121 research outputs found

    Evidence for directional selection at a novel major histocompatibility class I marker in wild common frogs (Rana temporaria) exposed to a viral pathogen (Ranavirus).

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    (c) 2009 Teacher et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Whilst the Major Histocompatibility Complex (MHC) is well characterized in the anuran Xenopus, this region has not previously been studied in another popular model species, the common frog (Rana temporaria). Nor, to date, have there been any studies of MHC in wild amphibian host-pathogen systems. We characterise an MHC class I locus in the common frog, and present primers to amplify both the whole region, and specifically the antigen binding region. As no more than two expressed haplotypes were found in over 400 clones from 66 individuals, it is likely that there is a single class I locus in this species. This finding is consistent with the single class I locus in Xenopus, but contrasts with the multiple loci identified in axolotls, providing evidence that the diversification of MHC class I into multiple loci likely occurred after the Caudata/Anura divergence (approximately 350 million years ago) but before the Ranidae/Pipidae divergence (approximately 230 mya). We use this locus to compare wild populations of common frogs that have been infected with a viral pathogen (Ranavirus) with those that have no history of infection. We demonstrate that certain MHC supertypes are associated with infection status (even after accounting for shared ancestry), and that the diseased populations have more similar supertype frequencies (lower F(ST)) than the uninfected. These patterns were not seen in a suite of putatively neutral microsatellite loci. We interpret this pattern at the MHC locus to indicate that the disease has imposed selection for particular haplotypes, and hence that common frogs may be adapting to the presence of Ranavirus, which currently kills tens of thousands of amphibians in the UK each year

    CMB-S4 Science Book, First Edition

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    This book lays out the scientific goals to be addressed by the next-generation ground-based cosmic microwave background experiment, CMB-S4, envisioned to consist of dedicated telescopes at the South Pole, the high Chilean Atacama plateau and possibly a northern hemisphere site, all equipped with new superconducting cameras. CMB-S4 will dramatically advance cosmological studies by crossing critical thresholds in the search for the B-mode polarization signature of primordial gravitational waves, in the determination of the number and masses of the neutrinos, in the search for evidence of new light relics, in constraining the nature of dark energy, and in testing general relativity on large scales

    A rock-surface microweathering index from Schmidt hammer R-values and its preliminary application to some common rock types in southern Norway

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    An index of the degree of rock-surface microweathering based on Schmidt hammer R-values is developed for use in the field without laboratory testing. A series of indices - I2 to In, where n is the number of successive blows with the hammer - is first proposed based on the assumption that the R-values derived from successive impacts on the same spot on a weathered rock surface converge on the value characteristic of an unweathered surface of the same lithology. Of these indices, the I5 index, which measures the difference between the mean R-value derived from first and fifth impacts as a proportion of the mean R-value from the fifth impact, is regarded as optimal: use of fewer impacts (e.g. in an I2 index) underestimates the degree of weathering whereas use of more impacts (e.g. in an I10 index) makes little difference and is therefore inefficient and may also induce an artificial weakening of the rock. Field tests of these indices on weathered glacially-scoured bedrock outcrops of nine common metamorphic and igneous rock types from southern Norway show, however, that even after ten impacts, successive R-values fail to approach the values characteristic of unweathered rock surfaces (e.g. bedrock from glacier forelands and road cuttings). An improved *I5 index is therefore preferred, in which the estimated true R-value of an unweathered rock surface is substituted. Weathered rock surfaces exposed to the atmosphere for ~10,000 years in southern Norway exhibit *I5 indices of 36-57%, values that reflect a similarly high degree of weathering irrespective of the rock type

    A second planet transiting LTT 1445A and a determination of the masses of both worlds

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    K.H. acknowledges support from STFC grant ST/R000824/1.LTT 1445 is a hierarchical triple M-dwarf star system located at a distance of 6.86 pc. The primary star LTT 1445A (0.257 M⊙) is known to host the transiting planet LTT 1445Ab with an orbital period of 5.36 days, making it the second-closest known transiting exoplanet system, and the closest one for which the host is an M dwarf. Using Transiting Exoplanet Survey Satellite data, we present the discovery of a second planet in the LTT 1445 system, with an orbital period of 3.12 days. We combine radial-velocity measurements obtained from the five spectrographs, Echelle Spectrograph for Rocky Exoplanets and Stable Spectroscopic Observations, High Accuracy Radial Velocity Planet Searcher, High-Resolution Echelle Spectrometer, MAROON-X, and Planet Finder Spectrograph to establish that the new world also orbits LTT 1445A. We determine the mass and radius of LTT 1445Ab to be 2.87 ± 0.25 M⊕ and 1.304-0.060+0.067 R⊕, consistent with an Earth-like composition. For the newly discovered LTT 1445Ac, we measure a mass of 1.54-0.19+0.20 M⊕ and a minimum radius of 1.15 R⊕, but we cannot determine the radius directly as the signal-to-noise ratio of our light curve permits both grazing and nongrazing configurations. Using MEarth photometry and ground-based spectroscopy, we establish that star C (0.161 M⊙) is likely the source of the 1.4 day rotation period, and star B (0.215 M⊙) has a likely rotation period of 6.7 days. We estimate a probable rotation period of 85 days for LTT 1445A. Thus, this triple M-dwarf system appears to be in a special evolutionary stage where the most massive M dwarf has spun down, the intermediate mass M dwarf is in the process of spinning down, while the least massive stellar component has not yet begun to spin down.Publisher PDFPeer reviewe

    Platelet-Related Variants Identified by Exomechip Meta-analysis in 157,293 Individuals

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    Platelet production, maintenance, and clearance are tightly controlled processes indicative of platelets important roles in hemostasis and thrombosis. Platelets are common targets for primary and secondary prevention of several conditions. They are monitored clinically by complete blood counts, specifically with measurements of platelet count (PLT) and mean platelet volume (MPV). Identifying genetic effects on PLT and MPV can provide mechanistic insights into platelet biology and their role in disease. Therefore, we formed the Blood Cell Consortium (BCX) to perform a large-scale meta-analysis of Exomechip association results for PLT and MPV in 157,293 and 57,617 individuals, respectively. Using the low-frequency/rare coding variant-enriched Exomechip genotyping array, we sought to identify genetic variants associated with PLT and MPV. In addition to confirming 47 known PLT and 20 known MPV associations, we identified 32 PLT and 18 MPV associations not previously observed in the literature across the allele frequency spectrum, including rare large effect (FCER1A), low-frequency (IQGAP2, MAP1A, LY75), and common (ZMIZ2, SMG6, PEAR1, ARFGAP3/PACSIN2) variants. Several variants associated with PLT/MPV (PEAR1, MRVI1, PTGES3) were also associated with platelet reactivity. In concurrent BCX analyses, there was overlap of platelet-associated variants with red (MAP1A, TMPRSS6, ZMIZ2) and white (PEAR1, ZMIZ2, LY75) blood cell traits, suggesting common regulatory pathways with shared genetic architecture among these hematopoietic lineages. Our large-scale Exomechip analyses identified previously undocumented associations with platelet traits and further indicate that several complex quantitative hematological, lipid, and cardiovascular traits share genetic factors

    The ASTUTE Health study protocol: deliberative stakeholder engagements to inform implementation approaches to healthcare disinvestment

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    BACKGROUND Governments and other payers are yet to determine optimal processes by which to review the safety, effectiveness, and cost-effectiveness of technologies and procedures that are in active use within health systems, and rescind funding (partially or fully) from those that display poor profiles against these parameters. To further progress a disinvestment agenda, a model is required to support payers in implementing disinvestment in a transparent manner that may withstand challenge from vested interests and concerned citizens. Combining approaches from health technology assessment and deliberative democratic theory, this project seeks to determine if and how wide stakeholder engagement can contribute to improved decision-making processes, wherein the views of both vested and non-vested stakeholders are seen to contribute to informing policy implementation within a disinvestment context. METHODS/DESIGN Systematic reviews pertaining to illustrative case studies were developed and formed the evidence base for discussion. Review findings were presented at a series of deliberative, evidence-informed stakeholder engagements, including partisan (clinicians and consumers) and non-partisan (representative community members) stakeholders. Participants were actively facilitated towards identifying shared and dissenting perspectives regarding public funding policy for each of the case studies and developing their own funding models in response to the evidence presented. Policy advisors will subsequently be invited to evaluate disinvestment options based on the scientific and colloquial evidence presented to them, and to explore the value of this information to their decision-making processes with reference to disinvestment. DISCUSSION Analysis of the varied outputs of the deliberative engagements will contribute to the methodological development around how to best integrate scientific and colloquial evidence for consideration by policy advisors. It may contribute to the legitimization of broad and transparent stakeholder engagement in this context. It is anticipated that decision making will benefit from the knowledge delivered through informed deliberation with engaged stakeholders, and this will be explored through interviews with key decision makers.Amber M Watt, Janet E Hiller, Annette J Braunack-Mayer, John R Moss, Heather Buchan, Janet Wale, Dagmara E Riitano, Katherine Hodgetts, Jackie M Street and Adam G Elshaug, for the ASTUTE Health study grou

    Federated learning enables big data for rare cancer boundary detection.

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    Although machine learning (ML) has shown promise across disciplines, out-of-sample generalizability is concerning. This is currently addressed by sharing multi-site data, but such centralization is challenging/infeasible to scale due to various limitations. Federated ML (FL) provides an alternative paradigm for accurate and generalizable ML, by only sharing numerical model updates. Here we present the largest FL study to-date, involving data from 71 sites across 6 continents, to generate an automatic tumor boundary detector for the rare disease of glioblastoma, reporting the largest such dataset in the literature (n = 6, 314). We demonstrate a 33% delineation improvement for the surgically targetable tumor, and 23% for the complete tumor extent, over a publicly trained model. We anticipate our study to: 1) enable more healthcare studies informed by large diverse data, ensuring meaningful results for rare diseases and underrepresented populations, 2) facilitate further analyses for glioblastoma by releasing our consensus model, and 3) demonstrate the FL effectiveness at such scale and task-complexity as a paradigm shift for multi-site collaborations, alleviating the need for data-sharing
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