Elucidating the interactions between the adhesive and transcriptioanl functions of beta-catenin in normal and cancerous cells

Wnt signalling is involved in a wide range of physiological and pathological processes. The presence of an extracellular Wnt stimulus induces cytoplasmic stabilisation and nuclear translocation of beta-catenin, a protein that also plays an essential role in cadherin-mediated adhesion. Two main hypotheses have been proposed concerning the balance between beta-catenin's adhesive and transcriptional functions: either beta-catenin's fate is determined by competition between its binding partners, or Wnt induces folding of beta-catenin into a conformation allocated preferentially to transcription. The experimental data supporting each hypotheses remain inconclusive. In this paper we present a new mathematical model of the Wnt pathway that incorporates beta-catenin's dual function. We use this model to carry out a series of in silico experiments and compare the behaviour of systems governed by each hypothesis. Our analytical results and model simulations provide further insight into the current understanding of Wnt signalling and, in particular, reveal differences in the response of the two modes of interaction between adhesion and signalling in certain in silico settings. We also exploit our model to investigate the impact of the mutations most commonly observed in human colorectal cancer. Simulations show that the amount of functional APC required to maintain a normal phenotype increases with increasing strength of the Wnt signal, a result which illustrates that the environment can substantially influence both tumour initiation and phenotype.

Queering religious texts: An exploration of British non-heterosexual Christians’ and Muslims’ strategy of constructing sexuality-affirming hermeneutics.

Religious authority figures often use religious texts as the primary basis for censuring homosexuality. In recent years, however, non-heterosexual Christians and Muslims have begun to contest the discursively produced boundary of sexual morality.Drawing upon two research projects on non-heterosexual Christians and Muslims, this article explores the three approaches embedded in this strategy.While acknowledging that homosexuality is indeed portrayed negatively in some parts of religious texts, the participants critique traditional hermeneutics by highlighting its inaccuracy and socio-cultural specificity, and arguing for a contextualized and culturally relevant interpretation. They also critique the credibility of institutional interpretive authority by highlighting its inadequacy and ideology, and relocating authentic interpretive authority to personal experience. Finally, they recast religious texts to construct resources for their spiritual nourishment.This strategy generally reflects the contemporary western religious landscape that prioritizes the authority of the self over that of religious institution.

Are we teaching our students what they need to know about ageing? Results from the National Survey of Undergraduate Teaching in Ageing and Geriatric Medicine

Introduction - Learning about ageing and the appropriate management of older patients is important for all doctors. This survey set out to evaluate what medical undergraduates in the UK are taught about ageing and geriatric medicine and how this teaching is delivered. Methods – An electronic questionnaire was developed and sent to the 28/31 UK medical schools which agreed to participate. Results – Full responses were received from 17 schools. 8/21 learning objectives were recorded as taught, and none were examined, across every school surveyed. Elder abuse and terminology and classification of health were taught in only 8/17 and 2/17 schools respectively. Pressure ulcers were taught about in 14/17 schools but taught formally in only 7 of these and examined in only 9. With regard to bio- and socio- gerontology, only 9/17 schools reported teaching in social ageing, 7/17 in cellular ageing and 9/17 in the physiology of ageing. Discussion – Even allowing for the suboptimal response rate, this study presents significant cause for concern with UK undergraduate education related to ageing. The failure to teach comprehensively on elder abuse and pressure sores, in particular, may be significantly to the detriment of older patients.