The roles played by signaling pathways and neural activity during the development of circuits have been studied in several different contexts. However, the mechanisms involved in maintaining neuronal integrity once circuits are established are less well understood, despite their potential relevance to neurodegeneration. We demonstrate that maintenance of adult Drosophila olfactory sensory neurons requires cell-autonomous neuronal activity. When activity is silenced, development occurs normally, but neurons degenerate in adulthood. These detrimental effects can be compensated by downregulating Glycogen synthase kinase-3β (Gsk-3β). Conversely, ectopic expression of activated Gsk-3β or downregulation of Wnt effectors also affect neuron stability, demonstrating a role for Wnt signaling in neuroprotection. This is supported by our observation that activated adult neurons are capable of increased Wingless release, and its targeted expression can protect neurons against degeneration. The role of Wnt signaling in this process is non-transcriptional, and may act on cellular mechanisms that regulate axonal or synaptic stability. Together, we provide evidence that Gsk-3β is a key sensor involved in neural circuit integrity, maintaining axon stability through neural activity and the Wnt pathway.

BackgroundThe antennal lobe of Drosophila is perhaps one of the best understood neural circuits, because of its well-described anatomical and functional organization and ease of genetic manipulation. Olfactory lobe interneurons - key elements of information processing in this network - are thought to be generated by three identified central brain neuroblasts, all of which generate projection neurons. One of these neuroblasts, located lateral to the antennal lobe, also gives rise to a population of local interneurons, which can either be inhibitory (GABAergic) or excitatory (cholinergic). Recent studies of local interneuron number and diversity suggest that additional populations of this class of neurons exist in the antennal lobe. This implies that other, as yet unidentified, neuroblast lineages may contribute a substantial number of local interneurons to the olfactory circuitry of the antennal lobe.ResultsWe identified and characterized a novel glutamatergic local interneuron lineage in the Drosophila antennal lobe. We used MARCM (mosaic analysis with a repressible cell marker) and dual-MARCM clonal analysis techniques to identify this novel lineage unambiguously, and to characterize interneurons contained in the lineage in terms of structure, neurotransmitter identity, and development. We demonstrated the glutamatergic nature of these interneurons by immunohistochemistry and use of an enhancer-trap strain, which reports the expression of the Drosophila vesicular glutamate transporter (DVGLUT). We also analyzed the neuroanatomical features of these local interneurons at single-cell resolution, and documented the marked diversity in their antennal lobe glomerular innervation patterns. Finally, we tracked the development of these dLim-1 and Cut positive interneurons during larval and pupal stages.ConclusionsWe have identified a novel neuroblast lineage that generates neurons in the antennal lobe of Drosophila. This lineage is remarkably homogeneous in three respects. All of the progeny are local interneurons, which are uniform in their glutamatergic neurotransmitter identity, and form oligoglomerular or multiglomerular innervations within the antennal lobe. The identification of this novel lineage and the elucidation of the innervation patterns of its local interneurons (at single cell resolution) provides a comprehensive cellular framework for emerging studies on the formation and function of potentially excitatory local interactions in the circuitry of the Drosophila antennal lobe.

Xin deficiency leads to a myopathic condition characterized by increased muscle fatigability, impaired regeneration and SC dysfunction.

Objectives: According to the CanMEDS’ Scholar competency, physicians are expected to facilitate the learning of colleagues, patients and other health professionals. However, most medical students are not provided with formal opportunities to gain teaching experience with objective feedback. Methods: To address this, the University’s Medical Education Interest Group (MEIG) created a pilot teaching program in January 2015 entitled ‘MedTalks’. Four 3-hour sessions were held at the University Faculty of Medicine, where first and second year medical students taught clinically oriented topics to undergraduate university students. Each extracurricular session included three 30-minute content lectures, and a 90-minute small group session on physical examination skills. Each medical student-teacher received formal feedback from undergraduate students and from faculty educators regarding teaching style, communication abilities, and professionalism. In addition, medical student-teachers self-evaluated their own teaching experience. Results: Over 50 medical students from the University participated as medical student-teachers. Based on quantitative and qualitative evaluation surveys, 100% of medical students agreed that MedTalks was a useful way to develop teaching skills and 92% gained a greater confidence in individual teaching capabilities, based largely on the opportunity to gain experience (with feedback) in teaching roles. Conclusions: A program designed to give medical students multi-source teaching experience (lecture- and small group-based) and feedback on their teaching (from learners and Faculty observers, in addition to their own self-reflection) can improve medical student confidence and enthusiasm towards teaching. Future studies will clarify if medical student self-perceived enhancements in teaching ability can be corroborated by independent (Faculty, learner) observations of future teaching activity.

This systematic review aims to assess the literature to determine the impact of EUS for diagnosing malignancy among indeterminate extrahepatic biliary strictures. A systematic review was performed using MEDLINE, EMBASE, Cochrane, and conference proceedings from inception to July 2016. Pooled results were calculated using random-effects model, and heterogeneity was explored using stratified meta-analysis and meta-regression. The main outcome was the incremental benefit of EUS (IBEUS) for the diagnosis of malignancy among patients who have undergone ERCP with brushing cytology for extrahepatic biliary strictures. Of 3131 identified citations, ten met the inclusion criteria and were included in the final analyses (study periods from 1998 to 2014). Pooled IBEUS estimate with the adjustment for publication bias was 14% (95% confidence interval, 7%–20%). Individual studies demonstrate that the IBEUS is greater for distal biliary strictures or when an extrinsic mass is identified on cross-sectional imaging. EUS increases the identification of malignancy for indeterminate biliary strictures following a nondiagnostic ERCP, particularly those that are distal or related to extrinsic compression.