👤 Gunjan Vasudeva

Monogenic obesity is a rare form of obesity due to pathogenic variants in genes implicated in the leptin-melanocortin signaling pathway and accounts for around 5% of severe early-onset obesity. Mutations in the genes encoding the MC4R, leptin, and leptin receptor are commonly reported in various populations to cause monogenic obesity. Determining the genetic cause has important clinical benefits as novel therapeutic interventions are now available for some forms of monogenic obesity. To unravel the genetic causes of early-onset obesity in the population of Qatar. In total, 243 patients with early-onset obesity (above the 95% percentile) and age of onset below 10 years were screened for monogenic obesity variants using a targeted gene panel, consisting of 52 obesity-related genes. Thirty rare variants potentially associated with obesity were identified in 36 of 243 (14.8%) probands in 15 candidate genes (LEP, LEPR, POMC, MC3R, MC4R, MRAP2, SH2B1, BDNF, NTRK2, DYRK1B, SIM1, GNAS, ADCY3, RAI1, and BBS2). Twenty-three of the variants identified were novel to this study and the rest, 7 variants, were previously reported in literature. Variants in MC4R were the most common cause of obesity in our cohort (19%) and the c.485C>T p.T162I variant was the most frequent MC4R variant seen in 5 patients. We identified likely pathogenic/pathogenic variants that seem to explain the phenotype of around 14.8% of our cases. Variants in the MC4R gene are the commonest cause of early-onset obesity in our population. Our study represents the largest monogenic obesity cohort in the Middle East and revealed novel obesity variants in this understudied population. Functional studies will be required to elucidate the molecular mechanism of their pathogenicity. Show less

Monkeypox virus (MPXV) is a double-stranded DNA virus from the family Poxviridae, which is endemic in West and Central Africa. Various human outbreaks occurred in the 1980s, resulting from a cessation of smallpox vaccination. Recently, MPXV cases have reemerged in non-endemic nations, and the 2022 outbreak has been declared a public health emergency. Treatment optionsare limited, and many countries lack the infrastructure to provide symptomatic treatments. The development of cost-effective antivirals could ease severe health outcomes. G-quadruplexes have been a target of interest in treating viral infections with different chemicals. In the present work, a genomic-scale mapping of different MPXV isolates highlighted two conserved putative quadruplex-forming sequences MPXV-exclusive in 590 isolates. Subsequently, we assessed the G-quadruplex formation using circular dichroism spectroscopy and solution small-angle X-ray scattering. Furthermore, biochemical assays indicated the ability of MPXV quadruplexes to be recognized by two specific G4-binding partners-Thioflavin T and DHX36. Additionally, our work also suggests that a quadruplex binding small-molecule with previously reported antiviral activity, TMPyP4, interacts with MPXV G-quadruplexes with nanomolar affinity in the presence and absence of DHX36. Finally, cell biology experiments suggests that TMPyP4 treatment substantially reduced gene expression of MPXV proteins. In summary, our work provides insights into the G-quadruplexes from the MPXV genome that can be further exploited to develop therapeutics. Show less

The common effluent treatment plant (CETP) located at Baddi treats the industrial effluent from various industries, leading to the pooling of a diverse range of substrates and metabolites. The nutrient loading and its availability decide the balance of the microbial community and its diversity. The samples thus collected from the activated sludge (BS14) of CETP and Sirsa river (SR1) from the vicinity of CETP effluent discharge were processed for the whole metagenome analysis to reveal the microbial community and its functional potential. The taxonomic classification of the BS14 sample showed the dominance of the bacterial community with 96% of abundance, whereas the SR1 was populated by eukaryotes representing 50.4% of the community of SR1. The bacterial community of SR1 was constituted of 47.2%. The functional analysis of BS14 and SR1 with GhostKOALA against the KEGG database assigned 43.7% and 27.8% of the open reading frames (ORFs) with functions. It revealed the xenobiotic degradation modules with complete pathways along with resistance against the beta-lactams. The analysis with the comprehensive antibiotic resistance database (CARD) revealed 33 and 32 unique types of antimicrobial resistance in BS14 and SR1, respectively. Both the samples were dominated by the beta-lactam resistance genes. The carbohydrate-active enzyme (CAZy) database assigned a total of 6,611 and 2,941 active enzymes to BS14 and SR1, respectively. In contrast, the glycosyl hydrolases (GH) and glycosyltransferases (GT) class of enzymes were found to be abundant in both the samples as compared with polysaccharide lyases (PL), auxiliary activities (AA), carbohydrate esterases (CE), and carbohydrate-binding module (CBM). Show less