モト サイバンカン ノ ホウカ ダイガクイン キョウジュ ノ ザダンカイ ホウカ ダイガクイン ニ キンムシテ ホウカ ダイガクイン ノ ゲンジョウ ト カダイ

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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

SWRO-PRO System in “Mega-ton Water System” for Energy Reduction and Low Environmental Impact

Reverse osmosis (RO) membranes have been widely applied in seawater desalination (SWRO) and wastewater reclamation as the main desalination technology since 2000. SWRO plants face challenges to reduce energy consumption and brine disposal to lessen marine pollution. To tackle these challenges, a SWRO-PRO (Pressure Retarded Osmosis) System was proposed in the “Mega-ton Water System” project under the Japanese national project of the “Funding Program for World-Leading Innovative R&D on Science and Technology” (FIRST Program). To reduce the energy consumption of the main SWRO plant, an innovative low-pressure SWRO membrane and a next generation energy recovery device (ERD) were developed by the “Mega-ton Water System” project. In addition to this research and development, a new membrane process has been proposed and confirmed as a low-pressure multi-stage SWRO (LMS). A brine conversion two-stage SWRO system was invented 20 years ago, and has been in operation for over 15 years. Application of the SWRO membrane process to actual commercial plants was an important research theme. The low-pressure multi-stage SWRO System (LMS) was an innovative method of introducing a low-pressure membrane and the membrane element in the pressure vessel was designed to avoid heavy fouling of lead elements. As a result of these developments at mega-ton scale SWRO plants, a 20% energy reduction was possible in the SWRO system of the “Mega-ton Water System”. In the development of the PRO process, a PRO hollow fiber membrane module with a maximum 13.3 w/m2 of membrane power density using a 10-inch module was established at a prototype PRO plant. Thus, a 30% energy reduction was possible using the SWRO-PRO System in the “Mega-ton Water System” at mega-ton scale SWRO plants. The brine disposal problem was also solved by this system

A Reliable Seawater Desalination System Based on Membrane Technology and Biotechnology Considering Reduction of the Environmental Impact

The application of seawater desalination technology using a reverse osmosis (RO) membrane has been expanding because it requires less energy compared with other distillation methods. Even in Middle Eastern countries where energy costs are lower such as Saudi Arabia, UAE, Qatar, and Kuwait, almost all desalination plants where only water production is required have adopted the RO method. However, large plants in excess of half mega-ton size are required, and Seawater Reverse Osmosis (SWRO) operation lacks reliability due to heavy biofouling and large amounts of briny discharge contaminated with chemicals. For reliable desalination systems with lower environmental impact, membrane-processing technology, including biotechnology (such as marine bacteria), has been examined as national research in Japan in the “Mega-ton Water System„ project. We examined the influence of chlorination on marine bacteria using the fluorescence microscopic observation method and found that the effect of chlorination is limited. Chlorination sterilization triggers biofouling and sodium bisulfate (SBS) addition as a de-chlorinating agent also triggers biofouling, so a process with no chlorine or SBS addition would reduce biofouling. As polyamide SWRO membranes have low chlorine resistivity, such a process would enable longer membrane life in real plants. We used a biofouling monitoring technology, the Membrane Biofilm Formation Rate (mBFR), to design a process that involves no chlorine or SBS addition and verified it in the Arabian Gulf Sea, of Saudi Arabia, which is one of the most difficult and challenging seawaters in which to control biofouling. Furthermore, by minimizing the addition of a sterilizer, the desalination system became more environmentally friendly