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

Multichannel Feedforward Active Noise Control System with Optimal Reference Microphone SelectorBased on Time Difference of Arrival

In this paper, we propose a multichannel active noise control (ANC) system with an optimal reference microphone selector based on the time difference of arrival (TDOA). A multichannel feedforward ANC system using upstream reference signals can reduce various noises such as broadband noise by arranging reference microphones close to noise sources. However, the noise reduction performance of an ANC system degrades when the noise environment changes, such as the arrival direction. This is because some reference microphones do not satisfy the causality constraint that the unwanted noise propagates to the control point faster than the anti-noise used to cancel the unwanted noise. To solve this problem, we propose a multichannel ANC system with an optimal reference microphone selector. This selector chooses the reference microphones that satisfy the causality constraint based on the TDOA. Some experimental results demonstrate that the proposed system can choose the optimal reference microphones and effectively reduce unwanted acoustic noise

Phenotypic variation for quantitative traits in soybean mutants obtained via ion-beam irradiation

We have previously obtained populations of plants harboring mutants of soybean cultivars. In the present study, we analyzed the stability of altered flowering time and chlorophyll content for four to five generations in the field. Differences in the extent of phenotypic changes were detected between generations; the extent of generational variation also differed between plant lines. These results imply the presence of a genetic mechanism that influences the extent of phenotypic changes, which presumably responds to environmental signals.日本育種学会第134回講演

Y3Fe5O12 film with multi-domain epitaxy on single-crystalline LiNbO3 substrate

Y3Fe5O12 is one of the magnetic insulators that can realize high-speed and low-power-consuming spintronics devices. However, it is hard to prepare a high-quality Y3Fe5O12 film via a conventional sputtering process owing to its low crystalline texture, which leads to a crucial increase in the Gilbert damping constant. Moreover, a single crystalline Gd3Ga5O12 substrate, whose lattice constant is well matched with Y3Fe5O12, is indispensable to improve the crystallinity of the Y3Fe5O12 film. In this article, we demonstrated an epitaxial growth of multiple domains for a 30-nm-thick Y3Fe5O12 film by means of magnetron sputtering on a single crystalline 128° Y–X LiNbO3 substrate , which has been widely utilized in surface acoustic wave devices. From the pole figure of x-ray diffraction, an oblique epitaxial growth of Y3Fe5O12(400) is successfully observed on the 128° Y–X LiNbO3 substrate after a high-temperature post-annealing. The saturation magnetization is equivalent to the value of the epitaxial Y3Fe5O12 film on the Gd3Ga5O12 substrate. The relatively low effective Gilbert damping constant of 0.0039 also supports the high crystalline texture of the Y3Fe5O12 film. The developed growth technique will pave the way for the application of the Y3Fe5O12 film on magneto-acoustic devices

Ion-beam irradiation frequently induces simultaneous alterations of multiple traits in soybean

We have obtained soybean mutants harboring chlorophyll deficiency through mutagenesis using ion-beam irradiation. In the present study, we found that progeny of these soybean mutants had distinct chlorophyll content, flowering time and seed component relative to the wild type. Among these mutant lines, some exhibited coincidentally altered phenotypes in terms of these traits. The generation of a wide spectrum of mutations indicates the plasticity of soybean genome, which is manifested when combined with the highly mutagenic activity of ion-beam irradiation.日本育種学会第132回講演