Ahnak1 modulates L-type Ca(2+) channel inactivation of rodent cardiomyocytes

Ahnak1, a giant 700 kDa protein, has been implicated in Ca(2+) signalling in various cells. Previous work suggested that the interaction between ahnak1 and Cavbeta(2) subunit plays a role in L-type Ca(2+) current (I (CaL)) regulation. Here, we performed structure-function studies with the most C-terminal domain of ahnak1 (188 amino acids) containing a PxxP consensus motif (designated as 188-PSTP) using ventricular cardiomyocytes isolated from rats, wild-type (WT) mice and ahnak1-deficient mice. In vitro binding studies revealed that 188-PSTP conferred high-affinity binding to Cavbeta(2) (K (d) approximately 60 nM). Replacement of proline residues by alanines (188-ASTA) decreased Cavbeta(2) affinity about 20-fold. Both 188-PSTP and 188-ASTA were functional in ahnak1-expressing rat and mouse cardiomyocytes during whole-cell patch clamp. Upon intracellular application, they increased the net Ca(2+) influx by enhancing I (CaL) density and/or increasing I (CaL) inactivation time course without altering voltage dependency. Specifically, 188-ASTA, which failed to affect I (CaL) density, markedly slowed I (CaL) inactivation resulting in a 50-70% increase in transported Ca(2+) during a 0 mV depolarising pulse. Both ahnak1 fragments also slowed current inactivation with Ba(2+) as charge carrier. By contrast, neither 188-PSTP nor 188-ASTA affected any I (CaL) characteristics in ahnak1-deficient mouse cardiomyocytes. Our results indicate that the presence of endogenous ahnak1 is required for tuning the voltage-dependent component of I (CaL) inactivation by ahnak1 fragments. We suggest that ahnak1 modulates the accessibility of molecular determinants in Cavbeta(2) and/or scaffolds selectively different beta-subunit isoforms in the heart

On Nonperturbative Calculations in Quantum Electrodynamics

A new approach to nonperturbative calculations in quantum electrodynamics is proposed. The approach is based on a regular iteration scheme for solution of Schwinger-Dyson equations for generating functional of Green functions. The approach allows one to take into account the gauge invariance conditions (Ward identities) and to perform the renormalization program. The iteration scheme can be realized in two versions. The first one ("perturbative vacuum") corresponds to chain summation in the diagram language. In this version in four-dimensional theory the non-physical singularity (Landau pole) arises which leads to the triviality of the renormalized theory. The second version ("nonperturbative vacuum") corresponds to ladder summation and permits one to make non-perturbative calculations of physical quantities in spite of the triviality problem. For chiral-symmetrical leading approximation two terms of the expansion of the first-step vertex function over photon momentum are calculated. A formula for anomalous magnetic moment is obtained. A problem of dynamical chiral symmetry breaking (DCSB) is considered, the calculations are performed for renormalized theory in Minkowsky space. In the strong coupling region DCSB-solutions arise. For the renormalized theory a DCSB-solution is also possible in the weak coupling region but with a subsidiary condition on the value of $\alpha$.Comment: 31 pages, Plain LaTex, no figures. Journal version: some discussion and refs. are adde

Second Order Dissipative Fluid Dynamics for Ultra-Relativistic Nuclear Collisions

The M\"uller-Israel-Stewart second order theory of relativistic imperfect fluids based on Grad's moment method is used to study the expansion of hot matter produced in ultra-relativistic heavy ion collisions. The temperature evolution is investigated in the framework of the Bjorken boost-invariant scaling limit. The results of these second-order theories are compared to those of first-order theories due to Eckart and to Landau and Lifshitz and those of zeroth order (perfect fluid) due to Euler.Comment: 5 pages, 4 figures, size of y-axis tick marks for Figs. 3 and 4 fixe

Alkaloids, Diarylheptanoid and Naphthalene Carboxylic Acid Ester from Rhoiptelea chiliantha

Two pyrrolidine alkaloids (1, 2) were isolated from the fruits of Rhoiptelea chiliantha DIEL et HAND.-MAZZ. (Rhoipteleaceae). A diphenyl ether-type diarylheptanoid (3), and a naphthalene carboxylic acid methyl ester (4) which is biogenetically-related to juglone were isolated from the branches of the same plant. Their chemical structures were elucidated on the basis of spectroscopic analysis and chemical evidence

Holographic Roberge-Weiss Transitions

We investigate N=4 SYM coupled to fundamental flavours at nonzero imaginary quark chemical potential in the strong coupling and large N limit, using gauge/gravity duality applied to the D3-D7 system, treating flavours in the probe approximation. The interplay between Z(N) symmetry and the imaginary chemical potential yields a series of first-order Roberge-Weiss transitions. An additional thermal transition separates phases where quarks are bound/unbound into mesons. This results in a set of Roberge-Weiss endpoints: we establish that these are triple points, determine the Roberge-Weiss temperature, give the curvature of the phase boundaries and confirm that the theory is analytic in mu^2 when mu^2~0.Comment: 37 pages, 13 figures; minor comments added, to appear in JHE

Association of Tannins and Related Polyphenols with the Cyclic Peptide Gramicidin S

The association of 10 different tannins and related polyphenols with gramicidin S, a cyclic peptide having a rigid β-turn structure, has been examined using 1H-NMR spectroscopy. In the presence of pentagalloylglucose and epigallocatechin-3-O-gallate, the proton signals due to proline and the adjacent phenylalanine moieties selectively shifted to up field, suggesting a regioselective association with the β-turn structure. The association was also supported by the observation of intermolecular nuclear Overhauser effects between epigallocatechin-3-O-gallate and the peptide. In contrast, ellagitannins, biogenetically derived from pentagalloylglucose, showed small and non-selective chemical shift changes, suggesting that interaction with these tannins is relatively weak. The hydrophobicity of the tannin molecules and the steric hindrance of the interaction site are thought to be important in the association

Iridoids and Anthraquinones from the Malaysian Medicinal Plant, Saprosma scortechinii (Rubiaceae)

A further investigation of the leaves and stems of Saprosma scortechinii afforded 13 compounds, of which 10 are new compounds. These were elucidated as the bis-iridoid glucosides, saprosmosides G (1) and H (2), the iridoid glucoside, 6-O-epi-acetylscandoside (3), and the anthraquinones, 1-methoxy-3-hydroxy-2-carbomethoxy-9,10-anthraquinone (4), 1-methoxy-3-hydroxy-2-carbomethoxy-9,10-anthraquinone 3-O-β-primeveroside (5), 1,3-dihydroxy-2-carbomethoxy-9,10-anthraquinone 3-O-β-primeveroside (6), 1,3,6-trihydroxy-2-methoxymethyl-9,10-anthraquinone (7), 1-methoxy-3,6-dihydroxy-2-hydroxymethyl-9,10-anthraquinone (8), 1,3,6-trihydroxy-2-hydroxymethyl-9,10-anthraquinone 3-O-β-primeveroside (9), and 3,6-dihydroxy-2-hydroxymethyl-9,10-anthraquinone (10). Structure assignments for all compounds were established by means of mass and NMR spectroscopies, chemical methods, and comparison with published data. The new anthraquinones were derivatives of munjistin and lucidin