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

The Structure and Properties of XZnO-(67-X)SnO-P₂O₅ Glasses: (I) Optical and Thermal Properties, Raman and Infrared Spectroscopies

Glasses with nominal molar compositions xZnO-(67-x)SnO-33P2O5 were prepared and their thermal and optical properties are reported. Density, glass transition temperature, thermal expansion coefficient, viscosity, and refractive index change systematically when ZnO replaces SnO. Raman and infrared spectroscopies provide information about the phosphate anions that constitute the glass network. The compositional trends in glass properties are explained considering the linkages between Sn- and Zn-polyhedra and these different phosphate anions. Property trends fall into three compositional ranges defined by low ZnO concentration (0 ≤ x ≤ 20, region I), intermediate ZnO concentration (20 \u3c x ≤ 40, II), and large ZnO concentrations (40 \u3c x ≤ 50, III)

Corticospinal excitability during motor imagery is diminished by continuous repetition-induced fatigue

Application of continuous repetition of motor imagery can improve the performance of exercise tasks. However, there is a lack of more detailed neurophysiological evidence to support the formulation of clear standards for interventions using motor imagery. Moreover, identification of motor imagery intervention time is necessary because it exhibits possible central fatigue. Therefore, the purpose of this study was to elucidate the development of fatigue during continuous repetition of motor imagery through objective and subjective evaluation. The study involved two experiments. In experiment 1, 14 healthy young volunteers were required to imagine grasping and lifting a 1.5-L plastic bottle using the whole hand. Each participant performed the motor imagery task 100 times under each condition with 48 hours interval between two conditions: 500 mL or 1500 mL of water in the bottle during the demonstration phase. Mental fatigue and a decrease in pinch power appeared under the 1500-mL condition. There were changes in concentration ability or corticospinal excitability, as assessed by motor evoked potentials, between each set with continuous repetition of motor imagery also under the 1500-mL condition. Therefore, in experiment 2, 12 healthy volunteers were required to perform the motor imagery task 200 times under the 1500-mL condition. Both concentration ability and corticospinal excitability decreased. This is the first study to show that continuous repetition of motor imagery can decrease corticospinal excitability in addition to producing mental fatigue. This study was approved by the Institutional Ethics Committee at the Nagasaki University Graduate School of Biomedical and Health Sciences (approval No. 18121302) on January 30, 2019

Noninvasive regional cerebral oxygen saturation for neurological prognostication of patients with out-of-hospital cardiac arrest: a prospective multicenter observational study.

[Aim]To investigate the association between regional brain oxygen saturation (rSO2) at hospital arrival and neurological outcomes at 90 days in patients with out-of-hospital cardiac arrest (OHCA). [Methods]The Japan-Prediction of neurological Outcomes in patients post cardiac arrest (J-POP) registry is a prospective, multicenter, cohort study to test whether rSO2 predicts neurological outcomes after OHCA. We measured rSO2 in OHCA patients immediately after hospital arrival using a near-infrared spectrometer placed on the forehead with non-blinded fashion. The primary endpoint was “neurological outcomes” at 90 days after OHCA. [Results]EMS providers are not permitted to terminate CPR in the field in Japan, and so most patients with OHCA who are treated by EMS personnel are transported to emergency hospitals. Among 1017 OHCA patients, 672 patients including 52 comatose patients with pulses detectable (8%) and 620 cardiac arrest patients (92%) at hospital arrival were enrolled prospectively and consecutively. Twenty-nine patients with good neurological outcome had a significantly higher value of rSO2 at hospital arrival than 643 patients with poor neurological outcome (mean [±SD] 55.6 ± 20.8% vs. 19.7 ± 11.0%, p 42% for predicting good neurological outcome, with sensitivity 0.79 (95% confidence interval [CI], 0.60?0.92), specificity 0.95 (95% CI, 0.93?0.96), positive predictive value, 0.41 (95% CI, 0.28?0.55), negative predictive value, 0.99 (95% CI, 0.98?1.00), and area under the curve 0.90 (95% CI, 0.88?0.92). [ConclusionThe rSO2 at hospital arrival can predict good neurological outcome at 90 days after OHCA