Degradation of Internalized αvβ5 Integrin Is Controlled by uPAR Bound uPA: Effect on β1 Integrin Activity and α-SMA Stress Fiber Assembly

Myofibroblasts (Mfs) that persist in a healing wound promote extracellular matrix (ECM) accumulation and excessive tissue contraction. Increased levels of integrin αvβ5 promote the Mf phenotype and other fibrotic markers. Previously we reported that maintaining uPA (urokinase plasminogen activator) bound to its cell-surface receptor, uPAR prevented TGFβ-induced Mf differentiation. We now demonstrate that uPA/uPAR controls integrin β5 protein levels and in turn, the Mf phenotype. When cell-surface uPA was increased, integrin β5 levels were reduced (61%). In contrast, when uPA/uPAR was silenced, integrin β5 total and cell-surface levels were increased (2–4 fold). Integrin β5 accumulation resulted from a significant decrease in β5 ubiquitination leading to a decrease in the degradation rate of internalized β5. uPA-silencing also induced α-SMA stress fiber organization in cells that were seeded on collagen, increased cell area (1.7 fold), and increased integrin β1 binding to the collagen matrix, with reduced activation of β1. Elevated cell-surface integrin β5 was necessary for these changes after uPA-silencing since blocking αvβ5 function reversed these effects. Our data support a novel mechanism by which downregulation of uPA/uPAR results in increased integrin αvβ5 cell-surface protein levels that regulate the activity of β1 integrins, promoting characteristics of the persistent Mf

African Americans, Gentrification, and Neoliberal Urbanization: the Case of Fort Greene, Brooklyn

This article examines the gentrification of Fort Greene, which is located in the western part of black Brooklyn, one of the largest contiguous black urban areas in the USA. Between the late 1960s and 2003, gentrification in Fort Greene followed the patterns discovered by scholars of black neighborhoods; the gentrifying agents were almost exclusively black and gentrification as a process was largely bottom-up because entities interested in the production of space were mostly not involved. Since 2003, this has changed. Whites have been moving to Fort Greene in large numbers and will soon represent the numerical majority. Public and private interventions in and around Fort Greene have created a new top-down version of gentrification, which is facilitating this white influx. Existing black residential and commercial tenants are replaced and displaced in the name of urban economic development

The burden of unintended pregnancies in Brazil: a social and public health system cost analysis

Hoa H Le,1 Mark P Connolly,1,2 Luis Bahamondes,3 Jose G Cecatti,3 Jingbo Yu,4 Henry X Hu4 1Department of Pharmacoeconomics and Pharmacoepidemiology, University of Groningen, Groningen, the Netherlands; 2Global Market Access Solutions, Saint-Prex, Switzerland; 3Department of Obstetrics and Gynecology, School of Medical Sciences, University of Campinas, Campinas, Brazil; 4Merck & Co, Whitehouse Station, NJ, USA Background: Unintended pregnancy (UP) is an unmet medical need with consequences worldwide. We evaluate the costs of UP based on pregnancies in Brazil from for the year 2010. Methods: The consequences of UP were evaluated using decision analysis based on pregnancy rates and outcomes as miscarriage, induced abortion, and live birth, which were factored into the analysis. The model discriminated between maternal and child outcomes and accounted for costs (in Brazilian currency [Real$, R$]) within the Brazilian public health service attributed to preterm birth, neonatal admission, cerebral palsy, and neonatal and maternal mortality. Event probabilities were obtained from local resources. Results: We estimate that 1.8 million UPs resulted in 159,151 miscarriages, 48,769 induced abortions, 1.58 million live births, and 312 maternal deaths, including ten (3%) attributed to unsafe abortions. The total estimated costs attributed to UP are R$4.1 billion annually, including R$32 million (0.8%) and R$4.07 billion (99.2$1.22 billion (30.0%), with labor and delivery responsible for most costs (R$988 million; 24.3$2.84 billion; 72.3%) with hospital readmission during the first year accounting for approximately R$2.15 billion (52.9$2,293. Conclusion: Despite weaknesses in precise estimates in annual pregnancies and induced abortions, our estimates reflect the costs of UP for different pregnancy outcomes. The main costs associated with UP are in those carried to parturition. The health cost of abortion represents a small proportion of total costs as these are paid for outside of the public health system. Consequently, reductions in UP will generate not only cost savings, but reductions in woman and child morbidity and mortality. Keywords: unintended pregnancy, public health, Brazil, abortio