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

PRMT1 Deficiency in Mouse Juvenile Heart Induces Dilated Cardiomyopathy and Reveals Cryptic Alternative Splicing Products

Protein arginine methyltransferase 1 (PRMT1) catalyzes the asymmetric dimethylation of arginine residues in proteins and methylation of various RNA-binding proteins and is associated with alternative splicing in vitro. Although PRMT1 has essential in vivo roles in embryonic development, CNS development, and skeletal muscle regeneration, the functional importance of PRMT1 in the heart remains to be elucidated. Here, we report that juvenile cardiomyocyte-specific PRMT1-deficient mice develop severe dilated cardiomyopathy and exhibit aberrant cardiac alternative splicing. Furthermore, we identified previously undefined cardiac alternative splicing isoforms of four genes (Asb2, Fbxo40, Nrap, and Eif4a2) in PRMT1-cKO mice and revealed that eIF4A2 protein isoforms translated from alternatively spliced mRNA were differentially ubiquitinated and degraded by the ubiquitin-proteasome system. These findings highlight the essential roles of PRMT1 in cardiac homeostasis and alternative splicing regulation

実践医療用語の語構成要素への分割と意味ラベル付与の試み

National Institute for Japanese Language and LinguisticsSeinan Jo Gakuin UniversitySeinan Jo Gakuin UniversityMejiro UniversityOsaka University会議名: 言語資源活用ワークショップ2019, 開催地: 国立国語研究所, 会期: 2019年9月2日−4日, 主催: 国立国語研究所 コーパス開発センター本発表では、電子医療記録に含まれる実践医療用語の語構成を明らかにするために、独自に設計した語構成要素への分割とそれに対する意味ラベルの付与を行い、意味ラベルによる語構成のパターンを調査した。調査対象は、ComeJisyoSjis-1（111,664語）から、『分類語彙表 増補改訂版』に収録されている語を含む約7,000語から抽出した1,000語である。これらを短単位よりやや長めの語構成要素に分割し、意味ラベルを付与した。意味ラベルは、石井（2007）の複合名詞の語構造把握のための意味分類を参考にしたが、実践医療用語のために独自に設けたものも多い。分析結果から、以下のような点が明らかになった。(1)語構成要素数が2個と3個のものが全体の8割以上を占める。(2)意味ラベルは、「疾患」「身体部位」「状態」「症状」「医療行為」「時間」「生理」の7つで全体の約8割を占める。(3)意味ラベルは、語頭により多く出現するもの（「身体部位」「時間」）や語末により多く出現するもの（「医療行為」「症状」「障害」）などがあり、分布に偏りが見られる

実践医療用語の語構成要素抽出の試み

Shonan Institute of TechnologyNational Institute for Japanese Language and LinguisticsMejiro UniversitySeinan Jo Gakuin UniversityNational Institute for Japanese Language and LinguisticsSeinan Jo Gakuin University会議名: 言語資源活用ワークショップ2018, 開催地: 国立国語研究所, 会期: 2018年9月4日-5日, 主催: 国立国語研究所 コーパス開発センター医療現場で用いられる電子カルテなどの記録文書（医療記録）に専門用語としての医療用語が大量に含まれている。医療記録に記載された言語情報を正確に理解・活用するためにはこれらの医療用語の理解が必要となる。医療記録に含まれる語には、複数の語からなる複合語や臨時一語も多く、これらは、病名、身体の部位名、処置名、薬剤名等、様々な用語から構成されている。しかし、現在はこの語構成要素の組み合わせのパターンや語構成要素間の関係などが曖昧である。そこで、本研究では複数の語からなる実践医療用語の語構成要素の抽出を試みた。語構成要素の条件を独自で定義した後、ComJisyoV5、と今後公開予定のV6の登録候補語に対象として、MecabMeCab0.996とUniDic-cwj-2.2.0を利用して形態素解析を行った。分割された単語の品詞情報を手がかりにして、単一単位となり得る品詞列を抽出した。次に抽出した候補リスト以外に語構成要素となる品詞列があるかについて検討を行った

Fluid flow-induced left-right asymmetric decay of Dand5 mRNA in the mouse embryo requires a Bicc1-Ccr4 RNA degradation complex

Molecular left-right (L-R) asymmetry is established at the node of the mouse embryo as a result of the sensing of a leftward fluid flow by immotile cilia of perinodal crown cells and the consequent degradation of Dand5 mRNA on the left side. We here examined how the fluid flow induces Dand5 mRNA decay. We found that the first 200 nucleotides in the 3′ untranslated region (3′-UTR) of Dand5 mRNA are necessary and sufficient for the left-sided decay and to mediate the response of a 3′-UTR reporter transgene to Ca2+, the cation channel Pkd2, the RNA-binding protein Bicc1 and their regulation by the flow direction. We show that Bicc1 preferentially recognizes GACR and YGAC sequences, which can explain the specific binding to a conserved GACGUGAC motif located in the proximal Dand5 3′-UTR. The Cnot3 component of the Ccr4-Not deadenylase complex interacts with Bicc1 and is also required for Dand5 mRNA decay at the node. These results suggest that Ca2+ currents induced by leftward fluid flow stimulate Bicc1 and Ccr4-Not to mediate Dand5 mRNA degradation specifically on the left side of the node

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

Reading beyond Literal Comprehension : Categorisation of Questions and Analysis of Textbooks

Many studies point out the importance of questions in the instruction of reading and classify questions so that they may help the reader understand the text. Few attempts have been made, however, to examine ways of questioning appropriate for literary works contained in the textbooks for Japanese high school students. This paper claims that categorising questions into three types, namely literal questions, inferential questions and interpretational questions will contribute to the students' appreciation of literature. Using the three categories, we analysed the questions attached to Ibuse's Black Rain (translated into English) in a textbook for senior high school students. Most of the questions fell into literal questions, one into interpretational, and none into inferential. Black Rain (in the original) is also used in a senior high school textbook for the Japanese language. Having a wider variety of questions than its English counterpart, the Japanese textbook encourages a student to read between the lines or present his/her interpretation of the text. We conclude that it is essential for the English teachers to help their students read literature beyond its literal meaning by asking various questions which range from literal, through inferential, to interpretational ones

Questions for Literary Texts as English Teaching Materials : In the Case of Hemingway's "A Day's Wait"

In The Course of Study for Upper Secondary School to be implemented in 2013 the overall objective of learning foreign languages is: "To develop students' communication abilities such as accurately understanding and appropriately conveying information, ideas, etc., deepening their understanding of language and culture, and fostering a positive attitude toward communication through foreign languages." We claim that literature can contribute to developing all the abilities articulated here. This paper, however, pays particular attention to the last ability, maintaining that students can foster "a positive attitude" toward reading through literature written in English. To put Roland Barthes' theory simply, a "text" which is open to interpretation gives us "pleasure" of reading. Few people would object that literature is more open to interpretation than any other writing. It follows, therefore, that students, through literature, might find pleasure in reading and foster "a positive attitude" toward it. Many studies emphasize the importance of questions in the instruction of reading. As Fukazawa (2008) and Takehisa & Ono (2010) point out, however, most of the questions in the textbooks authorized by The Ministry of Education, Culture, Sports, Science and Technology can be categorized as "questions requiring literal comprehension of the texts." According to Tsuido (1989), this type of question does not really enhance learners' reading abilities because it only makes them "look for" answers in the text. To make reading more stimulating and beneficial to learners, we maintain that not only literal but also inferential or interpretational questions are needed. And this is particularly true for literary texts, which require us to read between the lines and are open to a variety of interpretations. Hemingway's short story, "A Day's Wait" is included in a textbook for senior high school students published in 2007. The story is put in the original, not being simplified or abridged. The problem is that the text does not have any questions, exercises or tasks that would help students comprehend the story. All it has is a very short introduction to the story and some notes on words or phrases assumed to be difficult for high school students. So, in this paper, we have developed 18 questions which we hope would lead to students' comprehension and appreciation of the story. The questions can be divided into three types, namely (1) Type A: Literal Questions, (2) Type B: Inferential Questions and (3) Type C: Interpretational Questions. The ratio among the three types is 11:6:7. (The total number, 24 does not correspond with the number of the questions, 18. This is because we regarded 6 questions as covering two types.