6 research outputs found

    Do prior diel thermal cycles influence the physiological response of Atlantic salmon (Salmo salar) to subsequent heat stress?

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    We designed two environmentally relevant thermal cycling regimes using monitoring data from an Atlantic salmon river to determine if exposure to prior diel cycles stimulated protective mechanisms (e.g. heat hardening), and/or resulted in physiological and cellular stress. Wild fish were exposed to three days of diel cycling in the lab and then exposed to an acute thermal challenge near their upper reported critical temperature. We measured routine metabolic rate across the time course as well as indicators of physiological status (e.g. plasma glucose and osmolality) and cellular stress (e.g. heat shock protein 70). We observed that thermal cycling altered physiological and cellular responses, compared to an acute heat shock, but saw no differences between cycling regimes. Unique temperature regime and tissue specific responses were observed in heat shock protein induction, metabolites, haematology and osmotic indicators. Routine metabolic rate was not affected by the thermal cycling and increased according to Q10 predictions. While we report unique physiological and cellular responses between all treatment groups, we did not observe a clear indication of a heat hardening response.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

    Effects of Phosphorylation of Threonine 160 on Cyclin-dependent Kinase 2 Structure and Activity

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    International audienceWe have prepared phosphorylated cyclin-dependent protein kinase 2 (CDK2) for crystallization using the CDK-activating kinase 1 (CAK1) from Saccharomyces cerevisiae and have grown crystals using microseeding techniques. Phosphorylation of monomeric human CDK2 by CAK1 is more efficient than phosphorylation of the binary CDK2-cyclin A complex. Phosphorylated CDK2 exhibits histone H1 kinase activity corresponding to approximately 0.3% of that observed with the fully activated phosphorylated CDK2-cyclin A complex. Fluorescence measurements have shown that Thr160 phosphorylation increases the affinity of CDK2 for both histone substrate and ATP and decreases its affinity for ADP. By contrast, phosphorylation of CDK2 has a negligible effect on the affinity for cyclin A. The crystal structures of the ATP-bound forms of phosphorylated CDK2 and unphosphorylated CDK2 have been solved at 2.1-A resolution. The structures are similar, with the major difference occurring in the activation segment, which is disordered in phosphorylated CDK2. The greater mobility of the activation segment in phosphorylated CDK2 and the absence of spontaneous crystallization suggest that phosphorylated CDK2 may adopt several different mobile states. The majority of these states are likely to correspond to inactive conformations, but a small fraction of phosphorylated CDK2 may be in an active conformation and hence explain the basal activity observed

    Solutions for Kids in Pain: A Knowledge Mobilization Network Built on a Foundation of Patient Partnership

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    Background: Patient engagement is an approach that is expected or required to be part of a project, initiative or network by many research funding organizations. Solutions for Kids in Pain (SKIP) is a national knowledge mobilization network in Canada that was competitively funded and built on a foundation of engaging with patients (children and youth) and caregivers (parents) in its mission and vision. At the core of SKIP’s foundation was the PatientsIncludedTM charter, on which it grew and evolved its patient engagement efforts. Main Body: SKIP’s mission is to mobilize evidence-based solutions for children’s pain management. Unique to its funding requirements, SKIP was co-led by an academic institution (Dalhousie University) and a knowledge user partner (Children’s Healthcare Canada). SKIP is hosted at the university, where its central administration team is located, with six knowledge mobilization hubs based in cities across Canada. Patient engagement has been crucial to SKIP’s work with patient partners included in SKIP’s governance, management, committees, and knowledge mobilization activities. This paper shares and provides context for SKIP’s approach to patient partnership. How SKIP tailored its approach depending on the specific project context is demonstrated with three case studies. These case studies include SKIP’s Patient and Caregiver Advisory Committee which also developed resources that others may wish to use, the Youth in Pain Project which led to open calls for partnerships and unique approaches to listening and undertaking patient-informed projects, and Canada’s first national health standard for Pediatric Pain Management, which was co-developed with patient partners. Each unique case study demonstrates foundational principles to SKIP’s patient partnership such as offering compensation, creating a safe space, and others. Conclusion: Over its lifespan, SKIP committed to and wove patient partnership throughout all aspects of its network. We share the evolution of and insights gained from SKIP’s patient partnership activities, including resources for others to take and make their own. We encourage other research and knowledge mobilization networks to learn from this important patient partnership work and adopt and adapt what we share to their own contexts
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