Orexin A Enhances Pro-Opiomelanocortin Transcription Regulated by BMP-4 in Mouse Corticotrope AtT20 Cells

Orexin is expressed mainly in the hypothalamus and is known to activate the hypothalamic-pituitary-adrenal (HPA) axis that is involved in various stress responses and its resilience. However, the effects of orexin on the endocrine function of pituitary corticotrope cells remain unclear. In this study, we investigated the roles of orexin A in pro-opiomelanocortin (POMC) transcription using mouse corticotrope AtT20 cells, focusing on the bone morphogenetic protein (BMP) system expressed in the pituitary. Regarding the receptors for orexin, type 2 (OXR2) rather than type 1 (OX1R) receptor mRNA was predominantly expressed in AtT20 cells. It was found that orexin A treatment enhanced POMC expression, induced by corticotropin-releasing hormone (CRH) stimulation through upregulation of CRH receptor type-1 (CRHR1). Orexin A had no direct effect on the POMC transcription suppressed by BMP-4 treatment, whereas it suppressed Smad1/5/9 phosphorylation and Id-1 mRNA expression induced by BMP-4. It was further revealed that orexin A had no significant effect on the expression levels of type I and II BMP receptors but upregulated inhibitory Smad6/7 mRNA and protein levels in AtT20 cells. The results demonstrated that orexin A upregulated CRHR signaling and downregulated BMP-Smad signaling, leading to an enhancement of POMC transcription by corticotrope cells

ニッケル触媒による1, 2, 3－トリアゾ化合物の脱窒素反応を起点とする新しい挿入反応の開発

京都大学0048新制・課程博士博士(工学)甲第15404号工博第3283号新制||工||1494(附属図書館)27882京都大学大学院工学研究科合成・生物化学専攻(主査)教授 村上 正浩, 教授 杉野目 道紀, 教授 吉田 潤一学位規則第4条第1項該当Doctor of Philosophy (Engineering)Kyoto UniversityDFA

Experimental study on long friction-type bolted joint combined with interference fit bolt

In recent years, high-strength bolts with friction-type joints have been lengthened to withstand increased traffic load. However, with increase in the joint length, the force able to be resisted by bolted joints has decreased owing to uneven distribution of the bolts within the joint. In addition, the proximity of secondary members to the joint has restricted the allowable size of the splice plates. It is therefore necessary to reduce the joint length while maintaining its design strength. In this study, interference fit bolts were assembled at both ends of a friction-type bolted joint to form a hybrid joint, and tensile tests were conducted to elucidate the load transmission mechanism, analyse the slip resistance, and verify whether the addition of the interference fit bolts improves the strength of the friction-type joint. It was concluded that despite a minor slip in the hybrid joint, the slip resistance was approximately 10% higher than that of the friction-type joint, and the overall load–deformation relationship maintained a quasi-linear behaviour up to 1.1 times the slip resistance of the friction-type joint. In addition, the hybrid joint had smaller data scattering than the friction-type joint, suggesting that the uneven load distribution and deformation in the joint was slightly improved by installing the interference fit bolts. The performance of hybrid joints is superior to that of the existing friction-type joints under the current slip limit specification.</p

Static to inducibly dynamic stereocontrol: The convergent use of racemic β-substituted ketones.

The synthesis of stereochemically complex molecules in the pharmaceutical and agrochemical industries requires precise control over each distinct stereocenter, a feat that can be challenging and time consuming using traditional asymmetric synthesis. Although stereoconvergent processes have the potential to streamline and simplify synthetic routes, they are currently limited by a narrow scope of inducibly dynamic stereocenters that can be readily epimerized. Here, we report the use of photoredox catalysis to enable the racemization of traditionally static, unreactive stereocenters through the intermediacy of prochiral radical species. This technology was applied in conjunction with biocatalysts such as ketoreductases and aminotransferases to realize stereoconvergent syntheses of stereodefined γ-substituted alcohols and amines from β-substituted ketones