阿尔茨海默病PS-1基因突变的研究

采用聚合酶链反应及基因测序技术探讨阿尔茨海默病（Alzheimer病，AD）早老素-1（Presenilin-1，PS-1）基因第3、4、5、8外显子的突变特点，对13例散发性Alzheimer病（sporadic Alzheimer＇s disease，SAD）患者、12例血管性痴呆（vascular demendia，VD）患者及31名正常老年人的PS-1基因第3、4、5、8外显子片段进行扩增与序列分析．编号为SAD5的患者PS-1基因第3外显子扩增片段上存在1个缺失突变位点，编号为SAD3的患者PS-1基因第8外显子扩增片段的近3’端处发现2个插入突变位点．12例VD患者与31名正常老年人的PS-1基因第3、4、5、8外显子均未发现突变．实验结果表明，SAD患者PS-1基因中存在第3、第8外显子的突变．     

同义密码子的频率分布

本文提出了关于同义密码子非无规分布的一个机制,从主方程出发,如果只考虑同义突变由图论方法证明了密码子的均匀分布,但是如果考虑了不同氮基酸间的突变,便可导出同义密码子的非无规分布。后者反映了选择约束对密码子分布的影响。     

Gene inactivation triggered by recognition between DNA repeats

This chapter focuses on phenomena of gene inactivation resulting from the presence of repeated gene copies within the genome of plants and fungi, and on their possible relationships to homologous DNA-DNA interactions. Emphasis is given to two related premeiotic processes: Methylation Induced Premeiotically (MIP) and Repeat-Induced Point mutation (RIP) which take place in the fungiAscobolus immersus andNeurospora crassa, respectively. The relationships between these processes and genetic recombination are discussed.     

PIK3CA基因突变及PTEN表达与西妥昔单抗疗效的关系

 对西妥昔单抗治疗的KRAS野生型结直肠癌患者进行疗效评估及随访,收集每例患者的癌组织标本及临床病理资料,检测每例患者BRAF、PIK3CA基因的突变情况,采用免疫组织化学染色检测PTEN在癌及癌旁组织中的表达情况.结果显示,KRAS、BRAF及PIK3CA基因均为野生型的患者对单抗治疗的反应率为62.5%(CR+PR),而存在BRAF及PIK3CA突变患者的反应率分别为0,28.6%,证实BRAF及PIK3CA的突变可显著影响西妥昔单抗(C225)的疗效.PTEN主要表达在细胞核内,在癌组织中表达降低或缺失,在正常组织中表达正常,并且PTEN的表达与C225的疗效密切相关,PTEN表达阳性及阴性患者的反应率(CR+PR)分别为42.9%,36.4%(P＜0.05).BRAF、PIK3CA的突变和PTEN的表达缺失可以显著影响C225的疗效.     

Glutathione synthetase deficiency

Glutathione (GSH), one of the most important antioxidants in the eukaryotic organism, is synthesized in a two-step procedure where the last step is catalysed by the enzyme glutathione synthetase (GSS). GSS deficiency is inherited autosomal recessively, and patients with this disease can be divided into three groups, according to their clinical phenotype. Mildly affected patients have mutations affecting the stability of the enzyme, causing a compensated haemolytic anaemia; moderately affected patients have, in addition, metabolic acidosis; and severely affected patients also develop neurological defects and show increased susceptibility to bacterial infections. Moderately and severely affected patients have mutations that compromise the catalytic properties of the enzyme. 5-Oxoprolinuria appears in all three groups, but is more pronounced in the two latter groups. Today, no cure can be offered these patients; they are given vitamins C and E to boost their antioxidant levels, and bicarbonate to correct metabolic acidosis.Received 20 April 2005; received after revision 19 May 2005; accepted 20 May 2005     

Exendin-4抗噬菌体工程菌的选育

利用自然突变法成功选育出了抗噬菌体的Exendin-4工程菌.该菌株抗性好,融合蛋白表达量高.但该菌株3次传代后菌种发生了衰退,稳定性下降,目的蛋白表达量下降,杂蛋白增多,已经不适合作为发酵菌株.而初代表达效果良好,保存菌种时应选用最先获得的初代菌株.     

Cytokinin signal transduction： Known simplicity and unknown complexity

Cytokinin plays a critical role in plant growth and development by regulating cell divisions and cell differentiation. Recent studies suggest that cytokinin signaling is presumably mediated by a two-component system analogous to those found in bacteria and fungi, which transduces an external signal via a phosphorelay from the plasma membrane-anchored receptors to downstream effectors and regulators. Moreover, cytokinin signaling is highly interactive with other pathways, and many components of the pathway appear to be functionally redundant. Proper address of these questions will be crucial for our further understanding on this important network.     

KRAS、BRAF及PIK3CA基因突变与转移性结直肠癌的关系

 为了联合检测并分析KRAS、BRAF和PIK3CA突变与临床病理指标之间的关系,探讨基因突变在结直肠癌(CRC)发生、发展中的生物学意义,收集第四军医大学西京消化病医院及兰州军区兰州总医院2008—2009年入院治疗的150例结直肠癌患者的癌组织标本,提取DNA行PCR扩增后,采用焦磷酸测序法联合检测KRAS、BRAF及PIK3CA基因的突变率,统计分析基因突变与患者临床病理(包括患者的年龄、性别、肿瘤位置、Dukes'分期、TNM分期、组织病理学分型及转移)之间的关系。结果表明,在150例患者中,KRAS突变率为32%(48/150),BRAF突变率为8%(12/150),PIK3CA突变突变率为12%(18/150),其中9号外显子突变率为6%(9/150),20号外显子突变率为6%(9/150)。KRAS和PIK3CA的突变与患者的Dukes'分期关系密切,KRAS、BRAF和PIK3CA的突变与CRC患者的年龄、性别、肿瘤位置、组织病理学分型之间无明显的关系。     

SLC26A4基因突变与耳聋

耳聋是最常见感觉障碍之一,与遗传关系密切.SLC26A4基因作为第二位的耳聋基因,与Pendred综合征(PS)和非综合征性聋DFNB4密切相关.SLC26A4基因突变主要与PS及DFNB4共同表现出的前庭水管扩大(EVA)相关,且不同种族及地区EVA患者该基因的突变频率及热点突变大不相同.SLC26A4基因的表现型与突变的类型关系不大,而是与等位基因数目相关.但目前SLC26A4基因突变的研究仍不完善.本文主要综述了近年来耳聋及SLC26A4基因的研究进展.     

一种基于突变信号分析和最小二乘法的指纹图像分割算法

针对指纹图像分割的问题,笔者提出了一种基于小波变换突变信号分析原理对指纹边缘进行检测。并结合最小二乘法拟合方法的指纹检测和分割算法。该算法首先将原指纹图像利用平滑函数进行平滑处理,然后使用高斯函数的一阶导数卷积计算水平和垂直方向的突变点,最后使用最小二乘法从不同方向拟合突变点。实验结果表明,该方法能够准确地将指纹图像从背景图像中分割出来。