Protocol: A randomised controlled trial evaluation of Cancer Focus NI’s ‘Dead Cool’ smoking prevention programme in post-primary schools

This paper presents a research protocol for a randomised controlled efficacy trial of the ‘Dead Cool’ smoking prevention programme. Dead Cool is a three to four-hour programme designed to be used by teachers with Year 9 students in Northern Ireland. The main outcome of the programme is to prevent students from starting to smoke. The protocol reports a research design intended to test the efficacy of the programme in 20 post-primary school settings. Selected schools included those from secondary /grammar/integrated/single sex/coeducational, rural and urban schools from both the maintained and controlled state sector and independent sector schools. Outcome measures include self-reported behaviours, monitoring of carbon monoxide (CO) in exhaled breath and focus groups designed to assess implementation fidelity and opinions on efficacy in intervention schools and explore the ‘counterfactual’ potential treatments in control schools.

von Hippel Lindau binding protein 1-mediated degradation of integrase affects HIV-1 gene expression at a postintegration step

HIV-1 integrase, the viral enzyme responsible for provirus integration into the host genome, can be actively degraded by the ubiquitin-proteasome pathway. Here, we identify von Hippel-Lindau binding protein 1(VBP1), a subunit of the prefoldin chaperone, as an integrase cellular binding protein that bridges interaction between integrase and the cullin2 (Cul2)-based von Hippel-Lindau (VHL) ubiquitin ligase. We demonstrate that VBP1 and Cul2/VHL are required for proper HIV-1 expression at a step between integrase-dependent proviral integration into the host genome and transcription of viral genes. Using both an siRNA approach and Cul2/VHL mutant cells, we show that VBP1 and the Cul2/VHL ligase cooperate in the efficient polyubiquitylation of integrase and its subsequent proteasome-mediated degradation. Results presented here support a role for integrase degradation by the prefoldin-VHL-proteasome pathway in the integration-transcription transition of the viral replication cycle.