Sample records for global expression response

  1. Global Genetic Response in a Cancer Cell: Self-Organized Coherent Expression Dynamics

    PubMed Central

    Tsuchiya, Masa; Hashimoto, Midori; Takenaka, Yoshiko; Motoike, Ikuko N.; Yoshikawa, Kenichi

    2014-01-01

    Understanding the basic mechanism of the spatio-temporal self-control of genome-wide gene expression engaged with the complex epigenetic molecular assembly is one of major challenges in current biological science. In this study, the genome-wide dynamical profile of gene expression was analyzed for MCF-7 breast cancer cells induced by two distinct ErbB receptor ligands: epidermal growth factor (EGF) and heregulin (HRG), which drive cell proliferation and differentiation, respectively. We focused our attention to elucidate how global genetic responses emerge and to decipher what is an underlying principle for dynamic self-control of genome-wide gene expression. The whole mRNA expression was classified into about a hundred groups according to the root mean square fluctuation (rmsf). These expression groups showed characteristic time-dependent correlations, indicating the existence of collective behaviors on the ensemble of genes with respect to mRNA expression and also to temporal changes in expression. All-or-none responses were observed for HRG and EGF (biphasic statistics) at around 10–20 min. The emergence of time-dependent collective behaviors of expression occurred through bifurcation of a coherent expression state (CES). In the ensemble of mRNA expression, the self-organized CESs reveals distinct characteristic expression domains for biphasic statistics, which exhibits notably the presence of criticality in the expression profile as a route for genomic transition. In time-dependent changes in the expression domains, the dynamics of CES reveals that the temporal development of the characteristic domains is characterized as autonomous bistable switch, which exhibits dynamic criticality (the temporal development of criticality) in the genome-wide coherent expression dynamics. It is expected that elucidation of the biophysical origin for such critical behavior sheds light on the underlying mechanism of the control of whole genome. PMID:24831017

  2. Global gene expression analysis of the heat shock response in the phytopathogen Xylella fastidiosa.

    PubMed

    Koide, Tie; Vêncio, Ricardo Z N; Gomes, Suely L

    2006-08-01

    Xylella fastidiosa is a phytopathogenic bacterium that is responsible for diseases in many economically important crops. Although different strains have been studied, little is known about X. fastidiosa stress responses. One of the better characterized stress responses in bacteria is the heat shock response, which induces the expression of specific genes to prevent protein misfolding and aggregation and to promote degradation of the irreversibly denatured polypeptides. To investigate X. fastidiosa genes involved in the heat shock response, we performed a whole-genome microarray analysis in a time course experiment. Globally, 261 genes were induced (9.7%) and 222 genes were repressed (8.3%). The expression profiles of the differentially expressed genes were grouped, and their expression patterns were validated by quantitative reverse transcription-PCR experiments. We determined the transcription start sites of six heat shock-inducible genes and analyzed their promoter regions, which allowed us to propose a putative consensus for sigma(32) promoters in Xylella and to suggest additional genes as putative members of this regulon. Besides the induction of classical heat shock protein genes, we observed the up-regulation of virulence-associated genes such as vapD and of genes for hemagglutinins, hemolysin, and xylan-degrading enzymes, which may indicate the importance of heat stress to bacterial pathogenesis. In addition, we observed the repression of genes related to fimbriae, aerobic respiration, and protein biosynthesis and the induction of genes related to the extracytoplasmic stress response and some phage-related genes, revealing the complex network of genes that work together in response to heat shock.

  3. Gene expression profiling--Opening the black box of plant ecosystem responses to global change

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Leakey, A.D.B.; Ainsworth, E.A.; Bernard, S.M.

    The use of genomic techniques to address ecological questions is emerging as the field of genomic ecology. Experimentation under environmentally realistic conditions to investigate the molecular response of plants to meaningful changes in growth conditions and ecological interactions is the defining feature of genomic ecology. Since the impact of global change factors on plant performance are mediated by direct effects at the molecular, biochemical and physiological scales, gene expression analysis promises important advances in understanding factors that have previously been consigned to the 'black box' of unknown mechanism. Various tools and approaches are available for assessing gene expression in modelmore » and non-model species as part of global change biology studies. Each approach has its own unique advantages and constraints. A first generation of genomic ecology studies in managed ecosystems and mesocosms have provided a testbed for the approach and have begun to reveal how the experimental design and data analysis of gene expression studies can be tailored for use in an ecological context.« less

  4. Global analysis of gene expression reveals mRNA superinduction is required for the inducible immune response to a bacterial pathogen

    PubMed Central

    Barry, Kevin C; Ingolia, Nicholas T; Vance, Russell E

    2017-01-01

    The inducible innate immune response to infection requires a concerted process of gene expression that is regulated at multiple levels. Most global analyses of the innate immune response have focused on transcription induced by defined immunostimulatory ligands, such as lipopolysaccharide. However, the response to pathogens involves additional complexity, as pathogens interfere with virtually every step of gene expression. How cells respond to pathogen-mediated disruption of gene expression to nevertheless initiate protective responses remains unclear. We previously discovered that a pathogen-mediated blockade of host protein synthesis provokes the production of specific pro-inflammatory cytokines. It remains unclear how these cytokines are produced despite the global pathogen-induced block of translation. We addressed this question by using parallel RNAseq and ribosome profiling to characterize the response of macrophages to infection with the intracellular bacterial pathogen Legionella pneumophila. Our results reveal that mRNA superinduction is required for the inducible immune response to a bacterial pathogen. DOI: http://dx.doi.org/10.7554/eLife.22707.001 PMID:28383283

  5. Global differential gene expression in response to growth temperature alteration in group A Streptococcus.

    PubMed

    Smoot, L M; Smoot, J C; Graham, M R; Somerville, G A; Sturdevant, D E; Migliaccio, C A; Sylva, G L; Musser, J M

    2001-08-28

    Pathogens are exposed to different temperatures during an infection cycle and must regulate gene expression accordingly. However, the extent to which virulent bacteria alter gene expression in response to temperatures encountered in the host is unknown. Group A Streptococcus (GAS) is a human-specific pathogen that is responsible for illnesses ranging from superficial skin infections and pharyngitis to severe invasive infections such as necrotizing fasciitis and streptococcal toxic shock syndrome. GAS survives and multiplies at different temperatures during human infection. DNA microarray analysis was used to investigate the influence of temperature on global gene expression in a serotype M1 strain grown to exponential phase at 29 degrees C and 37 degrees C. Approximately 9% of genes were differentially expressed by at least 1.5-fold at 29 degrees C relative to 37 degrees C, including genes encoding transporter proteins, proteins involved in iron homeostasis, transcriptional regulators, phage-associated proteins, and proteins with no known homologue. Relatively few known virulence genes were differentially expressed at this threshold. However, transcription of 28 genes encoding proteins with predicted secretion signal sequences was altered, indicating that growth temperature substantially influences the extracellular proteome. TaqMan real-time reverse transcription-PCR assays confirmed the microarray data. We also discovered that transcription of genes encoding hemolysins, and proteins with inferred roles in iron regulation, transport, and homeostasis, was influenced by growth at 40 degrees C. Thus, GAS profoundly alters gene expression in response to temperature. The data delineate the spectrum of temperature-regulated gene expression in an important human pathogen and provide many unforeseen lines of pathogenesis investigation.

  6. Haloperidol induces pharmacoepigenetic response by modulating miRNA expression, global DNA methylation and expression profiles of methylation maintenance genes and genes involved in neurotransmission in neuronal cells.

    PubMed

    Swathy, Babu; Banerjee, Moinak

    2017-01-01

    Haloperidol has been extensively used in various psychiatric conditions. It has also been reported to induce severe side effects. We aimed to evaluate whether haloperidol can influence host methylome, and if so what are the possible mechanisms for it in neuronal cells. Impact on host methylome and miRNAs can have wide spread alterations in gene expression, which might possibly help in understanding how haloperidol may impact treatment response or induce side effects. SK-N-SH, a neuroblasoma cell line was treated with haloperidol at 10μm concentration for 24 hours and global DNA methylation was evaluated. Methylation at global level is maintained by methylation maintenance machinery and certain miRNAs. Therefore, the expression of methylation maintenance genes and their putative miRNA expression profiles were assessed. These global methylation alterations could result in gene expression changes. Therefore genes expressions for neurotransmitter receptors, regulators, ion channels and transporters were determined. Subsequently, we were also keen to identify a strong candidate miRNA based on biological and in-silico approach which can reflect on the pharmacoepigenetic trait of haloperidol and can also target the altered neuroscience panel of genes used in the study. Haloperidol induced increase in global DNA methylation which was found to be associated with corresponding increase in expression of various epigenetic modifiers that include DNMT1, DNMT3A, DNMT3B and MBD2. The expression of miR-29b that is known to putatively regulate the global methylation by modulating the expression of epigenetic modifiers was observed to be down regulated by haloperidol. In addition to miR-29b, miR-22 was also found to be downregulated by haloperidol treatment. Both these miRNA are known to putatively target several genes associated with various epigenetic modifiers, pharmacogenes and neurotransmission. Interestingly some of these putative target genes involved in neurotransmission

  7. Haloperidol induces pharmacoepigenetic response by modulating miRNA expression, global DNA methylation and expression profiles of methylation maintenance genes and genes involved in neurotransmission in neuronal cells

    PubMed Central

    Swathy, Babu

    2017-01-01

    Introduction Haloperidol has been extensively used in various psychiatric conditions. It has also been reported to induce severe side effects. We aimed to evaluate whether haloperidol can influence host methylome, and if so what are the possible mechanisms for it in neuronal cells. Impact on host methylome and miRNAs can have wide spread alterations in gene expression, which might possibly help in understanding how haloperidol may impact treatment response or induce side effects. Methods SK-N-SH, a neuroblasoma cell line was treated with haloperidol at 10μm concentration for 24 hours and global DNA methylation was evaluated. Methylation at global level is maintained by methylation maintenance machinery and certain miRNAs. Therefore, the expression of methylation maintenance genes and their putative miRNA expression profiles were assessed. These global methylation alterations could result in gene expression changes. Therefore genes expressions for neurotransmitter receptors, regulators, ion channels and transporters were determined. Subsequently, we were also keen to identify a strong candidate miRNA based on biological and in-silico approach which can reflect on the pharmacoepigenetic trait of haloperidol and can also target the altered neuroscience panel of genes used in the study. Results Haloperidol induced increase in global DNA methylation which was found to be associated with corresponding increase in expression of various epigenetic modifiers that include DNMT1, DNMT3A, DNMT3B and MBD2. The expression of miR-29b that is known to putatively regulate the global methylation by modulating the expression of epigenetic modifiers was observed to be down regulated by haloperidol. In addition to miR-29b, miR-22 was also found to be downregulated by haloperidol treatment. Both these miRNA are known to putatively target several genes associated with various epigenetic modifiers, pharmacogenes and neurotransmission. Interestingly some of these putative target genes

  8. Global gene expression and systems biology analysis of bovine monocyte-derived macrophages in response to in vitro challenge with Mycobacterium bovis.

    PubMed

    Magee, David A; Taraktsoglou, Maria; Killick, Kate E; Nalpas, Nicolas C; Browne, John A; Park, Stephen D E; Conlon, Kevin M; Lynn, David J; Hokamp, Karsten; Gordon, Stephen V; Gormley, Eamonn; MacHugh, David E

    2012-01-01

    Mycobacterium bovis, the causative agent of bovine tuberculosis, is a major cause of mortality in global cattle populations. Macrophages are among the first cell types to encounter M. bovis following exposure and the response elicited by these cells is pivotal in determining the outcome of infection. Here, a functional genomics approach was undertaken to investigate global gene expression profiles in bovine monocyte-derived macrophages (MDM) purified from seven age-matched non-related females, in response to in vitro challenge with M. bovis (multiplicity of infection 2:1). Total cellular RNA was extracted from non-challenged control and M. bovis-challenged MDM for all animals at intervals of 2 hours, 6 hours and 24 hours post-challenge and prepared for global gene expression analysis using the Affymetrix® GeneChip® Bovine Genome Array. Comparison of M. bovis-challenged MDM gene expression profiles with those from the non-challenged MDM controls at each time point identified 3,064 differentially expressed genes 2 hours post-challenge, with 4,451 and 5,267 differentially expressed genes detected at the 6 hour and 24 hour time points, respectively (adjusted P-value threshold ≤ 0.05). Notably, the number of downregulated genes exceeded the number of upregulated genes in the M. bovis-challenged MDM across all time points; however, the fold-change in expression for the upregulated genes was markedly higher than that for the downregulated genes. Systems analysis revealed enrichment for genes involved in: (1) the inflammatory response; (2) cell signalling pathways, including Toll-like receptors and intracellular pathogen recognition receptors; and (3) apoptosis. The increased number of downregulated genes is consistent with previous studies showing that M. bovis infection is associated with the repression of host gene expression. The results also support roles for MyD88-independent signalling and intracellular PRRs in mediating the host response to M. bovis.

  9. Culturally Responsive: Art Education in a Global Era

    ERIC Educational Resources Information Center

    Lai, Alice

    2012-01-01

    Facing the era of globalization, culturally responsive art teachers must recognize that students' home culture, including local artistic expression, is inevitably influenced by global forces. They should strive to engage with students systems and issues of globalization and its impact on their community culture and art. In this article, the author…

  10. Global Gene-Expression Analysis to Identify Differentially Expressed Genes Critical for the Heat Stress Response in Brassica rapa

    PubMed Central

    Dong, Xiangshu; Yi, Hankuil; Lee, Jeongyeo; Nou, Ill-Sup; Han, Ching-Tack; Hur, Yoonkang

    2015-01-01

    Genome-wide dissection of the heat stress response (HSR) is necessary to overcome problems in crop production caused by global warming. To identify HSR genes, we profiled gene expression in two Chinese cabbage inbred lines with different thermotolerances, Chiifu and Kenshin. Many genes exhibited >2-fold changes in expression upon exposure to 0.5– 4 h at 45°C (high temperature, HT): 5.2% (2,142 genes) in Chiifu and 3.7% (1,535 genes) in Kenshin. The most enriched GO (Gene Ontology) items included ‘response to heat’, ‘response to reactive oxygen species (ROS)’, ‘response to temperature stimulus’, ‘response to abiotic stimulus’, and ‘MAPKKK cascade’. In both lines, the genes most highly induced by HT encoded small heat shock proteins (Hsps) and heat shock factor (Hsf)-like proteins such as HsfB2A (Bra029292), whereas high-molecular weight Hsps were constitutively expressed. Other upstream HSR components were also up-regulated: ROS-scavenging genes like glutathione peroxidase 2 (BrGPX2, Bra022853), protein kinases, and phosphatases. Among heat stress (HS) marker genes in Arabidopsis, only exportin 1A (XPO1A) (Bra008580, Bra006382) can be applied to B. rapa for basal thermotolerance (BT) and short-term acquired thermotolerance (SAT) gene. CYP707A3 (Bra025083, Bra021965), which is involved in the dehydration response in Arabidopsis, was associated with membrane leakage in both lines following HS. Although many transcription factors (TF) genes, including DREB2A (Bra005852), were involved in HS tolerance in both lines, Bra024224 (MYB41) and Bra021735 (a bZIP/AIR1 [Anthocyanin-Impaired-Response-1]) were specific to Kenshin. Several candidate TFs involved in thermotolerance were confirmed as HSR genes by real-time PCR, and these assignments were further supported by promoter analysis. Although some of our findings are similar to those obtained using other plant species, clear differences in Brassica rapa reveal a distinct HSR in this species. Our data

  11. Global analysis of transcriptome responses and gene expression profiles to cold stress of Jatropha curcas L.

    PubMed

    Wang, Haibo; Zou, Zhurong; Wang, Shasha; Gong, Ming

    2013-01-01

    Jatropha curcas L., also called the Physic nut, is an oil-rich shrub with multiple uses, including biodiesel production, and is currently exploited as a renewable energy resource in many countries. Nevertheless, because of its origin from the tropical MidAmerican zone, J. curcas confers an inherent but undesirable characteristic (low cold resistance) that may seriously restrict its large-scale popularization. This adaptive flaw can be genetically improved by elucidating the mechanisms underlying plant tolerance to cold temperatures. The newly developed Illumina Hiseq™ 2000 RNA-seq and Digital Gene Expression (DGE) are deep high-throughput approaches for gene expression analysis at the transcriptome level, using which we carefully investigated the gene expression profiles in response to cold stress to gain insight into the molecular mechanisms of cold response in J. curcas. In total, 45,251 unigenes were obtained by assembly of clean data generated by RNA-seq analysis of the J. curcas transcriptome. A total of 33,363 and 912 complete or partial coding sequences (CDSs) were determined by protein database alignments and ESTScan prediction, respectively. Among these unigenes, more than 41.52% were involved in approximately 128 known metabolic or signaling pathways, and 4,185 were possibly associated with cold resistance. DGE analysis was used to assess the changes in gene expression when exposed to cold condition (12°C) for 12, 24, and 48 h. The results showed that 3,178 genes were significantly upregulated and 1,244 were downregulated under cold stress. These genes were then functionally annotated based on the transcriptome data from RNA-seq analysis. This study provides a global view of transcriptome response and gene expression profiling of J. curcas in response to cold stress. The results can help improve our current understanding of the mechanisms underlying plant cold resistance and favor the screening of crucial genes for genetically enhancing cold resistance

  12. Global gene expression of Prochlorococcus ecotypes in response to changes in nitrogen availability

    PubMed Central

    Tolonen, Andrew C; Aach, John; Lindell, Debbie; Johnson, Zackary I; Rector, Trent; Steen, Robert; Church, George M; Chisholm, Sallie W

    2006-01-01

    Nitrogen (N) often limits biological productivity in the oceanic gyres where Prochlorococcus is the most abundant photosynthetic organism. The Prochlorococcus community is composed of strains, such as MED4 and MIT9313, that have different N utilization capabilities and that belong to ecotypes with different depth distributions. An interstrain comparison of how Prochlorococcus responds to changes in ambient nitrogen is thus central to understanding its ecology. We quantified changes in MED4 and MIT9313 global mRNA expression, chlorophyll fluorescence, and photosystem II photochemical efficiency (Fv/Fm) along a time series of increasing N starvation. In addition, the global expression of both strains growing in ammonium-replete medium was compared to expression during growth on alternative N sources. There were interstrain similarities in N regulation such as the activation of a putative NtcA regulon during N stress. There were also important differences between the strains such as in the expression patterns of carbon metabolism genes, suggesting that the two strains integrate N and C metabolism in fundamentally different ways. PMID:17016519

  13. Global Analysis of Transcriptome Responses and Gene Expression Profiles to Cold Stress of Jatropha curcas L.

    PubMed Central

    Wang, Haibo; Zou, Zhurong; Wang, Shasha; Gong, Ming

    2013-01-01

    Background Jatropha curcas L., also called the Physic nut, is an oil-rich shrub with multiple uses, including biodiesel production, and is currently exploited as a renewable energy resource in many countries. Nevertheless, because of its origin from the tropical MidAmerican zone, J. curcas confers an inherent but undesirable characteristic (low cold resistance) that may seriously restrict its large-scale popularization. This adaptive flaw can be genetically improved by elucidating the mechanisms underlying plant tolerance to cold temperatures. The newly developed Illumina Hiseq™ 2000 RNA-seq and Digital Gene Expression (DGE) are deep high-throughput approaches for gene expression analysis at the transcriptome level, using which we carefully investigated the gene expression profiles in response to cold stress to gain insight into the molecular mechanisms of cold response in J. curcas. Results In total, 45,251 unigenes were obtained by assembly of clean data generated by RNA-seq analysis of the J. curcas transcriptome. A total of 33,363 and 912 complete or partial coding sequences (CDSs) were determined by protein database alignments and ESTScan prediction, respectively. Among these unigenes, more than 41.52% were involved in approximately 128 known metabolic or signaling pathways, and 4,185 were possibly associated with cold resistance. DGE analysis was used to assess the changes in gene expression when exposed to cold condition (12°C) for 12, 24, and 48 h. The results showed that 3,178 genes were significantly upregulated and 1,244 were downregulated under cold stress. These genes were then functionally annotated based on the transcriptome data from RNA-seq analysis. Conclusions This study provides a global view of transcriptome response and gene expression profiling of J. curcas in response to cold stress. The results can help improve our current understanding of the mechanisms underlying plant cold resistance and favor the screening of crucial genes for

  14. Global Genetic Variations Predict Brain Response to Faces

    PubMed Central

    Dickie, Erin W.; Tahmasebi, Amir; French, Leon; Kovacevic, Natasa; Banaschewski, Tobias; Barker, Gareth J.; Bokde, Arun; Büchel, Christian; Conrod, Patricia; Flor, Herta; Garavan, Hugh; Gallinat, Juergen; Gowland, Penny; Heinz, Andreas; Ittermann, Bernd; Lawrence, Claire; Mann, Karl; Martinot, Jean-Luc; Nees, Frauke; Nichols, Thomas; Lathrop, Mark; Loth, Eva; Pausova, Zdenka; Rietschel, Marcela; Smolka, Michal N.; Ströhle, Andreas; Toro, Roberto; Schumann, Gunter; Paus, Tomáš

    2014-01-01

    Face expressions are a rich source of social signals. Here we estimated the proportion of phenotypic variance in the brain response to facial expressions explained by common genetic variance captured by ∼500,000 single nucleotide polymorphisms. Using genomic-relationship-matrix restricted maximum likelihood (GREML), we related this global genetic variance to that in the brain response to facial expressions, as assessed with functional magnetic resonance imaging (fMRI) in a community-based sample of adolescents (n = 1,620). Brain response to facial expressions was measured in 25 regions constituting a face network, as defined previously. In 9 out of these 25 regions, common genetic variance explained a significant proportion of phenotypic variance (40–50%) in their response to ambiguous facial expressions; this was not the case for angry facial expressions. Across the network, the strength of the genotype-phenotype relationship varied as a function of the inter-individual variability in the number of functional connections possessed by a given region (R2 = 0.38, p<0.001). Furthermore, this variability showed an inverted U relationship with both the number of observed connections (R2 = 0.48, p<0.001) and the magnitude of brain response (R2 = 0.32, p<0.001). Thus, a significant proportion of the brain response to facial expressions is predicted by common genetic variance in a subset of regions constituting the face network. These regions show the highest inter-individual variability in the number of connections with other network nodes, suggesting that the genetic model captures variations across the adolescent brains in co-opting these regions into the face network. PMID:25122193

  15. Terrestrial Feedbacks Incorporated in Global Vegetation Models through Observed Trait-Environment Responses

    NASA Astrophysics Data System (ADS)

    Bodegom, P. V.

    2015-12-01

    Most global vegetation models used to evaluate climate change impacts rely on plant functional types to describe vegetation responses to environmental stresses. In a traditional set-up in which vegetation characteristics are considered constant within a vegetation type, the possibility to implement and infer feedback mechanisms are limited as feedback mechanisms will likely involve a changing expression of community trait values. Based on community assembly concepts, we implemented functional trait-environment relationships into a global dynamic vegetation model to quantitatively assess this feature. For the current climate, a different global vegetation distribution was calculated with and without the inclusion of trait variation, emphasizing the importance of feedbacks -in interaction with competitive processes- for the prevailing global patterns. These trait-environmental responses do, however, not necessarily imply adaptive responses of vegetation to changing conditions and may locally lead to a faster turnover in vegetation upon climate change. Indeed, when running climate projections, simulations with trait variation did not yield a more stable or resilient vegetation than those without. Through the different feedback expressions, global and regional carbon and water fluxes were -however- strongly altered. At a global scale, model projections suggest an increased productivity and hence an increased carbon sink in the next decades to come, when including trait variation. However, by the end of the century, a reduced carbon sink is projected. This effect is due to a downregulation of photosynthesis rates, particularly in the tropical regions, even when accounting for CO2-fertilization effects. Altogether, the various global model simulations suggest the critical importance of including vegetation functional responses to changing environmental conditions to grasp terrestrial feedback mechanisms at global scales in the light of climate change.

  16. Global Analysis of Gene Expression in Response to Whole-Chromosome Aneuploidy in Hexaploid Wheat1[OPEN

    PubMed Central

    Zhang, Ai; Li, Ning; Gong, Lei; Gou, Xiaowan; Wang, Bin; Deng, Xin; Li, Changping; Dong, Qianli; Zhang, Huakun

    2017-01-01

    Aneuploidy, a condition of unbalanced chromosome content, represents a large-effect mutation that bears significant relevance to human health and microbe adaptation. As such, extensive studies of aneuploidy have been conducted in unicellular model organisms and cancer cells. Aneuploidy also frequently is associated with plant polyploidization, but its impact on gene expression and its relevance to polyploid genome evolution/functional innovation remain largely unknown. Here, we used a panel of diverse types of whole-chromosome aneuploidy of hexaploid wheat (Triticum aestivum), all under the common genetic background of cv Chinese Spring, to systemically investigate the impact of aneuploidy on genome-, subgenome-, and chromosome-wide gene expression. Compared with prior findings in haploid or diploid aneuploid systems, we unravel additional and novel features of alteration in global gene expression resulting from the two major impacts of aneuploidy, cis- and trans-regulation, as well as dosage compensation. We show that the expression-altered genes map evenly along each chromosome, with no evidence for coregulating aggregated expression domains. However, chromosomes and subgenomes in hexaploid wheat are unequal in their responses to aneuploidy with respect to the number of genes being dysregulated. Strikingly, homeologous chromosomes do not differ from nonhomologous chromosomes in terms of aneuploidy-induced trans-acting effects, suggesting that the three constituent subgenomes of hexaploid wheat are largely uncoupled at the transcriptional level of gene regulation. Together, our findings shed new insights into the functional interplay between homeologous chromosomes and interactions between subgenomes in hexaploid wheat, which bear implications to further our understanding of allopolyploid genome evolution and efforts in breeding new allopolyploid crops. PMID:28821592

  17. Global Expression Profiling in Atopic Eczema Reveals Reciprocal Expression of Inflammatory and Lipid Genes

    PubMed Central

    Sääf, Annika M.; Tengvall-Linder, Maria; Chang, Howard Y.; Adler, Adam S.; Wahlgren, Carl-Fredrik; Scheynius, Annika; Nordenskjöld, Magnus; Bradley, Maria

    2008-01-01

    Background Atopic eczema (AE) is a common chronic inflammatory skin disorder. In order to dissect the genetic background several linkage and genetic association studies have been performed. Yet very little is known about specific genes involved in this complex skin disease, and the underlying molecular mechanisms are not fully understood. Methodology/Findings We used human DNA microarrays to identify a molecular picture of the programmed responses of the human genome to AE. The transcriptional program was analyzed in skin biopsy samples from lesional and patch-tested skin from AE patients sensitized to Malassezia sympodialis (M. sympodialis), and corresponding biopsies from healthy individuals. The most notable feature of the global gene-expression pattern observed in AE skin was a reciprocal expression of induced inflammatory genes and repressed lipid metabolism genes. The overall transcriptional response in M. sympodialis patch-tested AE skin was similar to the gene-expression signature identified in lesional AE skin. In the constellation of genes differentially expressed in AE skin compared to healthy control skin, we have identified several potential susceptibility genes that may play a critical role in the pathological condition of AE. Many of these genes, including genes with a role in immune responses, lipid homeostasis, and epidermal differentiation, are localized on chromosomal regions previously linked to AE. Conclusions/Significance Through genome-wide expression profiling, we were able to discover a distinct reciprocal expression pattern of induced inflammatory genes and repressed lipid metabolism genes in skin from AE patients. We found a significant enrichment of differentially expressed genes in AE with cytobands associated to the disease, and furthermore new chromosomal regions were found that could potentially guide future region-specific linkage mapping in AE. The full data set is available at http://microarray-pubs.stanford.edu/eczema. PMID

  18. Self-Organizing Global Gene Expression Regulated through Criticality: Mechanism of the Cell-Fate Change

    PubMed Central

    Tsuchiya, Masa; Giuliani, Alessandro; Hashimoto, Midori; Erenpreisa, Jekaterina; Yoshikawa, Kenichi

    2016-01-01

    Background A fundamental issue in bioscience is to understand the mechanism that underlies the dynamic control of genome-wide expression through the complex temporal-spatial self-organization of the genome to regulate the change in cell fate. We address this issue by elucidating a physically motivated mechanism of self-organization. Principal Findings Building upon transcriptome experimental data for seven distinct cell fates, including early embryonic development, we demonstrate that self-organized criticality (SOC) plays an essential role in the dynamic control of global gene expression regulation at both the population and single-cell levels. The novel findings are as follows: i) Mechanism of cell-fate changes: A sandpile-type critical transition self-organizes overall expression into a few transcription response domains (critical states). A cell-fate change occurs by means of a dissipative pulse-like global perturbation in self-organization through the erasure of initial-state critical behaviors (criticality). Most notably, the reprogramming of early embryo cells destroys the zygote SOC control to initiate self-organization in the new embryonal genome, which passes through a stochastic overall expression pattern. ii) Mechanism of perturbation of SOC controls: Global perturbations in self-organization involve the temporal regulation of critical states. Quantitative evaluation of this perturbation in terminal cell fates reveals that dynamic interactions between critical states determine the critical-state coherent regulation. The occurrence of a temporal change in criticality perturbs this between-states interaction, which directly affects the entire genomic system. Surprisingly, a sub-critical state, corresponding to an ensemble of genes that shows only marginal changes in expression and consequently are considered to be devoid of any interest, plays an essential role in generating a global perturbation in self-organization directed toward the cell-fate change

  19. Different Temporal Effects of Ebola Virus VP35 and VP24 Proteins on Global Gene Expression in Human Dendritic Cells.

    PubMed

    Ilinykh, Philipp A; Lubaki, Ndongala M; Widen, Steven G; Renn, Lynnsey A; Theisen, Terence C; Rabin, Ronald L; Wood, Thomas G; Bukreyev, Alexander

    2015-08-01

    Ebola virus (EBOV) causes a severe hemorrhagic fever with a deficient immune response, lymphopenia, and lymphocyte apoptosis. Dendritic cells (DC), which trigger the adaptive response, do not mature despite EBOV infection. We recently demonstrated that DC maturation is unblocked by disabling the innate response antagonizing domains (IRADs) in EBOV VP35 and VP24 by the mutations R312A and K142A, respectively. Here we analyzed the effects of VP35 and VP24 with the IRADs disabled on global gene expression in human DC. Human monocyte-derived DC were infected by wild-type (wt) EBOV or EBOVs carrying the mutation in VP35 (EBOV/VP35m), VP24 (EBOV/VP24m), or both (EBOV/VP35m/VP24m). Global gene expression at 8 and 24 h was analyzed by deep sequencing, and the expression of interferon (IFN) subtypes up to 5 days postinfection was analyzed by quantitative reverse transcription-PCR (qRT-PCR). wt EBOV induced a weak global gene expression response, including markers of DC maturation, cytokines, chemokines, chemokine receptors, and multiple IFNs. The VP35 mutation unblocked the expression, resulting in a dramatic increase in expression of these transcripts at 8 and 24 h. Surprisingly, DC infected with EBOV/VP24m expressed lower levels of many of these transcripts at 8 h after infection, compared to wt EBOV. In contrast, at 24 h, expression of the transcripts increased in DC infected with any of the three mutants, compared to wt EBOV. Moreover, sets of genes affected by the two mutations only partially overlapped. Pathway analysis demonstrated that the VP35 mutation unblocked pathways involved in antigen processing and presentation and IFN signaling. These data suggest that EBOV IRADs have profound effects on the host adaptive immune response through massive transcriptional downregulation of DC. This study shows that infection of DC with EBOV, but not its mutant forms with the VP35 IRAD and/or VP24 IRAD disabled, causes a global block in expression of host genes. The temporal

  20. Neural responses to facial expression and face identity in the monkey amygdala.

    PubMed

    Gothard, K M; Battaglia, F P; Erickson, C A; Spitler, K M; Amaral, D G

    2007-02-01

    The amygdala is purported to play an important role in face processing, yet the specificity of its activation to face stimuli and the relative contribution of identity and expression to its activation are unknown. In the current study, neural activity in the amygdala was recorded as monkeys passively viewed images of monkey faces, human faces, and objects on a computer monitor. Comparable proportions of neurons responded selectively to images from each category. Neural responses to monkey faces were further examined to determine whether face identity or facial expression drove the face-selective responses. The majority of these neurons (64%) responded both to identity and facial expression, suggesting that these parameters are processed jointly in the amygdala. Large fractions of neurons, however, showed pure identity-selective or expression-selective responses. Neurons were selective for a particular facial expression by either increasing or decreasing their firing rate compared with the firing rates elicited by the other expressions. Responses to appeasing faces were often marked by significant decreases of firing rates, whereas responses to threatening faces were strongly associated with increased firing rate. Thus global activation in the amygdala might be larger to threatening faces than to neutral or appeasing faces.

  1. From conceptual pluralism to practical agreement on policy: global responsibility for global health.

    PubMed

    Ruger, Jennifer Prah; Hammonds, Rachel; Ooms, Gorik; Barry, Donna; Chapman, Audrey; Van Damme, Wim

    2015-10-28

    As the human cost of the global economic crisis becomes apparent the ongoing discussions surrounding the post-2015 global development framework continue at a frenzied pace. Given the scale and scope of increased globalization moving forward in a post-Millennium Development Goals era, to protect and realize health equity for all people, has never been more challenging or more important. The unprecedented nature of global interdependence underscores the importance of proposing policy solutions that advance realizing global responsibility for global health. This article argues for advancing global responsibility for global health through the creation of a Global Fund for Health. It suggests harnessing the power of the exceptional response to the combined epidemics of AIDS, TB and Malaria, embodied in the Global Fund to Fight AIDS, Tuberculosis and Malaria, to realize an expanded, reconceptualized Global Fund for Health. However this proposal creates both an analytical quandary embedded in conceptual pluralism and a practical dilemma for the scope and raison d'etre of a new Global Fund for Health. To address these issues we offer a logical framework for moving from conceptual pluralism in the theories supporting global responsibility for health to practical agreement on policy to realize this end. We examine how the innovations flowing from this exceptional response can be coupled with recent ideas and concepts, for example a global social protection floor, a Global Health Constitution or a Framework Convention for Global Health, that share the global responsibility logic that underpins a Global Fund for Health. The 2014 Lancet Commission on Global Governance for Health Report asks whether a single global health protection fund would be better for global health than the current patchwork of global and national social transfers. We concur with this suggestion and argue that there is much room for practical agreement on a Global Fund for Health that moves from the

  2. Global gene expression analysis of early response to chemotherapy treatment in ovarian cancer spheroids.

    PubMed

    L'Espérance, Sylvain; Bachvarova, Magdalena; Tetu, Bernard; Mes-Masson, Anne-Marie; Bachvarov, Dimcho

    2008-02-26

    Chemotherapy (CT) resistance in ovarian cancer (OC) is broad and encompasses diverse unrelated drugs, suggesting more than one mechanism of resistance. To better understand the molecular mechanisms controlling the immediate response of OC cells to CT exposure, we have performed gene expression profiling in spheroid cultures derived from six OC cell lines (OVCAR3, SKOV3, TOV-112, TOV-21, OV-90 and TOV-155), following treatment with 10,0 microM cisplatin, 2,5 microM paclitaxel or 5,0 microM topotecan for 72 hours. Exposure of OC spheroids to these CT drugs resulted in differential expression of genes associated with cell growth and proliferation, cellular assembly and organization, cell death, cell cycle control and cell signaling. Genes, functionally involved in DNA repair, DNA replication and cell cycle arrest were mostly overexpressed, while genes implicated in metabolism (especially lipid metabolism), signal transduction, immune and inflammatory response, transport, transcription regulation and protein biosynthesis, were commonly suppressed following all treatments. Cisplatin and topotecan treatments triggered similar alterations in gene and pathway expression patterns, while paclitaxel action was mainly associated with induction of genes and pathways linked to cellular assembly and organization (including numerous tubulin genes), cell death and protein synthesis. The microarray data were further confirmed by pathway and network analyses. Most alterations in gene expression were directly related to mechanisms of the cytotoxics actions in OC spheroids. However, the induction of genes linked to mechanisms of DNA replication and repair in cisplatin- and topotecan-treated OC spheroids could be associated with immediate adaptive response to treatment. Similarly, overexpression of different tubulin genes upon exposure to paclitaxel could represent an early compensatory effect to this drug action. Finally, multicellular growth conditions that are known to alter gene

  3. Establishment of CDC Global Rapid Response Team to Ensure Global Health Security.

    PubMed

    Stehling-Ariza, Tasha; Lefevre, Adrienne; Calles, Dinorah; Djawe, Kpandja; Garfield, Richard; Gerber, Michael; Ghiselli, Margherita; Giese, Coralie; Greiner, Ashley L; Hoffman, Adela; Miller, Leigh Ann; Moorhouse, Lisa; Navarro-Colorado, Carlos; Walsh, James; Bugli, Dante; Shahpar, Cyrus

    2017-12-01

    The 2014-2016 Ebola virus disease epidemic in West Africa highlighted challenges faced by the global response to a large public health emergency. Consequently, the US Centers for Disease Control and Prevention established the Global Rapid Response Team (GRRT) to strengthen emergency response capacity to global health threats, thereby ensuring global health security. Dedicated GRRT staff can be rapidly mobilized for extended missions, improving partner coordination and the continuity of response operations. A large, agencywide roster of surge staff enables rapid mobilization of qualified responders with wide-ranging experience and expertise. Team members are offered emergency response training, technical training, foreign language training, and responder readiness support. Recent response missions illustrate the breadth of support the team provides. GRRT serves as a model for other countries and is committed to strengthening emergency response capacity to respond to outbreaks and emergencies worldwide, thereby enhancing global health security.

  4. Global transcriptional responses of Bacillus subtilis to xenocoumacin 1.

    PubMed

    Zhou, T; Zeng, H; Qiu, D; Yang, X; Wang, B; Chen, M; Guo, L; Wang, S

    2011-09-01

    To determine the global transcriptional response of Bacillus subtilis to an antimicrobial agent, xenocoumacin 1 (Xcn1). Subinhibitory concentration of Xcn1 applied to B. subtilis was measured according to Hutter's method for determining optimal concentrations. cDNA microarray technology was used to study the global transcriptional response of B. subtilis to Xcn1. Real-time RT-PCR was employed to verify alterations in the transcript levels of six genes. The subinhibitory concentration was determined to be 1 μg ml(-1). The microarray data demonstrated that Xcn1 treatment of B. subtilis led to more than a 2.0-fold up-regulation of 480 genes and more than a 2.0-fold down-regulation of 479 genes (q ≤ 0.05). The transcriptional responses of B. subtilis to Xcn1 were determined, and several processes were affected by Xcn1. Additionally, cluster analysis of gene expression profiles after treatment with Xcn1 or 37 previously studied antibiotics indicated that Xcn1 has similar mechanisms of action to protein synthesis inhibitors. These microarray data showed alterations of gene expression in B. subtilis after exposure to Xcn1. From the results, we identified various processes affected by Xcn1. This study provides a whole-genome perspective to elucidate the action of Xcn1 as a potential antimicrobial agent. © 2011 The Authors. Journal of Applied Microbiology © 2011 The Society for Applied Microbiology.

  5. Ezrin Inhibition Up-regulates Stress Response Gene Expression*

    PubMed Central

    Çelik, Haydar; Bulut, Gülay; Han, Jenny; Graham, Garrett T.; Minas, Tsion Z.; Conn, Erin J.; Hong, Sung-Hyeok; Pauly, Gary T.; Hayran, Mutlu; Li, Xin; Özdemirli, Metin; Ayhan, Ayşe; Rudek, Michelle A.; Toretsky, Jeffrey A.; Üren, Aykut

    2016-01-01

    Ezrin is a member of the ERM (ezrin/radixin/moesin) family of proteins that links cortical cytoskeleton to the plasma membrane. High expression of ezrin correlates with poor prognosis and metastasis in osteosarcoma. In this study, to uncover specific cellular responses evoked by ezrin inhibition that can be used as a specific pharmacodynamic marker(s), we profiled global gene expression in osteosarcoma cells after treatment with small molecule ezrin inhibitors, NSC305787 and NSC668394. We identified and validated several up-regulated integrated stress response genes including PTGS2, ATF3, DDIT3, DDIT4, TRIB3, and ATF4 as novel ezrin-regulated transcripts. Analysis of transcriptional response in skin and peripheral blood mononuclear cells from NSC305787-treated mice compared with a control group revealed that, among those genes, the stress gene DDIT4/REDD1 may be used as a surrogate pharmacodynamic marker of ezrin inhibitor compound activity. In addition, we validated the anti-metastatic effects of NSC305787 in reducing the incidence of lung metastasis in a genetically engineered mouse model of osteosarcoma and evaluated the pharmacokinetics of NSC305787 and NSC668394 in mice. In conclusion, our findings suggest that cytoplasmic ezrin, previously considered a dormant and inactive protein, has important functions in regulating gene expression that may result in down-regulation of stress response genes. PMID:27137931

  6. Fungal symbionts alter plant responses to global change.

    PubMed

    Kivlin, Stephanie N; Emery, Sarah M; Rudgers, Jennifer A

    2013-07-01

    While direct plant responses to global change have been well characterized, indirect plant responses to global change, via altered species interactions, have received less attention. Here, we examined how plants associated with four classes of fungal symbionts (class I leaf endophytes [EF], arbuscular mycorrhizal fungi [AMF], ectomycorrhizal fungi [ECM], and dark septate endophytes [DSE]) responded to four global change factors (enriched CO2, drought, N deposition, and warming). We performed a meta-analysis of 434 studies spanning 174 publications to search for generalizable trends in responses of plant-fungal symbioses to future environments. Specifically, we addressed the following questions: (1) Can fungal symbionts ameliorate responses of plants to global change? (2) Do fungal symbiont groups differ in the degree to which they modify plant response to global change? (3) Do particular global change factors affect plant-fungal symbioses more than others? In all global change scenarios, except elevated CO2, fungal symbionts significantly altered plant responses to global change. In most cases, fungal symbionts increased plant biomass in response to global change. However, increased N deposition reduced the benefits of symbiosis. Of the global change factors we considered, drought and N deposition resulted in the strongest fungal mediation of plant responses. Our analysis highlighted gaps in current knowledge for responses of particular fungal groups and revealed the importance of considering not only the nonadditive effects of multiple global change factors, but also the interactive effects of multiple fungal symbioses. Our results show that considering plant-fungal symbioses is critical to predicting ecosystem response to global change.

  7. 78 FR 18376 - Promotional Rates for Global Express Guaranteed Service

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-26

    ... POSTAL SERVICE Promotional Rates for Global Express Guaranteed Service AGENCY: Postal Service\\TM\\. ACTION: Notice of Promotional Rates. SUMMARY: The Postal Service gives notice of promotional rates for Global Express Guaranteed[supreg] (GXG[supreg]) service consistent with Governors' Decision No. 12-02...

  8. Mechanical Strain Promotes Oligodendrocyte Differentiation by Global Changes of Gene Expression

    PubMed Central

    Jagielska, Anna; Lowe, Alexis L.; Makhija, Ekta; Wroblewska, Liliana; Guck, Jochen; Franklin, Robin J. M.; Shivashankar, G. V.; Van Vliet, Krystyn J.

    2017-01-01

    Differentiation of oligodendrocyte progenitor cells (OPC) to oligodendrocytes and subsequent axon myelination are critical steps in vertebrate central nervous system (CNS) development and regeneration. Growing evidence supports the significance of mechanical factors in oligodendrocyte biology. Here, we explore the effect of mechanical strains within physiological range on OPC proliferation and differentiation, and strain-associated changes in chromatin structure, epigenetics, and gene expression. Sustained tensile strain of 10–15% inhibited OPC proliferation and promoted differentiation into oligodendrocytes. This response to strain required specific interactions of OPCs with extracellular matrix ligands. Applied strain induced changes in nuclear shape, chromatin organization, and resulted in enhanced histone deacetylation, consistent with increased oligodendrocyte differentiation. This response was concurrent with increased mRNA levels of the epigenetic modifier histone deacetylase Hdac11. Inhibition of HDAC proteins eliminated the strain-mediated increase of OPC differentiation, demonstrating a role of HDACs in mechanotransduction of strain to chromatin. RNA sequencing revealed global changes in gene expression associated with strain. Specifically, expression of multiple genes associated with oligodendrocyte differentiation and axon-oligodendrocyte interactions was increased, including cell surface ligands (Ncam, ephrins), cyto- and nucleo-skeleton genes (Fyn, actinins, myosin, nesprin, Sun1), transcription factors (Sox10, Zfp191, Nkx2.2), and myelin genes (Cnp, Plp, Mag). These findings show how mechanical strain can be transmitted to the nucleus to promote oligodendrocyte differentiation, and identify the global landscape of signaling pathways involved in mechanotransduction. These data provide a source of potential new therapeutic avenues to enhance OPC differentiation in vivo. PMID:28473753

  9. Global identification and expression analysis of stress-responsive genes of the Argonaute family in apple.

    PubMed

    Xu, Ruirui; Liu, Caiyun; Li, Ning; Zhang, Shizhong

    2016-12-01

    Argonaute (AGO) proteins, which are found in yeast, animals, and plants, are the core molecules of the RNA-induced silencing complex. These proteins play important roles in plant growth, development, and responses to biotic stresses. The complete analysis and classification of the AGO gene family have been recently reported in different plants. Nevertheless, systematic analysis and expression profiling of these genes have not been performed in apple (Malus domestica). Approximately 15 AGO genes were identified in the apple genome. The phylogenetic tree, chromosome location, conserved protein motifs, gene structure, and expression of the AGO gene family in apple were analyzed for gene prediction. All AGO genes were phylogenetically clustered into four groups (i.e., AGO1, AGO4, MEL1/AGO5, and ZIPPY/AGO7) with the AGO genes of Arabidopsis. These groups of the AGO gene family were statistically analyzed and compared among 31 plant species. The predicted apple AGO genes are distributed across nine chromosomes at different densities and include three segment duplications. Expression studies indicated that 15 AGO genes exhibit different expression patterns in at least one of the tissues tested. Additionally, analysis of gene expression levels indicated that the genes are mostly involved in responses to NaCl, PEG, heat, and low-temperature stresses. Hence, several candidate AGO genes are involved in different aspects of physiological and developmental processes and may play an important role in abiotic stress responses in apple. To the best of our knowledge, this study is the first to report a comprehensive analysis of the apple AGO gene family. Our results provide useful information to understand the classification and putative functions of these proteins, especially for gene members that may play important roles in abiotic stress responses in M. hupehensis.

  10. Global-Local Precedence in the Perception of Facial Age and Emotional Expression by Children with Autism and Other Developmental Disabilities

    ERIC Educational Resources Information Center

    Gross, Thomas F.

    2005-01-01

    Global information processing and perception of facial age and emotional expression was studied in children with autism, language disorders, mental retardation, and a clinical control group. Children were given a global-local task and asked to recognize age and emotion in human and canine faces. Children with autism made fewer global responses and…

  11. Ezrin Inhibition Up-regulates Stress Response Gene Expression.

    PubMed

    Çelik, Haydar; Bulut, Gülay; Han, Jenny; Graham, Garrett T; Minas, Tsion Z; Conn, Erin J; Hong, Sung-Hyeok; Pauly, Gary T; Hayran, Mutlu; Li, Xin; Özdemirli, Metin; Ayhan, Ayşe; Rudek, Michelle A; Toretsky, Jeffrey A; Üren, Aykut

    2016-06-17

    Ezrin is a member of the ERM (ezrin/radixin/moesin) family of proteins that links cortical cytoskeleton to the plasma membrane. High expression of ezrin correlates with poor prognosis and metastasis in osteosarcoma. In this study, to uncover specific cellular responses evoked by ezrin inhibition that can be used as a specific pharmacodynamic marker(s), we profiled global gene expression in osteosarcoma cells after treatment with small molecule ezrin inhibitors, NSC305787 and NSC668394. We identified and validated several up-regulated integrated stress response genes including PTGS2, ATF3, DDIT3, DDIT4, TRIB3, and ATF4 as novel ezrin-regulated transcripts. Analysis of transcriptional response in skin and peripheral blood mononuclear cells from NSC305787-treated mice compared with a control group revealed that, among those genes, the stress gene DDIT4/REDD1 may be used as a surrogate pharmacodynamic marker of ezrin inhibitor compound activity. In addition, we validated the anti-metastatic effects of NSC305787 in reducing the incidence of lung metastasis in a genetically engineered mouse model of osteosarcoma and evaluated the pharmacokinetics of NSC305787 and NSC668394 in mice. In conclusion, our findings suggest that cytoplasmic ezrin, previously considered a dormant and inactive protein, has important functions in regulating gene expression that may result in down-regulation of stress response genes. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  12. Global gene expression analysis by combinatorial optimization.

    PubMed

    Ameur, Adam; Aurell, Erik; Carlsson, Mats; Westholm, Jakub Orzechowski

    2004-01-01

    Generally, there is a trade-off between methods of gene expression analysis that are precise but labor-intensive, e.g. RT-PCR, and methods that scale up to global coverage but are not quite as quantitative, e.g. microarrays. In the present paper, we show how how a known method of gene expression profiling (K. Kato, Nucleic Acids Res. 23, 3685-3690 (1995)), which relies on a fairly small number of steps, can be turned into a global gene expression measurement by advanced data post-processing, with potentially little loss of accuracy. Post-processing here entails solving an ancillary combinatorial optimization problem. Validation is performed on in silico experiments generated from the FANTOM data base of full-length mouse cDNA. We present two variants of the method. One uses state-of-the-art commercial software for solving problems of this kind, the other a code developed by us specifically for this purpose, released in the public domain under GPL license.

  13. Global depression in gene expression as a response to rapid thermal changes in vent mussels

    PubMed Central

    Boutet, Isabelle; Tanguy, Arnaud; Le Guen, Dominique; Piccino, Patrice; Hourdez, Stéphane; Legendre, Pierre; Jollivet, Didier

    2009-01-01

    Hydrothermal vent mussels belonging to the genus Bathymodiolus are distributed worldwide and dominate communities at shallow Atlantic hydrothermal sites. While organisms inhabiting coastal ecosystems are subjected to predictable oscillations of physical and chemical variables owing to tidal cycles, the vent mussels sustain pronounced temperature changes over short periods of time, correlated to the alternation of oxic/anoxic phases. In this context, we focused on the short-term adaptive response of mussels to temperature change at a molecular level. The mRNA expression of 23 genes involved in various cell functions of the vent mussel Bathymodiolus azoricus was followed after heat shocks for either 30 or 120 min, at 25 and 30°C over a 48 h recovery period at 5°C. Mussels were genotyped at 10 enzyme loci to explore a relationship between natural genetic variation, gene expression and temperature adaptation. Results indicate that the mussel response to increasing temperature is a depression in gene expression, such a response being genotypically correlated at least for the Pgm-1 locus. This suggests that an increase in temperature could be a signal triggering anaerobiosis for B. azoricus or this latter alternatively behaves more like a ‘cold’ stenotherm species, an attribute more related to its phylogenetic history, a cold seeps/wood fall origin. PMID:19515664

  14. Global gene expression analyses of hematopoietic stem cell-like cell lines with inducible Lhx2 expression

    PubMed Central

    Richter, Karin; Wirta, Valtteri; Dahl, Lina; Bruce, Sara; Lundeberg, Joakim; Carlsson, Leif; Williams, Cecilia

    2006-01-01

    Background Expression of the LIM-homeobox gene Lhx2 in murine hematopoietic cells allows for the generation of hematopoietic stem cell (HSC)-like cell lines. To address the molecular basis of Lhx2 function, we generated HSC-like cell lines where Lhx2 expression is regulated by a tet-on system and hence dependent on the presence of doxycyclin (dox). These cell lines efficiently down-regulate Lhx2 expression upon dox withdrawal leading to a rapid differentiation into various myeloid cell types. Results Global gene expression of these cell lines cultured in dox was compared to different time points after dox withdrawal using microarray technology. We identified 267 differentially expressed genes. The majority of the genes overlapping with HSC-specific databases were those down-regulated after turning off Lhx2 expression and a majority of the genes overlapping with those defined as late progenitor-specific genes were the up-regulated genes, suggesting that these cell lines represent a relevant model system for normal HSCs also at the level of global gene expression. Moreover, in situ hybridisations of several genes down-regulated after dox withdrawal showed overlapping expression patterns with Lhx2 in various tissues during embryonic development. Conclusion Global gene expression analysis of HSC-like cell lines with inducible Lhx2 expression has identified genes putatively linked to self-renewal / differentiation of HSCs, and function of Lhx2 in organ development and stem / progenitor cells of non-hematopoietic origin. PMID:16600034

  15. Global analysis of epigenetic regulation of gene expression in response to drought stress in Sorghum.

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Reddy, Anireddy; Ben-Hur, Asa

    Abiotic stresses including drought are major limiting factors of crop yields and cause significant crop losses. Acquisition of stress tolerance to abiotic stresses requires coordinated regulation of a multitude of biochemical and physiological changes, and most of these changes depend on alterations in gene expression. The goal of this work is to perform global analysis of differential regulation of gene expression and alternative splicing, and their relationship with chromatin landscape in drought sensitive and tolerant cultivars. our Iso-Seq study revealed transcriptome-wide full-length isoforms at an unprecedented scale with over 11000 novel splice isoforms. Additionally, we uncovered alternative polyadenylation sites ofmore » ~11000 expressed genes and many novel genes. Overall, Iso-Seq results greatly enhanced sorghum gene annotations that are not only useful in analyzing all our RNA-seq, ChIP-seq and ATAC-seq data but also serve as a great resource to the plant biology community. Our studies identified differentially expressed genes and splicing events that are correlated with the drought-resistant phenotype. An association between alternative splicing and chromatin accessibility was also revealed. Several computational tools developed here (TAPIS and iDiffIR) have been made freely available to the research community in analyzing alternative splicing and differential alternative splicing.« less

  16. Mars Express Seen by Mars Global Surveyor

    NASA Image and Video Library

    2005-05-19

    This picture of the European Space Agency Mars Express spacecraft by the Mars Orbiter Camera on NASA Mars Global Surveyor is from the first successful imaging of any spacecraft orbiting Mars taken by another spacecraft orbiting Mars.

  17. Sparse feature selection methods identify unexpected global cellular response to strontium-containing materials

    PubMed Central

    Autefage, Hélène; Littmann, Elena; Hedegaard, Martin A. B.; Von Erlach, Thomas; O’Donnell, Matthew; Burden, Frank R.; Winkler, David A.; Stevens, Molly M.

    2015-01-01

    Despite the increasing sophistication of biomaterials design and functional characterization studies, little is known regarding cells’ global response to biomaterials. Here, we combined nontargeted holistic biological and physical science techniques to evaluate how simple strontium ion incorporation within the well-described biomaterial 45S5 bioactive glass (BG) influences the global response of human mesenchymal stem cells. Our objective analyses of whole gene-expression profiles, confirmed by standard molecular biology techniques, revealed that strontium-substituted BG up-regulated the isoprenoid pathway, suggesting an influence on both sterol metabolite synthesis and protein prenylation processes. This up-regulation was accompanied by increases in cellular and membrane cholesterol and lipid raft contents as determined by Raman spectroscopy mapping and total internal reflection fluorescence microscopy analyses and by an increase in cellular content of phosphorylated myosin II light chain. Our unexpected findings of this strong metabolic pathway regulation as a response to biomaterial composition highlight the benefits of discovery-driven nonreductionist approaches to gain a deeper understanding of global cell–material interactions and suggest alternative research routes for evaluating biomaterials to improve their design. PMID:25831522

  18. 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

  19. Global Gene Expression Profiling in Lung Tissues of Rat Exposed to Lunar Dust Particles

    NASA Technical Reports Server (NTRS)

    Yeshitla, Samrawit A.; Lam, Chiu-Wing; Kidane, Yared H.; Feiveson, Alan H.; Ploutz-Snyder, Robert; Wu, Honglu; James, John T.; Meyers, Valerie E.; Zhang, Ye

    2014-01-01

    The Moon's surface is covered by a layer of fine, potential reactive dust. Lunar dust contain about 1-2% respirable very fine dust (less than 3 micrometers). The habitable area of any lunar landing vehicle and outpost would inevitably be contaminated with lunar dust that could pose a health risk. The purpose of the study is to analyze the dynamics of global gene expression changes in lung tissues of rats exposed to lunar dust particles. F344 rats were exposed for 4 weeks (6h/d; 5d/wk) in nose-only inhalation chambers to concentrations of 0 (control air), 2.1, 6.8, 21, and 61 mg/m3 of lunar dust. Animals were euthanized at 1 day and 13 weeks after the last inhalation exposure. After being lavaged, lung tissue from each animal was collected and total RNA was isolated. Four samples of each dose group were analyzed using Agilent Rat GE v3 microarray to profile global gene expression of 44K transcripts. After background subtraction, normalization, and log transformation, t tests were used to compare the mean expression levels of each exposed group to the control group. Correction for multiple testing was made using the method of Benjamini, Krieger, and Yekuteli (1) to control the false discovery rate. Genes with significant changes of at least 1.75 fold were identified as genes of interest. Both low and high doses of lunar dust caused dramatic, dose-dependent global gene expression changes in the lung tissues. However, the responses of lung tissue to low dose lunar dust are distinguished from those of high doses, especially those associated with 61mg/m3 dust exposure. The data were further integrated into the Ingenuity system to analyze the gene ontology (GO), pathway distribution and putative upstream regulators and gene targets. Multiple pathways, functions, and upstream regulators have been identified in response to lunar dust induced damage in the lung tissue.

  20. Global gene expression in cotton (Gossypium hirsutum L.) leaves to waterlogging stress.

    PubMed

    Zhang, Yanjun; Kong, Xiangqiang; Dai, Jianlong; Luo, Zhen; Li, Zhenhuai; Lu, Hequan; Xu, Shizhen; Tang, Wei; Zhang, Dongmei; Li, Weijiang; Xin, Chengsong; Dong, Hezhong

    2017-01-01

    Cotton is sensitive to waterlogging stress, which usually results in stunted growth and yield loss. To date, the molecular mechanisms underlying the responses to waterlogging in cotton remain elusive. Cotton was grown in a rain-shelter and subjected to 0 (control)-, 10-, 15- and 20-d waterlogging at flowering stage. The fourth-leaves on the main-stem from the top were sampled and immediately frozen in liquid nitrogen for physiological measurement. Global gene transcription in the leaves of 15-d waterlogged plants was analyzed by RNA-Seq. Seven hundred and ninety four genes were up-regulated and 1018 genes were down-regulated in waterlogged cotton leaves compared with non-waterlogged control. The differentially expressed genes were mainly related to photosynthesis, nitrogen metabolism, starch and sucrose metabolism, glycolysis and plant hormone signal transduction. KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis indicated that most genes related to flavonoid biosynthesis, oxidative phosphorylation, amino acid metabolism and biosynthesis as well as circadian rhythm pathways were differently expressed. Waterlogging increased the expression of anaerobic fermentation related genes, such as alcohol dehydrogenase (ADH), but decreased the leaf chlorophyll concentration and photosynthesis by down-regulating the expression of photosynthesis related genes. Many genes related to plant hormones and transcription factors were differently expressed under waterlogging stress. Most of the ethylene related genes and ethylene-responsive factor-type transcription factors were up-regulated under water-logging stress, suggesting that ethylene may play key roles in the survival of cotton under waterlogging stress.

  1. Global gene expression in cotton (Gossypium hirsutum L.) leaves to waterlogging stress

    PubMed Central

    Zhang, Yanjun; Kong, Xiangqiang; Dai, Jianlong; Luo, Zhen; Li, Zhenhuai; Lu, Hequan; Xu, Shizhen; Tang, Wei; Zhang, Dongmei; Li, Weijiang; Xin, Chengsong

    2017-01-01

    Cotton is sensitive to waterlogging stress, which usually results in stunted growth and yield loss. To date, the molecular mechanisms underlying the responses to waterlogging in cotton remain elusive. Cotton was grown in a rain-shelter and subjected to 0 (control)-, 10-, 15- and 20-d waterlogging at flowering stage. The fourth-leaves on the main-stem from the top were sampled and immediately frozen in liquid nitrogen for physiological measurement. Global gene transcription in the leaves of 15-d waterlogged plants was analyzed by RNA-Seq. Seven hundred and ninety four genes were up-regulated and 1018 genes were down-regulated in waterlogged cotton leaves compared with non-waterlogged control. The differentially expressed genes were mainly related to photosynthesis, nitrogen metabolism, starch and sucrose metabolism, glycolysis and plant hormone signal transduction. KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis indicated that most genes related to flavonoid biosynthesis, oxidative phosphorylation, amino acid metabolism and biosynthesis as well as circadian rhythm pathways were differently expressed. Waterlogging increased the expression of anaerobic fermentation related genes, such as alcohol dehydrogenase (ADH), but decreased the leaf chlorophyll concentration and photosynthesis by down-regulating the expression of photosynthesis related genes. Many genes related to plant hormones and transcription factors were differently expressed under waterlogging stress. Most of the ethylene related genes and ethylene-responsive factor-type transcription factors were up-regulated under water-logging stress, suggesting that ethylene may play key roles in the survival of cotton under waterlogging stress. PMID:28953908

  2. Shared control of gene expression in bacteria by transcription factors and global physiology of the cell

    PubMed Central

    Berthoumieux, Sara; de Jong, Hidde; Baptist, Guillaume; Pinel, Corinne; Ranquet, Caroline; Ropers, Delphine; Geiselmann, Johannes

    2013-01-01

    Gene expression is controlled by the joint effect of (i) the global physiological state of the cell, in particular the activity of the gene expression machinery, and (ii) DNA-binding transcription factors and other specific regulators. We present a model-based approach to distinguish between these two effects using time-resolved measurements of promoter activities. We demonstrate the strength of the approach by analyzing a circuit involved in the regulation of carbon metabolism in E. coli. Our results show that the transcriptional response of the network is controlled by the physiological state of the cell and the signaling metabolite cyclic AMP (cAMP). The absence of a strong regulatory effect of transcription factors suggests that they are not the main coordinators of gene expression changes during growth transitions, but rather that they complement the effect of global physiological control mechanisms. This change of perspective has important consequences for the interpretation of transcriptome data and the design of biological networks in biotechnology and synthetic biology. PMID:23340840

  3. Comparative transcriptional and translational analysis of leptospiral outer membrane protein expression in response to temperature.

    PubMed

    Lo, Miranda; Cordwell, Stuart J; Bulach, Dieter M; Adler, Ben

    2009-12-08

    Leptospirosis is a global zoonosis affecting millions of people annually. Transcriptional changes in response to temperature were previously investigated using microarrays to identify genes potentially expressed upon host entry. Past studies found that various leptospiral outer membrane proteins are differentially expressed at different temperatures. However, our microarray studies highlighted a divergence between protein abundance and transcript levels for some proteins. Given the abundance of post-transcriptional expression control mechanisms, this finding highlighted the importance of global protein analysis systems. To complement our previous transcription study, we evaluated differences in the proteins of the leptospiral outer membrane fraction in response to temperature upshift. Outer membrane protein-enriched fractions from Leptospira interrogans grown at 30 degrees C or overnight upshift to 37 degrees C were isolated and the relative abundance of each protein was determined by iTRAQ analysis coupled with two-dimensional liquid chromatography and tandem mass spectrometry (2-DLC/MS-MS). We identified 1026 proteins with 99% confidence; 27 and 66 were present at elevated and reduced abundance respectively. Protein abundance changes were compared with transcriptional differences determined from the microarray studies. While there was some correlation between the microarray and iTRAQ data, a subset of genes that showed no differential expression by microarray was found to encode temperature-regulated proteins. This set of genes is of particular interest as it is likely that regulation of their expression occurs post-transcriptionally, providing an opportunity to develop hypotheses about the molecular dynamics of the outer membrane of Leptospira in response to changing environments. This is the first study to compare transcriptional and translational responses to temperature shift in L. interrogans. The results thus provide an insight into the mechanisms used by L

  4. 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.

  5. Global gene expression profiling in infants with acute respiratory syncytial virus broncholitis demonstrates systemic activation of interferon signaling networks

    USDA-ARS?s Scientific Manuscript database

    Respiratory syncytial virus (RSV) is a leading cause of pediatric lower respiratory tract infections and has a high impact on pediatric emergency department utilization. Variation in host response may influence the pathogenesis and disease severity. We evaluated global gene expression profiles to be...

  6. Altered gene expression changes in Arabidopsis leaf tissues and protoplasts in response to Plum pox virus infection

    PubMed Central

    Babu, Mohan; Griffiths, Jonathan S; Huang, Tyng-Shyan; Wang, Aiming

    2008-01-01

    Background Virus infection induces the activation and suppression of global gene expression in the host. Profiling gene expression changes in the host may provide insights into the molecular mechanisms that underlie host physiological and phenotypic responses to virus infection. In this study, the Arabidopsis Affymetrix ATH1 array was used to assess global gene expression changes in Arabidopsis thaliana plants infected with Plum pox virus (PPV). To identify early genes in response to PPV infection, an Arabidopsis synchronized single-cell transformation system was developed. Arabidopsis protoplasts were transfected with a PPV infectious clone and global gene expression changes in the transfected protoplasts were profiled. Results Microarray analysis of PPV-infected Arabidopsis leaf tissues identified 2013 and 1457 genes that were significantly (Q ≤ 0.05) up- (≥ 2.5 fold) and downregulated (≤ -2.5 fold), respectively. Genes associated with soluble sugar, starch and amino acid, intracellular membrane/membrane-bound organelles, chloroplast, and protein fate were upregulated, while genes related to development/storage proteins, protein synthesis and translation, and cell wall-associated components were downregulated. These gene expression changes were associated with PPV infection and symptom development. Further transcriptional profiling of protoplasts transfected with a PPV infectious clone revealed the upregulation of defence and cellular signalling genes as early as 6 hours post transfection. A cross sequence comparison analysis of genes differentially regulated by PPV-infected Arabidopsis leaves against uniEST sequences derived from PPV-infected leaves of Prunus persica, a natural host of PPV, identified orthologs related to defence, metabolism and protein synthesis. The cross comparison of genes differentially regulated by PPV infection and by the infections of other positive sense RNA viruses revealed a common set of 416 genes. These identified genes

  7. The Impact of Endurance Training on Human Skeletal Muscle Memory, Global Isoform Expression and Novel Transcripts

    PubMed Central

    Lindholm, Maléne E; Giacomello, Stefania; Werne Solnestam, Beata; Kjellqvist, Sanela

    2016-01-01

    Regularly performed endurance training has many beneficial effects on health and skeletal muscle function, and can be used to prevent and treat common diseases e.g. cardiovascular disease, type II diabetes and obesity. The molecular adaptation mechanisms regulating these effects are incompletely understood. To date, global transcriptome changes in skeletal muscles have been studied at the gene level only. Therefore, global isoform expression changes following exercise training in humans are unknown. Also, the effects of repeated interventions on transcriptional memory or training response have not been studied before. In this study, 23 individuals trained one leg for three months. Nine months later, 12 of the same subjects trained both legs in a second training period. Skeletal muscle biopsies were obtained from both legs before and after both training periods. RNA sequencing analysis of all 119 skeletal muscle biopsies showed that training altered the expression of 3,404 gene isoforms, mainly associated with oxidative ATP production. Fifty-four genes had isoforms that changed in opposite directions. Training altered expression of 34 novel transcripts, all with protein-coding potential. After nine months of detraining, no training-induced transcriptome differences were detected between the previously trained and untrained legs. Although there were several differences in the physiological and transcriptional responses to repeated training, no coherent evidence of an endurance training induced transcriptional skeletal muscle memory was found. This human lifestyle intervention induced differential expression of thousands of isoforms and several transcripts from unannotated regions of the genome. It is likely that the observed isoform expression changes reflect adaptational mechanisms and processes that provide the functional and health benefits of regular physical activity. PMID:27657503

  8. DoD Global Emerging Infections Surveillance & Response System (DoD-GEIS). Global Influenza Surveillance Efforts

    DTIC Science & Technology

    2007-01-08

    DoD Global Emerging Infections Surveillance & Response System (DoD-GEIS) Global Influenza Surveillance Efforts 8 January 2007 COL (Ret.) Jose L...SUBTITLE DoD Global Emerging Infections Surveillance & Response System (DoD-GEIS) Global Influenza Surveillance Efforts 5a. CONTRACT NUMBER 5b. GRANT...PAGE unclassified Standard Form 298 (Rev. 8-98) Prescribed by ANSI Std Z39-18 Lab-Based Influenza Surveillance • Sentinel Surveillance • Air Force

  9. Suppressing Sorbitol Synthesis Substantially Alters the Global Expression Profile of Stress Response Genes in Apple (Malus domestica) Leaves.

    PubMed

    Wu, Ting; Wang, Yi; Zheng, Yi; Fei, Zhangjun; Dandekar, Abhaya M; Xu, Kenong; Han, Zhenhai; Cheng, Lailiang

    2015-09-01

    Sorbitol is a major product of photosynthesis in apple (Malus domestica) that is involved in carbohydrate metabolism and stress tolerance. However, little is known about how the global transcript levels in apple leaves respond to decreased sorbitol synthesis. In this study we used RNA sequencing (RNA-seq) profiling to characterize the transcriptome of leaves from transgenic lines of the apple cultivar 'Greensleeves' exhibiting suppressed expression of aldose-6-phosphate reductase (A6PR) to gain insights into sorbitol function and the consequences of decreased sorbitol synthesis on gene expression. We observed that, although the leaves of the low sorbitol transgenic lines accumulate higher levels of various primary metabolites, only very limited changes were found in the levels of transcripts associated with primary metabolism. We suggest that this is indicative of post-transcriptional and/or post-translational regulation of primary metabolite accumulation and central carbon metabolism. However, we identified significantly enriched gene ontology terms belonging to the 'stress related process' category in the antisense lines (P-value < 0.05). These include genes involved in the synthesis/degradation of abscisic acid, salicylic acid and jasmonic acid, nucleotide-binding site leucine-rich repeat (NBS-LRR) disease resistance genes and ATP-binding cassette (ABC) transporter genes. This suggests that sorbitol plays a role in the responses of apple trees to abiotic and biotic stresses. © 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.

  10. Time-Course Analysis of Gene Expression During the Saccharomyces cerevisiae Hypoxic Response.

    PubMed

    Bendjilali, Nasrine; MacLeon, Samuel; Kalra, Gurmannat; Willis, Stephen D; Hossian, A K M Nawshad; Avery, Erica; Wojtowicz, Olivia; Hickman, Mark J

    2017-01-05

    Many cells experience hypoxia, or low oxygen, and respond by dramatically altering gene expression. In the yeast Saccharomyces cerevisiae, genes that respond are required for many oxygen-dependent cellular processes, such as respiration, biosynthesis, and redox regulation. To more fully characterize the global response to hypoxia, we exposed yeast to hypoxic conditions, extracted RNA at different times, and performed RNA sequencing (RNA-seq) analysis. Time-course statistical analysis revealed hundreds of genes that changed expression by up to 550-fold. The genes responded with varying kinetics suggesting that multiple regulatory pathways are involved. We identified most known oxygen-regulated genes and also uncovered new regulated genes. Reverse transcription-quantitative PCR (RT-qPCR) analysis confirmed that the lysine methyltransferase EFM6 and the recombinase DMC1, both conserved in humans, are indeed oxygen-responsive. Looking more broadly, oxygen-regulated genes participate in expected processes like respiration and lipid metabolism, but also in unexpected processes like amino acid and vitamin metabolism. Using principle component analysis, we discovered that the hypoxic response largely occurs during the first 2 hr and then a new steady-state expression state is achieved. Moreover, we show that the oxygen-dependent genes are not part of the previously described environmental stress response (ESR) consisting of genes that respond to diverse types of stress. While hypoxia appears to cause a transient stress, the hypoxic response is mostly characterized by a transition to a new state of gene expression. In summary, our results reveal that hypoxia causes widespread and complex changes in gene expression to prepare the cell to function with little or no oxygen. Copyright © 2017 Bendjilali et al.

  11. Assessing Global Transcriptome Changes in Response to South African Cassava Mosaic Virus [ZA-99] Infection in Susceptible Arabidopsis thaliana.

    PubMed

    Pierce, Erica J; Rey, M E Chrissie

    2013-01-01

    In susceptible plant hosts, co-evolution has favoured viral strategies to evade host defenses and utilize resources to their own benefit. The degree of manipulation of host gene expression is dependent on host-virus specificity and certain abiotic factors. In order to gain insight into global transcriptome changes for a geminivirus pathosystem, South African cassava mosaic virus [ZA:99] and Arabidopsis thaliana, 4×44K Agilent microarrays were adopted. After normalization, a log2 fold change filtering of data (p<0.05) identified 1,743 differentially expressed genes in apical leaf tissue. A significant increase in differential gene expression over time correlated with an increase in SACMV accumulation, as virus copies were 5-fold higher at 24 dpi and 6-fold higher at 36 dpi than at 14 dpi. Many altered transcripts were primarily involved in stress and defense responses, phytohormone signalling pathways, cellular transport, cell-cycle regulation, transcription, oxidation-reduction, and other metabolic processes. Only forty-one genes (2.3%) were shown to be continuously expressed across the infection period, indicating that the majority of genes were transient and unique to a particular time point during infection. A significant number of pathogen-responsive genes were suppressed during the late stages of pathogenesis, while during active systemic infection (14 to 24 dpi), there was an increase in up-regulated genes in several GO functional categories. An adaptive response was initiated to divert energy from growth-related processes to defense, leading to disruption of normal biological host processes. Similarities in cell-cycle regulation correlated between SACMV and Cabbage leaf curl virus (CaLCuV), but differences were also evident. Differences in gene expression between the two geminiviruses clearly demonstrated that, while some global transcriptome responses are generally common in plant virus infections, temporal host-specific interactions are required for

  12. Assessing Global Transcriptome Changes in Response to South African Cassava Mosaic Virus [ZA-99] Infection in Susceptible Arabidopsis thaliana

    PubMed Central

    Pierce, Erica J.; Rey, M. E. Chrissie

    2013-01-01

    In susceptible plant hosts, co-evolution has favoured viral strategies to evade host defenses and utilize resources to their own benefit. The degree of manipulation of host gene expression is dependent on host-virus specificity and certain abiotic factors. In order to gain insight into global transcriptome changes for a geminivirus pathosystem, South African cassava mosaic virus [ZA:99] and Arabidopsis thaliana, 4×44K Agilent microarrays were adopted. After normalization, a log2 fold change filtering of data (p<0.05) identified 1,743 differentially expressed genes in apical leaf tissue. A significant increase in differential gene expression over time correlated with an increase in SACMV accumulation, as virus copies were 5-fold higher at 24 dpi and 6-fold higher at 36 dpi than at 14 dpi. Many altered transcripts were primarily involved in stress and defense responses, phytohormone signalling pathways, cellular transport, cell-cycle regulation, transcription, oxidation-reduction, and other metabolic processes. Only forty-one genes (2.3%) were shown to be continuously expressed across the infection period, indicating that the majority of genes were transient and unique to a particular time point during infection. A significant number of pathogen-responsive genes were suppressed during the late stages of pathogenesis, while during active systemic infection (14 to 24 dpi), there was an increase in up-regulated genes in several GO functional categories. An adaptive response was initiated to divert energy from growth-related processes to defense, leading to disruption of normal biological host processes. Similarities in cell-cycle regulation correlated between SACMV and Cabbage leaf curl virus (CaLCuV), but differences were also evident. Differences in gene expression between the two geminiviruses clearly demonstrated that, while some global transcriptome responses are generally common in plant virus infections, temporal host-specific interactions are required for

  13. Global gene expression during stringent response in Corynebacterium glutamicum in presence and absence of the rel gene encoding (p)ppGpp synthase

    PubMed Central

    Brockmann-Gretza, Olaf; Kalinowski, Jörn

    2006-01-01

    Background The stringent response is the initial reaction of microorganisms to nutritional stress. During stringent response the small nucleotides (p)ppGpp act as global regulators and reprogram bacterial transcription. In this work, the genetic network controlled by the stringent response was characterized in the amino acid-producing Corynebacterium glutamicum. Results The transcriptome of a C. glutamicum rel gene deletion mutant, unable to synthesize (p)ppGpp and to induce the stringent response, was compared with that of its rel-proficient parent strain by microarray analysis. A total of 357 genes were found to be transcribed differentially in the rel-deficient mutant strain. In a second experiment, the stringent response was induced by addition of DL-serine hydroxamate (SHX) in early exponential growth phase. The time point of the maximal effect on transcription was determined by real-time RT-PCR using the histidine and serine biosynthetic genes. Transcription of all of these genes reached a maximum at 10 minutes after SHX addition. Microarray experiments were performed comparing the transcriptomes of SHX-induced cultures of the rel-proficient strain and the rel mutant. The differentially expressed genes were grouped into three classes. Class A comprises genes which are differentially regulated only in the presence of an intact rel gene. This class includes the non-essential sigma factor gene sigB which was upregulated and a large number of genes involved in nitrogen metabolism which were downregulated. Class B comprises genes which were differentially regulated in response to SHX in both strains, independent of the rel gene. A large number of genes encoding ribosomal proteins fall into this class, all being downregulated. Class C comprises genes which were differentially regulated in response to SHX only in the rel mutant. This class includes genes encoding putative stress proteins and global transcriptional regulators that might be responsible for the complex

  14. Global transcriptomic analysis of the response of Corynebacterium glutamicum to ferulic acid.

    PubMed

    Chen, Can; Pan, Junfeng; Yang, Xiaobing; Xiao, He; Zhang, Yaoling; Si, Meiru; Shen, Xihui; Wang, Yao

    2017-03-01

    Corynebacterium glutamicum can survive by using ferulic acid as the sole carbon source. In this study, we assessed the response of C. glutamicum to ferulic acid stress by means of a global transcriptional response analysis. The transcriptional data showed that several genes involved in degradation of ferulic acid were affected. Moreover, several genes related to the stress response; protein protection or degradation and DNA repair; replication, transcription and translation; and the cell envelope were differentially expressed. Deletion of the katA or sigE gene in C. glutamicum resulted in a decrease in cell viability under ferulic acid stress. These insights will facilitate further engineering of model industrial strains, with enhanced tolerance to ferulic acid to enable easy production of biofuels from lignocellulose.

  15. Global transcriptomic responses of Escherichia coli K-12 to volatile organic compounds.

    PubMed

    Yung, Pui Yi; Grasso, Letizia Lo; Mohidin, Abeed Fatima; Acerbi, Enzo; Hinks, Jamie; Seviour, Thomas; Marsili, Enrico; Lauro, Federico M

    2016-01-28

    Volatile organic compounds (VOCs) are commonly used as solvents in various industrial settings. Many of them present a challenge to receiving environments, due to their toxicity and low bioavailability for degradation. Microorganisms are capable of sensing and responding to their surroundings and this makes them ideal detectors for toxic compounds. This study investigates the global transcriptomic responses of Escherichia coli K-12 to selected VOCs at sub-toxic levels. Cells grown in the presence of VOCs were harvested during exponential growth, followed by whole transcriptome shotgun sequencing (RNAseq). The analysis of the data revealed both shared and unique genetic responses compared to cells without exposure to VOCs. Results suggest that various functional gene categories, for example, those relating to Fe/S cluster biogenesis, oxidative stress responses and transport proteins, are responsive to selected VOCs in E. coli. The differential expression (DE) of genes was validated using GFP-promoter fusion assays. A variety of genes were differentially expressed even at non-inhibitory concentrations and when the cells are at their balanced-growth. Some of these genes belong to generic stress response and others could be specific to VOCs. Such candidate genes and their regulatory elements could be used as the basis for designing biosensors for selected VOCs.

  16. Global transcriptomic responses of Escherichia coli K-12 to volatile organic compounds

    PubMed Central

    Yung, Pui Yi; Grasso, Letizia Lo; Mohidin, Abeed Fatima; Acerbi, Enzo; Hinks, Jamie; Seviour, Thomas; Marsili, Enrico; Lauro, Federico M.

    2016-01-01

    Volatile organic compounds (VOCs) are commonly used as solvents in various industrial settings. Many of them present a challenge to receiving environments, due to their toxicity and low bioavailability for degradation. Microorganisms are capable of sensing and responding to their surroundings and this makes them ideal detectors for toxic compounds. This study investigates the global transcriptomic responses of Escherichia coli K-12 to selected VOCs at sub-toxic levels. Cells grown in the presence of VOCs were harvested during exponential growth, followed by whole transcriptome shotgun sequencing (RNAseq). The analysis of the data revealed both shared and unique genetic responses compared to cells without exposure to VOCs. Results suggest that various functional gene categories, for example, those relating to Fe/S cluster biogenesis, oxidative stress responses and transport proteins, are responsive to selected VOCs in E. coli. The differential expression (DE) of genes was validated using GFP-promoter fusion assays. A variety of genes were differentially expressed even at non-inhibitory concentrations and when the cells are at their balanced-growth. Some of these genes belong to generic stress response and others could be specific to VOCs. Such candidate genes and their regulatory elements could be used as the basis for designing biosensors for selected VOCs. PMID:26818886

  17. Spatio-temporal dynamics in global rice gene expression (Oryza sativa L.) in response to high ammonium stress.

    PubMed

    Sun, Li; Di, Dongwei; Li, Guangjie; Kronzucker, Herbert J; Shi, Weiming

    2017-05-01

    Ammonium (NH 4 + ) is the predominant nitrogen (N) source in many natural and agricultural ecosystems, including flooded rice fields. While rice is known as an NH 4 + -tolerant species, it nevertheless suffers NH 4 + toxicity at elevated soil concentrations. NH 4 + excess rapidly leads to the disturbance of various physiological processes that ultimately inhibit shoot and root growth. However, the global transcriptomic response to NH 4 + stress in rice has not been examined. In this study, we mapped the spatio-temporal specificity of gene expression profiles in rice under excess NH 4 + and the changes in gene expression in root and shoot at various time points by RNA-Seq (Quantification) using Illumina HiSeqTM 2000. By comparative analysis, 307 and 675 genes were found to be up-regulated after 4h and 12h of NH 4 + exposure in the root, respectively. In the shoot, 167 genes were up-regulated at 4h, compared with 320 at 12h. According to KEGG analysis, up-regulated DEGs mainly participate in phenylpropanoid (such as flavonoid) and amino acid (such as proline, cysteine, and methionine) metabolism, which is believed to improve NH 4 + stress tolerance through adjustment of energy metabolism in the shoot, while defense and signaling pathways, guiding whole-plant acclimation, play the leading role in the root. We furthermore critically assessed the roles of key phytohormones, and found abscisic acid (ABA) and ethylene (ET) to be the major regulatory molecules responding to excess NH 4 + and activating the MAPK (mitogen-activated protein kinase) signal-transduction pathway. Moreover, we found up-regulated hormone-associated genes are involved in regulating flavonoid biosynthesis and are regulated by tissue flavonoid accumulation. Copyright © 2017 Elsevier GmbH. All rights reserved.

  18. Mothers' pupillary responses to infant facial expressions.

    PubMed

    Yrttiaho, Santeri; Niehaus, Dana; Thomas, Eileen; Leppänen, Jukka M

    2017-02-06

    Human parental care relies heavily on the ability to monitor and respond to a child's affective states. The current study examined pupil diameter as a potential physiological index of mothers' affective response to infant facial expressions. Pupillary time-series were measured from 86 mothers of young infants in response to an array of photographic infant faces falling into four emotive categories based on valence (positive vs. negative) and arousal (mild vs. strong). Pupil dilation was highly sensitive to the valence of facial expressions, being larger for negative vs. positive facial expressions. A separate control experiment with luminance-matched non-face stimuli indicated that the valence effect was specific to facial expressions and cannot be explained by luminance confounds. Pupil response was not sensitive to the arousal level of facial expressions. The results show the feasibility of using pupil diameter as a marker of mothers' affective responses to ecologically valid infant stimuli and point to a particularly prompt maternal response to infant distress cues.

  19. Forced Migration and Global Responsibility for Health

    PubMed Central

    Bozorgmehr, Kayvan; Razum, Oliver

    2017-01-01

    Forced migration has become a world-wide phenomenon in the past century, affecting increasing numbers of countries and people. It entails important challenges from a global health perspective. Leppold et al have critically discussed the Japanese interpretation of global responsibility for health in the context of forced migration. This commentary complements their analysis by outlining three priority areas of global health responsibility for European Union (EU) countries. We highlight important stages of the migration phases related to forced migration and propose three arguments. First, the chronic neglect of the large number of internally displaced persons (IDPs) in the discourses on the "refugee crisis" needs to be corrected in order to develop sustainable solutions with a framework of the Sustainable Development Goals (SDGs). Second, protection gaps in the global system of protection need to be effectively closed to resolve conflicts with border management and normative global health frameworks. Third, effective policies need to be developed and implemented to meet the health and humanitarian needs of forced migrants; at the same time, the solidarity crisis within the EU needs to be overcome. These stakes are high. EU countries, being committed to global health, should urgently address these areas. PMID:28812838

  20. GLOBAL EMERGING INFECTIONS SURVEILLANCE AND RESPONSE SYSTEM

    EPA Science Inventory

    Department of Defense (DoD) Gonococcal Isolate Surveillance Project (GISP). The DoD Global Emerging Infections Surveillance and Response System (DoD-GEIS) partners with the Centers for Disease Control and Prevention (CDC) and the World Health Organization (WHO) in the global surv...

  1. 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.

  2. Growth-rate dependent global effects on gene expression in bacteria

    PubMed Central

    Klumpp, Stefan; Zhang, Zhongge; Hwa, Terence

    2010-01-01

    Summary Bacterial gene expression depends not only on specific regulations but also directly on bacterial growth, because important global parameters such as the abundance of RNA polymerases and ribosomes are all growth-rate dependent. Understanding these global effects is necessary for a quantitative understanding of gene regulation and for the robust design of synthetic genetic circuits. The observed growth-rate dependence of constitutive gene expression can be explained by a simple model using the measured growth-rate dependence of the relevant cellular parameters. More complex growth dependences for genetic circuits involving activators, repressors and feedback control were analyzed, and salient features were verified experimentally using synthetic circuits. The results suggest a novel feedback mechanism mediated by general growth-dependent effects and not requiring explicit gene regulation, if the expressed protein affects cell growth. This mechanism can lead to growth bistability and promote the acquisition of important physiological functions such as antibiotic resistance and tolerance (persistence). PMID:20064380

  3. 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

  4. Express path analysis identifies a tyrosine kinase Src-centric network regulating divergent host responses to Mycobacterium tuberculosis infection.

    PubMed

    Karim, Ahmad Faisal; Chandra, Pallavi; Chopra, Aanchal; Siddiqui, Zaved; Bhaskar, Ashima; Singh, Amit; Kumar, Dhiraj

    2011-11-18

    Global gene expression profiling has emerged as a major tool in understanding complex response patterns of biological systems to perturbations. However, a lack of unbiased analytical approaches has restricted the utility of complex microarray data to gain novel system level insights. Here we report a strategy, express path analysis (EPA), that helps to establish various pathways differentially recruited to achieve specific cellular responses under contrasting environmental conditions in an unbiased manner. The analysis superimposes differentially regulated genes between contrasting environments onto the network of functional protein associations followed by a series of iterative enrichments and network analysis. To test the utility of the approach, we infected THP1 macrophage cells with a virulent Mycobacterium tuberculosis strain (H37Rv) or the attenuated non-virulent strain H37Ra as contrasting perturbations and generated the temporal global expression profiles. EPA of the results provided details of response-specific and time-dependent host molecular network perturbations. Further analysis identified tyrosine kinase Src as the major regulatory hub discriminating the responses between wild-type and attenuated Mtb infection. We were then able to verify this novel role of Src experimentally and show that Src executes its role through regulating two vital antimicrobial processes of the host cells (i.e. autophagy and acidification of phagolysosome). These results bear significant potential for developing novel anti-tuberculosis therapy. We propose that EPA could prove extremely useful in understanding complex cellular responses for a variety of perturbations, including pathogenic infections.

  5. Complex modulation of androgen responsive gene expression by methoxyacetic acid

    PubMed Central

    2011-01-01

    Background Optimal androgen signaling is critical for testicular development and spermatogenesis. Methoxyacetic acid (MAA), the primary active metabolite of the industrial chemical ethylene glycol monomethyl ether, disrupts spermatogenesis and causes testicular atrophy. Transcriptional trans-activation studies have indicated that MAA can enhance androgen receptor activity, however, whether MAA actually impacts the expression of androgen-responsive genes in vivo, and which genes might be affected is not known. Methods A mouse TM3 Leydig cell line that stably expresses androgen receptor (TM3-AR) was prepared and analyzed by transcriptional profiling to identify target gene interactions between MAA and testosterone on a global scale. Results MAA is shown to have widespread effects on androgen-responsive genes, affecting processes ranging from apoptosis to ion transport, cell adhesion, phosphorylation and transcription, with MAA able to enhance, as well as antagonize, androgenic responses. Moreover, testosterone is shown to exert both positive and negative effects on MAA gene responses. Motif analysis indicated that binding sites for FOX, HOX, LEF/TCF, STAT5 and MEF2 family transcription factors are among the most highly enriched in genes regulated by testosterone and MAA. Notably, 65 FOXO targets were repressed by testosterone or showed repression enhanced by MAA with testosterone; these include 16 genes associated with developmental processes, six of which are Hox genes. Conclusions These findings highlight the complex interactions between testosterone and MAA, and provide insight into the effects of MAA exposure on androgen-dependent processes in a Leydig cell model. PMID:21453523

  6. The global response of Nostoc punctiforme ATCC 29133 to UVA stress, assessed in a temporal DNA microarray study.

    PubMed

    Soule, Tanya; Gao, Qunjie; Stout, Valerie; Garcia-Pichel, Ferran

    2013-01-01

    Cyanobacteria in nature are exposed not only to the visible spectrum of sunlight but also to its harmful ultraviolet components (UVA and UVB). We used Nostoc punctiforme ATCC 29133 as a model to study the UVA response by analyzing global gene expression patterns using genomic microarrays. UVA exposure resulted in the statistically detectable differential expression of 573 genes of the 6903 that were probed, compared with that of the control cultures. Of those genes, 473 were up-regulated, while only 100 were down-regulated. Many of the down-regulated genes were involved in photosynthetic pigment biosynthesis, indicating a significant shift in this metabolism. As expected, we detected the up-regulation of genes encoding antioxidant enzymes and the sunscreen, scytonemin. However, a majority of the up-regulated genes, 47%, were unassignable bioinformatically to known functional categories, suggesting that the UVA stress response is not well understood. Interestingly, the most dramatic up-regulation involved several contiguous genes of unassigned metabolism on plasmid A. This is the first global UVA stress response analysis of any phototrophic microorganism and the differential expression of 8% of the genes of the Nostoc genome indicates that adaptation to UVA in Nostoc has been an evolutionary force of significance. © 2012 Wiley Periodicals, Inc. Photochemistry and Photobiology © 2012 The American Society of Photobiology.

  7. New Insights on Drought Stress Response by Global Investigation of Gene Expression Changes in Sheepgrass (Leymus chinensis)

    PubMed Central

    Zhao, Pincang; Liu, Panpan; Yuan, Guangxiao; Jia, Junting; Li, Xiaoxia; Qi, Dongmei; Chen, Shuangyan; Ma, Tian; Liu, Gongshe; Cheng, Liqin

    2016-01-01

    Water is a critical environmental factor that restricts the geographic distribution of plants. Sheepgrass [Leymus chinensis, (Trin.) Tzvel] is an important forage grass in the Eurasia Steppe and a close germplasm for wheat and barley. This native grass adapts well to adverse environments such as cold, salinity, alkalinity and drought, and it can survive when the soil moisture may be less than 6% in dry seasons. However, little is known about how sheepgrass tolerates water stress at the molecular level. Here, drought stress experiment and RNA-sequencing (RNA-seq) was performed in three pools of RNA samples (control, drought stress, and rewatering). We found that sheepgrass seedlings could still survive when the soil water content (SWC) was reduced to 14.09%. Differentially expressed genes (DEGs) analysis showed that 7320 genes exhibited significant responses to drought stress. Of these DEGs, 2671 presented opposite expression trends before and after rewatering. Furthermore, ~680 putative sheepgrass-specific water responsive genes were revealed that can be studied deeply. Gene ontology (GO) annotation revealed that stress-associated genes were activated extensively by drought treatment. Interestingly, cold stress-related genes were up-regulated greatly after drought stress. The DEGs of MAPK and calcium signal pathways, plant hormone ABA, jasmonate, ethylene, brassinosteroid signal pathways, cold response CBF pathway participated coordinatively in sheepgrass drought stress response. In addition, we identified 288 putative transcription factors (TFs) involved in drought response, among them, the WRKY, NAC, AP2/ERF, bHLH, bZIP, and MYB families were enriched, and might play crucial and significant roles in drought stress response of sheepgrass. Our research provided new and valuable information for understanding the mechanism of drought tolerance in sheepgrass. Moreover, the identification of genes involved in drought response can facilitate the genetic improvement of

  8. Impact of Neutron Exposure on Global Gene Expression in a Human Peripheral Blood Model

    PubMed Central

    Broustas, Constantinos G.; Xu, Yanping; Harken, Andrew D.; Chowdhury, Mashkura; Garty, Guy; Amundson, Sally A.

    2017-01-01

    The detonation of an improvised nuclear device would produce prompt radiation consisting of both photons (gamma rays) and neutrons. While much effort in recent years has gone into the development of radiation biodosimetry methods suitable for mass triage, the possible effect of neutrons on the endpoints studied has remained largely uninvestigated. We have used a novel neutron irradiator with an energy spectrum based on that 1–1.5 km from the epicenter of the Hiroshima blast to begin examining the effect of neutrons on global gene expression, and the impact this may have on the development of gene expression signatures for radiation biodosimetry. We have exposed peripheral blood from healthy human donors to 0.1, 0.3, 0.5 or 1 Gy of neutrons ex vivo using our neutron irradiator, and compared the transcriptomic response 24 h later to that resulting from sham exposure or exposure to 0.1, 0.3, 0.5, 1, 2 or 4 Gy of photons (X rays). We identified 125 genes that responded significantly to both radiation qualities as a function of dose, with the magnitude of response to neutrons generally being greater than that seen after X-ray exposure. Gene ontology analysis suggested broad involvement of the p53 signaling pathway and general DNA damage response functions across all doses of both radiation qualities. Regulation of immune response and chromatin-related functions were implicated only following the highest doses of neutrons, suggesting a physiological impact of greater DNA damage. We also identified several genes that seem to respond primarily as a function of dose, with less effect of radiation quality. We confirmed this pattern of response by quantitative real-time RT-PCR for BAX, TNFRSF10B, ITLN2 and AEN and suggest that gene expression may provide a means to differentiate between total dose and a neutron component. PMID:28140791

  9. Impact of Neutron Exposure on Global Gene Expression in a Human Peripheral Blood Model.

    PubMed

    Broustas, Constantinos G; Xu, Yanping; Harken, Andrew D; Chowdhury, Mashkura; Garty, Guy; Amundson, Sally A

    2017-04-01

    The detonation of an improvised nuclear device would produce prompt radiation consisting of both photons (gamma rays) and neutrons. While much effort in recent years has gone into the development of radiation biodosimetry methods suitable for mass triage, the possible effect of neutrons on the endpoints studied has remained largely uninvestigated. We have used a novel neutron irradiator with an energy spectrum based on that 1-1.5 km from the epicenter of the Hiroshima blast to begin examining the effect of neutrons on global gene expression, and the impact this may have on the development of gene expression signatures for radiation biodosimetry. We have exposed peripheral blood from healthy human donors to 0.1, 0.3, 0.5 or 1 Gy of neutrons ex vivo using our neutron irradiator, and compared the transcriptomic response 24 h later to that resulting from sham exposure or exposure to 0.1, 0.3, 0.5, 1, 2 or 4 Gy of photons (X rays). We identified 125 genes that responded significantly to both radiation qualities as a function of dose, with the magnitude of response to neutrons generally being greater than that seen after X-ray exposure. Gene ontology analysis suggested broad involvement of the p53 signaling pathway and general DNA damage response functions across all doses of both radiation qualities. Regulation of immune response and chromatin-related functions were implicated only following the highest doses of neutrons, suggesting a physiological impact of greater DNA damage. We also identified several genes that seem to respond primarily as a function of dose, with less effect of radiation quality. We confirmed this pattern of response by quantitative real-time RT-PCR for BAX, TNFRSF10B, ITLN2 and AEN and suggest that gene expression may provide a means to differentiate between total dose and a neutron component.

  10. Expression of the SIN3 homologue from banana, MaSIN3, suppresses ABA responses globally during plant growth in Arabidopsis.

    PubMed

    Luxmi, Raj; Garg, Rashmi; Srivastava, Sudhakar; Sane, Aniruddha P

    2017-11-01

    The SIN3 family of co-repressors is a family of highly conserved eukaryotic repressor proteins that regulates diverse functions in yeasts and animals but remains largely uncharacterized functionally even in plants like Arabidopsis. The sole SIN3 homologue in banana, MaSIN3, was identified as a 1408 amino acids, nuclear localized protein conserved to other SIN3s in the PAH, HID and HCR domains. Interestingly, MaSIN3 over-expression in Arabidopsis mimics a state of reduced ABA responses throughout plant development affecting growth processes such as germination, root growth, stomatal closure and water loss, flowering and senescence. The reduction in ABA responses is not due to reduced ABA levels but due to suppression of expression of several transcription factors mediating ABA responses. Transcript levels of negative regulators of germination (ABI3, ABI5, PIL5, RGL2 and RGL3) are reduced post-imbibition while those responsible for GA biosynthesis are up-regulated in transgenic MaSIN3 over-expressers. ABA-associated transcription factors are also down-regulated in response to ABA treatment. The HDAC inhibitors, SAHA and sodium butyrate, in combination with ABA differentially suppress germination in control and transgenic lines suggesting the recruitment by MaSIN3 of HDACs involved in suppression of ABA responses in different processes. The studies provide an insight into the ability of MaSIN3 to specifically affect a subset of developmental processes governed largely by ABA. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Global Expressions Landscape of NAC Transcription Factor Family and Their Responses to Abiotic Stresses in Citrullus lanatus

    PubMed Central

    Lv, Xiaolong; Lan, Shanrong; Guy, Kateta Malangisha; Yang, Jinghua; Zhang, Mingfang; Hu, Zhongyuan

    2016-01-01

    Watermelon (Citrullus lanatus) is one xerophyte that has relative higher tolerance to drought and salt stresses as well as more sensitivity to cold stress, compared with most model plants. These characteristics facilitate it a potential model crop for researches on salt, drought or cold tolerance. In this study, a genome-wide comprehensive analysis of the ClNAC transcription factor (TF) family was carried out for the first time, to investigate their transcriptional profiles and potential functions in response to these abiotic stresses. The expression profiling analysis reveals that several NAC TFs are highly responsive to abiotic stresses and development, for instance, subfamily IV NACs may play roles in maintaining water status under drought or salt conditions, as well as water and metabolites conduction and translocation toward fruit. In contrast, rapid and negative responses of most of the ClNACs to low-temperature adversity may be related to the sensitivity to cold stress. Crosstalks among these abiotic stresses and hormone (abscisic acid and jasmonic acid) pathways were also discussed based on the expression of ClNAC genes. Our results will provide useful insights for the functional mining of NAC family in watermelon, as well as into the mechanisms underlying abiotic tolerance in other cash crops. PMID:27491393

  12. Global Expressions Landscape of NAC Transcription Factor Family and Their Responses to Abiotic Stresses in Citrullus lanatus.

    PubMed

    Lv, Xiaolong; Lan, Shanrong; Guy, Kateta Malangisha; Yang, Jinghua; Zhang, Mingfang; Hu, Zhongyuan

    2016-08-05

    Watermelon (Citrullus lanatus) is one xerophyte that has relative higher tolerance to drought and salt stresses as well as more sensitivity to cold stress, compared with most model plants. These characteristics facilitate it a potential model crop for researches on salt, drought or cold tolerance. In this study, a genome-wide comprehensive analysis of the ClNAC transcription factor (TF) family was carried out for the first time, to investigate their transcriptional profiles and potential functions in response to these abiotic stresses. The expression profiling analysis reveals that several NAC TFs are highly responsive to abiotic stresses and development, for instance, subfamily IV NACs may play roles in maintaining water status under drought or salt conditions, as well as water and metabolites conduction and translocation toward fruit. In contrast, rapid and negative responses of most of the ClNACs to low-temperature adversity may be related to the sensitivity to cold stress. Crosstalks among these abiotic stresses and hormone (abscisic acid and jasmonic acid) pathways were also discussed based on the expression of ClNAC genes. Our results will provide useful insights for the functional mining of NAC family in watermelon, as well as into the mechanisms underlying abiotic tolerance in other cash crops.

  13. Conceptualizing psychological processes in response to globalization: Components, antecedents, and consequences of global orientations.

    PubMed

    Chen, Sylvia Xiaohua; Lam, Ben C P; Hui, Bryant P H; Ng, Jacky C K; Mak, Winnie W S; Guan, Yanjun; Buchtel, Emma E; Tang, Willie C S; Lau, Victor C Y

    2016-02-01

    The influences of globalization have permeated various aspects of life in contemporary society, from technical innovations, economic development, and lifestyles, to communication patterns. The present research proposed a construct termed global orientation to denote individual differences in the psychological processes of acculturating to the globalizing world. It encompasses multicultural acquisition as a proactive response and ethnic protection as a defensive response to globalization. Ten studies examined the applicability of global orientations among majority and minority groups, including immigrants and sojourners, in multicultural and relatively monocultural contexts, and across Eastern and Western cultures. Multicultural acquisition is positively correlated with both independent and interdependent self-construals, bilingual proficiency and usage, and dual cultural identifications. Multicultural acquisition is promotion-focused, while ethnic protection is prevention-focused and related to acculturative stress. Global orientations affect individuating and modest behavior over and above multicultural ideology, predict overlap with outgroups over and above political orientation, and predict psychological adaptation, sociocultural competence, tolerance, and attitudes toward ethnocultural groups over and above acculturation expectations/strategies. Global orientations also predict English and Chinese oral presentation performance in multilevel analyses and the frequency and pleasantness of intercultural contact in cross-lagged panel models. We discuss how the psychological study of global orientations contributes to theory and research on acculturation, cultural identity, and intergroup relations. (c) 2016 APA, all rights reserved).

  14. Global Proteomics Analysis of the Response to Starvation in C. elegans*

    PubMed Central

    Larance, Mark; Pourkarimi, Ehsan; Wang, Bin; Brenes Murillo, Alejandro; Kent, Robert; Lamond, Angus I.; Gartner, Anton

    2015-01-01

    Periodic starvation of animals induces large shifts in metabolism but may also influence many other cellular systems and can lead to adaption to prolonged starvation conditions. To date, there is limited understanding of how starvation affects gene expression, particularly at the protein level. Here, we have used mass-spectrometry-based quantitative proteomics to identify global changes in the Caenorhabditis elegans proteome due to acute starvation of young adult animals. Measuring changes in the abundance of over 5,000 proteins, we show that acute starvation rapidly alters the levels of hundreds of proteins, many involved in central metabolic pathways, highlighting key regulatory responses. Surprisingly, we also detect changes in the abundance of chromatin-associated proteins, including specific linker histones, histone variants, and histone posttranslational modifications associated with the epigenetic control of gene expression. To maximize community access to these data, they are presented in an online searchable database, the Encyclopedia of Proteome Dynamics (http://www.peptracker.com/epd/). PMID:25963834

  15. Cigarette Smoking Decreases Global MicroRNA Expression in Human Alveolar Macrophages

    PubMed Central

    Graff, Joel W.; Powers, Linda S.; Dickson, Anne M.; Kim, Jongkwang; Reisetter, Anna C.; Hassan, Ihab H.; Kremens, Karol; Gross, Thomas J.

    2012-01-01

    Human alveolar macrophages are critical components of the innate immune system. Cigarette smoking-induced changes in alveolar macrophage gene expression are linked to reduced resistance to pulmonary infections and to the development of emphysema/COPD. We hypothesized that microRNAs (miRNAs) could control, in part, the unique messenger RNA (mRNA) expression profiles found in alveolar macrophages of cigarette smokers. Activation of macrophages with different stimuli in vitro leads to a diverse range of M1 (inflammatory) and M2 (anti-inflammatory) polarized phenotypes that are thought to mimic activated macrophages in distinct tissue environments. Microarray mRNA data indicated that smoking promoted an “inverse” M1 mRNA expression program, defined by decreased expression of M1-induced transcripts and increased expression of M1-repressed transcripts with few changes in M2-regulated transcripts. RT-PCR arrays identified altered expression of many miRNAs in alveolar macrophages of smokers and a decrease in global miRNA abundance. Stratification of human subjects suggested that the magnitude of the global decrease in miRNA abundance was associated with smoking history. We found that many of the miRNAs with reduced expression in alveolar macrophages of smokers were predicted to target mRNAs upregulated in alveolar macrophages of smokers. For example, miR-452 is predicted to target the transcript encoding MMP12, an important effector of smoking-related diseases. Experimental antagonism of miR-452 in differentiated monocytic cells resulted in increased expression of MMP12. The comprehensive mRNA and miRNA expression profiles described here provide insight into gene expression regulation that may underlie the adverse effects cigarette smoking has on alveolar macrophages. PMID:22952876

  16. Global Analysis of Gene Expression Profiles in Physic Nut (Jatropha curcas L.) Seedlings Exposed to Salt Stress

    PubMed Central

    Wu, Pingzhi; Chen, Yaping; Li, Meiru; Jiang, Huawu; Wu, Guojiang

    2014-01-01

    Background Salt stress interferes with plant growth and production. Plants have evolved a series of molecular and morphological adaptations to cope with this abiotic stress, and overexpression of salt response genes reportedly enhances the productivity of various crops. However, little is known about the salt responsive genes in the energy plant physic nut (Jatropha curcas L.). Thus, excavate salt responsive genes in this plant are informative in uncovering the molecular mechanisms for the salt response in physic nut. Methodology/Principal Findings We applied next-generation Illumina sequencing technology to analyze global gene expression profiles of physic nut plants (roots and leaves) 2 hours, 2 days and 7 days after the onset of salt stress. A total of 1,504 and 1,115 genes were significantly up and down-regulated in roots and leaves, respectively, under salt stress condition. Gene ontology (GO) analysis of physiological process revealed that, in the physic nut, many “biological processes” were affected by salt stress, particular those categories belong to “metabolic process”, such as “primary metabolism process”, “cellular metabolism process” and “macromolecule metabolism process”. The gene expression profiles indicated that the associated genes were responsible for ABA and ethylene signaling, osmotic regulation, the reactive oxygen species scavenging system and the cell structure in physic nut. Conclusions/Significance The major regulated genes detected in this transcriptomic data were related to trehalose synthesis and cell wall structure modification in roots, while related to raffinose synthesis and reactive oxygen scavenger in leaves. The current study shows a comprehensive gene expression profile of physic nut under salt stress. The differential expression genes detected in this study allows the underling the salt responsive mechanism in physic nut with the aim of improving its salt resistance in the future. PMID:24837971

  17. Global analysis of gene expression profiles in physic nut (Jatropha curcas L.) seedlings exposed to salt stress.

    PubMed

    Zhang, Lin; Zhang, Chao; Wu, Pingzhi; Chen, Yaping; Li, Meiru; Jiang, Huawu; Wu, Guojiang

    2014-01-01

    Salt stress interferes with plant growth and production. Plants have evolved a series of molecular and morphological adaptations to cope with this abiotic stress, and overexpression of salt response genes reportedly enhances the productivity of various crops. However, little is known about the salt responsive genes in the energy plant physic nut (Jatropha curcas L.). Thus, excavate salt responsive genes in this plant are informative in uncovering the molecular mechanisms for the salt response in physic nut. We applied next-generation Illumina sequencing technology to analyze global gene expression profiles of physic nut plants (roots and leaves) 2 hours, 2 days and 7 days after the onset of salt stress. A total of 1,504 and 1,115 genes were significantly up and down-regulated in roots and leaves, respectively, under salt stress condition. Gene ontology (GO) analysis of physiological process revealed that, in the physic nut, many "biological processes" were affected by salt stress, particular those categories belong to "metabolic process", such as "primary metabolism process", "cellular metabolism process" and "macromolecule metabolism process". The gene expression profiles indicated that the associated genes were responsible for ABA and ethylene signaling, osmotic regulation, the reactive oxygen species scavenging system and the cell structure in physic nut. The major regulated genes detected in this transcriptomic data were related to trehalose synthesis and cell wall structure modification in roots, while related to raffinose synthesis and reactive oxygen scavenger in leaves. The current study shows a comprehensive gene expression profile of physic nut under salt stress. The differential expression genes detected in this study allows the underling the salt responsive mechanism in physic nut with the aim of improving its salt resistance in the future.

  18. The Role of Civil Society Organizations in Monitoring the Global AIDS Response.

    PubMed

    Smith, Julia; Mallouris, Christoforos; Lee, Kelley; Alfvén, Tobias

    2017-07-01

    Civil society organizations (CSOs) are recognized as playing an exceptional role in the global AIDS response. However, there is little detailed research to date on how they contribute to specific governance functions. This article uses Haas' framework on global governance functions to map CSO's participation in the monitoring of global commitments to the AIDS response by institutions and states. Drawing on key informant interviews and primary documents, it focuses specifically on CSO participation in Global AIDS Response Progress Reporting and in Global Fund to Fight AIDS, Tuberculosis and Malaria processes. It argues that the AIDS response is unique within global health governance, in that CSOs fulfill both formal and informal monitoring functions, and considers the strengths and weaknesses of these contributions. It concludes that future global health governance arrangements should include provisions and resources for monitoring by CSOs because their participation creates more inclusive global health governance and contributes to strengthening commitments to human rights.

  19. Phylogenetic responses of forest trees to global change.

    PubMed

    Senior, John K; Schweitzer, Jennifer A; O'Reilly-Wapstra, Julianne; Chapman, Samantha K; Steane, Dorothy; Langley, Adam; Bailey, Joseph K

    2013-01-01

    In a rapidly changing biosphere, approaches to understanding the ecology and evolution of forest species will be critical to predict and mitigate the effects of anthropogenic global change on forest ecosystems. Utilizing 26 forest species in a factorial experiment with two levels each of atmospheric CO2 and soil nitrogen, we examined the hypothesis that phylogeny would influence plant performance in response to elevated CO2 and nitrogen fertilization. We found highly idiosyncratic responses at the species level. However, significant, among-genetic lineage responses were present across a molecularly determined phylogeny, indicating that past evolutionary history may have an important role in the response of whole genetic lineages to future global change. These data imply that some genetic lineages will perform well and that others will not, depending upon the environmental context.

  20. Global gene expression analysis using RNA-seq uncovered a new role for SR1/CAMTA3 transcription factor in salt stress

    PubMed Central

    Prasad, Kasavajhala V. S. K.; Abdel-Hameed, Amira A. E.; Xing, Denghui; Reddy, Anireddy S. N.

    2016-01-01

    Abiotic and biotic stresses cause significant yield losses in all crops. Acquisition of stress tolerance in plants requires rapid reprogramming of gene expression. SR1/CAMTA3, a member of signal responsive transcription factors (TFs), functions both as a positive and a negative regulator of biotic stress responses and as a positive regulator of cold stress-induced gene expression. Using high throughput RNA-seq, we identified ~3000 SR1-regulated genes. Promoters of about 60% of the differentially expressed genes have a known DNA binding site for SR1, suggesting that they are likely direct targets. Gene ontology analysis of SR1-regulated genes confirmed previously known functions of SR1 and uncovered a potential role for this TF in salt stress. Our results showed that SR1 mutant is more tolerant to salt stress than the wild type and complemented line. Improved tolerance of sr1 seedlings to salt is accompanied with the induction of salt-responsive genes. Furthermore, ChIP-PCR results showed that SR1 binds to promoters of several salt-responsive genes. These results suggest that SR1 acts as a negative regulator of salt tolerance by directly repressing the expression of salt-responsive genes. Overall, this study identified SR1-regulated genes globally and uncovered a previously uncharacterized role for SR1 in salt stress response. PMID:27251464

  1. Differential global gene expression in red and white skeletal muscle

    NASA Technical Reports Server (NTRS)

    Campbell, W. G.; Gordon, S. E.; Carlson, C. J.; Pattison, J. S.; Hamilton, M. T.; Booth, F. W.

    2001-01-01

    The differences in gene expression among the fiber types of skeletal muscle have long fascinated scientists, but for the most part, previous experiments have only reported differences of one or two genes at a time. The evolving technology of global mRNA expression analysis was employed to determine the potential differential expression of approximately 3,000 mRNAs between the white quad (white muscle) and the red soleus muscle (mixed red muscle) of female ICR mice (30-35 g). Microarray analysis identified 49 mRNA sequences that were differentially expressed between white and mixed red skeletal muscle, including newly identified differential expressions between muscle types. For example, the current findings increase the number of known, differentially expressed mRNAs for transcription factors/coregulators by nine and signaling proteins by three. The expanding knowledge of the diversity of mRNA expression between white and mixed red muscle suggests that there could be quite a complex regulation of phenotype between muscles of different fiber types.

  2. Social responsibility of nursing: a global perspective.

    PubMed

    Tyer-Viola, Lynda; Nicholas, Patrice K; Corless, Inge B; Barry, Donna M; Hoyt, Pamela; Fitzpatrick, Joyce J; Davis, Sheila M

    2009-05-01

    This study addresses social responsibility in the discipline of nursing and implications for global health. The concept of social responsibility is explicated and its relevance for nursing is examined, grounded in the American Nurses Association Code of Ethics and the International Council of Nurses Code of Ethics. Social justice, human rights, nurse migration, and approaches to nursing education are discussed within the framework of nursing's social responsibility. Strategies for addressing nursing workforce issues and education within a framework of social responsibility are explored.

  3. Expression of the alaE gene is positively regulated by the global regulator Lrp in response to intracellular accumulation of l-alanine in Escherichia coli.

    PubMed

    Ihara, Kohei; Sato, Kazuki; Hori, Hatsuhiro; Makino, Yumiko; Shigenobu, Shuji; Ando, Tasuke; Isogai, Emiko; Yoneyama, Hiroshi

    2017-04-01

    The alaE gene in Escherichia coli encodes an l-alanine exporter that catalyzes the active export of l-alanine using proton electrochemical potential. In our previous study, alaE expression was shown to increase in the presence of l-alanyl-l-alanine (Ala-Ala). In this study, the global regulator leucine-responsive regulatory protein (Lrp) was identified as an activator of the alaE gene. A promoter less β-galactosidase gene was fused to an alaE upstream region (240 nucleotides). Cells that were lacZ-deficient and harbored this reporter plasmid showed significant induction of β-galactosidase activity (approximately 17-fold) in the presence of 6 mM l-alanine, l-leucine, and Ala-Ala. However, a reporter plasmid possessing a smaller alaE upstream region (180 nucleotides) yielded transformants with strikingly low enzyme activity under the same conditions. In contrast, lrp-deficient cells showed almost no β-galactosidase induction, indicating that Lrp positively regulates alaE expression. We next performed an electrophoretic mobility shift assay (EMSA) and a DNase I footprinting assay using purified hexahistidine-tagged Lrp (Lrp-His). Consequently, we found that Lrp-His binds to the alaE upstream region spanning nucleotide -161 to -83 with a physiologically relevant affinity (apparent K D , 288.7 ± 83.8 nM). Furthermore, the binding affinity of Lrp-His toward its cis-element was increased by l-alanine and l-leucine, but not by Ala-Ala and d-alanine. Based on these results, we concluded that the gene expression of the alaE is regulated by Lrp in response to intracellular levels of l-alanine, which eventually leads to intracellular homeostasis of l-alanine concentrations. Copyright © 2016 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  4. Dehydration-responsive miRNAs in foxtail millet: genome-wide identification, characterization and expression profiling.

    PubMed

    Yadav, Amita; Khan, Yusuf; Prasad, Manoj

    2016-03-01

    A set of novel and known dehydration-responsive miRNAs have been identified in foxtail millet. These findings provide new insights into understanding the functional role of miRNAs and their respective targets in regulating plant response to dehydration stress. MicroRNAs perform significant regulatory roles in growth, development and stress response of plants. Though the miRNA-mediated gene regulatory networks under dehydration stress remain largely unexplored in plant including foxtail millet (Setaria italica), which is a natural abiotic stress tolerant crop. To find out the dehydration-responsive miRNAs at the global level, four small RNA libraries were constructed from control and dehydration stress treated seedlings of two foxtail millet cultivars showing contrasting tolerance behavior towards dehydration stress. Using Illumina sequencing technology, 55 known and 136 novel miRNAs were identified, representing 22 and 48 miRNA families, respectively. Eighteen known and 33 novel miRNAs were differentially expressed during dehydration stress. After the stress treatment, 32 dehydration-responsive miRNAs were up-regulated in tolerant cultivar and 22 miRNAs were down-regulated in sensitive cultivar, suggesting that miRNA-mediated molecular regulation might play important roles in providing contrasting characteristics to these cultivars. Predicted targets of identified miRNAs were found to encode various transcription factors and functional enzymes, indicating their involvement in broad spectrum regulatory functions and biological processes. Further, differential expression patterns of seven known miRNAs were validated by northern blot and expression of ten novel dehydration-responsive miRNAs were confirmed by SL-qRT PCR. Differential expression behavior of five miRNA-target genes was verified under dehydration stress treatment and two of them also validated by RLM RACE. Overall, the present study highlights the importance of dehydration stress-associated post

  5. Global Transcriptional Profiles of the Copper Responses in the Cyanobacterium Synechocystis sp. PCC 6803

    PubMed Central

    Giner-Lamia, Joaquin; López-Maury, Luis; Florencio, Francisco J.

    2014-01-01

    Copper is an essential element involved in fundamental processes like respiration and photosynthesis. However, it becomes toxic at high concentration, which has forced organisms to control its cellular concentration. We have recently described a copper resistance system in the cyanobacterium Synechocystis sp. PCC 6803, which is mediated by the two-component system, CopRS, a RND metal transport system, CopBAC and a protein of unknown function, CopM. Here, we report the transcriptional responses to copper additions at non-toxic (0.3 µM) and toxic concentrations (3 µM) in the wild type and in the copper sensitive copR mutant strain. While 0.3 µM copper slightly stimulated metabolism and promoted the exchange between cytochrome c6 and plastocyanin as soluble electron carriers, the addition of 3 µM copper catalyzed the formation of ROS, led to a general stress response and induced expression of Fe-S cluster biogenesis genes. According to this, a double mutant strain copRsufR, which expresses constitutively the sufBCDS operon, tolerated higher copper concentration than the copR mutant strain, suggesting that Fe-S clusters are direct targets of copper toxicity in Synechocystis. In addition we have also demonstrated that InrS, a nickel binding transcriptional repressor that belong to the CsoR family of transcriptional factor, was involved in heavy metal homeostasis, including copper, in Synechocystis. Finally, global gene expression analysis of the copR mutant strain suggested that CopRS only controls the expression of copMRS and copBAC operons in response to copper. PMID:25268225

  6. Inactivation of the budding yeast cohesin loader Scc2 alters gene expression both globally and in response to a single DNA double strand break

    PubMed Central

    Lindgren, Emma; Hägg, Sara; Giordano, Fosco; Björkegren, Johan; Ström, Lena

    2014-01-01

    Genome integrity is fundamental for cell survival and cell cycle progression. Important mechanisms for keeping the genome intact are proper sister chromatid segregation, correct gene regulation and efficient repair of damaged DNA. Cohesin and its DNA loader, the Scc2/4 complex have been implicated in all these cellular actions. The gene regulation role has been described in several organisms. In yeast it has been suggested that the proteins in the cohesin network would effect transcription based on its role as insulator. More recently, data are emerging indicating direct roles for gene regulation also in yeast. Here we extend these studies by investigating whether the cohesin loader Scc2 is involved in regulation of gene expression. We performed global gene expression profiling in the absence and presence of DNA damage, in wild type and Scc2 deficient G2/M arrested cells, when it is known that Scc2 is important for DNA double strand break repair and formation of damage induced cohesion. We found that not only the DNA damage specific transcriptional response is distorted after inactivation of Scc2 but also the overall transcription profile. Interestingly, these alterations did not correlate with changes in cohesin binding. PMID:25483075

  7. Global transcriptional responses of Acidithiobacillus ferrooxidans Wenelen under different sulfide minerals.

    PubMed

    Latorre, Mauricio; Ehrenfeld, Nicole; Cortés, María Paz; Travisany, Dante; Budinich, Marko; Aravena, Andrés; González, Mauricio; Bobadilla-Fazzini, Roberto A; Parada, Pilar; Maass, Alejandro

    2016-01-01

    In order to provide new information about the adaptation of Acidithiobacillus ferrooxidans during the bioleaching process, the current analysis presents the first report of the global transcriptional response of the native copper mine strain Wenelen (DSM 16786) oxidized under different sulfide minerals. Microarrays were used to measure the response of At. ferrooxidans Wenelen to shifts from iron supplemented liquid cultures (reference state) to the addition of solid substrates enriched in pyrite or chalcopyrite. Genes encoding for energy metabolism showed a similar transcriptional profile for the two sulfide minerals. Interestingly, four operons related to sulfur metabolism were over-expressed during growth on a reduced sulfur source. Genes associated with metal tolerance (RND and ATPases type P) were up-regulated in the presence of pyrite or chalcopyrite. These results suggest that At. ferrooxidans Wenelen presents an efficient transcriptional system developed to respond to environmental conditions, namely the ability to withstand high copper concentrations. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Construction and comparison of gene co-expression networks shows complex plant immune responses

    PubMed Central

    López, Camilo; López-Kleine, Liliana

    2014-01-01

    Gene co-expression networks (GCNs) are graphic representations that depict the coordinated transcription of genes in response to certain stimuli. GCNs provide functional annotations of genes whose function is unknown and are further used in studies of translational functional genomics among species. In this work, a methodology for the reconstruction and comparison of GCNs is presented. This approach was applied using gene expression data that were obtained from immunity experiments in Arabidopsis thaliana, rice, soybean, tomato and cassava. After the evaluation of diverse similarity metrics for the GCN reconstruction, we recommended the mutual information coefficient measurement and a clustering coefficient-based method for similarity threshold selection. To compare GCNs, we proposed a multivariate approach based on the Principal Component Analysis (PCA). Branches of plant immunity that were exemplified by each experiment were analyzed in conjunction with the PCA results, suggesting both the robustness and the dynamic nature of the cellular responses. The dynamic of molecular plant responses produced networks with different characteristics that are differentiable using our methodology. The comparison of GCNs from plant pathosystems, showed that in response to similar pathogens plants could activate conserved signaling pathways. The results confirmed that the closeness of GCNs projected on the principal component space is an indicative of similarity among GCNs. This also can be used to understand global patterns of events triggered during plant immune responses. PMID:25320678

  9. Global Metabolic Responses to Salt Stress in Fifteen Species

    PubMed Central

    Pollak, Georg R.; Kuehne, Andreas; Sauer, Uwe

    2016-01-01

    Cells constantly adapt to unpredictably changing extracellular solute concentrations. A cornerstone of the cellular osmotic stress response is the metabolic supply of energy and building blocks to mount appropriate defenses. Yet, the extent to which osmotic stress impinges on the metabolic network remains largely unknown. Moreover, it is mostly unclear which, if any, of the metabolic responses to osmotic stress are conserved among diverse organisms or confined to particular groups of species. Here we investigate the global metabolic responses of twelve bacteria, two yeasts and two human cell lines exposed to sustained hyperosmotic salt stress by measuring semiquantitative levels of hundreds of cellular metabolites using nontargeted metabolomics. Beyond the accumulation of osmoprotectants, we observed significant changes of numerous metabolites in all species. Global metabolic responses were predominantly species-specific, yet individual metabolites were characteristically affected depending on species’ taxonomy, natural habitat, envelope structure or salt tolerance. Exploiting the breadth of our dataset, the correlation of individual metabolite response magnitudes across all species implicated lower glycolysis, tricarboxylic acid cycle, branched-chain amino acid metabolism and heme biosynthesis to be generally important for salt tolerance. Thus, our findings place the global metabolic salt stress response into a phylogenetic context and provide insights into the cellular phenotype associated with salt tolerance. PMID:26848578

  10. Comparative Digital Gene Expression Analysis of the Arabidopsis Response to Volatiles Emitted by Bacillus amyloliquefaciens

    PubMed Central

    Hao, Hai-Ting; Zhao, Xia; Shang, Qian-Han; Wang, Yun; Guo, Zhi-Hong; Zhang, Yu-Bao; Xie, Zhong-Kui; Wang, Ruo-Yu

    2016-01-01

    Some plant growth-promoting rhizobacteria (PGPR) regulated plant growth and elicited plant basal immunity by volatiles. The response mechanism to the Bacillus amyloliquefaciens volatiles in plant has not been well studied. We conducted global gene expression profiling in Arabidopsis after treatment with Bacillus amyloliquefaciens FZB42 volatiles by Illumina Digital Gene Expression (DGE) profiling of different growth stages (seedling and mature) and tissues (leaves and roots). Compared with the control, 1,507 and 820 differentially expressed genes (DEGs) were identified in leaves and roots at the seedling stage, respectively, while 1,512 and 367 DEGs were identified in leaves and roots at the mature stage. Seventeen genes with different regulatory patterns were validated using quantitative RT-PCR. Numerous DEGs were enriched for plant hormones, cell wall modifications, and protection against stress situations, which suggests that volatiles have effects on plant growth and immunity. Moreover, analyzes of transcriptome difference in tissues and growth stage using DGE profiling showed that the plant response might be tissue-specific and/or growth stage-specific. Thus, genes encoding flavonoid biosynthesis were downregulated in leaves and upregulated in roots, thereby indicating tissue-specific responses to volatiles. Genes related to photosynthesis were downregulated at the seedling stage and upregulated at the mature stage, respectively, thereby suggesting growth period-specific responses. In addition, the emission of bacterial volatiles significantly induced killing of cells of other organism pathway with up-regulated genes in leaves and the other three pathways (defense response to nematode, cell morphogenesis involved in differentiation and trichoblast differentiation) with up-regulated genes were significantly enriched in roots. Interestingly, some important alterations in the expression of growth-related genes, metabolic pathways, defense response to biotic

  11. Optimal function explains forest responses to global change

    Treesearch

    Roderick Dewar; Oskar Franklin; Annikki Makela; Ross E. McMurtrie; Harry T. Valentine

    2009-01-01

    Plant responses to global changes in carbon dioxide (CO2), nitrogen, and water availability are critical to future atmospheric CO2 concentrations, hydrology, and hence climate. Our understanding of those responses is incomplete, however. Multiple-resource manipulation experiments and empirical observations have revealed a...

  12. Global Citizenship Incorporated: Competing Responsibilities in the Education of Global Citizens

    ERIC Educational Resources Information Center

    Hartung, Catherine

    2017-01-01

    Interest in the education of young people to be 'responsible global citizens' has grown exponentially since the turn of the century, led by increasingly diverse networks of sectors, including government, community, business and philanthropy. These networks now have a significant influence on education policy and practice, indicative of wider…

  13. Global Transcriptional, Physiological, and Metabolite Analyses of the Responses of Desulfovibrio vulgaris Hildenborough to Salt Adaptation ▿ †

    PubMed Central

    He, Zhili; Zhou, Aifen; Baidoo, Edward; He, Qiang; Joachimiak, Marcin P.; Benke, Peter; Phan, Richard; Mukhopadhyay, Aindrila; Hemme, Christopher L.; Huang, Katherine; Alm, Eric J.; Fields, Matthew W.; Wall, Judy; Stahl, David; Hazen, Terry C.; Keasling, Jay D.; Arkin, Adam P.; Zhou, Jizhong

    2010-01-01

    The response of Desulfovibrio vulgaris Hildenborough to salt adaptation (long-term NaCl exposure) was examined by performing physiological, global transcriptional, and metabolite analyses. Salt adaptation was reflected by increased expression of genes involved in amino acid biosynthesis and transport, electron transfer, hydrogen oxidation, and general stress responses (e.g., heat shock proteins, phage shock proteins, and oxidative stress response proteins). The expression of genes involved in carbon metabolism, cell growth, and phage structures was decreased. Transcriptome profiles of D. vulgaris responses to salt adaptation were compared with transcriptome profiles of D. vulgaris responses to salt shock (short-term NaCl exposure). Metabolite assays showed that glutamate and alanine accumulated under salt adaptation conditions, suggesting that these amino acids may be used as osmoprotectants in D. vulgaris. Addition of amino acids (glutamate, alanine, and tryptophan) or yeast extract to the growth medium relieved salt-related growth inhibition. A conceptual model that links the observed results to currently available knowledge is proposed to increase our understanding of the mechanisms of D. vulgaris adaptation to elevated NaCl levels. PMID:20038696

  14. Global transcriptomic response of Anoxybacillus sp. SK 3-4 to aluminum exposure.

    PubMed

    Lim, Jia Chun; Thevarajoo, Suganthi; Selvaratnam, Chitra; Goh, Kian Mau; Shamsir, Mohd Shahir; Ibrahim, Zaharah; Chong, Chun Shiong

    2017-02-01

    Anoxybacillus sp. SK 3-4 is a Gram-positive, rod-shaped bacterium and a member of family Bacillaceae. We had previously reported that the strain is an aluminum resistant thermophilic bacterium. This is the first report to provide a detailed analysis of the global transcriptional response of Anoxybacillus when the cells were exposed to 600 mg L -1 of aluminum. The transcriptome was sequenced using Illumina MiSeq sequencer. Total of 708 genes were differentially expressed (fold change >2.00) with 316 genes were up-regulated while 347 genes were down-regulated, in comparing to control with no aluminum added in the culture. Based on Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, the majority of genes encoding for cell metabolism such as glycolysis, sulfur metabolism, cysteine and methionine metabolism were up-regulated; while most of the gene associated with tricarboxylic acid cycle (TCA cycle) and valine, leucine and isoleucine metabolism were down-regulated. In addition, a significant number of the genes encoding ABC transporters, metal ions transporters, and some stress response proteins were also differentially expressed following aluminum exposure. The findings provide further insight and help us to understand on the resistance of Anoxybacillus sp. SK 3-4 toward aluminium. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Global Gene Expression Profiling in PAI-1 Knockout Murine Heart and Kidney: Molecular Basis of Cardiac-Selective Fibrosis

    PubMed Central

    Ghosh, Asish K.; Murphy, Sheila B.; Kishore, Raj; Vaughan, Douglas E.

    2013-01-01

    Fibrosis is defined as an abnormal matrix remodeling due to excessive synthesis and accumulation of extracellular matrix proteins in tissues during wound healing or in response to chemical, mechanical and immunological stresses. At present, there is no effective therapy for organ fibrosis. Previous studies demonstrated that aged plasminogen activator inhibitor-1(PAI-1) knockout mice develop spontaneously cardiac-selective fibrosis without affecting any other organs. We hypothesized that differential expressions of profibrotic and antifibrotic genes in PAI-1 knockout hearts and unaffected organs lead to cardiac selective fibrosis. In order to address this prediction, we have used a genome-wide gene expression profiling of transcripts derived from aged PAI-1 knockout hearts and kidneys. The variations of global gene expression profiling were compared within four groups: wildtype heart vs. knockout heart; wildtype kidney vs. knockout kidney; knockout heart vs. knockout kidney and wildtype heart vs. wildtype kidney. Analysis of illumina-based microarray data revealed that several genes involved in different biological processes such as immune system processing, response to stress, cytokine signaling, cell proliferation, adhesion, migration, matrix organization and transcriptional regulation were affected in hearts and kidneys by the absence of PAI-1, a potent inhibitor of urokinase and tissue-type plasminogen activator. Importantly, the expressions of a number of genes, involved in profibrotic pathways including Ankrd1, Pi16, Egr1, Scx, Timp1, Timp2, Klf6, Loxl1 and Klotho, were deregulated in PAI-1 knockout hearts compared to wildtype hearts and PAI-1 knockout kidneys. While the levels of Ankrd1, Pi16 and Timp1 proteins were elevated during EndMT, the level of Timp4 protein was decreased. To our knowledge, this is the first comprehensive report on the influence of PAI-1 on global gene expression profiling in the heart and kidney and its implication in fibrogenesis and

  16. Cerebral responses to local and global auditory novelty under general anesthesia

    PubMed Central

    Uhrig, Lynn; Janssen, David; Dehaene, Stanislas; Jarraya, Béchir

    2017-01-01

    Primate brains can detect a variety of unexpected deviations in auditory sequences. The local-global paradigm dissociates two hierarchical levels of auditory predictive coding by examining the brain responses to first-order (local) and second-order (global) sequence violations. Using the macaque model, we previously demonstrated that, in the awake state, local violations cause focal auditory responses while global violations activate a brain circuit comprising prefrontal, parietal and cingulate cortices. Here we used the same local-global auditory paradigm to clarify the encoding of the hierarchical auditory regularities in anesthetized monkeys and compared their brain responses to those obtained in the awake state as measured with fMRI. Both, propofol, a GABAA-agonist, and ketamine, an NMDA-antagonist, left intact or even enhanced the cortical response to auditory inputs. The local effect vanished during propofol anesthesia and shifted spatially during ketamine anesthesia compared with wakefulness. Under increasing levels of propofol, we observed a progressive disorganization of the global effect in prefrontal, parietal and cingulate cortices and its complete suppression under ketamine anesthesia. Anesthesia also suppressed thalamic activations to the global effect. These results suggest that anesthesia preserves initial auditory processing, but disturbs both short-term and long-term auditory predictive coding mechanisms. The disorganization of auditory novelty processing under anesthesia relates to a loss of thalamic responses to novelty and to a disruption of higher-order functional cortical networks in parietal, prefrontal and cingular cortices. PMID:27502046

  17. Thiol peroxidases mediate specific genome-wide regulation of gene expression in response to hydrogen peroxide

    PubMed Central

    Fomenko, Dmitri E.; Koc, Ahmet; Agisheva, Natalia; Jacobsen, Michael; Kaya, Alaattin; Malinouski, Mikalai; Rutherford, Julian C.; Siu, Kam-Leung; Jin, Dong-Yan; Winge, Dennis R.; Gladyshev, Vadim N.

    2011-01-01

    Hydrogen peroxide is thought to regulate cellular processes by direct oxidation of numerous cellular proteins, whereas antioxidants, most notably thiol peroxidases, are thought to reduce peroxides and inhibit H2O2 response. However, thiol peroxidases have also been implicated in activation of transcription factors and signaling. It remains unclear if these enzymes stimulate or inhibit redox regulation and whether this regulation is widespread or limited to a few cellular components. Herein, we found that Saccharomyces cerevisiae cells lacking all eight thiol peroxidases were viable and withstood redox stresses. They transcriptionally responded to various redox treatments, but were unable to activate and repress gene expression in response to H2O2. Further studies involving redox transcription factors suggested that thiol peroxidases are major regulators of global gene expression in response to H2O2. The data suggest that thiol peroxidases sense and transfer oxidative signals to the signaling proteins and regulate transcription, whereas a direct interaction between H2O2 and other cellular proteins plays a secondary role. PMID:21282621

  18. Mechanisms of crystalline silica-induced pulmonary toxicity revealed by global gene expression profiling

    PubMed Central

    Sellamuthu, Rajendran; Umbright, Christina; Li, Shengqiao; Kashon, Michael; Joseph, Pius

    2015-01-01

    A proper understanding of the mechanisms underlying crystalline silica-induced pulmonary toxicity has implications in the management and potential prevention of the adverse health effects associated with silica exposure including silicosis, cancer and several auto-immune diseases. Human lung type II epithelial cells and rat lungs exposed to crystalline silica were employed as experimental models to determine global gene expression changes in order to understand the molecular mechanisms underlying silica-induced pulmonary toxicity. The differential gene expression profile induced by silica correlated with its toxicity in the A549 cells. The biological processes perturbed by silica exposure in the A549 cells and rat lungs, as identified by the bioinformatics analysis of the differentially expressed genes, demonstrated significant similarity. Functional categorization of the differentially expressed genes identified cancer, cellular movement, cellular growth and proliferation, cell death, inflammatory response, cell cycle, cellular development, and genetic disorder as top ranking biological functions perturbed by silica exposure in A549 cells and rat lungs. Results of our study, in addition to confirming several previously identified molecular targets and mechanisms involved in silica toxicity, identified novel molecular targets and mechanisms potentially involved in silica-induced pulmonary toxicity. Further investigations, including those focused on the novel molecular targets and mechanisms identified in the current study may result in better management and, possibly, reduction and/or prevention of the potential adverse health effects associated with crystalline silica exposure. PMID:22087542

  19. Global Rsh-dependent transcription profile of Brucella suis during stringent response unravels adaptation to nutrient starvation and cross-talk with other stress responses

    PubMed Central

    2013-01-01

    Background In the intracellular pathogen Brucella spp., the activation of the stringent response, a global regulatory network providing rapid adaptation to growth-affecting stress conditions such as nutrient deficiency, is essential for replication in the host. A single, bi-functional enzyme Rsh catalyzes synthesis and hydrolysis of the alarmone (p)ppGpp, responsible for differential gene expression under stringent conditions. Results cDNA microarray analysis allowed characterization of the transcriptional profiles of the B. suis 1330 wild-type and Δrsh mutant in a minimal medium, partially mimicking the nutrient-poor intramacrophagic environment. A total of 379 genes (11.6% of the genome) were differentially expressed in a rsh-dependent manner, of which 198 were up-, and 181 were down-regulated. The pleiotropic character of the response was confirmed, as the genes encoded an important number of transcriptional regulators, cell envelope proteins, stress factors, transport systems, and energy metabolism proteins. Virulence genes such as narG and sodC, respectively encoding respiratory nitrate reductase and superoxide dismutase, were under the positive control of (p)ppGpp, as well as expression of the cbb3-type cytochrome c oxidase, essential for chronic murine infection. Methionine was the only amino acid whose biosynthesis was absolutely dependent on stringent response in B. suis. Conclusions The study illustrated the complexity of the processes involved in adaptation to nutrient starvation, and contributed to a better understanding of the correlation between stringent response and Brucella virulence. Most interestingly, it clearly indicated (p)ppGpp-dependent cross-talk between at least three stress responses playing a central role in Brucella adaptation to the host: nutrient, oxidative, and low-oxygen stress. PMID:23834488

  20. Global expression pattern comparison between low phosphorus insensitive 4 and WT Arabidopsis reveals an important role of reactive oxygen species and jasmonic acid in the root tip response to phosphate starvation

    PubMed Central

    Chacón-López, Alejandra; Ibarra-Laclette, Enrique; Sánchez-Calderón, Lenin; Gutiérrez-Alanís, Dolores

    2011-01-01

    Plants are exposed to several biotic and abiotic stresses. A common environmental stress that plants have to face both in natural and agricultural ecosystems that impacts both its growth and development is low phosphate (Pi) availability. There has been an important progress in the knowledge of the molecular mechanisms by which plants cope with Pi deficiency. However, the mechanisms that mediate alterations in the architecture of the Arabidopsis root system responses to Pi starvation are still largely unknown. One of the most conspicuous developmental effects of low Pi on the Arabidopsis root system is the inhibition of primary root growth that is accompanied by loss of root meristematic activity. To identify signalling pathways potentially involved in the Arabidpsis root meristem response to Pi-deprivation, here we report the global gene expression analysis of the root tip of wild type and low phosphorus insensitive4 (lpi4) mutant grown under Pi limiting conditions. Differential gene expression analysis and physiological experiments show that changes in the redox status, probably mediated by jasmonic acid and ethylene, play an important role in the primary root meristem exhaustion process triggered by Pi-starvation. PMID:21368582

  1. RNA expression of genes involved in cytarabine metabolism and transport predicts cytarabine response in acute myeloid leukemia.

    PubMed

    Abraham, Ajay; Varatharajan, Savitha; Karathedath, Sreeja; Philip, Chepsy; Lakshmi, Kavitha M; Jayavelu, Ashok Kumar; Mohanan, Ezhilpavai; Janet, Nancy Beryl; Srivastava, Vivi M; Shaji, Ramachandran V; Zhang, Wei; Abraham, Aby; Viswabandya, Auro; George, Biju; Chandy, Mammen; Srivastava, Alok; Mathews, Vikram; Balasubramanian, Poonkuzhali

    2015-07-01

    Variation in terms of outcome and toxic side effects of treatment exists among acute myeloid leukemia (AML) patients on chemotherapy with cytarabine (Ara-C) and daunorubicin (Dnr). Candidate Ara-C metabolizing gene expression in primary AML cells is proposed to account for this variation. Ex vivo Ara-C sensitivity was determined in primary AML samples using MTT assay. mRNA expression of candidate Ara-C metabolizing genes were evaluated by RQPCR analysis. Global gene expression profiling was carried out for identifying differentially expressed genes between exvivo Ara-C sensitive and resistant samples. Wide interindividual variations in ex vivo Ara-C cytotoxicity were observed among samples from patients with AML and were stratified into sensitive, intermediately sensitive and resistant, based on IC50 values obtained by MTT assay. RNA expression of deoxycytidine kinase (DCK), human equilibrative nucleoside transporter-1 (ENT1) and ribonucleotide reductase M1 (RRM1) were significantly higher and cytidine deaminase (CDA) was significantly lower in ex vivo Ara-C sensitive samples. Higher DCK and RRM1 expression in AML patient's blast correlated with better DFS. Ara-C resistance index (RI), a mathematically derived quotient was proposed based on candidate gene expression pattern. Ara-C ex vivo sensitive samples were found to have significantly lower RI compared with resistant as well as samples from patients presenting with relapse. Patients with low RI supposedly highly sensitive to Ara-C were found to have higher incidence of induction death (p = 0.002; RR: 4.35 [95% CI: 1.69-11.22]). Global gene expression profiling undertaken to find out additional contributors of Ara-C resistance identified many apoptosis as well as metabolic pathway genes to be differentially expressed between Ara-C resistant and sensitive samples. This study highlights the importance of evaluating expression of candidate Ara-C metabolizing genes in predicting ex vivo drug response as well as

  2. Global empirical model of TEC response to geomagnetic activity

    NASA Astrophysics Data System (ADS)

    Mukhtarov, P.; Andonov, B.; Pancheva, D.

    2013-10-01

    global total electron content (TEC) model response to geomagnetic activity described by the Kp index is built by using the Center for Orbit Determination of Europe (CODE) TEC data for a full 13 years, January 1999 to December 2011. The model describes the most probable spatial distribution and temporal variability of the geomagnetically forced TEC anomalies assuming that these anomalies at a given modified dip latitude depend mainly on the Kp index, local time (LT), and longitude. The geomagnetic anomalies are expressed by the relative deviation of TEC from its 15 day median and are denoted as rTEC. The rTEC response to the geomagnetic activity is presented by a sum of two responses with different time delay constants and different signs of the cross-correlation function. It has been found that the mean dependence of rTEC on Kp index can be expressed by a cubic function. The LT dependence of rTEC is described by Fourier time series which includes the contribution of four diurnal components with periods 24, 12, 8, and 6 h. The rTEC dependence on longitude is presented by Fourier series which includes the contribution of zonal waves with zonal wave numbers up to 6. In order to demonstrate how the model is able to reproduce the rTEC response to geomagnetic activity, three geomagnetic storms at different seasons and solar activity conditions are presented. The model residuals clearly reveal two types of the model deviation from the data: some underestimation of the largest TEC response to the geomagnetic activity and randomly distributed errors which are the data noise or anomalies generated by other sources. The presented TEC model fits to the CODE TEC input data with small negative bias of -0.204, root mean squares error RMSE = 4.592, and standard deviation error STDE = 4.588. The model offers TEC maps which depend on geographic coordinates (5° × 5° in latitude and longitude) and universal time (UT) at given geomagnetic activity and day of the year. It could be

  3. Time-lag effects of global vegetation responses to climate change.

    PubMed

    Wu, Donghai; Zhao, Xiang; Liang, Shunlin; Zhou, Tao; Huang, Kaicheng; Tang, Bijian; Zhao, Wenqian

    2015-09-01

    Climate conditions significantly affect vegetation growth in terrestrial ecosystems. Due to the spatial heterogeneity of ecosystems, the vegetation responses to climate vary considerably with the diverse spatial patterns and the time-lag effects, which are the most important mechanism of climate-vegetation interactive effects. Extensive studies focused on large-scale vegetation-climate interactions use the simultaneous meteorological and vegetation indicators to develop models; however, the time-lag effects are less considered, which tends to increase uncertainty. In this study, we aim to quantitatively determine the time-lag effects of global vegetation responses to different climatic factors using the GIMMS3g NDVI time series and the CRU temperature, precipitation, and solar radiation datasets. First, this study analyzed the time-lag effects of global vegetation responses to different climatic factors. Then, a multiple linear regression model and partial correlation model were established to statistically analyze the roles of different climatic factors on vegetation responses, from which the primary climate-driving factors for different vegetation types were determined. The results showed that (i) both the time-lag effects of the vegetation responses and the major climate-driving factors that significantly affect vegetation growth varied significantly at the global scale, which was related to the diverse vegetation and climate characteristics; (ii) regarding the time-lag effects, the climatic factors explained 64% variation of the global vegetation growth, which was 11% relatively higher than the model ignoring the time-lag effects; (iii) for the area with a significant change trend (for the period 1982-2008) in the global GIMMS3g NDVI (P < 0.05), the primary driving factor was temperature; and (iv) at the regional scale, the variation in vegetation growth was also related to human activities and natural disturbances. Considering the time-lag effects is quite

  4. Model-based synthesis of locally contingent responses to global market signals

    NASA Astrophysics Data System (ADS)

    Magliocca, N. R.

    2015-12-01

    Rural livelihoods and the land systems on which they depend are increasingly influenced by distant markets through economic globalization. Place-based analyses of land and livelihood system sustainability must then consider both proximate and distant influences on local decision-making. Thus, advancing land change theory in the context of economic globalization calls for a systematic understanding of the general processes as well as local contingencies shaping local responses to global signals. Synthesis of insights from place-based case studies of land and livelihood change is a path forward for developing such systematic knowledge. This paper introduces a model-based synthesis approach to investigating the influence of local socio-environmental and agent-level factors in mediating land-use and livelihood responses to changing global market signals. A generalized agent-based modeling framework is applied to six case-study sites that differ in environmental conditions, market access and influence, and livelihood settings. The largest modeled land conversions and livelihood transitions to market-oriented production occurred in sties with relatively productive agricultural land and/or with limited livelihood options. Experimental shifts in the distributions of agents' risk tolerances generally acted to attenuate or amplify responses to changes in global market signals. Importantly, however, responses of agents at different points in the risk tolerance distribution varied widely, with the wealth gap growing wider between agents with higher or lower risk tolerance. These results demonstrate model-based synthesis is a promising approach to overcome many of the challenges of current synthesis methods in land change science, and to identify generalized as well as locally contingent responses to global market signals.

  5. The acute phase response of cod (Gadus morhua L.): expression of immune response genes.

    PubMed

    Audunsdottir, Sigridur S; Magnadottir, Bergljot; Gisladottir, Berglind; Jonsson, Zophonias O; Bragason, Birkir Th

    2012-02-01

    An acute phase response (APR) was experimentally induced in Atlantic cod (Gadus morhua L.) by intramuscular injection of turpentine oil. The change in the expression of immune related genes was monitored in the anterior kidney and the spleen over a period of 7 days. The genes examined were two types of pentraxins, apolipoprotein A1 (ApoA-I), the complement component C3, interleukin-1β (IL-1β), transferrin, cathelicidin, and hepcidin. All genes were constitutively expressed in both organs and their expression amplified by the turpentine injection. A pattern of response was observed both with respect to the organ preference and to the timing of a maximum response. The increased gene expression of the pentraxins, ApoA-I and C3 was restricted to the anterior kidney, the gene expression of IL-1β, cathelicidin, and transferrin increased in both organs, while hepcidin gene expression was only significantly increased in the spleen. The pentraxins and ApoA-I appear to be early mediators of APR in cod, possibly stimulating C3 and IL-1β response, while the antimicrobial peptides may play a minor role. The increase in transferrin gene expression in both organs, and apparent indifference to cortisol release associated with the turpentine injection, suggests that this could be a typical acute phase protein in cod. Copyright © 2011 Elsevier Ltd. All rights reserved.

  6. Diverse Responses of Global Vegetation to Climate Changes: Spatial Patterns and Time-lag Effects

    NASA Astrophysics Data System (ADS)

    Wu, D.; Zhao, X.; Zhou, T.; Huang, K.; Xu, W.

    2014-12-01

    Global climate changes have enormous influences on vegetation growth, meanwhile, response of vegetation to climate express space diversity and time-lag effects, which account for spatial-temporal disparities of climate change and spatial heterogeneity of ecosystem. Revelation of this phenomenon will help us further understanding the impact of climate change on vegetation. Assessment and forecast of global environmental change can be also improved under further climate change. Here we present space diversity and time-lag effects patterns of global vegetation respond to three climate factors (temperature, precipitation and solar radiation) based on quantitative analysis of satellite data (NDVI) and Climate data (Climate Research Unit). We assessed the time-lag effects of global vegetation to main climate factors based on the great correlation fitness between NDVI and the three climate factors respectively among 0-12 months' temporal lags. On this basis, integrated response model of NDVI and the three climate factors was built to analyze contribution of different climate factors to vegetation growth with multiple regression model and partial correlation model. In the result, different vegetation types have distinct temporal lags to the three climate factors. For the precipitation, temporal lags of grasslands are the shortest while the evergreen broad-leaf forests are the longest, which means that grasslands are more sensitive to precipitation than evergreen broad-leaf forests. Analysis of different climate factors' contribution to vegetation reveal that vegetation are dominated by temperature in the high northern latitudes; they are mainly restricted by precipitation in arid and semi-arid areas (Australia, Western America); in humid areas of low and intermediate latitudes (Amazon, Eastern America), vegetation are mainly influenced by solar radiation. Our results reveal the time-lag effects and major driving factors of global vegetation growth and explain the

  7. Defining global neuroendocrine gene expression patterns associated with reproductive seasonality in fish.

    PubMed

    Zhang, Dapeng; Xiong, Huiling; Mennigen, Jan A; Popesku, Jason T; Marlatt, Vicki L; Martyniuk, Christopher J; Crump, Kate; Cossins, Andrew R; Xia, Xuhua; Trudeau, Vance L

    2009-06-05

    Many vertebrates, including the goldfish, exhibit seasonal reproductive rhythms, which are a result of interactions between external environmental stimuli and internal endocrine systems in the hypothalamo-pituitary-gonadal axis. While it is long believed that differential expression of neuroendocrine genes contributes to establishing seasonal reproductive rhythms, no systems-level investigation has yet been conducted. In the present study, by analyzing multiple female goldfish brain microarray datasets, we have characterized global gene expression patterns for a seasonal cycle. A core set of genes (873 genes) in the hypothalamus were identified to be differentially expressed between May, August and December, which correspond to physiologically distinct stages that are sexually mature (prespawning), sexual regression, and early gonadal redevelopment, respectively. Expression changes of these genes are also shared by another brain region, the telencephalon, as revealed by multivariate analysis. More importantly, by examining one dataset obtained from fish in October who were kept under long-daylength photoperiod (16 h) typical of the springtime breeding season (May), we observed that the expression of identified genes appears regulated by photoperiod, a major factor controlling vertebrate reproductive cyclicity. Gene ontology analysis revealed that hormone genes and genes functionally involved in G-protein coupled receptor signaling pathway and transmission of nerve impulses are significantly enriched in an expression pattern, whose transition is located between prespawning and sexually regressed stages. The existence of seasonal expression patterns was verified for several genes including isotocin, ependymin II, GABA(A) gamma2 receptor, calmodulin, and aromatase b by independent samplings of goldfish brains from six seasonal time points and real-time PCR assays. Using both theoretical and experimental strategies, we report for the first time global gene expression

  8. Defining Global Neuroendocrine Gene Expression Patterns Associated with Reproductive Seasonality in Fish

    PubMed Central

    Mennigen, Jan A.; Popesku, Jason T.; Marlatt, Vicki L.; Martyniuk, Christopher J.; Crump, Kate; Cossins, Andrew R.; Xia, Xuhua; Trudeau, Vance L.

    2009-01-01

    Background Many vertebrates, including the goldfish, exhibit seasonal reproductive rhythms, which are a result of interactions between external environmental stimuli and internal endocrine systems in the hypothalamo-pituitary-gonadal axis. While it is long believed that differential expression of neuroendocrine genes contributes to establishing seasonal reproductive rhythms, no systems-level investigation has yet been conducted. Methodology/Principal Findings In the present study, by analyzing multiple female goldfish brain microarray datasets, we have characterized global gene expression patterns for a seasonal cycle. A core set of genes (873 genes) in the hypothalamus were identified to be differentially expressed between May, August and December, which correspond to physiologically distinct stages that are sexually mature (prespawning), sexual regression, and early gonadal redevelopment, respectively. Expression changes of these genes are also shared by another brain region, the telencephalon, as revealed by multivariate analysis. More importantly, by examining one dataset obtained from fish in October who were kept under long-daylength photoperiod (16 h) typical of the springtime breeding season (May), we observed that the expression of identified genes appears regulated by photoperiod, a major factor controlling vertebrate reproductive cyclicity. Gene ontology analysis revealed that hormone genes and genes functionally involved in G-protein coupled receptor signaling pathway and transmission of nerve impulses are significantly enriched in an expression pattern, whose transition is located between prespawning and sexually regressed stages. The existence of seasonal expression patterns was verified for several genes including isotocin, ependymin II, GABAA gamma2 receptor, calmodulin, and aromatase b by independent samplings of goldfish brains from six seasonal time points and real-time PCR assays. Conclusions/Significance Using both theoretical and experimental

  9. Analysis of global and absorption, distribution, metabolism, and elimination gene expression in the progressive stages of human nonalcoholic fatty liver disease.

    PubMed

    Lake, April D; Novak, Petr; Fisher, Craig D; Jackson, Jonathan P; Hardwick, Rhiannon N; Billheimer, D Dean; Klimecki, Walter T; Cherrington, Nathan J

    2011-10-01

    Nonalcoholic fatty liver disease (NAFLD) is characterized by a series of pathological changes that range from simple fatty liver to nonalcoholic steatohepatitis (NASH). The objective of this study is to describe changes in global gene expression associated with the progression of human NAFLD. This study is focused on the expression levels of genes responsible for the absorption, distribution, metabolism, and elimination (ADME) of drugs. Differential gene expression between three clinically defined pathological groups-normal, steatosis, and NASH-was analyzed. Genome-wide mRNA levels in samples of human liver tissue were assayed with Affymetrix GeneChip Human 1.0ST arrays. A total of 11,633 genes exhibited altered expression out of 33,252 genes at a 5% false discovery rate. Most gene expression changes occurred in the progression from steatosis to NASH. Principal component analysis revealed that hepatic disease status was the major determinant of differential ADME gene expression rather than age or sex of sample donors. Among the 515 drug transporters and 258 drug-metabolizing enzymes (DMEs) examined, uptake transporters but not efflux transporters or DMEs were significantly over-represented in the number of genes down-regulated. These results suggest that uptake transporter genes are coordinately targeted for down-regulation at the global level during the pathological development of NASH and that these patients may have decreased drug uptake capacity. This coordinated regulation of uptake transporter genes is indicative of a hepatoprotective mechanism acting to prevent accumulation of toxic intermediates in disease-compromised hepatocytes.

  10. Population-expression models of immune response

    NASA Astrophysics Data System (ADS)

    Stromberg, Sean P.; Antia, Rustom; Nemenman, Ilya

    2013-06-01

    The immune response to a pathogen has two basic features. The first is the expansion of a few pathogen-specific cells to form a population large enough to control the pathogen. The second is the process of differentiation of cells from an initial naive phenotype to an effector phenotype which controls the pathogen, and subsequently to a memory phenotype that is maintained and responsible for long-term protection. The expansion and the differentiation have been considered largely independently. Changes in cell populations are typically described using ecologically based ordinary differential equation models. In contrast, differentiation of single cells is studied within systems biology and is frequently modeled by considering changes in gene and protein expression in individual cells. Recent advances in experimental systems biology make available for the first time data to allow the coupling of population and high dimensional expression data of immune cells during infections. Here we describe and develop population-expression models which integrate these two processes into systems biology on the multicellular level. When translated into mathematical equations, these models result in non-conservative, non-local advection-diffusion equations. We describe situations where the population-expression approach can make correct inference from data while previous modeling approaches based on common simplifying assumptions would fail. We also explore how model reduction techniques can be used to build population-expression models, minimizing the complexity of the model while keeping the essential features of the system. While we consider problems in immunology in this paper, we expect population-expression models to be more broadly applicable.

  11. Separate and combined effects of genetic variants and pre-treatment whole blood gene expression on response to exposure-based cognitive behavioural therapy for anxiety disorders.

    PubMed

    Coleman, Jonathan R I; Lester, Kathryn J; Roberts, Susanna; Keers, Robert; Lee, Sang Hyuck; De Jong, Simone; Gaspar, Héléna; Teismann, Tobias; Wannemüller, André; Schneider, Silvia; Jöhren, Peter; Margraf, Jürgen; Breen, Gerome; Eley, Thalia C

    2017-04-01

    Exposure-based cognitive behavioural therapy (eCBT) is an effective treatment for anxiety disorders. Response varies between individuals. Gene expression integrates genetic and environmental influences. We analysed the effect of gene expression and genetic markers separately and together on treatment response. Adult participants (n ≤ 181) diagnosed with panic disorder or a specific phobia underwent eCBT as part of standard care. Percentage decrease in the Clinical Global Impression severity rating was assessed across treatment, and between baseline and a 6-month follow-up. Associations with treatment response were assessed using expression data from 3,233 probes, and expression profiles clustered in a data- and literature-driven manner. A total of 3,343,497 genetic variants were used to predict treatment response alone and combined in polygenic risk scores. Genotype and expression data were combined in expression quantitative trait loci (eQTL) analyses. Expression levels were not associated with either treatment phenotype in any analysis. A total of 1,492 eQTLs were identified with q < 0.05, but interactions between genetic variants and treatment response did not affect expression levels significantly. Genetic variants did not significantly predict treatment response alone or in polygenic risk scores. We assessed gene expression alone and alongside genetic variants. No associations with treatment outcome were identified. Future studies require larger sample sizes to discover associations.

  12. Global Response to Local Ionospheric Mass Ejection

    NASA Technical Reports Server (NTRS)

    Moore, T. E.; Fok, M.-C.; Delcourt, D. C.; Slinker, S. P.; Fedder, J. A.

    2010-01-01

    We revisit a reported "Ionospheric Mass Ejection" using prior event observations to guide a global simulation of local ionospheric outflows, global magnetospheric circulation, and plasma sheet pressurization, and comparing our results with the observed global response. Our simulation framework is based on test particle motions in the Lyon-Fedder-Mobarry (LFM) global circulation model electromagnetic fields. The inner magnetosphere is simulated with the Comprehensive Ring Current Model (CRCM) of Fok and Wolf, driven by the transpolar potential developed by the LFM magnetosphere, and includes an embedded plasmaspheric simulation. Global circulation is stimulated using the observed solar wind conditions for the period 24-25 Sept 1998. This period begins with the arrival of a Coronal Mass Ejection, initially with northward, but later with southward interplanetary magnetic field. Test particles are launched from the ionosphere with fluxes specified by local empirical relationships of outflow to electrodynamic and particle precipitation imposed by the MIlD simulation. Particles are tracked until they are lost from the system downstream or into the atmosphere, using the full equations of motion. Results are compared with the observed ring current and a simulation of polar and auroral wind outflows driven globally by solar wind dynamic pressure. We find good quantitative agreement with the observed ring current, and reasonable qualitative agreement with earlier simulation results, suggesting that the solar wind driven global simulation generates realistic energy dissipation in the ionosphere and that the Strangeway relations provide a realistic local outflow description.

  13. Global challenges as inspiration: a classroom strategy to foster social responsibility.

    PubMed

    Vanasupa, Linda; Slivovsky, Lynn; Chen, Katherine C

    2006-04-01

    Social responsibility is at the heart of the Engineer's Creed embodied in the pledge that we will dedicate [our] professional knowledge and skill to the advancement and betterment of human welfare... [placing] public welfare above all other considerations. However, half century after the original creed was written, we find ourselves in a world with great technological advances and great global-scale technologically-enabled peril. These issues can be naturally integrated into the engineering curriculum in a way that enhances the development of the technological skill set. We have found that these global challenges create a natural opportunity to foster social responsibility within the engineering students whom we educate. In freshman through senior-level materials engineering courses, we used five guiding principles to shape several different classroom activities and assignments. Upon testing an initial cohort of 28 students had classroom experiences based on these five principles, we saw a shift in attitude: before the experience, 18% of the cohort viewed engineers as playing an active role in solving global problems; after the experiences, 79% recognized the engineer's role in solving global-scale problems. In this paper, we present how global issues can be used to stimulate thinking for socially-responsible engineering solutions. We set forth five guiding principles that can foster the mindset for socially responsible actions along with examples of how these principles translate into classroom activities.

  14. Nonlinear, interacting responses to climate limit grassland production under global change.

    PubMed

    Zhu, Kai; Chiariello, Nona R; Tobeck, Todd; Fukami, Tadashi; Field, Christopher B

    2016-09-20

    Global changes in climate, atmospheric composition, and pollutants are altering ecosystems and the goods and services they provide. Among approaches for predicting ecosystem responses, long-term observations and manipulative experiments can be powerful approaches for resolving single-factor and interactive effects of global changes on key metrics such as net primary production (NPP). Here we combine both approaches, developing multidimensional response surfaces for NPP based on the longest-running, best-replicated, most-multifactor global-change experiment at the ecosystem scale-a 17-y study of California grassland exposed to full-factorial warming, added precipitation, elevated CO2, and nitrogen deposition. Single-factor and interactive effects were not time-dependent, enabling us to analyze each year as a separate realization of the experiment and extract NPP as a continuous function of global-change factors. We found a ridge-shaped response surface in which NPP is humped (unimodal) in response to temperature and precipitation when CO2 and nitrogen are ambient, with peak NPP rising under elevated CO2 or nitrogen but also shifting to lower temperatures. Our results suggest that future climate change will push this ecosystem away from conditions that maximize NPP, but with large year-to-year variability.

  15. The expression of Longus type 4 pilus of enterotoxigenic Escherichia coli is regulated by LngR and LngS and by H-NS, CpxR and CRP global regulators.

    PubMed

    De la Cruz, Miguel A; Ruiz-Tagle, Alejandro; Ares, Miguel A; Pacheco, Sabino; Yáñez, Jorge A; Cedillo, Lilia; Torres, Javier; Girón, Jorge A

    2017-05-01

    Enterotoxigenic Escherichia coli produces a long type 4 pilus called Longus. The regulatory elements and the environmental signals controlling the expression of Longus-encoding genes are unknown. We identified two genes lngR and lngS in the Longus operon, whose predicted products share homology with transcriptional regulators. Isogenic lngR and lngS mutants were considerably affected in transcription of lngA pilin gene. The expression of lngA, lngR and lngS genes was optimally expressed at 37°C at pH 7.5. The presence of glucose and sodium chloride had a positive effect on Longus expression. The presence of divalent ions, particularly calcium, appears to be an important stimulus for Longus production. In addition, we studied H-NS, CpxR and CRP global regulators, on Longus expression. The response regulator CpxR appears to function as a positive regulator of lng genes as the cpxR mutant showed reduced levels of lngRSA expression. In contrast, H-NS and CRP function as negative regulators since expression of lngA was up-regulated in isogenic hns and crp mutants. H-NS and CRP were required for salt- and glucose-mediated regulation of Longus. Our data suggest the existence of a complex regulatory network controlling Longus expression, involving both local and global regulators in response to different environmental signals. © 2016 Society for Applied Microbiology and John Wiley & Sons Ltd.

  16. Behavioural responses to facial and postural expressions of emotion: An interpersonal circumplex approach.

    PubMed

    Aan Het Rot, Marije; Enea, Violeta; Dafinoiu, Ion; Iancu, Sorina; Taftă, Steluţa A; Bărbuşelu, Mariana

    2017-11-01

    While the recognition of emotional expressions has been extensively studied, the behavioural response to these expressions has not. In the interpersonal circumplex, behaviour is defined in terms of communion and agency. In this study, we examined behavioural responses to both facial and postural expressions of emotion. We presented 101 Romanian students with facial and postural stimuli involving individuals ('targets') expressing happiness, sadness, anger, or fear. Using an interpersonal grid, participants simultaneously indicated how communal (i.e., quarrelsome or agreeable) and agentic (i.e., dominant or submissive) they would be towards people displaying these expressions. Participants were agreeable-dominant towards targets showing happy facial expressions and primarily quarrelsome towards targets with angry or fearful facial expressions. Responses to targets showing sad facial expressions were neutral on both dimensions of interpersonal behaviour. Postural versus facial expressions of happiness and anger elicited similar behavioural responses. Participants responded in a quarrelsome-submissive way to fearful postural expressions and in an agreeable way to sad postural expressions. Behavioural responses to the various facial expressions were largely comparable to those previously observed in Dutch students. Observed differences may be explained from participants' cultural background. Responses to the postural expressions largely matched responses to the facial expressions. © 2017 The British Psychological Society.

  17. Global vegetation productivity response to climatic oscillations during the satellite era.

    PubMed

    Gonsamo, Alemu; Chen, Jing M; Lombardozzi, Danica

    2016-10-01

    Climate control on global vegetation productivity patterns has intensified in response to recent global warming. Yet, the contributions of the leading internal climatic variations to global vegetation productivity are poorly understood. Here, we use 30 years of global satellite observations to study climatic variations controls on continental and global vegetation productivity patterns. El Niño-Southern Oscillation (ENSO) phases (La Niña, neutral, and El Niño years) appear to be a weaker control on global-scale vegetation productivity than previously thought, although continental-scale responses are substantial. There is also clear evidence that other non-ENSO climatic variations have a strong control on spatial patterns of vegetation productivity mainly through their influence on temperature. Among the eight leading internal climatic variations, the East Atlantic/West Russia Pattern extensively controls the ensuing year vegetation productivity of the most productive tropical and temperate forest ecosystems of the Earth's vegetated surface through directionally consistent influence on vegetation greenness. The Community Climate System Model (CCSM4) simulations do not capture the observed patterns of vegetation productivity responses to internal climatic variations. Our analyses show the ubiquitous control of climatic variations on vegetation productivity and can further guide CCSM and other Earth system models developments to represent vegetation response patterns to unforced variability. Several winter time internal climatic variation indices show strong potentials on predicting growing season vegetation productivity two to six seasons ahead which enables national governments and farmers forecast crop yield to ensure supplies of affordable food, famine early warning, and plan management options to minimize yield losses ahead of time. © 2016 John Wiley & Sons Ltd.

  18. Global Gene Expression Change Induced by Major Thoracoabdominal Surgery.

    PubMed

    Allen, Casey J; Griswold, Anthony J; Schulman, Carl I; Sleeman, Danny; Levi, Joe U; Livingstone, Alan S; Proctor, Kenneth G

    2017-12-01

    To test the hypothesis that major thoracoabdominal surgery induces gene expression changes associated with adverse outcomes. Widely different traumatic injuries evoke surprisingly similar gene expression profiles, but there is limited information on whether the iatrogenic injury caused by major surgery is associated with similar patterns. With informed consent, blood samples were obtained from 50 patients before and after open transhiatal esophagectomy or pancreaticoduodenectomy. Twelve cases with complicated recoveries (death, infection, venous thromboembolism) were matched with 12 cases with uneventful recoveries. Global gene expression was assayed using human microarray chips. A 2-fold change with a corrected P < 0.05 was considered differentially expressed. In these 24 patients, 522 genes were differentially expressed after surgery; 248 (48%) were upregulated (innate immunity and inflammation) and 274 (52%) were downregulated [adaptive immunity (antigen presentation, T-cell function)]. Hierarchical clustering of the profile reliably predicted pre- and postoperative status. The within-patient change was 3.08 ± 0.91-fold. There was no measurable association with age, malignancy, procedure, surgery length, operative blood loss, or transfusion requirements, but was positively associated with postoperative infection (3.81 ± 0.97 vs 2.79 ± 0.73; P = 0.009) and hospital length of stay (r = 0.583, P = 0.003). Venous thromboembolism and mortality each occurred in one patient, thus no associations were possible. Major surgery induces a quantifiable pattern of gene expression change that is associated with adverse outcome. This could reflect early impaired adaptive immunity and suggests potential therapeutic targets to improve postoperative recovery.

  19. The Yeast Anaerobic Response Element AR1b Regulates Aerobic Antifungal Drug-dependent Sterol Gene Expression*

    PubMed Central

    Gallo-Ebert, Christina; Donigan, Melissa; Liu, Hsing-Yin; Pascual, Florencia; Manners, Melissa; Pandya, Devanshi; Swanson, Robert; Gallagher, Denise; Chen, WeiWei; Carman, George M.; Nickels, Joseph T.

    2013-01-01

    Saccharomyces cerevisiae ergosterol biosynthesis, like cholesterol biosynthesis in mammals, is regulated at the transcriptional level by a sterol feedback mechanism. Yeast studies defined a 7-bp consensus sterol-response element (SRE) common to genes involved in sterol biosynthesis and two transcription factors, Upc2 and Ecm22, which direct transcription of sterol biosynthetic genes. The 7-bp consensus SRE is identical to the anaerobic response element, AR1c. Data indicate that Upc2 and Ecm22 function through binding to this SRE site. We now show that it is two novel anaerobic AR1b elements in the UPC2 promoter that direct global ERG gene expression in response to a block in de novo ergosterol biosynthesis, brought about by antifungal drug treatment. The AR1b elements are absolutely required for auto-induction of UPC2 gene expression and protein and require Upc2 and Ecm22 for function. We further demonstrate the direct binding of recombinant expressed S. cerevisiae ScUpc2 and pathogenic Candida albicans CaUpc2 and Candida glabrata CgUpc2 to AR1b and SRE/AR1c elements. Recombinant endogenous promoter studies show that the UPC2 anaerobic AR1b elements act in trans to regulate ergosterol gene expression. Our results indicate that Upc2 must occupy UPC2 AR1b elements in order for ERG gene expression induction to take place. Thus, the two UPC2-AR1b elements drive expression of all ERG genes necessary for maintaining normal antifungal susceptibility, as wild type cells lacking these elements have increased susceptibility to azole antifungal drugs. Therefore, targeting these specific sites for antifungal therapy represents a novel approach to treat systemic fungal infections. PMID:24163365

  20. Paleobotany and Global Change: Important Lessons for Species to Biomes from Vegetation Responses to Past Global Change.

    PubMed

    McElwain, Jennifer C

    2018-04-29

    Human carbon use during the next century will lead to atmospheric carbon dioxide concentrations (pCO 2 ) that have been unprecedented for the past 50-100+ million years according to fossil plant-based CO 2 estimates. The paleobotanical record of plants offers key insights into vegetation responses to past global change, including suitable analogs for Earth's climatic future. Past global warming events have resulted in transient poleward migration at rates that are equivalent to the lowest climate velocities required for current taxa to keep pace with climate change. Paleobiome reconstructions suggest that the current tundra biome is the biome most threatened by global warming. The common occurrence of paleoforests at high polar latitudes when pCO 2 was above 500 ppm suggests that the advance of woody shrub and tree taxa into tundra environments may be inevitable. Fossil pollen studies demonstrate the resilience of wet tropical forests to global change up to 700 ppm CO 2 , contrary to modeled predictions of the future. The paleobotanical record also demonstrates a high capacity for functional trait evolution as an additional strategy to migration and maintenance of a species' climate envelope in response to global change.

  1. Effects of oral exposure to bisphenol A on gene expression and global genomic DNA methylation in the prostate, female mammary gland, and uterus of NCTR Sprague-Dawley rats

    PubMed Central

    Camacho, Luísa; Basavarajappa, Mallikarjuna S.; Chang, Ching-Wei; Han, Tao; Kobets, Tetyana; Koturbash, Igor; Surratt, Gordon; Lewis, Sherry M.; Vanlandingham, Michelle M.; Fuscoe, James C.; da Costa, Gonçalo Gamboa; Pogribny, Igor P.; Delclos, K. Barry

    2015-01-01

    Bisphenol A (BPA), an industrial chemical used in the manufacture of polycarbonate and epoxy resins, binds to the nuclear estrogen receptor with an affinity 4–5 orders of magnitude lower than that of estradiol. We reported previously that “high BPA” (100,000 and 300,000 μg/kg body weight (bw)/day), but not “low BPA” [2.5–2700 μg/kg bw/day], induced clear adverse effects in NCTR Sprague-Dawley rats gavaged daily from gestation day 6 through postnatal day 90. The “high BPA” effects partially overlapped those of ethinyl estradiol (EE2, 0.5 and 5.0 μg/kg bw/day). To evaluate further the potential of “low BPA” to induce biological effects, here we assessed the global genomic DNA methylation and gene expression in the prostate and female mammary glands, tissues identified previously as potential targets of BPA, and uterus, a sensitive estrogen-responsive tissue. Both doses of EE2 modulated gene expression, including of known estrogen-responsive genes, and PND 4 global gene expression data showed a partial overlap of the “high BPA” effects with those of EE2. The “low BPA” doses modulated the expression of several genes; however, the absence of a dose response reduces the likelihood that these changes were causally linked to the treatment. These results are consistent with the toxicity outcomes. PMID:25862956

  2. Species as Stressors: Heterospecific Interactions and the Cellular Stress Response under Global Change.

    PubMed

    Gunderson, Alex R; King, Emily E; Boyer, Kirsten; Tsukimura, Brian; Stillman, Jonathon H

    2017-07-01

    Anthropogenic global change is predicted to increase the physiological stress of organisms through changes in abiotic conditions such as temperature, pH, and pollution. However, organisms can also experience physiological stress through interactions with other species, especially parasites, predators, and competitors. The stress of species interactions could be an important driver of species' responses to global change as the composition of biological communities change through factors such as distributional and phenological shifts. Interactions between biotic and abiotic stressors could also induce non-linear physiological stress responses under global change. One of the primary means by which organisms deal with physiological stress is through the cellular stress response (CSR), which is broadly the upregulation of a conserved set of genes that facilitate the removal and repair of damaged macromolecules. Here, we present data on behavioral interactions and CSR gene expression for two competing species of intertidal zone porcelain crab (Petrolisthes cinctipes and Petrolisthes manimaculis). We found that P. cinctipes and P. manimaculis engage in more agonistic behaviors when interacting with heterospecifics than conspecifics; however, we found no evidence that heterospecific interactions induced a CSR in these species. In addition to our new data, we review the literature with respect to CSR induction via species interactions, focusing on predator-prey systems and heterospecific competition. We find extensive evidence for predators to induce cellular stress and aspects of the CSR in prey, even in the absence of direct physical contact between species. Effects of heterospecific competition on the CSR have been studied far less, but we do find evidence that agonistic interactions with heterospecifics can induce components of the CSR. Across all published studies, there is clear evidence that species interactions can lead to cellular stress and induction of the CSR

  3. Transposon integration enhances expression of stress response genes.

    PubMed

    Feng, Gang; Leem, Young-Eun; Levin, Henry L

    2013-01-01

    Transposable elements possess specific patterns of integration. The biological impact of these integration profiles is not well understood. Tf1, a long-terminal repeat retrotransposon in Schizosaccharomyces pombe, integrates into promoters with a preference for the promoters of stress response genes. To determine the biological significance of Tf1 integration, we took advantage of saturated maps of insertion activity and studied how integration at hot spots affected the expression of the adjacent genes. Our study revealed that Tf1 integration did not reduce gene expression. Importantly, the insertions activated the expression of 6 of 32 genes tested. We found that Tf1 increased gene expression by inserting enhancer activity. Interestingly, the enhancer activity of Tf1 could be limited by Abp1, a host surveillance factor that sequesters transposon sequences into structures containing histone deacetylases. We found the Tf1 promoter was activated by heat treatment and, remarkably, only genes that themselves were induced by heat could be activated by Tf1 integration, suggesting a synergy of Tf1 enhancer sequence with the stress response elements of target promoters. We propose that the integration preference of Tf1 for the promoters of stress response genes and the ability of Tf1 to enhance the expression of these genes co-evolved to promote the survival of cells under stress.

  4. Transposon integration enhances expression of stress response genes

    PubMed Central

    Feng, Gang; Leem, Young-Eun; Levin, Henry L.

    2013-01-01

    Transposable elements possess specific patterns of integration. The biological impact of these integration profiles is not well understood. Tf1, a long-terminal repeat retrotransposon in Schizosaccharomyces pombe, integrates into promoters with a preference for the promoters of stress response genes. To determine the biological significance of Tf1 integration, we took advantage of saturated maps of insertion activity and studied how integration at hot spots affected the expression of the adjacent genes. Our study revealed that Tf1 integration did not reduce gene expression. Importantly, the insertions activated the expression of 6 of 32 genes tested. We found that Tf1 increased gene expression by inserting enhancer activity. Interestingly, the enhancer activity of Tf1 could be limited by Abp1, a host surveillance factor that sequesters transposon sequences into structures containing histone deacetylases. We found the Tf1 promoter was activated by heat treatment and, remarkably, only genes that themselves were induced by heat could be activated by Tf1 integration, suggesting a synergy of Tf1 enhancer sequence with the stress response elements of target promoters. We propose that the integration preference of Tf1 for the promoters of stress response genes and the ability of Tf1 to enhance the expression of these genes co-evolved to promote the survival of cells under stress. PMID:23193295

  5. Global transcriptional, physiological and metabolite analyses of Desulfovibrio vulgaris Hildenborough responses to salt adaptation

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    He, Z.; Zhou, A.; Baidoo, E.

    2009-12-01

    The response of Desulfovibrio vulgaris Hildenborough to salt adaptation (long-term NaCl exposure) was examined by physiological, global transcriptional, and metabolite analyses. The growth of D. vulgaris was inhibited by high levels of NaCl, and the growth inhibition could be relieved by the addition of exogenous amino acids (e.g., glutamate, alanine, tryptophan) or yeast extract. Salt adaptation induced the expression of genes involved in amino acid biosynthesis and transport, electron transfer, hydrogen oxidation, and general stress responses (e.g., heat shock proteins, phage shock proteins, and oxidative stress response proteins). Genes involved in carbon metabolism, cell motility, and phage structures were repressed.more » Comparison of transcriptomic profiles of D. vulgaris responses to salt adaptation with those of salt shock (short-term NaCl exposure) showed some similarity as well as a significant difference. Metabolite assays showed that glutamate and alanine were accumulated under salt adaptation, suggesting that they may be used as osmoprotectants in D. vulgaris. A conceptual model is proposed to link the observed results to currently available knowledge for further understanding the mechanisms of D. vulgaris adaptation to elevated NaCl.« less

  6. Global gene expression analysis of peripheral blood mononuclear cells in rhesus monkey infants with CA16 infection-induced HFMD.

    PubMed

    Song, Jie; Hu, Yajie; Hu, Yunguang; Wang, Jingjing; Zhang, Xiaolong; Wang, Lichun; Guo, Lei; Wang, Yancui; Ning, Ruotong; Liao, Yun; Zhang, Ying; Zheng, Huiwen; Shi, Haijing; He, Zhanlong; Li, Qihan; Liu, Longding

    2016-03-02

    Coxsackievirus A16 (CA16) is a dominant pathogen that results in hand, foot, and mouth disease and causes outbreaks worldwide, particularly in the Asia-Pacific region. However, the underlying molecular mechanisms remain unclear. Our previous study has demonstrated that the basic CA16 pathogenic process was successfully mimicked in rhesus monkey infant. The present study focused on the global gene expression changes in peripheral blood mononuclear cells of rhesus monkey infants with hand, foot, and mouth disease induced by CA16 infection at different time points. Genome-wide expression analysis was performed with Agilent whole-genome microarrays and established bioinformatics tools. Nine hundred and forty-eight significant differentially expressed genes that were associated with 5 gene ontology categories, including cell communication, cell cycle, immune system process, regulation of transcription and metabolic process were identified. Subsequently, the mapping of genes related to the immune system process by PANTHER pathway analysis revealed the predominance of inflammation mediated by chemokine and cytokine signaling pathways and the interleukin signaling pathway. Ultimately, co-expressed genes and their networks were analyzed. The results revealed the gene expression profile of the immune system in response to CA16 in rhesus monkey infants and suggested that such an immune response was generated as a result of the positive mobilization of the immune system. This initial microarray study will provide insights into the molecular mechanism of CA16 infection and will facilitate the identification of biomarkers for the evaluation of vaccines against this virus. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Stress-Related Gene Expression Reflects Morphophysiological Responses to Water Deficit.

    PubMed

    Rymaszewski, Wojciech; Vile, Denis; Bediee, Alexis; Dauzat, Myriam; Luchaire, Nathalie; Kamrowska, Dominika; Granier, Christine; Hennig, Jacek

    2017-07-01

    Acclimation to water deficit (WD) enables plants to maintain growth under unfavorable environmental conditions, although the mechanisms are not completely understood. In this study, the natural variation of long-term acclimation to moderate and severe soil WD was investigated in 18 Arabidopsis ( Arabidopsis thaliana ) accessions using PHENOPSIS, an automated phenotyping platform. Soil water content was adjusted at an early stage of plant development and maintained at a constant level until reproductive age was achieved. The accessions were selected based on the expression levels of ANNEXIN1 , a drought-related marker. Severe WD conditions had a greater effect on most of the measured morphophysiological traits than moderate WD conditions. Multivariate analyses indicated that trait responses associated with plant size and water management drove most of the variation. Accessions with similar responses at these two levels were grouped in clusters that displayed different response strategies to WD The expression levels of selected stress-response genes revealed large natural variation under WD conditions. Responses of morphophysiological traits, such as projected rosette area, transpiration rate, and rosette water content, were correlated with changes in the expression of stress-related genes, such as NINE-CIS-EPOXYCAROTENOID DIOXYGENASE3 and N-MYC DOWNREGULATED-LIKE1 ( NDL1 ), in response to WD Interestingly, the morphophysiological acclimation response to WD also was reflected in the gene expression levels (most notably those of NDL1 , CHALCONE SYNTHASE , and MYB DOMAIN PROTEIN44 ) in plants cultivated under well-watered conditions. Our results may lead to the development of biomarkers and predictors of plant morphophysiological responses based on gene expression patterns. © 2017 American Society of Plant Biologists. All Rights Reserved.

  8. Host genetic variation influences gene expression response to rhinovirus infection.

    PubMed

    Çalışkan, Minal; Baker, Samuel W; Gilad, Yoav; Ober, Carole

    2015-04-01

    Rhinovirus (RV) is the most prevalent human respiratory virus and is responsible for at least half of all common colds. RV infections may result in a broad spectrum of effects that range from asymptomatic infections to severe lower respiratory illnesses. The basis for inter-individual variation in the response to RV infection is not well understood. In this study, we explored whether host genetic variation is associated with variation in gene expression response to RV infections between individuals. To do so, we obtained genome-wide genotype and gene expression data in uninfected and RV-infected peripheral blood mononuclear cells (PBMCs) from 98 individuals. We mapped local and distant genetic variation that is associated with inter-individual differences in gene expression levels (eQTLs) in both uninfected and RV-infected cells. We focused specifically on response eQTLs (reQTLs), namely, genetic associations with inter-individual variation in gene expression response to RV infection. We identified local reQTLs for 38 genes, including genes with known functions in viral response (UBA7, OAS1, IRF5) and genes that have been associated with immune and RV-related diseases (e.g., ITGA2, MSR1, GSTM3). The putative regulatory regions of genes with reQTLs were enriched for binding sites of virus-activated STAT2, highlighting the role of condition-specific transcription factors in genotype-by-environment interactions. Overall, we suggest that the 38 loci associated with inter-individual variation in gene expression response to RV-infection represent promising candidates for affecting immune and RV-related respiratory diseases.

  9. Globalisation of tobacco industry influence and new global responses

    PubMed Central

    Yach, D.; Bettcher, D.

    2000-01-01

    The globalisation of tobacco marketing, trade, research, and industry influence represents a major threat to public health worldwide. Drawing upon tobacco industry strategy documents prepared over several decades, this paper will demonstrate how the tobacco industry operates as a global force, regarding the world as its operating market by planning, developing, and marketing its products on a global scale. The industry has used a wide range of methods to buy influence and power, and penetrate markets across the world. It has an annual turnover of almost US$400 billion. In contrast, until recently tobacco control lacked global leadership and strategic direction and had been severely underfunded. As part of moving towards a more sustainable form of globalisation, a global enabling environment linked to local actions should focus on the following strategies: global information management; development of nationally and locally grounded action; global regulation, legal instruments, and foreign policy; and establishment of strong partnerships with purpose. As the vector of the tobacco epidemic, the tobacco industry's actions fall far outside of the boundaries of global corporate responsibility. Therefore, global and local actions should not provide the tobacco industry with the two things that it needs to ensure its long term profitability: respectability and predictability.


Keywords: globalisation of tobacco marketing PMID:10841858

  10. Globalisation of tobacco industry influence and new global responses.

    PubMed

    Yach, D; Bettcher, D

    2000-06-01

    The globalisation of tobacco marketing, trade, research, and industry influence represents a major threat to public health worldwide. Drawing upon tobacco industry strategy documents prepared over several decades, this paper will demonstrate how the tobacco industry operates as a global force, regarding the world as its operating market by planning, developing, and marketing its products on a global scale. The industry has used a wide range of methods to buy influence and power, and penetrate markets across the world. It has an annual turnover of almost US$400 billion. In contrast, until recently tobacco control lacked global leadership and strategic direction and had been severely underfunded. As part of moving towards a more sustainable form of globalisation, a global enabling environment linked to local actions should focus on the following strategies: global information management; development of nationally and locally grounded action; global regulation, legal instruments, and foreign policy; and establishment of strong partnerships with purpose. As the vector of the tobacco epidemic, the tobacco industry's actions fall far outside of the boundaries of global corporate responsibility. Therefore, global and local actions should not provide the tobacco industry with the two things that it needs to ensure its long term profitability: respectability and predictability.

  11. Gene Expression Signatures Characterized by Longitudinal Stability and Interindividual Variability Delineate Baseline Phenotypic Groups with Distinct Responses to Immune Stimulation.

    PubMed

    Scheid, Adam D; Van Keulen, Virginia P; Felts, Sara J; Neier, Steven C; Middha, Sumit; Nair, Asha A; Techentin, Robert W; Gilbert, Barry K; Jen, Jin; Neuhauser, Claudia; Zhang, Yuji; Pease, Larry R

    2018-03-01

    Human immunity exhibits remarkable heterogeneity among individuals, which engenders variable responses to immune perturbations in human populations. Population studies reveal that, in addition to interindividual heterogeneity, systemic immune signatures display longitudinal stability within individuals, and these signatures may reliably dictate how given individuals respond to immune perturbations. We hypothesize that analyzing relationships among these signatures at the population level may uncover baseline immune phenotypes that correspond with response outcomes to immune stimuli. To test this, we quantified global gene expression in peripheral blood CD4 + cells from healthy individuals at baseline and following CD3/CD28 stimulation at two time points 1 mo apart. Systemic CD4 + cell baseline and poststimulation molecular immune response signatures (MIRS) were defined by identifying genes expressed at levels that were stable between time points within individuals and differential among individuals in each state. Iterative differential gene expression analyses between all possible phenotypic groupings of at least three individuals using the baseline and stimulated MIRS gene sets revealed shared baseline and response phenotypic groupings, indicating the baseline MIRS contained determinants of immune responsiveness. Furthermore, significant numbers of shared phenotype-defining sets of determinants were identified in baseline data across independent healthy cohorts. Combining the cohorts and repeating the analyses resulted in identification of over 6000 baseline immune phenotypic groups, implying that the MIRS concept may be useful in many immune perturbation contexts. These findings demonstrate that patterns in complex gene expression variability can be used to define immune phenotypes and discover determinants of immune responsiveness. Copyright © 2018 by The American Association of Immunologists, Inc.

  12. Regional Brain Responses Are Biased Toward Infant Facial Expressions Compared to Adult Facial Expressions in Nulliparous Women.

    PubMed

    Li, Bingbing; Cheng, Gang; Zhang, Dajun; Wei, Dongtao; Qiao, Lei; Wang, Xiangpeng; Che, Xianwei

    2016-01-01

    Recent neuroimaging studies suggest that neutral infant faces compared to neutral adult faces elicit greater activity in brain areas associated with face processing, attention, empathic response, reward, and movement. However, whether infant facial expressions evoke larger brain responses than adult facial expressions remains unclear. Here, we performed event-related functional magnetic resonance imaging in nulliparous women while they were presented with images of matched unfamiliar infant and adult facial expressions (happy, neutral, and uncomfortable/sad) in a pseudo-randomized order. We found that the bilateral fusiform and right lingual gyrus were overall more activated during the presentation of infant facial expressions compared to adult facial expressions. Uncomfortable infant faces compared to sad adult faces evoked greater activation in the bilateral fusiform gyrus, precentral gyrus, postcentral gyrus, posterior cingulate cortex-thalamus, and precuneus. Neutral infant faces activated larger brain responses in the left fusiform gyrus compared to neutral adult faces. Happy infant faces compared to happy adult faces elicited larger responses in areas of the brain associated with emotion and reward processing using a more liberal threshold of p < 0.005 uncorrected. Furthermore, the level of the test subjects' Interest-In-Infants was positively associated with the intensity of right fusiform gyrus response to infant faces and uncomfortable infant faces compared to sad adult faces. In addition, the Perspective Taking subscale score on the Interpersonal Reactivity Index-Chinese was significantly correlated with precuneus activity during uncomfortable infant faces compared to sad adult faces. Our findings suggest that regional brain areas may bias cognitive and emotional responses to infant facial expressions compared to adult facial expressions among nulliparous women, and this bias may be modulated by individual differences in Interest-In-Infants and

  13. Regional Brain Responses Are Biased Toward Infant Facial Expressions Compared to Adult Facial Expressions in Nulliparous Women

    PubMed Central

    Zhang, Dajun; Wei, Dongtao; Qiao, Lei; Wang, Xiangpeng; Che, Xianwei

    2016-01-01

    Recent neuroimaging studies suggest that neutral infant faces compared to neutral adult faces elicit greater activity in brain areas associated with face processing, attention, empathic response, reward, and movement. However, whether infant facial expressions evoke larger brain responses than adult facial expressions remains unclear. Here, we performed event-related functional magnetic resonance imaging in nulliparous women while they were presented with images of matched unfamiliar infant and adult facial expressions (happy, neutral, and uncomfortable/sad) in a pseudo-randomized order. We found that the bilateral fusiform and right lingual gyrus were overall more activated during the presentation of infant facial expressions compared to adult facial expressions. Uncomfortable infant faces compared to sad adult faces evoked greater activation in the bilateral fusiform gyrus, precentral gyrus, postcentral gyrus, posterior cingulate cortex-thalamus, and precuneus. Neutral infant faces activated larger brain responses in the left fusiform gyrus compared to neutral adult faces. Happy infant faces compared to happy adult faces elicited larger responses in areas of the brain associated with emotion and reward processing using a more liberal threshold of p < 0.005 uncorrected. Furthermore, the level of the test subjects’ Interest-In-Infants was positively associated with the intensity of right fusiform gyrus response to infant faces and uncomfortable infant faces compared to sad adult faces. In addition, the Perspective Taking subscale score on the Interpersonal Reactivity Index-Chinese was significantly correlated with precuneus activity during uncomfortable infant faces compared to sad adult faces. Our findings suggest that regional brain areas may bias cognitive and emotional responses to infant facial expressions compared to adult facial expressions among nulliparous women, and this bias may be modulated by individual differences in Interest-In-Infants and

  14. Facial responsiveness of psychopaths to the emotional expressions of others

    PubMed Central

    Mokros, Andreas; Olderbak, Sally; Wilhelm, Oliver

    2018-01-01

    Psychopathic individuals show selfish, manipulative, and antisocial behavior in addition to emotional detachment and reduced empathy. Their empathic deficits are thought to be associated with a reduced responsiveness to emotional stimuli. Immediate facial muscle responses to the emotional expressions of others reflect the expressive part of emotional responsiveness and are positively related to trait empathy. Empirical evidence for reduced facial muscle responses in adult psychopathic individuals to the emotional expressions of others is rare. In the present study, 261 male criminal offenders and non-offenders categorized dynamically presented facial emotion expressions (angry, happy, sad, and neutral) during facial electromyography recording of their corrugator muscle activity. We replicated a measurement model of facial muscle activity, which controls for general facial responsiveness to face stimuli, and modeled three correlated emotion-specific factors (i.e., anger, happiness, and sadness) representing emotion specific activity. In a multi-group confirmatory factor analysis, we compared the means of the anger, happiness, and sadness latent factors between three groups: 1) non-offenders, 2) low, and 3) high psychopathic offenders. There were no significant mean differences between groups. Our results challenge current theories that focus on deficits in emotional responsiveness as leading to the development of psychopathy and encourage further theoretical development on deviant emotional processes in psychopathic individuals. PMID:29324826

  15. The global workforce shortages and the migration of medical professions: the Australian policy response

    PubMed Central

    Smith, Saxon D

    2008-01-01

    Medical migration sees the providers of medical services (in particular medical practitioners) moving from one region or country to another. This creates problems for the provision of public health and medical services and poses challenges for laws in the nation state and for laws in the global community. There exists a global shortage of healthcare professionals. Nation states and health rights movements have been both responsible for, and responsive to, this global community shortage through a variety of health policy, regulation and legislation which directly affects the migration of medical providers. The microcosm responses adopted by individual nation states, such as Australia, to this workforce shortage further impact on the global workforce shortage through active recruitment of overseas-trained healthcare professionals. "Push" and "pull" factors exist which encourage medical migration of healthcare professionals. A nation state's approach to health policy, regulation and legislation dramatically helps to create these "push factors" and "pull factors". A co-ordinated global response is required with individual nation states being cognisant of the impact of their health policy, regulations and legislation on the global community through the medical migration of healthcare professionals. PMID:18507867

  16. Evaluation of folate receptor 1 (FOLR1) mRNA expression, its specific promoter methylation and global DNA hypomethylation in type I and type II ovarian cancers.

    PubMed

    Notaro, Sara; Reimer, Daniel; Fiegl, Heidi; Schmid, Gabriel; Wiedemair, Annamarie; Rössler, Julia; Marth, Christian; Zeimet, Alain Gustave

    2016-08-02

    has been found to be a reliable indicator of improved platinum responsiveness reflecting a transient better one-year follow up outcome in highly FOLR1 expressing type I cancers. An independent prognostic role of global DNA hypomethylation was demonstrated in type I tumours.

  17. Global Expression Profiling of Low Temperature Induced Genes in the Chilling Tolerant Japonica Rice Jumli Marshi

    PubMed Central

    Chawade, Aakash; Lindlöf, Angelica; Olsson, Björn; Olsson, Olof

    2013-01-01

    Low temperature is a key factor that limits growth and productivity of many important agronomical crops worldwide. Rice (Oryza sativa L.) is negatively affected already at temperatures below +10°C and is therefore denoted as chilling sensitive. However, chilling tolerant rice cultivars exist and can be commercially cultivated at altitudes up to 3,050 meters with temperatures reaching as low as +4°C. In this work, the global transcriptional response to cold stress (+4°C) was studied in the Nepalese highland variety Jumli Marshi (spp. japonica) and 4,636 genes were identified as significantly differentially expressed within 24 hours of cold stress. Comparison with previously published microarray data from one chilling tolerant and two sensitive rice cultivars identified 182 genes differentially expressed (DE) upon cold stress in all four rice cultivars and 511 genes DE only in the chilling tolerant rice. Promoter analysis of the 182 genes suggests a complex cross-talk between ABRE and CBF regulons. Promoter analysis of the 511 genes identified over-represented ABRE motifs but not DRE motifs, suggesting a role for ABA signaling in cold tolerance. Moreover, 2,101 genes were DE in Jumli Marshi alone. By chromosomal localization analysis, 473 of these cold responsive genes were located within 13 different QTLs previously identified as cold associated. PMID:24349120

  18. Expression of OsMYB55 in maize activates stress-responsive genes and enhances heat and drought tolerance.

    PubMed

    Casaretto, José A; El-Kereamy, Ashraf; Zeng, Bin; Stiegelmeyer, Suzy M; Chen, Xi; Bi, Yong-Mei; Rothstein, Steven J

    2016-04-29

    Plant response mechanisms to heat and drought stresses have been considered in strategies for generating stress tolerant genotypes, but with limited success. Here, we analyzed the transcriptome and improved tolerance to heat stress and drought of maize plants over-expressing the OsMYB55 gene. Over-expression of OsMYB55 in maize decreased the negative effects of high temperature and drought resulting in improved plant growth and performance under these conditions. This was evidenced by the higher plant biomass and reduced leaf damage exhibited by the transgenic lines compared to wild type when plants were subjected to individual or combined stresses and during or after recovery from stress. A global transcriptomic analysis using RNA sequencing revealed that several genes induced by heat stress in wild type plants are constitutively up-regulated in OsMYB55 transgenic maize. In addition, a significant number of genes up-regulated in OsMYB55 transgenic maize under control or heat treatments have been associated with responses to abiotic stresses including high temperature, dehydration and oxidative stress. The latter is a common and major consequence of imposed heat and drought conditions, suggesting that this altered gene expression may be associated with the improved stress tolerance in these transgenic lines. Functional annotation and enrichment analysis of the transcriptome also pinpoint the relevance of specific biological processes for stress responses. Our results show that expression of OsMYB55 can improve tolerance to heat stress and drought in maize plants. Enhanced expression of stress-associated genes may be involved in OsMYB55-mediated stress tolerance. Possible implications for the improved tolerance to heat stress and drought of OsMYB55 transgenic maize are discussed.

  19. Genome-Wide Gene Expression Analysis Shows AKAP13-Mediated PKD1 Signaling Regulates the Transcriptional Response to Cardiac Hypertrophy.

    PubMed

    Johnson, Keven R; Nicodemus-Johnson, Jessie; Spindler, Mathew J; Carnegie, Graeme K

    2015-01-01

    In the heart, scaffolding proteins such as A-Kinase Anchoring Proteins (AKAPs) play a crucial role in normal cellular function by serving as a signaling hub for multiple protein kinases including protein kinase D1 (PKD1). Under cardiac hypertrophic conditions AKAP13 anchored PKD1 activates the transcription factor MEF2 leading to subsequent fetal gene activation and hypertrophic response. We used an expression microarray to identify the global transcriptional response in the hearts of wild-type mice expressing the native form of AKAP13 compared to a gene-trap mouse model expressing a truncated form of AKAP13 that is unable to bind PKD1 (AKAP13-ΔPKD1). Microarray analysis showed that AKAP13-ΔPKD1 mice broadly failed to exhibit the transcriptional profile normally associated with compensatory cardiac hypertrophy following trans-aortic constriction (TAC). The identified differentially expressed genes in WT and AKAP13-ΔPKD1 hearts are vital for the compensatory hypertrophic response to pressure-overload and include myofilament, apoptotic, and cell growth/differentiation genes in addition to genes not previously identified as affected by AKAP13-anchored PKD1. Our results show that AKAP13-PKD1 signaling is critical for transcriptional regulation of key contractile, cell death, and metabolic pathways during the development of compensatory hypertrophy in vivo.

  20. Genome-Wide Gene Expression Analysis Shows AKAP13-Mediated PKD1 Signaling Regulates the Transcriptional Response to Cardiac Hypertrophy

    PubMed Central

    Johnson, Keven R.; Nicodemus-Johnson, Jessie; Spindler, Mathew J.

    2015-01-01

    In the heart, scaffolding proteins such as A-Kinase Anchoring Proteins (AKAPs) play a crucial role in normal cellular function by serving as a signaling hub for multiple protein kinases including protein kinase D1 (PKD1). Under cardiac hypertrophic conditions AKAP13 anchored PKD1 activates the transcription factor MEF2 leading to subsequent fetal gene activation and hypertrophic response. We used an expression microarray to identify the global transcriptional response in the hearts of wild-type mice expressing the native form of AKAP13 compared to a gene-trap mouse model expressing a truncated form of AKAP13 that is unable to bind PKD1 (AKAP13-ΔPKD1). Microarray analysis showed that AKAP13-ΔPKD1 mice broadly failed to exhibit the transcriptional profile normally associated with compensatory cardiac hypertrophy following trans-aortic constriction (TAC). The identified differentially expressed genes in WT and AKAP13-ΔPKD1 hearts are vital for the compensatory hypertrophic response to pressure-overload and include myofilament, apoptotic, and cell growth/differentiation genes in addition to genes not previously identified as affected by AKAP13-anchored PKD1. Our results show that AKAP13-PKD1 signaling is critical for transcriptional regulation of key contractile, cell death, and metabolic pathways during the development of compensatory hypertrophy in vivo. PMID:26192751

  1. Pregnancy Complicated by Obesity Induces Global Transcript Expression Alterations in Visceral and Subcutaneous Fat

    PubMed Central

    Bashiri, Asher; Heo, Hye J.; Ben-Avraham, Danny; Mazor, Moshe; Budagov, Temuri; Einstein, Francine H.; Atzmon, Gil

    2014-01-01

    Maternal obesity is a significant risk factor for development of both maternal and fetal metabolic complications. Increase in visceral fat and insulin resistance is a metabolic hallmark of pregnancy, yet little is known how obesity alters adipose cellular function and how this may contribute to pregnancy morbidities. We sought to identify alterations in genome-wide transcription expression in both visceral (omental) and abdominal subcutaneous fat deposits in pregnancy complicated by obesity. Visceral and abdominal subcutaneous fat deposits were collected from normal weight and obese pregnant women (n=4/group) at time of scheduled uncomplicated cesarean section. A genome-wide expression array (Affymetrix Human Exon 1.0 st platform), validated by quantitative real-time PCR, was utilized to establish the gene transcript expression profile in both visceral and abdominal subcutaneous fat in normal weight and obese pregnant women. Global alteration in gene expression was identified in pregnancy complicated by obesity. These regions of variations lead to identification of indolethylamine N-methyltransferase (INMT), tissue factor pathway inhibitor-2 (TFPI-2), and ephrin type-B receptor 6 (EPHB6), not previously associated with fat metabolism during pregnancy. In addition, subcutaneous fat of obese pregnant women demonstrated increased coding protein transcripts associated with apoptosis compared to lean counterparts. Global alteration of gene expression in adipose tissue may contribute to adverse pregnancy outcomes associated with obesity. PMID:24696292

  2. Soybean DREB1/CBF-type transcription factors function in heat and drought as well as cold stress-responsive gene expression.

    PubMed

    Kidokoro, Satoshi; Watanabe, Keitaro; Ohori, Teppei; Moriwaki, Takashi; Maruyama, Kyonoshin; Mizoi, Junya; Myint Phyu Sin Htwe, Nang; Fujita, Yasunari; Sekita, Sachiko; Shinozaki, Kazuo; Yamaguchi-Shinozaki, Kazuko

    2015-02-01

    Soybean (Glycine max) is a globally important crop, and its growth and yield are severely reduced by abiotic stresses, such as drought, heat, and cold. The cis-acting element DRE (dehydration-responsive element)/CRT plays an important role in activating gene expression in response to these stresses. The Arabidopsis DREB1/CBF genes that encode DRE-binding proteins function as transcriptional activators in the cold stress responsive gene expression. In this study, we identified 14 DREB1-type transcription factors (GmDREB1s) from a soybean genome database. The expression of most GmDREB1 genes in soybean was strongly induced by a variety of abiotic stresses, such as cold, drought, high salt, and heat. The GmDREB1 proteins activated transcription via DREs (dehydration-responsive element) in Arabidopsis and soybean protoplasts. Transcriptome analyses using transgenic Arabidopsis plants overexpressing GmDREB1s indicated that many of the downstream genes are cold-inducible and overlap with those of Arabidopsis DREB1A. We then comprehensively analyzed the downstream genes of GmDREB1B;1, which is closely related to DREB1A, using a transient expression system in soybean protoplasts. The expression of numerous genes induced by various abiotic stresses were increased by overexpressing GmDREB1B;1 in soybean, and DREs were the most conserved element in the promoters of these genes. The downstream genes of GmDREB1B;1 included numerous soybean-specific stress-inducible genes that encode an ABA receptor family protein, GmPYL21, and translation-related genes, such as ribosomal proteins. We confirmed that GmDREB1B;1 directly activates GmPYL21 expression and enhances ABRE-mediated gene expression in an ABA-independent manner. These results suggest that GmDREB1 proteins activate the expression of numerous soybean-specific stress-responsive genes under diverse abiotic stress conditions. © 2014 The Authors The Plant Journal © 2014 John Wiley & Sons Ltd.

  3. Quantifying global soil carbon losses in response to warming.

    PubMed

    Crowther, T W; Todd-Brown, K E O; Rowe, C W; Wieder, W R; Carey, J C; Machmuller, M B; Snoek, B L; Fang, S; Zhou, G; Allison, S D; Blair, J M; Bridgham, S D; Burton, A J; Carrillo, Y; Reich, P B; Clark, J S; Classen, A T; Dijkstra, F A; Elberling, B; Emmett, B A; Estiarte, M; Frey, S D; Guo, J; Harte, J; Jiang, L; Johnson, B R; Kröel-Dulay, G; Larsen, K S; Laudon, H; Lavallee, J M; Luo, Y; Lupascu, M; Ma, L N; Marhan, S; Michelsen, A; Mohan, J; Niu, S; Pendall, E; Peñuelas, J; Pfeifer-Meister, L; Poll, C; Reinsch, S; Reynolds, L L; Schmidt, I K; Sistla, S; Sokol, N W; Templer, P H; Treseder, K K; Welker, J M; Bradford, M A

    2016-11-30

    The majority of the Earth's terrestrial carbon is stored in the soil. If anthropogenic warming stimulates the loss of this carbon to the atmosphere, it could drive further planetary warming. Despite evidence that warming enhances carbon fluxes to and from the soil, the net global balance between these responses remains uncertain. Here we present a comprehensive analysis of warming-induced changes in soil carbon stocks by assembling data from 49 field experiments located across North America, Europe and Asia. We find that the effects of warming are contingent on the size of the initial soil carbon stock, with considerable losses occurring in high-latitude areas. By extrapolating this empirical relationship to the global scale, we provide estimates of soil carbon sensitivity to warming that may help to constrain Earth system model projections. Our empirical relationship suggests that global soil carbon stocks in the upper soil horizons will fall by 30 ± 30 petagrams of carbon to 203 ± 161 petagrams of carbon under one degree of warming, depending on the rate at which the effects of warming are realized. Under the conservative assumption that the response of soil carbon to warming occurs within a year, a business-as-usual climate scenario would drive the loss of 55 ± 50 petagrams of carbon from the upper soil horizons by 2050. This value is around 12-17 per cent of the expected anthropogenic emissions over this period. Despite the considerable uncertainty in our estimates, the direction of the global soil carbon response is consistent across all scenarios. This provides strong empirical support for the idea that rising temperatures will stimulate the net loss of soil carbon to the atmosphere, driving a positive land carbon-climate feedback that could accelerate climate change.

  4. Quantifying global soil carbon losses in response to warming

    NASA Astrophysics Data System (ADS)

    Crowther, T. W.; Todd-Brown, K. E. O.; Rowe, C. W.; Wieder, W. R.; Carey, J. C.; Machmuller, M. B.; Snoek, B. L.; Fang, S.; Zhou, G.; Allison, S. D.; Blair, J. M.; Bridgham, S. D.; Burton, A. J.; Carrillo, Y.; Reich, P. B.; Clark, J. S.; Classen, A. T.; Dijkstra, F. A.; Elberling, B.; Emmett, B. A.; Estiarte, M.; Frey, S. D.; Guo, J.; Harte, J.; Jiang, L.; Johnson, B. R.; Kröel-Dulay, G.; Larsen, K. S.; Laudon, H.; Lavallee, J. M.; Luo, Y.; Lupascu, M.; Ma, L. N.; Marhan, S.; Michelsen, A.; Mohan, J.; Niu, S.; Pendall, E.; Peñuelas, J.; Pfeifer-Meister, L.; Poll, C.; Reinsch, S.; Reynolds, L. L.; Schmidt, I. K.; Sistla, S.; Sokol, N. W.; Templer, P. H.; Treseder, K. K.; Welker, J. M.; Bradford, M. A.

    2016-12-01

    The majority of the Earth’s terrestrial carbon is stored in the soil. If anthropogenic warming stimulates the loss of this carbon to the atmosphere, it could drive further planetary warming. Despite evidence that warming enhances carbon fluxes to and from the soil, the net global balance between these responses remains uncertain. Here we present a comprehensive analysis of warming-induced changes in soil carbon stocks by assembling data from 49 field experiments located across North America, Europe and Asia. We find that the effects of warming are contingent on the size of the initial soil carbon stock, with considerable losses occurring in high-latitude areas. By extrapolating this empirical relationship to the global scale, we provide estimates of soil carbon sensitivity to warming that may help to constrain Earth system model projections. Our empirical relationship suggests that global soil carbon stocks in the upper soil horizons will fall by 30 ± 30 petagrams of carbon to 203 ± 161 petagrams of carbon under one degree of warming, depending on the rate at which the effects of warming are realized. Under the conservative assumption that the response of soil carbon to warming occurs within a year, a business-as-usual climate scenario would drive the loss of 55 ± 50 petagrams of carbon from the upper soil horizons by 2050. This value is around 12-17 per cent of the expected anthropogenic emissions over this period. Despite the considerable uncertainty in our estimates, the direction of the global soil carbon response is consistent across all scenarios. This provides strong empirical support for the idea that rising temperatures will stimulate the net loss of soil carbon to the atmosphere, driving a positive land carbon-climate feedback that could accelerate climate change.

  5. Global Scale Periodic Responses in Saturn’s Magnetosphere

    NASA Astrophysics Data System (ADS)

    Jia, Xianzhe; Kivelson, Margaret G.

    2017-10-01

    Despite having an axisymmetric internal magnetic field, Saturn’s magnetosphere exhibits periodic modulations in a variety of properties at periods close to the planetary rotation period. While the source of the periodicity remains unidentified, it is evident from Cassini observations that much of Saturn’s magnetospheric structure and dynamics is dominated by global-scale responses to the driving source of the periodicity. We have developed a global MHD model in which a rotating field-aligned current system is introduced by imposing vortical flows in the high-latitude ionosphere in order to simulate the magnetospheric periodicities. The model has been utilized to quantitatively characterize various periodic responses in the magnetosphere, such as the displacement of the magnetopause and bow shock and flapping of the tail plasma sheet, all of which show quantitative agreement with Cassini observations. One of our model predictions is periodic release of plasmoids in the tail that occurs preferentially in the midnight-to-dawn local time sector during each rotation cycle. Here we present detailed analysis of the periodic responses seen in our simulations focusing on the properties of plasmoids predicted by the model, including their spatial distribution, occurrence frequency, and mass loss rate. We will compare these modeled parameters with published Cassini observations, and discuss their implications for interpreting in-situ measurements.

  6. Metabolomic analysis of the selection response of Drosophila melanogaster to environmental stress: are there links to gene expression and phenotypic traits?

    NASA Astrophysics Data System (ADS)

    Malmendal, Anders; Sørensen, Jesper Givskov; Overgaard, Johannes; Holmstrup, Martin; Nielsen, Niels Chr.; Loeschcke, Volker

    2013-05-01

    We investigated the global metabolite response to artificial selection for tolerance to stressful conditions such as cold, heat, starvation, and desiccation, and for longevity in Drosophila melanogaster. Our findings were compared to data from other levels of biological organization, including gene expression, physiological traits, and organismal stress tolerance phenotype. Overall, we found that selection for environmental stress tolerance changes the metabolomic 1H NMR fingerprint largely in a similar manner independent of the trait selected for, indicating that experimental evolution led to a general stress selection response at the metabolomic level. Integrative analyses across data sets showed little similarity when general correlations between selection effects at the level of the metabolome and gene expression were compared. This is likely due to the fact that the changes caused by these selection regimes were rather mild and/or that the dominating determinants for gene expression and metabolite levels were different. However, expression of a number of genes was correlated with the metabolite data. Many of the identified genes were general stress response genes that are down-regulated in response to selection for some of the stresses in this study. Overall, the results illustrate that selection markedly alters the metabolite profile and that the coupling between different levels of biological organization indeed is present though not very strong for stress selection at this level. The results highlight the extreme complexity of environmental stress adaptation and the difficulty of extrapolating and interpreting responses across levels of biological organization.

  7. International volunteerism and global responsibility

    PubMed Central

    2017-01-01

    To review the current status of volunteerism in the field of urology as a global responsibility, a PubMed search was done with keywords: international volunteer, urology, global health, international resident education. Furthermore, internet search using Google and Bing as search engines for the same key words was done. Websites of multinational urological organizations was researched for available information. Expert opinions of key individuals in the arena were obtained. There is a paucity of published literature as to the efforts and outcomes of volunteerism in Urology; most of the information is related to the fistula repair outcomes in medical literature. There is credible information on the impact on resident training in the field of dentistry, general surgery, orthopedics and plastic surgery. The desire to volunteer is demonstrated in a survey of urologists, the delivery of volunteer missions is fragmented, the outcomes or impact of these efforts is less well documented. There is a need to create pathways to harness the desire of urologists to volunteer. Simultaneously, the effort to establish ethical standards and guidelines for surgical care in LMIC countries by visiting doctors is important. There is a tremendous opportunity for resident education in this arena, as demonstrated by the ACGME approved path in general surgery. PMID:28540233

  8. Social Alienation in Schizophrenia Patients: Association with Insula Responsiveness to Facial Expressions of Disgust

    PubMed Central

    Lindner, Christian; Dannlowski, Udo; Walhöfer, Kirsten; Rödiger, Maike; Maisch, Birgit; Bauer, Jochen; Ohrmann, Patricia; Lencer, Rebekka; Zwitserlood, Pienie; Kersting, Anette; Heindel, Walter; Arolt, Volker

    2014-01-01

    Introduction Among the functional neuroimaging studies on emotional face processing in schizophrenia, few have used paradigms with facial expressions of disgust. In this study, we investigated whether schizophrenia patients show less insula activation to macro-expressions (overt, clearly visible expressions) and micro-expressions (covert, very brief expressions) of disgust than healthy controls. Furthermore, departing from the assumption that disgust faces signal social rejection, we examined whether perceptual sensitivity to disgust is related to social alienation in patients and controls. We hypothesized that high insula responsiveness to facial disgust predicts social alienation. Methods We used functional magnetic resonance imaging to measure insula activation in 36 schizophrenia patients and 40 healthy controls. During scanning, subjects passively viewed covert and overt presentations of disgust and neutral faces. To measure social alienation, a social loneliness scale and an agreeableness scale were administered. Results Schizophrenia patients exhibited reduced insula activation in response to covert facial expressions of disgust. With respect to macro-expressions of disgust, no between-group differences emerged. In patients, insula responsiveness to covert faces of disgust was positively correlated with social loneliness. Furthermore, patients' insula responsiveness to covert and overt faces of disgust was negatively correlated with agreeableness. In controls, insula responsiveness to covert expressions of disgust correlated negatively with agreeableness. Discussion Schizophrenia patients show reduced insula responsiveness to micro-expressions but not macro-expressions of disgust compared to healthy controls. In patients, low agreeableness was associated with stronger insula response to micro- and macro-expressions of disgust. Patients with a strong tendency to feel uncomfortable with social interactions appear to be characterized by a high sensitivity for

  9. Social alienation in schizophrenia patients: association with insula responsiveness to facial expressions of disgust.

    PubMed

    Lindner, Christian; Dannlowski, Udo; Walhöfer, Kirsten; Rödiger, Maike; Maisch, Birgit; Bauer, Jochen; Ohrmann, Patricia; Lencer, Rebekka; Zwitserlood, Pienie; Kersting, Anette; Heindel, Walter; Arolt, Volker; Kugel, Harald; Suslow, Thomas

    2014-01-01

    Among the functional neuroimaging studies on emotional face processing in schizophrenia, few have used paradigms with facial expressions of disgust. In this study, we investigated whether schizophrenia patients show less insula activation to macro-expressions (overt, clearly visible expressions) and micro-expressions (covert, very brief expressions) of disgust than healthy controls. Furthermore, departing from the assumption that disgust faces signal social rejection, we examined whether perceptual sensitivity to disgust is related to social alienation in patients and controls. We hypothesized that high insula responsiveness to facial disgust predicts social alienation. We used functional magnetic resonance imaging to measure insula activation in 36 schizophrenia patients and 40 healthy controls. During scanning, subjects passively viewed covert and overt presentations of disgust and neutral faces. To measure social alienation, a social loneliness scale and an agreeableness scale were administered. Schizophrenia patients exhibited reduced insula activation in response to covert facial expressions of disgust. With respect to macro-expressions of disgust, no between-group differences emerged. In patients, insula responsiveness to covert faces of disgust was positively correlated with social loneliness. Furthermore, patients' insula responsiveness to covert and overt faces of disgust was negatively correlated with agreeableness. In controls, insula responsiveness to covert expressions of disgust correlated negatively with agreeableness. Schizophrenia patients show reduced insula responsiveness to micro-expressions but not macro-expressions of disgust compared to healthy controls. In patients, low agreeableness was associated with stronger insula response to micro- and macro-expressions of disgust. Patients with a strong tendency to feel uncomfortable with social interactions appear to be characterized by a high sensitivity for facial expression signaling social

  10. Face inversion decreased information about facial identity and expression in face-responsive neurons in macaque area TE.

    PubMed

    Sugase-Miyamoto, Yasuko; Matsumoto, Narihisa; Ohyama, Kaoru; Kawano, Kenji

    2014-09-10

    To investigate the effect of face inversion and thatcherization (eye inversion) on temporal processing stages of facial information, single neuron activities in the temporal cortex (area TE) of two rhesus monkeys were recorded. Test stimuli were colored pictures of monkey faces (four with four different expressions), human faces (three with four different expressions), and geometric shapes. Modifications were made in each face-picture, and its four variations were used as stimuli: upright original, inverted original, upright thatcherized, and inverted thatcherized faces. A total of 119 neurons responded to at least one of the upright original facial stimuli. A majority of the neurons (71%) showed activity modulations depending on upright and inverted presentations, and a lesser number of neurons (13%) showed activity modulations depending on original and thatcherized face conditions. In the case of face inversion, information about the fine category (facial identity and expression) decreased, whereas information about the global category (monkey vs human vs shape) was retained for both the original and thatcherized faces. Principal component analysis on the neuronal population responses revealed that the global categorization occurred regardless of the face inversion and that the inverted faces were represented near the upright faces in the principal component analysis space. By contrast, the face inversion decreased the ability to represent human facial identity and monkey facial expression. Thus, the neuronal population represented inverted faces as faces but failed to represent the identity and expression of the inverted faces, indicating that the neuronal representation in area TE cause the perceptual effect of face inversion. Copyright © 2014 the authors 0270-6474/14/3412457-13$15.00/0.

  11. Global expression analysis of gene regulatory pathways during endocrine pancreatic development.

    PubMed

    Gu, Guoqiang; Wells, James M; Dombkowski, David; Preffer, Fred; Aronow, Bruce; Melton, Douglas A

    2004-01-01

    To define genetic pathways that regulate development of the endocrine pancreas, we generated transcriptional profiles of enriched cells isolated from four biologically significant stages of endocrine pancreas development: endoderm before pancreas specification, early pancreatic progenitor cells, endocrine progenitor cells and adult islets of Langerhans. These analyses implicate new signaling pathways in endocrine pancreas development, and identified sets of known and novel genes that are temporally regulated, as well as genes that spatially define developing endocrine cells from their neighbors. The differential expression of several genes from each time point was verified by RT-PCR and in situ hybridization. Moreover, we present preliminary functional evidence suggesting that one transcription factor encoding gene (Myt1), which was identified in our screen, is expressed in endocrine progenitors and may regulate alpha, beta and delta cell development. In addition to identifying new genes that regulate endocrine cell fate, this global gene expression analysis has uncovered informative biological trends that occur during endocrine differentiation.

  12. Analysis of Gene Expression and Physiological Responses in Three Mexican Maize Landraces under Drought Stress and Recovery Irrigation

    PubMed Central

    Hayano-Kanashiro, Corina; Calderón-Vázquez, Carlos; Ibarra-Laclette, Enrique; Herrera-Estrella, Luis; Simpson, June

    2009-01-01

    Background Drought is one of the major constraints for plant productivity worldwide. Different mechanisms of drought-tolerance have been reported for several plant species including maize. However, the differences in global gene expression between drought-tolerant and susceptible genotypes and their relationship to physiological adaptations to drought are largely unknown. The study of the differences in global gene expression between tolerant and susceptible genotypes could provide important information to design more efficient breeding programs to produce maize varieties better adapted to water limiting conditions. Methodology/Principal Findings Changes in physiological responses and gene expression patterns were studied under drought stress and recovery in three Mexican maize landraces which included two drought tolerant (Cajete criollo and Michoacán 21) and one susceptible (85-2) genotypes. Photosynthesis, stomatal conductance, soil and leaf water potentials were monitored throughout the experiment and microarray analysis was carried out on transcripts obtained at 10 and 17 days following application of stress and after recovery irrigation. The two tolerant genotypes show more drastic changes in global gene expression which correlate with different physiological mechanisms of adaptation to drought. Differences in the kinetics and number of up- and down-regulated genes were observed between the tolerant and susceptible maize genotypes, as well as differences between the two tolerant genotypes. Interestingly, the most dramatic differences between the tolerant and susceptible genotypes were observed during recovery irrigation, suggesting that the tolerant genotypes activate mechanisms that allow more efficient recovery after a severe drought. Conclusions/Significance A correlation between levels of photosynthesis and transcription under stress was observed and differences in the number, type and expression levels of transcription factor families were also

  13. Global gene expression in channel catfish after vaccination with an attenuated Edwardsiella ictaluri

    USDA-ARS?s Scientific Manuscript database

    To understand the global gene expression in channel catfish after immersion vaccination with an attenuated Edwardsiella ictaluri (AquaVac ESCTM), microarray analysis of 65,182 UniGene transcripts were performed. With a filter of false-discovery rate less than 0.05 and fold change greater than 2, a t...

  14. Global Gene Expression Analysis in PKCα-/- Mouse Skin Reveals Structural Changes in the Dermis and Defective Wound Granulation Tissue.

    PubMed

    Cooper, Nichola H; Balachandra, Jeya P; Hardman, Matthew J

    2015-12-01

    The skin's mechanical integrity is maintained by an organized and robust dermal extracellular matrix (ECM). Resistance to mechanical disruption hinges primarily on homeostasis of the dermal collagen fibril architecture, which is regulated, at least in part, by members of the small leucine-rich proteoglycan (SLRP) family. Here we present data linking protein kinase C alpha (PKCα) to the regulated expression of multiple ECM components including SLRPs. Global microarray profiling reveals deficiencies in ECM gene expression in PKCα-/- skin correlating with abnormal collagen fibril morphology, disorganized dermal architecture, and reduced skin strength. Detailed analysis of the skin and wounds from wild-type and PKCα-/- mice reveals a failure to upregulate collagen and other ECM components in response to injury, resulting in delayed granulation tissue deposition in PKCα-/- wounds. Thus, our data reveal a previously unappreciated role for PKCα in the regulation of ECM structure and deposition during skin wound healing.

  15. A global × global test for testing associations between two large sets of variables.

    PubMed

    Chaturvedi, Nimisha; de Menezes, Renée X; Goeman, Jelle J

    2017-01-01

    In high-dimensional omics studies where multiple molecular profiles are obtained for each set of patients, there is often interest in identifying complex multivariate associations, for example, copy number regulated expression levels in a certain pathway or in a genomic region. To detect such associations, we present a novel approach to test for association between two sets of variables. Our approach generalizes the global test, which tests for association between a group of covariates and a single univariate response, to allow high-dimensional multivariate response. We apply the method to several simulated datasets as well as two publicly available datasets, where we compare the performance of multivariate global test (G2) with univariate global test. The method is implemented in R and will be available as a part of the globaltest package in R. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Age and meloxicam modify the response of the glutamate vesicular transporters (VGLUTs) after transient global cerebral ischemia in the rat brain.

    PubMed

    Llorente, Irene L; Pérez-Rodríguez, Diego; Burgin, Taiana C; Gonzalo-Orden, José M; Martínez-Villayandre, Beatriz; Fernández-López, Arsenio

    2013-05-01

    This study analyzes how age and inflammation modify the response of the vesicular glutamate transporters (VGLUTs), VGLUT1-3 to global brain ischemia/reperfusion (I/R) in brain areas with different I/R vulnerabilities. Global ischemia was induced in 3- and 18-month-old male Sprague-Dawley rats and CA1 and CA3 hippocampal areas, dentate gyrus and cerebral cortex of sham-operated and I/R animals were removed 48 h after insult. Real-time PCR analysis revealed that I/R challenge resulted in a significant decrease of the VGLUT mRNA levels in young animals. Western blot assays showed a lessened age-dependent response to the ischemic damage in VGLUT1 and VGLUT3, while VGLUT2 presented an age and structure-dependent response to challenge. The use of the anti-inflammatory agent meloxicam following challenge showed that COX2 inhibition promotes the expression of VGLUTs in both sham and injured animals, which results in a lessened response to I/R injury. VGLUT1 and VGLUT3 presented an age-dependent response to ischemic damage, while this VGLUT response was age both and structure-dependent. In addition, COX-2 inhibition resulted in an increase of VGLUT1 and VGLUT2 protein amounts both in sham and injured animals together with a lessening of the transporters' response to ischemia. Copyright © 2013 Elsevier Inc. All rights reserved.

  17. Analysis of Gene Expression in Escherichia coli in Response to Changes of Growth-Limiting Nutrient in Chemostat Cultures

    PubMed Central

    Hua, Qiang; Yang, Chen; Oshima, Taku; Mori, Hirotada; Shimizu, Kazuyuki

    2004-01-01

    Studies of steady-state metabolic fluxes in Escherichia coli grown in nutrient-limited chemostat cultures suggest remarkable flux alterations in response to changes of growth-limiting nutrient in the medium (Hua et al., J. Bacteriol. 185:7053-7067, 2003). To elucidate the physiological adaptation of cells to the nutrient condition through the flux change and understand the molecular mechanisms underlying the change in the flux, information on gene expression is of great importance. DNA microarray analysis was performed to investigate the global transcriptional responses of steady-state cells grown in chemostat cultures with limited glucose or ammonia while other environmental conditions and the growth rate were kept constant. In slow-growing cells (specific growth rate of 0.10 h−1), 9.8% of a total of 4,071 genes investigated, especially those involved in amino acid metabolism, central carbon and energy metabolism, transport system and cell envelope, were observed to be differentially expressed between the two nutrient-limited cultures. One important characteristic of E. coli grown under nutrient limitation was its capacity to scavenge carbon or nitrogen from the medium through elevating the expression of the corresponding transport and assimilation genes. The number of differentially expressed genes in faster-growing cells (specific growth rate of 0.55 h−1), however, decreased to below half of that in slow-growing cells, which could be explained by diverse transcriptional responses to the growth rate under different nutrient limitations. Independent of the growth rate, 92 genes were identified as being differentially expressed. Genes tightly related to the culture conditions were highlighted, some of which may be used to characterize nutrient-limited growth. PMID:15066832

  18. Gene expression changes in uterine myomas in response to ulipristal acetate treatment.

    PubMed

    Courtoy, Guillaume E; Donnez, Jacques; Ambroise, Jérôme; Arriagada, Pablo; Luyckx, Mathieu; Marbaix, Etienne; Dolmans, Marie-Madeleine

    2018-05-07

    Does ulipristal acetate (UPA) modify the expression of genes related to apoptosis or the extracellular matrix in uterine myomas and are any modifications associated with a clinical response? Targeted analysis of 176 apoptosis- or extracellular-matrix-related genes was conducted using polymerase chain reaction (PCR) arrays. Relevant results were validated by quantitative PCR. Four groups were established: responsive short-term (one course, n = 9), responsive long-term (two to four courses, n = 9), non-responsive (n = 9), and the control group who was not given any hormone therapy (n = 9). The clinical response was monitored by medical imagery and considered significant when volume reduction was greater than 25%. Compared with untreated myomas, significant changes in expression of four genes were found in UPA-treated myomas. Gene expression of integrin subunit beta 4 was repressed by UPA treatment (fold change [FC] = -12.50, P < 0.001, q < 0.001), tenascin-C expression was downregulated in UPA-responsive patients (FC = -2.50, P = 0.010, q = 0.090), survivin was repressed in short-term UPA-responsive tumours (FC = -7.69, P < 0.001, q = 0.010), and catenin delta 2 gene expression was upregulated in non-responsive myomas (FC = +7.36, P < 0.001, q = 0.010). This characterization provides the first molecular distinction between myomas responsive or non-responsive to UPA treatment. Copyright © 2018 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

  19. Facial expression recognition under partial occlusion based on fusion of global and local features

    NASA Astrophysics Data System (ADS)

    Wang, Xiaohua; Xia, Chen; Hu, Min; Ren, Fuji

    2018-04-01

    Facial expression recognition under partial occlusion is a challenging research. This paper proposes a novel framework for facial expression recognition under occlusion by fusing the global and local features. In global aspect, first, information entropy are employed to locate the occluded region. Second, principal Component Analysis (PCA) method is adopted to reconstruct the occlusion region of image. After that, a replace strategy is applied to reconstruct image by replacing the occluded region with the corresponding region of the best matched image in training set, Pyramid Weber Local Descriptor (PWLD) feature is then extracted. At last, the outputs of SVM are fitted to the probabilities of the target class by using sigmoid function. For the local aspect, an overlapping block-based method is adopted to extract WLD features, and each block is weighted adaptively by information entropy, Chi-square distance and similar block summation methods are then applied to obtain the probabilities which emotion belongs to. Finally, fusion at the decision level is employed for the data fusion of the global and local features based on Dempster-Shafer theory of evidence. Experimental results on the Cohn-Kanade and JAFFE databases demonstrate the effectiveness and fault tolerance of this method.

  20. Facial EMG responses to emotional expressions are related to emotion perception ability.

    PubMed

    Künecke, Janina; Hildebrandt, Andrea; Recio, Guillermo; Sommer, Werner; Wilhelm, Oliver

    2014-01-01

    Although most people can identify facial expressions of emotions well, they still differ in this ability. According to embodied simulation theories understanding emotions of others is fostered by involuntarily mimicking the perceived expressions, causing a "reactivation" of the corresponding mental state. Some studies suggest automatic facial mimicry during expression viewing; however, findings on the relationship between mimicry and emotion perception abilities are equivocal. The present study investigated individual differences in emotion perception and its relationship to facial muscle responses - recorded with electromyogram (EMG)--in response to emotional facial expressions. N° = °269 participants completed multiple tasks measuring face and emotion perception. EMG recordings were taken from a subsample (N° = °110) in an independent emotion classification task of short videos displaying six emotions. Confirmatory factor analyses of the m. corrugator supercilii in response to angry, happy, sad, and neutral expressions showed that individual differences in corrugator activity can be separated into a general response to all faces and an emotion-related response. Structural equation modeling revealed a substantial relationship between the emotion-related response and emotion perception ability, providing evidence for the role of facial muscle activation in emotion perception from an individual differences perspective.

  1. Local and global responses in complex gene regulation networks

    NASA Astrophysics Data System (ADS)

    Tsuchiya, Masa; Selvarajoo, Kumar; Piras, Vincent; Tomita, Masaru; Giuliani, Alessandro

    2009-04-01

    An exacerbated sensitivity to apparently minor stimuli and a general resilience of the entire system stay together side-by-side in biological systems. This apparent paradox can be explained by the consideration of biological systems as very strongly interconnected network systems. Some nodes of these networks, thanks to their peculiar location in the network architecture, are responsible for the sensitivity aspects, while the large degree of interconnection is at the basis of the resilience properties of the system. One relevant feature of the high degree of connectivity of gene regulation networks is the emergence of collective ordered phenomena influencing the entire genome and not only a specific portion of transcripts. The great majority of existing gene regulation models give the impression of purely local ‘hard-wired’ mechanisms disregarding the emergence of global ordered behavior encompassing thousands of genes while the general, genome wide, aspects are less known. Here we address, on a data analysis perspective, the discrimination between local and global scale regulations, this goal was achieved by means of the examination of two biological systems: innate immune response in macrophages and oscillating growth dynamics in yeast. Our aim was to reconcile the ‘hard-wired’ local view of gene regulation with a global continuous and scalable one borrowed from statistical physics. This reconciliation is based on the network paradigm in which the local ‘hard-wired’ activities correspond to the activation of specific crucial nodes in the regulation network, while the scalable continuous responses can be equated to the collective oscillations of the network after a perturbation.

  2. Global analysis of gene expression in response to L-Cysteine deprivation in the anaerobic protozoan parasite Entamoeba histolytica

    PubMed Central

    2011-01-01

    Background Entamoeba histolytica, an enteric protozoan parasite, causes amebic colitis and extra intestinal abscesses in millions of inhabitants of endemic areas. E. histolytica completely lacks glutathione metabolism but possesses L-cysteine as the principle low molecular weight thiol. L-Cysteine is essential for the structure, stability, and various protein functions, including catalysis, electron transfer, redox regulation, nitrogen fixation, and sensing for regulatory processes. Recently, we demonstrated that in E. histolytica, L-cysteine regulates various metabolic pathways including energy, amino acid, and phospholipid metabolism. Results In this study, employing custom-made Affymetrix microarrays, we performed time course (3, 6, 12, 24, and 48 h) gene expression analysis upon L-cysteine deprivation. We identified that out of 9,327 genes represented on the array, 290 genes encoding proteins with functions in metabolism, signalling, DNA/RNA regulation, electron transport, stress response, membrane transport, vesicular trafficking/secretion, and cytoskeleton were differentially expressed (≥3 fold) at one or more time points upon L-cysteine deprivation. Approximately 60% of these modulated genes encoded proteins of no known function and annotated as hypothetical proteins. We also attempted further functional analysis of some of the most highly modulated genes by L-cysteine depletion. Conclusions To our surprise, L-cysteine depletion caused only limited changes in the expression of genes involved in sulfur-containing amino acid metabolism and oxidative stress defense. In contrast, we observed significant changes in the expression of several genes encoding iron sulfur flavoproteins, a major facilitator super-family transporter, regulator of nonsense transcripts, NADPH-dependent oxido-reductase, short chain dehydrogenase, acetyltransferases, and various other genes involved in diverse cellular functions. This study represents the first genome-wide analysis of

  3. Spontaneous Facial Mimicry in Response to Dynamic Facial Expressions

    ERIC Educational Resources Information Center

    Sato, Wataru; Yoshikawa, Sakiko

    2007-01-01

    Based on previous neuroscientific evidence indicating activation of the mirror neuron system in response to dynamic facial actions, we hypothesized that facial mimicry would occur while subjects viewed dynamic facial expressions. To test this hypothesis, dynamic/static facial expressions of anger/happiness were presented using computer-morphing…

  4. A Conceptual Framework for Responsive Global Engagement in Communication Sciences and Disorders

    ERIC Educational Resources Information Center

    Hyter, Yvette D.

    2014-01-01

    The field of speech-language pathology needs a conceptual framework to guide the provision of services in a globalized world. Proposed in this article is a conceptual framework designed to facilitate responsive global engagement for professionals such as speech-language pathologists, who are increasingly serving diverse populations around the…

  5. Facial EMG Responses to Emotional Expressions Are Related to Emotion Perception Ability

    PubMed Central

    Künecke, Janina; Hildebrandt, Andrea; Recio, Guillermo; Sommer, Werner; Wilhelm, Oliver

    2014-01-01

    Although most people can identify facial expressions of emotions well, they still differ in this ability. According to embodied simulation theories understanding emotions of others is fostered by involuntarily mimicking the perceived expressions, causing a “reactivation” of the corresponding mental state. Some studies suggest automatic facial mimicry during expression viewing; however, findings on the relationship between mimicry and emotion perception abilities are equivocal. The present study investigated individual differences in emotion perception and its relationship to facial muscle responses - recorded with electromyogram (EMG) - in response to emotional facial expressions. N° = °269 participants completed multiple tasks measuring face and emotion perception. EMG recordings were taken from a subsample (N° = °110) in an independent emotion classification task of short videos displaying six emotions. Confirmatory factor analyses of the m. corrugator supercilii in response to angry, happy, sad, and neutral expressions showed that individual differences in corrugator activity can be separated into a general response to all faces and an emotion-related response. Structural equation modeling revealed a substantial relationship between the emotion-related response and emotion perception ability, providing evidence for the role of facial muscle activation in emotion perception from an individual differences perspective. PMID:24489647

  6. El Nino/Southern Oscillation response to global warming.

    PubMed

    Latif, M; Keenlyside, N S

    2009-12-08

    The El Niño/Southern Oscillation (ENSO) phenomenon, originating in the Tropical Pacific, is the strongest natural interannual climate signal and has widespread effects on the global climate system and the ecology of the Tropical Pacific. Any strong change in ENSO statistics will therefore have serious climatic and ecological consequences. Most global climate models do simulate ENSO, although large biases exist with respect to its characteristics. The ENSO response to global warming differs strongly from model to model and is thus highly uncertain. Some models simulate an increase in ENSO amplitude, others a decrease, and others virtually no change. Extremely strong changes constituting tipping point behavior are not simulated by any of the models. Nevertheless, some interesting changes in ENSO dynamics can be inferred from observations and model integrations. Although no tipping point behavior is envisaged in the physical climate system, smooth transitions in it may give rise to tipping point behavior in the biological, chemical, and even socioeconomic systems. For example, the simulated weakening of the Pacific zonal sea surface temperature gradient in the Hadley Centre model (with dynamic vegetation included) caused rapid Amazon forest die-back in the mid-twenty-first century, which in turn drove a nonlinear increase in atmospheric CO(2), accelerating global warming.

  7. Identification of Mouse Serum miRNA Endogenous References by Global Gene Expression Profiles

    PubMed Central

    Mi, Qing-Sheng; Weiland, Matthew; Qi, Rui-Qun; Gao, Xing-Hua; Poisson, Laila M.; Zhou, Li

    2012-01-01

    MicroRNAs (miRNAs) are recently discovered small non-coding RNAs and can serve as serum biomarkers for disease diagnosis and prognoses. Lack of reliable serum miRNA endogenous references for normalization in miRNA gene expression makes single miRNA assays inaccurate. Using TaqMan® real-time PCR miRNA arrays with a global gene expression normalization strategy, we have analyzed serum miRNA expression profiles of 20 female mice of NOD/ShiLtJ (n = 8), NOR/LtJ (n = 6), and C57BL/6J (n = 6) at different ages and disease conditions. We identified five miRNAs, miR-146a, miR-16, miR-195, miR-30e and miR-744, to be stably expressed in all strains, which could serve as mouse serum miRNA endogenous references for single assay experiments. PMID:22348064

  8. Progress in global surveillance and response capacity 10 years after severe acute respiratory syndrome.

    PubMed

    Braden, Christopher R; Dowell, Scott F; Jernigan, Daniel B; Hughes, James M

    2013-06-01

    Ten years have elapsed since the World Health Organization issued its first global alert for an unexplained illness named severe acute respiratory syndrome (SARS). The anniversary provides an opportunity to reflect on the international response to this new global microbial threat. While global surveillance and response capacity for public health threats have been strengthened, critical gaps remain. Of 194 World Health Organization member states that signed on to the International Health Regulations (2005), <20% had achieved compliance with the core capacities required by the deadline in June 2012. Lessons learned from the global SARS outbreak highlight the need to avoid complacency, strengthen efforts to improve global capacity to address the next pandemic using all available 21st century tools, and support research to develop new treatment options, countermeasures, and insights while striving to address the global inequities that are the root cause of many of these challenges.

  9. Global Expression Studies of Yersinia Pestis Pathogenicity

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Garcia, E; Motin, V; Brubaker, R

    2002-10-15

    The aim of these studies continues to be the investigation into the molecular mechanisms that underlie the virulence process in Yersinia pestis. In particular, the focus of this work centers on the identification of novel genes and pathways responsible for the pathogenic properties of this organism. In spite of more than four decades of intense investigation in this field, the dilemma as to what makes Y. pestis such a virulent and lethal pathogen remains unanswered. The method being employed makes use microarray technology (DNA chip) that enables the examination of the global activities of the whole complement of genes inmore » this pathogen. Two primary resources available to the investigators (one directly obtained from a separate CBNP-funded project) make these studies possible: (1) Whole genome comparisons of the genes in Y. pestis and its near neighbors with attenuated or non pathogenic characteristics, and (2) the ability to duplicate in vitro, conditions that mimic the infection process of this pathogen. This year we have extended our studies from the original work of characterizing the global transcriptional regulation in Y. pestis triggered during temperature transition from 26 C to 37 C (roughly conditions found in the flea vector and the mammalian host, respectively) to studies of regulation encountered during shift between growth from conditions of neutral pH to acidic pH (the latter conditions, those mimic the environment found inside macrophages, a likely environment found by these cells during infection.). For this work, DNA arrays containing some 5,000 genes (the entire genome of Y. pestis plus those genes found uniquely in the enteropathogen, and near neighbor, Y. pseudotuberculosis) are used to monitor the simultaneous expression levels of each gene of known and unknown function in Y. pestis. Those genes that are up-regulate under the experimental conditions represent genes potentially involved in the pathogenic process. The ultimate role in

  10. Changes in gene expression associated with response to neoadjuvant chemotherapy in breast cancer.

    PubMed

    Hannemann, Juliane; Oosterkamp, Hendrika M; Bosch, Cathy A J; Velds, Arno; Wessels, Lodewyk F A; Loo, Claudette; Rutgers, Emiel J; Rodenhuis, Sjoerd; van de Vijver, Marc J

    2005-05-20

    At present, clinically useful markers predicting response of primary breast carcinomas to either doxorubicin-cyclophosphamide (AC) or doxorubicin-docetaxel (AD) are lacking. We investigated whether gene expression profiles of the primary tumor could be used to predict treatment response to either of those chemotherapy regimens. Within a single-institution, randomized, phase II trial, patients with locally advanced breast cancer received six courses of either AC (n = 24) or AD (n = 24) neoadjuvant chemotherapy. Gene expression profiles were generated from core-needle biopsies obtained before treatment and correlated with the response of the primary tumor to the chemotherapy administered. Additionally, pretreatment gene expression profiles were compared with those in tumors remaining after chemotherapy. Ten (20%) of 48 patients showed a (near) pathologic complete remission of the primary tumor after treatment. No gene expression pattern correlating with response could be identified for all patients or for the AC or AD groups separately. The comparison of the pretreatment biopsy and the tumor excised after chemotherapy revealed differences in gene expression in tumors that showed a partial remission but not in tumors that did not respond to chemotherapy. No gene expression profile predicting the response of primary breast carcinomas to AC- or AD-based neoadjuvant chemotherapy could be detected in this interim analysis. More subtle differences in gene expression are likely to be present but can only be reliably identified by studying a larger group of patients. Response of a breast tumor to neoadjuvant chemotherapy results in alterations in gene expression.

  11. A Robust Response of Precipitation to Global Warming from CMIP5 Models

    NASA Technical Reports Server (NTRS)

    Lau, K. -M.; Wu, H. -T.; Kim, K. -M.

    2012-01-01

    How precipitation responds to global warming is a major concern to society and a challenge to climate change research. Based on analyses of rainfall probability distribution functions of 14 state-of-the-art climate models, we find a robust, canonical global rainfall response to a triple CO2 warming scenario, featuring 100 250% more heavy rain, 5-10% less moderate rain, and 10-15% more very light or no-rain events. Regionally, a majority of the models project a consistent response with more heavy rain events over climatologically wet regions of the deep tropics, and more dry events over subtropical and tropical land areas. Results suggest that increased CO2 emissions induce basic structural changes in global rain systems, increasing risks of severe floods and droughts in preferred geographic locations worldwide.

  12. Differential Gene Expression Reveals Candidate Genes for Drought Stress Response in Abies alba (Pinaceae)

    PubMed Central

    Ziegenhagen, Birgit; Liepelt, Sascha

    2015-01-01

    Increasing drought periods as a result of global climate change pose a threat to many tree species by possibly outpacing their adaptive capabilities. Revealing the genetic basis of drought stress response is therefore implemental for future conservation strategies and risk assessment. Access to informative genomic regions is however challenging, especially for conifers, partially due to their large genomes, which puts constraints on the feasibility of whole genome scans. Candidate genes offer a valuable tool to reduce the complexity of the analysis and the amount of sequencing work and costs. For this study we combined an improved drought stress phenotyping of needles via a novel terahertz water monitoring technique with Massive Analysis of cDNA Ends to identify candidate genes for drought stress response in European silver fir (Abies alba Mill.). A pooled cDNA library was constructed from the cotyledons of six drought stressed and six well-watered silver fir seedlings, respectively. Differential expression analyses of these libraries revealed 296 candidate genes for drought stress response in silver fir (247 up- and 49 down-regulated) of which a subset was validated by RT-qPCR of the twelve individual cotyledons. A majority of these genes code for currently uncharacterized proteins and hint on new genomic resources to be explored in conifers. Furthermore, we could show that some traditional reference genes from model plant species (GAPDH and eIF4A2) are not suitable for differential analysis and we propose a new reference gene, TPC1, for drought stress expression profiling in needles of conifer seedlings. PMID:25924061

  13. Global map of physical interactions among differentially expressed genes in multiple sclerosis relapses and remissions.

    PubMed

    Tuller, Tamir; Atar, Shimshi; Ruppin, Eytan; Gurevich, Michael; Achiron, Anat

    2011-09-15

    Multiple sclerosis (MS) is a central nervous system autoimmune inflammatory T-cell-mediated disease with a relapsing-remitting course in the majority of patients. In this study, we performed a high-resolution systems biology analysis of gene expression and physical interactions in MS relapse and remission. To this end, we integrated 164 large-scale measurements of gene expression in peripheral blood mononuclear cells of MS patients in relapse or remission and healthy subjects, with large-scale information about the physical interactions between these genes obtained from public databases. These data were analyzed with a variety of computational methods. We find that there is a clear and significant global network-level signal that is related to the changes in gene expression of MS patients in comparison to healthy subjects. However, despite the clear differences in the clinical symptoms of MS patients in relapse versus remission, the network level signal is weaker when comparing patients in these two stages of the disease. This result suggests that most of the genes have relatively similar expression levels in the two stages of the disease. In accordance with previous studies, we found that the pathways related to regulation of cell death, chemotaxis and inflammatory response are differentially expressed in the disease in comparison to healthy subjects, while pathways related to cell adhesion, cell migration and cell-cell signaling are activated in relapse in comparison to remission. However, the current study includes a detailed report of the exact set of genes involved in these pathways and the interactions between them. For example, we found that the genes TP53 and IL1 are 'network-hub' that interacts with many of the differentially expressed genes in MS patients versus healthy subjects, and the epidermal growth factor receptor is a 'network-hub' in the case of MS patients with relapse versus remission. The statistical approaches employed in this study enabled us

  14. Responses in the right posterior superior temporal sulcus show a feature-based response to facial expression.

    PubMed

    Flack, Tessa R; Andrews, Timothy J; Hymers, Mark; Al-Mosaiwi, Mohammed; Marsden, Samuel P; Strachan, James W A; Trakulpipat, Chayanit; Wang, Liang; Wu, Tian; Young, Andrew W

    2015-08-01

    The face-selective region of the right posterior superior temporal sulcus (pSTS) plays an important role in analysing facial expressions. However, it is less clear how facial expressions are represented in this region. In this study, we used the face composite effect to explore whether the pSTS contains a holistic or feature-based representation of facial expression. Aligned and misaligned composite images were created from the top and bottom halves of faces posing different expressions. In Experiment 1, participants performed a behavioural matching task in which they judged whether the top half of two images was the same or different. The ability to discriminate the top half of the face was affected by changes in the bottom half of the face when the images were aligned, but not when they were misaligned. This shows a holistic behavioural response to expression. In Experiment 2, we used fMR-adaptation to ask whether the pSTS has a corresponding holistic neural representation of expression. Aligned or misaligned images were presented in blocks that involved repeating the same image or in which the top or bottom half of the images changed. Increased neural responses were found in the right pSTS regardless of whether the change occurred in the top or bottom of the image, showing that changes in expression were detected across all parts of the face. However, in contrast to the behavioural data, the pattern did not differ between aligned and misaligned stimuli. This suggests that the pSTS does not encode facial expressions holistically. In contrast to the pSTS, a holistic pattern of response to facial expression was found in the right inferior frontal gyrus (IFG). Together, these results suggest that pSTS reflects an early stage in the processing of facial expression in which facial features are represented independently. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Global Transcriptional Responses to Osmotic, Oxidative, and Imipenem Stress Conditions in Pseudomonas putida.

    PubMed

    Bojanovič, Klara; D'Arrigo, Isotta; Long, Katherine S

    2017-04-01

    Bacteria cope with and adapt to stress by modulating gene expression in response to specific environmental cues. In this study, the transcriptional response of Pseudomonas putida KT2440 to osmotic, oxidative, and imipenem stress conditions at two time points was investigated via identification of differentially expressed mRNAs and small RNAs (sRNAs). A total of 440 sRNA transcripts were detected, of which 10% correspond to previously annotated sRNAs, 40% to novel intergenic transcripts, and 50% to novel transcripts antisense to annotated genes. Each stress elicits a unique response as far as the extent and dynamics of the transcriptional changes. Nearly 200 protein-encoding genes exhibited significant changes in all stress types, implicating their participation in a general stress response. Almost half of the sRNA transcripts were differentially expressed under at least one condition, suggesting possible functional roles in the cellular response to stress conditions. The data show a larger fraction of differentially expressed sRNAs than of mRNAs with >5-fold expression changes. The work provides detailed insights into the mechanisms through which P. putida responds to different stress conditions and increases understanding of bacterial adaptation in natural and industrial settings. IMPORTANCE This study maps the complete transcriptional response of P. putida KT2440 to osmotic, oxidative, and imipenem stress conditions at short and long exposure times. Over 400 sRNA transcripts, consisting of both intergenic and antisense transcripts, were detected, increasing the number of identified sRNA transcripts in the strain by a factor of 10. Unique responses to each type of stress are documented, including both the extent and dynamics of the gene expression changes. The work adds rich detail to previous knowledge of stress response mechanisms due to the depth of the RNA sequencing data. Almost half of the sRNAs exhibit significant expression changes under at least one

  16. Global Transcriptional Responses to Osmotic, Oxidative, and Imipenem Stress Conditions in Pseudomonas putida

    PubMed Central

    Bojanovič, Klara; D'Arrigo, Isotta

    2017-01-01

    ABSTRACT Bacteria cope with and adapt to stress by modulating gene expression in response to specific environmental cues. In this study, the transcriptional response of Pseudomonas putida KT2440 to osmotic, oxidative, and imipenem stress conditions at two time points was investigated via identification of differentially expressed mRNAs and small RNAs (sRNAs). A total of 440 sRNA transcripts were detected, of which 10% correspond to previously annotated sRNAs, 40% to novel intergenic transcripts, and 50% to novel transcripts antisense to annotated genes. Each stress elicits a unique response as far as the extent and dynamics of the transcriptional changes. Nearly 200 protein-encoding genes exhibited significant changes in all stress types, implicating their participation in a general stress response. Almost half of the sRNA transcripts were differentially expressed under at least one condition, suggesting possible functional roles in the cellular response to stress conditions. The data show a larger fraction of differentially expressed sRNAs than of mRNAs with >5-fold expression changes. The work provides detailed insights into the mechanisms through which P. putida responds to different stress conditions and increases understanding of bacterial adaptation in natural and industrial settings. IMPORTANCE This study maps the complete transcriptional response of P. putida KT2440 to osmotic, oxidative, and imipenem stress conditions at short and long exposure times. Over 400 sRNA transcripts, consisting of both intergenic and antisense transcripts, were detected, increasing the number of identified sRNA transcripts in the strain by a factor of 10. Unique responses to each type of stress are documented, including both the extent and dynamics of the gene expression changes. The work adds rich detail to previous knowledge of stress response mechanisms due to the depth of the RNA sequencing data. Almost half of the sRNAs exhibit significant expression changes under at least

  17. Global effects of the DEAD-box RNA helicase DeaD (CsdA) on gene expression over a broad range of temperatures

    PubMed Central

    Vakulskas, Christopher A.; Pannuri, Archana; Cortés-Selva, Diana; Zere, Tesfalem R.; Ahmer, Brian M.; Babitzke, Paul; Romeo, Tony

    2014-01-01

    Summary In Escherichia coli, activity of the global regulatory RNA binding protein CsrA is antagonized by two noncoding sRNAs, CsrB and CsrC, which sequester it away from its lower affinity mRNA targets. Transcription of csrB/C requires the BarA-UvrY two component signal transduction system, which responds to short chain carboxylates. We show that two DEAD-box RNA helicases, DeaD and SrmB, activate csrB/C expression by different pathways. DeaD facilitates uvrY translation by counteracting the inhibitory effect of long distance basepairing between the uvrY mRNA leader and coding region, while SrmB does not affect UvrY or UvrY-phosphate levels. Contrary to the prevailing notion that these helicases act primarily at low temperatures, DeaD and SrmB activated csrB expression over a wide temperature range. High-throughput sequencing of RNA isolated by crosslinking immunoprecipitation (HITS-CLIP) revealed in vivo interactions of DeaD with 39 mRNAs, including those of uvrY and 9 other regulatory genes. Studies on the expression of several of the identified genes revealed regulatory effects of DeaD in all cases and diverse temperature response patterns. Our findings uncover an expanded regulatory role for DeaD, which is mediated through novel mRNA targets, important global regulators and under physiological conditions that were considered to be incompatible with its function. PMID:24708042

  18. A Bulk Segregant Gene Expression Analysis of a Peach Population Reveals Components of the Underlying Mechanism of the Fruit Cold Response

    PubMed Central

    Pons, Clara; Martí, Cristina; Forment, Javier; Crisosto, Carlos H.; Dandekar, Abhaya M.; Granell, Antonio

    2014-01-01

    Peach fruits subjected for long periods of cold storage are primed to develop chilling injury once fruits are shelf ripened at room temperature. Very little is known about the molecular changes occurring in fruits during cold exposure. To get some insight into this process a transcript profiling analyses was performed on fruits from a PopDG population segregating for chilling injury CI responses. A bulked segregant gene expression analysis based on groups of fruits showing extreme CI responses indicated that the transcriptome of peach fruits was modified already during cold storage consistently with eventual CI development. Most peach cold-responsive genes have orthologs in Arabidopsis that participate in cold acclimation and other stresses responses, while some of them showed expression patterns that differs in fruits according to their susceptibility to develop mealiness. Members of ICE1, CBF1/3 and HOS9 regulons seem to have a prominent role in differential cold responses between low and high sensitive fruits. In high sensitive fruits, an alternative cold response program is detected. This program is probably associated with dehydration/osmotic stress and regulated by ABA, auxins and ethylene. In addition, the observation that tolerant siblings showed a series of genes encoding for stress protective activities with higher expression both at harvest and during cold treatment, suggests that preprogrammed mechanisms could shape fruit ability to tolerate postharvest cold-induced stress. A number of genes differentially expressed were validated and extended to individual genotypes by medium-throughput RT-qPCR. Analyses presented here provide a global view of the responses of peach fruits to cold storage and highlights new peach genes that probably play important roles in the tolerance/sensitivity to cold storage. Our results provide a roadmap for further experiments and would help to develop new postharvest protocols and gene directed breeding strategies to better

  19. A bulk segregant gene expression analysis of a peach population reveals components of the underlying mechanism of the fruit cold response.

    PubMed

    Pons, Clara; Martí, Cristina; Forment, Javier; Crisosto, Carlos H; Dandekar, Abhaya M; Granell, Antonio

    2014-01-01

    Peach fruits subjected for long periods of cold storage are primed to develop chilling injury once fruits are shelf ripened at room temperature. Very little is known about the molecular changes occurring in fruits during cold exposure. To get some insight into this process a transcript profiling analyses was performed on fruits from a PopDG population segregating for chilling injury CI responses. A bulked segregant gene expression analysis based on groups of fruits showing extreme CI responses indicated that the transcriptome of peach fruits was modified already during cold storage consistently with eventual CI development. Most peach cold-responsive genes have orthologs in Arabidopsis that participate in cold acclimation and other stresses responses, while some of them showed expression patterns that differs in fruits according to their susceptibility to develop mealiness. Members of ICE1, CBF1/3 and HOS9 regulons seem to have a prominent role in differential cold responses between low and high sensitive fruits. In high sensitive fruits, an alternative cold response program is detected. This program is probably associated with dehydration/osmotic stress and regulated by ABA, auxins and ethylene. In addition, the observation that tolerant siblings showed a series of genes encoding for stress protective activities with higher expression both at harvest and during cold treatment, suggests that preprogrammed mechanisms could shape fruit ability to tolerate postharvest cold-induced stress. A number of genes differentially expressed were validated and extended to individual genotypes by medium-throughput RT-qPCR. Analyses presented here provide a global view of the responses of peach fruits to cold storage and highlights new peach genes that probably play important roles in the tolerance/sensitivity to cold storage. Our results provide a roadmap for further experiments and would help to develop new postharvest protocols and gene directed breeding strategies to better

  20. Transcriptome assembly and expression profiling of molecular responses to cadmium toxicity in hepatopancreas of the freshwater crab Sinopotamon henanense

    NASA Astrophysics Data System (ADS)

    Sun, Min; Ting Li, Yi; Liu, Yang; Chin Lee, Shao; Wang, Lan

    2016-01-01

    Cadmium (Cd) pollution is a serious global problem, which causes irreversible toxic effects on animals. Freshwater crab, Sinopotamon henanense, is a useful environmental indicator since it is widely distributed in benthic habitats whereby it tends to accumulate Cd and other toxicants. However, its molecular responses to Cd toxicity remain unclear. In this study, we performed transcriptome sequencing and gene expression analyses of its hepatopancreas with and without Cd treatments. A total of 7.78 G clean reads were obtained from the pooled samples, and 68,648 unigenes with an average size of 622 bp were assembled, in which 5,436 were metabolism-associated and 2,728 were stimulus response-associated that include 380 immunity-related unigenes. Expression profile analysis demonstrated that most genes involved in macromolecular metabolism, oxidative phosphorylation, detoxification and anti-oxidant defense were up-regulated by Cd exposure, whereas immunity-related genes were down-regulated, except the genes involved in phagocytosis were up-regulated. The current data indicate that Cd exposure alters gene expressions in a concentration-dependent manner. Therefore, our results provide the first comprehensive S.henanense transcriptome dataset, which is useful for biological and ecotoxicological studies on this crab and its related species at molecular level, and some key Cd-responsive genes may provide candidate biomarkers for monitoring aquatic pollution by heavy metals.

  1. Global changes in gene expression during compatible and incompatible interactions of cowpea (Vigna unguiculata L.) with the root parasitic angiosperm Striga gesnerioides.

    PubMed

    Huang, Kan; Mellor, Karolina E; Paul, Shom N; Lawson, Mark J; Mackey, Aaron J; Timko, Michael P

    2012-08-17

    Cowpea, Vigna unguiculata L. Walp., is one of the most important food and forage legumes in the semi-arid tropics. While most domesticated forms of cowpea are susceptible to the root parasitic weed Striga gesnerioides, several cultivars have been identified that show race-specific resistance. Cowpea cultivar B301 contains the RSG3-301 gene for resistance to S. gesnerioides race SG3, but is susceptible to race SG4z. When challenged by SG3, roots of cultivar B301 develop a strong resistance response characterized by a hypersensitive reaction and cell death at the site of parasite attachment. In contrast, no visible response occurs in B301 roots parasitized by SG4z. Gene expression in the roots of the cowpea cultivar B301 during compatible (susceptible) and incompatible (resistant) interactions with S. gesnerioides races SG4z and SG3, respectively, were investigated at the early (6 days post-inoculation (dpi)) and late (13 dpi) stages of the resistance response using a Nimblegen custom design cowpea microarray. A total of 111 genes were differentially expressed in B301 roots at 6 dpi; this number increased to 2102 genes at 13 dpi. At 13 dpi, a total of 1944 genes were differentially expressed during compatible (susceptible) interactions of B301 with SG4z. Genes and pathways involved in signal transduction, programmed cell death and apoptosis, and defense response to biotic and abiotic stress were differentially expressed in the early resistance response; at the later time point, enrichment was primarily for defense-related gene expression, and genes encoding components of lignifications and secondary wall formation. In compatible interactions (B301-SG4z), multiple defense pathways were repressed, including those involved in lignin biosynthesis and secondary cell wall modifications, while cellular transport processes for nitrogen and sulfur were increased. Distinct changes in global gene expression profiles occur in host roots following successful and unsuccessful

  2. Global changes in gene expression during compatible and incompatible interactions of cowpea (Vigna unguiculata L.) with the root parasitic angiosperm Striga gesnerioides

    PubMed Central

    2012-01-01

    Background Cowpea, Vigna unguiculata L. Walp., is one of the most important food and forage legumes in the semi-arid tropics. While most domesticated forms of cowpea are susceptible to the root parasitic weed Striga gesnerioides, several cultivars have been identified that show race-specific resistance. Cowpea cultivar B301 contains the RSG3-301 gene for resistance to S. gesnerioides race SG3, but is susceptible to race SG4z. When challenged by SG3, roots of cultivar B301 develop a strong resistance response characterized by a hypersensitive reaction and cell death at the site of parasite attachment. In contrast, no visible response occurs in B301 roots parasitized by SG4z. Results Gene expression in the roots of the cowpea cultivar B301 during compatible (susceptible) and incompatible (resistant) interactions with S. gesnerioides races SG4z and SG3, respectively, were investigated at the early (6 days post-inoculation (dpi)) and late (13 dpi) stages of the resistance response using a Nimblegen custom design cowpea microarray. A total of 111 genes were differentially expressed in B301 roots at 6 dpi; this number increased to 2102 genes at 13 dpi. At 13 dpi, a total of 1944 genes were differentially expressed during compatible (susceptible) interactions of B301 with SG4z. Genes and pathways involved in signal transduction, programmed cell death and apoptosis, and defense response to biotic and abiotic stress were differentially expressed in the early resistance response; at the later time point, enrichment was primarily for defense-related gene expression, and genes encoding components of lignifications and secondary wall formation. In compatible interactions (B301 – SG4z), multiple defense pathways were repressed, including those involved in lignin biosynthesis and secondary cell wall modifications, while cellular transport processes for nitrogen and sulfur were increased. Conclusion Distinct changes in global gene expression profiles occur in host roots

  3. Pathogenic Leptospires Modulate Protein Expression and Post-translational Modifications in Response to Mammalian Host Signals.

    PubMed

    Nally, Jarlath E; Grassmann, Andre A; Planchon, Sébastien; Sergeant, Kjell; Renaut, Jenny; Seshu, Janakiram; McBride, Alan J; Caimano, Melissa J

    2017-01-01

    Pathogenic species of Leptospira cause leptospirosis, a bacterial zoonotic disease with a global distribution affecting over one million people annually. Reservoir hosts of leptospirosis, including rodents, dogs, and cattle, exhibit little to no signs of disease but shed large numbers of organisms in their urine. Transmission occurs when mucosal surfaces or abraded skin come into contact with infected urine or urine-contaminated water or soil. Whilst little is known about how Leptospira adapt to and persist within a reservoir host, in vitro studies suggest that leptospires alter their transcriptomic and proteomic profiles in response to environmental signals encountered during mammalian infection. We applied the dialysis membrane chamber (DMC) peritoneal implant model to compare the whole cell proteome of in vivo derived leptospires with that of leptospires cultivated in vitro at 30°C and 37°C by 2-dimensional difference in-gel electrophoresis (2-D DIGE). Of 1,735 protein spots aligned across 9 2-D DIGE gels, 202 protein spots were differentially expressed ( p < 0.05, fold change >1.25 or < -1.25) across all three conditions. Differentially expressed proteins were excised for identification by mass spectrometry. Data are available via ProteomeXchange with identifier PXD006995. The greatest differences were detected when DMC-cultivated leptospires were compared with IV30- or IV37-cultivated leptospires, including the increased expression of multiple isoforms of Loa22, a known virulence factor. Unexpectedly, 20 protein isoforms of LipL32 and 7 isoforms of LipL41 were uniformly identified by DIGE as differentially expressed, suggesting that unique post-translational modifications (PTMs) are operative in response to mammalian host conditions. To test this hypothesis, a rat model of persistent renal colonization was used to isolate leptospires directly from the urine of experimentally infected rats. Comparison of urinary derived leptospires to IV30 leptospires by 2-D

  4. Circuitry Linking the Csr and Stringent Response Global Regulatory Systems

    PubMed Central

    Edwards, Adrianne N.; Patterson-Fortin, Laura M.; Vakulskas, Christopher A.; Mercante, Jeffrey W.; Potrykus, Katarzyna; Vinella, Daniel; Camacho, Martha I.; Fields, Joshua A.; Thompson, Stuart A.; Georgellis, Dimitris; Cashel, Michael; Babitzke, Paul; Romeo, Tony

    2011-01-01

    Summary CsrA protein regulates important cellular processes by binding to target mRNAs and altering their translation and/or stability. In Escherichia coli, CsrA binds to sRNAs, CsrB and CsrC, which sequester CsrA and antagonize its activity. Here, mRNAs for relA, spoT and dksA of the stringent response system were found among 721 different transcripts that copurified with CsrA. Many of the transcripts that copurified with CsrA were previously determined to respond to ppGpp and/or DksA. We examined multiple regulatory interactions between the Csr and stringent response systems. Most importantly, DksA and ppGpp robustly activated csrB/C transcription (10-fold), while they modestly activated csrA expression. We propose that CsrA-mediated regulation is relieved during the stringent response. Gel shift assays confirmed high affinity binding of CsrA to relA mRNA leader and weaker interactions with dksA and spoT. Reporter fusions, qRT-PCR, and immunoblotting showed that CsrA repressed relA expression, and (p)ppGpp accumulation during stringent response was enhanced in a csrA mutant. CsrA had modest to negligible effects on dksA and spoT expression. Transcription of dksA was negatively autoregulated via a feedback loop that tended to mask CsrA effects. We propose that the Csr system fine-tunes the stringent response and discuss biological implications of the composite circuitry. PMID:21488981

  5. Trends in TIMSS Responses over Time: Evidence of Global Forces in Education?

    ERIC Educational Resources Information Center

    Rutkowski, Leslie; Rutkowski, David

    2009-01-01

    In this article, the influence of global processes on international mathematics curricula as evidenced by item responses to 3 Trends in International Mathematics and Science Study (TIMSS) administrations (1995, 1999, and 2003) is considered. Based on Dale's (2000) argument, we set out to test 2 plausible impacts of global processes on education.…

  6. Steady-state and dynamic gene expression programs in Saccharomyces cerevisiae in response to variation in environmental nitrogen

    PubMed Central

    Airoldi, Edoardo M.; Miller, Darach; Athanasiadou, Rodoniki; Brandt, Nathan; Abdul-Rahman, Farah; Neymotin, Benjamin; Hashimoto, Tatsu; Bahmani, Tayebeh; Gresham, David

    2016-01-01

    Cell growth rate is regulated in response to the abundance and molecular form of essential nutrients. In Saccharomyces cerevisiae (budding yeast), the molecular form of environmental nitrogen is a major determinant of cell growth rate, supporting growth rates that vary at least threefold. Transcriptional control of nitrogen use is mediated in large part by nitrogen catabolite repression (NCR), which results in the repression of specific transcripts in the presence of a preferred nitrogen source that supports a fast growth rate, such as glutamine, that are otherwise expressed in the presence of a nonpreferred nitrogen source, such as proline, which supports a slower growth rate. Differential expression of the NCR regulon and additional nitrogen-responsive genes results in >500 transcripts that are differentially expressed in cells growing in the presence of different nitrogen sources in batch cultures. Here we find that in growth rate–controlled cultures using nitrogen-limited chemostats, gene expression programs are strikingly similar regardless of nitrogen source. NCR expression is derepressed in all nitrogen-limiting chemostat conditions regardless of nitrogen source, and in these conditions, only 34 transcripts exhibit nitrogen source–specific differential gene expression. Addition of either the preferred nitrogen source, glutamine, or the nonpreferred nitrogen source, proline, to cells growing in nitrogen-limited chemostats results in rapid, dose-dependent repression of the NCR regulon. Using a novel means of computational normalization to compare global gene expression programs in steady-state and dynamic conditions, we find evidence that the addition of nitrogen to nitrogen-limited cells results in the transient overproduction of transcripts required for protein translation. Simultaneously, we find that that accelerated mRNA degradation underlies the rapid clearing of a subset of transcripts, which is most pronounced for the highly expressed NCR

  7. Stress-Related Gene Expression Reflects Morphophysiological Responses to Water Deficit1[OPEN

    PubMed Central

    Vile, Denis; Bediee, Alexis; Dauzat, Myriam; Luchaire, Nathalie; Kamrowska, Dominika; Granier, Christine

    2017-01-01

    Acclimation to water deficit (WD) enables plants to maintain growth under unfavorable environmental conditions, although the mechanisms are not completely understood. In this study, the natural variation of long-term acclimation to moderate and severe soil WD was investigated in 18 Arabidopsis (Arabidopsis thaliana) accessions using PHENOPSIS, an automated phenotyping platform. Soil water content was adjusted at an early stage of plant development and maintained at a constant level until reproductive age was achieved. The accessions were selected based on the expression levels of ANNEXIN1, a drought-related marker. Severe WD conditions had a greater effect on most of the measured morphophysiological traits than moderate WD conditions. Multivariate analyses indicated that trait responses associated with plant size and water management drove most of the variation. Accessions with similar responses at these two levels were grouped in clusters that displayed different response strategies to WD. The expression levels of selected stress-response genes revealed large natural variation under WD conditions. Responses of morphophysiological traits, such as projected rosette area, transpiration rate, and rosette water content, were correlated with changes in the expression of stress-related genes, such as NINE-CIS-EPOXYCAROTENOID DIOXYGENASE3 and N-MYC DOWNREGULATED-LIKE1 (NDL1), in response to WD. Interestingly, the morphophysiological acclimation response to WD also was reflected in the gene expression levels (most notably those of NDL1, CHALCONE SYNTHASE, and MYB DOMAIN PROTEIN44) in plants cultivated under well-watered conditions. Our results may lead to the development of biomarkers and predictors of plant morphophysiological responses based on gene expression patterns. PMID:28522456

  8. Myosin heavy chain isoform expression in human extraocular muscles: longitudinal variation and patterns of expression in global and orbital layers.

    PubMed

    Park, Kyung-Ah; Lim, Jeonghee; Sohn, Seongsoo; Oh, Sei Yeul

    2012-05-01

    We investigated the distribution of myosin heavy chain (MyHC) isoforms along the length of the global and orbital layers of human extraocular muscles (EOMs). Whole muscle tissue extracts of human EOMs were cross-sectioned consecutively and separated into orbital and global layers. The extracts from these layers were subjected to electrophoretic analysis, followed by quantification with scanning densitometry. MyHC isoforms displayed different distributions along the lengths of EOMs. In the orbital and global layers of all EOMs except for the superior oblique muscle, MyHCeom was enriched in the central regions. MyHCIIa and MyHCI were most abundant in the proximal and distal ends. A variation in MyHC isoform expression was apparent along the lengths of human EOMs. These results provide a basis for understanding the molecular mechanisms underlying the functional diversity of EOMs. Copyright © 2012 Wiley Periodicals, Inc.

  9. Global Earth Response to Loading by Ocean Tide Models

    NASA Technical Reports Server (NTRS)

    Estes, R. H.; Strayer, J. M.

    1979-01-01

    Mathematical and programming techniques to numerically calculate Earth response to global semidiurnal and diurnal ocean tide models were developed. Global vertical crustal deformations were evaluated for M sub 2, S sub 2, N sub 2, K sub 2, K sub 1, O sub 1, and P sub 1 ocean tide loading, while horizontal deformations were evaluated for the M sub 2 tidal load. Tidal gravity calculations were performed for M sub 2 tidal loads, and strain tensor elements were evaluated for M sub 2 loads. The M sub 2 solution used for the ocean tide included the effects of self-gravitation and crustal loading.

  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

    2018-02-01

    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. Genomic expression catalogue of a global collection of BCG vaccine strains show evidence for highly diverged metabolic and cell-wall adaptations

    PubMed Central

    Abdallah, Abdallah M.; Hill-Cawthorne, Grant A.; Otto, Thomas D.; Coll, Francesc; Guerra-Assunção, José Afonso; Gao, Ge; Naeem, Raeece; Ansari, Hifzur; Malas, Tareq B.; Adroub, Sabir A.; Verboom, Theo; Ummels, Roy; Zhang, Huoming; Panigrahi, Aswini Kumar; McNerney, Ruth; Brosch, Roland; Clark, Taane G.; Behr, Marcel A.; Bitter, Wilbert; Pain, Arnab

    2015-01-01

    Although Bacillus Calmette-Guérin (BCG) vaccines against tuberculosis have been available for more than 90 years, their effectiveness has been hindered by variable protective efficacy and a lack of lasting memory responses. One factor contributing to this variability may be the diversity of the BCG strains that are used around the world, in part from genomic changes accumulated during vaccine production and their resulting differences in gene expression. We have compared the genomes and transcriptomes of a global collection of fourteen of the most widely used BCG strains at single base-pair resolution. We have also used quantitative proteomics to identify key differences in expression of proteins across five representative BCG strains of the four tandem duplication (DU) groups. We provide a comprehensive map of single nucleotide polymorphisms (SNPs), copy number variation and insertions and deletions (indels) across fourteen BCG strains. Genome-wide SNP characterization allowed the construction of a new and robust phylogenic genealogy of BCG strains. Transcriptional and proteomic profiling revealed a metabolic remodeling in BCG strains that may be reflected by altered immunogenicity and possibly vaccine efficacy. Together, these integrated-omic data represent the most comprehensive catalogue of genetic variation across a global collection of BCG strains. PMID:26487098

  12. Social responsibility and global health: lessons from the Rio Olympics Zika controversy.

    PubMed

    Hellmann, Fernando; Rohde, Luzilena de Souza Prudêncio; Verdi, Marta; Garrafa, Volnei; Manchola-Castillo, Camilo

    2018-03-30

    The outbreak of Zika virus infection in the Americas and its possible association with microcephaly raised several concerns among global health authorities regarding the organisation of the Olympic and Paralympic Games scheduled for August and September 2016, in the city of Rio de Janeiro, Brazil. It generated an international controversy over the continuation of the Games with debates on the ethical principle of social responsibility. Based on the principles of social responsibility and health in the Universal Declaration of Bioethics and Human Rights, the present comment ponders on the application of such principles in the context of mega-events and global health.

  13. Global Emerging Infection Surveillance and Response (GEIS)- Avian Influenza Pandemic Influenza (AI/PI) Program

    DTIC Science & Technology

    2008-10-01

    the fact that acute respiratory infections are one of the leading causes of morbidity. This capability now exists in Kenya with the first site brought...AD_________________ Award Number: W81XWH-07-2-0082 TITLE: Global Emerging Infection Surveillance and Response (GEIS)- Avian...TYPE Annual 3. DATES COVERED 13 Sep 07 – 12 Sep 08 4. TITLE AND SUBTITLE Global Emerging Infection Surveillance and Response (GEIS)- Avian

  14. MLH1 expression predicts the response to preoperative therapy and is associated with PD-L1 expression in esophageal cancer.

    PubMed

    Momose, Kota; Yamasaki, Makoto; Tanaka, Koji; Miyazaki, Yasuhiro; Makino, Tomoki; Takahashi, Tsuyoshi; Kurokawa, Yukinori; Nakajima, Kiyokazu; Takiguchi, Shuji; Mori, Masaki; Doki, Yuichiro

    2017-07-01

    Programmed death-ligand 1 (PD-1/PD-L1) inhibition therapy demonstrates potential as a future treatment for esophageal cancer. Mismatch repair status and tumor PD-L1 expression are the candidate predictive biomarkers for response to this therapy. In colorectal cancer, mismatch repair-deficient tumors are associated with improved survival, although they are not sensitive to 5-fluorouracil-based chemotherapy. The purpose of the present study was to investigate the association between MutL homolog 1 (MLH1) expression and prognosis, response to therapy and PD-L1 expression in esophageal cancer. Immunohistochemistry was used to evaluate MLH1 and PD-L1 expression in 251 resected specimens. Of the specimens, 30.3% exhibited low MLH1 expression and 15.5% exhibited high PD-L1 expression. The 5-year overall survival rates for the high MLH1 expression group and the low MLH1 expression group were 51.3 and 55.6%, respectively (P=0.5260). The responder ratio was 45.7% in the high MLH1 expression group and 15.4% in the low MLH1 expression group (P<0.0001). The frequency of high PD-L1 expression was 11.4% in the high MLH1 expression group (P=0.0064) and 25.0% in the low MLH1 expression group. MLH1 expression may be a predictive factor for the response to preoperative therapy in esophageal cancer, and esophageal cancer with low MLH1 expression may have a mechanism that assists in promoting tumor PD-L1 expression.

  15. Global and domestic legal preparedness and response: 2014 Ebola outbreak.

    PubMed

    Hodge, James G

    2015-02-01

    The global rise of Ebola viral diseases in 2014 necessitates legal responses that promote effective public health responses and respect for the health and human rights of populations. Compulsory public health interventions, approval and administration of experimental drugs or vaccines, and allocation of finite resources require difficult choices in law and policy. Crafting legal decisions in real-time emergencies is neither easy nor predictable, but it is essential to controlling epidemics and saving lives.

  16. Global miRNA expression profile reveals novel molecular players in aneurysmal subarachnoid haemorrhage.

    PubMed

    Lopes, Katia de Paiva; Vinasco-Sandoval, Tatiana; Vialle, Ricardo Assunção; Paschoal, Fernando Mendes; Bastos, Vanessa Albuquerque P Aviz; Bor-Seng-Shu, Edson; Teixeira, Manoel Jacobsen; Yamada, Elizabeth Sumi; Pinto, Pablo; Vidal, Amanda Ferreira; Ribeiro-Dos-Santos, Arthur; Moreira, Fabiano; Santos, Sidney; Paschoal, Eric Homero Albuquerque; Ribeiro-Dos-Santos, Ândrea

    2018-06-08

    The molecular mechanisms behind aneurysmal subarachnoid haemorrhage (aSAH) are still poorly understood. Expression patterns of miRNAs may help elucidate the post-transcriptional gene expression in aSAH. Here, we evaluate the global miRNAs expression profile (miRnome) of patients with aSAH to identify potential biomarkers. We collected 33 peripheral blood samples (27 patients with cerebral aneurysm, collected 7 to 10 days after the haemorrhage, when usually is the cerebral vasospasm risk peak, and six controls). Then, were performed small RNA sequencing using an Illumina Next Generation Sequencing (NGS) platform. Differential expression analysis identified eight differentially expressed miRNAs. Among them, three were identified being up-regulated, and five down-regulated. miR-486-5p was the most abundant expressed and is associated with poor neurological admission status. In silico miRNA gene target prediction showed 148 genes associated with at least two differentially expressed miRNAs. Among these, THBS1 and VEGFA, known to be related to thrombospondin and vascular endothelial growth factor. Moreover, MYC gene was found to be regulated by four miRNAs, suggesting an important role in aneurysmal subarachnoid haemorrhage. Additionally, 15 novel miRNAs were predicted being expressed only in aSAH, suggesting possible involvement in aneurysm pathogenesis. These findings may help the identification of novel biomarkers of clinical interest.

  17. PKG in honey bees: spatial expression, Amfor gene expression, sucrose responsiveness, and division of labor.

    PubMed

    Thamm, Markus; Scheiner, Ricarda

    2014-06-01

    Division of labor is a hallmark of social insects. In honey bees, division of labor involves transition of female workers from one task to the next. The most distinct tasks are nursing (providing food for the brood) and foraging (collecting pollen and nectar). The brain mechanisms regulating this form of behavioral plasticity have largely remained elusive. Recently, it was suggested that division of labor is based on nutrition-associated signaling pathways. One highly conserved gene associated with food-related behavior across species is the foraging gene, which encodes a cyclic guanosine monophosphate (cGMP)-dependent protein kinase (PKG). Our analysis of this gene reveals the presence of alternative splicing in the honey bee. One isoform is expressed in the brain. Expression of this isoform is most pronounced in the mushroom bodies, the subesophageal ganglion, and the corpora allata. Division of labor and sucrose responsiveness in honey bees correlate significantly with foraging gene expression in distinct brain regions. Activating PKG selectively increases sucrose responsiveness in nurse bees to the level of foragers, whereas the same treatment does not affect responsiveness to light. These findings demonstrate a direct link between PKG signaling in distinct brain areas and division of labor. Furthermore, they demonstrate that the difference in sensory responsiveness between nurse bees and foragers can be compensated for by activating PKG. Our findings on the function of PKG in regulating specific sensory responsiveness and social organization offer valuable indications for the function of the cGMP/PKG pathway in many other insects and vertebrates. Copyright © 2013 Wiley Periodicals, Inc.

  18. A gene expression profile indicative of early stage HER2 targeted therapy response.

    PubMed

    O'Neill, Fiona; Madden, Stephen F; Clynes, Martin; Crown, John; Doolan, Padraig; Aherne, Sinéad T; O'Connor, Robert

    2013-07-01

    Efficacious application of HER2-targetting agents requires the identification of novel predictive biomarkers. Lapatinib, afatinib and neratinib are tyrosine kinase inhibitors (TKIs) of HER2 and EGFR growth factor receptors. A panel of breast cancer cell lines was treated with these agents, trastuzumab, gefitinib and cytotoxic therapies and the expression pattern of a specific panel of genes using RT-PCR was investigated as a potential marker of early drug response to HER2-targeting therapies. Treatment of HER2 TKI-sensitive SKBR3 and BT474 cell lines with lapatinib, afatinib and neratinib induced an increase in the expression of RB1CC1, ERBB3, FOXO3a and NR3C1. The response directly correlated with the degree of sensitivity. This expression pattern switched from up-regulated to down-regulated in the HER2 expressing, HER2-TKI insensitive cell line MDAMB453. Expression of the CCND1 gene demonstrated an inversely proportional response to drug exposure. A similar expression pattern was observed following the treatment with both neratinib and afatinib. These patterns were retained following exposure to traztuzumab and lapatinib plus capecitabine. In contrast, gefitinib, dasatinib and epirubicin treatment resulted in a completely different expression pattern change. In these HER2-expressing cell line models, lapatinib, neratinib, afatinib and trastuzumab treatment generated a characteristic and specific gene expression response, proportionate to the sensitivity of the cell lines to the HER2 inhibitor.Characterisation of the induced changes in expression levels of these genes may therefore give a valuable, very early predictor of the likely extent and specificity of tumour HER2 inhibitor response in patients, potentially guiding more specific use of these agents.

  19. Circuitry linking the Csr and stringent response global regulatory systems.

    PubMed

    Edwards, Adrianne N; Patterson-Fortin, Laura M; Vakulskas, Christopher A; Mercante, Jeffrey W; Potrykus, Katarzyna; Vinella, Daniel; Camacho, Martha I; Fields, Joshua A; Thompson, Stuart A; Georgellis, Dimitris; Cashel, Michael; Babitzke, Paul; Romeo, Tony

    2011-06-01

    CsrA protein regulates important cellular processes by binding to target mRNAs and altering their translation and/or stability. In Escherichia coli, CsrA binds to sRNAs, CsrB and CsrC, which sequester CsrA and antagonize its activity. Here, mRNAs for relA, spoT and dksA of the stringent response system were found among 721 different transcripts that copurified with CsrA. Many of the transcripts that copurified with CsrA were previously determined to respond to ppGpp and/or DksA. We examined multiple regulatory interactions between the Csr and stringent response systems. Most importantly, DksA and ppGpp robustly activated csrB/C transcription (10-fold), while they modestly activated csrA expression. We propose that CsrA-mediated regulation is relieved during the stringent response. Gel shift assays confirmed high affinity binding of CsrA to relA mRNA leader and weaker interactions with dksA and spoT. Reporter fusions, qRT-PCR and immunoblotting showed that CsrA repressed relA expression, and (p)ppGpp accumulation during stringent response was enhanced in a csrA mutant. CsrA had modest to negligible effects on dksA and spoT expression. Transcription of dksA was negatively autoregulated via a feedback loop that tended to mask CsrA effects. We propose that the Csr system fine-tunes the stringent response and discuss biological implications of the composite circuitry. © Published 2011. This article is a US Government work and is in the public domain in the USA.

  20. Cosmopolitan Species As Models for Ecophysiological Responses to Global Change: The Common Reed Phragmites australis.

    PubMed

    Eller, Franziska; Skálová, Hana; Caplan, Joshua S; Bhattarai, Ganesh P; Burger, Melissa K; Cronin, James T; Guo, Wen-Yong; Guo, Xiao; Hazelton, Eric L G; Kettenring, Karin M; Lambertini, Carla; McCormick, Melissa K; Meyerson, Laura A; Mozdzer, Thomas J; Pyšek, Petr; Sorrell, Brian K; Whigham, Dennis F; Brix, Hans

    2017-01-01

    Phragmites australis is a cosmopolitan grass and often the dominant species in the ecosystems it inhabits. Due to high intraspecific diversity and phenotypic plasticity, P. australis has an extensive ecological amplitude and a great capacity to acclimate to adverse environmental conditions; it can therefore offer valuable insights into plant responses to global change. Here we review the ecology and ecophysiology of prominent P. australis lineages and their responses to multiple forms of global change. Key findings of our review are that: (1) P. australis lineages are well-adapted to regions of their phylogeographic origin and therefore respond differently to changes in climatic conditions such as temperature or atmospheric CO 2 ; (2) each lineage consists of populations that may occur in geographically different habitats and contain multiple genotypes; (3) the phenotypic plasticity of functional and fitness-related traits of a genotype determine the responses to global change factors; (4) genotypes with high plasticity to environmental drivers may acclimate or even vastly expand their ranges, genotypes of medium plasticity must acclimate or experience range-shifts, and those with low plasticity may face local extinction; (5) responses to ancillary types of global change, like shifting levels of soil salinity, flooding, and drought, are not consistent within lineages and depend on adaptation of individual genotypes. These patterns suggest that the diverse lineages of P. australis will undergo intense selective pressure in the face of global change such that the distributions and interactions of co-occurring lineages, as well as those of genotypes within-lineages, are very likely to be altered. We propose that the strong latitudinal clines within and between P. australis lineages can be a useful tool for predicting plant responses to climate change in general and present a conceptual framework for using P. australis lineages to predict plant responses to global

  1. Iron regulates expression of Bacillus cereus hemolysin II via global regulator Fur.

    PubMed

    Sineva, Elena; Shadrin, Andrey; Rodikova, Ekaterina A; Andreeva-Kovalevskaya, Zhanna I; Protsenko, Alexey S; Mayorov, Sergey G; Galaktionova, Darya Yu; Magelky, Erica; Solonin, Alexander S

    2012-07-01

    The capacity of pathogens to respond to environmental signals, such as iron concentration, is key to bacterial survival and establishment of a successful infection. Bacillus cereus is a widely distributed bacterium with distinct pathogenic properties. Hemolysin II (HlyII) is one of its pore-forming cytotoxins and has been shown to be involved in bacterial pathogenicity in a number of cell and animal models. Unlike many other B. cereus pathogenicity factors, HlyII is not regulated by pleiotropic transcriptional regulator PlcR but is controlled by its own regulator, HlyIIR. Using a combination of in vivo and in vitro techniques, we show that hlyII expression is also negatively regulated by iron by the global regulator Fur via direct interaction with the hlyII promoter. DNase I footprinting and in vitro transcription experiments indicate that Fur prevents RNA polymerase binding to the hlyII promoter. HlyII expression profiles demonstrate that both HlyIIR and Fur regulate HlyII expression in a concerted fashion, with the effect of Fur being maximal in the early stages of bacterial growth. In sum, these results show that Fur serves as a transcriptional repressor for hlyII expression.

  2. Using co-expression analysis and stress-based screens to uncover Arabidopsis peroxisomal proteins involved in drought response

    DOE PAGES

    Li, Jiying; Hu, Jianping; Bassham, Diane

    2015-09-14

    Peroxisomes are essential organelles that house a wide array of metabolic reactions important for plant growth and development. However, our knowledge regarding the role of peroxisomal proteins in various biological processes, including plant stress response, is still incomplete. Recent proteomic studies of plant peroxisomes significantly increased the number of known peroxisomal proteins and greatly facilitated the study of peroxisomes at the systems level. The objectives of this study were to determine whether genes that encode peroxisomal proteins with related functions are co-expressed in Arabidopsis and identify peroxisomal proteins involved in stress response using in silico analysis and mutant screens. Usingmore » microarray data from online databases, we performed hierarchical clustering analysis to generate a comprehensive view of transcript level changes for Arabidopsis peroxisomal genes during development and under abiotic and biotic stress conditions. Many genes involved in the same metabolic pathways exhibited co-expression, some genes known to be involved in stress response are regulated by the corresponding stress conditions, and function of some peroxisomal proteins could be predicted based on their coexpression pattern. Since drought caused expression changes to the highest number of genes that encode peroxisomal proteins, we subjected a subset of Arabidopsis peroxisomal mutants to a drought stress assay. Mutants of the LON2 protease and the photorespiratory enzyme hydroxypyruvate reductase 1 (HPR1) showed enhanced susceptibility to drought, suggesting the involvement of peroxisomal quality control and photorespiration in drought resistance. Lastly, our study provided a global view of how genes that encode peroxisomal proteins respond to developmental and environmental cues and began to reveal additional peroxisomal proteins involved in stress response, thus opening up new avenues to investigate the role of peroxisomes in plant adaptation to

  3. Ethical responsibilities of health research funders to advance global health justice.

    PubMed

    Pratt, Bridget; Hyder, Adnan A

    2018-05-04

    Research funders from high-income countries have an ethical obligation to support health research in low and middle-income countries that promotes justice in global health. Conceptual work from bioethics proposes funders should do so through their design of grants programs, investments, and grants management. That work has begun to specify the content of funders' ethical responsibility with regards to health systems research, but it has thus far not been informed by their practice. As a first step to bridge that gap, this paper focuses on health systems research funders' design of grants programs. It aims to test the content of funders' proposed ethical responsibility against recent empirical work describing how they design their health systems research grants programs to help address global health disparities. Based on that analysis, recommendations are made for how to better articulate the content of health systems research funders' obligation. Such recommendations may be pertinent to funders of other types of international research. The paper also provides an initial picture of how well health systems research grants programs' designs may align with the ideals of global health justice.

  4. Characterization of the Humoral Immune Response during Staphylococcus aureus Bacteremia and Global Gene Expression by Staphylococcus aureus in Human Blood

    PubMed Central

    den Reijer, Paul Martijn; Lemmens-den Toom, Nicole; Kant, Samantha; Snijders, Susan V.; Boelens, Hélène; Tavakol, Mehri; Verkaik, Nelianne J.; van Belkum, Alex; Verbrugh, Henri A.; van Wamel, Willem J. B.

    2013-01-01

    Attempts to develop an efficient anti-staphylococcal vaccine in humans have so far been unsuccessful. Therefore, more knowledge of the antigens that are expressed by Staphylococcus aureus in human blood and induce an immune response in patients is required. In this study we further characterize the serial levels of IgG and IgA antibodies against 56 staphylococcal antigens in multiple serum samples of 21 patients with a S. aureus bacteremia, compare peak IgG levels between patients and 30 non-infected controls, and analyze the expression of 3626 genes by two genetically distinct isolates in human blood. The serum antibody levels were measured using a bead-based flow cytometry technique (xMAP®, Luminex corporation). Gene expression levels were analyzed using a microarray (BµG@s microarray). The initial levels and time taken to reach peak IgG and IgA antibody levels were heterogeneous in bacteremia patients. The antigen SA0688 was associated with the highest median initial-to-peak antibody fold-increase for IgG (5.05-fold) and the second highest increase for IgA (2.07-fold). Peak IgG levels against 27 antigens, including the antigen SA0688, were significantly elevated in bacteremia patients versus controls (P≤0.05). Expression of diverse genes, including SA0688, was ubiquitously high in both isolates at all time points during incubation in blood. However, only a limited number of genes were specifically up- or downregulated in both isolates when cultured in blood, compared to the start of incubation in blood or during incubation in BHI broth. In conclusion, most staphylococcal antigens tested in this study, including many known virulence factors, do not induce uniform increases in the antibody levels in bacteremia patients. In addition, the expression of these antigens by S. aureus is not significantly altered by incubation in human blood over time. One immunogenic and ubiquitously expressed antigen is the putative iron-regulated ABC transporter SA0688. PMID

  5. Immune response genes receptors expression and polymorphisms in relation to multiple sclerosis susceptibility and response to INF-β therapy.

    PubMed

    Karam, Rehab A; Rezk, Noha A; Amer, Mona M; Fathy, Hala A

    2016-09-01

    Interferon (IFN)-β is one of the disease modifying drugs used in the treatment of multiple sclerosis. A predictive marker that indicates good or poor response to the treatment is highly desirable. We aimed to investigate the relation between the immune response genes receptors (IFNAR1, IFNAR2, and CCR5) expression and their polymorhic variants and multiple sclerosis (MS) susceptibility as well as the response to IFN-β therapy. The immune response genes receptors expression and genotyping were analyzed in 80 patients with MS, treated with IFN-β and in 110 healthy controls. There was a significant decrease of IFNAR1 and IFNAR2 mRNA expression and a significant increase of CCR5 mRNA expression in MS patients compared with the control group. Also, the level of IFNAR1, IFNAR2, and CCR5 mRNA expression was found to be significantly lower in the responders than nonresponders. Carriers of IFNAR1 18417 C/C genotype and C allele had an increased risk of developing MS. There was a significant relation between CCR5 Δ32 allele and IFN-β treatment response in MS patients. Our results highlighted the significance of IFNAR and CCR5 genes in multiple sclerosis risk and the response to IFN-β therapy. © 2016 IUBMB Life, 68(9):727-734, 2016. © 2016 International Union of Biochemistry and Molecular Biology.

  6. First cellular approach of the effects of global warming on groundwater organisms: a study of the HSP70 gene expression.

    PubMed

    Colson-Proch, Céline; Morales, Anne; Hervant, Frédéric; Konecny, Lara; Moulin, Colette; Douady, Christophe J

    2010-05-01

    Whereas the consequences of global warming at population or community levels are well documented, studies at the cellular level are still scarce. The study of the physiological or metabolic effects of such small increases in temperature (between +2 degrees C and +6 degrees C) is difficult because they are below the amplitude of the daily or seasonal thermal variations occurring in most environments. In contrast, subterranean biotopes are highly thermally buffered (+/-1 degrees C within a year), and underground water organisms could thus be particularly well suited to characterise cellular responses of global warming. To this purpose, we studied genes encoding chaperone proteins of the HSP70 family in amphipod crustaceans belonging to the ubiquitous subterranean genus Niphargus. An HSP70 sequence was identified in eight populations of two complexes of species of the Niphargus genus (Niphargus rhenorhodanensis and Niphargus virei complexes). Expression profiles were determined for one of these by reverse transcription and quantitative polymerase chain reaction, confirming the inducible nature of this gene. An increase in temperature of 2 degrees C seemed to be without effect on N. rhenorhodanensis physiology, whereas a heat shock of +6 degrees C represented an important thermal stress for these individuals. Thus, this study shows that although Niphargus individuals do not undergo any daily or seasonal thermal variations in underground water, they display an inducible HSP70 heat shock response. This controlled laboratory-based physiological experiment constitutes a first step towards field investigations of the cellular consequences of global warming on subterranean organisms.

  7. A wearable device for emotional recognition using facial expression and physiological response.

    PubMed

    Jangho Kwon; Da-Hye Kim; Wanjoo Park; Laehyun Kim

    2016-08-01

    This paper introduces a glasses-typed wearable system to detect user's emotions using facial expression and physiological responses. The system is designed to acquire facial expression through a built-in camera and physiological responses such as photoplethysmogram (PPG) and electrodermal activity (EDA) in unobtrusive way. We used video clips for induced emotions to test the system suitability in the experiment. The results showed a few meaningful properties that associate emotions with facial expressions and physiological responses captured by the developed wearable device. We expect that this wearable system with a built-in camera and physiological sensors may be a good solution to monitor user's emotional state in daily life.

  8. Global Analysis of WRKY Genes and Their Response to Dehydration and Salt Stress in Soybean.

    PubMed

    Song, Hui; Wang, Pengfei; Hou, Lei; Zhao, Shuzhen; Zhao, Chuanzhi; Xia, Han; Li, Pengcheng; Zhang, Ye; Bian, Xiaotong; Wang, Xingjun

    2016-01-01

    WRKY proteins are plant specific transcription factors involved in various developmental and physiological processes, especially in biotic and abiotic stress resistance. Although previous studies suggested that WRKY proteins in soybean (Glycine max var. Williams 82) involved in both abiotic and biotic stress responses, the global information of WRKY proteins in the latest version of soybean genome (Wm82.a2v1) and their response to dehydration and salt stress have not been reported. In this study, we identified 176 GmWRKY proteins from soybean Wm82.a2v1 genome. These proteins could be classified into three groups, namely group I (32 proteins), group II (120 proteins), and group III (24 proteins). Our results showed that most GmWRKY genes were located on Chromosome 6, while chromosome 11, 12, and 20 contained the least number of this gene family. More GmWRKY genes were distributed on the ends of chromosomes to compare with other regions. The cis-acting elements analysis suggested that GmWRKY genes were transcriptionally regulated upon dehydration and salt stress. RNA-seq data analysis indicated that three GmWRKY genes responded negatively to dehydration, and 12 genes positively responded to salt stress at 1, 6, and 12 h, respectively. We confirmed by qRT-PCR that the expression of GmWRKY47 and GmWRKY 58 genes was decreased upon dehydration, and the expression of GmWRKY92, 144 and 165 genes was increased under salt treatment.

  9. Will surface winds weaken in response to global warming?

    NASA Astrophysics Data System (ADS)

    Ma, Jian; Foltz, Gregory R.; Soden, Brian J.; Huang, Gang; He, Jie; Dong, Changming

    2016-12-01

    The surface Walker and tropical tropospheric circulations have been inferred to slow down from historical observations and model projections, yet analysis of large-scale surface wind predictions is lacking. Satellite measurements of surface wind speed indicate strengthening trends averaged over the global and tropical oceans that are supported by precipitation and evaporation changes. Here we use corrected anemometer-based observations to show that the surface wind speed has not decreased in the averaged tropical oceans, despite its reduction in the region of the Walker circulation. Historical simulations and future projections for climate change also suggest a near-zero wind speed trend averaged in space, regardless of the Walker cell change. In the tropics, the sea surface temperature pattern effect acts against the large-scale circulation slow-down. For higher latitudes, the surface winds shift poleward along with the eddy-driven mid-latitude westerlies, resulting in a very small contribution to the global change in surface wind speed. Despite its importance for surface wind speed change, the influence of the SST pattern change on global-mean rainfall is insignificant since it cannot substantially alter the global energy balance. As a result, the precipitation response to global warming remains ‘muted’ relative to atmospheric moisture increase. Our results therefore show consistency between projections and observations of surface winds and precipitation.

  10. A meta-analysis of responses of soil biota to global change.

    PubMed

    Blankinship, Joseph C; Niklaus, Pascal A; Hungate, Bruce A

    2011-03-01

    Global environmental changes are expected to impact the abundance of plants and animals aboveground, but comparably little is known about the responses of belowground organisms. Using meta-analysis, we synthesized results from over 75 manipulative experiments in order to test for patterns in the effects of elevated CO(2), warming, and altered precipitation on the abundance of soil biota related to taxonomy, body size, feeding habits, ecosystem type, local climate, treatment magnitude and duration, and greenhouse CO(2) enrichment. We found that the positive effect size of elevated CO(2) on the abundance of soil biota diminished with time, whereas the negative effect size of warming and positive effect size of precipitation intensified with time. Trophic group, body size, and experimental approaches best explained the responses of soil biota to elevated CO(2), whereas local climate and ecosystem type best explained responses to warming and altered precipitation. The abundance of microflora and microfauna, and particularly detritivores, increased with elevated CO(2), indicative of microbial C limitation under ambient CO(2). However, the effects of CO(2) were smaller in field studies than in greenhouse studies and were not significant for higher trophic levels. Effects of warming did not depend on taxon or body size, but reduced abundances were more likely to occur at the colder and drier sites. Precipitation limited all taxa and trophic groups, particularly in forest ecosystems. Our meta-analysis suggests that the responses of soil biota to global change are predictable and unique for each global change factor.

  11. Canada's international response to HIV during times of global transition: a qualitative inquiry.

    PubMed

    Nixon, Stephanie

    2011-04-01

    Canada's international response to HIV may be under threat given CIDA's new aid priorities that appear to exclude health. Drivers of this recent priority shift have been the influence of global aid trends among public sector donors and changes within the global HIV milieu itself. However, this is not the first time Canada has shifted in response to these two global trends. The era from 2000-2004 also witnessed dramatic changes in both the HIV field and in global thinking around international aid. As such, this article presents an evaluation of the Government of Canada's international response to HIV during the first era of transition (2000-2004) in order to derive lessons for decision-making around HIV in the current climate of change. In-depth, semi-structured interviews were conducted with 23 key informants with expertise regarding Canada's international response to HIV over time. Analysis involved multiple readings of transcripts to identify descriptive codes and establish intimacy with the data. Descriptive codes were then collapsed into thematic categories using a process of inductive reasoning. Canada's international response to HIV was perceived to be exemplary at times (e.g. seminal funding to WHO's "3-by-5" strategy), but also inconsistent (e.g., underutilized technical assistance capacity) and non-strategic (e.g., contradiction between investing in training health providers while poaching professionals to bolster Canada's workforce). Lessons from the 2000-2004 era of transition focus on strategic investments, the inextricable connection between HIV and development and strategy coherence. These results highlight that it is more constructive to ensure that Canadian development responses in all areas engage with both the upstream drivers of HIV as well as the impacts of the epidemic itself in order to achieve the greatest results from international investment and the most effective contributions to the lives of the people that these endeavours seek to

  12. Global temperature responses to current emissions from the transport sectors

    PubMed Central

    Berntsen, Terje; Fuglestvedt, Jan

    2008-01-01

    Transport affects climate directly and indirectly through mechanisms that cause both warming and cooling of climate, and the effects operate on very different timescales. We calculate climate responses in terms of global mean temperature and find large differences between the transport sectors with respect to the size and mix of short- and long-lived effects, and even the sign of the temperature response. For year 2000 emissions, road transport has the largest effect on global mean temperature. After 20 and 100 years the response in net temperature is 7 and 6 times higher, respectively, than for aviation. Aviation and shipping have strong but quite uncertain short-lived warming and cooling effects, respectively, that dominate during the first decades after the emissions. For shipping the net cooling during the first 4 decades is due to emissions of SO2 and NOx. On a longer timescale, the current emissions from shipping cause net warming due to the persistence of the CO2 perturbation. If emissions stay constant at 2000 levels, the warming effect from road transport will continue to increase and will be almost 4 times larger than that of aviation by the end of the century. PMID:19047640

  13. A gene expression profile indicative of early stage HER2 targeted therapy response

    PubMed Central

    2013-01-01

    Background Efficacious application of HER2-targetting agents requires the identification of novel predictive biomarkers. Lapatinib, afatinib and neratinib are tyrosine kinase inhibitors (TKIs) of HER2 and EGFR growth factor receptors. A panel of breast cancer cell lines was treated with these agents, trastuzumab, gefitinib and cytotoxic therapies and the expression pattern of a specific panel of genes using RT-PCR was investigated as a potential marker of early drug response to HER2-targeting therapies. Results Treatment of HER2 TKI-sensitive SKBR3 and BT474 cell lines with lapatinib, afatinib and neratinib induced an increase in the expression of RB1CC1, ERBB3, FOXO3a and NR3C1. The response directly correlated with the degree of sensitivity. This expression pattern switched from up-regulated to down-regulated in the HER2 expressing, HER2-TKI insensitive cell line MDAMB453. Expression of the CCND1 gene demonstrated an inversely proportional response to drug exposure. A similar expression pattern was observed following the treatment with both neratinib and afatinib. These patterns were retained following exposure to traztuzumab and lapatinib plus capecitabine. In contrast, gefitinib, dasatinib and epirubicin treatment resulted in a completely different expression pattern change. Conclusions In these HER2-expressing cell line models, lapatinib, neratinib, afatinib and trastuzumab treatment generated a characteristic and specific gene expression response, proportionate to the sensitivity of the cell lines to the HER2 inhibitor. Characterisation of the induced changes in expression levels of these genes may therefore give a valuable, very early predictor of the likely extent and specificity of tumour HER2 inhibitor response in patients, potentially guiding more specific use of these agents. PMID:23816254

  14. Global Landscape of a Co-Expressed Gene Network in Barley and its Application to Gene Discovery in Triticeae Crops

    PubMed Central

    Mochida, Keiichi; Uehara-Yamaguchi, Yukiko; Yoshida, Takuhiro; Sakurai, Tetsuya; Shinozaki, Kazuo

    2011-01-01

    Accumulated transcriptome data can be used to investigate regulatory networks of genes involved in various biological systems. Co-expression analysis data sets generated from comprehensively collected transcriptome data sets now represent efficient resources that are capable of facilitating the discovery of genes with closely correlated expression patterns. In order to construct a co-expression network for barley, we analyzed 45 publicly available experimental series, which are composed of 1,347 sets of GeneChip data for barley. On the basis of a gene-to-gene weighted correlation coefficient, we constructed a global barley co-expression network and classified it into clusters of subnetwork modules. The resulting clusters are candidates for functional regulatory modules in the barley transcriptome. To annotate each of the modules, we performed comparative annotation using genes in Arabidopsis and Brachypodium distachyon. On the basis of a comparative analysis between barley and two model species, we investigated functional properties from the representative distributions of the gene ontology (GO) terms. Modules putatively involved in drought stress response and cellulose biogenesis have been identified. These modules are discussed to demonstrate the effectiveness of the co-expression analysis. Furthermore, we applied the data set of co-expressed genes coupled with comparative analysis in attempts to discover potentially Triticeae-specific network modules. These results demonstrate that analysis of the co-expression network of the barley transcriptome together with comparative analysis should promote the process of gene discovery in barley. Furthermore, the insights obtained should be transferable to investigations of Triticeae plants. The associated data set generated in this analysis is publicly accessible at http://coexpression.psc.riken.jp/barley/. PMID:21441235

  15. Blood gene expression profiling of an early acetaminophen response.

    PubMed

    Bushel, P R; Fannin, R D; Gerrish, K; Watkins, P B; Paules, R S

    2017-06-01

    Acetaminophen can adversely affect the liver especially when overdosed. We used whole blood as a surrogate to identify genes as potential early indicators of an acetaminophen-induced response. In a clinical study, healthy human subjects were dosed daily with 4 g of either acetaminophen or placebo pills for 7 days and evaluated over the course of 14 days. Alanine aminotransferase (ALT) levels for responders to acetaminophen increased between days 4 and 9 after dosing, and 12 genes were detected with expression profiles significantly altered within 24 h. The early responsive genes separated the subjects by class and dose period. In addition, the genes clustered patients who overdosed on acetaminophen apart from controls and also predicted the exposure classifications with 100% accuracy. The responsive genes serve as early indicators of an acetaminophen exposure, and their gene expression profiles can potentially be evaluated as molecular indicators for further consideration.

  16. Blood Gene Expression Profiling of an Early Acetaminophen Response

    PubMed Central

    Bushel, Pierre R.; Fannin, Rick D.; Gerrish, Kevin; Watkins, Paul B.; Paules, Richard S.

    2018-01-01

    Acetaminophen can adversely affect the liver especially when overdosed. We used whole blood as a surrogate to identify genes as potential early indicators of an acetaminophen-induced response. In a clinical study, healthy human subjects were dosed daily with 4g of either acetaminophen or placebo pills for 7 days and evaluated over the course of 14 days. Alanine aminotransferase (ALT) levels for responders to acetaminophen increased between days 4 and 9 after dosing and 12 genes were detected with expression profiles significantly altered within 24 hrs. The early responsive genes separated the subjects by class and dose period. In addition, the genes clustered patients who overdosed on acetaminophen apart from controls and also predicted the exposure classifications with 100% accuracy. The responsive genes serve as early indicators of an acetaminophen exposure and their gene expression profiles can potentially be evaluated as molecular indicators for further consideration. PMID:26927286

  17. Divergent Gene Expression Responses to Complicated Grief and Non-complicated Grief

    PubMed Central

    Irwin, Michael R.; Arevalo, Jesusa M. G.; Cole, Steven W.

    2014-01-01

    The “widowhood effect” (i.e., morbidity/mortality in recently bereaved spouses) may be related to changes in immune function, but little is known about the impact of bereavement on gene transcription in immune cells. This study examined how Complicated Grief and Non-complicated Grief responses to bereavement differentially affect leukocyte gene expression. Genome-wide transcriptional profiling and bioinformatic analyses were completed on 63 older adults. Thirty-six of them had lost their spouse/partner on average 2 years ago, and 27 were nonbereaved, married controls. Twelve of the bereaved participants met criteria for Complicated Grief. Compared to nonbereaved controls, bereavement (both Complicated Grief and Non-complicated Grief) was associated with upregulated expression of genes involved in general immunologic activation and a selective downregulation of genes involved in B lymphocyte responses. However, Complicated Grief and Non-complicated Grief differed markedly in their expression of Type I interferon-related transcripts, with Non-complicated Grief subjects showing substantial upregulation relative to nonbereaved controls and Complicated Grief subjects showing substantial downregulation. Bereavement significantly modulates immune function gene expression. The magnitude of bereavement-related distress (i.e., Complicated Grief vs. Non-complicated Grief) is linked to differential patterns of transcription factor activation and gene expression involved in innate antiviral responses. These findings provide a molecular framework for understanding the health effects of bereavement, as well as new insights into the particular gene modules that are most sensitive to the individual's psychological response to loss. PMID:24380850

  18. Ocean salinities reveal strong global water cycle intensification during 1950 to 2000.

    PubMed

    Durack, Paul J; Wijffels, Susan E; Matear, Richard J

    2012-04-27

    Fundamental thermodynamics and climate models suggest that dry regions will become drier and wet regions will become wetter in response to warming. Efforts to detect this long-term response in sparse surface observations of rainfall and evaporation remain ambiguous. We show that ocean salinity patterns express an identifiable fingerprint of an intensifying water cycle. Our 50-year observed global surface salinity changes, combined with changes from global climate models, present robust evidence of an intensified global water cycle at a rate of 8 ± 5% per degree of surface warming. This rate is double the response projected by current-generation climate models and suggests that a substantial (16 to 24%) intensification of the global water cycle will occur in a future 2° to 3° warmer world.

  19. Mean-state SST Response to global warming caused by the ENSO Nonlinearity

    NASA Astrophysics Data System (ADS)

    Kohyama, T.; Hartmann, D. L.

    2017-12-01

    The majority of the models that participated in the Coupled Model Intercomparison Project phase 5 (CMIP5) exhibit El Niño-like trends under global warming. GFDL-ESM2M, however, is an exception that exhibits a La Niña-like response with strengthened trade winds. Our previous studies have shown that this La Niña-like trend could be a physically consistent warming response, and we proposed the Nonlinear ENSO Warming Suppression (NEWS) mechanism to explain this La Niña-like response to global warming. The most important necessary condition of NEWS is the ENSO skewness (El Niños are stronger than La Niñas). Most CMIP5 models do not reproduce the observed ENSO skewness, while GFDL-ESM2M exhibits the realistic ENSO skewness, which suggests that, despite being in the minority, the La Niña-like trend of GFDL-ESM2M could be a plausible equatorial Pacific response to warming. In this study, we introduce another interesting outlier, MIROC5, which reproduces the observed skewness, yet exhibits an El Niño-like response. By decomposing the source of the ENSO nonlinearity into the following three components: "SST anomalies modulate winds", "winds excite oceanic waves", and "oceanic waves modulate the subsurface temperature", we show that the large inter-model spread of the third component appears to explain the most important cause of the poor reproducibility of the ENSO nonlinearity in CMIP5 models. It is concluded that the change in the response of subsurface temperature to oceanic waves is the primary explanation for the different warming response of GFDL-ESM2M and MIROC5. Our analyses suggest that the difference of the warming response are caused by difference in the climatological thermal stratification. This study may shed new light on the fundamental question of why observed ENSO has a strong skewness and on the implications of this skewed ENSO for the mean-state sea surface temperature response to global warming.

  20. Cytokine expression in response to root canal infection in gnotobiotic mice.

    PubMed

    Maciel, K F; Neves de Brito, L C; Tavares, W L F; Moreira, G; Nicoli, J R; Vieira, L Q; Ribeiro Sobrinho, A P

    2012-04-01

    To examine cytokine expression profiles during periapical lesion development in response to synergetic human pathogens in a gnotobiotic mouse model. Human strains of Fusobacterium nucleatum and Peptostreptococcus prevotii were inoculated into the root canals of germ-free mice in either mono- or bi-association. Animals were killed 7 and 14 days after infection, and periapical tissues were collected. mRNA expression of the cytokines IFN-γ, TNF-α, Receptor activator of nuclear factor kappa-B ligand (RANKL), IL-10, IL-4 and transforming growth factor β (TGF-β) was assessed using real-time PCR. Levene's test was used to assess the equality of variance of the data, whereas a t-test for independent samples was used to evaluate the significance of the differences between groups (P < 0.05). The mRNA expression of IFN-γ and TNF-α was up-regulated by F. nucleatum during the acute (day 7) and chronic phase (day 14) of periapical lesion development. However, in bi-infection the expression of IFN-γ and TNF-α were effectively absent at both time-points. RANKL mRNA expression was down-regulated during dual infection at the chronic phase. As IL-4 expression was similar at both time-points, IL-4 does not appear to be involved in the periapical response to these bacterial strains. IL-10 was up-regulated during the chronic phase by mono-infection with either F. nucleatum or P. prevotii. Dual infection increased TGF-β mRNA expression on day 7, which paralleled the decrease in IFN-γ and TNF-α mRNA levels at the same time-point. F. nucleatum increased TGF-β mRNA expression during the chronic phase. Cytokine profiles depend on the nature of the bacterial challenge. Both TGF-β and IL-10 appeared to be regulating the proinflammatory cytokine responses at both time-points of the periapical immune response. © 2012 International Endodontic Journal.

  1. Global response of the growing season to soil moisture and topography

    NASA Astrophysics Data System (ADS)

    Guevara, M.; Arroyo, C.; Warner, D. L.; Equihua, J.; Lule, A. V.; Schwartz, A.; Taufer, M.; Vargas, R.

    2017-12-01

    Soil moisture has a direct influence in plant productivity. Plant productivity and its greenness can be inferred by remote sensing with higher spatial detail than soil moisture. The objective was to improve the coarse scale of currently available satellite soil moisture estimates and identify areas of strong coupling between the interannual variability soil moisture and the maximum greenness vegetation fraction (MGVF) at the global scale. We modeled, cross-validated and downscaled remotely sensed soil moisture using machine learning and digital terrain analysis across 23 years (1991-2013) of available data. Improving the accuracy (0.69-0.87 % of cross-validated explained variance) and the spatial detail (from 27 to 15km) of satellite soil moisture, we filled temporal gaps of information across vegetated areas where satellite soil moisture does not work properly. We found that 7.57% of global vegetated area shows strong correlation with our downscaled product (R2>0.5, Fig. 1). We found a dominant positive response of vegetation greenness to topography-based soil moisture across water limited environments, however, the tropics and temperate environments of higher latitudes showed a sparse negative response. We conclude that topography can be used to effectively improve the spatial detail of globally available remotely sensed soil moisture, which is convenient to generate unbiased comparisons with global vegetation dynamics, and better inform land and crop modeling efforts.

  2. Diversity in Expression of Phosphorus (P) Responsive Genes in Cucumis melo L

    PubMed Central

    Fita, Ana; Bowen, Helen C.; Hayden, Rory M.; Nuez, Fernando; Picó, Belén; Hammond, John P.

    2012-01-01

    Background Phosphorus (P) is a major limiting nutrient for plant growth in many soils. Studies in model species have identified genes involved in plant adaptations to low soil P availability. However, little information is available on the genetic bases of these adaptations in vegetable crops. In this respect, sequence data for melon now makes it possible to identify melon orthologues of candidate P responsive genes, and the expression of these genes can be used to explain the diversity in the root system adaptation to low P availability, recently observed in this species. Methodology and Findings Transcriptional responses to P starvation were studied in nine diverse melon accessions by comparing the expression of eight candidate genes (Cm-PAP10.1, Cm-PAP10.2, Cm-RNS1, Cm-PPCK1, Cm-transferase, Cm-SQD1, Cm-DGD1 and Cm-SPX2) under P replete and P starved conditions. Differences among melon accessions were observed in response to P starvation, including differences in plant morphology, P uptake, P use efficiency (PUE) and gene expression. All studied genes were up regulated under P starvation conditions. Differences in the expression of genes involved in P mobilization and remobilization (Cm-PAP10.1, Cm-PAP10.2 and Cm-RNS1) under P starvation conditions explained part of the differences in P uptake and PUE among melon accessions. The levels of expression of the other studied genes were diverse among melon accessions, but contributed less to the phenotypical response of the accessions. Conclusions This is the first time that these genes have been described in the context of P starvation responses in melon. There exists significant diversity in gene expression levels and P use efficiency among melon accessions as well as significant correlations between gene expression levels and phenotypical measurements. PMID:22536378

  3. The Global Outbreak Alert and Response Network

    PubMed Central

    Mackenzie, John S.; Drury, Patrick; Arthur, Ray R.; Ryan, Michael J.; Grein, Thomas; Slattery, Raphael; Suri, Sameera; Domingo, Christine Tiffany; Bejtullahu, Armand

    2014-01-01

    The Global Outbreak Alert and Response Network (GOARN) was established in 2000 as a network of technical institutions, research institutes, universities, international health organisations and technical networks willing to contribute and participate in internationally coordinated responses to infectious disease outbreaks. It reflected a recognition of the need to strengthen and coordinate rapid mobilisation of experts in responding to international outbreaks and to overcome the sometimes chaotic and fragmented operations characterising previous responses. The network partners agreed that the World Health Organization would coordinate the network and provide a secretariat, which would also function as the operational support team. The network has evolved to comprise 153 institutions/technical partners and 37 additional networks, the latter encompassing a further 355 members and has been directly involved in 137 missions to 79 countries, territories or areas. Future challenges will include supporting countries to achieve the capacity to detect and respond to outbreaks of international concern, as required by the International Health Regulations (2005). GOARN's increasing regional focus and expanding geographic composition will be central to meeting these challenges. The paper summarises some of network's achievements over the past 13 years and presents some of the future challenges. PMID:25186571

  4. The global outbreak alert and response network.

    PubMed

    Mackenzie, John S; Drury, Patrick; Arthur, Ray R; Ryan, Michael J; Grein, Thomas; Slattery, Raphael; Suri, Sameera; Domingo, Christine Tiffany; Bejtullahu, Armand

    2014-01-01

    The Global Outbreak Alert and Response Network (GOARN) was established in 2000 as a network of technical institutions, research institutes, universities, international health organisations and technical networks willing to contribute and participate in internationally coordinated responses to infectious disease outbreaks. It reflected a recognition of the need to strengthen and coordinate rapid mobilisation of experts in responding to international outbreaks and to overcome the sometimes chaotic and fragmented operations characterising previous responses. The network partners agreed that the World Health Organization would coordinate the network and provide a secretariat, which would also function as the operational support team. The network has evolved to comprise 153 institutions/technical partners and 37 additional networks, the latter encompassing a further 355 members and has been directly involved in 137 missions to 79 countries, territories or areas. Future challenges will include supporting countries to achieve the capacity to detect and respond to outbreaks of international concern, as required by the International Health Regulations (2005). GOARN's increasing regional focus and expanding geographic composition will be central to meeting these challenges. The paper summarises some of network's achievements over the past 13 years and presents some of the future challenges.

  5. 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

  6. Escherichia coli global gene expression in urine from women with urinary tract infection.

    PubMed

    Hagan, Erin C; Lloyd, Amanda L; Rasko, David A; Faerber, Gary J; Mobley, Harry L T

    2010-11-11

    Murine models of urinary tract infection (UTI) have provided substantial data identifying uropathogenic E. coli (UPEC) virulence factors and assessing their expression in vivo. However, it is unclear how gene expression in these animal models compares to UPEC gene expression during UTI in humans. To address this, we used a UPEC strain CFT073-specific microarray to measure global gene expression in eight E. coli isolates monitored directly from the urine of eight women presenting at a clinic with bacteriuria. The resulting gene expression profiles were compared to those of the same E. coli isolates cultured statically to exponential phase in pooled, sterilized human urine ex vivo. Known fitness factors, including iron acquisition and peptide transport systems, were highly expressed during human UTI and support a model in which UPEC replicates rapidly in vivo. While these findings were often consistent with previous data obtained from the murine UTI model, host-specific differences were observed. Most strikingly, expression of type 1 fimbrial genes, which are among the most highly expressed genes during murine experimental UTI and encode an essential virulence factor for this experimental model, was undetectable in six of the eight E. coli strains from women with UTI. Despite the lack of type 1 fimbrial expression in the urine samples, these E. coli isolates were generally capable of expressing type 1 fimbriae in vitro and highly upregulated fimA upon experimental murine infection. The findings presented here provide insight into the metabolic and pathogenic profile of UPEC in urine from women with UTI and represent the first transcriptome analysis for any pathogenic E. coli during a naturally occurring infection in humans.

  7. Global change and biodiversity loss: Some impediments to response

    NASA Technical Reports Server (NTRS)

    Borza, Karen; Jamieson, Dale

    1991-01-01

    Discussed here are the effects of anthropogenic global climate change on biodiversity. The focus is on human responses to the problem. Greenhouse warming-induced climate change may shift agricultural growing belts, reduce forests of the Northern Hemisphere and drive many species to extinction, among other effects. If these changes occur together with the mass extinctions already occurring, we may suffer a profound loss of biological diversity.

  8. Superoxide-responsive gene expression in Arabidopsis thaliana and Zea mays.

    PubMed

    Xu, Junhuan; Tran, Thu; Padilla Marcia, Carmen S; Braun, David M; Goggin, Fiona L

    2017-08-01

    Superoxide (O 2 - ) and other reactive oxygen species (ROS) are generated in response to numerous biotic and abiotic stresses. Different ROS have been reported to elicit different transcriptional responses in plants, and so ROS-responsive marker genes and promoter::reporter gene fusions have been proposed as indirect means of detecting ROS and discriminating among different species. However, further information about the specificity of transcriptional responses to O 2 - is needed in order to assess potential markers for this critical stress-responsive signaling molecule. Using qRT-PCR, the expression of 12 genes previously reported to be upregulated by O 2 - was measured in Arabidopsis thaliana plants exposed to elicitors of common stress-responsive ROS: methyl viologen (an inducer of O 2 - ), rose bengal (an inducer of singlet oxygen, 1 ΔO 2 ), and exogenous hydrogen peroxide (H 2 O 2 ). Surprisingly, Zinc-Finger Protein 12 (AtZAT12), which had previously been used as a reporter for H 2 O 2 , responded more strongly to O 2 - than to H 2 O 2 ; moreover, the expression of an AtZAT12 promoter-reporter fusion (AtZAT12::Luc) was enhanced by diethyldithiocarbamate, which inhibits dismutation of O 2 - to H 2 O 2 . These results suggest that AtZAT12 is transcriptionally upregulated in response to O 2 - , and that AtZAT12::Luc may be a useful biosensor for detecting O 2 - generation in vivo. In addition, transcripts encoding uncoupling proteins (AtUCPs) showed selectivity for O 2 - in Arabidopsis, and an AtUCP homolog upregulated by methyl viologen was also identified in maize (Zea mays L.), indicating that there are O 2 - -responsive members of this family in monocots. These results expand our limited knowledge of ROS-responsive gene expression in monocots, as well as O 2 - -selective responses in dicots. Copyright © 2017 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

  9. Global gene expression profile of peripheral blood mononuclear cells challenged with Theileria annulata in crossbred and indigenous cattle.

    PubMed

    Kumar, Amod; Gaur, Gyanendra Kumar; Gandham, Ravi Kumar; Panigrahi, Manjit; Ghosh, Shrikant; Saravanan, B C; Bhushan, Bharat; Tiwari, Ashok Kumar; Sulabh, Sourabh; Priya, Bhuvana; V N, Muhasin Asaf; Gupta, Jay Prakash; Wani, Sajad Ahmad; Sahu, Amit Ranjan; Sahoo, Aditya Prasad

    2017-01-01

    Bovine tropical theileriosis is an important haemoprotozoan disease associated with high rates of morbidity and mortality particularly in exotic and crossbred cattle. It is one of the major constraints of the livestock development programmes in India and Southeast Asia. Indigenous cattle (Bos indicus) are reported to be comparatively less affected than exotic and crossbred cattle. However, genetic basis of resistance to tropical theileriosis in indigenous cattle is not well documented. Recent studies incited an idea that differentially expressed genes in exotic and indigenous cattle play significant role in breed specific resistance to tropical theileriosis. The present study was designed to determine the global gene expression profile in peripheral blood mononuclear cells derived from indigenous (Tharparkar) and cross-bred cattle following in vitro infection of T. annulata (Parbhani strain). Two separate microarray experiments were carried out each for cross-bred and Tharparkar cattle. The cross-bred cattle showed 1082 differentially expressed genes (DEGs). Out of total DEGs, 597 genes were down-regulated and 485 were up-regulated. Their fold change varied from 2283.93 to -4816.02. Tharparkar cattle showed 875 differentially expressed genes including 451 down-regulated and 424 up-regulated. The fold change varied from 94.93 to -19.20. A subset of genes was validated by qRT-PCR and results were correlated well with microarray data indicating that microarray results provided an accurate report of transcript level. Functional annotation study of DEGs confirmed their involvement in various pathways including response to oxidative stress, immune system regulation, cell proliferation, cytoskeletal changes, kinases activity and apoptosis. Gene network analysis of these DEGs plays an important role to understand the interaction among genes. It is therefore, hypothesized that the different susceptibility to tropical theileriosis exhibited by indigenous and crossbred cattle

  10. Earth's changing global atmospheric energy cycle in response to climate change

    PubMed Central

    Pan, Yefeng; Li, Liming; Jiang, Xun; Li, Gan; Zhang, Wentao; Wang, Xinyue; Ingersoll, Andrew P.

    2017-01-01

    The Lorenz energy cycle is widely used to investigate atmospheres and climates on planets. However, the long-term temporal variations of such an energy cycle have not yet been explored. Here we use three independent meteorological data sets from the modern satellite era, to examine the temporal characteristics of the Lorenz energy cycle of Earth's global atmosphere in response to climate change. The total mechanical energy of the global atmosphere basically remains constant with time, but the global-average eddy energies show significant positive trends. The spatial investigations suggest that these positive trends are concentrated in the Southern Hemisphere. Significant positive trends are also found in the conversion, generation and dissipation rates of energies. The positive trends in the dissipation rates of kinetic energies suggest that the efficiency of the global atmosphere as a heat engine increased during the modern satellite era. PMID:28117324

  11. The differential expression of alternatively polyadenylated transcripts is a common stress-induced response mechanism that modulates mammalian mRNA expression in a quantitative and qualitative fashion.

    PubMed

    Hollerer, Ina; Curk, Tomaz; Haase, Bettina; Benes, Vladimir; Hauer, Christian; Neu-Yilik, Gabriele; Bhuvanagiri, Madhuri; Hentze, Matthias W; Kulozik, Andreas E

    2016-09-01

    Stress adaptation plays a pivotal role in biological processes and requires tight regulation of gene expression. In this study, we explored the effect of cellular stress on mRNA polyadenylation and investigated the implications of regulated polyadenylation site usage on mammalian gene expression. High-confidence polyadenylation site mapping combined with global pre-mRNA and mRNA expression profiling revealed that stress induces an accumulation of genes with differentially expressed polyadenylated mRNA isoforms in human cells. Specifically, stress provokes a global trend in polyadenylation site usage toward decreased utilization of promoter-proximal poly(A) sites in introns or ORFs and increased utilization of promoter-distal polyadenylation sites in intergenic regions. This extensively affects gene expression beyond regulating mRNA abundance by changing mRNA length and by altering the configuration of open reading frames. Our study highlights the impact of post-transcriptional mechanisms on stress-dependent gene regulation and reveals the differential expression of alternatively polyadenylated transcripts as a common stress-induced mechanism in mammalian cells. © 2016 Hollerer et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

  12. Global Deletion of TSPO Does Not Affect the Viability and Gene Expression Profile

    PubMed Central

    Wang, Huaishan; Yang, Jia; Yang, Qi; Fu, Yi; Hu, Yu; Liu, Fang; Wang, Weiqing; Cui, Lianxian; Chen, Hui; Zhang, Jianmin; He, Wei

    2016-01-01

    Translocator Protein (18kDa, TSPO) is a mitochondrial outer membrane transmembrane protein. Its expression is elevated during inflammation and injury. However, the function of TSPO in vivo is still controversial. Here, we constructed a TSPO global knockout (KO) mouse with a Cre-LoxP system that abolished TSPO protein expression in all tissues and showed normal phenotypes in the physiological condition. The birth rates of TSPO heterozygote (Het) x Het or KO x KO breeding were consistent with Mendel’s Law, suggesting a normal viability of TSPO KO mice at birth. RNA-seq analysis showed no significant difference in the gene expression profile of lung tissues from TSPO KO mice compared with wild type mice, including the genes associated with bronchial alveoli immune homeostasis. The alveolar macrophage population was not affected by TSPO deletion in the physiological condition. Our findings contradict the results of Papadopoulos, but confirmed Selvaraj’s findings. This study confirms TSPO deficiency does not affect viability and bronchial alveolar immune homeostasis. PMID:27907096

  13. Gene expression of corals in response to macroalgal competitors.

    PubMed

    Shearer, Tonya L; Snell, Terry W; Hay, Mark E

    2014-01-01

    As corals decline and macroalgae proliferate on coral reefs, coral-macroalgal competition becomes more frequent and ecologically important. Whether corals are damaged by these interactions depends on susceptibility of the coral and traits of macroalgal competitors. Investigating changes in gene expression of corals and their intracellular symbiotic algae, Symbiodinium, in response to contact with different macroalgae provides insight into the biological processes and cellular pathways affected by competition with macroalgae. We evaluated the gene expression profiles of coral and Symbiodinium genes from two confamilial corals, Acropora millepora and Montipora digitata, after 6 h and 48 h of contact with four common macroalgae that differ in their allelopathic potency to corals. Contacts with macroalgae affected different biological pathways in the more susceptible (A. millepora) versus the more resistant (M. digitata) coral. Genes of coral hosts and of their associated Symbiodinium also responded in species-specific and time-specific ways to each macroalga. Changes in number and expression intensity of affected genes were greater after 6 h compared to 48 h of contact and were greater following contact with Chlorodesmis fastigiata and Amphiroa crassa than following contact with Galaxaura filamentosa or Turbinaria conoides. We documented a divergence in transcriptional responses between two confamilial corals and their associated Symbiodinium, as well as a diversity of dynamic responses within each coral species with respect to the species of macroalgal competitor and the duration of exposure to that competitor. These responses included early initiation of immune processes by Montipora, which is more resistant to damage after long-term macroalgal contact. Activation of the immune response by corals that better resist algal competition is consistent with the hypothesis that some macroalgal effects on corals may be mediated by microbial pathogens.

  14. Global 2000: The Presidential Task Force on Resources and the Environment--A Series of Responses.

    ERIC Educational Resources Information Center

    Scrofani, E. Robert; And Others

    A series of responses to "The Global 2000 Report to the President" is presented. The Global 2000 Report examines the issues and interdependencies of population, resources, and environment in the long term global perspective (ED 188 935). According to the above report, if present trends continue, serious stresses of overcrowding, pollution,…

  15. The responsible subject in the global age.

    PubMed

    Pulcini, Elena

    2010-09-01

    The first thesis of this article is that the concept of responsibility takes on an unprecedented meaning in the twentieth century resulting from the emergence of a new dimension of the other: to be responsible comes to mean not just to account for oneself in relation to the other, but also to take the other into account, to take care of the other-what I call responsibility towards (the other). The main reason for this change consists in the emergence of global risks and the necessity, as underlined by Hans Jonas, to be responsible for the destiny of the world and future generations. The problem, as explored in the article's second thesis, is that this implies the existence of a subject who is capable of responsibility. Jonas's insights on this point are insufficient, since he only recognizes duty as the fundament for his ethics of responsibility and thus neglects the problem of motivation. This is a particularly crucial problem today as we are witnessing the presence of a pathological subject, characterized by a split in his faculties (between doing and imagining, knowing and feeling). To underline this fact, this article makes use of Günther Anders's reflections, which provide a psycho-anthropological analysis of the subject, showing his pathologies and the necessity, from a moral perspective, to overcome his scission. Finally, this author suggests, as the article's third thesis, that this overcoming is the necessary fundament for the perception of risk, which in turn reinstates the subject's perception of his own vulnerability. Responsibility thus finds a motivation, which is neither altruistic nor duty-centred, in the awareness of our own vulnerability and the bond with the destiny of humankind as a whole.

  16. Modelling the perceptual similarity of facial expressions from image statistics and neural responses.

    PubMed

    Sormaz, Mladen; Watson, David M; Smith, William A P; Young, Andrew W; Andrews, Timothy J

    2016-04-01

    The ability to perceive facial expressions of emotion is essential for effective social communication. We investigated how the perception of facial expression emerges from the image properties that convey this important social signal, and how neural responses in face-selective brain regions might track these properties. To do this, we measured the perceptual similarity between expressions of basic emotions, and investigated how this is reflected in image measures and in the neural response of different face-selective regions. We show that the perceptual similarity of different facial expressions (fear, anger, disgust, sadness, happiness) can be predicted by both surface and feature shape information in the image. Using block design fMRI, we found that the perceptual similarity of expressions could also be predicted from the patterns of neural response in the face-selective posterior superior temporal sulcus (STS), but not in the fusiform face area (FFA). These results show that the perception of facial expression is dependent on the shape and surface properties of the image and on the activity of specific face-selective regions. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. The return of epidemics and the politics of global-local health.

    PubMed

    Sivaramakrishnan, Kavita

    2011-06-01

    With fears of global health epidemics (of reemerging infectious diseases) having escalated over the past few decades, we must ask how we understand the diverse responses to such outbreaks. I explore a single event that merits revisiting--the 1994 outbreak of plague in Surat, the commercial capital of the Indian state of Gujarat--in an attempt to answer this question. I trace responses at various intersecting levels of public health and political authority-global, national, and local-as they interacted with each other and expressed specific political concerns and social anxieties during this outbreak.

  18. A modified impulse-response representation of the global near-surface air temperature and atmospheric concentration response to carbon dioxide emissions

    NASA Astrophysics Data System (ADS)

    Millar, Richard J.; Nicholls, Zebedee R.; Friedlingstein, Pierre; Allen, Myles R.

    2017-06-01

    Projections of the response to anthropogenic emission scenarios, evaluation of some greenhouse gas metrics, and estimates of the social cost of carbon often require a simple model that links emissions of carbon dioxide (CO2) to atmospheric concentrations and global temperature changes. An essential requirement of such a model is to reproduce typical global surface temperature and atmospheric CO2 responses displayed by more complex Earth system models (ESMs) under a range of emission scenarios, as well as an ability to sample the range of ESM response in a transparent, accessible and reproducible form. Here we adapt the simple model of the Intergovernmental Panel on Climate Change 5th Assessment Report (IPCC AR5) to explicitly represent the state dependence of the CO2 airborne fraction. Our adapted model (FAIR) reproduces the range of behaviour shown in full and intermediate complexity ESMs under several idealised carbon pulse and exponential concentration increase experiments. We find that the inclusion of a linear increase in 100-year integrated airborne fraction with cumulative carbon uptake and global temperature change substantially improves the representation of the response of the climate system to CO2 on a range of timescales and under a range of experimental designs.

  19. Title: Freshwater phytoplankton responses to global warming.

    PubMed

    Wagner, Heiko; Fanesi, Andrea; Wilhelm, Christian

    2016-09-20

    Global warming alters species composition and function of freshwater ecosystems. However, the impact of temperature on primary productivity is not sufficiently understood and water quality models need to be improved in order to assess the quantitative and qualitative changes of aquatic communities. On the basis of experimental data, we demonstrate that the commonly used photosynthetic and water chemistry parameters alone are not sufficient for modeling phytoplankton growth under changing temperature regimes. We present some new aspects of the acclimation process with respect to temperature and how contrasting responses may be explained by a more complete physiological knowledge of the energy flow from photons to new biomass. We further suggest including additional bio-markers/traits for algal growth such as carbon allocation patterns to increase the explanatory power of such models. Although carbon allocation patterns are promising and functional cellular traits for growth prediction under different nutrient and light conditions, their predictive power still waits to be tested with respect to temperature. A great challenge for the near future will be the prediction of primary production efficiencies under the global change scenario using a uniform model for phytoplankton assemblages. Copyright © 2016 Elsevier GmbH. All rights reserved.

  20. Strategies for rapid global earthquake impact estimation: the Prompt Assessment of Global Earthquakes for Response (PAGER) system

    USGS Publications Warehouse

    Jaiswal, Kishor; Wald, D.J.

    2013-01-01

    This chapter summarizes the state-of-the-art for rapid earthquake impact estimation. It details the needs and challenges associated with quick estimation of earthquake losses following global earthquakes, and provides a brief literature review of various approaches that have been used in the past. With this background, the chapter introduces the operational earthquake loss estimation system developed by the U.S. Geological Survey (USGS) known as PAGER (for Prompt Assessment of Global Earthquakes for Response). It also details some of the ongoing developments of PAGER’s loss estimation models to better supplement the operational empirical models, and to produce value-added web content for a variety of PAGER users.

  1. A Pipeline for High-Throughput Concentration Response Modeling of Gene Expression for Toxicogenomics

    PubMed Central

    House, John S.; Grimm, Fabian A.; Jima, Dereje D.; Zhou, Yi-Hui; Rusyn, Ivan; Wright, Fred A.

    2017-01-01

    Cell-based assays are an attractive option to measure gene expression response to exposure, but the cost of whole-transcriptome RNA sequencing has been a barrier to the use of gene expression profiling for in vitro toxicity screening. In addition, standard RNA sequencing adds variability due to variable transcript length and amplification. Targeted probe-sequencing technologies such as TempO-Seq, with transcriptomic representation that can vary from hundreds of genes to the entire transcriptome, may reduce some components of variation. Analyses of high-throughput toxicogenomics data require renewed attention to read-calling algorithms and simplified dose–response modeling for datasets with relatively few samples. Using data from induced pluripotent stem cell-derived cardiomyocytes treated with chemicals at varying concentrations, we describe here and make available a pipeline for handling expression data generated by TempO-Seq to align reads, clean and normalize raw count data, identify differentially expressed genes, and calculate transcriptomic concentration–response points of departure. The methods are extensible to other forms of concentration–response gene-expression data, and we discuss the utility of the methods for assessing variation in susceptibility and the diseased cellular state. PMID:29163636

  2. Zika virus alters the microRNA expression profile and elicits an RNAi response in Aedes aegypti mosquitoes

    PubMed Central

    Hart, Charles E.; Widen, Steven G.; Wood, Thomas G.; Thangamani, Saravanan; Asgari, Sassan

    2017-01-01

    Zika virus (ZIKV), a flavivirus transmitted primarily by Aedes aegypti, has recently spread globally in an unprecedented fashion, yet we have a poor understanding of host-microbe interactions in this system. To gain insights into the interplay between ZIKV and the mosquito, we sequenced the small RNA profiles in ZIKV-infected and non-infected Ae. aegypti mosquitoes at 2, 7 and 14 days post-infection. ZIKA induced an RNAi response in the mosquito with virus-derived short interfering RNAs and PIWI-interacting RNAs dramatically increased in abundance post-infection. Further, we found 17 host microRNAs (miRNAs) that were modulated by ZIKV infection at all time points. Strikingly, many of these regulated miRNAs have been reported to have their expression altered by dengue and West Nile viruses, while the response was divergent from that induced by the alphavirus Chikungunya virus in mosquitoes. This suggests that conserved miRNA responses occur within mosquitoes in response to flavivirus infection. This study expands our understanding of ZIKV-vector interactions and provides potential avenues to be further investigated to target ZIKV in the mosquito host. PMID:28715413

  3. Registered Nurses' and nurse assistants' responses to older persons' expressions of emotional needs in home care.

    PubMed

    Höglander, Jessica; Eklund, Jakob Håkansson; Eide, Hilde; Holmström, Inger K; Sundler, Annelie J

    2017-12-01

    This study aims to explore nurse assistants' and Registered Nurses' responses to older persons' expressions of emotional needs during home care visits. Communication is a central aspect of care. Older persons might express different emotions and needs during home care visits and such expressions can be challenging to respond to. Little is known about communication in home care or nursing staff responses to older persons' expressed emotional needs. Descriptive, cross-sectional design on nursing staff responses to older persons' negative emotions in home care. Collected data consisted of audio recordings of home care visits between older persons and nursing staff. Data were collected between August 2014-November 2015. The nursing staff responses to older persons' negative emotions in the communication were analysed with the Verona Coding Definitions of Emotional Sequences (VR-CoDES). The nursing staff most often give non-explicit responses, providing space for further disclosure of older persons' expressed negative emotions. Such responses were more frequent if the nursing staff had elicited the older persons' expressions of a negative emotion than if such expressions were elicited by the older persons themselves. Most frequent types of responses were backchannel, active invitation or information advice. The nursing staff responses were mainly non-explicit responses providing space for older persons to tell more about their experiences. Such responses can be discussed in terms of person-centred communication and is important for the comfort of emotional concerns. © 2017 John Wiley & Sons Ltd.

  4. Neural responses to facial expressions support the role of the amygdala in processing threat

    PubMed Central

    Sormaz, Mladen; Flack, Tessa; Asghar, Aziz U. R.; Fan, Siyan; Frey, Julia; Manssuer, Luis; Usten, Deniz; Young, Andrew W.; Andrews, Timothy J.

    2014-01-01

    The amygdala is known to play an important role in the response to facial expressions that convey fear. However, it remains unclear whether the amygdala’s response to fear reflects its role in the interpretation of danger and threat, or whether it is to some extent activated by all facial expressions of emotion. Previous attempts to address this issue using neuroimaging have been confounded by differences in the use of control stimuli across studies. Here, we address this issue using a block design functional magnetic resonance imaging paradigm, in which we compared the response to face images posing expressions of fear, anger, happiness, disgust and sadness with a range of control conditions. The responses in the amygdala to different facial expressions were compared with the responses to a non-face condition (buildings), to mildly happy faces and to neutral faces. Results showed that only fear and anger elicited significantly greater responses compared with the control conditions involving faces. Overall, these findings are consistent with the role of the amygdala in processing threat, rather than in the processing of all facial expressions of emotion, and demonstrate the critical importance of the choice of comparison condition to the pattern of results. PMID:24097376

  5. DKK1 and Kremen Expression Predicts the Osteoblastic Response to Bone Metastasis.

    PubMed

    Clines, Katrina L; Clines, Gregory A

    2018-05-14

    Bone metastasis is a complication of advanced breast and prostate cancer. Tumor-secreted Dickkopf homolog 1 (DKK1), an inhibitor of canonical Wnt signaling and osteoblast differentiation, was proposed to regulate the osteoblastic response to metastatic cancer in bone. The objectives of this study were to compare DKK1 expression with the in vivo osteoblastic response in a panel of breast and prostate cancer cell lines, and to discover mechanisms that regulate cancer DKK1 expression. DKK1 expression was highest in MDA-MB-231 and PC3 cells that produce osteolytic lesions, and hence a suppressed osteoblastic response, in animal models of bone metastasis. LnCaP, C4-2B, LuCaP23.1, T47D, ZR-75-1, MCF-7, ARCaP and ARCaP M cancer cells that generate osteoblastic, mixed or no bone lesions had the lowest DKK1 expression. The cell lines with negligible expression, LnCaP, C4-2B and T47D, exhibited methylation of the DKK1 promoter. Canonical Wnt signaling activity was then determined and found in all cell lines tested, even in the MDA-MB-231 and PC3 cell lines despite sizeable amounts of DKK1 protein expression expected to block canonical Wnt signaling. A mechanism of DKK1 resistance in the osteolytic cell lines was investigated and determined to be at least partially due to down-regulation of the DKK1 receptors Kremen1 and Kremen2 in the MDA-MB-231 and PC3 cell lines. Combined DKK1 and Kremen expression in cancer cells may serve as predictive markers of the osteoblastic response of breast and prostate cancer bone metastasis. Published by Elsevier Inc.

  6. Mentoring health researchers globally: Diverse experiences, programmes, challenges and responses.

    PubMed

    Cole, Donald C; Johnson, Nancy; Mejia, Raul; McCullough, Hazel; Turcotte-Tremblay, Anne-Marie; Barnoya, Joaquin; Falabella Luco, María Soledad

    2016-10-01

    Mentoring experiences and programmes are becoming increasingly recognised as important by those engaged in capacity strengthening in global health research. Using a primarily qualitative study design, we studied three experiences of mentorship and eight mentorship programmes for early career global health researchers based in high-income and low- and middle-income countries. For the latter, we drew upon programme materials, existing unpublished data and more formal mixed-method evaluations, supplemented by individual email questionnaire responses. Research team members wrote stories, and the team assembled and analysed them for key themes. Across the diverse experiences and programmes, key emergent themes included: great mentors inspire others in an inter-generational cascade, mentorship is transformative in personal and professional development and involves reciprocity, and finding the right balance in mentoring relationships and programmes includes responding creatively to failure. Among the challenges encountered were: struggling for more level playing fields for new health researchers globally, changing mindsets in institutions that do not have a culture of mentorship and building collaboration not competition. Mentoring networks spanning institutions and countries using multiple virtual and face-to-face methods are a potential avenue for fostering organisational cultures supporting quality mentorship in global health research.

  7. Emotional Responses to Music: Experience, Expression, and Physiology

    ERIC Educational Resources Information Center

    Lundqvist, Lars-Olov; Carlsson, Fredrik; Hilmersson, Per; Juslin, Patrik N.

    2009-01-01

    A crucial issue in research on music and emotion is whether music evokes genuine emotional responses in listeners (the emotivist position) or whether listeners merely perceive emotions expressed by the music (the cognitivist position). To investigate this issue, we measured self-reported emotion, facial muscle activity, and autonomic activity in…

  8. Profiles of Global Gene Expression in Ionizing-Radiation–Damaged Human Diploid Fibroblasts Reveal Synchronization behind the G1 Checkpoint in a G0-like State of Quiescence

    PubMed Central

    Zhou, Tong; Chou, Jeff W.; Simpson, Dennis A.; Zhou, Yingchun; Mullen, Thomas E.; Medeiros, Margarida; Bushel, Pierre R.; Paules, Richard S.; Yang, Xuebin; Hurban, Patrick; Lobenhofer, Edward K.; Kaufmann, William K.

    2006-01-01

    Cell cycle arrest and stereotypic transcriptional responses to DNA damage induced by ionizing radiation (IR) were quantified in telomerase-expressing human diploid fibroblasts. Analysis of cytotoxicity demonstrated that 1.5 Gy IR inactivated colony formation by 40–45% in three fibroblast lines; this dose was used in all subsequent analyses. Fibroblasts exhibited > 90% arrest of progression from G2 to M at 2 hr post-IR and a similarly severe arrest of progression from G1 to S at 6 and 12 hr post-IR. Normal rates of DNA synthesis and mitosis 6 and 12 hr post-IR caused the S and M compartments to empty by > 70% at 24 hr. Global gene expression was analyzed in IR-treated cells. A microarray analysis algorithm, EPIG, identified nine IR-responsive patterns of gene expression that were common to the three fibroblast lines, including a dominant p53-dependent G1 checkpoint response. Many p53 target genes, such as CDKN1A, GADD45, BTG2, and PLK3, were significantly up-regulated at 2 hr post-IR. Many genes whose expression is regulated by E2F family transcription factors, including CDK2, CCNE1, CDC6, CDC2, MCM2, were significantly down-regulated at 24 hr post-IR. Numerous genes that participate in DNA metabolism were also markedly repressed in arrested fibroblasts apparently as a result of cell synchronization behind the G1 checkpoint. However, cluster and principal component analyses of gene expression revealed a profile 24 hr post-IR with similarity to that of G0 growth quiescence. The results reveal a highly stereotypic pattern of response to IR in human diploid fibroblasts that reflects primarily synchronization behind the G1 checkpoint but with prominent induction of additional markers of G0 quiescence such as GAS1. PMID:16581545

  9. The Impact of Continental Configuration on Global Response to Large Igneous Province Eruptions

    NASA Astrophysics Data System (ADS)

    Stellmann, J.; West, A. J.; Ridgwell, A.; Becker, T. W.

    2017-12-01

    The impact of Large Igneous Province eruptions as recorded in the geologic record varies widely; some eruptions cause global warming, large scale ocean acidification and anoxia and mass extinctions while others cause some or none of these phenomena. There are several potential factors which may determine the global response to a Large Igneous Province eruption; here we consider continental configuration. The arrangement of continents controls the extent of shallow seas, ocean circulation and planetary albedo; all factors which impact global climate and its response to sudden changes in greenhouse gas concentrations. To assess the potential impact of continental configuration, a suite of simulated eruptions was carried out using the cGENIE Earth system model in two end-member continental configurations: the end-Permian supercontinent and the modern. Eruptions simulated are comparable to an individual pulse of a Large Igneous Province eruption with total CO2 emissions of 1,000 or 10,000 GtC erupted over 1,000 or 10,000 years, spanning eruptions rates of .1-10 GtC/yr. Global response is characterized by measuring the magnitude and duration of changes to atmospheric concentration of CO2, saturation state of calcite and ocean oxygen levels. Preliminary model results show that end-Permian continental configuration and conditions (radiative balance, ocean chemistry) lead to smaller magnitude and shorter duration changes in atmospheric pCO2 and ocean saturation state of calcite following the simulated eruption than the modern configuration.

  10. Global, Energy-Dependent Ring Current Response During Two Large Storms

    NASA Astrophysics Data System (ADS)

    Goldstein, J.; Angelopoulos, V.; Burch, J. L.; De Pascuale, S.; Fuselier, S. A.; Genestreti, K. J.; Kurth, W. S.; LLera, K.; McComas, D. J.; Reeves, G. D.; Spence, H. E.; Valek, P. W.

    2015-12-01

    Two recent large (~200 nT) geomagnetic storms occurred during 17--18 March 2015 and 22--23 June 2015. The global, energy-dependent ring current response to these two extreme events is investigated using both global imaging and multi-point in situ observations. Energetic neutral atom (ENA) imaging by the Two Wide-angle Imaging Neutral-atom Spectrometers (TWINS) mission provides a global view of ring current ions. Local measurements are provided by two multi-spacecraft missions. The two Van Allen Probes measure in situ plasma (including ion composition) and fields at ring current and plasmaspheric L values. The recently launched Magnetospheric Multiscale (MMS) comprises four spacecraft that have just begun to measure particles (including ion composition) and fields at outer magnetospheric L-values. We analyze the timing and energetics of the stormtime evolution of ring current ions, both trapped and precipitating, using TWINS ENA images and in situ data by the Van Allen Probes and MMS.

  11. Profiling of differential gene expression in the hypothalamus of broiler-type Taiwan country chickens in response to acute heat stress.

    PubMed

    Tu, Wei-Lin; Cheng, Chuen-Yu; Wang, Shih-Han; Tang, Pin-Chi; Chen, Chih-Feng; Chen, Hsin-Hsin; Lee, Yen-Pai; Chen, Shuen-Ei; Huang, San-Yuan

    2016-02-01

    Acute heat stress severely impacts poultry production. The hypothalamus acts as a crucial center to regulate body temperature, detect temperature changes, and modulate the autonomic nervous system and endocrine loop for heat retention and dissipation. The purpose of this study was to investigate global gene expression in the hypothalamus of broiler-type B strain Taiwan country chickens after acute heat stress. Twelve 30-week-old hens were allocated to four groups. Three heat-stressed groups were subjected to acute heat stress at 38 °C for 2 hours without recovery (H2R0), with 2 hours of recovery (H2R2), and with 6 hours of recovery (H2R6). The control hens were maintained at 25 °C. At the end, hypothalamus samples were collected for gene expression analysis. The results showed that 24, 11, and 25 genes were upregulated and 41, 15, and 42 genes were downregulated in H2R0, H2R2, and H2R6 treatments, respectively. The expressions of gonadotropin-releasing hormone 1 (GNRH1), heat shock 27-kDa protein 1 (HSPB1), neuropeptide Y (NPY), and heat shock protein 25 (HSP25) were upregulated at all recovery times after heat exposure. Conversely, the expression of TPH2 was downregulated at all recovery times. A gene ontology analysis showed that most of the differentially expressed genes were involved in biological processes including cellular processes, metabolic processes, localization, multicellular organismal processes, developmental processes, and biological regulation. A functional annotation analysis showed that the differentially expressed genes were related to the gene networks of responses to stress and reproductive functions. These differentially expressed genes might be essential and unique key factors in the heat stress response of the hypothalamus in chickens. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Dynamic gene expression response to altered gravity in human T cells.

    PubMed

    Thiel, Cora S; Hauschild, Swantje; Huge, Andreas; Tauber, Svantje; Lauber, Beatrice A; Polzer, Jennifer; Paulsen, Katrin; Lier, Hartwin; Engelmann, Frank; Schmitz, Burkhard; Schütte, Andreas; Layer, Liliana E; Ullrich, Oliver

    2017-07-12

    We investigated the dynamics of immediate and initial gene expression response to different gravitational environments in human Jurkat T lymphocytic cells and compared expression profiles to identify potential gravity-regulated genes and adaptation processes. We used the Affymetrix GeneChip® Human Transcriptome Array 2.0 containing 44,699 protein coding genes and 22,829 non-protein coding genes and performed the experiments during a parabolic flight and a suborbital ballistic rocket mission to cross-validate gravity-regulated gene expression through independent research platforms and different sets of control experiments to exclude other factors than alteration of gravity. We found that gene expression in human T cells rapidly responded to altered gravity in the time frame of 20 s and 5 min. The initial response to microgravity involved mostly regulatory RNAs. We identified three gravity-regulated genes which could be cross-validated in both completely independent experiment missions: ATP6V1A/D, a vacuolar H + -ATPase (V-ATPase) responsible for acidification during bone resorption, IGHD3-3/IGHD3-10, diversity genes of the immunoglobulin heavy-chain locus participating in V(D)J recombination, and LINC00837, a long intergenic non-protein coding RNA. Due to the extensive and rapid alteration of gene expression associated with regulatory RNAs, we conclude that human cells are equipped with a robust and efficient adaptation potential when challenged with altered gravitational environments.

  13. Transcriptomic responses to wounding: meta-analysis of gene expression microarray data.

    PubMed

    Sass, Piotr Andrzej; Dąbrowski, Michał; Charzyńska, Agata; Sachadyn, Paweł

    2017-11-07

    A vast amount of microarray data on transcriptomic response to injury has been collected so far. We designed the analysis in order to identify the genes displaying significant changes in expression after wounding in different organisms and tissues. This meta-analysis is the first study to compare gene expression profiles in response to wounding in as different tissues as heart, liver, skin, bones, and spinal cord, and species, including rat, mouse and human. We collected available microarray transcriptomic profiles obtained from different tissue injury experiments and selected the genes showing a minimum twofold change in expression in response to wounding in prevailing number of experiments for each of five wound healing stages we distinguished: haemostasis & early inflammation, inflammation, early repair, late repair and remodelling. During the initial phases after wounding, haemostasis & early inflammation and inflammation, the transcriptomic responses showed little consistency between different tissues and experiments. For the later phases, wound repair and remodelling, we identified a number of genes displaying similar transcriptional responses in all examined tissues. As revealed by ontological analyses, activation of certain pathways was rather specific for selected phases of wound healing, such as e.g. responses to vitamin D pronounced during inflammation. Conversely, we observed induction of genes encoding inflammatory agents and extracellular matrix proteins in all wound healing phases. Further, we selected several genes differentially upregulated throughout different stages of wound response, including established factors of wound healing in addition to those previously unreported  in this context such as PTPRC and AQP4. We found that transcriptomic responses to wounding showed similar traits in a diverse selection of tissues including skin, muscles, internal organs and nervous system. Notably, we distinguished transcriptional induction of inflammatory

  14. Global signal modulation of single-trial fMRI response variability: Effect on positive vs negative BOLD response relationship.

    PubMed

    Mayhew, S D; Mullinger, K J; Ostwald, D; Porcaro, C; Bowtell, R; Bagshaw, A P; Francis, S T

    2016-06-01

    In functional magnetic resonance imaging (fMRI), the relationship between positive BOLD responses (PBRs) and negative BOLD responses (NBRs) to stimulation is potentially informative about the balance of excitatory and inhibitory brain responses in sensory cortex. In this study, we performed three separate experiments delivering visual, motor or somatosensory stimulation unilaterally, to one side of the sensory field, to induce PBR and NBR in opposite brain hemispheres. We then assessed the relationship between the evoked amplitudes of contralateral PBR and ipsilateral NBR at the level of both single-trial and average responses. We measure single-trial PBR and NBR peak amplitudes from individual time-courses, and show that they were positively correlated in all experiments. In contrast, in the average response across trials the absolute magnitudes of both PBR and NBR increased with increasing stimulus intensity, resulting in a negative correlation between mean response amplitudes. Subsequent analysis showed that the amplitude of single-trial PBR was positively correlated with the BOLD response across all grey-matter voxels and was not specifically related to the ipsilateral sensory cortical response. We demonstrate that the global component of this single-trial response modulation could be fully explained by voxel-wise vascular reactivity, the BOLD signal standard deviation measured in a separate resting-state scan (resting state fluctuation amplitude, RSFA). However, bilateral positive correlation between PBR and NBR regions remained. We further report that modulations in the global brain fMRI signal cannot fully account for this positive PBR-NBR coupling and conclude that the local sensory network response reflects a combination of superimposed vascular and neuronal signals. More detailed quantification of physiological and noise contributions to the BOLD signal is required to fully understand the trial-by-trial PBR and NBR relationship compared with that of

  15. Functional genomics reveals the induction of inflammatory response and metalloproteinase gene expression during lethal Ebola virus infection.

    PubMed

    Cilloniz, Cristian; Ebihara, Hideki; Ni, Chester; Neumann, Gabriele; Korth, Marcus J; Kelly, Sara M; Kawaoka, Yoshihiro; Feldmann, Heinz; Katze, Michael G

    2011-09-01

    Ebola virus is the etiologic agent of a lethal hemorrhagic fever in humans and nonhuman primates with mortality rates of up to 90%. Previous studies with Zaire Ebola virus (ZEBOV), mouse-adapted virus (MA-ZEBOV), and mutant viruses (ZEBOV-NP(ma), ZEBOV-VP24(ma), and ZEBOV-NP/VP24(ma)) allowed us to identify the mutations in viral protein 24 (VP24) and nucleoprotein (NP) responsible for acquisition of high virulence in mice. To elucidate specific molecular signatures associated with lethality, we compared global gene expression profiles in spleen samples from mice infected with these viruses and performed an extensive functional analysis. Our analysis showed that the lethal viruses (MA-ZEBOV and ZEBOV-NP/VP24(ma)) elicited a strong expression of genes 72 h after infection. In addition, we found that although the host transcriptional response to ZEBOV-VP24(ma) was nearly the same as that to ZEBOV-NP/VP24(ma), the contribution of a mutation in the NP gene was required for a lethal phenotype. Further analysis indicated that one of the most relevant biological functions differentially regulated by the lethal viruses was the inflammatory response, as was the induction of specific metalloproteinases, which were present in our newly identify functional network that was associated with Ebola virus lethality. Our results suggest that this dysregulated proinflammatory response increased the severity of disease. Consequently, the newly discovered molecular signature could be used as the starting point for the development of new drugs and therapeutics. To our knowledge, this is the first study that clearly defines unique molecular signatures associated with Ebola virus lethality.

  16. Co-expression of Interleukin-15 Enhances the Protective Immune Responses Induced by Immunization with a Murine Malaria MVA-Based Vaccine Encoding the Circumsporozoite Protein.

    PubMed

    Parra, Marcela; Liu, Xia; Derrick, Steven C; Yang, Amy; Molina-Cruz, Alvaro; Barillas-Mury, Carolina; Zheng, Hong; Thao Pham, Phuong; Sedegah, Martha; Belmonte, Arnel; Litilit, Dianne D; Waldmann, Thomas A; Kumar, Sanjai; Morris, Sheldon L; Perera, Liyanage P

    2015-01-01

    Malaria remains a major global public health problem with an estimated 200 million cases detected in 2012. Although the most advanced candidate malaria vaccine (RTS,S) has shown promise in clinical trials, its modest efficacy and durability have created uncertainty about the impact of RTS,S immunization (when used alone) on global malaria transmission. Here we describe the development and characterization of a novel modified vaccinia virus Ankara (MVA)-based malaria vaccine which co-expresses the Plasmodium yoelii circumsporozoite protein (CSP) and IL-15. Vaccination/challenge studies showed that C57BL/6 mice immunized with the MVA-CSP/IL15 vaccine were protected significantly better against a P. yoelii 17XNL sporozoite challenge than either mice immunized with an MVA vaccine expressing only CSP or naïve controls. Importantly, the levels of total anti-CSP IgG were elevated about 100-fold for the MVA-CSP/IL15 immunized group compared to mice immunized with the MVA-CSP construct that does not express IL-15. Among the IgG subtypes, the IL-15 expressing MVA-CSP vaccine induced levels of IgG1 (8 fold) and IgG2b (80 fold) higher than the MVA-CSP construct. The significantly enhanced humoral responses and protection detected after immunization with the MVA-CSP/IL15 vaccine suggest that this IL-15 expressing MVA construct could be considered in the development of future malaria immunization strategies.

  17. Global gene expression analysis of the response of physic nut (Jatropha curcas L.) to medium- and long-term nitrogen deficiency

    PubMed Central

    Wu, Pingzhi; Chen, Yaping; Li, Meiru; Jiang, Huawu

    2017-01-01

    Jatropha curcas L. is an important biofuel plant with excellent tolerance of barren environments. However, studies on the regulatory mechanisms that operate in this plant in response to nitrogen (N) shortage are scarce. In this study, genome-wide transcriptional profiles of the roots and leaves of 8-week old physic nut seedlings were analyzed after 2 and 16 days of N starvation. Enrichment results showed that genes associated with N metabolism, processing and regulation of RNA, and transport predominated among those showing alterations in expression. Genes encoding transporter families underwent major changes in expression in both roots and leaves; in particular, those with roles in ammonia, amino acid and peptide transport were generally up-regulated after long-term starvation, while AQUAPORIN genes, whose products function in osmoregulation, were down-regulated. We also found that ASPARA−GINASE B1 and SARCOSINE OXIDASE genes were up-regulated in roots and leaves after 2 and 16 d N starvation. Genes associated with ubiquitination-mediated protein degradation were significantly up-regulated. In addition, genes in the JA biosynthesis pathway were strongly activated while expression of those in GA signaling was inhibited in leaves. We showed that four major classes of genes, those with roles in N uptake, N reutilization, C/N ratio balance, and cell structure and synthesis, were particularly influenced by long-term N limitation. Our discoveries may offer clues to the molecular mechanisms that regulate N reallocation and reutilization so as to maintain or increase plant performance even under adverse environmental conditions. PMID:28817702

  18. Global gene expression analysis of the response of physic nut (Jatropha curcas L.) to medium- and long-term nitrogen deficiency.

    PubMed

    Kuang, Qi; Zhang, Sheng; Wu, Pingzhi; Chen, Yaping; Li, Meiru; Jiang, Huawu; Wu, Guojiang

    2017-01-01

    Jatropha curcas L. is an important biofuel plant with excellent tolerance of barren environments. However, studies on the regulatory mechanisms that operate in this plant in response to nitrogen (N) shortage are scarce. In this study, genome-wide transcriptional profiles of the roots and leaves of 8-week old physic nut seedlings were analyzed after 2 and 16 days of N starvation. Enrichment results showed that genes associated with N metabolism, processing and regulation of RNA, and transport predominated among those showing alterations in expression. Genes encoding transporter families underwent major changes in expression in both roots and leaves; in particular, those with roles in ammonia, amino acid and peptide transport were generally up-regulated after long-term starvation, while AQUAPORIN genes, whose products function in osmoregulation, were down-regulated. We also found that ASPARA-GINASE B1 and SARCOSINE OXIDASE genes were up-regulated in roots and leaves after 2 and 16 d N starvation. Genes associated with ubiquitination-mediated protein degradation were significantly up-regulated. In addition, genes in the JA biosynthesis pathway were strongly activated while expression of those in GA signaling was inhibited in leaves. We showed that four major classes of genes, those with roles in N uptake, N reutilization, C/N ratio balance, and cell structure and synthesis, were particularly influenced by long-term N limitation. Our discoveries may offer clues to the molecular mechanisms that regulate N reallocation and reutilization so as to maintain or increase plant performance even under adverse environmental conditions.

  19. Integrated Phloem Sap mRNA and Protein Expression Analysis Reveals Phytoplasma-infection Responses in Mulberry.

    PubMed

    Gai, Yingping; Yuan, Shuo-Shuo; Liu, Zhao-Yang; Zhao, Huai-Ning; Liu, Qi; Qin, Yong-Li; Fang, Li-Jing; Ji, Xian-Ling

    2018-05-30

    To gain insight into the response of mulberry to phytoplasma-infection, the expression profiles of mRNAs and proteins in mulberry phloem sap were examined. A total of 955 unigenes and 136 proteins were found to be differentially expressed between the healthy and infected phloem sap. These differentially expressed mRNAs and proteins are involved in signalling, hormone metabolism, stress responses, etc. Interestingly, we found that both the mRNA and protein levels of the major latex protein-like 329 ( MuMLPL329 ) gene were increased in the infected phloem saps. Expression of the MuMLPL329 gene was induced by pathogen inoculation and was responsive to jasmonic acid. Ectopic expression of MuMLPL329 in Arabidopsis enhances transgenic plant resistance to Botrytis cinerea, Pseudomonas syringae pv tomato DC3000 ( Pst. DC3000 ) and phytoplasma. Further analysis revealed that MuMLPL329 can enhance the expression of some defense genes and might be involved in altering flavonoid content resulting in increased resistance of plants to pathogen infection. Finally, the roles of the differentially expressed mRNAs and proteins and the potential molecular mechanisms of their changes were discussed. It was likely that the phytoplasma-responsive mRNAs and proteins in the phloem saps were involved in multiple pathways of mulberry responses to phytoplasma-infection, and their changes may be partially responsible for some symptoms in the phytoplasma infected plants. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

  20. 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

  1. Evolutionary History Underlies Plant Physiological Responses to Global Change Since the Last Glacial Maximum

    NASA Astrophysics Data System (ADS)

    Becklin, K. M.; Medeiros, J. S.; Sale, K. R.; Ward, J. K.

    2014-12-01

    Assessing family and species-level variation in physiological responses to global change across geologic time is critical for understanding factors that underlie changes in species distributions and community composition. Ancient plant specimens preserved within packrat middens are invaluable in this context since they allow for comparisons between co-occurring plant lineages. Here we used modern and ancient plant specimens preserved within packrat middens from the Snake Range, NV to investigate the physiological responses of a mixed montane conifer community to global change since the last glacial maximum. We used a conceptual model to infer relative changes in stomatal conductance and maximum photosynthetic capacity from measures of leaf carbon isotopes, stomatal characteristics, and leaf nitrogen content. Our results indicate that most of the sampled taxa decreased stomatal conductance and/or photosynthetic capacity from glacial to modern times. However, plant families differed in the timing and magnitude of these physiological responses. Additionally, leaf-level responses were more similar within plant families than within co-occurring species assemblages. This suggests that adaptation at the level of leaf physiology may not be the main determinant of shifts in community composition, and that plant evolutionary history may drive physiological adaptation to global change over recent geologic time.

  2. Global Analysis of Ecosystem Evapotranspiration Response to Precipitation Deficits

    NASA Astrophysics Data System (ADS)

    He, Bin; Wang, Haiyan; Guo, Lanlan; Liu, Junjie

    2017-12-01

    Changes in ecosystem evapotranspiration (ET) due to precipitation deficits (PD) can relieve or aggravate soil moisture shortages, thus impacting drought severity. Previous findings have conflicted with regard to response of ET to PD. The present study relies on a global land ET synthesis data set (ETsyn) and observations from eddy-covariance towers (ETobs) to thoroughly examine the sensitivity of ET to PD, which is represented by the standardized precipitation index. There was a contrast in the response to PD between arid and humid ecosystems. ETsyn of arid ecosystems was typically reduced promptly in response to a reduction of precipitation, while ETsyn in humid ecosystems experienced a two-staged change: First, there was an enhancement, and then a reduction associated with persisting PD. Compared with ETsyn, ETobs suggests the occurrence of a more significant ET transition in response to PD. In arid ecosystems, ET typically negatively correlated with low PD, but this was limited by a large PD. Findings from this study are crucial for understanding the role of ET in drought evolution.

  3. Global mapping of binding sites for Nrf2 identifies novel targets in cell survival response through ChIP-Seq profiling and network analysis

    PubMed Central

    Malhotra, Deepti; Portales-Casamar, Elodie; Singh, Anju; Srivastava, Siddhartha; Arenillas, David; Happel, Christine; Shyr, Casper; Wakabayashi, Nobunao; Kensler, Thomas W.; Wasserman, Wyeth W.; Biswal, Shyam

    2010-01-01

    The Nrf2 (nuclear factor E2 p45-related factor 2) transcription factor responds to diverse oxidative and electrophilic environmental stresses by circumventing repression by Keap1, translocating to the nucleus, and activating cytoprotective genes. Nrf2 responses provide protection against chemical carcinogenesis, chronic inflammation, neurodegeneration, emphysema, asthma and sepsis in murine models. Nrf2 regulates the expression of a plethora of genes that detoxify oxidants and electrophiles and repair or remove damaged macromolecules, such as through proteasomal processing. However, many direct targets of Nrf2 remain undefined. Here, mouse embryonic fibroblasts (MEF) with either constitutive nuclear accumulation (Keap1−/−) or depletion (Nrf2−/−) of Nrf2 were utilized to perform chromatin-immunoprecipitation with parallel sequencing (ChIP-Seq) and global transcription profiling. This unique Nrf2 ChIP-Seq dataset is highly enriched for Nrf2-binding motifs. Integrating ChIP-Seq and microarray analyses, we identified 645 basal and 654 inducible direct targets of Nrf2, with 244 genes at the intersection. Modulated pathways in stress response and cell proliferation distinguish the inducible and basal programs. Results were confirmed in an in vivo stress model of cigarette smoke-exposed mice. This study reveals global circuitry of the Nrf2 stress response emphasizing Nrf2 as a central node in cell survival response. PMID:20460467

  4. The Global Emerging Infection Surveillance and Response System (GEIS), a U.S. government tool for improved global biosurveillance: a review of 2009

    PubMed Central

    2011-01-01

    The Armed Forces Health Surveillance Center, Global Emerging Infections Surveillance and Response System (AFHSC-GEIS) has the mission of performing surveillance for emerging infectious diseases that could affect the United States (U.S.) military. This mission is accomplished by orchestrating a global portfolio of surveillance projects, capacity-building efforts, outbreak investigations and training exercises. In 2009, this portfolio involved 39 funded partners, impacting 92 countries. This article discusses the current biosurveillance landscape, programmatic details of organization and implementation, and key contributions to force health protection and global public health in 2009. PMID:21388562

  5. Internationalization as a Response to Globalization: Radical Shifts in University Environments

    ERIC Educational Resources Information Center

    Stromquist, Nelly P.

    2007-01-01

    This case study probes recent developments in a number of academic and non-academic aspects of a private research university in response to current globalization trends. Under the name of internationalization, university administrators and external firms are emerging as powerful decision-makers shaping academic content and even academic…

  6. Clouds and the extratropical circulation response to global warming in a hierarchy of global atmosphere models

    NASA Astrophysics Data System (ADS)

    Voigt, A.

    2017-12-01

    Climate models project that global warming will lead to substantial changes in extratropical jet streams. Yet, many quantitative aspects of warming-induced jet stream changes remain uncertain, and recent work has indicated an important role of clouds and their radiative interactions. Here, I will investigate how cloud-radiative changes impact the zonal-mean extratropical circulation response under global warming using a hierarchy of global atmosphere models. I will first focus on aquaplanet setups with prescribed sea-surface temperatures (SSTs), which reproduce the model spread found in realistic simulations with interactive SSTs. Simulations with two CMIP5 models MPI-ESM and IPSL-CM5A and prescribed clouds show that half of the circulation response can be attributed to cloud changes. The rise of tropical high-level clouds and the upward and poleward movement of midlatitude high-level clouds lead to poleward jet shifts. High-latitude low-level cloud changes shift the jet poleward in one model but not in the other. The impact of clouds on the jet operates via the atmospheric radiative forcing that is created by the cloud changes and is qualitatively reproduced in a dry Held-Suarez model, although the latter is too sensitive because of its simplified treatment of diabatic processes. I will then show that the aquaplanet results also hold when the models are used in a realistic setup that includes continents and seasonality. I will further juxtapose these prescribed-SST simulations with interactive-SST simulations and show that atmospheric and surface cloud-radiative interactions impact the jet poleward jet shifts in about equal measure. Finally, I will discuss the cloud impact on regional and seasonal circulation changes.

  7. Methyl-methanesulfonate sensitivity 19 expression is associated with metastasis and chemoradiotherapy response in esophageal cancer

    PubMed Central

    Zhang, Jin-Liang; Wang, Hui-Yun; Yang, Qing; Lin, Shi-Yong; Luo, Guang-Yu; Zhang, Rong; Xu, Guo-Liang

    2015-01-01

    AIM: To investigate the clinical significance of methyl-methanesulfonate sensitivity 19 (MMS19) expression in esophageal squamous cell carcinoma (ESCC). METHODS: Between June 2008 and May 2013, specimens from 103 patients who underwent endoscopic biopsy for the diagnosis of ESCC at the endoscopy center of Sun Yat-Sen University Cancer Center were collected; 52 matched-normal esophageal squamous epithelium samples were biopsied as controls. MMS19 protein expression was measured by immunohistochemistry. Of the 103 cases of ESCC, 49 received radical surgery following neoadjuvant chemoradiotherapy consisting of concurrent radiation in a total dose of 40 Gy and two cycles of chemotherapy with vinorelbine and cisplatin. Relationships between MMS19 expression, clinicopathologic characteristics and chemoradiotherapy response were analyzed. RESULTS: The MMS19 protein could be detected in both the cytoplasm and nucleus of most specimens. High cytoplasmic expression of MMS19 was detected in 63.1% of ESCC samples, whereas high nuclear expression of MMS19 was found in 35.0%. High cytoplasmic MMS19 expression was associated with regional lymph node metastases (OR = 11.3, 95%CI: 2.3-54.7; P < 0.001) and distant metastases (OR = 13.1, 95%CI: 1.7-103.0; P = 0.002). Furthermore, high cytoplasmic MMS19 expression was associated with a response of ESCC to chemoradiotherapy (OR = 11.5, 95%CI: 3.0-44.5; P < 0.001), with a high cytoplasmic MMS19 expression rates in 79.3% and 25.0% of patients from the good chemoradiotherapy response group and poor response group, respectively. Nuclear MMS19 expression did not show any significant association with clinicopathologic characteristics or chemoradiotherapy response in ESCC. CONCLUSION: The results of our preliminary study suggest that MMS19 may be a potential new predictor of metastasis and chemoradiotherapy response in ESCC. PMID:25892874

  8. Global miRNA expression and correlation with mRNA levels in primary human bone cells

    PubMed Central

    Laxman, Navya; Rubin, Carl-Johan; Mallmin, Hans; Nilsson, Olle; Pastinen, Tomi; Grundberg, Elin; Kindmark, Andreas

    2015-01-01

    MicroRNAs (miRNAs) are important post-transcriptional regulators that have recently introduced an additional level of intricacy to our understanding of gene regulation. The aim of this study was to investigate miRNA–mRNA interactions that may be relevant for bone metabolism by assessing correlations and interindividual variability in miRNA levels as well as global correlations between miRNA and mRNA levels in a large cohort of primary human osteoblasts (HOBs) obtained during orthopedic surgery in otherwise healthy individuals. We identified differential expression (DE) of 24 miRNAs, and found 9 miRNAs exhibiting DE between males and females. We identified hsa-miR-29b, hsa-miR-30c2, and hsa-miR-125b and their target genes as important modulators of bone metabolism. Further, we used an integrated analysis of global miRNA–mRNA correlations, mRNA-expression profiling, DE, bioinformatics analysis, and functional studies to identify novel target genes for miRNAs with the potential to regulate osteoblast differentiation and extracellular matrix production. Functional studies by overexpression and knockdown of miRNAs showed that, the differentially expressed miRNAs hsa-miR-29b, hsa-miR-30c2, and hsa-miR-125b target genes highly relevant to bone metabolism, e.g., collagen, type I, α1 (COL1A1), osteonectin (SPARC), Runt-related transcription factor 2 (RUNX2), osteocalcin (BGLAP), and frizzled-related protein (FRZB). These miRNAs orchestrate the activities of key regulators of osteoblast differentiation and extracellular matrix proteins by their convergent action on target genes and pathways to control the skeletal gene expression. PMID:26078267

  9. Expression profiling during arabidopsis/downy mildew interaction reveals a highly-expressed effector that attenuates responses to salicylic acid.

    PubMed

    Asai, Shuta; Rallapalli, Ghanasyam; Piquerez, Sophie J M; Caillaud, Marie-Cécile; Furzer, Oliver J; Ishaque, Naveed; Wirthmueller, Lennart; Fabro, Georgina; Shirasu, Ken; Jones, Jonathan D G

    2014-10-01

    Plants have evolved strong innate immunity mechanisms, but successful pathogens evade or suppress plant immunity via effectors delivered into the plant cell. Hyaloperonospora arabidopsidis (Hpa) causes downy mildew on Arabidopsis thaliana, and a genome sequence is available for isolate Emoy2. Here, we exploit the availability of genome sequences for Hpa and Arabidopsis to measure gene-expression changes in both Hpa and Arabidopsis simultaneously during infection. Using a high-throughput cDNA tag sequencing method, we reveal expression patterns of Hpa predicted effectors and Arabidopsis genes in compatible and incompatible interactions, and promoter elements associated with Hpa genes expressed during infection. By resequencing Hpa isolate Waco9, we found it evades Arabidopsis resistance gene RPP1 through deletion of the cognate recognized effector ATR1. Arabidopsis salicylic acid (SA)-responsive genes including PR1 were activated not only at early time points in the incompatible interaction but also at late time points in the compatible interaction. By histochemical analysis, we found that Hpa suppresses SA-inducible PR1 expression, specifically in the haustoriated cells into which host-translocated effectors are delivered, but not in non-haustoriated adjacent cells. Finally, we found a highly-expressed Hpa effector candidate that suppresses responsiveness to SA. As this approach can be easily applied to host-pathogen interactions for which both host and pathogen genome sequences are available, this work opens the door towards transcriptome studies in infection biology that should help unravel pathogen infection strategies and the mechanisms by which host defense responses are overcome.

  10. El Niño/Southern Oscillation response to global warming

    PubMed Central

    Latif, M.; Keenlyside, N. S.

    2009-01-01

    The El Niño/Southern Oscillation (ENSO) phenomenon, originating in the Tropical Pacific, is the strongest natural interannual climate signal and has widespread effects on the global climate system and the ecology of the Tropical Pacific. Any strong change in ENSO statistics will therefore have serious climatic and ecological consequences. Most global climate models do simulate ENSO, although large biases exist with respect to its characteristics. The ENSO response to global warming differs strongly from model to model and is thus highly uncertain. Some models simulate an increase in ENSO amplitude, others a decrease, and others virtually no change. Extremely strong changes constituting tipping point behavior are not simulated by any of the models. Nevertheless, some interesting changes in ENSO dynamics can be inferred from observations and model integrations. Although no tipping point behavior is envisaged in the physical climate system, smooth transitions in it may give rise to tipping point behavior in the biological, chemical, and even socioeconomic systems. For example, the simulated weakening of the Pacific zonal sea surface temperature gradient in the Hadley Centre model (with dynamic vegetation included) caused rapid Amazon forest die-back in the mid-twenty-first century, which in turn drove a nonlinear increase in atmospheric CO2, accelerating global warming. PMID:19060210

  11. Mentoring health researchers globally: Diverse experiences, programmes, challenges and responses

    PubMed Central

    Cole, Donald C.; Johnson, Nancy; Mejia, Raul; McCullough, Hazel; Turcotte-Tremblay, Anne-Marie; Barnoya, Joaquin; Falabella Luco, (María) Soledad

    2016-01-01

    ABSTRACT Mentoring experiences and programmes are becoming increasingly recognised as important by those engaged in capacity strengthening in global health research. Using a primarily qualitative study design, we studied three experiences of mentorship and eight mentorship programmes for early career global health researchers based in high-income and low- and middle-income countries. For the latter, we drew upon programme materials, existing unpublished data and more formal mixed-method evaluations, supplemented by individual email questionnaire responses. Research team members wrote stories, and the team assembled and analysed them for key themes. Across the diverse experiences and programmes, key emergent themes included: great mentors inspire others in an inter-generational cascade, mentorship is transformative in personal and professional development and involves reciprocity, and finding the right balance in mentoring relationships and programmes includes responding creatively to failure. Among the challenges encountered were: struggling for more level playing fields for new health researchers globally, changing mindsets in institutions that do not have a culture of mentorship and building collaboration not competition. Mentoring networks spanning institutions and countries using multiple virtual and face-to-face methods are a potential avenue for fostering organisational cultures supporting quality mentorship in global health research. PMID:26234691

  12. Chemopreventive agents alters global gene expression pattern: predicting their mode of action and targets.

    PubMed

    Narayanan, Bhagavathi A

    2006-12-01

    Chemoprevention has the potential to be a major component of colon, breast, prostate and lung cancer control. Epidemiological, experimental, and clinical studies provide evidence that antioxidants, anti-inflammatory agents, n-3 polyunsaturated fatty acids and several other phytochemicals possess unique modes of action against cancer growth. However, the mode of action of several of these agents at the gene transcription level is not completely understood. Completion of the human genome sequence and the advent of DNA microarrays using cDNAs enhanced the detection and identification of hundreds of differentially expressed genes in response to anticancer drugs or chemopreventive agents. In this review, we are presenting an extensive analysis of the key findings from studies using potential chemopreventive agents on global gene expression patterns, which lead to the identification of cancer drug targets. The summary of the study reports discussed in this review explains the extent of gene alterations mediated by more than 20 compounds including antioxidants, fatty acids, NSAIDs, phytochemicals, retinoids, selenium, vitamins, aromatase inhibitor, lovastatin, oltipraz, salvicine, and zinc. The findings from these studies further reveal the utility of DNA microarray in characterizing and quantifying the differentially expressed genes that are possibly reprogrammed by the above agents against colon, breast, prostate, lung, liver, pancreatic and other cancer types. Phenolic antioxidant resveratrol found in berries and grapes inhibits the formation of prostate tumors by acting on the regulatory genes such as p53 while activating a cascade of genes involved in cell cycle and apoptosis including p300, Apaf-1, cdk inhibitor p21, p57 (KIP2), p53 induced Pig 7, Pig 8, Pig 10, cyclin D, DNA fragmentation factor 45. The group of genes significantly altered by selenium includes cyclin D1, cdk5, cdk4, cdk2, cdc25A and GADD 153. Vitamine D shows impact on p21(Waf1/Cip1) p27 cyclin B

  13. Global Magnetospheric Response to an Interplanetary Shock: THEMIS Observations

    NASA Technical Reports Server (NTRS)

    Zhang, Hui; Sibeck, David G.; Zong, Q.-G.; McFadden, James P.; Larson, Davin; Glassmeier, K.-H.; Angelopoulos, V.

    2011-01-01

    We investigate the global response of geospace plasma environment to an interplanetary shock at approx. 0224 UT on May 28, 2008 from multiple THEMIS spacecraft observations in the magnetosheath (THEMIS B and C) and the mid-afternoon (THEMIS A) and dusk magnetosphere (THEMIS D and E). The interaction of the transmitted interplanetary shock with the magnetosphere has global effects. Consequently, it can affect geospace plasma significantly. After interacting with the bow shock, the interplanetary shock transmitted a fast shock and a discontinuity which propagated through the magnetosheath toward the Earth at speeds of 300 km/s and 137 km/s respectively. THEMIS A observations indicate that the plasmaspheric plume changed significantly by the interplanetary shock impact. The plasmaspheric plume density increased rapidly from 10 to 100/ cubic cm in 4 min and the ion distribution changed from isotropic to strongly anisotropic distribution. Electromagnetic ion cyclotron (EMIC) waves observed by THEMIS A are most likely excited by the anisotropic ion distributions caused by the interplanetary shock impact. To our best knowledge, this is the first direct observation of the plasmaspheric plume response to an interplanetary shock's impact. THEMIS A, but not D or E, observed a plasmaspheric plume in the dayside magnetosphere. Multiple spacecraft observations indicate that the dawn-side edge of the plasmaspheric plume was located between THEMIS A and D (or E).

  14. Less approach, more avoidance: Response inhibition has motivational consequences for sexual stimuli that reflect changes in affective value not a lingering global brake on behavior.

    PubMed

    Driscoll, Rachel L; de Launay, Keelia Quinn; Fenske, Mark J

    2018-02-01

    Response inhibition negatively impacts subsequent hedonic evaluations of motivationally relevant stimuli and reduces the behavioral incentive to seek and obtain such items. Here we expand the investigation of the motivational consequences of inhibition by presenting sexually appealing and nonappealing images in a go/no-go task and a subsequent image-viewing task. Each initially obscured image in the viewing task could either be made more visible or less visible by repeatedly pressing different keys. Fewer key presses were made to obtain better views of preferred-sex images when such images had previously been inhibited as no-go items than when previously encountered as noninhibited go items. This finding replicates prior results and is consistent with the possibility that motor-response suppression has lingering effects that include global reductions in all behavioral expression. However, for nonpreferred images, prior inhibition resulted in more key presses to obscure their visibility than when such images had not been inhibited. This novel finding suggests that the motivational consequences of response inhibition are not due to a global brake on action but are instead linked to negative changes in stimulus value that induce corresponding increases in avoidance and decreases in approach.

  15. Mitigation/adaptation and health: health policymaking in the global response to climate change and implications for other upstream determinants.

    PubMed

    Wiley, Lindsay F

    2010-01-01

    The time is ripe for innovation in global health governance if we are to achieve global health and development objectives in the face of formidable challenges. Integration of global health concerns into the law and governance of other, related disciplines should be given high priority. This article explores opportunities for health policymaking in the global response to climate change. Climate change and environmental degradation will affect weather disasters, food and water security, infectious disease patterns, and air pollution. Although scientific research has pointed to the interdependence of the global environment and human health, policymakers have been slow to integrate their approaches to environmental and health concerns. A robust response to climate change will require improved integration on two fronts: health concerns must be given higher priority in the response to climate change and threats associated with climate change and environmental degradation must be more adequately addressed by global health law and governance. The mitigation/adaptation response paradigm developing within and beyond the United Nations Framework Convention on Climate Change provides a useful framework for thinking about global health law and governance with respect to climate change, environmental degradation, and possibly other upstream determinants of health as well. © 2010 American Society of Law, Medicine & Ethics, Inc.

  16. CalQuo: automated, simultaneous single-cell and population-level quantification of global intracellular Ca2+ responses.

    PubMed

    Fritzsche, Marco; Fernandes, Ricardo A; Colin-York, Huw; Santos, Ana M; Lee, Steven F; Lagerholm, B Christoffer; Davis, Simon J; Eggeling, Christian

    2015-11-13

    Detecting intracellular calcium signaling with fluorescent calcium indicator dyes is often coupled with microscopy techniques to follow the activation state of non-excitable cells, including lymphocytes. However, the analysis of global intracellular calcium responses both at the single-cell level and in large ensembles simultaneously has yet to be automated. Here, we present a new software package, CalQuo (Calcium Quantification), which allows the automated analysis and simultaneous monitoring of global fluorescent calcium reporter-based signaling responses in up to 1000 single cells per experiment, at temporal resolutions of sub-seconds to seconds. CalQuo quantifies the number and fraction of responding cells, the temporal dependence of calcium signaling and provides global and individual calcium-reporter fluorescence intensity profiles. We demonstrate the utility of the new method by comparing the calcium-based signaling responses of genetically manipulated human lymphocytic cell lines.

  17. Difference of protein 53 expression based on radiation therapy response in cervical cancer

    NASA Astrophysics Data System (ADS)

    Pasaribu, H. P.; Lubis, L. I.; Dina, S.; Simanjuntak, R. Y.; Siregar, H. S.; Rivany, R.

    2018-03-01

    Cervical cancer is one of most common gynecological cancer in women and the leading cause of death in developing countries. An analytic study with the case-control design was conducted to determine the difference of p53 expression based on radiation therapy response in cervical cancer. The study was performed in Obstetric and Gynecology Department and Pathology Department of Adam Malik General Hospital Medan from January to February 2017. 15 paraffin blocks of acervical cancer patient with incomplete response were obtained as study samples, and 15 paraffin blocks of acervical cancer patient with complete response were obtained as control samples, The samples were collected by consecutive sampling, andan immunohistochemical assessment of p53 expression was done to assessapoptosis count and radiation response. Data were analyzed using Kruskal-Wallis with confidence interval 83.5% and p<0.05 was considered statistically significant. The study found that an increase of p53 expressionin samples with abundant apoptosis (≥5 apoptosis cells/5 HPF), p=0.033, and in incomplete response group, p=0.046. It means that p53 expression before radiation therapy can be used as an early marker for radiation therapy response in cervical cancer.

  18. Understanding amygdala responsiveness to fearful expressions through the lens of psychopathy and altruism.

    PubMed

    Marsh, Abigail A

    2016-06-01

    Because the face is the central focus of human social interactions, emotional facial expressions provide a unique window into the emotional lives of others. They play a particularly important role in fostering empathy, which entails understanding and responding to others' emotions, especially distress-related emotions such as fear. This Review considers how fearful facial as well as vocal and postural expressions are interpreted, with an emphasis on the role of the amygdala. The amygdala may be best known for its role in the acquisition and expression of conditioned fear, but it also supports the perception and recognition of others' fear. Various explanations have been supplied for the amygdala's role in interpreting and responding to fearful expressions. They include theories that amygdala responses to fearful expressions 1) reflect heightened vigilance in response to uncertain danger, 2) promote heightened attention to the eye region of faces, 3) represent a response to an unconditioned aversive stimulus, or 4) reflect the generation of an empathic fear response. Among these, only empathic fear explains why amygdala lesions would impair fear recognition across modalities. Supporting the possibility of a link between fundamental empathic processes and amygdala responses to fear is evidence that impaired fear recognition in psychopathic individuals results from amygdala dysfunction, whereas enhanced fear recognition in altruistic individuals results from enhanced amygdala function. Empathic concern and caring behaviors may be fostered by sensitivity to signs of acute distress in others, which relies on intact functioning of the amygdala. © 2015 Wiley Periodicals, Inc.

  19. Effects of unexpected chords and of performer's expression on brain responses and electrodermal activity.

    PubMed

    Koelsch, Stefan; Kilches, Simone; Steinbeis, Nikolaus; Schelinski, Stefanie

    2008-07-09

    There is lack of neuroscientific studies investigating music processing with naturalistic stimuli, and brain responses to real music are, thus, largely unknown. This study investigates event-related brain potentials (ERPs), skin conductance responses (SCRs) and heart rate (HR) elicited by unexpected chords of piano sonatas as they were originally arranged by composers, and as they were played by professional pianists. From the musical excerpts played by the pianists (with emotional expression), we also created versions without variations in tempo and loudness (without musical expression) to investigate effects of musical expression on ERPs and SCRs. Compared to expected chords, unexpected chords elicited an early right anterior negativity (ERAN, reflecting music-syntactic processing) and an N5 (reflecting processing of meaning information) in the ERPs, as well as clear changes in the SCRs (reflecting that unexpected chords also elicited emotional responses). The ERAN was not influenced by emotional expression, whereas N5 potentials elicited by chords in general (regardless of their chord function) differed between the expressive and the non-expressive condition. These results show that the neural mechanisms of music-syntactic processing operate independently of the emotional qualities of a stimulus, justifying the use of stimuli without emotional expression to investigate the cognitive processing of musical structure. Moreover, the data indicate that musical expression affects the neural mechanisms underlying the processing of musical meaning. Our data are the first to reveal influences of musical performance on ERPs and SCRs, and to show physiological responses to unexpected chords in naturalistic music.

  20. Effects of Unexpected Chords and of Performer's Expression on Brain Responses and Electrodermal Activity

    PubMed Central

    Koelsch, Stefan; Kilches, Simone; Steinbeis, Nikolaus; Schelinski, Stefanie

    2008-01-01

    Background There is lack of neuroscientific studies investigating music processing with naturalistic stimuli, and brain responses to real music are, thus, largely unknown. Methodology/Principal Findings This study investigates event-related brain potentials (ERPs), skin conductance responses (SCRs) and heart rate (HR) elicited by unexpected chords of piano sonatas as they were originally arranged by composers, and as they were played by professional pianists. From the musical excerpts played by the pianists (with emotional expression), we also created versions without variations in tempo and loudness (without musical expression) to investigate effects of musical expression on ERPs and SCRs. Compared to expected chords, unexpected chords elicited an early right anterior negativity (ERAN, reflecting music-syntactic processing) and an N5 (reflecting processing of meaning information) in the ERPs, as well as clear changes in the SCRs (reflecting that unexpected chords also elicited emotional responses). The ERAN was not influenced by emotional expression, whereas N5 potentials elicited by chords in general (regardless of their chord function) differed between the expressive and the non-expressive condition. Conclusions/Significance These results show that the neural mechanisms of music-syntactic processing operate independently of the emotional qualities of a stimulus, justifying the use of stimuli without emotional expression to investigate the cognitive processing of musical structure. Moreover, the data indicate that musical expression affects the neural mechanisms underlying the processing of musical meaning. Our data are the first to reveal influences of musical performance on ERPs and SCRs, and to show physiological responses to unexpected chords in naturalistic music. PMID:18612459

  1. Drug effects on responses to emotional facial expressions: recent findings

    PubMed Central

    Miller, Melissa A.; Bershad, Anya K.; de Wit, Harriet

    2016-01-01

    Many psychoactive drugs increase social behavior and enhance social interactions, which may, in turn, increase their attractiveness to users. Although the psychological mechanisms by which drugs affect social behavior are not fully understood, there is some evidence that drugs alter the perception of emotions in others. Drugs can affect the ability to detect, attend to, and respond to emotional facial expressions, which in turn may influence their use in social settings. Either increased reactivity to positive expressions or decreased response to negative expressions may facilitate social interaction. This article reviews evidence that psychoactive drugs alter the processing of emotional facial expressions using subjective, behavioral, and physiological measures. The findings lay the groundwork for better understanding how drugs alter social processing and social behavior more generally. PMID:26226144

  2. Drug effects on responses to emotional facial expressions: recent findings.

    PubMed

    Miller, Melissa A; Bershad, Anya K; de Wit, Harriet

    2015-09-01

    Many psychoactive drugs increase social behavior and enhance social interactions, which may, in turn, increase their attractiveness to users. Although the psychological mechanisms by which drugs affect social behavior are not fully understood, there is some evidence that drugs alter the perception of emotions in others. Drugs can affect the ability to detect, attend to, and respond to emotional facial expressions, which in turn may influence their use in social settings. Either increased reactivity to positive expressions or decreased response to negative expressions may facilitate social interaction. This article reviews evidence that psychoactive drugs alter the processing of emotional facial expressions using subjective, behavioral, and physiological measures. The findings lay the groundwork for better understanding how drugs alter social processing and social behavior more generally.

  3. Expressive inhibition in response to stress: Implications for emotional processing following trauma

    PubMed Central

    Clapp, Joshua D.; Patton, Samantha C.; Beck, J. Gayle

    2015-01-01

    Expressive inhibition - the willful restriction of expressed emotion - is documented in individuals reporting trauma-related distress, but its impact on global affective functioning remains unclear. Theoretical models propose that chronic activation of negative emotion and deliberate restriction of affect operate synergistically to produce trauma-related emotional deficits. The current project examined the impact of these factors on subjective experience and physiological activation following exposure to an analog trauma. University students (N = 192; Mage = 20, 57% female, 42% White/Non-Hispanic) viewed a graphic film depicting scenes of a televised suicide. Participants then viewed either a sadness- or humor-eliciting film under instructions to inhibit [nsadness = 45, nhumor = 52] or naturally express emotion [nsadness = 48, nhumor = 47]. Expressive inhibition was associated with restricted amusement specifically among participants viewing the humor film. Inhibition also produced attenuated sympathetic and parasympathetic recovery, irrespective of film assignment. Evidence of disruptions in emotional processing supports models identifying inhibition as a possible mechanism in post-trauma affect dysregulation. PMID:25576773

  4. Transgenic carrot expressing fusion protein comprising M. tuberculosis antigens induces immune response in mice.

    PubMed

    Permyakova, Natalia V; Zagorskaya, Alla A; Belavin, Pavel A; Uvarova, Elena A; Nosareva, Olesya V; Nesterov, Andrey E; Novikovskaya, Anna A; Zav'yalov, Evgeniy L; Moshkin, Mikhail P; Deineko, Elena V

    2015-01-01

    Tuberculosis remains one of the major infectious diseases, which continues to pose a major global health problem. Transgenic plants may serve as bioreactors to produce heterologous proteins including antibodies, antigens, and hormones. In the present study, a genetic construct has been designed that comprises the Mycobacterium tuberculosis genes cfp10, esat6 and dIFN gene, which encode deltaferon, a recombinant analog of the human γ-interferon designed for expression in plant tissues. This construct was transferred to the carrot (Daucus carota L.) genome by Agrobacterium-mediated transformation. This study demonstrates that the fusion protein CFP10-ESAT6-dIFN is synthesized in the transgenic carrot storage roots. The protein is able to induce both humoral and cell-mediated immune responses in laboratory animals (mice) when administered either orally or by injection. It should be emphasized that M. tuberculosis antigens contained in the fusion protein have no cytotoxic effect on peripheral blood mononuclear cells.

  5. The Power of an Infant's Smile: Maternal Physiological Responses to Infant Emotional Expressions.

    PubMed

    Mizugaki, Sanae; Maehara, Yukio; Okanoya, Kazuo; Myowa-Yamakoshi, Masako

    2015-01-01

    Infant emotional expressions, such as distress cries, evoke maternal physiological reactions. Most of which involve accelerated sympathetic nervous activity. Comparatively little is known about effects of positive infant expressions, such as happy smiles, on maternal physiological responses. This study investigated how physiological and psychological maternal states change in response to infants' emotional expressions. Thirty first-time mothers viewed films of their own 6- to 7-month-old infants' affective behavior. Each observed a video of a distress cry followed by a video showing one of two expressions (randomly assigned): a happy smiling face (smile condition) or a calm neutral face (neutral condition). Both before and after the session, participants completed a self-report inventory assessing their emotional states. The results of the self-report inventory revealed no effects of exposure to the infant videos. However, the mothers in the smile condition, but not in the neutral condition, showed deceleration of skin conductance. These findings demonstrate that the mothers who observed their infants smiling showed decreased sympathetic activity. We propose that an infant's positive emotional expression may affect the branch of the maternal stress-response system that modulates the homeostatic balance of the sympathetic and parasympathetic nervous systems.

  6. Plant molecular responses to the elevated ambient temperatures expected under global climate change.

    PubMed

    Fei, Qionghui; Li, Jingjing; Luo, Yunhe; Ma, Kun; Niu, Bingtao; Mu, Changjun; Gao, Huanhuan; Li, Xiaofeng

    2018-01-02

    Environmental temperatures affect plant distribution, growth, and development. The Intergovernmental Panel on Climate Change (IPCC) predicts that global temperatures will rise by at least 1.5°C by the end of this century. Global temperature changes have already had a discernable impact on agriculture, phenology, and ecosystems. At the molecular level, extensive literature exists on the mechanism controlling plant responses to high temperature stress. However, few studies have focused on the molecular mechanisms behind plant responses to mild increases in ambient temperature. Previous research has found that moderately higher ambient temperatures can induce hypocotyl elongation and early flowering. Recent evidence demonstrates roles for the phytohormones auxin and ethylene in adaptive growth of plant roots to slightly higher ambient temperatures.

  7. Adverse remodeling of the electrophysiological response to ischemia-reperfusion in human heart failure is associated with remodeling of metabolic gene expression.

    PubMed

    Ng, Fu Siong; Holzem, Katherine M; Koppel, Aaron C; Janks, Deborah; Gordon, Fabiana; Wit, Andrew L; Peters, Nicholas S; Efimov, Igor R

    2014-10-01

    Ventricular arrhythmias occur more frequently in heart failure during episodes of ischemia-reperfusion although the mechanisms underlying this in humans are unclear. We assessed, in explanted human hearts, the remodeled electrophysiological response to acute ischemia-reperfusion in heart failure and its potential causes, including the remodeling of metabolic gene expression. We optically mapped coronary-perfused left ventricular wedge preparations from 6 human end-stage failing hearts (F) and 6 donor hearts rejected for transplantation (D). Preparations were subjected to 30 minutes of global ischemia, followed by 30 minutes of reperfusion. Failing hearts had exaggerated electrophysiological responses to ischemia-reperfusion, with greater action potential duration shortening (P<0.001 at 8-minute ischemia; P=0.001 at 12-minute ischemia) and greater conduction slowing during ischemia, delayed recovery of electric excitability after reperfusion (F, 4.8±1.8 versus D, 1.0±0 minutes; P<0.05), and incomplete restoration of action potential duration and conduction velocity early after reperfusion. Expression of 46 metabolic genes was probed using custom-designed TaqMan arrays, using extracted RNA from 15 failing and 9 donor hearts. Ten genes important in cardiac metabolism were downregulated in heart failure, with SLC27A4 and KCNJ11 significantly downregulated at a false discovery rate of 0%. We demonstrate, for the first time in human hearts, that the electrophysiological response to ischemia-reperfusion in heart failure is accelerated during ischemia with slower recovery after reperfusion. This can enhance spatial conduction and repolarization gradients across the ischemic border and increase arrhythmia susceptibility. This adverse response was associated with downregulation of expression of cardiac metabolic genes. © 2014 American Heart Association, Inc.

  8. Widespread expression of prostate apoptosis response-4 in nasopharyngeal carcinoma.

    PubMed

    Lee, Jeng-Woei; Hsiao, Wei-Ting; Lee, Kuei-Fang; Sheu, Lai-Fa; Hsu, Hsue-Yin; Hsu, Lee-Ping; Su, Borcherng; Lee, Moon-Sing; Hsu, Yih-Chih; Chang, Chung-Hsing

    2010-07-01

    Prostate apoptosis response-4 (Par-4) augments apoptosis in various tumors, either during apoptotic insult or by ectopic overexpression. However, investigation of Par-4 expression in nasopharyngeal carcinoma (NPC) is lacking. Specimens from patients with NPC, hypopharyngeal carcinoma (HPC), or oral cavity cancer were examined for Par-4 expression using immunohistochemistry. NPC cell proliferation and apoptosis were analyzed using immunohistochemical staining for Ki67, B-cell lymphoma 2 (Bcl-2), and in situ terminal deoxyribonucleotidyl transferase (TdT)-mediated biotin-16-dUTP nick end-labeling (TUNEL) assay, respectively. Par-4 was ubiquitously expressed in NPC biopsies (96.2%, 25/26) and was significantly higher than in HPC (47.6%, 50/105, p < .0001) and oral cavity cancers (38.7%, 12/31, p < .0001). Remarkably, apoptosis of NPC cells was absent and Par-4 expression was associated with obvious expression of Bcl-2 and Ki67 in all patients tested with NPC. Immunohistochemistry results showed widespread expression of Par-4 in NPC and revealed sustainable proliferation of NPC cells regardless of Par-4 expression. .(c) 2009 Wiley Periodicals, Inc.

  9. Predicting the Responses of Soil Nitrite-Oxidizers to Multi-Factorial Global Change: A Trait-Based Approach

    DOE PAGES

    Le Roux, Xavier; Bouskill, Nicholas J.; Niboyet, Audrey; ...

    2016-05-17

    Soil microbial diversity is huge and a few grams of soil contain more bacterial taxa than there are bird species on Earth. This high diversity often makes predicting the responses of soil bacteria to environmental change intractable and restricts our capacity to predict the responses of soil functions to global change. Here, using a long-term field experiment in a California grassland, we studied the main and interactive effects of three global change factors (increased atmospheric CO 2 concentration, precipitation and nitrogen addition, and all their factorial combinations, based on global change scenarios for central California) on the potential activity, abundancemore » and dominant taxa of soil nitrite-oxidizing bacteria (NOB). Using a trait-based model, we then tested whether categorizing NOB into a few functional groups unified by physiological traits enables understanding and predicting how soil NOB respond to global environmental change. Contrasted responses to global change treatments were observed between three main NOB functional types. In particular, putatively mixotrophic Nitrobacter, rare under most treatments, became dominant under the 'High CO 2 +Nitrogen+Precipitation' treatment. The mechanistic trait-based model, which simulated ecological niches of NOB types consistent with previous ecophysiological reports, helped predicting the observed effects of global change on NOB and elucidating the underlying biotic and abiotic controls. Our results are a starting point for representing the overwhelming diversity of soil bacteria by a few functional types that can be incorporated into models of terrestrial ecosystems and biogeochemical processes.« less

  10. Predicting the Responses of Soil Nitrite-Oxidizers to Multi-Factorial Global Change: A Trait-Based Approach

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Le Roux, Xavier; Bouskill, Nicholas J.; Niboyet, Audrey

    Soil microbial diversity is huge and a few grams of soil contain more bacterial taxa than there are bird species on Earth. This high diversity often makes predicting the responses of soil bacteria to environmental change intractable and restricts our capacity to predict the responses of soil functions to global change. Here, using a long-term field experiment in a California grassland, we studied the main and interactive effects of three global change factors (increased atmospheric CO 2 concentration, precipitation and nitrogen addition, and all their factorial combinations, based on global change scenarios for central California) on the potential activity, abundancemore » and dominant taxa of soil nitrite-oxidizing bacteria (NOB). Using a trait-based model, we then tested whether categorizing NOB into a few functional groups unified by physiological traits enables understanding and predicting how soil NOB respond to global environmental change. Contrasted responses to global change treatments were observed between three main NOB functional types. In particular, putatively mixotrophic Nitrobacter, rare under most treatments, became dominant under the 'High CO 2 +Nitrogen+Precipitation' treatment. The mechanistic trait-based model, which simulated ecological niches of NOB types consistent with previous ecophysiological reports, helped predicting the observed effects of global change on NOB and elucidating the underlying biotic and abiotic controls. Our results are a starting point for representing the overwhelming diversity of soil bacteria by a few functional types that can be incorporated into models of terrestrial ecosystems and biogeochemical processes.« less

  11. Meta-analysis of human gene expression in response to Mycobacterium tuberculosis infection reveals potential therapeutic targets.

    PubMed

    Wang, Zhang; Arat, Seda; Magid-Slav, Michal; Brown, James R

    2018-01-10

    With the global emergence of multi-drug resistant strains of Mycobacterium tuberculosis, new strategies to treat tuberculosis are urgently needed such as therapeutics targeting potential human host factors. Here we performed a statistical meta-analysis of human gene expression in response to both latent and active pulmonary tuberculosis infections from nine published datasets. We found 1655 genes that were significantly differentially expressed during active tuberculosis infection. In contrast, no gene was significant for latent tuberculosis. Pathway enrichment analysis identified 90 significant canonical human pathways, including several pathways more commonly related to non-infectious diseases such as the LRRK2 pathway in Parkinson's disease, and PD-1/PD-L1 signaling pathway important for new immuno-oncology therapies. The analysis of human genome-wide association studies datasets revealed tuberculosis-associated genetic variants proximal to several genes in major histocompatibility complex for antigen presentation. We propose several new targets and drug-repurposing opportunities including intravenous immunoglobulin, ion-channel blockers and cancer immuno-therapeutics for development as combination therapeutics with anti-mycobacterial agents. Our meta-analysis provides novel insights into host genes and pathways important for tuberculosis and brings forth potential drug repurposing opportunities for host-directed therapies.

  12. ALK Inhibitor Response in Melanomas Expressing EML4-ALK Fusions and Alternate ALK Isoforms.

    PubMed

    Couts, Kasey L; Bemis, Judson; Turner, Jacqueline A; Bagby, Stacey M; Murphy, Danielle; Christiansen, Jason; Hintzsche, Jennifer D; Le, Anh; Pitts, Todd M; Wells, Keith; Applegate, Allison; Amato, Carol; Multani, Pratik; Chow-Maneval, Edna; Tentler, John J; Shellman, Yiqun G; Rioth, Matthew J; Tan, Aik-Choon; Gonzalez, Rene; Medina, Theresa; Doebele, Robert C; Robinson, William A

    2018-01-01

    Oncogenic ALK fusions occur in several types of cancer and can be effectively treated with ALK inhibitors; however, ALK fusions and treatment response have not been characterized in malignant melanomas. Recently, a novel isoform of ALK ( ALK ATI ) was reported in 11% of melanomas but the response of melanomas expressing ALK ATI to ALK inhibition has not been well characterized. We analyzed 45 melanoma patient-derived xenograft models for ALK mRNA and protein expression. ALK expression was identified in 11 of 45 (24.4%) melanomas. Ten melanomas express wild-type (wt) ALK and/or ALK ATI and one mucosal melanoma expresses multiple novel EML4-ALK fusion variants. Melanoma cells expressing different ALK variants were tested for response to ALK inhibitors. Whereas the melanoma expressing EML4-ALK were sensitive to ALK inhibitors in vitro and in vivo , the melanomas expressing wt ALK or ALK ATI were not sensitive to ALK inhibitors. In addition, a patient with mucosal melanoma expressing ALK ATI was treated with an ALK/ROS1/TRK inhibitor (entrectinib) on a phase I trial but did not respond. Our results demonstrate ALK fusions occur in malignant melanomas and respond to targeted therapy, whereas melanomas expressing ALK ATI do not respond to ALK inhibitors. Targeting ALK fusions is an effective therapeutic option for a subset of melanoma patients, but additional clinical studies are needed to determine the efficacy of targeted therapies in melanomas expressing wt ALK or ALK ATI Mol Cancer Ther; 17(1); 222-31. ©2017 AACR . ©2017 American Association for Cancer Research.

  13. Fly-By medical care: Conceptualizing the global and local social responsibilities of medical tourists and physician voluntourists.

    PubMed

    Snyder, Jeremy; Dharamsi, Shafik; Crooks, Valorie A

    2011-04-06

    Medical tourism is a global health practice where patients travel abroad to receive health care. Voluntourism is a practice where physicians travel abroad to deliver health care. Both of these practices often entail travel from high income to low and middle income countries and both have been associated with possible negative impacts. In this paper, we explore the social responsibilities of medical tourists and voluntourists to identify commonalities and distinctions that can be used to develop a wider understanding of social responsibility in global health care practices. Social responsibility is a responsibility to promote the welfare of the communities to which one belongs or with which one interacts. Physicians stress their social responsibility to care for the welfare of their patients and their domestic communities. When physicians choose to travel to another county to provide medical care, this social responsibility is expanded to this new community. Patients too have a social responsibility to use their community's health resources efficiently and to promote the health of their community. When these patients choose to go abroad to receive medical care, this social responsibility applies to the new community as well. While voluntourists and medical tourists both see the scope of their social responsibilities expand by engaging in these global practices, the social responsibilities of physician voluntourists are much better defined than those of medical tourists. Guidelines for engaging in ethical voluntourism and training for voluntourists still need better development, but medical tourism as a practice should follow the lead of voluntourism by developing clearer norms for ethical medical tourism. Much can be learned by examining the social responsibilities of medical tourists and voluntourists when they engage in global health practices. While each group needs better guidance for engaging in responsible forms of these practices, patients are at a

  14. Fly-By medical care: Conceptualizing the global and local social responsibilities of medical tourists and physician voluntourists

    PubMed Central

    2011-01-01

    Background Medical tourism is a global health practice where patients travel abroad to receive health care. Voluntourism is a practice where physicians travel abroad to deliver health care. Both of these practices often entail travel from high income to low and middle income countries and both have been associated with possible negative impacts. In this paper, we explore the social responsibilities of medical tourists and voluntourists to identify commonalities and distinctions that can be used to develop a wider understanding of social responsibility in global health care practices. Discussion Social responsibility is a responsibility to promote the welfare of the communities to which one belongs or with which one interacts. Physicians stress their social responsibility to care for the welfare of their patients and their domestic communities. When physicians choose to travel to another county to provide medical care, this social responsibility is expanded to this new community. Patients too have a social responsibility to use their community's health resources efficiently and to promote the health of their community. When these patients choose to go abroad to receive medical care, this social responsibility applies to the new community as well. While voluntourists and medical tourists both see the scope of their social responsibilities expand by engaging in these global practices, the social responsibilities of physician voluntourists are much better defined than those of medical tourists. Guidelines for engaging in ethical voluntourism and training for voluntourists still need better development, but medical tourism as a practice should follow the lead of voluntourism by developing clearer norms for ethical medical tourism. Summary Much can be learned by examining the social responsibilities of medical tourists and voluntourists when they engage in global health practices. While each group needs better guidance for engaging in responsible forms of these practices

  15. The financial crisis and global health: the International Monetary Fund's (IMF) policy response.

    PubMed

    Ruckert, Arne; Labonté, Ronald

    2013-09-01

    In this article, we interrogate the policy response of the International Monetary Fund (IMF) to the global financial crisis, and discuss the likely global health implications, especially in low-income countries. In doing so, we ask if the IMF has meaningfully loosened its fiscal deficit targets in light of the economic challenges posed by the financial crisis and adjusted its macro-economic policy advice to this new reality; or has the rhetoric of counter-cyclical spending failed to translate into additional fiscal space for IMF loan-recipient countries, with negative health consequences? To answer these questions, we assess several post-crisis IMF lending agreements with countries requiring financial assistance, and draw upon recent academic studies and civil society reports examining policy conditionalities still being prescribed by the IMF. We also reference recent studies examining the health impacts of these conditionalities. We demonstrate that while the IMF has been somewhat more flexible in its crisis response than in previous episodes of financial upheaval, there has been no meaningful rethinking in the application of dominant neoliberal macro-economic policies. After showing some flexibility in the initial crisis response, the IMF is pushing for excessive contraction in most low and middle-income countries. We conclude that there remains a wide gap between the rhetoric and the reality of the IMF's policy and programming advice, with negative implications for global health.

  16. De Novo assembly of expressed transcripts and global transcriptomic analysis from seedlings of the paper mulberry (Broussonetia kazinoki x Broussonetia papyifera).

    PubMed

    Xianjun, Peng; Linhong, Teng; Xiaoman, Wang; Yucheng, Wang; Shihua, Shen

    2014-01-01

    The paper mulberry is one of the multifunctional tree species in agroforestry systems and is also commonly utilized in traditional medicine in China and other Asian countries. However, little is known about its molecular genetics, which hinders research on and exploitation of this valuable resource. To discern the correlation between gene expression and the essential properties of the paper mulberry, we performed a transcriptomics analysis, assembling a total of 37,725 unigenes from 54,638,676 reads generated by RNA-seq. Among these, 22,692 unigenes showed greater than 60% similarity with genes from other species. The lengths of 13,566 annotated unigenes were longer than 1,000 bp. Functional clustering analysis with COG (Cluster of Orthologous Groups) revealed that 17,184 unigenes are primarily involved in transcription, translation, signal transduction, carbohydrate metabolism, secondary metabolism, and energy metabolism. GO (Gene Ontology) annotation suggests enrichment of genes encoding antioxidant activity, transporter activity, biosynthesis, metabolism and stress response, with a total of 30,659 unigenes falling in these categories. KEGG (Kyoto Encyclopedia of Genes and Genomes) metabolic pathway analysis showed that 7,199 unigenes are associated with 119 metabolic pathways. In addition to the basic metabolism, these genes are enriched for plant pathogen interaction, flavonoid metabolism and other secondary metabolic processes. Furthermore, differences in the transcriptomes of leaf, stem and root tissues were analyzed and 7,233 specifically expressed unigenes were identified. This global expression analysis provided novel insights about the molecular mechanisms of the biosynthesis of flavonoid, lignin and cellulose, as well as on the response to biotic and abiotic stresses including the remediation of contaminated soil by the paper mulberry.

  17. Global Soil Respiration: Interaction with Environmental Variables and Response to Climate Change

    NASA Astrophysics Data System (ADS)

    Jian, J.; Steele, M.

    2016-12-01

    Background, methods, objectivesTerrestrial ecosystems take up around 1.7 Pg C per year; however, the role of terrestrial ecosystems as a carbon sink may change to carbon source by 2050, as a result of positive feedback of soil respiration response to global warming. Nevertheless, limited evidence shows that soil carbon is decreasing and the role of terrestrial ecosystems is changing under warming. One possibility is the positive feedback may slow due to the acclimation of soil respiration as a result of decreasing temperature sensitivity (Q10) with warming. To verify and quantify the uncertainty in soil carbon cycling and feedbacks to climate change, we assembled soil respiration observations from 1961 to 2014 from 724 publications into a monthly global soil respiration database (MSRDB), which included 13482 soil respiration measurements together with 38 other ancillary measurements from 538 sites. Using this database we examined macroscale variation in the relationship between soil respiration and air temperature, precipitation, leaf area index and soil properties. We also quantified global soil respiration, the sources of uncertainty, and its feedback to warming based on climate region-oriented models with variant Q10function. Results and ConclusionsOur results showed substantial heterogeneity in the relationship between soil respiration and environmental factors across different climate regions. For example, soil respiration was strongly related to vegetation (via leaf area index) in colder regions, but not in tropical region. Only in tropical and arid regions did soil properties explain any variation in soil respiration. Global annual mean soil respiration from 1961 to 2014 was estimated to be 72.41 Pg C yr-1 based on monthly global soil respiration database, 25 Pg lower than estimated based on yearly soil respiration database. By using the variable Q10 models, we estimated that global soil respiration increased at a rate of 0.03 Pg C yr-1 from 1961 to 2014

  18. Changes in aridity in response to the global warming hiatus

    NASA Astrophysics Data System (ADS)

    Guan, Xiaodan; Huang, Jianping; Guo, Ruixia

    2017-02-01

    The global warming slowdown or warming hiatus, began around the year 2000 and has persisted for nearly 15 years. Most studies have focused on the interpretation of the hiatus in temperature. In this study, changes in a global aridity index (AI) were analyzed by using a newly developed dynamical adjustment method that can successfully identify and separate dynamically induced and radiatively forced aridity changes in the raw data. The AI and Palmer Drought Severity Index produced a wetting zone over the mid-to-high latitudes of the Northern Hemisphere in recent decades. The dynamical adjustment analysis suggested that this wetting zone occurred in response to the global warming hiatus. The dynamically induced AI (DAI) played a major role in the AI changes during the hiatus period, and its relationships with the North Atlantic Oscillation (NAO), Pacific Decadal Oscillation (PDO), and Atlantic Multi-decadal Oscillation (AMO) also indicated that different phases of the NAO, PDO, and AMO contributed to different performances of the DAI over the Northern Hemisphere. Although the aridity wetting over the mid-to-high latitudes may relieve long-term drying in certain regions, the hiatus is temporary, and so is the relief. Accelerated global warming will return when the NAO, PDO, and AMO revert to their opposite phases in the future, and the wetting zone is likely to disappear.

  19. Annotation of Differential Gene Expression in Small Yellow Follicles of a Broiler-Type Strain of Taiwan Country Chickens in Response to Acute Heat Stress.

    PubMed

    Cheng, Chuen-Yu; Tu, Wei-Lin; Wang, Shih-Han; Tang, Pin-Chi; Chen, Chih-Feng; Chen, Hsin-Hsin; Lee, Yen-Pai; Chen, Shuen-Ei; Huang, San-Yuan

    2015-01-01

    This study investigated global gene expression in the small yellow follicles (6-8 mm diameter) of broiler-type B strain Taiwan country chickens (TCCs) in response to acute heat stress. Twelve 30-wk-old TCC hens were divided into four groups: control hens maintained at 25°C and hens subjected to 38°C acute heat stress for 2 h without recovery (H2R0), with 2-h recovery (H2R2), and with 6-h recovery (H2R6). Small yellow follicles were collected for RNA isolation and microarray analysis at the end of each time point. Results showed that 69, 51, and 76 genes were upregulated and 58, 15, 56 genes were downregulated after heat treatment of H2R0, H2R2, and H2R6, respectively, using a cutoff value of two-fold or higher. Gene ontology analysis revealed that these differentially expressed genes are associated with the biological processes of cell communication, developmental process, protein metabolic process, immune system process, and response to stimuli. Upregulation of heat shock protein 25, interleukin 6, metallopeptidase 1, and metalloproteinase 13, and downregulation of type II alpha 1 collagen, discoidin domain receptor tyrosine kinase 2, and Kruppel-like factor 2 suggested that acute heat stress induces proteolytic disintegration of the structural matrix and inflamed damage and adaptive responses of gene expression in the follicle cells. These suggestions were validated through gene expression, using quantitative real-time polymerase chain reaction. Functional annotation clarified that interleukin 6-related pathways play a critical role in regulating acute heat stress responses in the small yellow follicles of TCC hens.

  20. Annotation of Differential Gene Expression in Small Yellow Follicles of a Broiler-Type Strain of Taiwan Country Chickens in Response to Acute Heat Stress

    PubMed Central

    Wang, Shih-Han; Tang, Pin-Chi; Chen, Chih-Feng; Chen, Hsin-Hsin; Lee, Yen-Pai; Chen, Shuen-Ei; Huang, San-Yuan

    2015-01-01

    This study investigated global gene expression in the small yellow follicles (6–8 mm diameter) of broiler-type B strain Taiwan country chickens (TCCs) in response to acute heat stress. Twelve 30-wk-old TCC hens were divided into four groups: control hens maintained at 25°C and hens subjected to 38°C acute heat stress for 2 h without recovery (H2R0), with 2-h recovery (H2R2), and with 6-h recovery (H2R6). Small yellow follicles were collected for RNA isolation and microarray analysis at the end of each time point. Results showed that 69, 51, and 76 genes were upregulated and 58, 15, 56 genes were downregulated after heat treatment of H2R0, H2R2, and H2R6, respectively, using a cutoff value of two-fold or higher. Gene ontology analysis revealed that these differentially expressed genes are associated with the biological processes of cell communication, developmental process, protein metabolic process, immune system process, and response to stimuli. Upregulation of heat shock protein 25, interleukin 6, metallopeptidase 1, and metalloproteinase 13, and downregulation of type II alpha 1 collagen, discoidin domain receptor tyrosine kinase 2, and Kruppel-like factor 2 suggested that acute heat stress induces proteolytic disintegration of the structural matrix and inflamed damage and adaptive responses of gene expression in the follicle cells. These suggestions were validated through gene expression, using quantitative real-time polymerase chain reaction. Functional annotation clarified that interleukin 6-related pathways play a critical role in regulating acute heat stress responses in the small yellow follicles of TCC hens. PMID:26587838

  1. Improving Global Building Exposure Data for Disaster Forecasting, Mitigation, and Response

    NASA Astrophysics Data System (ADS)

    Chen, R. S.; Huyck, C.; Lewis, G.; Becker, M.; Vinay, S.; Tralli, D.; Eguchi, R.

    2013-12-01

    This paper describes an exploratory study being performed under the NASA Applied Sciences Program where the goal is to integrate Earth science data and information for disaster forecasting, mitigation and response. Specifically, we are delivering EO-derived built environment data and information for use in catastrophe (CAT) models and loss estimation tools. CAT models and loss estimation tools typically use GIS exposure databases to characterize the real-world environment. These datasets are often a source of great uncertainty in the loss estimates, particularly in international events, because the data are incomplete, and sometimes inaccurate and disparate in quality from one region to another. Preliminary research by project team members as part of the Global Earthquake Model (GEM) consortium suggests that a strong relationship exists between the height and volume of built-up areas and NASA data products from the Suomi National Polar-Orbiting Partnership (NPP) Visible Infrared Imaging Radiometer Suite (VIIRS), the Moderate Resolution Imaging Spectroradiometer (MODIS), and the NASA Socioeconomic Data and Applications Center (SEDAC). Applying this knowledge within the framework of the GEM Global Exposure Database (GED) is significantly enhancing our ability to quantify building exposure, particularly in developing countries and emerging insurance markets. Global insurance products that have a more comprehensive basis for assessing risk and exposure - as from EO-derived data and information assimilated into CAT models and loss estimation tools - will help a) help to transform the way in which we measure, monitor and assess the vulnerability of our communities globally, and in turn, b) help encourage the investments needed - especially in the developing world - stimulating economic growth and actions that would lead to a more disaster-resilient world. Improved building exposure data will also be valuable for near-real time applications such as emergency response

  2. Transcriptional regulation of brain gene expression in response to a territorial intrusion

    PubMed Central

    Sanogo, Yibayiri O.; Band, Mark; Blatti, Charles; Sinha, Saurabh; Bell, Alison M.

    2012-01-01

    Aggressive behaviour associated with territorial defence is widespread and has fitness consequences. However, excess aggression can interfere with other important biological functions such as immunity and energy homeostasis. How the expression of complex behaviours such as aggression is regulated in the brain has long intrigued ethologists, but has only recently become amenable for molecular dissection in non-model organisms. We investigated the transcriptomic response to territorial intrusion in four brain regions in breeding male threespined sticklebacks using expression microarrays and quantitative polymerase chain reaction (qPCR). Each region of the brain had a distinct genomic response to a territorial challenge. We identified a set of genes that were upregulated in the diencephalon and downregulated in the cerebellum and the brain stem. Cis-regulatory network analysis suggested transcription factors that regulated or co-regulated genes that were consistently regulated in all brain regions and others that regulated gene expression in opposing directions across brain regions. Our results support the hypothesis that territorial animals respond to social challenges via transcriptional regulation of genes in different brain regions. Finally, we found a remarkably close association between gene expression and aggressive behaviour at the individual level. This study sheds light on the molecular mechanisms in the brain that underlie the response to social challenges. PMID:23097509

  3. Global Mineralogical and Aqueous Mars History Derived from OMEGA/Mars Express Data

    NASA Astrophysics Data System (ADS)

    Bibring, Jean-Pierre; Langevin, Yves; Mustard, John F.; Poulet, François; Arvidson, Raymond; Gendrin, Aline; Gondet, Brigitte; Mangold, Nicolas; Pinet, P.; Forget, F.; OMEGA Team; Berthé, Michel; Gomez, Cécile; Jouglet, Denis; Soufflot, Alain; Vincendon, Mathieu; Combes, Michel; Drossart, Pierre; Encrenaz, Thérèse; Fouchet, Thierry; Merchiorri, Riccardo; Belluci, GianCarlo; Altieri, Francesca; Formisano, Vittorio; Capaccioni, Fabricio; Cerroni, Pricilla; Coradini, Angioletta; Fonti, Sergio; Korablev, Oleg; Kottsov, Volodia; Ignatiev, Nikolai; Moroz, Vassilli; Titov, Dimitri; Zasova, Ludmilla; Loiseau, Damien; Pinet, Patrick; Doute, Sylvain; Schmitt, Bernard; Sotin, Christophe; Hauber, Ernst; Hoffmann, Harald; Jaumann, Ralf; Keller, Uwe; Arvidson, Ray; Duxbury, Tom; Neukum, G.

    2006-04-01

    Global mineralogical mapping of Mars by the Observatoire pour la Mineralogie, l'Eau, les Glaces et l'Activité (OMEGA) instrument on the European Space Agency's Mars Express spacecraft provides new information on Mars' geological and climatic history. Phyllosilicates formed by aqueous alteration very early in the planet's history (the ``phyllocian'' era) are found in the oldest terrains; sulfates were formed in a second era (the ``theiikian'' era) in an acidic environment. Beginning about 3.5 billion years ago, the last era (the ``siderikian'') is dominated by the formation of anhydrous ferric oxides in a slow superficial weathering, without liquid water playing a major role across the planet.

  4. Strongly-motivated positive affects induce faster responses to local than global information of visual stimuli: an approach using large-size Navon letters.

    PubMed

    Noguchi, Yasuki; Tomoike, Kouta

    2016-01-12

    Recent studies argue that strongly-motivated positive emotions (e.g. desire) narrow a scope of attention. This argument is mainly based on an observation that, while humans normally respond faster to global than local information of a visual stimulus (global advantage), positive affects eliminated the global advantage by selectively speeding responses to local (but not global) information. In other words, narrowing of attentional scope was indirectly evidenced by the elimination of global advantage (the same speed of processing between global and local information). No study has directly shown that strongly-motivated positive affects induce faster responses to local than global information while excluding a bias for global information (global advantage) in a baseline (emotionally-neutral) condition. In the present study, we addressed this issue by eliminating the global advantage in a baseline (neutral) state. Induction of positive affects under this state resulted in faster responses to local than global information. Our results provided direct evidence that positive affects in high motivational intensity narrow a scope of attention.

  5. In tobacco BY-2 cells xyloglucan oligosaccharides alter the expression of genes involved in cell wall metabolism, signalling, stress responses, cell division and transcriptional control.

    PubMed

    González-Pérez, Lien; Perrotta, Lara; Acosta, Alexis; Orellana, Esteban; Spadafora, Natasha; Bruno, Leonardo; Bitonti, Beatrice M; Albani, Diego; Cabrera, Juan Carlos; Francis, Dennis; Rogers, Hilary J

    2014-10-01

    Xyloglucan oligosaccharides (XGOs) are breakdown products of XGs, the most abundant hemicelluloses of the primary cell walls of non-Poalean species. Treatment of cell cultures or whole plants with XGOs results in accelerated cell elongation and cell division, changes in primary root growth, and a stimulation of defence responses. They may therefore act as signalling molecules regulating plant growth and development. Previous work suggests an interaction with auxins and effects on cell wall loosening, however their mode of action is not fully understood. The effect of an XGO extract from tamarind (Tamarindus indica) on global gene expression was therefore investigated in tobacco BY-2 cells using microarrays. Over 500 genes were differentially regulated with similar numbers and functional classes of genes up- and down-regulated, indicating a complex interaction with the cellular machinery. Up-regulation of a putative XG endotransglycosylase/hydrolase-related (XTH) gene supports the mechanism of XGO action through cell wall loosening. Differential expression of defence-related genes supports a role for XGOs as elicitors. Changes in the expression of genes related to mitotic control and differentiation also support previous work showing that XGOs are mitotic inducers. XGOs also affected expression of several receptor-like kinase genes and transcription factors. Hence, XGOs have significant effects on expression of genes related to cell wall metabolism, signalling, stress responses, cell division and transcriptional control.

  6. Is Social Anhedonia related to Emotional Responsivity and Expressivity? A laboratory study in Women

    PubMed Central

    Leung, Winnie W.; Couture, Shannon M.; Blanchard, Jack J.; Lin, Stephanie; Llerena, Katiah

    2010-01-01

    Social anhedonia is an important feature of schizophrenia and it is a promising indicator of schizotypy. Although social anhedonia is defined as an affective construct (less pleasure derived from social encounters), little is known about the emotional responsivity and expressivity of individuals with high levels of social anhedonia. After screening a large sample of female undergraduate students (N = 1 085), a cohort of psychometrically identified individuals with high levels of social anhedonia (n = 34) and normally hedonic controls (n = 45) participated in laboratory assessments involving trait affectivity, self-reported dispositional emotional expressiveness, and the expression and experience of emotion in response to neutral, nonaffiliative (i.e., comedy) and affiliative film clips. Results revealed that individuals with high levels of social anhedonia are characterized by lower positive affect, both as a trait and in response to emotionally evocative stimuli, and are less facially expressive, both by their own self-report and in response to film clips. Attenuated positive affect was observed across film stimuli, indicating a general reduction in affective response rather than a specific decrease in responsivity for affiliative stimuli. Future work should continue to investigate whether there is a unique role for social stimuli in the emotional lives of individuals with high levels of social anhedonia or whether these individuals tend to experience anhedonia more broadly regardless of social context. PMID:20620020

  7. Systems analysis of transcriptome data provides new hypotheses about Arabidopsis root response to nitrate treatments

    PubMed Central

    Canales, Javier; Moyano, Tomás C.; Villarroel, Eva; Gutiérrez, Rodrigo A.

    2014-01-01

    Nitrogen (N) is an essential macronutrient for plant growth and development. Plants adapt to changes in N availability partly by changes in global gene expression. We integrated publicly available root microarray data under contrasting nitrate conditions to identify new genes and functions important for adaptive nitrate responses in Arabidopsis thaliana roots. Overall, more than 2000 genes exhibited changes in expression in response to nitrate treatments in Arabidopsis thaliana root organs. Global regulation of gene expression by nitrate depends largely on the experimental context. However, despite significant differences from experiment to experiment in the identity of regulated genes, there is a robust nitrate response of specific biological functions. Integrative gene network analysis uncovered relationships between nitrate-responsive genes and 11 highly co-expressed gene clusters (modules). Four of these gene network modules have robust nitrate responsive functions such as transport, signaling, and metabolism. Network analysis hypothesized G2-like transcription factors are key regulatory factors controlling transport and signaling functions. Our meta-analysis highlights the role of biological processes not studied before in the context of the nitrate response such as root hair development and provides testable hypothesis to advance our understanding of nitrate responses in plants. PMID:24570678

  8. Sustained conditioned responses in prelimbic prefrontal neurons are correlated with fear expression and extinction failure.

    PubMed

    Burgos-Robles, Anthony; Vidal-Gonzalez, Ivan; Quirk, Gregory J

    2009-07-01

    During auditory fear conditioning, it is well established that lateral amygdala (LA) neurons potentiate their response to the tone conditioned stimulus, and that this potentiation is required for conditioned fear behavior. Conditioned tone responses in LA, however, last only a few hundred milliseconds and cannot be responsible for sustained fear responses to a tone lasting tens of seconds. Recent evidence from inactivation and stimulation studies suggests that the prelimbic (PL) prefrontal cortex is necessary for expression of learned fears, but the timing of PL tone responses and correlations with fear behavior have not been studied. Using multichannel unit recording techniques in behaving rats, we observed sustained conditioned tone responses in PL that were correlated with freezing behavior on a second-to-second basis during the presentation of a 30 s tone. PL tone responses were also correlated with conditioned freezing across different experimental phases (habituation, conditioning, extinction). Moreover, the persistence of PL responses after extinction training was associated with failure to express extinction memory. Together with previous inactivation findings, the present results suggest that PL transforms transient amygdala inputs to a sustained output that drives conditioned fear responses and gates the expression of extinction. Given the relatively long latency of conditioned responses we observed in PL (approximately 100 ms after tone onset), we propose that PL integrates inputs from the amygdala, hippocampus, and other cortical sources to regulate the expression of fear memories.

  9. Induction of humoral responses to BHV-1 glycoprotein D expressed by HSV-1 amplicon vectors

    PubMed Central

    Blanc, Andrea Maria; Berois, Mabel Beatriz; Tomé, Lorena Magalí; Epstein, Alberto L.

    2012-01-01

    Herpes simplex virus type-1 (HSV-1) amplicon vectors are versatile and useful tools for transferring genes into cells that are capable of stimulating a specific immune response to their expressed antigens. In this work, two HSV-1-derived amplicon vectors were generated. One of these expressed the full-length glycoprotein D (gD) of bovine herpesvirus 1 while the second expressed the truncated form of gD (gDtr) which lacked the trans-membrane region. After evaluating gD expression in the infected cells, the ability of both vectors to induce a specific gD immune response was tested in BALB/c mice that were intramuscularly immunized. Specific serum antibody responses were detected in mice inoculated with both vectors, and the response against truncated gD was higher than the response against full-length gD. These results reinforce previous findings that HSV-1 amplicon vectors can potentially deliver antigens to animals and highlight the prospective use of these vectors for treating infectious bovine rhinotracheitis disease. PMID:22437537

  10. A Canonical Response in Rainfall Characteristics to Global Warming: Projections by IPCC CMIP5 Models

    NASA Technical Reports Server (NTRS)

    Lau, William K. M.; Wu, H. T.; Kim, K. M.

    2012-01-01

    Changes in rainfall characteristics induced by global warming are examined based on probability distribution function (PDF) analysis, from outputs of 14 IPCC (Intergovernmental Panel on Climate Change), CMIP (5th Coupled Model Intercomparison Project) models under various scenarios of increased CO2 emissions. Results show that collectively CMIP5 models project a robust and consistent global and regional rainfall response to CO2 warming. Globally, the models show a 1-3% increase in rainfall per degree rise in temperature, with a canonical response featuring large increase (100-250 %) in frequency of occurrence of very heavy rain, a reduction (5-10%) of moderate rain, and an increase (10-15%) of light rain events. Regionally, even though details vary among models, a majority of the models (>10 out of 14) project a consistent large scale response with more heavy rain events in climatologically wet regions, most pronounced in the Pacific ITCZ and the Asian monsoon. Moderate rain events are found to decrease over extensive regions of the subtropical and extratropical oceans, but increases over the extratropical land regions, and the Southern Oceans. The spatial distribution of light rain resembles that of moderate rain, but mostly with opposite polarity. The majority of the models also show increase in the number of dry events (absence or only trace amount of rain) over subtropical and tropical land regions in both hemispheres. These results suggest that rainfall characteristics are changing and that increased extreme rainfall events and droughts occurrences are connected, as a consequent of a global adjustment of the large scale circulation to global warming.

  11. Role of Adrenal Glucocorticoid Signaling in Prefrontal Cortex Gene Expression and Acute Behavioral Responses to Ethanol

    PubMed Central

    Costin, Blair N.; Wolen, Aaron R.; Fitting, Sylvia; Shelton, Keith L.; Miles, Michael F.

    2012-01-01

    Background Glucocorticoid hormones modulate acute and chronic behavioral and molecular responses to drugs of abuse including psychostimulants and opioids. There is growing evidence that glucocorticoids might also modulate behavioral responses to ethanol. Acute ethanol activates the HPA axis, causing release of adrenal glucocorticoid hormones. Our prior genomic studies suggest glucocorticoids play a role in regulating gene expression in the prefrontal cortex (PFC) of DBA2/J (D2) mice following acute ethanol administration. However, few studies have analyzed the role of glucocorticoid signaling in behavioral responses to acute ethanol. Such work could be significant, given the predictive value for level of response to acute ethanol in the risk for alcoholism. Methods We studied whether the glucocorticoid receptor (GR) antagonist, RU-486, or adrenalectomy (ADX) altered male D2 mouse behavioral responses to acute (locomotor activation, anxiolysis or loss-of-righting reflex (LORR)) or repeated (sensitization) ethanol treatment. Whole genome microarray analysis and bioinformatics approaches were used to identify PFC candidate genes possibly responsible for altered behavioral responses to ethanol following ADX. Results ADX and RU-486 both impaired acute ethanol (2 g/kg) induced locomotor activation in D2 mice without affecting basal locomotor activity. However, neither ADX nor RU-486 altered initiation of ethanol sensitization (locomotor activation or jump counts), ethanol-induced anxiolysis or LORR. ADX mice showed microarray gene expression changes in PFC that significantly overlapped with acute ethanol-responsive gene sets derived by our prior microarray studies. Q-rtPCR analysis verified that ADX decreased PFC expression of Fkbp5 while significantly increasing Gpr6 expression. In addition, high dose RU-486 pre-treatment blunted ethanol-induced Fkbp5 expression. Conclusions Our studies suggest that ethanol’s activation of adrenal glucocorticoid release and subsequent

  12. Asymmetric responses to simulated global warming by populations of Colobanthus quitensis along a latitudinal gradient.

    PubMed

    Acuña-Rodríguez, Ian S; Torres-Díaz, Cristian; Hereme, Rasme; Molina-Montenegro, Marco A

    2017-01-01

    The increase in temperature as consequence of the recent global warming has been reported to generate new ice-free areas in the Antarctic continent, facilitating the colonization and spread of plant populations. Consequently, Antarctic vascular plants have been observed extending their southern distribution. But as the environmental conditions toward southern localities become progressively more departed from the species' physiological optimum, the ecophysiological responses and survival to the expected global warming could be reduced. However, if processes of local adaptation are the main cause of the observed southern expansion, those populations could appear constrained to respond positively to the expected global warming. Using individuals from the southern tip of South America, the South Shetland Islands and the Antarctic Peninsula, we assess with a long term experiment (three years) under controlled conditions if the responsiveness of Colobanthus quitensis populations to the expected global warming, is related with their different foliar traits and photoprotective mechanisms along the latitudinal gradient. In addition, we tested if the release of the stress condition by the global warming in these cold environments increases the ecophysiological performance. For this, we describe the latitudinal pattern of net photosynthetic capacity, biomass accumulation, and number of flowers under current and future temperatures respective to each site of origin after three growing seasons. Overall, was found a clinal trend was found in the foliar traits and photoprotective mechanisms in the evaluated C. quitensis populations. On the other hand, an asymmetric response to warming was observed for southern populations in all ecophysiological traits evaluated, suggesting that low temperature is limiting the performance of C. quitensis populations. Our results suggest that under a global warming scenario, plant populations that inhabiting cold zones at high latitudes could

  13. Asymmetric responses to simulated global warming by populations of Colobanthus quitensis along a latitudinal gradient

    PubMed Central

    Acuña-Rodríguez, Ian S.; Torres-Díaz, Cristian; Hereme, Rasme

    2017-01-01

    The increase in temperature as consequence of the recent global warming has been reported to generate new ice-free areas in the Antarctic continent, facilitating the colonization and spread of plant populations. Consequently, Antarctic vascular plants have been observed extending their southern distribution. But as the environmental conditions toward southern localities become progressively more departed from the species’ physiological optimum, the ecophysiological responses and survival to the expected global warming could be reduced. However, if processes of local adaptation are the main cause of the observed southern expansion, those populations could appear constrained to respond positively to the expected global warming. Using individuals from the southern tip of South America, the South Shetland Islands and the Antarctic Peninsula, we assess with a long term experiment (three years) under controlled conditions if the responsiveness of Colobanthus quitensis populations to the expected global warming, is related with their different foliar traits and photoprotective mechanisms along the latitudinal gradient. In addition, we tested if the release of the stress condition by the global warming in these cold environments increases the ecophysiological performance. For this, we describe the latitudinal pattern of net photosynthetic capacity, biomass accumulation, and number of flowers under current and future temperatures respective to each site of origin after three growing seasons. Overall, was found a clinal trend was found in the foliar traits and photoprotective mechanisms in the evaluated C. quitensis populations. On the other hand, an asymmetric response to warming was observed for southern populations in all ecophysiological traits evaluated, suggesting that low temperature is limiting the performance of C. quitensis populations. Our results suggest that under a global warming scenario, plant populations that inhabiting cold zones at high latitudes could

  14. Public Health Control Measures in Response to Global Pandemics and Drug Resistance.

    PubMed

    Price, Polly J

    2015-01-01

    These teaching materials provide problem-based exercises exploring the specific powers of governments to implement control measures in response to communicable disease. Topics include global pandemic disease and, in the United States, legal issues in tuberculosis control. © 2015 American Society of Law, Medicine & Ethics, Inc.

  15. Emergency Management and Tourism Stakeholder Responses to Crises: A Global Survey.

    PubMed

    Morakabati, Yeganeh; Page, Stephen J; Fletcher, John

    2017-03-01

    This article examines the contested area of the responsibility for destinations and tourists, within emergency settings. It incorporates a Delphi-Scenario technique to facilitate a structured discussion of emergency management for different destination stakeholders. The Delphi exercise engaged 123 senior international stakeholders, from 9 different industry sectors, across 34 countries to provide a global perspective. The study's principal focus is on the notion of emergency management, to identify the challenges that stakeholders would face within a disaster scenario. The exercise asked stakeholders to identify with whom the responsibility rests for 18 distinct disaster-related activities. The study proposes a responsibility allocation building-block framework that could help speed up the emergency management responses by "knowing who is going to do what" with a particular focus on dealing with international tourists as a community in a disaster zone.

  16. 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.

  17. Patient Expression of Emotions and Neurologist Responses in First Multiple Sclerosis Consultations

    PubMed Central

    Del Piccolo, Lidia; Pietrolongo, Erika; Radice, Davide; Tortorella, Carla; Confalonieri, Paolo; Pugliatti, Maura; Lugaresi, Alessandra; Giordano, Andrea; Heesen, Christoph; Solari, Alessandra

    2015-01-01

    Background Anxiety and depression are common in people with multiple sclerosis (MS), but data on emotional communication during MS consultations are lacking. We assessed patient expressions of emotion and neurologist responses during first-ever MS consultations using the Verona Coding Definitions of Emotional Sequences (VR-CoDES). Methods We applied VR-CoDES to recordings/transcripts of 88 outpatient consultations (10 neurologists, four MS Italian centers). Before consultation, patients completed the Hospital Anxiety and Depression Scale (HADS). Multilevel sequential analysis was performed on the number of cues/concerns expressed by patients, and the proportion of reduce space responses by neurologists. Results Patients expressed 492 cues and 45 concerns (median 4 cues and 1 concern per consultation). The commonest cues were verbal hints of hidden worries (cue type b, 41%) and references to stressful life events (type d, 26%). Variables independently associated with number of cues/concerns were: anxiety (HADS-Anxiety score >8) (incidence risk ratio, IRR 1.08, 95% CI 1.06-1.09; p<0.001); patient age (IRR 0.98, 95% CI 0.98-0.99; p<0.001); neurologist age (IRR 0.94, 95% CI 0.92-0.96; p=0.03); and second opinion consultation (IRR 0.72, 95% CI 0.60-0.86; p=0.007). Neurologists reacted to patient emotions by reducing space (changing subject, taking no notice, giving medical advice) for 58% of cues and 76% of concerns. Anxiety was the only variable significantly associated with ‘reduce space’ responses (odds ratio 2.17, 95% CI 1.32-3.57; p=0.003). Conclusions Patient emotional expressions varied widely, but VR-CoDES cues b and d were expressed most often. Patient anxiety was directly associated with emotional expressions; older age of patients and neurologists, and second opinion consultations were inversely associated with patient emotional expression. In over 50% of instances, neurologists responded to these expressions by reducing space, more so in anxious patients

  18. Time course of discrimination between emotional facial expressions: the role of visual saliency.

    PubMed

    Calvo, Manuel G; Nummenmaa, Lauri

    2011-08-01

    Saccadic and manual responses were used to investigate the speed of discrimination between happy and non-happy facial expressions in two-alternative-forced-choice tasks. The minimum latencies of correct saccadic responses indicated that the earliest time point at which discrimination occurred ranged between 200 and 280ms, depending on type of expression. Corresponding minimum latencies for manual responses ranged between 440 and 500ms. For both response modalities, visual saliency of the mouth region was a critical factor in facilitating discrimination: The more salient the mouth was in happy face targets in comparison with non-happy distracters, the faster discrimination was. Global image characteristics (e.g., luminance) and semantic factors (i.e., categorical similarity and affective valence of expression) made minor or no contribution to discrimination efficiency. This suggests that visual saliency of distinctive facial features, rather than the significance of expression, is used to make both early and later expression discrimination decisions. Copyright © 2011 Elsevier Ltd. All rights reserved.

  19. Alterations of Global DNA Methylation and DNA Methyltransferase Expression in T and B Lymphocytes from Patients with Newly Diagnosed Autoimmune Thyroid Diseases After Treatment: A Follow-Up Study.

    PubMed

    Guo, Qingling; Wu, Dan; Yu, Huixin; Bao, Jiandong; Peng, Shiqiao; Shan, Zhongyan; Guan, Haixia; Teng, Weiping

    2018-03-01

    Dysregulated DNA methylation in lymphocytes has been linked to autoimmune disorders. The aims of this study were to identify global DNA methylation patterns in patients with autoimmune thyroid diseases and to observe methylation changes after treatment for these conditions. A cross-sectional study was conducted, including the following patients: 51 with newly diagnosed Graves' disease (GD), 28 with autoimmune hypothyroidism (AIT), 29 with positive thyroid autoantibodies, and 39 matched healthy volunteers. Forty GD patients treated with radioiodine or antithyroid drugs and 28 AIT patients treated with L-thyroxine were followed for three months. Serum free triiodothyronine, free thyroxine, thyrotropin, thyroid peroxidase antibodies, thyroglobulin antibodies, and thyrotropin receptor antibodies were assayed using electrochemiluminescent immunoassays. CD3 + T and CD19 + B cells were separated by flow cytometry for total DNA and RNA extraction. Global DNA methylation levels were determined by absorptiometry using a methylation quantification kit. DNA methyltransferase (DNMT) expression levels were detected by real-time polymerase chain reaction. Hypomethylation and down-regulated DNMT1 expression in T and B lymphocytes were observed in the newly diagnosed GD patients. Neither the AIT patients nor the positive thyroid autoantibodies patients exhibited differences in their global DNA methylation status or DNMT mRNA levels compared with healthy controls. Antithyroid drugs restored global methylation and DNMT1 expression in both T and B lymphocytes, whereas radioiodine therapy affected only T cells. L-thyroxine replacement did not alter the methylation or DNMT expression levels in lymphocytes. The global methylation levels of B cells were negatively correlated with the serum thyroid peroxidase antibodies in patients with autoimmune thyroid diseases. Hyperthyroid patients with newly diagnosed GD had global hypomethylation and lower DNMT1 expression in T and B lymphocytes

  20. Forced Migration and Global Responsibility for Health Comment on "Defining and Acting on Global Health: The Case of Japan and the Refugee Crisis".

    PubMed

    Bozorgmehr, Kayvan; Razum, Oliver

    2016-11-05

    Forced migration has become a world-wide phenomenon in the past century, affecting increasing numbers of countries and people. It entails important challenges from a global health perspective. Leppold et al have critically discussed the Japanese interpretation of global responsibility for health in the context of forced migration. This commentary complements their analysis by outlining three priority areas of global health responsibility for European Union (EU) countries. We highlight important stages of the migration phases related to forced migration and propose three arguments. First, the chronic neglect of the large number of internally displaced persons (IDPs) in the discourses on the "refugee crisis" needs to be corrected in order to develop sustainable solutions with a framework of the Sustainable Development Goals (SDGs). Second, protection gaps in the global system of protection need to be effectively closed to resolve conflicts with border management and normative global health frameworks. Third, effective policies need to be developed and implemented to meet the health and humanitarian needs of forced migrants; at the same time, the solidarity crisis within the EU needs to be overcome. These stakes are high. EU countries, being committed to global health, should urgently address these areas. © 2017 The Author(s); Published by Kerman University of Medical Sciences. This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

  1. The host-pathogen interaction between wheat and yellow rust induces temporally coordinated waves of gene expression.

    PubMed

    Dobon, Albor; Bunting, Daniel C E; Cabrera-Quio, Luis Enrique; Uauy, Cristobal; Saunders, Diane G O

    2016-05-20

    Understanding how plants and pathogens modulate gene expression during the host-pathogen interaction is key to uncovering the molecular mechanisms that regulate disease progression. Recent advances in sequencing technologies have provided new opportunities to decode the complexity of such interactions. In this study, we used an RNA-based sequencing approach (RNA-seq) to assess the global expression profiles of the wheat yellow rust pathogen Puccinia striiformis f. sp. tritici (PST) and its host during infection. We performed a detailed RNA-seq time-course for a susceptible and a resistant wheat host infected with PST. This study (i) defined the global gene expression profiles for PST and its wheat host, (ii) substantially improved the gene models for PST, (iii) evaluated the utility of several programmes for quantification of global gene expression for PST and wheat, and (iv) identified clusters of differentially expressed genes in the host and pathogen. By focusing on components of the defence response in susceptible and resistant hosts, we were able to visualise the effect of PST infection on the expression of various defence components and host immune receptors. Our data showed sequential, temporally coordinated activation and suppression of expression of a suite of immune-response regulators that varied between compatible and incompatible interactions. These findings provide the framework for a better understanding of how PST causes disease and support the idea that PST can suppress the expression of defence components in wheat to successfully colonize a susceptible host.

  2. Changes in global gene expression profiles induced by HPV 16 E6 oncoprotein variants in cervical carcinoma C33-A cells

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zacapala-Gómez, Ana Elvira, E-mail: zak_ana@yahoo.com.mx; Del Moral-Hernández, Oscar, E-mail: odelmoralh@gmail.com; Villegas-Sepúlveda, Nicolás, E-mail: nvillega@cinvestav.mx

    We analyzed the effects of the expression of HPV 16 E6 oncoprotein variants (AA-a, AA-c, E-A176/G350, E-C188/G350, E-G350), and the E-Prototype in global gene expression profiles in an in vitro model. E6 gene was cloned into an expression vector fused to GFP and was transfected in C33-A cells. Affymetrix GeneChip Human Transcriptome Array 2.0 platform was used to analyze the expression of over 245,000 coding transcripts. We found that HPV16 E6 variants altered the expression of 387 different genes in comparison with E-Prototype. The altered genes are involved in cellular processes related to the development of cervical carcinoma, such asmore » adhesion, angiogenesis, apoptosis, differentiation, cell cycle, proliferation, transcription and protein translation. Our results show that polymorphic changes in HPV16 E6 natural variants are sufficient to alter the overall gene expression profile in C33-A cells, explaining in part the observed differences in oncogenic potential of HPV16 variants. - Highlights: • Amino acid changes in HPV16 E6 variants modulate the transciption of specific genes. • This is the first comparison of global gene expression profile of HPV 16 E6 variants. • Each HPV 16 E6 variant appears to have its own molecular signature.« less

  3. Expressive inhibition in response to stress: implications for emotional processing following trauma.

    PubMed

    Clapp, Joshua D; Patton, Samantha C; Beck, J Gayle

    2015-01-01

    Expressive inhibition--the willful restriction of expressed emotion--is documented in individuals reporting trauma-related distress, but its impact on global affective functioning remains unclear. Theoretical models propose that chronic activation of negative emotion and deliberate restriction of affect operate synergistically to produce trauma-related emotional deficits. The current project examined the impact of these factors on subjective experience and physiological activation following exposure to an analog trauma. University students (N=192; Mage=20, 57% female, 42% White/Non-Hispanic) viewed a graphic film depicting scenes of a televised suicide. Participants then viewed either a sadness- or humor-eliciting film under instructions to inhibit [nsadness=45, nhumor=52] or naturally express emotion [nsadness=48, nhumor=47]. Expressive inhibition was associated with restricted amusement specifically among participants viewing the humor film. Inhibition also produced attenuated sympathetic and parasympathetic recovery, irrespective of film assignment. Evidence of disruptions in emotional processing supports models identifying inhibition as a possible mechanism in post-trauma affect dysregulation. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. WHO-REMPAN for global health security and strengthening preparedness and response to radiation emergencies.

    PubMed

    Carr, Zhanat

    2010-06-01

    In response to the changing global environment and emerging new issues related to health security, the World Health Organization (WHO) is putting in place new tools for collective defense, such as the revised International Health Regulations (IHR) (2005). The new framework puts additional responsibilities on both Member States and WHO itself in order to effectively implement the IHR (2005) and react effectively in case of public health emergency events of any nature. Since its establishment in 1987, the Radiation Emergency Medical Preparedness and Assistance Network of WHO (WHO-REMPAN) has become an important asset for the organization's capacity to respond to radiation emergencies and to assist its Member States to strengthen their own response capacities. The paper describes in detail the framework for the WHO's role in preparedness and response to radiation emergencies, including Emergency Conventions and IHR (2005), and how the WHO-REMPAN, through its activities (i.e., technical guidelines development, training, education, research, and information sharing), provides a significant contribution to the organization's program of work towards achievement of the global health security goal.

  5. Transcriptional Orchestration of the Global Cellular Response of a Model Pennate Diatom to Diel Light Cycling under Iron Limitation.

    PubMed

    Smith, Sarah R; Gillard, Jeroen T F; Kustka, Adam B; McCrow, John P; Badger, Jonathan H; Zheng, Hong; New, Ashley M; Dupont, Chris L; Obata, Toshihiro; Fernie, Alisdair R; Allen, Andrew E

    2016-12-01

    Environmental fluctuations affect distribution, growth and abundance of diatoms in nature, with iron (Fe) availability playing a central role. Studies on the response of diatoms to low Fe have either utilized continuous (24 hr) illumination or sampled a single time of day, missing any temporal dynamics. We profiled the physiology, metabolite composition, and global transcripts of the pennate diatom Phaeodactylum tricornutum during steady-state growth at low, intermediate, and high levels of dissolved Fe over light:dark cycles, to better understand fundamental aspects of genetic control of physiological acclimation to growth under Fe-limitation. We greatly expand the catalog of genes involved in the low Fe response, highlighting the importance of intracellular trafficking in Fe-limited diatoms. P. tricornutum exhibited transcriptomic hallmarks of slowed growth leading to prolonged periods of cell division/silica deposition, which could impact biogeochemical carbon sequestration in Fe-limited regions. Light harvesting and ribosome biogenesis transcripts were generally reduced under low Fe while transcript levels for genes putatively involved in the acquisition and recycling of Fe were increased. We also noted shifts in expression towards increased synthesis and catabolism of branched chain amino acids in P. tricornutum grown at low Fe whereas expression of genes involved in central core metabolism were relatively unaffected, indicating that essential cellular function is protected. Beyond the response of P. tricornutum to low Fe, we observed major coordinated shifts in transcript control of primary and intermediate metabolism over light:dark cycles which contribute to a new view of the significance of distinctive diatom pathways, such as mitochondrial glycolysis and the ornithine-urea cycle. This study provides new insight into transcriptional modulation of diatom physiology and metabolism across light:dark cycles in response to Fe availability, providing mechanistic

  6. Transcriptional Orchestration of the Global Cellular Response of a Model Pennate Diatom to Diel Light Cycling under Iron Limitation

    PubMed Central

    McCrow, John P.; Badger, Jonathan H.; Zheng, Hong; New, Ashley M.; Dupont, Chris L.; Obata, Toshihiro; Fernie, Alisdair R.; Allen, Andrew E.

    2016-01-01

    Environmental fluctuations affect distribution, growth and abundance of diatoms in nature, with iron (Fe) availability playing a central role. Studies on the response of diatoms to low Fe have either utilized continuous (24 hr) illumination or sampled a single time of day, missing any temporal dynamics. We profiled the physiology, metabolite composition, and global transcripts of the pennate diatom Phaeodactylum tricornutum during steady-state growth at low, intermediate, and high levels of dissolved Fe over light:dark cycles, to better understand fundamental aspects of genetic control of physiological acclimation to growth under Fe-limitation. We greatly expand the catalog of genes involved in the low Fe response, highlighting the importance of intracellular trafficking in Fe-limited diatoms. P. tricornutum exhibited transcriptomic hallmarks of slowed growth leading to prolonged periods of cell division/silica deposition, which could impact biogeochemical carbon sequestration in Fe-limited regions. Light harvesting and ribosome biogenesis transcripts were generally reduced under low Fe while transcript levels for genes putatively involved in the acquisition and recycling of Fe were increased. We also noted shifts in expression towards increased synthesis and catabolism of branched chain amino acids in P. tricornutum grown at low Fe whereas expression of genes involved in central core metabolism were relatively unaffected, indicating that essential cellular function is protected. Beyond the response of P. tricornutum to low Fe, we observed major coordinated shifts in transcript control of primary and intermediate metabolism over light:dark cycles which contribute to a new view of the significance of distinctive diatom pathways, such as mitochondrial glycolysis and the ornithine-urea cycle. This study provides new insight into transcriptional modulation of diatom physiology and metabolism across light:dark cycles in response to Fe availability, providing mechanistic

  7. Glucocorticoid receptor expression on circulating leukocytes in healthy and asthmatic adolescents in response to exercise

    PubMed Central

    Lu, Kim D.; Cooper, Dan; Haddad, Fadia; Zaldivar, Frank; Kraft, Monica; Radom-Aizik, Shlomit

    2017-01-01

    Background Poor aerobic fitness is associated with worsening of asthma symptoms and fitness training may improve asthma control. The mechanism linking fitness with asthma is not known. We hypothesized that repeated bouts of exercise would lead to a downregulation of glucocorticoid receptor (GR) expression on circulating leukocytes reflecting a reduced responsiveness to stress. Methods In a prospective exercise training intervention of healthy and asthmatic adolescents, GR expression in leukocytes was measured using flow cytometry in response to a brief exercise challenge before and after the training intervention. PBMC gene expression of GR, GRβ, HSP70, and TGFβ1, 2 were determined using RT-PCR. Results Peak V̇O2 increased by 14.6 ± 2.3% indicating an effective training (p<0.01). There was a significant difference in GR expression among leukocyte subtypes, with highest expression in eosinophils. Following the training intervention, there was a significant decrease in baseline GR expression (p<0.05) in leukocyte and monocyte subtypes in both healthy and asthmatic adolescents. Conclusions This is the first study in adolescents to show that exercise training reduces GR expression on circulating leukocytes. We speculate that exercise training downregulates the stress response in general, manifested by decreased GR expression, and may explain why improving fitness improves asthma health. PMID:28796240

  8. Hemodynamic response of children with attention-deficit and hyperactive disorder (ADHD) to emotional facial expressions.

    PubMed

    Ichikawa, Hiroko; Nakato, Emi; Kanazawa, So; Shimamura, Keiichi; Sakuta, Yuiko; Sakuta, Ryoichi; Yamaguchi, Masami K; Kakigi, Ryusuke

    2014-10-01

    Children with attention-deficit/hyperactivity disorder (ADHD) have difficulty recognizing facial expressions. They identify angry expressions less accurately than typically developing (TD) children, yet little is known about their atypical neural basis for the recognition of facial expressions. Here, we used near-infrared spectroscopy (NIRS) to examine the distinctive cerebral hemodynamics of ADHD and TD children while they viewed happy and angry expressions. We measured the hemodynamic responses of 13 ADHD boys and 13 TD boys to happy and angry expressions at their bilateral temporal areas, which are sensitive to face processing. The ADHD children showed an increased concentration of oxy-Hb for happy faces but not for angry faces, while TD children showed increased oxy-Hb for both faces. Moreover, the individual peak latency of hemodynamic response in the right temporal area showed significantly greater variance in the ADHD group than in the TD group. Such atypical brain activity observed in ADHD boys may relate to their preserved ability to recognize a happy expression and their difficulty recognizing an angry expression. We firstly demonstrated that NIRS can be used to detect atypical hemodynamic response to facial expressions in ADHD children. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  9. Modulation of yeast genome expression in response to defective RNA polymerase III-dependent transcription.

    PubMed

    Conesa, Christine; Ruotolo, Roberta; Soularue, Pascal; Simms, Tiffany A; Donze, David; Sentenac, André; Dieci, Giorgio

    2005-10-01

    We used genome-wide expression analysis in Saccharomyces cerevisiae to explore whether and how the expression of protein-coding, RNA polymerase (Pol) II-transcribed genes is influenced by a decrease in RNA Pol III-dependent transcription. The Pol II transcriptome was characterized in four thermosensitive, slow-growth mutants affected in different components of the RNA Pol III transcription machinery. Unexpectedly, we found only a modest correlation between altered expression of Pol II-transcribed genes and their proximity to class III genes, a result also confirmed by the analysis of single tRNA gene deletants. Instead, the transcriptome of all of the four mutants was characterized by increased expression of genes known to be under the control of the Gcn4p transcriptional activator. Indeed, GCN4 was found to be translationally induced in the mutants, and deleting the GCN4 gene eliminated the response. The Gcn4p-dependent expression changes did not require the Gcn2 protein kinase and could be specifically counteracted by an increased gene dosage of initiator tRNA(Met). Initiator tRNA(Met) depletion thus triggers a GCN4-dependent reprogramming of genome expression in response to decreased Pol III transcription. Such an effect might represent a key element in the coordinated transcriptional response of yeast cells to environmental changes.

  10. Roles of relSpn in Stringent Response, Global Regulation, and Virulence of Serotype 2 Streptococcus pneumoniae D39

    PubMed Central

    Kazmierczak, Krystyna M.; Wayne, Kyle J.; Rechtsteiner, Andreas; Winkler, Malcolm E.

    2009-01-01

    Summary RelA/ SpoT homolog (RSH) proteins have (p)ppGpp synthetase and hydrolase activities that mediate major global responses to nutrient limitation and other stresses. RSH proteins are conserved in most bacteria and play diverse roles in bacterial pathogenesis. We report here that the RSH protein of S. pneumoniae, RelSpn, can be deleted and is the primary source of (p)ppGpp synthesis in virulent strain D39 under some conditions. A D39 ΔrelSpn mutant grew well in complex medium, but did not grow in chemically defined medium unless supplemented with the metals copper and manganese. Transcriptome analysis of D39 rel+Spn and ΔreSpn strains treated with mupirocin revealed relSpn-independent (translation stress), relSpn-dependent (stringent response), and ΔrelSpn-dependent changes suggesting that relSpn and (p)ppGpp amount play wide-ranging homeostatic roles in pneumococcal physiology, besides adjusting macromolecular synthesis and transport in response to nutrient availability. Notably, the relSpn-dependent response included significant up-regulation of the ply operon encoding pneumolysin toxin, whereas the ΔrelSpn-dependent response affected expression linked to the VicRK and CiaRH two component systems. Finally, a D39 ΔrelSpn mutant was severely attenuated and displayed a significantly altered course of disease progression in a mouse model of infection, which was restored to normal by an ectopic copy of rel+Spn. PMID:19426208

  11. Study of formation of green eggshell color in ducks through global gene expression.

    PubMed

    Xu, Fa Qiong; Li, Ang; Lan, Jing Jing; Wang, Yue Ming; Yan, Mei Jiao; Lian, Sen Yang; Wu, Xu

    2018-01-01

    The green eggshell color produced by ducks is a threshold trait that can be influenced by various factors, such as hereditary, environment and nutrition. The aim of this study was to investigate the genetic regulation of the formation of eggs with green shells in Youxian ducks. We performed integrative analysis of mRNAs and miRNAs expression profiling in the shell gland samples from ducks by RNA-Seq. We found 124 differentially expressed genes that were associated with various pathways, such as the ATP-binding cassette (ABC) transporter and solute carrier supper family pathways. A total of 31 differentially expressed miRNAs were found between ducks laying green eggs and white eggs. KEGG pathway analysis of the predicted miRNA target genes also indicated the functional characteristics of these miRNAs; they were involved in the ABC transporter pathway and the solute carrier (SLC) supper family. Analysis with qRT-PCR was applied to validate the results of global gene expression, which showed a correlation between results obtained by RNA-seq and RT-qPCR. Moreover, a miRNA-mRNA interaction network was established using correlation analysis of differentially expressed mRNA and miRNA. Compared to ducks that lay white eggs, ducks that lay green eggs include six up-regulated miRNAs that had regulatory effects on 35 down-regulated genes, and seven down-regulated miRNAs which influenced 46 up-regulated genes. For example, the ABC transporter pathway could be regulated by expressing gga-miR-144-3p (up-regulated) with ABCG2 (up-regulated) and other miRNAs and genes. This study provides valuable information about mRNA and miRNA regulation in duck shell gland tissues, and provides foundational information for further study on the eggshell color formation and marker-assisted selection for Youxian duck breeding.

  12. Global antioxidant response of meat.

    PubMed

    Carrillo, Celia; Barrio, Ángela; Del Mar Cavia, María; Alonso-Torre, Sara

    2017-06-01

    The global antioxidant response (GAR) method uses an enzymatic digestion to release antioxidants from foods. Owing to the importance of digestion for protein breakdown and subsequent release of bioactive compounds, the aim of the present study was to compare the GAR method for meat with the existing methodologies: the extraction-based method and QUENCHER. Seven fresh meats were analyzed using ABTS and FRAP assays. Our results indicated that the GAR of meat was higher than the total antioxidant capacity (TAC) assessed with the traditional extraction-based method. When evaluated with GAR, the thermal treatment led to an increase in the TAC of the soluble fraction, contrasting with a decreased TAC after cooking measured using the extraction-based method. The effect of thermal treatment on the TAC assessed by the QUENCHER method seemed to be dependent on the assay applied, since results from ABTS differed from FRAP. Our results allow us to hypothesize that the activation of latent bioactive peptides along the gastrointestinal tract should be taken into consideration when evaluating the TAC of meat. Therefore, we conclude that the GAR method may be more appropriate for assessing the TAC of meat than the existing, most commonly used methods. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

  13. Gene Expression Dynamics Accompanying the Sponge Thermal Stress Response.

    PubMed

    Guzman, Christine; Conaco, Cecilia

    2016-01-01

    Marine sponges are important members of coral reef ecosystems. Thus, their responses to changes in ocean chemistry and environmental conditions, particularly to higher seawater temperatures, will have potential impacts on the future of these reefs. To better understand the sponge thermal stress response, we investigated gene expression dynamics in the shallow water sponge, Haliclona tubifera (order Haplosclerida, class Demospongiae), subjected to elevated temperature. Using high-throughput transcriptome sequencing, we show that these conditions result in the activation of various processes that interact to maintain cellular homeostasis. Short-term thermal stress resulted in the induction of heat shock proteins, antioxidants, and genes involved in signal transduction and innate immunity pathways. Prolonged exposure to thermal stress affected the expression of genes involved in cellular damage repair, apoptosis, signaling and transcription. Interestingly, exposure to sublethal temperatures may improve the ability of the sponge to mitigate cellular damage under more extreme stress conditions. These insights into the potential mechanisms of adaptation and resilience of sponges contribute to a better understanding of sponge conservation status and the prediction of ecosystem trajectories under future climate conditions.

  14. Genome-wide analysis reveals inositol, not choline, as the major effector of Ino2p-Ino4p and unfolded protein response target gene expression in yeast.

    PubMed

    Jesch, Stephen A; Zhao, Xin; Wells, Martin T; Henry, Susan A

    2005-03-11

    In the yeast Saccharomyces cerevisiae, the transcription of many genes encoding enzymes of phospholipid biosynthesis are repressed in cells grown in the presence of the phospholipid precursors inositol and choline. A genome-wide approach using cDNA microarray technology was used to profile the changes in the expression of all genes in yeast that respond to the exogenous presence of inositol and choline. We report that the global response to inositol is completely distinct from the effect of choline. Whereas the effect of inositol on gene expression was primarily repressing, the effect of choline on gene expression was activating. Moreover, the combination of inositol and choline increased the number of repressed genes compared with inositol alone and enhanced the repression levels of a subset of genes that responded to inositol. In all, 110 genes were repressed in the presence of inositol and choline. Two distinct sets of genes exhibited differential expression in response to inositol or the combination of inositol and choline in wild-type cells. One set of genes contained the UASINO sequence and were bound by Ino2p and Ino4p. Many of these genes were also negatively regulated by OPI1, suggesting a common regulatory mechanism for Ino2p, Ino4p, and Opi1p. Another nonoverlapping set of genes was coregulated by the unfolded protein response pathway, an ER-localized stress response pathway, but was not dependent on OPI1 and did not show further repression when choline was present together with inositol. These results suggest that inositol is the major effector of target gene expression, whereas choline plays a minor role.

  15. Genome Wide Analysis Reveals Inositol, not Choline, as the Major Effector of Ino2p-Ino4p and Unfolded Protein Response Target Gene Expression in Yeast

    PubMed Central

    Jesch, Stephen A.; Zhao, Xin; Wells, Martin T.; Henry, Susan A.

    2005-01-01

    SUMMARY In the yeast Saccharomyces cerevisiae the transcription of many genes encoding enzymes of phospholipid biosynthesis are repressed in cells grown in the presence of the phospholipid precursors inositol and choline. A genome-wide approach using cDNA microarray technology was utilized to profile the changes in the expression of all genes in yeast that respond to the exogenous presence of inositol and choline. We report that the global response to inositol is completely distinct from the effect of choline. Whereas the effect of inositol on gene expression was primarily repressing, the effect of choline on gene expression was activating. Moreover, the combination inositol and choline increased the number of repressed genes compared to inositol alone and enhanced the repression levels of a subset of genes that responded to inositol. In all, 110 genes were repressed in the presence of inositol and choline. Two distinct sets of genes exhibited differential expression in response to inositol or the combination of inositol and choline in wild type cells. One set of genes contained the UASINO sequence and were bound by Ino2p and Ino4p. Many of these genes were also negatively regulated by OPI1, suggesting a common regulatory mechanism for Ino2p, Ino4p, and Opi1p. Another non-overlapping set of genes were coregulated by the unfolded protein response pathway, an ER-localized stress response pathway, but were not dependent on OPI1 and did not show further repression when choline was present together with inositol. These results suggest that inositol is the major effector of target gene expression, while choline plays a minor role. PMID:15611057

  16. Bryophyte-cyanobacteria associations as regulators of the northern latitude carbon balance in response to global change.

    PubMed

    Lindo, Zoë; Nilsson, Marie-Charlotte; Gundale, Michael J

    2013-07-01

    Ecosystems in the far north, including arctic and boreal biomes, are a globally significant pool of carbon (C). Global change is proposed to influence both C uptake and release in these ecosystems, thereby potentially affecting whether they act as C sources or sinks. Bryophytes (i.e., mosses) serve a variety of key functions in these systems, including their association with nitrogen (N2 )-fixing cyanobacteria, as thermal insulators of the soil, and producers of recalcitrant litter, which have implications for both net primary productivity (NPP) and heterotrophic respiration. While ground-cover bryophytes typically make up a small proportion of the total biomass in northern systems, their combined physical structure and N2 -fixing capabilities facilitate a disproportionally large impact on key processes that control ecosystem C and N cycles. As such, the response of bryophyte-cyanobacteria associations to global change may influence whether and how ecosystem C balances are influenced by global change. Here, we review what is known about their occurrence and N2 -fixing activity, and how bryophyte systems will respond to several key global change factors. We explore the implications these responses may have in determining how global change influences C balances in high northern latitudes. © 2013 Blackwell Publishing Ltd.

  17. Micro124-mediated AHR expression regulates the inflammatory response of chronic rhinosinusitis (CRS) with nasal polyps.

    PubMed

    Liu, C C; Xia, M; Zhang, Y J; Jin, P; Zhao, L; Zhang, J; Li, T; Zhou, X M; Tu, Y Y; Kong, F; Sun, C; Shi, L; Zhao, M Q

    2018-06-02

    MicroRNAs represent a component of the innate immune responses that can restrain inflammatory signaling, miR124 is an important member of inflammation-associated miRNAs, and abnormal miR124 expression is observed in many inflammatory diseases and immune disorders. However, the role and signaling pathways of miR124 in chronic rhinosinusitis with nasal polyps (CRSwNPs) have not been studied in detail. The aryl hydrocarbon receptor (AHR) is a ligand-inducible transcription factor that is highly conserved in evolution and plays important roles in the inflammatory response process. In our study, we describe the role of miR124 in the inflammatory response of CRS with nasal polyps. We found that the expression of miR124 was decreased in nasal polyps, and negatively correlated with the expression of AHR. MiR124 can inhibit AHR expression by directly target 3' untranslated region (3'-UTR) of AHR. To further investigate the relationship between miR124, AHR and CRS inflammatory response, we transfect HNEpC cells with miR124 mimic, miR124 inhibitors or siRNA of AHR, then all the results showed that miR124 could regulates cellular inflammatory response through negatively regulating AHR expression. This study demonstrated that the regulation of AHR expression by miR124 is critical to the development of inflammatory response in CRSwNPs. Copyright © 2018. Published by Elsevier Inc.

  18. ROS Modifiers and NOX4 Affect the Expression of the Survivin-Associated Radio-Adaptive Response.

    PubMed

    Murley, Jeffrey S; Arbiser, Jack L; Weichselbaum, Ralph R; Grdina, David J

    2018-04-13

    The survivin-associated radio-adaptive response can be induced following exposure to ionizing radiation in the dose range from 5 to 100 mGy, and its magnitude of expression is dependent upon the TP53 mutational status of cells and ROS signaling. The purpose of the study was to investigate the potential role of ROS in the development of the survivin-associated adaptive response. Utilizing human colon carcinoma HCT116 TP53 wild type (WT) and HCT116 isogenic TP53 null mutant (Mut) cell cultures, the roles of inter- and intracellular ROS signaling on expression of the adaptive response as evidenced by changes in intracellular translocation of survivin measured by ELISA, and cell survival determined by a standard colony forming assay were investigated using ROS modifying agents that include emodin, N-acetyl-l-cysteine (NAC), fulvene-5, honokiol, metformin and rotenone. The role of NADPH oxidase 4 (NOX4) in the survivin-associated adaptive response was investigated by transfecting HCT116 cells, both WT and Mut, with two different NOX4 siRNA oligomers and Western blotting. A dose of 5 mGy or a 15min exposure to 50µM of the ROS producing drug emodin were equally effective in inducing a pro-survival adaptive response in TP53 WT and a radio-sensitization adaptive response in TP53 Mut HCT116 cells. Each response was associated with a corresponding translocation of survivin into the cytoplasm or nucleus, respectively. Exposure to 10mM NAC completely inhibited both responses. Exposure to 10µM honokiol induced responses similar to those observed following NAC exposure in TP53 WT and Mut cells. The mitochondrial complex 1 inhibitor rotenone was effective in reducing both cytoplasmic and nuclear survivin levels, but was ineffective in altering the expression of the adaptive response in either TP53 WT or Mut cells. In contrast, both metformin and fulvene-5, inhibitors of NOX4, facilitated the reversal of TP53 WT and Mut adaptive responses from pro-survival to radio

  19. Accepting responsibility for long-term care--a paradox in times of a global nursing shortage?

    PubMed

    Hirschfeld, Miriam J

    2009-03-01

    Need for long-term care (LTC) is increasing globally, and nurses have a professional imperative to address the growing need for long-term care (LTC). The author reviews the effect of globalization and the epidemiologic transition upon the growing need for LTC. I also summarize the lessons learned in the developing world, as well as in the industrialized world, based on the existing research evidence. The purpose of this paper is to explain the need for nursing as a profession to accept responsibility for LTC as part of nursing's raison d'etre, despite the global nursing shortage. This includes responsibility for innovative policy, health service, practice, research, nursing education development, and health promotion, because prevention is key to slowing the steep increase in LTC needs. Nurses must develop strategies for clinical practice, management, education, and research in order to increase our ability to meet future needs for LTC.

  20. Global changes in gene expression, assayed by microarray hybridization and quantitative RT-PCR, during acclimation of three Arabidopsis thaliana accessions to sub-zero temperatures after cold acclimation.

    PubMed

    Le, Mai Q; Pagter, Majken; Hincha, Dirk K

    2015-01-01

    During cold acclimation plants increase in freezing tolerance in response to low non-freezing temperatures. This is accompanied by many physiological, biochemical and molecular changes that have been extensively investigated. In addition, plants of many species, including Arabidopsis thaliana, become more freezing tolerant during exposure to mild, non-damaging sub-zero temperatures after cold acclimation. There is hardly any information available about the molecular basis of this adaptation. Here, we have used microarrays and a qRT-PCR primer platform covering 1,880 genes encoding transcription factors (TFs) to monitor changes in gene expression in the Arabidopsis accessions Columbia-0, Rschew and Tenela during the first 3 days of sub-zero acclimation at -3 °C. The results indicate that gene expression during sub-zero acclimation follows a tighly controlled time-course. Especially AP2/EREBP and WRKY TFs may be important regulators of sub-zero acclimation, although the CBF signal transduction pathway seems to be less important during sub-zero than during cold acclimation. Globally, we estimate that approximately 5% of all Arabidopsis genes are regulated during sub-zero acclimation. Particularly photosynthesis-related genes are down-regulated and genes belonging to the functional classes of cell wall biosynthesis, hormone metabolism and RNA regulation of transcription are up-regulated. Collectively, these data provide the first global analysis of gene expression during sub-zero acclimation and allow the identification of candidate genes for forward and reverse genetic studies into the molecular mechanisms of sub-zero acclimation.

  1. Assessment of global and gene-specific DNA methylation in rat liver and kidney in response to non-genotoxic carcinogen exposure

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ozden, Sibel, E-mail: stopuz@istanbul.edu.tr; Turgut Kara, Neslihan; Sezerman, Osman Ugur

    Altered expression of tumor suppressor genes and oncogenes, which is regulated in part at the level of DNA methylation, is an important event involved in non-genotoxic carcinogenesis. This may serve as a marker for early detection of non-genotoxic carcinogens. Therefore, we evaluated the effects of non-genotoxic hepatocarcinogens, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), hexachlorobenzene (HCB), methapyrilene (MPY) and male rat kidney carcinogens, d-limonene, p-dichlorobenzene (DCB), chloroform and ochratoxin A (OTA) on global and CpG island promoter methylation in their respective target tissues in rats. No significant dose-related effects on global DNA hypomethylation were observed in tissues of rats compared to vehicle controls using LC–MS/MSmore » in response to short-term non-genotoxic carcinogen exposure. Initial experiments investigating gene-specific methylation using methylation-specific PCR and bisulfite sequencing, revealed partial methylation of p16 in the liver of rats treated with HCB and TCDD. However, no treatment related effects on the methylation status of Cx32, e-cadherin, VHL, c-myc, Igfbp2, and p15 were observed. We therefore applied genome-wide DNA methylation analysis using methylated DNA immunoprecipitation combined with microarrays to identify alterations in gene-specific methylation. Under the conditions of our study, some genes were differentially methylated in response to MPY and TCDD, whereas d-limonene, DCB and chloroform did not induce any methylation changes. 90-day OTA treatment revealed enrichment of several categories of genes important in protein kinase activity and mTOR cell signaling process which are related to OTA nephrocarcinogenicity. - Highlights: • Studied non-genotoxic carcinogens caused no change on global DNA hypomethylation. • d-Limonene, DCB and chloroform did not show any genome-wide methylation changes. • Some genes were differentially methylated in response to MPY, TCDD and OTA. • Protein kinase

  2. Analysis of global gene expression profiles to identify differentially expressed genes critical for embryo development in Brassica rapa.

    PubMed

    Zhang, Yu; Peng, Lifang; Wu, Ya; Shen, Yanyue; Wu, Xiaoming; Wang, Jianbo

    2014-11-01

    Embryo development represents a crucial developmental period in the life cycle of flowering plants. To gain insights into the genetic programs that control embryo development in Brassica rapa L., RNA sequencing technology was used to perform transcriptome profiling analysis of B. rapa developing embryos. The results generated 42,906,229 sequence reads aligned with 32,941 genes. In total, 27,760, 28,871, 28,384, and 25,653 genes were identified from embryos at globular, heart, early cotyledon, and mature developmental stages, respectively, and analysis between stages revealed a subset of stage-specific genes. We next investigated 9,884 differentially expressed genes with more than fivefold changes in expression and false discovery rate ≤ 0.001 from three adjacent-stage comparisons; 1,514, 3,831, and 6,633 genes were detected between globular and heart stage embryo libraries, heart stage and early cotyledon stage, and early cotyledon and mature stage, respectively. Large numbers of genes related to cellular process, metabolism process, response to stimulus, and biological process were expressed during the early and middle stages of embryo development. Fatty acid biosynthesis, biosynthesis of secondary metabolites, and photosynthesis-related genes were expressed predominantly in embryos at the middle stage. Genes for lipid metabolism and storage proteins were highly expressed in the middle and late stages of embryo development. We also identified 911 transcription factor genes that show differential expression across embryo developmental stages. These results increase our understanding of the complex molecular and cellular events during embryo development in B. rapa and provide a foundation for future studies on other oilseed crops.

  3. Linear Response Path Following: A Molecular Dynamics Method To Simulate Global Conformational Changes of Protein upon Ligand Binding.

    PubMed

    Tamura, Koichi; Hayashi, Shigehiko

    2015-07-14

    Molecular functions of proteins are often fulfilled by global conformational changes that couple with local events such as the binding of ligand molecules. High molecular complexity of proteins has, however, been an obstacle to obtain an atomistic view of the global conformational transitions, imposing a limitation on the mechanistic understanding of the functional processes. In this study, we developed a new method of molecular dynamics (MD) simulation called the linear response path following (LRPF) to simulate a protein's global conformational changes upon ligand binding. The method introduces a biasing force based on a linear response theory, which determines a local reaction coordinate in the configuration space that represents linear coupling between local events of ligand binding and global conformational changes and thus provides one with fully atomistic models undergoing large conformational changes without knowledge of a target structure. The overall transition process involving nonlinear conformational changes is simulated through iterative cycles consisting of a biased MD simulation with an updated linear response force and a following unbiased MD simulation for relaxation. We applied the method to the simulation of global conformational changes of the yeast calmodulin N-terminal domain and successfully searched out the end conformation. The atomistically detailed trajectories revealed a sequence of molecular events that properly lead to the global conformational changes and identified key steps of local-global coupling that induce the conformational transitions. The LRPF method provides one with a powerful means to model conformational changes of proteins such as motors and transporters where local-global coupling plays a pivotal role in their functional processes.

  4. Global analysis of gene expression profiles in developing physic nut (Jatropha curcas L.) seeds.

    PubMed

    Jiang, Huawu; Wu, Pingzhi; Zhang, Sheng; Song, Chi; Chen, Yaping; Li, Meiru; Jia, Yongxia; Fang, Xiaohua; Chen, Fan; Wu, Guojiang

    2012-01-01

    Physic nut (Jatropha curcas L.) is an oilseed plant species with high potential utility as a biofuel. Furthermore, following recent sequencing of its genome and the availability of expressed sequence tag (EST) libraries, it is a valuable model plant for studying carbon assimilation in endosperms of oilseed plants. There have been several transcriptomic analyses of developing physic nut seeds using ESTs, but they have provided limited information on the accumulation of stored resources in the seeds. We applied next-generation Illumina sequencing technology to analyze global gene expression profiles of developing physic nut seeds 14, 19, 25, 29, 35, 41, and 45 days after pollination (DAP). The acquired profiles reveal the key genes, and their expression timeframes, involved in major metabolic processes including: carbon flow, starch metabolism, and synthesis of storage lipids and proteins in the developing seeds. The main period of storage reserves synthesis in the seeds appears to be 29-41 DAP, and the fatty acid composition of the developing seeds is consistent with relative expression levels of different isoforms of acyl-ACP thioesterase and fatty acid desaturase genes. Several transcription factor genes whose expression coincides with storage reserve deposition correspond to those known to regulate the process in Arabidopsis. The results will facilitate searches for genes that influence de novo lipid synthesis, accumulation and their regulatory networks in developing physic nut seeds, and other oil seeds. Thus, they will be helpful in attempts to modify these plants for efficient biofuel production.

  5. Cytokine expression in response to root repair agents.

    PubMed

    Oliveira, R R; Tavares, W L F; Reis, A L; Silva, V A; Vieira, L Q; Ribeiro Sobrinho, A P

    2018-05-06

    To evaluate the expression of TNF-α, IL-6, IFN-γ, TGF-β, IL-4, IL-10, RANKL, RANK and OPG on mouse calvarial bone treated with MTA, Geristore ® and Emdogain ® . Bone wounds were made on the heads of C57BL/6 mice, breaking the periosteum and the cortical surface of the calvaria. Each repair agent was inserted into sectioned Eppendorf microtubes and placed on the bone wound, and soft tissues were sutured. At 14 and 21 days, animals were sacrificed and the treated region was dissected. The calvaria bone was removed, and RNA was extracted. mRNA expression of the aforementioned cytokines was assessed using real-time PCR. Data were analysed by nonparametric methods, including the Mann-Whitney and Kruskal-Wallis tests (p<0.05). Following treatment with Emdogain ® and MTA, mRNA expression of RANKL, RANK and OPG increased significantly (p <0.05) between days 14 to 21. Geristore ® did not alter the basal expression of these mediators during the same period of evaluation. While treatment with Emdogain ® did cause a significant increase in TNF-α mRNA expression between days 14 and 21 (p <0.05), treatment with MTA did not alter the basal expression of this cytokine at either experimental time point. However, TNF-α mRNA expression was down-regulated significantly at day 21 (p <0.05) when Geristore ® was applied. A significant increase in the mRNA expression of IL-6, TGF-β, IL-10, IL-4 and IFN-γ was observed with Emdogain ® and MTA treatment between days 14 to 21, whereas Geristore ® reduced significantly the expression of IL-6, TGF-β and IL-4 (p <0.05). The clinical indication of these repair agents depends on the root resorption diagnosis. While MTA and Emdogain ® induce a pro- and anti-inflammatory response early and late, respectively, Geristore ® was not associated with an inflammatory reaction when compared to both repair agents. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  6. Adaptive changes in global gene expression profile of lung carcinoma A549 cells acutely exposed to distinct types of AhR ligands.

    PubMed

    Procházková, Jiřina; Strapáčová, Simona; Svržková, Lucie; Andrysík, Zdeněk; Hýžďalová, Martina; Hrubá, Eva; Pěnčíková, Kateřina; Líbalová, Helena; Topinka, Jan; Kléma, Jiří; Espinosa, Joaquín M; Vondráček, Jan; Machala, Miroslav

    2018-08-01

    Exposure to persistent ligands of aryl hydrocarbon receptor (AhR) has been found to cause lung cancer in experimental animals, and lung adenocarcinomas are often associated with enhanced AhR expression and aberrant AhR activation. In order to better understand the action of toxic AhR ligands in lung epithelial cells, we performed global gene expression profiling and analyze TCDD-induced changes in A549 transcriptome, both sensitive and non-sensitive to CH223191 co-treatment. Comparison of our data with results from previously reported microarray and ChIP-seq experiments enabled us to identify candidate genes, which expression status reflects exposure of lung cancer cells to TCDD, and to predict processes, pathways (e.g. ER stress, Wnt/β-cat, IFNɣ, EGFR/Erbb1), putative TFs (e.g. STAT, AP1, E2F1, TCF4), which may be implicated in adaptive response of lung cells to TCDD-induced AhR activation. Importantly, TCDD-like expression fingerprint of selected genes was observed also in A549 cells exposed acutely to both toxic (benzo[a]pyrene, benzo[k]fluoranthene) and endogenous AhR ligands (2-(1H-Indol-3-ylcarbonyl)-4-thiazolecarboxylic acid methyl ester and 6-formylindolo[3,2-b]carbazole). Overall, our results suggest novel cellular candidates, which could help to improve monitoring of AhR-dependent transcriptional activity during acute exposure of lung cells to distinct types of environmental pollutants. Copyright © 2018 Elsevier B.V. All rights reserved.

  7. Orotate phosphoribosyl transferase mRNA expression and the response of cholangiocarcinoma to 5-fluorouracil

    PubMed Central

    Hahnvajanawong, Chariya; Chaiyagool, Jariya; Seubwai, Wunchana; Bhudhisawasdi, Vajarabhongsa; Namwat, Nisana; Khuntikeo, Narong; Sripa, Banchob; Pugkhem, Ake; Tassaneeyakul, Wichittra

    2012-01-01

    AIM: To determine whether expression of certain enzymes related to 5-fluorouracil (5-FU) metabolism predicts 5-FU chemosensitivity in cholangiocarcinoma (CCA). METHODS: The histoculture drug response assay (HDRA) was performed using surgically resected CCA tissues. Tumor cell viability was determined morphologically with hematoxylin and eosin- and terminal deoxynucleotide transferase-mediated dUTP nick-end labeling-stained tissues. The mRNA expression of thymidine phosphorylase (TP), orotate phosphoribosyl transferase (OPRT), thymidylate synthase (TS), and dihydropyrimidine dehydrogenase (DPD) was determined with real-time reverse transcriptase-polymerase chain reaction. The levels of gene expression and the sensitivity to 5-FU were evaluated. RESULTS: Twenty-three CCA tissues were obtained from patients who had been diagnosed with intrahepatic CCA and who underwent surgical resection at Srinagarind Hospital, Khon Kaen University from 2007 to 2009. HDRA was used to determine the response of these CCA tissues to 5-FU. Based on the dose-response curve, 200 μg/mL 5-FU was selected as the test concentration. The percentage of inhibition index at the median point was selected as the cut-off point to differentiate the responding and non-responding tumors to 5-FU. When the relationship between TP, OPRT, TS and DPD mRNA expression levels and the sensitivity of CCA tissues to 5-FU was examined, only OPRT mRNA expression was significantly correlated with the response to 5-FU. The mean expression level of OPRT was significantly higher in the responder group compared to the non-responder group (0.41 ± 0.25 vs 0.22 ± 0.12, P < 0.05). CONCLUSION: OPRT mRNA expression may be a useful predictor of 5-FU chemosensitivity of CCA. Whether OPRT mRNA could be used to predict the success of 5-FU chemotherapy in CCA patients requires confirmation in patients. PMID:22912546

  8. Response of marine bacterioplankton pH homeostasis gene expression to elevated CO2

    NASA Astrophysics Data System (ADS)

    Bunse, Carina; Lundin, Daniel; Karlsson, Christofer M. G.; Akram, Neelam; Vila-Costa, Maria; Palovaara, Joakim; Svensson, Lovisa; Holmfeldt, Karin; González, José M.; Calvo, Eva; Pelejero, Carles; Marrasé, Cèlia; Dopson, Mark; Gasol, Josep M.; Pinhassi, Jarone

    2016-05-01

    Human-induced ocean acidification impacts marine life. Marine bacteria are major drivers of biogeochemical nutrient cycles and energy fluxes; hence, understanding their performance under projected climate change scenarios is crucial for assessing ecosystem functioning. Whereas genetic and physiological responses of phytoplankton to ocean acidification are being disentangled, corresponding functional responses of bacterioplankton to pH reduction from elevated CO2 are essentially unknown. Here we show, from metatranscriptome analyses of a phytoplankton bloom mesocosm experiment, that marine bacteria responded to lowered pH by enhancing the expression of genes encoding proton pumps, such as respiration complexes, proteorhodopsin and membrane transporters. Moreover, taxonomic transcript analysis showed that distinct bacterial groups expressed different pH homeostasis genes in response to elevated CO2. These responses were substantial for numerous pH homeostasis genes under low-chlorophyll conditions (chlorophyll a <2.5 μg l-1) however, the changes in gene expression under high-chlorophyll conditions (chlorophyll a >20 μg l-1) were low. Given that proton expulsion through pH homeostasis mechanisms is energetically costly, these findings suggest that bacterioplankton adaptation to ocean acidification could have long-term effects on the economy of ocean ecosystems.

  9. Global gene expression profiling of brown to white adipose tissue transformation in sheep reveals novel transcriptional components linked to adipose remodeling.

    PubMed

    Basse, Astrid L; Dixen, Karen; Yadav, Rachita; Tygesen, Malin P; Qvortrup, Klaus; Kristiansen, Karsten; Quistorff, Bjørn; Gupta, Ramneek; Wang, Jun; Hansen, Jacob B

    2015-03-19

    Large mammals are capable of thermoregulation shortly after birth due to the presence of brown adipose tissue (BAT). The majority of BAT disappears after birth and is replaced by white adipose tissue (WAT). We analyzed the postnatal transformation of adipose in sheep with a time course study of the perirenal adipose depot. We observed changes in tissue morphology, gene expression and metabolism within the first two weeks of postnatal life consistent with the expected transition from BAT to WAT. The transformation was characterized by massively decreased mitochondrial abundance and down-regulation of gene expression related to mitochondrial function and oxidative phosphorylation. Global gene expression profiling demonstrated that the time points grouped into three phases: a brown adipose phase, a transition phase and a white adipose phase. Between the brown adipose and the transition phase 170 genes were differentially expressed, and 717 genes were differentially expressed between the transition and the white adipose phase. Thirty-eight genes were shared among the two sets of differentially expressed genes. We identified a number of regulated transcription factors, including NR1H3, MYC, KLF4, ESR1, RELA and BCL6, which were linked to the overall changes in gene expression during the adipose tissue remodeling. Finally, the perirenal adipose tissue expressed both brown and brite/beige adipocyte marker genes at birth, the expression of which changed substantially over time. Using global gene expression profiling of the postnatal BAT to WAT transformation in sheep, we provide novel insight into adipose tissue plasticity in a large mammal, including identification of novel transcriptional components linked to adipose tissue remodeling. Moreover, our data set provides a useful resource for further studies in adipose tissue plasticity.

  10. Phase II Investigator-Initiated Study of Brentuximab Vedotin in Mycosis Fungoides and Sézary Syndrome With Variable CD30 Expression Level: A Multi-Institution Collaborative Project

    PubMed Central

    Kim, Youn H.; Tavallaee, Mahkam; Sundram, Uma; Salva, Katrin A.; Wood, Gary S.; Li, Shufeng; Rozati, Sima; Nagpal, Seema; Krathen, Michael; Reddy, Sunil; Hoppe, Richard T.; Nguyen-Lin, Annie; Weng, Wen-Kai; Armstrong, Randall; Pulitzer, Melissa; Advani, Ranjana H.; Horwitz, Steven M.

    2015-01-01

    Purpose In contrast to Hodgkin lymphoma and systemic anaplastic large-cell lymphoma, CD30 expression of malignant lymphocytes in mycosis fungoides (MF) and Sézary syndrome (SS) is quite variable. Clinical activity and safety of brentuximab vedotin, a CD30 targeting antibody-drug conjugate, was evaluated in MF and SS. Tissue and blood biomarkers of clinical response were explored. Patients and Methods In this phase II study, patients with MF or SS with negligible to 100% CD30 expression levels were treated with brentuximab vedotin (1.8 mg/kg) every 3 weeks for a maximum of sixteen doses. The primary end point was overall global response rate. Secondary end points included correlation of tissue CD30 expression level with clinical response, time to response, duration of response, progression-free and event-free survivals, and safety. Results Of the 32 patients enrolled and treated, 30 patients had available efficacy evaluations. Objective global response was observed in 21 (70%) of 30 patients (90% CI, 53% to 83%). CD30 expression assessed by immunohistochemistry was highly variable, with a median CD30max of 13% (range, 0% to 100%). Those with <5% CD30 expression had a lower likelihood of global response than did those with 5% or greater CD30 expression (P < .005). CD163 positive tumor-associated macrophages, many of which coexpress CD30, were abundant in tissue. Peripheral neuropathy was the most common adverse event. Conclusion Brentuximab vedotin demonstrated significant clinical activity in treatment-refractory or advanced MF or SS with a wide range of CD30 expression levels. Additional biomarker studies may help optimize rational design of combination therapies with brentuximab vedotin. PMID:26195720

  11. Global Transcriptome Analysis of Aedes aegypti Mosquitoes in Response to Zika Virus Infection

    PubMed Central

    Etebari, Kayvan; Hegde, Shivanand; Saldaña, Miguel A.; Widen, Steven G.; Wood, Thomas G.

    2017-01-01

    ABSTRACT Zika virus (ZIKV) of the Flaviviridae family is a recently emerged mosquito-borne virus that has been implicated in the surge of the number of microcephaly instances in South America. The recent rapid spread of the virus led to its declaration as a global health emergency by the World Health Organization. The virus is transmitted mainly by the mosquito Aedes aegypti, which is also the vector of dengue virus; however, little is known about the interactions of the virus with the mosquito vector. In this study, we investigated the transcriptome profiles of whole A. aegypti mosquitoes in response to ZIKV infection at 2, 7, and 14 days postinfection using transcriptome sequencing. Results showed changes in the abundance of a large number of transcripts at each time point following infection, with 18 transcripts commonly changed among the three time points. Gene ontology analysis revealed that most of the altered genes are involved in metabolic processes, cellular processes, and proteolysis. In addition, 486 long intergenic noncoding RNAs that were altered upon ZIKV infection were identified. Further, we found changes of a number of potential mRNA target genes correlating with those of altered host microRNAs. The outcomes provide a basic understanding of A. aegypti responses to ZIKV and help to determine host factors involved in replication or mosquito host antiviral response against the virus. IMPORTANCE Vector-borne viruses pose great risks to human health. Zika virus has recently emerged as a global threat, rapidly expanding its distribution. Understanding the interactions of the virus with mosquito vectors at the molecular level is vital for devising new approaches in inhibiting virus transmission. In this study, we embarked on analyzing the transcriptional response of Aedes aegypti mosquitoes to Zika virus infection. Results showed large changes in both coding and long noncoding RNAs. Analysis of these genes showed similarities with other flaviviruses

  12. Global Transcriptome Analysis of Aedes aegypti Mosquitoes in Response to Zika Virus Infection.

    PubMed

    Etebari, Kayvan; Hegde, Shivanand; Saldaña, Miguel A; Widen, Steven G; Wood, Thomas G; Asgari, Sassan; Hughes, Grant L

    2017-01-01

    Zika virus (ZIKV) of the Flaviviridae family is a recently emerged mosquito-borne virus that has been implicated in the surge of the number of microcephaly instances in South America. The recent rapid spread of the virus led to its declaration as a global health emergency by the World Health Organization. The virus is transmitted mainly by the mosquito Aedes aegypti , which is also the vector of dengue virus; however, little is known about the interactions of the virus with the mosquito vector. In this study, we investigated the transcriptome profiles of whole A. aegypti mosquitoes in response to ZIKV infection at 2, 7, and 14 days postinfection using transcriptome sequencing. Results showed changes in the abundance of a large number of transcripts at each time point following infection, with 18 transcripts commonly changed among the three time points. Gene ontology analysis revealed that most of the altered genes are involved in metabolic processes, cellular processes, and proteolysis. In addition, 486 long intergenic noncoding RNAs that were altered upon ZIKV infection were identified. Further, we found changes of a number of potential mRNA target genes correlating with those of altered host microRNAs. The outcomes provide a basic understanding of A. aegypti responses to ZIKV and help to determine host factors involved in replication or mosquito host antiviral response against the virus. IMPORTANCE Vector-borne viruses pose great risks to human health. Zika virus has recently emerged as a global threat, rapidly expanding its distribution. Understanding the interactions of the virus with mosquito vectors at the molecular level is vital for devising new approaches in inhibiting virus transmission. In this study, we embarked on analyzing the transcriptional response of Aedes aegypti mosquitoes to Zika virus infection. Results showed large changes in both coding and long noncoding RNAs. Analysis of these genes showed similarities with other flaviviruses, including

  13. Yeast-expressed recombinant As16 protects mice against Ascaris suum infection through induction of a Th2-skewed immune response

    PubMed Central

    Liu, Zhuyun; Keegan, Brian; Gazzinelli-Guimarães, Ana Clara; Fujiwara, Ricardo T.; Briggs, Neima; Jones, Kathryn M.; Strych, Ulrich; Beaumier, Coreen M.; Bottazzi, Maria Elena; Zhan, Bin

    2017-01-01

    Background Ascariasis remains the most common helminth infection in humans. As an alternative or complementary approach to global deworming, a pan-anthelminthic vaccine is under development targeting Ascaris, hookworm, and Trichuris infections. As16 and As14 have previously been described as two genetically related proteins from Ascaris suum that induced protective immunity in mice when formulated with cholera toxin B subunit (CTB) as an adjuvant, but the exact protective mechanism was not well understood. Methodology/Principal findings As16 and As14 were highly expressed as soluble recombinant proteins (rAs16 and rAs14) in Pichia pastoris. The yeast-expressed rAs16 was highly recognized by immune sera from mice infected with A. suum eggs and elicited 99.6% protection against A. suum re-infection. Mice immunized with rAs16 formulated with ISA720 displayed significant larva reduction (36.7%) and stunted larval development against A. suum eggs challenge. The protective immunity was associated with a predominant Th2-type response characterized by high titers of serological IgG1 (IgG1/IgG2a > 2000) and high levels of IL-4 and IL-5 produced by restimulated splenocytes. A similar level of protection was observed in mice immunized with rAs16 formulated with alum (Alhydrogel), known to induce mainly a Th2-type immune response, whereas mice immunized with rAs16 formulated with MPLA or AddaVax, both known to induce a Th1-type biased response, were not significantly protected against A. suum infection. The rAs14 protein was not recognized by A. suum infected mouse sera and mice immunized with rAs14 formulated with ISA720 did not show significant protection against challenge infection, possibly due to the protein’s inaccessibility to the host immune system or a Th1-type response was induced which would counter a protective Th2-type response. Conclusions/Significance Yeast-expressed rAs16 formulated with ISA720 or alum induced significant protection in mice against A. suum

  14. Glutathione-s-transferase-pi expression in early breast cancer: association with outcome and response to chemotherapy.

    PubMed

    Arun, Banu K; Granville, Laura A; Yin, Guosheng; Middleton, Lavinia P; Dawood, Shaheenah; Kau, Shu-Wan; Kamal, Arif; Hsu, Limin; Hortobagyi, Gabriel N; Sahin, Aysegul A

    2010-06-01

    Glutathione-S-transferase-pi (GST-pi) is a detoxification enzyme expressed in breast cancer; however its involvement in chemotherapy sensitivity and prognosis is not well understood. We evaluated the expression of GSTpi and its predictive role of chemotherapy response. Breast tumor samples from 166 patients at stage I/II of the disease were immunostained for GST-pi, and the expression was 96 %. There was a trend toward improved disease-free survival with high GST-pi expression (p =.09). There was a statistically non-significant association between high GST-pi expression and improved outcome with adjuvant chemotherapy (p =.055). Further studies should evaluate the role of GST-pi expression in relation to response to different chemotherapies.

  15. Assessment of global ischemic/reperfusion and Tacrolimus administration on CA1 region of hippocampus: gene expression profiles of BAX and BCL2 genes.

    PubMed

    Badr, R; Hashemi, M; Javadi, G; Movafagh, A; Mahdian, R

    2016-01-01

    It is well known that hippocampus has a pivotal role in learning, formation and consolidation of memory. Global cerebral ischemia causes severe damage to pyramidal neurons of the CA1 region and usually results in residual neurological deficits following a recovery from ischemia. Scientists investigate to find the molecular mechanism of apoptosis and to use this cell death for clinical treatment. In this investigation, we evaluated the molecular mechanism of FK-506 in apoptosis using gene expression quantification of BAX and BCL-2 genes in hippocampus following global ischemic/reperfusion. In the present experimental study, adult male Wistar rats were obtained and housed under standard conditions. Each experimental group consisted of five rats and was equally distributed in the normal control, ischemia/reperfusion, ischemia/reperfusion followed by FK-506. Global ischemia was induced for animals in ischemia and drug groups. In the drug group, moreover, two doses of FK-506 were injected as IV injection and intra-peritoneal (IP) injection after 48 h. Then, hippocampus tissue was removed. Consequently, RNA isolated, cDNA was synthesized and Real-Time PCR was performed. Finally, the obtained data was analyzed statistically (p<0.05). The quantitative results showed the BAX expression ratio increased approximately 3-times in ischemia/reperfusion (3.11 ± 0.28) group compared to the untreated (NR) and the drug group (p<0.001). The statistical analysis showed a significant difference for BCL-2 expression between the experimental groups (p<0.001). The mRNA level of BCL-2 decreased in the ischemia/reperfusion group, while it was without alteration in the other groups. The results showed that global cerebral ischemia/reperfusion induced BAX as pro-apoptotic gene and tacrolimus a neuroprotective drug inhibited BAX gene expression and induced BCL-2 gene expression as anti-apoptotic gene (Tab. 2, Fig. 3, Ref. 21).

  16. A rare subset of skin-tropic regulatory T cells expressing Il10/Gzmb inhibits the cutaneous immune response.

    PubMed

    Ikebuchi, Ryoyo; Teraguchi, Shunsuke; Vandenbon, Alexis; Honda, Tetsuya; Shand, Francis H W; Nakanishi, Yasutaka; Watanabe, Takeshi; Tomura, Michio

    2016-10-19

    Foxp3 + regulatory T cells (Tregs) migrating from the skin to the draining lymph node (dLN) have a strong immunosuppressive effect on the cutaneous immune response. However, the subpopulations responsible for their inhibitory function remain unclear. We investigated single-cell gene expression heterogeneity in Tregs from the dLN of inflamed skin in a contact hypersensitivity model. The immunosuppressive genes Ctla4 and Tgfb1 were expressed in the majority of Tregs. Although Il10-expressing Tregs were rare, unexpectedly, the majority of Il10-expressing Tregs co-expressed Gzmb and displayed Th1-skewing. Single-cell profiling revealed that CD43 + CCR5 + Tregs represented the main subset within the Il10/Gzmb-expressing cell population in the dLN. Moreover, CD43 + CCR5 + CXCR3 - Tregs expressed skin-tropic chemokine receptors, were preferentially retained in inflamed skin and downregulated the cutaneous immune response. The identification of a rare Treg subset co-expressing multiple immunosuppressive molecules and having tissue-remaining capacity offers a novel strategy for the control of skin inflammatory responses.

  17. Muscle myeloid type I interferon gene expression may predict therapeutic responses to rituximab in myositis patients

    PubMed Central

    Nagaraju, Kanneboyina; Ghimbovschi, Svetlana; Rayavarapu, Sree; Phadke, Aditi; Rider, Lisa G.; Hoffman, Eric P.

    2016-01-01

    Abstract Objective. To identify muscle gene expression patterns that predict rituximab responses and assess the effects of rituximab on muscle gene expression in PM and DM. Methods. In an attempt to understand the molecular mechanism of response and non-response to rituximab therapy, we performed Affymetrix gene expression array analyses on muscle biopsy specimens taken before and after rituximab therapy from eight PM and two DM patients in the Rituximab in Myositis study. We also analysed selected muscle-infiltrating cell phenotypes in these biopsies by immunohistochemical staining. Partek and Ingenuity pathway analyses assessed the gene pathways and networks. Results. Myeloid type I IFN signature genes were expressed at higher levels at baseline in the skeletal muscle of rituximab responders than in non-responders, whereas classic non-myeloid IFN signature genes were expressed at higher levels in non-responders at baseline. Also, rituximab responders have a greater reduction of the myeloid and non-myeloid type I IFN signatures than non-responders. The decrease in the type I IFN signature following administration of rituximab may be associated with the decreases in muscle-infiltrating CD19 + B cells and CD68 + macrophages in responders. Conclusion. Our findings suggest that high levels of myeloid type I IFN gene expression in skeletal muscle predict responses to rituximab in PM/DM and that rituximab responders also have a greater decrease in the expression of these genes. These data add further evidence to recent studies defining the type I IFN signature as both a predictor of therapeutic responses and a biomarker of myositis disease activity. PMID:27215813

  18. Global Agenda, Local Responses: Changing Education Governance in Hong Kong's Higher Education

    ERIC Educational Resources Information Center

    Chan, David K. K.

    2007-01-01

    Hong Kong has undergone a series of educational reforms since the mid 1990s in response to the tidal wave of globalisation. This article tries to examine the recent education reforms in Hong Kong's higher education within the global context, by putting into perspective a discussion of its policy implications of marketisation, privatisation and…

  19. Identification of rice genes associated with cosmic-ray response via co-expression gene network analysis.

    PubMed

    Hwang, Sun-Goo; Kim, Dong Sub; Hwang, Jung Eun; Han, A-Reum; Jang, Cheol Seong

    2014-05-15

    In order to better understand the biological systems that are affected in response to cosmic ray (CR), we conducted weighted gene co-expression network analysis using the module detection method. By using the Pearson's correlation coefficient (PCC) value, we evaluated complex gene-gene functional interactions between 680 CR-responsive probes from integrated microarray data sets, which included large-scale transcriptional profiling of 1000 microarray samples. These probes were divided into 6 distinct modules that contained 20 enriched gene ontology (GO) functions, such as oxidoreductase activity, hydrolase activity, and response to stimulus and stress. In particular, modules 1 and 2 commonly showed enriched annotation categories such as oxidoreductase activity, including enriched cis-regulatory elements known as ROS-specific regulators. These results suggest that the ROS-mediated irradiation response pathway is affected by CR in modules 1 and 2. We found 243 ionizing radiation (IR)-responsive probes that exhibited similarities in expression patterns in various irradiation microarray data sets. The expression patterns of 6 randomly selected IR-responsive genes were evaluated by quantitative reverse transcription polymerase chain reaction following treatment with CR, gamma rays (GR), and ion beam (IB); similar patterns were observed among these genes under these 3 treatments. Moreover, we constructed subnetworks of IR-responsive genes and evaluated the expression levels of their neighboring genes following GR treatment; similar patterns were observed among them. These results of network-based analyses might provide a clue to understanding the complex biological system related to the CR response in plants. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Global transcriptomic profiling demonstrates induction of oxidative stress and of compensatory cellular stress responses in brown trout exposed to glyphosate and Roundup.

    PubMed

    Uren Webster, Tamsyn M; Santos, Eduarda M

    2015-01-31

    Glyphosate, the active ingredient in Roundup formulations, is the most widely used herbicide worldwide, and as a result contaminates surface waters and has been detected in food residues, drinking water and human urine, raising concerns for potential environmental and human health impacts. Research has shown that glyphosate and Roundup can induce a broad range of biological effects in exposed organisms, particularly via generation of oxidative stress. However, there has been no comprehensive investigation of the global molecular mechanisms of toxicity of glyphosate and Roundup for any species. We aimed to characterise and compare the global mechanisms of toxicity of glyphosate and Roundup in the liver of brown trout (Salmo trutta), an ecologically and economically important vertebrate species, using RNA-seq on an Illumina HiSeq 2500 platform. To do this, we exposed juvenile female brown trout to 0, 0.01, 0.5 and 10 mg/L of glyphosate and Roundup (glyphosate acid equivalent) for 14 days, and sequenced 6 replicate liver samples from each treatment. We assembled the brown trout transcriptome using an optimised de novo approach, and subsequent differential expression analysis identified a total of 1020 differentially-regulated transcripts across all treatments. These included transcripts encoding components of the antioxidant system, a number of stress-response proteins and pro-apoptotic signalling molecules. Functional analysis also revealed over-representation of pathways involved in regulating of cell-proliferation and turnover, and up-regulation of energy metabolism and other metabolic processes. These transcriptional changes are consistent with generation of oxidative stress and the widespread induction of compensatory cellular stress response pathways. The mechanisms of toxicity identified were similar across both glyphosate and Roundup treatments, including for environmentally relevant concentrations. The significant alterations in transcript expression observed

  1. A growing global network’s role in outbreak response: AFHSC-GEIS 2008-2009

    PubMed Central

    2011-01-01

    A cornerstone of effective disease surveillance programs comprises the early identification of infectious threats and the subsequent rapid response to prevent further spread. Effectively identifying, tracking and responding to these threats is often difficult and requires international cooperation due to the rapidity with which diseases cross national borders and spread throughout the global community as a result of travel and migration by humans and animals. From Oct.1, 2008 to Sept. 30, 2009, the United States Department of Defense’s (DoD) Armed Forces Health Surveillance Center Global Emerging Infections Surveillance and Response System (AFHSC-GEIS) identified 76 outbreaks in 53 countries. Emerging infectious disease outbreaks were identified by the global network and included a wide spectrum of support activities in collaboration with host country partners, several of which were in direct support of the World Health Organization’s (WHO) International Health Regulations (IHR) (2005). The network also supported military forces around the world affected by the novel influenza A/H1N1 pandemic of 2009. With IHR (2005) as the guiding framework for action, the AFHSC-GEIS network of international partners and overseas research laboratories continues to develop into a far-reaching system for identifying, analyzing and responding to emerging disease threats. PMID:21388563

  2. Influence of Genetic Variations in Selenoprotein Genes on the Pattern of Gene Expression after Supplementation with Brazil Nuts

    PubMed Central

    Rogero, Marcelo M.; Hesketh, John

    2017-01-01

    Selenium (Se) is an essential micronutrient for human health. Its beneficial effects are exerted by selenoproteins, which can be quantified in blood and used as molecular biomarkers of Se status. We hypothesize that the presence of genetic polymorphisms in selenoprotein genes may: (1) influence the gene expression of specific selenoproteins and (2) influence the pattern of global gene expression after Brazil nut supplementation. The study was conducted with 130 healthy volunteers in Sao Paulo, Brazil, who consumed one Brazil nut (300 μg/Se) a day for eight weeks. Gene expression of GPX1 and SELENOP and genotyping were measured by real-time PCR using TaqMan Assays. Global gene expression was assessed by microarray using Illumina HumanHT-12 v4 BeadChips. Brazil nut supplementation significantly increased GPX1 mRNA expression only in subjects with CC genotype at rs1050450 (p < 0.05). SELENOP mRNA expression was significantly higher in A-carriers at rs7579 either before or after supplementation (p < 0.05). Genotype for rs713041 in GPX4 affected the pattern of blood cell global gene expression. Genetic variations in selenoprotein genes modulated both GPX1 and SELENOP selenoprotein gene expression and global gene expression in response to Brazil nut supplementation. PMID:28696394

  3. Preferential epigenetic programming of estrogen response after in utero xenoestrogen (bisphenol-A) exposure

    PubMed Central

    Jorgensen, Elisa M.; Alderman, Myles H.; Taylor, Hugh S.

    2016-01-01

    Bisphenol-A (BPA) is an environmentally ubiquitous estrogen-like endocrine-disrupting compound. Exposure to BPA in utero has been linked to female reproductive disorders, including endometrial hyperplasia and breast cancer. Estrogens are an etiological factor in many of these conditions. We sought to determine whether in utero exposure to BPA altered the global CpG methylation pattern of the uterine genome, subsequent gene expression, and estrogen response. Pregnant mice were exposed to an environmentally relevant dose of BPA or DMSO control. Uterine DNA and RNA were examined by using methylated DNA immunoprecipitation methylation microarray, expression microarray, and quantitative PCR. In utero BPA exposure altered the global CpG methylation profile of the uterine genome and subsequent gene expression. The effect on gene expression was not apparent until sexual maturation, which suggested that estrogen response was the primary alteration. Indeed, prenatal BPA exposure preferentially altered adult estrogen-responsive gene expression. Changes in estrogen response were accompanied by altered methylation that preferentially affected estrogen receptor-α (ERα)–binding genes. The majority of genes that demonstrated both altered expression and ERα binding had decreased methylation. BPA selectively altered the normal developmental programming of estrogen-responsive genes via modification of the genes that bind ERα. Gene–environment interactions driven by early life xenoestrogen exposure likely contributes to increased risk of estrogen-related disease in adults.—Jorgensen, E. M., Alderman, M. H., III, Taylor, H. S. Preferential epigenetic programming of estrogen response after in utero xenoestrogen (bisphenol-A) exposure. PMID:27312807

  4. Plant responses to soil heterogeneity and global environmental change

    PubMed Central

    García-Palacios, Pablo; Maestre, Fernando T.; Bardgett, Richard D.; de Kroon, Hans

    2015-01-01

    Summary Recent evidence suggests that soil nutrient heterogeneity, a ubiquitous feature of terrestrial ecosystems, modulates plant responses to ongoing global change (GC). However, we know little about the overall trends of such responses, the GC drivers involved, and the plant attributes affected. We synthesized literature to answer the question: Does soil heterogeneity significantly affect plant responses to main GC drivers, such as elevated atmospheric carbon dioxide concentration (CO2), nitrogen (N) enrichment and changes in rainfall regime? Overall, most studies have addressed short-term effects of N enrichment on the performance of model plant communities using experiments conducted under controlled conditions. The role of soil heterogeneity as a modulator of plant responses to elevated CO2 may depend on the plasticity in nutrient uptake patterns. Soil heterogeneity does interact with N enrichment to determine plant growth and nutrient status, but the outcome of this interaction has been found to be both synergistic and inhibitory. The very few studies published on interactive effects of soil heterogeneity and changes in rainfall regime prevented us from identifying any general pattern. We identify the long-term consequences of soil heterogeneity on plant community dynamics in the field, and the ecosystem level responses of the soil heterogeneity × GC driver interaction, as the main knowledge gaps in this area of research. In order to fill these gaps and take soil heterogeneity and GC research a step forward, we propose the following research guidelines: 1) combining morphological and physiological plant responses to soil heterogeneity with field observations of community composition and predictions from simulation models; and 2) incorporating soil heterogeneity into a trait-based response-effect framework, where plant resource-use traits are used as both response variables to this heterogeneity and GC, and predictors of ecosystem functioning. Synthesis

  5. Expressive suppression and neural responsiveness to nonverbal affective cues

    PubMed Central

    Petrican, Raluca; Rosenbaum, R. Shayna; Grady, Cheryl

    2016-01-01

    responsiveness to nonverbal affective cues, while also suggesting one explanation for the suppressors’ poorer cognitive performance in social situations. Moreover, our results point to a potential neural mechanism supporting the development and perpetuation of expressive suppression as an emotion regulation strategy. PMID:26365712

  6. Impaired Overt Facial Mimicry in Response to Dynamic Facial Expressions in High-Functioning Autism Spectrum Disorders

    ERIC Educational Resources Information Center

    Yoshimura, Sayaka; Sato, Wataru; Uono, Shota; Toichi, Motomi

    2015-01-01

    Previous electromyographic studies have reported that individuals with autism spectrum disorders (ASD) exhibited atypical patterns of facial muscle activity in response to facial expression stimuli. However, whether such activity is expressed in visible facial mimicry remains unknown. To investigate this issue, we videotaped facial responses in…

  7. Changes in cerebral blood flow and vasoreactivity in response to acetazolamide in patients with transient global amnesia

    PubMed Central

    Sakashita, Y.; Kanai, M.; Sugimoto, T.; Taki, S.; Takamori, M.

    1997-01-01

    OBJECTIVE—Previous reports about changes in cerebral blood flow (CBF) in transient global amnesia disclosed decreased flow in some parts of the brain. However, CBF analyses in most reports were qualitative but not quantitative. The purpose of this study was to determine changes in CBF in transient global amnesia.
METHODS—The CBF was measured and the vasoreactive response to acetazolamide was evaluated in six patients with transient global amnesia using technetium-99m hexamethylpropylene amine oxime single-photon emission computed tomography (SPECT). The CBF was measured during an attack in two patients and soon after an attack in the other four. About one month later, CBF was re-evaluated in each patient.
RESULTS—Two patients examined during an attack and one patient examined five hours after an attack had increased blood flow in the occipital cortex and cerebellum. Three patients examined at six to 10 hours after an attack had decreased blood flow in the thalamus, cerebellum, or putamen. These abnormalities of blood flow almost disappeared in all patients one month after onset. The vasodilatory response to acetazolamide, which was evaluated initially using SPECT, was poor in areas of increased blood flow. By the second evaluation of CBF with acetazolamide, the vasodilatory response had returned to normal.
CONCLUSIONS—In a patient with transient global amnesia, CBF increased in the vertebrobasilar territory during the attack and decreased afterwards. The vasodilatory response to acetazolamide may be impaired in the parts of the brain with increased blood flow. It is suggested that transient global amnesia is distinct from migraine but may share the same underlying mechanism.

 PMID:9408101

  8. Hospital response to a global budget program under universal health insurance in Taiwan.

    PubMed

    Cheng, Shou-Hsia; Chen, Chi-Chen; Chang, Wei-Ling

    2009-10-01

    Global budget programs are utilized in many countries to control soaring healthcare expenditures. The present study was designed to evaluate the responses of Taiwanese hospitals to a new global budget program implemented in 2002. Using data obtained from the Bureau of National Health Insurance (NHI) and two nationwide surveys conducted before and after the global budget program, changes in the length of stay, treatment intensity, insurance claims, and out-of-pocket fees were compared in 2002 and 2004. The analysis was conducted using the Generalized Estimating Equations (GEEs) method. Regression models revealed that implementation of the global budget was followed by a 7% increase in length of stay and a 15% increase in the number of prescribed procedures and medications per admission. The claim expenses increased by 14%, and out-of-pocket fees per admission increased by 6%. Among the hospitals, no coalition action was found during the study period. In the present study, it appears that hospitals attempted to increase per-case expense claims to protect their reimbursement from possible discounts under a global budget cap. How Taiwanese hospitals respond to this challenge in the future deserves continued, long-term observation.

  9. A global synthesis of animal phenological responses to climate change

    NASA Astrophysics Data System (ADS)

    Cohen, Jeremy M.; Lajeunesse, Marc J.; Rohr, Jason R.

    2018-03-01

    Shifts in phenology are already resulting in disruptions to the timing of migration and breeding, and asynchronies between interacting species1-5. Recent syntheses have concluded that trophic level1, latitude6 and how phenological responses are measured7 are key to determining the strength of phenological responses to climate change. However, researchers still lack a comprehensive framework that can predict responses to climate change globally and across diverse taxa. Here, we synthesize hundreds of published time series of animal phenology from across the planet to show that temperature primarily drives phenological responses at mid-latitudes, with precipitation becoming important at lower latitudes, probably reflecting factors that drive seasonality in each region. Phylogeny and body size are associated with the strength of phenological shifts, suggesting emerging asynchronies between interacting species that differ in body size, such as hosts and parasites and predators and prey. Finally, although there are many compelling biological explanations for spring phenological delays, some examples of delays are associated with short annual records that are prone to sampling error. Our findings arm biologists with predictions concerning which climatic variables and organismal traits drive phenological shifts.

  10. Global transgenerational gene expression dynamics in two newly synthesized allohexaploid wheat (Triticum aestivum) lines

    PubMed Central

    2012-01-01

    genes showing non-additive expression exhibited a significant enrichment for vesicle-function. Conclusions Our results show that two patterns of global alteration in gene expression are conditioned by allohexaploidization in wheat, that is, parental dominance expression and non-additive expression. Both altered patterns of gene expression but not the identity of the genes involved are likely to play functional roles in stabilization and establishment of the newly formed allohexaploid plants, and hence, relevant to speciation and evolution of T. aestivum. PMID:22277161

  11. Transcriptome Analysis of Beta macrocarpa and Identification of Differentially Expressed Transcripts in Response to Beet Necrotic Yellow Vein Virus Infection.

    PubMed

    Fan, Huiyan; Zhang, Yongliang; Sun, Haiwen; Liu, Junying; Wang, Ying; Wang, Xianbing; Li, Dawei; Yu, Jialin; Han, Chenggui

    2015-01-01

    Rhizomania is one of the most devastating diseases of sugar beet. It is caused by Beet necrotic yellow vein virus (BNYVV) transmitted by the obligate root-infecting parasite Polymyxa betae. Beta macrocarpa, a wild beet species widely used as a systemic host in the laboratory, can be rub-inoculated with BNYVV to avoid variation associated with the presence of the vector P. betae. To better understand disease and resistance between beets and BNYVV, we characterized the transcriptome of B. macrocarpa and analyzed global gene expression of B. macrocarpa in response to BNYVV infection using the Illumina sequencing platform. The overall de novo assembly of cDNA sequence data generated 75,917 unigenes, with an average length of 1054 bp. Based on a BLASTX search (E-value ≤ 10-5) against the non-redundant (NR, NCBI) protein, Swiss-Prot, the Gene Ontology (GO), Clusters of Orthologous Groups of proteins (COG) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, there were 39,372 unigenes annotated. In addition, 4,834 simple sequence repeats (SSRs) were also predicted, which could serve as a foundation for various applications in beet breeding. Furthermore, comparative analysis of the two transcriptomes revealed that 261 genes were differentially expressed in infected compared to control plants, including 128 up- and 133 down-regulated genes. GO analysis showed that the changes in the differently expressed genes were mainly enrichment in response to biotic stimulus and primary metabolic process. Our results not only provide a rich genomic resource for beets, but also benefit research into the molecular mechanisms of beet- BNYV Vinteraction.

  12. Dimorphous expressions of positive emotion: displays of both care and aggression in response to cute stimuli.

    PubMed

    Aragón, Oriana R; Clark, Margaret S; Dyer, Rebecca L; Bargh, John A

    2015-03-01

    Extremely positive experiences, and positive appraisals thereof, produce intense positive emotions that often generate both positive expressions (e.g., smiles) and expressions normatively reserved for negative emotions (e.g., tears). We developed a definition of these dimorphous expressions and tested the proposal that their function is to regulate emotions. We showed that individuals who express emotions in this dimorphous manner do so as a general response across a variety of emotionally provoking situations, which suggests that these expressions are responses to intense positive emotion rather than unique to one particular situation. We used cute stimuli (an elicitor of positive emotion) to demonstrate both the existence of these dimorphous expressions and to provide preliminary evidence of their function as regulators of emotion. © The Author(s) 2015.

  13. Post-weaning selenium and folate supplementation affects gene and protein expression and global DNA methylation in mice fed high-fat diets.

    PubMed

    Bermingham, Emma N; Bassett, Shalome A; Young, Wayne; Roy, Nicole C; McNabb, Warren C; Cooney, Janine M; Brewster, Di T; Laing, William A; Barnett, Matthew P G

    2013-03-05

    Consumption of high-fat diets has negative impacts on health and well-being, some of which may be epigenetically regulated. Selenium and folate are two compounds which influence epigenetic mechanisms. We investigated the hypothesis that post-weaning supplementation with adequate levels of selenium and folate in offspring of female mice fed a high-fat, low selenium and folate diet during gestation and lactation will lead to epigenetic changes of potential importance for long-term health. Female offspring of mothers fed the experimental diet were either maintained on this diet (HF-low-low), or weaned onto a high-fat diet with sufficient levels of selenium and folate (HF-low-suf), for 8 weeks. Gene and protein expression, DNA methylation, and histone modifications were measured in colon and liver of female offspring. Adequate levels of selenium and folate post-weaning affected gene expression in colon and liver of offspring, including decreasing Slc2a4 gene expression. Protein expression was only altered in the liver. There was no effect of adequate levels of selenium and folate on global histone modifications in the liver. Global liver DNA methylation was decreased in mice switched to adequate levels of selenium and folate, but there was no effect on methylation of specific CpG sites within the Slc2a4 gene in liver. Post-weaning supplementation with adequate levels of selenium and folate in female offspring of mice fed high-fat diets inadequate in selenium and folate during gestation and lactation can alter global DNA methylation in liver. This may be one factor through which the negative effects of a poor diet during early life can be ameliorated. Further research is required to establish what role epigenetic changes play in mediating observed changes in gene and protein expression, and the relevance of these changes to health.

  14. Post-weaning selenium and folate supplementation affects gene and protein expression and global DNA methylation in mice fed high-fat diets

    PubMed Central

    2013-01-01

    Background Consumption of high-fat diets has negative impacts on health and well-being, some of which may be epigenetically regulated. Selenium and folate are two compounds which influence epigenetic mechanisms. We investigated the hypothesis that post-weaning supplementation with adequate levels of selenium and folate in offspring of female mice fed a high-fat, low selenium and folate diet during gestation and lactation will lead to epigenetic changes of potential importance for long-term health. Methods Female offspring of mothers fed the experimental diet were either maintained on this diet (HF-low-low), or weaned onto a high-fat diet with sufficient levels of selenium and folate (HF-low-suf), for 8 weeks. Gene and protein expression, DNA methylation, and histone modifications were measured in colon and liver of female offspring. Results Adequate levels of selenium and folate post-weaning affected gene expression in colon and liver of offspring, including decreasing Slc2a4 gene expression. Protein expression was only altered in the liver. There was no effect of adequate levels of selenium and folate on global histone modifications in the liver. Global liver DNA methylation was decreased in mice switched to adequate levels of selenium and folate, but there was no effect on methylation of specific CpG sites within the Slc2a4 gene in liver. Conclusions Post-weaning supplementation with adequate levels of selenium and folate in female offspring of mice fed high-fat diets inadequate in selenium and folate during gestation and lactation can alter global DNA methylation in liver. This may be one factor through which the negative effects of a poor diet during early life can be ameliorated. Further research is required to establish what role epigenetic changes play in mediating observed changes in gene and protein expression, and the relevance of these changes to health. PMID:23497688

  15. Two estrogen response element sequences near the PCNA gene are not responsible for its estrogen-enhanced expression in MCF7 cells.

    PubMed

    Wang, Cheng; Yu, Jie; Kallen, Caleb B

    2008-01-01

    The proliferating cell nuclear antigen (PCNA) is an essential component of DNA replication, cell cycle regulation, and epigenetic inheritance. High expression of PCNA is associated with poor prognosis in patients with breast cancer. The 5'-region of the PCNA gene contains two computationally-detected estrogen response element (ERE) sequences, one of which is evolutionarily conserved. Both of these sequences are of undocumented cis-regulatory function. We recently demonstrated that estradiol (E2) enhances PCNA mRNA expression in MCF7 breast cancer cells. MCF7 cells proliferate in response to E2. Here, we demonstrate that E2 rapidly enhanced PCNA mRNA and protein expression in a process that requires ERalpha as well as de novo protein synthesis. One of the two upstream ERE sequences was specifically bound by ERalpha-containing protein complexes, in vitro, in gel shift analysis. Yet, each ERE sequence, when cloned as a single copy, or when engineered as two tandem copies of the ERE-containing sequence, was not capable of activating a luciferase reporter construct in response to E2. In MCF7 cells, neither ERE-containing genomic region demonstrated E2-dependent recruitment of ERalpha by sensitive ChIP-PCR assays. We conclude that E2 enhances PCNA gene expression by an indirect process and that computational detection of EREs, even when evolutionarily conserved and when near E2-responsive genes, requires biochemical validation.

  16. p53 and PCNA expression in advanced colorectal cancer: response to chemotherapy and long-term prognosis.

    PubMed

    Paradiso, A; Rabinovich, M; Vallejo, C; Machiavelli, M; Romero, A; Perez, J; Lacava, J; Cuevas, M A; Rodriquez, R; Leone, B; Sapia, M G; Simone, G; De Lena, M

    1996-12-20

    In a series of 71 patients with advanced colorectal cancer treated with biochemically modulated 5-fluorouracil (5-FU) and methotrexate (MTX), we investigated the relationship between the proliferating-cell nuclear antigen (PCNA) (PC10) and p53 (Pab1801) primary-tumor immunohistochemical expression with respect to clinical response and long-term prognosis. Nuclear p53 expression was demonstrated in 44% of samples (any number of positive tumor cells) while all tumors showed a certain degree of PCNA immunostaining. PCNA immunostaining was correlated with histopathologic grade and p53 expression, while p53 was not correlated with any of the parameters considered. The probability of clinical response to biochemically modulated 5-FU was independent of p53 and PCNA expression. p53 expression (all cut-off values) was not associated with short- or long-term clinical prognosis, whereas patients with higher PCNA primary-tumor expression showed longer survival from treatment and survival from diagnosis, according to univariate and multivariate analysis, particularly in the sub-set of colon-cancer patients. We conclude that the clinical response of advanced-colorectal-cancer patients to biochemically modulated 5-FU and MTX cannot be predicted by PCNA and p53 primary-tumor expression, but high PCNA expression appears to be independently related to long-term prognosis.

  17. Global Analysis of Gene Expression Profiles in Developing Physic Nut (Jatropha curcas L.) Seeds

    PubMed Central

    Jiang, Huawu; Wu, Pingzhi; Zhang, Sheng; Song, Chi; Chen, Yaping; Li, Meiru; Jia, Yongxia; Fang, Xiaohua; Chen, Fan; Wu, Guojiang

    2012-01-01

    Background Physic nut (Jatropha curcas L.) is an oilseed plant species with high potential utility as a biofuel. Furthermore, following recent sequencing of its genome and the availability of expressed sequence tag (EST) libraries, it is a valuable model plant for studying carbon assimilation in endosperms of oilseed plants. There have been several transcriptomic analyses of developing physic nut seeds using ESTs, but they have provided limited information on the accumulation of stored resources in the seeds. Methodology/Principal Findings We applied next-generation Illumina sequencing technology to analyze global gene expression profiles of developing physic nut seeds 14, 19, 25, 29, 35, 41, and 45 days after pollination (DAP). The acquired profiles reveal the key genes, and their expression timeframes, involved in major metabolic processes including: carbon flow, starch metabolism, and synthesis of storage lipids and proteins in the developing seeds. The main period of storage reserves synthesis in the seeds appears to be 29–41 DAP, and the fatty acid composition of the developing seeds is consistent with relative expression levels of different isoforms of acyl-ACP thioesterase and fatty acid desaturase genes. Several transcription factor genes whose expression coincides with storage reserve deposition correspond to those known to regulate the process in Arabidopsis. Conclusions/Significance The results will facilitate searches for genes that influence de novo lipid synthesis, accumulation and their regulatory networks in developing physic nut seeds, and other oil seeds. Thus, they will be helpful in attempts to modify these plants for efficient biofuel production. PMID:22574177

  18. Expression of putative immune response genes during early ontogeny in the coral Acropora millepora.

    PubMed

    Puill-Stephan, Eneour; Seneca, François O; Miller, David J; van Oppen, Madeleine J H; Willis, Bette L

    2012-01-01

    Corals, like many other marine invertebrates, lack a mature allorecognition system in early life history stages. Indeed, in early ontogeny, when corals acquire and establish associations with various surface microbiota and dinoflagellate endosymbionts, they do not efficiently distinguish between closely and distantly related individuals from the same population. However, very little is known about the molecular components that underpin allorecognition and immunity responses or how they change through early ontogeny in corals. Patterns in the expression of four putative immune response genes (apextrin, complement C3, and two CELIII type lectin genes) were examined in juvenile colonies of Acropora millepora throughout a six-month post-settlement period using quantitative real-time PCR (qPCR). Expression of a CELIII type lectin gene peaked in the fourth month for most of the coral juveniles sampled and was significantly higher at this time than at any other sampling time during the six months following settlement. The timing of this increase in expression levels of putative immune response genes may be linked to allorecognition maturation which occurs around this time in A. millepora. Alternatively, the increase may represent a response to immune challenges, such as would be involved in the recognition of symbionts (such as Symbiodinium spp. or bacteria) during winnowing processes as symbioses are fine-tuned. Our data, although preliminary, are consistent with the hypothesis that lectins may play an important role in the maturation of allorecognition responses in corals. The co-expression of lectins with apextrin during development of coral juveniles also raises the possibility that these proteins, which are components of innate immunity in other invertebrates, may influence the innate immune systems of corals through a common pathway or system. However, further studies investigating the expression of these genes in alloimmune-challenged corals are needed to further

  19. Nicotinic alpha 7 receptor expression and modulation of the lung epithelial response to lipopolysaccharide

    PubMed Central

    Myers, Elizabeth J.; Dunn, Diane M.; Weiss, Robert B.; Rogers, Scott W.

    2017-01-01

    Nicotine modulates multiple inflammatory responses in the lung through the nicotinic acetylcholine receptor subtype alpha7 (α7). Previously we reported that α7 modulates both the hematopoietic and epithelium responses in the lung to the bacterial inflammogen, lipopolysaccharide (LPS). Here we apply immunohistochemistry, flow cytometry and RNA-Seq analysis of isolated distal lung epithelium to further define α7-expression and function in this tissue. Mouse lines were used that co-express a bicistronic tau-green fluorescent protein (tGFP) as a reporter of α7 (α7G) expression and that harbor an α7 with a specific point mutation (α7E260A:G) that selectively uncouples it from cell calcium-signaling mechanisms. The tGFP reporter reveals strong cell-specific α7-expression by alveolar macrophages (AM), Club cells and ATII cells. Ciliated cells do not express detectible tGFP, but their numbers decrease by one-third in the α7E260A:G lung compared to controls. Transcriptional comparisons (RNA-Seq) between α7G and α7E260A:G enriched lung epithelium 24 hours after challenge with either intra-nasal (i.n.) saline or LPS reveals a robust α7-genotype impact on both the stasis and inflammatory response of this tissue. Overall the α7E260A:G lung epithelium exhibits reduced inflammatory cytokine/chemokine expression to i.n. LPS. Transcripts specific to Club cells (e.g., CC10, secretoglobins and Muc5b) or to ATII cells (e.g., surfactant proteins) were constitutively decreased in in the α7E260A:G lung, but they were strongly induced in response to i.n. LPS. Protein analysis applying immunohistochemistry and ELISA also revealed α7-associated differences suggested by RNA-Seq including altered mucin protein 5b (Muc5b) accumulation in the α7E260A:G bronchia, that in some cases appeared to form airway plugs, and a substantial increase in extracellular matrix deposits around α7E260A:G airway bronchia linings that was not seen in controls. Our results show that α7 is an

  20. Gene expression profile of the fibrotic response in the peritoneal cavity.

    PubMed

    Le, S J; Gongora, M; Zhang, B; Grimmond, S; Campbell, G R; Campbell, J H; Rolfe, B E

    2010-01-01

    The cellular response to materials implanted in the peritoneal cavity has been utilised to produce tissue for grafting to hollow smooth muscle organs (blood vessels, bladder, uterus and vas deferens). To gain insight into the regulatory mechanisms involved in encapsulation of a foreign object, and subsequent differentiation of encapsulating cells, the present study used microarray technology and real-time RT-PCR to identify the temporal changes in gene expression associated with tissue development. Immunohistochemical analysis showed that 3-7 days post-implantation of foreign objects (cubes of boiled egg white) into rats, they were encapsulated by tissue comprised primarily of haemopoietic (CD45(+)) cells, mainly macrophages (CD68(+), CCR1(+)). By day 14, tissue capsule cells no longer expressed CD68, but were positive for myofibroblast markers alpha-smooth muscle (SM) actin and SM22. In accordance with these results, gene expression data showed that early capsule (days 3-7) development was dominated by the expression of monocyte/macrophage-specific genes (CD14, CSF-1, CSF-1R, MCP-1) and pro-inflammatory mediators such as transforming growth factor (TGF-beta). As tissue capsule development progressed (days 14-21), myofibroblast-associated and pro-fibrotic genes (associated with TGF-beta and Wnt/beta-catenin signalling pathways, including Wnt 4, TGFbetaRII, connective tissue growth factor (CTGF), SMADs-1, -2, -4 and collagen-1 subunits) were significantly up-regulated. The up-regulation of genes associated with Cardiovascular and Skeletal and Muscular System Development at later time-points suggests the capacity of cells within the tissue capsule for further differentiation to smooth muscle, and possibly other cell types. The identification of key regulatory pathways and molecules associated with the fibrotic response to implanted materials has important applications not only for optimising tissue engineering strategies, but also to control deleterious fibrotic

  1. Fear across the senses: brain responses to music, vocalizations and facial expressions

    PubMed Central

    Angulo-Perkins, Arafat; Peretz, Isabelle; Concha, Luis; Armony, Jorge L.

    2015-01-01

    Intrinsic emotional expressions such as those communicated by faces and vocalizations have been shown to engage specific brain regions, such as the amygdala. Although music constitutes another powerful means to express emotions, the neural substrates involved in its processing remain poorly understood. In particular, it is unknown whether brain regions typically associated with processing ‘biologically relevant’ emotional expressions are also recruited by emotional music. To address this question, we conducted an event-related functional magnetic resonance imaging study in 47 healthy volunteers in which we directly compared responses to basic emotions (fear, sadness and happiness, as well as neutral) expressed through faces, non-linguistic vocalizations and short novel musical excerpts. Our results confirmed the importance of fear in emotional communication, as revealed by significant blood oxygen level-dependent signal increased in a cluster within the posterior amygdala and anterior hippocampus, as well as in the posterior insula across all three domains. Moreover, subject-specific amygdala responses to fearful music and vocalizations were correlated, consistent with the proposal that the brain circuitry involved in the processing of musical emotions might be shared with the one that have evolved for vocalizations. Overall, our results show that processing of fear expressed through music, engages some of the same brain areas known to be crucial for detecting and evaluating threat-related information. PMID:24795437

  2. Sex differences in the expression of lung inflammatory mediators in response to ozone

    PubMed Central

    Cabello, Noe; Mishra, Vikas; Sinha, Utkarshna; DiAngelo, Susan L.; Chroneos, Zissis C.; Ekpa, Ndifreke A.; Cooper, Timothy K.; Caruso, Carla R.

    2015-01-01

    Sex differences in the incidence of respiratory diseases have been reported. Women are more susceptible to inflammatory lung disease induced by air pollution and show worse adverse pulmonary health outcomes than men. However, the mechanisms underlying these differences remain unknown. In the present study, we hypothesized that sex differences in the expression of lung inflammatory mediators affect sex-specific immune responses to environmental toxicants. We focused on the effects of ground-level ozone, a major air pollutant, in the expression and regulation of lung immunity genes. We exposed adult male and female mice to 2 ppm of ozone or filtered air (control) for 3 h. We compared mRNA levels of 84 inflammatory genes in lungs harvested 4 h postexposure using a PCR array. We also evaluated changes in lung histology and bronchoalveolar lavage fluid cell counts and protein content at 24 and 72 h postexposure. Our results revealed sex differences in lung inflammation triggered by ozone exposure and in the expression of genes involved in acute phase and inflammatory responses. Major sex differences were found in the expression of neutrophil-attracting chemokines (Ccl20, Cxcl5, and Cxcl2), the proinflammatory cytokine interleukin-6, and oxidative stress-related enzymes (Ptgs2, Nos2). In addition, the phosphorylation of STAT3, known to mediate IL-6-related immune responses, was significantly higher in ozone-exposed mice. Together, our observations suggest that a differential regulation of the lung immune response could be implicated in the observed increased susceptibility to adverse health effects from ozone observed in women vs. men. PMID:26342085

  3. Gene expression profiles responses to aphid feeding in chrysanthemum (Chrysanthemum morifolium).

    PubMed

    Xia, Xiaolong; Shao, Yafeng; Jiang, Jiafu; Ren, Liping; Chen, Fadi; Fang, Weimin; Guan, Zhiyong; Chen, Sumei

    2014-12-02

    Chrysanthemum is an important ornamental plant all over the world. It is easily attacked by aphid, Macrosiphoniella sanbourni. The molecular mechanisms of plant defense responses to aphid are only partially understood. Here, we investigate the gene expression changes in response to aphid feeding in chrysanthemum leaf by RNA-Seq technology. Three libraries were generated from pooled leaf tissues of Chrysanthemum morifolium 'nannongxunzhang' that were collected at different time points with (Y) or without (CK) aphid infestations and mock puncture treatment (Z), and sequenced using an Illumina HiSeqTM 2000 platform. A total of 7,363,292, 7,215,860 and 7,319,841 clean reads were obtained in library CK, Y and Z, respectively. The proportion of clean reads was >97.29% in each library. Approximately 76.35% of the clean reads were mapped to a reference gene database including all known chrysanthemum unigene sequences. 1,157, 527 and 340 differentially expressed genes (DEGs) were identified in the comparison of CK-VS-Y, CK-VS-Z and Z-VS-Y, respectively. These DEGs were involved in phytohormone signaling, cell wall biosynthesis, photosynthesis, reactive oxygen species (ROS) pathway and transcription factor regulatory networks, and so on. Changes in gene expression induced by aphid feeding are shown to be multifaceted. There are various forms of crosstalk between different pathways those genes belonging to, which would allow plants to fine-tune its defense responses.

  4. Expression of disease resistance in genetically modified grapevines correlates with the contents of viral sequences in the T-DNA and global genome methylation.

    PubMed

    Dal Bosco, Daniela; Sinski, Iraci; Ritschel, Patrícia S; Camargo, Umberto A; Fajardo, Thor V M; Harakava, Ricardo; Quecini, Vera

    2018-06-06

    Increased tolerance to pathogens is an important goal in conventional and biotechnology-assisted grapevine breeding programs worldwide. Fungal and viral pathogens cause direct losses in berry production, but also affect the quality of the final products. Precision breeding strategies allow the introduction of resistance characters in elite cultivars, although the factors determining the plant's overall performance are not fully characterized. Grapevine plants expressing defense proteins, from fungal or plant origins, or of the coat protein gene of grapevine leafroll-associated virus 3 (GLRaV-3) were generated by Agrobacterium-mediated transformation of somatic embryos and shoot apical meristems. The responses of the transformed lines to pathogen challenges were investigated by biochemical, phytopathological and molecular methods. The expression of a Metarhizium anisopliae chitinase gene delayed pathogenesis and disease progression against the necrotrophic pathogen Botrytis cinerea. Modified lines expressing a Solanum nigrum osmotin-like protein also exhibited slower disease progression, but to a smaller extent. Grapevine lines carrying two hairpin-inducing constructs had lower GLRaV-3 titers when challenged by grafting, although disease symptoms and viral multiplication were detected. The levels of global genome methylation were determined for the genetically engineered lines, and correlation analyses demonstrated the association between higher levels of methylated DNA and larger portions of virus-derived sequences. Resistance expression was also negatively correlated with the contents of introduced viral sequences and genome methylation, indicating that the effectiveness of resistance strategies employing sequences of viral origin is subject to epigenetic regulation in grapevine.

  5. Global pressures, specific responses: effects of nutrient enrichment in streams from different biomes

    NASA Astrophysics Data System (ADS)

    Artigas, Joan; García-Berthou, Emili; Bauer, Delia E.; Castro, Maria I.; Cochero, Joaquín; Colautti, Darío C.; Cortelezzi, Agustina; Donato, John C.; Elosegi, Arturo; Feijoó, Claudia; Giorgi, Adonis; Gómez, Nora; Leggieri, Leonardo; Muñoz, Isabel; Rodrigues-Capítulo, Alberto; Romaní, Anna M.; Sabater, Sergi

    2013-03-01

    We assessed the effects of nutrient enrichment on three stream ecosystems running through distinct biomes (Mediterranean, Pampean and Andean). We increased the concentrations of N and P in the stream water 1.6-4-fold following a before-after control-impact paired series (BACIPS) design in each stream, and evaluated changes in the biomass of bacteria, primary producers, invertebrates and fish in the enriched (E) versus control (C) reaches after nutrient addition through a predictive-BACIPS approach. The treatment produced variable biomass responses (2-77% of explained variance) among biological communities and streams. The greatest biomass response was observed for algae in the Andean stream (77% of the variance), although fish also showed important biomass responses (about 9-48%). The strongest biomass response to enrichment (77% in all biological compartments) was found in the Andean stream. The magnitude and seasonality of biomass responses to enrichment were highly site specific, often depending on the basal nutrient concentration and on windows of ecological opportunity (periods when environmental constraints other than nutrients do not limit biomass growth). The Pampean stream, with high basal nutrient concentrations, showed a weak response to enrichment (except for invertebrates), whereas the greater responses of Andean stream communities were presumably favored by wider windows of ecological opportunity in comparison to those from the Mediterranean stream. Despite variation among sites, enrichment globally stimulated the algal-based food webs (algae and invertebrate grazers) but not the detritus-based food webs (bacteria and invertebrate shredders). This study shows that nutrient enrichment tends to globally enhance the biomass of stream biological assemblages, but that its magnitude and extent within the food web are complex and are strongly determined by environmental factors and ecosystem structure.

  6. Stability of Lentiviral Vector-Mediated Transgene Expression in the Brain in the Presence of Systemic Antivector Immune Responses

    PubMed Central

    ABORDO-ADESIDA, EVELYN; FOLLENZI, ANTONIA; BARCIA, CARLOS; SCIASCIA, SANDRA; CASTRO, MARIA G.; NALDINI, LUIGI; LOWENSTEIN, PEDRO R.

    2009-01-01

    Lentiviral vectors are promising tools for gene therapy in the CNS. It is therefore important to characterize their interactions with the immune system in the CNS. This work characterizes transgene expression and brain inflammation in the presence or absence of immune responses generated after systemic immunization with lentiviral vectors. We characterized transduction with SIN-LV vectors in the CNS. A dose—response curve using SIN-LV-GFP demonstrated detectable transgene expression in the striatum at a dose of 102, and maximum expression at 106, transducing units of lentiviral vector, with minimal increase in inflammatory markers between the lowest and highest dose of vector injected. Our studies demonstrate that injection of a lentiviral vector into the CNS did not cause a measurable inflammatory response. Systemic immunization after CNS injection, with the lentiviral vector expressing the same transgene as a vector injected into the CNS, caused a decrease in transgene expression in the CNS, concomitantly with an infiltration of inflammatory cells into the CNS parenchyma at the injection site. However, peripheral immunization with a lentiviral vector carrying a different transgene did not diminish transgene expression, or cause CNS inflammation. Systemic immunization preceding injection of lentiviral vectors into the CNS determined that preexisting antilentiviral immunity, regardless of the transgene, did not affect transgene expression. Furthermore, we showed that the transgene, but not the virion or vector components, is responsible for providing antigenic epitopes to the activated immune system, on systemic immunization with lentivirus. Low immunogenicity and prolonged transgene expression in the presence of preexisting lentiviral immunity are encouraging data for the future use of lentiviral vectors in CNS gene therapy. In summary, the lentiviral vectors tested induced undetectable activation of innate immune responses, and stimulation of adaptive immune

  7. Genome-wide Gene Expression Profiling of Acute Metal Exposures in Male Zebrafish

    DTIC Science & Technology

    2014-10-23

    Data in Brief Genome-wide gene expression profiling of acute metal exposures in male zebrafish Christine E. Baer a,⁎, Danielle L. Ippolito b, Naissan... Zebrafish Whole organism Nickel Chromium Cobalt Toxicogenomics To capture global responses to metal poisoning and mechanistic insights into metal...toxicity, gene expression changes were evaluated in whole adult male zebrafish following acute 24 h high dose exposure to three metals with known human

  8. Response to "The Shaky Legal Foundations of the Global Human Rights Education Project"

    ERIC Educational Resources Information Center

    Tibbitts, Felisa

    2015-01-01

    This article is a response to "The Shaky Legal Foundations of the Global Human Rights Education Project," an article written by Barend Vlaardingerbroek, in which Vlaardingerbroek characterizes current practices of human rights education (HRE) as having an overriding agenda of activism, one that can draw on an ideologically-driven…

  9. Stress, and pathogen response gene expression in modeled microgravity

    NASA Technical Reports Server (NTRS)

    Sundaresan, Alamelu; Pellis, Neal R.

    2006-01-01

    Purpose: Immune suppression in microgravity has been well documented. With the advent of human exploration and long-term space travel, the immune system of the astronaut must be optimally maintained. It is important to investigate the expression patterns of cytokine genes, because they are directly related to immune response. Heat shock proteins (HSPs), also called stress proteins, are a group of proteins that are present in the cells of every life form. These proteins are induced when a cell responds to stressors such as heat, cold and oxygen deprivation. Microgravity is another stressor that may regulate HSPs. Heat shock proteins trigger immune response through activities that occur both inside the cell (intracellular) and outside the cell (extracellular). Knowledge about these two gene groups could lead to establishment of a blueprint of the immune response and adaptation-related genes in the microgravity environment. Methods: Human peripheral blood cells were cultured in 1g (T flask) and modeled microgravity (MMG, rotating-wall vessel) for 24 and 72 hours. Cell samples were collected and subjected to gene array analysis using the Affymetrix HG_U95 array. Data was collected and subjected to a two-way analysis of variance. The genes related to immune and stress responses were analyzed. Results and Conclusions: HSP70 was up-regulated by more than two fold in microgravity culture, while HSP90 was significantly down-regulated. HSP70 is not typically expressed in all kinds of cells, but it is expressed at high levels in stress conditions. HSP70 participates in translation, protein translocation, proteolysis and protein folding, suppressing aggregation and reactivating denatured proteins. Increased serum HSP70 levels correlate with a better outcome for heat-stroke or severe trauma patients. At the same time, elevated serum levels of HSP70 have been detected in patients with peripheral or renal vascular disease. HSP90 has been identified in the cytosol, nucleus and

  10. Provider Behavior Under Global Budgeting and Policy Responses

    PubMed Central

    Chang, Chao-Kai; Xirasagar, Sudha; Chen, Brian; Hussey, James R.; Wang, I-Jong; Chen, Jen-Chieh; Lian, Ie-Bin

    2015-01-01

    Third-party payer systems are consistently associated with health care cost escalation. Taiwan’s single-payer, universal coverage National Health Insurance (NHI) adopted global budgeting (GB) to achieve cost control. This study captures ophthalmologists’ response to GB, specifically service volume changes and service substitution between low-revenue and high-revenue services following GB implementation, the subsequent Bureau of NHI policy response, and the policy impact. De-identified eye clinic claims data for the years 2000, 2005, and 2007 were analyzed to study the changes in Simple Claim Form (SCF) claims versus Special Case Claims (SCCs). The 3 study years represent the pre-GB period, post-GB but prior to region-wise service cap implementation period, and the post-service cap period, respectively. Repeated measures multilevel regression analysis was used to study the changes adjusting for clinic characteristics and competition within each health care market. SCF service volume (low-revenue, fixed-price patient visits) remained constant throughout the study period, but SCCs (covering services involving variable provider effort and resource use with flexibility for discretionary billing) increased in 2005 with no further change in 2007. The latter is attributable to a 30% cap negotiated by the NHI Bureau with the ophthalmology association and enforced by the association. This study demonstrates that GB deployed with ongoing monitoring and timely policy responses that are designed in collaboration with professional stakeholders can contain costs in a health insurance–financed health care system. PMID:26324511

  11. The Temporal Dynamics of Two Response-Focused Forms of Emotion Regulation: Experiential, Expressive, and Autonomic Consequences

    PubMed Central

    Dan-Glauser, Elise S.; Gross, James J.

    2011-01-01

    This study examines the early affective consequences of two close forms of suppression. Participants (N=37) were shown negative, positive, and neutral pictures and cued either to attend to the pictures, or to perform expressive or physiological suppression (i.e. reduce body reactions). Continuous measures of experience, expressivity, and autonomic responses showed that both suppression strategies produced rapid response modulation. Common effects of the two strategies included a transient increase in negative feeling, a durable decrease in positive feeling, and a decrease in expressivity, cardiovascular activity, and oxygenation. The two strategies were significantly different only in response to positive stimuli, with physiological suppression showing a larger decrease in experience intensity and blood pressure. These results suggest a strong overlap between the two suppression strategies in terms of their early impact on emotional responses. PMID:21361967

  12. Identification of PEG-induced water stress responsive transcripts using co-expression network in Eucalyptus grandis.

    PubMed

    Ghosh Dasgupta, Modhumita; Dharanishanthi, Veeramuthu

    2017-09-05

    Ecophysiological studies in Eucalyptus have shown that water is the principal factor limiting stem growth. Effect of water deficit conditions on physiological and biochemical parameters has been extensively reported in Eucalyptus. The present study was conducted to identify major polyethylene glycol induced water stress responsive transcripts in Eucalyptus grandis using gene co-expression network. A customized array representing 3359 water stress responsive genes was designed to document their expression in leaves of E. grandis cuttings subjected to -0.225MPa of PEG treatment. The differentially expressed transcripts were documented and significantly co-expressed transcripts were used for construction of network. The co-expression network was constructed with 915 nodes and 3454 edges with degree ranging from 2 to 45. Ninety four GO categories and 117 functional pathways were identified in the network. MCODE analysis generated 27 modules and module 6 with 479 nodes and 1005 edges was identified as the biologically relevant network. The major water responsive transcripts represented in the module included dehydrin, osmotin, LEA protein, expansin, arabinogalactans, heat shock proteins, major facilitator proteins, ARM repeat proteins, raffinose synthase, tonoplast intrinsic protein and transcription factors like DREB2A, ARF9, AGL24, UNE12, WLIM1 and MYB66, MYB70, MYB 55, MYB 16 and MYB 103. The coordinated analysis of gene expression patterns and coexpression networks developed in this study identified an array of transcripts that may regulate PEG induced water stress responses in E. grandis. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Characterization of Changes in Global Genes Expression in the Distal Colon of Loperamide-Induced Constipation SD Rats in Response to the Laxative Effects of Liriope platyphylla

    PubMed Central

    Kim, Ji Eun; Park, So Hae; Kwak, Moon Hwa; Go, Jun; Koh, Eun Kyoung; Song, Sung Hwa; Sung, Ji Eun; Lee, Hee Seob; Hong, Jin Tae; Hwang, Dae Youn

    2015-01-01

    To characterize the changes in global gene expression in the distal colon of constipated SD rats in response to the laxative effects of aqueous extracts of Liriope platyphylla (AEtLP), including isoflavone, saponin, oligosaccharide, succinic acid and hydroxyproline, the total RNA extracted from the distal colon of AEtLP-treated constipation rats was hybridized to oligonucleotide microarrays. The AEtLP treated rats showed an increase in the number of stools, mucosa thickness, flat luminal surface thickness, mucin secretion, and crypt number. Overall, compared to the controls, 581 genes were up-regulated and 216 genes were down-regulated by the constipation induced by loperamide in the constipated rats. After the AEtLP treatment, 67 genes were up-regulated and 421 genes were down-regulated. Among the transcripts up-regulated by constipation, 89 were significantly down-regulated and 22 were recovered to the normal levels by the AEtLP treatment. The major genes in the down-regulated categories included Slc9a5, klk10, Fgf15, and Alpi, whereas the major genes in the recovered categories were Cyp2b2, Ace, G6pc, and Setbp1. On the other hand, after the AEtLP treatment, ten of these genes down-regulated by constipation were up-regulated significantly and five were recovered to the normal levels. The major genes in the up-regulated categories included Serpina3n, Lcn2 and Slc5a8, whereas the major genes in the recovered categories were Tmem45a, Rerg and Rgc32. These results indicate that several gene functional groups and individual genes as constipation biomarkers respond to an AEtLP treatment in constipated model rats. PMID:26151867

  14. Global gene expression profiles in brain regions reflecting abnormal neuronal and glial functions targeting myelin sheaths after 28-day exposure to cuprizone in rats

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Abe, Hajime

    Both developmental and postpubertal cuprizone (CPZ) exposure impairs hippocampal neurogenesis in rats. We previously found that developmental CPZ exposure alters the expression of genes related to neurogenesis, myelination, and synaptic transmission in specific brain regions of offspring. Here, we examined neuronal and glial toxicity profiles in response to postpubertal CPZ exposure by using expression microarray analysis in the hippocampal dentate gyrus, corpus callosum, cerebral cortex, and cerebellar vermis of 5-week-old male rats exposed to 0, 120, and 600 mg/kg CPZ for 28 days. Genes showing transcript upregulation were subjected to immunohistochemical analysis. We found transcript expression alterations at 600 mg/kgmore » for genes related to synaptic transmission, Ache and Prima1, and cell cycle regulation, Tfap4 and Cdkn1a, in the dentate gyrus, which showed aberrant neurogenesis in the subgranular zone. This dose downregulated myelination-related genes in multiple brain regions, whereas KLOTHO{sup +} oligodendrocyte density was decreased only in the corpus callosum. The corpus callosum showed an increase in transcript levels for inflammatory response-related genes and in the number of CD68{sup +} microglia, MT{sup +} astrocytes, and TUNEL{sup +} apoptotic cells. These results suggest that postpubertal CPZ exposure targets synaptic transmission and cell cycle regulation to affect neurogenesis in the dentate gyrus. CPZ suppressed myelination in multiple brain regions and KLOTHO-mediated oligodendrocyte maturation only in the corpus callosum. The increased number of CD68{sup +} microglia, MT{sup +} astrocytes, and TUNEL{sup +} apoptotic cells in the corpus callosum may be involved in the induction of KLOTHO{sup +} oligodendrocyte death and be a protective mechanism against myelin damage following CPZ exposure. - Highlights: • Target gene expression profiles were examined in rats after 28-day CPZ exposure. • Multiple brain region-specific global gene

  15. Gene expression profiling of single cells on large-scale oligonucleotide arrays

    PubMed Central

    Hartmann, Claudia H.; Klein, Christoph A.

    2006-01-01

    Over the last decade, important insights into the regulation of cellular responses to various stimuli were gained by global gene expression analyses of cell populations. More recently, specific cell functions and underlying regulatory networks of rare cells isolated from their natural environment moved to the center of attention. However, low cell numbers still hinder gene expression profiling of rare ex vivo material in biomedical research. Therefore, we developed a robust method for gene expression profiling of single cells on high-density oligonucleotide arrays with excellent coverage of low abundance transcripts. The protocol was extensively tested with freshly isolated single cells of very low mRNA content including single epithelial, mature and immature dendritic cells and hematopoietic stem cells. Quantitative PCR confirmed that the PCR-based global amplification method did not change the relative ratios of transcript abundance and unsupervised hierarchical cluster analysis revealed that the histogenetic origin of an individual cell is correctly reflected by the gene expression profile. Moreover, the gene expression data from dendritic cells demonstrate that cellular differentiation and pathway activation can be monitored in individual cells. PMID:17071717

  16. Expression of Multiple Stress Response Genes by Escherichia Coli Under Modeled Reduced Gravity

    NASA Astrophysics Data System (ADS)

    Vukanti, Raja; Leff, Laura G.

    2012-09-01

    Bacteria, in response to changes in their environment, quickly regulate gene expression; hence, transcriptional profiling has been widely used to characterize bacterial responses to various environmental conditions. In this study, we used clinorotation to grow bacteria under low-sedimentation, -shear, and -turbulence conditions (referred to as modeled reduced gravity, MRG, below) which profoundly impacts bacteria including causing elevated resistance to multiple environmental stresses. To explore potential mechanisms behind the multiple stress resistance response to MRG, we assessed expression levels of E. coli genes, using reverse transcription followed by real-time-PCR, involved in specific stress and general stress responses under MRG and normal gravity (NG) in nutritionally rich and minimal media, and during exponential and stationary phases of growth. In addition, growth rates as well as physico-chemical parameters of culture media were examined. Over-expression of stress response genes (csiD, cstA, katE, otsA, treA) occurred under MRG compared to NG controls, but only during the later stages of growth in rich medium demonstrating that bacterial response to MRG varies with growth-medium and -phase. At stationary phase in rich medium under MRG and NG, E. coli had similar growth rates (based on rRNA-leader abundance) and yields (cell mass and numbers); this coupled, with observations of simultaneous induction of starvation response genes (csiD and cstA) suggests the multiple stress resistance phenotype under MRG could be attributable to microzones of nutrient unavailability around cells. Overall, in rich medium, the response resembled the general stress response (GSR) that E. coli develops during stationary phase of growth. Along these same lines, induction of genes coding for GSR was reversed by improving nutritional conditions under MRG. The reversal of GSR under MRG suggests that the multiple stress response exhibited is not specific to MRG but may result

  17. Global analysis of glycoproteins identifies markers of endotoxin tolerant monocytes and GPR84 as a modulator of TNFα expression.

    PubMed

    Müller, Mario M; Lehmann, Roland; Klassert, Tilman E; Reifenstein, Stella; Conrad, Theresia; Moore, Christoph; Kuhn, Anna; Behnert, Andrea; Guthke, Reinhard; Driesch, Dominik; Slevogt, Hortense

    2017-04-12

    Exposure of human monocytes to lipopolysaccharide (LPS) induces a temporary insensitivity to subsequent LPS challenges, a cellular state called endotoxin tolerance. In this study, we investigated the LPS-induced global glycoprotein expression changes of tolerant human monocytes and THP-1 cells to identify markers and glycoprotein targets capable to modulate the immunosuppressive state. Using hydrazide chemistry and LC-MS/MS analysis, we analyzed glycoprotein expression changes during a 48 h LPS time course. The cellular snapshots at different time points identified 1491 glycoproteins expressed by monocytes and THP-1 cells. Label-free quantitative analysis revealed transient or long-lasting LPS-induced expression changes of secreted or membrane-anchored glycoproteins derived from intracellular membrane coated organelles or from the plasma membrane. Monocytes and THP-1 cells demonstrated marked differences in glycoproteins differentially expressed in the tolerant state. Among the shared differentially expressed glycoproteins G protein-coupled receptor 84 (GPR84) was identified as being capable of modulating pro-inflammatory TNFα mRNA expression in the tolerant cell state when activated with its ligand Decanoic acid.

  18. A Global Drought Observatory for Emergency Response

    NASA Astrophysics Data System (ADS)

    Vogt, Jürgen; de Jager, Alfred; Carrão, Hugo; Magni, Diego; Mazzeschi, Marco; Barbosa, Paulo

    2016-04-01

    Droughts are occurring on all continents and across all climates. While in developed countries they cause significant economic and environmental damages, in less developed countries they may cause major humanitarian catastrophes. The magnitude of the problem and the expected increase in drought frequency, extent and severity in many, often highly vulnerable regions of the world demand a change from the current reactive, crisis-management approach towards a more pro-active, risk management approach. Such approach needs adequate and timely information from global to local scales as well as adequate drought management plans. Drought information systems are important for continuous monitoring and forecasting of the situation in order to provide timely information on developing drought events and their potential impacts. Against this background, the Joint Research Centre (JRC) is developing a Global Drought Observatory (GDO) for the European Commission's humanitarian services, providing up-to-date information on droughts world-wide and their potential impacts. Drought monitoring is achieved by a combination of meteorological and biophysical indicators, while the societal vulnerability to droughts is assessed through the targeted analysis of a series of social, economic and infrastructural indicators. The combination of the information on the occurrence and severity of a drought, on the assets at risk and on the societal vulnerability in the drought affected areas results in a likelihood of impact, which is expressed by a Likelihood of Drought Impact (LDI) indicator. The location, extent and magnitude of the LDI is then further analyzed against the number of people and land use/land cover types affected in order to provide the decision bodies with information on the potential humanitarian and economic bearings in the affected countries or regions. All information is presented through web-mapping interfaces based on OGC standards and customized reports can be drawn by the

  19. Epigallocatechin-3-O-gallate modulates global microRNA expression in interleukin-1β-stimulated human osteoarthritis chondrocytes: potential role of EGCG on negative co-regulation of microRNA-140-3p and ADAMTS5.

    PubMed

    Rasheed, Zafar; Rasheed, Naila; Al-Shaya, Osama

    2018-04-01

    MicroRNAs (miRNAs) are short, non-coding RNAs involved in almost all cellular processes. Epigallocatechin-3-O-gallate (EGCG) is a green tea polyphenol and is known to exert anti-arthritic effects by inhibiting genes associated with osteoarthritis (OA). This study was undertaken to investigate the global effect of EGCG on interleukin-1β (IL-1β)-induced expression of miRNAs in human chondrocytes. Human chondrocytes were derived from OA cartilage and then treated with EGCG and IL-1β. Human miRNA microarray technology was used to determine the expression profile of 1347 miRNAs. Microarray results were verified by taqman assays and transfection of chondrocytes with miRNA inhibitors. Out of 1347 miRNAs, EGCG up-regulated expression of 19 miRNAs and down-regulated expression of 17 miRNAs, whereas expression of 1311 miRNAs remains unchanged in IL-1β-stimulated human OA chondrocytes. Bioinformatics approach showed that 3`UTR of ADAMTS5 mRNA contains the 'seed-matched-sequence' for hsa-miR-140-3p. IL-1β-induced expression of ADAMTS5 correlated with down-regulation of hsa-miR-140-3p. Importantly, EGCG inhibited IL-1β-induced ADAMTS5 expression and up-regulated the expression of hsa-miR-140-3p. This EGCG-induced co-regulation between ADAMTS5 and hsa-miR-140-3p becomes reversed in OA chondrocytes transfected with anti-miR-140-3p. This study provides an important insight into the molecular basis of the reported anti-arthritic effects of EGCG. Our data indicate that the potential of EGCG in OA chondrocytes may be related to its ability to globally inhibit inflammatory response via modulation of miRNAs expressions.

  20. Global Gene Expression Profiling of the Asymptomatic Bacteriuria Escherichia coli Strain 83972 in the Human Urinary Tract†

    PubMed Central

    Roos, Viktoria; Klemm, Per

    2006-01-01

    Urinary tract infections (UTIs) are an important health problem worldwide, with many million cases each year. Escherichia coli is the most common organism causing UTIs in humans. The asymptomatic bacteriuria E. coli strain 83972 is an excellent colonizer of the human urinary tract, where it causes long-term bladder colonization. The strain has been used for prophylactic purposes in patients prone to more severe and recurrent UTIs. For this study, we used DNA microarrays to monitor the expression profile of strain 83972 in the human urinary tract. Significant differences in expression levels were seen between the in vivo expression profiles of strain 83972 in three patients and the corresponding in vitro expression profiles in lab medium and human urine. The data revealed an in vivo lifestyle of microaerobic growth with respiration of nitrate coupled to degradation of sugar acids and amino acids, with no signs of attachment to host tissues. Interestingly, genes involved in NO protection and metabolism showed significant up-regulation in the patients. This is one of the first studies to address bacterial whole-genome expression in humans and the first study to investigate global gene expression of an E. coli strain in the human urinary tract. PMID:16714589

  1. Muscle myeloid type I interferon gene expression may predict therapeutic responses to rituximab in myositis patients.

    PubMed

    Nagaraju, Kanneboyina; Ghimbovschi, Svetlana; Rayavarapu, Sree; Phadke, Aditi; Rider, Lisa G; Hoffman, Eric P; Miller, Frederick W

    2016-09-01

    To identify muscle gene expression patterns that predict rituximab responses and assess the effects of rituximab on muscle gene expression in PM and DM. In an attempt to understand the molecular mechanism of response and non-response to rituximab therapy, we performed Affymetrix gene expression array analyses on muscle biopsy specimens taken before and after rituximab therapy from eight PM and two DM patients in the Rituximab in Myositis study. We also analysed selected muscle-infiltrating cell phenotypes in these biopsies by immunohistochemical staining. Partek and Ingenuity pathway analyses assessed the gene pathways and networks. Myeloid type I IFN signature genes were expressed at higher levels at baseline in the skeletal muscle of rituximab responders than in non-responders, whereas classic non-myeloid IFN signature genes were expressed at higher levels in non-responders at baseline. Also, rituximab responders have a greater reduction of the myeloid and non-myeloid type I IFN signatures than non-responders. The decrease in the type I IFN signature following administration of rituximab may be associated with the decreases in muscle-infiltrating CD19(+) B cells and CD68(+) macrophages in responders. Our findings suggest that high levels of myeloid type I IFN gene expression in skeletal muscle predict responses to rituximab in PM/DM and that rituximab responders also have a greater decrease in the expression of these genes. These data add further evidence to recent studies defining the type I IFN signature as both a predictor of therapeutic responses and a biomarker of myositis disease activity. Published by Oxford University Press on behalf British Society for Rheumatology 2016. This work is written by US Government employees and is in the public domain in the US.

  2. The next 5 years of global HIV/AIDS policy: critical gaps and strategies for effective responses.

    PubMed

    Szekeres, Greg

    2008-08-01

    The University of California, Los Angeles Program in Global Health performed a landscape analysis based on interviews conducted between November 2006 and February 2007 with 35 key informants from major international organizations conducting HIV/AIDS work. Institutions represented included multilateral organizations, foundations, and governmental and non-governmental organizations. The purpose of this analysis is to assist major foundations and other institutions to understand better the international HIV/AIDS policy landscape and to formulate research and development programmes that can make a significant contribution to moving important issues forward in the HIV/AIDS policy arena. Topics identified during the interviews were organized around the four major themes of the Ford Foundation's Global HIV/AIDS Initiative: leadership and leadership development; equity; accountability; and global partnerships. Key informants focused on the need for a visionary response to the HIV pandemic, the need to maintain momentum, ways to improve the scope of leadership development programmes, ideas for improving gender equity and addressing regional disparities and the needs of vulnerable populations, recommendations for strengthening accountability mechanisms among governments, foundations, and civil society and on calling for increased collaboration and partnership among key players in the global HIV/AIDS response.

  3. A global response to a global problem: the epidemic of overnutrition.

    PubMed Central

    Chopra, Mickey; Galbraith, Sarah; Darnton-Hill, Ian

    2002-01-01

    It is estimated that by 2020 two-thirds of the global burden of disease will be attributable to chronic noncommunicable diseases, most of them strongly associated with diet. The nutrition transition towards refined foods, foods of animal origin, and increased fats plays a major role in the current global epidemics of obesity, diabetes and cardiovascular diseases, among other noncommunicable conditions. Sedentary lifestyles and the use of tobacco are also significant risk factors. The epidemics cannot be ended simply by encouraging people to reduce their risk factors and adopt healthier lifestyles, although such encouragement is undoubtedly beneficial if the targeted people can respond. Unfortunately, increasingly obesogenic environments, reinforced by many of the cultural changes associated with globalization, make even the adoption of healthy lifestyles, especially by children and adolescents, more and more difficult. The present paper examines some possible mechanisms for, and WHO's role in, the development of a coordinated global strategy on diet, physical activity and health. The situation presents many countries with unmanageable costs. At the same time there are often continuing problems of undernutrition. A concerted multisectoral approach, involving the use of policy, education and trade mechanisms, is necessary to address these matters. PMID:12571723

  4. Expressive suppression and neural responsiveness to nonverbal affective cues.

    PubMed

    Petrican, Raluca; Rosenbaum, R Shayna; Grady, Cheryl

    2015-10-01

    Optimal social functioning occasionally requires concealment of one's emotions in order to meet one's immediate goals and environmental demands. However, because emotions serve an important communicative function, their habitual suppression disrupts the flow of social exchanges and, thus, incurs significant interpersonal costs. Evidence is accruing that the disruption in social interactions, linked to habitual expressive suppression use, stems not only from intrapersonal, but also from interpersonal causes, since the suppressors' restricted affective displays reportedly inhibit their interlocutors' emotionally expressive behaviors. However, expressive suppression use is not known to lead to clinically significant social impairments. One explanation may be that over the lifespan, individuals who habitually suppress their emotions come to compensate for their interlocutors' restrained expressive behaviors by developing an increased sensitivity to nonverbal affective cues. To probe this issue, the present study used functional magnetic resonance imaging (fMRI) to scan healthy older women while they viewed silent videos of a male social target displaying nonverbal emotional behavior, together with a brief verbal description of the accompanying context, and then judged the target's affect. As predicted, perceivers who reported greater habitual use of expressive suppression showed increased neural processing of nonverbal affective cues. This effect appeared to be coordinated in a top-down manner via cognitive control. Greater neural processing of nonverbal cues among perceivers who habitually suppress their emotions was linked to increased ventral striatum activity, suggestive of increased reward value/personal relevance ascribed to emotionally expressive nonverbal behaviors. These findings thus provide neural evidence broadly consistent with the hypothesized link between habitual use of expressive suppression and compensatory development of increased responsiveness to

  5. Global transcriptional profiling of a cold-tolerant rice variety under moderate cold stress reveals different cold stress response mechanisms.

    PubMed

    Zhao, Junliang; Zhang, Shaohong; Yang, Tifeng; Zeng, Zichong; Huang, Zhanghui; Liu, Qing; Wang, Xiaofei; Leach, Jan; Leung, Hei; Liu, Bin

    2015-07-01

    Gene expression profiling under severe cold stress (4°C) has been conducted in plants including rice. However, rice seedlings are frequently exposed to milder cold stresses under natural environments. To understand the responses of rice to milder cold stress, a moderately low temperature (8°C) was used for cold treatment prior to genome-wide profiling of gene expression in a cold-tolerant japonica variety, Lijiangxintuanheigu (LTH). A total of 5557 differentially expressed genes (DEGs) were found at four time points during moderate cold stress. Both the DEGs and differentially expressed transcription factor genes were clustered into two groups based on their expression, suggesting a two-phase response to cold stress and a determinative role of transcription factors in the regulation of stress response. The induction of OsDREB2A under cold stress is reported for the first time in this study. Among the anti-oxidant enzyme genes, glutathione peroxidase (GPX) and glutathione S-transferase (GST) were upregulated, suggesting that the glutathione system may serve as the main reactive oxygen species (ROS) scavenger in LTH. Changes in expression of genes in signal transduction pathways for auxin, abscisic acid (ABA) and salicylic acid (SA) imply their involvement in cold stress responses. The induction of ABA response genes and detection of enriched cis-elements in DEGs suggest that ABA signaling pathway plays a dominant role in the cold stress response. Our results suggest that rice responses to cold stress vary with the specific temperature imposed and the rice genotype. © 2014 Scandinavian Plant Physiology Society.

  6. Coordinated approaches to quantify long-term ecosystem dynamics in response to global change

    Treesearch

    Yiqi Luo; Jerry Melillo; Shuli Niu; Claus Beier; James S. Clark; Aime E.T. Classen; Eric Dividson; Jeffrey S. Dukes; R. Dave Evans; Christopher B. Field; Claudia I. Czimczik; Michael Keller; Bruce A. Kimball; Lara M. Kueppers; Richard J. Norby; Shannon L. Pelini; Elise Pendall; Edward Rastetter; Johan Six; Melinda Smith; Mark G. Tjoelker; Margaret S. Torn

    2011-01-01

    Many serious ecosystem consequences of climate change will take decades or even centuries to emerge. Long-term ecological responses to global change are strongly regulated by slow processes, such as changes in species composition, carbon dynamics in soil and by long-lived plants, and accumulation of nutrient capitals. Understanding and predicting these processes...

  7. Biomarker discovery and gene expression responses in Lycopersicon esculentum root exposed to lead.

    PubMed

    Hou, Jing; Bai, Lili; Xie, Yujia; Liu, Xinhui; Cui, Baoshan

    2015-12-15

    Gene expression analysis has shown particular promise for the identification of molecular biomarkers that can be used for further evaluation of potential toxicity of chemicals present in agricultural soil. In the study, we focused on the development of molecular markers to detect Pb toxicity in agricultural soil. Using the results obtained from microarray analysis, twelve Pb-responsive genes were selected and tested in different Pb concentrations to examine their concentration-response characteristics using real-time quantitative polymerase chain reaction (RT-qPCR). All the Pb treatments set in our study could generally induce the differential expression of the 12 genes, while the lowest observable adverse effect concentration (LOAEC) of Pb for seed germination, root elongation, biomass and structural modification derived from 1,297, 177, 177, and 1,297 mg Pb/kg soil, respectively, suggesting that the transcriptional approach was more sensitive than the traditional end points of death, growth, and morphology for the evaluation of Pb toxicity. The relative expression of glycoalkaloid metabolism 1 (P=-0.790), ethylene-responsive transcription factor ERF017 (P=-0.686) and CASP-like protein 4C2 (P=-0.652) demonstrates a dose-dependent response with Pb content in roots, implying that the three genes can be used as sensitive bioindicators of Pb stress in Lycopersicon esculentum. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Transcriptional Orchestration of the Global Cellular Response of a Model Pennate Diatom to Diel Light Cycling under Iron Limitation

    DOE PAGES

    Smith, Sarah R.; Gillard, Jeroen T. F.; Kustka, Adam B.; ...

    2016-12-14

    Environmental fluctuations affect distribution, growth and abundance of diatoms in nature, with iron (Fe) availability playing a central role. Studies on the response of diatoms to low Fe have either utilized continuous (24 hr) illumination or sampled a single time of day, missing any temporal dynamics. We profiled the physiology, metabolite composition, and global transcripts of the pennate diatom Phaeodactylum tricornutum during steady-state growth at low, intermediate, and high levels of dissolved Fe over light:dark cycles, to better understand fundamental aspects of genetic control of physiological acclimation to growth under Fe-limitation. We greatly expand the catalog of genes involved inmore » the low Fe response, highlighting the importance of intracellular trafficking in Fe-limited diatoms. P. tricornutum exhibited transcriptomic hallmarks of slowed growth leading to prolonged periods of cell division/silica deposition, which could impact biogeochemical carbon sequestration in Fe-limited regions. Light harvesting and ribosome biogenesis transcripts were generally reduced under low Fe while transcript levels for genes putatively involved in the acquisition and recycling of Fe were increased. We also noted shifts in expression towards increased synthesis and catabolism of branched chain amino acids in P. tricornutum grown at low Fe whereas expression of genes involved in central core metabolism were relatively unaffected, indicating that essential cellular function is protected. Beyond the response of P. tricornutum to low Fe, we observed major coordinated shifts in transcript control of primary and intermediate metabolism over light:dark cycles which contribute to a new view of the significance of distinctive diatom pathways, such as mitochondrial glycolysis and the ornithine-urea cycle. This study provides new insight into transcriptional modulation of diatom physiology and metabolism across light:dark cycles in response to Fe availability, providing

  9. Transcriptional Orchestration of the Global Cellular Response of a Model Pennate Diatom to Diel Light Cycling under Iron Limitation

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Smith, Sarah R.; Gillard, Jeroen T. F.; Kustka, Adam B.

    Environmental fluctuations affect distribution, growth and abundance of diatoms in nature, with iron (Fe) availability playing a central role. Studies on the response of diatoms to low Fe have either utilized continuous (24 hr) illumination or sampled a single time of day, missing any temporal dynamics. We profiled the physiology, metabolite composition, and global transcripts of the pennate diatom Phaeodactylum tricornutum during steady-state growth at low, intermediate, and high levels of dissolved Fe over light:dark cycles, to better understand fundamental aspects of genetic control of physiological acclimation to growth under Fe-limitation. We greatly expand the catalog of genes involved inmore » the low Fe response, highlighting the importance of intracellular trafficking in Fe-limited diatoms. P. tricornutum exhibited transcriptomic hallmarks of slowed growth leading to prolonged periods of cell division/silica deposition, which could impact biogeochemical carbon sequestration in Fe-limited regions. Light harvesting and ribosome biogenesis transcripts were generally reduced under low Fe while transcript levels for genes putatively involved in the acquisition and recycling of Fe were increased. We also noted shifts in expression towards increased synthesis and catabolism of branched chain amino acids in P. tricornutum grown at low Fe whereas expression of genes involved in central core metabolism were relatively unaffected, indicating that essential cellular function is protected. Beyond the response of P. tricornutum to low Fe, we observed major coordinated shifts in transcript control of primary and intermediate metabolism over light:dark cycles which contribute to a new view of the significance of distinctive diatom pathways, such as mitochondrial glycolysis and the ornithine-urea cycle. This study provides new insight into transcriptional modulation of diatom physiology and metabolism across light:dark cycles in response to Fe availability, providing

  10. Rapid-response flood mapping during Hurricanes Harvey, Irma and Maria by the Global Flood Partnership (GFP)

    NASA Astrophysics Data System (ADS)

    Cohen, S.; Alfieri, L.; Brakenridge, G. R.; Coughlan, E.; Galantowicz, J. F.; Hong, Y.; Kettner, A.; Nghiem, S. V.; Prados, A. I.; Rudari, R.; Salamon, P.; Trigg, M.; Weerts, A.

    2017-12-01

    The Global Flood Partnership (GFP; https://gfp.jrc.ec.europa.eu) is a multi-disciplinary group of scientists, operational agencies and flood risk managers focused on developing efficient and effective global flood management tools. Launched in 2014, its aim is to establish a partnership for global flood forecasting, monitoring and impact assessment to strengthen preparedness and response and to reduce global disaster losses. International organizations, the private sector, national authorities, universities and research agencies contribute to the GFP on a voluntary basis and benefit from a global network focused on flood risk reduction. At the onset of Hurricane Harvey, GFP was `activated' using email requests via its mailing service. Soon after, flood inundation maps, based on remote sensing analysis and modeling, were shared by different agencies, institutions, and individuals. These products were disseminated, to varying degrees of effectiveness, to federal, state and local agencies via emails and data-sharing services. This generated a broad data-sharing network which was utilized at the early stages of Hurricane Irma's impact, just two weeks after Harvey. In this presentation, we will describe the extent and chronology of the GFP response to both Hurricanes Harvey, Irma and Maria. We will assess the potential usefulness of this effort for event managers in various types of organizations and discuss future improvements to be implemented.

  11. Fear across the senses: brain responses to music, vocalizations and facial expressions.

    PubMed

    Aubé, William; Angulo-Perkins, Arafat; Peretz, Isabelle; Concha, Luis; Armony, Jorge L

    2015-03-01

    Intrinsic emotional expressions such as those communicated by faces and vocalizations have been shown to engage specific brain regions, such as the amygdala. Although music constitutes another powerful means to express emotions, the neural substrates involved in its processing remain poorly understood. In particular, it is unknown whether brain regions typically associated with processing 'biologically relevant' emotional expressions are also recruited by emotional music. To address this question, we conducted an event-related functional magnetic resonance imaging study in 47 healthy volunteers in which we directly compared responses to basic emotions (fear, sadness and happiness, as well as neutral) expressed through faces, non-linguistic vocalizations and short novel musical excerpts. Our results confirmed the importance of fear in emotional communication, as revealed by significant blood oxygen level-dependent signal increased in a cluster within the posterior amygdala and anterior hippocampus, as well as in the posterior insula across all three domains. Moreover, subject-specific amygdala responses to fearful music and vocalizations were correlated, consistent with the proposal that the brain circuitry involved in the processing of musical emotions might be shared with the one that have evolved for vocalizations. Overall, our results show that processing of fear expressed through music, engages some of the same brain areas known to be crucial for detecting and evaluating threat-related information. © The Author (2014). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  12. Leveraging the laboratory response network model for the global health security agenda.

    PubMed

    Mangal, Chris N; Maryogo-Robinson, Lucy

    2014-01-01

    Promoting global health security as an international priority is a challenge; the US Centers for Disease Control and Prevention (CDC) in its Global Health Security Agenda has articulated the importance of accelerating progress toward a world safe and secure from infectious disease threats. The goals are to (1) prevent and reduce the likelihood of outbreaks-natural, accidental, or intentional; (2) detect threats early to save lives; and (3) respond rapidly and effectively using multisectoral, international coordination and communication. Foundational to this agenda is the World Health Organization (WHO) Revised International Health Regulations (IHR) of 2005, which provide the legal framework for countries to strengthen their health systems in order to be able to respond to any public health emergency of international concern. This article proposes leveraging the distributed structure of the US-managed Laboratory Response Network for Biological Threats Preparedness (LRN-B) to develop the core capacity of laboratory testing and to fulfill the laboratory-strengthening component of the Global Health Security Agenda. The LRN model offers an effective mechanism to detect and respond to public health emergencies of international concern.

  13. Leveraging the Laboratory Response Network Model for the Global Health Security Agenda

    PubMed Central

    Maryogo-Robinson, Lucy

    2014-01-01

    Promoting global health security as an international priority is a challenge; the US Centers for Disease Control and Prevention (CDC) in its Global Health Security Agenda has articulated the importance of accelerating progress toward a world safe and secure from infectious disease threats. The goals are to (1) prevent and reduce the likelihood of outbreaks—natural, accidental, or intentional; (2) detect threats early to save lives; and (3) respond rapidly and effectively using multisectoral, international coordination and communication. Foundational to this agenda is the World Health Organization (WHO) Revised International Health Regulations (IHR) of 2005, which provide the legal framework for countries to strengthen their health systems in order to be able to respond to any public health emergency of international concern. This article proposes leveraging the distributed structure of the US-managed Laboratory Response Network for Biological Threats Preparedness (LRN-B) to develop the core capacity of laboratory testing and to fulfill the laboratory-strengthening component of the Global Health Security Agenda. The LRN model offers an effective mechanism to detect and respond to public health emergencies of international concern. PMID:25254916

  14. Notch-ligand expression by NALT dendritic cells regulates mucosal Th1- and Th2-type responses

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Fukuyama, Yoshiko; Tokuhara, Daisuke; Division of Mucosal Immunology, Institute of Medical Science, University of Tokyo, Tokyo 108-8639

    Highlights: Black-Right-Pointing-Pointer Nasal Ad-FL effectively up-regulates APC function by CD11c{sup +} DCs in mucosal tissues. Black-Right-Pointing-Pointer Nasal Ad-FL induces Notch ligand (L)-expressing CD11c{sup +} DCs. Black-Right-Pointing-Pointer Notch L-expressing DCs support the induction of Th1- and Th2-type cytokine responses. -- Abstract: Our previous studies showed that an adenovirus (Ad) serotype 5 vector expressing Flt3 ligand (Ad-FL) as nasal adjuvant activates CD11c{sup +} dendritic cells (DCs) for the enhancement of antigen (Ag)-specific IgA antibody (Ab) responses. In this study, we examined the molecular mechanism for activation of CD11c{sup +} DCs and their roles in induction of Ag-specific Th1- and Th2-cell responses. Ad-FLmore » activated CD11c{sup +} DCs expressed increased levels of the Notch ligand (L)-expression and specific mRNA. When CD11c{sup +} DCs from various mucosal and systemic lymphoid tissues of mice given nasal OVA plus Ad-FL were cultured with CD4{sup +} T cells isolated from non-immunized OVA TCR-transgenic (OT II) mice, significantly increased levels of T cell proliferative responses were noted. Furthermore, Ad-FL activated DCs induced IFN-{gamma}, IL-2 and IL-4 producing CD4{sup +} T cells. Of importance, these APC functions by Ad-FL activated DCs were down-regulated by blocking Notch-Notch-L pathway. These results show that Ad-FL induces CD11c{sup +} DCs to the express Notch-ligands and these activated DCs regulate the induction of Ag-specific Th1- and Th2-type cytokine responses.« less

  15. A Gene Expression Profile of BRCAness That Predicts for Responsiveness to Platinum and PARP Inhibitors

    DTIC Science & Technology

    2015-10-01

    1 Award Number: W81XWH-10-1-0585 TITLE: A Gene Expression Profile of BRCAness That Predicts for Responsiveness to Platinum and PARP Inhibitors...TITLE AND SUBTITLE A Gene Expression Profile of BRCAness That Predicts for Responsiveness to Platinum and PARP Inhibitors 5a. CONTRACT NUMBER W81XWH...BRCAlike, i.e. not HR deficient and are resistant to PARPis but are sensitive to platinum . These tumors exhibit alterations in another DNA repair

  16. Characterization of a type-A response regulator differentially expressed during adventitious caulogenesis in Pinus pinaster.

    PubMed

    Alvarez, José M; Cortizo, Millán; Ordás, Ricardo J

    2012-12-15

    The molecular cloning and characterization of PipsRR1, a type-A response regulator in Pinus pinaster, is reported here. Type-A response regulators mediate downstream responses to cytokinin and act as negative feedback regulators of the signal transduction pathway. Some type-A response regulators in Arabidopsis have been related to de novo meristem formation. However, little information exists in Pinus spp. The PipsRR1 gene contains 5 exons, as do all type-A response regulators in Arabidopsis, and the deduced protein contains a receiver domain with the conserved DDK residues and a short C terminal extension. Expression analysis showed that the PipsRR1 gene is differentially expressed during the first phases of adventitious caulogenesis induced by benzyladenine in P. pinaster cotyledons, suggesting that PipsRR1 plays a role in caulogenesis in conifers. Additionally, a binary vector carrying the PipsRR1 promoter driving GFP:GUS expression was constructed to analyze the promoter activity in P. pinaster somatic embryos. The results of genetic transformation showed GUS activity during somatic embryo mass proliferation and embryo maturation. Copyright © 2012 Elsevier GmbH. All rights reserved.

  17. Global Initiatives for Early Childhood Care and Education: Global Guidelines and Global Guidelines Assessment

    ERIC Educational Resources Information Center

    Trube, Mary Barbara

    2015-01-01

    This report focuses on the Association for Childhood Education International's (ACEI) Global Guidelines (GG) and Global Guidelines Assessment (GGA), which were developed in response to and in keeping with the prominence that the issue of quality early childhood care, development, and education has reached globally. Further, the paper positions the…

  18. Terrestrial water flux responses to global warming in tropical rainforest areas

    NASA Astrophysics Data System (ADS)

    Lan, Chia-Wei; Lo, Min-Hui; Chou, Chia; Kumar, Sanjiv

    2016-05-01

    Precipitation extremes are expected to become more frequent in the changing global climate, which may considerably affect the terrestrial hydrological cycle. In this study, Coupled Model Intercomparison Project Phase 5 archives have been examined to explore the changes in normalized terrestrial water fluxes (precipitation minus evapotranspiration minus total runoff, divided by the precipitation climatology) in three tropical rainforest areas: Maritime Continent, Congo, and Amazon. Results show that a higher frequency of intense precipitation events is predicted for the Maritime Continent in the future climate than in the present climate, but not for the Amazon or Congo rainforests. Nonlinear responses to extreme precipitation lead to a reduced groundwater recharge and a proportionately greater amount of direct runoff, particularly for the Maritime Continent, where both the amount and intensity of precipitation increase under global warming. We suggest that the nonlinear response is related to the existence of a higher near-surface soil moisture over the Maritime Continent than that over the Amazon and Congo rainforests. The wetter soil over the Maritime Continent also leads to an increased subsurface runoff. Thus, increased precipitation extremes and concomitantly reduced terrestrial water fluxes lead to an intensified hydrological cycle for the Maritime Continent. This has the potential to result in a strong temporal heterogeneity in soil water distribution affecting the ecosystem of the rainforest region and increasing the risk of flooding and/or landslides.

  19. Expression of multidrug resistance efflux pump gene norA is iron responsive in Staphylococcus aureus.

    PubMed

    Deng, Xin; Sun, Fei; Ji, Quanjiang; Liang, Haihua; Missiakas, Dominique; Lan, Lefu; He, Chuan

    2012-04-01

    Staphylococcus aureus utilizes efflux transporter NorA to pump out a wide range of structurally dissimilar drugs, conferring low-level multidrug resistance. The regulation of norA expression has yet to be fully understood although past studies have revealed that this gene is under the control of the global transcriptional regulator MgrA and the two-component system ArlRS. To identify additional regulators of norA, we screened a transposon library in strain Newman expressing the transcriptional fusion norA-lacZ for altered β-galactosidase activity. We identify a transposon insertion in fhuB, a gene that encodes a ferric hydroxamate uptake system permease, and propose that the norA transcription is iron responsive. In agreement with this observation, addition of FeCl(3) repressed the induction of norA-lacZ, suggesting that bacterial iron uptake plays an important role in regulating norA transcription. In addition, a fur (ferric uptake regulator) deletion exhibited compromised norA transcription and reduced resistance to quinolone compared to the wild-type strain, indicating that fur functions as a positive regulator of norA. A putative Fur box identified in the promoter region of norA was confirmed by electrophoretic mobility shift and DNase I footprint assays. Finally, by employing a siderophore secretion assay, we reveal that NorA may contribute to the export of siderophores. Collectively, our experiments uncover some novel interactions between cellular iron level and norA regulation in S. aureus.

  20. Expression of Multidrug Resistance Efflux Pump Gene norA Is Iron Responsive in Staphylococcus aureus

    PubMed Central

    Deng, Xin; Sun, Fei; Ji, Quanjiang; Liang, Haihua; Missiakas, Dominique; Lan, Lefu

    2012-01-01

    Staphylococcus aureus utilizes efflux transporter NorA to pump out a wide range of structurally dissimilar drugs, conferring low-level multidrug resistance. The regulation of norA expression has yet to be fully understood although past studies have revealed that this gene is under the control of the global transcriptional regulator MgrA and the two-component system ArlRS. To identify additional regulators of norA, we screened a transposon library in strain Newman expressing the transcriptional fusion norA-lacZ for altered β-galactosidase activity. We identify a transposon insertion in fhuB, a gene that encodes a ferric hydroxamate uptake system permease, and propose that the norA transcription is iron responsive. In agreement with this observation, addition of FeCl3 repressed the induction of norA-lacZ, suggesting that bacterial iron uptake plays an important role in regulating norA transcription. In addition, a fur (ferric uptake regulator) deletion exhibited compromised norA transcription and reduced resistance to quinolone compared to the wild-type strain, indicating that fur functions as a positive regulator of norA. A putative Fur box identified in the promoter region of norA was confirmed by electrophoretic mobility shift and DNase I footprint assays. Finally, by employing a siderophore secretion assay, we reveal that NorA may contribute to the export of siderophores. Collectively, our experiments uncover some novel interactions between cellular iron level and norA regulation in S. aureus. PMID:22267518

  1. GloboLakes: A global observatory of lake responses to environmental change.

    NASA Astrophysics Data System (ADS)

    Groom, Steve; Tyler, Andrew; Hunter, Peter; Spyrakos, Evangelos; Martinez-Vicente, Victor; Merchant, Chris; Cutler, Mark; Rowan, John; Dawson, Terry; Maberly, Stephen; Cavalho, Laurence; Elliot, Alex; Thackery, Stephen; Miller, Claire; Scott, Marian

    2014-05-01

    The world's freshwater ecosystems are vital components of the global biosphere, yet are vulnerable to climate and other human-induced change. There is increasing recognition that lakes play an important role in global biogeochemical cycling and provide key ecosystem services. However, our understanding of how lakes respond to environmental change at a global scale, and how this impacts on their status and function, is hampered by limited information on their chemical, physical and ecological condition. There are estimated to be over 300 million lakes globally, of which over 17,000 are greater than 10 km2 in surface area. These numbers have limited the systematic study of lake ecosystems. GloboLakes is a five-year UK research programme investigating the state of lakes and their response to climatic and other environmental drivers of change. It will establish a satellite-based observatory with archive and near-real time data processing to produce a time series of observed biogeochemical parameters and lake temperature for over 1000 lakes globally. This will be supported by linked ancillary data on climate and catchment land-use. The ability to monitor a large number of lakes consistently at high frequency and globally will facilitate a paradigm shift in our understanding of how lakes respond to environmental change at different spatial and temporal scales. A key requirement is to validate satellite retrieval algorithms and test the time-series of resulting lake properties such as chlorophyll-a by comparison with in situ data. To support the former extensive bio-optical and constituent data were taken in year 1 of the project in a number of UK lakes with a variety of trophic states. Furthermore, for wider validation activities GloboLakes has established the LIMNADES initiative to create a centralised database of ground bio-optical measurements of worldwide lakes through voluntary cooperation across the international scientific community. This presentation will

  2. Digital Health Communication and Global Public Influence: A Study of the Ebola Epidemic.

    PubMed

    Roberts, Hal; Seymour, Brittany; Fish, Sands Alden; Robinson, Emily; Zuckerman, Ethan

    2017-01-01

    Scientists and health communication professionals expressed frustration over the relationship between misinformation circulating on the Internet and global public perceptions of and responses to the Ebola epidemic originating in West Africa. Using the big data platform Media Cloud, we analyzed all English-language stories about keyword "Ebola" published from 1 July 2014 to 17 November 2014 from the media sets U.S. Mainstream Media, U.S. Regional Media, U.S. Political Blogs, U.S. Popular Blogs, Europe Media Monitor, and Global Voices to understand how social network theory and models of the networked global public may have contributed to health communication efforts. 109,400 stories met our inclusion criteria. The CDC and WHO were the two media sources with the most inlinks (hyperlinks directed to their sites). Twitter was fourth Significantly more public engagement on social media globally was directed toward stories about risks of U.S. domestic Ebola infections than toward stories focused on Ebola infections in West Africa or on science-based information. Corresponding public sentiments about Ebola were reflected in the policy responses of the international community, including violations of the International Health Regulations and the treatment of potentially exposed individuals. The digitally networked global public may have influenced the discourse, sentiment, and response to the Ebola epidemic.

  3. Differential Gene Expression in Primary Human Skin Keratinocytes and Fibroblasts in Response to Ionizing Radiation

    PubMed Central

    Warters, Raymond L.; Packard, Ann T.; Kramer, Gwen F.; Gaffney, David K.; Moos, Philip J.

    2009-01-01

    Although skin is usually exposed during human exposures to ionizing radiation, there have been no thorough examinations of the transcriptional response of skin fibroblasts and keratinocytes to radiation. The transcriptional response of quiescent primary fibroblasts and keratinocytes exposed to from 10 cGy to 5 Gy and collected 4 h after treatment was examined. RNA was isolated and examined by microarray analysis for changes in the levels of gene expression. Exposure to ionizing radiation altered the expression of 279 genes across both cell types. Changes in RNA expression could be arranged into three main categories: (1) changes in keratinocytes but not in fibroblasts, (2) changes in fibroblasts but not in keratinocytes, and (3) changes in both. All of these changes were primarily of p53 target genes. Similar radiation-induced changes were induced in immortalized fibroblasts or keratinocytes. In separate experiments, protein was collected and analyzed by Western blotting for expression of proteins observed in microarray experiments to be overexpressed at the mRNA level. Both Q-PCR and Western blot analysis experiments validated these transcription changes. Our results are consistent with changes in the expression of p53 target genes as indicating the magnitude of cell responses to ionizing radiation. PMID:19580510

  4. Global regulators ExpA (GacA) and KdgR modulate extracellular enzyme gene expression through the RsmA-rsmB system in Erwinia carotovora subsp. carotovora.

    PubMed

    Hyytiäinen, H; Montesano, M; Palva, E T

    2001-08-01

    The production of the main virulence determinants, the extracellular plant cell wall-degrading enzymes, and hence virulence of Erwinia carotovora subsp. carotovora is controlled by a complex regulatory network. One of the global regulators, the response regulator ExpA, a GacA homolog, is required for transcriptional activation of the extracellular enzyme genes of this soft-rot pathogen. To elucidate the mechanism of ExpA control as well as interactions with other regulatory systems, we isolated second-site transposon mutants that would suppress the enzyme-negative phenotype of an expA (gacA) mutant. Inactivation of kdgR resulted in partial restoration of extracellular enzyme production and virulence to the expA mutant, suggesting an interaction between the two regulatory pathways. This interaction was mediated by the RsmA-rsmB system. Northern analysis was used to show that the regulatory rsmB RNA was under positive control of ExpA. Conversely, the expression of rsmA encoding a global repressor was under negative control of ExpA and positive control of KdgR. This study indicates a central role for the RsmA-rsmB regulatory system during pathogenesis, integrating signals from the ExpA (GacA) and KdgR global regulators of extracellular enzyme production in E. carotovora subsp. carotovora.

  5. Corporate social responsibility in global health: an exploratory study of multinational pharmaceutical firms.

    PubMed

    Droppert, Hayley; Bennett, Sara

    2015-04-09

    As pharmaceutical firms experience increasing civil society pressure to act responsibly in a changing globalized world, many are expanding and/or reforming their corporate social responsibility (CSR) strategies. We sought to understand how multinational pharmaceutical companies currently engage in CSR activities in the developing world aimed at global health impact, their motivations for doing so and how their CSR strategies are evolving. We conducted a small-scale, exploratory study combining (i) an in-depth review of publicly available data on pharmaceutical firms' CSR with (ii) interviews of representatives from 6 firms, purposively selected, from the highest earning pharmaceutical firms worldwide. Corporate social responsibility differed for each firm particularly with respect to how CSR is defined, organizational structures for managing CSR, current CSR activities, and motivations for CSR. Across the firms studied, the common CSR activities were: differential pharmaceutical pricing, strengthening developing country drug distribution infrastructure, mHealth initiatives, and targeted research and development. Primary factors that motivated CSR engagement were: reputational benefits, recruitment and employee satisfaction, better rankings in sustainability indices, entrance into new markets, long-term economic returns, and improved population health. In terms of CSR strategy, firms were at different points on a spectrum ranging from philanthropic donations to integrated systemic shared value business models. CSR is of increasing importance for multinational pharmaceutical firms yet understanding of the array of CSR strategies employed and their effects is nascent. Our study points to the need to (i) develop clearer and more standardized definitions of CSR in global health (2) strengthen indices to track CSR strategies and their public health effects in developing countries and (iii) undertake more country level studies that investigate how CSR engages with

  6. Differential gene expressions in testes of L2 strain Taiwan country chicken in response to acute heat stress.

    PubMed

    Wang, Shih-Han; Cheng, Chuen-Yu; Tang, Pin-Chi; Chen, Chih-Feng; Chen, Hsin-Hsin; Lee, Yen-Pai; Huang, San-Yuan

    2013-01-15

    Acute heat stress affects genes involved in spermatogenesis in mammals. However, there is apparently no elaborate research on the effects of acute heat stress on gene expression in avian testes. The purpose of this study was to investigate global gene expression in testes of the L2 strain of Taiwan country chicken after acute heat stress. Twelve roosters, 45 weeks old, were allocated into four groups, including control roosters kept at 25 °C, roosters subjected to 38 °C acute heat stress for 4 hours without recovery, with 2-hour recovery, and with 6-hour recovery, respectively. Testis samples were collected for RNA isolation and microarray analysis. Based on gene expression profiles, 169 genes were upregulated and 140 genes were downregulated after heat stress using a cutoff value of twofold or greater change. Based on gene ontology analysis, differentially expressed genes were mainly related to response to stress, transport, signal transduction, and metabolism. A functional network analysis displayed that heat shock protein genes and related chaperones were the major upregulated groups in chicken testes after acute heat stress. A quantitative real-time polymerase chain reaction analysis of mRNA expressions of HSP70, HSP90AA1, BAG3, SERPINB2, HSP25, DNAJA4, CYP3A80, CIRBP, and TAGLN confirmed the results of the microarray analysis. Because the HSP genes (HSP25, HSP70, and HSP90AA1) and the antiapoptotic BAG3 gene were dramatically altered in heat-stressed chicken testes, we concluded that these genes were important factors in the avian testes under acute heat stress. Whether these genes could be candidate genes for thermotolerance in roosters requires further investigation. Copyright © 2013 Elsevier Inc. All rights reserved.

  7. Expression of Putative Immune Response Genes during Early Ontogeny in the Coral Acropora millepora

    PubMed Central

    Puill-Stephan, Eneour; Seneca, François O.; Miller, David J.; van Oppen, Madeleine J. H.; Willis, Bette L.

    2012-01-01

    Background Corals, like many other marine invertebrates, lack a mature allorecognition system in early life history stages. Indeed, in early ontogeny, when corals acquire and establish associations with various surface microbiota and dinoflagellate endosymbionts, they do not efficiently distinguish between closely and distantly related individuals from the same population. However, very little is known about the molecular components that underpin allorecognition and immunity responses or how they change through early ontogeny in corals. Methodology/Principal Findings Patterns in the expression of four putative immune response genes (apextrin, complement C3, and two CELIII type lectin genes) were examined in juvenile colonies of Acropora millepora throughout a six-month post-settlement period using quantitative real-time PCR (qPCR). Expression of a CELIII type lectin gene peaked in the fourth month for most of the coral juveniles sampled and was significantly higher at this time than at any other sampling time during the six months following settlement. The timing of this increase in expression levels of putative immune response genes may be linked to allorecognition maturation which occurs around this time in A.millepora. Alternatively, the increase may represent a response to immune challenges, such as would be involved in the recognition of symbionts (such as Symbiodinium spp. or bacteria) during winnowing processes as symbioses are fine-tuned. Conclusions/Significance Our data, although preliminary, are consistent with the hypothesis that lectins may play an important role in the maturation of allorecognition responses in corals. The co-expression of lectins with apextrin during development of coral juveniles also raises the possibility that these proteins, which are components of innate immunity in other invertebrates, may influence the innate immune systems of corals through a common pathway or system. However, further studies investigating the expression of

  8. On the response of MODIS cloud coverage to global mean surface air temperature

    NASA Astrophysics Data System (ADS)

    Yue, Qing; Kahn, Brian H.; Fetzer, Eric J.; Wong, Sun; Frey, Richard; Meyer, Kerry G.

    2017-01-01

    The global surface temperature change (ΔTs) mediated cloud cover response is directly related to cloud-climate feedback. Using satellite remote sensing data to relate cloud and climate requires a well-calibrated, stable, and consistent long-term cloud data record. The Collection 5.1 (C5) Moderate Resolution Imaging Spectroradiometer (MODIS) cloud observations have been widely used for this purpose. However, the MODIS data quality varies greatly with the surface type, spectral region, cloud type, and time periods of study, which calls for additional caution when applying such data to studies on cloud cover temporal trends and variability. Using 15 years of cloud observations made by Terra and Aqua MODIS, we analyze the ΔTs-mediated cloud cover response for different cloud types by linearly regressing the monthly anomaly of cloud cover (ΔC) with the monthly anomaly of global Ts. The Collection 6 (C6) Aqua data exhibit a similar cloud response to the long-term counterpart simulated by advanced climate models. A robust increase in altitude with increasing ΔTs is found for high clouds, while a robust decrease of ΔC is noticed for optically thick low clouds. The large differences between C5 and C6 results are from improvements in calibration and cloud retrieval algorithms. The large positive cloud cover responses with data after 2010 and the strong sensitivity to time period obtained from the Terra (C5 and C6) data are likely due to calibration drift that has not been corrected, suggesting that the previous estimate of the short-term cloud cover response from the these data should be revisited.

  9. Differential Fairness Decisions and Brain Responses after Expressed Emotions of Others in Boys with Autism Spectrum Disorders

    ERIC Educational Resources Information Center

    Klapwijk, Eduard T.; Aghajani, Moji; Lelieveld, Gert-Jan; van Lang, Natasja D. J.; Popma, Arne; van der Wee, Nic J. A.; Colins, Olivier F.; Vermeiren, Robert R. J. M.

    2017-01-01

    Little is known about how emotions expressed by others influence social decisions and associated brain responses in autism spectrum disorders (ASD). We investigated the neural mechanisms underlying fairness decisions in response to explicitly expressed emotions of others in boys with ASD and typically developing (TD) boys. Participants with ASD…

  10. CIRCULATING CD11B EXPRESSION CORRELATES WITH THE NEUTROPHIL RESPONSE AND AIRWAY MCD-14 EXPRESSION IS ENHANCED FOLLOWING OZONE EXPOSURE IN HUMANS

    EPA Science Inventory

    We recently reported that baseline expression of circulating CD11b is associated with the magnitude of the neutrophil response following inhaled endotoxin. In this study, we examined whether circulating CD11b plays a similar role in the inflammatory response following inhaled ozo...

  11. The Bacterial Response Regulator ArcA Uses a Diverse Binding Site Architecture to Regulate Carbon Oxidation Globally

    PubMed Central

    Park, Dan M.; Akhtar, Md. Sohail; Ansari, Aseem Z.; Landick, Robert; Kiley, Patricia J.

    2013-01-01

    Despite the importance of maintaining redox homeostasis for cellular viability, how cells control redox balance globally is poorly understood. Here we provide new mechanistic insight into how the balance between reduced and oxidized electron carriers is regulated at the level of gene expression by mapping the regulon of the response regulator ArcA from Escherichia coli, which responds to the quinone/quinol redox couple via its membrane-bound sensor kinase, ArcB. Our genome-wide analysis reveals that ArcA reprograms metabolism under anaerobic conditions such that carbon oxidation pathways that recycle redox carriers via respiration are transcriptionally repressed by ArcA. We propose that this strategy favors use of catabolic pathways that recycle redox carriers via fermentation akin to lactate production in mammalian cells. Unexpectedly, bioinformatic analysis of the sequences bound by ArcA in ChIP-seq revealed that most ArcA binding sites contain additional direct repeat elements beyond the two required for binding an ArcA dimer. DNase I footprinting assays suggest that non-canonical arrangements of cis-regulatory modules dictate both the length and concentration-sensitive occupancy of DNA sites. We propose that this plasticity in ArcA binding site architecture provides both an efficient means of encoding binding sites for ArcA, σ70-RNAP and perhaps other transcription factors within the same narrow sequence space and an effective mechanism for global control of carbon metabolism to maintain redox homeostasis. PMID:24146625

  12. Angiotensin converting enzyme over expression in myelocytes enhances the immune response

    PubMed Central

    Bernstein, Kenneth E.; Gonzalez-Villalobos, Romer A.; Giani, Jorge F.; Shah, Kandarp; Bernstein, Ellen; Janjulia, Tea; Koronyo, Yosef; Shi, Peng D.; Koronyo-Hamaoui, Maya; Fuchs, Sebastien; Shen, Xiao Z.

    2015-01-01

    Angiotensin converting enzyme (ACE) plays an important role in blood pressure control. ACE also has effects on renal function, reproduction, hematopoiesis and several aspects of the immune response. ACE 10/10 mice over express ACE in monocytic cells; macrophages from ACE 10/10 mice demonstrate increased polarization towards a proinflammatory phenotype. As a result, ACE 10/10 mice have a highly effective immune response following challenge with either melanoma, bacterial infection or Alzheimer’s disease. The ACE 10/10 mice suggest that enhanced monocytic function greatly contributes to the ability of the immune response to defend against a wide variety of antigenic and non-antigenic challenges. PMID:24633750

  13. Probiotic lactobacillus and estrogen effects on vaginal epithelial gene expression responses to Candida albicans.

    PubMed

    Wagner, R Doug; Johnson, Shemedia J

    2012-06-20

    Vaginal epithelial cells have receptors, signal transduction mechanisms, and cytokine secretion capabilities to recruit host defenses against Candida albicans infections. This research evaluates how probiotic lactobacilli affect the defensive epithelial response. This study used quantitative reverse transcription-polymerase chain reaction assay (qRT-PCR), flow cytometry, and a multiplex immunoassay to observe changes in the regulation of gene expression related to cytokine responses in the VK2 (E6/E7) vaginal epithelial cell line treated with 17β-estradiol, exposed to probiotic Lactobacillus rhamnosus GR-1® and Lactobacillus reuteri RC-14® and challenged with C. albicans. Data were statistically evaluated by repeated measures analysis of variance and paired t-tests where appropriate. C. albicans induced mRNA expression of genes related to inflammatory cytokine responses associated with nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signal transduction pathways. 17β-estradiol suppressed expression of interleukin-1α (IL-1α), IL-6, IL-8, and tumor necrosis factor alpha (TNFα) mRNA. Probiotic lactobacilli suppressed C. albicans-induced nuclear factor-kappa B inhibitor kinase kinase alpha (Iκκα), Toll-like receptor-2 (TLR2), TLR6, IL-8, and TNFα, also suggesting inhibition of NF-κB signaling. The lactobacilli induced expression of IL-1α, and IL-1β mRNA, which was not inhibited by curcumin, suggesting that they induce an alternate inflammatory signal transduction pathway to NF-κB, such as the mitogen activated protein kinase and activator protein-1 (MAPK/AP-1) signal transduction pathway. Curcumin inhibited IL-13 secretion, suggesting that expression of this cytokine is mainly regulated by NF-κB signaling in VK2 cells. The results suggest that C. albicans infection induces pro-inflammatory responses in vaginal epithelial cells, and estrogen and lactobacilli suppress expression of NF-κB-related inflammatory genes. Probiotic

  14. Predicting response to primary chemotherapy: gene expression profiling of paraffin-embedded core biopsy tissue.

    PubMed

    Mina, Lida; Soule, Sharon E; Badve, Sunil; Baehner, Fredrick L; Baker, Joffre; Cronin, Maureen; Watson, Drew; Liu, Mei-Lan; Sledge, George W; Shak, Steve; Miller, Kathy D

    2007-06-01

    Primary chemotherapy provides an ideal opportunity to correlate gene expression with response to treatment. We used paraffin-embedded core biopsies from a completed phase II trial to identify genes that correlate with response to primary chemotherapy. Patients with newly diagnosed stage II or III breast cancer were treated with sequential doxorubicin 75 mg/M2 q2 wks x 3 and docetaxel 40 mg/M2 weekly x 6; treatment order was randomly assigned. Pretreatment core biopsy samples were interrogated for genes that might correlate with pathologic complete response (pCR). In addition to the individual genes, the correlation of the Oncotype DX Recurrence Score with pCR was examined. Of 70 patients enrolled in the parent trial, core biopsies samples with sufficient RNA for gene analyses were available from 45 patients; 9 (20%) had inflammatory breast cancer (IBC). Six (14%) patients achieved a pCR. Twenty-two of the 274 candidate genes assessed correlated with pCR (p < 0.05). Genes correlating with pCR could be grouped into three large clusters: angiogenesis-related genes, proliferation related genes, and invasion-related genes. Expression of estrogen receptor (ER)-related genes and Recurrence Score did not correlate with pCR. In an exploratory analysis we compared gene expression in IBC to non-inflammatory breast cancer; twenty-four (9%) of the genes were differentially expressed (p < 0.05), 5 were upregulated and 19 were downregulated in IBC. Gene expression analysis on core biopsy samples is feasible and identifies candidate genes that correlate with pCR to primary chemotherapy. Gene expression in IBC differs significantly from noninflammatory breast cancer.

  15. 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

  16. Global Screening of Antiviral Genes that Suppress Baculovirus Transgene Expression in Mammalian Cells.

    PubMed

    Wang, Chia-Hung; Naik, Nenavath Gopal; Liao, Lin-Li; Wei, Sung-Chan; Chao, Yu-Chan

    2017-09-15

    Although baculovirus has been used as a safe and convenient gene delivery vector in mammalian cells, baculovirus-mediated transgene expression is less effective in various mammalian cell lines. Identification of the negative regulators in host cells is necessary to improve baculovirus-based expression systems. Here, we performed high-throughput shRNA library screening, targeting 176 antiviral innate immune genes, and identified 43 host restriction factor genes in a human A549 lung carcinoma cell line. Among them, suppression of receptor interaction protein kinase 1 (RIP1, also known as RIPK1) significantly increased baculoviral transgene expression without resulting in significant cell death. Silencing of RIP1 did not affect viral entry or cell viability, but it did inhibit nuclear translocation of the IRF3 and NF-κB transcription factors. Also, activation of downstream signaling mediators (such as TBK1 and IRF7) was affected, and subsequent interferon and cytokine gene expression levels were abolished. Further, Necrostatin-1 (Nec-1)-an inhibitor of RIP1 kinase activity-dramatically increased baculoviral transgene expression in RIP1-silenced cells. Using baculovirus as a model system, this study presents an initial investigation of large numbers of human cell antiviral innate immune response factors against a "nonadaptive virus." In addition, our study has made baculovirus a more efficient gene transfer vector for some of the most frequently used mammalian cell systems.

  17. Gender Differences in Emotional Response: Inconsistency between Experience and Expressivity.

    PubMed

    Deng, Yaling; Chang, Lei; Yang, Meng; Huo, Meng; Zhou, Renlai

    2016-01-01

    The present study investigated gender differences in both emotional experience and expressivity. Heart rate (HR) was recorded as an indicator of emotional experience while the participants watched 16 video clips that induced eight types of emotion (sadness, anger, horror, disgust, neutrality, amusement, surprise, and pleasure). We also asked the participants to report valence, arousal, and motivation as indicators of emotional expressivity. Overall, the results revealed gender differences in emotional experience and emotional expressivity. When watching videos that induced anger, amusement, and pleasure, men showed larger decreases in HR, whereas women reported higher levels of arousal. There was no gender difference in HR when the participants watched videos that induced horror and disgust, but women reported lower valence, higher arousal, and stronger avoidance motivation than did men. Finally, no gender difference was observed in sadness or surprise, although there was one exception-women reported higher arousal when watching videos that induced sadness. The findings suggest that, when watching videos that induce an emotional response, men often have more intense emotional experiences, whereas women have higher emotional expressivity, particularly for negative emotions. In addition, gender differences depend on the specific emotion type but not the valence.

  18. Gender Differences in Emotional Response: Inconsistency between Experience and Expressivity

    PubMed Central

    Deng, Yaling; Chang, Lei; Yang, Meng; Huo, Meng

    2016-01-01

    The present study investigated gender differences in both emotional experience and expressivity. Heart rate (HR) was recorded as an indicator of emotional experience while the participants watched 16 video clips that induced eight types of emotion (sadness, anger, horror, disgust, neutrality, amusement, surprise, and pleasure). We also asked the participants to report valence, arousal, and motivation as indicators of emotional expressivity. Overall, the results revealed gender differences in emotional experience and emotional expressivity. When watching videos that induced anger, amusement, and pleasure, men showed larger decreases in HR, whereas women reported higher levels of arousal. There was no gender difference in HR when the participants watched videos that induced horror and disgust, but women reported lower valence, higher arousal, and stronger avoidance motivation than did men. Finally, no gender difference was observed in sadness or surprise, although there was one exception—women reported higher arousal when watching videos that induced sadness. The findings suggest that, when watching videos that induce an emotional response, men often have more intense emotional experiences, whereas women have higher emotional expressivity, particularly for negative emotions. In addition, gender differences depend on the specific emotion type but not the valence. PMID:27362361

  19. Addressing the implementation gap in global road safety: exploring features of an effective response and introducing a 10-country program.

    PubMed

    Hyder, Adnan A; Allen, Katharine A; Di Pietro, Gayle; Adriazola, Claudia A; Sobel, Rochelle; Larson, Kelly; Peden, Margie

    2012-06-01

    Yearly, more than 1.2 million people are killed by road traffic injuries (RTIs) around the globe, and another 20 to 50 million are injured. The global burden of RTIs is predicted to rise. We explored the need for concerted action for global road safety and propose characteristics of an effective response to the gap in addressing RTIs. We propose that a successful response includes domains such as strong political will, capacity building, use of evidence-based interventions, rigorous evaluation, increased global funding, multisectoral action, and sustainability. We also present a case study of the global Road Safety in 10 Countries project, which is a new, 5-year, multipartner initiative to address the burden of RTIs in 10 low- and middle-income countries.

  20. Addressing the Implementation Gap in Global Road Safety: Exploring Features of an Effective Response and Introducing a 10-Country Program

    PubMed Central

    Allen, Katharine A.; Di Pietro, Gayle; Adriazola, Claudia A.; Sobel, Rochelle; Larson, Kelly; Peden, Margie

    2012-01-01

    Yearly, more than 1.2 million people are killed by road traffic injuries (RTIs) around the globe, and another 20 to 50 million are injured. The global burden of RTIs is predicted to rise. We explored the need for concerted action for global road safety and propose characteristics of an effective response to the gap in addressing RTIs. We propose that a successful response includes domains such as strong political will, capacity building, use of evidence-based interventions, rigorous evaluation, increased global funding, multisectoral action, and sustainability. We also present a case study of the global Road Safety in 10 Countries project, which is a new, 5-year, multipartner initiative to address the burden of RTIs in 10 low- and middle-income countries. PMID:22515864

  1. Integration of Genome-Wide Computation DRE Search, AhR ChIP-chip and Gene Expression Analyses of TCDD-Elicited Responses in the Mouse Liver

    PubMed Central

    2011-01-01

    Background The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor (TF) that mediates responses to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Integration of TCDD-induced genome-wide AhR enrichment, differential gene expression and computational dioxin response element (DRE) analyses further elucidate the hepatic AhR regulatory network. Results Global ChIP-chip and gene expression analyses were performed on hepatic tissue from immature ovariectomized mice orally gavaged with 30 μg/kg TCDD. ChIP-chip analysis identified 14,446 and 974 AhR enriched regions (1% false discovery rate) at 2 and 24 hrs, respectively. Enrichment density was greatest in the proximal promoter, and more specifically, within ± 1.5 kb of a transcriptional start site (TSS). AhR enrichment also occurred distal to a TSS (e.g. intergenic DNA and 3' UTR), extending the potential gene expression regulatory roles of the AhR. Although TF binding site analyses identified over-represented DRE sequences within enriched regions, approximately 50% of all AhR enriched regions lacked a DRE core (5'-GCGTG-3'). Microarray analysis identified 1,896 number of TCDD-responsive genes (|fold change| ≥ 1.5, P1(t) > 0.999). Integrating this gene expression data with our ChIP-chip and DRE analyses only identified 625 differentially expressed genes that involved an AhR interaction at a DRE. Functional annotation analysis of differentially regulated genes associated with AhR enrichment identified overrepresented processes related to fatty acid and lipid metabolism and transport, and xenobiotic metabolism, which are consistent with TCDD-elicited steatosis in the mouse liver. Conclusions Details of the AhR regulatory network have been expanded to include AhR-DNA interactions within intragenic and intergenic genomic regions. Moreover, the AhR can interact with DNA independent of a DRE core suggesting there are alternative mechanisms of AhR-mediated gene regulation. PMID:21762485

  2. BIRC6/Apollon gene expression in childhood acute leukemia: impact on therapeutic response and prognosis.

    PubMed

    Ismail, Eman Abdel Rahman; Mahmoud, Hanan Mohamed; Tawfik, Lamis Mohamed; Habashy, Deena Mohamed; Adly, Amira Abdel Moneam; El-Sherif, Nayera Hazaa; Abdelwahab, Mahmoud Ahmed

    2012-02-01

    Although BIRC6/Apollon seems to play a critical role as an antiapoptotic regulator, its clinical relevance in acute leukemia remains largely elusive. Therefore, we aimed to investigate BIRC6 gene expression in childhood acute leukemia in relation to clinicopathological characteristics at presentation, therapeutic response, and prognosis. BIRC6 expression level was assessed in 75 children with acute leukemia; 30 patients with acute myeloblastic leukemia (AML) and 45 patients with acute lymphoblastic leukemia (ALL) using real-time quantitative reverse transcriptase-polymerase chain reaction. The median level of BIRC6 expression did not differ significantly between AML and ALL patients. BIRC6 expression level was higher in patients with AML and ALL with extramedullary involvement, white blood cell (WBC) count ≥ 10 × 10(9) /L, and unfavorable cytogenetics at diagnosis. BIRC6 gene expression was higher in patients with unfavorable response to therapy at day 14, those who developed relapse or died in both leukemic groups. The best cutoff value of BIRC6 to predict therapeutic response and disease outcome was determined. AML and ALL patients with BIRC6 overexpression had significantly shorter overall and disease free survivals. This is the first report to study BIRC6 gene in pediatric ALL. Our results suggested that BIRC6 gene expression could be considered as an adverse risk factor in childhood acute leukemia and, hence, could be used to guide therapeutic regimens. © 2012 John Wiley & Sons A/S.

  3. Global circular RNA expression profile of human gastric cancer and its clinical significance.

    PubMed

    Shao, Yongfu; Li, Jinyun; Lu, Rongdan; Li, Tianwen; Yang, Yunben; Xiao, Bingxiu; Guo, Junming

    2017-06-01

    Circular RNAs (circRNAs) are a new class of noncoding RNAs. However, the expression profile and clinical significance of circRNAs in human gastric cancer is unclear. The global circRNA expression profile in human gastric cancer was measured by circRNA microarray. Hsa_circ_0014717, one of the most downregulated circRNAs in microarray, was selected as a targeted circRNA to explore its levels in gastric tissues and gastric juice. Freeze-thaw experiment and incubation experiment confirmed the stability of gastric juice circRNAs. A total of 308 circRNAs, including 107 (34.74%) upregulated and 201 (65.26%) downregulated circRNAs, were found significantly aberrantly expressed in gastric cancer tissues. The top ten upregulated in gastric cancer tissues were hsa_circ_0035445, hsa_circ_0003789, hsa_circ_0063809, hsa_circ_0074362, hsa_circ_0006282, hsa_circ_0011107, hsa_circ_0084606, hsa_circ_0005556, hsa_circ_0050547, and hsa_circ_0006470, while the top ten downregulated ones were hsa_circ_0007099, hsa_circ_0001897, hsa_circ_0007707, hsa_circ_0008832, hsa_circ_0001546, hsa_circ_0002089, hsa_circ_0004680, hsa_circ_0000154, hsa_circ_0004458, and hsa_circ_0008394. The hot-point chromosomes were chr1, chr2, chr3, chr9, and chr17. Hsa_circ_0014717 was significantly downregulated in 77.2% (74/96) gastric cancer tissues. Its levels in gastric cancer tissues were related to tumor stage (P = 0.037), distal metastasis (P = 0.048), tissue carcinoembryonic antigen (P = 0.001), and carbohydrate antigen 19-9 expression (P = 0.021). More importantly, hsa_circ_0014717 can stably exist in human gastric juice; and its nature meets the requirements of clinical detection. Our study uncovered the circRNA expression profile in human gastric cancer. Moreover, some circRNAs can stably exist in human body fluid, and has the potential to be used as novel biomarkers for the screening of high-risk gastric cancer patients. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  4. A differential neural response to threatening and non-threatening negative facial expressions in paranoid and non-paranoid schizophrenics.

    PubMed

    Phillips, M L; Williams, L; Senior, C; Bullmore, E T; Brammer, M J; Andrew, C; Williams, S C; David, A S

    1999-11-08

    Several studies have demonstrated impaired facial expression recognition in schizophrenia. Few have examined the neural basis for this; none have compared the neural correlates of facial expression perception in different schizophrenic patient subgroups. We compared neural responses to facial expressions in 10 right-handed schizophrenic patients (five paranoid and five non-paranoid) and five normal volunteers using functional Magnetic Resonance Imaging (fMRI). In three 5-min experiments, subjects viewed alternating 30-s blocks of black-and-white facial expressions of either fear, anger or disgust contrasted with expressions of mild happiness. After scanning, subjects categorised each expression. All patients were less accurate in identifying expressions, and showed less activation to these stimuli than normals. Non-paranoids performed poorly in the identification task and failed to activate neural regions that are normally linked with perception of these stimuli. They categorised disgust as either anger or fear more frequently than paranoids, and demonstrated in response to disgust expressions activation in the amygdala, a region associated with perception of fearful faces. Paranoids were more accurate in recognising expressions, and demonstrated greater activation than non-paranoids to most stimuli. We provide the first evidence for a distinction between two schizophrenic patient subgroups on the basis of recognition of and neural response to different negative facial expressions.

  5. Our Journal Unites Us: Global Responsibilities and Possibilities for Pediatric Physical Therapy.

    PubMed

    Van Sant, Ann F

    2018-04-01

    This article was designed to describe personal and social responsibilities for strengthening the science of pediatric physical therapy and effective international research collaboration and communication. Common flaws in research design and analysis are reviewed with recommendations for developing research students' design and analytical skills. Our social responsibility to be informed by global knowledge is highlighted. Barriers to scientific collaboration and communication including international disparities in scientific development and language barriers are presented. Suggestions to reduce these barriers are outlined. The importance of free access to scientific literature in developing countries is reviewed. The journal should assume a leadership role in building a strong science of pediatric physical therapy through encouraging personal and social responsibility in research and serving as a model of international collaboration and communication. Treatment for children with movement disorders will be improved by stronger science, international collaboration, and communication.

  6. Push, pull, and reverse: self-interest, responsibility, and the global health care worker shortage.

    PubMed

    Kirby, Katherine E; Siplon, Patricia

    2012-06-01

    The world is suffering from a dearth of health care workers, and sub-Saharan Africa, an area of great need, is experiencing the worst shortage. Developed countries are making the problem worse by luring health care workers away from the countries that need them most, while developing countries do not have the resources to stem the flow or even replace those lost. Postmodern philosopher Emmanuel Levinas offers a unique ethical framework that is helpful in assessing both the irresponsibility inherent in the current global health care situation and the responsibility and obligation held by the stakeholders involved in this global crisis. Drawing on Levinas' exploration of individual freedom and self-pursuit, infinite responsibility for the Other, and the potential emergence of a just community, we demonstrate its effectiveness in explaining the health care worker crisis, and we argue in favor of a variety of policy and development assistance measures that are grounded in an orientation of non-indifference toward Others.

  7. Delays in Global Disease Outbreak Responses: Lessons from H1N1, Ebola, and Zika

    PubMed Central

    Silverberg, Sarah L.

    2018-01-01

    In global disease outbreaks, there are significant time delays between the source of an outbreak and collective action. Some delay is necessary, but recent delays have been extended by insufficient surveillance capacity and time-consuming efforts to mobilize action. Three public health emergencies of international concern (PHEICs)—H1N1, Ebola, and Zika—allow us to identify and compare sources of delays and consider seven hypotheses about what influences the length of delays. These hypotheses can then motivate further research that empirically tests them. The three PHEICs suggest that deferred global mobilization is a greater source of delay than is poor surveillance capacity. These case study outbreaks support hypotheses that we see quicker responses for novel diseases when outbreaks do not coincide with holidays and when US citizens are infected. They do not support hypotheses that we see quicker responses for more severe outbreaks or those that threaten larger numbers of people. Better understanding the reason for delays can help target policy interventions and identify the kind of global institutional changes needed to reduce the spread and severity of future PHEICs. PMID:29345996

  8. Implications of the global financial crisis for the response to diseases of poverty within overall health sector development: the case of tuberculosis.

    PubMed

    Maher, Dermot

    2010-01-01

    The global financial crisis poses a threat to global health, and may exacerbate diseases of poverty, e.g. HIV, malaria and tuberculosis. Exploring the implications of the global financial crisis for the health sector response to tuberculosis is useful to illustrate the practical problems and propose possible solutions. The response to tuberculosis is considered in the context of health sector development. Problems and solutions are considered in five key areas: financing, prioritization, government regulation, integration and decentralization. Securing health gains in global tuberculosis control depends on protecting expenditure by governments of countries badly affected by tuberculosis and by donors, taking measures to increase efficiencies, prioritizing health expenditures and strengthening government regulation. Lessons learned will be valuable for stakeholders involved in the health sector response to tuberculosis and other diseases of poverty.

  9. Dryland responses to global change suggest the potential for rapid non-linear responses to some changes but resilience to others

    NASA Astrophysics Data System (ADS)

    Reed, S.; Ferrenberg, S.; Tucker, C.; Rutherford, W. A.; Wertin, T. M.; McHugh, T. A.; Morrissey, E.; Kuske, C.; Belnap, J.

    2017-12-01

    Drylands represent our planet's largest terrestrial biome, making up over 35% of Earth's land surface. In the context of this vast areal extent, it is no surprise that recent research suggests dryland inter-annual variability and responses to change have the potential to drive biogeochemical cycles and climate at the global-scale. Further, the data we do have suggest drylands can respond rapidly and non-linearly to change. Nevertheless, our understanding of the cross-system consistency of and mechanisms behind dryland responses to a changed environment remains relatively poor. This poor understanding hinders not only our larger understanding of terrestrial ecosystem function, but also our capacity to forecast future global biogeochemical cycles and climate. Here we present data from a series of Colorado Plateau manipulation experiments - including climate, land use, and nitrogen deposition manipulations - to explore how vascular plants, microbial communities, and biological soil crusts (a community of mosses, lichens, and/or cyanobacteria living in the interspace among vascular plants in arid and semiarid ecosystems worldwide) respond to a host of environmental changes. These responses include not only assessments of community composition, but of their function as well. We will explore photosynthesis, net soil CO2 exchange, soil carbon stocks and chemistry, albedo, and nutrient cycling. The experiments were begun with independent questions and cover a range of environmental change drivers and scientific approaches, but together offer a relatively holistic picture of how some drylands can change their structure and function in response to change. In particular, the data show very high ecosystem vulnerability to particular drivers, but surprising resilience to others, suggesting a multi-faceted response of these diverse systems.

  10. Curcumin activates human glutathione S-transferase P1 expression through antioxidant response element.

    PubMed

    Nishinaka, Toru; Ichijo, Yusuke; Ito, Maki; Kimura, Masayoshi; Katsuyama, Masato; Iwata, Kazumi; Miura, Takeshi; Terada, Tomoyuki; Yabe-Nishimura, Chihiro

    2007-05-15

    Curcumin is a plant-derived diferuloylmethane compound extracted from Curcuma longa, possessing antioxidative and anticarcinogenic properties. Antioxidants and oxidative stress are known to induce the expression of certain classes of detoxification enzymes. Since the upregulation of detoxifying enzymes affects the drug metabolism and cell defense system, it is important to understand the gene regulation by such agents. In this study, we demonstrated that curcumin could induce the expression of human glutathione S-transferase P1 (GSTP1). In HepG2 cells treated with 20muM curcumin, the level of GSTP1 mRNA was significantly increased. In luciferase reporter assays, curcumin augmented the promoter activity of a reporter construct carrying 336bp upstream of the 5'-flanking region of the GSTP1 gene. Mutation analyses revealed that the region including antioxidant response element (ARE), which overlaps AP1 in sequence, was essential to the response to curcumin. While the introduction of a wild-type Nrf2 expression construct augmented the promoter activity of the GSTP1 gene, co-expression of a dominant-negative Nrf2 abolished the responsiveness to curcumin. In addition, curcumin activated the expression of the luciferase gene from a reporter construct carrying multiple ARE consensus sequences but not one with multiple AP1 sites. In a gel mobility shift assay with an oligonucleotide with GSTP1 ARE, an increase in the amount of the binding complex was observed in the nuclear extracts of curcumin-treated HepG2 cells. These results suggested that ARE is the primary sequence for the curcumin-induced transactivation of the GSTP1 gene. The induction of GSTP1 may be one of the mechanisms underlying the multiple actions of curcumin.

  11. Evaluation and expression analysis of alfalfa genotypes in response to prolonged salt stress

    USDA-ARS?s Scientific Manuscript database

    Salinity is one of the most important abiotic stresses that adversely affect plant growth and productivity globally. In order to tackle this complex problem, it is important to link the biochemical and physiological responses with the underlying genetic mechanisms. In this study, we used 12 previous...

  12. Application of Whole Genome Expression Analysis to Assess Bacterial Responses to Environmental Conditions

    NASA Astrophysics Data System (ADS)

    Vukanti, R. V.; Mintz, E. M.; Leff, L. G.

    2005-05-01

    Bacterial responses to environmental signals are multifactorial and are coupled to changes in gene expression. An understanding of bacterial responses to environmental conditions is possible using microarray expression analysis. In this study, the utility of microarrays for examining changes in gene expression in Escherichia coli under different environmental conditions was assessed. RNA was isolated, hybridized to Affymetrix E. coli Genome 2.0 chips and analyzed using Affymetrix GCOS and Genespring software. Major limiting factors were obtaining enough quality RNA (107-108 cells to get 10μg RNA)and accounting for differences in growth rates under different conditions. Stabilization of RNA prior to isolation and taking extreme precautions while handling RNA were crucial. In addition, use of this method in ecological studies is limited by availability and cost of commercial arrays; choice of primers for cDNA synthesis, reproducibility, complexity of results generated and need to validate findings. This method may be more widely applicable with the development of better approaches for RNA recovery from environmental samples and increased number of available strain-specific arrays. Diligent experimental design and verification of results with real-time PCR or northern blots is needed. Overall, there is a great potential for use of this technology to discover mechanisms underlying organisms' responses to environmental conditions.

  13. Diversity in global gene expression and morphology across a watercress (Nasturtium officinale R. Br.) germplasm collection: first steps to breeding

    PubMed Central

    Payne, Adrienne C.; Clarkson, Graham J.J.; Rothwell, Steve; Taylor, Gail

    2015-01-01

    Watercress (Nasturtium officinale R. Br.) is a nutrient intense, leafy crop that is consumed raw or in soups across the globe, but for which, currently no genomic resources or breeding programme exists. Promising morphological, biochemical and functional genomic variation was identified for the first time in a newly established watercress germplasm collection, consisting of 48 watercress accessions sourced from contrasting global locations. Stem length, stem diameter and anti-oxidant (AO) potential varied across the accessions. This variation was used to identify three extreme contrasting accessions for further analysis. Variation in global gene expression was investigated using an Affymetrix Arabidopsis ATH1 microarray gene chip, using the commercial control (C), an accession selected for dwarf phenotype with a high AO potential (dwarfAO, called ‘Boldrewood’) and one with high AO potential alone. A set of transcripts significantly differentially expressed between these three accessions, were identified, including transcripts involved in the regulation of growth and development and those involved in secondary metabolism. In particular, when differential gene expression was compared between C and dwarfAO, the dwarfAO was characterised by increased expression of genes encoding glucosinolates, which are known precursors of phenethyl isothiocyanate, linked to the anti-carcinogenic effects well-documented in watercress. This study provides the first analysis of natural variation across the watercress genome and has identified important underpinning information for future breeding for enhanced anti-carcinogenic properties and morphology traits in this nutrient-intense crop. PMID:26504575

  14. Thermosphere Global Time Response to Geomagnetic Storms Caused by Coronal Mass Ejections

    NASA Astrophysics Data System (ADS)

    Oliveira, D. M.; Zesta, E.; Schuck, P. W.; Sutton, E. K.

    2017-10-01

    We investigate, for the first time with a spatial superposed epoch analysis study, the thermosphere global time response to 159 geomagnetic storms caused by coronal mass ejections (CMEs) observed in the solar wind at Earth's orbit during the period of September 2001 to September 2011. The thermosphere neutral mass density is obtained from the CHAMP (CHAllenge Mini-Satellite Payload) and GRACE (Gravity Recovery Climate Experiment) spacecraft. All density measurements are intercalibrated against densities computed by the Jacchia-Bowman 2008 empirical model under the regime of very low geomagnetic activity. We explore both the effects of the pre-CME shock impact on the thermosphere and of the storm main phase onset by taking their times of occurrence as zero epoch times (CME impact and interplanetary magnetic field Bz southward turning) for each storm. We find that the shock impact produces quick and transient responses at the two high-latitude regions with minimal propagation toward lower latitudes. In both cases, thermosphere is heated in very high latitude regions within several minutes. The Bz southward turning of the storm onset has a fast heating manifestation at the two high-latitude regions, and it takes approximately 3 h for that heating to propagate down to equatorial latitudes and to globalize in the thermosphere. This heating propagation is presumably accomplished, at least in part, with traveling atmospheric disturbances and complex meridional wind structures. Current models use longer lag times in computing thermosphere density dynamics during storms. Our results suggest that the thermosphere response time scales are shorter and should be accordingly adjusted in thermospheric empirical models.

  15. The Hydrological Sensitivity to Global Warming and Solar Geoengineering Derived from Thermodynamic Constraints

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kleidon, Alex; Kravitz, Benjamin S.; Renner, Maik

    2015-01-16

    We derive analytic expressions of the transient response of the hydrological cycle to surface warming from an extremely simple energy balance model in which turbulent heat fluxes are constrained by the thermodynamic limit of maximum power. For a given magnitude of steady-state temperature change, this approach predicts the transient response as well as the steady-state change in surface energy partitioning and the hydrologic cycle. We show that the transient behavior of the simple model as well as the steady state hydrological sensitivities to greenhouse warming and solar geoengineering are comparable to results from simulations using highly complex models. Many ofmore » the global-scale hydrological cycle changes can be understood from a surface energy balance perspective, and our thermodynamically-constrained approach provides a physically robust way of estimating global hydrological changes in response to altered radiative forcing.« less

  16. LtmA, a novel cyclic di-GMP-responsive activator, broadly regulates the expression of lipid transport and metabolism genes in Mycobacterium smegmatis

    PubMed Central

    Li, Weihui; He, Zheng-Guo

    2012-01-01

    In a bis-(3′-5′)-cyclic dimeric guanosine monophosphate (c-di-GMP)/transcription factor binding screen, we identified Mycobacterium smegmatis Ms6479 as the first c-di-GMP-responsive transcriptional factor in mycobacteria. Ms6479 could specifically bind with c-di-GMP and recognize the promoters of 37 lipid transport and metabolism genes. c-di-GMP could enhance the ability of Ms6479 to bind to its target DNA. Furthermore, our results establish Ms6479 as a global activator that positively regulates the expression of diverse target genes. Overexpression of Ms6479 in M. smegmatis significantly reduced the permeability of the cell wall to crystal violet and increased mycobacterial resistance to anti-tuberculosis antibiotics. Interestingly, Ms6479 lacks the previously reported c-di-GMP binding motifs. Our findings introduce Ms6479 (here designated LtmA for lipid transport and metabolism activator) as a new c-di-GMP-responsive regulator. PMID:23047950

  17. Alternate Bearing in Citrus: Changes in the Expression of Flowering Control Genes and in Global Gene Expression in ON- versus OFF-Crop Trees

    PubMed Central

    Shalom, Liron; Samuels, Sivan; Zur, Naftali; Shlizerman, Lyudmila; Zemach, Hanita; Weissberg, Mira; Ophir, Ron; Blumwald, Eduardo; Sadka, Avi

    2012-01-01

    Alternate bearing (AB) is the process in fruit trees by which cycles of heavy yield (ON crop) one year are followed by a light yield (OFF crop) the next. Heavy yield usually reduces flowering intensity the following year. Despite its agricultural importance, how the developing crop influences the following year's return bloom and yield is not fully understood. It might be assumed that an ‘AB signal’ is generated in the fruit, or in another organ that senses fruit presence, and moves into the bud to determine its fate—flowering or vegetative growth. The bud then responds to fruit presence by altering regulatory and metabolic pathways. Determining these pathways, and when they are altered, might indicate the nature of this putative AB signal. We studied bud morphology, the expression of flowering control genes, and global gene expression in ON- and OFF-crop buds. In May, shortly after flowering and fruit set, OFF-crop buds were already significantly longer than ON-crop buds. The number of differentially expressed genes was higher in May than at the other tested time points. Processes differentially expressed between ON- and OFF-crop trees included key metabolic and regulatory pathways, such as photosynthesis and secondary metabolism. The expression of genes of trehalose metabolism and flavonoid metabolism was validated by nCounter technology, and the latter was confirmed by metabolomic analysis. Among genes induced in OFF-crop trees was one homologous to SQUAMOSA PROMOTER BINDING-LIKE (SPL), which controls juvenile-to-adult and annual phase transitions, regulated by miR156. The expression pattern of SPL-like, miR156 and other flowering control genes suggested that fruit load affects bud fate, and therefore development and metabolism, a relatively long time before the flowering induction period. Results shed light on some of the metabolic and regulatory processes that are altered in ON and OFF buds. PMID:23071667

  18. Alternate bearing in citrus: changes in the expression of flowering control genes and in global gene expression in ON- versus OFF-crop trees.

    PubMed

    Shalom, Liron; Samuels, Sivan; Zur, Naftali; Shlizerman, Lyudmila; Zemach, Hanita; Weissberg, Mira; Ophir, Ron; Blumwald, Eduardo; Sadka, Avi

    2012-01-01

    Alternate bearing (AB) is the process in fruit trees by which cycles of heavy yield (ON crop) one year are followed by a light yield (OFF crop) the next. Heavy yield usually reduces flowering intensity the following year. Despite its agricultural importance, how the developing crop influences the following year's return bloom and yield is not fully understood. It might be assumed that an 'AB signal' is generated in the fruit, or in another organ that senses fruit presence, and moves into the bud to determine its fate-flowering or vegetative growth. The bud then responds to fruit presence by altering regulatory and metabolic pathways. Determining these pathways, and when they are altered, might indicate the nature of this putative AB signal. We studied bud morphology, the expression of flowering control genes, and global gene expression in ON- and OFF-crop buds. In May, shortly after flowering and fruit set, OFF-crop buds were already significantly longer than ON-crop buds. The number of differentially expressed genes was higher in May than at the other tested time points. Processes differentially expressed between ON- and OFF-crop trees included key metabolic and regulatory pathways, such as photosynthesis and secondary metabolism. The expression of genes of trehalose metabolism and flavonoid metabolism was validated by nCounter technology, and the latter was confirmed by metabolomic analysis. Among genes induced in OFF-crop trees was one homologous to SQUAMOSA PROMOTER BINDING-LIKE (SPL), which controls juvenile-to-adult and annual phase transitions, regulated by miR156. The expression pattern of SPL-like, miR156 and other flowering control genes suggested that fruit load affects bud fate, and therefore development and metabolism, a relatively long time before the flowering induction period. Results shed light on some of the metabolic and regulatory processes that are altered in ON and OFF buds.

  19. Age Dependent Variability in Gene Expression in Fischer 344 ...

    EPA Pesticide Factsheets

    Recent evidence suggests older adults may be a sensitive population with regard to environmental exposure to toxic compounds. One source of this sensitivity could be an enhanced variability in response. Studies on phenotypic differences have suggested that variation in response does increase with age. However, few reports address the question of variation in gene expression as an underlying cause for increased variability of phenotypic response in the aged. In this study, we utilized global analysis to compare variation in constitutive gene expression in the retinae of young (4 mos), middle-aged (11 mos) and aged (23 mos) Fischer 344 rats. Three hundred and forty transcripts were identified in which variance in expression increased from 4 to 23 mos of age, while only twelve transcripts were found for which it decreased. Functional roles for identified genes were clustered in basic biological categories including cell communication, function, metabolism and response to stimuli. Our data suggest that population stochastically-induced variability should be considered in assessing sensitivity due to old age. Recent evidence suggests older adults may be a sensitive population with regard to environmental exposure to toxic compounds. One source of this sensitivity could be an enhanced variability in response. Studies on phenotypic differences have suggested that variation in response does increase with age. However, few reports address the question of variation in

  20. Generation of novel pharmacogenomic candidates in the response to methotrexate in juvenile idiopathic arthritis: correlation between gene expression and genotype

    PubMed Central

    Moncrieffe, Halima; Hinks, Anne; Ursu, Simona; Kassoumeri, Laura; Etheridge, Angela; Hubank, Mike; Martin, Paul; Weiler, Tracey; Glass, David N; Thompson, Susan D.; Thomson, Wendy; Wedderburn, Lucy R

    2010-01-01

    Objectives Little is known about mechanisms of efficacy of methotrexate (MTX) in childhood arthritis, or genetic influences upon response to MTX. The aims of this study were to use gene expression profiling to identify novel pathways/genes altered by MTX and then investigate these genes for genotype associations with response to MTX treatment. Methods Gene expression profiling before and after MTX treatment was performed on 11 children with juvenile idiopathic arthritis (JIA) treated with MTX, in whom response at 6 months of treatment was defined. Genes showing the most differential gene expression after treatment were selected for SNP genotyping. Genotype frequencies were compared between non-responders and responders (ACR-Ped70). An independent cohort was available for validation. Results Gene expression profiling before and after MTX treatment revealed 1222 differentially expressed probes sets (fold change >1.7, p< 0.05) and 1065 when restricted to full responder cases only. Six highly differentially expressed genes were analysed for genetic association to response to MTX. Three SNPs in the SLC16A7 gene showed significant association with MTX response. One SNP showed validated association in an independent cohort. Conclusions This study is the first, to our knowledge, to evaluate gene expression profiles in children with JIA before and after MTX, and to analyse genetic variation in differentially expressed genes. We have identified a gene which may contribute to genetic variability in MTX response in JIA, and established as proof of principle that genes which are differentially expressed at mRNA level after drug administration may also be good candidates for genetic analysis. PMID:20827233

  1. Terrestrial Water Flux Responses to Global Warming in Tropical Rainforest Area

    NASA Astrophysics Data System (ADS)

    Lan, C. W.; Lo, M. H.; Kumar, S.

    2016-12-01

    Precipitation extremes are expected to become more frequent in the changing global climate, which may considerably affect the terrestrial hydrological cycle. In this study, Coupled Model Intercomparison Project Phase 5 (CMIP5) archives have been examined to explore the changes in normalized terrestrial water fluxes (TWFn) (precipitation minus evapotranspiration minus total runoff, divided by the precipitation climatology) in three tropical rainforest areas: Maritime Continent, Congo, and Amazon. Results reveal that a higher frequency of intense precipitation events is predicted for the Maritime Continent in the future climate than in the present climate, but not for the Amazon or Congo rainforests. Nonlinear responses to extreme precipitation lead to a reduced groundwater recharge and a proportionately greater amount of direct runoff, particularly for the Maritime Continent, where both the amount and intensity of precipitation increase under global warming. We suggest that the nonlinear response is related to the existence of a higher near-surface soil moisture over the Maritime Continent than that over the Amazon and Congo rainforests. The wetter soil over the Maritime Continent also leads to an increased subsurface runoff. Thus, increased precipitation extremes and concomitantly reduced terrestrial water fluxes (TWF) lead to an intensified hydrological cycle for the Maritime Continent. This has the potential to result in a strong temporal heterogeneity in soil water distribution affecting the ecosystem of the rainforest region and increasing the risk of flooding and/or landslides.

  2. Plant ecophysiology and forest response to global change.

    PubMed

    Buchmann, N

    2002-11-01

    There are many ways of studying forest responses to global change. Most current national and international programs focus on net gas exchange of the terrestrial biosphere and are typically interdisciplinary, multi-scale projects. Key objectives of these programs are surprisingly similar to those of classical plant ecophysiology studies, i.e., to explore functional relationships of plant or plant community responses to environmental change. Thus, common research questions that link plant ecophysiology to ecosystem functioning can be identified for both research communities, promising complementarity and synergism for joint research projects. Although some well-established ecophysiological relationships, such as light responses or stomatal limitations of photosynthetic gas exchange, are currently employed in many ecosystem-scale net flux studies for gap-filling or modeling, only 14% (n = 27) of all eddy covariance flux studies in forests (n = 196; published between 1992 and April 2002) include plant ecophysiological measurements (n = 24) or biomass and growth estimates (n = 8). Generally, emphasis is on CO2 exchange measurements at various scales (foliage, shoots, branches; n = 14) and water relations measurements (n = 11). These measurements do not fully support the typical parameterization of stand and regional models, which often need information on canopy architecture and nitrogen nutrition. By means of a complementary research approach, valuable information can be acquired that is unobtainable by means of a single approach. This additional information is important for the identification of underlying biotic and environmental drivers, for the regulation of net ecosystem fluxes and their partitioning, and the independent validation of measured net ecosystem fluxes. Thus, combining micrometeorology and ecophysiology at flux sites is strongly recommended for ecosystem functioning studies.

  3. The time course of face processing: startle eyeblink response modulation by face gender and expression.

    PubMed

    Duval, Elizabeth R; Lovelace, Christopher T; Aarant, Justin; Filion, Diane L

    2013-12-01

    The purpose of this study was to investigate the effects of both facial expression and face gender on startle eyeblink response patterns at varying lead intervals (300, 800, and 3500ms) indicative of attentional and emotional processes. We aimed to determine whether responses to affective faces map onto the Defense Cascade Model (Lang et al., 1997) to better understand the stages of processing during affective face viewing. At 300ms, there was an interaction between face expression and face gender with female happy and neutral faces and male angry faces producing inhibited startle. At 3500ms, there was a trend for facilitated startle during angry compared to neutral faces. These findings suggest that affective expressions are perceived differently in male and female faces, especially at short lead intervals. Future studies investigating face processing should take both face gender and expression into account. © 2013.

  4. Intra- and interspecies gene expression models for predicting drug response in canine osteosarcoma.

    PubMed

    Fowles, Jared S; Brown, Kristen C; Hess, Ann M; Duval, Dawn L; Gustafson, Daniel L

    2016-02-19

    Genomics-based predictors of drug response have the potential to improve outcomes associated with cancer therapy. Osteosarcoma (OS), the most common primary bone cancer in dogs, is commonly treated with adjuvant doxorubicin or carboplatin following amputation of the affected limb. We evaluated the use of gene-expression based models built in an intra- or interspecies manner to predict chemosensitivity and treatment outcome in canine OS. Models were built and evaluated using microarray gene expression and drug sensitivity data from human and canine cancer cell lines, and canine OS tumor datasets. The "COXEN" method was utilized to filter gene signatures between human and dog datasets based on strong co-expression patterns. Models were built using linear discriminant analysis via the misclassification penalized posterior algorithm. The best doxorubicin model involved genes identified in human lines that were co-expressed and trained on canine OS tumor data, which accurately predicted clinical outcome in 73 % of dogs (p = 0.0262, binomial). The best carboplatin model utilized canine lines for gene identification and model training, with canine OS tumor data for co-expression. Dogs whose treatment matched our predictions had significantly better clinical outcomes than those that didn't (p = 0.0006, Log Rank), and this predictor significantly associated with longer disease free intervals in a Cox multivariate analysis (hazard ratio = 0.3102, p = 0.0124). Our data show that intra- and interspecies gene expression models can successfully predict response in canine OS, which may improve outcome in dogs and serve as pre-clinical validation for similar methods in human cancer research.

  5. "Mad Scared" versus "I Was Sad": Emotional expression and response in urban adolescent males.

    PubMed

    Reigeluth, Christopher S; Pollastri, Alisha R; Cardemil, Esteban V; Addis, Michael E

    2016-06-01

    Decades of masculinity research have concluded that society places higher demands on males to adhere to norms for low emotional expression; yet, countless studies find that emotional expression is integral to well-being. Unfortunately, this contradiction places boys and men in a tenuous position as they must navigate a bombardment of societal messages about the importance of emotional stoicism and invincibility. For urban adolescents, the situation is more complicated as they encounter environmental stressors that place greater emphasis on projecting a tough façade. Thus, our primary aim was to assess to what degree dyads of close adolescent male friends from urban, low-income neighborhoods are able to engage in emotional expression and response and to explore some of the underlying mechanisms and interpersonal processes. Qualitative findings from our sample suggest that urban boys exhibit a wide range of behaviors when participating in dyadic emotional disclosure and response, including being highly emotionally expressive and supportive in the context of close male friendship. Copyright © 2016 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.

  6. Transcriptome-wide analysis of WRKY transcription factors in wheat and their leaf rust responsive expression profiling.

    PubMed

    Satapathy, Lopamudra; Singh, Dharmendra; Ranjan, Prashant; Kumar, Dhananjay; Kumar, Manish; Prabhu, Kumble Vinod; Mukhopadhyay, Kunal

    2014-12-01

    WRKY, a plant-specific transcription factor family, has important roles in pathogen defense, abiotic cues and phytohormone signaling, yet little is known about their roles and molecular mechanism of function in response to rust diseases in wheat. We identified 100 TaWRKY sequences using wheat Expressed Sequence Tag database of which 22 WRKY sequences were novel. Identified proteins were characterized based on their zinc finger motifs and phylogenetic analysis clustered them into six clades consisting of class IIc and class III WRKY proteins. Functional annotation revealed major functions in metabolic and cellular processes in control plants; whereas response to stimuli, signaling and defense in pathogen inoculated plants, their major molecular function being binding to DNA. Tag-based expression analysis of the identified genes revealed differential expression between mock and Puccinia triticina inoculated wheat near isogenic lines. Gene expression was also performed with six rust-related microarray experiments at Gene Expression Omnibus database. TaWRKY10, 15, 17 and 56 were common in both tag-based and microarray-based differential expression analysis and could be representing rust specific WRKY genes. The obtained results will bestow insight into the functional characterization of WRKY transcription factors responsive to leaf rust pathogenesis that can be used as candidate genes in molecular breeding programs to improve biotic stress tolerance in wheat.

  7. Global Influences and Local Responses: The Restructuring of the University of Botswana, 1990-2000

    ERIC Educational Resources Information Center

    Tabulawa, Richard

    2007-01-01

    The University of Botswana has not escaped the reform fever currently gripping higher education institutions the world-over. In the late 1980s the University initiated an administrative/management restructuring exercise whose resultant structure was implemented between 1998 and 2000. The exercise, in many respects, was a response to globalization.…

  8. Identification and expression analysis of cold and freezing stress responsive genes of Brassica oleracea.

    PubMed

    Ahmed, Nasar Uddin; Jung, Hee-Jeong; Park, Jong-In; Cho, Yong-Gu; Hur, Yoonkang; Nou, Ill-Sup

    2015-01-10

    Cold and freezing stress is a major environmental constraint to the production of Brassica crops. Enhancement of tolerance by exploiting cold and freezing tolerance related genes offers the most efficient approach to address this problem. Cold-induced transcriptional profiling is a promising approach to the identification of potential genes related to cold and freezing stress tolerance. In this study, 99 highly expressed genes were identified from a whole genome microarray dataset of Brassica rapa. Blast search analysis of the Brassica oleracea database revealed the corresponding homologous genes. To validate their expression, pre-selected cold tolerant and susceptible cabbage lines were analyzed. Out of 99 BoCRGs, 43 were differentially expressed in response to varying degrees of cold and freezing stress in the contrasting cabbage lines. Among the differentially expressed genes, 18 were highly up-regulated in the tolerant lines, which is consistent with their microarray expression. Additionally, 12 BoCRGs were expressed differentially after cold stress treatment in two contrasting cabbage lines, and BoCRG54, 56, 59, 62, 70, 72 and 99 were predicted to be involved in cold regulatory pathways. Taken together, the cold-responsive genes identified in this study provide additional direction for elucidating the regulatory network of low temperature stress tolerance and developing cold and freezing stress resistant Brassica crops. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. Transgene Expression and Host Cell Responses to Replication-Defective, Single-Cycle, and Replication-Competent Adenovirus Vectors.

    PubMed

    Crosby, Catherine M; Barry, Michael A

    2017-02-18

    Most adenovirus (Ad) vectors are E1 gene deleted replication defective (RD-Ad) vectors that deliver one transgene to the cell and all expression is based on that one gene. In contrast, E1-intact replication-competent Ad (RC-Ad) vectors replicate their DNA and their transgenes up to 10,000-fold, amplifying transgene expression markedly higher than RD-Ad vectors. While RC-Ad are more potent, they run the real risk of causing adenovirus infections in vector recipients and those that administer them. To gain the benefits of transgene amplification, but avoid the risk of Ad infections, we developed "single cycle" Ad (SC-Ad) vectors. SC-Ads amplify transgene expression and generated markedly stronger and more persistent immune responses than RD-Ad as expected. However, they also unexpectedly generated stronger immune responses than RC-Ad vectors. To explore the basis of this potency here, we compared gene expression and the cellular responses to infection to these vectors in vitro and in vivo. In vitro, in primary human lung epithelial cells, SC- and RC-Ad amplified their genomes more than 400-fold relative to RD-Ad with higher replication by SC-Ad. This replication translated into higher green fluorescent protein (GFP) expression for 48 h by SC- and RC-Ad than by RD-Ad. In vitro, in the absence of an immune system, RD-Ad expression became higher by 72 h coincident with cell death mediated by SC- and RC-Ad and release of transgene product from the dying cells. When the vectors were compared in human THP-1 Lucia- interferon-stimulated gene (ISG) cells, which are a human monocyte cell line that have been modified to quantify ISG activity, RC-Ad6 provoked significantly stronger ISG responses than RD- or SC-Ad. In mice, intravenous or intranasal injection produced up to 100-fold genome replication. Under these in vivo conditions in the presence of the immune system, luciferase expression by RC and SC-Ad was markedly higher than that by RD-Ad. In immunodeficient mice, SC

  10. ATM-dependent DNA damage checkpoint functions regulate gene expression in human fibroblasts

    PubMed Central

    Zhou, Tong; Chou, Jeff; Zhou, Yingchun; Simpson, Dennis A.; Cao, Feng; Bushel, Pierre R.; Paules, Richard S.; Kaufmann, William K.

    2013-01-01

    The relationships between profiles of global gene expression and DNA damage checkpoint functions were studied in cells from patients with ataxia telangiectasia (AT). Three telomerase-expressing AT fibroblast lines displayed the expected hypersensitivity to ionizing radiation (IR) and defects in DNA damage checkpoints. Profiles of global gene expression in AT cells were determined at 2, 6 and 24 h after treatment with 1.5 Gy IR or sham-treatment, and were compared to those previously recognized in normal human fibroblasts. Under basal conditions 160 genes or ESTs were differentially expressed in AT and normal fibroblasts, and these were associated by gene ontology with insulin-like growth factor binding and regulation of cell growth. Upon DNA damage, 1091 gene mRNAs were changed in at least two of the three AT cell lines. When compared with the 1811 genes changed in normal human fibroblasts after the same treatment, 715 were found in both AT and normal fibroblasts, including most genes categorized by gene ontology into cell cycle, cell growth and DNA damage response pathways. However, the IR-induced changes in these 715 genes in AT cells usually were delayed or attenuated in comparison to normal cells. The reduced change in DNA-damage-response genes and the attenuated repression of cell-cycle-regulated genes may account for the defects in cell cycle checkpoint function in AT cells. PMID:17699107

  11. Unique signatures of long noncoding RNA expression in response to virus infection and altered innate immune signaling.

    PubMed

    Peng, Xinxia; Gralinski, Lisa; Armour, Christopher D; Ferris, Martin T; Thomas, Matthew J; Proll, Sean; Bradel-Tretheway, Birgit G; Korth, Marcus J; Castle, John C; Biery, Matthew C; Bouzek, Heather K; Haynor, David R; Frieman, Matthew B; Heise, Mark; Raymond, Christopher K; Baric, Ralph S; Katze, Michael G

    2010-10-26

    Studies of the host response to virus infection typically focus on protein-coding genes. However, non-protein-coding RNAs (ncRNAs) are transcribed in mammalian cells, and the roles of many of these ncRNAs remain enigmas. Using next-generation sequencing, we performed a whole-transcriptome analysis of the host response to severe acute respiratory syndrome coronavirus (SARS-CoV) infection across four founder mouse strains of the Collaborative Cross. We observed differential expression of approximately 500 annotated, long ncRNAs and 1,000 nonannotated genomic regions during infection. Moreover, studies of a subset of these ncRNAs and genomic regions showed the following. (i) Most were similarly regulated in response to influenza virus infection. (ii) They had distinctive kinetic expression profiles in type I interferon receptor and STAT1 knockout mice during SARS-CoV infection, including unique signatures of ncRNA expression associated with lethal infection. (iii) Over 40% were similarly regulated in vitro in response to both influenza virus infection and interferon treatment. These findings represent the first discovery of the widespread differential expression of long ncRNAs in response to virus infection and suggest that ncRNAs are involved in regulating the host response, including innate immunity. At the same time, virus infection models provide a unique platform for studying the biology and regulation of ncRNAs.

  12. Unique Signatures of Long Noncoding RNA Expression in Response to Virus Infection and Altered Innate Immune Signaling

    PubMed Central

    Peng, Xinxia; Gralinski, Lisa; Armour, Christopher D.; Ferris, Martin T.; Thomas, Matthew J.; Proll, Sean; Bradel-Tretheway, Birgit G.; Korth, Marcus J.; Castle, John C.; Biery, Matthew C.; Bouzek, Heather K.; Haynor, David R.; Frieman, Matthew B.; Heise, Mark; Raymond, Christopher K.; Baric, Ralph S.; Katze, Michael G.

    2010-01-01

    Studies of the host response to virus infection typically focus on protein-coding genes. However, non-protein-coding RNAs (ncRNAs) are transcribed in mammalian cells, and the roles of many of these ncRNAs remain enigmas. Using next-generation sequencing, we performed a whole-transcriptome analysis of the host response to severe acute respiratory syndrome coronavirus (SARS-CoV) infection across four founder mouse strains of the Collaborative Cross. We observed differential expression of approximately 500 annotated, long ncRNAs and 1,000 nonannotated genomic regions during infection. Moreover, studies of a subset of these ncRNAs and genomic regions showed the following. (i) Most were similarly regulated in response to influenza virus infection. (ii) They had distinctive kinetic expression profiles in type I interferon receptor and STAT1 knockout mice during SARS-CoV infection, including unique signatures of ncRNA expression associated with lethal infection. (iii) Over 40% were similarly regulated in vitro in response to both influenza virus infection and interferon treatment. These findings represent the first discovery of the widespread differential expression of long ncRNAs in response to virus infection and suggest that ncRNAs are involved in regulating the host response, including innate immunity. At the same time, virus infection models provide a unique platform for studying the biology and regulation of ncRNAs. PMID:20978541

  13. VIRTIS on Venus Express: retrieval of real surface emissivity on global scales

    NASA Astrophysics Data System (ADS)

    Arnold, Gabriele E.; Kappel, David; Haus, Rainer; Telléz Pedroza, Laura; Piccioni, Giuseppe; Drossart, Pierre

    2015-09-01

    The extraction of surface emissivity data provides the data base for surface composition analyses and enables to evaluate Venus' geology. The Visible and InfraRed Thermal Imaging Spectrometer (VIRTIS) aboard ESA's Venus Express mission measured, inter alia, the nightside thermal emission of Venus in the near infrared atmospheric windows between 1.0 and 1.2 μm. These data can be used to determine information about surface properties on global scales. This requires a sophisticated approach to understand and consider the effects and interferences of different atmospheric and surface parameters influencing the retrieved values. In the present work, results of a new technique for retrieval of the 1.0 - 1.2 μm - surface emissivity are summarized. It includes a Multi-Window Retrieval Technique, a Multi-Spectrum Retrieval technique (MSR), and a detailed reliability analysis. The MWT bases on a detailed radiative transfer model making simultaneous use of information from different atmospheric windows of an individual spectrum. MSR regularizes the retrieval by incorporating available a priori mean values, standard deviations as well as spatial-temporal correlations of parameters to be retrieved. The capability of this method is shown for a selected surface target area. Implications for geologic investigations are discussed. Based on these results, the work draws conclusions for future Venus surface composition analyses on global scales using spectral remote sensing techniques. In that context, requirements for observational scenarios and instrumental performances are investigated, and recommendations are derived to optimize spectral measurements for Venus' surface studies.

  14. Development of the U.S. Geological Survey's PAGER system (Prompt Assessment of Global Earthquakes for Response)

    USGS Publications Warehouse

    Wald, D.J.; Earle, P.S.; Allen, T.I.; Jaiswal, K.; Porter, K.; Hearne, M.

    2008-01-01

    The Prompt Assessment of Global Earthquakes for Response (PAGER) System plays a primary alerting role for global earthquake disasters as part of the U.S. Geological Survey’s (USGS) response protocol. We provide an overview of the PAGER system, both of its current capabilities and our ongoing research and development. PAGER monitors the USGS’s near real-time U.S. and global earthquake origins and automatically identifies events that are of societal importance, well in advance of ground-truth or news accounts. Current PAGER notifications and Web pages estimate the population exposed to each seismic intensity level. In addition to being a useful indicator of potential impact, PAGER’s intensity/exposure display provides a new standard in the dissemination of rapid earthquake information. We are currently developing and testing a more comprehensive alert system that will include casualty estimates. This is motivated by the idea that an estimated range of possible number of deaths will aid in decisions regarding humanitarian response. Underlying the PAGER exposure and loss models are global earthquake ShakeMap shaking estimates, constrained as quickly as possible by finite-fault modeling and observed ground motions and intensities, when available. Loss modeling is being developed comprehensively with a suite of candidate models that range from fully empirical to largely analytical approaches. Which of these models is most appropriate for use in a particular earthquake depends on how much is known about local building stocks and their vulnerabilities. A first-order country-specific global building inventory has been developed, as have corresponding vulnerability functions. For calibrating PAGER loss models, we have systematically generated an Atlas of 5,000 ShakeMaps for significant global earthquakes during the last 36 years. For many of these, auxiliary earthquake source and shaking intensity data are also available. Refinements to the loss models are ongoing

  15. Dynamic processes at stress promoters regulate the bimodal expression of HOG response genes

    PubMed Central

    2011-01-01

    Osmotic stress triggers the activation of the HOG (high osmolarity glycerol) pathway in Saccharomyces cerevisiae. This signaling cascade culminates in the activation of the MAPK (mitogen-activated protein kinase) Hog1. Quantitative single cell measurements revealed a discrepancy between kinase- and transcriptional activities of Hog1. While kinase activity increases proportionally to stress stimulus, gene expression is inhibited under low stress conditions. Interestingly, a slow stochastic gene activation process is responsible for setting a tunable threshold for gene expression under basal or low stress conditions, which generates a bimodal expression pattern at intermediate stress levels. PMID:22446531

  16. Unpredictable, unpreventable and impersonal medicine: global disaster response in the 21st century.

    PubMed

    Andrews, Russell J; Quintana, Leonidas M

    2015-01-01

    The United Nations has recognized the devastating consequences of "unpredictable, unpreventable and impersonal" disasters-at least US $2 trillion in economic damage and more than 1.3 million lives lost from natural disasters in the last two decades alone. In many disasters (both natural and man-made) hundreds-and in major earthquakes, thousands-of lives are lost in the first days following the event because of the lack of medical/surgical facilities to treat those with potentially survivable injuries. Disasters disrupt and destroy not only medical facilities in the disaster zone but also infrastructure (roads, airports, electricity) and potentially local healthcare personnel as well. To minimize morbidity and mortality from disasters, medical treatment must begin immediately, within minutes ideally, but certainly within 24 h (not the days to weeks currently seen in medical response to disasters). This requires that all resources-medical equipment and support, and healthcare personnel-be portable and readily available; transport to the disaster site will usually require helicopters, as military medical response teams in developed countries have demonstrated. Some of the resources available and in development for immediate medical response for disasters-from portable CT scanners to telesurgical capabilities-are described. For immediate deployment, these resources-medical equipment and personnel-must be ready for deployment on a moment's notice and not require administrative approvals or bureaucratic authorizations from numerous national and international agencies, as is presently the case. Following the "trauma center/stroke center" model, disaster response incorporating "disaster response centers" would be seamlessly integrated into the ongoing daily healthcare delivery systems worldwide, from medical education and specialty training (resident/registrar) to acute and subacute intensive care to long-term rehabilitation. The benefits of such a global disaster

  17. Redox Protein Expression Predicts Radiotherapeutic Response in Early-Stage Invasive Breast Cancer Patients

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Woolston, Caroline M.; Al-Attar, Ahmad; Storr, Sarah J.

    2011-04-01

    Purpose: Early-stage invasive breast cancer patients have commonly undergone breast-conserving surgery and radiotherapy. In a large majority of these patients, the treatment is effective; however, a proportion will develop local recurrence. Deregulated redox systems provide cancer cells protection from increased oxidative stress, such as that induced by ionizing radiation. Therefore, the expression of redox proteins was examined in tumor specimens from this defined cohort to determine whether such expression could predict response. Methods and Materials: The nuclear and cytoplasmic expression of nine redox proteins (glutathione, glutathione reductase, glutaredoxin, glutathione peroxidase 1, 3, and 4, and glutathione S-transferase-{theta}, -{pi}, and -{alpha})more » was assessed using conventional immunohistochemistry on a tissue microarray of 224 tumors. Results: A high cytoplasmic expression of glutathione S-transferase-{theta} significantly correlated with a greater risk of local recurrence (p = .008) and, when combined with a low nuclear expression (p = .009), became an independent predictive factor (p = .002) for local recurrence. High cytoplasmic expression of glutathione S-transferase-{theta} also correlated with a worse overall survival (p = .009). Low nuclear and cytoplasmic expression of glutathione peroxidase 3 (p = .002) correlated with a greater risk of local recurrence and was an independent predictive factor (p = .005). These proteins did not correlate with tumor grade, suggesting their function might be specific to the regulation of oxidative stress rather than alterations of tumor phenotype. Only nuclear (p = .005) and cytoplasmic (p = .001) expression of glutathione peroxidase 4 correlated with the tumor grade. Conclusions: Our results support the use of redox protein expression, namely glutathione S-transferase-{theta} and glutathione peroxidase 3, to predict the response to radiotherapy in early-stage breast cancer patients. If incorporated

  18. Changes in Dorsal Root Ganglion Gene Expression in Response to Spinal Cord Stimulation.

    PubMed

    Tilley, Dana M; Cedeño, David L; Kelley, Courtney A; DeMaegd, Margaret; Benyamin, Ramsin; Vallejo, Ricardo

    Spinal cord stimulation (SCS) has been shown to influence pain-related genes in the spinal cord directly under the stimulating electrodes. There is limited information regarding changes occurring at the dorsal root ganglion (DRG). This study evaluates gene expression in the DRG in response to SCS therapy. Rats were randomized into experimental or control groups (n = 6 per group). Experimental animals underwent spared-nerve injury, implantation of lead, and continuous SCS (72 hours). Behavioral assessment for mechanical hyperalgesia was conducted to compare responses after injury and treatment. Ipsilateral DRG tissue was collected, and gene expression quantified for interleukin 1b (IL-1b), interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), GABA B receptor 1 (GABAbr1), substance P (subP), Integrin alpha M (ITGAM), sodium/potassium ATP-ase (Na/K ATPase), fos proto-oncogene (cFOS), serotonin receptor 3A (5HT3r), galanin (Gal), vasoactive intestinal peptide (VIP), neuropeptide Y (NpY), glial fibrillary acidic protein (GFAP), and brain derived neurotropic factor (BDNF) via quantitative polymerase chain reaction. Statistical significance was established using analysis of variance (ANOVA), independent t tests, and Pearson correlation tests. Expression of IL-1b and IL-6 was reversed following SCS therapy relative to the increase caused by the injury model. Both GABAbr1 and Na/K ATPase were significantly up-regulated upon implantation of the lead, and SCS therapy reversed their expression to within control levels. Pearson correlation analyses reveal that GABAbr1 and Na/K ATPase expression was dependent on the stimulating current intensity. Spinal cord stimulation modulates expression of key pain-related genes in the DRG. Specifically, SCS led to reversal of IL-1b and IL-6 expression induced by injury. Interleukin 6 expression was still significantly larger than in sham animals, which may correlate to residual sensitivity following continuous SCS treatment. In addition

  19. Genomic expression patterns of cardiac tissues from dogs with dilated cardiomyopathy.

    PubMed

    Oyama, Mark A; Chittur, Sridar

    2005-07-01

    To evaluate global genome expression patterns of left ventricular tissues from dogs with dilated cardiomyopathy (DCM). Tissues obtained from the left ventricle of 2 Doberman Pinschers with end-stage DCM and 5 healthy control dogs. Transcriptional activities of 23,851 canine DNA sequences were determined by use of an oligonucleotide microarray. Genome expression patterns of DCM tissue were evaluated by measuring the relative amount of complementary RNA hybridization to the microarray probes and comparing it with gene expression for tissues from 5 healthy control dogs. 478 transcripts were differentially expressed (> or = 2.5-fold change). In DCM tissue, expression of 173 transcripts was upregulated and expression of 305 transcripts was downregulated, compared with expression for control tissues. Of the 478 transcripts, 167 genes could be specifically identified. These genes were grouped into 1 of 8 categories on the basis of their primary physiologic function. Grouping revealed that pathways involving cellular energy production, signaling and communication, and cell structure were generally downregulated, whereas pathways involving cellular defense and stress responses were upregulated. Many previously unreported genes that may contribute to the pathophysiologic aspects of heart disease were identified. Evaluation of global expression patterns provides a molecular portrait of heart failure, yields insights into the pathophysiologic aspects of DCM, and identifies intriguing genes and pathways for further study.

  20. Global analysis of the Brucella melitensis proteome: Identification of proteins expressed in laboratory-grown culture.

    PubMed

    Wagner, Mary Ann; Eschenbrenner, Michel; Horn, Troy A; Kraycer, Jo Ann; Mujer, Cesar V; Hagius, Sue; Elzer, Philip; DelVecchio, Vito G

    2002-08-01

    Brucella melitensis is a facultative intracellular bacterial pathogen that causes brucellosis, a zoonotic disease primarily infecting sheep and goats, characterized by undulant fever, arthritic pain and other neurological disorders in humans. A comprehensive proteomic study of strain 16M was conducted to identify and characterize the proteins expressed in laboratory-grown culture. Using overlapping narrow range immobilized pH gradient strips for two-dimensional gel electrophoresis, 883 protein spots were detected between pH 3.5 and 11. The average isoelectric point and molecular weight values of the detected spots were 5.22 and 46.5 kDa, respectively. Of the 883 observed protein spots, 440 have been identified by matrix-assisted laser desorption/ionization-mass spectrometry. These proteins represent 187 discrete open reading frames (ORFs) or 6% of the predicted 3197 ORFs contained in the genome. The corresponding ORFs of the identified proteins are distributed evenly between each of the two circular B. melitensis chromosomes, indicating that both replicons are functionally active. The presented proteome map lists those protein spots identified to date in this study. This map may serve as a baseline reference for future proteomic studies aimed at the definition of biochemical pathways associated with stress responses, host specificity, pathogenicity and virulence. It will also assist in characterization of global proteomic effects in gene-knockout mutants. Ultimately, it may aid in our overall understanding of the cell biology of B. melitensis, an important bacterial pathogen.

  1. Aging-dependent alterations in gene expression and a mitochondrial signature of responsiveness to human influenza vaccination.

    PubMed

    Thakar, Juilee; Mohanty, Subhasis; West, A Phillip; Joshi, Samit R; Ueda, Ikuyo; Wilson, Jean; Meng, Hailong; Blevins, Tamara P; Tsang, Sui; Trentalange, Mark; Siconolfi, Barbara; Park, Koonam; Gill, Thomas M; Belshe, Robert B; Kaech, Susan M; Shadel, Gerald S; Kleinstein, Steven H; Shaw, Albert C

    2015-01-01

    To elucidate gene expression pathways underlying age-associated impairment in influenza vaccine response, we screened young (age 21-30) and older (age≥65) adults receiving influenza vaccine in two consecutive seasons and identified those with strong or absent response to vaccine, including a subset of older adults meeting criteria for frailty. PBMCs obtained prior to vaccination (Day 0) and at day 2 or 4, day 7 and day 28 post-vaccine were subjected to gene expression microarray analysis. We defined a response signature and also detected induction of a type I interferon response at day 2 and a plasma cell signature at day 7 post-vaccine in young responders. The response signature was dysregulated in older adults, with the plasma cell signature induced at day 2, and was never induced in frail subjects (who were all non-responders). We also identified a mitochondrial signature in young vaccine responders containing genes mediating mitochondrial biogenesis and oxidative phosphorylation that was consistent in two different vaccine seasons and verified by analyses of mitochondrial content and protein expression. These results represent the first genome-wide transcriptional profiling analysis of age-associated dynamics following influenza vaccination, and implicate changes in mitochondrial biogenesis and function as a critical factor in human vaccine responsiveness.

  2. PFS/Mars Express first results: water vapour and carbon monoxide global distribution

    NASA Astrophysics Data System (ADS)

    Ignatiev, N. I.; Titov, D. V.; Formisano, V.; Moroz, V. I.; Lellouch, E.; Encrenaz, Th.; Fouchet, T.; Grassi, D.; Giuranna, M.; Atreya, S.; Pfs Team

    Planetary Fourier Spectrometer onboard Mars Express, with its wide spectral range (1.2--45 um) and high spectral resolution (1.4 cm-1), makes it possible to study in a self-consistent manner the Martian atmosphere by means of simultaneous analysis of spectral features in several spectral regions. As concerned small species, we observe 30--50, 6.3, 2.56, 1.87 and 1.38 μ m H2O bands, and 4.7 and 2.35 μ m CO bands. The most favourable, with respect to the instrument performance, 2.56 μ m H2O and 4.7 μ m CO bands, are used to study the variations of column abundance of water vapour and carbon monoxide on a global scale from pole to pole. All necessary atmospheric parameters, namely temperature profiles, surface pressure, and dust density are obtained from the same spectra, whenever possible.

  3. Matrix metalloproteinase-9 expression correlated with tumor response in patients with locally advanced rectal cancer undergoing preoperative chemoradiotherapy

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Unsal, Diclehan; Uner, Aytug; Akyurek, Nalan

    2007-01-01

    Purpose: To analyze whether the expression of matrix metalloproteinases (MMPs) and their tissue inhibitors are associated with tumor response to preoperative chemoradiotherapy in rectal cancer patients. Methods and Materials: Forty-four patients who had undergone preoperative chemoradiotherapy were evaluated retrospectively. Treatment consisted of pelvic radiotherapy and two cycles of 5-fluorouracil plus leucovorin. Surgery was performed 6-8 weeks later. MMP-2, MMP-9, and tissue inhibitors of metalloproteinase-1 and -2 expression was analyzed by immunohistochemistry of the preradiation biopsy and surgical specimens. The intensity and extent of staining were evaluated separately, and a final score was calculated by multiplying the two scores. The primarymore » endpoint was the correlation of expression with tumor response, with the secondary endpoint the effect of chemoradiotherapy on the expression. Results: Preoperative treatment resulted in downstaging in 20 patients (45%) and no clinical response in 24 (55%). The pathologic tumor response was complete in 11 patients (25%), partial in 23 (52%), and none in 10 (23%). Positive MMP-9 staining was observed in 20 tumors (45%) and was associated with the clinical nodal stage (p = 0.035) and the pathologic and clinical response (p < 0.0001). The staining status of the other markers was associated with neither stage nor response. The overall pathologic response rate was 25% in MMP-9-positive patients vs. 52% in MMP-9-negative patients (p = 0.001). None of the 11 patients with pathologic complete remission was MMP-9 positive. Conclusions: Matrix metalloproteinase-9 expression correlated with a poor tumor response to preoperative chemoradiotherapy in rectal carcinoma patients.« less

  4. Surviving in a toxic world: transcriptomics and gene expression profiling in response to environmental pollution in the critically endangered European eel.

    PubMed

    Pujolar, Jose Martin; Marino, Ilaria A M; Milan, Massimo; Coppe, Alessandro; Maes, Gregory E; Capoccioni, Fabrizio; Ciccotti, Eleonora; Bervoets, Lieven; Covaci, Adrian; Belpaire, Claude; Cramb, Gordon; Patarnello, Tomaso; Bargelloni, Luca; Bortoluzzi, Stefania; Zane, Lorenzo

    2012-09-25

    Genomic and transcriptomic approaches have the potential for unveiling the genome-wide response to environmental perturbations. The abundance of the catadromous European eel (Anguilla anguilla) stock has been declining since the 1980s probably due to a combination of anthropogenic and climatic factors. In this paper, we explore the transcriptomic dynamics between individuals from high (river Tiber, Italy) and low pollution (lake Bolsena, Italy) environments, which were measured for 36 PCBs, several organochlorine pesticides and brominated flame retardants and nine metals. To this end, we first (i) updated the European eel transcriptome using deep sequencing data with a total of 640,040 reads assembled into 44,896 contigs (Eeelbase release 2.0), and (ii) developed a transcriptomic platform for global gene expression profiling in the critically endangered European eel of about 15,000 annotated contigs, which was applied to detect differentially expressed genes between polluted sites. Several detoxification genes related to metabolism of pollutants were upregulated in the highly polluted site, including genes that take part in phase I of the xenobiotic metabolism (CYP3A), phase II (glutathione-S-transferase) and oxidative stress (glutathione peroxidase). In addition, key genes in the mitochondrial respiratory chain and oxidative phosphorylation were down-regulated at the Tiber site relative to the Bolsena site. Together with the induced high expression of detoxification genes, the suggested lowered expression of genes supposedly involved in metabolism suggests that pollution may also be associated with decreased respiratory and energy production.

  5. Surviving in a toxic world: transcriptomics and gene expression profiling in response to environmental pollution in the critically endangered European eel

    PubMed Central

    2012-01-01

    Background Genomic and transcriptomic approaches have the potential for unveiling the genome-wide response to environmental perturbations. The abundance of the catadromous European eel (Anguilla anguilla) stock has been declining since the 1980s probably due to a combination of anthropogenic and climatic factors. In this paper, we explore the transcriptomic dynamics between individuals from high (river Tiber, Italy) and low pollution (lake Bolsena, Italy) environments, which were measured for 36 PCBs, several organochlorine pesticides and brominated flame retardants and nine metals. Results To this end, we first (i) updated the European eel transcriptome using deep sequencing data with a total of 640,040 reads assembled into 44,896 contigs (Eeelbase release 2.0), and (ii) developed a transcriptomic platform for global gene expression profiling in the critically endangered European eel of about 15,000 annotated contigs, which was applied to detect differentially expressed genes between polluted sites. Several detoxification genes related to metabolism of pollutants were upregulated in the highly polluted site, including genes that take part in phase I of the xenobiotic metabolism (CYP3A), phase II (glutathione-S-transferase) and oxidative stress (glutathione peroxidase). In addition, key genes in the mitochondrial respiratory chain and oxidative phosphorylation were down-regulated at the Tiber site relative to the Bolsena site. Conclusions Together with the induced high expression of detoxification genes, the suggested lowered expression of genes supposedly involved in metabolism suggests that pollution may also be associated with decreased respiratory and energy production. PMID:23009661

  6. Isoprene emission response to drought and the impact on global atmospheric chemistry

    NASA Astrophysics Data System (ADS)

    Jiang, Xiaoyan; Guenther, Alex; Potosnak, Mark; Geron, Chris; Seco, Roger; Karl, Thomas; Kim, Saewung; Gu, Lianhong; Pallardy, Stephen

    2018-06-01

    Biogenic isoprene emissions play a very important role in atmospheric chemistry. These emissions are strongly dependent on various environmental conditions, such as temperature, solar radiation, plant water stress, ambient ozone and CO2 concentrations, and soil moisture. Current biogenic emission models (i.e., Model of Emissions of Gases and Aerosols from Nature, MEGAN) can simulate emission responses to some of the major driving variables, such as short-term variations in temperature and solar radiation, but the other factors are either missing or poorly represented. In this paper, we propose a new modelling approach that considers the physiological effects of drought stress on plant photosynthesis and isoprene emissions for use in the MEGAN3 biogenic emission model. We test the MEGAN3 approach by integrating the algorithm into the existing MEGAN2.1 biogenic emission model framework embedded into the global Community Land Model of the Community Earth System Model (CLM4.5/CESM1.2). Single-point simulations are compared against available field measurements at the Missouri Ozarks AmeriFlux (MOFLUX) field site. The modelling results show that the MEGAN3 approach of using of a photosynthesis parameter (Vcmax) and soil wetness factor (βt) to determine the drought activity factor leads to better simulated isoprene emissions in non-drought and drought periods. The global simulation with the MEGAN3 approach predicts a 17% reduction in global annual isoprene emissions, in comparison to the value predicted using the default CLM4.5/MEGAN2.1 without any drought effect. This reduction leads to changes in surface ozone and oxidants in the areas where the reduction of isoprene emissions is observed. Based on the results presented in this study, we conclude that it is important to simulate the drought-induced response of biogenic isoprene emission accurately in the coupled Earth System model.

  7. Melanocortin-3 receptors expressed in Nkx2.1(+ve) neurons are sufficient for controlling appetitive responses to hypocaloric conditioning

    PubMed Central

    Girardet, Clémence; Mavrikaki, Maria M.; Stevens, Joseph R.; Miller, Courtney A.; Marks, Daniel L.; Butler, Andrew A.

    2017-01-01

    Melanocortin-3 receptors (MC3R) have a contextual role in appetite control that is amplified with hypocaloric conditioning. C57BL/6J (B6) mice subjected to hypocaloric feeding schedules (HFS) exhibit compulsive behavioral responses involving food anticipatory activity (FAA) and caloric loading following food access. These homeostatic responses to calorie-poor environs are attenuated in B6 mice in which Mc3r transcription is suppressed by a lox-stop-lox sequence in the 5’UTR (Mc3rTB/TB). Here, we report that optimization of caloric loading in B6 mice subject to HFS, characterized by increased meal size and duration, is not observed in Mc3rTB/TB mice. Analysis of hypothalamic and neuroendocrine responses to HFS throughout the light-dark cycle suggests uncoupling of hypothalamic responses involving appetite-stimulating fasting-responsive hypothalamic neurons expressing agouti-related peptide (AgRP) and neuropeptide Y (Npy). Rescuing Mc3rs expression in Nkx2.1(+ve) neurons is sufficient to restore normal hypothalamic responses to negative energy balance. In addition, Mc3rs expressed in Nkx2.1(+ve) neurons are also sufficient to restore FAA and caloric loading of B6 mice subjected to HFS. In summary, MC3Rs expressed in Nkx2.1(+ve) neurons are sufficient to coordinate hypothalamic response and expression of compulsive behavioral responses involving meal anticipation and consumption of large meals during situations of prolonged negative energy balance. PMID:28294152

  8. Asthma-Related Immune Responses in Youth With Asthma: Associations With Maternal Responsiveness and Expressions of Positive and Negative Affect in Daily Life

    PubMed Central

    Tobin, Erin T.; Kane, Heidi S.; Saleh, Daniel J.; Wildman, Derek E.; Breen, Elizabeth Crabb; Secord, Elizabeth; Slatcher, Richard B.

    2015-01-01

    Objective Stressful family environments early in life have negative effects on physical health. However, less is known about the health effects of positive aspects of families. We examined the associations between maternal responsiveness and immune markers among youth with asthma and identified youth expressions of positive affect as a potential mechanism of these associations. Methods Forty-three youths with asthma (26 males; aged 10-17) wore the Electronically Activated Recorder (EAR) for four days to assess maternal responsiveness and youth expressions of affect from audio-recordings of daily life. Trained coders rated EAR sound files for expressions of maternal responsiveness and affect displayed by the youth. Peripheral blood mononuclear cells were isolated, cultured, and assayed to determine stimulated levels of interleukin(IL)-5, IL-13, and interferon(IFN)- γ. Results Greater maternal responsiveness was associated with decreased stimulated production of IL-5 (r = −.38, p = .012) and IL-13 (r = −.33, p = .031). Greater total positive affect in youth was linked with decreased stimulated production of IL-5 (r = −.46, p = .002) and IL-13 (r = −.37, p = .014). Total negative affect among youth was unrelated to immune responses. There was a significant indirect effect of maternal responsiveness via positive affect in youth on lower levels of IL-5 (95% CI = −3.41, −.03) and IL-13 (95% CI = −2.34, −.01) when adjusting for caregiver-youth conflict and negative affect among youth. Conclusions These results indicate the importance of positive family interactions for youth and provide preliminary evidence for a mechanism through which parenting can influence immune responses in youths with asthma. PMID:26407226

  9. Asthma-Related Immune Responses in Youth With Asthma: Associations With Maternal Responsiveness and Expressions of Positive and Negative Affect in Daily Life.

    PubMed

    Tobin, Erin T; Kane, Heidi S; Saleh, Daniel J; Wildman, Derek E; Breen, Elizabeth Crabb; Secord, Elizabeth; Slatcher, Richard B

    2015-10-01

    Stressful family environments early in life have negative effects on physical health. However, less is known about the health effects of positive aspects of families. We examined the associations between maternal responsiveness and immune markers among youth with asthma and identified youth expressions of positive affect as a potential mechanism of these associations. Forty-three youths with asthma (26 boys; aged 10-17 years) wore the Electronically Activated Recorder for 4 days to assess maternal responsiveness and youth expressions of affect from audio-recordings of daily life. Trained coders rated Electronically Activated Recorder sound files for expressions of maternal responsiveness and affect displayed by the youth. Peripheral blood mononuclear cells were isolated, cultured, and assayed to determine stimulated levels of interleukin (IL)-5, IL-13, and interferon-γ. Greater maternal responsiveness was associated with decreased stimulated production of IL-5 (r = -0.38, p = .012) and IL-13 (r = -0.33, p = .031). Greater total positive affect in youth was linked to decreased stimulated production of IL-5 (r = -0.46, p = .002) and IL-13 (r = -0.37, p = .014). Total negative affect among youth was unrelated to immune responses. There was a significant indirect effect of maternal responsiveness via positive affect in youth on lower levels of IL-5 (95% confidence interval = -3.41 to -0.03) and IL-13 (95% confidence interval = -2.34 to -0.01) when adjusting for caregiver-youth conflict and negative affect among youth. These results indicate the importance of positive family interactions for youth and provide preliminary evidence for a mechanism through which parenting can influence immune responses in youth with asthma.

  10. Response of seafloor ecosystems to abrupt global climate change

    PubMed Central

    Moffitt, Sarah E.; Hill, Tessa M.; Roopnarine, Peter D.; Kennett, James P.

    2015-01-01

    Anthropogenic climate change is predicted to decrease oceanic oxygen (O2) concentrations, with potentially significant effects on marine ecosystems. Geologically recent episodes of abrupt climatic warming provide opportunities to assess the effects of changing oxygenation on marine communities. Thus far, this knowledge has been largely restricted to investigations using Foraminifera, with little being known about ecosystem-scale responses to abrupt, climate-forced deoxygenation. We here present high-resolution records based on the first comprehensive quantitative analysis, to our knowledge, of changes in marine metazoans (Mollusca, Echinodermata, Arthropoda, and Annelida; >5,400 fossils and trace fossils) in response to the global warming associated with the last glacial to interglacial episode. The molluscan archive is dominated by extremophile taxa, including those containing endosymbiotic sulfur-oxidizing bacteria (Lucinoma aequizonatum) and those that graze on filamentous sulfur-oxidizing benthic bacterial mats (Alia permodesta). This record, from 16,100 to 3,400 y ago, demonstrates that seafloor invertebrate communities are subject to major turnover in response to relatively minor inferred changes in oxygenation (>1.5 to <0.5 mL⋅L−1 [O2]) associated with abrupt (<100 y) warming of the eastern Pacific. The biotic turnover and recovery events within the record expand known rates of marine biological recovery by an order of magnitude, from <100 to >1,000 y, and illustrate the crucial role of climate and oceanographic change in driving long-term successional changes in ocean ecosystems. PMID:25825727

  11. Response of seafloor ecosystems to abrupt global climate change

    NASA Astrophysics Data System (ADS)

    Moffitt, Sarah E.; Hill, Tessa M.; Roopnarine, Peter D.; Kennett, James P.

    2015-04-01

    Anthropogenic climate change is predicted to decrease oceanic oxygen (O2) concentrations, with potentially significant effects on marine ecosystems. Geologically recent episodes of abrupt climatic warming provide opportunities to assess the effects of changing oxygenation on marine communities. Thus far, this knowledge has been largely restricted to investigations using Foraminifera, with little being known about ecosystem-scale responses to abrupt, climate-forced deoxygenation. We here present high-resolution records based on the first comprehensive quantitative analysis, to our knowledge, of changes in marine metazoans (Mollusca, Echinodermata, Arthropoda, and Annelida; >5,400 fossils and trace fossils) in response to the global warming associated with the last glacial to interglacial episode. The molluscan archive is dominated by extremophile taxa, including those containing endosymbiotic sulfur-oxidizing bacteria (Lucinoma aequizonatum) and those that graze on filamentous sulfur-oxidizing benthic bacterial mats (Alia permodesta). This record, from 16,100 to 3,400 y ago, demonstrates that seafloor invertebrate communities are subject to major turnover in response to relatively minor inferred changes in oxygenation (>1.5 to <0.5 mLṡL-1 [O2]) associated with abrupt (<100 y) warming of the eastern Pacific. The biotic turnover and recovery events within the record expand known rates of marine biological recovery by an order of magnitude, from <100 to >1,000 y, and illustrate the crucial role of climate and oceanographic change in driving long-term successional changes in ocean ecosystems.

  12. The Global Error Assessment (GEA) model for the selection of differentially expressed genes in microarray data.

    PubMed

    Mansourian, Robert; Mutch, David M; Antille, Nicolas; Aubert, Jerome; Fogel, Paul; Le Goff, Jean-Marc; Moulin, Julie; Petrov, Anton; Rytz, Andreas; Voegel, Johannes J; Roberts, Matthew-Alan

    2004-11-01

    Microarray technology has become a powerful research tool in many fields of study; however, the cost of microarrays often results in the use of a low number of replicates (k). Under circumstances where k is low, it becomes difficult to perform standard statistical tests to extract the most biologically significant experimental results. Other more advanced statistical tests have been developed; however, their use and interpretation often remain difficult to implement in routine biological research. The present work outlines a method that achieves sufficient statistical power for selecting differentially expressed genes under conditions of low k, while remaining as an intuitive and computationally efficient procedure. The present study describes a Global Error Assessment (GEA) methodology to select differentially expressed genes in microarray datasets, and was developed using an in vitro experiment that compared control and interferon-gamma treated skin cells. In this experiment, up to nine replicates were used to confidently estimate error, thereby enabling methods of different statistical power to be compared. Gene expression results of a similar absolute expression are binned, so as to enable a highly accurate local estimate of the mean squared error within conditions. The model then relates variability of gene expression in each bin to absolute expression levels and uses this in a test derived from the classical ANOVA. The GEA selection method is compared with both the classical and permutational ANOVA tests, and demonstrates an increased stability, robustness and confidence in gene selection. A subset of the selected genes were validated by real-time reverse transcription-polymerase chain reaction (RT-PCR). All these results suggest that GEA methodology is (i) suitable for selection of differentially expressed genes in microarray data, (ii) intuitive and computationally efficient and (iii) especially advantageous under conditions of low k. The GEA code for R

  13. Global patterns in lake ecosystem responses to warming based on the temperature dependence of metabolism.

    PubMed

    Kraemer, Benjamin M; Chandra, Sudeep; Dell, Anthony I; Dix, Margaret; Kuusisto, Esko; Livingstone, David M; Schladow, S Geoffrey; Silow, Eugene; Sitoki, Lewis M; Tamatamah, Rashid; McIntyre, Peter B

    2017-05-01

    Climate warming is expected to have large effects on ecosystems in part due to the temperature dependence of metabolism. The responses of metabolic rates to climate warming may be greatest in the tropics and at low elevations because mean temperatures are warmer there and metabolic rates respond exponentially to temperature (with exponents >1). However, if warming rates are sufficiently fast in higher latitude/elevation lakes, metabolic rate responses to warming may still be greater there even though metabolic rates respond exponentially to temperature. Thus, a wide range of global patterns in the magnitude of metabolic rate responses to warming could emerge depending on global patterns of temperature and warming rates. Here we use the Boltzmann-Arrhenius equation, published estimates of activation energy, and time series of temperature from 271 lakes to estimate long-term (1970-2010) changes in 64 metabolic processes in lakes. The estimated responses of metabolic processes to warming were usually greatest in tropical/low-elevation lakes even though surface temperatures in higher latitude/elevation lakes are warming faster. However, when the thermal sensitivity of a metabolic process is especially weak, higher latitude/elevation lakes had larger responses to warming in parallel with warming rates. Our results show that the sensitivity of a given response to temperature (as described by its activation energy) provides a simple heuristic for predicting whether tropical/low-elevation lakes will have larger or smaller metabolic responses to warming than higher latitude/elevation lakes. Overall, we conclude that the direct metabolic consequences of lake warming are likely to be felt most strongly at low latitudes and low elevations where metabolism-linked ecosystem services may be most affected. © 2016 John Wiley & Sons Ltd.

  14. In situ aromatase expression in primary tumor is associated with estrogen receptor expression but is not predictive of response to endocrine therapy in advanced breast cancer

    PubMed Central

    2009-01-01

    Background New, third-generation aromatase inhibitors (AIs) have proven comparable or superior to the anti-estrogen tamoxifen for treatment of estrogen receptor (ER) and/or progesterone receptor (PR) positive breast cancer. AIs suppress total body and intratumoral estrogen levels. It is unclear whether in situ carcinoma cell aromatization is the primary source of estrogen production for tumor growth and whether the aromatase expression is predictive of response to endocrine therapy. Due to methodological difficulties in the determination of the aromatase protein, COX-2, an enzyme involved in the synthesis of aromatase, has been suggested as a surrogate marker for aromatase expression. Methods Primary tumor material was retrospectively collected from 88 patients who participated in a randomized clinical trial comparing the AI letrozole to the anti-estrogen tamoxifen for first-line treatment of advanced breast cancer. Semi-quantitative immunohistochemical (IHC) analysis was performed for ER, PR, COX-2 and aromatase using Tissue Microarrays (TMAs). Aromatase was also analyzed using whole sections (WS). Kappa analysis was applied to compare association of protein expression levels. Univariate Wilcoxon analysis and the Cox-analysis were performed to evaluate time to progression (TTP) in relation to marker expression. Results Aromatase expression was associated with ER, but not with PR or COX-2 expression in carcinoma cells. Measurements of aromatase in WS were not comparable to results from TMAs. Expression of COX-2 and aromatase did not predict response to endocrine therapy. Aromatase in combination with high PR expression may select letrozole treated patients with a longer TTP. Conclusion TMAs are not suitable for IHC analysis of in situ aromatase expression and we did not find COX-2 expression in carcinoma cells to be a surrogate marker for aromatase. In situ aromatase expression in tumor cells is associated with ER expression and may thus point towards good

  15. CrMAPK3 regulates the expression of iron-deficiency-responsive genes in Chlamydomonas reinhardtii.

    PubMed

    Fei, Xiaowen; Yu, Junmei; Li, Yajun; Deng, Xiaodong

    2017-05-16

    Under iron-deficient conditions, Chlamydomonas exhibits high affinity for iron absorption. Nevertheless, the response, transmission, and regulation of downstream gene expression in algae cells have not to be investigated. Considering that the MAPK pathway is essential for abiotic stress responses, we determined whether this pathway is involved in iron deficiency signal transduction in Chlamydomonas. Arabidopsis MAPK gene sequences were used as entry data to search for homologous genes in Chlamydomonas reinhardtii genome database to investigate the functions of mitogen-activated protein kinase (MAPK) gene family in C. reinhardtii under iron-free conditions. Results revealed 16 C. reinhardtii MAPK genes labeled CrMAPK2-CrMAPK17 with TXY conserved domains and low homology to MAPK in yeast, Arabidopsis, and humans. The expression levels of these genes were then analyzed through qRT-PCR and exposure to high salt (150 mM NaCl), low nitrogen, or iron-free conditions. The expression levels of these genes were also subjected to adverse stress conditions. The mRNA levels of CrMAPK2, CrMAPK3, CrMAPK4, CrMAPK5, CrMAPK6, CrMAPK8, CrMAPK9, and CrMAPK11 were remarkably upregulated under iron-deficient stress. The increase in CrMAPK3 expression was 43-fold greater than that in the control. An RNA interference vector was constructed and transformed into C. reinhardtii 2A38, an algal strain with an exogenous FOX1:ARS chimeric gene, to silence CrMAPK3. After this gene was silenced, the mRNA levels and ARS activities of FOX1:ARS chimeric gene and endogenous CrFOX1 were decreased. The mRNA levels of iron-responsive genes, such as CrNRAMP2, CrATX1, CrFTR1, and CrFEA1, were also remarkably reduced. CrMAPK3 regulates the expression of iron-deficiency-responsive genes in C. reinhardtii.

  16. Transcriptome profiling and expression analyses of genes critical to wheat adaptation to low temperature

    USDA-ARS?s Scientific Manuscript database

    Background: To identify the genes involved in the development of low temperature (LT) tolerance in hexaploid wheat, we examined the global changes in expression in response to cold of the 55,052 potentially unique genes represented in the Affymetrix Wheat Genome microarray. We compared the expressi...

  17. Blockage of hemichannels alters gene expression in osteocytes in a high magneto-gravitational environment

    PubMed Central

    Xu, Huiyun; Ning, Dandan; Zhao, Dezhi; Chen, Yunhe; Zhao, Dongdong; Gu, Sumin; Jiang, Jean X.; Shang, Peng

    2017-01-01

    Osteocytes, the most abundant cells in bone, are highly responsive to external environmental changes. We tested how Cx43 hemichannels which mediate the exchange of small molecules between cells and extracellular environment impact genome wide gene expression under conditions of abnormal gravity and magnetic field. To this end, we subjected osteocytic MLO-Y4 cells to a high magneto-gravitational environment and used microarray to examine global gene expression and a specific blocking antibody was used to assess the role of Cx43 hemichannels. While 3 hr exposure to abnormal gravity and magnetic field had relatively minor effects on global gene expression, blocking hemichannels significantly impacted the expression of a number of genes which are involved in cell viability, apoptosis, mineral absorption, protein absorption and digestion, and focal adhesion. Also, blocking of hemichannels enriched genes in multiple signaling pathways which are enaged by TGF-beta, Jak-STAT and VEGF. These results show the role of connexin hemichannels in bone cells in high magneto-gravitational environments. PMID:27814646

  18. Transcriptional Profiling of the Oral Pathogen Streptococcus mutans in Response to Competence Signaling Peptide XIP.

    PubMed

    Wenderska, Iwona B; Latos, Andrew; Pruitt, Benjamin; Palmer, Sara; Spatafora, Grace; Senadheera, Dilani B; Cvitkovitch, Dennis G

    2017-01-01

    In the cariogenic Streptococcus mutans , competence development is regulated by the ComRS signaling system comprised of the ComR regulator and the ComS prepeptide to the competence signaling peptide XIP (ComX-inducing peptide). Aside from competence development, XIP signaling has been demonstrated to regulate cell lysis, and recently, the expression of bacteriocins, small antimicrobial peptides used by bacteria to inhibit closely related species. Our study further explores the effect of XIP signaling on the S. mutans transcriptome. RNA sequencing revealed that XIP induction resulted in a global change in gene expression that was consistent with a stress response. An increase in several membrane-bound regulators, including HdrRM and BrsRM, involved in bacteriocin production, and the VicRKX system, involved in acid tolerance and biofilm formation, was observed. Furthermore, global changes in gene expression corresponded to changes observed during the stringent response to amino acid starvation. Effects were also observed on genes involved in sugar transport and carbon catabolite repression and included the levQRST and levDEFG operons. Finally, our work identified a novel heat shock-responsive intergenic region, encoding a small RNA, with a potential role in competence shutoff. IMPORTANCE Genetic competence provides bacteria with an opportunity to increase genetic diversity or acquire novel traits conferring a survival advantage. In the cariogenic pathogen Streptococcus mutans , DNA transformation is regulated by the competence stimulating peptide XIP (ComX-inducing peptide). The present study utilizes high-throughput RNA sequencing (RNAseq) to provide a greater understanding of how global gene expression patterns change in response to XIP. Overall, our work demonstrates that in S. mutans , XIP signaling induces a response that resembles the stringent response to amino acid starvation. We further identify a novel heat shock-responsive intergenic region with a

  19. Drought responsive gene expression regulatory divergence between upland and lowland ecotypes of a perennial C4 grass.

    PubMed

    Lovell, John T; Schwartz, Scott; Lowry, David B; Shakirov, Eugene V; Bonnette, Jason E; Weng, Xiaoyu; Wang, Mei; Johnson, Jenifer; Sreedasyam, Avinash; Plott, Christopher; Jenkins, Jerry; Schmutz, Jeremy; Juenger, Thomas E

    2016-04-01

    Climatic adaptation is an example of a genotype-by-environment interaction (G×E) of fitness. Selection upon gene expression regulatory variation can contribute to adaptive phenotypic diversity; however, surprisingly few studies have examined how genome-wide patterns of gene expression G×E are manifested in response to environmental stress and other selective agents that cause climatic adaptation. Here, we characterize drought-responsive expression divergence between upland (drought-adapted) and lowland (mesic) ecotypes of the perennial C4 grass,Panicum hallii, in natural field conditions. Overall, we find that cis-regulatory elements contributed to gene expression divergence across 47% of genes, 7.2% of which exhibit drought-responsive G×E. While less well-represented, we observe 1294 genes (7.8%) with transeffects.Trans-by-environment interactions are weaker and much less common than cis G×E, occurring in only 0.7% oft rans-regulated genes. Finally, gene expression heterosis is highly enriched in expression phenotypes with significant G×E. As such, modes of inheritance that drive heterosis, such as dominance or overdominance, may be common among G×E genes. Interestingly, motifs specific to drought-responsive transcription factors are highly enriched in the promoters of genes exhibiting G×E and transregulation, indicating that expression G×E and heterosis may result from the evolution of transcription factors or their binding sites.P. hallii serves as the genomic model for its close relative and emerging biofuel crop, switchgrass (Panicum virgatum). Accordingly, the results here not only aid in the discovery of the genetic mechanisms that underlie local adaptation but also provide a foundation to improve switchgrass yield under water-limited conditions. © 2016 Lovell et al.; Published by Cold Spring Harbor Laboratory Press.

  20. Drought responsive gene expression regulatory divergence between upland and lowland ecotypes of a perennial C4 grass

    PubMed Central

    Lovell, John T.; Schwartz, Scott; Lowry, David B.; Shakirov, Eugene V.; Bonnette, Jason E.; Weng, Xiaoyu; Wang, Mei; Johnson, Jenifer; Sreedasyam, Avinash; Plott, Christopher; Jenkins, Jerry; Schmutz, Jeremy; Juenger, Thomas E.

    2016-01-01

    Climatic adaptation is an example of a genotype-by-environment interaction (G×E) of fitness. Selection upon gene expression regulatory variation can contribute to adaptive phenotypic diversity; however, surprisingly few studies have examined how genome-wide patterns of gene expression G×E are manifested in response to environmental stress and other selective agents that cause climatic adaptation. Here, we characterize drought-responsive expression divergence between upland (drought-adapted) and lowland (mesic) ecotypes of the perennial C4 grass, Panicum hallii, in natural field conditions. Overall, we find that cis-regulatory elements contributed to gene expression divergence across 47% of genes, 7.2% of which exhibit drought-responsive G×E. While less well-represented, we observe 1294 genes (7.8%) with trans effects. Trans-by-environment interactions are weaker and much less common than cis G×E, occurring in only 0.7% of trans-regulated genes. Finally, gene expression heterosis is highly enriched in expression phenotypes with significant G×E. As such, modes of inheritance that drive heterosis, such as dominance or overdominance, may be common among G×E genes. Interestingly, motifs specific to drought-responsive transcription factors are highly enriched in the promoters of genes exhibiting G×E and trans regulation, indicating that expression G×E and heterosis may result from the evolution of transcription factors or their binding sites. P. hallii serves as the genomic model for its close relative and emerging biofuel crop, switchgrass (Panicum virgatum). Accordingly, the results here not only aid in the discovery of the genetic mechanisms that underlie local adaptation but also provide a foundation to improve switchgrass yield under water-limited conditions. PMID:26953271

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