The mechanisms underlying transcriptional inhibition by interferon-γ (IFN-γ) are poorly understood despite the existence of a large number of genes that are regulated in this manner and the key role of this cytokine in inflammatory disorders such as atherosclerosis. We have previously identified a novel mechanism for transcriptional inhibition by IFN-γ that involves a reduction in the binding of transcription factors Sp1 and Sp3 to regulatory sequences in the lipoprotein lipase (LPL) gene. In the present study, we have investigated the signalling pathways that impact on the IFN-γ-mediated regulation of Sp1/Sp3 binding and LPL gene transcription in macrophages. The IFN-γ-mediated inhibition of LPL promoter activity was prevented by expression of dominant negative forms of casein kinase 2 (CK2) and protein kinase B (PKB), a key downstream component of the phosphoinositide-3-kinase (PI3K) pathway. IFN-γ activated both the catalytic subunits of CK2 without affecting their expression. CK2 interacted with both Sp1 and Sp3 and this association was increased by IFN-γ. Electrophoretic mobility shift assays showed that a CK2-mediated phosphorylation of either cellular extracts or recombinant Sp1 reduced binding to the regulatory region in the LPL gene. The action of PKB was potentially mediated through mammalian target for rapamycin proteins. Taken together, these results suggest a key role for CK2 and PI3K signalling pathways in the IFN-γ-mediated inhibition of macrophage LPL gene transcription through the regulation of Sp1/Sp3 binding.

No abstract

This article addresses the development and validation of the Factors Influencing Pursuit of Higher Education (FIPHE) Questionnaire, a 92-item self-report measure that investigates factors that influence individuals to pursue higher education. Reliability estimates for the nine FIPHE scale scores ranged from .66 to .90. An exploratory factor analysis was conducted on data from a sample ( N = 509) of college students enrolled in two south-eastern universities. The data were subjected to principal components analysis with varimax rotation. Although the researchers hypothesized 10 scales for the questionnaire, the results revealed that a nine-factor solution produced the most interpretable factor patterns. The nine-factor solution accounted for 43% of the common variance. Limitations of the research and implications for future research are discussed.

A theory of change approach uses logic models to articulate how a programme is intended to operate and to test empirically whether and if so how it achieves its stated objectives. Theories of change have been used in evaluation research across a range disciplines and public policy domains. This article considers their application to research on sport and physical activity programmes. Applying a theory of change approach to the 'Calls for Action' programme, which seeks to increase participation among traditionally 'hard to reach' groups, the article explores the strengths and limitations of the method. It argues that a theory of change approach offers a rigorous and systematic way of framing and conducting research on interventions designed to encourage engagement in sport and other forms of physical activity. The article demonstrates how the approach can link project outcomes to wider programme and policy objectives. It also shows the value of making explicit and testing the assumptions which underpin interventions at both programme and project levels. By developing a theory of change approach policy makers and practitioners can clarify what they are seeking to achieve and promote a better understanding among partner organisations which have different priorities for and perspectives on an intervention. Future research could usefully focus on ways of extending the theory of change methods described in this article to test for causality and analyse the links between sport participation and wider policy goals, particularly health outcomes and improvements in well-being.

No abstract