Comparison of intra-individual coefficients of variation on the paired sampling data when inter-individual variations are different between measures

Additional file 2. Supplemental figures for the pain intensity data (residual plots, P–P plots and Cook’s distance against leverage/(1-leverage))

Population genetic structure ofYamato-sllijimi clam in Lake Sbinji, Japan

Yamato-shijimiclam Corbicula japonica is the best-known bivalve inhabiting ln brackish estuaries and lakes around Japan and one of the most commercially important species in inland fisheries. Althoughthe amotmt of C japonica from Lake Shinji has accotmted for the large part of the domestic catch, itsamolmt has dramatically fallen in recent years･ This study was conducted to verifythe genetic structtue and reproduction mechanism of C･ japonica, both of which are essential to its stock management in Lake Shinji. Weanalyzed sequence polymorphism of the 588 bp portion ofthemitochondrial DNA cytochrome oxidase subunit I (Col) gene to determinethe population genetic structure of C･ japonica in Lake Shinji･Among a total of 177 C･ japonica specimens collected from 4 colonies, 37 haplotypes were obtained, and 2 major haplotypes were apparent withrelatively highabtmdance in all colonies･ Well correspondingmismatch distributions along the Col gene were determined for the data sets of the individual colonies, and the pairwise population estimates FsT among the individual colonies were also generally low, Such small genetic differentiation of C japonica is derived kom highgeneflow in Lake Shinji, and this could be caused by a lake-wide dispersion of its larvae mediated by the water movements･Article信州大学山地水環境教育研究センター研究報告 6: 115-124(2010)departmental bulletin pape

Prevalence of gastroesophageal reflux disorder in arrhythmic patients and adjunctive effects of proton pump inhibitors on comorbid atrial fibrillation

Background: Although the coexistence of atrial fibrillation (AF) and gastroesophageal reflux disorder (GERD) has been reported, the prevalence of GERD in arrhythmic patients remains unknown. This study aimed to investigate the relationship between GERD and several kinds of arrhythmia, and the therapeutic effects of proton pump inhibitors (PPI) on AF.Methods: In Study 1, patients with various kinds of arrhythmia (n=147) including AF (n=98) were administered a GERD-specific questionnaire (F-scale). In Study 2, patients with AF and GERD (n=27) responded to an AF-specific questionnaire (AFQLQ) before and after the additive PPI therapy to explore the effects of PPI on comorbid AF. In Study 3, device memory was assessed as it is related to PPI administration in pacemaker patients with GERD and AF (n=5) to study the effects of PPI on device-documented AF.Results: Left atrial (LA) size and F-scale scores in AF patients were the largest among the arrhythmic patients in Study 1. Logistic regression analysis showed no independent determinants of GERD. F-scale scores and AFQLQ scores showed temporal and partial correlations and significant improvement after starting PPI in Study 2. However, device interrogation confirmed limited AF improvement by starting PPI in Study 3.Conclusions: GERD is prevalent in AF patients. LA size is not an independent determinant of GERD. Symptoms of AF were improved, whereas device-documented paroxysms of AF were not ameliorated by PPI administration. A large-scale prospective study is required to conclude the efficacy of PPI on the comorbid AF

The relationship between attention and avoidance coping in anorexia nervosa: functional magnetic resonance imaging study

[Background] Numerous studies have demonstrated attentional control difficulties and high avoidance coping in patients with anorexia nervosa. Attention is a critical coping resource because it enables individuals to demonstrate self-control and complete goal-directed behaviours. [Aims] We aimed to examine whether attentional control difficulty is related to high avoidance coping, and investigate the neural underpinnings of attentional control difficulties in individuals with anorexia nervosa. [Method] Twenty-three patients with anorexia nervosa and 17 healthy controls completed questionnaires that assessed attention and coping, and underwent functional magnetic resonance imaging while performing a go/no-go task. [Results] Patients with anorexia nervosa showed weaker attentional control, higher omission error rates and higher avoidance coping compared with healthy controls. Attentional control difficulty was associated with higher avoidance coping in both groups. Functional magnetic resonance imaging analysis showed less deactivation in regions representing internal mental processing, such as the praecuneus, cuneus and left lingual gyrus, during the no-go condition. Moreover, weakened deactivation of the left lingual gyrus was associated with higher commission error rate in the anorexia nervosa group. [Conclusions] Our results suggest that patients with anorexia nervosa may have difficulty in maintaining attention to external ongoing events because of disturbance from internal self-related thought, and support the notion that attentional control difficulties underlie the frequent use of avoidance coping in anorexia nervosa

Cyclic ADP-ribose as a universal calcium signal molecule in the nervous system

金沢大学大学院医学系研究科脳細胞分子学β-NAD+ is as abundant as ATP in neuronal cells. β-NAD+ functions not only as a coenzyme but also as a substrate. β-NAD+-utilizing enzymes are involved in signal transduction. We focus on ADP-ribosyl cyclase/CD38 which synthesizes cyclic ADP-ribose (cADPR), a universal Ca2+ mobilizer from intracellular stores, from β-NAD+. cADPR acts through activation/modulation of ryanodine receptor Ca2+ releasing Ca2+ channels. cADPR synthesis in neuronal cells is stimulated or modulated via different pathways and various factors. Subtype-specific coupling of various neurotransmitter receptors with ADP-ribosyl cyclase confirms the involvement of the enzyme in signal transduction in neurons and glial cells. Moreover, cADPR/CD38 is critical in oxytocin release from the hypothalamic cell dendrites and nerve terminals in the posterior pituitary. Therefore, it is possible that pharmacological manipulation of intracellular cADPR levels through ADP-ribosyl cyclase activity or synthetic cADPR analogues may provide new therapeutic opportunities for treatment of neurodevelopmental disorders. © 2007

LECT2 functions as a hepatokine that links obesity to skeletal muscle insulin resistance

Recent articles have reported an association between fatty liver disease and systemic insulin resistance in humans, but the causal relationship remains unclear. The liver may contribute to muscle insulin resistance by releasing secretory proteins called hepatokines. Here we demonstrate that leukocyte cell-derived chemotaxin 2 (LECT2), an energy-sensing hepatokine, is a link between obesity and skeletal muscle insulin resistance. Circulating LECT2 positively correlated with the severity of both obesity and insulin resistance in humans. LECT2 expression was negatively regulated by starvation-sensing kinase adenosine monophosphate-activated protein kinase in H4IIEC hepatocytes. Genetic deletion of LECT2 in mice increased insulin sensitivity in the skeletal muscle. Treatment with recombinant LECT2 protein impaired insulin signaling via phosphorylation of Jun NH2-terminal kinase in C2C12 myocytes. These results demonstrate the involvement of LECT2 in glucose metabolism and suggest that LECT2 may be a therapeutic target for obesity-associated insulin resistance. © 2014 by the American Diabetes Association

ショク ノ タヨウセイ オ ツイキュウ スル

第13回日本機能性食品医用学会総会会長講

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