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

Usability Study on Geometry Resources Website

Math courses are major classes in high school and are often required for graduation. Geometry is one of the math courses required for graduation and it is crucial for students to pass this course in order to graduate on time. However, in some high school geometry classes with more than 30 students, there are some students who struggle to grasp the content. To facilitate student learning in geometry, teachers should accommodate students by using 21st century skills and providing more visual aid with animations. However, teachers need to be interested and know how to use these resources before presenting them to their students. The researcher utilized learning principles and visual design to develop an informational website about online geometry resources. The website targeted high school geometry teachers. After building the website, the researcher conducted three rounds of usability testing to evaluate ease of use and level of interest. The researcher collected data from 13 participants (n = 13) as they thought aloud about the website, completed four task-based scenarios, and completed surveys. The results from the usability study and the surveys indicated that participants found the website easy to use and helpful. The final product could be shared among geometry teachers and used as a place to find resources to use during class to help students increase their understanding of geometry