Overview of the Nishinoshima comprehensive scientific research project, in 2021

小笠原諸島の西之島は2013年から2021年までに5度の噴火で元の陸地は全域が溶岩に覆われ、火山灰が堆積して大地がリセットされた。この島は太平洋上に孤立し、最寄の陸地から130kmも隔離された無人島であることから、海洋島における生態系の一次遷移を人為的影響のない状態で観察できる世界に例のない場所と言える。生物、地質及び火山活動における網羅的な分野の調査を噴火直後から実施することで、火山島の形成過程、噴火による生物相への影響、新たな遷移の開始時点の状況等を把握することができる。そこで、西之島の自然環境の最新情報を記録して科学的価値を評価するための総合学術調査が企画され、2019年調査に続き、2021年7月、9月の2度にわたり、モニタリング調査を実施した。新規に海域調査を実施したほか、UAVやAUVを活用した新規の調査も取り入れた。本調査は環境省とともに、東京大学及び日本放送協会との連携により行われている。調査の実施に当たっては、火山活動が活発な島における安全管理には十分配慮したほか、調査による人為的な影響を最小限に抑えるため、外来生物の侵入を防止するための検疫を徹底した。Nishinoshima Island in the Ogasawara Islands has erupted five times between 2013 and 2021. The entire original land area was covered by lava, as well as by thick deposits of volcanic ash that have reset the land surface. As an uninhabited island isolated in the Pacific Ocean and 130 km apart from the nearest land, it offers an unique opportunity to observe primary succession on an oceanic island without human impacts. Thus, it is important to conduct comprehensive field surveys on its biota, geology and volcanic activities immediately after the eruption in order to understand the formation process of the volcanic island, the impact of the eruption on the biota, and the situations at the start of primary succession. Therefore, a comprehensive scientific survey was planned to record the latest information on the nature of Nishinoshima Island and assess its scientific value. It was conducted twice, in July and September 2021, following the 2019 survey. This is the first survey of marine biota around Nishinoshima Island, and UAVs and AUVs were also actively used to conduct the survey safely during volcanic activity. The survey was carried out in collaboration with the Ministry of the Environment, the University of Tokyo and the Japan Broadcasting Corporation (NHK). In carrying out the survey, sufficient attention was paid to safety management on the volcanically active island, and quarantine was also strictly enforced as a measure to prevent the invasion of alien species in order to eliminate any human impact of the survey.departmental bulletin pape

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

Live Imaging of Radiation-Induced Apoptosis by Yolk Injection of Acridine Orange in the Developing Optic Tectum of Medaka

For sequential observation of radiation-induced apoptosis in a living embryo, we injected Acridine Orange (AO) solution into the yolk of embryo and visualized radiation-induced apoptosis in developing optic tectum (OT). Medaka embryos at stage 28, when neural cells proliferate rapidly in the OT, were irradiated with 5 Gy X-rays which is non-lethal dose for irradiated embryos at hatching. The irradiated embryos hatched normally without morphological abnormalities in their brains, even though a large number of apoptotic cells were induced transiently in OT. By yolk injection, apoptotic cells in OT were distinguished as AO-positive small nuclei at 3 h after irradiation. At 8-10 h after irradiation, AO-positive rosette-shaped clusters were obviously distinguished in marginal tectal regions of OT where cells are proliferating intensely. The AO-positive clusters became bigger and more obvious, but its number did not increase up to 24 h after irradiation and completely disappeared up to 49 h after irradiation. This characteristic appearance of the AO-positive nuclei/clusters is in a good agreement with our previous results based on the examination of fixed specimens stained with AO by injection into the peri-vitelline space, suggesting that the AO-yolk injection method is highly reliable for detecting apoptotic cells in living embryos. The live imaging of apoptotic cells in developing Medaka embryos by AO-yolk injection method is expected to reveal more in details of dynamics of the apoptotic responses in the irradiated brain and other tissues

Live imaging of AO-stained apoptosis and the assessment of cell proliferation after low dose irradiation during a period of extreme growth of tectum mesencephali in the Medaka

The 2nd Asian Congress of Radiation Researc