The rate of occurrence of Type 2 Diabetes Mellitus (T2DM) has been exponentially increasing worldwide. The current management of this disease is not deeming to be sufficient and further efforts need to be placed in this regard. The conduction of genome-wide association studies (GWAS) and pharmacogenetics (PG) have unlocked unlimited potential in more efficiently assessing disease susceptibility and drug response. These efforts have indicated the necessity of executing such studies to further understand the underlying genetic causes that are tailored to specific populations for a more personalized approach. The current literature on such findings is heavily dedicated to those of European ancestry, indicating the lack of focus on the Arabian Peninsula. Specifically, genetic initiatives to tackling T2DM that are yet to be addressed within the United Arab Emirates (UAE) are of great necessity to ensure its inclusion in these advancements for a more enhanced disease management of T2DM.
Obesity results in reduced life expectancy due to its associated comorbidities including diabetes mellitus and cardiovascular diseases. Obesity is a multifactorial disorder which results from the intricate interplay between genetic and environmental factors. The fat mass and obesity-associated (FTO) gene was identified as the first gene harboring strongest genetic association with common polygenic obesity. Genome-wide association studies (GWAS) identified single-nucleotide polymorphisms (SNPs) within the first intron of FTO in association with human obesity. In this project, we aim to produce Emirati-specific induced-pluripotent stem cells (iPSCs) as the first in-vitro model of obesity in the UAE, which shall be used to investigate the effect of an FTO variant and its potential implications on FTO underlying molecular pathways in adipogenesis.
The classical class II haplotypes of the Major Histocompatibility Complex (MHC) that are associated with type 1 diabetes (T1D) were identified in five families from the United Arab Emirates (UAE). Using HLA data, segregation analysis were performed on 5 families with the disease, 3 with one child and 2 with 2 children diagnosed with T1D. The youngest parent was born in the 1980s. In two families, the HLA-DR and HLA-DQ genotypes were identical between the parent; who was unaffected; and offsprings who were diagnosed with T1D at a young age. Therefore, we hypothesize that epistatic and additive interactions between candidate genes within or separate from the MHC could be at play. There is also the possibility of an environmental trigger. The socioeconomic condition of the UAE changed rapidly in the 1980s, and dramatic modifications to diet, healthcare, sanitation and lifestyle could be potential causes of T1D in the younger generation.
Low-density lipoprotein receptor related protein 6 (LRP6) is a member of the low density lipoprotein receptor with multiple functions through its canonical Wnt signaling pathway. Genetic variants in LRP6 gene have been linked to human diseases and conclusively with coronary artery diseases (CADs). Here we investigate the effects of these missense mutations on the LRP6 protein subcellular localization, stability and transport using several cellular and biochemical methods, including immunocytochemistry. Our results show that some of these mutations cause retention of LRP6 in the endoplasmic reticulum (ER), where the protein could be possibly subjected to ER associated degradation (ERAD), contributing to the pathogenicity of these CAD-associated LRP6 variants. This study will lead to better understanding of the pathogenesis of LRP6 mutations with potential applications in clinical diagnosis and development of new therapies.
Hereditary hemorrhagic telangiectasia type 1 (HHT1) is an autosomaly dominant inherited disease that is generally characterized by vascular malformation and fragility. HHT1 has been associated with mutations in the TGF beta co-receptor Endoglin, encoded by ENG gene. We have previously demonstrated that some Endoglin variants are trapped in the Endoplasmic Reticulum (ER) and fail to traffic to their normal localization in plasma membrane, which suggested the involvement of ER associated protein degradation (ERAD) in their molecular pathology. In this study we used stably transfected HEK293 cell line harboring WT and mutant variants of Endoglin in order to elucidate their degradation pathway. Our data shows, for the first time, that WT Endoglin is degraded through both proteasomal and lysosomal pathways, while mutant variants, trapped in the ER, undergo proteasomal degradation. These results pave the way for exploring the possibility of overcoming ERAD as a potential therapeutic target for HHT1.
The analysis of human faces has been an attractive mean for automatic people identification due to its unobtrusive character and non-cooperative nature. Retrieving face morphology via DNA analysis is of great interest in forensic investigations, especially in the lack of other phenotypic information by the suspect(e.g. eye color, hair color/type). However, this goal is still a great challenge. Indeed, the current forensic face reconstruction needs skeletal evidence and mostly used for identifying a victim, whereas DNA traces may be the only clue available in the crime scene. In this paper we are assessing the state-of-the-art regarding 32 selected single nucleotide polymorphisms(SNPs) in the UAE local population. The selected SNPs have been associated with facial phenotypes in other populations. A total of 28 spatial face measurements of 20 UAE locals are obtained in order to test for correlation.Bivariate analysis yielded significant correlation between 40% of the selected SNPs with face measurements.
Bacteria and their products have countless practical applications across several fields spanning biomedical, therapeutic, agricultural, biocontrol, and biotechnology industries to name a few. Despite the impressively practical applications of bacteria, more than 99% of the potentially 1011-1012 microbial species remain undiscovered to date due to our inability to culture these organisms in the lab. These "uncultured" bacteria coined "The Microbial Dark Matter" and their potential benefits remain out of reach. Our lab has developed a method to cultivate these bacteria, and we have successfully cultivated over 150 novel "uncultured" strains. In this work we have performed de novo whole-genome sequencing and assembly of one of these strains in an effort to unravel its identity and potential application. The size of the draft genome generated was 3.62Mb, encoding 3591 genes. Based on the 16S-rRNA gene homology, this uncultured bacterium appears to represent a previously uncharacterized genus belonging to the phylum Actinobacteria.
Excessive production of reactive oxygen species (ROS) is implicated in the pathogenesis of aging-related disorders like cardiovascular diseases. However, monitoring of ROS in vivo remains elusive due to the short half-lives. ROS level can be assessed by measuring the level of malondialdehyde (MDA), biomarker of lipid oxidation induced by ROS. There are many noninvasive techniques to measure MDA, though, they are expensive, and time consuming. In this study, non-invasive and cost-effective method is introduced to detect urinary MDA by utilizing chemicals that react with MDA to produce a colorimetric solution. Three colorimetric methods, p-anisidine, Schiff reagent and methyl-2-phenylindole (MPI), were compared in specificity and sensitivity of MDA by reacting with MDA at normal (0.2 μM) and diseased (0.6 μM and 1 μM) saliva conditions. Only MPI was sensitive enough to identify MDA in diseased conditions. This study supports the efficiency of MPI to detect MDA, indicating the presence of ROS.
Waterfront communities are facing unprecedented challenges with global Sea Level Rise (SLR) becoming a reality. Many of the proposed protection strategies against SLR are at regional levels, and their goals are usually to achieve the greater good for the whole region. However, the distribution of the benefits or burdens may be unequal across different communities. Many waterfront communities are considered disadvantaged because of the concentration of minority and low-income families. The present paper illustrates transportation inequality by quantifying the impact of potential protection strategies on different communities. A case study of the San Francisco Bay Area indicates that the improvements of mobility, resulting from protecting access to the bay-crossing bridges, are often greater in disadvantaged communities than in others. However, many of the disadvantaged communities located next to the entrances to the bridges are negatively impacted. Additional measures should be taken on relieving these communities to reduce transportation inequality.
This paper develops and applies a mathematical model with the objective of locating Hydrogen Refuel Stations (HRS) by maximizing the distance among them through the interstate connectivity from Canada to Mexico on the west coast of United States. The study is focused on the interstate modality of HRS placement while the tendency on the hydrogen market is targeting the use of hydrogen fuel-cell electric (FCEV) heavy-duty trucks as the prototype being released by Nikola Corporation in 2021. The research also considers the characterization of the HRS determining by the distance to the closes current Hydrogen Power Plant generation for delivery and on-site production when the placement is feasible to incorporate green energy to produce hydrogen to achieve sustainable solution combining green and gray hydrogen production.
