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

Correction to: Dexmedetomidine administration in a patient with status epilepticus under color density spectral array monitoring

Following publication of the original article [1], the authors reported an error in Fig. 1b and c. A black bar and arrows were added

Food Search Strategy Changes in Caenorhabditis elegans under Chronic Starvation Conditions.

Starvation is a primary threat to survival in nature. This study investigated the effects of starvation on animal behavior and neural function using a nematode model. Nematodes exhibit chemotactic responses to various compounds, including diacetyl produced by food bacteria. Locomotion, chemotactic behavior, and olfactory adaptation were measured following chronic starvation. Our results revealed a starvation-dependent reduction in locomotor activity. Chemotaxis response to the odorant diacetyl was attenuated after 2-38 hr of starvation. However, chemotactic behavior increased significantly after 48 hr of starvation compared with that after 38 hr of starvation, suggesting that food search behavior was enhanced after 48 hr of starvation. Inhibition of diacetyl adaptation was observed in the nematodes after 48 hr of starvation. However, exogenous exposure to serotonin during 48 hr of starvation caused the inhibition of diacetyl adaptation to be attenuated in following 24 hr period of normal feeding.Therefore, the inhibitory effects of starvation on olfactory adaptation may reduce chemotaxis response to the odorant diacetyl in a manner mediated by serotonin

Expression of Keratin 75 (K6hf) in Oral Squamous Cell Carcinoma

Cytokeratin is commonly used diagnostic markers of oral squamous cell carcinoma (OSCC). Especially, Keratin17 (K17) is reported to be up-regulated in OSCC. Recently, identification and quantification of proteins from tissue section become possible by using laser microdissection and LC/MS/MS method. In this study, we performed nano-flow liquid chromatography, mass spectrometry and protein identification by tandem mass spectrometry (LC/MS/MS) analysis on pooled protein extracts from OSCC tissue section and compared the results with those from normal epithelium. As a result, Keratin 6hf is considered as a candidate marker of OSCC. From more validation, the expression of K6hf may be associated with malignancy of oral epithelial lesion. In previous study, K6hf is known to be specifically expressed in a hair follicle and specifically cross a partner with K17. But, there are no report about correlation between K6hf and carcinoma. In conclusion, K6hf expression may play an important role in the carcinogenesis progression of OSCC. However, further studies on the molecular function of K6hf are encouraged to clear the precise mechanism of K6hf in OSCC

Availability of Four Square Step Test for Community-Dwelling Elders

敏捷性は日常生活の中でも重要な運動機能の一つであり, 加齢による運動機能低下の一つとしても考えられている.本研究の目的は, 地域居住高齢者に対してWayne Dite らにより考案されたFour Square Step Test (以下FSST)を用いて敏捷性を評価し, また他の身体運動機能評価項目とどのような関係があるかを明らかにすることである. 対象は地域に居住する健常高齢者63名(平均年齢73.5歳) とした. 評価項目はFour Square Step Test (FSST) の他,その他の身体運動機能評価項目として, 膝伸展筋群筋力(LES), 長座位体前屈距離(FFD), 片脚立位保持時間(SLS), Timed Up and Go test (TUG), 10ｍ最大歩行速度(10MWS) を計測した. 結果, Four Square Step Test の平均値は5.8±1.1sec となり, またFSST とその他の評価項目間においてFSST とSLS (ｒ＝－.597, P＜.0001), TUG (ｒ＝.717, P＜.0001), 10MWS (ｒ＝.589, P＜.0001) と, それぞれに相関関係が認められた. SLS・TUG・10MWS の評価項目は運動能力, 特にバランス能力を示す評価項目として一般的に確立されているため, 今回の結果は, 敏捷性の評価も身体運動機能を表す重要な評価指標と考えられ, また日常生活に結びつく重要な運動プログラムの一つと成りうることが示唆された.The purpose of this study was to assess the physical agility and to determine the relationship between Physical agility and Other Physical Motor Functions in healthy community-dwelling elderly people. Physical agility is the ability to change the direction of the body in an efficient and effective manner. Elderly people tend to fall easily due to the loss of this physical ability. Therefore to prevent falling, it is important to assess physical agility in elderly people. Sixty three functionally independent community dwelling elderly people volunteered to participate in the study. Four Square Step Test (FSST) was used as a test of physical agility. The other physical motor function assessments were composed of 10m walking time (10MWT), Timed Up and Go test (TUG), Single leg standing (SLS), lower extremity strength (LES), and Finger floor distance (FFD). Pearson’s correlation was used to investigate the relationship between physical agility and the other physical assessments. The level of statistical significance was set at p＜0.05. This study shows significant correlation between FSST and SLS (r＝－.597, P＜.0001), TUG (r＝.717, P＜.0001), and 10MWS (r＝.589, P＜.0001) respectively. To prevent falling, it is very important to approach muscle strength, balance, and flexibility. However, the assessment of physical agility is also very important for elderly people. Since there were significant correlations between FSST and SLS, TUG, and 10MWS, physical agility needs to be assessed