Novel GATA5 loss-of-function mutations underlie familial atrial fibrillation

OBJECTIVE: This study aimed to identify novel GATA5 mutations that underlie familial atrial fibrillation. METHODS: A total of 110 unrelated patients with familial atrial fibrillation and 200 unrelated, ethnically matched healthy controls were recruited. The entire coding region of the GATA5 gene was sequenced in 110 atrial fibrillation probands. The available relatives of the mutation carriers and 200 controls were subsequently genotyped for the identified mutations. The functional effect of the mutated GATA5 was characterized using a luciferase reporter assay system. RESULTS: Two novel heterozygous GATA5 mutations (p.Y138F and p.C210G) were identified in two of the 110 unrelated atrial fibrillation families. These missense mutations cosegregated with AF in the families and were absent in the 400 control chromosomes. A cross-species alignment of GATA5 protein sequence showed that the altered amino acids were completely conserved evolutionarily. A functional analysis revealed that the mutant GATA5 proteins were associated with significantly decreased transcriptional activation when compared with their wild-type counterpart. CONCLUSION: The findings expand the spectrum of GATA5 mutations linked to AF and provide novel insights into the molecular mechanism involved in the pathogenesis of atrial fibrillation, suggesting potential implications for the early prophylaxis and personalized treatment of this common arrhythmia

3,5-Dihydr­oxy-N′-[(2-hydr­oxy-1-naph­thyl)methyl­ene]benzohydrazide

In the title compound, C18H14N2O4, the dihedral angle between the benzene ring and the naphthyl ring system is 10.1 (2)°. The mol­ecule is nearly planar, with a mean deviation from the plane of 0.141 (2) Å for 24 non-H atoms. An intra­molecular O—H⋯N hydrogen bond forms a pseudo-6-membered ring and the mol­ecules are linked into sheets by inter­molecular N—H⋯O and O—H⋯O hydrogen bonds

1-[3-(4-Methoxy­phen­yl)-6-methyl-1,6-dihydro-1,2,4,5-tetra­zin-1-yl]propanone

In the title compound, C13H16N4O2, the central tetra­zine ring adopts an unsymmetrical boat conformation with the two C atoms as flagpoles. This compound can be considered as having homoaromaticity

A Genetic Algorithm for Locating the Multiscale Critical Slip Surface in Jointed Rock Mass Slopes

The joints have great influence on the strength of jointed rock mass and lead to the multiscale, nonhomogeneous, and anisotropic characteristics. In order to consider these effects, a new model based on a genetic algorithm is proposed for locating the critical slip surface (CSS) in jointed rock mass slope (JRMS) from its stress field. A finite element method (FEM) was employed to analyze the stress field. A method of calculating the mechanical persistence ratio (MPR) was used. The calculated multiscale and anisotropic characteristics of the MPR were used in the fitness function of genetic algorithm (GA) to calculate the factor of safety. The GA was used to solve optimization problems of JRMS stability. Some numerical examples were given. The results show that the multiscale and anisotropic characteristics of the MPR played an important role in locating the CSS in JRMS. The proposed model calculated the CSS and the factor of safety of the slope with satisfactory precision