Enhancement of memory function in aged mice by a novel derivative of xanomeline

In age-related cognitive deficits and Alzheimer＇s disease （AD）, one of the most common pathological changes appears to be the loss of cholinergic neurons in the forebrain and the depletion of cortical cholinergic axons [1]. Accordingly, attempts have been made to generate therapies that aim to reverse the cognitive deficits associated with AD and aging by direct stimulation of mAChRs with specific agonists.     

黄浦江和苏州河上游鱼类多样性组成的时空特征

为初步了解黄浦江和苏州河的鱼类多样性组成及其时空分布特征,2005年6月至2006年5月,对黄浦江上游河段的淀峰、松浦大桥两个站点,以及苏州河上游河段的白鹤、黄渡两个站点进行了逐月的鱼类监测。四个站点共采集到鱼类44种,隶属10目14科35属,其中苏州河上游30种,隶属6目10科25属,黄浦江上游39种,隶属10目13科32属。黄浦江上游鱼类的物种多样性明显高于苏州河上游,白鹤、松浦大桥、淀峰之间的鱼类群落为中等相似,黄渡与松浦大桥、淀峰之间的鱼类群落为中等不相似。各站点的鱼类具明显的季节性变化,夏、秋季大于冬、春季。四个站点的鱼类均以杂食性和定居性的物种为主,杂食性鱼类物种数占51.5–62.5%。松浦大桥站的江海洄游性和河湖洄游性鱼类数量明显多于其他站点。鱼类物种的时空重现率计算结果反映了黄浦江、苏州河上游各水域的鱼类群落具相对独立性。初步研究结果表明长期恶化的水质问题和较差的水系连通度可能是影响苏州河上游鱼类多样性的关键因素,而黄浦江具更大水域面积,以及较好水质状况和水系连通度,有利于丰富鱼类多样性。     

西藏土壤中铜含量及分布

Cu content in soils sampled from different sites in Tibet was analyzed.The results showed that the average Cu content of soils was 19.6mg穔g^-1,lower than the average content in China.The content of Cu was distributed in Tibet with a total of gradually decreasing from the southeast to the northwest,which was consistent with the direction of change in the zonal successions of soil in Tibet.The variation of the content of Cu in the soils developed from different soil parent materials in Tibet was very remarkable,and the content of Cu in the soil developed from shale was greatly higher than that in the soil developed from other soil parent material.     

西藏土壤中铜含是及分布

1　引　　言目前 ,西藏的生态环境基本保持原生状态 ,是至今地球上受人类活动影响和污染最少的地区之一 .所以 ,西藏是进行生态环境本底调查和表生地球化学研究最为理想的场所 .西藏的土壤中Ｃｕ含量数据 ,不但有助于进一步研究西藏高原表生环境中Ｃｕ的地球化学特征 ,而且还可以为这一地区环境监测与评价等提供基础信息和依据 ,也可以成为全国乃至全世界土壤生态环境背景的永久性参比资料 .2　材料与方法2 1　供试材料样品采自北起唐古拉山 ,南至亚东、樟木、吉隆、普兰 ,东从金沙江 ,西到班公错—除羌唐高原北部以外的西藏广大地区 ,共计…     

Change of apocytocrhome c translocation across membrane in consequence of hydrophobic segment deletion

Wild-type apocytochrome c and its hydrophobic segment deleted mutants, named 28–39, 72–86 and 28–29/72–86 were constructed, expressed and highly purified respectively. Insertion ability into phospholipid monolayer, inducing leakage of entrapped fluorescent dye fluorescein sulfonate (FS) from liposomes, and translocation across model membrane system showed that the wild-type apoprotein and 28–39 almost exhibited the same characteristics, while mutants with segment 72–86 deletion did not. Furthermore, CD spectra, intrinsic fluorescence emission spectra, and the accessibility of the protein to the fluorescence quenchers: KI, acrylamide and HB demonstrated that the segment 72–86 deletion has a significant effect on the conformational changes of apocytochrome c following its interaction with phospholipid. On the basis of these results it is postulated that the C-terminal hydrophobic segment 72–86 plays an important role in the translocation of apocytochrome c across membrane.     

Nitric oxide uptake by erythrocytes is primarily limited by extracellular diffusion not membrane resistance

The process of NO transfer into erythrocytes (RBCs) is of critical biological importance because it regulates the bioavailability and diffusional distance of endothelial-derived NO. It has been reported that the rate of NO reaction with oxyhemoglobin (Hb) within RBCs is nearly three orders of magnitude slower than that by equal amounts of free oxyhemoglobin. Consistent with early studies on oxygen uptake by RBCs, the process of extracellular diffusion was reported to explain this much lower NO uptake by RBC encapsulated Hb (Liu, X., Miller, M. J., Joshi, M. S., Sadowska-Krowicka, H., Clark, D. A., and Lancaster, J. R., Jr. (1998) J. Biol. Chem. 273, 18709-18713). However, it was subsequently proposed that the RBC membrane provides the main resistance to NO uptake rather than the process of extracellular diffusion (Vaughn, M. W., Huang, K. T., Kuo, L., and Liao, J. C. (2000) J. Biol. Chem. 275, 2342-2348). This conclusion was based on competition experiments that were assumed to be able to determine the rate constant of NO uptake by RBCs without extracellular diffusion limitation. To test the validity of this hypothesis, we theoretically analyzed competition experiments. Here, we show that competition experiments do not eliminate the extracellular diffusion limitation. Simulation of the competition data indicates that the main resistance to NO uptake by RBCs is caused by extracellular diffusion in the unstirred layer surrounding each RBC but not by the RBC membrane. This extracellular diffusion resistance is responsible for preventing interference of NO signaling in the endothelium without the need for special NO uptake by intracellular hemoglobin or a unique membrane resistance mechanism.     

Enhancement of alpha -helicity in the HIV-1 inhibitory peptide DP178 leads to an increased affinity for human monoclonal antibody 2F5 but does not elicit neutralizing responses in vitro. Implications for vaccine design

The synthetic peptide DP178, derived from the carboxyl-terminal heptad repeat region of human immunodeficiency virus type 1 GP41 protein is a potent inhibitor of viral-mediated fusion and contains the sequence ELDKWA, which constitutes the recognition epitope for the broadly neutralizing human monoclonal antibody 2F5. Efforts at eliciting a 2F5-like immune response by immunization with peptides or fusion proteins containing this sequence have not met with success, possibly because of incorrect structural presentation of the epitope. Although the structure of the carboxyl-terminal heptad repeat on the virion is not known, several recent reports have suggested a propensity for alpha-helical conformation. We have examined DP178 in the context of a model for optimized alpha-helices and show that the native sequence conforms poorly to the model. Solution conformation of DP178 was studied by circular dichroism and NMR spectroscopy and found to be predominantly random, consistent with previous reports. NMR mapping was used to show that the low percentage of alpha-helix present was localized to residues Glu(662) through Asn(671), a region encompassing the 2F5 epitope. Using NH(2)-terminal extensions derived from either GP41 or the yeast GCN4 leucine zipper dimerization domain, we designed peptide analogs in which the average helicity is significantly increased compared with DP178 and show that these peptides exhibit both a modest increase in affinity for 2F5 using a novel competitive solution-based binding assay and an increased ability to inhibit viral entry in a single-cycle infectivity model. Selected peptides were conjugated to carrier protein and used for guinea pig immunizations. High peptide-specific titers were achieved using these immunogens, but the resulting sera were incapable of viral neutralization. We discuss these findings in terms of structural and immunological considerations as to the utility of a 2F5-like response.