Anti-amyloidogenic therapies: strategies for prevention and treatment of Alzheimer’s disease

Deposition of amyloid β-protein (Aβ) in the brain is an early and invariant neuropathological feature of Alzheimer’s disease (AD). The current search for anti-AD drugs is mainly focused on modification of the process of accumulation of Aβ in the brain. Here, we review four anti-amyloidogenic strategies: (i) reduction of Aβ production, which has mainly been approached with secretase inhibition, (ii) promotion of the Aβ degrading catabolic pathway, including an Aβ degrading enzyme, neprilysin, (iii) immunotherapy for Aβ and (iv) inhibition of Aβ aggregation. We have reported that AD patients have a favorable molecular environment for Aβ aggregation and that various compounds, such as polyphenols, interfere with Aβ aggregation and destabilize preformed Aβ fibrils. Received 21 December 2005; received after revision 14 February 2006; accepted 29 March 2006     

Climate-driven trends in contemporary ocean productivity

Contributing roughly half of the biosphere's net primary production (NPP), photosynthesis by oceanic phytoplankton is a vital link in the cycling of carbon between living and inorganic stocks. Each day, more than a hundred million tons of carbon in the form of CO2 are fixed into organic material by these ubiquitous, microscopic plants of the upper ocean, and each day a similar amount of organic carbon is transferred into marine ecosystems by sinking and grazing. The distribution of phytoplankton biomass and NPP is defined by the availability of light and nutrients (nitrogen, phosphate, iron). These growth-limiting factors are in turn regulated by physical processes of ocean circulation, mixed-layer dynamics, upwelling, atmospheric dust deposition, and the solar cycle. Satellite measurements of ocean colour provide a means of quantifying ocean productivity on a global scale and linking its variability to environmental factors. Here we describe global ocean NPP changes detected from space over the past decade. The period is dominated by an initial increase in NPP of 1,930 teragrams of carbon a year (Tg C yr(-1)), followed by a prolonged decrease averaging 190 Tg C yr(-1). These trends are driven by changes occurring in the expansive stratified low-latitude oceans and are tightly coupled to coincident climate variability. This link between the physical environment and ocean biology functions through changes in upper-ocean temperature and stratification, which influence the availability of nutrients for phytoplankton growth. The observed reductions in ocean productivity during the recent post-1999 warming period provide insight on how future climate change can alter marine food webs.     

Magnetic vortex core reversal by excitation with short bursts of an alternating field

The vortex state, characterized by a curling magnetization, is one of the equilibrium configurations of soft magnetic materials and occurs in thin ferromagnetic square and disk-shaped elements of micrometre size and below. The interplay between the magnetostatic and the exchange energy favours an in-plane, closed flux domain structure. This curling magnetization turns out of the plane at the centre of the vortex structure, in an area with a radius of about 10 nanometres--the vortex core. The vortex state has a specific excitation mode: the in-plane gyration of the vortex structure about its equilibrium position. The sense of gyration is determined by the vortex core polarization. Here we report on the controlled manipulation of the vortex core polarization by excitation with small bursts of an alternating magnetic field. The vortex motion was imaged by time-resolved scanning transmission X-ray microscopy. We demonstrate that the sense of gyration of the vortex structure can be reversed by applying short bursts of the sinusoidal excitation field with amplitude of about 1.5 mT. This reversal unambiguously indicates a switching of the out-of-plane core polarization. The observed switching mechanism, which can be understood in the framework of micromagnetic theory, gives insights into basic magnetization dynamics and their possible application in data storage.     

HIV-1 superinfection despite broad CD8+ T-cell responses containing replication of the primary virus

Early treatment of acute HIV-1 infection followed by treatment interruptions has shown promise for enhancing immune control of infection. A subsequent loss of control, however, allows the correlates of protective immunity to be assessed. Here we show that sudden breakthrough of plasma viraemia occurred after prolonged immune containment in an individual infected with HIV-1 at a time when 25 distinct CD8+ T-cell epitopes in the viral proteins Gag, RT, Integrase, Env, Nef, Vpr, Vif and Rev were being targeted. Sequencing of the virus in plasma and cells showed that superinfection with a second clade-B virus was coincident with the loss of immune control. This sudden increase in viraemia was associated with a decline in half of the CD8+ T-cell responses. The declining CD8+ T-cell responses were coupled with sequence changes relative to the initial virus that resulted in impaired recognition. Our data show that HIV-1 superinfection can occur in the setting of a strong and broadly directed virus-specific CD8+ T-cell response. The lack of cross-protective immunity for closely related HIV-1 strains, despite persistent recognition of multiple CD8 epitopes, has important implications for public health and vaccine development.     

Numerous potentially functional but non-genic conserved sequences on human chromosome 21

The use of comparative genomics to infer genome function relies on the understanding of how different components of the genome change over evolutionary time. The aim of such comparative analysis is to identify conserved, functionally transcribed sequences such as protein-coding genes and non-coding RNA genes, and other functional sequences such as regulatory regions, as well as other genomic features. Here, we have compared the entire human chromosome 21 with syntenic regions of the mouse genome, and have identified a large number of conserved blocks of unknown function. Although previous studies have made similar observations, it is unknown whether these conserved sequences are genes or not. Here we present an extensive experimental and computational analysis of human chromosome 21 in an effort to assign function to sequences conserved between human chromosome 21 (ref. 8) and the syntenic mouse regions. Our data support the presence of a large number of potentially functional non-genic sequences, probably regulatory and structural. The integration of the properties of the conserved components of human chromosome 21 to the rapidly accumulating functional data for this chromosome will improve considerably our understanding of the role of sequence conservation in mammalian genomes.     

热预处理对细胞分裂效率的影响

以发酵酵母为研究对象，采用超声波空蚀和高压均质方法对细胞进行机械细胞分裂，研究了热预处理对微生物细胞分裂效率的作用。结果表明：酵母悬浮液的温度经热预处理从室温（22±1）℃上升到40-50℃时，达到相同程度的细胞分裂效率所需的能量降低了；当酵母悬浮液的温度经热预处理上升到50℃时，蛋白质浓度达到最大值，蛋白质发生变质的热预处理温度≥52℃。     

sBLM味觉物质生物敏感器件的研究

本文研究以琼脂糖为基的固体支撑双层脂膜（ｓＢＬＭ）对味觉物质（乙酸、盐酸喹咛、蔗糖）的响应．这三种味觉物质显著地改变了膜电位，盐酸喹咛、蔗糖对膜电阻有一定影响，脂膜对乙酸和盐酸喹咛也有良好的线性响应．检测灵敏度分别为１２μｍｏｌ／Ｌ和１．３μｍｏｌ／Ｌ，其响应特性、检测灵敏度都达到或优于现有的其它检测方法．用Ｃ６０修饰卵磷脂双层脂膜，加大了膜强度，用它检测上述三种物质，得到了相同结果．     

光学头定位系统的输入成形控制

光学头定位控制由于快速性的要求使得系统产生振荡,影响定位精度.本文应用输入成形方法抑制光头在定位时的振动.通过建立光学头机电系统的数学模型,对于无参数摄动和有参数摄动两种情形分别应用零振荡()和零振荡加微分()两种输入成形控制器进行振动抑制,计算机数值仿真结果表明,该方法对于抑制光学头定位过程中的振动具有较好的效果.