7 research outputs found

    Peuplement de poissons de la Loire entre Grangent et Villerest

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    SIGLEAvailable from INIST (FR), Document Supply Service, under shelf-number : GR 1765 / INIST-CNRS - Institut de l'Information Scientifique et TechniqueFRFranc

    Modeling Radiation Chemistry and Biology in the Geant4 Toolkit

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    Simulation of biological effects of ionizing radiation at the DNA scale requires not only the modeling of direct damages induced on DNA by the incident radiation and by secondary particles but also the modeling of indirect effects of radiolytic products resulting from water radiolysis. They can provoke single and double strand breaks by reacting with DNA. The Geant4 Monte Carlo toolkit is currently being extended for the simulation of biological damages of ionizing radiation at the DNA scale in the framework of the "Geant4-DNA" project. Physics models for the modeling of direct effects are already available in Geant4. In the present paper, an approach for the modeling of radiation chemistry in pure liquid water within Geant4 is presented. In particular, this modeling includes Brownian motion and chemical reactions between molecules following water radiolysis. First results on time-dependent radiochemical yields1 from 1 picosecond up to 1 microsecond after irradiation are compared to published data and discussed

    Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

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    BackgroundWe previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15-20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in similar to 80% of cases.MethodsWe report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded.ResultsNo gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5-528.7, P=1.1x10(-4)) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR=3.70[95%CI 1.3-8.2], P=2.1x10(-4)). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR=19.65[95%CI 2.1-2635.4], P=3.4x10(-3)), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR=4.40[9%CI 2.3-8.4], P=7.7x10(-8)). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD]=43.3 [20.3] years) than the other patients (56.0 [17.3] years; P=1.68x10(-5)).ConclusionsRare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old

    Correction: Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

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