Differential lactate and cholesterol synthetic activities in XY and XX Sertoli cells

SRY, a sex-determining gene, induces testis development in chromosomally female (XX) individuals. However, mouse XX Sertoli cells carrying Sry (XX/Sry Sertoli cells) are incapable of fully supporting germ cell development, even when the karyotype of the germ cells is XY. While it has therefore been assumed that XX/Sry Sertoli cells are not functionally equivalent to XY Sertoli cells, it has remained unclear which specific functions are affected. To elucidate the functional difference, we compared the gene expression of XY and XX/Sry Sertoli cells. Lactate and cholesterol metabolisms, essential for nursing the developing germ cells, were down-regulated in XX/Sry cells, which appears to be caused at least in part by the differential expression of histone modification enzymes SMCX/SMCY (H3K4me3 demethylase) and UTX/UTY (H3K27me3 demethylase) encoded by the sex chromosomes. We suggest that down-regulation of lactate and cholesterol metabolism that may be due to altered epigenetic modification affects the nursing functions of XX/Sry Sertoli cells.This work was supported by the Japan Society for the Promotion of Science (JSPS) KAKENHI Grant Number 21249018 and 16H05142 (K. Mo.), Ministry of Education, Culture, Sports, Science, and Technology, Japan (MEXT) KAKENHI Grant Number 22132002 (K. Mo.), the Uehara Memorial Foundation, and Takeda Science Foundation (T.B.)

Ad4BP/SF-1 regulates cholesterol synthesis to boost the production of steroids

Housekeeping metabolic pathways such as glycolysis are active in all cell types. In addition, many types of cells are equipped with cell-specific metabolic pathways. To properly perform their functions, housekeeping and cell-specific metabolic pathways must function cooperatively. However, the regulatory mechanisms that couple metabolic pathways remain largely unknown. Recently, we showed that the steroidogenic cell-specific nuclear receptor Ad4BP/ SF-1, which regulates steroidogenic genes, also regulates housekeeping glycolytic genes. Here, we identify cholesterogenic genes as the targets of Ad4BP/SF-1. Further, we reveal that Ad4BP/SF-1 regulates Hummr, a candidate mediator of cholesterol transport from endoplasmic reticula to mitochondria. Given that cholesterol is the starting material for steroidogenesis and is synthesized from acetyl-CoA, which partly originates from glucose, our results suggest that multiple biological processes involved in synthesizing steroid hormones are governed by Ad4BP/SF-1. To our knowledge, this study provides the first example where housekeeping and cell-specific metabolism are coordinated at the transcriptional level.This work was supported by Grants 16H05142 (K.M.), 17H06427 (K.M.), 16K08593 (T.B.), and 17J03270 (M.I.) from the Japan Society for the Promotion of Science (JSPS) KAKENHI; The Uehara Memorial Foundation (K.M.); Takeda Science Foundation (T.B.); The Shin-Nihon of Advanced Medical Research (T.B.).Supplementary information accompanies this paper at https://doi.org/10.1038/s42003-018-0020-z

First Case of Cytokine Release Syndrome after Nivolumab for Gastric Cancer

Introduction: Cytokine release syndrome (CRS) is a potentially life-threatening systemic disease that has been observed after treatment with antibodies and adoptive T cell therapies. In this case, we observed nivolumab-induced CRS in a patient with gastric cancer. Case Presentation: A 43-year-old male with advanced gastric cancer was treated with nivolumab as a third-line chemotherapy. He had no history of allergies. Eight days after the first administration of nivolumab, fever, tachycardia, appetite loss and increases in liver and biliary enzymes were observed. Computed tomography revealed neither bile duct obstruction nor progression of liver metastases but showed that there was edema of the Gleason sheath. Histopathological analysis of the liver revealed cholestatic liver injury with CD8+ T lymphocyte and macrophage infiltration. Neither viral infection nor autoimmune disease was revealed. His symptoms were similar to those of CRS observed after T cell therapy. We diagnosed his disease as nivolumab-induced liver injury and cholangitis accompanied by CRS based on his serum cytokine levels. Discussion/Conclusion: To the best of our knowledge, this is the first report of nivolumab-induced CRS in a patient with gastric cancer

Organized and Sustainable Education Program for Drug Abuse Prevention by Yogo-teachers

　学校における喫煙・飲酒・薬物乱用防止教育の充実には，問題行動が顕在化する中学校期だけでなく小学校期 における指導の推進が重要であり，系統的な指導計画を立て，指導者や時間の確保，教材作成などに組織的に取 組み，継続可能なプログラム開発を行う必要がある。そこで，地区内12 校の養護教諭が協働して，発達段階に応 じた系統的・組織的かつ継続可能な地区共通の指導計画を開発し，各校の教育課程・年間計画に位置付けた実践 研究を行った。その結果，指導計画の実施状況は，小学校11 校中，学級活動10 校，ミニ保健指導10 校，長期 休業前指導6 校，広報活動9 校となり，特別支援学校1 校では広報活動のみを行うことができた。小学校におけ る喫煙・飲酒・薬物乱用防止教育の推進には，学校保健活動の中核的役割を担う養護教諭が専門性を活かし協働 して，系統的な指導計画を各校の教育課程に位置付け組織的で継続可能なプログラムとする取組が有効であった

Complete Genetic Correction of iPS Cells From Duchenne Muscular Dystrophy

Human artificial chromosome (HAC) has several advantages as a gene therapy vector, including stable episomal maintenance that avoids insertional mutations and the ability to carry large gene inserts including the regulatory elements. Induced pluripotent stem (iPS) cells have great potential for gene therapy, as such cells can be generated from the individual's own tissues, and when reintroduced can contribute to the specialized function of any tissue. As a proof of concept, we show herein the complete correction of a genetic deficiency in iPS cells derived from Duchenne muscular dystrophy (DMD) model (mdx) mice and a human DMD patient using a HAC with a complete genomic dystrophin sequence (DYS-HAC). Deletion or mutation of dystrophin in iPS cells was corrected by transferring the DYS-HAC via microcell-mediated chromosome transfer (MMCT). DMD patient- and mdx-specific iPS cells with the DYS-HAC gave rise to differentiation of three germ layers in the teratoma, and human dystrophin expression was detected in muscle-like tissues. Furthermore, chimeric mice from mdx-iPS (DYS-HAC) cells were produced and DYS-HAC was detected in all tissues examined, with tissue-specific expression of dystrophin. Therefore, the combination of patient-specific iPS cells and HAC-containing defective genes represents a powerful tool for gene and cell therapies

島根県民の運動習慣の実態とロコモ認知度

島根県民の運動習慣の実態とロコモ認知度を明らかにするため、18歳以上の県内在住者に質問紙によるモニター調査を行った。484名の回答を得て451名を分析した（有効回答率93.2％）。約7割は運動習慣がないが、その多くは運動不足解消の意思を有し、50代以下と60代以上の運動習慣（p<.05）に有意差があった。ロコモ認知の割合は3割程度で、認知あり群となし群の運動習慣に有意差（p<.05）があった。以上のことから、50代以下の者の多くは運動への関心はあるが行動変容まで至っていないと示唆された。運動を習慣化する者の増加を目指し、幅広い年代層のロコモ認知度を高める必要がある

VDT作業労働者に対するオリジナル健康体操プログラムの評価

VDT作業労働者にオリジナル健康体操の実施を働きかけた。本研究の目的は介入プログラムの効果の検証である。対象者に１か月間，就業前後の体操実施を促した。実施回数をカードに記録するよう依頼し，調査の終了時に回収した。さらに，介入前後に自記式質問紙調査を行った。評価の主要アウトカムは体操実施状況とした。分析対象者は14名で実施平均は30.73 ± 10.24回であった。職場での健康体操は身体活動として習慣化しやすいことが示唆された。また，副次的アウトカムとした肩こり・腰痛のVAS に有意差はなかったが健康QOL は介入前後で社会生活機能・心の健康が有意に改善し，本プログラムの精神的健康への寄与が示唆された