility genes in women with endometriosis.

    PubMed

    Burney, Richard O; Talbi, Said; Hamilton, Amy E; Vo, Kim Chi; Nyegaard, Mette; Nezhat, Camran R; Lessey, Bruce A; Giudice, Linda C

    2007-08-01

    The identification of molecular differences in the endometrium of women with endometriosis is an important step toward understanding the pathogenesis of this condition and toward developing novel strategies for the treatment of associated infertility and pain. In this study, we conducted global gene expression analysis of endometrium from women with and without moderate/severe stage endometriosis and compared the gene expression signatures across various phases of the menstrual cycle. The transcriptome analysis revealed molecular dysregulation of the proliferative-to-secretory transition in endometrium of women with endometriosis. Paralleled gene expression analysis of endometrial specimens obtained during the early secretory phase demonstrated a signature of enhanced cellular survival and persistent expression of genes involved in DNA synthesis and cellular mitosis in the setting of endometriosis. Comparative gene expression analysis of progesterone-regulated genes in secretory phase endometrium confirmed the observation of attenuated progesterone response. Additionally, interesting candidate susceptibility genes were identified that may be associated with this disorder, including FOXO1A, MIG6, and CYP26A1. Collectively these findings provide a framework for further investigations on causality and mechanisms underlying attenuated progesterone response in endometrium of women with endometriosis.

  5. Multilocus sequence analysis reveals high genetic diversity in clinical isolates of Burkholderia cepacia complex from India

    PubMed Central

    Gautam, Vikas; Patil, Prashant P.; Kumar, Sunil; Midha, Samriti; Kaur, Mandeep; Kaur, Satinder; Singh, Meenu; Mali, Swapna; Shastri, Jayanthi; Arora, Anita; Ray, Pallab; Patil, Prabhu B.

    2016-01-01

    Burkholderia cepacia complex (Bcc) is a complex group of bacteria causing opportunistic infections in immunocompromised and cystic fibrosis (CF) patients. Herein, we report multilocus sequence typing and analysis of the 57 clinical isolates of Bcc collected over the period of seven years (2005–2012) from several hospitals across India. A total of 21 sequence types (ST) including two STs from cystic fibrosis patient’s isolates and twelve novel STs were identified in the population reflecting the extent of genetic diversity. Multilocus sequence analysis revealed two lineages in population, a major lineage belonging to B. cenocepacia and a minor lineage belonging to B. cepacia. Split-decomposition analysis suggests absence of interspecies recombination and intraspecies recombination contributed in generating genotypic diversity amongst isolates. Further linkage disequilibrium analysis indicates that recombination takes place at a low frequency, which is not sufficient to break down the clonal relationship. This knowledge of the genetic structure of Bcc population from a rapidly developing country will be invaluable in the epidemiology, surveillance and understanding global diversity of this group of a pathogen. PMID:27767197

  6. Multilocus sequence analysis reveals high genetic diversity in clinical isolates of Burkholderia cepacia complex from India.

    PubMed

    Gautam, Vikas; Patil, Prashant P; Kumar, Sunil; Midha, Samriti; Kaur, Mandeep; Kaur, Satinder; Singh, Meenu; Mali, Swapna; Shastri, Jayanthi; Arora, Anita; Ray, Pallab; Patil, Prabhu B

    2016-10-21

    Burkholderia cepacia complex (Bcc) is a complex group of bacteria causing opportunistic infections in immunocompromised and cystic fibrosis (CF) patients. Herein, we report multilocus sequence typing and analysis of the 57 clinical isolates of Bcc collected over the period of seven years (2005-2012) from several hospitals across India. A total of 21 sequence types (ST) including two STs from cystic fibrosis patient's isolates and twelve novel STs were identified in the population reflecting the extent of genetic diversity. Multilocus sequence analysis revealed two lineages in population, a major lineage belonging to B. cenocepacia and a minor lineage belonging to B. cepacia. Split-decomposition analysis suggests absence of interspecies recombination and intraspecies recombination contributed in generating genotypic diversity amongst isolates. Further linkage disequilibrium analysis indicates that recombination takes place at a low frequency, which is not sufficient to break down the clonal relationship. This knowledge of the genetic structure of Bcc population from a rapidly developing country will be invaluable in the epidemiology, surveillance and understanding global diversity of this group of a pathogen.

  7. A Global Sensitivity Analysis Methodology for Multi-physics Applications

    SciTech Connect

    Tong, C H; Graziani, F R

    2007-02-02

    Experiments are conducted to draw inferences about an entire ensemble based on a selected number of observations. This applies to both physical experiments as well as computer experiments, the latter of which are performed by running the simulation models at different input configurations and analyzing the output responses. Computer experiments are instrumental in enabling model analyses such as uncertainty quantification and sensitivity analysis. This report focuses on a global sensitivity analysis methodology that relies on a divide-and-conquer strategy and uses intelligent computer experiments. The objective is to assess qualitatively and/or quantitatively how the variabilities of simulation output responses can be accounted for by input variabilities. We address global sensitivity analysis in three aspects: methodology, sampling/analysis strategies, and an implementation framework. The methodology consists of three major steps: (1) construct credible input ranges; (2) perform a parameter screening study; and (3) perform a quantitative sensitivity analysis on a reduced set of parameters. Once identified, research effort should be directed to the most sensitive parameters to reduce their uncertainty bounds. This process is repeated with tightened uncertainty bounds for the sensitive parameters until the output uncertainties become acceptable. To accommodate the needs of multi-physics application, this methodology should be recursively applied to individual physics modules. The methodology is also distinguished by an efficient technique for computing parameter interactions. Details for each step will be given using simple examples. Numerical results on large scale multi-physics applications will be available in another report. Computational techniques targeted for this methodology have been implemented in a software package called PSUADE.

  8. Time course gene expression profiling of yeast spore germination reveals a network of transcription factors orchestrating the global response.

    PubMed

    Geijer, Cecilia; Pirkov, Ivan; Vongsangnak, Wanwipa; Ericsson, Abraham; Nielsen, Jens; Krantz, Marcus; Hohmann, Stefan

    2012-10-15

    Spore germination of the yeast Saccharomyces cerevisiae is a multi-step developmental path on which dormant spores re-enter the mitotic cell cycle and resume vegetative growth. Upon addition of a fermentable carbon source and nutrients, the outer layers of the protective spore wall are locally degraded, the tightly packed spore gains volume and an elongated shape, and eventually the germinating spore re-enters the cell cycle. The regulatory pathways driving this process are still largely unknown. Here we characterize the global gene expression profiles of germinating spores and identify potential transcriptional regulators of this process with the aim to increase our understanding of the mechanisms that control the transition from cellular dormancy to proliferation. Employing detailed gene expression time course data we have analysed the reprogramming of dormant spores during the transition to proliferation stimulated by a rich growth medium or pure glucose. Exit from dormancy results in rapid and global changes consisting of different sequential gene expression subprograms. The regulated genes reflect the transition towards glucose metabolism, the resumption of growth and the release of stress, similar to cells exiting a stationary growth phase. High resolution time course analysis during the onset of germination allowed us to identify a transient up-regulation of genes involved in protein folding and transport. We also identified a network of transcription factors that may be regulating the global response. While the expression outputs following stimulation by rich glucose medium or by glucose alone are qualitatively similar, the response to rich medium is stronger. Moreover, spores sense and react to amino acid starvation within the first 30 min after germination initiation, and this response can be linked to specific transcription factors. Resumption of growth in germinating spores is characterized by a highly synchronized temporal organisation of up- and down

  9. Time course gene expression profiling of yeast spore germination reveals a network of transcription factors orchestrating the global response

    PubMed Central

    2012-01-01

    Background Spore germination of the yeast Saccharomyces cerevisiae is a multi-step developmental path on which dormant spores re-enter the mitotic cell cycle and resume vegetative growth. Upon addition of a fermentable carbon source and nutrients, the outer layers of the protective spore wall are locally degraded, the tightly packed spore gains volume and an elongated shape, and eventually the germinating spore re-enters the cell cycle. The regulatory pathways driving this process are still largely unknown. Here we characterize the global gene expression profiles of germinating spores and identify potential transcriptional regulators of this process with the aim to increase our understanding of the mechanisms that control the transition from cellular dormancy to proliferation. Results Employing detailed gene expression time course data we have analysed the reprogramming of dormant spores during the transition to proliferation stimulated by a rich growth medium or pure glucose. Exit from dormancy results in rapid and global changes consisting of different sequential gene expression subprograms. The regulated genes reflect the transition towards glucose metabolism, the resumption of growth and the release of stress, similar to cells exiting a stationary growth phase. High resolution time course analysis during the onset of germination allowed us to identify a transient up-regulation of genes involved in protein folding and transport. We also identified a network of transcription factors that may be regulating the global response. While the expression outputs following stimulation by rich glucose medium or by glucose alone are qualitatively similar, the response to rich medium is stronger. Moreover, spores sense and react to amino acid starvation within the first 30 min after germination initiation, and this response can be linked to specific transcription factors. Conclusions Resumption of growth in germinating spores is characterized by a highly synchronized

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

    PubMed

    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 < 0.05) and ~70% were negative. The 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.

  11. Global field synchronization reveals rapid eye movement sleep as most synchronized brain state in the human EEG.

    PubMed

    Achermann, Peter; Rusterholz, Thomas; Dürr, Roland; König, Thomas; Tarokh, Leila

    2016-10-01

    Sleep is characterized by a loss of consciousness, which has been attributed to a breakdown of functional connectivity between brain regions. Global field synchronization (GFS) can estimate functional connectivity of brain processes. GFS is a frequency-dependent measure of global synchronicity of multi-channel EEG data. Our aim was to explore and extend the hypothesis of disconnection during sleep by comparing GFS spectra of different vigilance states. The analysis was performed on eight healthy adult male subjects. EEG was recorded during a baseline night, a recovery night after 40 h of sustained wakefulness and at 3 h intervals during the 40 h of wakefulness. Compared to non-rapid eye movement (NREM) sleep, REM sleep showed larger GFS values in all frequencies except in the spindle and theta bands, where NREM sleep showed a peak in GFS. Sleep deprivation did not affect GFS spectra in REM and NREM sleep. Waking GFS values were lower compared with REM and NREM sleep except for the alpha band. Waking alpha GFS decreased following sleep deprivation in the eyes closed condition only. Our surprising finding of higher synchrony during REM sleep challenges the view of REM sleep as a desynchronized brain state and may provide insight into the function of REM sleep.

  12. Global field synchronization reveals rapid eye movement sleep as most synchronized brain state in the human EEG

    PubMed Central

    Achermann, Peter; Rusterholz, Thomas; Dürr, Roland; König, Thomas

    2016-01-01

    Sleep is characterized by a loss of consciousness, which has been attributed to a breakdown of functional connectivity between brain regions. Global field synchronization (GFS) can estimate functional connectivity of brain processes. GFS is a frequency-dependent measure of global synchronicity of multi-channel EEG data. Our aim was to explore and extend the hypothesis of disconnection during sleep by comparing GFS spectra of different vigilance states. The analysis was performed on eight healthy adult male subjects. EEG was recorded during a baseline night, a recovery night after 40 h of sustained wakefulness and at 3 h intervals during the 40 h of wakefulness. Compared to non-rapid eye movement (NREM) sleep, REM sleep showed larger GFS values in all frequencies except in the spindle and theta bands, where NREM sleep showed a peak in GFS. Sleep deprivation did not affect GFS spectra in REM and NREM sleep. Waking GFS values were lower compared with REM and NREM sleep except for the alpha band. Waking alpha GFS decreased following sleep deprivation in the eyes closed condition only. Our surprising finding of higher synchrony during REM sleep challenges the view of REM sleep as a desynchronized brain state and may provide insight into the function of REM sleep. PMID:27853537

  13. Global pattern analysis and classification of dermoscopic images using textons

    NASA Astrophysics Data System (ADS)

    Sadeghi, Maryam; Lee, Tim K.; McLean, David; Lui, Harvey; Atkins, M. Stella

    2012-02-01

    Detecting and classifying global dermoscopic patterns are crucial steps for detecting melanocytic lesions from non-melanocytic ones. An important stage of melanoma diagnosis uses pattern analysis methods such as 7-point check list, Menzies method etc. In this paper, we present a novel approach to investigate texture analysis and classification of 5 classes of global lesion patterns (reticular, globular, cobblestone, homogeneous, and parallel pattern) in dermoscopic images. Our statistical approach models the texture by the joint probability distribution of filter responses using a comprehensive set of the state of the art filter banks. This distribution is represented by the frequency histogram of filter response cluster centers called textons. We have also examined other two methods: Joint Distribution of Intensities (JDI) and Convolutional Restricted Boltzmann Machine (CRBM) to learn the pattern specific features to be used for textons. The classification performance is compared over the Leung and Malik filters (LM), Root Filter Set (RFS), Maximum Response Filters (MR8), Schmid, Laws and our proposed filter set as well as CRBM and JDI. We analyzed 375 images of the 5 classes of the patterns. Our experiments show that the joint distribution of color (JDC) in the L*a*b* color space outperforms the other color spaces with a correct classification rate of 86.8%.

  14. Acetylproteomic analysis reveals functional implications of lysine acetylation in human spermatozoa (sperm).

    PubMed

    Yu, Heguo; Diao, Hua; Wang, Chunmei; Lin, Yan; Yu, Fudong; Lu, Hui; Xu, Wei; Li, Zheng; Shi, Huijuan; Zhao, Shimin; Zhou, Yuchuan; Zhang, Yonglian

    2015-04-01

    Male infertility is a medical condition that has been on the rise globally. Lysine acetylation of human sperm, an essential posttranslational modification involved in the etiology of sperm abnormality, is not fully understood. Therefore, we first generated a qualified pan-anti-acetyllysine monoclonal antibody to characterize the global lysine acetylation of uncapacitated normal human sperm with a proteomics approach. With high enrichment ratios that were up to 31%, 973 lysine-acetylated sites that matched to 456 human sperm proteins, including 671 novel lysine acetylation sites and 205 novel lysine-acetylated proteins, were identified. These proteins exhibited conserved motifs XXXKYXXX, XXXKFXXX, and XXXKHXXX, were annotated to function in multiple metabolic processes, and were localized predominantly in the mitochondrion and cytoplasmic fractions. Between the uncapacitated and capacitated sperm, different acetylation profiles in regard to functional proteins involved in sperm capacitation, sperm-egg recognition, sperm-egg plasma fusion, and fertilization were observed, indicating that acetylation of functional proteins may be required during sperm capacitation. Bioinformatics analysis revealed association of acetylated proteins with diseases and drugs. Novel acetylation of voltage-dependent anion channel proteins was also found. With clinical sperm samples, we observed differed lysine acetyltransferases and lysine deacetylases expression between normal sperm and abnormal sperm of asthenospermia or necrospermia. Furthermore, with sperm samples impaired by epigallocatechin gallate to mimic asthenospermia, we observed that inhibition of sperm motility was partly through the blockade of voltage-dependent anion channel 2 Lys-74 acetylation combined with reduced ATP levels and mitochondrial membrane potential. Taken together, we obtained a qualified pan-anti-acetyllysine monoclonal antibody, analyzed the acetylproteome of uncapacitated human sperm, and revealed

  15. Acetylproteomic Analysis Reveals Functional Implications of Lysine Acetylation in Human Spermatozoa (sperm)*

    PubMed Central

    Yu, Heguo; Diao, Hua; Wang, Chunmei; Lin, Yan; Yu, Fudong; Lu, Hui; Xu, Wei; Li, Zheng; Shi, Huijuan; Zhao, Shimin; Zhou, Yuchuan; Zhang, Yonglian

    2015-01-01

    Male infertility is a medical condition that has been on the rise globally. Lysine acetylation of human sperm, an essential posttranslational modification involved in the etiology of sperm abnormality, is not fully understood. Therefore, we first generated a qualified pan-anti-acetyllysine monoclonal antibody to characterize the global lysine acetylation of uncapacitated normal human sperm with a proteomics approach. With high enrichment ratios that were up to 31%, 973 lysine-acetylated sites that matched to 456 human sperm proteins, including 671 novel lysine acetylation sites and 205 novel lysine-acetylated proteins, were identified. These proteins exhibited conserved motifs XXXKYXXX, XXXKFXXX, and XXXKHXXX, were annotated to function in multiple metabolic processes, and were localized predominantly in the mitochondrion and cytoplasmic fractions. Between the uncapacitated and capacitated sperm, different acetylation profiles in regard to functional proteins involved in sperm capacitation, sperm-egg recognition, sperm-egg plasma fusion, and fertilization were observed, indicating that acetylation of functional proteins may be required during sperm capacitation. Bioinformatics analysis revealed association of acetylated proteins with diseases and drugs. Novel acetylation of voltage-dependent anion channel proteins was also found. With clinical sperm samples, we observed differed lysine acetyltransferases and lysine deacetylases expression between normal sperm and abnormal sperm of asthenospermia or necrospermia. Furthermore, with sperm samples impaired by epigallocatechin gallate to mimic asthenospermia, we observed that inhibition of sperm motility was partly through the blockade of voltage-dependent anion channel 2 Lys-74 acetylation combined with reduced ATP levels and mitochondrial membrane potential. Taken together, we obtained a qualified pan-anti-acetyllysine monoclonal antibody, analyzed the acetylproteome of uncapacitated human sperm, and revealed

  16. Ultra-deep sequencing reveals high prevalence and broad structural diversity of hepatitis B surface antigen mutations in a global population.

    PubMed

    Gencay, Mikael; Hübner, Kirsten; Gohl, Peter; Seffner, Anja; Weizenegger, Michael; Neofytos, Dionysios; Batrla, Richard; Woeste, Andreas; Kim, Hyon-Suk; Westergaard, Gaston; Reinsch, Christine; Brill, Eva; Thu Thuy, Pham Thi; Hoang, Bui Huu; Sonderup, Mark; Spearman, C Wendy; Pabinger, Stephan; Gautier, Jérémie; Brancaccio, Giuseppina; Fasano, Massimo; Santantonio, Teresa; Gaeta, Giovanni B; Nauck, Markus; Kaminski, Wolfgang E

    2017-01-01

    The diversity of the hepatitis B surface antigen (HBsAg) has a significant impact on the performance of diagnostic screening tests and the clinical outcome of hepatitis B infection. Neutralizing or diagnostic antibodies against the HBsAg are directed towards its highly conserved major hydrophilic region (MHR), in particular towards its "a" determinant subdomain. Here, we explored, on a global scale, the genetic diversity of the HBsAg MHR in a large, multi-ethnic cohort of randomly selected subjects with HBV infection from four continents. A total of 1553 HBsAg positive blood samples of subjects originating from 20 different countries across Africa, America, Asia and central Europe were characterized for amino acid variation in the MHR. Using highly sensitive ultra-deep sequencing, we found 72.8% of the successfully sequenced subjects (n = 1391) demonstrated amino acid sequence variation in the HBsAg MHR. This indicates that the global variation frequency in the HBsAg MHR is threefold higher than previously reported. The majority of the amino acid mutations were found in the HBV genotypes B (28.9%) and C (25.4%). Collectively, we identified 345 distinct amino acid mutations in the MHR. Among these, we report 62 previously unknown mutations, which extends the worldwide pool of currently known HBsAg MHR mutations by 22%. Importantly, topological analysis identified the "a" determinant upstream flanking region as the structurally most diverse subdomain of the HBsAg MHR. The highest prevalence of "a" determinant region mutations was observed in subjects from Asia, followed by the African, American and European cohorts, respectively. Finally, we found that more than half (59.3%) of all HBV subjects investigated carried multiple MHR mutations. Together, this worldwide ultra-deep sequencing based genotyping study reveals that the global prevalence and structural complexity of variation in the hepatitis B surface antigen have, to date, been significantly underappreciated.

  17. Ultra-deep sequencing reveals high prevalence and broad structural diversity of hepatitis B surface antigen mutations in a global population

    PubMed Central

    Gencay, Mikael; Hübner, Kirsten; Gohl, Peter; Seffner, Anja; Weizenegger, Michael; Neofytos, Dionysios; Batrla, Richard; Woeste, Andreas; Kim, Hyon-suk; Westergaard, Gaston; Reinsch, Christine; Brill, Eva; Thu Thuy, Pham Thi; Hoang, Bui Huu; Sonderup, Mark; Spearman, C. Wendy; Pabinger, Stephan; Gautier, Jérémie; Brancaccio, Giuseppina; Fasano, Massimo; Santantonio, Teresa; Gaeta, Giovanni B.; Nauck, Markus; Kaminski, Wolfgang E.

    2017-01-01

    The diversity of the hepatitis B surface antigen (HBsAg) has a significant impact on the performance of diagnostic screening tests and the clinical outcome of hepatitis B infection. Neutralizing or diagnostic antibodies against the HBsAg are directed towards its highly conserved major hydrophilic region (MHR), in particular towards its “a” determinant subdomain. Here, we explored, on a global scale, the genetic diversity of the HBsAg MHR in a large, multi-ethnic cohort of randomly selected subjects with HBV infection from four continents. A total of 1553 HBsAg positive blood samples of subjects originating from 20 different countries across Africa, America, Asia and central Europe were characterized for amino acid variation in the MHR. Using highly sensitive ultra-deep sequencing, we found 72.8% of the successfully sequenced subjects (n = 1391) demonstrated amino acid sequence variation in the HBsAg MHR. This indicates that the global variation frequency in the HBsAg MHR is threefold higher than previously reported. The majority of the amino acid mutations were found in the HBV genotypes B (28.9%) and C (25.4%). Collectively, we identified 345 distinct amino acid mutations in the MHR. Among these, we report 62 previously unknown mutations, which extends the worldwide pool of currently known HBsAg MHR mutations by 22%. Importantly, topological analysis identified the “a” determinant upstream flanking region as the structurally most diverse subdomain of the HBsAg MHR. The highest prevalence of “a” determinant region mutations was observed in subjects from Asia, followed by the African, American and European cohorts, respectively. Finally, we found that more than half (59.3%) of all HBV subjects investigated carried multiple MHR mutations. Together, this worldwide ultra-deep sequencing based genotyping study reveals that the global prevalence and structural complexity of variation in the hepatitis B surface antigen have, to date, been significantly

  18. Comprehensive profiling of lysine acetylproteome analysis reveals diverse functions of lysine acetylation in common wheat.

    PubMed

    Zhang, Yumei; Song, Limin; Liang, Wenxing; Mu, Ping; Wang, Shu; Lin, Qi

    2016-02-15

    Lysine acetylation of proteins, a dynamic and reversible post-translational modification, plays a critical regulatory role in both eukaryotes and prokaryotes. Several researches have been carried out on acetylproteome in plants. However, until now, there have been no data on common wheat, the major cereal crop in the world. In this study, we performed a global acetylproteome analysis of common wheat variety (Triticum aestivum L.), Chinese Spring. In total, 416 lysine modification sites were identified on 277 proteins, which are involved in a wide variety of biological processes. Consistent with previous studies, a large proportion of the acetylated proteins are involved in metabolic process. Interestingly, according to the functional enrichment analysis, 26 acetylated proteins are involved in photosynthesis and Calvin cycle, suggesting an important role of lysine acetylation in these processes. Moreover, protein interaction network analysis reveals that diverse interactions are modulated by protein acetylation. These data represent the first report of acetylome in common wheat and serve as an important resource for exploring the physiological role of lysine acetylation in this organism and likely in all plants.

  19. Comprehensive profiling of lysine acetylproteome analysis reveals diverse functions of lysine acetylation in common wheat

    PubMed Central

    Zhang, Yumei; Song, Limin; Liang, Wenxing; Mu, Ping; Wang, Shu; Lin, Qi

    2016-01-01

    Lysine acetylation of proteins, a dynamic and reversible post-translational modification, plays a critical regulatory role in both eukaryotes and prokaryotes. Several researches have been carried out on acetylproteome in plants. However, until now, there have been no data on common wheat, the major cereal crop in the world. In this study, we performed a global acetylproteome analysis of common wheat variety (Triticum aestivum L.), Chinese Spring. In total, 416 lysine modification sites were identified on 277 proteins, which are involved in a wide variety of biological processes. Consistent with previous studies, a large proportion of the acetylated proteins are involved in metabolic process. Interestingly, according to the functional enrichment analysis, 26 acetylated proteins are involved in photosynthesis and Calvin cycle, suggesting an important role of lysine acetylation in these processes. Moreover, protein interaction network analysis reveals that diverse interactions are modulated by protein acetylation. These data represent the first report of acetylome in common wheat and serve as an important resource for exploring the physiological role of lysine acetylation in this organism and likely in all plants. PMID:26875666

  20. Global assessment of small RNAs reveals a non-coding transcript involved in biofilm formation and attachment in Acinetobacter baumannii ATCC 17978

    PubMed Central

    Pérez, Astrid; Gómez, Manuel J.; Gayoso, Carmen; Vallejo, Juan A.; Ohneck, Emily J.; Valle, Jaione; Actis, Luis A.; Beceiro, Alejandro; Bou, Germán

    2017-01-01

    Many strains of Acinetobacter baumannii have been described as being able to form biofilm. Small non-coding RNAs (sRNAs) control gene expression in many regulatory circuits in bacteria. The aim of the present work was to provide a global description of the sRNAs produced both by planktonic and biofilm-associated (sessile) cells of A. baumannii ATCC 17978, and to compare the corresponding gene expression profiles to identify sRNAs molecules associated to biofilm formation and virulence. sRNA was extracted from both planktonic and sessile cells and reverse transcribed. cDNA was subjected to 454-pyrosequencing using the GS-FLX Titanium chemistry. The global analysis of the small RNA transcriptome revealed different sRNA expression patterns in planktonic and biofilm associated cells, with some of the transcripts only expressed or repressed in sessile bacteria. A total of 255 sRNAs were detected, with 185 of them differentially expressed in the different types of cells. A total of 9 sRNAs were expressed only in biofilm cells, while the expression of other 21 coding regions were repressed only in biofilm cells. Strikingly, the expression level of the sRNA 13573 was 120 times higher in biofilms than in planktonic cells, an observation that prompted us to further investigate the biological role of this non-coding transcript. Analyses of an isogenic mutant and over-expressing strains revealed that the sRNA 13573 gene is involved in biofilm formation and attachment to A549 human alveolar epithelial cells. The present work serves as a basis for future studies examining the complex regulatory network that regulate biofilm biogenesis and attachment to eukaryotic cells in A. baumannii ATCC 17978. PMID:28763494

  1. Range wide molecular data and niche modeling revealed the Pleistocene history of a global invader (Halyomorpha halys).

    PubMed

    Zhu, Geng-Ping; Ye, Zhen; Du, Juan; Zhang, Dan-Li; Zhen, Ya-hui; Zheng, Chen-guang; Zhao, Li; Li, Min; Bu, Wen-Jun

    2016-03-21

    Invasive species' Pleistocene history contains much information on its present population structure, dispersability and adaptability. In this study, the Pleistocene history of a global invasive pest (Brown Marmorated Stink Bug BMSB, Halyomorpha halys) was unveiled using the coupled approach of phylogeography and ecological niche modelling. Rangewide molecular data suggests that the Taiwan and other native populations had diverged in mid-Pleistocene. In mainland China, the native BMSB did not experience population contraction and divergence during last glacial, but persisted in interconnected populations. Combined Bayesian Skyline Plot (BSP) and niche modelling revealed a rapid expansion occurred during the transition of Last Inter Glacial (LIG) to Last Glacial Maximum (LGM). High genetic diversity and multi-reticular haplotypes network exist in the original sources populations of BMSB invasion in northern China. They were speculated to be colonized from the central China, with many derived haplotypes evolved to adapt the novel environment. The ENM future prediction suggest that BMSB may expand northward to higher latitudes in the US and Europe, because of its high invasive ability, together with the available suitable climate space there.

  2. Range wide molecular data and niche modeling revealed the Pleistocene history of a global invader (Halyomorpha halys)

    PubMed Central

    Zhu, Geng-Ping; Ye, Zhen; Du, Juan; Zhang, Dan-Li; Zhen, Ya-hui; Zheng, Chen-guang; Zhao, Li; Li, Min; Bu, Wen-Jun

    2016-01-01

    Invasive species’ Pleistocene history contains much information on its present population structure, dispersability and adaptability. In this study, the Pleistocene history of a global invasive pest (Brown Marmorated Stink Bug BMSB, Halyomorpha halys) was unveiled using the coupled approach of phylogeography and ecological niche modelling. Rangewide molecular data suggests that the Taiwan and other native populations had diverged in mid-Pleistocene. In mainland China, the native BMSB did not experience population contraction and divergence during last glacial, but persisted in interconnected populations. Combined Bayesian Skyline Plot (BSP) and niche modelling revealed a rapid expansion occurred during the transition of Last Inter Glacial (LIG) to Last Glacial Maximum (LGM). High genetic diversity and multi-reticular haplotypes network exist in the original sources populations of BMSB invasion in northern China. They were speculated to be colonized from the central China, with many derived haplotypes evolved to adapt the novel environment. The ENM future prediction suggest that BMSB may expand northward to higher latitudes in the US and Europe, because of its high invasive ability, together with the available suitable climate space there. PMID:26996353

  3. Global Analysis of Several Bands of the CF_4 Molecule

    NASA Astrophysics Data System (ADS)

    Carlos, Mickaël; Gruson, Océane; Boudon, Vincent; Georges, Robert; Pirali, Olivier; Asselin, Pierre

    2016-06-01

    Carbon tetrafluoride is a powerful greenhouse gas, mainly of anthropogenic origin. Its absorption spectrum is, however, still badly modeled, especially for hot bands in the strongly absorbing ν_3 region. To overcome this problem, we have undertaken a systematic study of all the lower rovibrational transitions of this molecule. In particular, new far-infrared spectra recorded at the SOLEIL Synchrotron facility give access to bands implying the ``forbidden'' modes ν_1 and ν_2 which have only been investigated previously thanks to stimulated Raman spectroscopy, that is with a lower accuracy and much less data. Combined with the previous analyses performed in our group, we thus report here a new global fit of line positions of CF_4 by considering several transitions altogether: ν_2, 2ν_2-ν_2, ν_4, 2ν_4, ν_3 and ν_3-2ν_2. This gives a consistent set of molecular parameters that will be of great help for the analysis of hot bands like ν_3+ν_2-ν_2. A second separate global fit including the ν_1, ν_1-ν_4 and 2ν_1-ν_1 bands will also be presented. V. Boudon, D. Bermejo, R. Z. Martinez, J. Raman Spectrosc. 44, 731?738 (2013). V. Boudon, J. Mitchell, A. Domanskaya, C. Maul, R; Georges, A. Benidar, W. G. Harter, Mol. Phys. 109, 17--18 (2011)

  4. Revisiting global body politics in Nepal: A reflexive analysis.

    PubMed

    Harcourt, Wendy

    2016-01-01

    Using the example of a human rights training in Nepal, the author looks at global body politics in a reflexive piece on her engagement in development practices that translate western feminist ideas on gender inequality and empowerment via UN human rights policies into non-western contexts. It firsts look at postcolonial and critical literature on feminist engagement in gender and development processes including a discussion on the concept of global body politics before examining briefly the framing of gender-based violence in Nepal. The core of the paper is a reflexive analysis and interrogation of the training in Nepal in order to bring out the tensions and contradictions around western developmental, feminist and human rights discourses. The discussion looks at how difficult it is for feminist, human rights and developmental discourses and practices to unmoor themselves from the notion of the 'expert' and those who do the rights/work/righting rights training and those who are perennially seen as requiring training. The conclusion reflects on possibilities of other epistemic practices found in intercultural dialogues.

  5. Global review of open access risk assessment software packages valid for global or continental scale analysis

    NASA Astrophysics Data System (ADS)

    Daniell, James; Simpson, Alanna; Gunasekara, Rashmin; Baca, Abigail; Schaefer, Andreas; Ishizawa, Oscar; Murnane, Rick; Tijssen, Annegien; Deparday, Vivien; Forni, Marc; Himmelfarb, Anne; Leder, Jan

    2015-04-01

    Over the past few decades, a plethora of open access software packages for the calculation of earthquake, volcanic, tsunami, storm surge, wind and flood have been produced globally. As part of the World Bank GFDRR Review released at the Understanding Risk 2014 Conference, over 80 such open access risk assessment software packages were examined. Commercial software was not considered in the evaluation. A preliminary analysis was used to determine whether the 80 models were currently supported and if they were open access. This process was used to select a subset of 31 models that include 8 earthquake models, 4 cyclone models, 11 flood models, and 8 storm surge/tsunami models for more detailed analysis. By using multi-criteria analysis (MCDA) and simple descriptions of the software uses, the review allows users to select a few relevant software packages for their own testing and development. The detailed analysis evaluated the models on the basis of over 100 criteria and provides a synopsis of available open access natural hazard risk modelling tools. In addition, volcano software packages have since been added making the compendium of risk software tools in excess of 100. There has been a huge increase in the quality and availability of open access/source software over the past few years. For example, private entities such as Deltares now have an open source policy regarding some flood models (NGHS). In addition, leaders in developing risk models in the public sector, such as Geoscience Australia (EQRM, TCRM, TsuDAT, AnuGA) or CAPRA (ERN-Flood, Hurricane, CRISIS2007 etc.), are launching and/or helping many other initiatives. As we achieve greater interoperability between modelling tools, we will also achieve a future wherein different open source and open access modelling tools will be increasingly connected and adapted towards unified multi-risk model platforms and highly customised solutions. It was seen that many software tools could be improved by enabling user

  6. Transcriptome analysis reveals manifold mechanisms of cyst development in ADPKD.

    PubMed

    de Almeida, Rita M C; Clendenon, Sherry G; Richards, William G; Boedigheimer, Michael; Damore, Michael; Rossetti, Sandro; Harris, Peter C; Herbert, Britney-Shea; Xu, Wei Min; Wandinger-Ness, Angela; Ward, Heather H; Glazier, James A; Bacallao, Robert L

    2016-11-21

    Autosomal dominant polycystic kidney disease (ADPKD) causes progressive loss of renal function in adults as a consequence of the accumulation of cysts. ADPKD is the most common genetic cause of end-stage renal disease. Mutations in polycystin-1 occur in 87% of cases of ADPKD and mutations in polycystin-2 are found in 12% of ADPKD patients. The complexity of ADPKD has hampered efforts to identify the mechanisms underlying its pathogenesis. No current FDA (Federal Drug Administration)-approved therapies ameliorate ADPKD progression. We used the de Almeida laboratory's sensitive new transcriptogram method for whole-genome gene expression data analysis to analyze microarray data from cell lines developed from cell isolates of normal kidney and of both non-cystic nephrons and cysts from the kidney of a patient with ADPKD. We compared results obtained using standard Ingenuity Volcano plot analysis, Gene Set Enrichment Analysis (GSEA) and transcriptogram analysis. Transcriptogram analysis confirmed the findings of Ingenuity, GSEA, and published analysis of ADPKD kidney data and also identified multiple new expression changes in KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways related to cell growth, cell death, genetic information processing, nucleotide metabolism, signal transduction, immune response, response to stimulus, cellular processes, ion homeostasis and transport and cofactors, vitamins, amino acids, energy, carbohydrates, drugs, lipids, and glycans. Transcriptogram analysis also provides significance metrics which allow us to prioritize further study of these pathways. Transcriptogram analysis identifies novel pathways altered in ADPKD, providing new avenues to identify both ADPKD's mechanisms of pathogenesis and pharmaceutical targets to ameliorate the progression of the disease.

  7. Genomic analysis of methanogenic archaea reveals a shift towards energy conservation.

    PubMed

    Gilmore, Sean P; Henske, John K; Sexton, Jessica A; Solomon, Kevin V; Seppälä, Susanna; Yoo, Justin I; Huyett, Lauren M; Pressman, Abe; Cogan, James Z; Kivenson, Veronika; Peng, Xuefeng; Tan, YerPeng; Valentine, David L; O'Malley, Michelle A

    2017-08-21

    The metabolism of archaeal methanogens drives methane release into the environment and is critical to understanding global carbon cycling. Methanogenesis operates at a very low reducing potential compared to other forms of respiration and is therefore critical to many anaerobic environments. Harnessing or altering methanogen metabolism has the potential to mitigate global warming and even be utilized for energy applications. Here, we report draft genome sequences for the isolated methanogens Methanobacterium bryantii, Methanosarcina spelaei, Methanosphaera cuniculi, and Methanocorpusculum parvum. These anaerobic, methane-producing archaea represent a diverse set of isolates, capable of methylotrophic, acetoclastic, and hydrogenotrophic methanogenesis. Assembly and analysis of the genomes allowed for simple and rapid reconstruction of metabolism in the four methanogens. Comparison of the distribution of Clusters of Orthologous Groups (COG) proteins to a sample of genomes from the RefSeq database revealed a trend towards energy conservation in genome composition of all methanogens sequenced. Further analysis of the predicted membrane proteins and transporters distinguished differing energy conservation methods utilized during methanogenesis, such as chemiosmotic coupling in Msar. spelaei and electron bifurcation linked to chemiosmotic coupling in Mbac. bryantii and Msph. cuniculi. Methanogens occupy a unique ecological niche, acting as the terminal electron acceptors in anaerobic environments, and their genomes display a significant shift towards energy conservation. The genome-enabled reconstructed metabolisms reported here have significance to diverse anaerobic communities and have led to proposed substrate utilization not previously reported in isolation, such as formate and methanol metabolism in Mbac. bryantii and CO2 metabolism in Msph. cuniculi. The newly proposed substrates establish an important foundation with which to decipher how methanogens behave in

  8. Transcriptome profiling of peanut gynophores revealed global reprogramming of gene expression during early pod development in darkness

    PubMed Central

    2013-01-01

    Background After the zygote divides few times, the development of peanut pre-globular embryo and fruit is arrested under white or red light. Embryo development could be resumed in dark condition after gynophore is buried in soil. It is interesting to study the mechanisms of gynophore development and pod formation in peanut. Results In this study, transcriptome analysis of peanut gynophore was performed using Illumina HiSeq™ 2000 to understand the mechanisms of geocarpy. More than 13 million short sequences were assembled into 72527 unigenes with average size of 394 bp. A large number of genes that were not identified previously in peanut EST projects were identified in this study, including most genes involved in plant circadian rhythm, intra-cellular transportation, plant spliceosome, eukaryotes basal transcription factors, genes encoding ribosomal proteins, brassinosteriod biosynthesis, light-harvesting chlorophyll protein complex, phenylpropanoid biosynthesis and TCA cycle. RNA-seq based gene expression profiling results showed that before and after gynophore soil penetration, the transcriptional level of a large number of genes changed significantly. Genes encoding key enzymes for hormone metabolism, signaling, photosynthesis, light signaling, cell division and growth, carbon and nitrogen metabolism as well as genes involved in stress responses were high lighted. Conclusions Transcriptome analysis of peanut gynophore generated a large number of unigenes which provide useful information for gene cloning and expression study. Digital gene expression study suggested that gynophores experience global changes and reprogram from light to dark grown condition to resume embryo and fruit development. PMID:23895441

  9. Transcriptome profiling of peanut gynophores revealed global reprogramming of gene expression during early pod development in darkness.

    PubMed

    Xia, Han; Zhao, Chuanzhi; Hou, Lei; Li, Aiqin; Zhao, Shuzhen; Bi, Yuping; An, Jing; Zhao, Yanxiu; Wan, Shubo; Wang, Xingjun

    2013-07-29

    After the zygote divides few times, the development of peanut pre-globular embryo and fruit is arrested under white or red light. Embryo development could be resumed in dark condition after gynophore is buried in soil. It is interesting to study the mechanisms of gynophore development and pod formation in peanut. In this study, transcriptome analysis of peanut gynophore was performed using Illumina HiSeq™ 2000 to understand the mechanisms of geocarpy. More than 13 million short sequences were assembled into 72527 unigenes with average size of 394 bp. A large number of genes that were not identified previously in peanut EST projects were identified in this study, including most genes involved in plant circadian rhythm, intra-cellular transportation, plant spliceosome, eukaryotes basal transcription factors, genes encoding ribosomal proteins, brassinosteriod biosynthesis, light-harvesting chlorophyll protein complex, phenylpropanoid biosynthesis and TCA cycle. RNA-seq based gene expression profiling results showed that before and after gynophore soil penetration, the transcriptional level of a large number of genes changed significantly. Genes encoding key enzymes for hormone metabolism, signaling, photosynthesis, light signaling, cell division and growth, carbon and nitrogen metabolism as well as genes involved in stress responses were high lighted. Transcriptome analysis of peanut gynophore generated a large number of unigenes which provide useful information for gene cloning and expression study. Digital gene expression study suggested that gynophores experience global changes and reprogram from light to dark grown condition to resume embryo and fruit development.

  10. Global NLO Analysis of Nuclear Parton Distribution Functions

    SciTech Connect

    Hirai, M.; Kumano, S.; Nagai, T.-H.

    2008-02-21

    Nuclear parton distribution functions (NPDFs) are determined by a global analysis of experimental measurements on structure-function ratios F{sub 2}{sup A}/F{sub 2}{sup A{sup '}} and Drell-Yan cross section ratios {sigma}{sub DY}{sup A}/{sigma}{sub DY}{sup A{sup '}}, and their uncertainties are estimated by the Hessian method. The NPDFs are obtained in both leading order (LO) and next-to-leading order (NLO) of {alpha}{sub s}. As a result, valence-quark distributions are relatively well determined, whereas antiquark distributions at x>0.2 and gluon distributions in the whole x region have large uncertainties. The NLO uncertainties are slightly smaller than the LO ones; however, such a NLO improvement is not as significant as the nucleonic case.

  11. Global Positioning System Analysis of a High School Football Scrimmage.

    PubMed

    Gleason, Benjamin H; Sams, Matthew L; Salley, John T; Pustina, A Andrew; Stone, Michael H

    2017-08-01

    Gleason, BH, Sams, M, Salley, JT, Pustina, A, and Stone, MH. Global positioning system analysis of a high school football scrimmage. J Strength Cond Res 31(8): 2183-2188, 2017-The purpose of this study was to examine the physical demands of a high school American football scrimmage. Male high school football players (N = 25) participated in a spring scrimmage. Global positioning system data and game film were recorded throughout the entirety of the scrimmage to determine the total distance covered, the distance covered in different velocity bands, the number of accelerations and decelerations performed, and the work-to-rest ratio of the scrimmage. The athletes were divided into 2 groups: linemen (L) (N = 7) vs. nonlinemen (NL) (N = 8) for statistical analysis, and independent T-tests with Holm's sequential Bonferroni adjustment were used to determine differences in movement characteristics between the L and NL groups. Average play duration was 5.7 ± 2.1 seconds, whereas the rest interval was 33.4 ± 13.6 seconds between plays, for an overall exercise-to-rest ratio of 1:5.9. Total distance, standing and walking distance, running distance, striding distance, sprinting distance, and total high-speed running distance covered by NL was greater than L (statistically significant at p ≤ 0.05). Distances traveled in each velocity band by position and by play are also included to provide context of our findings. Data from the present study add to the pool of support for the use of position-specific training in preparing high school football players for competition.

  12. Global/local methods research using a common structural analysis framework

    NASA Technical Reports Server (NTRS)

    Knight, Norman F., Jr.; Ransom, Jonathan B.; Griffin, O. H., Jr.; Thompson, Danniella M.

    1991-01-01

    Methodologies for global/local stress analysis are described including both two- and three-dimensional analysis methods. These methods are being developed within a common structural analysis framework. Representative structural analysis problems are presented to demonstrate the global/local methodologies being developed.

  13. Global/local methods research using a common structural analysis framework

    NASA Technical Reports Server (NTRS)

    Knight, Norman F., Jr.; Ransom, Jonathan B.; Griffin, O. H., Jr.; Thompson, Danniella M.

    1991-01-01

    Methodologies for global/local stress analysis are described including both two- and three-dimensional analysis methods. These methods are being developed within a common structural analysis framework. Representative structural analysis problems are presented to demonstrate the global/local methodologies being developed.

  14. Analysis of a global database containing tritium in precipitation

    SciTech Connect

    Buckley, R. L.; Rabun, R. L.; Heath, M.

    2016-02-17

    The International Atomic Energy Agency (IAEA) directed the collection of tritium in water samples from the mid-1950s to 2009. The Global Network of Isotopes in Precipitation (GNIP) data examined the airborne movement of isotope releases to the environment, with an objective of collecting spatial data on the isotope content of precipitation across the globe. The initial motivation was to monitor atmospheric thermonuclear test fallout through tritium, deuterium, and oxygen isotope concentrations, but after the 1970s the focus changed to being an observation network of stable hydrogen and oxygen isotope data for hydrologic studies. The GNIP database provides a wealth of tritium data collections over a long period of time. The work performed here primarily examined data features in the past 30 years (after much of the effects of above-ground nuclear testing in the late 1950s to early 1960s decayed away), revealing potentially unknown tritium sources. The available data at GNIP were reorganized to allow for evaluation of trends in the data both temporally and spatially. Several interesting cases were revealed, including relatively high measured concentrations in the Atlantic and Indian Oceans, Russia, Norway, as well as an increase in background concentration at a collector in South Korea after 2004. Recent data from stations in the southeastern United States nearest to the Savannah River Site do not indicate any high values. Meteorological impacts have not been considered in this study. Further research to assess the likely source location of interesting cases using transport simulations and/or literature searches is warranted.

  15. Reliability-based design optimization using efficient global reliability analysis.

    SciTech Connect

    Bichon, Barron J.; Mahadevan, Sankaran; Eldred, Michael Scott

    2010-05-01

    Finding the optimal (lightest, least expensive, etc.) design for an engineered component that meets or exceeds a specified level of reliability is a problem of obvious interest across a wide spectrum of engineering fields. Various methods for this reliability-based design optimization problem have been proposed. Unfortunately, this problem is rarely solved in practice because, regardless of the method used, solving the problem is too expensive or the final solution is too inaccurate to ensure that the reliability constraint is actually satisfied. This is especially true for engineering applications involving expensive, implicit, and possibly nonlinear performance functions (such as large finite element models). The Efficient Global Reliability Analysis method was recently introduced to improve both the accuracy and efficiency of reliability analysis for this type of performance function. This paper explores how this new reliability analysis method can be used in a design optimization context to create a method of sufficient accuracy and efficiency to enable the use of reliability-based design optimization as a practical design tool.

  16. Quantitative proteomic analysis reveals posttranslational responses to aneuploidy in yeast.

    PubMed

    Dephoure, Noah; Hwang, Sunyoung; O'Sullivan, Ciara; Dodgson, Stacie E; Gygi, Steven P; Amon, Angelika; Torres, Eduardo M

    2014-07-29

    Aneuploidy causes severe developmental defects and is a near universal feature of tumor cells. Despite its profound effects, the cellular processes affected by aneuploidy are not well characterized. Here, we examined the consequences of aneuploidy on the proteome of aneuploid budding yeast strains. We show that although protein levels largely scale with gene copy number, subunits of multi-protein complexes are notable exceptions. Posttranslational mechanisms attenuate their expression when their encoding genes are in excess. Our proteomic analyses further revealed a novel aneuploidy-associated protein expression signature characteristic of altered metabolism and redox homeostasis. Indeed aneuploid cells harbor increased levels of reactive oxygen species (ROS). Interestingly, increased protein turnover attenuates ROS levels and this novel aneuploidy-associated signature and improves the fitness of most aneuploid strains. Our results show that aneuploidy causes alterations in metabolism and redox homeostasis. Cells respond to these alterations through both transcriptional and posttranscriptional mechanisms. Copyright © 2014, Dephoure et al.

  17. Subfield profitability analysis reveals an economic case for cropland diversification

    NASA Astrophysics Data System (ADS)

    Brandes, E.; McNunn, G. S.; Schulte, L. A.; Bonner, I. J.; Muth, D. J.; Babcock, B. A.; Sharma, B.; Heaton, E. A.

    2016-01-01

    Public agencies and private enterprises increasingly desire to achieve ecosystem service outcomes in agricultural systems, but are limited by perceived conflicts between economic and ecosystem service goals and a lack of tools enabling effective operational management. Here we use Iowa—an agriculturally homogeneous state representative of the Maize Belt—to demonstrate an economic rationale for cropland diversification at the subfield scale. We used a novel computational framework that integrates disparate but publicly available data to map ˜3.3 million unique potential management polygons (9.3 Mha) and reveal subfield opportunities to increase overall field profitability. We analyzed subfield profitability for maize/soybean fields during 2010-2013—four of the most profitable years in recent history—and projected results for 2015. While cropland operating at a loss of US 250 ha-1 or more was negligible between 2010 and 2013 at 18 000-190 000 ha (<2% of row-crop land), the extent of highly unprofitable land increased to 2.5 Mha, or 27% of row-crop land, in the 2015 projection. Aggregation of these areas to the township level revealed ‘hotspots’ for potential management change in Western, Central, and Northeast Iowa. In these least profitable areas, incorporating conservation management that breaks even (e.g., planting low-input perennials), into low-yielding portions of fields could increase overall cropland profitability by 80%. This approach is applicable to the broader region and differs substantially from the status quo of ‘top-down’ land management for conservation by harnessing private interest to align profitability with the production of ecosystem services.

  18. Trophic hierarchies revealed via amino acid isotopic analysis

    USDA-ARS?s Scientific Manuscript database

    Despite the potential of isotopic methods to illuminate trophic function, accurate estimates of lifetime feeding tendencies have remained elusive. A relatively new approach—referred to as compound-specific isotopic analysis (CSIA)—has emerged, centering on the measurement of 15N:14N ratios in amino ...

  19. Network analysis reveals multiscale controls on streamwater chemistry

    Treesearch

    Kevin J. McGuire; Christian E. Torgersen; Gene E. Likens; Donald C. Buso; Winsor H. Lowe; Scott W. Bailey

    2014-01-01

    By coupling synoptic data from a basin-wide assessment of streamwater chemistry with network-based geostatistical analysis, we show that spatial processes differentially affect biogeochemical condition and pattern across a headwater stream network. We analyzed a high-resolution dataset consisting of 664 water samples collected every 100 m throughout 32 tributaries in...

  20. Analysis of copy number variations reveals differences among cattle breeds

    USDA-ARS?s Scientific Manuscript database

    Genomic structural variation is an important and abundant source of genetic and phenotypic variation. Here we describe the first systematic and genome-wide analysis of copy number variations (CNVs) in the modern domesticated cattle using array comparative genomic hybridization (array CGH) and quanti...

  1. Systematic proteomic analysis of human hepotacellular carcinoma cells reveals molecular pathways and networks involved in metastasis.

    PubMed

    Yu, Yanyan; Shen, Huali; Yu, Hongxiu; Zhong, Fan; Zhang, Yang; Zhang, Chen; Zhao, Jian; Li, Hong; Chen, Jie; Liu, Yinkun; Yang, Pengyuan

    2011-06-01

    Systematic proteomic studying of the mechanism of hepatocellular carcinoma (HCC) metastasis remains challenging. We performed comparative proteomic and pathway analysis of four human metastatic HCC cell lines to identify metastasis-associated proteins. These HCC cell lines had a similar genetic background but with an increasing potential of metastasis. Using a combination of two dimensional electrophoresis (2-DE) and MALDI-TOF mass spectrometry, a total of 125 proteins and their post-translational modification forms or isoforms were found to be differentially expressed in the cell lines. Among them, 29 were gradually up-regulated whereas 17 were down-regulated with increasing metastatic potential. Instead of a traditional single-gene readout, global bioinformatics analysis was carried out, which revealed that the glycolysis pathway was the most significantly enriched pathway. The heat shock proteins (HSPs) centered and NF-kappaB centered networks were also enriched in the result, which may imply the key function of inflaming on metastasis. Meanwhile, knockdown of HDGF, an up-regulated protein and a target of NF-kappaB, induced cell apoptosis in the metastatic HCC cells. This work provides a demonstration that a combination of bioinformatics and comparative proteomics can help in finding out potential biomarkers associated with HCC metastasis on the level of pathways.

  2. Analysis of spatial-temporal gene expression patterns reveals dynamics and regionalization in developing mouse brain.

    PubMed

    Chou, Shen-Ju; Wang, Chindi; Sintupisut, Nardnisa; Niou, Zhen-Xian; Lin, Chih-Hsu; Li, Ker-Chau; Yeang, Chen-Hsiang

    2016-01-20

    Allen Brain Atlas (ABA) provides a valuable resource of spatial/temporal gene expressions in mammalian brains. Despite rich information extracted from this database, current analyses suffer from several limitations. First, most studies are either gene-centric or region-centric, thus are inadequate to capture the superposition of multiple spatial-temporal patterns. Second, standard tools of expression analysis such as matrix factorization can capture those patterns but do not explicitly incorporate spatial dependency. To overcome those limitations, we proposed a computational method to detect recurrent patterns in the spatial-temporal gene expression data of developing mouse brains. We demonstrated that regional distinction in brain development could be revealed by localized gene expression patterns. The patterns expressed in the forebrain, medullary and pontomedullary, and basal ganglia are enriched with genes involved in forebrain development, locomotory behavior, and dopamine metabolism respectively. In addition, the timing of global gene expression patterns reflects the general trends of molecular events in mouse brain development. Furthermore, we validated functional implications of the inferred patterns by showing genes sharing similar spatial-temporal expression patterns with Lhx2 exhibited differential expression in the embryonic forebrains of Lhx2 mutant mice. These analysis outcomes confirm the utility of recurrent expression patterns in studying brain development.

  3. WATERSHED BOUNDARY CONDITIONS FOR GLOBAL CHANGE IMPACT ANALYSIS

    EPA Science Inventory

    The US Global Change Research Program (USGCRP) studies (among other issues) the impact of global change on water quality. This field study evaluates the impact of global changes (land-use change and climate change) on source water quality. Changes in source water quality change...

  4. WATERSHED BOUNDARY CONDITIONS FOR GLOBAL CHANGE IMPACT ANALYSIS

    EPA Science Inventory

    The US Global Change Research Program (USGCRP) studies (among other issues) the impact of global change on water quality. This field study evaluates the impact of global changes (land-use change and climate change) on source water quality. Changes in source water quality change...

  5. MRI Texture Analysis Reveals Bulbar Abnormalities in Friedreich Ataxia.

    PubMed

    Santos, T A; Maistro, C E B; Silva, C B; Oliveira, M S; França, M C; Castellano, G

    2015-12-01

    Texture analysis is an image processing technique that can be used to extract parameters able to describe meaningful features of an image or ROI. Texture analysis based on the gray level co-occurrence matrix gives a second-order statistical description of the image or ROI. In this work, the co-occurrence matrix texture approach was used to extract information from brain MR images of patients with Friedreich ataxia and a control group, to see whether texture parameters were different between these groups. A longitudinal analysis was also performed. Twenty patients and 21 healthy controls participated in the study. Both groups had 2 sets of T1-weighted MR images obtained 1 year apart for every subject. ROIs chosen for analysis were the medulla oblongata and pons. Texture parameters were obtained for these ROIs for every subject, for the 2 sets of images. These parameters were compared longitudinally within groups and transversally between groups. The comparison between patients and the control group showed a significant differences for the medulla oblongata (t test, P < .05, Bonferroni-corrected) but did not show a statistically significant difference for the pons. Longitudinal comparison of images obtained 1 year apart did not show differences for either patients or for controls, in any of the analyzed structures. Gray level co-occurrence matrix-based texture analysis showed statistically significant differences for the medulla oblongata of patients with Friedreich ataxia compared with controls. These results highlight the medulla as an important site of damage in Friedreich ataxia. © 2015 by American Journal of Neuroradiology.

  6. Seasonal Transport in Mars' Mesosphere revealed by Nitric Oxide Nightglow vertical profiles and global images from IUVS/MAVEN

    NASA Astrophysics Data System (ADS)

    Stiepen, Arnaud; Stewart, Ian; Jain, Sonal; Schneider, Nicholas; Deighan, Justin; Gonzàlez-Galindo, Francisco; Gérard, Jean-Claude; Stevens, Michael; Bougher, Stephen; Milby, Zachariah; Evans, Scott; Chaffin, Michael; McClintock, William; Clarke, John; Holsclaw, Greg; Montmessin, Franck; Lefèvre, Franck; Lo, Daniel; Jakosky, Bruce

    2017-04-01

    We analyze the ultraviolet nightglow in the atmosphere of Mars through Nitric Oxide (NO) δ and γ bands emissions. On the dayside thermosphere of Mars, solar extreme ultraviolet radiation partly dissociates CO2 and N2 molecules. O(3P) and N(4S) atoms are carried by the day-to-night hemispheric transport. They preferentially descend in the nightside mesosphere in the winter hemisphere, where they can radiatively recombine to form NO(C2Π). The excited molecules promptly relax by emitting photons in the UV δ bands and in the γ bands through cascades via the A2Σ, v' = 0 state. These emissions are thus indicators of the N and O atom fluxes transported from the dayside to Mars' nightside and the winter descending circulation pattern from the nightside thermosphere to the mesosphere (e.g. Bertaux et al., 2005 ; Bougher et al., 1990 ; Cox et al., 2008 ; Gagné et al., 2013 ; Gérard et al., 2008 ; Stiepen et al., 2015). Observations of these emissions have been accumulated on a large dataset of nightside disk images and vertical profiles obtained at the limb by the Imaging Ultraviolet Spectrograph (IUVS, McClintock et al., 2015) instrument when the Mars Atmosphere and Volatile EvolutioN (MAVEN) spacecraft is at its apoapsis and its periapsis phases along its orbit, respectively. We present discussion on the variability in the brightness, altitude and topside scale height of the emission with season, geographical position and local time and possible interpretation for local and global changes in the mesosphere dynamics. IUVS images and limb scans reveal unexpected complex structure of the emission. The brightest emission is observed close to the winter pole. The emission is also surprisingly more intense in some sectors located close to the equator : at 120˚ and 150˚ longitude. Observations also reveal spots and streaks, indicating irregularities in the wind circulation pattern and possible impact of waves and tides. The disk images and limb profiles are compared to

  7. Molecular phylogeny of bark and ambrosia beetles reveals multiple origins of fungus farming during periods of global warming.

    PubMed

    Jordal, Bjarte H; Cognato, Anthony I

    2012-08-01

    Fungus farming is an unusual life style in insects that has evolved many times in the wood boring weevils named 'ambrosia beetles'. Multiple occurrences of this behaviour allow for a detailed comparison of the different origins of fungus farming through time, its directionality, and possible ancestral states. We tested these hypotheses with a phylogeny representing the largest data set to date, nearly 4 kb of nucleotides from COI, EF-1α, CAD, ArgK, 28S, and 200 scolytine taxa. Phylogenetic analyses using Bayesian or parsimony approaches placed the root of Scolytinae close to the tribe Scolytini and Microborus, but otherwise indicated low resolution at older nodes. More recent clades were well resolved, including ten origins of fungus farming. There were no subsequent reversals to bark or phloem feeding in the fungus farming clades. The oldest origin of fungus farming was estimated near 50 Ma, long after the origin of Scolytinae (100-120 Ma). Younger origins included the species rich Xyleborini, dated to 21 Ma. Sister group comparisons and test of independence between traits indicated that neither gregarious larval feeding nor regular inbreeding by sibling mating was strongly correlated with the origin of fungus farming. Origins of fungus farming corresponded mainly with two periods of global warming in the Cenozoic era, which were characterised by broadly distributed tropical forests. Hence, it seems likely that warm climates and expanding tropical angiosperm forests played critical roles in the successful radiation of diverse fungus farming groups. However, further investigation will likely reveal additional biological factors that promote fungus farming.

  8. Global transcription profiling reveals differential responses to chronic nitrogen stress and putative nitrogen regulatory components in Arabidopsis

    PubMed Central

    Bi, Yong-Mei; Wang, Rong-Lin; Zhu, Tong; Rothstein, Steven J

    2007-01-01

    Background A large quantity of nitrogen (N) fertilizer is used for crop production to achieve high yields at a significant economic and environmental cost. Efforts have been directed to understanding the molecular basis of plant responses to N and identifying N-responsive genes in order to manipulate their expression, thus enabling plants to use N more efficiently. No studies have yet delineated these responses at the transcriptional level when plants are grown under chronic N stress and the understanding of regulatory elements involved in N response is very limited. Results To further our understanding of the response of plants to varying N levels, a growth system was developed where N was the growth-limiting factor. An Arabidopsis whole genome microarray was used to evaluate global gene expression under different N conditions. Differentially expressed genes under mild or severe chronic N stress were identified. Mild N stress triggered only a small set of genes significantly different at the transcriptional level, which are largely involved in various stress responses. Plant responses were much more pronounced under severe N stress, involving a large number of genes in many different biological processes. Differentially expressed genes were also identified in response to short- and long-term N availability increases. Putative N regulatory elements were determined along with several previously known motifs involved in the responses to N and carbon availability as well as plant stress. Conclusion Differentially expressed genes identified provide additional insights into the coordination of the complex N responses of plants and the components of the N response mechanism. Putative N regulatory elements were identified to reveal possible new components of the regulatory network for plant N responses. A better understanding of the complex regulatory network for plant N responses will help lead to strategies to improve N use efficiency. PMID:17705847

  9. Molecular phylogeny of bark and ambrosia beetles reveals multiple origins of fungus farming during periods of global warming

    PubMed Central

    2012-01-01

    Background Fungus farming is an unusual life style in insects that has evolved many times in the wood boring weevils named ‘ambrosia beetles’. Multiple occurrences of this behaviour allow for a detailed comparison of the different origins of fungus farming through time, its directionality, and possible ancestral states. We tested these hypotheses with a phylogeny representing the largest data set to date, nearly 4 kb of nucleotides from COI, EF-1α, CAD, ArgK, 28S, and 200 scolytine taxa. Results Phylogenetic analyses using Bayesian or parsimony approaches placed the root of Scolytinae close to the tribe Scolytini and Microborus, but otherwise indicated low resolution at older nodes. More recent clades were well resolved, including ten origins of fungus farming. There were no subsequent reversals to bark or phloem feeding in the fungus farming clades. The oldest origin of fungus farming was estimated near 50 Ma, long after the origin of Scolytinae (100-120 Ma). Younger origins included the species rich Xyleborini, dated to 21 Ma. Sister group comparisons and test of independence between traits indicated that neither gregarious larval feeding nor regular inbreeding by sibling mating was strongly correlated with the origin of fungus farming. Conclusion Origins of fungus farming corresponded mainly with two periods of global warming in the Cenozoic era, which were characterised by broadly distributed tropical forests. Hence, it seems likely that warm climates and expanding tropical angiosperm forests played critical roles in the successful radiation of diverse fungus farming groups. However, further investigation will likely reveal additional biological factors that promote fungus farming. PMID:22852794

  10. Global Transcriptome Profiling Reveals Molecular Mechanisms of Metal Tolerance in a Chronically Exposed Wild Population of Brown Trout

    PubMed Central

    2013-01-01

    Worldwide, a number of viable populations of fish are found in environments heavily contaminated with metals, including brown trout (Salmo trutta) inhabiting the River Hayle in South-West of England. This population is chronically exposed to a water-borne mixture of metals, including copper and zinc, at concentrations lethal to naïve fish. We aimed to investigate the molecular mechanisms employed by the River Hayle brown trout to tolerate high metal concentrations. To achieve this, we combined tissue metal analysis with whole-transcriptome profiling using RNA-seq on an Illumina platform. Metal concentrations in the Hayle trout, compared to fish from a relatively unimpacted river, were significantly increased in the gills, liver and kidney (63-, 34- and 19-fold respectively), but not the gut. This confirms that these fish can tolerate considerable metal accumulation, highlighting the importance of these tissues in metal uptake (gill), storage and detoxification (liver, kidney). We sequenced, assembled and annotated the brown trout transcriptome using a de novo approach. Subsequent gene expression analysis identified 998 differentially expressed transcripts and functional analysis revealed that metal- and ion-homeostasis pathways are likely to be the most important mechanisms contributing to the metal tolerance exhibited by this population. PMID:23834071

  11. Transcriptome profiling analysis reveals metabolic changes across various growth phases in Bacillus pumilus BA06.

    PubMed

    Han, Lin-Li; Shao, Huan-Huan; Liu, Yong-Cheng; Liu, Gang; Xie, Chao-Ying; Cheng, Xiao-Jie; Wang, Hai-Yan; Tan, Xue-Mei; Feng, Hong

    2017-07-11

    Bacillus pumilus can secret abundant extracellular enzymes, and may be used as a potential host for the industrial production of enzymes. It is necessary to understand the metabolic processes during cellular growth. Here, an RNA-seq based transcriptome analysis was applied to examine B. pumilus BA06 across various growth stages to reveal metabolic changes under two conditions. Based on the gene expression levels, changes to metabolism pathways that were specific to various growth phases were enriched by KEGG analysis. Upon entry into the transition from the exponential growth phase, striking changes were revealed that included down-regulation of the tricarboxylic acid cycle, oxidative phosphorylation, flagellar assembly, and chemotaxis signaling. In contrast, the expression of stress-responding genes was induced when entering the transition phase, suggesting that the cell may suffer from stress during this growth stage. As expected, up-regulation of sporulation-related genes was continuous during the stationary growth phase, which was consistent with the observed sporulation. However, the expression pattern of the various extracellular proteases was different, suggesting that the regulatory mechanism may be distinct for various proteases. In addition, two protein secretion pathways were enriched with genes responsive to the observed protein secretion in B. pumilus. However, the expression of some genes that encode sporulation-related proteins and extracellular proteases was delayed by the addition of gelatin to the minimal medium. The transcriptome data depict global alterations in the genome-wide transcriptome across the various growth phases, which will enable an understanding of the physiology and phenotype of B. pumilus through gene expression.

  12. Phenotypic Analysis Reveals that the 2010 Haiti Cholera Epidemic Is Linked to a Hypervirulent Strain.

    PubMed

    Satchell, Karla J F; Jones, Christopher J; Wong, Jennifer; Queen, Jessica; Agarwal, Shivani; Yildiz, Fitnat H

    2016-09-01

    Vibrio cholerae O1 El Tor strains have been responsible for pandemic cholera since 1961. These strains have evolved over time, spreading globally in three separate waves. Wave 3 is caused by altered El Tor (AET) variant strains, which include the strain with the signature ctxB7 allele that was introduced in 2010 into Haiti, where it caused a devastating epidemic. In this study, we used phenotypic analysis to compare an early isolate from the Haiti epidemic to wave 1 El Tor isolates commonly used for research. It is demonstrated that the Haiti isolate has increased production of cholera toxin (CT) and hemolysin, increased motility, and a reduced ability to form biofilms. This strain also outcompetes common wave 1 El Tor isolates for colonization of infant mice, indicating that it has increased virulence. Monitoring of CT production and motility in additional wave 3 isolates revealed that this phenotypic variation likely evolved over time rather than in a single genetic event. Analysis of available whole-genome sequences and phylogenetic analyses suggested that increased virulence arose from positive selection for mutations found in known and putative regulatory genes, including hns and vieA, diguanylate cyclase genes, and genes belonging to the lysR and gntR regulatory families. Overall, the studies presented here revealed that V. cholerae virulence potential can evolve and that the currently prevalent wave 3 AET strains are both phenotypically distinct from and more virulent than many El Tor isolates. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  13. Visualization and analysis of eddies in a global ocean simulation

    SciTech Connect

    Williams, Sean J; Hecht, Matthew W; Petersen, Mark; Strelitz, Richard; Maltrud, Mathew E; Ahrens, James P; Hlawitschka, Mario; Hamann, Bernd

    2010-10-15

    Eddies at a scale of approximately one hundred kilometers have been shown to be surprisingly important to understanding large-scale transport of heat and nutrients in the ocean. Due to difficulties in observing the ocean directly, the behavior of eddies below the surface is not very well understood. To fill this gap, we employ a high-resolution simulation of the ocean developed at Los Alamos National Laboratory. Using large-scale parallel visualization and analysis tools, we produce three-dimensional images of ocean eddies, and also generate a census of eddy distribution and shape averaged over multiple simulation time steps, resulting in a world map of eddy characteristics. As expected from observational studies, our census reveals a higher concentration of eddies at the mid-latitudes than the equator. Our analysis further shows that mid-latitude eddies are thicker, within a range of 1000-2000m, while equatorial eddies are less than 100m thick.

  14. Different gene regulation strategies revealed by analysis of binding motifs.

    PubMed

    Wunderlich, Zeba; Mirny, Leonid A

    2009-10-01

    Coordinated regulation of gene expression relies on transcription factors (TFs) binding to specific DNA sites. Our large-scale information-theoretical analysis of > 950 TF-binding motifs demonstrates that prokaryotes and eukaryotes use strikingly different strategies to target TFs to specific genome locations. Although bacterial TFs can recognize a specific DNA site in the genomic background, eukaryotic TFs exhibit widespread, nonfunctional binding and require clustering of sites to achieve specificity. We find support for this mechanism in a range of experimental studies and in our evolutionary analysis of DNA-binding domains. Our systematic characterization of binding motifs provides a quantitative assessment of the differences in transcription regulation in prokaryotes and eukaryotes.

  15. Molecular Analysis of Sarcoidosis Granulomas Reveals Antimicrobial Targets.

    PubMed

    Rotsinger, Joseph E; Celada, Lindsay J; Polosukhin, Vasiliy V; Atkinson, James B; Drake, Wonder P

    2016-07-01

    Sarcoidosis is a granulomatous disease of unknown cause. Prior molecular and immunologic studies have confirmed the presence of mycobacterial virulence factors, such as catalase peroxidase and superoxide dismutase A, within sarcoidosis granulomas. Molecular analysis of granulomas can identify targets of known antibiotics classes. Currently, major antibiotics are directed against DNA synthesis, protein synthesis, and cell wall formation. We conducted molecular analysis of 40 sarcoidosis diagnostic specimens and compared them with 33 disease control specimens for the presence of mycobacterial genes that encode antibiotic targets. We assessed for genes involved in DNA synthesis (DNA gyrase A [gyrA] and DNA gyrase B), protein synthesis (RNA polymerase subunit β), cell wall synthesis (embCAB operon and enoyl reductase), and catalase peroxidase. Immunohistochemical analysis was conducted to investigate the locale of mycobacterial genes such as gyrA within 12 sarcoidosis specimens and 12 disease controls. Mycobacterial DNA was detected in 33 of 39 sarcoidosis specimens by quantitative real-time polymerase chain reaction compared with 2 of 30 disease control specimens (P < 0.001, two-tailed Fisher's test). Twenty of 39 were positive for three or more mycobacterial genes, compared with 1 of 30 control specimens (P < 0.001, two-tailed Fisher's test). Immunohistochemistry analysis localized mycobacterial gyrA nucleic acids to sites of granuloma formation in 9 of 12 sarcoidosis specimens compared with 1 of 12 disease controls (P < 0.01). Microbial genes encoding enzymes that can be targeted by currently available antimycobacterial antibiotics are present in sarcoidosis specimens and localize to sites of granulomatous inflammation. Use of antimicrobials directed against target enzymes may be an innovative treatment alternative.

  16. Diversity of Dilepididae (Cestoda: Cyclophyllidea) revealed by cytogenetic analysis.

    PubMed

    Petkeviciūte, R; Binkiene, R; Komisarovas, J

    2006-03-01

    Karyotypes of three dilepidid species: Molluscotaenia crassiscolex, Anomotaenia bacilligera and Dilepis undula, which have not been recorded previously, were studied using conventional Giemsa staining and comparative karyometric analysis. Twelve small biarmed chromosomes were observed in mitotic cells of M. crassiscolex, 16 biarmed chromosomes of gradually decreasing size were found in cells of A. bacilligera, while 18 elements were characteristic for D. undula. These data, together with information available in literature, prove the heterogeneity and possible polyphyletic nature of the family Dilepididae.

  17. Interindividual variability in auditory scene analysis revealed by confidence judgements.

    PubMed

    Pelofi, C; de Gardelle, V; Egré, P; Pressnitzer, D

    2017-02-19

    Because musicians are trained to discern sounds within complex acoustic scenes, such as an orchestra playing, it has been hypothesized that musicianship improves general auditory scene analysis abilities. Here, we compared musicians and non-musicians in a behavioural paradigm using ambiguous stimuli, combining performance, reaction times and confidence measures. We used 'Shepard tones', for which listeners may report either an upward or a downward pitch shift for the same ambiguous tone pair. Musicians and non-musicians performed similarly on the pitch-shift direction task. In particular, both groups were at chance for the ambiguous case. However, groups differed in their reaction times and judgements of confidence. Musicians responded to the ambiguous case with long reaction times and low confidence, whereas non-musicians responded with fast reaction times and maximal confidence. In a subsequent experiment, non-musicians displayed reduced confidence for the ambiguous case when pure-tone components of the Shepard complex were made easier to discern. The results suggest an effect of musical training on scene analysis: we speculate that musicians were more likely to discern components within complex auditory scenes, perhaps because of enhanced attentional resolution, and thus discovered the ambiguity. For untrained listeners, stimulus ambiguity was not available to perceptual awareness.This article is part of the themed issue 'Auditory and visual scene analysis'.

  18. Genome-Wide Association Mapping in the Global Diversity Set Reveals New QTL Controlling Root System and Related Shoot Variation in Barley

    PubMed Central

    Reinert, Stephan; Kortz, Annika; Léon, Jens; Naz, Ali A.

    2016-01-01

    The fibrous root system is a visible sign of ecological adaptation among barley natural populations. In the present study, we utilized rich barley diversity to dissect the genetic basis of root system variation and its link with shoot attributes under well-water and drought conditions. Genome-wide association mapping of phenotype data using a dense genetic map (5892 SNP markers) revealed 17 putative QTL for root and shoot traits. Among these, at 14 loci the preeminence of exotic QTL alleles resulted in trait improvements. The most promising QTL were quantified using haplotype analysis at local and global genome levels. The strongest QTL was found on chromosome 1H which accounted for root dry weight and tiller number simultaneously. Candidate gene analysis across the targeted region detected a crucial amino acid substitution mutation in the conserved domain of a WRKY29 transcription factor among genotypes bearing major and minor QTL alleles. Similarly, the drought inducible QTL QRdw.5H (5H, 95.0 cM) seems to underlie 37 amino acid deletion and substitution mutations in the conserved domain of two related genes CBF10B and CBF10A, respectively. The identification and further characterization of these candidate genes will be essential to decipher genetics behind developmental and natural adaptation mechanisms of barley. PMID:27486472

  19. Proteomic Analysis of Hylocereus polyrhizus Reveals Metabolic Pathway Changes

    PubMed Central

    Hua, Qingzhu; Zhou, Qianjun; Gan, Susheng; Wu, Jingyu; Chen, Canbin; Li, Jiaqiang; Ye, Yaoxiong; Zhao, Jietang; Hu, Guibing; Qin, Yonghua

    2016-01-01

    Red dragon fruit or red pitaya (Hylocereus polyrhizus) is the only edible fruit that contains betalains. The color of betalains ranges from red and violet to yellow in plants. Betalains may also serve as an important component of health-promoting and disease-preventing functional food. Currently, the biosynthetic and regulatory pathways for betalain production remain to be fully deciphered. In this study, isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomic analyses were used to reveal the molecular mechanism of betalain biosynthesis in H. polyrhizus fruits at white and red pulp stages, respectively. A total of 1946 proteins were identified as the differentially expressed between the two samples, and 936 of them were significantly highly expressed at the red pulp stage of H. polyrhizus. RNA-seq and iTRAQ analyses showed that some transcripts and proteins were positively correlated; they belonged to “phenylpropanoid biosynthesis”, “tyrosine metabolism”, “flavonoid biosynthesis”, “ascorbate and aldarate metabolism”, “betalains biosynthesis” and “anthocyanin biosynthesis”. In betalains biosynthesis pathway, several proteins/enzymes such as polyphenol oxidase, CYP76AD3 and 4,5-dihydroxy-phenylalanine (DOPA) dioxygenase extradiol-like protein were identified. The present study provides a new insight into the molecular mechanism of the betalain biosynthesis at the posttranscriptional level. PMID:27690004

  20. Integrative network analysis reveals molecular mechanisms of blood pressure regulation

    PubMed Central

    Huan, Tianxiao; Meng, Qingying; Saleh, Mohamed A; Norlander, Allison E; Joehanes, Roby; Zhu, Jun; Chen, Brian H; Zhang, Bin; Johnson, Andrew D; Ying, Saixia; Courchesne, Paul; Raghavachari, Nalini; Wan