Heterodimerization of apelin receptor and neurotensin receptor 1 induces phosphorylation of ERK1/2 and cell proliferation via Gαq-mediated mechanism

Dimerization of G protein-coupled receptors (GPCRs) is crucial for receptor function including agonist affinity, efficacy, trafficking and specificity of signal transduction, including G protein coupling. Emerging data suggest that the cardiovascular system is the main target of apelin, which exerts an overall neuroprotective role, and is a positive regulator of angiotensin-converting enzyme 2 (ACE2) in heart failure. Moreover, ACE2 cleaves off C-terminal residues of vasoactive peptides including apelin-13, and neurotensin that activate the apelin receptor (APJ) and neurotensin receptor 1 (NTSR1) respectively, that belong to the A class of GPCRs. Therefore, based on the similar mode of modification by ACE2 at peptide level, the homology at amino acid level and the capability of forming dimers with other GPCRs, we have been suggested that APJ and NTSR1 can form a functional heterodimer. Using co-immunoprecipitation, BRET and FRET, we provided conclusive evidence of heterodimerization between APJ and NTSR1 in a constitutive and induced form. Upon agonist stimulation, hetrodimerization enhanced ERK1/2 activation and increased proliferation via activation of Gq α-subunits. These novel data provide evidence for a physiological role of APJ/NTSR1 heterodimers in terms of ERK1/2 activation and increased intracellular calcium and induced cell proliferation and provide potential new pharmaceutical targets for cardiovascular disease. © 2014 The Authors

Consistency of Markov chain quasi-Monte Carlo on continuous state spaces

The random numbers driving Markov chain Monte Carlo (MCMC) simulation are usually modeled as independent U(0,1) random variables. Tribble [Markov chain Monte Carlo algorithms using completely uniformly distributed driving sequences (2007) Stanford Univ.] reports substantial improvements when those random numbers are replaced by carefully balanced inputs from completely uniformly distributed sequences. The previous theoretical justification for using anything other than i.i.d. U(0,1) points shows consistency for estimated means, but only applies for discrete stationary distributions. We extend those results to some MCMC algorithms for continuous stationary distributions. The main motivation is the search for quasi-Monte Carlo versions of MCMC. As a side benefit, the results also establish consistency for the usual method of using pseudo-random numbers in place of random ones.Comment: Published in at http://dx.doi.org/10.1214/10-AOS831 the Annals of Statistics (http://www.imstat.org/aos/) by the Institute of Mathematical Statistics (http://www.imstat.org

Large Chern Number Quantum Anomalous Hall Effect In Thin-film Topological Crystalline Insulators

Quantum anomalous Hall (QAH) insulators are two-dimensional (2D) insulating states exhibiting properties similar to those of quantum Hall states but without external magnetic field. They have quantized Hall conductance $\sigma^H=Ce^2/h$, where integer $C$ is called the Chern number, and represents the number of gapless edge modes. Recent experiments demonstrated that chromium doped thin-film (Bi,Sb)$_2$Te$_3$ is a QAH insulator with Chern number $C=\pm1$. Here we theoretically predict that thin-film topological crystalline insulators (TCI) can host various QAH phases, when doped by ferromagnetically ordered dopants. Any Chern number between $\pm4$ can, in principle, be reached as a result of the interplay between (a) the induced Zeeman field, depending on the magnetic doping concentration, (b) the structural distortion, either intrinsic or induced by a piezoelectric material through proximity effect and (c) the thickness of the thin film. The tunable Chern numbers found in TCI possess significant potential for ultra-low power information processing applications.Comment: References update

Thermodynamic consistency of liquid-gas lattice Boltzmann simulations

Lattice Boltzmann simulations have been very successful in simulating liquid-gas and other multi-phase fluid systems. However, the underlying second order analysis of the equation of motion has long been known to be insufficient to consistently derive the fourth order terms that are necessary to represent an extended interface. These same terms are also responsible for thermodynamic consistency, i.e. to obtain a true equilibrium solution with both a constant chemical potential and a constant pressure. In this article we present an equilibrium analysis of non-ideal lattice Boltzmann methods of sufficient order to identify those higher order terms that lead to a lack of thermodynamic consistency. We then introduce a thermodynamically consistent forcing method.Comment: 12 pages, 8 figure

Spinless Topological Insulators without Time-Reversal Symmetry

We explore the 32 crystallographic point groups and identify topological phases of matter with robust surface modes. For n =3,4 and 6 of the C_{nv} groups, we find the first-known 3D topological insulators without spin-orbit coupling, and with surface modes that are protected only by point groups, i.e., not needing time-reversal symmetry. To describe these C_{nv} systems, we introduce the notions of (a) a halved mirror chirality: an integer invariant which characterizes half-mirror-planes in the 3D Brillouin zone, and (b) a bent Chern number: the traditional TKNN invariant generalized to bent 2D manifolds. We find that a Weyl semimetallic phase intermediates two gapped phases with distinct halved chiralities