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

Guidelines for obstetrical practice in Japan : Japan Society of Obstetrics and Gynecology (JSOG) and Japan Association of Obstetricians and Gynecologists (JAOG) 2011 edition

Clinical guidelines for obstetrical practice were first published by the Japan Society of Obstetrics and Gynecology (JSOG) and the Japan Association of Obstetricians and Gynecologists (JAOG) in 2008, and a revised version was published in 2011. The aims of this publication include the determination of current standard care practices for pregnant women in Japan, the widespread use of standard care practices, the enhancement of safety in obstetrical practice, the reduction in burdens associated with medico-legal and medico-economical problems, and a better understanding between pregnant women and maternity-service providers. These guidelines include a total of 87 Clinical Questions followed by several Answers (CQ&A), a Discussion, a List of References, and some Tables and Figures covering common problems and questions encountered in obstetrical practice. Each answer with a recommendation level of A, B or C has been prepared based principally on "evidence" or a consensus among Japanese obstetricians in situations where "evidence" is weak or lacking. Answers with a recommendation level of A or B represent current standard care practices in Japan. All 87 CQ&As are presented herein to promote a better understanding of the current standard care practices for pregnant women in Japan

Interrelationship between myofiber type composition and intramuscular-fat content in muscles of Japanese Black cattle

黒毛和牛骨格筋における筋線維型構成と骨格筋内脂肪含量の関係について検討した．26－29カ月齢まで肥育された黒毛和牛より屠殺後，食肉生産上，重要な骨格筋である胸最長筋，大腿二頭筋，半膜様筋，半腱様筋，外側広筋，胸腹鋸筋および大腿直筋を摘出した．酵素組織化学的方法により筋線維をI型，IIA型およびIIB型筋線維に分類し（Brooke and Kaiser, 1970），筋線維型構成の算出を行った．またソックスレイ法によりそれぞれの骨格筋内の脂肪含量割合を測定した．黒毛和牛骨格筋の筋線維型構成に関して，骨格筋の種類により割合が異なった．すなわちI型筋線維を多く持つ胸腹鋸筋（61.7％），胸最長筋（45.8％），大腿二頭筋上部（52％），中程度持つ外側広筋（30.0％），大腿二頭筋下部（32.6％），およびI型筋線維がさらに少ない半腱様筋（24.6％），半膜様筋（26.4％），大腿直筋（23.3％）に分類された．一方，II型筋線維はI型筋線維と逆の傾向を示しその傾向はIIA型筋線維の変化というよりはIB型筋線維の変化として現れた．各骨格筋内の脂肪含量割合も骨格筋間で著しい差異が認められた．胸腹鋸筋は57.4％と最も大きく，以下胸最長筋27.9％，大腿二頭筋上部22.8％，大腿直筋15.7％，大腿二頭筋下部13.5％，外側広筋12.2％，半膜様筋10.6％，および半腱様筋10.4％の順で減少した．筋線維型構成割合と骨格筋内脂肪含量割合の相関関係を見ると，I型筋線維の割合とは正の，逆にIIA型およびIIB型筋線維の割合とは負の有意な相関関係が認められた．本研究より黒毛和牛去勢肥育牛において，骨格筋の種類により骨格筋内に蓄積される脂肪含量割合は著しく異なり，それは筋線維型構成と密接に関係していることが明らかになった．The interrelationship between myofiber type composition and intramuscular-fat content was investigated in muscles of Japanese Black cattle. The cattle were mainly fed with concentrate and slaughtered at 26-29 mo of age. After slaughter, M.longissimus thracis, M.biceps femoris, M.semimembranosus, M.semitendinosus, M. vastus lateralis, M.serratus ventralis and M.rectus femoris were removed from each carcass. Myofibers were enzyme-histochemically classified into type I, IIA and IIB myofibers according to the nomenclature of Brooke and Kaiser(1970). The percentage of intramuscular-fat content in each muscle was measured with Soxhlet method. In these muscles, the percentage of each type myofiber was related significantly to the percentage of intramuscular-fat content of each muscle at 26-29 mo of age. Correlation coefficient between the percentage of Type I myofiber and intramuscular-fat content was positive significant (p<0.005). Conversely, correlation coefficient between the percentages of type IIA, IIB myofiber and intramuscular-fat content was negative significant (p<0.05). These results indicated that the percentage of Type I myofiber was significantly related to the accumulation of intramuscular-fat in the muscles of Japanese Black cattle