Aluminium in Alzheimer’s disease: are we still at a crossroad?

Aluminium, an environmentally abundant non-redox trivalent cation has long been implicated in the pathogenesis of Alzheimers disease (AD). However, the definite mechanism of aluminium toxicity in AD is not known. Evidence suggests that trace metal homeostasis plays a crucial role in the normal functioning of the brain, and any disturbance in it can exacerbate events associated with AD. The present paper reviews the scientific literature linking aluminium with AD. The focus is on aluminium levels in brain, region-specific and subcellular distribution, its relation to neurofibrillary tangles, amyloid beta, and other metals. A detailed mechanism of the role of aluminium in oxidative stress and cell death is highlighted. The importance of complex speciation chemistry of aluminium in relation to biology has been emphasized. The debatable role of aluminium in AD and the cross-talk between aluminium and genetic susceptibility are also discussed. Finally, it is concluded based on extensive literature that the neurotoxic effects of aluminium are beyond any doubt, and aluminium as a factor in AD cannot be discarded. However, whether aluminium is a sole factor in AD and whether it is a factor in all AD cases still needs to be understood.Received 22 July 2004; received after revision 3 September 2004; accepted 16 September 2004     

制备泡沫铝的一种新方法:烧结溶解法

烧结溶解法是近几年发展起来的一种制造泡沫铝的新工艺，具有可以精确控制孔洞形状，尺寸和孔隙率及其分布等特点，具有较好的质量价格综合指数，是生产均匀或梯度微细开孔中密度泡沫铝的有效方法，所制泡沫铝在吸能，吸音等领域有广泛的应用前景。本文简要介绍烧结溶解法的原理与工艺，所制泡沫铝的组织特征与机械性能，并讨论与其它各类现有方法相比所具有的优势与局限。     

泡沫铝汽车碰撞吸能器仿真分析

提出了在汽车保险杠和前纵梁之间安装泡沫铝吸能器的方案,并对此结构进行了总体设计.采用 CATIA ANSYS DYNA3D联合建模求解技术对汽车碰撞进行了仿真分析,得出了安装泡沫铝吸能器前后汽车质心加速度曲线、吸能曲线及车体应力分布图.结果表明,应用泡沫铝汽车碰撞缓冲吸能器可提高汽车的安全性.本研究为泡沫铝在汽车中的应用提供了参考依据,也为汽车满足轻质、节能、环保、安全等方面的需要提供了新途径     

Possibility of metabolic control of membrane excitation

In the guinea pig taenia coli, when glycogen is depleted by repeating Ca-induced contracture in excess K solution containing no glucose, the tension cannot be maintained. The decrease in tension is accompanied by reduction of high energy phosphate compounds and oxygen consumption. When substrate is readmitted to the glycogen-depleted preparation in the presence of 2.4 mM Ca and 20 mM K, the first response is hyperpolarization of the membrane and relaxation, and this is followed by depolarization and development of contracture. The latter response is blocked by verapamil, suggesting that energy supply increases the Ca conductance of the plasma membrane. The early response is considered to be due to activation of electrogenic Ca pump, since this is not affected by ouabain as well as removal of Na and K. ATP produced by substrate readmission is probably preferentially utilized for Ca pump activation to reduce the intracellular Ca. The recovery of tension is likely to be brought about by ATP supply not only to the contractile machinery but also to the plasma membrane to remove inactivation of Ca conductance. It is postulated that as the energy source is depleted, energy consumption is automatically limited by suppressing Ca influx, as a self-defence mechanism. Since beta HB is as effective as glucose in the recovery of these processes, and also in the activation of electrogenic Na pump, the metabolic pathway of oxidative phosphorylation alone can support these functions without a contribution of the glycolytic pathway.     

Space-filling molecular models of oxiranes (epoxides)

Summary An oxirane unit was constructed from aluminium spheres to fit the popular CPK system of space-filling molecular models.The author thanks W. Arnold and F. Stehlin of the Institut für Organische Chemie for their careful machining of the aluminium models. Financial support by the Swiss National Science Foundation (project No. 2.837-0.80) is gratefully acknowledged.     

The physiology of the smooth muscle: an interdisciplinary review—part II

Summary In the guinea pig taenia coli, when glycogen is depleted by repeating Ca-induced contracture in excess K solution containing no glucose, the tension cannot be maintained. The decrease in tension is accompanied by reduction of high energy phosphate compounds and oxygen consumption. When substrate is readmitted to the glycogendepleted preparation in the presence of 2.4 mM Ca and 20 mM K, the first response is hyperpolarization of the membrane and relaxation, and this is followed by depolarization and development of contracture. The latter response is blocked by verapamil, suggesting that energy supply increases the Ca conductance of the plasma membrane. The early response is considered to be due to activation of electrogenic Ca pump, since this is not affected by ouabain as well as removal of Na and K. ATP produced by substrate readmission is probably preferentially utilized for Ca pump activation to reduce the intracellular. Ca. The recovery of tension is likely to be brought about by ATP supply not only to the contractile machinery but also to the plasma membrane to remove inactivation of Ca conductance. It is postulated that as the energy source is depleted, energy consumption is automatically limited by suppressing Ca influx, as a selfdefence mechanism. Since HB is as effective as glucose in the recovery of these processes, and also in the activation of electrogenic Na pump, the matabolic pathway of oxidative phosphorylation alone can support these functions without a contribution of the glycolytic pathway.     

Role of Sam68 as an adaptor protein in signal transduction

Sam68, the substrate of Src in mitosis, belongs to the family of RNA binding proteins. Sam68 contains consensus sequences to interact with other proteins via specific domains. Thus, Sam68 has various proline-rich sequences to interact with SH3 domain-containing proteins. Moreover, Sam68 also has a C-terminal domain rich in tyrosine residues that is a substrate for tyrosine kinases. Tyrosine phosphorylation of Sam68 promotes its interaction with SH2 containing proteins. The association of Sam68 with SH3 domain-containing proteins, and its tyrosine phosphorylation may negatively regulate its RNA binding activity. The presence of these consensus sequences to interact with different domains allows this protein to participate in signal transduction pathways triggered by tyrosine kinases. Thus, Sam68 participates in the signaling of T cell receptors, leptin and insulin receptors. In these systems Sam68 is tyrosine phosphorylated and recruited to specific signaling complexes. The participation of Sam68 in signaling suggests that it may function as an adaptor molecule, working as a dock to recruit other signaling molecules. Finally, the connection between this role of Sam68 in protein-protein interaction with RNA binding activity may connect signal transduction of tyrosine kinases with the regulation of RNA metabolism.Received 16 July 2004; received after revision 12 August 2004; accepted 18 August 2004     

Pharmacological manipulation of L-carnitine transport into L6 cells with stable overexpression of human OCTN2

The high-affinity Na+-dependent carnitine transporter OCTN2 (SLC22A5) has a high renal expression and reabsorbs most filtered carnitine. To gain more insight into substrate specificity of OCTN2, we overexpressed hOCTN2 in L6 cells and characterized the structural requirements of substances acting as human OCTN2 (hOCTN2) inhibitors. A 1905-bp fragment containing the hOCTN2 complete coding sequence was introduced into the pWpiresGFP vector, and L6 cells were stably transduced using a lentiviral system. The transduced L6 cells revealed increased expression of hOCTN2 on the mRNA, protein and functional levels. Structural requirements for hOCTN2 inhibition were predicted in silico and investigated in vitro. Essential structural requirements for OCTN2 inhibition include a constantly positively charged nitrogen atom and a carboxyl, nitrile or ester group connected by a 2-4-atom linker. Our cell system is suitable for studying in vitro interactions with OCTN2, which can subsequently be investigated in vivo.     

Ni2MnGa铁磁形状记忆材料

铁磁形状记忆合金 (FSMA)是在一定温度范围马氏体相稳定同时又具铁磁性的一类特殊的形状记忆合金。Ni2MnGa铁磁形状记忆合金近年来成为呈现磁场驱动大应变的新型驱动材料 ,这些应变来自磁场诱发马氏体孪晶的重排 ,而不是磁场对奥氏体至马氏体相变的作用。孪晶变体的重排在宏观上呈现为正或切应变 ,一非化学计量比Ni2 MnGa单晶于室温加 0 .4T磁场能产生6 %的应变 ,Ni Mn Ga单晶在高至 15 0Hz的交变磁场仍可得到 2 .5 %的应变。本文阐述了与这种磁控形状记忆效应相关的孪晶界迁动的磁学和晶体学理论。马氏体相的大磁晶各向异性能使磁化沿c轴方向有利 ,穿过孪晶界c轴刚好转动 90度 ,同时 ,这个孪晶界也构成了约 90度的畴界。在各向异性的情况下 ,孪晶界的迁动仅有相邻孪晶变体的Zeeman能差驱动 ,μ0 ΔMis·Hi。磁场和外应力对应变的影响通过对一简单的自由能表达式取极小值来表示 ,自由能表达式包括Zeeman能、磁晶各向异性能和外应力以及在某些情况下需考虑的内部弹性能 ,模型的所有参数可通过应力 应变曲线和磁化曲线测量得到。铁磁形状记忆合金的磁场诱发应变可类比传统热弹性形状记忆效应 ,与更为人们所熟知的磁致伸缩现象不同。     

钛合金及其表面处理的现状与展望

钛合金具有抗腐蚀能力强、比强度高、中温性能稳定等一系列优点，另一方面，它也有对粘着磨损和微动磨损非常敏感，耐磨性差，易氧化，对聚合物、金属及陶瓷涂层附着力差等缺点，这些缺点的存在限制了它的进一步应用，为克服钛合金这些缺点采取了一些相应的表面处理对策与手段，如表面微弧氧化、表面合金化、离子注入表面改性等。研究表明在钛合金表面形成TiC、TiN、TiO、(TiAl)N等纳米级，复合，渗、镀、注入层今后仍然是钛合金表面处理的发展方向。     

用于细胞培养的聚乙烯醇水凝胶力学性能模拟及定量控制

采用化学交联法制备聚乙烯醇（PVA）水凝胶，以此作为细胞体外培养基底。通过改进的拉伸法测量材料的杨氏模量（E），并讨论交联剂与羟基单体的摩尔比（d）、PVA的初始浓度（C0）对E的影响。利用回归分析建立E与C0、d关系的数学模型，实现对E的定量控制，模拟细胞在体内生长的生物物理环境。结果表明：该数学模型模拟的相对误差不超过0．08，可实现对PVA力学性能的定量控制。此外，研究了基底硬度对L02细胞铺展及形态学特征的影响，细胞更倾向于在硬基底上铺展，在软的基底上，细胞的形态更趋近于圆形。     

The anatomical and physiological bibliography of George E. Day (1815–1872)

The history of the Greenlandic mineral cryolite is outlined from its discovery in late-eighteenth century to the mid-nineteenth century, when its potential for industrial use was first recognized by the Danish chemist Julius Thomsen. During the 1850s, several attempts were made to exploit cryolite for the production of soda and/or aluminium, of which only the soda process became implemented on an industrial scale. The main part of the paper examines the early cryolite soda manufacture, its chemical basis as well as its industrial significance. The focus is thus the intersection of chemical science and technology. It is argued that Thomsen's process depended intimately on current chemical knowledge, and that, with regard to the science-technology relationship, the cryolite soda manufacture signified a new kind of industrial chemistry.     

Structural and biological aspects of carotenoid cleavage

Apo-carotenoid compounds such as retinol (vitamin A) are involved in a variety of cellular processes and are found in all kingdoms of life. Instead of being synthesized from small precursors, they are commonly produced by oxidative cleavage and subsequent modification of larger carotenoid compounds. The cleavage reaction is catalyzed by a family of related enzymes, which convert specific substrate double bonds to the corresponding aldehydes or ketones. The individual family members differ in their substrate preference and the position of the cleaved double bond, giving rise to a remarkable number of products starting from a limited number of carotenoid substrate molecules. The recent determination of the structure of a member of this family has provided insight into the reaction mechanism, showing how substrate specificity is achieved. This review will focus on the biochemistry of carotenoid oxygenases and the structural determinants of the cleavage reaction.     

Control of the behaviour of leaf-cutting ants by their ‘symbiotic’ fungus

There is an obligatory relationship between leaf-cutting ants of the generaAtta andAcromyrmex (Hymenoptera; Attini) and the fungus,Attamyces bromatificus Kreisel, for which they provide a substrate of cut plant material. We show that the ants learn to reject plant material that contains chemicals injurious to the fungus. After an initial period of acceptance, ants from laboratory nests stopped harvesting granular bait containing a fungicidal agent (cycloheximide) and orange peel. This rejection was maintained for many weeks. These colonies also rejected control bait containing no cycloheximide. Some generalisation of the response was observed; colonies rejecting orange granules also rejected grapefruit granules, although they still accepted blackcurrant granules. Rejection of fungicidal bait by colonies in the field was restricted to ants on foraging trails exposed to experimental bait. We conclude that a semiochemical from the fungus, circulated by trophallaxis and grooming, regulates the selection of plant material by foragers. The fungus gains more advantages from the symbiotic relationship than is often realised. The ants provide the fungus with housing, sanitation, defence against disease and predators, pre-selected food, and a means of dissemination, at the cost to itself of providing food for the ant brood.     

Myocardial function and energy metabolism in carnitine-deficient rats

Carnitine is essential for mitochondrial metabolism of long-chain fatty acids and thus for myocardial energy production. Accordingly, carnitine deficiency can be associated with cardiomyopathy. To better understand this disease, we determined myocardial function and energy metabolism in a rat model of carnitine deficiency. Carnitine deficiency was induced by a 3- or 6-week diet containing N-trimethyl-hydrazine-3-propionate, reducing cardiac and plasma carnitine by 70-85%. Myocardial function was investigated in isolated isovolumic heart preparations. Carnitine-deficient hearts showed left ventricular systolic dysfunction, reduced contractile reserve, and a blunted frequency-force relationship independently of the substrate used (glucose or palmitate). After glycogen depletion, palmitate could not sustain myocardial function. Histology and activities of carnitine palmitoyl transferase, citrate synthase, and cytochrome c oxidase were unaltered. Thus, as little as 3-6 weeks of systemic carnitine deficiency can lead to abnormalities in myocardial function. These abnormalities are masked by endogenous glycogen and are not accompanied by structural alterations of the myocardium or by altered activities of important mitochondrial enzymes.     

Covariance estimation for multivariate conditionally Gaussian dynamic linear models

In multivariate time series, estimation of the covariance matrix of observation innovations plays an important role in forecasting as it enables computation of standardized forecast error vectors as well as the computation of confidence bounds of forecasts. We develop an online, non‐iterative Bayesian algorithm for estimation and forecasting. It is empirically found that, for a range of simulated time series, the proposed covariance estimator has good performance converging to the true values of the unknown observation covariance matrix. Over a simulated time series, the new method approximates the correct estimates, produced by a non‐sequential Monte Carlo simulation procedure, which is used here as the gold standard. The special, but important, vector autoregressive (VAR) and time‐varying VAR models are illustrated by considering London metal exchange data consisting of spot prices of aluminium, copper, lead and zinc. Copyright © 2007 John Wiley & Sons, Ltd.     

The PREPL A protein, a new member of the prolyl oligopeptidase family, lacking catalytic activity

The PREPL (previously called KIAA0436) gene encodes a putative serine peptidase from the prolyl oligopeptidase family. A chromosomal deletion involving the PREPL gene leads to a severe syndrome with multiple symptoms. Homology with oligopeptidase B suggested that the enzyme cleaves after an arginine or lysine residue. Several PREPL splice variants have been identified, and a 638-residue variant (PREPL A) was expressed in Escherichia coli and purified. Its secondary structure was similar to that of oligopeptidase B, but differential-scanning calorimetry indicated a higher conformational stability. Dimerization may account for the enhanced stability. Unexpectedly, the PREPL A protein did not cleave peptide substrates containing a P1 basic residue, but did slowly hydrolyse an activated ester substrate, and reacted with diisopropyl fluorophosphate. These results indicated that the catalytic serine is a reactive residue. However, the negligible hydrolytic activity suggests that the function of PREPL A is different from that of the other members of the prolyl oligopeptidase family.     

Effects of aresenite and oxamate on the in vitro functional activity of estrogen-dominated rate uterine horns.

Arsenite but not oxamate produce in vitro a distinct depression of estrogen-dominated uterine motility, both in the absence of substrate as well as in the presence of exogenous glucose or lactate. The addition of oxamate to preparations suspended in a medium with lactate as the sole external substrate ameliorates the depression of uterine motility elicited by arsenic.     

Effects of glycolytic metabolites on preservation of high energy phosphate level and synaptic transmission in the granule cells of guinea pig hippocampal slices

The present study was undertaken to investigate whether neural activity of hippocampal slices can be preserved after replacingd-glucose with glycolytic intermediate metabolites such as lactate, pyruvate and citrate or with other sugars such as fructose, mannose, maltose, glucosamine, sucrose and galactose. As an index of neural activity, population spikes (PS) were recorded in the granule cell layers after electrical stimulation to the perforant path of guinea pig hippocampal slices. In addition, we determined the levels of ATP and creatine phosphate (CrP) in each slice after the replacement ofd-glucose with these substrates, and correlated it with the neural activity. Substrates other thand-glucose could not maintain the PS for even 20 min although the slices perfused with medium containing lactate, pyruvate, galactose, fructose and maltose maintained similar levels of ATP and CrP as in slices incubated in thed-glucose-containing medium. These results indicate thatd-glucose is essential for the preservation of synaptic activity in addition to its main role as the substrate for energy production to maintain the levels of high energy phosphates.