Type 2 diabetes (T2D) is a complex disease with an elusive link between its molecular aetiology and clinical presentation. Although, the role of visceral adipose tissue in insulin-resistance and T2D is known, limited information is available on the role of peripheral-subcutaneous adipose tissue especially in Asian Indians. In this microarray-based study of diabetic and normal glucose tolerant Asian Indians, we generated the transcriptome of their thigh adipose tissue and analyzed differentially expressed genes (DEGs) using weighted gene co-expression network analysis; further we identified perturbed pathways implicated by these DEGs in relevant co-expression modules. We also attempted to link these pathways with known aspects of T2D pathophysiology in terms of their association with some of their intermediate traits, namely; adipocyte size, HOMA-B, HOMA-R, Hb1Ac, insulin, glucose-level, TNF-α, IL-6, VLDLs, LDLs, HDLs, and NEFAs. It was observed that several modules of co-expressed genes show an association with diabetes and some of its intermediate phenotypic traits mentioned above. Therefore, these findings suggest a role of peripheral subcutaneous adipose tissue in the pathophsiology of T2D in Asian Indians. Additionally, our study indicated that the peripheral subcutaneous adipose tissue in diabetics shows pathologic changes characterized by adipocyte hypertrophy and up-regulation of inflammation-related pathways.
We demonstrate the application of whole exome sequencing to discover the rare variants for congenital pouch colon, acronymed CPC. For 18 affected individuals in a total of 64 samples, we sequenced coding regions to a mean coverage of 100×. A sufficient depth of ca. 94% of targeted exomes was achieved. Filtering against the public SNP/variant repositories, we identified a host of candidate genes, EPB41L4A and CTC1 associated with colon, neural/brain muscles and Dyskeratosis Congenita maladies. Furthermore, the stop gain mutations in the form of JAG1,OR5AR1,SLC22A24,PEX16,TSPAN32,TAF1B,MAP2K3 and SLC25A19 appears to be localized to Chromosomes 2, 11, 17 and 20 in addition to the three stop lost mutations across three genes, viz. OAS2, GBA3 and PKD1L2 affecting the colon tissue. While our results have paved way for transcendence of monogenic traits in identifying the genes underlying rare genetic disorders, it will provide helpful clues for further investigating genetic factors associated with anorectal anomalies, particularly CPC.
We performed a systematic analysis of genes implicated in thigh subcutaneous adipose tissue of Asian Indian Type 2 Diabetes Mellitus (AIT2DM) and created a phenome-interactome network. This analysis was performed on 60 subjects specific to limb thigh fat by integrating phenotypic traits and similarity scores associated with AIT2DM. Using a phenotypic attribute, a contextual neighbor was identified across all the traits, viz. body mass index (BMI) statistics, adipocyte size, lipid parameters, homeostatic model assessment- insulin resistance (HOMA-IR), HOMA-ß. In this work, we have attempted to characterize transcription signatures using the phenome-interactome maps where each of the traits under study including the intermediary phenotypes has a distinct set of genes forming the hubs. Furthermore, we have identified various clinical, biochemical, and radiological parameters which show significant correlation with distinct hubs. We observed a number of novel pathways and genes including those that are non-coding RNAs implicated in AIT2DM.We showed that they appear to be associated with pathways, viz. tyrosine kinase JAK2, NOTCH thereby recruiting signaling molecules such as STAT5 and Src family kinases on the cell surface regulated them and our analyses comprising significant hubs suggest that thigh subcutaneous adipose tissue plays a role in pathophysiology of AIT2DM.
Alongside antibiotic resistance, co-selection of antibiotics, biocides, and metal resistance is a growing concern. While hospital wastewater is considered a hotspot for antibiotic-resistant bacteria (ARB) and genes (ARGs), the scenario in India, one of the biggest consumers of antibiotics, remains poorly described. In this study, we used metagenomic sequencing to characterize ARGs and biocide/metal resistance genes (BMRGs) in four wastewater treatment plants (WWTPs) in Jaipur City of India. We observed a significantly lower richness and abundance of ARGs in the influent of a WWTP exclusively receiving hospital wastewater when compared to other three WWTPs involving municipal wastewater treatment. Several tetracycline and macrolide-lincosamide-streptogramin resistance genes were enriched in influents of these three municipal wastewater-related treatment plants, whereas hospital wastewater had a higher abundance of genes conferring resistance to disinfectant-related compounds such as synergize and wex-cide-128, reflecting the patterns of antibiotic/disinfectant use. Of note, in the wastewater system with more chemicals, there was a strong correlation between the numbers of ARGs and BMRGs potentially harbored by common hosts. Our study highlights significant influxes of ARGs from non-hospital sources in Jaipur City, and thus more attention should be paid on the emergence of ARGs in general communities.
Wastewater-based surveillance has been emerging as an efficient and advantageous tool to predict COVID-19 prevalence in the population, much earlier (7–28 days) than reported clinical cases, thus providing sufficient time to organize resources and optimize their use in managing COVID-19. Since the commencement of the COVID-19 pandemic, SARS-CoV-2 genetic lineages have emerged and are circulating all over the world. The assessment of SARS-CoV-2 variants of concern (VOCs) in wastewater has recently been proven to be successful. The present research demonstrates a case study utilizing an established approach to perform monitoring of SARS-CoV-2 variants from 11 distinct wastewater treatment plants across Jaipur (India) during the second peak period of COVID-19 (from 19 February 2021 to 8 June 2021). The sequences obtained were analyzed to detect lineage using the Pangolin tool and SNPs using the mpileup utility of Samtools, which reported high genome coverage. The mutation analyses successfully identified the penetration of the B.1. in the first two weeks of sampling (19–26 February), followed by the B.1.617.2 variant into Jaipur in the first week of March 2021. B.1.617.2 was initially discovered in India in October 2020; however, it was not reported until early April 2021.The present study identified the presence of B.1.617.2 in early March, which correlates well with the clinical patient’s data (290 cases were reported much later by the government on 10 May 2021). The average total genome coverage of the samples is 94.39% when mapped onto the severe acute respiratory syndrome coronavirus 2 isolate Wuhan-Hu-1; a complete genome (NC_045512.2) sequence and SNP analysis showed that 37–51 SNPs were identified in each sample. The current study demonstrates that sewage surveillance for variant characterization is a reliable and practical method for tracking the diversity of SARS-CoV-2 strains in the community that is considerably faster than clinical genomic surveillance. As a result, this method can predict the advent of epidemiologically or clinically important mutations/variants, which can help with public health decision making.
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