The 3′-Phosphoadenosine 5′-Phosphosulfate Transporters, PAPST1 and 2, Contribute to the Maintenance and Differentiation of Mouse Embryonic Stem Cells

Recently, we have identified two 3′-phosphoadenosine 5′-phosphosulfate (PAPS) transporters (PAPST1 and PAPST2), which contribute to PAPS transport into the Golgi, in both human and Drosophila. Mutation and RNA interference (RNAi) of the Drosophila PAPST have shown the importance of PAPST-dependent sulfation of carbohydrates and proteins during development. However, the functional roles of PAPST in mammals are largely unknown. Here, we investigated whether PAPST-dependent sulfation is involved in regulating signaling pathways required for the maintenance of mouse embryonic stem cells (mESCs), differentiation into the three germ layers, and neurogenesis. By using a yeast expression system, mouse PAPST1 and PAPST2 proteins were shown to have PAPS transport activity with an apparent Km value of 1.54 µM or 1.49 µM, respectively. RNAi-mediated knockdown of each PAPST induced the reduction of chondroitin sulfate (CS) chain sulfation as well as heparan sulfate (HS) chain sulfation, and inhibited mESC self-renewal due to defects in several signaling pathways. However, we suggest that these effects were due to reduced HS, not CS, chain sulfation, because knockdown of mouse N-deacetylase/N-sulfotransferase, which catalyzes the first step of HS sulfation, in mESCs gave similar results to those observed in PAPST-knockdown mESCs, but depletion of CS chains did not. On the other hand, during embryoid body formation, PAPST-knockdown mESCs exhibited abnormal differentiation, in particular neurogenesis was promoted, presumably due to the observed defects in BMP, FGF and Wnt signaling. The latter were reduced as a result of the reduction in both HS and CS chain sulfation. We propose that PAPST-dependent sulfation of HS or CS chains, which is regulated developmentally, regulates the extrinsic signaling required for the maintenance and normal differentiation of mESCs

緩和ケアにおける人材育成研修の成果と課題 : 修了生の看護実践・自己の姿勢への活用

A県における緩和ケアの研修を修了した修了生173名に、研修後の看護実践と自己の行動の変化について質問紙調査を行った。その結果、身体症状の緩和や傾聴、日常生活への支援に関する看護実践、自己の姿勢・態度の変容に活かしやすく、精神症状の緩和、遺族ケア、意思決定、地域連携に関する看護実践には活かしにくかった。一方、スキルアップの動機づけにもなっていた。今後は、難しいと感じる分野の研修内容・方法の検討、モチベーションの維持・向上のための環境調整やフォローアップの機会が必要であることが明らかになった

Crossing with Animals : An existential exercise emerging from the Theory of Experiencing

自分の生きざまを動物に喩えて、その動物は何をしているのかなどと形容しながらペアで話し合うワークを考案し、それを「アニクロ」(Crossing with Animals)と命名した。本論では、その理論背景として実存哲学、メタファー論やジェンドリン哲学を含む体験過程理論について論じたあと、その実践を３つの側面から検討した。それらは、アニクロ初体験者に対するアンケート結果について、産業メンタルヘルス研修でのアニクロの応用について、そしてゲシュタルトセラピーにおけるアニクロの実践についてである。アニクロは多用な実践が可能であるが、その基本原理はフォーカシングであり、本論は最後に、アニクロを通してみたフォーカシングの基礎理論を考察した。This paper introduces and discusses an exercise where one expresses one\u27s own sense of living as an animal and dialogues with a partner on how the animal exists. The paper terms this exercise "crossing with animals." First, the theory of experiencing, a theory that includes aspects of existential philosophy, metaphor theory, and the philosophy of Eugene Gendlin, is discussed as a theoretical basis of crossing with animals. Then the practice of crossing with animals is discussed from three aspects : (1) the results of a questionnaire administered to those who were new to the exercise ; (2) the use of crossing with animals in corporate mental health training ; and (3) the use of crossing with animals in Gestalt therapy. Although crossing with animals can be practiced in diverse populations, it is a form of Focusing, and the paper concludes with a theoretical discussion of Focusing principles in relation to the practice of crossing with animals

ABJ theory in the higher spin limit

This article is distributed under the terms of the Creative Commons Attribution License (CC-BY 4.0), which permits any use, distribution and reproduction in any medium, provided the original author(s) and source are creditedArticle funded by SCOAP3 .Article funded by SCOAP3 .The work of SH was supported in part by the National Research Foundation of South Africa and DSTNRF Centre of Excellence in Mathematical and Statistical Sciences (CoE-MaSS). Opinions expressed and conclusions arrived at are those of the author and are not necessarily to be attributed to the NRF or the CoE-MaSS. The work of KO was supported in part by JSPS Grant-in-Aid for Young Scientists (B) 23740178. MS is grateful to the Weizmann Institute for the stimulating environment at the “Black Holes and Quantum Information” workshop. The work of MS was supported in part by Grant-in-Aid for Young Scientists (B) 24740159 from the Japan Society for the Promotion of Science (JSPS)

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