Analysis of gut microbiome, host genetics, and plasma metabolites reveals gut microbiome-host interactions in the Japanese population

Interaction between the gut microbiome and host plays a key role in human health. Here, we perform a metagenome shotgun-sequencing-based analysis of Japanese participants to reveal associations between the gut microbiome, host genetics, and plasma metabolome. A genome-wide association study (GWAS) for microbial species (n = 524) identifies associations between the PDE1C gene locus and Bacteroides intestinalis and between TGIF2 and TGIF2-RAB5IF gene loci and Bacteroides acidifiaciens. In a microbial gene ortholog GWAS, agaE and agaS, which are related to the metabolism of carbohydrates forming the blood group A antigen, are associated with blood group A in a manner depending on the secretor status determined by the East Asian-specific FUT2 variant. A microbiome-metabolome association analysis (n = 261) identifies associations between bile acids and microbial features such as bile acid metabolism gene orthologs including bai and 7β-hydroxysteroid dehydrogenase. Our publicly available data will be a useful resource for understanding gut microbiome-host interactions in an underrepresented population.Tomofuji Yoshihiko, Kishikawa Toshihiro, Sonehara Kyuto, et al. Analysis of gut microbiome, host genetics, and plasma metabolites reveals gut microbiome-host interactions in the Japanese population. Cell Reports 42, 113324 (2023); https://doi.org/10.1016/j.celrep.2023.113324

The invariance of asymptotic laws of stochastic systems under discretization

The stochastic trapezoidal rule provides the only discretization scheme from the family of implicit Euler methods (see [11]) which possesses the same asymptotic (stationary) law as underlying linear continuous time stochastic systems with white or coloured noise. This identity is shown for systems with multiplicative (para- metric) and additive noise using fixed point principles and the theory of positive operators. The key result is useful for adequate implementation of stochastic algorithms applied to numerical solution of autonomous stochastic differential equations. In particular it has practical importance when accurate long time integration is required such as in the process of estimation of Lyapunov exponents or stationary measures for oscillators in Mechanical Engineering

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

メンタルヘルス不調者へのセルフマネジメントプログラムの効果に関する研究

本研究の目的は、心療内科に通院するメンタルへルス不調者に、セルフマネジメントプログラムを用いた介入を行い、セルフマネジメント力を高める効果があるかを実証的に検証することである。方法は、「治療のみの変化」「介入による変化」「介入後の持続効果」を比較した群間比較研究である。対象は、うつ・不安障害などで心療内科に通院している患者10 名で、1 回2 時間、3 回からなるプログラムに参加し、その前後と1ヶ月後に質問紙調査を実施した。調査内容は、自己効力感、自己抑制型行動特性、問題解決型行動特性、抑うつ度とした。プログラム内容は、メンタルヘルス不調の心理教育、自己理解、イメージセラピー、エンカウンターグループで構成した。調査の結果、介入前後の比較において、自己抑制型行動特性、問題解決型行動特性に有意差は認められなかった。自己効力感（p＜0.5）、抑うつ（p＜0.1〉で有意な改善が認められた。また、自己効力感の下位因子であるネガティブ因子に有意傾向が認められた（p＜1）。これらの効果は介入1ヵ月後まで維持されていた。さらに、治療のみの期間における尺度の変化は認められなかったことから、介入前後の変化は介入による効果の可能性が高い。セルフマネジメントプログラム実施により、抑うつ気分の改善と自己効力認知の改善が認められ、セルフマネジメントに向けた効果が確認された。自己抑制型行動特性と問題解決型行動特性に変化は認められず、行動変容に至る期間を加味した長期的なフォローアップが必要である。一部の参加者の記述から気分と認知にセルフマネジメントに向けた肯定的な変化があり、統計的分析結果が参加者の主観からも裏付けられた。The purpose of this study is to empirically indicate whether intervention of patientswith mental health disorders, who regularly see doctors, with a self-management program is effective in improving their self-management capabilities.The method used was intergroup research comparing “change only by treatment”,“change by intervention”and“continuing effects after intervention”.Subjects were10patients who regularly saw psychosomatic doctors with the symptoms of depression,anxiety disorder, etc. The program was comprised of three2-hour sessions, and a questionnaire survey was taken before and after those sessions plus one month later.Survey contents included a feeling of self-efficacy,self-restraint behavioral characteristics, problem solving behavioral characteristics,and degree of depression.The program was comprised of psychoeducation of mental health disorders,self-understanding,image therapy, and encounter groups.The results did not show any significance in self-restraint behavioral characteristics or problem solving behavioral characteristics when comparing the before and after intervention, but significant improvement was confirmed on self-efficacy（p<0.5）and depression（p<0.1）.Additionally, a negativefactor, which is the hypostatic factor of self-efficacy, showed a tendency of marginal significance（p<1）.These effects remained1month after intervention. Since the scale didn’t change in the period of only receiving doctor’s treatment, it is highly possible that the intervention was responsible for the effective changes.Improvement in depression and recognition of self-efficacy from the intervention was recognized and the researchers confirmed its effect toward patients’self-management. Some of the written answers from participants stated they had positive changes in their mood and cognition,which confirmed the results of the statistical analysis from the participants’subjective viewpoint

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Mutations conferring SO42- pumping ability on the cyanobacterial anion pump rhodopsin and the resultant unique features of the mutant

Membrane transport proteins can be divided into two types: those that bind substrates in a resting state and those that do not. In this study, we demonstrate that these types can be converted by mutations through a study of two cyanobacterial anion-pumping rhodopsins, Mastigocladopsis repens halorhodopsin (MrHR) and Synechocystis halorhodopsin (SyHR). Anion pump rhodopsins, including MrHR and SyHR, initially bind substrate anions to the protein center and transport them upon illumination. MrHR transports only smaller halide ions, Cl- and Br-, but SyHR also transports SO42-, despite the close sequence similarity to MrHR. We sought a determinant that could confer SO42- pumping ability on MrHR and found that the removal of a negative charge at the anion entrance is a prerequisite for SO42- transport by MrHR. Consistently, the reverse mutation in SyHR significantly weakened SO42- pump activity. Notably, the MrHR and SyHR mutants did not show SO42- induced absorption spectral shifts or changes in the photoreactions, suggesting no bindings of SO42- in their initial states or the bindings to the sites far from the protein centers. In other words, unlike wild-type SyHR, these mutants take up SO42- into their centers after illumination and release it before the ends of the photoreactions