Coxsackie and adenovirus receptor is a modifier of cardiac conduction and arrhythmia vulnerability in the setting of myocardial ischemia.

OBJECTIVES: The aim of this study was to investigate the modulatory effect of the coxsackie and adenovirus receptor (CAR) on ventricular conduction and arrhythmia vulnerability in the setting of myocardial ischemia. BACKGROUND: A heritable component in the risk of ventricular fibrillation during myocardial infarction has been well established. A recent genome-wide association study of ventricular fibrillation during acute myocardial infarction led to the identification of a locus on chromosome 21q21 (rs2824292) in the vicinity of the CXADR gene. CXADR encodes the CAR, a cell adhesion molecule predominantly located at the intercalated disks of the cardiomyocyte. METHODS: The correlation between CAR transcript levels and rs2824292 genotype was investigated in human left ventricular samples. Electrophysiological studies and molecular analyses were performed using CAR haploinsufficient (CAR(+/-)) mice. RESULTS: In human left ventricular samples, the risk allele at the chr21q21 genome-wide association study locus was associated with lower CXADR messenger ribonucleic acid levels, suggesting that decreased cardiac levels of CAR predispose to ischemia-induced ventricular fibrillation. Hearts from CAR(+/-) mice displayed slowing of ventricular conduction in addition to an earlier onset of ventricular arrhythmias during the early phase of acute myocardial ischemia after ligation of the left anterior descending artery. Expression and distribution of connexin 43 were unaffected, but CAR(+/-) hearts displayed increased arrhythmia susceptibility on pharmacological electrical uncoupling. Patch-clamp analysis of isolated CAR(+/-) myocytes showed reduced sodium current magnitude specifically at the intercalated disk. Moreover, CAR coprecipitated with NaV1.5 in vitro, suggesting that CAR affects sodium channel function through a physical interaction with NaV1.5. CONCLUSIONS: CAR is a novel modifier of ventricular conduction and arrhythmia vulnerability in the setting of myocardial ischemia. Genetic determinants of arrhythmia susceptibility (such as CAR) may constitute future targets for risk stratification of potentially lethal ventricular arrhythmias in patients with coronary artery disease

Assessing bundles of ecosystem services from regional to landscape scale: Insights from the French Alps

Copyright © 2015 The Authors. Journal of Applied Ecology © 2015 British Ecological SocietyAssessments of ecosystem services (ES) and biodiversity (hereafter ecological parameters) provide a comprehensive view of the links between landscapes, ecosystem functioning and human well-being. The investigation of consistent associations between ecological parameters, called bundles, and of their links to landscape composition and structure is essential to inform management and policy, yet it is still in its infancy. We mapped over the French Alps an unprecedented array of 18 ecological parameters (16 ES and two biodiversity parameters) and explored their co-occurrence patterns underpinning the supply of multiple ecosystem services in landscapes. We followed a three-step analytical framework to i) detect the ES and biodiversity associations relevant at regional scale, ii) identify the clusters supplying consistent bundles of ES at subregional scale and iii) explore the links between landscape heterogeneity and ecological parameter associations at landscape scale. We used successive correlation coefficients, overlap values and self-organizing maps to characterize ecological bundles specific to given land cover types and geographical areas of varying biophysical characteristics and human uses at nested scales from regional to local. The joint analysis of land cover richness and ES gamma diversity demonstrated that local landscape heterogeneity alone did not imply compatibility across multiple ecosystem services, as some homogeneous landscape could supply multiple ecosystem services. Synthesis and applications. Bundles of ecosystem services and biodiversity parameters are shaped by the joint effects of biophysical characteristics and of human history. Due to spatial congruence and to underlying functional interdependencies, ecological parameters should be managed as bundles even when management targets specific objectives. Moreover, depending on the abiotic context, the supply of multiple ecosystem services can arise either from deliberate management in homogeneous landscapes or from spatial heterogeneity.ERAnet BiodivERsA project CONNECTFrench Agence Nationale pour la RechercheEU project VOLANT

Genetic Risk Factors for Atypical Femoral Fractures (AFFs): A Systematic Review

Atypical femoral fractures (AFFs) are uncommon and have been associated particularly with long-term antiresorptive therapy, including bisphosphonates. Although the pathogenesis of AFFs is unknown, their identification in bisphosphonate-naïve individuals and in monogenetic bone disorders has led to the hypothesis that genetic factors predispose to AFF. Our aim was to review and summarize the evidence for genetic factors in individuals with AFF. We conducted structured literature searches and hand-searching of conference abstracts/reference lists for key words relating to AFF and identified 2566 citations. Two individuals independently reviewed citations for (i) cases of AFF in monogenetic bone diseases and (ii) genetic studies in individuals with AFF. AFFs were reported in 23 individuals with the following 7 monogenetic bone disorders (gene): osteogenesis imperfecta (COL1A1/COL1A2), pycnodysostosis (CTSK), hypophosphatasia (ALPL), X-linked osteoporosis (PLS3), osteopetrosis, X-linked hypophosphatemia (PHEX), and osteoporosis pseudoglioma syndrome (LRP5). In 8 cases (35%), the monogenetic bone disorder was uncovered after the AFF occurred. Cases of bisphosphonate-naïve AFF were reported in pycnodysostosis, hypophosphatasia, osteopetrosis, X-linked hypophosphatemia, and osteoporosis pseudoglioma syndrome. A pilot study in 13 AFF patients and 268 controls identified a greater number of rare variants in AFF cases using exon array analysis. A whole-exome sequencing study in 3 sisters with AFFs showed, among 37 shared genetic variants, a p.Asp188Tyr mutation in the GGPS1 gene in the mevalonate pathway, critical to osteoclast function, which is also inhibited by bisphosphonates. Two studies completed targeted ALPL gene sequencing, an ALPL heterozygous mutation was found in 1 case of a cohort of 11 AFFs, whereas the second study comprising 10 AFF cases did not find mutations in ALPL. Targeted sequencing of ALPL, COL1A1, COL1A2, and SOX9 genes in 5 cases of AFF identified a variant in COL1A2 in 1 case. These findings suggest a genetic susceptibility for AFFs.

Constraints on the Electrical Charge Asymmetry of the Universe

We use the isotropy of the Cosmic Microwave Background to place stringent constraints on a possible electrical charge asymmetry of the universe. We find the excess charge per baryon to be $q_{e-p}<10^{-26}e$ in the case of a uniform distribution of charge, where $e$ is the charge of the electron. If the charge asymmetry is inhomogeneous, the constraints will depend on the spectral index, $n$, of the induced magnetic field and range from $q_{e-p}<5\times 10^{-20}e$ ($n=-2$) to $q_{e-p}<2\times 10^{-26}e$ ($n\geq 2$). If one could further assume that the charge asymmetries of individual particle species are not anti-correlated so as to cancel, this would imply, for photons, $q_\gamma< 10^{-35}e$; for neutrinos, $q_\nu<4\times10^{-35}e$; and for heavy (light) dark matter particles $q_{\rm dm}<4\times10^{-24}e$ ($q_{\rm dm}<4\times10^{-30}e$).Comment: New version to appear in JCA

Sneutrino Mixing Phenomena

In any model with nonzero Majorana neutrino masses, the sneutrino and antisneutrino of the supersymmetric extended theory mix. We outline the conditions under which sneutrino-antisneutrino mixing is experimentally observable. The mass-splitting of the sneutrino mass eigenstates and sneutrino oscillation phenomena are considered.Comment: 12 pages, revtex + axodraw, 1 figure included. Minor change

Evidence of two viscous relaxation processes in the collective dynamics of liquid lithium

New inelastic X-ray scattering experiments have been performed on liquid lithium in a wide wavevector range. With respect to the previous measurements, the instrumental resolution, improved up to 1.5 meV, allows to accurately investigate the dynamical processes determining the observed shape of the the dynamic structure factor, $S(Q,\omega)$. A detailed analysis of the lineshapes shows the co-existence of relaxation processes with both a slow and a fast characteristic timescales, and therefore that pictures of the relaxation mechanisms based on a simple viscoelastic model must be abandoned.Comment: 5 pages, 4 .PS figure

Density fluctuations and single-particle dynamics in liquid lithium

The single-particle and collective dynamical properties of liquid lithium have been evaluated at several thermodynamic states near the triple point. This is performed within the framework of mode-coupling theory, using a self-consistent scheme which, starting from the known static structure of the liquid, allows the theoretical calculation of several dynamical properties. Special attention is devoted to several aspects of the single-particle dynamics, which are discussed as a function of the thermodynamic state. The results are compared with those of Molecular Dynamics simulations and other theoretical approaches.Comment: 31 pages (in preprint format), 14 figures. Submitted to Phys. Rev.

Collective dynamics of liquid aluminum probed by Inelastic X-ray Scattering

An inelastic X-ray scattering experiment has been performed in liquid aluminum with the purpose of studying the collective excitations at wavevectors below the first sharp diffraction peak. The high instrumental resolution (up to 1.5 meV) allows an accurate investigation of the dynamical processes in this liquid metal on the basis of a generalized hydrodynamics framework. The outcoming results confirm the presence of a viscosity relaxation scenario ruled by a two timescale mechanism, as recently found in liquid lithium.Comment: 8 pages, 7 figure

Enhanced absorption Hanle effect on the Fg=F->Fe=F+1 closed transitions

We analyse the Hanle effect on a closed $F_g\to F_e=F_g+1$ transition. Two configurations are examined, for linear- and circular-polarized laser radiation, with the applied magnetic field collinear to the laser light wavevector. We describe the peculiarities of the Hanle signal for linearly-polarized laser excitation, characterized by narrow bright resonances at low laser intensities. The mechanism behind this effect is identified, and numerical solutions for the optical Bloch equations are presented for different transitions.Comment: to be published in J. Opt. B, special issue on Quantum Coherence and Entanglement (February 2001