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Introduction: Long term follow up of patients with inflammatory bowel disease (IBD) is rarely critically audited. At this Trust, IBD patients are reviewed either in one of 3 general gastroenterology [...]

Introduction: Chronic idiopathic intestinal pseudo-obstruction (CIIP) is characterised by a failure of intestinal propulsion in the absence of mechanical obstruction. Patients with CIIP may have characteristic histological, radiographic, or manometric [...]

Introduction: Patients with chronic idiopathic intestinal pseudo-obstruction (CIIP) often suffer severe pain, vomiting, constipation, and abdominal distension. There are currently few data published on the quality of life (QoL) of [...]

This paper describes the authors’ experience of remixing two existing OER courses to provide an OER course for a particular purpose and context. The developing country target environment is stated as well as the original resources’ provenance. The motivation for remixing these OER is explored, and the design of the adapted resource is described followed by notes on the implementation and evaluation of the remixed ‘Facilitating Online Learning’ pilot course. Lessons learned include that remixing existing OER courses with similar licenses is an achievable undertaking, and OER will be reused if they are deemed to be contextually relevant. It follows that the content, nature, and deployment environment of the OER is important as is its licensing for reuse. The practical illustration of a simple remix experience is significant, as there is little literature available on remixing OER. Sharing this experience is intended to encourage and inform other such remix projects.

Long-term potentiation (LTP) is a form of synaptic plasticity that is an excellent model for the molecular mechanisms that underlie memory. LTP, like memory, is persistent, and both are widely believed to be maintained by a coordinated genomic response. Recently, a novel class of non-coding RNA, microRNA, has been implicated in the regulation of LTP. MicroRNA negatively regulate protein synthesis by binding to specific messenger RNA (mRNA) response elements. The aim of this review is to summarize experimental evidence for the proposal that microRNA play a major role in the regulation of LTP. We discuss a growing body of research which indicates that specific microRNA regulate synaptic proteins relevant to LTP maintenance, as well as studies that have reported differential expression of microRNA in response to LTP induction. We conclude that microRNA are ideally suited to contribute to the regulation of LTP-related gene expression; microRNA are pleiotropic, synaptically-located, tightly regulated, and function in response to synaptic activity. The potential impact of microRNA on LTP maintenance as regulators of gene expression is enormous.

Coordinated regulation of gene expression is essential for consolidation of the memory mechanism, long-term potentiation (LTP). Triggering LTP by N-methyl-D-aspartate receptor (NMDAR) activation rapidly activates constitutive and inducible transcription factors that promote expression of genes responsible for LTP maintenance. As microRNA (miRNA) coordinate expression of related genes, we hypothesise that miRNA contribute to the LTP-induced gene response. MiRNA function primarily as negative regulators of gene expression. As LTP promotes a generalised rapid up-regulation of gene expression, we predicted a complementary rapid down-regulation of miRNA. Accordingly, we carried out global miRNA expression profiling in rat dentate gyrus 20 min post-LTP induction in vivo. Consistent with our hypothesis, we found a large number of differentially expressed miRNA, the majority down-regulated. Detailed analysis of miR-34a-5p and miR-132-3p revealed this down-regulation was transient and NMDAR-dependent, whereby block of NMDARs released an activity-associated inhibitory mechanism. Furthermore, down-regulation of mature miR-34a-5p and miR-132-3p occurred solely by post-transcriptional mechanisms, despite up-regulation of the pri-miR-132 transcript. To understand how down-regulation of miR-34a-5p and miR-132-3p intersects with the molecular events occurring following LTP, we used bioinformatics to identify potential targets. Previously validated targets included the key LTP-regulated genes Arc and glutamate receptor subunits. Predicted targets included the LTP-linked kinase, Mapk1, and neuropil-associated transcripts Hn1 and Klhl11, which were validated using luciferase reporter assays. Furthermore, p42-Mapk1 levels were up-regulated following LTP. Together, these data support the interpretation that miRNA, in particular miR-34a-5p and miR-132-3p, make a surprisingly rapid contribution to synaptic plasticity via dis-inhibition of translation of key plasticity-related molecules.