1,060 research outputs found

    The challenges of change:Exploring the dynamics of police reform in Scotland

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    Despite a long tradition of pessimism regarding the scope for meaningful change in police practices, recent structural reforms to police organizations in several European countries suggest that significant change in policing is possible. Drawing on recent research into the establishment and consequences of a national police force in Scotland, this article uses instrumental, cultural and myth perspectives taken from organization theory to examine how change happened and with what effects. It highlights how police reform involves a complex interplay between the strategic aims of government, the cultural norms of police organizations and the importance of alignment with wider views about the nature of the public sector. The article concludes by identifying a set of wider lessons from the experience of organizational change in policing

    Structure of protease-cleaved escherichia coliα-2-macroglobulin reveals a putative mechanism of conformational activation for protease entrapment

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    Bacterial -2-macroglobulins have been suggested to function in defence as broad-spectrum inhibitors of host proteases that breach the outer membrane. Here, the X-ray structure of protease-cleaved Escherichia coli -2-macroglobulin is described, which reveals a putative mechanism of activation and conformational change essential for protease inhibition. In this competitive mechanism, protease cleavage of the bait-region domain results in the untethering of an intrinsically disordered region of this domain which disrupts native interdomain interactions that maintain E. coli -2-macroglobulin in the inactivated form. The resulting global conformational change results in entrapment of the protease and activation of the thioester bond that covalently links to the attacking protease. Owing to the similarity in structure and domain architecture of Escherichia coli -2-macroglobulin and human -2-macro­globulin, this protease-activation mechanism is likely to operate across the diverse members of this group

    Plural policing in Europe:relationships and governance in contemporary security system

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    References to ‘plural policing’, ‘policing beyond the police’ and the ‘extended policing family’ are now commonplace in many discussions of policing in late modern societies. There is a danger that claims about the dynamic and changing nature of plural policing themselves become a new orthodoxy and begin to lose a sense of local nuance and recognition of the importance of place-based specificity and context in understanding the particularities of policing. It is this need to unpack the complex ways in which contemporary plural policing is now configured at a local level within different national political environments that provides the underpinning rationale for this Special Issue. Focussing on aspects of relationships and governance in six jurisdictions across northern and western Europe, it provides important insights into how the policies, practices and narratives around plural policing reflect the influence of particular histories and geographies. The first three articles are focused primarily on the relationships which have emerged in the public sector through its own processes of pluralisation, in particular, through the introduction of policing auxiliaries or municipal policing in Scotland, England and The Netherlands. The fourth article considers both relationships and governance in pluralised policing in Paris, France. A detailed analysis of the governance of safety and security is taken up in the final two articles, examining the cases of Austria and Belgium. These articles clearly demonstrate that experiences of pluralised policing vary widely within Europe and call into question the assumed dominance of neo-liberal forces in this area

    The Effect of Hypoxia on G Protein Coupled (CB1) Receptor Gene Expression in Cortical B50 Neurons in Culture

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    The authors acknowledge Queen Margaret University, Edinburgh for the award of the Martlet research Scholarship and the Ahmadu Bello University Zaria-Nigeria for awarding the first author study fellowship to undertake this research studies. The authors would like to thank Promega Corporation for generously providing us with free samples and assay kits and reagents. Our special thanks go to Drs Paul Kelly and Linda Ferrington of the Centre for Neuroscience, University of Edinburgh for their help and guidance in RT-PCR technique. Our thanks goes to Dr Elizabeth Fashola- Stone, Technical Manager European collection of cell cultures (ECACC), for providing specialist and technical advice on the use of B50 cells.Hypoxia adversely affects cells and tissues, and neuronal cells in particular have been shown to be more susceptible to the injurious effects of hypoxia in which they may begin to die when oxygen supply is reduced or completely eliminated. Cannabinoid (CB1) receptor agonists have been shown to elicit several Central Nervous System (CNS) effects, mediated via G protein-coupled receptors. The aim of this study was to examine the effect of hypoxia on G protein coupled receptor (CB1) gene expression in cortical neuronal B50 cell lines in culture. The B50 cells were cultured in normoxia (21% O2; 5% CO2) and hypoxia (5% O2; 5% CO2), and were treated with cannabinoid agonists to determine their effects on hypoxia-induced changes. Three cannabinoid agonists [Win55,212-2 mesylate (Win), arachidonoylethanolamide (AEA) and 2- arachidonylglycerol (2-AG)], were administered to the cells as treatment for 48 hours after 48hours of initial culture for a total of 96hours of culture in hypoxic conditions at concentrations of 10, 50 and 100 nM. The levels of G-protein coupled receptor (CB1) mRNAs were assessed using RT-PCR. The results showed that hypoxia induced morphological changes in B50 cells in hypoxia while the CB1 RT-PCR mRNA levels showed no appreciable changes in normal, hypoxic and treated cells. The results show that B50 neuronal cells are susceptible to damage and injurious effects of hypoxia, as are most brain cells and the cannabinoid agonist treatments showed there were no changes in the level of CB1 receptor gene expression due to hypoxia or agonist treatment in neuronal B50 cells in culture.sch_dieAguado, T., A. Carracedo, B. Julien, G. Velasco, G. Milman, R. Mechoulam, L. Alvarez, M. Guzman and I. Galve-Roperh, 2007. Cannabinoids induce glioma stem-like cell differentiation and inhibit gliomagenesis. J. Biol. Chem., 282(9): 6854-6862. Begg, M., P. Pacher, S. Batkai, D. Osei-Hyiaman, L. Offertaler, F.M. Mo, J. Liu and G. Kunos 2005. Evidence for novel cannabinoid receptors. Pharmacol Ther., 106(2):133-145. Berghuis, P., M.B. Dobszay, R.M. Ibanez, P. Ernfors and T. Harkany, 2004. 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    The Roles of Opioid Receptors and Agonists in Health and Disease Conditions

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    The authors graciously acknowledge Queen Margaret University, Edinburgh for the award of the Martlet research Scholarship and the Ahmadu Bello University Zaria-Nigeria for awarding the first author study fellowship to undertake this research studies.Opioid receptors are found in the Central Nervous System (CNS) and are classified as mu (µ), kappa (κ), delta (δ) and sigma (σ) opioid receptors. Opioid receptors belong to the large family of G Protein Coupled Receptors (GPCRs), and have diverse and important physiological roles. The aim of the present review is to discuss the roles played by opioid receptors, their agonists and antagonists in health and disease conditions. Opioid receptors are not uniformly distributed in the CNS and are found in areas concerned with pain, with the highest concentration in the cerebral cortex, followed by the amygdala, septum, thalamus, hypothalamus, midbrain and spinal cord. Activated delta opioid receptors are coupled to Gi1 while activated mu opioid receptors are coupled to Gi3 in neuroblastoma cells. Mu opioid receptors are activated by mu receptor agonists and are coupled through the Gi1 and GoA. Both mu and kappa opioid receptors are coupled via both Gi and Gz and opioid receptors are important targets for thousands of pharmacological agents. GPCRs typically require activation by agonists for their signalling activity to be initiated but some of the GPCRs may display basal or spontaneous signalling activity in the absence of an agonist. The stimulation of these receptors triggers analgesic effects and affects the function of the nervous system, gastrointestinal tract and other body systems. Hundreds of analogs of opioid peptides have been synthesized in an effort to make the compounds more active, selective, and resistant to biodegradation than the endogenous ligands. 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Cannabinoid and heroin activation of mesolimbic dopamine transmission by a common mu1 opioid receptor mechanism. Science, 276(5321): 2048-2050. Thorat, S.N. and H.N. Bhargava, 1994. Evidence for a bidirectional cross-tolerance between morphine and 9- tetrahydrocannabinol in mice. Eur. J. Pharmacol., 260: 5-13. Tso, P.H. and Y.H. Wong, 2000. G(z) can mediate the acute actions of mu- and kappa -opioids but is not involved in opioid-induced adenylyl cyclase supersensitization. J. Pharmacol. Exp. Ther., 295(1): 168-176. Br. J. Pharmacol. Toxicol., 2(2): 84-91, 2011 91 Valverde, O., R. Maldonado, E. Valjent, A.M. Zimmer and A. Zimmer, 2000. Cannabinoid withdrawal syndrome is reduced in pre-proenkephalin knock-out mice. J. Neurosci., 20: 9284-9289. Valverde, O., F. Noble, F. Beslot, V. Dauge, M.C. Fournie-Zaluski and B.P. Roques, 2001. 9- tetrahydrocannabinol releases, facilitates the effects of endogenous enkephalins: reduction in morphine withdrawal syndrome without change in rewarding effect. Eur. J. Neurosci., 13: 1816-1824. Vela, G., M. Ruiz-Gayo and J.A. Fuentes, 1995. Anandamide decreases naloxone-precipitated withdrawal signs in mice chronically treated with morphine. Neuro Pharmacol., 34: 665-668. Vigan_, D., T. Rubino and D. Parolaro, 2005. Molecular and cellular basis of cannabinoid and opioid interactions. Pharmacol. Biochem. Behav., 81(2): 360-368. Wang, J., Q. Gao, J. Shen, T.M. Ye and Q. Xia, 2007. Kappa-opioid receptor mediates the cardioprotective effect of ischemic postconditioning. Zhejiang Da Xue Xue Bao Yi Xue Ban, 36(1): 41-47. Williams, J.T., M.J. Christie and O. Manzoni, 2001. Cellular and synaptic adaptations mediating opioid dependence. Physiol. Rev., 81: 299-343. Xiong, L.Z., J. Yang, Q. Wang and Z.H. Lu, 2007. Involvement of delta-and mu-opioid receptors in the delayed cerebral ischemic tolerance induced by repeated electroacupuncture preconditioning in rats. Chin. Med. J. (Engl), 120(5): 394-3992pub2726pub

    Characterising Australian memory clinics: current practice and service needs informing national service guidelines

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    Background: Memory clinics (MCs) play a key role in accurate and timely diagnoses and treatment of dementia and mild cognitive impairment. However, within Australia, there are little data available on current practices in MCs, which hinder international comparisons for best practice, harmonisation efforts and national coordination. Here, we aimed to characterise current service profiles of Australian MCs. Methods: The ‘Australian Dementia Network Survey of Expert Opinion on Best Practice and the Current Clinical Landscape’ was conducted between August-September 2020 as part of a larger-scale Delphi process deployed to develop national MC guidelines. In this study, we report on the subset of questions pertaining to current practice including wait-times and post-diagnostic care. Results: Responses were received from 100 health professionals representing 60 separate clinics (45 public, 11 private, and 4 university/research clinics). The majority of participants were from clinics in metropolitan areas (79%) and in general were from high socioeconomic areas. While wait-times varied, only 28.3% of clinics were able to offer an appointment within 1-2 weeks for urgent referrals, with significantly more private clinics (58.3%) compared to public clinics (19.5%) being able to do so. Wait-times were less than 8 weeks for 34.5% of non-urgent referrals. Only 20.0 and 30.9% of clinics provided cognitive interventions or post-diagnostic support respectively, with 7.3% offering home-based reablement programs, and only 12.7% offering access to group-based education. Metropolitan clinics utilised neuropsychological assessments for a broader range of cases and were more likely to offer clinical trials and access to research opportunities. Conclusions: In comparison to similar countries with comprehensive government-funded public healthcare systems (i.e., United Kingdom, Ireland and Canada), wait-times for Australian MCs are long, and post-diagnostic support or evidence-based strategies targeting cognition are not common practice. The timely and important results of this study highlight a need for Australian MCs to adopt a more holistic service of multidisciplinary assessment and post-diagnostic support, as well as the need for the number of Australian MCs to be increased to match the rising number of dementia cases

    The Roles of Guanine Nucleotide Binding Proteins in Health and Disease

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    G-proteins are important mediators of cellular and tissue functions and are characterised by a recognition site for Guanine Triphosphate (GTP), Guanine Diphosphate (GDP) and possess intrinsic GTPase activity. They play important roles in signal transduction responsible for cytoskeletal remodelling, cellular differentiation and vesicular transport. They are made up of three types namely, the small G-proteins, the sensors and the heterotrimeric G-proteins. The G-protein heterotrimers consist of G-alpha (G), G-beta (G)andGgamma(G()subunits.EachheterotrimericGproteinhavedifferentsubunitsandthecombinationofthesesubunitsdefinethespecificroleofeachGprotein.TheactivationofGsubunitsregulatestheactivityofeffectorenzymesandionchannelswhileG) and G-gamma (G() subunits. Each heterotrimeric G-protein have different subunits and the combination of these subunits define the specific role of each G-protein. The activation of G subunits regulates the activity of effector enzymes and ion channels while G( subunits function in the regulation of mitogen-activated protein kinase (MAP-kinase) pathway. The G-protein-mediated signal transduction is important in the regulation of a cells morphological and physiological response to external stimuli. MAPKs are involved in the phosphorylation of transcription factors that stimulate gene transcription. Gs stimulates adenylate cyclase, thereby increasing cyclic adenosine monophosphate (cAMP) leading to the phosphorylation and subsequent activation of Ca_+ channels. G proteins are involved in disease pathology through several mechanisms which interfere with the G protein activity. 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    Traumatic quadriceps rupture in a patient with patellectomy: a case report

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    <p>Abstract</p> <p>Introduction</p> <p>Acute traumatic, unilateral, quadriceps rupture after patellectomy is rare.</p> <p>Case presentation</p> <p>We present a 42-year old male who experienced a unilateral left quadriceps tendon rupture following assault by four people. Twenty-seven years before this injury, the patient had suffered ipsilateral femur and comminuted patellar fractures, which were managed by intramedullary nailing and patellectomy respectively. We performed primary end to end repair of the torn tendon. Postoperatively, histology revealed findings consistent with pre-existent degenerative changes. The patient made good recovery, and returned to his former occupation which was reliant on his ability to drive.</p> <p>Conclusion</p> <p>Degenerative changes of the tendon of the extensor mechanism of knee following patellectomy may predispose the quadriceps tendon to traumatic rupture. Early operative intervention and protracted rehabilitation are required to obtain the best functional results.</p

    Nunalleq, Stories from the Village of Our Ancestors:Co-designing a multivocal educational resource based on an archaeological excavation

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    This work was funded by the UK-based Arts and Humanities Research Council through grants (AH/K006029/1) and (AH/R014523/1), a University of Aberdeen IKEC Award with additional support for travel and subsistence from the University of Dundee, DJCAD Research Committee RS2 project funding. Thank you to the many people who contributed their support, knowledge, feedback, voices and faces throughout the project, this list includes members of the local community, colleagues, specialists, students, and volunteers. If we have missed out any names we apologize but know that your help was appreciated. Jimmy Anaver, John Anderson, Alice Bailey, Kieran Baxter, Pauline Beebe, Ellinor Berggren, Dawn Biddison, Joshua Branstetter, Brendan Body, Lise Bos, Michael Broderick, Sarah Brown, Crystal Carter, Joseph Carter, Lucy Carter, Sally Carter, Ben Charles, Mary Church, Willard Church, Daniele Clementi, Annie Cleveland, Emily Cleveland, Joshua Cleveland, Aron Crowell, Neil Curtis, Angie Demma, Annie Don, Julia Farley, Veronique Forbes, Patti Fredericks, Tricia Gillam, Sean Gleason, Sven Haakanson, Cheryl Heitman, Grace Hill, Diana Hunter, Joel Isaak, Warren Jones, Stephan Jones, Ana Jorge, Solveig Junglas, Melia Knecht, Rick Knecht, Erika Larsen, Paul Ledger, Jonathan Lim Soon, Amber Lincoln, Steve Luke, Francis Lukezic, Eva Malvich, Pauline Matthews, Roy Mark, Edouard Masson-MacLean, Julie Masson-MacLean, Mhairi Maxwell, Chuna Mcintyre, Drew Michael, Amanda Mina, Anna Mossolova, Carl Nicolai Jr, Chris Niskanen, Molly Odell, Tom Paxton, Lauren Phillips, Lucy Qin, Charlie Roberts, Chris Rowe, Rufus Rowe,Chris Rowland, John Rundall, Melissa Shaginoff, Monica Shah, Anna Sloan, Darryl Small Jr, John Smith, Mike Smith, Joey Sparaga, Hannah Strehlau, Dora Strunk, Larissa Strunk, Lonny Strunk, Larry Strunk, Robbie Strunk, Sandra Toloczko, Richard Vanderhoek, the Qanirtuuq Incorporated Board, the Quinhagak Dance Group and the staff at Kuinerrarmiut Elitnaurviat. We also extend our thanks to three anonymous reviewers for their valuable comments on our paper.Peer reviewedPublisher PD
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