AN AUTOPSY CASE OF PORTOPULMONARY HYPERTENSION ASSOCIATED WITH ALCOHOLIC LIVER CIRRHOSIS

We report an autopsy case of pulmonary pexogenic arteriopathy associated with portal hypertension due to alcoholic liver cirrhosis, termed portopulmonary hypertension (PPHT). A 49-year-old man who has had alcoholic liver cirrhosis for 10 years complained of severe dyspnea (Fletcher-Hugh-Jones V). Chest CT revealed marked enlargement of bilateral hilar pulmonary arteries and cardiomegaly associated with right ventricular hypertrophy. The patient died from hepatic. encephalopathy and respiratory failure. Autopsy c1early revealed the wall thickness of pulmonary small vessels diffusely in peripheral fields on cut surfaces and marked dilatation of the main pulmonary artery, together with liver cirrhosis. Microscopically, the pulmonary small arteries demonstrated grade 5 pulmonary plexogenic arteriopathy inc1uding plexiform lesions and a micronodule resembling an arachnoid granulation or meningioma throughout the lungs. This case suggested that a typical plexogenic arteriopathy morphologically and definitely contributed to confirm PPHT, although the patient was c1inically suspected of hepatopulmonary syndrome (HPS)

Time-dependent approach to many-particle tunneling in one-dimension

Employing the time-dependent approach, we investigate a quantum tunneling decay of many-particle systems. We apply it to a one-dimensional three-body problem with a heavy core nucleus and two valence protons. We calculate the decay width for two-proton emission from the survival probability, which well obeys the exponential decay-law after a sufficient time. The effect of the correlation between the two emitted protons is also studied by observing the time evolution of the two-particle density distribution. It is shown that the pairing correlation significantly enhances the probability for the simultaneous diproton decay.Comment: 9 pages, 10 eps figure

Temperature Changes in Brown Adipocytes Detected with a Bimaterial Microcantilever

AbstractMammalian cells must produce heat to maintain body temperature and support other biological activities. Methods to measure a cell’s thermogenic ability by inserting a thermometer into the cell or measuring the rate of oxygen consumption in a closed vessel can disturb its natural state. Here, we developed a noninvasive system for measuring a cell’s heat production with a bimaterial microcantilever. This method is suitable for investigating the heat-generating properties of cells in their native state, because changes in cell temperature can be measured from the bending of the microcantilever, without damaging the cell and restricting its supply of dissolved oxygen. Thus, we were able to measure increases in cell temperature of <1 K in a small number of murine brown adipocytes (n = 4–7 cells) stimulated with norepinephrine, and observed a slow increase in temperature over several hours. This long-term heat production suggests that, in addition to converting fatty acids into heat energy, brown adipocytes may also adjust protein expression to raise their own temperature, to generate more heat. We expect this bimaterial microcantilever system to prove useful for determining a cell’s state by measuring thermal characteristics

Lesson Study Manual for Teacher Educators International Edition

1. 授業研究への誘い －本マニュアルの構成と見方 － … 1 2. なぜ教師教育者に授業研究が必要なのか … 3 3. 授業研究の手順 … 5 　ステップ1　授業研究の組織を作る … 5 　ステップ2　事前協議会を行う … 7 　ステップ3　研究授業を実施し，観察する … 11 　ステップ4　事後協議会を行う … 15 　ステップ5　自分の授業を見直し，改善していく … 19 　ステップ6　授業研究の仲間を増やし，拡げる … 20 ４．おわりに … 22 ５．よくあるＱ＆Ａ … 23 執筆者・翻訳者一覧 … 2

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