The COMT Val158 Met polymorphism as an associated risk factor for Alzheimer disease and mild cognitive impairment in APOE 4 carriers

<p>Abstract</p> <p>Background</p> <p>The aim of this study is to examine the influence of the <it>catechol-O-methyltranferase (COMT) </it>gene (polymorphism Val158 Met) as a risk factor for Alzheimer's disease (AD) and mild cognitive impairment of amnesic type (MCI), and its synergistic effect with the <it>apolipoprotein E gene (APOE)</it>.</p> <p>A total of 223 MCI patients, 345 AD and 253 healthy controls were analyzed. Clinical criteria and neuropsychological tests were used to establish diagnostic groups.</p> <p>The DNA Bank of the University of the Basque Country (UPV-EHU) (Spain) determined <it>COMT </it>Val158 Met and <it>APOE </it>genotypes using real time polymerase chain reaction (rtPCR) and polymerase chain reaction (PCR), and restriction fragment length polymorphism (RFLPs), respectively. Multinomial logistic regression models were used to determine the risk of AD and MCI.</p> <p>Results</p> <p>Neither <it>COMT </it>alleles nor genotypes were independent risk factors for AD or MCI. The high activity genotypes (GG and AG) showed a synergistic effect with <it>APOE ε4 </it>allele, increasing the risk of AD (OR = 5.96, 95%CI 2.74-12.94, p < 0.001 and OR = 6.71, 95%CI 3.36-13.41, p < 0.001 respectivily). In AD patients this effect was greater in women.</p> <p>In MCI patients such as synergistic effect was only found between AG and <it>APOE ε4 </it>allele (OR = 3.21 95%CI 1.56-6.63, p = 0.02) and was greater in men (OR = 5.88 95%CI 1.69-20.42, p < 0.01).</p> <p>Conclusion</p> <p><it>COMT </it>(Val158 Met) polymorphism is not an independent risk factor for AD or MCI, but shows a synergistic effect with <it>APOE ε4 </it>allele that proves greater in women with AD.</p

Regulation of the Na+/K+-ATPase Ena1 Expression by Calcineurin/Crz1 under High pH Stress: A Quantitative Study

[EN] Regulated expression of the Ena1 Na+-ATPase is a crucial event for adaptation to high salt and/or alkaline pH stress in the budding yeast Saccharomyces cerevisiae. ENA1 expression is under the control of diverse signaling pathways, including that mediated by the calcium-regulatable protein phosphatase calcineurin and its downstream transcription factor Crz1. We present here a quantitative study of the expression of Ena1 in response to alkalinization of the environment and we analyze the contribution of Crz1 to this response. Experimental data and mathematical models substantiate the existence of two stress-responsive Crz1-binding sites in the ENA1 promoter and estimate that the contribution of Crz1 to the early response of the ENA1 promoter is about 60%. The models suggest the existence of a second input with similar kinetics, which would be likely mediated by high pH-induced activation of the Snf1 kinase.This work was supported by grants BFU2011-30197-C3-01, BFU2014-54591-C2-1-P and EUI2009-04147 (SysMo2) to JA. (Ministry of Industry and Competitivity, Spain, and Fondo Europeo de Desarrollo Regional [FEDER]). JA is the recipient of an Ajut 2014SGR-4 award (Generalitat de Catalunya). DC was recipient of a predoctoral fellowship from the Spanish Ministry of Education. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Petrezsélyová, S.; López-Malo, M.; Canadell, D.; Roque, A.; Serra-Cardona, A.; Marques Romero, MC.; Vilaprinyó, E.... (2016). Regulation of the Na+/K+-ATPase Ena1 Expression by Calcineurin/Crz1 under High pH Stress: A Quantitative Study. PLoS ONE. 11(6):e0158424-e0158424. https://doi.org/10.1371/journal.pone.0158424Se0158424e015842411

Endocytic regulation of alkali metal transport proteins in mammals, yeast and plants

The relative concentrations of ions and solutes inside cells are actively maintained by several classes of transport proteins, in many cases against their concentration gradient. These transport processes, which consume a large portion of cellular energy, must be constantly regulated. Many structurally distinct families of channels, carriers, and pumps have been characterized in considerable detail during the past decades and defects in the function of some of these proteins have been linked to a growing list of human diseases. The dynamic regulation of the transport proteins present at the cell surface is vital for both normal cellular function and for the successful adaptation to changing environments. The composition of proteins present at the cell surface is controlled on both the transcriptional and post-translational level. Post-translational regulation involves highly conserved mechanisms of phosphorylation- and ubiquitylation-dependent signal transduction routes used to modify the cohort of receptors and transport proteins present under any given circumstances. In this review, we will summarize what is currently known about one facet of this regulatory process: the endocytic regulation of alkali metal transport proteins. The physiological relevance, major contributors, parallels and missing pieces of the puzzle in mammals, yeast and plants will be discussed.This work was supported by grant BFU2011-30197-C03-03 from the Ministerio de Ciencia e Innovacion (Spain). V.L.-T. is supported by a fellowship from the Universidad Politecnica de Valencia. C. P. is supported by a fellowship from the Consejo Superior de Investigaciones Cientificas (Spain).Mulet Salort, JM.; Llopis Torregrosa, V.; Primo Planta, C.; Marques Romero, MC.; Yenush, L. (2013). 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A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

The Methodological Challenges Related to Assess the Outcomes of Knowledge Management Initiatives: The Case of Communities of Practice

Part 8: Knowledge Management and Information SharingInternational audienceIn any organizational project where the use of limited resources represents a challenge, it’s necessary to assess the outcomes generated. The methodological approach on how to assess outcomes reveals many questions, namely: What is the best way to do so? What dimensions to assess? From what criteria? How to estimate them? In the case of communities of practice (CoP), these questions become accurate. Indeed, in the case of Communities of Practice, the participants represent the cornerstone of the project because there are the ones who generate knowledge. So to assess outcomes generated by CoP within an organization, it’s necessary to identify an adapted methodological frame which will allow to take into account the critical aspects of the CoP and the user perspective. Our proposal aims to present a hybrid path (qualitative-quantitative) in order to minimize the limits and uplift advantages related to both approaches. The addition of these two approaches must generate a more stronger one and a better reliability of concept. For that purpose, the structure of the article concerns the following aspects: the context of knowledge management initiatives and particularly communities of practice; notions of assessment and outcomes; the current methodologies used to assess the outcomes of the CoP as well as their limits; the criteria to be respected for the choice as a strong methodology; the choice of a new approach (qualitative-quantitative) and its future application in the CoP