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 New Spectrophotometer System for Measuring Hemispherical Reflectance and Normal Emittance of Real Surfaces Simultaneously

A new spectrophotometer system is developed for the study of thermal radiation characteristics of real surfaces in thermal engineering environments. The system measures spectra of normal incidence hemispherical reflectance RNH and normal emittance EN in the near-ultraviolet through infrared region of wavelength of 0.30 μm to 11 μm simultaneously and repeatedly with a cycle time of 4 s. The system enables evaluation of the normal incidence absorptance AN in this wide spectral region. Transitions of spectra of specular-finished and rough-finished nickel surfaces in a high-temperature air-oxidation process are measured to demonstrate the performance of the system. Clear interference behaviors are found even in the spectra of hemispherical reflectance RNH and emittance EN of a rough-finished surface

New Spectrophotometer System for Measuring Thermal Radiation Characteristics of Real Surfaces of Thermal Engineering Entirely

In this work we develop a new spectrophotometer system for measuring thermal radiation characteristics of real surfaces of thermal engineering. This system measures transition of spectra of normal incidence hemispherical reflectance RNH, normal incidence specular reflectance RNN, normal incidence diffuse reflectance RND, normal incidence absorptance AN and normal emittance εN of real surfaces in a near-ultraviolet through infrared region of wavelength 0.30∼11 µm simultaneously and repeatedly with a cycle time of 6 s. The system is applied to measure the spectrum transition of the reflectances, absorptance and emittance of a nickel surface which is prepared as a clean optically smooth surface and is oxidized in high-temperature air to be changed to an oxidized rough real surface. Microscopic mechanisms of the spectrum transition are discussed, to illustrate the performance of the developed spectrophotometer system for thermal engineering applications

Interference of spherical wave of thermal radiation emitted by a film system

This paper deals with the interference of spherical waves of thermal radiation emitted by a surface film system which consists of a metal substrate and a semi-transparent film. A spectroscopic experiment is made to reconfirm the clear interference in emission spectra of the film system. We present a theoretical model in which an electromagnetic theory for a spherical wave is combined with Planck’s theory of thermal radiation. The mechanism of interference of spherical waves is discussed, and it is suggested that thermal radiation waves emitted by a number of dipoles of the metal might be coherent among each other