慢性腎臓病では，腸管トランスポーターの機能不全によってカルニチン/有機カチオントランスポーター 1-エルゴチオネイン系が障害される

第17 回　高安賞優秀論文賞受賞 Kidney International 92(6):1356-1369, 2017　平成29 年12 月掲

Occult Hepatitis B Virus Infection With Increased Virus DNA Levels in a Chronic Hemodialysis Patient

金沢大学医薬保健研究域医学系Embargo Period 12 month

Fibrocytes are involved in the pathogenesis of human chronic kidney disease

金沢大学医薬保健研究域医学系The presence of chronic kidney disease in humans is associated with a risk of kidney function loss as well as the development of cardiovascular disease. Fibrocytes have been shown to contribute to organ fibrosis. In this study, the presence of fibrocytes was investigated immunohistochemically in kidney biopsy specimens from 100 patients with chronic kidney disease. In addition, 6 patients with thin basement membrane disease were studied as a disease control. In patients with chronic kidney disease, the infiltration of fibrocytes was observed mainly in the interstitium. The number of interstitial fibrocytes in patients with chronic kidney disease was higher than that in patients with thin basement membrane disease. The number of infiltrated fibrocytes in the interstitium correlated well with the severity of tubulointerstitial lesions, such as interstitial fibrosis, in patients with chronic kidney disease. In addition, there were significant correlations between the number of interstitial fibrocytes and the number of CD68-positive macrophages in the interstitium as well as urinary monocyte chemoattractant protein-1/CCL2 levels. In particular, there was an inverse correlation between the number of interstitial fibrocytes and kidney function at the time of biopsy. Finally, the numbers of interstitial fibrocytes and macrophages as well as urinary CCL2 levels were significantly decreased during convalescence induced by glucocorticoid therapy. These results suggest that fibrocytes may be involved in the pathogenesis of chronic kidney disease through the interaction with macrophages as well as CCL2. © 2010 Elsevier Inc. All rights reserved

Collagen adhesion gene is associated with blood stream infections caused by methicillin-resistant Staphylococcus aureus

Objectives: Methicillin-resistant Staphylococcus aureus (MRSA) causes hospital- and community-acquired infections. It is not clear whether genetic characteristics of the bacteria contribute to disease pathogenesis in MRSA infection. We hypothesized that whole genome analysis of MRSA strains could reveal the key gene loci and/or the gene mutations that affect clinical manifestations of MRSA infection. Methods: Whole genome sequences (WGS) of MRSA of 154 strains were analyzed with respect to clinical manifestations and data. Further, we evaluated the association between clinical manifestations in MRSA infection and genomic information. Results: WGS revealed gene mutations that correlated with clinical manifestations of MRSA infection. Moreover, 12 mutations were selected as important mutations by Random Forest analysis. Cluster analysis revealed strains associated with a high frequency of bloodstream infection (BSI). Twenty seven out of 34 strains in this cluster caused BSI. These strains were all positive for collagen adhesion gene (cna) and have mutations in the locus, those were selected by Random Forest analysis. Univariate and multivariate analysis revealed that these gene mutations were the predictor for the incidence of BSI. Interestingly, mutant CNA protein showed lower attachment ability to collagen, suggesting that the mutant protein might contribute to the dissemination of bacteria. Conclusions: These findings suggest that the bacterial genotype affects the clinical characteristics of MRSA infection. (c) 2019 The Author(s). Published by Elsevier Ltd on behalf of International Society for Infectious Diseases

Curated genome annotation of Oryza sativa ssp. japonica and comparative genome analysis with Arabidopsis thaliana

We present here the annotation of the complete genome of rice Oryza sativa L. ssp. japonica cultivar Nipponbare. All functional annotations for proteins and non-protein-coding RNA (npRNA) candidates were manually curated. Functions were identified or inferred in 19,969 (70%) of the proteins, and 131 possible npRNAs (including 58 antisense transcripts) were found. Almost 5000 annotated protein-coding genes were found to be disrupted in insertional mutant lines, which will accelerate future experimental validation of the annotations. The rice loci were determined by using cDNA sequences obtained from rice and other representative cereals. Our conservative estimate based on these loci and an extrapolation suggested that the gene number of rice is ~32,000, which is smaller than previous estimates. We conducted comparative analyses between rice and Arabidopsis thaliana and found that both genomes possessed several lineage-specific genes, which might account for the observed differences between these species, while they had similar sets of predicted functional domains among the protein sequences. A system to control translational efficiency seems to be conserved across large evolutionary distances. Moreover, the evolutionary process of protein-coding genes was examined. Our results suggest that natural selection may have played a role for duplicated genes in both species, so that duplication was suppressed or favored in a manner that depended on the function of a gene

Hitomi (ASTRO-H) X-ray Astronomy Satellite

The Hitomi (ASTRO-H) mission is the sixth Japanese x-ray astronomy satellite developed by a large international collaboration, including Japan, USA, Canada, and Europe. The mission aimed to provide the highest energy resolution ever achieved at E  >  2  keV, using a microcalorimeter instrument, and to cover a wide energy range spanning four decades in energy from soft x-rays to gamma rays. After a successful launch on February 17, 2016, the spacecraft lost its function on March 26, 2016, but the commissioning phase for about a month provided valuable information on the onboard instruments and the spacecraft system, including astrophysical results obtained from first light observations. The paper describes the Hitomi (ASTRO-H) mission, its capabilities, the initial operation, and the instruments/spacecraft performances confirmed during the commissioning operations for about a month

慢性腎臓病と臓器連関の病態におけるergothioneine/OCTN1の関与

金沢大学医薬保健研究域医学系本研究は，慢性腎臓病と腸管トランスポーターとの関連を，OCTN1およびその基質である食餌由来の抗酸化物質，ergothioneineに着目して検討したものである．CKDモデルマウスの小腸では，管腔側の細胞膜上に局在するOCTN1が減少し，ergothioneineの取り込みが低下していた．Ergothioneineが欠乏しているOCTN1ノックアウトマウスのCKDモデルでは，酸化ストレスが増大し，腎線維化が増悪することが確認された．これらの結果は，慢性腎臓病において腎臓と腸管との間に臓器連関が存在すること，および腎臓-腸管連関がCKDの進展に関与している可能性を示すものである．This study examined the association between chronic kidney disease and intestinal transporter. We focused on organic cation transporter 1 (OCTN1) and its substrate, ergothioneine, which is the antioxidant material derived from diet. OCTN1 expression on the apical side of intestinal cell membrane decreased in chronic kidney disease (CKD) model mice, and the uptake of ergothioneine also decreased. In the OCTN1 knockout mice, which lacked ergothioneine, the increase of oxidative stress and exacerbation of kidney fibrosis were confirmed in CKD model. These results showed the presence of the linkage between CKD and intestinal transporter and this linkage might associate with clinical progress of CKD.研究課題/領域番号:26860631, 研究期間(年度):2014-04-01 – 2016-03-3