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A systematic study of electric transport through thin (2-8 nm) CoFe2O4 films deposited on epitaxial SrRuO3 bottom electrodes was performed by conducting atomic force microscopy (CAFM). Experimental procedures to investigate transport through thin insulating films by CAFM are critically revised, and the potential of CoFe2O4 films for the use as spin-filtering barriers is assessed. It is concluded that, at room-temperature, a non-tunnel channel significantly contributes to the electric transport, thus limiting the spin-filtering efficiency. [ABSTRACT FROM AUTHOR]

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a rare cardiac disease characterized by myocardial fibrofatty replacement, which can lead to sudden death. Previous studies have described a reduction of plakoglobin (PKG) protein at the level of intercalated disks as the hallmark of ARVC. The main objective of this study was to investigate the involvement of desmosome mutations in the histological phenotype of ARVC. We performed a genetic analysis of ARVC cases, and histological characterization of ARVC heart tissue samples. We genetically analyzed 48 ARVC cases distributed into two groups: 42 human tissue heart samples with conclusive diagnoses of ARVC after post-mortem examination; and six DNA samples from peripheral blood of living patients who were clinically diagnosed. Sequenom MassARRAY analysis revealed three ARVC-associated variants in three patients in 42 tissue samples (7.14 %). Three individuals carried one single pathogenic mutation, p.R811S _ PKP2, p.S824L_ DSC2, and p.T526M_ PKP2 in postmortem samples. In the living patients group, Sequenom MassARRAY revealed no mutation, however, later Sanger sequencing analysis identified three ARVC mutations in 2/6 patients not included in the Sequenom design. In post-mortem tissue samples we performed immunohistochemical labeling for desmosomal proteins and Connexin 43. This study revealed that PKP2 carriers present either absent or clearly reduced PKG immunolabeling, while the DSC2 carrier showed PKG immunolabeling similar to control samples. Immunolabeling for Cx43 did not show any differences compared to controls. The present Sequenom MassARRAY design is a useful tool for post-mortem genetic diagnosis of ARVC. Plakoglobin reduction occurs at intercalated disks, while other desmosome proteins and Cx43 remain unaltered. [ABSTRACT FROM AUTHOR]

Long QT Syndrome (LQTS) is a rare inherited cardiac disorder with a high risk of sudden cardiac death in a structurally normal heart. To date, pathogenic mutations have been described as responsible for approximately 70-75% of LQTS patients, mainly in ion channel genes. Mutations in genes encoding the sodium channel α subunit or other regulatory proteins, affecting cardiac sodium current, have been previously related to LQTS. Five sodium channel β subunits have been identified, which are encoded by four genes (SCN1B-4B). Pathogenic mutations in the SCN4B gene, but not in other β subunits, have been reported in LQTS. We tested whether mutations in SCN1B-4B could be responsible for LQTS in patients without mutations in the common LQTS-related genes.We screened for mutations in SCN1B-4B genes in 30 non-related patients clinically diagnosed with LQTS carrying no mutations in the major LQTS-related genes. The screening revealed a novel mutation in the SCN1B gene in an 8-year-old boy. The base change resulted in an amino acid variation from proline to threonine in the alternative C-terminus of the sodium channel β1 subunit (β1b).Using the patch clamp technique, we measured sodium current density, and Nav1.5 gaiting properties, in HEK cells transiently transfected with Nav1.5 and β1b subunits. Our electrophysiological analysis revealed that the mutant β1b altered Nav1.5 function by shifting the window current to negative potentials, increasing recovery from inactivation, decreasing slow inactivation, and increasing late sodium current. In addition, we recorded action potentials from mouse atrial cardiomyocytes, HL-1 cells, transfected with β1b subunits. These experiments revealed that the action potential duration significantly increased when the mutant β1b was overexpressed compared to β1bWT.These findings suggest that the mutation in β1b could explain the LQTS in our patient, revealing SCN1Bb as a new susceptibility gene for LQTS. Our results confirm the importance of sodium channel β subunits in the modulation of cardiac sodium channel. In addition, they highlight the need for further investigation to detect new candidate genes underlying the LQTS patients that currently remain without genetic diagnosis. [ABSTRACT FROM AUTHOR]