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

Photo-acoustic sub-micrometer modifications of glass by pair of femtosecond laser pulses

We present time-resolved studies of glass densification created by an acoustic phenomenon: collision of the transverse and longitudinal sound waves inside glass. Localization of the permanent denisfied region has a lateral cross section similar to 0.4 mu m and is approximately half of the wavelength of femtosecond laser pulses which were used to generate breakdown and launched shock waves inside glass. Controlled time delay between two closely spaced irradiation spots reveals dynamics and relaxation (electronic, thermal, stress) of glass after excitation. The observed phenomenon is important for femtosecond direct laser writing and recording of waveguide couplers using multiple beams

Time-resolved axial-view of the dielectric breakdown under tight focusing in glass

We present time-resolved studies of the dielectric breakdown using tightly focused femtosecond (fs) laser pulses in glass. Axial evolution of the breakdown and material modifications have been retrieved over the time span from 0 to 1 ns with a 50 fs resolution and ∼ 1 μm spatial resolution using interferometric pump-probe technique. It is shown that even at pulse power slightly above critical Pcr ≃ 1 MW/pulse, the filamentation was limited at tight focusing and the central focal region with resolidified glass was localised axially within ∼ 10 μm; it can be used for the waveguide recording. Mechanisms of light-matter interaction at tight focusing and application potential are discussed. The electron-ion scattering time, τe–i ≃ 1.1 fs, for the glass at electron concentration ne ≃ (4–5)×1020 cm−3 was determined within Drude approximation

Frictional Characteristics of a Small Aerostatic Linear Bearing

Frictional characteristics of a small aerostatic linear bearing are accurately evaluated by means of a method, in which the force acting on the moving part of the bearing is measured as the inertial force. An optical interferometer is newly developed to measure the Doppler shift frequency of the laser light reflected on the small moving part. From the measured time-varying Doppler shift frequency, the velocity, the position, the acceleration and the inertial force of the moving part are numerically calculated. It is confirmed that the dynamic frictional force acting inside the bearing is almost proportional to the velocity of the moving part and is similar to the theoretical value calculated under the assumption that the flow inside the bearing is the Couette flow

A Method for Evaluating the Electro-Mechanical Characteristics of Piezoelectric Actuators during Motion

The electro-mechanical characteristics of piezoelectric actuators which have being driven are evaluated in this paper. The force generated by actuators is measured as an inertial force of a corner cub prism which is attached to the actuators. The Doppler frequency shift of a laser beam, due to the motion of actuator, is accurately measured by a heterodyne interferometer. Subsequently, the mechanical quantities, such as velocity, acceleration, force, power and displacement, are calculated from the Doppler frequency shift. With the measurement results of current and voltage of the actuator, the relationships between electrical and mechanical characteristics are evaluated

Abuse Prevention of Street Camera Network by Browsing-History Disclosure

A street camera network, in which many street cameras are installed at a high density, similar to street lights throughout a nation, will have a stronger positive effect in suspect tracking and crime deterrence in the near future. On the other hand, it will also have a stronger negative effect related to the violation of privacy of ordinary citizens. In order to make such a stronger surveillance camera system, which forcibly captures the images of passersby for the public interest, be accepted as an essential social infrastructure by a society, it is necessary for this camera system to make ordinary citizens be convinced that it is used only for the public interest. To realize this, a new concept, in which the abuse of a street camera network is deterred by browsing-history disclosure, is proposed