創作活動における内発的動機づけ機構の解明

Intrinsic motivation is a fundamental basis for creativity. However, little is known about which factors are essential in a behavioral environment for creative activity. I propose a hypothesis that intrinsic motivation in creative activity is facilitated by a higher variety of expressions using simpler rules. To examine the hypothesis, I conducted a novel human behavioral experiment with 42 participants using the original game designed based on the Game of Life cellular automata. The simplicity of a rule is controlled by the parameters of state transition function and quantified by the complexity measures formulated in the theory of cellular automata. The variety of expression is quantified by the features of the cell states, such as entropy of local patterns and empowerment. The degree of intrinsic motivation is measured by subjective enjoyment, playing time, and frequency of touch interaction. The results of two-way ANOVA of the scores of enjoyment for the four rules showed that participants were more intrinsically motivated with a higher variety of expression and a simpler rule, which supports the hypothesis. Regression analyses revealed that the variety of local patterns was a major factor for subjective enjoyment and also suggested two types of subjects. Subgroup analyses showed that participants had opposite preferences for simple and complex rules. The present results are generally consistent with the hypothesis but point to the necessity of considering individual differences.Okinawa Institute of Science and Technology Graduate Universit

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

Highly sulfated hyaluronic acid maintains human induced pluripotent stem cells under feeder-free and bFGF-free conditions

Human induced pluripotent stem (hiPS) cells are attracting attention as a tool for regenerative medicine. However, several problems need to be overcome for their widespread and safe use, for example, the high cost of maintaining hiPS cells and the possibility of xenogeneic cell contamination in hiPS cell cultures. One of the main contributors to the high cost of maintaining hiPS cells is basic fibroblast growth factor (bFGF), which is essential for such cultures. Xenogeneic contamination can occur because of the use of mouse-derived feeder cells to culture hiPS cells. To overcome the problems of cell culture cost and xenogeneic contamination, we have developed a novel culture method in which the undifferentiated state and pluripotency of hiPS cells can be maintained under feeder-free and bFGF-free conditions. Our new approach involves the addition to the culture medium of highly sulfated hyaluronic acid (HA-HS), in which the hydroxyl groups of d-glucuronic acid (GlcA) and N-acetyl-d-glucosamine (GlcNAc) are chemically sulfated. HA-HS promotes bFGF signaling and maintains the undifferentiated state and pluripotency of hiPS cells under feeder-free and bFGF-free conditions. By contrast, non-sulfated hyaluronic acid and low sulfated hyaluronic acid do not maintain the undifferentiated state and pluripotency of hiPS cells. These results indicate that the maintenance of hiPS cells under feeder-free and bFGF-free conditions is an HA-HS specific effect. This study is the first to demonstrate the effects of sulfated hyaluronic acid on mammalian pluripotent stem cells, and provides a novel method for maintaining hiPS cells using HA-HS

Carriers of HLA-DRB1*04:05 have a better clinical response to abatacept in rheumatoid arthritis

Abstract HLA-DRB1 shared epitope risk alleles are the strongest genetic risk factors for rheumatoid arthritis (RA) and potential biomarkers for treatment response to biological disease-modifying antirheumatic drugs (bDMARDs). This study aimed to investigate the association between treatment response and individual HLA-DRB1 alleles in RA patients receiving different bDMARDs. We recruited 106 patients with active RA who had started abatacept, tocilizumab, or TNF inhibitors as a first-line bDMARDs. We examined the relationship between Simplified Disease Activity Index (SDAI) improvement at 3 months and HLA-DRB1 allele carriage. The results revealed that the HLA-DRB1*04:05 allele, a shared-epitope allele, was significantly associated with better SDAI improvement only after abatacept treatment (SDAI improvement 28.5% without the allele vs 59.8% with allele, p = 0.003). However, no significant association was found with other treatments. Both multivariate linear regression and mediation analysis confirmed that the HLA-DRB1*04:05 allele was independently associated with abatacept treatment response, regardless of anti-CCP antibody titers. The study concluded that in patients with RA receiving their first-line bDMARD treatment, carrying the HLA-DRB1*04:05 allele was associated with better SDAI improvement specifically in abatacept-treated patients. These disease-risk HLA alleles have the potential to serve as genomic biomarkers for predicting treatment response with co-stimulation blockage therapy

Table_1_Dyslexia and dysgraphia of primary progressive aphasia in Chinese: A systematic review.docx

IntroductionCurrently, little is known about Chinese-speaking primary progressive aphasia (PPA) patients compared to patients who speak Indo-European languages. We examined the demographics and clinical manifestations, particularly reading and writing characteristics, of Chinese patients with PPA over the last two decades to establish a comprehensive profile and improve diagnosis and care.MethodsWe reviewed the demographic features, clinical manifestations, and radiological features of Chinese-speaking PPA patients from 56 articles published since 1994. We then summarized the specific reading and writing errors of Chinese-speaking patients.ResultsThe average age of onset for Chinese-speaking patients was in their early 60's, and there were slightly more male patients than female patients. The core symptoms and images of Chinese-speaking patients were similar to those of patients who speak Indo-European languages. Reading and writing error patterns differed due to Chinese's distinct tone and orthography. The types of reading errors reported in Chinese-speaking patients with PPA included tonal errors, regularization errors, visually related errors, semantic errors, phonological errors, unrelated errors, and non-response. Among these errors, regularization errors were the most common in semantic variant PPA, and tonal errors were specific to Chinese. Writing errors mainly consisted of non-character errors (stroke, radical/component, visual, pictograph, dyskinetic errors, and spatial errors), phonologically plausible errors, orthographically similar errors, semantic errors, compound word errors, sequence errors, unrelated errors, and non-response.ConclusionThis paper provides the latest comprehensive demographic information and unique presentations on the reading and writing of Chinese-speaking patients with PPA. More detailed studies are needed to address the frequency of errors in reading and writing and their anatomical substrates.</p

The Reliabilities of Several Measurement Methods of Cervical Sagittal Alignment in Cases with Cervical Spine Rotation Using X-ray Findings in Cervical Spine Disorders

Introduction: Several measurement methods designed to provide an understanding of cervical sagittal alignment have been reported, but few studies have compared the reliabilities of these measurement methods. The purpose of the present study was to investigate the intraexaminer and interexaminer reliabilities of several cervical sagittal alignment measurement methods and of the rotated cervical spine using plain lateral cervical spine X-rays of patients with cervical spine disorders. Methods: Five different measurement methods (Borden's method; Ishihara index method (Ishihara method); C2-7 Cobb method (C2-7 Cobb); posterior tangent method: absolute rotation angle C2-7 (ARA); and classification of cervical spine alignment (CCSA)) were applied by seven examiners to plain lateral cervical spine X-rays of 20 patients (10 randomly extracted cases from a rotated cervical spine group and 10 from a nonrotated group) with cervical spine disorders. Case 1 and Case 2 intraclass correlation coefficients (ICCs) were used to analyze intraexaminer and interexaminer reliabilities. The necessary number of measurements and the necessary number of examiners were also determined. The target coefficient of correlation was set at 0.81 (almost perfect ICC). Results: In both groups, an ICC(1, 1) 0.81 was obtained with Borden's method, the Ishihara method, C2-7 Cobb, and ARA by all examiners. The necessary number of measurements was 1. With CCSA, a kappa coefficient of at least 0.9 was obtained. In both groups, with Borden's method, the Ishihara method, C2-7 Cobb, and ARA, the ICC(2, 1) was 0.9, indicating that the necessary number of examiners was 1. The standard error of measurement (SEM) was lowest with Borden's method, and the Ishihara method and C2-7 Cobb had almost the same values. Conclusions: Among cervical sagittal alignment measurement methods for cervical spine disorders, regardless of cervical spine rotation, Borden's method, Ishihara method, and C2-7 Cobb offer stronger reliability in terms of the ICC and SEM