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

Electromyographic analysis of the cervical flexion during different body positions

Author: Hirofumi Sageshima Title: Electromyographic analysis of the cervical flexion during different body positions Aim and Purpose: The aim of this study is to find out the muscle activity and the muscle coordination during cervical flexion in 3 different positions - standing, sitting and supine - with electromyographic analysis in young healthy adults. Methods: This study compared superficial cervical flexor muscles activity during conventional cervical flexion to 20 volunteered healthy subjects with surface electromyography (EMG). The activity of 5 paired muscles - sternocleidomastoid, scalenus, suprahyoid, infrahyoid and superior part of trapezius - were measured when they performed 15-time cyclic cervical flexion-extension from neutral to maximum cervical flexion on 3 different positions - sitting, standing and supine - in random order. Results: Significantly higher EMG amplitude was detected from all measured muscles on supine position than sitting and standing (p < 0.05). It was also confirmed that muscle activation pattern was different according to positions; its amplitude on supine reach the peak in the earlier phase of movement, while it was delayed on 2 other positions (p < 0.05). In terms of onset, all cervical flexors activated together in the very beginning. However, on sitting and..

Eletromyografická analyza cervikální flexe v závislosti na pozicích těla

Autor: Hirofumi Sageshima Titul: Elektromyografická analýza cervikální flexe v různých polohách těla Cíl a účel: Cílem této studie je zjistit svalovou aktivitu a koordinaci svalů během cervikální flexe ve 3 různých polohách - ve stoje, v sedě a vleže - s elektromyografickou analýzou u mladých zdravých dospělých. Metody: Tato studie porovnávala aktivitu povrchových flexorů krčního svalstva během konvenční krční flexe u 20 zdravých dobrovolníků s povrchovou elektromyografií (EMG). Aktivita 5 párových svalů - m. sternocleidomastoideus, mm.scaleni, m. suprahyoideus, m. infrahyoideus a proximální částí m.trapezius - byla změřena, během 15 cyklů cervikální flexi-extenzi z neutrálního na maximální cervikální flexi na 3 různých pozicích - ve stoje, v sedě a v leže - v náhodném pořadí. Výsledek: Signifikantně vyšší amplituda EMG byla detekována u všech měřených svalů v poloze vleže než v sedu a ve stoje (p <0.05). Bylo také potvrzeno, že vzor aktivace svalů se lišil podle polohy; jeho amplituda vleže dosahuje vrcholu v dřívější fázi pohybu, zatímco byla zpožděna na 2 dalších pozicích (p <0.05). Pokud jde o začátek, všechny krční flexory se aktivovaly společně hned na začátku. Avšak při sezení a stání měl suprahyoidní sval dříve začátek než mm.scaleni, zatímco neexistovaly žádné statistické rozdíly mezi...Author: Hirofumi Sageshima Title: Electromyographic analysis of the cervical flexion during different body positions Aim and Purpose: The aim of this study is to find out the muscle activity and the muscle coordination during cervical flexion in 3 different positions - standing, sitting and supine - with electromyographic analysis in young healthy adults. Methods: This study compared superficial cervical flexor muscles activity during conventional cervical flexion to 20 volunteered healthy subjects with surface electromyography (EMG). The activity of 5 paired muscles - sternocleidomastoid, scalenus, suprahyoid, infrahyoid and superior part of trapezius - were measured when they performed 15-time cyclic cervical flexion-extension from neutral to maximum cervical flexion on 3 different positions - sitting, standing and supine - in random order. Results: Significantly higher EMG amplitude was detected from all measured muscles on supine position than sitting and standing (p < 0.05). It was also confirmed that muscle activation pattern was different according to positions; its amplitude on supine reach the peak in the earlier phase of movement, while it was delayed on 2 other positions (p < 0.05). In terms of onset, all cervical flexors activated together in the very beginning. However, on sitting and...FyzioterapieFaculty of Physical Education and SportFakulta tělesné výchovy a sport

Onset Timing of Hyoid Muscles Activation during Cervical Flexion Is Position-Dependent: An EMG Study

Due to the high prevalence of neck pain, considerable attention is paid to the function of cervical flexor muscles. Although the deep and superficial cervical flexor muscles have been evaluated, the impact of hyoid muscles on cervical flexion is still not well known. We, therefore, aimed to investigate the activation of hyoid muscles during physiological cervical flexion, and to determine the impact of different starting positions on cervical flexion muscle activation. The activities of bilateral sternocleidomastoid, scalene, suprahyoid, and infrahyoid muscles were evaluated by surface electromyography (EMG) in twenty young healthy volunteers. They performed a repetitive cervical flexion-extension movement, from neutral position of the head to the maximum flexion with the same speed set at eight seconds in a cycle, in three various positions (sitting, standing, and supine). In sitting and standing positions, the group of suprahyoid muscles was activated in advance of other cervical flexor muscles despite only significant differences were found in scalene muscles, and the activation of the group of infrahyoid muscles was time-synchronous with sternocleidomastoid muscles. On the other hand, in supine position, the activation of all measured cervical flexor muscles was significantly earlier and longer than in the other two positions. This study confirmed the empirical suggestion that hyoid muscles contributed to cervical flexion, and it confirmed that muscle activation was position dependent, even if the given movement is nearly identical