Rabbit Anti-Human JUP polyclonal antibody

Mutations in the lamin A/C gene (LMNA) were associated with dilated cardiomyopathy (DCM) and, recently, were related to severe forms of arrhythmogenic right ventricular cardiomyopathy (ARVC). Both genetic and phenotypic overlap between DCM and ARVC was observed; molecular pathomechanisms leading to the cardiac phenotypes caused by LMNA mutations are not yet fully elucidated. This study involved a large Italian family, spanning 4 generations, with arrhythmogenic cardiomyopathy of different phenotypes, including ARVC, DCM, system conduction defects, ventricular arrhythmias, and sudden cardiac death. Mutation screening of LMNA and ARVC-related genes PKP2, DSP, DSG2, DSC2, JUP, and CTNNA3 was performed. We identified a novel heterozygous mutation (c.418_438dup) in LMNA gene exon 2, occurring in a highly conserved protein domain across several species. This newly identified variant was not found in 250 ethnically-matched control subjects. Genotype-phenotype correlation studies suggested a co-segregation of the LMNA mutation with the disease phenotype and an incomplete and age-related penetrance. Based on clinical, pedigree, and molecular genetic data, this mutation was considered likely disease-causing. To clarify its potential pathophysiologic impact, functional characterization of this LMNA mutant was performed in cultured cardiomyocytes expressing EGFP-tagged wild-type and mutated LMNA constructs, and indicated an increased nuclear envelope fragility, leading to stress-induced apoptosis as the main pathogenetic mechanism. This study further expands the role of the LMNA gene in the pathogenesis of cardiac laminopathies, suggesting that LMNA should be included in mutation screening of patients with suspected arrhythmogenic cardiomyopathy, particularly when they have ECG evidence for conduction defects. The combination of clinical, genetic, and functional data contribute insights into the pathogenesis of this form of life-threatening arrhythmogenic cardiac laminopathy.

We analyze the combined Spitzer and ground-based data for OGLE-2017-BLG-1140 and show that the event was generated by a Jupiter-class (m(p) similar or equal to 1.6 M-Jup) planet orbiting a mid-late M dwarf (M similar or equal to 0.2 M-circle dot) that lies DLS similar or equal to 1.0 kpc in the foreground of the microlensed Galactic-bar source star. The planet-host projected separation is a(perpendicular to) similar or equal to 1.0 au, i.e., well beyond the snow line. By measuring the source proper motion mu(s) from ongoing long-term OGLE imaging and combining this with the lens-source relative proper motion mu(rel) derived from the microlensing solution, we show that the lens proper motion mu(l) = mu(rel) + mu(s) consistent with the lens lying in the Galactic disk, although a bulge lens is not ruled out. We show that while the Spitzer and ground-based data are comparably well fitted by planetary (i.e., binary-lens (2L1S)) and binary-source (1L2S) models, the combination of Spitzer and ground-based data decisively favors the planetary model. This is a new channel to resolve the 2L1S/1L2S degeneracy, which can be difficult to break in some cases.