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

An Investigation on the Effective Use of Fly Ash ―Fine Grinding of Limestone with Fly Ash as a Grinding Aid―

In this study, the role of fly ash as a grinding aid to facilitate fine grinding of limestone for improved flowability was examined by carrying out batch grinding test for varying feed amount and grinding time, while maintaining the limestone to fly ash ratio at 5 :1. As a result, it was found that fly ash was an effective grinding aid for the fine grinding of limestone, and the optimum feed amount of limestone and fly ash to the grinding mill increased with increase of grinding time

A Fundamental Study of Dry and Wet Grinding from the Viewpoint of Bending Tests by Drop Weight Method

The preparation of fine powders by grinding may be accomplished by either a wet or a dry process and the differences between these have been discussed. The difference of breaking strength in different atmospheres affects the grindabilities. In this study, bending tests were carried out using a drop weight method on glass material in order to investigate the quantitative effect of water atmosphere on strength. The influence of the crack length of the glass surface on the difference of fracture probability in water and in air was also studied. As a result, it was found that the fracture probability in water was larger than that in air when the input energy in specimen was constant. Then, the difference of the fracture energy in water and in air increased with decreasing the crack length

Mechanical Properties of Brittle Materials and Their Single Fracture under Dynamic Loading

The meaning of study on single particle crushing is recognized at which it is regarded the accumulation of single particle crushing as the comminution performed in practical operations stochastic phenomena. Especially, experimental data concerning the mechanical properties of brittle solids measured under dynamic loading are so far very few. Further, the experimental data concerning compressive strength, sphere compressive strength, fracture energy, new surface produced and fracture surface energy in single particle crushing under dynamic loading are next to nothing. From these situation in this field, thus experimental results arranged in order are reported in this paper. Besides, the parameters on single particle crushing are considered to be necessary to clarify on the following themes in the future. These are the effect of environmental conditions on single particle crushing, the conversion of fracture energy in single particle crushing and the correlation between ordinary grinding and single particle crushing. In this study, the entire experimental data were obtained under the loading state by keeping the mechanical force balance between internal force and external corresponding to the specimen and loading machine. When the experiment is carried out under impact loading with a shock, a little different data are expected to be obtained. With respect to this issue, as it is in the midst of the investigation, the results will be presented in the near future. The new surface produced of fractured product having a wide range of size distribution was estimated by assuming the shape factor is to be 6.0 in this paper. These experimental values do not give the real new surface produced in its strict meaning. Therefore, the measurement of surface area of irregular particles having a wide range of size distribution is also necessary to be investigated in the future

男性のロボット支援回腸導管造設術において患者側外科医は重要な役割を果たす

The influence of the console surgeon on the feasibility and outcome of various robot-assisted surgeries has been evaluated. These variables may be partially affected by the skills of the patient-side surgeon (PSS), but this has not been evaluated using objective data. This study aimed to describe the surgical techniques of the PSS in robot-assisted radical cystectomy (RARC) and intracorporeal ileal conduit (ICIC) urinary diversion and objectively examine the changes in surgical outcomes with increasing PSS experience. During a 3-year period, 28 men underwent RARC and ICIC urinary diversion. Clinical characteristics and surgical outcomes were compared between patients who underwent surgery early (first half group) or late in the study period (second half group). The pre-docking incision enabled easy specimen removal. The glove port technique widened the working space of the PSS. The stay suture allowed the PSS to control the distal portion of the conduit, facilitating the passage of the ureteral stents. During stoma creation, pneumoperitoneum pressure was lost by opening the abdominal cavity. To overcome this problem, the robotic arm was used to lift the abdominal wall to maintain the surgical field and facilitate the PSS procedure. Compared with the first half group, the second half group had significantly shorter times for urinary diversion (202 min vs 148 min, p < 0.001), ileal isolation and anastomosis (73 min vs 45 min, p < 0.001), and stenting (23.0 min vs 6.5 min, p < 0.001). As the experience of the PSS increased, the time of the PSS procedures decreased