50 research outputs found

    Cmr1/WDR76 defines a nuclear genotoxic stress body linking genome integrity and protein quality control

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    DNA replication stress is a source of genomic instability. Here we identify ​changed mutation rate 1 (​Cmr1) as a factor involved in the response to DNA replication stress in Saccharomyces cerevisiae and show that ​Cmr1—together with ​Mrc1/​Claspin, ​Pph3, the chaperonin containing ​TCP1 (CCT) and 25 other proteins—define a novel intranuclear quality control compartment (INQ) that sequesters misfolded, ubiquitylated and sumoylated proteins in response to genotoxic stress. The diversity of proteins that localize to INQ indicates that other biological processes such as cell cycle progression, chromatin and mitotic spindle organization may also be regulated through INQ. Similar to ​Cmr1, its human orthologue ​WDR76 responds to proteasome inhibition and DNA damage by relocalizing to nuclear foci and physically associating with CCT, suggesting an evolutionarily conserved biological function. We propose that ​Cmr1/​WDR76 plays a role in the recovery from genotoxic stress through regulation of the turnover of sumoylated and phosphorylated proteins

    Functionalisation of Ti6Al4V components fabricated using selective laser melting with a bioactive compound

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    Surface modification of an implant with a biomolecule is used to improve its biocompatibility and to reduce post-implant complications. In this study, a novel approach has been used to functionalise phosphonic acid monolayers with a drug. Ti6Al4V components fabricated using selective laser melting (SLM) were functionalised with Paracetamol (a pharmaceutically relevant biomolecule) using phosphonic acid based self-assembled monolayers (SAMs). The attachment, stability of the monolayers on the SLM fabricated surface and functionalisation of SAMs with Paracetamol were studied using X-ray photoelectron spectroscopy (XPS) and surface wettability measurements. The obtained results confirmed that SAMs were stable on the Ti6Al4V surface for over four weeks and then began to desorb from the surface. The reaction used to functionalise the phosphonic acid monolayers with Paracetamol was noted to be successful. Thus, the proposed method has the potential to immobilise drugs/proteins to SAM coated surfaces and improve their biocompatibility and reduce post-implant complications

    Police Perfection: Examining the Effect of Trait Maximization on Police Decision-Making

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    Police officers around the world must often select between equally unappealing, uncertain courses of action in an attempt to achieve the best outcome. Despite the immense importance of such decisions, there remains a lack of understanding in the study of individual differences in police decision-making. Here, using a sample of senior police officers recruited from decision-making training events across the United Kingdom (n = 96), we used the Least-worst Uncertain Choice Inventory For Emergency Responses (LUCIFER) to measure the effect of maximization on both domain-specific (police) and domain-general (military) decisions. In line with a wealth of research on traditional "consumer" decisions, we found that police officers who were "maximizers" found decisions more difficult. Gender and previous military experience also influenced the process of decision-making. Specifically, police officers with military experience took more time to assess the situation but were faster to choose a course of action and commit to it. Female police officers also were slower to assess the situation. As recent events show, the outcomes of police decisions have significant consequences for the public, the officers involved, the police force as a whole, and the wider population, yet psychological research has yet to fully explore the role of individual differences in how such decisions are made. While this study does not seek to identify factors associated with "good" or "better" decision-makers, it provides strong support for the need to factor in perspectives of the individual when creating theory, or applied tools, in support of police decision-making

    Effectiveness of school food environment policies on children's dietary behaviors: A systematic review and meta-analysis.

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    BACKGROUND: School food environment policies may be a critical tool to promote healthy diets in children, yet their effectiveness remains unclear. OBJECTIVE: To systematically review and quantify the impact of school food environment policies on dietary habits, adiposity, and metabolic risk in children. METHODS: We systematically searched online databases for randomized or quasi-experimental interventions assessing effects of school food environment policies on children's dietary habits, adiposity, or metabolic risk factors. Data were extracted independently and in duplicate, and pooled using inverse-variance random-effects meta-analysis. Habitual (within+outside school) dietary intakes were the primary outcome. Heterogeneity was explored using meta-regression and subgroup analysis. Funnel plots, Begg's and Egger's test evaluated potential publication bias. RESULTS: From 6,636 abstracts, 91 interventions (55 in US/Canada, 36 in Europe/New Zealand) were included, on direct provision of healthful foods/beverages (N = 39 studies), competitive food/beverage standards (N = 29), and school meal standards (N = 39) (some interventions assessed multiple policies). Direct provision policies, which largely targeted fruits and vegetables, increased consumption of fruits by 0.27 servings/d (n = 15 estimates (95%CI: 0.17, 0.36)) and combined fruits and vegetables by 0.28 servings/d (n = 16 (0.17, 0.40)); with a slight impact on vegetables (n = 11; 0.04 (0.01, 0.08)), and no effects on total calories (n = 6; -56 kcal/d (-174, 62)). In interventions targeting water, habitual intake was unchanged (n = 3; 0.33 glasses/d (-0.27, 0.93)). Competitive food/beverage standards reduced sugar-sweetened beverage intake by 0.18 servings/d (n = 3 (-0.31, -0.05)); and unhealthy snacks by 0.17 servings/d (n = 2 (-0.22, -0.13)), without effects on total calories (n = 5; -79 kcal/d (-179, 21)). School meal standards (mainly lunch) increased fruit intake (n = 2; 0.76 servings/d (0.37, 1.16)) and reduced total fat (-1.49%energy; n = 6 (-2.42, -0.57)), saturated fat (n = 4; -0.93%energy (-1.15, -0.70)) and sodium (n = 4; -170 mg/d (-242, -98)); but not total calories (n = 8; -38 kcal/d (-137, 62)). In 17 studies evaluating adiposity, significant decreases were generally not identified; few studies assessed metabolic factors (blood lipids/glucose/pressure), with mixed findings. Significant sources of heterogeneity or publication bias were not identified. CONCLUSIONS: Specific school food environment policies can improve targeted dietary behaviors; effects on adiposity and metabolic risk require further investigation. These findings inform ongoing policy discussions and debates on best practices to improve childhood dietary habits and health
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