The gene encoding ganglioside-induced differentiation-associated protein 1 is mutated in axonal Charcot-Marie-Tooth type 4A disease.

We identified three distinct mutations and six mutant alleles in GDAP1 in three families with axonal Charcot-Marie-Tooth (CMT) neuropathy and vocal cord paresis, which were previously linked to the CMT4A locus on chromosome 8q21.1. These results establish the molecular etiology of CMT4A (MIM 214400) and suggest that it may be associated with both axonal and demyelinating phenotypes.     

Mechanism for the learning deficits in a mouse model of neurofibromatosis type 1.

Neurofibromatosis type I (NF1) is one of the most common single-gene disorders that causes learning deficits in humans. Mice carrying a heterozygous null mutation of the Nfl gene (Nfl(+/-) show important features of the learning deficits associated with NF1 (ref. 2). Although neurofibromin has several known properties and functions, including Ras GTPase-activating protein activity, adenylyl cyclase modulation and microtubule binding, it is unclear which of these are essential for learning in mice and humans. Here we show that the learning deficits of Nf1(+/-) mice can be rescued by genetic and pharmacological manipulations that decrease Ras function. We also show that the Nf1(+/-) mice have increased GABA (gamma-amino butyric acid)-mediated inhibition and specific deficits in long-term potentiation, both of which can be reversed by decreasing Ras function. Our results indicate that the learning deficits associated with NF1 may be caused by excessive Ras activity, which leads to impairments in long-term potentiation caused by increased GABA-mediated inhibition. Our findings have implications for the development of treatments for learning deficits associated with NF1.     

The failing heart.

Cardiomyopathies are disorders affecting heart muscle that usually result in inadequate pumping of the heart. They are the most common cause of heart failure and each year kill more than 10,000 people in the United States. In recent years, there have been breakthroughs in understanding the molecular mechanisms involved in this group of conditions, with knowledge of the genetic basis for cardiomyopathies perhaps seeing the largest advance, enabling clinicians to devise improved diagnostic strategies and preparing the stage for new therapies.     

格值诱导空间的若干特征定理

讨论了格值诱导空间及相关的弱诱导空间和满层空间的代数特征和拓扑特征。     

一类新型双杂环衍生物的合成及其杀菌活性

三唑并嘧啶类杂环衍生物由于其分子结构中同时包含了三唑及嘧啶这两类重要的活性结构单元 ,因而往往表现出广泛的生物活性[1～ 4] ,既可以用于医药 ,也可以用于农药 .因此 ,近年来关于三唑并嘧啶类衍生物的合成及其生物活性的研究受到了人们的广泛关注 -二甲基 - 1 ,2 ,4-三唑     

山东威海卫饮用天然矿泉水生成背景与水质评价的研究

本文论述了山东威海卫饮用天然矿泉水的生成条件，对其界限指标、限量指标、污染物指标、微生物指标等进行了综合评价，确定其为重碳酸型的含锶、偏硅酸优质矿泉水．     

A calcium sensor in the sodium channel modulates cardiac excitability.

Sodium channels are principal molecular determinants responsible for myocardial conduction and maintenance of the cardiac rhythm. Calcium ions (Ca2+) have a fundamental role in the coupling of cardiac myocyte excitation and contraction, yet mechanisms whereby intracellular Ca2+ may directly modulate Na channel function have yet to be identified. Here we show that calmodulin (CaM), a ubiquitous Ca2+-sensing protein, binds to the carboxy-terminal 'IQ' domain of the human cardiac Na channel (hH1) in a Ca2+-dependent manner. This binding interaction significantly enhances slow inactivation-a channel-gating process linked to life-threatening idiopathic ventricular arrhythmias. Mutations targeted to the IQ domain disrupted CaM binding and eliminated Ca2+/CaM-dependent slow inactivation, whereas the gating effects of Ca2+/CaM were restored by intracellular application of a peptide modelled after the IQ domain. A naturally occurring mutation (A1924T) in the IQ domain altered hH1 function in a manner characteristic of the Brugada arrhythmia syndrome, but at the same time inhibited slow inactivation induced by Ca2+/CaM, yielding a clinically benign (arrhythmia free) phenotype.     

一个计算金属半径的近似公式

本文提出一个计算金属原子半径新的近似公式，并计算了５８种金属的原子半径，其结果与实验测定值非常接近。     

氮－烃类二元低温混合工质的工作机理分析

用ＰＲ方程计算氮－烃类二元混合物的自由焓，提出判别氨－烃类二元混合物互溶性的方法，并计算了该类混合工质的汽液平衡、液液平衡和汽液液平衡特性，为寻求新的混合工质对提供了一种有效的理论预测方法。     

炼钢─连铸─热轧直接热装一体化计划

从计划角度重点分析了钢铁生产中炼钢、连铸、热轧三者之间联接的较高模式－直接热装轧制计划系统的实现方式，并给出了较为具体的方案。