Copper and zinc dismetabolism in the mouse brain upon chronic cuprizone treatment

Recent reports describe successful treatment using copper chelation therapy in neurodegenerative animal models. However, the success claimed for chelation therapy in neurodegenerative diseases is still rather controversial. To acquire new information on copper metabolism/homeostasis, we utilized cuprizone, a very sensitive and selective copper-chelating agent with well-known neurotoxic properties, as a relevant chemical model in mice. Upon cuprizone treatment, mice developed a pronounced astrocytosis, with brain oedema and spongiosis characterised by vacuolisations of the neuropil predominantly in the white matter. In addition, cuprizone treatment severely altered copper and zinc homeostasis in the central nervous system (CNS) as well as in all other tissues examined, with increasing metal ion concentrations particularly in the CNS. Concomitant with this increase in the Cu and Zn concentration in the brain, metallothionein-I and -II were also highly immunoreactive in astrocyte, consistent with the astrocytosis and demyelination observed in our and other laboratories.Received 23 February 2005; received after revision 3 May 2005; accepted 13 May 2005     

Mechanisms underlying celiac disease and its neurologic manifestations

The extra-intestinal manifestations of celiac disease (CD), including ataxia and peripheral neuropathy, are increasingly being recognized as the presenting symptoms of this autoimmune disease. Although there is a greater understanding of the pathogenesis of the intestinal lesions in CD the mechanisms behind the neurologic manifestations of CD have not been elucidated. In this article, the authors review the cellular and molecular mechanisms behind the histopathologic changes in the intestine, discuss the presentation and characteristics of neurologic manifestations of CD, review the data on the mechanisms behind these manifestations, and discuss the diagnosis and treatment of CD. Molecular mimicry and intermolecular help may play a role in the development of neurologic complications.Received 11 March 2004; received after revision 29 October 2004; accepted 12 November 2004     

Newly discovered endocrine functions of white adipose tissue: possible relevance in obesity-related diseases

During recent years our view of adipose tissue has been revolutionized. White adipose tissue (WAT) is no longer seen as mere energy store or provider of thermal and mechanical insulation. Neglect of WAT has been overcome by surprising discoveries in recent years, changing the view of this tissue towards a highly endocrine organ that is involved in a wide variety of physiological and pathophysiological processes. In this brief article we will focus on new developments in adipocyte and WAT biology. The appreciation of WAT as an endocrine organ will provide the basis for new and promising perspectives in the management of obesity and obesity-related diseases including diabetes, mellitus type II and arterial hypertension.     

Algorithmic compression of empirical data: reply to Twardy, Gardner, and Dowe

This discussion note responds to objections by Twardy, Gardner, and Dowe to my earlier claim that empirical data sets are algorithmically incompressible. Twardy, Gardner, and Dowe hold that many empirical data sets are compressible by Minimum Message Length technique and offer this as evidence that these data sets are algorithmically compressible. I reply that the compression achieved by Minimum Message Length technique is different from algorithmic compression. I conclude that Twardy, Gardner, and Dowe fail to establish that empirical data sets are algorithmically compressible.     

常规及偶应力轴对称有限元分片检验函数

我们提出的增强型分片检验可以用于检验一类非齐次阶微分方程的有限元的收敛性.由此,建立了常规轴对称问题和轴对称偶应力/应变梯度C1理论有限元增强型分片检验的检验函数,并得到重要结论：这类轴对称有限元的分片检验函数不含常剪应力项.     

N原子掺杂对富勒烯C20分子电子结构与传输特性的影响

构建了Au原子面为电极的富勒烯C20分子及C20分子内掺杂N原子后的分子的电子输运模型,使用非平衡格林函数方法(NEGF)对构建的分子器件进行了电子结构和输运性质的计算.得出了电子结构和电子传输谱,分析了产生这个分子器件电子输运性质的原因.结果显示N原子的掺入有利于提高C20分子的电子传输功能.     

腾冲嗜酸两性菌硫氧化还原酶分子结构中铁原子结合位点的新特征

前期研究表明, 铁原子对于嗜酸两性菌中硫氧化还原酶(SOR)的活性至关重要. 本研究表明, 2,2′-联吡啶、1,2-二羟基苯-3,5-二磺酸钠、8-羟基喹啉等特异性铁离子螯合剂强烈抑制腾冲嗜酸两性菌SOR酶活性, 进一步表明铁原子是SOR酶活必需. 对目前基因组数据库中的SOR基因或者SOR类似基因进行序列比对, 发现了一个潜在的铁原子结合模体(H⁸⁶-X₃- H⁹⁰-X_n-E¹¹⁴-X_n-E¹²⁹). 据此, 本研究采用定点突变技术, 将氨基酸残基H⁸⁶, H⁹⁰和E¹²⁹分别突变为苯丙氨酸或者丙氨酸, 圆二色光谱测定发现突变体(H⁸⁶F, H⁹⁰F和E¹²⁹A)的二级结构没有明显改变, 但是这3个突变体全部丧失了酶活性. 突变体蛋白中铁原子含量测定结果表明, 3个突变体全部或者部分丢失了铁原子, 而之前研究中获得的3个半胱氨酸突变体(完全丧失了酶活)铁原子含量没有变化. 根据本研究并结合前期实验结果可知, SOR分子中模体C³¹-X_n-C¹⁰¹-X₂-C¹⁰⁴是底物硫分子活化区域; 而模体H⁸⁶-X₃-H⁹⁰-X₂₃-E¹¹⁴-X_¹⁴-(E/D)¹²⁹是SOR分子中铁原子的结合区域, 与铁原子结合形成一个非卟啉铁中心, 是SOR的氧化还原中心; 这两个区域均是SOR酶活性的必需部分.     

修正表面张力系数的包膜气泡动力学模型

基于包膜造影剂气泡的实际应用, 在传统的三层模型基础上提出了一个修正的动力学模型来描绘包膜气泡的动力学行为. 通过衔接三层模型中包膜的两个边界条件, 得到一个两层模型并简化了方程的结构. 为了使动力平衡更加准确, 在建立边界条件时考虑了包膜质量, 并将包膜层厚度与气泡半径的关系具体化. 更为重要的是, 我们对绝大多数文献中的表面张力系数不变的假设进行了修正, 认为其随半径变化呈非线性变化, 且通过数值计算对表面张力系数修正带来的变化进行了讨论. 此外, 我们应用本文模型对实验得到的Optison及Sonozoid微气泡的动力学曲线进行了拟合, 并与其他经典模型的拟合结果进行了比较, 结论证明了本文模型具有很好的适用性.