Segmented multifunctional poly(ether ester) polymers containing H-bonding units. Preparation and charactization

A series of poly(ether ester)s containing amide and carbamate groups as H-bonding units and 13-50 mol-% of poly(ethylene glycol) (PEG) segments were prepared by polycondensation in bulk using Ti(OBu)4 as a catalyst. The copolymers were obtained starting from PEG/1,4-butanediol mixtures and a synthetic monomer carrying H-bonding groups. These polymers were designed for biomedical applications, where material biodegradability is required. The influence of the nature of the H-bonding units, the length of the polymethylene spacer between the H-bonding groups and the PEG content on the thermal and solubility properties of the copolymers was investigated. Amide-containing copolymers were more thermally stable than those containing carbamate groups. The PEG content also slightly affected the polymer thermal stability. The DSC traces of all samples presented multiple transitions, whose shape and peak temperature were strongly dependent on the PEG content. Polymer hydrophilicity, surface free energy and equilibrium swelling in phosphate buffer solution (PBS) at 37 °C were mainly influenced by the PEG content, whereas the nature of the H-bonding groups had little effect

Western Diet-Fed, Aortic-Banded Ossabaw Swine: A Preclinical Model of Cardio-Metabolic Heart Failure.

The development of new treatments for heart failure lack animal models that encompass the increasingly heterogeneous disease profile of this patient population. This report provides evidence supporting the hypothesis that Western Diet-fed, aortic-banded Ossabaw swine display an integrated physiological, morphological, and genetic phenotype evocative of cardio-metabolic heart failure. This new preclinical animal model displays a distinctive constellation of findings that are conceivably useful to extending the understanding of how pre-existing cardio-metabolic syndrome can contribute to developing HF

Knockout of the BK β2 subunit abolishes inactivation of BK currents in mouse adrenal chromaffin cells and results in slow-wave burst activity

Rat and mouse adrenal medullary chromaffin cells (CCs) express an inactivating BK current. This inactivation is thought to arise from the assembly of up to four β2 auxiliary subunits (encoded by the kcnmb2 gene) with a tetramer of pore-forming Slo1 α subunits. Although the physiological consequences of inactivation remain unclear, differences in depolarization-evoked firing among CCs have been proposed to arise from the ability of β2 subunits to shift the range of BK channel activation. To investigate the role of BK channels containing β2 subunits, we generated mice in which the gene encoding β2 was deleted (β2 knockout [KO]). Comparison of proteins from wild-type (WT) and β2 KO mice allowed unambiguous demonstration of the presence of β2 subunit in various tissues and its coassembly with the Slo1 α subunit. We compared current properties and cell firing properties of WT and β2 KO CCs in slices and found that β2 KO abolished inactivation, slowed action potential (AP) repolarization, and, during constant current injection, decreased AP firing. These results support the idea that the β2-mediated shift of the BK channel activation range affects repetitive firing and AP properties. Unexpectedly, CCs from β2 KO mice show an increased tendency toward spontaneous burst firing, suggesting that the particular properties of BK channels in the absence of β2 subunits may predispose to burst firing

Monitoring Actives Volcanoes by Using of Envisat and Ers Data: First Results of the Eurorisk-Preview Project

In the framework of the Eurorisk-Preview project, funded by the European Union, a task is dedicated to the assessment, prevention and management of volcanic risk. We are developing a multidisciplinary approach, integrating the geophysical prospecting at local scale and large scale remote sensing data. To achieve this task, two volcanic test sites have been identified: Mt. Etna, in Sicily (Italy), and Tenerife, in Canary Islands (Spain). We investigate the surface deformation and the volcanic emission in the atmosphere by using SAR series and multispectral data, requested in the ESA Category 1 (n. 3560). For Mt. Etna data from historical to recent eruptions (1992 – 2006) has been analysed while for Tenerife archived SAR data from 1992 to 2005 has been analysed, individuating anomaly ground deformations in Pico de Teide and surrounding areas as suggested by GPS campaigns

Developing cardiac and skeletal muscle share fast-skeletal myosin heavy chain and cardiac troponin-I expression

Skeletal muscle derived stem cells (MDSCs) transplanted into injured myocardium can differentiate into fast skeletal muscle specific myosin heavy chain (sk-fMHC) and cardiac specific troponin-I (cTn-I) positive cells sustaining recipient myocardial function. We have recently found that MDSCs differentiate into a cardiomyocyte phenotype within a three-dimensional gel bioreactor. It is generally accepted that terminally differentiated myocardium or skeletal muscle only express cTn-I or sk-fMHC, respectively. Studies have shown the presence of non-cardiac muscle proteins in the developing myocardium or cardiac proteins in pathological skeletal muscle. In the current study, we tested the hypothesis that normal developing myocardium and skeletal muscle transiently share both sk-fMHC and cTn-I proteins. Immunohistochemistry, western blot, and RT-PCR analyses were carried out in embryonic day 13 (ED13) and 20 (ED20), neonatal day 0 (ND0) and 4 (ND4), postnatal day 10 (PND10), and 8 week-old adult female Lewis rat ventricular myocardium and gastrocnemius muscle. Confocal laser microscopy revealed that sk-fMHC was expressed as a typical striated muscle pattern within ED13 ventricular myocardium, and the striated sk-fMHC expression was lost by ND4 and became negative in adult myocardium. cTn-I was not expressed as a typical striated muscle pattern throughout the myocardium until PND10. Western blot and RT-PCR analyses revealed that gene and protein expression patterns of cardiac and skeletal muscle transcription factors and sk-fMHC within ventricular myocardium and skeletal muscle were similar at ED20, and the expression patterns became cardiac or skeletal muscle specific during postnatal development. These findings provide new insight into cardiac muscle development and highlight previously unknown common developmental features of cardiac and skeletal muscle. © 2012 Clause et al

Recurrent and founder mutations in the Netherlands: cardiac Troponin I (TNNI3) gene mutations as a cause of severe forms of hypertrophic and restrictive cardiomyopathy

Background About 2-7% of familial cardiomyopathy cases are caused by a mutation in the gene encoding cardiac troponin 1 (TNNI3). The related clinical phenotype is usually severe with early onset. Here we report on all currently known mutations in the Dutch population and compared these with those described in literature. Methods TheTNNI3 gene was screened for mutations in all coding exons and flanking intronic sequences in a large cohort of cardiomyopathy patients. All Dutch index cases carrying a TNNI3 mutation that are described in this study underwent extensive cardiological evaluation and were listed by their postal codes. Results In 30 families, 14 different mutations were identified. Three TNNI3 mutations were found relatively frequently in both familial and non-familial cases of hypertrophic cardiomyopathy (HCM) or restrictive cardiomyopathy (RCM). Haplotype analysis showed that p. Arg145Trp and p.Ser166Phe are founder mutations in the Netherlands, while p.Glu209Ala is not. The majority of Dutch TNNI3 mutations were associated with a HCM phenotype. Mean age at diagnosis was 36.5 years. Mutations causing RCM occurred less frequently, but were identified in very young children with a poor prognosis. Conclusion In line with previously published data, we found TNNI3 mutations to be rare and associated with early onset and severe clinical presentation