The Niemann-Pick type C1 (NPC1) protein is a key participant in intracellular trafficking of low density lipoprotein cholesterol, but its role in regulation of sterol homeostasis is not well understood. To characterize further the function of NPC1, we generated stable Chinese hamster ovary (CHO) cell lines overexpressing the human NPC1 protein (CHO/NPC1). NPC1 overexpression increases the rate of trafficking of low density lipoprotein cholesterol to the endoplasmic reticulum and the rate of delivery of endosomal cholesterol to the plasma membrane (PM). CHO/NPC1 cells exhibit a 1.5-fold increase in total cellular cholesterol and up to a 2.9-fold increase in PM cholesterol. This increase in PM cholesterol is closely paralleled by a 3-fold increase in de novo cholesterol synthesis. Inhibition of cholesterol synthesis results in marked redistribution of PM cholesterol to intracellular sites, suggesting an unsuspected role for NPC1 in internalization of PM cholesterol. Despite elevated total cellular cholesterol, CHO/NPC1 cells exhibit increased cholesterol synthesis, which may be attributable to both resistance to oxysterol suppression of sterol-regulated gene expression and to reduced endoplasmic reticulum cholesterol levels under basal conditions. Taken together, these studies provide important new insights into the role of NPC1 in the determination of the levels and distribution of cellular cholesterol.Intracellular cholesterol sorting and transport pathways play an important role in the physiologic utilization of lipoprotein-derived cholesterol. Low density lipoprotein (LDL) 1 and modified lipoprotein particles are trafficked to lysosomes, where the cholesteryl esters are hydrolyzed to free cholesterol (1). The bulk of LDL cholesterol is mobilized from lysosomes to the plasma membrane (PM) and subsequently cycles back to the endoplasmic reticulum (ER) (2). Approximately one-third of the unesterified lysosomal cholesterol is delivered directly to the ER via a PM-independent transport pathway (3). Cholesterol levels in the ER regulate cellular cholesterol homeostasis through a feedback regulatory mechanism that controls de novo synthesis and cellular uptake of cholesterol. This regulatory system principally involves membrane-bound transcription factors known as sterol regulatory element-binding proteins (SREBPs) (4). When cells are sterol-depleted, the NH 2 -terminal regions of the SREBPs are released through a twostep proteolytic cleavage and translocate to the nucleus to promote transcription of multiple genes involved in cholesterol and fatty acid homeostasis. When cells are replete with sterols, proteolytic cleavage of SREBPs is prevented, resulting in attenuation of SREBP-dependent gene transcription.The Niemann-Pick type C1 (NPC1) protein has been identified as a key participant in the intracellular trafficking of LDL cholesterol. Cells that harbor mutations in NPC1 accumulate cholesterol in lysosomes and exhibit delayed sterol-regulated gene expression (5). The human NPC1 gene and its murine ortholog have b...

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Undergraduate medical studentsChoice of specialty a b s t r a c t Background: Empathy is essentially a desirable quality among clinicians and can be developed during medical education. Studies from outside India have shown that higher empathy is related to better competency and choice of specialty may be related to empathy levels in them. Change in empathy levels among undergraduate medical students with progressive training has been often ascribed to reasons such as curriculum content, timing of clinical rotations. Gender differences in empathy levels also vary among different countries. Since many of such factors differ in India there is a need therefore to understand empathy and its correlates among medical students in India.Method: A cross sectional study was undertaken in a large medical college among the undergraduates of first, third, fifth, seventh and ninth semesters to measure their empathy levels. The evaluation was done using the Jefferson's Scale for Physician's Empathy-Student version.Results: The study revealed highest empathy at entry level and a significant fall by seventh semester (p ¼ 0.002). Female students had significantly higher empathy levels than male students (p ¼ 0.012) across all semesters. The variance in empathy scores according specialty chosen is not statistically significant (p ¼ 0.2468). Conclusion:The progressive decline in empathy levels with years in medical college here is seen much later than in western studies. Female students are more empathetic than male students. The relation of mean empathy scores and choice of specialty is inconclusive and at variance from other studies.ª 2014, Armed Forces Medical Services (AFMS). All rights reserved.* Corresponding author. Tel.: þ91 9657167900 (mobile). E-mail address: sribuj@yahoo.com (R. Shashikumar).Available online at www.sciencedirect.com ScienceDirect journal homepage: w ww.el sevier.com/locate/mjafi m e d i c a l j o u r n a l a r m e d f o r c e s i n d i a 7 0 ( 2 0 1 4 ) 1 7 9 e1 8 5

Job satisfaction among health-care professionals acquires significance for the purpose of maximization of human resource potential. This article is aimed at emphasizing importance of studying various aspects of job satisfaction in health-care organizations.

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