アカスタ片麻岩体苦鉄質岩の岩石学的・地球化学的特徴から示唆される冥王代マントル進化

学位の種別: 課程博士審査委員会委員 : （主査）東京大学教授 平田 岳史, 東京大学准教授 小宮 剛, 東京大学教授 佐野 有司, 東京大学教授 磯崎 行雄, 東京大学講師 飯塚 毅University of Tokyo(東京大学

Geology of the Eoarchean, >3.95Ga, Nulliak supracrustal rocks in the Saglek Block, northern Labrador, Canada: the oldest geological evidence for plate tectonics

The Earth is a unique planet, which has been highly evolved, diversified and complicated through geologic time, and underwent many key events, including giant impact, magma ocean, core formation, large-scale mantle differentiation and late heavy bombardment, especially in its dawn. But, our knowledge of early Earth is limited due to the lack of the Hadean supracrustal rocks. The supracrustal rocks with the Eoarchean ages provide key evidence for the Earth's early evolution, but few supracrustal rocks have been comprehensively investigated. Therefore, we mapped in seven areas of the Saglek Block, northern Labrador, where ancient supracrustal sequences are interleaved with a diverse assemblage of orthogneisses. Early studies suggested that some of them have the Mesoarchean ages because of the lack of the Mesoarchean Saglek dyke, but we found the Saglek dykes in the areas to recognize the Eoarchean Nulliak supracrustal rocks and Uivak Gneiss in all the areas. Recent reassessment of U–Pb dating and cathodoluminescence observation of zircons from the oldest suites of the Uivak Gneiss showed that the Uivak Gneiss has the Eoarchean age, > 3.95 Ga, and forms the Iqaluk–Uivak Gneiss series. Because our geological survey clearly showed that the Iqaluk–Uivak Gneisses were intruded into the Nulliak supracrustal belts, the Nulliak supracrustal rocks are the oldest supracrustal rock in the world. The supracrustal belts consist of piles of fault-bounded blocks, which are composed of the ultramafic rocks, mafic rocks and sedimentary rocks in ascending order, similar to modern ocean plate stratigraphy (OPS). In addition, small-scale duplex structures are found over the areas. The presence of duplex structure and OPS indicates that the > 3.95 Ga Nulliak supracrustal belts originate from an accretionary complex. The presence of the accretionary complex, ophiolite and granitic continental crust provides the oldest evidence for the plate tectonics on the early Earth

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

The Effects of γ-tocopherol Administration on Pretibial Edema in Young Women with Premenstrual Syndrome

Gamma-tocopherol is largely metabolized to 2,7,8-trimethyl-2-(2\u27-carboxyethyl)-6-hydroxychroman (γ-CEHC), which has natriuretic activity that is mediated via inhibition of 70 pS ATP-sensitive K+ channels in the thick ascending limb of the loop of Henle. However, the effects of γ-tocopherol administration on edema are unclear. To determine the effects of γ-tocopherol administration on pretibial edema, we measured urinary γ-CEHC concentration by high-performance liquid chromatography with electrochemical detection (HPLC-ECD) after administration of γ-tocopherol. Twenty young women who had a history of pretibial edema due to premenstrual syndrome were randomly divided into two groups. The γ-tocopherol group received 4 "γ-tocopherol capsules" (each containing 100mg of γ-tocopherol), and the control group received 4 "placebo capsules" (each containing 250mg of soybean oil) per day for 7 days. Urinary sodium and potassium secretion and urine volume did not increase after cessation of γ-tocopherol administration, yet the degree of pretibial edema improved in all participants in the γ-tocopherol group. The serum γ-tocopherol concentration significantly increased in the γ-tocopherol group. Urinary excretion of γ-CEHC significantly increased after γ-tocopherol administration. Our results suggest that orally administered γ-tocopherol on renal sodium handling is not apparent, but γ-tocopherol is a precursor of prolonged natriuresis of γ-CEHC and may be effective for edema