Endothelial differentiation gene (Edg) proteins are G-protein-coupled receptors activated by lysophospholipid mediators: sphingosine-1-phosphate (S1P) or lysophosphatidic acid. We show that in the CNS, expression of Edg8/S1P5, a high-affinity S1P receptor, is restricted to oligodendrocytes and expressed throughout development from the immature stages to the mature myelin-forming cell. S1P activation of Edg8/S1P5 on O4-positive pre-oligodendrocytes induced process retraction via a Rho kinase/collapsin response-mediated protein signaling pathway, whereas no retraction was elicited by S1P on these cells derived from Edg8/S1P5-deficient mice. Edg8/S1P5-mediated process retraction was restricted to immature cells and was no longer observed at later developmental stages. In contrast, S1P activation promoted the survival of mature oligodendrocytes but not of pre-oligodendrocytes. The S1P-induced survival of mature oligodendrocytes was mediated through a pertussis toxin-sensitive, Akt-dependent pathway. Our data demonstrate that Edg8/S1P5 activation on oligodendroglial cells modulates two distinct functional pathways mediating either process retraction or cell survival and that these effects depend on the developmental stage of the cell.
This paper concerns two practices, public consultation and user involvement, whose adoption has been urged upon the UK National Health Service in recent years. Public consultation is a local attempt to seek the views of a broad constituency of persons. User involvement is a local attempt to include organized groups of service users in the planning, and occasionally the management, of such services. The paper has four objectives. First, it locates the topic in the context of several related current debates. Second, it outlines the main findings of a recent empirical study of public consultation as they relate to the above debates. Third, it summarizes the relevant findings of an empirical study of user involvement. Finally, it examines these two practices as "technologies of legitimation" which can be seen as a means by which managerial legitimacy is maintained in the context of an increasingly pluralistic policy arena.
a b s t r a c tRural communities in many parts of the tropics are dependent of forests for their livelihoods and for environmental services. Forest resources in the tropics have declined rapidly over the past century and therefore many developing countries in the tropics have reforestation programs. Although reforestation is a long-term process with long-term benefits, existing evaluations of the success of these programs tends to focus on short-term establishment success indicators. This paper presents a review of reforestation assessment that highlights the need to not only consider short-term establishment success, but also longer-term growth and maturation success, environmental success and socio-economic success. In addition, we argue that reforestation assessment should not be based on success indicators alone, but should incorporate the drivers of success, which encompasses an array of biophysical, socio-economic, institutional and project characteristics. This is needed in order to understand the reasons why reforestation projects succeed or fail and therefore to design more successful projects in future. The paper presents a conceptual model for reforestation success assessment that links key groups of success indicators and drivers. This conceptual model provides the basis for a more comprehensive evaluation of reforestation success and the basis for the development of predictive systems-based assessment models. These models will be needed to better guide reforestation project planning and policy design and therefore assist rural communities in tropical developing countries to alleviate poverty and achieve a better quality of life.Crown
1 Urotensin-II (U-II) and its receptor (UT) represent novel therapeutic targets for management of a variety of cardiovascular diseases. To test such hypothesis, it will be necessary to develop experimental animal models for the manipulation of U-II/UT receptor system. The goal of this study was to clone mouse and primate preproU-II and UT for pharmacological pro®ling. 2 Monkey and mouse preproU-II genes were identi®ed to encode 123 and 125 amino acids. Monkey and mouse UT receptors were 389, and 386 amino acids, respectively. Genomic organization of mouse genes showed that the preproU-II has four exons, while the UT receptor has one exon. 3 Although initially viewed by many exclusively as cardiovascular targets, the present study demonstrates expression of mouse and monkey U-II/UT receptor mRNA in extra-vascular tissue including lung, pancreas, skeletal muscle, kidney and liver. 4 Ligand binding studies showed that [ 125 I]h U-II bound to a single sites to the cloned receptors in a saturable/high a nity manner (K d 654+154 and 214+65 pM and B max of 1011+125 and 497+68 fmol mg 71 for mouse and monkey UT receptors, respectively). Competition binding analysis demonstrated equipotent, high a nity binding of numerous mammalian, amphibian and piscine U-II isopeptides to these receptors (K i =0.8 ± 3 nM). Fluorescein isothiocyanate (FITC) labelled U-II, bound speci®cally to HEK-293 cells expressing mouse or monkey UT receptor, con®rming cell surface expression of recombinant UT receptor. 5 Exposure of these cells to human U-II resulted in an increase in intracellular [Ca 2+ ] concentrations (EC 50 3.2+0.8 and 1.1+0.3 nM for mouse and monkey UT receptors, respectively) and inositol phosphate (Ip) formation (EC 50 7.2+1.8 and 0.9+0.2 nM for mouse and monkey UT receptors, respectively) consistent with the primary signalling pathway for UT receptor involving phospholipase C activation.
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