Molecular Dissection of Neuroligin 2 and Slitrk3 Reveals an Essential Framework for GABAergic Synapse Development

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this record In the brain, many types of interneurons make functionally diverse inhibitory synapses onto principal neurons. Although numerous molecules have been identified to function in inhibitory synapse development, it remains unknown whether there is a unifying mechanism for development of diverse inhibitory synapses. Here we report a general molecular mechanism underlying hippocampal inhibitory synapse development. In developing neurons, the establishment of GABAergic transmission depends on Neuroligin 2 (NL2), a synaptic cell adhesion molecule (CAM). During maturation, inhibitory synapse development requires both NL2 and Slitrk3 (ST3), another CAM. Importantly, NL2 and ST3 interact with nanomolar affinity through their extracellular domains to synergistically promote synapse development. Selective perturbation of the NL2-ST3 interaction impairs inhibitory synapse development with consequent disruptions in hippocampal network activity and increased seizure susceptibility. Our findings reveal how unique postsynaptic CAMs work in concert to control synaptogenesis and establish a general framework for GABAergic synapse development. Li et al. report a hierarchical process mediated by Neuroligin 2 and Slitrk3 for GABAergic synapse development. Neuroligin 2 also interacts with Slitrk3 to regulate GABAergic synaptogenesis. Selective perturbation of this interaction decreases GABAergic synaptic transmission and impairs hippocampal network activities.NIH/NINDS Intramural Research ProgramNIH/NICHD Intramural Research ProgramNIH/NEI Intramural Research Progra

What do patients with strabismus expect post surgery? The development and validation a questionnaire

Aims: To develop and validate a short questionnaire to assess patients’ expectations about outcomes post strabismus surgery. Methods: Questionnaire items were extracted from previous literature and reviewed by a multidisciplinary team. A cross-sectional study was then undertaken with 220 adult patients due to undergo strabismus surgery. Participants completed the 17-item questionnaire. Scale structure was explored using principal component analysis (PCA), and the subscales analysed in relation to demographic and clinical characteristics and psychosocial well-being in order to establish validity. Results: PCA revealed a 3-factor solution for the Expectations of Strabismus Surgery Questionnaire (ESSQ): (a) intimacy and appearance-related issues, (b) visual functioning, (c) social relationships. This 3-factor solution explained 59.30% of the overall variance in the ESSQ. Internal consistency, content and nomological and concurrent validity were considered acceptable. Conclusions: Patients with strabismus have high expectations about their postsurgical outcomes. This questionnaire provides a useful tool to assess the expectations patients have about their surgery, whether these expectations change over time and how they impact on postsurgical outcomes

A Critical Appraisal of RAFT-Mediated Polymerization-Induced Self-Assembly

Recently, polymerization-induced self-assembly (PISA) has become widely recognized as a robust and efficient route to produce block copolymer nanoparticles of controlled size, morphology, and surface chemistry. Several reviews of this field have been published since 2012, but a substantial number of new papers have been published in the last three years. In this Perspective, we provide a critical appraisal of the various advantages offered by this approach, while also pointing out some of its current drawbacks. Promising future research directions as well as remaining technical challenges and unresolved problems are briefly highlighted