Isolation of a Novel β4 Integrin-binding Protein (p27BBP) Highly Expressed in Epithelial Cells

The integrin beta4 has a long cytodomain necessary for hemidesmosome formation. A yeast two-hybrid screen using beta4 cytodomain uncovered a protein called p27(BBP) that represents a beta4 interactor. Both in yeast and in vitro, p27(BBP) binds the two NH2-terminal fibronectin type III modules of beta4, a region required for signaling and hemidesmosome formation. Sequence analysis of p27(BBP) revealed that p27(BBP) was not previously known and has no homology with any isolated mammalian protein, but 85% identical to a yeast gene product of unknown function. Expression studies by Northern analysis and in situ hybridization showed that, in vivo, p27(BBP) mRNA is highly expressed in epithelia and proliferating embryonic epithelial cells. An antibody raised against p27(BBP) COOH-terminal domain showed that all beta4-containing epithelial cell lines expressed p27(BBP). The p27(BBP) protein is insoluble and present in the intermediate filament pool. Furthermore, subcellular fractionation indicated the presence of p27(BBP) both in the cytoplasm and in the nucleus. Confocal analysis of cultured cells showed that part of p27(BBP) immunoreactivity was both nuclear and in the membrane closely apposed to beta4. These results suggest that the p27(BBP) is an in vivo interactor of beta4, possibly linking beta4 to the intermediate filament cytoskeleton

Fire risk reduction on the margins of an urbanizing world

Globally, over 95% of fire related deaths and injuries occur in low- and middle-income countries. Within informal settlements, the risk of fire resulting in injury or death is particularly high. This paper examines fire risks in informal settlements in New Delhi and Cape Town, and tented informal settlements in Lebanon. Our analysis draws on primary sources, secondary literature, statistical data and qualitative interviews. The distribution of fire risk across urban societies is a fundamentally political issue. Residential fire risk can be tackled by accessible, affordable, safety-compliant housing. That said, important interim measures can be taken to mitigate fire risk. Some of the risks requiring attention are similar across our case studies, driven by high population densities; flammable housing materials; unreliable or inaccessible access to safe power sources; and - in the case of Cape Town and New Delhi particularly - the inability of fire services to reach sites of fire. However, these common risks are embedded in distinct social, economic and political contexts that must be placed at the centre of any intervention. Interventions must also be aware that the risk of fire is not spread evenly within informal settlements, intersecting as it does with factors like gender, age, health and disability. Informal settlement fires have been under-studied to date. The studies that do exist tend to operate within disciplinary silos. This paper represents an important interdisciplinary approach to fire within informal settlements, which grounds technical data, modelling and experiments in political, social and economic realities

Nkx2-5+Islet1+ Mesenchymal Precursors Generate Distinct Spleen Stromal Cell Subsets and Participate in Restoring Stromal Network Integrity

SummarySecondary lymphoid organ stromal cells comprise different subsets whose origins remain unknown. Herein, we exploit a genetic lineage-tracing approach to show that splenic fibroblastic reticular cells (FRCs), follicular dendritic cells (FDCs), marginal reticular cells (MRCs), and mural cells, but not endothelial cells, originate from embryonic mesenchymal progenitors of the Nkx2-5+Islet1+ lineage. This lineage include embryonic mesenchymal cells with lymphoid tissue organizer (LTo) activity capable also of supporting ectopic lymphoid-like structures and a subset of resident spleen stromal cells that proliferate and regenerate the splenic stromal microenvironment following resolution of a viral infection. These findings identify progenitor cells that generate stromal diversity in spleen development and repair and suggest the existence of multipotent stromal progenitors in the adult spleen with regenerative capacity