Catestatin Increases the Expression of Anti-Apoptotic and Pro-Angiogenetic Factors in the Post-Ischemic Hypertrophied Heart of SHR.

BACKGROUND:In the presence of comorbidities the effectiveness of many cardioprotective strategies is blunted. The goal of this study was to assess in a hypertensive rat model if the early reperfusion with anti-hypertensive and pro-angiogenic Chromogranin A-derived peptide, Catestatin (CST:hCgA352-372; CST-Post), protects the heart via Reperfusion-Injury-Salvage-Kinases (RISK)-pathway activation, limiting infarct-size and apoptosis, and promoting angiogenetic factors (e.g., hypoxia inducible factor, HIF-1α, and endothelial nitric oxide synthase, eNOS, expression). METHODS AND RESULTS:The effects of CST-Post on infarct-size, apoptosis and pro-angiogenetic factors were studied in isolated hearts of spontaneously hypertensive rats (SHR), which underwent the following protocols: (a) 30-min ischemia and 120-min reperfusion (I/R); (b) 30-min ischemia and 20-min reperfusion (I/R-short), both with and without CST-Post (75 nM for 20-min at the beginning of reperfusion). In unprotected Wistar-Kyoto hearts, used as normal counterpart, infarct-size resulted smaller than in SHR. CST-Post reduced significantly infarct-size and improved post-ischemic cardiac function in both strains. After 20-min reperfusion, CST-Post induced S-nitrosylation of calcium channels and phosphorylation of RISK-pathway in WKY and SHR hearts. Yet specific inhibitors of the RISK pathway blocked the CST-Post protective effects against infarct in the 120-min reperfusion groups. Moreover, apoptosis (evaluated by TUNEL, ARC and cleaved caspase) was reduced by CST-Post. Importantly, CST-Post increased expression of pro-angiogenetic factors (i.e., HIF-1α and eNOS expression) after two-hour reperfusion. CONCLUSIONS:CST-Post limits reperfusion damages and reverses the hypertension-induced increase of I/R susceptibility. Moreover, CST-Post triggers antiapoptotic and pro-angiogenetic factors suggesting that CST-Post can be used as an anti-maladaptive remodeling treatment

Role of catestatin as such as slowly released by fibronectin-coated pharmacologically active microcarriers (Fn-Pam) in limiting hypoxicinduced cell death

Objectives: Catestatin (CST), a 21-amino acid derivate of Chromogranin A, exerts several biological functions, including inhibition of catecholamine release and cardioprotective role. Moreover positive effect of CST on monocyte migration in vitro and the induction of angiogenesis, arteriogenesis and vasculogenesis in the mouse hind limb ischemia model have been demonstrated. Collateral arteries may provide a biological bypass for occluded atherosclerotic vessels, increasing blood flow to ischemic tissue. In such a prospective, CST is a very promising agent for revascularization purposes, in “NO-OPTION” patients. However, proteins have a very short half-life after administration and must be conveniently protected. FN-PAMs, biodegradable and biocompatible polymeric microspheres, have ideal characteristic for this purpose: besides to convey peptides and allow in situ prolonged/controlled delivery, they may also convey cells on their biomimetic surface and may favor their survival and engraftment after cell transplantation. In this study, we show that CST can be incorporated within FN-PAM and aim to demonstrate that CST may be released in a slowly/prolonged manner by FN-PAM. We also aim to demonstrate that CST released by FN-PAM may reduce cell death under different stress conditions. Materials and methods: CST has to be precipitated to ensure its stability upon subsequent encapsulation. Protein precipitate is formed from aqueous solution by the addition of a watermiscible organic solvent. PLGA–P188–PLGA (triblock) copolymeric microspheres are prepared using solid/oil/water emulsion solvent evaporation–extraction technique. PAMs are coated with Fibronectin and characterized by Immunofluroscence (confocal microscopy). Mesenchymal stem cells (MSC) are exposed to hypoxia (72 h in 1–2%O2) and reoxygenation (6 h in 21% O2) in a hypoxic chamber with or without CTS, FN-PAMs or CTS-FN-PAMs. The protective effects of treatments are detected by MTT assay. Results: To define the optimum condition of nanoprecipitation we used an experimental design, modifying parameters influencing protein precipitation: ionic strength, mixing and centrifugation time. Nanoprecipitation of CST was found to be 72%. Controlled release of CST from CTS-FNPAM greatly limits hypoxic MSC death and enhances MSC survival in post-hypoxic environment. Conclusions: FN-PAMs are successfully formulated with CST. By an experimental design, we found optimal conditions to obtain a good CTS nanoprecipitation yield. MSC readily adhere to the FN-PAM and CST-FN-PAMs reduce MSC death enhancing survival in post-hypoxic environment. Data suggest that CST-FN-PAMs are promising tools for therapeutic purpose

Traces of Fallback Breccia on the Rim of Barringer Meteorite Crater (a.k.a. Meteor Crater), Arizona

Barringer Meteorite Crater (a.k.a. Meteor Crater), Arizona, is one of the youngest and best preserved impact craters on Earth. For that rea-son, it provides a baseline for similar craters formed in the geologic past, formed elsewhere in the Solar Sys-tem, and illuminates the astronomical and geological processes that produce them. The crater has not, how-ever, escaped erosion completely. While Shoemaker [1] mapped a breccia with fallback components inside the crater, he did not locate it beyond the crater rim. He only found remnants of that type of debris in re-worked alluvium [1; see also 2]. Fallback breccia and any base-surge deposits have, thus, been missing components in studies of material ejected beyond the transient crater rim

Uptake of home-based voluntary HIV testing in sub-Saharan Africa: a systematic review and meta-analysis

Improving access to HIV testing is a key priority in scaling up HIV treatment and prevention services. Home-based voluntary counselling and testing (HBT) as an approach to delivering wide-scale HIV testing is explored here

Agglomeration, Inequality and Economic Growth (WP)

The impact of income inequality on economic growth is dependent on several factors, including the time horizon considered, the initial level of income and its initial distribution. Yet, as growth and inequality are also uneven across space, it is also pertinent to consider the effects of the geographical agglomeration of economic activity. Moreover, it would also seem pertinent to consider not just the levels of inequality and agglomeration, but also the changes they undergo -i.e., their within-country evolution- and how these two processes interact with each other. By applying different econometric specifications and by introducing different measures of agglomeration at country level -specifically, urbanization and urban concentration rates-, this study analyzes how inequality and agglomeration -both their levels and their evolution- influence economic growth in function of the country’s level of development and its initial income distribution. Our results suggest, in line with previous studies, that while high inequality levels are a limiting factor for long-run growth, increasing inequality and increasing agglomeration have the potential to enhance growth in low-income countries where income distribution remains relatively equal, but can result in congestion diseconomies in high-income countries, especially if income distribution becomes particularly unequal

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