CNS myelination defects occur in mice deficient in receptor-like protein tyrosine phosphatase alpha (PTPα). Here, we investigated the role of PTPα in oligodendrocyte differentiation and myelination using cells and tissues from wild-type (WT) and PTPα knockout (KO) mice. PTPα promoted the timely differentiation of neural stem cell-derived oligodendrocyte progenitor cells (OPCs). Compared to WT OPCs, KO OPC cultures had more NG2+ progenitors, fewer myelin basic protein (MBP)+ oligodendrocytes, and reduced morphological complexity. In longer co-cultures with WT neurons, more KO than WT OPCs remained NG2+ and while equivalent MBP+ populations of WT and KO cells formed, the reduced area occupied by the MBP+ KO cells suggested that their morphological maturation was impeded. These defects were associated with reduced myelin formation in KO OPC/WT neuron co-cultures. Myelin formation was also impaired when WT OPCs were co-cultured with KO neurons, revealing a novel role for neuronal PTPα in myelination. Canonical Wnt/β-catenin signaling is an important regulator of OPC differentiation and myelination. Wnt signaling activity was not dysregulated in OPCs lacking PTPα, but suppression of Wnt signaling by the small molecule XAV939 remediated defects in KO oligodendrocyte differentiation and enhanced myelin formation by KO oligodendrocytes. However, the myelin segments that formed were significantly shorter than those produced by WT oligodendrocytes, raising the possibility of a role for glial PTPα in myelin extension distinct from its pro-differentiating actions. Altogether, this study reveals PTPα as a molecular coordinator of oligodendroglial and neuronal signals that controls multiple aspects of oligodendrocyte development and myelination.
ObjectivesInjury prevention should be informed by timely surveillance data. Unfortunately, most injury surveillance only captures patients with severe injuries and is not available in real time, hampering prevention efforts. We aimed to develop and pilot a simple injury surveillance strategy that can be integrated into routine emergency department (ED) workflow to collect more robust mechanism of injury information at time of visit for all injured ED patients with minimal impact on workflow.MethodsWe reviewed ED injury surveillance systems and considered ED workflow. Forms were developed to collect injury-related information on ED patients and refined to address workload concerns raised by key stakeholders. Research assistants observed ED staff as they registered injured patients and noted the time required to collect data and any ambiguities or concerns encountered. Interobserver agreement was recorded.ResultsInjury surveillance questions were based on a modification of the International Classification of External Causes of Injury. Research assistants observed 222 injured patients being admitted by registration clerks. The mean time required to complete the surveillance form was 64.9 s (95% CI 59.9 s to 69.9 s) for paper-based forms (120 cases) and 44.5 s (95% CI 41.7s to 47.4s) with direct electronic data entry (102 cases). Interobserver agreement (26 cases) was 100% for intent (kappa=1.0) of injury and 96% for mechanism of injury (kappa=0.74).ConclusionsWe report a simple injury surveillance strategy that ED staff can use to collect meaningful injury data in real time with minimal impact on workflow. This strategy can be adapted to enhance regional injury surveillance efforts.
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