Biology subjects

Anwar, S.

Publications and source records attributed to Anwar, S..

23 records · Page 2Linked to original sources

bioRxiv2020

Kinome-wide RNAi screen uncovers role of Ballchen in maintenance of gene activation by trithorax group in Drosophila

Polycomb group (PcG) and trithorax group (trxG) proteins are evolutionary conserved factors that contribute to cell fate determination and maintenance of cellular identities during development of multicellular organisms. The PcG behaves as repressors to maintain heritable patterns of gene silencing and trxG act as anti-silencing factors by maintaining activation of cell type specific genes. Genetic and molecular analysis has revealed extensive details about how different PcG and trxG complexes antagonize each other to maintain cell fates, however the cellular signaling components that contribute to maintenance of gene expression by PcG/trxG remain elusive. Here, we report an ex vivo kinome-wide RNAi screen in Drosophila aimed to identify cell signaling genes that facilitate trxG to counteract PcG mediated repression. From the list of trxG candidates, Ballchen (BALL), a histone kinase, known to phosphorylate histone H2A at threonine 119 (H2AT119p), was characterized as a trxG regulator. The ball mutant exhibit strong genetic interaction with Polycomb (Pc) and trithorax (trx) mutants and loss of BALL also affects expressions of trxG target genes in ball mutant embryos. BALL co-localizes with Trithorax on chromatin and depletion of BALL results in increased H2AK118 ubiquitination, a histone mark central to PcG mediated gene silencing. Moreover, analysis of genome-wide binding profile of BALL shows an overlap with 85% known binding sites of TRX across the genome. Both BALL and TRX are highly enriched at actively transcribed genes, which also correlate with presence of H3K4me3 and H3K27ac. We propose that BALL mediated signal positively contributes to the maintenance of gene activation by trxG by counteracting the repressive effect of PcG.

molecular biology↗

bioRxiv2020

Genetic analysis of SARS-CoV-2 isolates collected from Bangladesh: insights into the origin, mutation spectrum, and possible pathomechanism

As the coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), rages across the world, killing hundreds of thousands and infecting millions, researchers are racing against time to elucidate the viral genome. Some Bangladeshi institutes are also in this race, sequenced a few isolates of the virus collected from Bangladesh. Here, we present a genomic analysis of 14 isolates. The analysis revealed that SARS-CoV-2 isolates sequenced from Dhaka and Chittagong were the lineage of Europe and the Middle East, respectively. Our analysis identified a total of 42 mutations, including three large deletions, half of which were synonymous. Most of the missense mutations in Bangladeshi isolates found to have weak effects on the pathogenesis. Some mutations may lead the virus to be less pathogenic than the other countries. Molecular docking analysis to evaluate the effect of the mutations on the interaction between the viral spike proteins and the human ACE2 receptor, though no significant interaction was observed. This study provides some preliminary insights into the origin of Bangladeshi SARS-CoV-2 isolates, mutation spectrum and its possible pathomechanism, which may give an essential clue for designing therapeutics and management of COVID-19 in Bangladesh.

genomics↗

bioRxiv2020

Novel insights into the structure and transport mechanisms of TAPT1

Transmembrane anterior-posterior transformation protein 1 (TAPT1), encoded by the TAPT1 gene expressed in the basal ciliary body, plays a crucial role in cilia formation as well as axial skeletal patterning. Mutations in this gene have been reported to cause several ciliopathies and osteo-related diseases. Unfortunately, the cellular and molecular pathogenic mechanisms are still unclear also due to the lack of X-ray crystallographic structure and further characterization of TAPT1 protein. In this study, we attempted to characterize this protein by in silico techniques. A 3D structure of TAPT1 was generated by the ab initio method, which was further used for the analysis of the substrate-binding site, to determine pore size and for the prediction of the possible substrate(s). Validation by using different software packages revealed a reliable 3D model of TAPT1. Topology modeling revealed that TAPT1 has eight transmembrane helices with a total number of 27 helices in secondary structure. The amino acid residues H235, R323, K443, N446, S447, L450, K453, S454, Y457, K511, N513, D533, K535, D536, and T538 were found to form the pore surface as well as involved in the binding interaction with the substrate(s). This study predicted flavonoids as the possible substrate for TAPT1, which could further be confirmed by ingenuity pathway analysis. Moreover, our analysis indicated that TAPT1 might localize in the mitochondrial membrane in addition to the ciliary basal body. Our study gives novel insights for TAPT1 structure and its function.

biochemistry↗

bioRxiv2020

Situation of antibiotic resistance in Bangladesh and its association with resistance genes for horizontal transfer

The study investigated the spectrum of antibiotic resistance and the associated genes for aminoglycoside, macrolide and ESBL class of antibiotics using clinical isolates. A total of 430 preserved bacterial strains (Acinetobacter baumannii, n= 20; Pseudomonas aeruginosa, n= 26; Klebsiella pneumoniae, n= 42; E.coli, n= 85; Staphylococcus aureus, n= 84; Salmonella Typhi, n= 82; Enterococcus spp., n= 27; Streptococcus pneumoniae, n= 36 and CNS, n= 28) were examined. The strains were isolated from patients admitted to various tertiary hospitals of Dhaka city between 2015 and 2019 with either acute respiratory infections, wound infections, typhoid fever or diarrhea. The isolates were reconfirmed by appropriate microbiological and biochemical methods. Antimicrobial susceptibility tests were done using Kirby-Bauer disk diffusion approach. PCR amplification using resistance gene-specific primers for aminoglycoside, macrolide and ESBL class of antibiotics was done and the amplified products were confirmed by Sanger sequencing. Of the total isolates, 53% came out as MDR with 96.6% of E. coli and 90% of Staphylococcus aureus. There was a year-wise gradual increase of MDR isolates from 2015-2018 and by 2019 the increase in MDR isolates became almost 2-fold compared to 2015. Among the five ESBL genes investigated, CTXM-1 came out as the most prevalent (63%) followed by NDM-1 (22%) and E. coli isolates were the predominant reservoir of these genes. ErmB (55%) was the most frequently detected macrolide resistance gene, whereas aac(6)-Ib (35.44%) was the most prevalent aminoglycoside resistance gene and these genes were most prevalent in E. coli and P. aeruginosa isolates, respectively. CTXM-1 and ErmB (16.66%) were the most frequent partners of coexistence followed by CTXM-1 and aac(3)-II.

microbiology↗

bioRxiv2019

Chikungunya Outbreak in Bangladesh (2017): Clinical and hematological findings

A massive outbreak of Chikungunya occurred in Bangladesh during the period of April-September, 2017 and over two million people were at risk of getting infected by the virus. A prospective cohort of viremic patients was constituted and analyzed to define the clinical, hematological and long-term aspects of this outbreak. A 35-day long comprehensive survey was conducted in two major, neighboring cities, Dhaka and Mymensingh. One-hundred and eighty-seven clinically proven Chikungunya cases were enrolled in the cross-sectional cohort study. Additionally, a smaller group of 48 Chikungunya patients was monitored for post-infection effects for 12 months. Clinical data revealed that a combination of fever and arthralgia (oligoarthralgia and/or polyarthralgia) was the cardinal hallmark (97.9% of cases) of the infection. Hematological analysis showed that, irrespective of age groups, hemoglobin level significantly decreased and erythrocyte sedimentation rate remarkably increased in Chikungunya confirmed patients. However, the majority of the patients had a normal range of whole WBC and platelet counts; RBC counts for mid aged (40 - 60 years) and senior (61+ years) patients (especially in the females) were beyond the reference values. The post-infection study revealed that children had an early recovery from the infection compared to the adults. Moreover, post-infection weakness, successive relapse of arthralgic pain and memory problems were the most significant aftereffects, which had an impact on daily activities of patients. This study represents a comprehensive overview of clinical and epidemiological features of the 2017 outbreak of Chikungunya in Bangladesh as well as its chronic outcomes till the 12th month. It provides insights into the natural history of this disease which may help to improve management of the Chikungunya patients.\n\nAuthor summeryThe clinical profile, epidemiology and the economic impacts during the acute phase of Chikungunya infection has been studied quite rigorously. However, studies regarding the hematological features and chronic consequences are very limited. In this study, a dataset of 187 clinically proven chikungunya patients were analyzed for the clinical and hematological features at acute phase of the infection. Additionally, the long-term consequences till month 12 after the infection were studied for a smaller group of 48 patients. Clinical data revealed that a combination of fever and joint pain (arthralgia) was the cardinal hallmark in the acute phase of the infection. Hematological analysis showed that, hemoglobin levels of the patients were significantly reduced and erythrocyte sedimentation rate increased remarkably. Also, RBC counts for mid-aged and older patients were beyond the reference values. The post-infection consequence study unveiled that children recovered better from the infection compared to the adults. Further, post-infection weakness, successive relapse of joint pain and memory problems were the most significant aftereffects. Overall, the infection had moderate to severe impact on daily activities of the respondents. This study provides insights into the clinical and hematological aspects of Chikungunya infection during the acute phase as well as describes an account for its chronic outcomes which puts forward to the knowledge for clinicians and epidemiologists regarding the infection diversity and to help improved patient management.

epidemiology↗