1,472 research outputs found

    Association of the HLA locus and TNF with type I autoimmune hepatitis susceptibility in New Zealand Caucasians

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    PURPOSE: The precise etiology of autoimmune hepatitis (AIH) remains unknown, although a number of genetic loci have been implicated in the susceptibility of type 1 AIH. The purpose of this study was to test for association of these loci with type 1 AIH in New Zealand Caucasians. METHODS: 77 AIH patients and 485 healthy controls were genotyped for the SNPs rs2187668 (HLA-DRB*03:01), rs660895 (HLA-DRB*04:01), rs3749971 (HLA-A1-B8-DR3), rs231775 (CLTLA4), rs1800629 (TNF), and rs1800682 (FAS) using predesigned TaqMan SNP genotyping assays. Chi square analysis was used to test for association of allele and genotype with overall AIH, and with severe fibrosis and ALT levels at 6 months. RESULTS: Significant risk of AIH was conferred by the minor alleles of rs2187668 (OR = 2.45, 95% CI 1.65-3.61, p < 0.0001), rs3749971 (OR = 1.89, 95% CI 1.21-2.94, p = 0.004) and rs1800629 (OR = 2.06, 95% CI 1.41-3.01, p = 0.0001). Multivariate analysis showed that rs2187668 was independently associated with type 1 AIH susceptibility (OR = 2.40, 95% CI 1.46-3.93, p = 0.001). The C allele of FAS SNP rs1800682 was associated with increased risk of severe fibrosis at diagnosis (OR = 2.03, 95% CI 1.05-3.93, p = 0.035) and with incomplete normalization of ALT levels at 6 months post-diagnosis (OR = 3.94, 95% CI 1.62-9.54, p = 0.0015). CONCLUSIONS: This is the first population-based study to investigate genetic risk loci for type 1 AIH in New Zealand Caucasians. We report significant independent association of HLA-DRB1*03:01 with overall susceptibility to type 1 AIH, as well as FAS with a more aggressive disease phenotype

    Dynamics of Trophoblast Differentiation in Peri-Implantation–Stage Human Embryos

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    Single-cell RNA sequencing of cells from cultured human blastocysts has enabled us to define the transcriptomic landscape of placental trophoblast (TB) that surrounds the epiblast and associated embryonic tissues during the enigmatic day 8 (D8) to D12 peri-implantation period before the villous placenta forms. We analyzed the transcriptomes of 3 early placental cell types, cytoTB (CTB), syncytioTB (STB), and migratoryTB (MTB), picked manually from cultured embryos dissociated with trypsin and were able to follow sublineages that emerged from proliferating CTB at the periphery of the conceptus. A unique form of CTB with some features of STB was detectable at D8, while mature STB was at its zenith at D10. A form of MTB with a mixed MTB/CTB phenotype arose around D10. By D12, STB generation was in decline, CTB had entered a new phase of proliferation, and mature MTB cells had begun to move from the main body of the conceptus. Notably, the MTB transcriptome at D12 indicated enrichment of transcripts associated with IFN signaling, migration, and invasion and upregulation of HLA-C, HLA-E, and HLA-G. The STB, which is distinct from the STB of later villous STB, had a phenotype consistent with intense protein export and placental hormone production, as well as migration and invasion. The studies show that TB associated with human embryos is in rapid developmental flux during periimplantation period when it must invade, signal robustly to the mother to ensure that the pregnancy continues, and make first contact with the maternal immune system

    Conscientiousness and fruit and vegetable consumption: exploring behavioural intention as a mediator

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    Clear associations have emerged between conscientiousness and health behaviours, such that higher levels of conscientiousness are predictive of beneficial health behaviours. This study investigated the conscientiousness-fruit and vegetable consumption relationship and whether behavioural intention mediated this relationship. A large sample of adults (N = 2136) completed an online battery of questionnaires measuring conscientiousness, behavioural intentions to consume fruit and vegetables, together with self-reported behaviour. Correlation analysis revealed that conscientiousness and each of its facets were positively associated with behavioural intention and self-reported behaviour. Hierarchical multiple regression analyses revealed that after controlling for age, gender and education, total conscientiousness, and the facets of responsibility, industriousness, order and virtue predicted self-reported behaviour. Further analysis revealed that in line with the Theory of Planned Behaviour, behavioural intention fully mediated the conscientiousness-fruit and vegetable behaviour relationship. In conclusion, low levels of conscientiousness were found to be associated with lower fruit and vegetable intentions, with the latter also associated with fruit and vegetable consumption

    Direct Imaging in Reflected Light: Characterization of Older, Temperate Exoplanets With 30-m Telescopes

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    Direct detection, also known as direct imaging, is a method for discovering and characterizing the atmospheres of planets at intermediate and wide separations. It is the only means of obtaining spectra of non-transiting exoplanets. Characterizing the atmospheres of planets in the <5 AU regime, where RV surveys have revealed an abundance of other worlds, requires a 30-m-class aperture in combination with an advanced adaptive optics system, coronagraph, and suite of spectrometers and imagers - this concept underlies planned instruments for both TMT (the Planetary Systems Imager, or PSI) and the GMT (GMagAO-X). These instruments could provide astrometry, photometry, and spectroscopy of an unprecedented sample of rocky planets, ice giants, and gas giants. For the first time habitable zone exoplanets will become accessible to direct imaging, and these instruments have the potential to detect and characterize the innermost regions of nearby M-dwarf planetary systems in reflected light. High-resolution spectroscopy will not only illuminate the physics and chemistry of exo-atmospheres, but may also probe rocky, temperate worlds for signs of life in the form of atmospheric biomarkers (combinations of water, oxygen and other molecular species). By completing the census of non-transiting worlds at a range of separations from their host stars, these instruments will provide the final pieces to the puzzle of planetary demographics. This whitepaper explores the science goals of direct imaging on 30-m telescopes and the technology development needed to achieve them.Comment: (March 2018) Submitted to the Exoplanet Science Strategy committee of the NA

    The Lantern Vol. 41, No. 1, Fall 1974

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    • The Fable • Landscape - Clear Weather in the Valley • Josephine Palooka • Don\u27t Bark Twice - It\u27s All Right • Masks • Suicide Note From a Lemming • The Death of Dame Sexton • Come September • Leaves • Spruce Grove • The Class of \u2775 • The Promise • Images • Sixth Station • Borealis • To Gemhttps://digitalcommons.ursinus.edu/lantern/1105/thumbnail.jp

    A stochastic neuronal model predicts random search behaviors at multiple spatial scales in C. elegans

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    Random search is a behavioral strategy used by organisms from bacteria to humans to locate food that is randomly distributed and undetectable at a distance. We investigated this behavior in the nematode Caenorhabditis elegans, an organism with a small, well-described nervous system. Here we formulate a mathematical model of random search abstracted from the C. elegans connectome and fit to a large-scale kinematic analysis of C. elegans behavior at submicron resolution. The model predicts behavioral effects of neuronal ablations and genetic perturbations, as well as unexpected aspects of wild type behavior. The predictive success of the model indicates that random search in C. elegans can be understood in terms of a neuronal flip-flop circuit involving reciprocal inhibition between two populations of stochastic neurons. Our findings establish a unified theoretical framework for understanding C. elegans locomotion and a testable neuronal model of random search that can be applied to other organisms
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