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 & Politics. The organization has 6082 authors who have published 13455 publications receiving 245407 citations. The organization is also known as: JNU.

Functional analysis of CaIPT1, a sphingolipid biosynthetic gene involved in multidrug resistance and morphogenesis of Candida albicans.

Abstract: In the present study we describe the isolation and functional analysis of a sphingolipid biosynthetic gene, IPT1 ,o fCandida albicans. The functional consequence of the disruption of both alleles of IPT1 was confirmed by mass analysis of its sphingolipid composition. The disruption of both alleles or a single allele of IPT1 did not lead to any change in growth phenotype or total sphingolipid, ergosterol, or phospholipid content of the mutant cells. The loss of mannosyl diinositol diphosphoceramide [M(IP)2C] in the ipt1 disruptant, however, resulted in increased sensitivity to drugs like 4-nitroquinoline oxide, terbinafine, o-phenanthroline, fluconazole, itraconazole, and ketoconazole. The increase in drug susceptibilities of ipt1 cells was linked to an altered sphingolipid composition, which appeared to be due to the impaired functionality of Cdr1p, a major drug efflux pump of C. albicans that belongs to the ATP binding cassette superfamily. Our confocal and Western blotting results demonstrated that surface localization of green fluorescent protein-tagged Cdr1p was affected in ipt1 disruptant cells. Poor surface localization of Cdr1p resulted in an impaired ability to efflux fluconazole and rhodamine 6G. The effect of mannosyl inositol phosphoceramide accumulation in the ipt1 mutant and the absence of M(IP)2C from the ipt1 mutant on the efflux of drug substrates was very selective. The efflux of methotrexate, a specific substrate of CaMdr1p, another major efflux pump of major facilitator superfamily, remained unaffected in ipt1 mutant cells. Interestingly, changes in sphingolipid composition affected the ability of mutant cells to form proper hyphae in various media. Taken together, our results demonstrate that an altered composition of sphingolipid, which is among the major constituents of membrane rafts, affects the drug susceptibilities and morphogenesis of C. albicans. The early steps in mammalian and fungal sphingolipid synthesis are conserved, but finally, they diverge to produce structurally and chemically different types of sphingoid bases, ceramides, and complex sphingolipids (12). Therefore, over the years, the sphingolipid biosynthetic pathway has been exploited as an antifungal drug target in pathogenic yeasts (24, 29). Unlike mammals, fungi do not have phosphatidylcholine as part of their polar head group in the sphingolipids; instead, they have phosphoinositol, which is transferred by Aur1p to the C-1 hydroxyl of ceramide to make inositol phosphoceramide (IPC) (6, 7). IPC is further modified by the addition of mannose by Csg1p, Csg2p, and Vrg4p to make mannosyl inositol phosphoceramide (MIPC) and the addition of a second inositol phosphate group by Ipt1p to make mannosyl diinositol diphosphoceramide [M(IP)2C] (6, 7). The biosynthesis of sphingolipids starts in the endoplasmic reticulum and proceeds up to the formation of ceramides (12). Subsequently, complex fungal sphingolipids [IPC, MIPC, and M(IP)2C] are synthesized in the Golgi apparatus. Recent reports have suggested that the biosynthesis of these sphingolipids is critical to the maintenance of plasma membrane (PM) function; however,

Gender Differentials in Self-Rated Health and Self-Reported Disability among Adults in India.

Abstract: Background The extant literature on gender differentials in health in developed countries suggests that women outlive men at all ages, but women report poorer health than men. It is well established that Indian women live longer than men, but few studies have been conducted to understand the gender dimension in self-rated health and self-reported disability. The present study investigates gender differentials in self-rated health (SRH) and self-reported disability (SRD) among adults in India, using a nationally representative data. Methods Using data on 10,736 respondents aged 18 and older in the 2007 WHO Study on Global Ageing and Adult Health in India, prevalence estimates of SRH are calculated separately for men and women by socio-economic and demographic characteristics. The association of SRH with gender is tested using a multinomial logistic regression method. SRD is assessed using 20 activities of daily living (ADL). Further, gender differences in total life expectancy (TLE), disability life expectancy (DLE) and the proportion of life spent with a disability at various adult ages are measured. Results The relative risk of reporting poor health by women was significantly higher than men (relative risk ratio: 1.660; 95% confidence Interval (CI): 1.430–1.927) after adjusting for socio-economic and demographic characteristics. Women reported higher prevalence of severe and extreme disability than men in 14 measures out of a total20 ADL measures. Women aged less than 60 years reported two times more than men in SRD ≥ 5 ADLs. Finally, both DLE and proportion of life spent with a disability were substantially higher for women irrespective of their ages. Conclusion Indian women live longer but report poorer health than men. A substantial gender differential is found in self-reported disability. This makes for an urgent call to health researchers and policy makers for gender-sensitive programs.