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.     

电离辐射诱发小鼠骨髓细胞依赖和不依赖P53基因的凋亡

细胞凋亡(apoptosis)或程序性细胞死亡(programmed cell death),是一种具有典型形态学和生化特征的细胞死亡模式。在胚胎发育,T,B细胞成熟和内分泌相关的组织萎缩等生命过程中发生的细胞死亡,就是一种生理性细胞凋亡,以此控制体内细胞数量。辐射和某些抗肿瘤药物等DNA损伤因子,亦能诱发细胞凋亡,并与某些肿瘤相关基因的诱导表达和蛋白稳定性的改变等事件发生相关。P53基因是一种抑癌基因,参与细胞增殖调控,使细胞生长停滞于G_1期。近年发现,P53基因在细胞DNA受损伤后引发的细胞凋亡过程中也起重要作用。不同学者分别报道,电离辐射诱发小鼠胸腺细胞和小肠上皮细胞的凋亡,是依赖于P53基因,包括P53基因表达增加和P53蛋白稳定性增强。在P53基因缺失纯合子小鼠中,电离辐射就不能有效地启动上述组织细胞的凋亡机制。本文利用基因打靶技术产生的P53基因突变小鼠模型,研究不同P53基因状态下,即野生型(P53+/+)、杂合子(P53+/-)和纯合子突变型(P53-/-),电离辐射诱发小鼠骨髓细胞的凋亡。     

重载流多芯电缆周围的磁场 Ⅰ. 理论模型

多芯电力电缆在低压配电系统中常被用作配电干线，这种重载流电缆周围的极低频磁场可能干扰附近敏感电子设备的正常运行，甚至影响暴露于该场下的人体的健康，为分析这种磁场的分布特性，建立了多芯电缆周围磁场的载流平行螺旋线模型，并推导了周围磁场的简化计算公式，基于所提出的理想模型对电缆周围电磁的特性进行了分析，发现在电缆的半径方向上磁场随距离衰减的速度大于指数衰减速度，在平行于电缆轴线的直线上和在电缆抽轴圆周线上，磁场的幅值和相角都随观测点的位置周期变化，理论计算结果表明，常用规格的多芯电力电缆在载额定电流的情况下，距电缆2m外空间中的磁场已小于有关国际标准的限值。     

智能化集成媒体通讯技术

多媒体数字化技术集成了文本、图像、声音、动画、视频等方面，移动媒体技术对多媒体的图像、声音质量、传输带宽等都提出了要求，本书讨论了一些适用于第三代移动媒体终端的方法和技术，主要是面向第三代移动服务。     

Temporal precision in the neural code and the timescales of natural vision

The timing of action potentials relative to sensory stimuli can be precise down to milliseconds in the visual system, even though the relevant timescales of natural vision are much slower. The existence of such precision contributes to a fundamental debate over the basis of the neural code and, specifically, what timescales are important for neural computation. Using recordings in the lateral geniculate nucleus, here we demonstrate that the relevant timescale of neuronal spike trains depends on the frequency content of the visual stimulus, and that 'relative', not absolute, precision is maintained both during spatially uniform white-noise visual stimuli and naturalistic movies. Using information-theoretic techniques, we demonstrate a clear role of relative precision, and show that the experimentally observed temporal structure in the neuronal response is necessary to represent accurately the more slowly changing visual world. By establishing a functional role of precision, we link visual neuron function on slow timescales to temporal structure in the response at faster timescales, and uncover a straightforward purpose of fine-timescale features of neuronal spike trains.     

Millennial- and orbital-scale changes in the East Asian monsoon over the past 224,000 years

High-resolution speleothem records from China have provided insights into the factors that control the strength of the East Asian monsoon. Our understanding of these factors remains incomplete, however, owing to gaps in the record of monsoon history over the past two interglacial-glacial cycles. In particular, missing sections have hampered our ability to test ideas about orbital-scale controls on the monsoon, the causes of millennial-scale events and relationships between changes in the monsoon and climate in other regions. Here we present an absolute-dated oxygen isotope record from Sanbao cave, central China, that completes a Chinese-cave-based record of the strength of the East Asian monsoon that covers the past 224,000 years. The record is dominated by 23,000-year-long cycles that are synchronous within dating errors with summer insolation at 65 degrees N (ref. 10), supporting the idea that tropical/subtropical monsoons respond dominantly and directly to changes in Northern Hemisphere summer insolation on orbital timescales. The cycles are punctuated by millennial-scale strong-summer-monsoon events (Chinese interstadials), and the new record allows us to identify the complete series of these events over the past two interglacial-glacial cycles. Their duration decreases and their frequency increases during glacial build-up in both the last and penultimate glacial periods, indicating that ice sheet size affects their character and pacing. The ages of the events are exceptionally well constrained and may thus serve as benchmarks for correlating and calibrating climate records.     

Constant darkness is a circadian metabolic signal in mammals

Environmental light is the 'zeitgeber' (time-giver) of circadian behaviour. Constant darkness is considered a 'free-running' circadian state. Mammals encounter constant darkness during hibernation. Ablation of the master clock synchronizer, the suprachiasmatic nucleus, abolishes torpor, a hibernation-like state, implicating the circadian clock in this phenomenon. Here we report a mechanism by which constant darkness regulates the gene expression of fat catabolic enzymes in mice. Genes for murine procolipase (mClps) and pancreatic lipase-related protein 2 (mPlrp2) are activated in a circadian manner in peripheral organs during 12 h dark:12 h dark (DD) but not light-dark (LD) cycles. This mechanism is deregulated in circadian-deficient mPer1-/-/mPer2m/m mice. We identified circadian-regulated 5'-AMP, which is elevated in the blood of DD mice, as a key mediator of this response. Synthetic 5'-AMP induced torpor and mClps expression in LD animals. Torpor induced by metabolic stress was associated with elevated 5'-AMP levels in DD mice. Levels of glucose and non-esterified fatty acid in the blood are reversed in DD and LD mice. Induction of mClps expression by 5'-AMP in LD mice was reciprocally linked to blood glucose levels. Our findings uncover a circadian metabolic rhythm in mammals.     

Persistence of soil organic matter as an ecosystem property

Globally, soil organic matter (SOM) contains more than three times as much carbon as either the atmosphere or terrestrial vegetation. Yet it remains largely unknown why some SOM persists for millennia whereas other SOM decomposes readily--and this limits our ability to predict how soils will respond to climate change. Recent analytical and experimental advances have demonstrated that molecular structure alone does not control SOM stability: in fact, environmental and biological controls predominate. Here we propose ways to include this understanding in a new generation of experiments and soil carbon models, thereby improving predictions of the SOM response to global warming.     

对正在泌乳的母羊给予促性腺激素后可提高其孕酮和妊娠率

<正> 在3、4月间,对产后20—31天正在泌乳的母羊诱导发情。发情时配种,配种后11、12和13天,用一种盐水或绒毛膜促性腺激素处理母羊(HCG;100国际单位)。对经过妊娠诊断的母羊,不论妊娠或未妊娠,发现配种后12、14和16天,用绒毛膜促性腺激素处理过的比用盐水处理过的血清中孕酮浓度增加(P<0.01)。用绒毛膜促性腺激素处理的母羊比用盐水(29％58标准液;P<0.05)处理的母羊妊娠率较高。从试验提供的资料指出,用绒毛膜