Changes in the number, size, and shape of dendritic spines are associated with synaptic plasticity, which underlies cognitive functions such as learning and memory. This plasticity is attributed to reorganization of actin, but the molecular signals that regulate this process are poorly understood. In this study, we show neural Wiskott-Aldrich syndrome protein (N-WASP) regulates the formation of dendritic spines and synapses in hippocampal neurons. N-WASP localized to spines and active, functional synapses as shown by loading with FM4 -64 dye. Knock down of endogenous N-WASP expression by RNA interference or inhibition of its activity by treatment with a specific inhibitor, wiskostatin, caused a significant decrease in the number of spines and excitatory synapses. Deletion of the C-terminal VCA region of N-WASP, which binds and activates the actinrelated protein 2/3 (Arp2/3) complex, dramatically decreased the number of spines and synapses, suggesting activation of the Arp2/3 complex is critical for spine and synapse formation. Consistent with this, Arp3, like N-WASP, was enriched in spines and excitatory synapses and knock down of Arp3 expression impaired spine and synapse formation. A similar defect in spine and synapse formation was observed when expression of an N-WASP activator, Cdc42, was knocked down. Thus, activation of N-WASP and, subsequently, the Arp2/3 complex appears to be an important molecular signal for regulating spines and synapses. Arp2/3-mediated branching of actin could be a mechanism by which dendritic spine heads enlarge and subsequently mature. Collectively, our results point to a critical role for N-WASP and the Arp2/3 complex in spine and synapse formation.

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Clinically relevant models of rotator cuff tendon injuries in mouse enable the use of genetic tools; lineage tracing suggests that distinct mechanisms of healing are activated with full detachment/repair injuries versus partial tear. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.

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Introduction: Ureteral access sheaths (UASs) are frequently used during ureteroscopy (URS), but their use is not without potential risk. We investigated patterns of UAS use and associated outcomes across practices in Michigan within a quality improvement collaborative. Methods: The Michigan Urological Surgery Improvement Collaborative (MUSIC) Reducing Operative Complications from Kidney Stones (ROCKS) initiative maintains a web-based, prospective clinical registry of patients undergoing URS for urinary stone disease (USD). We analyzed all patients undergoing primary URS for renal and ureteral stones from June 2016 to July 2018 in the ROCKS registry. We determined rates of UAS usage across practices and associated outcomes, including 30-day emergency department (ED) visits and hospitalization, as well as stone-free rates. Using multivariate logistical regression, we determined the predictors of UAS use as well as outcomes, including stone-free rates, ED visits, and hospitalizations, associated with UAS use. Results: Of the 5316 URS procedures identified, UASs were used in 1969 (37.7%) cases. Stones were significantly larger and more likely to be located in the kidney in cases with UAS use. UAS use during URS varied greatly across practices (1.9%-96%, p < 0.05). After adjusting for clinical and surgical risk factors, UAS use significantly increased the odds of postoperative ED visits (odds ratio [OR] = 1.50, 95% confidence interval [CI] 1.17-1.93, p < 0.05) and hospitalization (OR = 1.77, 95% CI 1.22-2.56, p < 0.05) as well as decreased the odds of being stone free (OR = 0.75, 95% CI 0.57-0.99, p < 0.05). Conclusions: In the current study, UAS use during URS for USD was not associated with an increased likelihood of being stone free; moreover, it increased the odds of a postoperative ED visit and or hospitalization. Our findings demonstrate that UAS use is not without risk and should be employed judiciously.

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