Genome-wide non-CpG methylation of the host genome during M. tuberculosis infection

A mammalian cell utilizes DNA methylation to modulate gene expression in response to environmental changes during development and differentiation. Aberrant DNA methylation changes as a correlate to diseased states like cancer, neurodegenerative conditions and cardiovascular diseases have been documented. Here we show genome-wide DNA methylation changes in macrophages infected with the pathogen M. tuberculosis. Majority of the affected genomic loci were hypermethylated in M. tuberculosis infected THP1 macrophages. Hotspots of differential DNA methylation were enriched in genes involved in immune response and chromatin reorganization. Importantly, DNA methylation changes were observed predominantly for cytosines present in non-CpG dinucleotide context. This observation was consistent with our previous finding that the mycobacterial DNA methyltransferase, Rv2966c, targets non-CpG dinucleotides in the host DNA during M. tuberculosis infection and reiterates the hypothesis that pathogenic bacteria use non-canonical epigenetic strategies during infection

Design and Implementation of Cognitive Assessment Tool for Working Memory and Attention based on PGI Memory Scale

983-988Cognitive function is one of the most fundamental psychological functions that play a significant role in person’s daily life. Impairment in cognitive function can impacts the daily functioning and overall performance of the person. A digital application could be an accessible and convenient method for the effective evaluation of cognition. The proposed Cognitive Assessment Digital Smart Tool (CADST) evaluates the Attention (ATT) and Working Memory (WM) parameters of cognition. The outcome measures of CADST were evaluated against PGI Memory Scale (PGIMS) and Montreal Cognitive Assessment (MoCA). Usability testing for the CADST tool was performed using the Post‒Study System Usability Questionnaire (PSSUQ). A total of 30 healthy participants were recruited (women = 12, men = 18; age (M ± SD) = 35.6 ± 10.63 y. o.). The feasibility study analysis revealed a significant moderate to strong correlation between the total scores of CADST and PGIMS (r = 0.75; p < 0.001) and a low to moderate correlation between the total scores of CADST and MoCA (r = 0.44; p < 0.001). Subtests of CADST and PGIMS showed strong correlation for ATT (r = 0.81; p < 0.001) and moderate correlation for WM (r = 0.51; p < 0.001). Similarly, subtests of CADST and MoCA showed moderate correlation for ATT (r = 0.63; p < 0.001) and low correlation for WM (r = 0.24; p = 1.82). CADST showed a high correlation with PGIMS for evaluating ATT and WM symptoms of cognition provide evidence of convergent validity. CADST is the first digital smart screening tool based on PGIMS for ATT and WM using web‒based technology. The overall usability ratings showed high acceptance for system usage, interface and information quality

The interaction of mycobacterial protein Rv2966c with host chromatin is mediated through non-CpG methylation and histone H₃/H₄ binding

To effectively modulate the gene expression within an infected mammalian cell, the pathogen Mycobacterium tuberculosis would need to bring about epigenetic modifications at appropriate genomic loci. Working on this hypothesis, we show in this study that the mycobacterial protein Rv2966c is a 5-methylcytosine-specific DNA methyltransferase that is secreted out from the mycobacterium and gets localized to the nucleus in addition to the cytoplasm inside the host cell. Importantly, Rv2966c binds to specific DNA sequences, methylates cytosines predominantly in a non-CpG context and its methylation activity is positively influenced by phosphorylation. Interestingly, like the mammalian DNA methyltransferase, DNMT3L, Rv2966c can also interact with histone proteins. Ours is the first study that identifies a protein from a pathogenic bacteria with potential to influence host DNA methylation in a non-canonical manner providing the pathogen with a novel mechanism to alter the host epigenetic machinery. This contention is supported by repression of host genes upon M. tuberculosis infection correlated with Rv2966c binding and non-CpG methylation