Institution
Jawaharlal Nehru University
Education•New Delhi, India•
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.
Papers published on a yearly basis
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TL;DR: The discovery of the critical interactions between PfRH5, PfRipr, and the GPI-anchored CyRPA clearly defines the components of the essential Pf RH5 adhesion complex for P. falciparum erythrocyte invasion and offers it as a previously unidentified potent target for antimalarial strategies that could abrogate formation of the crucial multiprotein complex.
Abstract: Erythrocyte invasion by Plasmodium falciparum merozoites is a highly intricate process in which Plasmodium falciparum reticulocyte binding-like homologous protein 5 (PfRH5) is an indispensable parasite ligand that binds with its erythrocyte receptor, Basigin. PfRH5 is a leading blood-stage vaccine candidate because it exhibits limited polymorphisms and elicits potent strain-transcending parasite neutralizing antibodies. However, the mechanism by which it is anchored to the merozoite surface remains unknown because both PfRH5 and the PfRH5-interacting protein (PfRipr) lack transmembrane domains and GPI anchors. Here we have identified a conserved GPI-linked parasite protein, Cysteine-rich protective antigen (CyRPA) as an interacting partner of PfRH5-PfRipr that tethers the PfRH5/PfRipr/CyRPA multiprotein complex on the merozoite surface. CyRPA was demonstrated to be GPI-linked, localized in the micronemes, and essential for erythrocyte invasion. Specific antibodies against the three proteins successfully detected the intact complex in the parasite and coimmunoprecipitated the three interacting partners. Importantly, full-length CyRPA antibodies displayed potent strain-transcending invasion inhibition, as observed for PfRH5. CyRPA does not bind with erythrocytes, suggesting that its parasite neutralizing antibodies likely block its critical interaction with PfRH5-PfRipr, leading to a blockade of erythrocyte invasion. Further, CyRPA and PfRH5 antibody combinations produced synergistic invasion inhibition, suggesting that simultaneous blockade of the PfRH5–Basigin and PfRH5/PfRipr/CyRPA interactions produced an enhanced inhibitory effect. Our discovery of the critical interactions between PfRH5, PfRipr, and the GPI-anchored CyRPA clearly defines the components of the essential PfRH5 adhesion complex for P. falciparum erythrocyte invasion and offers it as a previously unidentified potent target for antimalarial strategies that could abrogate formation of the crucial multiprotein complex.
146 citations
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TL;DR: Positive loading of most of the factors for heavy metal clearly shows landfill impact on ground water quality especially along the hydraulic gradient, and cluster analysis substantiates the impact of landfill.
Abstract: In present study focus has been given on estimating quality and toxicity of waste with respect to heavy metals and its impact on groundwater quality, using statistical and empirical relationships between different hydrochemical data, so that easy monitoring may be possible which in turn help the sustainable management of landfill site and municipal solid waste. Samples of solid waste, leachate and groundwater were analyzed to evaluate the impact of leachates on groundwater through the comparison of their hydrochemical nature. Results suggest the existence of an empirical relationship between some specific indicator parameters like heavy metals of all three above mentioned sample type. Further, K/Mg ratio also indicates three groundwater samples heavily impacted from leachate contamination. A good number of samples are also showing higher values for \( NO^{ - }_{3} \) and Pb than that of World Health Organization (WHO) drinking water regulation. Predominance of Fe and Zn in both groundwater and solid waste samples may be due to metal plating industries in the area. Factor analysis is used as a tool to explain observed relation between numerous variables in term of simpler relation, which may help to deduce the strength of relation. Positive loading of most of the factors for heavy metal clearly shows landfill impact on ground water quality especially along the hydraulic gradient. Cluster analysis, further substantiates the impact of landfill. Two major groups of samples obtained from cluster analysis suggest that one group comprises samples that are severely under the influence of landfill and contaminated leachates along the groundwater flow direction while other assorted with samples without having such influence.
146 citations
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TL;DR: This study provides evidence that increased stature and cognitive function have been positively selected in human evolution, whereas many important risk factors for late-onset complex diseases may not have been.
Abstract: Homozygosity has long been associated with rare, often devastating, Mendelian disorders, and Darwin was one of the first to recognize that inbreeding reduces evolutionary fitness. However, the effect of the more distant parental relatedness that is common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power. Here we use runs of homozygosity to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts, and find statistically significant associations between summed runs of homozygosity and four complex traits: height, forced expiratory lung volume in one second, general cognitive ability and educational attainment (P < 1 × 10(-300), 2.1 × 10(-6), 2.5 × 10(-10) and 1.8 × 10(-10), respectively). In each case, increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months' less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing evidence that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection, this study provides evidence that increased stature and cognitive function have been positively selected in human evolution, whereas many important risk factors for late-onset complex diseases may not have been.
145 citations
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TL;DR: This dose, which has been set as the safe limit for general public exposure by the Non-Ionizing Radiation Committee of the International Radiation Protection Association, may imply a need for (re)evaluation of the mutagenic potential of microwaves at the prescribedsafe limit for the personnel and people who are being exposed.
Abstract: The potential mutagenic effect of low power microwave at the DNA sequence level in the mouse genome was evaluated by direct DNA analysis. Animals were exposed to microwave at a power density of 1 mW/cm2 for 2 h/day at a frequency of 2.45 GHz over a period of 120, 150 and 200 days. HinfI digested DNA samples from testis and brain of control and exposed animals were hybridized with a synthetic oligo probe (OAT 36) comprising nine repeats of 5'-GACA-3'. As compared to control animals, band patterns in exposed animals were found to be distinctly altered in the range of 7-8 kb which was also substantiated by densitometric analysis. Though the mechanism of this rearrangement is not yet clear, the results obtained at the present dose are of significance. This dose, which has been set as the safe limit for general public exposure by the Non-Ionizing Radiation Committee of the International Radiation Protection Association, may imply a need for (re)evaluation of the mutagenic potential of microwaves at the prescribed safe limit for the personnel and people who are being exposed.
145 citations
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TL;DR: It is demonstrated for the first time that there is an interaction between membrane ergosterol and sphingolipids, that a reduction in the content of either of these two components results in a disruption of this interaction, and that this disruption has deleterious effects on the drug susceptibilities of C. albicans cells.
Abstract: In this study, we examined the importance of membrane ergosterol and sphingolipids in the drug susceptibilities of Candida albicans. We used three independent methods to test the drug susceptibilities of erg mutant cells, which were defective in ergosterol biosynthesis. While spot and filter disk assays revealed that erg2 and erg16 mutant cells of C. albicans became hypersensitive to almost all of the drugs tested (i.e., 4-nitroquinoline oxide, terbinafine, o-phenanthroline, itraconazole, and ketoconazole), determination of the MIC at which 80% of the cells were inhibited revealed more than fourfold increase in susceptibility to ketoconazole and terbinafine. Treatment of wild-type C. albicans cells with fumonisin B1 resulted in 45% inhibition of sphingolipid biosynthesis and caused cells to become hypersensitive to the above drugs. Although erg mutants displayed enhanced membrane fluidity and passive diffusion, these changes alone were not sufficient to elicit the observed hypersusceptibility phenotype of erg mutants. For example, the induction in vitro of a 12% change in the membrane fluidity of C. albicans cells by a membrane fluidizer, benzyl alcohol, did not affect the drug susceptibilities of Candida cells. Additionally, the surface localization of green fluorescent protein-tagged Cdr1p, a major drug efflux pump protein of C. albicans, revealed that any disruption in ergosterol and sphingolipid interactions also interfered with its proper surface localization and functioning. A 50% reduction in the efflux of the Cdr1p substrate, rhodamine 6G, in erg mutant cells or in cells with a reduced sphingolipid content suggested a strong correlation between these membrane lipid components and this major efflux pump protein. Taken together, the results of our study demonstrate for the first time that there is an interaction between membrane ergosterol and sphingolipids, that a reduction in the content of either of these two components results in a disruption of this interaction, and that this disruption has deleterious effects on the drug susceptibilities of C. albicans cells.
145 citations
Authors
Showing all 6255 results
Name | H-index | Papers | Citations |
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Ashok Kumar | 151 | 5654 | 164086 |
Rajesh Kumar | 149 | 4439 | 140830 |
Sanjay Gupta | 99 | 902 | 35039 |
Rakesh Kumar | 91 | 1959 | 39017 |
Praveen Kumar | 88 | 1339 | 35718 |
Rajendra Prasad | 86 | 945 | 29526 |
Mukesh K. Jain | 85 | 539 | 27485 |
Shiv Kumar Sarin | 84 | 740 | 28368 |
Gaurav Sharma | 82 | 1244 | 31482 |
Santosh Kumar | 80 | 1196 | 29391 |
Dinesh Mohan | 79 | 283 | 35775 |
Govindjee | 76 | 426 | 21800 |
Dipak K. Das | 75 | 327 | 17708 |
Amit Verma | 70 | 497 | 16162 |
Manoj Kumar | 65 | 408 | 16838 |