Finding new proteins interacting with bace by yeast two hybrid.

β-淀粉样前体蛋白APP（β-amyloidprecursorprotein）水解产生的β-淀粉样蛋白（β-amyloidpeptides，Aβ）在阿尔茨海默氏症（AlzheimerDisease，AD）的发病机理中起着重要的作用，BACE（β-siteAPP-cleavingenzyme）被认为是Aβ形成的关键酶，已经成为近年来阿尔茨海默氏症研究及筛选药物靶的热点之一。为了更好的认识和理解BACE在阿尔茨海默氏症病理过程中的作用机制，我们利用酵母双杂交法筛选与之有相互作用的蛋白。用BACE作为诱饵蛋白筛选人胎脑文库后，得到65个阳性克隆。经测序和序列比对，我们选择三个蛋白进行深入研究：分别为...The β-amyloid peptides (Aβ) derived from proteolytic cleavage of the amyloid precursor protein (APP) play a major role in the pathogenesis of Alzheimer’s disease (AD) by forming aggregated, fibrillary complexes that have been shown to be neurotoxic. The β-site APP cleaving enzyme (BACE) has been identified as a key enzyme leading to β-amyloid formation. To further understand the function a...学位：理学硕士院系专业：生命科学学院生物医学科学系_细胞生物学学号：20032608

β-secretase Interracts with Divalent Cation Tolerant Protein CUTA

淀粉样蛋白(β-amyloid,Aβ)沉积是阿尔茨海默病(Alzheimer disease,AD)的重要病理特征之一。Aβ是由淀粉样前体蛋白(amyloid precursor protein,APP)经β-分泌酶(BACE)和γ-分泌酶水解产生的,因此BACE1在AD的形成过程中发挥重要作用。为了进一步研究BACE1的作用机制,以BACE1胞内段构建诱饵蛋白用酵母双杂交方法筛选与之相互作用的蛋白质。结果得到了二价阳离子耐受蛋白(divalent cation tolerant protein,CUTA)的阳性克隆,β-半乳糖苷酶实验表明CUTA和BACE1胞内片段存在相互作用。构建了两者全长基因的表达载体,证明二者在哺乳动物细胞中同样可以相互作用。CUTA可能涉及铜的代谢动力学及乙酰胆碱酯酶(AchE)的膜锚定,而铜的代谢失衡和AchE水平与AD发病密切相关。实验结果为BACE生物学功能和AD发病机制的研究提供了条件。The deposition of β-amyloid (Aβ) is a pathologic hallmark of Alzheimer’s disease (AD). Aβ is derived from β-amyloid precursor protein (APP) through sequential proteolytic cleavages by β-secretase (BACE1) and γ-secretase. To further elucidate the roles of BACE1 in the development of AD, a yeast two-hybrid system was performed to screen proteins directly interacting with BACE1 from a human embryo brain cDNA library. One of the potential BACE1-interacting proteins identified from the positive clones is a copper-associated protein, divalent cation tolerant protein CUTA. The interaction between CUTA and BACE1 was confirmed by β-galactosidase activity and co-immunoprecipitation studies. CUTA may be involved in copper dynamics and the anchoring of AchE on the plasma membrane of cells, whereas dysregulation of copper balance and AchE levels are closely correlated with AD pathogenesis, our results suggest that CUTA may plays potential roles in the regulation of BACE1 activity/function and in the pathogenesis of Alzheimer’s disease.国家自然科学基金(No.30572077);; 细胞生物学与肿瘤细胞工程教育部重点实验室(厦门大学)(No.2005111)资助项目~

Study on Adaptability to Different Environment for Juvenile of Horseshoe Crab,Tachypleus tridentatus with Artificial Incubation

中国鲎由于具有很高的经济和药用价值,遭受大规模滥捕乱杀,鲎数量急剧锐减,目前我国鲎资源已面临枯竭的危险.人工育苗及海区放流是一种保护和恢复鲎资源种群有效可行的措施.我们从2004年7月至9月,在厦门水产技术推广站进行鲎人工授精,并以人工授精培育的鲎幼体为材料,模拟海区生态环境,自2004年10月14日至2005年3月15日进行鲎幼体钻沙、钻泥实验,并比较幼鲎在不同生态环境生长发育情况,共计152 d.结果表明,幼鲎具有钻入沙或泥的生活习性,且幼鲎在含沙或泥的海水比在普通海水中生长发育的情况更好.本实验结果为鲎苗海区人工增殖放流提供了实验依据.Horseshoe crabs have important economic and biomedical values.The amount of horseshoe crabs has declined rapidly due to uncontrolled exploitation and horseshoe crab resource will be exhausted in China.Artificial incubation and releasing is a useful method for protecting and restoring the horseshoe crab population.The juveniles were obtained through artificial fertilization in Xiamen Fishery Technical Extension Station from July to Sep 2004.The experiments of boring sand and mud were carried out under the simulated environment of sea area from Oct 14th,2004 to Sep 15th,2005.The development statuses of juveniles under different environment were compared.The results suggest that juveniles are used to bore into sand or mud and juveniles living in sea water with sand or mud will grow better and faster than in normal sea water.This will be provided a basis for the artificial propagation and artificial releasing of horseshoe crab′s juvenile.国家自然科学基金项目(30572077);; 厦门市海洋与渔业局基金项目(k53008)资

JUNO Sensitivity on Proton Decay p→νˉK+p\to \bar\nu K^+ Searches

The Jiangmen Underground Neutrino Observatory (JUNO) is a large liquid scintillator detector designed to explore many topics in fundamental physics. In this paper, the potential on searching for proton decay in $p\to \bar\nu K^+$ mode with JUNO is investigated.The kaon and its decay particles feature a clear three-fold coincidence signature that results in a high efficiency for identification. Moreover, the excellent energy resolution of JUNO permits to suppress the sizable background caused by other delayed signals. Based on these advantages, the detection efficiency for the proton decay via $p\to \bar\nu K^+$ is 36.9% with a background level of 0.2 events after 10 years of data taking. The estimated sensitivity based on 200 kton-years exposure is $9.6 \times 10^{33}$ years, competitive with the current best limits on the proton lifetime in this channel

JUNO sensitivity on proton decay p → ν K + searches*

The Jiangmen Underground Neutrino Observatory (JUNO) is a large liquid scintillator detector designed to explore many topics in fundamental physics. In this study, the potential of searching for proton decay in the $p\to \bar{\nu} K^+$ mode with JUNO is investigated. The kaon and its decay particles feature a clear three-fold coincidence signature that results in a high efficiency for identification. Moreover, the excellent energy resolution of JUNO permits suppression of the sizable background caused by other delayed signals. Based on these advantages, the detection efficiency for the proton decay via $p\to \bar{\nu} K^+$ is 36.9% ± 4.9% with a background level of $0.2\pm 0.05({\rm syst})\pm$$0.2({\rm stat})$ events after 10 years of data collection. The estimated sensitivity based on 200 kton-years of exposure is $9.6 \times 10^{33}$ years, which is competitive with the current best limits on the proton lifetime in this channel and complements the use of different detection technologies