Schwann cell/axonal interactions in peripheral nerve

Schwann cells are found in close proximity with axons from an early developmental stage, where, in adult nerve, they exist as either myelinating or non-myelinating Schwann cells. Reciprocal, contact-dependent signalling, between Schwann cells and axons, is central to the regulation of Schwann cell proliferation, survival and differentiation, as well as axonal survival. Cell adhesion molecules (CAMs) mediate homotypic and heterotypic interactions. They are required during development, in homeostatic nerve and in nerve repair following injury. Dysregulation of signal pathways and resulting aberrant CAM expression, can lead to irreversible Schwann cell/axonal dissociation, which is a hallmark of various peripheral neuropathies and nerve sheath tumours, e.g. neurofibromas in NF1 patients. In this thesis, I conducted a microarray screen to identify early mediators of Schwann cell/axonal interaction, using a Large-T (LT)-expressing Schwann cell that had spontaneously lost the ability to interact with axons, termed LT-derived (LTD) cells. This analysis revealed that multiple cell adhesion genes had become dysregulated including N-cadherin, Semaphorin-4F, Necl-4, NCAM and L1-CAM. This shift in adhesion profile suggested that a transcription factor, for example Sox2, might be the genetic lesion responsible; however, Sox2 was found not to be responsible for the LTD phenotype, although over-expression of Sox2 altered N-cadherin localisation at Schwann cell-cell junctions. Further study showed that N-cadherin was required for homotypic interactions and was an important mediator of heterotypic interactions, where heterologous N-cadherin expression in fibroblasts was sufficient to induce fibroblasts to recognise and partially associate with axons. In addition, N-cadherin was implicated in the regulation of the cell cycle; while N-cadherin silencing, in Schwann cells prior to axonal contact, was found to impede myelination in vitro. Finally, this work showed that N-cadherin and Semaphorin-4F operate at distinct stages of the interaction process, with N-cadherin mediating axonal recognition and Semaphorin-4F involved in stabilising the Schwann cell/axonal association

An Investigation into the Relationship between Depressive Symptoms, Approach-Related Affect, Cognitive Appraisals and Striving Behaviour

Theories of emotion see affective processes as important in guiding behaviour, and social/cognitive theories have implicated cognitive appraisals in a motivational context. The control-value theory combines these approaches, predicting that high levels of expectancy and control lead to associated levels of anticipatory affect in those approaching a goal. This theory, combined with literature on approach motivation in depression, led to the proposed model of the effect of depression on behavioural striving, and subsequent levels of depression. The current study aimed to test this model. Sixty participants completed measures of depression, approach-related affect, cognitive appraisals and striving behaviour in relation to their own personal goals, with follow-up measures of depression and striving behaviour completed two weeks later. They also participated in an experimental manipulation of approach-related cognitive appraisals. The model received mixed support, with strongest evidence for the proposed pathway from depression to anticipatory affect via cognitive appraisals, especially for those who were at least mildly depressed. However contrary to the model, depression was not found to be associated to striving, and no variables other than depression predicted future depression. The study was conducted with a non-clinical population, there was reduced power at follow-up, and the experimental manipulation may have been unsuccessful. This study provided preliminary support for the new model, and although findings were mixed, future research may be more conclusive. Findings suggest that therapy specifically tapping into approach-related cognitive appraisals, as well as approach-related affect, may be therapeutically beneficial in working with depression

Screening, Diagnostic and Prognostic Tests for COVID-19: A Comprehensive Review

From MDPI via Jisc Publications RouterHistory: accepted 2021-06-10, pub-electronic 2021-06-14Publication status: PublishedWhile molecular testing with real-time polymerase chain reaction (RT-PCR) remains the gold-standard test for COVID-19 diagnosis and screening, more rapid or affordable molecular and antigen testing options have been developed. More affordable, point-of-care antigen testing, despite being less sensitive compared to molecular assays, might be preferable for wider screening initiatives. Simple laboratory, imaging and clinical parameters could facilitate prognostication and triage. This comprehensive review summarises current evidence on the diagnostic, screening and prognostic tests for COVID-19