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Sirtuin 1 (SIRT1) is a class III histone deacetylase that deacetylates histone and nonhistone proteins to regulate gene transcription and protein function. Because SIRT1 regulates very diverse responses such as apoptosis, insulin sensitivity, autophagy, differentiation, and stem cell pluripotency, it has been a challenge to reconcile how it orchestrates such pleiotropic effects. Here we show that SIRT1 serves as an important regulator of Wnt signaling. We demonstrate that SIRT1 loss of function leads to a significant decrease in the levels of all three Dishevelled (Dvl) proteins. Furthermore, we demonstrate that SIRT1 and Dvl proteins complex in vivo and that inhibition of SIRT1 leads to changes in gene expression of Wnt target genes. Finally, we demonstrate that Wnt-stimulated cell migration is inhibited by a SIRT1 inhibitor. Because the three mammalian Dvl proteins serve as key messengers for as many as 19 Wnt ligands, SIRT1-mediated regulation of Dvl proteins may explain the diverse physiological responses observed in different cellular contexts. Previously, SIRT1 had only been shown to mediate the epigenetic silencing of Wnt antagonists. In contrast, here we report that SIRT1 regulates Dvl protein levels and Wnt signaling in several cellular contexts. These findings demonstrate that SIRT1 is a regulator of transient and constitutive Wnt signaling.+ -dependent histone deacetylase (HDAC) that regulates a very broad and complex array of physiological processes. As such, it has been the source of some controversy, as it has been difficult to reconcile the role it plays in the coordination of cellular responses and gene expression in both normal and pathophysiological settings. For example, SIRT1 has been shown to inhibit the maturation of preadipocytes (1, 2), antagonize p53-dependent apoptosis in response to stress (3, 4), and promote chemoresistance to conventional chemotherapeutic agents (5, 6), and is associated with microsatellite instability and CpG island methylator phenotype in human colorectal cancer (7). Furthermore, reports demonstrate that SIRT1 coordinates diverse metabolic responses to changes in nutrient availability (8), regulates autophagy (9), and controls key stages of spermatogenesis and germ stem cell proliferation and function (10, 11). Given the complex influence of SIRT1 on cell-fate decisions in multiple physiological settings, it is reasonable to anticipate that SIRT1 regulates one or more signaling networks recognized for their influence on these diverse cellular and organismal responses.It is well-established that Wnt signaling, likewise, regulates diverse processes such as adipogenesis (12), tumorigenesis (13), and stem cell pluripotency (14, 15). When Wnt ligands are present, they transmit signals through specific Frizzled (Fzd) or Fzd/LRP5/6 coreceptor complexes (16). This signal is then propagated via Dishevelled (Dvl) proteins that will direct canonical (β-catenindependent) or noncanonical (β-catenin-independent) signaling (17). Most of the mechanistic insights into Wnt signaling...

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Neighborhood watch grew out of a movement in the USA during the late 1960s that promoted greater involvement of citizens in the prevention of crime. Recent estimates suggest that over a quarter of the UK population and over 40% of the US population live in areas covered by neighborhood watch schemes. The current paper presents the results of a recent systematic review of evaluations of neighborhood watch. The main findings of the narrative review were that about half of the schemes evaluated showed that neighborhood watch was effective in reducing crime, with most of the other evaluations having uncertain effects. The main findings of the meta-analysis were that 15 of the 18 studies provided evidence that neighborhood watch reduced crime. While the results of the review are encouraging, it was concluded that more high-quality research needs to be done to help explain why study variations exist.