Materials science on mille-feullie structure -Developement of next-generation structural materials guided by a new strengthen principle-

金沢大学理工研究域機械工学系新学術領域「ミルフィーユの材料科学」では，ミルフィーユ構造を有する材料にキンクを形成するとその材料が強化されることを謳っている。本研究では，ナノリンクルフィルムの形成過程で「自発的にできた高分子のシワ」が，キンク強化理論で謳われるところの「応力が蓄積されたキンク」であることを計画班の研究者と連携して，実験および測定解析，シミュレーションにより明らかにする。そして，新たな高分子材料の強化法としてナノリンクルを導入し，従来キンク強化が難しいと思われた高分子材料を強化し，新たな高強度材料を創成する。本研究課題では重合阻害剤を溶解させた水面上に紫外線硬化樹脂を展開し，紫外線を照射することでサブミクロンスケールのしわを作製するナノリンクルフィルムをミルフィーユ構造と見立てて，ナノスケールのしわがフィルムの強度向上に寄与するかどうかを解明する研究である。ナノリンクルフィルムの強度を測定する際にナノインデンターを使用したが，ナノインデンターで測定を行うためには，平らなフィルムを作製する必要があった。ナノリンクルフィルムで平らなフィルムを作製することは困難を極めて，ナノインデンターに供する十分な数のフィルムを作製することができなかった。ナノリンクルフィルムの作製プロセスを見直して，平らでナノインデンテーション測定に供しやすいフィルムの作製を行えるようにプロセスの改善を行う必要がある。一方で，試行点数は少ないものの，リンクルのしわの間隔とフィルムの表面弾性率の関係には負の相関があることが分かった。すなわちリンクルのサイズを小さくしていくとフィルムの弾性率は増加した。最も小さな弾性率を示した２マイクロメートルの弾性率は，リンクルがないフィルムの弾性率と等しくなった。すなわちリンクルを作成してもフィルムの弾性率向上は見られなかった。更にリンクルのサイズを小さくし，サブミクロンスケールとすればリンクルの無いフィルムに比べて弾性率の向上が起こるかどうかについて現在検討している。研究課題/領域番号:19H05124, 研究期間(年度):2019-04-01 – 2021-03-31出典：研究課題「高分子ナノリンクルフィルムのシワに応力が集中しキンク強化が起こるという仮説の検証」課題番号19H05124（KAKEN：科学研究費助成事業データベース（国立情報学研究所）） （https://kaken.nii.ac.jp/ja/grant/KAKENHI-PUBLICLY-19H05124/）を加工して作

A Proteomic Approach for Comprehensively Screening Substrates of Protein Kinases Such as Rho-Kinase

BACKGROUND: Protein kinases are major components of signal transduction pathways in multiple cellular processes. Kinases directly interact with and phosphorylate downstream substrates, thus modulating their functions. Despite the importance of identifying substrates in order to more fully understand the signaling network of respective kinases, efficient methods to search for substrates remain poorly explored. METHODOLOGY/PRINCIPAL FINDINGS: We combined mass spectrometry and affinity column chromatography of the catalytic domain of protein kinases to screen potential substrates. Using the active catalytic fragment of Rho-kinase/ROCK/ROK as the model bait, we obtained about 300 interacting proteins from the rat brain cytosol fraction, which included the proteins previously reported as Rho-kinase substrates. Several novel interacting proteins, including doublecortin, were phosphorylated by Rho-kinase both in vitro and in vivo. CONCLUSIONS/SIGNIFICANCE: This method would enable identification of novel specific substrates for kinases such as Rho-kinase with high sensitivity

Инновационный потенциал и инновационная активность вузов УрФО

<p>Characteristics of the study patients.</p

The Overlapping Community Structure of Structural Brain Network in Young Healthy Individuals

Community structure is a universal and significant feature of many complex networks in biology, society, and economics. Community structure has also been revealed in human brain structural and functional networks in previous studies. However, communities overlap and share many edges and nodes. Uncovering the overlapping community structure of complex networks remains largely unknown in human brain networks. Here, using regional gray matter volume, we investigated the structural brain network among 90 brain regions (according to a predefined anatomical atlas) in 462 young, healthy individuals. Overlapped nodes between communities were defined by assuming that nodes (brain regions) can belong to more than one community. We demonstrated that 90 brain regions were organized into 5 overlapping communities associated with several well-known brain systems, such as the auditory/language, visuospatial, emotion, decision-making, social, control of action, memory/learning, and visual systems. The overlapped nodes were mostly involved in an inferior-posterior pattern and were primarily related to auditory and visual perception. The overlapped nodes were mainly attributed to brain regions with higher node degrees and nodal efficiency and played a pivotal role in the flow of informa- tion through the structural brain network. Our results revealed fuzzy boundaries between communities by identifying overlapped nodes and provided new insights into the understanding of the relationship between the structure and function of the human brain. This study provides the first report of the overlapping community structure of the structural network of the human brain

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