Genetic population structure of the polkadot skate (Dipturus chinensis) around Japan, based on mitochondrial DNA sequences and polymorphic microsatellite loci

The genetic population structure of the polkadot skate (Dipturus chinensis) around Japan was examined by using mitochondrial (mt) cytochrome (cyt) b gene sequences and polymorphic microsatellite (simple sequence repeat [SSR]) loci. Results of phylogenetic analysis based on mt cyt b gene sequences reveal 2 major lineages, clades A and B. Clade A consists of populations in the Sea of Japan and the East China Sea. Clade B contains populations in the Pacific Ocean and is divided into 2 subclades, clades B1 and B2, which correspond to the populations along the southern and northern coasts of Japan, respectively. This genetic differentiation is also supported by results from SSR analysis. The divergence of clades A and B may reflect isolation of the East China Sea from the Pacific Ocean in the Early Pleistocene. After diverging from clade A, clade B might have extended its distribution northward along the Pacific coast of Japan and divided into clades B1 and B2 in the Middle Pleistocene. The polkadot skate is clearly structured into 3 genetically discrete populations around Japan that should be treated as independent management units for management of this species in the future

The impact of triple drug immunosuppression on clinical results of cadaveric kidney transplantation: a comparison of conventional immunosuppression.

A retrospective study was carried out in 110 cadaveric kidney transplant recipients to compare the effects of low doses of cyclosporine (CsA), azathioprine (AZP) and steroids (triple-drug therapy) with those of higher doses of steroids plus AZP (conventional immunosuppression). Graft survival rate in the triple-drug therapy was 77%, 69%, and 69% at 1, 3, and 5 years, respectively. This was significantly better than 48%, 34%, and 29% in conventional immunosuppression. The incidence of acute rejection episodes was significantly lower in the triple-drug therapy than in conventional immunosuppression (25% vs 58%). In conclusion, our study shows that triple-drug therapy using low-dose cyclosporine is the safest of the immunosuppressive regimens and provides a beneficial effect on the long-term survival of cadaveric kidney transplants.</p

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

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

Comparative Verification of Radiation Noise Reduction Effect Using Spread Spectrum for Inductive Power Transfer System

This paper provides a comparative study on radiation noise reduction methods for inductive power transfer systems using spread spectrum. In the spread spectrum methods, the radiation noise is reduced by continuously changing an output frequency of the inverter according to pseudorandom numbers. The effects of the radiation noise reduction are evaluated with the inductive power transfer (IPT) system with series-parallel compensation and series-series compensation. The results show that the peak values of the radiation noise around the fundamental frequency are reduced by 7.8 and 8.1 dB&mu;A in maximum with the series-series compensation method and the series-parallel compensation method, respectively in comparison with the constant frequency operation. From these results, the proposed methods are effective for both the series-series compensation and series-parallel compensation method. Moreover, the efficiency of the IPT system with spread spectrum method is evaluated. The maximum DC-to-DC efficiency with the spread spectrum is 94.1% and 92.0% with the series-series compensation and the series-parallel compensation, respectively