Large Population of ALMA Galaxies at z>6 with Very High [OIII]88um to [CII]158um Flux Ratios: Evidence of Extremely High Ionization Parameter or PDR Deficit?

We present our new ALMA observations targeting [OIII]88um, [CII]158um, [NII]122um, and dust continuum emission for three Lyman break galaxies at z=6.0293-6.2037 identified in the Subaru/Hyper Suprime-Cam survey. We clearly detect [OIII] and [CII] lines from all of the galaxies at 4.3-11.8sigma levels, and identify multi-band dust continuum emission in two of the three galaxies, allowing us to estimate infrared luminosities and dust temperatures simultaneously. In conjunction with previous ALMA observations for six galaxies at z>6, we confirm that all the nine z=6-9 galaxies have high [OIII]/[CII] ratios of L[OIII]/L[CII]~3-20, ~10 times higher than z~0 galaxies. We also find a positive correlation between the [OIII]/[CII] ratio and the Lya equivalent width (EW) at the ~90% confidence level. We carefully investigate physical origins of the high [OIII]/[CII] ratios at z=6-9 using Cloudy, and find that high density of the interstellar medium, low C/O abundance ratio, and the cosmic microwave background attenuation are responsible to only a part of the z=6-9 galaxies. Instead, the observed high [OIII]/[CII] ratios are explained by 10-100 times higher ionization parameters or low photodissociation region (PDR) covering fractions of 0-10%, both of which are consistent with our [NII] observations. The latter scenario can be reproduced with a density bounded nebula with PDR deficit, which would enhance the Lya, Lyman continuum, and C+ ionizing photons escape from galaxies, consistent with the [OIII]/[CII]-Lya EW correlation we find.Comment: 20 pages, 18 figures, Accepted for publication in Ap

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

A case of mucoepidermoid carcinoma arising in mature cystic teratoma

卵巣粘表皮癌は卵巣悪性腫瘍の中で極めてまれな組織型に分類される。今回、我々は成熟嚢胞性奇形種より発生した卵巣粘表皮癌の症例を経験したので報告する。症例は、69歳、女性、両側の成熟嚢胞性奇形腫を認めたが、SCC 高値とCT、MRI にて左側の腫瘍内に造影される充実性部分を認めたこと、小腸に浸潤を疑う所見を認めたこと、から悪性転化を疑い、手術を施行した。開腹時、両側卵巣腫瘍を認め、左卵巣腫瘍はS状結腸と強固に癒着していた。卵巣腫瘍充実性部分の迅速病理にて低分化癌と診断し、単純子宮全摘出術、両側付属器摘出術、S状結腸合併切除、骨盤リンパ節郭清術、大網切除術を施行した。病理組織学的には、左卵巣腫瘍の嚢胞壁肥厚部に皮膚付属器、脂肪織、軟骨組織、リンパ球集簇、卵巣間質を認め、充実成分に低分化な浸潤性扁平上皮癌を認めた。充実成分には、粘表皮癌に特徴的な、豊富な胞体粘液（PASおよびAlcian blue 染色陽性）を有する異型細胞が胞巣状~不完全な腺管状を呈する領域があり、成熟嚢胞性奇形腫より発生した卵巣粘表皮癌IIb期(pT2bN0M0)と診断した。術後補助化学療法としてDC（ドセタキセル、カルボプラチン）療法を施行し、術後1年8ヶ月現在、再発を認めない。雑誌掲載論

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

New series of avenanthramides in oat seed

<div><p>Avenanthramides are characteristic constituents of oat seeds. We analyzed the methanol extract of oat seeds by HPLC and detected three compounds 1, 2, and 3 eluted at retention times similar to avenanthramides. The three compounds were purified by column chromatography and HPLC. Spectroscopic analyses of 1, 2, and 3 suggested that they are amides of 4,5-dihydroxyanthranilic acid with caffeic, <i>p</i>-coumaric, and ferulic acids, respectively. Their identities were confirmed by comparing spectra and chromatographic behavior with compounds synthesized from 4,5-dihydroxyanthranilic acid and <i>N</i>-hyrdroxysuccinimide esters of hydroxycinnamic acids. LC-MS/MS analysis with multiple reaction monitoring showed that the amounts of 1, 2, and 3 were 16.5–26.9% of corresponding avenanthamides with 5-hydroxyanthranilic acid. Compounds 1, 2, and 3 showed stronger 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging activity than the corresponding avenanthramides with 5-hydroxyanthranilic acid, indicating the involvement of 4,5-dihydroxyanthranilic acid moiety in the scavenging of DPPH radicals.</p></div