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

Universal holonomic quantum gates over geometric spin qubits with polarised microwaves

Holonomic quantum gates represent a promising route to noise-tolerant quantum operations. Here, the authors use polarised microwaves to implement nonadiabatic holonomic quantum gates at room temperature and zero magnetic field on NV centers, both on single-qubit and between electron and nuclear spins

高Crフェライト系耐熱鋼溶接継手における高温変形中の組織変化

修士（工学

Fuel Regression Characteristics of Axial-Injection End-Burning Hybrid Rocket Using Nitrous Oxide

This is an investigation of fuel regression characteristics in an axial-injection end-burning hybrid rocket using nitrous oxide. Experiments were conducted using 38 mm cylindrical fuel grains with an array of 0.8 mm ports made from curable resin. Previous studies of end-burning hybrid rockets used gaseous oxygen as oxidizer. Nitrous oxide may be more suitable than gaseous oxygen for use in space-based missions because of the weight savings associated with the oxidizer storage vessels, supply system, and motor mass. In this study, two types of nozzle closures were employed to increase the initial chamber pressure and promote the formation of stabilized combustion in multiport fuels. The results of 12 firing tests showed that the regression rates when using nitrous oxide as the oxidizer were as high as that from previous research (0.61–4.5 mm/s at 0.25–0.75 MPa) using gaseous oxygen as the oxidizer. These high regression rates were nearly five times higher than that of experiments using single-port fuels. It is clear from a visualization experiment that fuel flakes break off and travel downstream in solid form during firing, which could cause the fuel regression rate of multiport fuels to be higher than that of single-port fuels

The accuracy of reconstruction techniques for determining hybrid rocket fuel regression rate

This study is an investigation of the accuracy of reconstruction techniques for determining instantaneous fuel regression rate. Results of reconstruction techniques are compared with results obtained through the measurement of the pressure drop across the fuel in an Axial-Injection End-Burning hybrid rocket (EBHR). The results of numerous firing tests show that this method allows for the evaluation of the accuracy of the instantaneous fuel regression rates obtained by reconstruction techniques. The error bias of O/F values calculated by the reconstruction techniques were around ±10%, and were mainly caused by uncertainties in the measured values of oxidizer mass flowrate and the definition of firing duration. The instantaneous length of an EBHR-type fuel can be calculated from the measurement of the pressure drop across the fuel. However, the calculated fuel length history obtained by the pressure drop in a port does not coincide with that obtained by the reconstruction technique because of an underestimation in pressure drop

Monocaprin Enhances Bioavailability of Fucoxanthin in Diabetic/Obese KK-A(y) Mice

Fucoxanthin is a marine carotenoid found in brown seaweeds and several microalgae. It has been reported that fucoxanthin has health benefits such as anti-obesity and anti-diabetic effects. To facilitate fucoxanthin applications in the food industry, it is important to improve its low bioavailability. We attempted the combined feeding of fucoxanthin-containing seaweed oil (SO) and monocaprin in a powder diet and analyzed the fucoxanthin metabolite contents in the liver, small intestine and serum of diabetic/obese KK-A(y) mice. After 4 weeks of feeding with the experimental diets, the serum fucoxanthinol concentrations of the mice fed 0.2% SO and 0.5% monocaprin were higher than those of the 0.2% SO-fed mice. Furthermore, fucoxanthinol accumulation in the liver and small intestine tended to increase in a combination diet of 0.2% SO and 0.125-0.5% monocaprin compared with a diet of 0.2% SO alone, although amarouciaxanthin A accumulation was not different among the 0.2% SO-fed groups. These results suggest that a combination of monocaprin with fucoxanthin-containing SO is an effective treatment for improving the bioavailability of fucoxanthin