尿蛋白质组学在肾脏疾病研究中的应用

长期以来,肾脏病的治疗进展一直十分缓慢,这是因为目前一些肾脏病在诊断分型上存在很多缺陷,分型通常只能依靠细微的组织病理学差异,这使早期诊断、预后追踪以及疗效观察都十分困难。如果能发现像肌钙蛋白一样特异的生物学标志物,将有助于提高肾脏病的诊疗水平。由于尿液与泌尿系统之间存在着天然的联系,这使得尿液在反映泌尿系统功能方面具备"地理"优势。因此,尿蛋白质组学的兴起和发展为肾脏病及其他泌尿系统疾病的研究开启了一扇新的大门。该文综述了尿蛋白质组学技术的发展及其在各种泌尿系统疾病研究中的应用。     

From Virus Research to Molecular Biology: Tobacco Mosaic Virus in Germany, 1936-1956

In 1937, a group of researchers in Nazi Germany began investigating tobacco mosaic virus (TMV) with the hope of using the virus as a model system for understanding gene behavior in higher organisms. They soon developed a creative and interdisciplinary work style and were able to continue their research in the postwar era, when they made significant contributions to the history of molecular biology. This group is significant for two major reasons. First, it provides an example of how researchers were able to produce excellent scientific research in the midst of dictatorship and war.Coupled with the group's ongoing success in postwar Germany, the German TMV investigators provide a dramatic example of how scientific communities deal with adversity as well as rapid political and social change. Second, since the researchers focused heavily (though no exclusively) on TMV, their story allows us to analyze how an experimental system other than phage contributed to the emergence of molecular biology.     

Nucleoli and Stress Granules: Connecting Distant Relatives

Nucleoli and cytoplasmic stress granules (SGs) are subcellular compartments that modulate the response to endogenous and environmental signals to control cell survival. In our opinion, nucleoli and SGs are functionally linked; they are distant relatives that combine forces when cellular homeostasis is threatened. Several lines of evidence support this idea; nucleoli and SGs share molecular building blocks, are regulated by common signaling pathways and communicate when vital cellular functions become compromised. Together, nucleoli and SGs orchestrate physiological responses that are directly relevant to stress and human health. As both compartments have established roles in neurodegenerative diseases, cancer and virus infections, we propose that these conditions will benefit from therapeutic interventions that target simultaneously nucleoli and SGs.      

马传染性贫血病毒基因非编码区LTR嵌合克隆的构建

在已有全长感染性克隆pLGFD3-8和pD70344的基础上,根据马传贫弱毒疫苗致弱过程中不同代次毒株LTR序列的分析,在LTR U3区选取特定的酶切位点对EIAV非编码区LTR基因进行了部分替换.将替换的全基因克隆转染驴胎皮肤细胞(FDD)并以驴白细胞(DL)传代,用逆转录酶活性检测、RT-PCR方法及Real-time RT-PCR验证其感染性.结果发现,其衍生病毒感染上述两种细胞均出现明显的细胞病变;细胞培养上清可检测到RT酶活性和RT-PCR阳性.电镜下可见大量典型的EIAV颗粒.pLGFD9-12嵌合克隆衍生病毒与其父本克隆衍生病毒pLGFD3-8具有相似的复制水平,pLGFD9-12嵌合克隆衍生病毒在DL细胞上复制水平略高于FDD细胞.此结果为进一步深入研究LTR对马传染性贫血病毒复制水平和毒力的影响奠定了基础.     

Differential effect of three-repeat and four-repeat tau on mitochondrial axonal transport

Tau protein is present in six different splice forms in the human brain and interacts with microtubules via either 3 or 4 microtubule binding repeats. An increased ratio of 3 repeat to 4 repeat isoforms is associated with neurodegeneration in inherited forms of frontotemporal dementia. Tau over-expression diminishes axonal transport in several systems, but differential effects of 3 repeat and 4 repeat isoforms have not been studied. We examined the effects of tau on mitochondrial transport and found that both 3 repeat and 4 repeat tau change normal mitochondrial distribution within the cell body and reduce mitochondrial localization to axons; 4 repeat tau has a greater effect than 3 repeat tau. Further, we observed that the 3 repeat and 4 repeat tau cause different alterations in retrograde and anterograde transport dynamics with 3 repeat tau having a slightly stronger effect on axon transport dynamics. Our results indicate that tau-induced changes in axonal transport may be an underlying theme in neurodegenerative diseases associated with isoform specific changes in tau's interaction with microtubules.     

Effects of aphidicolin on retrovirus DNA synthesis in vivo

Renaturation of $\text{Aequorea}$ green-fluorescent protein (A-GFP) was achieved for the first time following denaturation in guanidine-HCl or acid. Denaturation was accompanied by the concerted loss of visible fluorescence, alteration of absorption characteristics, and large negative deflection of CD signal in the far UV. Dialysis of a guanidine-denatured sample at pH 8 resulted in 64% renaturation (return to native absorption) and neutralization of an acid-denatured sample restored 90% of the native absorption. Renatured GFP is highly fluorescent and indistinguishable from native GFP with respect to the shape of excitation and emission spectra. Both native and denatured proteins exhibit resistance to trypsin hydrolysis and have identically broad pH and heat stability profiles, all of which suggest full renaturation.     

EB病毒潜伏膜蛋白-1介导的信号传导

EB病毒编码LMP-1介导的信号传导途径已引起人们广泛的注意.它涉及TRAF/TRADD途径,AP-1途径,JAK/STAT及其他途径.就此作一综述,有助于人们认识LMP-1的致瘤效应.     

Association of RAGE gene polymorphism with circulating AGEs level and paraoxonase activity in relation to macro-vascular complications in Indian type 2 diabetes mellitus patients

Background and aims

Sustained interaction of advanced glycation end products (AGEs) with their receptor RAGE and subsequent signaling plays an important role in the development of diabetic complications. Genetic variation of RAGE gene may be associated with the development of vascular complications in type 2 diabetes mellitus (T2DM).

Objectives

The present study aimed to explore the possible association of RAGE gene polymorphisms namely − 374T/A, − 429T/C and G82S with serum level of AGEs, paraoxonase (PON1) activity and macro-vascular complications (MVC) in Indian type 2 diabetes mellitus patients (T2DM).

Methods

A total of 265 diabetic patients, including DM without any complications (n = 135), DM-MVC (n = 130) and 171 healthy individuals were enrolled. Genotyping of RAGE variants were assessed by polymerase chain reaction-restriction fragment length polymorphism. Serum AGEs were estimated by ELISA and fluorometrically. and PON1 activity was assessed spectrophotometrically.

Results

Of the three examined SNPs, association of − 429T/C polymorphism with MVC in T2DM was observed (OR = 3.001, p = 0.001) in the dominant model. Allele ‘A’ of − 374T/A polymorphism seems to confer better cardiac outcome in T2DM. Patients carrying C allele (− 429T/C) and S allele (G82S) had significantly higher AGEs levels. − 429T/C polymorphism was also found to be associated with low PON1 activity. Interaction analysis revealed that the risk of development of MVC was higher in T2DM patients carrying both a CC genotype of − 429T/C polymorphism and a higher level of AGEs (OR = 1.343, p = 0.040).

Conclusion

RAGE gene polymorphism has a significant effect on AGEs level and PON1 activity in diabetic subjects compared to healthy individuals. Diabetic patients with a CC genotype of − 429T/C are prone to develop MVC, more so if AGEs levels are high and PON1 activity is low.     

Bioinformatic analysis of BBTV satellite DNA in Hainan

Banana bunchy top virus (BBTV),family Nanaviridae,genus Babuvirus,is a single stranded DNA virus (ssDNA) that causes banana bunchy top disease (BBTD) in banana plants.It is the most common and most destructive of all viruses in these plants and is widespread throughout the Asia-Pacific region.In this study we isolated,cloned and sequenced a BBTV sample from Hainan Island,China.The results from sequencing and bioinformatics analysis indicate this isolate represents a satellite DNA component with 12 DNA sequences motifs.We also predicted the physical and chemical properties,structure,signal peptide,phosphorylation,secondary structure,tertiary structure and functional domains of its encoding protein,and compare them with the corresponding quantities in the replication initiation protein of BBTV DNA1.