30 research outputs found

    Hypoxia induced amoeboid microglial cell activation in postnatal rat brain is mediated by ATP receptor P2X4

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    <p>Abstract</p> <p>Background</p> <p>Activation of amoeboid microglial cells (AMC) and its related inflammatory response have been linked to the periventricular white matter damage after hypoxia in neonatal brain. Hypoxia increases free ATP in the brain and then induces various effects through ATP receptors. The present study explored the possible mechanism in ATP induced AMC activation in hypoxia.</p> <p>Results</p> <p>We first examined the immunoexpression of P2X4, P2X7 and P2Y12 in the corpus callosum (CC) and subependyma associated with the lateral ventricles where both areas are rich in AMC. Among the three purinergic receptors, P2X4 was most intensely expressed. By double immunofluorescence, P2X4 was specifically localized in AMC (from P0 to P7) but the immunofluorescence in AMC was progressively diminished with advancing age (P14). It was further shown that P2X4 expression was noticeably enhanced in P0 day rats subjected to hypoxia and killed at 4, 24, 72 h and 7 d versus their matching controls by double labeling and western blotting analysis. P2X4 expression was most intense at 7 d whence the inflammatory response was drastic after hypoxia. We then studied the association of P2X4 with cytokine release in AMC after hypoxic exposure. In primary microglial cells exposed to hypoxia, IL-1β and TNF-ι protein levels were up-regulated. Blockade of P2X4 receptor with 2', 3'-0-(2, 4, 6-Trinitrophenyl) adenosine 5'-triphosphate, a selective P2X1-7 blocker resulted in partial suppression of IL-1β (24% <it>vs </it>hypoxic group) and TNF-ι expression (40% <it>vs </it>hypoxic group). However, pyridoxal phosphate-6-azo (benzene-2, 4-disulfonic acid) tetrasodium salt hydrate, a selective P2X1-3, 5-7 blocker did not exert any significant effect on the cytokine expression.</p> <p>Conclusions</p> <p>It is concluded that P2X4 which is constitutively expressed by AMC in postnatal rats was enhanced in hypoxia. Hypoxia induced increase in IL-1β and TNF-ι expression was reversed by 2', 3'-0-(2, 4, 6-Trinitrophenyl) adenosine 5'-triphosphate suggesting that P2X4 mediates ATP induced AMC activation and its production of proinflammatory cytokines.</p

    Role of MC1R variants in uveal melanoma

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    Variants of the melanocortin-1 receptor (MC1R) gene have been linked to sun-sensitive skin types and hair colour, and may independently play a role in susceptibility to cutaneous melanoma. To assess the role of MC1R variants in uveal melanoma, we have analysed a cohort of 350 patients for the changes within the major region of the gene displaying sequence variation. Eight variants were detected – V60L, D84E, V92M, R151C, I155T, R160W, R163Q and D294H – 63% of these patients being hetero- or homozygous for at least one variant. Standard melanoma risk factor data were available on 119 of the patients. MC1R variants were significantly associated with hair colour (P¼0.03) but not skin or eye colour. The frequency of the variants detected in the 350 patients was comparable with those in the general population, and comparison of the cumulative tumour distribution by age at diagnosis in carriers and noncarriers provided no evidence that MC1R variants confer an increased risk of uveal melanoma. We interpret the data as indicating that MC1R variants do not appear to be major determinants of susceptibility to uveal melanoma. © 2003 Cancer Research U

    Case Studies From Elite Youth Soccer: Reflections on Talent Development Practices

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    With early specialisation being commonplace within elite youth soccer, knowledge of the psychosocial implications associated with talent development practices would be of considerable use for the coaching practitioner. This paper uses case studies as a platform to discuss potential psychosocial implications of early specialisation, and further, it also offers practical suggestions for the elite youth soccer coach. Three case studies were chosen; each is an account of observations that took place within a British soccer academy. Themes of the case studies included adult-led structures in early specialisation, awareness of need thwarting coach behaviours, and the retention or release of players. The case studies were deliberately chosen to prompt discussion, reflection, and action. Following the presentation of each case study, a theoretically driven discussion is formulated. Practical suggestions are then provided to assist in the management of talent development practices within elite youth soccer and to further enrich the experiences of players. Concluding thoughts and areas for future research are briefly discussed

    Transport planning for sustainable communities

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    Transport planning for sustainable communities

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    This groundbreaking new volume on social sustainability offers both critique and creative solutions. It challenges the conventional wisdoms of social sustainability and presents practical examples of projects that will help practitioners to think carefully and innovatively about the situations they are addressing. The book consists of original contributions from academics working in the fields of urban planning, housing, regeneration, transport and international sustainable development. Drawing on case study research gathered in the UK, Europe and Africa, it adopts an original, interdisciplinary approach to both theory and practice, illustrating the challenges and opportunities facing policy-makers and practitioners attempting to develop, manage and maintain sustainable communities. The authors argue that the dominant approach of 'how to do' small scale social sustainability fails to locate it within broader social processes. Ignoring the context not only sustains, but also actively reproduces wider inequalities. The book presents a new, more coherent and more complete approach to issues of social sustainability in urban areas. The book approaches current urban policy discourses in three different ways, represented by three sections: firstly focusing on small places within the urban fabric, secondly addressing the whole urban fabric by examining whether changing urban living and working patterns. The third section explores some of the ways that funding can be secured to achieve the aims of social sustainability and the social planning associated with it

    Calcium amido-bisoxazoline complexes in asymmetric hydroamination/cyclisation catalysis

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    Calcium complexes bearing bis(oxazolinylphenyl)amine (BOPA) ligands have been prepared, and their redistribution chemistry studied. The complexes [Ca(R-BOPA){N(SiMe3)2}(THF)] (R = iPr 1a, Ph 1b and Bn 1c) are active in hydroamination catalysis and give the highest enantioselectivity reported for a calcium complex

    Transport: challenging disabling environments

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    This article brings together the concerns of environmental and disability movements through examining the role of transport. Both movements critique current transport policy and practice. The disability movement has analysed how it marginalises the needs of disabled people, while environmentalists argue current transport trends are unsustainable and marginalise alternatives. Although these critiques operate independently and even seem opposed to each other, a common agenda can be developed through extending the social model of disability. The social model can be used to understand how car-dominated transport systems can be understood as disabling populations larger than those conventionally recognised as “disabled�. The car offers the technological fix of enabling abilities, in particular speed and strength, but in practice disables in a number of ways. Urban sprawl and traffic increase barriers to participation and access for many both “able-bodied� and “disabled�, while car dominance damages social interaction and limits sensory perception. Furthermore, the car economy is a major cause of impairment through crashes and physical inactivity. Understanding these together requires integrating the social model of disability with an eco-social model of impairment. This can show how unequal forms of social organisation are embodied in people and environments to produce patterns of impairment, disability and disadvantage. Finally we suggest policies to move towards sustainable societies with increased opportunities for broader social participation. The article argues that the two movements can create and benefit from a shared vision of socially inclusive, low-energy, sustainable transport
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