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

Servo System Design Considering Low-Stiffness of Robot

This paper describes the practical design method of an advanced servo system for industrial robot manipulators, where it includes a disturbance and velocity observer. It is first assumed that the feature on frequency response of the robot is approximated to the feature of two-mass mechanism. Actually this is confirmed by some experiments. On the other hand, it is insisted that the actual servo system should be simple for industrial use. The observer is designed for the load which has the feature of single moment of inertia. Based on the assumption that there is a difference between these features, it is introduced that the servo system can be effectively used if only the qualified gains are selected considering lowstiffness. The special relation between the frequency analysis and the pole allocations are then shown, and Finally the experimental results are introduced.</jats:p

Posture Estimation of Human Body Based on Connection Relations of 3D Ellipsoidal Models

We propose new method of estimating human body posture from connection relations of threedimensional (3D) ellipsoidal models. First, 3D ellipsoidal models with enlargement and reduction transformations are constructed. Next, two-dimensional (2D) appearance models are constructed from 2D projected images of the 3D model. The appearance models are related to each other by employing a network data structure. They are then matched with an image of the body made from actual thermal images. By using the connection relations between the head and body, the head and the body can be recognized. Differences between individuals can be simply treated by using different sized parts. Moreover, this method can be applied also to recognition of arms and legs.</jats:p