24 research outputs found
DOCK2 is involved in the host genetics and biology of severe COVID-19
Get PDF「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
Experiment investigation of turbulence generated by solitary wave over smooth beds
Get PDFTwo cases of solitary motion experiment have been conducted over smooth beds by using solitary wave
generation system facilitated by two types of rotating disk, th
e detail explanation about these rotating disks can be found in
the former publication (Tanaka et al. 2011). In the present study, a deep analysis has been done to verify the sufficiency of tranquil period between two peaks of “solitary-wave-like” motion in turbulent flow regime and also to validate the reliability or sensitivity of ensemble averaging to 50 wave numbers produces by continuous measurement. The analysis results show that the minimum number of “periodical” or continuous wave measurement to attain reliable ensemble average is 45 wave numbers for case of turbulent solitary motion with Reynolds number (Re) = 7.34 x 105
Experimental study on bottom boundary layer beneath solitary wave
Get PDFA tsunami as long wave and an oscillatory wave moves into shoaling water have behavior similar to solitary wave
and therefore comprehension on its bottom boundary layer characteristics come to be essential key on near-shore sediment transport modeling. In the present study, the hydraulics phenomena of solitary wave are studied in deep through experiments utilizing a closed conduit generation system. This result was examined by analytical and numerical laminar solution. Moreover, wave friction factor is discussed based on the present laboratory experiment and previous studies of (Sumer et al., 2010); (Vittory and Blondeaux, 2011, 2012). As conclusions, in-consistent critical Reynolds number was found for solitary wave case. This observable fact is distinct difference with sinusoidal wave case which has consistency in critical Reynolds number. As a main conclusion that a new generation system proposed in the present study will be able and applicable to shore up an experiment on sediment transport induced by solitary wave
