55 research outputs found
Fatal child abuse in Japan: does a trend exist toward tougher sentencing?
BACKGROUND: It has been pointed out in Japan that criminal punishment in domestic homicide cases, especially in fatal child abuse cases, tends to be more lenient than in public homicide cases that occur outside the home. In recent news accounts of fatal child abuse cases, however, the media has reported that court-imposed sentences have tended to be stricter every year.METHODS: Using the online databases of three major Japanese newspapers, we collected articles about fatal child abuse cases that had been published from January 2008 to December 2009. We analyzed these articles to determine, whether a tendency towards tougher penalties, as was put forward by the media, actually exists at present time in the criminal system in Japan. RESULTS: We found 24 cases, out of which 20 involved only one offender and 4 involved two offenders. These 28 offenders comprised nine biological fathers, 11 biological mothers, and eight other male relatives of the child victims. We found that the sentences handed down by the court clearly tended to be more lenient for female offenders. A new system of criminal jurisprudence, the so-called saiban-in system wherein citizens serve as “lay judges” in criminal trials involving serious crimes, was implemented in Japan at the start of 2009. Each, district court has gradually adopted this new system after a preparation period of approximately five years starting in 2004. CONCLUSIONS: Many figures in the Japanese media predicted that the gap between social expectations and court sentences for sanction against domestic homicide cases would be filled with the present transitional period of the Japanese criminal system. However, the present study found no significant difference in the laws regarding sentencing in fatal child abuse cases before and after the preparation period of the saiban-in system
Evaluation of Infliximab Effects on Gastrointestinal Bleeding in Crohn's Disease Using Double-Balloon Endoscopy
Tumor necrosis factor α plays an important role in the pathogenesis of Crohn's disease (CD). The effects of infliximab on gastrointestinal bleeding in CD have not yet been fully evaluated. Herein we describe three CD cases who presented with gastrointestinal bleeding and received infliximab treatment. In case 1, double-balloon endoscopy showed a large ulcer with several irregularly shaped ulcers in the terminal ileum; 8 weeks after infliximab administration, complete healing of all lesions was observed. In case 2, double-balloon endoscopy showed linear ulcers and mucosal edema in the jejunum and ileum; 5 weeks after infliximab administration, all lesions were decreased in size and were healed. In case 3, double-balloon endoscopy revealed ulcerations and stenosis in the terminal ileum; 12 weeks after infliximab administration, ulcer healing and an increased diameter of the ileal stenosis were observed. These three cases have been receiving ongoing infliximab maintenance therapy and are currently symptom-free. Infliximab thus appears to be useful for treatment of gastrointestinal bleeding in CD patients
Regulation of CCR4-NOT complex deadenylase activity and cellular responses by MK2-dependent phosphorylation of CNOT2
CCR4-NOT complex-mediated mRNA deadenylation serves critical functions in multiple biological processes, yet how this activity is regulated is not fully understood. Here, we show that osmotic stress induces MAPKAPK-2 (MK2)-mediated phosphorylation of CNOT2. Programmed cell death is greatly enhanced by osmotic stress in CNOT2-depleted cells, indicating that CNOT2 is responsible for stress resistance of cells. Although wild-type (WT) and non-phosphorylatable CNOT2 mutants reverse this sensitivity, a phosphomimetic form of CNOT2, in which serine at the phosphorylation site is replaced with glutamate, does not have this function. We also show that mRNAs have elongated poly(A) tails in CNOT2-depleted cells and that introduction of CNOT2 WT or a non-phosphorylatable mutant, but not phosphomimetic CNOT2, renders their poly(A) tail lengths comparable to those in control HeLa cells. Consistent with this, the CCR4-NOT complex containing phosphomimetic CNOT2 exhibits less deadenylase activity than that containing CNOT2 WT. These data suggest that CCR4-NOT complex deadenylase activity is regulated by post-translational modification, yielding dynamic control of mRNA deadenylation
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
Possible interpretations of the joint observations of UHECR arrival directions using data recorded at the Telescope Array and the Pierre Auger Observatory
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