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

Background: We 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 ~ 80% of cases. Methods: We 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. Results: No 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 = 1.1 × 10−4) 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 = 2.1 × 10−4). 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 = 3.4 × 10−3), 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 = 7.7 × 10−8). 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 = 1.68 × 10−5). Conclusions: Rare 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

Structure and texture of organic matter in CV and CO carbonaceous chondrites. Relationship to metamorphic process

Abstract 5199International audienc

Structure and texture of organic matter in CV and CO carbonaceous chondrites. Relationship to metamorphic process

Abstract 5199International audienc

Metamorphic Control of Noble Gas Abundances in Pristine Chondrites

International audienceThe structure and texture of IOM was studied by HRTEM in Kaba, Leoville, Mokoia, Allende,Tieschitz. We revisit the question of the metamorphic control of the Q (P1), P3 and P6 components, the carrier of the Q phase

Carbon Thermometry Applied To Chondrites and Terrestrial Rocks: Effect of Organic Precursor

International audienceWe evidence that carbon thermometers are precursor dependent and need internal calibration. We also report the first 244 nm excitation Raman measurements on kerogens

Maturation grade of coals as revealed by Raman spectroscopy: Progress and problems

International audienceThe present study questions the sensitivity and the accuracy of Raman spectroscopy as a tool for determining the maturity of natural organic matter (NOM). It focuses on the definition of optimized experimental parameters in order to maximize the quality of the Raman signal and control the accuracy and reproducibility of measurements. A series of 11 coals has been investigated, sampling a wide maturity range (2–7% vitrinite reflectance VR). The role of experimental parameters is first investigated. An excitation wavelength of 514.5 nm gives better results than 457.9 and 632.8 nm, minimizing the fluorescence background observed in the spectra of low-rank coals. Both Raman and fluorescence spectra were investigated with time-resolved experiments in air and argon. These data show that fluorescence and Raman spectra are sensitive to acquisition time and laser power parameters, and reveal a physicochemical instability of the samples under laser irradiation, mostly due to photo-oxidation processes. These data clearly show that the experiments, especially in air, should be performed with strictly constant acquisition parameters. In addition, the results of a whole series of coal measurements performed in air under constant experimental conditions show that Raman spectroscopy is definitely sensitive to the maturity of coal samples with VR > not, vert, similar1%. The most sensitive spectral maturity tracers are the width of the D-band (FWHM-D), the ratio of the peak intensities of the D- and G-bands (ID/IG), the normalized ratio of the band integrated intensities AD/[AD + AG] for the maturity range VR = 3–7% and the width of the G-band (FWHM-G) for VR = 1–5%. However, the accuracy and reproducibility are definitely weaker in such measurements compared to the standard VR. Future work must solve the problem of sample stability under laser irradiation, and greatly increase the number of samples to improve the statistical significance of the results

High velocity frictional properties of clay-bearing fault gouges : experiments and modelling

see Abstract volumeIstituto Nazionale di Geofisica e Vulcanologia, Italy (INGV) Centre National de la Recherche Scientifique (CNRS) ExxonMobil Upstream Research CompanyUnpublishedErice, Italyope

High velocity frictional properties of clay-bearing fault gouges : experiments and modelling

see Abstract volum

The High Resolution Transmission Electron Microscopy: A Powerful Tool for Studying the Organization of Terrestrial and Extra-Terrestrial Carbons

International audienceHigh Resolution Transmission Electron Microscopy (HRTEM) makes possible the imaging of the profile of the polyaromatic layers, allowing a knowledge of carbons, such as disordered natural carbons from meteorites and from Precambrian metasediment