81 research outputs found

    Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease

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    We identified rare coding variants associated with Alzheimer’s disease (AD) in a 3-stage case-control study of 85,133 subjects. In stage 1, 34,174 samples were genotyped using a whole-exome microarray. In stage 2, we tested associated variants (P<1×10-4) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, an additional 14,997 samples were used to test the most significant stage 2 associations (P<5×10-8) using imputed genotypes. We observed 3 novel genome-wide significant (GWS) AD associated non-synonymous variants; a protective variant in PLCG2 (rs72824905/p.P522R, P=5.38×10-10, OR=0.68, MAFcases=0.0059, MAFcontrols=0.0093), a risk variant in ABI3 (rs616338/p.S209F, P=4.56×10-10, OR=1.43, MAFcases=0.011, MAFcontrols=0.008), and a novel GWS variant in TREM2 (rs143332484/p.R62H, P=1.55×10-14, OR=1.67, MAFcases=0.0143, MAFcontrols=0.0089), a known AD susceptibility gene. These protein-coding changes are in genes highly expressed in microglia and highlight an immune-related protein-protein interaction network enriched for previously identified AD risk genes. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to AD development

    Fundamental Science and Engineering Questions in Planetary Cave Exploration

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    32 páginas.- 3 figuras.- 2 tablas.- 260 referenciasNearly half a century ago, two papers postulated the likelihood of lunar lava tube caves using mathematical models. Today, armed with an array of orbiting and fly-by satellites and survey instrumentation, we have now acquired cave data across our solar system-including the identification of potential cave entrances on the Moon, Mars, and at least nine other planetary bodies. These discoveries gave rise to the study of planetary caves. To help advance this field, we leveraged the expertise of an interdisciplinary group to identify a strategy to explore caves beyond Earth. Focusing primarily on astrobiology, the cave environment, geology, robotics, instrumentation, and human exploration, our goal was to produce a framework to guide this subdiscipline through at least the next decade. To do this, we first assembled a list of 198 science and engineering questions. Then, through a series of social surveys, 114 scientists and engineers winnowed down the list to the top 53 highest priority questions. This exercise resulted in identifying emerging and crucial research areas that require robust development to ultimately support a robotic mission to a planetary cave-principally the Moon and/or Mars. With the necessary financial investment and institutional support, the research and technological development required to achieve these necessary advancements over the next decade are attainable. Subsequently, we will be positioned to robotically examine lunar caves and search for evidence of life within Martian caves; in turn, this will set the stage for human exploration and potential habitation of both the lunar and Martian subsurface.The following funding sources are recognized for supporting several of the contributing authors: Human Frontiers Science Program grant #RGY0066/2018 (for AAB), NASA Innovative Advanced Concepts Grant #80HQTR19C0034 (HJ, UYW, and WLW), and European Research Council, ERC Consolidator Grant #818602 (AGF), the Spanish Ministry of Science and Innovation (project PID2019-108672RJ-I00) and the "Ramon y Cajal" post-doctoral contract (grant #RYC2019-026885-I (AZM)), and Contract #80NM0018D0004 between the Jet Propulsion Laboratory, California Institute of Technology and the National Aeronautics and Space Administration (AA, MJM, KU, and LK).Peer reviewe

    The diverse meteorology of Jezero crater over the first 250 sols of Perseverance on Mars

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    ASA’s Perseverance rover’s Mars Environmental Dynamics Analyzer is collecting data at Jezero crater, characterizing the physical processes in the lowest layer of the Martian atmosphere. Here we present measurements from the instrument’s first 250 sols of operation, revealing a spatially and temporally variable meteorology at Jezero. We find that temperature measurements at four heights capture the response of the atmospheric surface layer to multiple phenomena. We observe the transition from a stable night-time thermal inversion to a daytime, highly turbulent convective regime, with large vertical thermal gradients. Measurement of multiple daily optical depths suggests aerosol concentrations are higher in the morning than in the afternoon. Measured wind patterns are driven mainly by local topography, with a small contribution from regional winds. Daily and seasonal variability of relative humidity shows a complex hydrologic cycle. These observations suggest that changes in some local surface properties, such as surface albedo and thermal inertia, play an influential role. On a larger scale, surface pressure measurements show typical signatures of gravity waves and baroclinic eddies in a part of the seasonal cycle previously characterized as low wave activity. These observations, both combined and simultaneous, unveil the diversity of processes driving change on today’s Martian surface at Jezero crater

    Volatile and Organic Compositions of Sedimentary Rocks in Yellowknife Bay, Gale crater, Mars

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    H₂O, CO₂, SO₂, O₂, H₂, H₂S, HCl, chlorinated hydrocarbons, NO and other trace gases were evolved during pyrolysis of two mudstone samples acquired by the Curiosity rover at Yellowknife Bay within Gale crater, Mars. H₂O/OH-bearing phases included 2:1 phyllosilicate(s), bassanite, akaganeite, and amorphous materials. Thermal decomposition of carbonates and combustion of organic materials are candidate sources for the CO₂. Concurrent evolution of O₂ and chlorinated hydrocarbons suggest the presence of oxychlorine phase(s). Sulfides are likely sources for S-bearing species. Higher abundances of chlorinated hydrocarbons in the mudstone compared with Rocknest windblown materials previously analyzed by Curiosity suggest that indigenous martian or meteoritic organic C sources may be preserved in the mudstone; however, the C source for the chlorinated hydrocarbons is not definitively of martian origin

    Aqueous alteration processes in Jezero crater, Mars—implications for organic geochemistry

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    The Perseverance rover landed in Jezero crater, Mars, in February 2021. We used the Scanning Habitable Environments with Raman and Luminescence for Organics and Chemicals (SHERLOC) instrument to perform deep-ultraviolet Raman and fluorescence spectroscopy of three rocks within the crater. We identify evidence for two distinct ancient aqueous environments at different times. Reactions with liquid water formed carbonates in an olivine-rich igneous rock. A sulfate-perchlorate mixture is present in the rocks, which probably formed by later modifications of the rocks by brine. Fluorescence signatures consistent with aromatic organic compounds occur throughout these rocks and are preserved in minerals related to both aqueous environments
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