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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.

The article concludes that little attention has been paid outside of the United States to drug use among university students or to interventions designed to prevent it. However, there are signs that government policy in the United Kingdom is beginning to pay attention to the specific problems of drug misuse among university students.

Research that has investigated the association between specific drug types and crime has tended to focus on the specific drug type in isolation from other drugs. The main problem with this is that it cannot be assumed that the association between specific drug use and crime will be the same regardless of the additional drugs consumed. The research aimed to investigate whether there was a correlation between number and type of drugs used and involvement in crime. The analysis of multiple drug use was based on data collected as part of the New English and Welsh Arrestee Drug Abuse Monitoring program in the United Kingdom. The results showed that both the number of drug types consumed and the particular drug type combinations used explained offending rate. The research concluded that the investigation of links between multiple drug use and crime might help inform antidrugs strategies and treatment services.

Background: Recent research evidence has suggested that gambling is a public health concern. A number of studies report the association between gambling activity and increased instances of various other harms, including substance misuse and psychological disorders. In parallel to alcohol misuse, it is also becoming clear that gambling related harm is more of a continuum of harm, as opposed to traditionally accepted categorisations of gambling behavior: safe and responsible or "problem" and harmful. Previous effective treatment models for alcohol misuse have considered a public health approach to develop interventions. As such, the current research seeks to use a public health approach to both investigate the extent of gambling harm across Wales, and to identify upstream predictors of harm to inform future interventions. Method: A triangulation of data collection methods was utilized across Wales, UK. Two hundred and forty-eight participants completed a quantitative survey relating to gambling behavior and related harm, which included the Problem Severity Gambling Index, the Gambling Commission measure of frequency, The Gambling Motives Questionnaire and the Fast Alcohol Screening tool. Ninety-eight of these participants completed a qualitative subsection. Structured interviews were conducted with 20 individuals from 11 service providers. Semi-structured interviews were conducted for the five case studies of individuals who had previously sought help for gambling. The geographical density and distribution of Licensed Gambling Outlets was also mapped in local areas. Results: The findings provide further evidence of a continuum of gambling related harm. Twenty seven percent of survey participants demonstrate some indicators of risk of gambling harm. Social, cultural and environmental contexts play a role in initiation and maintenance of gambling behavior and the subsequent related harm. Accounts from individuals corroborated the quantitative findings. Conclusions: Findings from this Welsh sample are in line with and add support to the growing international research evidence that gambling harms are a universal issue that cross cultures. It is clear that action is needed by legislators at a policy level and that broadening the focus of intervention to a public health level is necessary to develop effective strategies for harm reduction.