A computer method for the comparison or the quantitative similarity between normal and abnormal collagen or between sequence data and experimental data

In this paper, a method is described to correlate collagen structural data obtained by electron microscopy with chemical sequence data, or to compare two experimental sets of data. In this respect, collagen provides a valuable model system, firstly for studying the chemical basis of ultrastructure and the menchanisms of various treatments on a protein, and secondly for detecting and locating the alterations collagen fibril structure produced by a collagen disorder.     

从美国 FDA 审评角度探讨新药研发的风险控制

众所周知,新药研发是一个漫长而艰难的过程,投入大,但成功率低。从项目的选择、分子结构最优化、靶点的选择、体外实 验结果与体内反应的一致性、药物安全性、临床试验设计优化以及对新药研发相关法规的理解、与监管部门的有效沟通等诸方面,探讨 对新药研发风险的把控。     

在中国北方汉族人群中血管紧张素转换酶基因I/D多态与G蛋白beta3亚基基因C825T多态对原发性高血压的联合作用

原发性高血压是一种复杂的多基因疾病,被认为是多个变异了的基因遗传交互以及环境因素共同作用的结果.证据表明,血管紧张素转换酶基因和G蛋白beta3亚基基因各自都是重要的原发性高血压的易感基因,并且可能存在共同的通路来导致高血压疾病的发展.为了探索这两个基因在中国北方汉族人群中是否对高血压有影响,挑选血管紧张素转换酶基因I/D多态与G蛋白beta3亚基基因C825T多态,在一个包含502个高血压病例和490个健康对照的样本中做了关联研究.连锁不平衡分析揭示,仅仅在男性中有显著性的非随机性分布,表明血管紧张素转换酶基因与G蛋白beta3亚基基因倾向在男性中造成高血压.调整了的单位点的多变量逐步回归分析展示,在男性显性模型中DD/ID对Ⅱ的比值比达到显著性水平(OR1.57;95%CI,1.09～2.27;P=0.016).在对性别进行分层后的联合分析中,在男性中经过调整后的比值比具有弱显著性水平:在血管紧张素转换酶基因的DD基因型中,TT对CC的比值比是0.11;95%CI,0.01～0.99;P=0.049;在G蛋白beta3亚基基因的CC CT基因型中,DD/ID对Ⅱ的比值比是1.52;95%CI,1.01～2.29;P=0.047.结果暗示,血管紧张素转换酶基因或附近的某个基因是具有男性性别倾向的高血压易感侯选基因,同时,在血管紧张素转换酶基因基因的D等位基因和G蛋白beta3亚基基因的825C等位基因之间,可能存在具有上位效应的基因-基因相互作用.     

酸溶辅助超声波法提取类球红细菌类胡萝卜素条件优化

通过单因素和正交试验,对类球红细菌3757产类胡萝卜素的提取条件进行了研究。先采用超声波法、酸溶法、研磨法、冻融法、酸溶辅助超声波法和冻融辅助超声波法优化了从类球红细菌3757菌株中提取类胡萝卜素的方法,然后开展了酸溶辅助超声波法的单因素和正交实验,最后进行了重复性实验。结果表明,酸溶辅助超声波法是较优的提取方法,丙酮是较好的提取溶剂。最佳提取条件为料液比110、超声波处理总时间20 min、酸浓度3 mol/L、酸溶时间25 min、超声波振幅40%、超声工作/间隔时间2 min/1 min、酸溶温度27℃,实验重现较好。优化后类胡萝卜素的提取率较优化前提高了74.8%,为其产业化创造了条件。     

Modulation by abscisic acid of storage protein accumulation in Vicia Faba L. cotyledons cultured in vitro

The effects of abscisic acid (ABA), high osmotica, fluridone (an inhibitor of carotenoid biosynthesis), gibberellic acid (GA₃) and an inhibitor of gibberellin biosynthesis, paclobutrazol (1-(4-chlorophenyl)-4,4-dimethyl-2-(1-24-triazol-1-yl)pentan-3-ol) on storage protein accumulation were studied in developing Vicia faba L. cotyledons cultured for 2 or 3 days in vitro. Extracts of these cotyledons were separated by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) under reducing conditions. ABA stimulated the accumulation of vicilin and legumin polypeptides. GA₃ did not noticeably stimulate the accumulation of any polypeptide. There was stimulation of vicilin and legumin polypeptide accumulation by high osmoticum (18% sucrose), which was further enhacedd by ABA and inhibited by fluridone. The fluridone inhibition was reversed by ABA addition.The data provides evidence that ABA modulates the synthesis of V. faba storage proteins.     

RNAi转基因作物安全评价研究进展

在秀丽隐杆线虫中首次发现双链RNA(dsRNA)能特异性地导致基因沉默(RNAi)现象后,人们开始大量地研究RNAi技术,并将其应用于功能基因的研究,来提高作物的抗性和改良遗传育种等。本文详细介绍了RNAi的技术原理,并且对RNAi技术与传统转基因技术的区别进行分析,阐述了该技术具有重要的生物学意义,以及在农作物害虫防治领域的占据独特优势。基于RNAi技术存在的潜在脱靶效应,从改良植物、靶标生物和生态环境的3个方面具体分析该技术可能存在的风险,为RNAi技术的风险评估提供参考。由于RNAi技术仍存在风险,为了维护生态多样性和保障人们的人身安全,应尽快建立起符合实际需求的安全性评价方法,本文针对RNAi转基因作物的环境安全和食用安全2个方面的评估方案进行概述。RNAi技术对减少害虫数量、提高水稻产量、降低种植成本以及减少化学农药污染、促进农业可持续发展来说具有重要意义,但该技术仍存在风险,需要进一步监管和研究,建立完善的生态评价系统,让RNAi技术在农业生产上发挥作用。     

从噬菌体随机肽库中筛选流感病毒神经氨酸酶的抑制多肽

目的:从噬菌体呈现12肽库中筛选与流感病毒神经氨酸酶特异性结合的肽。方法:以甲三型流感病毒裂解疫苗原液为靶分子,经过3轮生物淘选,从噬菌体随机肽库中筛选与之结合的噬菌体。用ELISA方法鉴定噬菌体克隆与靶分子的结合力,用荧光方法测定噬菌体克隆对流感病毒A/Sydney/5/97(H3N2)神经氨酸酶的抑制活性。对筛选到的阳性克隆进行DNA序列测定并推导出相应的氨基酸序列。结果:经过3轮筛选后,42个噬菌体克隆与靶分子有高度亲和力,23个噬菌体克隆对流感病毒A/Sydney/5/97(H3N2)神经氨酸酶有抑制活性。对27个噬菌体克隆的测序结果表明,分别有10个和2个克隆的序列是一致的,其氨基酸序列分别为KSLSRHDHIHHH和WPRHHHSASVQT。结论:通过噬菌体肽库筛选到抑制流感病毒神经氨酸酶的12肽,为进一步研究对流感病毒神经氨酸酶有抑制活性的分子药物奠定了基础。     

Emerging targets and new small molecule therapies in Parkinson’s disease treatment

Parkinson’s disease (PD) is a common chronic degenerative disease of the central nervous system. Due to a rapidly aging society worldwide, PD morbidity is on the rise; however, the treatment of PD with conventional drugs carries serious adverse reactions and cannot fix the root cause of PD, the degeneration of dopaminergic neurons, which limits conventional drug usage in clinical practice. In recent years, research on the pathogenesis of PD and its clinical manifestations has led to the discovery of an increasing number of novel targets in PD, including several small molecule targeted compounds. In this paper, we analyze and summarize the most recently published PD literature and review several recently discovered novel targets in PD and their small molecule targeted pharmacologically active agents based on their mechanisms of action and pharmacodynamic profiles.