Molecular and Genetic Interactions between CCN2 and CCN3 behind Their Yin-Yang Collaboration

Cellular communication network factor (CCN) 2 and 3 are the members of the CCN family that conduct the harmonized development of a variety of tissues and organs under interaction with multiple biomolecules in the microenvironment. Despite their striking structural similarities, these two members show contrastive molecular functions as well as temporospatial emergence in living tissues. Typically, CCN2 promotes cell growth, whereas CCN3 restrains it. Where CCN2 is produced, CCN3 disappears. Nevertheless, these two proteins collaborate together to execute their mission in a yin-yang fashion. The apparent functional counteractions of CCN2 and CCN3 can be ascribed to their direct molecular interaction and interference over the cofactors that are shared by the two. Recent studies have revealed the mutual negative regulation systems between CCN2 and CCN3. Moreover, the simultaneous and bidirectional regulatory system of CCN2 and CCN3 is also being clarified. It is of particular note that these regulations were found to be closely associated with glycolysis, a fundamental procedure of energy metabolism. Here, the molecular interplay and metabolic gene regulation that enable the yin-yang collaboration of CCN2 and CCN3 typically found in cartilage development/regeneration and fibrosis are described

Retrotransposons Manipulating Mammalian Skeletal Development in Chondrocytes

Retrotransposons are genetic elements that copy and paste themselves in the host genome through transcription, reverse-transcription, and integration processes. Along with their proliferation in the genome, retrotransposons inevitably modify host genes around the integration sites, and occasionally create novel genes. Even now, a number of retrotransposons are still actively editing our genomes. As such, their profound role in the evolution of mammalian genomes is obvious; thus, their contribution to mammalian skeletal evolution and development is also unquestionable. In mammals, most of the skeletal parts are formed and grown through a process entitled endochondral ossification, in which chondrocytes play central roles. In this review, current knowledge on the evolutional, physiological, and pathological roles of retrotransposons in mammalian chondrocyte differentiation and cartilage development is summarized. The possible biological impact of these mobile genetic elements in the future is also discussed

Investigation of electrical transport in anodized single TiO2 nanotubes

Electrical transport in anodized single titania nanotube (TNT) free from any structural effects of titania nanotube array (TNA) was investigated. An anodized TNA was disassembled into single TNTs with two-step anodization technique. Then, single TNT bridges between gold electrodes with a gap of 500 nm were prepared by dielectrophoretic alignment. Quantitative assessment of electron mobility inside single anatase and rutile TNT was carried out by 2-probe current-voltage measurement and analysis based on a metal-semiconductor-metal circuit model with Schottky barriers. Our approach to intrinsic electrical transport of single nanotube is quite effective for understanding the electronic and optical properties of TNA

The habu genome reveals accelerated evolution of venom protein genes

Evolution of novel traits is a challenging subject in biological research. Several snake lineages developed elaborate venom systems to deliver complex protein mixtures for prey capture. To understand mechanisms involved in snake venom evolution, we decoded here the ~1.4-Gb genome of a habu, Protobothrops flavoviridis. We identified 60 snake venom protein genes (SV) and 224 non-venom paralogs (NV), belonging to 18 gene families. Molecular phylogeny reveals early divergence of SV and NV genes, suggesting that one of the four copies generated through two rounds of whole-genome duplication was modified for use as a toxin. Among them, both SV and NV genes in four major components were extensively duplicated after their diversification, but accelerated evolution is evident exclusively in the SV genes. Both venom-related SV and NV genes are significantly enriched in microchromosomes. The present study thus provides a genetic background for evolution of snake venom composition

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

「緩和ケアを推進する看護師教育プログラム」の評価 : 修了者およびその上司への調査から

京都府立医科大学医学部看護学科京都府立医科大学附属病院看護部京都府立医科大学看護実践キャリア開発センター京都府立医科大学附属病院地域医療推進部School of Nursing, Kyoto Prefectural University of MedicineDepartment of Nursing, University Hospital Kyoto Prefectural University of MedicineKyoto Prefectural University of Medicine, Career Development Center for NursingPromotion Division of Regional Medicine, University Hospital Kyoto Prefectural University of Medicine　本研究の目的は、「緩和ケア実践看護師養成コース（以下Aコース）」「在宅緩和ケア推進看護師養成コース（以下Bコース）」を受講した修了者とその上司への調査からプログラム評価および看護実践への活用状況を指標にしてプログラムを評価することである。【方法】平成27～31年度の間に京都府立医科大学看護実践キャリア開発センターが開催する「緩和ケアを推進する看護師教育プログラム」のAコースまたはBコースを受講した修了者25名のうち、調査時点で受講時と同じ施設・病院で就労を継続している21名（Aコース14名、Bコース7名）、とその上司21名（Aコース14名、Bコース7名）を研究対象者とした。修了生の施設・病院に質問紙を郵送し、令和3年7月～8月に無記名の自記式質問紙調査を行った。調査項目は、基本属性、カリキュラムについて、教育目標について、受講内容の適切性について、学習内容の臨床での活用について、とした。なお所属する大学の医学倫理審査委員会の承認を得て実施した（ERB-E-444）。【結果】回答者は、Aコース修了者9名、Aコース上司7名、Bコース修了者5名、Bコース上司3名であった。受講した修了者の評価においては、プログラムの内容についてAコースの8割以上が、Bコースの全員が（とても・まあまあ）適切としている。自己能力の発揮状況について、Aコースは4～6割、Bコースについては4～8割ができているとしている。　上司からの評価では、両コースとも受講した講義・演習・実習が7割程度現在の看護実践に役立っていると答えた。期待される能力については両コースとも8割以上が現在の看護活動に活きていると答えた。【結論】平成27年度から開始された「緩和ケアを推進する看護師教育プログラム」に対して、受講した修了者とその上司に，研修が有用であったかを問うたところ、受講した修了者はプログラムの内容が看護の実践で活かされていると実感していることが明らかとなった。さらに、上司は、受講した修了者が研修を踏まえた看護実践ができていると評価していることが明らかになった。修了者、上司の評価からプログラムの効果を評価することができた

High-purity hydrogen generation by ultraviolet illumination with the membrane composed of titanium dioxide nanotube array and Pd layer

High-purity hydrogen generation was observed by using a membrane composed of a bilayer of an anodized titanium dioxide nanotube array (TNA) and a hydrogen permeable metal. This membrane was fabricated by transferring a TNA embedded in a titanium foil onto a sputtered 10-μm-thick palladium film. Alcohols are reformed photocatalytically and concurrently generated hydrogen is purified through the Pd layer. H2 with a purity of more than 99% was obtained from liquid alcohols under ultraviolet illumination onto the membrane. Thus, we demonstrated the integration of photocatalytic hydrogen production and purification within a single membrane