Rac1 changes the substrate specificity of gamma-secretase between amyloid precursor protein and Notch1

Beta amyloid peptide is generated from amyloid precursor protein (APP) by proteolytic cleavage of β- and γ-secretases, and plays a critical role in the pathogenesis of Alzheimer’s disease. Since γ-secretase cleaves several proteins including APP and Notch in a number of cell types, it is important to understand the conditions determining γ-secretase substrate specificity. In the present study, inhibition of Rac1 attenuated γ-secretase activity for APP, resulting in decreased production of the APP intracellular domain but accumulated C-terminal fragments (APP-CTF). In contrast, Rac1 inhibitor, NSC23766 increased production of the Notch1 intracellular domain but slightly decreased the ectodomain-shed form of Notch1 (NotchΔE). To elucidate the mechanism underlying these observations, we performed co-immunoprecipitation experiments to analyze the interaction between Rac1 and presenilin1 (PS1), a component of the γ-secretase complex. Inhibition of Rac1 enhanced its interaction with PS1. Under the same condition, PS1 interacted more strongly with NotchΔE than with APP-CTF. Our results suggested that PS1 determines the preferred substrate for γ-secretase between APP and Notch1, depending on the activation status of Rac1.     

Two conformational states of Ras GTPase exhibit differential GTP-binding kinetics

Previous ³¹P NMR studies revealed that small GTPases H-Ras and K-Ras in complex with GTP assume two interconverting conformational states, state 1 and state 2. While state 2 corresponds to an active conformation, little is known about the function of state 1, an inactive conformation incapable of effector binding. To address the biochemical properties of state 1, we measured the ³¹P NMR spectra of five Ras family small GTPases; H-Ras, M-Ras, Rap1A, Rap2A and RalA, and find that they exhibit distinctive state 2/state 1 populations with the ratios ranging from 0.072 for M-Ras to 16 for Rap2A. Further, we show that GTPases with higher populations of state 1 exhibit higher dissociation and association rate constants for GTP. These results imply that GTP loading to the nucleotide-free small GTPases preferentially yields state 1, which is subsequently converted to state 2, rendering the GTP-bound form functional.     

腊叶标本中微小种子SEM样品制备

腊叶标本中微小种子表面的污染物会影响对其表面特征的观察。经低浓度洗洁精(0．001％)浸泡→超声波振动(33kHz,50W)→系列酒精浓度清洗处理后,在SEM下,处理后的种子表面比处理前更加清晰。此方法操作简便、效果明显,并且安全和无污染。     

Self-structure induction in single stranded poly(A) by small molecules: Studies on DNA intercalators, partial intercalators and groove binding molecules

Self-structure induction in single stranded poly(A) has been one typical example of the various ways that could be used to modulate nucleic acid structural aspects through binding of small molecules. For the first time, the interaction between a series of small molecules and poly(A) has been investigated to understand the nature of the structural features in DNA binding small molecules that could be responsible for the formation of self-structure in single stranded poly(A) molecules. Classical intercalators like ethidium, coralyne, quinacrine and proflavine, partial intercalators like berberine and palmatine and classical minor groove binders like hoechst 33258 and DAPI have been chosen for this study. The binding of each of these molecules to poly(A) has been characterized by absorption spectral titration, job plot and isothermal titration calorimetry. Self-structure formation was monitored from circular dichroic melting, optical melting and differential scanning calorimetry. The results revealed that while all the intercalators studied induced self-structure formation, partial intercalators did not induce the same in poly(A). Of the two classical DNA minor groove binding molecules investigated, hoechst was effective in inducing self-structure while DAPI was ineffective. Self-structure induction in poly(A) was observed to be directly linked to the cooperative binding of the molecules to poly(A) in that all the molecules that bound cooperatively induced self-structure in poly(A). Structural and thermodynamic aspects of the interaction leading to self-structure formation are described.     

唐家河自然保护区小哺乳动物空间生态位初步研究

1989年4～11月,采用去除取样法,对四川省唐家河自然保护区内小哺乳动物的空间生态位宽度和重叠度进行了研究。共安置ll000铗日,捕获小哺乳动物14种846只。根据香农一威纳多样性指数公式以及Cowell和Futuyma公式分别计算了各小哺乳动物种群的空间生态位宽度和空间生态位重叠指数。在14种小哺乳动物中,社鼠的空间生态位宽度指数最大（1．00）,大足鼠、川I西长尾朐、川朐和灰麝朐的最小,均为0。14种小哺乳动物空间生态位重叠指数最大为1,最小为0,其中大足鼠与川西长尾朐及灰麝朐、针毛鼠与川朐的空间生态位彼此完全重叠;藏鼠兔与针毛鼠、大足鼠、洮洲绒鼠、川西长尾朐、川朐以及灰麝朐的空间生态位完全分离。空间生态位完全重叠的种类,是通过选择不同的食物以及不同的微生境来避免过度竞争。回归分析显示,小哺乳动物种群的空间生态位宽度指数与它们利用空间资源的平均值呈显著的正相关（r=0．8285,P〈0．05）。空间生态位宽度指数的季节变化表明,社鼠种群分布没有明显的季节差异,中华姬鼠和安氏白腹鼠每年可能有一个数量高峰期,高山姬鼠一年则可能有两个数量高峰。     

大鵟的食性改变:来自稳定性碳同位素的证据

通过对大规模灭鼠后的海北高寒草甸生态系统大鵟、小型哺乳类以及雀形目鸟类肌肉稳定性碳同位素比值的测定发现,大篱的肌肉稳定性碳同位素比值介于-22．60‰和-23．10‰之间;小型哺乳类和主要雀形目鸟类肌肉稳定性碳同位素比值分别介于-25．57‰和-25．78‰以及-24．81‰和-22．51‰之间,且它们之间差异性显著。基于碳同位素的分馏模式(即动物和它食物之间稳定性碳同位素分馏在1‰～2‰之间),我们推断经大规模灭鼠后,大篱的食性发生了较大变化,其食物主要来源于高寒草甸的雀形目鸟类,而非原来的小型哺乳类。通过稳定性同位素营养级模型的运算发现,大蔫处在4．23左右的营养级;雀形目鸟类处在2．4到3．39左右的营养级,而小型哺乳类则处在1．45到1．82左右的营养级。进而采用稳定性同位素质量平衡模型计算得出,大篱的食物由35．04％的小型哺乳类和64．96％的雀形目鸟类所组成,进一步说明小型哺乳类在大量灭鼠后仅占大篱食物的很小一部分。由此可见,采取大规模的化学灭鼠,不仅降低了小型啮齿类天敌——大鵟的数量,而日使得其食谱发毕了巨大改变而转向草甸主要雀形目鸟类[动物学报49(6)：764～768,2003]。     

恒河猴外周血及肾组织SV40病毒基因分析

SV40即猿猴病毒40 (simian virus 40),是DNA肿瘤病毒的原型代表,其基因结构为共价闭合环状双股DNA分子,标准参考株SV40-776含5243个核甘酸。不同分离株bp数略有差异。SV40病毒为强DNA肿瘤病毒,具有使啮齿类动物及人源多种组织培养细胞永生化和转化能力。SV40病毒早期基因编码两个早期非结构蛋白即小T抗原(ST-ag、)和大T抗原(LT-ag),与病毒诱导的肿瘤发生有关。近年来研究表明,从猴体组织新分离的SV40株与实验室参考株SV40-776及SV40-B株相比较,具有明显的遗传异质性,并且SV40遗传变     

小肠细菌过生长与非酒精性脂肪性肝炎的关系初步研究

目的：调查小肠细菌过生长在非酒精性脂肪性肝炎病人中的发生率。方法：研究病例包括非酒精性脂肪性肝炎39例、慢性乙型肝炎47例、健康对照27例。小肠细菌过生长以乳果糖H2呼气试验诊断。结果：小肠细菌过生长在非酒精性脂肪性肝炎的发生率为45．7％,慢性乙型肝炎为32．5％,健康对照4．2％,前二组差异无显著性,但都显著高于对照组。结论：小肠细菌过生长在非酒精性脂肪性肝炎病人有较高的发生率,但其因果关系尚需阐明。     

云南白草岭鼠形小兽群落结构及垂直分布

对云南白草岭鼠形小兽群落结构,垂直分布及动物区系进行了调查,结果共捕获小兽21种1028只,隶属于啮齿目(Rodenria)鼠科（Muridae）10种,仓鼠科（Cricetidae)2种,松鼠科（Sciuridae)2种;食虫目（Insectivora）Juqin科（Soricdae)6种,鼹科（Talpidae)1种。其中东洋界15种,占71．43％,古北界4种,占19．04％,广布种2种,占9．53％,各个垂直带鼠形小兽群落物种多样性指数分别为,Ⅰ,云南松林及山坡耕作地带（2000－2650m)1.3814;Ⅱ。温凉性针阔叶混交林带（2650－3150m)1．6126;Ⅲ．苍山冷杉林带（3150－3500m)1．3488;Ⅳ。亚高山灌丛草甸带（3500－3657m）1．5085。云南白草岭优势种主要由齐氏姬鼠（Aopdemus chevieri)、中华姬鼠（A.draco)、大耳姬鼠（A.latronum)、大绒鼠（Eothenomys miletus)和昭通绒鼠（E.olitor)5种组成。