局所温度制御デバイスの製作および熱ショック反応の計測

学位の種別: 課程博士審査委員会委員 : （主査）東京大学教授 金 範埈, 東京大学教授 藤井 輝夫, 東京大学教授 神保 泰彦, 東京大学教授 酒井 康行, 東京大学准教授 日暮 栄治, 東京大学准教授 小林 英津子University of Tokyo(東京大学

Thermal analysis, design and fabrication of microfluidic device with local temperature controls

This paper reports a microfluidic device with local temperature controls to stimulate bio-cells by heat. Thermal analysis on temperature distributions of microheaters as well as inside of fluidic channels was carried out. Moreover, temperature in microfluidic device was measured by on-chip resistive thermometers

Intestinal Tuberculosis with Hoarseness as a Chief Complaint due to Mediastinal Lymphadenitis

A 68-year-old woman was admitted to our hospital complaining of hoarseness. A chest X-ray detected an abnormal shadow on the upper right lung. Bronchoscopic examination revealed that the left vocal cord was fixed in the paramedian position, and therefore left recurrent nerve paralysis was suspected. Lymphadenopathy was found in the left supraclavicular area. Chest computed tomography showed that the pretracheal and subaortic lymph nodes were swollen. Gastroendoscopy showed a 2-cm protruding lesion with ulceration on the upper esophagus. Histological examination of the supraclavicular lymph nodes and biopsy specimens from the esophagus revealed non-specific inflammation. PET-CT showed abnormal accumulations not only on the upper right lung but also on the lower right of the abdomen. Colonoscopy was performed and multiple erosions on the terminal ileum were found. Polymerase chain reaction analysis of a specimen biopsied from the erosion of the terminal ileum was positive for Mycobacterium tuberculosis and intestinal tuberculosis was diagnosed. The patient was then treated with anti-tuberculous therapy. After treatment, the erosions on the terminal ileum, the swelling of the mediastinal lymphadenopathy, and the esophageal ulcer were all improved. The hoarseness was subsequently relieved. This is the first report of intestinal tuberculosis with hoarseness as a chief complaint due to mediastinal lymphadenitis

温泉排水由来の酵母による廃糖蜜からエタノール生産ならびに,55℃でエタノール発酵を認めた新規酵母株の分子系統解析

東京水産大学食品生産学科東京水産大学食品生産学科東京水産大学食品生産学

水圏環境における耐塩性・発酵性酵母の分布

東京水産大学生物資源化学講座東京水産大学生物資源化学講座東京水産大学生物資源化学講

LOCALIZED EXPRESSION OF HEAT SHOCK PROTEIN IN CELL POPULATION BY MICRO HEATER DEVICE

This paper reports on the localized expression of heat shock proteins (HSPs) in a cell population on a micron-scale. Thermal stimulation was realized by micro heaters on cells in microfluidic channels to investigate cell-cell interactions with precise temperature control of microfluidic channels utilizing temperature sensor

Cell surface markers of functional phenotypic corneal endothelial cells. Invest Ophthalmol Vis Sci 2014

PURPOSE. Cultured human corneal endothelial cells (HCECs) are anticipated to serve as an alternative to donor corneas for the treatment of corneal endothelial dysfunction. However, corneal endothelial cells (CECs) tend to exhibit fibroblastic transformation, thereby losing their functional phenotype when cultured. The purpose of this study was to investigate the usefulness of surface markers of CECs displaying fibroblastic phenotypes as a means of cell characterization. METHODS. The expression levels of 242 cell surface antigens were screened in cultured human and monkey CECs using flow cytometry. An expression intensity ratio of nonfibroblastic/ fibroblastic CECs > 2 and of fibroblastic/nonfibroblastic CECs > 2 were selected as indicating nonfibroblastic and fibroblastic markers, respectively. Nonfibroblastic and fibroblastic CECs were mixed, and CD73-positive and -negative cells were sorted using flow cytometry and further cultured. The functional phenotype of the sorted cells was evaluated according to morphology and the expression of function-related (Na þ /K þ -ATPase and ZO-1) and fibroblastic (type I collagen and fibronectin) markers. RESULTS. Flow cytometry analysis demonstrated that CD98, CD166, and CD340 are elevated in HCECs of nonfibroblastic phenotype, while CD9, CD49e, CD44, and CD73 are markers of fibroblastic phenotype HCECs. The CECs that sorted as CD73-negative exhibited normal hexagonal morphology and expressed functional markers, whereas CECs that sorted as CD73-positive exhibited the fibroblastic phenotype. CONCLUSIONS. These markers will be useful for quality control to characterize the phenotype of cells destined for tissue engineering-based therapy. In addition, this selection protocol will provide a novel method for purification of functional cells

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

Phase Transformation of MoSi2 Phase in MoSi2/Mo5Si3 Eutectic Alloy Containing Nb

Role of ternary solute element Nb on the C40→C11b phase transformation of the MoSi2 phase in MoSi2/Mo5Si3 eutectic alloys which occurs during heat treatment is discussed in this paper. In the case of stoichiometric MoSi2 a mixture of C40 and C11b phases can be prepared by low-pressure plasma spraying method, in which phase transformation from the metastable C40 to stable C11b is recognized during heating at around 800°C. It is found that the MoSi2 phase in an as-cast eutectic MoSi2/Mo5Si3 alloy with 8.5 at%Nb consist only of metastable C40 phase. The transformation from C40 to C11b in this alloy does not occur by heating up to 1200°C but a portion transforms into C11b by heating at 1400°C. It is shown that the Nb concentration in C40 phase is higher than that in C11b phase in this alloy, which must be relevant to the observed transformation behavior