Molecular Determinants and Dynamics of Hepatitis C Virus Secretion

The current model of hepatitis C virus (HCV) production involves the assembly of virions on or near the surface of lipid droplets, envelopment at the ER in association with components of VLDL synthesis, and egress via the secretory pathway. However, the cellular requirements for and a mechanistic understanding of HCV secretion are incomplete at best. We combined an RNA interference (RNAi) analysis of host factors for infectious HCV secretion with the development of live cell imaging of HCV core trafficking to gain a detailed understanding of HCV egress. RNAi studies identified multiple components of the secretory pathway, including ER to Golgi trafficking, lipid and protein kinases that regulate budding from the trans-Golgi network (TGN), VAMP1 vesicles and adaptor proteins, and the recycling endosome. Our results support a model wherein HCV is infectious upon envelopment at the ER and exits the cell via the secretory pathway. We next constructed infectious HCV with a tetracysteine (TC) tag insertion in core (TC-core) to monitor the dynamics of HCV core trafficking in association with its cellular cofactors. In order to isolate core protein movements associated with infectious HCV secretion, only trafficking events that required the essential HCV assembly factor NS2 were quantified. TC-core traffics to the cell periphery along microtubules and this movement can be inhibited by nocodazole. Sub-populations of TC-core localize to the Golgi and co-traffic with components of the recycling endosome. Silencing of the recycling endosome component Rab11a results in the accumulation of HCV core at the Golgi. The majority of dynamic core traffics in association with apolipoprotein E (ApoE) and VAMP1 vesicles. This study identifies many new host cofactors of HCV egress, while presenting dynamic studies of HCV core trafficking in infected cells

The effects of airline alliances: what do the aggregate data say?

Alliance, Airline, Cross-price elasticities, L11, L13, L41,

Does time have value? An empirical examination of the put option embedded in refundable U.S. air fares

Options, Airlines, Contingent claims, Ticket pricing, G13, G19,

Virtue ethics and social psychology

Virtue ethics has emerged as an alternative to deontological and utilitarian theory in recent moral philosophy. The basic notion of virtue ethics is to reassert the importance of virtuous character in ethical judgement in contrast to the emphasis on principles and consequences. Since questions of virtue have been largely neglected in modern moral theory, there has been a return to Aristotle’s account of virtue as character. This in turn has been questioned as the basis of virtue ethics and there has been a search for alternative accounts of moral agency. One aspect of this critical reflection on virtue ethics is an engagement with social psychology as a source of criticism of the Aristotelian conception of character and as a more plausible alternative foundation for a theory of moral character with contemporary relevance. This paper aims to introduce this area of moral theory to a psychological audience and reflect on the interpretation of social psychological theory and evidence in criticisms of virtuous character, focusing on the use of Milgram’s (1974) experiments on obedience to authority as an argument for situationism. A number of questions emerge concerning the interpretation and use of social psychological theory and evidence in debates within moral philosophy