Human CLU blocking peptide

Recommendation Systems have gained huge importance in recent years as they proffer most admissible choices explored out of large data sets and are analogous to the user's interests. But the notion of context that describes the user, item or how users interact with the recommendation system has become one of the most significant factors that has increased the potency of recommendation systems in distinct domains such as e-commerce, movies, music, tourism etc. The main key issues in context aware recommendations are how to utilize the contextual information efficiently. So to utilize this information efficiently, an innovative cluster based context-aware post-filtering approach has been propounded that implicitly segregates the users into clusters on the basis of high performing contextual dimensions; combine the clusters on the basis of contextual similarity and then re-rank the items according to the probability of relevance in a cluster. The proposed approach is validated on movies dataset consisting of different contextual dimensions. The empirical analysis validates that the propounded approach surpass various state-of-the-art approaches. (C) 2017 The Authors. Published by Elsevier B.V.

Genetic variants at PTK2B-CLU locus pose as high-risk factors for many age-related disorders. However, the role of these variants in disease progression is less characterized. In this study, we aimed to investigate the functional significance of a clusterin intronic SNP, rs2279590, that has been associated with pseudoexfoliation, Alzheimer's disease (AD) and diabetes. We have previously shown that the alleles at rs2279590 differentially regulate clusterin (CLU) gene expression in lens capsule tissues. This polymorphism resides in an active regulatory region marked by H3K27Ac and DNase I hypersensitive site and is an eQTL for CLU expression. Here, we report the presence of an enhancer element in surrounding region of rs2279590. Deletion of a 115 bp intronic region flanking the rs2279590 variant through CRISPR-Cas9 genome editing in HEK293 cells demonstrated a decreased clusterin gene expression. Electrophoretic mobility shift and chromatin immunoprecipitation assays show that rs2279590 with allele 'A' constitutes a transcription factor binding site for heat shock factor-1 (HSF1) but not with allele 'G'. By binding to allele 'A', HSF1 abrogates the enhancer effect of the locus as validated by reporter assays. Interestingly, rs2279590 locus has a widespread enhancer effect on two nearby genes, protein tyrosine kinase 2 beta (PTK2B) and epoxide hydrolase-2 (EPHX2); both of which have been previously associated with AD as risk factors. To summarize, our study unveils a mechanistic role of the common variant rs2279590 that can affect a variety of aging disorders by regulating the expression of a specific set of genes.