36 research outputs found
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
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The process of art-making:An analysis of artist’s modification of conditions in the art-making process
The present study investigated how younger and expert artistscreate artwork, paying special attention to the modification ofconditions in the art-making process. Here, “processmodification” is the means by which artists generate newartistic ideas/concepts by modifying elements of one’s ownprevious artwork. To examine whether younger artists usesuch modifications in the same manner as experts, weinterviewed 28 contemporary artists (including 14 experts).Results revealed that most of the younger artists modifiedtheir work unsystematically. Younger artists drasticallychanged the subject/motif, method, and concept for their newartwork. Experts, in contrast, actively used processmodification to create a new technique and generated a newconcept based on their creative vision
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Cognitive processes of artistic creation: A field study of a traditional Chinese ink painter’s drawing process
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A case study of formation of an art concept by a contemporary artist: Analysis ofthe utilization of drawing in the early phase
When producing a new series of artworks, an artist may engage in a variety of activities in the formation of an art concept.In a specific instance, a contemporary artist was demonstrated first to draw his ideas on paper, as an initial phase ofdeveloping his art concept. This paper utilizes data from a previous study to analyze the drawings and interviews conductedduring this drawing phase. The results show that the artist used various types of modification of his art-making process. Bychanging his own creative activity, the artist often reflected upon his creative process, asking himself what he really wantedto do, and explored new images in response to unexpected findings and the feeling of confusion at his own drawings
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Formation of an art concept: A case study using quantitative analysis of a contemporary artist’s interview data
The process of formation by an artist of an art concept for the
production of a new series of artwork has not yet been
empirically elucidated. The goal of this study is to describe
the process of art concept formation by a contemporary artist
through quantitative analyses of a text corpus based on
interviews with the artist. From an analysis of the frequency
of occurrence of items of vocabulary in the interview data and
the TF-IDF (term frequency–inverse document frequency),
we find that the second of three phases in the artist's creative
process was the most critical for the formation of the art
concept, as also shown in our previous qualitative study.
Further, based on an analysis of co-occurrence frequencies of
words, the structure of the art concept is deduced from the
importance of co-occurring vocabulary. By means of
visualizing the network of co-occurrence analysis, it is
clarified that the feature words "The Large Glass" functioned
in the first phase as the medium for dividing the structure of
the concept into two parts. In the second phase, these two
parts of the structure became integrated into one. In the last
phase, the structure of the concept was elaborated on with the
revived feature words, "White Noise" and "Duchamp"
Proton-pump inhibitors for the treatment of functional dyspepsia
In the Rome III classification, functional dyspepsia (FD) has been further subcategorized into two different syndromes, namely, epigastric pain syndrome (EPS) and postprandial distress syndrome (PDS). Acid-related pathophysiology seems to be mainly responsible for EPS, and antisecretory agents such as proton-pump inhibitors (PPIs) seem to be effective mainly against EPS. However, recent information as to the relationship between initial duodenal acid sensitization in the early postprandial phase and delayed gastric emptying in the later postprandial phase would suggest the amelioration of PDS by antisecretory agents. In the present review, we summarized the recent literature on the direct and indirect effect of PPIs in FD (including not only Rome III, but also Rome II criteria). The effects of PPIs against FD are heterogeneous, depending on the protocol of the clinical studies, and the inclusion criteria of each randomized controlled trial (primary care or tertiary care population). As the placebo effects cannot be ignored in this disease, a placebo-controlled study would be necessary, at least for the evaluation of the effect of each agent on symptom relief in patients with FD. Further studies directly comparing PPIs with suitable placebos in terms of their effects in reducing the symptoms of endoscopically confirmed, Rome III-based FD are awaited