The side chains of Pro474 and interacting amino acids are shown as connected spheres. b, Three cartoon views of an AlphaFold model of putative solute carrier family 22 member 31 (SLC22A31 UniProtKB: A6NKX4). The colour shows linkage disequilibrium (LD) with the missense variant rs117169628. ![]() We identify potentially druggable targets in multiple systems, including inflammatory signalling (JAK1), monocyte-macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).Ī, Effect-size plot for the effect of multiple variants on SLC22A31 expression (eQTLgen, x axis) against increasing susceptibility to critical COVID-19 ( β xy = 0.11 P xy = 1.3 × 10 −9). To investigate the therapeutic implications of these findings, we infer the structural consequences of protein-coding variants, and combine our GWAS results with gene expression data using a monocyte transcriptome-wide association study (TWAS) model, as well as gene and protein expression using Mendelian randomization. We find 49 genome-wide significant associations, of which 16 have not been reported previously. To put these results in the context of existing work, we conduct a meta-analysis of the new GenOMICC genome-wide association study (GWAS) results with previously published data. Here we analyse 24,202 cases of COVID-19 with critical illness comprising a combination of microarray genotype and whole-genome sequencing data from cases of critical illness in the international GenOMICC (11,440 cases) study, combined with other studies recruiting hospitalized patients with a strong focus on severe and critical disease: ISARIC4C (676 cases) and the SCOURGE consortium (5,934 cases). ![]() ![]() Despite the advanced stage of illness at presentation, we have shown that host genetics in patients who are critically ill with COVID-19 can identify immunomodulatory therapies with strong beneficial effects in this group 3. GenOMICC Investigators SCOURGE Consortium ISARICC Investigators 23andMe COVID-19 Team Jian YangĬritical illness in COVID-19 is an extreme and clinically homogeneous disease phenotype that we have previously shown 1 to be highly efficient for discovery of genetic associations 2. The main things you'll want in your zen den are a comfy blanket, a soft pillow, calming wallpaper or prints, a small table or two, and of course, some calming refreshments. Ayres says that any kind of electronics overstimulate us, which is the exact opposite goal of having a zen den. The one thing your zen den definitely shouldn't include is any form of technology-not even calming sound machines. “And those five things should have a variety of textures-things that will stimulate your senses and force you to be present.” “Do your best to pick no more than five things for your calm space,” she advised. Lucie Ayres, a Los Angeles-based interior designer, spoke to the Los Angeles Times back in 2017 about how to create your very own personalized zen den. Your zen den is personal to you-and you only. And you don't need to go all out building yourself a backyard guest house for you to meditate in they can be as simple as a small space in the corner of your bedroom. "Zen Dens are used as a meditation room or a space to practice yoga and-in an open floor plan-a nearby place to “get away” from too much activity."īasically, zen dens are a dedicated space in your home used to unplug, sit back, and relax. ![]() Zen Dens are "a designated area in a home devoted to expanding one’s self-awareness to experience maximum relaxation," according to the Plan Collection. One of the upcoming trends includes none other than a very health and wellness focused new version of the popular she shed-the zen den. The Plan Collection, a website providing homeowners and builders over 20,000 house plans, has gathered their top predictions for 2020 home design concepts-and they didn't disappoint. Taking care of yourself is all the rage (and super important) and your home-or at least, some spaces in your home-should also reflect that. There's no guessing what the next year's wave of design trends will consist of- DIY backyard guest houses? All-black kitchens? Backyard pools that rival waterparks? Whatever they may be, you can bet that health and wellness will be at the very forefront of the motive behind popular designs.
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