Preferable Forms of Relaxation for Health Promotion, and the Association between Recreational Activities and Self-perceived Health

Little research has been done on the association between relaxation and health. In the present study, by conducting a nationwide cross-sectional survey, we aimed to obtain scientific data on the preferable forms of relaxation for health promotion, and to clarify the associations between specific recreational activities and self-perceived mental and physical health. We selected 4,000 households by stratified random sampling from across Japan in November 2009 and used the interview method to collect data (number of subjects:2,206). The questionnaire contained items on sleep, recreation status, recreational activities, and self-perceived mental and physical health status. We obtained responses from 1,224 adults (response rate:55.5%). Insufficient rest from sleep, short sleep duration (＜6h/day), ineffective use of free time, and less free time used for activities other than rest showed independent positive associations with poor mental and physical health. The results of the logistic regression analyses showed significantly low adjusted odds ratios with regard to the status of poor mental and physical health for outings/walking among men (0.33 [95% confidence interval;0.16-0.68] and 0.49 [0.26-0.90], respectively), and for community activities among women (0.19 [0.04-0.79] and 0.27 [0.09-0.77], respectively). Relaxation for the promotion of health should include both passive relaxation (rest) and active relaxation (recreation). In addition, ensuring sufficient sleep duration is important for passive relaxation, and engaging in outings/walking for men and community activities for women are important for active relaxation

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

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

A 25-Year Study of the Population Dynamics of a Harvested Population of Sika Deer on Kyushu Island, Japan

Sika deer (Cervus nippon) populations have damaged habitats, agricultural crops, and commercial forests in many parts of the world, including Asia, Europe, northern America, and New Zealand. Population management of sika deer is an important task in those areas. To better understand large-scale management and improve management efficiency, the authors estimated spatio-temporal changes of density distribution and population dynamics of a managed population of sika deer on Kyushu Island (approximately 36,750 km2), Japan. The authors estimated these changes by using fecal pellet count surveys conducted from 1995 to 2019 and results from a vector autoregressive spatio-temporal model. No decreasing trend of populations were observed at the island and prefectural scales, even though the management goal has been to reduce the population by half, and harvesting on the island increased annually until it reached about 110,000 sika deer in 2014. A possible explanation for the stable population dynamics is that the population used to determine the harvest number under the prefectural management plan was originally underestimated. This study highlights not only the difficulties of wide-area management of sika deer but also three important factors for successful management: reducing the risk of management failure, using an adaptive management approach, and appropriate management scale

Benzbromarone Attenuates Oxidative Stress in Angiotensin II- and Salt-Induced Hypertensive Model Rats

Oxidative stress induced by hyperuricemia is closely associated with the renin-angiotensin system, as well as the onset and progression of cardiovascular disease (CVD) and chronic kidney disease (CKD). It is therefore important to reduce oxidative stress to treat hyperuricemia. We previously found that benzbromarone, a uricosuric agent, has a direct free radical scavenging effect in vitro. The antioxidant effects of benzbromarone were evaluated in vivo via oral administration of benzbromarone for 4 weeks to model rats with angiotensin II- and salt-induced hypertension. Benzbromarone did not alter plasma uric acid levels or blood pressure but significantly reduced the levels of advanced oxidation protein products, which are oxidative stress markers. Furthermore, dihydroethidium staining of the kidney revealed a reduction in oxidative stress after benzbromarone administration. These results suggest that benzbromarone has a direct antioxidant effect in vivo and great potential to prevent CVD and CKD

Characteristics of induced mutations in offspring derived from irradiated mouse spermatogonia and mature oocytes.

The exposure of germ cells to radiation introduces mutations in the genomes of offspring, and a previous whole-genome sequencing study indicated that the irradiation of mouse sperm induces insertions/deletions (indels) and multisite mutations (clustered single nucleotide variants and indels). However, the current knowledge on the mutation spectra is limited, and the effects of radiation exposure on germ cells at stages other than the sperm stage remain unknown. Here, we performed whole-genome sequencing experiments to investigate the exposure of spermatogonia and mature oocytes. We compared de novo mutations in a total of 24 F1 mice conceived before and after the irradiation of their parents. The results indicated that radiation exposure, 4 Gy of gamma rays, induced 9.6 indels and 2.5 multisite mutations in spermatogonia and 4.7 indels and 3.1 multisite mutations in mature oocytes in the autosomal regions of each F1 individual. Notably, we found two types of deletions, namely, small deletions (mainly 1~12 nucleotides) in non-repeat sequences, many of which showed microhomology at the breakpoint junction, and single-nucleotide deletions in mononucleotide repeat sequences. The results suggest that these deletions and multisite mutations could be a typical signature of mutations induced by parental irradiation in mammals