358 research outputs found

    Cosmic Star Formation Activity at z=2.2 Probed by H-alpha Emission Line Galaxies

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    We present a pilot narrow-band survey of H-alpha emitters at z=2.2 in the Great Observatories Origins Deep Survey North (GOODS-N) field with MOIRCS instrument on the Subaru telescope. The survey reached a 3 sigma limiting magnitude of 23.6 (NB209) which corresponds to a 3 sigma limiting line flux of 2.5 x 10^-17 erg s^-1 cm^-2 over a 56 arcmnin^2 contiguous area (excluding a shallower area). From this survey, we have identified 11 H-alpha emitters and one AGN at z=2.2 on the basis of narrow-band excesses and photometric redshifts. We obtained spectra for seven new objects among them, including one AGN, and an emission line above 3 sigma is detected from all of them. We have estimated star formation rates (SFR) and stellar masses (M_star) for individual galaxies. The average SFR and M_star is 27.8M_solar yr^-1 and 4.0 x 10^10M_solar, respectivly. Their specific star formation rates are inversely correlated with their stellar masses. Fitting to a Schechter function yields the H-alpha luminosity function with log L = 42.82, log phi = -2.78 and alpha = -1.37. The average star formation rate density in the survey volume is estimated to be 0.31M_solar yr^-1Mpc^-3 according to the Kennicutt relation between H-alpha luminosity and star formation rate. We compare our H-alpha emitters at z=2.2 in GOODS-N with narrow-band line emitters in other field and clusters to see their time evolution and environmental dependence. We find that the star formation activity is reduced rapidly from z=2.5 to z=0.8 in the cluster environment, while it is only moderately changed in the field environment. This result suggests that the timescale of galaxy formation is different among different environments, and the star forming activities in high density regions eventually overtake those in lower density regions as a consequence of "galaxy formation bias" at high redshifts.Comment: Accepted for publication in PASJ Subaru Special Issue, 11 pages, 10 figure

    The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

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    「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

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    「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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