Genetic Analysis of Variants of the MYH6 Gene Promoter in Congenital Atrial Septal Defects

Background:Atrial septal defect(ASD)is one of the common congenital heart diseases.The MYH6 gene has a critical role in cardiac development but the role of MYH6 promoter variants in patients with ASD has not been explored.Methods:In 613 subjects including 320 ASD patients,we investigated the MYH6 gene promoter variants and verified the effect on gene expression by using cellular functional experiments and bioinformatics analysis.Results:Eleven variants were identified in the MYH6 gene promoter,of which four variants were found only in ASD patients,and two variants(g.3434G>C and g.4524C>T)were identified for the first time.Cellular functional experiments indicated that all four variants reduced the transcriptional activity of the MYH6 gene promoter(p<0.05).Subsequent analysis through the JASPAR(A database of transcription factor binding profiles)suggests that these variants may alter transcription factor binding sites,which may in turn lead to changes in myocardin subunit expression and ASD formation.Conclusions:Our study for the first time focuses on variants in the promoter region of the MYH6 gene in Chinese patients with ASD and the discovered variants have functional significance.The study provides new insights in the role of the MYH6 gene promoter region to better understand the genetic basis of ASD formation and facilitates clinical diagnosis.

LES prediction of space-time correlations in turbulent shear flows

We compare the space-time correlations calculated from direct numerical simulation(DNS) and large-eddy simulation(LES) of turbulent channel flows.It is found from the comparisons that the LES with an eddy-viscosity subgrid scale(SGS) model over-predicts the space-time correlations than the DNS.The overpredictions are further quantified by the integral scales of directional correlations and convection velocities.A physical argument for the overprediction is provided that the eddy-viscosity SGS model alone does not includes the backscatter effects although it correctly represents the energy dissipations of SGS motions.This argument is confirmed by the recently developed elliptic model for space-time correlations in turbulent shear flows.It suggests that enstrophy is crucial to the LES prediction of spacetime correlations.The random forcing models and stochastic SGS models are proposed to overcome the overpredictions on space-time correlations.

Underlying principle of efficient propulsion in flexible plunging foils

Passive flexibility was found to enhance propulsive efficiency in swimming animals.In this study,we numerically investigate the roles of structural resonance and hydrodynamic wake resonance in optimizing efficiency of a flexible plunging foil.The results indicates that(1)optimal efficiency is not necessarily achieved when the driving frequency matches the structural eigenfrequency;(2)optimal efficiency always occurs when the driving frequency matches the wake resonant frequency of the time averaged velocity profile.Thus,the underlying principle of efficient propulsion in flexible plunging foil is the hydrodynamic wake resonance,rather than the structural resonance.In addition,we also found that whether the efficiency can be optimized at the structural resonant point depends on the strength of the leading edge vortex relative to that of the trailing edge vortex.The result of this work provides new insights into the role of passive flexibility in flapping-based propulsion.

The spanwise spectra in wall-bounded turbulence

The pre-multiplied spanwise energy spectra of streamwise velocity fluctuations are investigated in this paper. Two distinct spectral peaks in the spanwise spectra are observed in low-Reynolds-number wall-bounded turbulence.The spectra are calculated from direct numerical simulation(DNS) of turbulent channel flows and zero-pressure-gradient boundary layer flows. These two peaks locate in the nearwall and outer regions and are referred to as the inner peak and the outer peak, respectively. This result implies that the streamwise velocity fluctuations can be separated into large and small scales in the spanwise direction even though the friction Reynolds number Reτ can be as low as 1000. The properties of the inner and outer peaks in the spanwise spectra are analyzed. The locations of the inner peak are invariant over a range of Reynolds numbers. However, the locations of the outer peak are associated with the Reynolds number,which are much higher than those of the outer peak of the pre-multiplied streamwise energy spectra of the streamwise velocity.

Wall-modeled large-eddy simulation of noise generated by turbulence around an appended axisymmetric body of revolution

The directivity of the noise generated by turbulent flows around an underwater vehicle(the fully appended SUBOFF body)is investigated numerically,where the turbulent flows are simulated by using the large eddy simulation(LES)with a non-equilibrium wall model and the noise is calculated by using the Ffowcs Williams and Hawking formulation.The wall-modeled LES reproduces the features of turbulent flows around SUBOFF,such as the attached boundary layers around the hull,separated vortices from appendages and the wrapped vortices in wakes.The coefficients and power spectral density of the wall pressures obtained are in agreement with the previous numerical results and experimental measurements.It is found that the constructive and destructive interferences of lift and side-force dipoles lead to the deviations of the directivities of instantaneous sound pressures from the lift directions.This is different from noise generated by flows around a circular cylinder,where lift dipoles dominate the radiated noise.

Role of the PPAR pathway in atrial fibrillation associated with heart valve disease:transcriptomics and proteomics in human atrial tissue

Dear Editor,Atrial fibrillation(AF)is one of the most common cardiac arrhythmias.Its prevalence increases significantly with age.It is well known that patients with AF are associated with an increased risk of stroke,1 and AF is a great economic burden on the worldwide socioeconomic system.Previous studies have shown that electrical,contractile,and structural remodeling play key roles in the onset and maintenance of AF.2 Other possible pathogenesis mechanisms include calcium handling abnormalities,autonomic imbalance,and genetic factors.3 However,the exact molecular mechanism associated with AF remains unknown.