統合失調症患者の就労関連技能へ影響を及ぼす要因の検討

研究論文Original Articles　本研究は，統合失調症患者の就労関連技能に対し影響を及ぼす要因である認知機能，精神症状の関連性を明らかにすることを目的に仮説モデルを作成し，検討を実施した．対象者57 名に対し基本情報と就労関連技能（LASMI），社会認知機能（NMT，SCSQ），神経認知機能（BACS），全般的機能（GAF）を測定し，就労関連技能と各測定項目間の相関関係を確認した上で構造方程式モデリングを用い解析した．その結果, 就労関連技能へ直接影響を及ぼす因子として，社会認知機能のうち表情認知，原因帰属バイアスの指標である敵意バイアスと全般的機能が抽出された．また就労関連技能に対し，敵意バイアスを介し，他者の心を推測する心の理論と神経認知障害が間接的に影響を及ぼす認知機能間の関係性が明らかになった．本研究で得られた就労関連技能へ影響を及ぼす要因のモデルにより，作業療法士の統合失調症患者に対する就労支援の際，評価と介入において有用であると考えられた．　This present study aimed to develop and review a theoretical model with the goal of revealing the relationship among the key factors influencing the work-related abilities of patients with schizophrenia, namely cognitive function and psychiatric symptoms. In total, 57 participants were recruited in the present study. The analyzed measures included standard information, work-related ability, social cognitive function, neurocognitive function, and general function. After confirming the correlation between the work-related ability and each of the measurement items, these were further analyzed using structural equation modeling. As a result, the general function and the social cognitive function elements of facial expression recognition function and hostility bias—an indicator of causal attribution bias—were extracted as factors directly influencing the work-related ability. Furthermore, the relationship between the cognitive functions that were indirectly affected by neurocognitive disorder and the theory of mind for guessing the mental states of others was revealed through the hostility bias. These present findings indicated that this model of the key factors influencing the work-related ability in schizophrenia will be useful for measures of assessment and intervention by occupational therapists when providing employment support for patients with schizophrenia

Analysis of Chromosome Dynamics during Meiosis I of Arabidopsis thaliana Pollen Mother Cells by Fluorescent In Situ Hybridization(FISH)

Since insertion mutagenesis methods, which enabled us to identify the mutagenized genes routinely, were developed for plants, Arabidopsis thaliana has been playing a central role in plant meiosis research. Though several techniques to analyze meiotic chromosome behavior have been introduced into Arabidopsis research since Ross et al. reported the method to observe male meiotic chromosomes of this plant through light microscope in 1996 (Chromosome Res. 4-507-516), intimate analysis of the chromosome behavior has not been accomplished. Taking advantage of the recent development of new nucleotides labeled with fluorescent dyes, we investigated chromosome behavior during male meiosis by multicolor FISH. Telomeres found around nucleoli in premeiotic interphase cells dispersed after entering meiosis, then clustered in a bouquet-like configuration. Statistically, telomeres of homologous chromosomes paired earlier than centromeres, but when respective chromosomes were examined, the telomeres were not always quick to pair. At early prophase I, possibly at around the zygotene stage, the signals from telomeres reduced to less than ten. This reduction suggests that the paired telomeres of homologous chromosomes temporally associate with other telomeres to look for their real partners. When homologous chromosomes separated at anaphase I, telomeres were always last to segregate. This suggested that there was unknown interaction between the telomeres of homologs, connecting them until anaphase I started

Recent Results from LHD Experiment with Emphasis on Relation to Theory from Experimentalist’s View

he Large Helical Device (LHD) has been extending an operational regime of net-current free plasmas towardsthe fusion relevant condition with taking advantage of a net current-free heliotron concept and employing a superconducting coil system. Heating capability has exceeded 10 MW and the central ion and electron temperatureshave reached 7 and 10 keV, respectively. The maximum value of β and pulse length have been extended to 3.2% and 150 s, respectively. Many encouraging physical findings have been obtained. Topics from recent experiments, which should be emphasized from the aspect of theoretical approaches, are reviewed. Those are (1) Prominent features in the inward shifted configuration, i.e., mitigation of an ideal interchange mode in the configuration with magnetic hill, and confinement improvement due to suppression of both anomalous and neoclassical transport, (2) Demonstration ofbifurcation of radial electric field and associated formation of an internal transport barrier, and (3) Dynamics of magnetic islands and clarification of the role of separatrix

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