Lessons from the pandemic: An innovative scheme to support research in the North West Coast.

In 2021, a Clinical Research Fellow (CRF) scheme was created to serve the North West Coast (NWC) region in line with the key health priorities set out by the Clinical Research Network. Five doctors in pre-specialist training were placed in NHS trust research departments across the NWC. The scheme aimed to provide early career research experience while also enhancing the provision of research across the region. The CRFs were involved in writing clinical trial grant applications and study protocols, with the scheme providing additional experience in leadership roles and time management. In addition, the CRF scheme has had a positive impact in adopted NHS trusts, which have seen their overall research capacity and capability improve, through increased flexibility and medical oversight. Research departments have benefited from increased financial income and improved national reputations. Overall, this real-world experience provided a vital 'foot in the door', which is essential for research-interested medics to advance in a future academic career. In the wider NWC region, the CRF scheme successfully delivered achievable and financially sustainable research. Innovative programmes such as this one should be seen as a viable option for research provision through the NHS, in the UK.

Deletion of α-neurexin II results in autism-related behaviors in mice.

Autism is a common and frequently disabling neurodevelopmental disorder with a strong genetic basis. Human genetic studies have discovered mutations disrupting exons of the NRXN2 gene, which encodes the synaptic adhesion protein α-neurexin II (Nrxn2α), in two unrelated individuals with autism, but a causal link between NRXN2 and the disorder remains unclear. To begin to test the hypothesis that Nrxn2α deficiency contributes to the symptoms of autism, we employed Nrxn2α knockout (KO) mice that genetically model Nrxn2α deficiency in vivo. We report that Nrxn2α KO mice displayed deficits in sociability and social memory when exposed to novel conspecifics. In tests of exploratory activity, Nrxn2α KO mice displayed an anxiety-like phenotype in comparison with wild-type littermates, with thigmotaxis in an open field, less time spent in the open arms of an elevated plus maze, more time spent in the enclosure of an emergence test and less time spent exploring novel objects. However, Nrxn2α KO mice did not exhibit any obvious changes in prepulse inhibition or in passive avoidance learning. Real-time PCR analysis of the frontal cortex and hippocampus revealed significant decreases in the mRNA levels of genes encoding proteins involved in both excitatory and inhibitory transmission. Quantification of protein expression revealed that Munc18-1, encoded by Stxbp1, was significantly decreased in the hippocampus of Nrxn2α KO mice, which is suggestive of deficiencies in presynaptic vesicular release. Our findings demonstrate a causal role for the loss of Nrxn2α in the genesis of autism-related behaviors in mice.