👤 Mostafa Rafat

Following their domestication, chickens were translocated around the world to novel environments. Through a combination of natural and artificial selection, chickens adapted to these local conditions, creating significant genetic diversity across populations worldwide. Studying this diversity in the context of local environmental conditions may offer insights into mechanisms of adaptation to environmental stressors. In this study, we analyzed genomic data from the Chicken Genomic Diversity Consortium, applying multiple statistical approaches, including fixation index (F The online version contains supplementary material available at 10.1038/s41598-026-41813-8. Show less

Alzheimer's disease is a neurodegenerative disorder that causes significant cognitive impairment and memory loss. It is the leading cause of dementia on a global scale and is distinguished by the pathological build-up of amyloid-beta peptides and tau protein. This study presents the development of E-pharmacophore modeling, which utilizes reported co-crystal structure involving beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) to screen the eMolecules database. The present study comprehensively dealt with the virtual screening and structure-based prediction of thiazole compounds against BACE1 protein. To investigate the binding mode of virtual-screened hits (VS-hits), top 100 VS-hits were docked into BACE1 followed by in silico ADMET prediction. Top two VS-hits (CP1 and CP2) with highest docking scores along with co-crystalized ligand (CPZ) were further subjected to MESP, HOMO, LUMO, MD simulation, and MMGBSA analysis to inspect the dynamic stability of inhibitor-BACE1 complexes and the key molecular interaction responsible for their improved binding affinity toward BACE1. This research identified CP1 and CP2 as top two potential novel BACE1 inhibitors from the library of natural products, whose Glide docking scores range from -8.87 to -7.89 kcal/mol-1. Interestingly, both ligands were able to establish interactions with a set of conserved residues F108, I110, I118, L30, Q12, G13, G11, A335, S229, D228, G230, D32, G34, S35, and Y71. ADMET assessment of the selected compounds was also noted to be within acceptable ranges. The preliminary in-silico ADMET evaluation revealed encouraging results for all the modeled and in-house library compounds. The RMSD and RMSF analysis revealed that both ligands remained stable and maintained their interaction throughout the simulation time (100 nanoseconds). The MM/GBSA (ranging from -36.734 to -27.431 kcal/mol) predicted binding affinities are in strong correlation with that of the docking score, which not only supports the docking results but also suggests that CP1 exhibits superior binding affinity towards BACE1. Keeping in view these findings, CP1 might be a promising candidate for drug discovery against BACE1 inhibitors. The findings of this research have the potential to offer valuable recommendations for the advancement of novel, potent, and efficacious BACE1 inhibitors. Show less

Genetic research for the assessment of mastitis and milk production traits simultaneously has a long history. The main issue that arises in this context is the known existence of a positive correlation between the risk of mastitis and lactation performance due to selection. The transcriptome-wide association study (TWAS) approach endeavors to combine the expression quantitative trait loci and genome-wide association study summary statistics to decode complex traits or diseases. Accordingly, we used the farmgtex project results as a complete bovine database for mastitis and milk production. The results of colocalization and TWAS approaches were used for the detection of functional associated candidate genes with milk production and mastitis traits on multiple tissue-based transcriptome records. Also, we used the david database for gene ontology to identify significant terms and associated genes. For the identification of interaction networks, the genemania and string databases were used. Also, the available z-scores in TWAS results were used for the calculation of the correlation between tissues. Therefore, the present results confirm that LYNX1, DGAT1, C14H8orf33, and LY6E were identified as significant genes associated with milk production in eight, six, five, and five tissues, respectively. Also, FBXL6 was detected as a significant gene associated with mastitis trait. CLN3 and ZNF34 genes emerged via both the colocalization and TWAS approaches as significant genes for milk production trait. It is expected that TWAS and colocalization can improve our perception of the potential health status control mechanism in high-yielding dairy cows. Show less

Obesity plays a pivotal role in the development of metabolic syndrome-excessive body fat, spikes in blood glucose levels and hypertension-and ultimately leads to cardiovascular diseases and type 2 diabetes (T2D), if left unattended. The present study aimed to investigate the associated risk of T2D with obesity risk alleles of fat mass and obesity-associated (FTO) and melanocortin 4 receptor (MC4R) genes. The study includes 400 subjects (300 T2D diabetic cases and 100 healthy controls). Genetic analysis was done by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods. The findings of the study show no significant increase in odds of diabetes associated with the prevalence of FTO and MC4R minor alleles. Rare allele frequencies for "A" of FTO rs9939609 were 0.34 and 0.30 in cases and controls, respectively. Rare allele frequencies for A of MC4R rs12970134 were found to be more common in controls (0.45) than cases (0.41), but the difference was insignificant (p 0.246); however, an increase in body weight with the presence of allele "A" of the FTO gene (p value < 0.001) was found, indicating indirect involvement in the development of T2D. In addition, these were also correlated with the demographic/lifestyle and clinico-pathological parameters between T2D cases and controls. We found that T2D patients with a history of smoking and high consumption of alcohol, fast foods and sweetened beverages are at high risk of T2D compared to healthy controls (p  < 0.01*). The present study concludes that there is no direct association of rs9939609 of the FTO gene with the occurrence of diabetes in the Indian population, but its role in T2D development cannot be overlooked altogether. Furthermore, we conclude that the rs9939609 of FTO carries a potential risk of obesity and because of this FTO rs9939609 T > A is widely considered an obesity-associated allele/single-nucleotide polymorphism (SNP). Show less