Overview of Legal Systems in the Asia-Pacific Region: Japan

This article provides a general description of the legal system of Japan. It further discusses aspects of legal education and legal practice in that country

A Novel Serum-Free Monolayer Culture for Orderly Hematopoietic Differentiation of Human Pluripotent Cells via Mesodermal Progenitors

Elucidating the in vitro differentiation of human embryonic stem (ES) and induced pluripotent stem (iPS) cells is important for understanding both normal and pathological hematopoietic development in vivo. For this purpose, a robust and simple hematopoietic differentiation system that can faithfully trace in vivo hematopoiesis is necessary. In this study, we established a novel serum-free monolayer culture that can trace the in vivo hematopoietic pathway from ES/iPS cells to functional definitive blood cells via mesodermal progenitors. Stepwise tuning of exogenous cytokine cocktails induced the hematopoietic mesodermal progenitors via primitive streak cells. These progenitors were then differentiated into various cell lineages depending on the hematopoietic cytokines present. Moreover, single cell deposition assay revealed that common bipotential hemoangiogenic progenitors were induced in our culture. Our system provides a new, robust, and simple method for investigating the mechanisms of mesodermal and hematopoietic differentiation

Angioscopic Evaluation of Stabilizing Effects of Bezafibrate on Coronary Plaques in Patients With Coronary Artery Disease

Background Since long-term administrations of anti-hyperlipidemic agents result in reduction in % stenosis or increase in minimum lumen diameter (MLD) of stenotic coronary segments, it is generally believed that anti-hyperlipidemic agents stabilize vulnerable coronary plaques. However, recent pathologic and angioscopic studies revealed that vulnerability of coronary plaques is not related to severity of stenosis and the rims rather than top of the plaques disrupt, and therefore, angiography is not adequate for evaluation of vulnerability

Inhibitory action of iron on erythropoietin via oxidative stress-HIF-2α pathway

Renal anemia is a major complication in chronic kidney disease (CKD). Iron supplementation, as well as erythropoiesis-stimulating agents, are widely used for treatment of renal anemia. However, excess iron causes oxidative stress via the Fenton reaction, and iron supplementation might damage remnant renal function including erythropoietin (EPO) production in CKD. EPO gene expression was suppressed in mice following direct iron treatment. Hypoxia-inducible factor-2 alpha (HIF-2α), a positive regulator of the EPO gene, was also diminished in the kidney of mice following iron treatment. Anemia-induced increase in EPO and HIF-2α expression was also inhibited by iron-treatment. In in vitro experiments using EPO-producing HepG2 cells, iron stimulation reduced the expression of the EPO gene, as well as HIF-2α. Moreover, iron treatment augmented oxidative stress, and iron-induced reduction of EPO and HIF-2α expression was restored by tempol, an anti-oxidant compound. HIF-2α interaction with the EPO promoter was inhibited by iron treatment, and was restored by tempol. These findings suggested that iron supplementation reduced EPO gene expression via an oxidative stress-HIF-2α-dependent signaling pathway

Association between physical activity and metabolic syndrome in middle-aged Japanese: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Although many studies have reported an association between self-reported physical activity and metabolic syndrome (MetS), there is limited information on the optimal level of physical activity required to prevent MetS. This study aimed to determine the association between objectively measured physical activity and MetS in middle-aged Japanese individuals. We also determined the optimal cutoff value for physical activity required to decrease the risk of developing MetS.</p> <p>Methods</p> <p>A total of 179 men and 304 women, aged between 30 and 64 years, participated in this study. Participants were divided into two groups using the Japanese criteria for MetS as those with MetS or pre-MetS, and those without MetS. Participants were considered to be physically active if they achieved a physical activity level of 23 metabolic equivalents (METs) h/week, measured using a triaxial accelerometer. The association between physical activity and MetS was analyzed using logistic regression with the following covariates: sex, age, sedentary time, low intensity activity, calorie intake, smoking, menopause and body mass index. We also evaluated the factors that determined the association between the prevalence of MetS and pre-MetS and the physical activity cutoff value using classification and regression tree (CART) analysis.</p> <p>Results</p> <p>The odds ratio for MetS and pre-MetS was 2.20 for physically inactive participants (< 23 METs h/week), compared with physically active participants (≥ 23 METs h/week). The corresponding odds ratios for men and women were 2.27 (<it>P </it>< 0.01) and 1.95 (not significant), respectively. CART analyses revealed that moderate-vigorous physical activity of > 26.5 METs h/week was sufficient to decrease the prevalence of MetS and pre-MetS in middle-aged Japanese men and women.</p> <p>Conclusions</p> <p>The results of this cross-sectional study indicate that the Exercise and Physical Activity Reference for Health Promotion 2006 is inversely associated with the prevalence of MetS in men. Our results also suggest that moderate physical activity of > 26.5 METs h/week may decrease the risk of developing MetS and pre-MetS in middle-aged Japanese individuals.</p

Sequence-specific error profile of Illumina sequencers

We identified the sequence-specific starting positions of consecutive miscalls in the mapping of reads obtained from the Illumina Genome Analyser (GA). Detailed analysis of the miscall pattern indicated that the underlying mechanism involves sequence-specific interference of the base elongation process during sequencing. The two major sequence patterns that trigger this sequence-specific error (SSE) are: (i) inverted repeats and (ii) GGC sequences. We speculate that these sequences favor dephasing by inhibiting single-base elongation, by: (i) folding single-stranded DNA and (ii) altering enzyme preference. This phenomenon is a major cause of sequence coverage variability and of the unfavorable bias observed for population-targeted methods such as RNA-seq and ChIP-seq. Moreover, SSE is a potential cause of false single-nucleotide polymorphism (SNP) calls and also significantly hinders de novo assembly. This article highlights the importance of recognizing SSE and its underlying mechanisms in the hope of enhancing the potential usefulness of the Illumina sequencers

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