2型糖尿病入院患者の食後血糖値に影響を及ぼす栄養素等の要因

本研究は2型糖尿病患者の食後血糖値に影響する栄養素について明らかにすることを目的とした。対象は入院中の2型糖尿病患者で、食前および食後の血糖測定を実施した22名であった。分析は食後血糖値を従属変数に、エネルギー、たんぱく質、脂質、炭水化物、食物繊維、年齢、BMI、HbA1c、食前血糖値を独立変数とした重回帰分析を用いた。結果は全体としては食後血糖に影響する有意な要因は認められなかった。一方、朝食においてHbA1cと食物繊維に有意な値が認められた。すなわち、2型糖尿病入院患者において、食後血糖値を抑制する栄養素として最も影響を及ぼすのは食物繊維であると考えられる

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

A framework of high-quality transition fault ATPG for scan circuits

ABSTRACT This paper presents a framework of high-quality test generation for transition faults in full scan circuits. This work assumes a restricted broad-side testing as a test application method for two-pattern tests where control of primary inputs and observation of primary outputs are restricted. Because we use a modified time expansion model of a circuit-under-test during ATPG and fault simulation, conventional ATPG and fault simulation programs can work with minor change. The proposed ATPG method consists of two algorithms, which are activation-first and propagation-first, and for each fault it is decided which algorithm should be applied. Test patterns are generated such that transition faults with small delay can be detected, i.e. a path for fault excitation and propagation becomes as long as possible. In experimental results we evaluate test patterns generated by the proposed method using SDQM that calculates delay test quality, and show the effectiveness of the proposed method

Degradation of Tyrosinase by Melanosomal pH Change and a New Mechanism of Whitening with Propylparaben

Many active cosmetic ingredients formulated as medicated whitening products (quasi-drugs) achieve their effect through inhibition of tyrosinase activity, but no products can achieve this effect through degradation of intramelanosomal tyrosinase. Melanin is synthesized by tyrosinase, which is localized to the membrane of melanosomes in melanocytes. It has been reported that the optimal pH of tyrosinase activity is nearly neutral and decreases under acidic conditions. The environment in melanosomes that tyrosinase acts on has attracted attention from researchers. We found that tyrosinase was degraded by acidification of melanosomes, thereby decreasing its activity. We found that both inhibitors of aspartic protease and cysteine protease decreased the degradation of tyrosinase. It is thought that aspartic protease and cysteine protease are participating in the degradation of tyrosinase in acid melanosome. Melanosomal pH is regulated by Na+/H+ exchangers and V-ATPase. We investigated the mechanisms of the inhibitory effect of melanin production of propylparaben using B16 melanoma cells. The expression level of mRNA of tyrosinase and related proteins (Trp-1 and Dct) was not affected by propylparaben; however, the protein levels in melanosomes decreased. We investigated the mechanisms of the inhibitory effect of propylparaben on melanin production using B16 melanoma cells. The effects of propylparaben on the mRNA expression of Na+/H+ exchangers and Na+/Ca2+ exchangers, as well as the melanosome pH levels were examined. Propylparaben decreased gene expression in both exchangers. It was confirmed that propylparaben decreased melanosomal pH by staining using an intracellular pH indicator. The results suggest that propylparaben down-regulated melanin production through acidification of melanosomes

Promoting fertility awareness and preconception health using a chatbot: a randomized controlled trial

Research question What are the effects of using a fertility education chatbot, i.e. automatic conversation programme, on knowledge, intentions to improve preconception behaviour and anxiety? Design A three-armed, randomized controlled trial was conducted using an online social research panel. Participants included 927 women aged 20–34 years who were randomly allocated to one of three groups: a fertility education chatbot (intervention group), a document about fertility and preconception health (control group 1) or a document about an irrelevant topic (control group 2). Participants’ scores on the Cardiff Fertility Knowledge Scale and the State-Trait Anxiety Inventory, their intentions to optimize preconception behaviours, e.g. taking folic acid, and the free-text feedback provided by chatbot users were assessed. Results A repeated-measures analysis of variance showed significant fertility knowledge gains after the intervention in the intervention group (+9.1 points) and control group 1 (+14.9 points) but no significant change in control group 2 (+1.1 points). Post-test increases in the intentions to optimize behaviours were significantly higher in the intervention group than in control group 2, and were similar to those in control group 1. Post-test state anxiety scores were significantly lower in the intervention group than in control group 1 and control group 2. User feedbacks about the chatbot suggested technical limitations, e.g. low comprehension of users’ words, and pros and cons of using the chatbot, e.g. convenient versus coldness. Conclusions Providing fertility education using a chatbot improved fertility knowledge and intentions to optimize preconception behaviour without increasing anxiety, but the improvement in knowledge was small. Further technical development and exploration of personal affinity for technology is required