52 research outputs found
選択MBE成長法によるSi基板上GaAsヘテロエピタキシャル層の高品質化に関する研究
University of Tokyo (東京大学
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
Fermentation of Plant Extracts Supplemented with Milk Components by Lactic Acid Bacteria Produces Soluble Agonists for Toll-like Receptor 2 Possibly Suitable for Cosmetics
Stimulation of Toll-like receptor 2 (TLR2) on epidermal keratinocytes results in the tightening of cell–cell junctions between keratinocytes; therefore, appropriate agonists for TLR2 could be promising ingredients for cosmetics. However, a method to produce significant amounts of soluble TLR2 agonists using materials that are suitable for preparing cosmetics has not yet been developed. In this study, we tried to identify appropriate lactic acid bacterial strains and media for fermentation to obtain soluble TLR2 agonists from traditional fermented foods and natural food sources. We found that Lactobacillus delbrueckii subsp. lactis TL24 (TL24) and a combination of hot water extracts of asparagus edible stem and cow skimmed milk were the best strain and culture medium, respectively, for this purpose. The TL24 ferments effectively stimulated TLR2 in HEK293 reporter cells expressing human TLR2 on their surface and also inhibited paracellular molecular transfer in a cell sheet of human primary keratinocytes. Since these effects of the TL24 ferments were suppressed by anti-TLR2 neutralizing antibodies, it is proposed that TL24 ferments elicit these effects via TLR2. Taken together, these results suggest that TL24 ferments containing soluble TLR2 agonists are potential ingredients for cosmetics
Wide Area Ray-Launching for Pilot Pollution Analyses using Adaptive Object Selection
Abstract: We propose a new method of ray-launching estimation for high-speed and highly accurate analysis of pilot pollution, which often occurs in the upper floors of high-rise buildings. Our method simulates radio signals that reach from distant base stations much faster than a conventional raylaunching method. The mechanism of the fast calculation is due to an adaptive object selection approach, which excludes objects that have limited effects on a radio environment in the upper floors of high-rise buildings. It is confirmed that our method can make a calculation more than 20 times faster than a conventional ray-launching method with almost the same accuracy for the case with high base station antennas
Preparation of Biointeractive Glycoprotein-Conjugated Hydrogels through Metabolic Oligosacchalide Engineering
In
the current study, synthetic hydrogels containing metabolically
engineered glycoproteins of mammalian cells were prepared for the
first time and selectin-mediated cell adhesion on the hydrogel was
demonstrated. A culture of HL-60 cells was supplemented with an appropriate
volume of aqueous solution of <i>N</i>-methacryloyl mannosamine
(ManMA) to give a final concentration of 5 mM. The cells were then
incubated for 3 days to deliver methacryloyl groups to the glycoproteins
of the cells. A transparent hydrogel was formed via redox radical
polymerization of methacryloyl functionalized glycoproteins with 2-methacryloyloxyethyl
phosphorylcholine and a cross-linker. Conjugation of the glycoproteins
into the hydrogel was determined using Coomassie brilliant blue (CBB)
and periodic acid–Schiff (PAS) staining. The surface density
of P-selectin glycoprotein ligand-1 (PSGL-1) on the hydrogels was
also detected using gold-colloid-labeled immunoassay. Finally, selectin-mediated
cell adhesion on hydrogels containing glycoproteins was demonstrated.
Selectin-mediated cell adhesion is considered an essential step in
the progression of various diseases; therefore, hydrogels having glycoproteins
could be useful in therapeutic and diagnostic applications
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