Cyclic AMP-specific phosphodiesterase, PDE8A1, is activated by protein kinase A-mediated phosphorylation

The cyclic AMP-specific phosphodiesterase PDE8 has been shown to play a pivotal role in important processes such as steroidogenesis, T cell adhesion, regulation of heart beat and chemotaxis. However, no information exists on how the activity of this enzyme is regulated. We show that under elevated cAMP conditions, PKA acts to phosphorylate PDE8A on serine 359 and this action serves to enhance the activity of the enzyme. This is the first indication that PDE8 activity can be modulated by a kinase, and we propose that this mechanism forms a feedback loop that results in the restoration of basal cAMP levels. (C) 2012 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserve

Kaneohe Fishpond Master Plan

master plan intended to identify goals, directions, and measures to restore remaining fishponds for uses consistent with their historic function and intergrit

cGMP-dependent protein kinase Iα associates with the antidepressant-sensitive serotonin transporter and dictates rapid modulation of serotonin uptake

<p>Abstract</p> <p>Background</p> <p>The Na⁺/Cl^--dependent serotonin (5-hydroxytryptamine, 5-HT) transporter (SERT) is a critical element in neuronal 5-HT signaling, being responsible for the efficient elimination of 5-HT after release. SERTs are not only targets for exogenous addictive and therapeutic agents but also can be modulated by endogenous, receptor-linked signaling pathways. We have shown that neuronal A3 adenosine receptor activation leads to enhanced presynaptic 5-HT transport <it>in vitro </it>and an increased rate of SERT-mediated 5-HT clearance <it>in vivo</it>. SERT stimulation by A3 adenosine receptors derives from an elevation of cGMP and subsequent activation of both cGMP-dependent protein kinase (PKG) and p38 mitogen-activated protein kinase. PKG activators such as 8-Br-cGMP are known to lead to transporter phosphorylation, though how this modification supports SERT regulation is unclear.</p> <p>Results</p> <p>In this report, we explore the kinase isoform specificity underlying the rapid stimulation of SERT activity by PKG activators. Using immortalized, rat serotonergic raphe neurons (RN46A) previously shown to support 8-Br-cGMP stimulation of SERT surface trafficking, we document expression of PKGI, and to a lower extent, PKGII. Quantitative analysis of staining profiles using permeabilized or nonpermeabilized conditions reveals that SERT colocalizes with PKGI in both intracellular and cell surface domains of RN46A cell bodies, and exhibits a more restricted, intracellular pattern of colocalization in neuritic processes. In the same cells, SERT demonstrates a lack of colocalization with PKGII in either intracellular or surface membranes. In keeping with the ability of the membrane permeant kinase inhibitor DT-2 to block 8-Br-cGMP stimulation of SERT, we found that DT-2 treatment eliminated cGMP-dependent kinase activity in PKGI-immunoreactive extracts resolved by liquid chromatography. Similarly, treatment of SERT-transfected HeLa cells with small interfering RNAs targeting endogenous PKGI eliminated 8-Br-cGMP-induced regulation of SERT activity. Co-immunoprecipitation studies show that, in transporter/kinase co-transfected cells, PKGIα specifically associates with hSERT.</p> <p>Conclusion</p> <p>Our findings provide evidence of a physical and compartmentalized association between SERT and PKGIα that supports rapid, 8-Br-cGMP-induced regulation of SERT. We discuss a model wherein SERT-associated PKGIα supports sequentially the mobilization of intracellular transporter-containing vesicles, leading to enhanced surface expression, and the production of catalytic-modulatory SERT phosphorylation, leading to a maximal enhancement of 5-HT clearance capacity.</p

A theory of mobile library service delivery

Research indicates there is widespread acceptance that nomadicity of library users is a phenomenon that will continue to increase; however, mobile learning is a resource that relatively few academic libraries appear to be taking advantage of. This paper presents a model developed during an investigation using a grounded theory approach into factors that may contribute to the delivery of library services to mobile technologies. A sample of 42 professionally qualified library staff from the Australasian vocational education and training (VET) sector was investigated to determine how confident and capable library staff believed they were to respond to technology advancement challenges and the training and support required for that response. The resulting theoretical model explains the impact of mobile technologies on library services and highlights the complex factors contributing to mobile technology acceptance at both an organisational and individual level. The presence of a series of catalysing impacts forms a central core and their management can enable an organisation to move from a position of uncertainty to one where the consequences of mobile technologies have been normalised

Living with multimorbidity: medical and lay healthcare approaches

Multimorbidity is rapidly becoming the norm rather than the exception in healthcare. Research on this issue is increasing and this review discusses a selection of clinical and social science literature. The focus is on understanding the complexity of the lived experience of multimorbidity and how this is presented in clinical encounters, drawing on examples of arthritis within a multimorbidity context. Taking into account the biophysical, psychological, social and cultural factors that shape multimorbidity this paper calls for a re-conceptualization of the concept, allowing a more dynamic and holistic approach

From sulphur to perfume: spa and SPA at Monchique, Algarve

In the thermal village of Monchique, Algarve, different streams of water-related knowledge and practices coexisted for centuries. Those waters were traditionally known as águas santas (holy waters) and believed to have redemptive healing powers. In the seventeenth century, the Catholic church took control of the place, refashioned the bathing rituals, developed infrastructures and provided assistance to the patients, granting free treatment to the poor. In the nineteenth century, the state replaced the church and imposed that treatments should be provided by professionals trained in the scientific principles of medical hydrology. Secular and scientific as they were, clinical logbooks still allowed for the account of patients that embodied miracle-like redemptive cures ‘at the third bath’. People went to Monchique both for its magic and its medicine, bringing in the body ailments achieved in their lives of hard labour. They also went there for a socialising break while healing. From mendicants to rich landowners, coming mostly from the Algarve and neighbouring Alentejo, they crowded the place in summertime. In the twentieth century, as in other places in continental Europe, the spa evolved into a highly medicalised place that qualified for medical expenses reimbursements, which implied the eclipsing – at least from representation – of its leisure component. In the twenty-first century, a new trend of consumer-centred, market-based, post-water balneology with an emphasis on wellness and leisure reinvented the spa as place for lush and diversified consumption. This article argues that the seemingly contradictory systems (markets and medicine) coexist much in the same way that magic, religion and medicine coexisted in the old water sites. The new SPAs, rather than putting an end to the old spas, have enabled them to survive by reinventing thermal sites as places of attraction and leisure

The while of participation: A systematic review of participatory research involving people with sensory impairments and/or intellectual impairments.

This paper reports on the first systematic review of literature associated with participatory research involving people identified with sensory impairments and/or intel- lectual impairments. It was initiated as part of ARCHES, an European Union-funded heritage project. The review sought to examine processes and activities used for organising participatory research involving people identified with sensory and/or intellectual impairments. 54 papers were included, involving studies from 14 countries and varying numbers of participants across different time scales. Insights were gained into use of advisory groups, organisation and support, collecting and analysing data, sharing findings and activity types. Emergent themes enabled an identification of the while of participation. The while represents the tensions, outcomes and component parts which are evident within the multiple moments that span an experience of participatory research. Participation is not about types of activity but how any activity is undertaken

Developing and implementing an integrated delirium prevention system of care:a theory driven, participatory research study

Background: Delirium is a common complication for older people in hospital. Evidence suggests that delirium incidence in hospital may be reduced by about a third through a multi-component intervention targeted at known modifiable risk factors. We describe the research design and conceptual framework underpinning it that informed the development of a novel delirium prevention system of care for acute hospital wards. Particular focus of the study was on developing an implementation process aimed at embedding practice change within routine care delivery. Methods: We adopted a participatory action research approach involving staff, volunteers, and patient and carer representatives in three northern NHS Trusts in England. We employed Normalization Process Theory to explore knowledge and ward practices on delirium and delirium prevention. We established a Development Team in each Trust comprising senior and frontline staff from selected wards, and others with a potential role or interest in delirium prevention. Data collection included facilitated workshops, relevant documents/records, qualitative one-to-one interviews and focus groups with multiple stakeholders and observation of ward practices. We used grounded theory strategies in analysing and synthesising data. Results: Awareness of delirium was variable among staff with no attention on delirium prevention at any level; delirium prevention was typically neither understood nor perceived as meaningful. The busy, chaotic and challenging ward life rhythm focused primarily on diagnostics, clinical observations and treatment. Ward practices pertinent to delirium prevention were undertaken inconsistently. Staff welcomed the possibility of volunteers being engaged in delirium prevention work, but existing systems for volunteer support were viewed as a barrier. Our evolving conception of an integrated model of delirium prevention presented major implementation challenges flowing from minimal understanding of delirium prevention and securing engagement of volunteers alongside practice change. The resulting Prevention of Delirium (POD) Programme combines a multi-component delirium prevention and implementation process, incorporating systems and mechanisms to introduce and embed delirium prevention into routine ward practices. Conclusions: Although our substantive interest was in delirium prevention, the conceptual and methodological strategies pursued have implications for implementing and sustaining practice and service improvements more broadly

Considerations for preparing a randomized population health intervention trial: lessons from a South African–Canadian partnership to improve the health of health workers

Background: Community-based cluster-randomized controlled trials (RCTs) are increasingly being conducted to address pressing global health concerns. Preparations for clinical trials are well-described, as are the steps for multi-component health service trials. However, guidance is lacking for addressing the ethical and logistic challenges in (cluster) RCTs of population health interventions in low- and middle-income countries. Objective: We aimed to identify the factors that population health researchers must explicitly consider when planning RCTs within North–South partnerships. Design: We reviewed our experiences and identified key ethical and logistic issues encountered during the pre-trial phase of a recently implemented RCT. This trial aimed to improve tuberculosis (TB) and Human Immunodeficiency Virus (HIV) prevention and care for health workers by enhancing workplace assessment capability, addressing concerns about confidentiality and stigma, and providing onsite counseling, testing, and treatment. An iterative framework was used to synthesize this analysis with lessons taken from other studies. Results: The checklist of critical factors was grouped into eight categories: 1) Building trust and shared ownership; 2) Conducting feasibility studies throughout the process; 3) Building capacity; 4) Creating an appropriate information system; 5) Conducting pilot studies; 6) Securing stakeholder support, with a view to scale-up; 7) Continuously refining methodological rigor; and 8) Explicitly addressing all ethical issues both at the start and continuously as they arise. Conclusion: Researchers should allow for the significant investment of time and resources required for successful implementation of population health RCTs within North–South collaborations, recognize the iterative nature of the process, and be prepared to revise protocols as challenges emerge