CNVs in Three Psychiatric Disorders

BACKGROUND: We aimed to determine the similarities and differences in the roles of genic and regulatory copy number variations (CNVs) in bipolar disorder (BD), schizophrenia (SCZ), and autism spectrum disorder (ASD). METHODS: Based on high-resolution CNV data from 8708 Japanese samples, we performed to our knowledge the largest cross-disorder analysis of genic and regulatory CNVs in BD, SCZ, and ASD. RESULTS: In genic CNVs, we found an increased burden of smaller (500 kb) exonic CNVs in SCZ/ASD. Pathogenic CNVs linked to neurodevelopmental disorders were significantly associated with the risk for each disorder, but BD and SCZ/ASD differed in terms of the effect size (smaller in BD) and subtype distribution of CNVs linked to neurodevelopmental disorders. We identified 3 synaptic genes (DLG2, PCDH15, and ASTN2) as risk factors for BD. Whereas gene set analysis showed that BD-associated pathways were restricted to chromatin biology, SCZ and ASD involved more extensive and similar pathways. Nevertheless, a correlation analysis of gene set results indicated weak but significant pathway similarities between BD and SCZ or ASD (r = 0.25–0.31). In SCZ and ASD, but not BD, CNVs were significantly enriched in enhancers and promoters in brain tissue. CONCLUSIONS: BD and SCZ/ASD differ in terms of CNV burden, characteristics of CNVs linked to neurodevelopmental disorders, and regulatory CNVs. On the other hand, they have shared molecular mechanisms, including chromatin biology. The BD risk genes identified here could provide insight into the pathogenesis of BD

The potential function of steroid sulphatase activity in steroid production and steroidogenic acute regulatory protein expression.

The first step in the biosynthesis of steroid hormones is conversion of cholesterol into pregnenolone. StAR (steroidogenic acute regulatory) protein plays a crucial role in the intra-mitochondrial movement of cholesterol. STS (steroid sulphatase), which is present ubiquitously in mammalian tissues, including the placenta, adrenal gland, testis and ovary, desulphates a number of 3beta-hydroxysteroid sulphates, including cholesterol sulphate. The present study was designed to examine the effect of STS on StAR protein synthesis and steroidogenesis in cells. Steroidogenic activities of COS-1 cells that had been co-transfected with a vector for the cholesterol P450scc (cytochrome P450 side-chain-cleavage enzyme) system, named F2, a StAR expression vector (pStAR), and an STS expression vector (pSTS) were assayed. Whole-cell extracts were subjected to SDS/PAGE and then to Western blot analysis. pSTS co-expressed in COS-1 cells with F2 and pStAR increased pregnenolone synthesis 2-fold compared with that of co-expression with F2 and pStAR. Western blot analysis using COS-1 cells that had been co-transfected with pSTS, F2 and pStAR revealed that StAR protein levels increased, whereas STS and P450scc protein levels did not change. The amount of StAR protein translation products increased when pSTS was added to an in vitro transcription-translation reaction mixture. Pulse-chase experiments demonstrated that the 37 kDa StAR pre-protein disappeared significantly ( P <0.01) more slowly in COS-1 cells that had been transfected with pSTS than in COS-1 cells that had not been transfected with pSTS. The increase in StAR protein level is not a result of an increase in StAR gene expression, but is a result of both an increase in translation and a longer half-life of the 37 kDa pre-StAR protein. In conclusion, STS increases StAR protein expression level and stimulates steroid production

根治的前立腺摘除術による排尿機能への影響排尿筋機能に焦点をおいた前向きの尿流動態学的検討

17名の前立腺癌患者の術後の排尿機能への影響につき蓄尿期ならびに排出期の膀胱内圧測定を含めた泌尿器科学的評価をとおしてprospectiveに臨床的検討を行った.その結果, 術後3ヵ月の時点で排尿筋機能がweakと判定された症例は, それ以外の症例と比較して有意に尿失禁の割合が高かった(p<0.05).また, 3ヵ月以上尿失禁が持続した8名のうち, 7名(88%)は術後3ヵ月の時点で排尿筋機能はweak detrusorと診断された症例であった.それらのうち4名は術前評価では, 排尿筋機能はnormal detrusorと評価された症例であった.これらの症例では最大尿流量率が低下しており, また, 他の症例群に比較して有意にQOLスコアの悪化を認めた(p<0.05).以上, これらのことからも, 遷延する尿失禁や尿勢低下を伴う患者において排尿筋機能に影響する薬物治療を行う際には, 術前の排尿筋機能にかかわらず注意が必要であることが示唆された.また, 術後QOLを考慮するとき, 排尿筋機能も含めた尿流動態評価に基づいた適切な排尿管理を行うことが重要であると考えられたProstate cancer is common in aged men and radical prostatectomy is established as a therapeutic measure. However, to date there is little information about its impact on voiding function. We conducted a prospective clinical study to elucidate the impact of radical prostatectomy on voiding function in 17 patients with prostate cancer, by urological evaluation including filling and voiding cystometry (pressure flow study). The patients who were estimated as having weak detrusor function including very weak detrusor function at 3 months postoperatively had significantly more frequent urinary incontinence compared with the others (p < 0.05). Of 8 patients who showed urinary incontinence for more than 3 months, 7 (88%) patients developed weak detrusor function at 3 months after operation, but 4 of them were estimated as having normal detrusor function preoperatively. These patients revealed reduced maximum flow rate and significantly increased quality of life score compared with the other patients (p < 0.05). An initially reduced bladder compliance disclosed a tendency to a rapid return to normal with time after surgery. Detrusor overactivity itself and neoadjuvant antiandrogen therapy were not related to prolonged postoperative urinary incontinence. The present study indicates that caution is required when administering medication that could potentially affect detrusor function, regardless of the type of preoperative detrusor function, in patients with persistent urinary incontinence or a reduced urinary stream. Particular emphasis is laid on the importance of urodynamic assessment of post-prostatectomy detrusor function and appropriate management modalities based on the results

Development of Perylene-Based Non-Fullerene Acceptors through Bay-Functionalization Strategy

Perylene has had a tremendous impact in the history of material research for the molecular semiconductors. Among numerous derivatives of this polyaromatic hydrocarbon, perylene diimide (PDI) represents a promising class of organic materials envisioned as non-fullerene acceptors (NFAs) for the practical organic photovoltaic (OPV) applications due to their enhanced photo- and thermal stability and remarkably high electron affinity, some of which realize band-like transport properties. The present review guides some of the representative achievements in the development of rationally designed PDI systems, highlighting synthetic methodologies based on bay-functionalization strategies for creating well-designed molecular nanostructures and structure-performance relationship of perylene-based small molecular acceptors (SMAs) for the photovoltaic outcomes

Direct Evidence of Polycrystalline Silicon Thin Films Formation during Aluminum Induced Crystallization by In-Situ Heating TEM Observation

The formation behavior of polycrystalline silicon thin films during the aluminum induced crystallization (AIC) process was investigated by scanning transmission electron microscopy (STEM) and in-situ heating transmission electron microscopy (TEM) observations. The STEM observation and electron dispersive X-ray spectroscopy (EDS) analysis of ex-situ heat-treated specimen revealed that the a-Si layer and Al layer switched the positions with each other during the heat treatment, resulting the crystallization of the a-Si layer. Furthermore, the in-situ heating TEM observation and EDS analysis of as-deposited specimen revealed the mixed state of Si and Al in an a-Si/Al film and the lateral growth of crystalline Si grain during the heating. The mechanism of AIC and switching layers were also discussed from the experimental results and the binary phase diagram of Al-Si system

A Study of Transformation of the Beginning Teacher's Thinking in Physical Education Lessons of Elementary Schools : Focusing the Factor Which Promote the Transformation

This study aims to get ideas for improvement of in-service education for physical education through examining factors which promote transformation of beginning teacher X's thinking in physical education lessons during four years after his recruitment. The results are summarized as following points. The ideas which these process of beginning teacher X's development proposed for professional development about physical education were summarized as following 4 points. 1. Beginning teachers need their mentors' assistance according to their needs and daily discussion with their colleagues of their schools about their pupils. 2. School directors have to esteem their staff ideas and play an important role for creating atmosphere of which school teachers can think of their teaching mainly. 3. Beginning teachers need in-service training where they observe and discuss teaching of physical education and learn physical activities' skill in their schools. 4. School directors, their colleagues and local educational authorities have to assist that beginning teachers partake in an in-service training out of school for professional development of physical education