Locality and diel cycling of viral production revealed by a 24 h time course cross-omics analysis in a coastal region of Japan

International audienceViruses infecting microorganisms are ubiquitous and abundant in the ocean. However, it is unclear when and where the numerous viral particles we observe in the sea are produced and whether they are active. To address these questions, we performed time-series analyses of viral metagenomes and microbial metatranscriptomes collected over a period of 24 h at a Japanese coastal site. Through mapping the metatranscriptomic reads on three sets of viral genomes ((i) 878 contigs of Osaka Bay viromes (OBV), (ii) 1766 environmental viral genomes from marine viromes, and (iii) 2429 reference viral genomes), we revealed that all the local OBV contigs were transcribed in the host fraction. This indicates that the majority of viral populations detected in viromes are active, and suggests that virions are rapidly diluted as a result of diffusion, currents, and mixing. Our data further revealed a peak of cyanophage gene expression in the afternoon/dusk followed by an increase of genomes from their virions at night and less-coherent infectious patterns for viruses putatively infecting various groups of heterotrophs. This suggests that cyanophages drive the diel release of cyanobacteria-derived organic matter into the environment and viruses of heterotrophic bacteria might have adapted to the population-specific life cycles of hosts

Temporal increase in muscle cross-sectional area as an acute effect of resistance exercise in resistance-trained and untrained individuals

The purpose of this study was to compare the temporal increase in muscle cross-sectional area (CSA) as the acute response of resistance exercise (RE) between resistance-trained and untrained groups, and investigate the factors that affect the muscle CSA. Resistance-trained (n = 14) and untrained (n = 14) subjects performed four kinds of triceps brachii RE. Muscle CSA and intracellular hydration (IH), were measured prior to and 5-, 30-, and 60-minute after RE. Pearson's correlation coefficient was calculated to clarify the relationships among percent increases in muscle CSA and IH, area under the Oyx-Hb curve, blood lactate concentration, and % maximum voluntary contraction (MVC)-root-mean-square (RMS) of electromyogram (EMG). At 5-minute after RE, muscle CSA increased significantly to 120.2 ± 6.3% in the resistance-trained group and 105.5 ± 2.3% in the untrained group (p < 0.01). However, neither group showed a significant difference between the values before and 30-minute after RE. In the resistance-trained group, there was a significant increase in IH at 5-minute post-RH (p < 0.01), and correlations were found between percent increases in muscle CSA and IH (r = 0.70, p < 0.01), area under the Oxy-Hb curve (r = 0.77, p < 0.01), and % MVC-RMS of EMG (r = 0.72, p < 0.01). The findings of this study suggest that measurements of muscle CSA in studies of muscle hypertrophy should be performed 30-minute or more after the last resistance exercise session, and muscle pump exercises should be conducted just before participation in bodybuilding, and physique contests

A liver-derived secretory protein, selenoprotein P, causes insulin resistance

金沢大学医薬保健研究域医学系The liver may regulate glucose homeostasis by modulating the sensitivity/resistance of peripheral tissues to insulin, by way of the production of secretory proteins, termed hepatokines. Here, we demonstrate that selenoprotein P (SeP), a liver-derived secretory protein, causes insulin resistance. Using serial analysis of gene expression (SAGE) and DNA chip methods, we found that hepatic SeP mRNA levels correlated with insulin resistance in humans. Administration of purified SeP impaired insulin signaling and dysregulated glucose metabolism in both hepatocytes and myocytes. Conversely, both genetic deletion and RNA interference-mediated knockdown of SeP improved systemic insulin sensitivity and glucose tolerance in mice. The metabolic actions of SeP were mediated, at least partly, by inactivation of adenosine monophosphate-activated protein kinase (AMPK). In summary, these results demonstrate a role of SeP in the regulation of glucose metabolism and insulin sensitivity and suggest that SeP may be a therapeutic target for type 2 diabetes. © 2010 Elsevier Inc

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

食後に実施する短時間の階段昇降運動が2型糖尿病患者の食後高血糖および血糖コントロールに及ぼす影響

京都大学0048新制・課程博士博士(人間・環境学)甲第20464号人博第814号新制||人||195(附属図書館)28||人博||814(吉田南総合図書館)京都大学大学院人間・環境学研究科共生人間学専攻(主査)教授 林 達也, 教授 石原 昭彦, 准教授 久代 恵介学位規則第4条第1項該当Doctor of Human and Environmental StudiesKyoto UniversityDGA

Impact of Self-Reported Sitting Time and Transtheoretical Model Based on Exercise Behavior Change on Glycemic and Weight Control in Japanese Adults with Type 1 Diabetes: A Cross-Sectional Study

This cross-sectional study aimed to examine the associations among self-reported sitting time (ST), transtheoretical model (TTM) based on exercise behavior change, and glycemic and weight control in Japanese adults with type 1 diabetes (T1D). Forty-two adults (age, 44.0 (33.3&ndash;56.8) years) with uncomplicated T1D answered questions regarding their lifestyles, including ST per day, and TTM using self-administered questionnaires. The glycated hemoglobin (HbA1c) level correlated with age and ST (p &lt; 0.05, p &lt; 0.01, respectively), whereas body mass index correlated with duration of T1D and TTM (p &lt; 0.05, p &lt; 0.01, respectively). Logistic regression analysis showed that poor glycemic control (HbA1c, &gt;7%) was associated with ST (odds ratio, 3.53 (95% confidence interval, 1.54&ndash;8.11), p &lt; 0.01). In addition, the cut-off points for quartiles of ST were 4.6, 6.0, and 8.0 h/day, and the HbA1c level in the lowest quartile was 15% lower than that in the highest quartile (p &lt; 0.01). Although further studies with larger samples are needed, these results implied that expanded self-reported ST might be related to poor glycemic control in Japanese T1D adults, most of whom were lean, young and middle-aged, regardless of TTM based on exercise behavior change