Molecular and Structural Insights into Nuclear Hormone Receptor Repression Mediated by the Corepressor NCOR

Nuclear hormone receptors comprise a large family of ligand-sensitive transcription factors that can directly bind and regulate target genes to affect various physiological processes including development, differentiation, circadian rhythm and metabolism. Classically, activation of transcription by nuclear receptors (NRs) is due to a ligandinduced switch from corepressor- to coactivator-bound states. Highly analogous corepressors including NCoR and SMRT facilitate repression by NR via recruitment and activation of the histone deacetylase HDAC3. Liver X Receptor (LXR) is an NR that functions to regulate diverse physiological processes including cholesterol metabolism, lipid homeostasis, immunity and inflammation. Selective modulators of LXR to specifically target pathways for peripheral cholesterol efflux were developed and observed to function as partial agonists of LXR. We determined that the selective partial agonism of LXR by these ligands was indeed related to differential recruitment of the corepressor NCoR. Secondly, to understand the structural basis for physiological v repression of NR by NCoR we co-crystallized a small peptide comprising a region of the interaction domain of NCoR with the ligand-binding domain of Rev-erba. This revealed that the relative structural requirements for the previously reported antagonized PPARa- bound SMRT were distinct from that of the Rev-erba:NCoR complex. Altogether, these studies provide novel molecular insight into the function of NCoR in regulating transcription by nuclear hormone receptors

3D bioprinting a PCL/13-93B3 glass composite and its potential use as a bio-ink

A major limitation of using synthetic scaffolds in tissue engineering is little growth of incorporated cells in the interior of the scaffold, resulting in insufficient angiogenesis in the scaffold interior. Recently, cells have been 3D bioprinted concurrently with biomaterials to produce a cellularized, bioactive, angiogenic 3D environment. This thesis describes a novel solvent-extrusion method for printing polycaprolactone (PCL)/bioactive borate glass composite as a biomaterial for a cell-laden scaffold. Bioactive borate glass was added to a mixture of PCL and organic solvent to make an extrudable paste, creating scaffolds measuring 10×10×1 mm3 in overall dimensions with pore sizes ranging from 100-300 μm. We compared depositing hydrogel droplets to depositing hydrogel filaments in between the PCL/borate glass composite filaments. Degradation of the composite scaffold with and without the presence of hydrogel was investigated by soaking the scaffold in cell culture medium. The weight loss of the scaffold together with formation of a hydroxyapatite-like layer on the surface shows the excellent bioactivity of the scaffold. This work demonstrates that incorporating borate glass to increase the angiogenic capacity of the fabricated scaffolds is feasible. We also compared cell survival and viability between the composite bio-ink to two commonly used hydrogels, Matrigel and Pluronic F127. The viability and proliferation of cells in the different biomaterials were analyzed with different methods demonstrating that cell viability was similar between the different bio-inks. This 3D bioprinting method shows a high potential to create a bioactive, highly angiogenic 3D environment required for complex and dynamic interactions that govern the cell’s behavior in vivo --Abstract, page iii

Practice, Pedagogy and Policy: the influence of teachers’ creative writing practice on pedagogy in schools

This research aims to develop understanding of how teachers’ experience of practising creative writing influences pedagogy in schools. The research is located within a literary studies domain, responding to the context in which creative writing is most commonly taught in schools and in higher education. The central research question explored is: • How is the pedagogy of creative writing in schools influenced by teachers’ creative writing practice? The research explores the premise that creative writing practice has the potential to raise teachers’ ‘confidence as writers’, enabling them to ‘provide better models for pupils’ (Ofsted, 2009: p.6). This thesis examines what ‘creative writing practice’ means in the context of developing pedagogy; considers how creative writing is conceptualised by teachers; and investigates how teachers’ creative writing practice connects to pedagogic methods and approaches. The research sub questions that underpin the research are: • How has creative writing been conceptualised in educational policy, and how do these conceptions influence pedagogy in schools? • Does the practice of creative writing influence teachers’ conceptualisations of creative writing, and, if so, what is the impact on pedagogy? • Does the practice of creative writing influence teachers’ perceptions of themselves as writers, and, if so, what is the impact on pedagogy? • Does the experience of working with writers influence teachers’ pedagogic approaches in the classroom, and if so, how? The research includes a case study involving 14 primary and secondary school teachers, engaged in developing their own creative writing practice under the guidance of professional writers. The case study approach enables exploration of the research questions through analysis of participants’ lived experience of creative writing practice and pedagogy. The analysis of the case study at the heart of this research is situated within an interpretive framework, acknowledging the complexity of multiple meanings at play in socio-cultural learning contexts. The analysis draws on Bruner’s exploration of how pedagogical approaches imply conceptions of the learner’s mind and pedagogy (Bruner, 1996), and considers the interplay between teachers’ experiences of creative writing, and their choice of pedagogical methods and approaches

Mind the gap between research findings and policy change

This discursive article is intended as an advisory to novice scholar-researchers working in the field of policy change. It defines key policy change terms, presents a matrix of fifteen key theories of policy change, and explains the roles of policy advocate/entrepreneur and political entrepreneur in the process

Children and young people’s experiences and perceptions of self-management of type 1 diabetes: A qualitative meta-synthesis

The aim of this review was to conduct a meta-synthesis of the experiences and perceptions of self-management of type 1 diabetes of children and young people living with type 1 diabetes (CYPDs). Six databases were systematically searched for studies with qualitative findings relevant to CYPDs’ (aged 8–18 years) experiences of self-management. A thematic synthesis approach was used to combine articles and identify analytical themes. Forty articles met the inclusion criteria. Two analytical themes important to CYPDs’ experiences and perceptions of self-management were identified: (1) negotiating independence and (2) feeling in control. The synthesis contributes to knowledge on contextual factors underpinning self-management and what facilitates or impedes transition towards autonomous self-management for CYPDs

The value of cross border emergency management in adapting to climate change

Adapting to climate change is challenging in border regions where emergency situations can become amplified on a cross-border basis. Such amplification is largely the result of more agencies becoming involved in the response; groups that are often geographically dispersed, bring more divergent agendas to the ‘table’ and are often less well acquainted with each other. However, acting to build adaptive responses across international borders serves to increase resilience and decrease vulnerability to climate change. Over the coming decades climate change is likely to increase flood risk. On the island of Ireland, border regions are amongst the most vulnerable to hazards such as flooding. Developing effective cross-border emergency management will require collaborative planning, capacity building and innovative leadership. This paper sets out the urgency of adapting to climate change in border regions and provides an overview of progress and capacity building in moving towards greater shared services in border communities in Ireland