Irf6 is a key determinant of the keratinocyte proliferation-differentiation switch

The epidermis is a highly organized structure, the integrity of which is central to the protection of an organism. Development and subsequent maintenance of this tissue depends critically on the intricate balance between proliferation and differentiation of a resident stem cell population; however, the signals controlling the proliferation-differentiation switch in vivo remain elusive. Here, we show that mice carrying a homozygous missense mutation in interferon regulatory factor 6 (Irf6), the homolog of the gene mutated in the human congenital disorders Van der Woude syndrome and popliteal pterygium syndrome, have a hyperproliferative epidermis that fails to undergo terminal differentiation, resulting in soft tissue fusions. We further demonstrate that mice that are compound heterozygotes for mutations in Irf6 and the gene encoding the cell cycle regulator protein stratifin (Sfn; also known as 14-3-3sigma) show similar defects of keratinizing epithelia. Our results indicate that Irf6 is a key determinant of the keratinocyte proliferation-differentiation switch and that Irf6 and Sfn interact genetically in this process.     

A Soft Systems Methodology (SSM) Based Framework for Evaluating Managed Learning Environments

Managed Learning Environments (MLEs) in higher education institutions (HEIs) are relatively new to the arena of higher education, even though there are over 90% of institutions in the higher and further education sector who are currently engaged in some kind of MLE development activity (University of Brighton 2003). However, when it comes to the task of assessing the performance of an MLE there are no universally recognisable frameworks for evaluating MLEs in HEIs currently discussed within the literature. The paper advances a general systemic framework for evaluating MLEs based on Checkland’s SSM and reports on the first stages of our attempt to evaluate the MLE at Manchester Metropolitan University involving the team developing the system and the stakeholders concerned. Two of three iterations of this research have been completed and, whilst outside the scope of this paper, have found that SSM has coped with the criteria demanded of the evaluation framework within its context. After completing a stakeholder analysis, the criteria for evaluating an MLE, based on the stakeholders’ requirements, emerged. These iterations have tentatively concluded that by contextualising SSM to the evaluation requirements of an MLE in a UK HEI, the measures of performance suggested by SSM need to be adjusted. The final iteration will check this outcome.