Fe-K line probing of material around the AGN central engine with Suzaku

We systematically analyzed the high-quality Suzaku data of 88 Seyfert galaxies. We obtained a clear relation between the absorption column density and the equivalent width of the 6.4 keV line above 10$^{23}$ cm$^{-2}$, suggesting a wide-ranging column density of $10^{23-24.5}$ cm$^{-2}$ with a similar solid and a Fe abundance of 0.7--1.3 solar for Seyfert 2 galaxies. The EW of the 6.4 keV line for Seyfert 1 galaxies are typically 40--120 eV, suggesting the existence of Compton-thick matter like the torus with a column density of $>10^{23}$ cm$^{-2}$ and a solid angle of $(0.15-0.4)*4pi$, and no difference of neutral matter is visible between Seyfert 1 and 2 galaxies. An absorber with a lower column density of $10^{21-23}$ cm$^{-2}$ for Compton-thin Seyfert 2 galaxies is suggested to be not a torus but an interstellar medium. These constraints can be understood by the fact that the 6.4 keV line intensity ratio against the 10--50 keV flux is almost identical within a range of 2--3 in many Seyfert galaxies. Interestingly, objects exist with a low EW, 10--30 eV, of the 6.4 keV line, suggesting that those torus subtends only a small solid angle of $<0.2*4pi$. Ionized Fe-K$\alpha$ emission or absorption lines are detected from several percents of AGNs. Considering the ionization state and equivalent width, emitters and absorbers of ionized Fe-K lines can be explained by the same origin, and highly ionized matter is located at the broad line region. The rapid increase in EW of the ionized Fe-K emission lines at $N_{H}>10^{23}$ cm$^{-2}$ is found, like that of the cold material. It is found that these features seem to change for brighter objects with more than several $10^{44}$ erg/s such that the Fe-K line features become weak. We discuss this feature, together with the torus structure.Comment: 32 pages, 20 figures, ApJ accepte

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