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

A View on the Formation of Saline Waters in the Dry Valleys

The previous report by TORII et al. (Nankyoku Shiryo, 58,116,1977) on the salt balance in the Don Juan basin pointed out the presence of calcium in excess when the total salt deposits in the basin are assumed to have resulted simply from the evaporation of sea water. Concerning the evolutionary processes of saline waters in the Dry Valleys, sources of the salts other than trapped sea water were not necessarily excluded, and sea spray, ion exchange and rock weathering theories have been suggested by many investigators. This paper presents the results obtained by further examination of the processes of saline water formation, on the basis of the analytical results of the DVDP cores from the Wright Valley, the information on the chemical characteristics of the water systems in the Dry Valleys, and a recent reconnaissance in the Labyrinth and the Pearse Valley. It is more likely that the chemical composition of waters in these saline lakes is mainly due to the atmospheric salt rather than the modification of trapped sea salt

Distribution of trace elements around Syowa Station(II) Trace metals distribution in Langhovde

Trace metals (Cu, Fe, Mg, Mn and Zn) concentration distribution in water and sediment were determined by atomic absorption methods with flame and flameless systems using wet dissolution method. The samples were collected from Langhovde, Antarctica. The result showed an approximate log-normal distribution of concentration of metals in sediment of the Yukidori Valley

ショウワキチ シュウヘン ノ ビリョウ ゲンソ ノ ブンプ (II) ラングホブデ チイキ ノ タイセキブツ チュウ ノ ビリョウ キンゾク ブンプ

堆積物と水中に含有される重金属(銅,鉄,マグネシウム,マンガン,亜鉛)濃度を,湿式分解を使用し,フレームおよびフレームレス原子吸光によって測定した.試料はラングホブデ地区より採取した.その結果,特に雪鳥沢の堆積物中の濃度分布は,ほぼ対数正規分布を示した.Trace metals (Cu, Fe, Mg, Mn and Zn) concentration distribution in water and sediment were determined by atomic absorption methods with flame and flameless systems using wet dissolution method. The samples were collected from Langhovde, Antarctica. The result showed an approximate log-normal distribution of concentration of metals in sediment of the Yukidori Valley

V. Chemical Composition of Lake Waters (Report of the Japanese Summer Parties in Dry Valleys, Victoria Land, 1963-1965)

1963年から1965年の間にVictoria LandのDry Valleyにあるいくつかの湖について調査した結果,湖水の化学成分はそれが存在する谷によってそれぞれ特徴があり,化学組成は地域によってかなり異なっていることが判明した.Wright ValleyにあるDon Juan PondおよびLake VandaではCaとClが最も多いが,一つ南隣の谷,Taylor ValleyにあるLake BonneyではMgとCl,次にNaが多く,海に近いLake FryxellではNaとClが最も多く含まれている.その他,さらに南に位置する地域にある湖の多くは淡水湖であった.これらの湖の化学成分を主として報告する

Concentrations of Trace Metals in Tissues of Several Animals around Syowa Station

Concentrations of trace metals in lung, kidney and liver of Weddell seal, Adelie penguin and snow petrel living around the Syowa Station, Antarctica were determined by atomic absorption methods using flame or flameless system. The results of analysis revealed that the concentration levels of copper, iron, zinc, cadmium and lead in the kidneys of Adelie penguin were ranging 6.5～12.4, 188～255, 26～43, <0.005～0.002 and 0.01～0.03μg per gram dry tissue, respectively. Copper and cadmium were found most concentrated in the kidneys of snow petrels among the animals examined. Concentration ratios of pairs of metals in lungs of animals showed wide ranges both among animals and between right and left lungs except in the case of Weddell seal in which the ratios were exceedingly similar in the both lungs, Mg/Fe being about 0.1, Zn/Fe 0.02～0.03, Pb/Cu 0.01～0.02, and Pb/Zn about 0.004

Distribution of Nutrient Matters in Saline Lakes in the Dry Valleys, South Victoria Land, Antarctica

The distribution of nutrient matters in the saline lakes in the Dry Valleys was studied on the spot in the summers 1971-1972 and 1972-1973. The presence of a large amount of nitrogen compounds in the saline lakes was pointed out and their source was discussed together with the distribution pattern of the respective nitrogen compound in the lake water. Most of the nutrient matters were probably supplied by the melt water from the adjacent glaciers and by the decomposed organic matters in the bottom sediments of each lake