58 research outputs found

    TRPV2: A Key Player in Myelination Disorders of the Central Nervous System

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    Transient potential receptor vanilloid 2 (TRPV2) is widely expressed through the nervous system and specifically found in neuronal subpopulations and some glial cells. TRPV2 is known to be sensitized by methionine oxidation, which results from inflammation. Here we aim to characterize the expression and regulation of TRPV2 in myelination pathologies, such as hypomyelination and demyelination. We validated the interaction between TRPV2 and its putative interactor Opalin, an oligodendrocyte marker, in mixed glial cultures under pro- and anti-inflammatory conditions. Then, we characterized TRPV2 time-course expression in experimental animal models of hypomyelination (jimpy mice) and de-/remyelination (cuprizone intoxication and experimental autoimmune encephalomyelitis (EAE)). TRPV2 showed upregulation associated with remyelination, inflammation in cuprizone and EAE models, and downregulation in hypomyelinated jimpy mice. TRPV2 expression was altered in human samples of multiple sclerosis (MS) patients. Additionally, we analyzed the expression of methionine sulfoxide reductase A (MSRA), an enzyme that reduces oxidated methionines in TRPV2, which we found increased in inflammatory conditions. These results suggest that TRPV2 may be a key player in myelination in accordance with the recapitulation hypothesis, and that it may become an interesting clinical target in the treatment of demyelination disorders

    TRPV2 : a Key Player in Myelination Disorders of the Central Nervous System

    Get PDF
    Transient potential receptor vanilloid 2 (TRPV2) is widely expressed through the nervous system and specifically found in neuronal subpopulations and some glial cells. TRPV2 is known to be sensitized by methionine oxidation, which results from inflammation. Here we aim to characterize the expression and regulation of TRPV2 in myelination pathologies, such as hypomyelination and demyelination. We validated the interaction between TRPV2 and its putative interactor Opalin, an oligodendrocyte marker, in mixed glial cultures under pro- and anti-inflammatory conditions. Then, we characterized TRPV2 time-course expression in experimental animal models of hypomyelination (jimpy mice) and de-/remyelination (cuprizone intoxication and experimental autoimmune encephalomyelitis (EAE)). TRPV2 showed upregulation associated with remyelination, inflammation in cuprizone and EAE models, and downregulation in hypomyelinated jimpy mice. TRPV2 expression was altered in human samples of multiple sclerosis (MS) patients. Additionally, we analyzed the expression of methionine sulfoxide reductase A (MSRA), an enzyme that reduces oxidated methionines in TRPV2, which we found increased in inflammatory conditions. These results suggest that TRPV2 may be a key player in myelination in accordance with the recapitulation hypothesis, and that it may become an interesting clinical target in the treatment of demyelination disorders

    Non-invasive ventilation in obesity hypoventilation syndrome without severe obstructive sleep apnoea

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    Background Non-invasive ventilation (NIV) is an effective form of treatment in patients with obesity hypoventilation syndrome (OHS) who have concomitant severe obstructive sleep apnoea (OSA). However, there is a paucity of evidence on the efficacy of NIV in patients with OHS without severe OSA. We performed a multicentre randomised clinical trial to determine the comparative efficacy of NIV versus lifestyle modification (control group) using daytime arterial carbon dioxide tension (PaCO2) as the main outcome measure. Methods Between May 2009 and December 2014 we sequentially screened patients with OHS without severe OSA. Participants were randomised to NIV versus lifestyle modification and were followed for 2 months. Arterial blood gas parameters, clinical symptoms, health-related quality of life assessments, polysomnography, spirometry, 6-min walk distance test, blood pressure measurements and healthcare resource utilisation were evaluated. Statistical analysis was performed using intention-to-treat analysis. Results A total of 365 patients were screened of whom 58 were excluded. Severe OSA was present in 221 and the remaining 86 patients without severe OSA were randomised. NIV led to a significantly larger improvement in PaCO2 of -6 (95% CI -7.7 to -4.2) mm Hg versus -2.8 (95% CI -4.3 to -1.3) mm Hg, (p<0.001) and serum bicarbonate of -3.4 (95% CI -4.5 to -2.3) versus -1 (95% CI -1.7 to -0.2 95% CI) mmol/L (p<0.001). PaCO2 change adjusted for NIV compliance did not further improve the inter-group statistical significance. Sleepiness, some health-related quality of life assessments and polysomnographic parameters improved significantly more with NIV than with lifestyle modification. Additionally, there was a tendency towards lower healthcare resource utilisation in the NIV group. Conclusions NIV is more effective than lifestyle modification in improving daytime PaCO2, sleepiness and polysomnographic parameters. Long-term prospective studies are necessary to determine whether NIV reduces healthcare resource utilisation, cardiovascular events and mortality

    Sustainability program brands: Platforms for collaboration and co-creation

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    While CSR and Sustainability have been widely debated topics over the past decades, there is still evidence of unethical practices by businesses, as witnessed through corporate scandals across a number of industry sectors. This highlights the need for firms to collaborate to actively prevent malpractices and instead find ways to improve standards along the whole value chain. With the increased pressure from various stakeholders, calling for firms to address these issues in a collaborative and holistic manner, the development of models facilitating collaboration is vital. Taking a communication perspective, this paper seeks to improve the knowledge on how organisations can manage diverse stakeholders to improve value chain collaboration towards more sustainable practices. Based on a multiple case study methodology, involving in-depth interviews with senior directors in the food and drink value chain, a framework is developed, depicting the value of a branded sustainability program as a useful platform for stimulating collaboration and co-creation from diverse and/or competing stakeholders. The framework builds on, and contributes to several literature strands including CSR/Sustainability communication, Coopetition and Branding

    Does equality reduce growth? Some empirical evidence

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    This study intends to provide some empirical evidence on the connection between equality and growth. Accordingly, two different samples of countries have been explored over the last three decades using panel data. In the first subsample, encompassed by medium income nations, the relationship between equality (proxied by the Gini index) and growth seems to be hump shaped. In the second subsample, made up by high-income countries, the connection is unambiguously negative - more equality is detrimental for growth. These results suggest that the impact of equality on growth may be different at the various stages of development.

    A New Organisational Memory for Cross-Cultural Knowledge Management

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    Purpose – Effectively managing the cultural environment is an important stepping stone towards international business success. Cultural problems, especially between partners coming from diametrically different cultural categories represent one of the key challenges of knowledge management in international business co‐operations. The purpose of this paper is to investigate the influence of controversial cultural attitudes on collaboration and the use of most diverse knowledge capital of employees being regarded as a key resource for innovation and competitive advantage. Design/methodology/approach – Based on a comprehensive literature review, the very extensive data collection phase, applying the case study method, was carried out over a 13 month period. It mainly consisted of in‐depth interviews requiring 23 of them to reach theoretical saturation, non‐participant and participant observation (seven), focus groups (four) and fieldtrip notes in two culturally diverse Russian and Austrian research settings. Theoretical sampling was used to select the participants. The grounded theory method of constant comparative analysis was used to analyze the gathered data. Findings – The attitude towards sharing the precious resource of diverse employees' knowledge regarded as a prerequisite to international business success is influenced by national cultures. Protective attitudes for knowledge sharing limit the growth of humans' and the company's development. This paper suggests that providing the appropriate knowledge management tools and environment, especially referring to the soft aspects of emotions, will enhance and even change former institutionalised and ingrained patterns of behaviours. Therefore, the paper sheds light on the knowledge sharing contingency depending more on a social‐cognitive state rather than a static hierarchical status. Originality/value – The paper poses two innovative organizational memory conceptualizations based on respondents' needs and demands entailing a synthesis of knowledge management and interpersonal interactions to achieve the highest level of efficiency and high degrees of knowledge sharing and absorption. It bridges the gap of purely knowledge based and unemotional management tools towards a lively and engaging tool. This would appear to be the first time that an investigation of this type has been conducted explaining culturally influenced factors of knowledge management in Eastern and Western European co‐operations
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