The stress-sensing domain of activated IRE1α forms helical filaments in narrow ER membrane tubes

The signaling network of the unfolded protein response (UPR) adjusts the protein folding capacity of the endoplasmic reticulum (ER) according to need. The most conserved UPR sensor, IRE1α, spans the ER membrane and activates through oligomerization. IRE1α oligomers accumulate in dynamic foci. We determined the in-situ structure of IRE1α foci by cryogenic correlated light and electron microscopy (cryo-CLEM), combined with electron cryo-tomography (cryo-ET) and complementary immuno-electron microscopy. IRE1α oligomers localize to a network of narrow anastomosing ER tubes (diameter ~28 nm) with complex branching. The lumen of the tubes contains protein filaments, likely composed of linear arrays of IRE1α lumenal domain dimers, arranged in two intertwined, left-handed helices. Our findings define a previously unrecognized ER subdomain and suggest positive feedback in IRE1 signaling

Coordinated ground-based validation of ENVISAT atmospheric chemistry with NDSC network data : Commissioning phase report

International audienceIn the framework of the coordinated project called CINAMON, a list of ground-based stations associated with the Network for the Detection of Stratospheric Change (NDSC) contribute to the quasi-global validation of ENVISAT atmospheric chemistry data. This paper reports on such activities performed during the Commissioning Phase (CP) of the satellite. After a description of the correlative database generated during this period, preliminary ground-based studies relying on this database give a first picture of the quality of SCIAMACHY ozone and nitrogen dioxide columns, and GOMOS and MIPAS ozone profiles. Illustration of the global mapping of MIPAS ozone profile data is also presented. The paper concludes with perspectives for the Main Validation Phase of ENVISAT

Coordinated ground-based validation of ENVISAT atmospheric chemistry with NDSC network data : Commissioning phase report

International audienceIn the framework of the coordinated project called CINAMON, a list of ground-based stations associated with the Network for the Detection of Stratospheric Change (NDSC) contribute to the quasi-global validation of ENVISAT atmospheric chemistry data. This paper reports on such activities performed during the Commissioning Phase (CP) of the satellite. After a description of the correlative database generated during this period, preliminary ground-based studies relying on this database give a first picture of the quality of SCIAMACHY ozone and nitrogen dioxide columns, and GOMOS and MIPAS ozone profiles. Illustration of the global mapping of MIPAS ozone profile data is also presented. The paper concludes with perspectives for the Main Validation Phase of ENVISAT

Mapping the human genetic architecture of COVID-19

The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-191,2, host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases3–7. They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease