West Nile virus core protein; tetramer structure and ribbon formation

We have determined the crystal structure of the core (C) protein from the Kunjin subtype of West Nile virus (WNV), closely related to the NY99 strain of WNV, currently a major health threat in the U.S. WNV is a member of the Flaviviridae family of enveloped RNA viruses that contains many important human pathogens. The C protein is associated with the RNA genome and forms the internal core which is surrounded by the envelope in the virion. The C protein structure contains four alpha helices and forms dimers that are organized into tetramers. The tetramers form extended filamentous ribbons resembling the stacked alpha helices seen in HEAT protein structures.     

Dengue virus nonstructural protein 1 is expressed in a glycosyl-phosphatidylinositol-linked form that is capable of signal transduction.

Dengue virus nonstructural protein 1 (NS1) is expressed on the surface of infected cells and is a target of human antibody responses to dengue virus infection. We show here that dengue virus uses the cellular glycosyl-phosphatidylinositol (GPI) linkage pathway to express a GPI-anchored form of NS1 and that GPI anchoring imparts a capacity for signal transduction in response to binding of NS1-specific antibody. This study is the first to identify GPI linkage of a virus-encoded protein. The GPI anchor addition signal for NS1 was identified, by transfection of HeLa cells with dengue cDNA constructs, as a downstream hydrophobic domain in NS2A. GPI linkage of NS1 in both transfected and infected cells was demonstrated by cleavage of NS1 from the surface by PI-specific phospholipase C and by metabolic incorporation of the GPI-specific components ethanolamine and inositol. In common with other GPI-anchored proteins, addition of specific antibody resulted in signal transduction, as evidenced by tyrosine phosphorylation of cellular proteins. Antibody-induced signal transduction by GPI-linked NS1 suggests a mechanism of cellular activation that may contribute to the pathogenesis of human dengue disease. Signal transduction by a GPI-anchored viral antigen interacting with a specific antibody that it induces is a new concept in the pathogenesis of viral disease.     

Ten simple rules for establishing a mentorship programme

In recent years, a wide variety of mentorship programmes targeting issues that cannot be addressed through traditional teaching and learning methods alone have been developed. Mentoring plays significant roles in the growth and development of both mentors and mentees, and the positive impacts of mentoring have been well documented. Mentorship programmes are therefore increasingly being implemented in a wide variety of fields by organisations, academic institutes, businesses, and governments. While there is a growing body of literature on mentoring and mentorship programmes, gaining a clear overview of the field is often challenging. In this article, we therefore provide a concise summary of recommendations to consider when designing and establishing mentorship programmes. These recommendations are based on the collective knowledge and experiences of 4 different emerging and established mentorship programmes and can be adapted across various mentorship settings or contexts.     

Synthesis of 2-Deoxy-4-thio-D-ribofuranose and Its 3-Azido Analogue from L-Arabinose; Intermediates in the Synthesis of 4′-Thiodeoxynucleosides

Abstract

1-O-Acetyl-3,5-di-O-benzoyl-2-deoxy-4-thio-α,β-D-ribofuranose and its 3-azido analogue have been prepared by an efficient route starting from L-arabinose. A key intermediate in this route is 2-deoxy-4,5-O-isopropylidene-L-erythro-pentose dibenzyl dithioacetal which is readily substituted in the 3-position thus offering extensive scope for the synthesis of 3-substituted 2-deoxy-4-thio-α,β-D-ribofuranoses and subsequent nucleoside derivatives.     

Steroid UDP glucuronosyltransferases

The glucuronidation of steroids is a major process necessary for their elimination in the bile and urine. In general, steroid glucuronides are biologically less reactive than their parent steroids. However, in some cases often associated with disease and steroid therapy, more reactive or toxic glucuronides may be formed. The concentrations of specific steroid glucuronides in the blood may also indicate hormonal imbalances and may funnction as diagnostic markers of genetic defects in steroid synthesis and metabolism. In this review, the forms of UDP glucuronosyltransferase involved in steroid glucuronidation are described in terms of their specificities, functional domains and regulation. The available evidence suggests that steroid glucuronidation is mainly carried out by members of the UGT2B subfamily which are encoded by genes containing 6 exons. Members of this subfamily exhibit a regioselectively in their glucuronidation of steroids that is mediated by domains in the amino-terminal half on the protein encoded by exons 1 and 2. Although much of this review will describe studies in the rat, preliminary evidence indicates that a similar situation may exist in humans.