A high-density immunoblotting methodology for quantification of total protein levels and phosphorylation modifications

The components of many signaling pathways have been identified and there is now a need to conduct quantitative data-rich temporal experiments for systems biology and modeling approaches to better understand pathway dynamics and regulation. Here we present a modified Western blotting method that allows the rapid and reproducible quantification and analysis of hundreds of data points per day on proteins and their phosphorylation state at individual sites. The approach is of particular use where samples show a high degree of sample-to-sample variability such as primary cells from multiple donors. We present a case study on the analysis of >800 phosphorylation data points from three phosphorylation sites in three signaling proteins over multiple time points from platelets isolated from ten donors, demonstrating the technique's potential to determine kinetic and regulatory information from limited cell numbers and to investigate signaling variation within a population. We envisage the approach being of use in the analysis of many cellular processes such as signaling pathway dynamics to identify regulatory feedback loops and the investigation of potential drug/inhibitor responses, using primary cells and tissues, to generate information about how a cell's physiological state changes over time.

Low-grade inflammation, diet composition and health: current research evidence and its translation

The importance of chronic low-grade inflammation in the pathology of numerous age-related chronic conditions is now clear. An unresolved inflammatory response is likely to be involved from the early stages of disease development. The present position paper is the most recent in a series produced by the International Life Sciences Institute's European Branch (ILSI Europe). It is co-authored by the speakers from a 2013 workshop led by the Obesity and Diabetes Task Force entitled ‘Low-grade inflammation, a high-grade challenge: biomarkers and modulation by dietary strategies’. The latest research in the areas of acute and chronic inflammation and cardiometabolic, gut and cognitive health is presented along with the cellular and molecular mechanisms underlying inflammation–health/disease associations. The evidence relating diet composition and early-life nutrition to inflammatory status is reviewed. Human epidemiological and intervention data are thus far heavily reliant on the measurement of inflammatory markers in the circulation, and in particular cytokines in the fasting state, which are recognised as an insensitive and highly variable index of tissue inflammation. Potential novel kinetic and integrated approaches to capture inflammatory status in humans are discussed. Such approaches are likely to provide a more discriminating means of quantifying inflammation–health/disease associations, and the ability of diet to positively modulate inflammation and provide the much needed evidence to develop research portfolios that will inform new product development and associated health claims.

Achieving and evidencing research 'impact'? Tensions and dilemmas from an ethic of care perspective

While many academics are sceptical about the 'impact agenda', it may offer the potential to re-value feminist and participatory approaches to the co-production of knowledge. Drawing on my experiences of developing a UK Research Excellence Framework (REF) impact case study based on research on young caregiving in the UK, Tanzania and Uganda, I explore the dilemmas and tensions of balancing an ethic of care and participatory praxis with research management demands to evidence 'impact' in the neoliberal academy. The participatory dissemination process enabled young people to identify their support needs, which translated into policy and practice recommendations and in turn, produced 'impact'. It also revealed a paradox of action-oriented research: this approach may bring greater emotional investment of the participants in the project in potentially negative as well as positive ways, resulting in disenchantment that the research did not lead to tangible outcomes at local level. Participatory praxis may also pose ethical dilemmas for researchers who have responsibilities to care for both 'proximate' and 'distant' others. The 'more than research' relationship I developed with practitioners was motivated by my ethic of care rather than by the demands of the audit culture. Furthermore, my research and the impacts cited emerged slowly and incrementally from a series of small grants in an unplanned, serendipitous way at different scales, which may be difficult to fit within institutional audits of 'impact'. Given the growing pressures on academics, it seems ever more important to embody an ethic of care in university settings, as well as in the 'field'. We need to join the call for 'slow scholarship' and advocate a re-valuing of feminist and participatory action research approaches, which may have most impact at local level, in order to achieve meaningful shifts in the impact agenda and more broadly, the academy.

Creativity and discourse

This paper will consider the relationship between discourse analysis and creativity and elucidate the ways in which a discourse analytical approach to creativity might be distinguished from the ‘language and creativity’ approaches which currently dominate applied linguistics and sociolinguistics. In the ‘discourse and creativity’ approach I will be describing, creativity is located not in language per se, but in the strategic ways people use language in concrete situations in order to stimulate social change. I will explore how aspects of this approach are reflected in work carried out within the paradigm of world Englishes.