Mite-antigen Stimulates MAL Expression in Peripheral Blood T Cells of Mite-sensitive Subjects

ABSTRACTBackgroundDifferential gene expression in CD3+ T cells from allergic patients stimulated with allergen will provide important information on the responses of T cells.MethodsAfter stimulation of peripheral blood mononuclear cells (PBMCs) with mite extracts, levels of gene transcription were examined in CD3+ T cells from allergic patients.ResultsStimulation of PBMCs from mite specific IgE positive subjects resulted in specific upregulation of MAL transcription levels that was mediated by IL-4 secretion. The MAL protein in IL-4 stimulated primary T cells preferentially localized in glycolipid-enriched membrane (GEM) microdomains. When MAL was exogenously expressed in primary T cells, CD3ζ was concomitantly enriched, along with the expression of MAL, in GEM microdomains.ConclusionsGEMs are important for the formation and stabilization of TCR signaling complexes. Therefore, MAL may play a role in the formation of GEMs in activated T cells and the high expression of MAL may contribute to Th2 immune response

Constraints on the Intracluster Dust Emission in the Coma Cluster of Galaxies

We have undertaken a search for the infrared emission from the intracluster dust in the Coma cluster of galaxies by the Multiband Imaging Photometer for Spitzer. Our observations yield the deepest mid and far-infrared images of a galaxy cluster ever achieved. In each of the three bands, we have not detected a signature of the central excess component in contrast to the previous report on the detection by Infrared Space Observatory (ISO). We still find that the brightness ratio between 70 and 160 microns shows a marginal sign of the central excess, in qualitative agreement with the ISO result. Our analysis suggests that the excess ratio is more likely due to faint infrared sources lying on fluctuating cirrus foreground. Our observations yield the 2 sigma upper limits on the excess emission within 100 kpc of the cluster center as 5 x 10^-3 MJy/sr, 6 x 10^-2 MJy/sr, and 7 x 10^-2 MJy/sr, at 24, 70, and 160 microns, respectively. These values are in agreement with those found in other galaxy clusters and suggest that dust is deficient near the cluster center by more than 3 orders of magnitude compared to the interstellar medium.Comment: 10 pages, 9 figures, minor changes to match version published in Ap

A case of anti - neutrophil cytoplasmic autoantibody-associated vasculitis: Resolution after early diagnosis

症例は76歳男性03年前肺気腫と診断された｡今回呼吸器リハビリテーション目的で当院に入院の運びとなった｡入院時より37-38'Cの発熱を認め,下気道感染を疑い抗生剤で加療したが改善しなかった.入院時の検尿検査で蛋白･潜血陽性であり,血清MPO-ANCAが307U/mlと高値を示した｡血清クレアチニン値も徐々に上昇してきたため,MPO-ANCA関連血管炎と診断した.プレドニゾロン投与を開始したところ,症状及び検査所見は速やかに改善した.A 76-year-old man was admitted to our hospital for pulmonary rehabilitation. Three years before admission he was diagnosed as pulmonary emphysema. On the day of admission the patient was febrile[37-38°C]. Initially lower respiratory infection was suspected and antibiotics was given to the patient, but his fever sustained. On admission he presented proteinuria and hematuria and the following examination revealed the high titer [307U/ml] of myeloperoxidase specific anti -neutrophil cytoplasmic autoantibody (MPO-ANCA). A gradual rise in serum creatinine levels after admission was also observed. He was diagnosed as MPO-ANCA associated vasculitis. Prednisolone therapy was started, which improved his symptoms and laboratory data rapidly

The Far-Infrared Surveyor (FIS) for AKARI

The Far-Infrared Surveyor (FIS) is one of two focal plane instruments on the AKARI satellite. FIS has four photometric bands at 65, 90, 140, and 160 um, and uses two kinds of array detectors. The FIS arrays and optics are designed to sweep the sky with high spatial resolution and redundancy. The actual scan width is more than eight arcmin, and the pixel pitch is matches the diffraction limit of the telescope. Derived point spread functions (PSFs) from observations of asteroids are similar to the optical model. Significant excesses, however, are clearly seen around tails of the PSFs, whose contributions are about 30% of the total power. All FIS functions are operating well in orbit, and its performance meets the laboratory characterizations, except for the two longer wavelength bands, which are not performing as well as characterized. Furthermore, the FIS has a spectroscopic capability using a Fourier transform spectrometer (FTS). Because the FTS takes advantage of the optics and detectors of the photometer, it can simultaneously make a spectral map. This paper summarizes the in-flight technical and operational performance of the FIS.Comment: 23 pages, 10 figures, and 2 tables. Accepted for publication in the AKARI special issue of the Publications of the Astronomical Society of Japa

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