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81.
Soumitra Mohanty Lakshmanan Jagannathan Geetanjali Ganguli Avinash Padhi Debasish Roy Nader Alaridah Pratip Saha Upendra Nongthomba Gabriela Godaly Ramesh Kumar Gopal Sulagna Banerjee Avinash Sonawane 《The Journal of biological chemistry》2015,290(21):13321-13343
Mycobacterium tuberculosis employs various strategies to modulate host immune responses to facilitate its persistence in macrophages. The M. tuberculosis cell wall contains numerous glycoproteins with unknown roles in pathogenesis. Here, by using Concanavalin A and LC-MS analysis, we identified a novel mannosylated glycoprotein phosphoribosyltransferase, encoded by Rv3242c from M. tuberculosis cell walls. Homology modeling, bioinformatic analyses, and an assay of phosphoribosyltransferase activity in Mycobacterium smegmatis expressing recombinant Rv3242c (MsmRv3242c) confirmed the mass spectrometry data. Using Mycobacterium marinum-zebrafish and the surrogate MsmRv3242c infection models, we proved that phosphoribosyltransferase is involved in mycobacterial virulence. Histological and infection assays showed that the M. marinum mimG mutant, an Rv3242c orthologue in a pathogenic M. marinum strain, was strongly attenuated in adult zebrafish and also survived less in macrophages. In contrast, infection with wild type and the complemented ΔmimG:Rv3242c M. marinum strains showed prominent pathological features, such as severe emaciation, skin lesions, hemorrhaging, and more zebrafish death. Similarly, recombinant MsmRv3242c bacteria showed increased invasion in non-phagocytic epithelial cells and longer intracellular survival in macrophages as compared with wild type and vector control M. smegmatis strains. Further mechanistic studies revealed that the Rv3242c- and mimG-mediated enhancement of intramacrophagic survival was due to inhibition of autophagy, reactive oxygen species, and reduced activities of superoxide dismutase and catalase enzymes. Infection with MsmRv3242c also activated the MAPK pathway, NF-κB, and inflammatory cytokines. In summary, we show that a novel mycobacterial mannosylated phosphoribosyltransferase acts as a virulence and immunomodulatory factor, suggesting that it may constitute a novel target for antimycobacterial drugs. 相似文献
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Basak Supriyo Chakrabartty Ishani Hedaoo Vivek Shelke Rahul G. Rangan Latha 《Molecular biology reports》2019,46(1):177-189
Molecular Biology Reports - Genetic structure was evaluated among wild Alpinia nigra (Gaertn.) B.L. Burtt, populations. The information of genetic relatedness was developed using random amplified... 相似文献
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Ishani Deb Japashish Chakraborty Prasanta Kumar Gangopadhyay Susanta Roy Choudhury Sumantra Das 《Journal of neurochemistry》2010,112(2):486-496
The opioid receptor mu1 (OPRM1) mediates the action of morphine. Although genetic background plays an important role in the susceptibility toward abuse of drugs as evident from familial, adoption and twin studies, association of specific single‐nucleotide polymorphisms of OPRM1 gene with narcotic addiction is to be established. Here, we demonstrate the involvement of A118G polymorphism of exon1 of human OPRM1 gene (hOPRM1), with heroin and alcohol addiction, in a population in eastern India. Statistical analysis exhibited a significant association of G allele with both heroin and alcohol addiction with a risk factor of Ptrend < 0.05. The functional significance of G allele in A118G single‐nucleotide polymorphisms was evaluated by studying the regulation of protein kinase A (PKA), pCREB, and pERK1/2 by morphine in Neuro 2A cells, stably transfected with either wild type or A118G mutant hOPRM1. Unlike acute morphine treatment, both chronic morphine exposure and withdrawal precipitated by naloxone were differentially regulated by A118 and G118 receptor isoforms when both PKA and pERK1/2 activities were compared. Results suggest that the association of A118G polymorphism to heroin and alcohol addiction may be because of the altered regulation of PKA and pERK1/2 during opioid and alcohol exposures. 相似文献
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A well characterized naphthalene-degrading strain, Pseudomonas putida PpG7 was observed to utilize limonin, a highly-oxygenated triterpenoid compound as a sole source of carbon and energy. Limonin concentrations evidenced a 64% reduction over 48 h of growth in batch cultures. Attempts were made to acquire a plasmid-less derivative via various methods (viz. Ethidium Bromide, SDS, elevated temperature & mitomycin C), among which the method involving mitomycin C (20 ug/ml) proved successful. Concomitant with the loss of plasmid in P. putida PpG7 strain, the cured derivative was identified as a lim- phenotype. The lim+ phenotype could be conjugally transferred to the cured derivative. Based on the results of curing with mitomycin C, conjugation studies and presence of ndo gene encoding naphthalene 1,2 dioxygenase, it was demonstrated that genes for the limonin utilization were encoded on an 83 kb indigenous transmissible Inc. P9 NAH plasmid in Pseudomonas putida PpG7 strain. 相似文献
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In order to investigate chronic hypergastrinaemia in dogs, studies with various excluded antrum preparations were performed. Gastric secretion was collected from denervated fundic pouches and gastrin levels were measured pre- and postoperatively by radioimmunoassay. In some samples the gastrins were separated according to their molecular size. Distinct hypergastrinaemia and acid hypersecretion developed in dogs where the antrum was excluded by a mucosal septum. Gastrin levels rose to 349 +/- 64 pg/ml (normal 76 +/- 19 pg/ml). Analysis of the gastrin pattern showed a predominance of smaller gastrin components. Although there was marked hypersecretion in most of the dogs with hypergastrinaemia, no close correlation was evident between these parameters. Some of the dogs with hypergastrinaemia developed anastomotic ulcers. 相似文献
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