The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

Measurement of ZZ production in leptonic final states at {\surd}s of 1.96 TeV at CDF

In this paper we present a precise measurement of the total ZZ production cross section in pp collisions at {\surd}s= 1.96 TeV, using data collected with the CDF II detector corresponding to an integrated luminosity of approximately 6 fb-1. The result is obtained by combining separate measurements in the four-charged (lll'l'), and two-charged-lepton and two-neutral-lepton (llvv) decay modes of the Z. The combined measured cross section for pp {\to} ZZ is 1.64^(+0.44)_(-0.38) pb. This is the most precise measurement of the ZZ production cross section in 1.96 TeV pp collisions to date.Comment: submitted to Phys. Rev. Let

Coefficients of Resistance to Cold-Air-Drainage Winds of a Grass-Covered Slope

The cold-air-drainage (CAD) wind is one of the most familiar local winds in Japan. It is driven by the surplus of density, or the deficit of potential temperature produced by radiative cooling in the surface air layer on a slope, and is resisted by the ground surface and the surrounding atmosphere. The coefficients of resistance of the ground surface and the surrounding atmosphere change with the CAD wind speed. The observations made on a grass-covered slope of Mt. Kuju showed that the resistance exerted by the surrounding atmosphere was much larger than that by the ground surface, and the sum of two coefficients of resistance decreased by one order of magnitude when the CAD wind speed exceeded some critical value

Estimating Evaporation in Winter at a Field Irrigated Late in Autumn in Inner Mongolia, China

Shortage of water resources has been serious in the Yellow River basin. Therefore, it is expected to reduce the amount of irrigation water without reducing crop production. In the upper reaches, a large amount of water is irrigated late in autumn so that part of the irrigation water remain in a soil profile until next spring and is used for crop germination and development. We evaluated the overwinter water loss due to evaporation at a field irrigated late in autumn, which is a decisive factor for increasing irrigation efficiency. The aerodynamic method, with a dimensionless stability function deduced by Webb (1970), was used to measure the evaporation from a frozen soil surface. Daily evaporation was estimated to range from 0.09 mm to 0.92 mm, which summed up to about 60 mm for the period when the surface soil layer 10cm thick was frozen (23 November 2004-23 March 2005), which corresponds to about 25% of the amount of irrigation water (Kaneko et al., 2006)

Characteristics Related to the Groundwater Around a Saline Plot in Irrigated Areas

土壌の塩類化と地下水の関係を明らかにするために,黄河流域の非塩類化圃場と隣接する塩類化プロットにおいて,表層土の土性と土壌溶液や地下水の水質を調査するとともに,揚水試験を実施して帯水層の水理学的特性値を求めた塩類化プロットでは,非塩類化圃場と比較して,細粒土の割合が多く,Na^+やSO_4^<2->の含有量も多かった.これらはともに,土壌の透水性不良をもたらす要因となる.また,揚水試験の結果より,塩類化プロットでは透水量係数や貯留係数も相対的に小さいものと推定された.これらは間隙が小さく均一で,毛管上昇によって地下水から塩分は供給されやすいが,降雨や灌漑水によるリーチングは起こりにくいことを示唆する.In order to elucidate the relationship between soil salinization and groundwater, soil texture, soil solution and groundwater were examined in a non-saline field and a saline plot next to it in the Yellow River basin. Hydraulic constants of the aquifer also were determined by the pumping-out test. Contents of silt and clay in the surface soil, and contents of Na^+ and SO_4^<2-> in the soil solution were larger in the saline plot than in the non-saline field. These characteristics tend to cause poor drainage. Furthermore, it was supposed by the pumping-out test that both transmissibility coefficient and storage coefficient were small in the saline plot, as compared to the non-saline field. This means that soil pores in the saline plot are smaller and more uniform than those in the non-saline field, and is good for transporting salts upward from the water table by capillary action, but not good for leaching out salts from the soil profile