The medical student

The Medical Student was published from 1888-1921 by the students of Boston University School of Medicine

Farnesol-Induced Apoptosis in Candida albicans Is Mediated by Cdr1-p Extrusion and Depletion of Intracellular Glutathione

Farnesol is a key derivative in the sterol biosynthesis pathway in eukaryotic cells previously identified as a quorum sensing molecule in the human fungal pathogen Candida albicans. Recently, we demonstrated that above threshold concentrations, farnesol is capable of triggering apoptosis in C. albicans. However, the exact mechanism of farnesol cytotoxicity is not fully elucidated. Lipophilic compounds such as farnesol are known to conjugate with glutathione, an antioxidant crucial for cellular detoxification against damaging compounds. Glutathione conjugates act as substrates for ATP-dependent ABC transporters and are extruded from the cell. To that end, this current study was undertaken to validate the hypothesis that farnesol conjugation with intracellular glutathione coupled with Cdr1p-mediated extrusion of glutathione conjugates, results in total glutathione depletion, oxidative stress and ultimately fungal cell death. The combined findings demonstrated a significant decrease in intracellular glutathione levels concomitant with up-regulation of CDR1 and decreased cell viability. However, addition of exogenous reduced glutathione maintained intracellular glutathione levels and enhanced viability. In contrast, farnesol toxicity was decreased in a mutant lacking CDR1, whereas it was increased in a CDR1-overexpressing strain. Further, gene expression studies demonstrated significant up-regulation of the SOD genes, primary enzymes responsible for defense against oxidative stress, with no changes in expression in CDR1. This is the first study describing the involvement of Cdr1p-mediated glutathione efflux as a mechanism preceding the farnesol-induced apoptotic process in C. albicans. Understanding of the mechanisms underlying farnesol-cytotoxicity in C. albicans may lead to the development of this redox-cycling agent as an alternative antifungal agent

Constructing scientific Careers: Change, Continuity and Context

This article is Restricted Access. It was published in the journal, Organization Studies [© Sage]. The definitive version is available at: http://oss.sagepub.com/cgi/content/abstract/27/8/1131This paper examines the ways in which public sector research scientists make sense of and seek to develop their careers within their current organizational, policy, social and cultural contexts. It argues that to access such understandings, both structure and agency and the relationship between them need to be considered. Using empirical evidence from research in the United Kingdom and New Zealand, this paper further develops Barley’s (1989) structuration model of career. It highlights the diverse (and frequently intersecting) institutional contexts in which research scientists seek to develop their careers, and their characteristic modes of engagement with such contexts, and utilizes the concept of career scripts to illustrate the dynamic interaction between these dimensions