Prion: the chameleon protein

From Creutzfeldt-Jakob disease (CJD) to variant CJD through Gerstmann-Str?ussler-Scheinker syndrome, kuru and fatal familial insomnia, the journey leading to current understanding of the basic aspects of human prion diseases has been full of unexpected, but often dramatic and always fascinating twists. Recent progress in modeling prion diseases and characterization of the various prion protein forms reveal that such a wide spectrum of the diseases is associated with the chameleon-like conformational features of prions.     

Thiamine pyrophosphate: An essential cofactor for the α-oxidation in mammals – implications for thiamine deficiencies?

The identification of 2-hydroxyphytanoyl-CoA lyase (2-HPCL), a thiamine pyrophosphate (TPP)-dependent peroxisomal enzyme involved in the α-oxidation of phytanic acid and of 2-hydroxy straight chain fatty acids, pointed towards a role of TPP in these processes. Until then, TPP had not been implicated in mammalian peroxisomal metabolism. The effect of thiamine deficiency on 2-HPCL and α-oxidation has not been studied, nor have possible adverse effects of deficient α-oxidation been considered in the pathogenesis of diseases associated with thiamine shortage, such as thiamine-responsive megaloblastic anemia (TRMA). Experiments with cultured cells and animal models showed that α-oxidation is controlled by the thiamine status of the cell/tissue/organism, and suggested that some pathological consequences of thiamine starvation could be related to impaired α-oxidation. Whereas accumulation of phytanic acid and/or 2-hydroxyfatty acids or their α-oxidation intermediates in TRMA patients given a normal supply of thiamine is unlikely, this may not be true when malnourished. Received 23 December 2005; received after revision 10 April 2006; accepted 28 April 2006     

复杂系统熵聚堆算法及其在中风病临床的应用

对数据进行非监督聚类是中医临床研究的主流和难点.提出了一种非监督的复杂系统熵聚堆算法.它改进了关联度系数,不但能实现自组织非监督聚类,而且可以实现一个变量分在不同的类里;提出并证明了N-class相关的概念,加快算法的收敛速度.它运用到中风病临床数据中,非监督地提取出了中风病中常见的证候,结果十分符合临床; 参考数据的辨证结果对算法进行了验证,得到算法的敏感度为97.3%, 这验证了算法的有效性.它为中医临床治疗中风病的规范化奠定了数理基础.     

The specificity of binding of glycoprotein hormones to their receptors

The glycoprotein hormone receptor family is peculiar because, in contrast to other G protein-coupled receptors, a large N-terminal extracellular ectodomain is responsible for hormone recognition. Hormone-receptor pairs have evolved in such a manner that a limited number of positions both at the 'seat-belt' domain of the hormone and the leucine-rich repeats of the receptor, play attractive and repulsive interactions for binding and specificity, respectively. Surprisingly, the constitutive activity of the receptor, mostly modulated by highly conserved amino acids within the heptahelical domain of the receptor (i.e., outside the hormone binding region), also regulates effectiveness of hormone recognition by the extracellular part. In this review we analyze, at the molecular level, these important discriminating determinants for selective binding of glycoprotein hormones to their receptors, as well as natural mutations, observed in patients with gestational hyperthyroidism or ovarian hyperstimulation syndrome, that modify the selectivity of binding.     

基于策略模式的中医药数据智能挖掘平台设计与应用

针对目前大多数中医药数据挖掘研究中使用单一且基础的算法而出现的问题,设计并实现一种通过策略模式智能优选中医药数据挖掘方法的平台(TCM data strategy model analysis platform, TCMDP)。根据策略模式的思想,集成以下4个数据挖掘模块,统计学分析模块可对药物、药物种类、四气五味归经和药物功效进行统计学分析;关联规则挖掘模块可以分析处方中的药物关联性;聚类分析模块可获取药物组合得出聚类新方,通过分析结果来探讨肺癌处方的配伍规律;证型分类模块以电子病历的中医症状和四诊信息作为输入,将相关证型作为输出,构建证型分类模型。综上实现了基于策略模式的中医药数据智能挖掘平台,并运用该平台对中医临床治疗肺癌的中药处方进行用药规律和证型分类研究。结果表明：以痰瘀互结证肺癌病例为例,关联规则挖掘模块中WD-Get Rule算法的运行时间最少仅为0.038 s。聚类分析模块中CMC-DD算法分析时间略长但精确率高达87%。肺癌证型分类分析模块中PSO-ELM运行时间短为88.98 s,且模型平均精确率达88.44%,具有一定的临床参考价值。而本平台所采用的改进算法均优于...     

SARS相关冠状病毒刺突糖蛋白的研究(综述)

概述了SARS—CoV的S蛋白的结构及功能相关研究。严重急性呼吸综合症相关的冠状病毒(SARS-CoV)引起2003年我国南方非典型肺炎爆发流行，波及多个国家和地区。目前全球许多学对SARS-CoV进行了广泛的研究，发现S蛋白是病毒表面的主要蛋白，它构成冠状病毒科特征性的冠状样结构，在严重急性呼吸综合症的发病机制起着关键性作用，可介导表达相关受体的宿主细胞感染。现已鉴定出SARS-CoV的S蛋白相关受体，同时它在抗病毒感染中是一个关键靶蛋白。     

Multiple roles of the DSCR1 (Adapt78 or RCAN1) gene and its protein product Calcipressin 1 (or RCAN1) in disease

The DSCR1 (Adapt78) gene¹ is transiently induced by stresses to temporarily protect cells against further potentially lethal challenges. However, chronic expression of the DSCR1 (Adapt78) gene has now been implicated in several pathological conditions including Alzheimer’s disease, Down syndrome and cardiac hypertrophy. Calcipressin 1 has been shown to function through direct binding and inhibition of the serine threonine protein phosphatase Calcineurin. Pharmacological inhibition of calcineurin, by the immunosuppressive drugs cyclosporin A and FK506, affects a wide variety of diseases. It is, therefore, likely that this endogenous calcineurin inhibitor, calcipressin 1, may also play a role in a variety of human diseases. ¹Please note that the mammalian DSCR1 gene is also called Adapt78 or RCAN1, and its protein products have been named Calcipressin1, MCIP1 and RCAN1. A proposal to adopt a single gene name of RCAN1 and a protein name RCAN1 (for Regulator of Calcineurin) has been endorsed by the HUGO Gene Nomenclature Committee, but final approval must await agreement from a majority of researchers in the field. Received 2 March 2005; received after revision 27 May 2005; accepted 19 July 2005     

Biomedicine and diseases: the Klippel-Trenaunay syndrome, vascular anomalies and vascular morphogenesis

Vascular morphogenesis is a vital process for embryonic development, normal physiologic conditions (e.g. wound healing) and pathological processes (e.g. atherosclerosis, cancer). Genetic studies of vascular anomalies have led to identification of critical genes involved in vascular morphogenesis. A susceptibility gene, VG5Q (formally named AGGF1), was cloned for Klippel-Trenaunay syndrome (KTS). AGGF1 encodes a potent angiogenic factor, and KTS-associated mutations enhance angiogenic activity of AGGF1, defining ‘increased angiogenesis’ as one molecular mechanism for the pathogenesis of KTS. Similar studies have identified other genes involved in vascular anomalies as important genes for vascular morphogenesis, including TIE2, VEGFR-3, RASA1, KRIT1, MGC4607, PDCD10, glomulin, FOXC2, NEMO, SOX18, ENG, ACVRLK1, MADH4, NDP, TIMP3, Notch3, COL3A1 and PTEN. Future studies of vascular anomaly genes will provide insights into the molecular mechanisms for vascular morphogenesis, and may lead to the development of therapeutic strategies for treating these and other angiogenesis-related diseases, including coronary artery disease and cancer.Received 24 November 2004; received after revision 21 January 2005; accepted 2 March 2005     

Ethanol inhibits insulin expression and actions in the developing brain

Ethanol-induced cerebellar hypoplasia is associated with inhibition of insulin-stimulated survival signaling. The present work explores the mechanisms of impaired insulin signaling in a rat model of fetal alcohol syndrome. Real-time quantitative RT-PCR demonstrated reduced expression of the insulin gene in cerebella of ethanol-exposed pups. Although receptor expression was unaffected, insulin and insulin-like growth factor (IGF-I) receptor tyrosine kinase (RTK) activities were reduced by ethanol exposure, and these abnormalities were associated with increased PTP1b activity. In addition, glucose transporter molecule expression and steady-state levels of ATP were reduced in ethanol-exposed cerebellar tissue. Cultured cerebellar granule neurons from ethanol-exposed pups had reduced expression of genes encoding insulin, IGF-II, and the IGF-I and IGF-II receptors, and impaired insulin- and IGF-I-stimulated glucose uptake and ATP production. The results demonstrate that ethanol inhibits insulin-mediated actions in the developing brain by reducing local insulin production and insulin RTK activation, leading to inhibition of glucose transport and ATP production.Received 30 December 2004; received after revision 1 March 2005; accepted 10 March 2005     

血清中生物高分子活性中心离子分布与高血压病患者血液流变学参数之间的关系

计算高血压患者血清中生物高分子活性中心离子（Ti、V、Cr、Mn、Mo、Zn，Fe、Co、Ni、Cu等过渡金属元素）的分布，发现高血压患者可以分成阴平阳升、阴降阳升、阴平阳降、阴阳两降四型。进一步研究发现这四型患者血清中生物高分子活性中心离子的分布参数与中医高血压各证型（肝阳上亢、阴虚阳亢、肝肾阴虚、阴阳两虚）的血液流变学参数（η低切、η高切、Lb、Hct、ηp）之间有很明显的相关性。所以作者认为生物高分子活性中心离子的分布参数可以作为高血压中医辨证分型的微观定量依据之一。