34 research outputs found

    Gene and MicroRNA Expression Profile Changes in ISS Crewmembers Blood Samples

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    In space, living organisms are exposed to multiple stress factors including microgravity and space radiation. For humans, these harmful environmental factors have been known to cause negative health impacts such as immune dysfunction. Understanding the mechanisms by which spaceflight impacts human health at the molecular level is critical not only for accurately assessing the risks associated with spaceflight, but also for developing effective countermeasures. This study is part of the Functional Immune Project, intended to determine alterations in crewmember immunobiology before, during, and after spaceflight. It emphasizes the study of DNA damage in the ISS crewmembers peripheral blood mononuclear cells (PBMCs), expression patterns of damage-response and inflammatory process genes, and changes in latent virus reactivation biomarkers

    Genomic factors that shape craniofacial outcome and neural crest vulnerability in FASD

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    Prenatal alcohol exposure (PAE) causes distinctive facial characteristics in some pregnancies and not others; genetic factors may contribute to this differential vulnerability. Ethanol disrupts multiple events of neural crest development including induction, survival, migration, and differentiation. Animal models and genomic approaches have substantially advanced our understanding of the mechanisms underlying these facial changes. PAE during gastrulation produces craniofacial changes corresponding with human fetal alcohol syndrome. These result because PAE reduces prechordal plate extension and suppresses sonic hedgehog, leading to holoprosencephaly and malpositioned facial primordia. Haploinsufficiency in sonic hedgehog signaling increases vulnerability to facial deficits and may influence some PAE pregnancies. In contrast, PAE during early neurogenesis produces facial hypoplasia, preceded by neural crest reductions due to significant apoptosis. Factors mediating this apoptosis include intracellular calcium mobilization, elevated reactive oxygen species, and loss of trophic support from β-catenin/calcium, sonic hedgehog, and mTOR signaling. Genomewide SNP analysis links PDGF receptor genes with facial outcomes in human PAE. Multiple genomic-level comparisons of ethanol-sensitive and –resistant early embryos, in both mouse and chick, independently identify common candidate genes that may potentially modify craniofacial vulnerability, including ribosomal proteins, proteosome, RNA splicing, and focal adhesion. In summary, research using animal models with genome-level differences in ethanol vulnerability, as well as targeted loss- and gain-of-function mutants, has clarified the mechanisms mediating craniofacial change in PAE. The findings additionally suggest that craniofacial deficits may represent a gene-ethanol interaction for some affected individuals. Genetic-level changes may prime individuals toward greater sensitivity or resistance to ethanol's neurotoxicity

    The Integrative Conjugative Element clc (ICEclc) of Pseudomonas aeruginosa JB2

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    Integrative conjugative elements (ICE) are a diverse group of chromosomally integrated, self-transmissible mobile genetic elements (MGE) that are active in shaping the functions of bacteria and bacterial communities. Each type of ICE carries a characteristic set of core genes encoding functions essential for maintenance and self-transmission, and cargo genes that endow on hosts phenotypes beneficial for niche adaptation. An important area to which ICE can contribute beneficial functions is the biodegradation of xenobiotic compounds. In the biodegradation realm, the best-characterized ICE is ICEclc, which carries cargo genes encoding for ortho-cleavage of chlorocatechols (clc genes) and aminophenol metabolism (amn genes). The element was originally identified in the 3-chlorobenzoate-degrader Pseudomonas knackmussii B13, and the closest relative is a nearly identical element in Burkholderia xenovorans LB400 (designated ICEclc-B13 and ICEclc-LB400, respectively). In the present report, genome sequencing of the o-chlorobenzoate degrader Pseudomonas aeruginosa JB2 was used to identify a new member of the ICEclc family, ICEclc-JB2. The cargo of ICEclc-JB2 differs from that of ICEclc-B13 and ICEclc-LB400 in consisting of a unique combination of genes that encode for the utilization of o-halobenzoates and o-hydroxybenzoate as growth substrates (ohb genes and hyb genes, respectively) and which are duplicated in a tandem repeat. Also, ICEclc-JB2 lacks an operon of regulatory genes (tciR-marR-mfsR) that is present in the other two ICEclc, and which controls excision from the host. Thus, the mechanisms regulating intracellular behavior of ICEclc-JB2 may differ from that of its close relatives. The entire tandem repeat in ICEclc-JB2 can excise independently from the element in a process apparently involving transposases/insertion sequence associated with the repeats. Excision of the repeats removes important niche adaptation genes from ICEclc-JB2, rendering it less beneficial to the host. However, the reduced version of ICEclc-JB2 could now acquire new genes that might be beneficial to a future host and, consequently, to the survival of ICEclc-JB2. Collectively, the present identification and characterization of ICEclc-JB2 provides insights into roles of MGE in bacterial niche adaptation and the evolution of catabolic pathways for biodegradation of xenobiotic compounds

    A high-density SNP panel reveals extensive diversity, frequent recombination and multiple recombination hotspots within the chicken major histocompatibility complex B region between BG2 and CD1A1

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    Background: The major histocompatibility complex (MHC) is present within the genomes of all jawed vertebrates. MHC genes are especially important in regulating immune responses, but even after over 80 years of research on the MHC, much remains to be learned about how it influences adaptive and innate immune responses. In most species, the MHC is highly polymorphic and polygenic. Strong and highly reproducible associations are established for chicken MHC-B haplotypes in a number of infectious diseases. Here, we report (1) the development of a high-density SNP (single nucleotide polymorphism) panel for MHC-B typing that encompasses a 209,296 bp region in which 45 MHC-B genes are located, (2) how this panel was used to define chicken MHC-B haplotypes within a large number of lines/breeds and (3) the detection of recombinants which contributes to the observed diversity. Methods: A SNP panel was developed for the MHC-B region between the BG2 and CD1A1 genes. To construct this panel, each SNP was tested in end-point read assays on more than 7500 DNA samples obtained from inbred and commercially used egg-layer lines that carry known and novel MHC-B haplotypes. One hundred and one SNPs were selected for the panel. Additional breeds and experimentally-derived lines, including lines that carry MHC-B recombinant haplotypes, were then genotyped. Results: MHC-B haplotypes based on SNP genotyping were consistent with the MHC-B haplotypes that were assigned previously in experimental lines that carry B2, B5, B12, B13, B15, B19, B21, and B24 haplotypes. SNP genotyping resulted in the identification of 122 MHC-B haplotypes including a number of recombinant haplotypes, which indicate that crossing-over events at multiple locations within the region lead to the production of new MHC-B haplotypes. Furthermore, evidence of gene duplication and deletion was found. Conclusions: The chicken MHC-B region is highly polymorphic across the surveyed 209-kb region that contains 45 genes. Our results expand the number of identified haplotypes and provide insights into the contribution of recombination events to MHC-B diversity including the identification of recombination hotspots and an estimation of recombination frequency

    Data from: Genetic population structure of the blister beetle Gnathium minimum: core and peripheral populations

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    Populations on the periphery of a species’ range tend to contain lower genetic variation and increased genetic differentiation compared to populations at the core of a species range, although some exceptions to this generalization occur. The blister beetle Gnathium minimum (Say) exhibits a wide-ranging distribution in the western United States but has peripheral or disjunct populations in Mexico, Florida, and Wisconsin. We used amplified fragment length polymorphism (AFLP) to compare the genetic variation and magnitude of genetic differentiation of the Wisconsin peripheral population to western core populations (Colorado, Kansas, New Mexico, and Texas). The proportion of polymorphic loci was 53.6 and 54.3, and expected heterozygosity 0.1864 and 0.1933 for the Kansas/Colorado (n = 87) and New Mexico/Texas (n = 35) regions, respectively. Specimens from Wisconsin (n = 121) had a lower proportion of polymorphic loci (38.4) and expected heterozygosity (0.1475). Genetic cluster estimation with GENELAND and F ST values showed greater genetic differentiation among the sampling locations within Wisconsin compared to core regions. Significant isolation-by-distance (IBD) was also observed in Wisconsin but not within the core regions. Lower genetic variation and increased isolation may reduce the Wisconsin population’s ability to respond to change, thereby increasing their susceptibility to extinction

    Genetic Population Structure of the Blister Beetle, Gnathium minimum

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    Model America - Arizona extract from ORNL's AutoBEM

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    Oak Ridge National Laboratory (ORNL) has developed the Automatic Building Energy Modeling (AutoBEM) software suite to process multiple types of data, extract building-specific descriptors, generate building energy models, and simulate them on High Performance Computing (HPC) resources. For more information, see AutoBEM-related publications (bit.ly/AutoBEM). Two sets of sample data are provided for 550,656 buildings located within the boundary of Arizona in the United States: Data (884.3MB *.csv) - minimalist list of each building (rows) for the following fields (columns) ID - unique building ID Centroid - building center location in latitude/longitude (from Footprint2D) Footprint2D - building polygon of 2D footprint (lat1/lon1_lat2/lon2_...) State_abbr - state name Area - estimate of total conditioned floor area (ft2) Area2D - footprint area (ft2) Height - building height (ft) NumFloors - number of floors (above-grade) WWR_surfaces - percent of each facade (pair of points from Footprint2D) covered by fenestration/windows (average 14.5% for residential, 40% for commercial buildings) CZ - ASHRAE Climate Zone designation BuildingType - DOE prototype building designation (IECC=residential) as implemented by OpenStudio-standards Standard - building vintage Sample Models (21.74GB*.zip by county) – OpenStudio and EnergyPlus building energy models named according to ID This data is made free and openly available in hopes of stimulating any simulation-informed use case. Data is provided as-is with no warranties, express or implied, regarding fitness for a particular purpose. We wish to thank our sponsors which include Oak Ridge National Laboratory (ORNL), U.S. Dept. of Energy’s (DOE) Building Technologies Office (BTO), Office of Electricity (OE), and Biological and Environmental Research (BER)
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