Investigating Mutations to Reduce Huntingtin Aggregation by Increasing Htt-N-Terminal Stability and Weakening Interactions with PolyQ Domain

Huntington’s disease is a fatal autosomal genetic disorder characterized by an expanded glutamine-coding CAG repeat sequence in the huntingtin (Htt) exon 1 gene. The Htt protein associated with the disease misfolds into toxic oligomers and aggregate fibril structures. Competing models for the misfolding and aggregation phenomena have suggested the role of the Htt-N-terminal region and the CAG trinucleotide repeats (polyQ domain) in affecting aggregation propensities and misfolding. In particular, one model suggests a correlation between structural stability and the emergence of toxic oligomers, whereas a second model proposes that molecular interactions with the extended polyQ domain increase aggregation propensity. In this paper, we computationally explore the potential to reduce Htt aggregation by addressing the aggregation causes outlined in both models. We investigate the mutation landscape of the Htt-N-terminal region and explore amino acid residue mutations that affect its structural stability and hydrophobic interactions with the polyQ domain. Out of the millions of 3-point mutation combinations that we explored, the (L4K E12K K15E) was the most promising mutation combination that addressed aggregation causes in both models. The mutant structure exhibited extreme alpha-helical stability, low amyloidogenicity potential, a hydrophobic residue replacement, and removal of a solvent-inaccessible intermolecular side chain that assists oligomerization

A Novel Method to Investigate the Effect of Social Network “Hook” Images on Purchasing Prospects in E-Commerce

Background. Social network visual shopping trends are growing e-commerce at unprecedented levels. Images are used as product marketing material; however, image posts are triggering very low consumer behavior and low sales conversion. Objective. To explore how online stores can increase the purchasing prospects of their products using images on social networks. Methods. We introduce a theoretical probabilistic model to estimate consumer behavioral intention and purchasing prospect on social networks, outline parameters that can be exploited to increase click-rate and conversion, and motivate a new strategy to market products online. The model explores increasing online stores’ sales conversion by utilizing a product collection landing page that is marketed to consumers through a single “Hook” image. To implement the model, we developed a novel technological method that enabled online stores to post different “Hook” images on social networks and hyperlink them to the product collection landing pages they created. Results. Stores and marketers developed four types of “Hook” images: themed-collaged product images, single product images, lifestyle images, and model images. Themed-collaged product images accounted for 60% of consumer traffic from social network sites. Moreover, consumer purchasing click rate increased at least twofold (4.94%) with the use of product collection landing pages

A bibliometric analysis of socially responsible investment sukuk literature

Despite the impressive growth of socially responsible investment (SRI) Sukuk (Islamic bond) over the last five years, a handful of comprehensive research is documented in literature. Hence, the aim of this study is to systematically explore and cluster the SRI Sukuk literature to offer comprehensive guidelines for future research. A total of 232 peer reviewed papers from Web of Science database were considered for bibliometric analysis (using VOSviewer software) which are published over the period of 1970-May 2019. This analysis shows SRI Sukuk literature mainly falls in three research clusters: (1) nature of SRI Sukuk, (2) competitiveness of SRI Sukuk, and (3) determinants of SRI Sukuk. However, very few studies have explored the determinants of SRI Sukuk investment. The literature also indicates that, SRI Sukuk research are highly collaborated between Malaysia, Australia, and the USA yet the number is trifling. Thus, exploring motivational factors of SRI Sukuk investment and its impact on the nation's economic development in a cross-country setting would be worthwhile researching

Whole exome sequencing as a diagnostic tool for patients with ciliopathy-like phenotypes

Ciliopathies are a group of rare disorders characterized by a high genetic and phenotypic variability, which complicates their molecular diagnosis. Hence the need to use the latest powerful approaches to faster identify the genetic defect in these patients. We applied whole exome sequencing to six consanguineous families clinically diagnosed with ciliopathy-like disease, and for which mutations in predominant Bardet-Biedl syndrome (BBS) genes had previously been excluded. Our strategy, based on first applying several filters to ciliary variants and using many of the bioinformatics tools available, allowed us to identify causal mutations in BBS2, ALMS1 and CRB1 genes in four families, thus confirming the molecular diagnosis of ciliopathy. In the remaining two families, after first rejecting the presence of pathogenic variants in common cilia-related genes, we adopted a new filtering strategy combined with prioritisation tools to rank the final candidate genes for each case. Thus, we propose CORO2B, LMO7 and ZNF17 as novel candidate ciliary genes, but further functional studies will be needed to confirm their role. Our data show the usefulness of this strategy to diagnose patients with unclear phenotypes, and therefore the success of applying such technologies to achieve a rapid and reliable molecular diagnosis, improving genetic counselling for these patients. In addition, the described pipeline also highlights the common pitfalls associated to the large volume of data we have to face and the difficulty of assigning a functional role to these changes, hence the importance of designing the most appropriate strategy according to each case