Glycogen synthase kinase 3β and Alzheimer’s disease: pathophysiological and therapeutic significance

Alzheimer’s disease (AD) is a neurodegenerative disorder associated with cognitive and behavioral dysfunction and is the leading cause of dementia in the elderly. Several studies have implicated molecular and cellular signaling cascades involving the serine-threonine kinase, glycogen synthase kinase β(GSK-3β) in the pathogenesis of AD. GSK-3β may play an important role in the formation of neurofibrillary tangles and senile plaques, the two classical pathological hallmarks of AD. In this review, we discuss the interaction between GSK-3β and several key molecules involved in AD, including the presenilins, amyloid precursor protein, tau, and β-amyloid. We identify the signal transduction pathways involved in the pathogenesis of AD, including Wnt, Notch, and the PI3 kinase/Akt pathway. These may be potential therapeutic targets in AD. Received 19 December 2005; received after revision 24 January 2006; accepted 6 February 2006     

Phyllosilicates on Mars and implications for early martian climate

The recent identification of large deposits of sulphates by remote sensing and in situ observations has been considered evidence of the past presence of liquid water on Mars. Here we report the unambiguous detection of diverse phyllosilicates, a family of aqueous alteration products, on the basis of observations by the OMEGA imaging spectrometer on board the Mars Express spacecraft. These minerals are mainly associated with Noachian outcrops, which is consistent with an early active hydrological system, sustaining the long-term contact of igneous minerals with liquid water. We infer that the two main families of hydrated alteration products detected-phyllosilicates and sulphates--result from different formation processes. These occurred during two distinct climatic episodes: an early Noachian Mars, resulting in the formation of hydrated silicates, followed by a more acidic environment, in which sulphates formed.     

增强现实中虚拟物体的投影注册算法研究

研究增强现实的关键技术之一的虚拟物体注册技术,使增强现实系统中的增强信息更具有真实感,结合三色基准注册技术,借助三维空间中的坐标系变换和立体投影变换算法,建立增强现实系统中虚拟物体投影注册模型,提出并推导增强现实系统的虚拟物体立体视觉投影注册算法,该算法能够很好地实现已知几何描述的虚拟物体从其自身坐标系到增强现实系统坐标系的转换,并能够生成具有视差的左右眼立体图像,本算法结合视点的三然基准算法完整地实现了用于增强现实的三维注册。     

Direct imaging of the pores and cages of three-dimensional mesoporous materials

Mesostructured composite materials, with features ranging from 20 to 500 A in size, are obtained by the kinetically controlled competitive assembly of organic and inorganic species into nanostructured domains. Short-range order is limited, and long-range order is determined by weak forces such as van der Waals or hydrogen-bonding. Three-dimensional mesoporous materials obtained by removing the organic phase are of particular interest for applications such as catalysis and chemical sensing or separation, for which structural features such as cavity shape, connectivity and ordered bimodal porosity are critical. But atomic-scale structural characterization by the usual diffraction techniques is challenging for these partially ordered materials because of the difficulty in obtaining large (> 10 microm) single crystals, and because large repeat spacings cause diffraction intensities to fall off rapidly with scattering angle so that only limited small-angle data are available. Here we present a general approach for the direct determination of three-dimensional mesoporous structures by electron microscopy. The structure solutions are obtained uniquely without pre-assumed models or parametrization. We report high-resolution details of cage and pore structures of periodically ordered mesoporous materials, which reveal a highly ordered dual micro- and mesoscale pore structure.     

Angiotensin-converting enzyme 2 is an essential regulator of heart function

Cardiovascular diseases are predicted to be the most common cause of death worldwide by 2020. Here we show that angiotensin-converting enzyme 2 (ace2) maps to a defined quantitative trait locus (QTL) on the X chromosome in three different rat models of hypertension. In all hypertensive rat strains, ACE2 messenger RNA and protein expression were markedly reduced, suggesting that ace2 is a candidate gene for this QTL. Targeted disruption of ACE2 in mice results in a severe cardiac contractility defect, increased angiotensin II levels, and upregulation of hypoxia-induced genes in the heart. Genetic ablation of ACE on an ACE2 mutant background completely rescues the cardiac phenotype. But disruption of ACER, a Drosophila ACE2 homologue, results in a severe defect of heart morphogenesis. These genetic data for ACE2 show that it is an essential regulator of heart function in vivo.     

Stormwater Management in Hong Kong

IntroductionStormwater management(SWM) in Hong Kong isthe responsibility of the drainage servicesdepartment (DSD) of the Governmentof the HongKong Special Administrative Region.Thedepartment is charged with the formulation ofpolicy and the design,construction,operation andmaintenance of all public stormwater drainagesystems,as well as approving private drainsthrough an administrative framework.　 The principal concern of SWM is the reductionof the risk and extent of flooding.Thus,thesuc…     

HIV-1复合多表位基因的原核表达和多克隆抗体制备

为表达HIV-1复合多表位基因并制备其多克隆抗体.设计引物,以HIV-1标准株全长cDNA序列为模板,PCR扩增获得p24基因片段;合成改造后的多个表位基因MEG并且与p24片段相连接,克隆入大肠杆菌.将测序正确的p24MEG基因克隆入原核表达载体pET32a并诱导表达.采用Ni2 -NTA亲和柱纯化目的蛋白,以p24抗体对纯化蛋白进行Western-blot分析.将纯化的融合蛋白免疫家兔制备多克隆抗体.通过PCR成功获得长度为651 bp的HIV-1的p24片段,获得了与多表位基因连接后的p24MEG基因,通过诱导表达,显示在相对分子量约45 000处有预计大小的特异性条带,表明成功表达出融合蛋白.经此纯化的融合蛋白免疫的家兔能产生特异性抗体,其滴度达到1:3 200.纯化的融合蛋白和多克隆抗体为研究新型HIV疫苗奠定一定的理论和实践基础.     

Ankyrin and spectrin associate with voltage-dependent sodium channels in brain

The segregation of voltage-dependent sodium channels to specialized regions of the neuron is crucial for propagation of an action potential. Studies of their lateral mobility indicate that sodium channels are freely mobile on the neuronal cell body but are immobile at the axon hillock, presynaptic terminal and at focal points along the axon. To elucidate the mechanisms that regulate sodium channel topography and mobility, we searched for specific proteins from the brain that associate with sodium channels. Here we show that sodium channels labelled with 3H-saxitoxin (STX) are precipitated in the presence of exogenous brain ankyrin by anti-ankyrin antibodies and that 125I-labelled ankyrin binds with high affinity to sodium channels reconstituted into lipid vesicles. The cytoplasmic domain of the erythrocyte anion transporter competes for the latter interaction. Neither the neuronal GABA (gamma-aminobutyric acid) receptor channel complex nor the dihydropyridine (DHP) receptor bind brain ankyrin. The results indicate that brain ankyrin links the voltage-dependent sodium channel to the underlying cytoskeleton and may help to maintain axolemmal membrane heterogeneity and control sodium channel mobility.