Jawaharlal Nehru University

About: Jawaharlal Nehru University is a education organization based out in New Delhi, India. It is known for research contribution in the topics: Population & Candida albicans. The organization has 6082 authors who have published 13455 publications receiving 245407 citations. The organization is also known as: JNU.

Functional characterization of Candida albicans ABC transporter Cdr1p.

Abstract: In view of the importance of Candida drug resistance protein (Cdr1p) in azole resistance, we have characterized it by overexpressing it as a green fluorescent protein (GFP)-tagged fusion protein (Cdr1p-GFP). The overexpressed Cdr1p-GFP in Saccharomyces cerevisiae is shown to be specifically labeled with the photoaffinity analogs iodoarylazidoprazosin (IAAP) and azidopine, which have been used to characterize the drug-binding sites on mammalian drug-transporting P-glycoproteins. While nystatin could compete for the binding of IAAP, miconazole specifically competed for azidopine binding, suggesting that IAAP and azidopine bind to separate sites on Cdr1p. Cdr1p was subjected to site-directed mutational analysis. Among many mutant variants of Cdr1p, the phenotypes of F774A and ΔF774 were particularly interesting. The analysis of GFP-tagged mutant variants of Cdr1p revealed that a conserved F774, in predicted transmembrane segment 6, when changed to alanine showed increased binding of both photoaffinity analogues, while its deletion (ΔF774), as revealed by confocal microscopic analyses, led to mislocalization of the protein. The mislocalized ΔF774 mutant Cdr1p could be rescued to the plasma membrane as a functional transporter by growth in the presence of a Cdr1p substrate, cycloheximide. Our data for the first time show that the drug substrate-binding sites of Cdr1p exhibit striking similarities with those of mammalian drug-transporting P-glycoproteins and despite differences in topological organization, the transmembrane segment 6 in Cdr1p is also a major contributor to drug substrate-binding site(s).

Antifungal curcumin induces reactive oxygen species and triggers an early apoptosis but prevents hyphae development by targeting the global repressor TUP1 in Candida albicans.

Abstract: In the present study, we have investigated the antifungal effects of a natural polyphenol, CUR (curcumin), against albicans and non-albicans species of Candida and have shown its ability to inhibit the growth of all the tested strains. The inhibitory effects of CUR were independent of the status of the multidrug efflux pump proteins belonging to either ABC transporter (ATP-binding cassette transporter) or MFS (major facilitator) superfamilies of transporters. By using a systemic murine model of infection, we established that CUR and piperine, when administered together, caused a significant fungal load reduction (1.4log10) in kidneys of Swiss mice. Additionally, CUR raised the levels of ROS (reactive oxygen species), which, as revealed by annexin V-FITC labelling, triggered early apoptosis in Candida cells. Coincident with the raised ROS levels, mRNAs of tested oxidative stress-related genes [CAP1 (Candida albicans AP-1), CaIPF7817 (putative NADH-dependent flavin oxidoreductase), SOD2 (superoxide dismutase 2), GRP2 (NADPH-dependent methyl glyoxal reductase) and CAT1 (catalase 1)] were also elevated. The growth inhibitory effects of CUR could be reversed by the addition of natural and synthetic antioxidants. Notably, independent of ROS status, polyphenol CUR prevented hyphae development in both liquid and solid hypha-inducing media by targeting the global suppressor TUP1 (thymidine uptake 1). Taken together, our results provide the first evidence that CUR acts as an antifungal agent, via generation of oxidative stress, and inhibits hyphae development by targeting TUP1.

Texture and mineralogy of sediments from the Ganges-Brahmaputra-Meghna river system in the Bengal Basin, Bangladesh and their environmental implications

Abstract: The Bengal basin, Bangladesh, represents one of the most densely populated recent floodplains of the world. The sediment flux through the basin is one of the highest on a global scale. A significant portion of this sediment load find its sink in the basin itself because of its lower elevation and frequent flooding. The textural, mineralogical and chemical nature of the sediments thus have an important bearing on the environmental quality of the basin as well as for the Bay of Bengal. The sediment load of the Ganges-Brahmaputra-Meghna (GBM) river system consists exclusively of fine sand, silt and clay at their lower reaches within the Bengal basin, Bangladesh, and is deposited under uniformly fluctuating, unidirectional energy conditions. The sediments have a close simitarity in grain size with the sediments of the surrounding floodplain. The mineral assemblage is dominated by quartz and feldspars. Illite and kaolinite are the major clay minerals, and occur in almost equal proportion in bed sediments. The heavy mineral assemblage is dominated by unstable minerals which are mostly derived from high-rank metamorphic rocks. The characteristic smaller grain-size, i.e. having large surface-to-mass ratios, and the mineralogy of sediments suggests that they are susceptible to large chemical adsorptive reactions and thus could serve as a potential trap for contaminants. However, the sediments of the GBM river system in the Bengal basin, Bangladesh, shows lower concentration of Pb, Hg and As, and a marginally higher value for Cd as compared to that of standard shale. Considering population density and extensive agricultural practice in the basin, the sediments can in the long run become contaminated.