Functional visualization of NK Cell-mediated killing of metastatic single tumor cells

ナチュラルキラー（NK）細胞による転移がん細胞殺傷の可視化 --NK細胞とがん細胞の肺毛細血管上での戦いを実況中継する--. 京都大学プレスリリース. 2022-02-07.Natural killer (NK) cells lyse invading tumor cells to limit metastatic growth in the lung, but how some cancers evade this host protective mechanism to establish a growing lesion is unknown. Here we have combined ultra-sensitive bioluminescence imaging with intravital two-photon microscopy involving genetically-encoded biosensors to examine this question. NK cells eliminated disseminated tumor cells from the lung within 24 hrs of arrival, but not thereafter. Intravital dynamic imaging revealed that 50% of NK-tumor cell encounters lead to tumor cell death in the first 4 hrs after tumor cell arrival, but after 24 hrs of arrival, nearly 100% of the interactions result in the survival of the tumor cell. During this 24 hrs period, the probability of ERK activation in NK cells upon encountering the tumor cells was decreased from 68% to 8%, which correlated with the loss of the activating ligand CD155/PVR/Necl5 from the tumor cell surface. Thus, by quantitatively visualizing the NK-tumor cell interaction at the early stage of metastasis, we have revealed the crucial parameters of NK cell immune surveillance in the lung

The 3rd DBCLS BioHackathon: improving life science data integration with Semantic Web technologies.

BACKGROUND: BioHackathon 2010 was the third in a series of meetings hosted by the Database Center for Life Sciences (DBCLS) in Tokyo, Japan. The overall goal of the BioHackathon series is to improve the quality and accessibility of life science research data on the Web by bringing together representatives from public databases, analytical tool providers, and cyber-infrastructure researchers to jointly tackle important challenges in the area of in silico biological research. RESULTS: The theme of BioHackathon 2010 was the 'Semantic Web', and all attendees gathered with the shared goal of producing Semantic Web data from their respective resources, and/or consuming or interacting those data using their tools and interfaces. We discussed on topics including guidelines for designing semantic data and interoperability of resources. We consequently developed tools and clients for analysis and visualization. CONCLUSION: We provide a meeting report from BioHackathon 2010, in which we describe the discussions, decisions, and breakthroughs made as we moved towards compliance with Semantic Web technologies - from source provider, through middleware, to the end-consumer.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

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

Pre-Conceptional Anti-Thyroid Antibodies and Thyroid Function in Association with Natural Conception Rates

Thyroid functioning is an integral part of the endocrine system that supports conception and pregnancy. Frequent consumption of seafood and iodine by Japanese people may adversely affect their thyroid function. Thus, in this study, we aimed to analyze the associations between iodine intake, thyroid hormones, autoimmunity, and natural conception rates in Japanese women trying to conceive their first child. A prospective study of 24 weeks targeted 80 women with no history of infertility, who did not plan to undergo fertility treatment. Concentrations of urinary iodine concentration and thyroid biomarkers in the serum at enrollment were measured. Thirty-five women naturally conceived during the follow-up. The median (inter-quartile range) urinary concentration of iodine was 297 (165, 500) μg/L. Free triiodothyronine (T3) and free thyroxin (T4) negatively correlated with urinary iodine concentrations. Women with anti-thyroid peroxidase (anti-TPO) ≥ 16 IU/mL had lower conception rates (hazard ratio: 0.28, 95% confidence interval, 0.08–0.92) compared with those with anti-TPO < 16 IU/mL, after adjusting for age and coital frequency. None of anti-thyroglobulin antibody, free T3, free T4, or thyroid-stimulating hormone showed significant associations with conception rate after adjusting for age and coital frequency. The negative association between thyroid autoimmunity and natural conception rates warrants further investigation

Casual Sex and Sexlessness in Japan: A Cross-Sectional Study

Low fertility has persisted in Japan for decades. Sexless marriages may indirectly contribute to low fertility. Inactive sexual lives within intimate and committed relationships may be linked to sexual activity outside such relationships, called “casual sex”. This study aimed to explore the correlates of casual sex and sexlessness. A web-based questionnaire survey was conducted among married and single men (n = 4000) aged 20–54 years in Japan. Sexlessness were reported by 56% of men, whereas 11% had had casual sex and 31% had had non-casual sex (with spouse, fiancé, or girlfriends/boyfriends) in the last month. Among married men, higher income and long working hours were positively associated with casual sex. Regarding never-married men: those with lower educational status and without full-time jobs were more likely to report casual sex, those in rural areas were more likely to be sexless than those in urban and suburban areas, and those with depression were more likely to be sexless than those without depression. Matching app use was strongly associated with casual sex among married and never-married men, suggesting that such tools may facilitate sexual activity outside committed and intimate relationships. Sexual behavior is closely linked to one’s social and economic environment and health status

Casual Sex and Sexlessness in Japan: A Cross-Sectional Study

Low fertility has persisted in Japan for decades. Sexless marriages may indirectly contribute to low fertility. Inactive sexual lives within intimate and committed relationships may be linked to sexual activity outside such relationships, called “casual sex”. This study aimed to explore the correlates of casual sex and sexlessness. A web-based questionnaire survey was conducted among married and single men (n = 4000) aged 20–54 years in Japan. Sexlessness were reported by 56% of men, whereas 11% had had casual sex and 31% had had non-casual sex (with spouse, fiancé, or girlfriends/boyfriends) in the last month. Among married men, higher income and long working hours were positively associated with casual sex. Regarding never-married men: those with lower educational status and without full-time jobs were more likely to report casual sex, those in rural areas were more likely to be sexless than those in urban and suburban areas, and those with depression were more likely to be sexless than those without depression. Matching app use was strongly associated with casual sex among married and never-married men, suggesting that such tools may facilitate sexual activity outside committed and intimate relationships. Sexual behavior is closely linked to one’s social and economic environment and health status