Anti-SELE monoclonal antibody, clone CL2/6 [Biotin]

Background: Mutations in several genes expressed in podocytes, including Cd2ap, have been associated with focal segmental glomerulosclerosis in humans. Mutant mouse models provide an opportunity to better understand the molecular pathology that drives these diseases. Methods: In this report we use a battery of transgenic-GFP mice to facilitate the purification of all three major cell types of the glomerulus from Cd2ap mutant mice. Both microarrays and RNA-seq were used to characterize the gene expression profiles of the podocytes, mesangial cells and endothelial cells, providing a global dual platform cross-validating dataset. Results: The mesangial cells showed increased expression of profibrotic factors, including thrombospondin, Tgfb2 and Tgfb3, as well as the angiogenesis factor Vegf. They also showed upregulation of protective genes, including Aldh1a2, involved in retinoic acid synthesis and Decorin, a Tgfb antagonist. Of interest, the mesangial cells also showed significant expression of Wt1, which has generally been considered podocyte specific. The Cd2ap mutant podocytes showed upregulation of proteases as well as genes involved in muscle and vasculature development and showed a very strong gene expression signature indicating programmed cell death. Endothelial cells showed increased expression of the leukocyte adhesion associated factors Vcam1 and Sele, as well as Midkine (promoting angiogenesis), endothelin and many genes responsive to cytokines and interferons. Conclusions: This study provides a comprehensive analysis of the changing properties of the three cell types of the glomerulus in Cd2ap mutants, identifying activated and repressed pathways and responsible genes, thereby delivering a deeper molecular understanding of this genetic disease.

In order to assess the effects of possible future sea-level rise in the Sele plain, the lowlands prone to inundation and the rate of coastal erosion in the years 2050 and 2100 have been discussed and some conclusions are here proposed. The sea level at these two dates was calculated as the combination of three components: response of Italian coastal zones to the past deglaciation, variations in ocean volume due to the global warming and vertical land movements. The morpho-stratigraphical data, chronologically supported by C-14 and by archeo-tephro-stratigraphical dating, have allowed the identification of paleo-sea levels of the upper Pleistocene and Holocene (Amato et al. 2011). Such paleo-sea levels compared with those of the tectonically stable areas (Lambeck et al. 2011), permitted the detection of the different vertical land movements in the study area. In particular, in the SE sector of the coastal plain, the Holocene paleo-sea levels are slightly higher (ca. 1-2 m). These values could be considered due to a gentle uplift of the area during Holocene times (0.22 mm/year). In the central sector of the plain, near the Sele river mouth and in the NW sector, between the Sele and Tusciano river mouths, the altitude of the Late Quaternary coastal and lagoonal deposits are slightly lower (ca. 2-3 m). These values could be related to a gentle subsidence of the area during the Holocene (0.4 mm/year). The sea level rise of 5.9 mm/year (IPCC 2007) and 14 mm/year (Rahmstorf 2007) was considered to represent the maximum trends in the ocean volume variation at global scale. The third component, the glacio-hydro-isostasy, was represented by the value of 0.44 mm/year identified by Lambeck et al. (2011) at the Sele plain. The sum of these three components allowed to identify three sea-level scenarios slightly different for the northern and the southern sector of Sele plain, with values ranging from 357 to 1,526 mm and from 307 to 1,424 mm, respectively. For each scenario a simple approach was used, mainly based on the topographic elevation analysis of study area, applied to identify the extension of possible areas of inundation. It corresponds to a minimum value of about 0.42 km(2) for the 2050 AD and a maximum value of 7.6 km(2) for the 2100. Furthermore, according to the methodology proposed by Davidson-Arnott (2005), also the beach erosion was evaluated. The computations showed a potential mean landward retreat of the shoreline ranging from 19 to 93 m.