19 research outputs found

    NR5A2/LRH-1 regulates the PTGS2-PGE2-PTGER1 pathway contributing to pancreatic islet survival and function

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    LRH-1/NR5A2 is implicated in islet morphogenesis postnatally, and its activation using the agonist BL001 protects islets against apoptosis, reverting hyperglycemia in mouse models of Type 1 Diabetes Mellitus. Islet transcriptome profiling revealed that the expression of PTGS2/COX2 is increased by BL001. Herein, we sought to define the role of LRH-1 in postnatal islet morphogenesis and chart the BL001 mode of action conferring beta cell protection. LRH-1 ablation within developing beta cells impeded beta cell proliferation, correlating with mouse growth retardation, weight loss, and hypoglycemia leading to lethality. LRH-1 deletion in adult beta cells abolished the BL001 antidiabetic action, correlating with beta cell destruction and blunted Ptgs2 induction. Islet PTGS2 inactivation led to reduced PGE levels and loss of BL001 protection against cytokines as evidenced by increased cytochrome c release and cleaved-PARP. The PTGER1 antagonist—ONO-8130—negated BL001-mediated islet survival. Our results define the LRH-1/PTGS2/PGE/PTGER1 signaling axis as a key pathway mediating BL001 survival properties.The authors are supported by grants from the Consejería de Salud, Fundación Pública Andaluza Progreso y Salud, Junta de Andalucía (PI-0727-2010 to B.R.G., PI-0085-2013 to P.I.L., PI-0247-2016 to F.J.B.S.), the Consejería de Economía, Innovación y Ciencia (P10.CTS.6359 to B.R.G.), the Ministerio de Ciencia e Innovación co-funded by Fondos FEDER (PI10/00871, PI13/00593 and BFU2017-83588-P to B.R.G and PI17/01004 to F.J.B.S.), Vencer el Cancer (B.R.G), DiabetesCero (B.R.G.) and the Juvenile Diabetes Research Foundation Ltd (17-2013-372 and 2-SRA-2019-837-S-B to B.R.G.). E.M.V. is recipient of a Fellowship from the Ministerio de Ciencia e Innovación co-funded by Fondos FEDER (PRE2018-084907). F.J.B.S. is a recipient of a "Nicolás Monardes" research contracts from Consejería de Salud Junta de Andalucía, (C-0070-2012). A.M.M. is supported by CPII19/00023 and PI18/01590 from the Instituto de Salud Carlos III co-funded by Fondos FEDER. V.C. is supported by a AECC investigator award. CIBERDEM is an initiative of the Instituto de Salud Carlos III

    Spatial structure along an altitudinal gradient in the Italian central Alps suggests competition and facilitation among coniferous species

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    Questions: What is the structure of the anthropogenic upper forest-grassland ecotone and are there differences in the spatial relationships between the tree species involved? Location: Valfurva Valley, Italian central Alps. Methods: We conducted a spatial distribution and structure analysis in three 1-ha permanent plots along an altitudinal gradient, from the treeline to the sub- alpine forest. We reconstructed the age structure from cores from each individual with diameter > 4 cm at 50 cm height. Results: All tree species and age classes examined had a clumped structure. The cluster tendency was more evident at the treeline where the environmental conditions are more severe. In the sub- alpine forest there was a repulsion between Pinus cembra and Pinus mugo but at the treeline P. cembra was frequently found downslope from P. mugo. Conclusions: Although human influence has been the main driving force in shaping the present forest structure, in the last few decades natural dynamics have become the predominant force acting on forest structure and processes, showing a higher magnitude as altitude increases. Our results emphasize the existence of facilitating and interfering mechanisms between different species. P. cembra seems to be favoured compared to the other tree species

    Diachronic analysis of individual-tree mortality in a Norway spruce stand in the eastern Italian Alps

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    Understanding tree mortality processes across time requires long term studies. Spatiotemporal patterns of mortality in a 200 years-old mono-layered Norway spruce stand were evaluated to determine what factors affected individual-tree mortality. We performed an analysis on two surveys (1993 and 2005) in a 1-ha permanent plot in the Paneveggio forest (Eastern Italian Alps). Tree diameter and age distribution between surveys were compared. We examined spatial patterns of living and dead trees before 1993, in 1993 and in 2005 using univariate and bivariate Ripley's K(d) function, and a kernel estimator of local crowding. A logistic model was used to assess the effects of diameter, age, recent growth and competitive pressure on tree mortality. Spatial pattern analysis indicated mortality was associated to tree neighbourhood (neighbour effect at 2-5 m). An increment of regularization of tree spatial pattern occurred due to density-dependent mortality. Logistic regression showed tree diameter and recent growth were determinant on mortality risk during the monitoring period. Even if the stand is relatively aged, mortality dynamics are those typical of stem exclusion stage. Mortality was related to competitive dynamics, and small suppressed trees with slow growth rate had higher probability to die
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