Alzheimer's disease: fundamental and therapeutic aspects

Alzheimer's disease is the most common type of progressive and debilitating dementia affecting aged people. In some early — as well as late-onset familial cases, a genetic linkage with chromosomes 14, 21 (early-onset) or 19 (late-onset) has been indicated. Furthermore, a direct or indirect role has been attributed to normal or structurally altered amyloid -protein (concentrated in senile plaques) and/or excessively phosphorylated tau protein (located in neurofibrillary tangles). Degeneration of cholinergic neurons and concomitant impairment of cortical and hippocampal neurotransmission lead to cognitive and memory deficits. Several compounds are being tested in attempts to prevent and/or cure Alzheimer's disease, including tacrine, which has very modest efficacy in a sub-group of patients, and new acetylcholinesterase inhibitors. Pilot experiments have also been launched using nerve growth factor (NGF) to prevent or stabilize the processes of cholinergic pathway degeneration. Alternatively, antioxidants, free radical scavengers and/or non steroidal anti-inflammatory agents may be screened as potential therapies for neurodegenerative diseases induced by multiple endogenous and/or exogenous factors. The recent use of transgenic mice, in parallel with other genetic, biochemical and neurobiological systems, in vivo and/or in vitro (cell cultures), should accelerate the discovery and development of specific drugs for the treatment of Alzheimer's disease.     

Ligand effects on the structure and vibrational properties of the thiolated Au18 cluster

Most of the studies devoted to thiolated gold clusters suppose that their core and Au-S framework do not suffer from distortion independently of the protecting ligands (-SR) and it is assumed as correct to simplify the ligand as SCH3. In this work is delivered a systematic study of the structure and vibrational properties (IR and Raman) of the Au18(SR)14 cluster. The pursued goal is to understand the dependency of the displayed vibrational properties of the thiolated Au18 cluster with the ligands type. A set of six ligands was considered during calculations of the vibrational properties based on density functional theory (DFT) and in its dispersion-corrected approach (DFT-D).     

基于应力敏感系数的硅酸镓镧晶体声表面波应力敏感特性

从叠加偏载的运动方程出发,借助微扰理论推导了压电晶片上声表面波波速的应力敏感模型,提出了应力敏感系数的概念,计算了硅酸镓镧在二维旋转空间的应力敏感系数.讨论了应力敏感系数的应用,在平面应力条件下提出并验证了仅用2个系数(1α1 2α2=0)就可以方便地确定出晶体的应力补偿切向.通过对石英和硅酸镓镧两种晶体的理论计算和实验比较,证明了所提理论和方法的正确性.     

Extraction and Purification of Matrix Protein from the Nacre of Pearl Oyster Pinctada fucata

A soluble matrix protein P14 with an apparent molecular mass of 14.5 kDa was isolated from fragmented nacre of pearl oysters （Pinctada fucata） treated with 10% NaOH solution to investigate the nacre matrix proteins and their effect on the CaCO3 crystal. The protein was characterized by gel exclusion chromatography and reversed-phase high performance liquid chromatography after demineralization by 10% acetic acid. The X-ray diffraction pattern of P14 crystals indicates that P14 plays an important role in nacre biomineralization. P14 can induce aragonite formation, stimulate CaCO3 crystal formation, and accelerate aragonite precipitation. Heating of the acid insoluble nacre residue, which was named conchiolin, in 10% sodium dodecyl sulfate solution supplemented with 10% β-mercaptoethanol solution for 10-20 min at about 100℃ gave two other soluble proteins having molecular masses of 19.4 kDa and 25.0 kDa. The present study suggests that these two proteins are linked to the insoluble organic matrix by disulfide bridges because the extraction yield increases when β-mercaptoethanol is added to the medium.     

硅酸镓镧、钽酸镓镧和铌酸镓镧的声表面波传播特性

计算了硅酸镓镧、钽酸镓镧和铌酸镓镧的不同切向和传播方向的声表面波(SAW)传播特性，并对其和石英晶体上相应切向和传播方向的SAW传播特性做了对比分析．计算结果表明，这3种材料的SAW传播速度一般比石英低1km／s左右；和石英一样，具有零温度切向和纯模方向；机电耦合系数k^2却远高于石英，其中钽酸镓镧的k^2最大．对不同材料常数进行了对比计算，结果表明，不同材料常数的SAW传播特性有明显的差异，其中以频率温度系数差异最大．     

交流电刺激与环磷酰胺合用对小鼠U14生长的影响

探讨环磷酰胺(cyclophosphamide,CTX)与交流电刺激合用对小鼠U14生长的抑制效果.将右背皮下荷有U14的昆明小白鼠,随机分成4组,①D-E-,②D+E-,③D-E+,④D+E+,(D代表CTX,E代表交流电,+和-代表有和无).实验结果显示D+E+组(交流电120V,50Hz,刺激持续时间200ms,5个部位刺激,每个部位刺激2次)与D+E-相比较,有明显抑制U14的生长(P<0.05).说明环磷酰胺介导的交流电刺激为局部肿瘤的治疗提供了新思路.     

Development and differentiation of the intestinal epithelium

The gastrointestinal tract develops from a simple tube to a complex organ with patterns of differentiation along four axes of asymmetry. The organ is composed of all three germ layers signaling to each other during development to form the adult structure. The gut epithelium is a constitutively developing tissue, constantly differentiating from a stem cell in a progenitor pool throughout the life of the organism. Signals from the adjacent mesoderm and between epithelial cells are required for normal orderly development/differentiation, homeostasis, and apoptosis. Embryonically important patterning factors are used during adult stages for these processes. Such critical pathways as the hedgehog, bone morphogenetic protein, Notch, Sox, and Wnt systems are used both in embryologic and adult times of gut development. We focus on and review the roles of these factors in gut epithelial cell development and differentiation.Received 18 October 2002; received after revision 18 December 2002; accepted 18 December 2002     

Evidence for existence of a close association between CD14 and CXCR4 on monocytic cell line U937

The surface expression of HIV-1 coreceptors (CXCR4 and CCR5) on monocytes can be regulated by the ligand of CD14,and the susceptibility of the cells to HIV-1 is then changed.Our previous study found that monoclonal antibody against CD14 could dramatically inhibit CXCR4-mediated chemotaxis and cell-cell fusion.Based on these studies,we explored potential relationship between CD14 and CXCR4 on monocytic cell line U937.Flow cytometry analysis showed that anti-CXCR4 monoclonal antibody (mAb) 12G5 strongly inhibited binding of the FITC-conjugated anti-CD14 monoclonal antibodies (TUK4 and UCHM1) to U937,while another CX- CR4-specific mAb B-R24 did not show any effect on this binding.On the other hand,two anti-CD14 monoclonal antibodies (TUK4 and UCH-M1) obviously inhibited the binding of the PE-conjugated anti-CXCR4 mAb 12G5 to U937 but did not inhibit the binding of mAb 12G5 to CXCR4-transfected 3T3 cells (3T3.T4.CXCR4),which indicates that the blocking of mAb 12G5 binding to CXCR4 by CD14- specific mAbs is not involved in the possibility that CD14-specific mAbs directly bind to CXCR4.These results suggested existence of a close association between CD14 and CXCR4 on monocytic cell line U937.     

Up-regulation of endothelial nitric oxide synthase by cytochrome P450 arachidonic acid epoxygenase BM3F87V

Cytochrome P450 (CYP)-dependent metabolites of arachidonic acid, epoxyeicosatrienoic acids (EETs), have been suggested to be an endothelium-derived hyperpolarizing factor (EDHF). However, the interaction or relation between EDHF and endothelial nitric oxide synthase (eNOS) is still to be elucidated. In the present study, the regulation of eNOS by endogenous EDHF is examined. The cytochrome P450 epoxygenase BM3F87V is cloned into the mammalian expression vector pCB6. Cultured bovine aortic endothelial cells (BAECs) less than 4 passages are used and transfected with BM3F87V. The effects of endogenous EETs result from BM3F87V transfection on eNOS are assessed in the endothelial cells by Western blot and Northern blot, and eNOS activity is also measured by the conversion of L-arginine to L-citrulline. Compared to transfection with the empty pCB6 vector, transfection of BAECs with BM3F87V significantly elevates the levels of eNOS protein expression, which is markedly inhibited by treatment with CYP inhibitor 17-ODYA. BM3F87V transfection also elevates the eNOS mRNA level and increases the eNOS activity. This study suggests that EDHF up-regulates eNOS gene expression.