Mutations in the EGFr region of NOTCH3 gene and CADASIL phenotype / 国际脑血管病杂志

CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) is a hereditary small vessel disease originated from adult onset, which is caused by the mutation of NOTCH3 gene located in the region of chromosome 19p13. Its clinical features include recurrent ischemic stroke, progressive cognitive impairment, migraine and mental disorders. Recent studies have shown that the mutations in the EGFr region of NOTCH3 gene are associated with the course, clinical manifestations and imaging features of CADASIL. This article reviews the research progress of the NOTCH3 gene EGFr region mutation genotype, clinical phenotype of CADASIL and their correlation, hoping to provide ideas for the early diagnosis and pathogenesis of CADASIL.

Structural Characteristics of Seven IL-32 Variants

IL-32 exists as seven mRNA transcripts that can translate into distinct individual IL-32 variants with specific protein domains. These translated protein domains of IL-32 variants code for specific functions that allow for interaction with different molecules intracellularly or extracellularly. The longest variant is IL-32γ possessing 234 amino acid residues with all 11 protein domains, while the shortest variant is IL-32α possessing 131 amino acid residues with three of the protein domains. The first domain exists in 6 variants except IL-32δ variant, which has a distinct translation initiation codon due to mRNA splicing. The last eleventh domain is common domain for all seven IL-32 variants. Numerous studies in different fields, such as inflammation, autoimmunity, pathogen infection, and cancer biology, have claimed the specific biological activity of individual IL-32 variant despite the absence of sufficient data. There are 4 additional IL-32 variants without proper transcripts. In this review, the structural characteristics of seven IL-32 transcripts are described based on the specific protein domains.

Comparative Analysis of Some Proteins Encoded by Genes Significantly Related to Diabetes

Aims: The study was performed with the aim of understanding the role of protein structures encoded by a few of those genes which show the most significant alterations in their expression under normal versus diabetic conditions. Study Design: The study involved identifying a few relevant genes and analysis of various components of their protein structures. Methodology: Nine genes were shortlisted based on the extensive search of available secondary data. The structures of proteins encoded by them were generated using standard online tools. Comparative models of each of them were also generated in reference to the gene PPARγ due to its high significance in both diabetes as well as obesity, one of its predominant contributing factors. Results: Our studies indicate that the protein structures have domains which can interact with each other as well as other signaling molecules and thereby contribute towards the transfer of information across the cells. Moreover, some of these proteins show significant overlap with the protein encoded by the gene PPARγ, indicating probable interactions between them. Conclusion: These preliminary observations are indicative of probable protein-protein interactions which may contribute towards disease pathology. Further studies on interactions between these domains of various proteins may throw light on this aspect. Since diabetes incidences are increasing exponentially across the world, further detailed analysis of the individual components of the protein structures may help in obtaining a better understanding of the molecular mechanisms that are involved in this disease. This study substantiates those findings which have reported the importance of genetics in diabetes.

Hierarchic organization of globular proteins: Experimental studies on thermolysin.

Previous studies from this laboratory have shown that the thermolysin fragment 121-316, comprising entirely the “all-α” COOH-terminal structural domain 158–316, as well as fragment 206–316 (fragment FII) are able to refold into a native-like, stable structure independently from the rest of the protein molecule. The present report describes conformational properties of fragments 228–316 and 255–316 obtained by chemical and enzymatic cleavage of fragment FII, respectively. These subfragments are able to acquire a stable conformation of native-like characteristics, as judged by quantitative analysis of secondary structure from far-ultra-violet circular dichroism spectra and immunochemical properties using rabbit anti-thermolysin antibodies. Melting curves of the secondary structure of the fragments show cooperativity with a temperature of half-denaturation (Tm) of 65–66oC. The results of this study provide evidence that it is possible to isolate stable supersecondary structures (folding units) of globular proteins and correlate well with predictions of subdomains of the COOH-terminal structural domain 158–316 of thermolysin.