Novel precursor of Alzheimer's disease amyloid protein shows protease inhibitory activity

Alzheimer's disease is characterized by cerebral deposits of amyloid beta-protein (AP) as senile plaque core and vascular amyloid, and a complementary DNA encoding a precursor of this protein (APP) has been cloned from human brain. From a cDNA library of a human glioblastoma cell line, we have isolated a cDNA identical to that previously reported, together with a new cDNA which contains a 225-nucleotide insert. The sequence of the 56 amino acids at the N-terminal of the protein deduced from this insert is highly homologous to the basic trypsin inhibitor family, and the lysate from COS-1 cells transfected with the longer APP cDNA showed an increased inhibition of trypsin activity. Partial sequencing of the genomic DNA encoding APP showed that the 225 nucleotides are located in two exons. At least three messenger RNA species, apparently transcribed from a single APP gene by alternative splicing, were found in human brain. We suggest that protease inhibition by the longer APP(s) could be related to aberrant APP catabolism.     

The precursor of Alzheimer's disease amyloid A4 protein resembles a cell-surface receptor

Alzheimer's disease is characterized by a widespread functional disturbance of the human brain. Fibrillar amyloid proteins are deposited inside neurons as neurofibrillary tangles and extracellularly as amyloid plaque cores and in blood vessels. The major protein subunit (A4) of the amyloid fibril of tangles, plaques and blood vessel deposits is an insoluble, highly aggregating small polypeptide of relative molecular mass 4,500. The same polypeptide is also deposited in the brains of aged individuals with trisomy 21 (Down's syndrome). We have argued previously that the A4 protein is of neuronal origin and is the cleavage product of a larger precursor protein. To identify this precursor, we have now isolated and sequenced an apparently full-length complementary DNA clone coding for the A4 polypeptide. The predicted precursor consists of 695 residues and contains features characteristic of glycosylated cell-surface receptors. This sequence, together with the localization of its gene on chromosome 21, suggests that the cerebral amyloid deposited in Alzheimer's disease and aged Down's syndrome is caused by aberrant catabolism of a cell-surface receptor.     

甜叶菊斑枯病病原菌的生物学特性

甜叶菊斑枯病病原菌经鉴定为Septoria steviae Ishiba Yokoyama et Tani．,病菌分离菌株生长慢,在8种不同培养基上生长速度、产生分生孢子器和分生孢子的能力相差很大．光照对菌体产孢影响显,但对菌丝生长没有影响．降低马铃薯葡萄糖琼脂培养基中葡萄糖的含量,菌体生长慢,但可提高单位面积菌体产孢量．微量元素硼在一定范围内有促进产孢的作用．菌体在pH值3～10范围内均可生长,生长最适pH值是5．0～6．0．     

Protease inhibitor domain encoded by an amyloid protein precursor mRNA associated with Alzheimer's disease

Amyloid B-protein/amyloid A4 is a peptide present in the neuritic plaques, neurofibrillary tangles and cerebrovascular deposits in patients with Alzheimer's disease and Down's syndrome (trisomy 21) and may be involved in the pathogenesis of Alzheimer's disease. Recent molecular genetic studies have indicated that amyloid protein is encoded as part of a larger protein by a gene on human chromosome 21 (refs 6-9). The amyloid protein precursor (APP) gene is expressed in brain and in several peripheral tissues, but the specific biochemical events leading to deposition of amyloid are not known. We have now screened complementary DNA libraries constructed from peripheral tissues to determine whether the messenger RNA encoding APP in these tissues is identical to that expressed in brain, and we identify a second APP mRNA that encodes an additional internal domain with a sequence characteristic of a Kunitz-type serine protease inhibitor. The alternative APP mRNA is present in both brain and peripheral tissues of normal individuals and those with Alzheimer's disease, but its pattern of expression differs from that of the previously reported APP mRNA.     

利用可拓学原理分析外感病因因素的相关性

目的:对外感病的病因因素的相对性、可变性、多层次的复杂性进行定性定量的形式化描述.方法:采用可拓理论对常见中医外感病的病因因素进行可拓分析和优度评价.结果:风量大小与温差在外感病的发生中相关度最大,分别为0.151、0.063.结论:风量和温差与外感病的发生联系最为密切.     

中国对虾暴发性流行病杆状病毒的提取纯化及病原性实验

通过病毒纯化技术及电镜检测 ,发现患病的中国对虾体内有带囊膜的杆状病毒 .该病毒粒子大小为 (3 0 0～ 4 0 0 )nm× (1 60～ 1 80 )nm ,囊膜 2 0～4 0nm ,无包涵体 .人工回接实验表明 ,病虾的肝胰脏、中肠、胃、心肌组织内均分布有大量的病毒粒子 ,该病毒粒子在形态、大小、囊膜的有无及包涵体的有无等诸方面均与感染前部分纯化的病毒粒子一致 .根据柯氏法则 ,患病的中国对虾是由杆状病毒的侵袭所致 .     

Purification and cloning of amyloid precursor protein beta-secretase from human brain

Proteolytic processing of the amyloid precursor protein (APP) generates amyloid beta (Abeta) peptide, which is thought to be causal for the pathology and subsequent cognitive decline in Alzheimer's disease. Cleavage by beta-secretase at the amino terminus of the Abeta peptide sequence, between residues 671 and 672 of APP, leads to the generation and extracellular release of beta-cleaved soluble APP, and a corresponding cell-associated carboxy-terminal fragment. Cleavage of the C-terminal fragment by gamma-secretase(s) leads to the formation of Abeta. The pathogenic mutation K670M671-->N670L671 at the beta-secretase cleavage site in APP, which was discovered in a Swedish family with familial Alzheimer's disease, leads to increased beta-secretase cleavage of the mutant substrate. Here we describe a membrane-bound enzyme activity that cleaves full-length APP at the beta-secretase cleavage site, and find it to be the predominant beta-cleavage activity in human brain. We have purified this enzyme activity to homogeneity from human brain using a new substrate analogue inhibitor of the enzyme activity, and show that the purified enzyme has all the properties predicted for beta-secretase. Cloning and expression of the enzyme reveals that human brain beta-secretase is a new membrane-bound aspartic proteinase.     

Recent progress in the study of intracellular toxicity of amyloid P peptide in Alzheimer's disease

Amyloidβ(Aβ) deposition is one of the major pathological markers of Alzheimer's disease (AD). Extracellular Afi toxi-city has been studied for a long time in AD research field. However, controversial data show that extracellular Aβload does not correlate with the dementia levels of AD patients and extracellular Aβonly induces significant cell death at non-physiological high concentrations. With the evolvement of Afi hypothesis, considerable attention has been devoted to the study of intracellular Aβtoxicity recently. Intracellular Aβinduces dramatic cell loss in AD transgenic models and in human primary neurons (at pM concentrations) through p53, Bax and caspase-6 pathways. Here, we review the generation, toxicity and possible pathways of intracellular Aβtoxicity, and discuss the implication and current knowledge of intracellular Aβin neuronal cell loss in neurodegenerative diseases.     

川东北飞仙关组白云岩成因及其次生孔隙

白云岩以其次生晶间孔隙发育、易于形成高孔高渗优质油气储层为特征,长期以来受到地质学界的高度重视.早期白云石晶体自形程度及晶间孔隙的发育程度除受白云石化成岩流体的影响外,还受原岩储渗性能的控制.川东北宣汉-达县地区飞仙关组白云岩主要存在渗透回流白云石化、混合水白云石化和埋藏白云石化3种成因模式和至少3期次云化.白云岩化并...     

肉制品病原微生物的高压脉冲电场杀菌效果研究

高压脉冲电场广泛应用于牛奶、饮料等流质食品杀菌实验,本实验选用携菌鲜猪肉和鲜鱼肉为杀菌对象,磁场强度分别为0、2．4、5．16、10．36T,脉冲频率为50Hz,脉冲时长为5ms,脉冲数分别为0、10、20个,在上述条件作用下,并没有观察到杀菌效果,初步分析可能是肉制品状态不均一和电导率低所至。