Extracellular Protons Inhibit Charge Immobilization in the Cardiac Voltage-Gated Sodium Channel

AbstractLow pH depolarizes the voltage-dependence of cardiac voltage-gated sodium (NaV1.5) channel activation and fast inactivation and destabilizes the fast-inactivated state. The molecular basis for these changes in protein behavior has not been reported. We hypothesized that changes in the kinetics of voltage sensor movement may destabilize the fast-inactivated state in NaV1.5. To test this idea, we recorded NaV1.5 gating currents in Xenopus oocytes using a cut-open voltage-clamp with extracellular solution titrated to either pH 7.4 or pH 6.0. Reducing extracellular pH significantly depolarized the voltage-dependence of both the QON/V and QOFF/V curves, and reduced the total charge immobilized during depolarization. We conclude that destabilized fast-inactivation and reduced charge immobilization in NaV1.5 at low pH are functionally related effects

Implementation of a wind-farm specific operational wave forecasting tool in the North-Sea: methods and forcing sensitivity

Water Qualit

Combinations of DIPs and Dprs control organization of olfactory receptor neuron terminals in Drosophila

In Drosophila, 50 classes of olfactory receptor neurons (ORNs) connect to 50 class-specific and uniquely positioned glomeruli in the antennal lobe. Despite the identification of cell surface receptors regulating axon guidance, how ORN axons sort to form 50 stereotypical glomeruli remains unclear. Here we show that the heterophilic cell adhesion proteins, DIPs and Dprs, are expressed in ORNs during glomerular formation. Many ORN classes express a unique combination of DIPs/dprs, with neurons of the same class expressing interacting partners, suggesting a role in class-specific self-adhesion between ORN axons. Analysis of DIP/Dpr expression revealed that ORNs that target neighboring glomeruli have different combinations, and ORNs with very similar DIP/Dpr combinations can project to distant glomeruli in the antennal lobe. DIP/Dpr profiles are dynamic during development and correlate with sensilla type lineage for some ORN classes. Perturbations of DIP/dpr gene function result in local projection defects of ORN axons and glomerular positioning, without altering correct matching of ORNs with their target neurons. Our results suggest that context-dependent differential adhesion through DIP/Dpr combinations regulate self-adhesion and sort ORN axons into uniquely positioned glomeruli

Selected nucleon form factors and a composite scalar diquark

A covariant, composite scalar diquark, Fadde'ev amplitude model for the nucleon is used to calculate pseudoscalar, isoscalar- and isovector-vector, axial-vector and scalar nucleon form factors. The last yields the nucleon sigma-term and on-shell sigma-nucleon coupling. The calculated form factors are soft, and the couplings are generally in good agreement with experiment and other determinations. Elements in the dressed-quark-axial-vector vertex that are not constrained by the Ward-Takahashi identity contribute ~20% to the magnitude of g_A. The calculation of the nucleon sigma-term elucidates the only unambiguous means of extrapolating meson-nucleon couplings off the meson mass-shell.Comment: 12 pages, REVTEX, 5 figures, epsfi

High-energy gamma-ray emission from the inner jet of LS I+61 303: the hadronic contribution revisited

LS I+61 303 has been detected by the Cherenkov telescope MAGIC at very high energies, presenting a variable flux along the orbital motion with a maximum clearly separated from the periastron passage. In the light of the new observational constraints, we revisit the discussion of the production of high-energy gamma rays from particle interactions in the inner jet of this system. The hadronic contribution could represent a major fraction of the TeV emission detected from this source. The spectral energy distribution resulting from p-p interactions is recalculated. Opacity effects introduced by the photon fields of the primary star and the stellar decretion disk are shown to be essential in shaping the high-energy gamma-ray light curve at energies close to 200 GeV. We also present results of Monte Carlo simulations of the electromagnetic cascades developed very close to the periastron passage. We conclude that a hadronic microquasar model for the gamma-ray emission in LS I +61 303 can reproduce the main features of its observed high-energy gamma-ray flux.Comment: 6 pages. Sligth improvements made. Accepted version by Astrophysics and Space Scienc

Reduction of Couplings in Quantum Field Theories with applications in Finite Theories and the MSSM

We apply the method of reduction of couplings in a Finite Unified Theory and in the MSSM. The method consists on searching for renormalization group invariant relations among couplings of a renormalizable theory holding to all orders in perturbation theory. It has a remarkable predictive power since, at the unification scale, it leads to relations between gauge and Yukawa couplings in the dimensionless sectors and relations involving the trilinear terms and the Yukawa couplings, as well as a sum rule among the scalar masses and the unified gaugino mass in the soft breaking sector. In both the MSSM and the FUT model we predict the masses of the top and bottom quarks and the light Higgs in remarkable agreement with the experiment. Furthermore we also predict the masses of the other Higgses, as well as the supersymmetric spectrum, both being in very confortable agreement with the LHC bounds on Higgs and supersymmetric particles.Comment: 18 pages, 4 figures. To appear in the proceedings of LT-10, Varna. Based on invited talks given at: LT-10, Varna; PACT-2013, Madrid; SQS'2013, Dubna; CORFU 2013, Corfu, and in several invited seminar

Superconformal Ward Identities and N=2 Yang-Mills Theory

A reformulation of the superconformal Ward identities that combines all the superconformal currents and the associated parameters in one multiplet is given for theories with rigid N=1 or N=2 supersymmetry. This form of the Ward Identities is applied to spontaneously broken N=2 Yang-Mills theory and used to derive a condition on the low energy effective action. This condition is satisfied by the solution proposed by Seiberg and Witten.Comment: 25 pages, plain Te

Evaluation of bioadhesive capacity and immunoadjuvant properties of vitamin B(12)-Gantrez nanoparticles.

PURPOSE: To design bioadhesive Gantrez AN (poly[methyl vinyl ether-co-maleic anhydride], PVM/MA) nanoparticles (NP) coated with Vitamin B12 (Vit B12), and investigate their application in oral antigen delivery. METHODS: The association of Vit B12 to Gantrez AN nanoparticles was performed by the direct attachment of reactive Vit B12 to the surface of the nanoparticles (NPB), or linking to the copolymer chains in dimethylformamide prior to NP formation (NPBDMF). Nanoparticles were characterized by measuring the size, zeta potential, Vit B12 association efficacy, and stability of Vit B12 on the surface of the nanoparticles. In vivo bioadhesion study was performed by the oral administration of fluorescently-labeled nanoparticle formulations to rats. Both systemic and mucosal immune responses were evaluated after oral and subcutaneous immunization with ovalbumin (OVA) containing Vit B12-coated nanoparticles. RESULTS: The Vit B12 nanoparticles displayed homogenous size distribution with a mean diameter of about 200 nm and a negative surface charge. The association efficiency of Vit B12 to NPB-DMF formulation was about two times higher than to the NPB, showing also a higher surface stability of Vit B12. The bioadhesion study demonstrated that NPB-DMF had an important tropism to the distal portions of the gut, which was about 2 and 3.5 times higher than the tropism observed for NPB and control NP, respectively (P< 0.05). Oral administration of OVA-NPB-DMF induced also stronger and more balanced serum anti-OVA titers of IgG2a (Th1) and IgG1 (Th2) compared to control OVA-NP. In addition, oral immunization with OVA-NPB-DMF induced a higher mucosal IgA response than subcutaneous administration. CONCLUSIONS: These results indicate the benefits of bioadhesive Vit B12-coated nanoparticles in oral antigen delivery eliciting systemic and mucosal immune response

The twin paradox and Mach's principle

The problem of absolute motion in the context of the twin paradox is discussed. It is shown that the various versions of the clock paradox feature some aspects which Mach might have been appreciated. However, the ultimate cause of the behavior of the clocks must be attributed to the autonomous status of spacetime, thereby proving the relational program advocated by Mach as impracticable.Comment: Latex2e, 11 pages, 6 figures, 33 references, no tables. Accepted for publication in The European Physical Journal PLUS (EPJ PLUS