β-adrenergic-mediated dynamic augmentation of sarcolemmal CaV 1.2 clustering and co-operativity in ventricular myocytes.

Key pointsPrevailing dogma holds that activation of the β-adrenergic receptor/cAMP/protein kinase A signalling pathway leads to enhanced L-type CaV 1.2 channel activity, resulting in increased Ca2+ influx into ventricular myocytes and a positive inotropic response. However, the full mechanistic and molecular details underlying this phenomenon are incompletely understood. CaV 1.2 channel clusters decorate T-tubule sarcolemmas of ventricular myocytes. Within clusters, nanometer proximity between channels permits Ca2+ -dependent co-operative gating behaviour mediated by physical interactions between adjacent channel C-terminal tails. We report that stimulation of cardiomyocytes with isoproterenol, evokes dynamic, protein kinase A-dependent augmentation of CaV 1.2 channel abundance along cardiomyocyte T-tubules, resulting in the appearance of channel 'super-clusters', and enhanced channel co-operativity that amplifies Ca2+ influx. On the basis of these data, we suggest a new model in which a sub-sarcolemmal pool of pre-synthesized CaV 1.2 channels resides in cardiomyocytes and can be mobilized to the membrane in times of high haemodynamic or metabolic demand, to tune excitation-contraction coupling.AbstractVoltage-dependent L-type CaV 1.2 channels play an indispensable role in cardiac excitation-contraction coupling. Activation of the β-adrenergic receptor (βAR)/cAMP/protein kinase A (PKA) signalling pathway leads to enhanced CaV 1.2 activity, resulting in increased Ca2+ influx into ventricular myocytes and a positive inotropic response. CaV 1.2 channels exhibit a clustered distribution along the T-tubule sarcolemma of ventricular myocytes where nanometer proximity between channels permits Ca2+ -dependent co-operative gating behaviour mediated by dynamic, physical, allosteric interactions between adjacent channel C-terminal tails. This amplifies Ca2+ influx and augments myocyte Ca2+ transient and contraction amplitudes. We investigated whether βAR signalling could alter CaV 1.2 channel clustering to facilitate co-operative channel interactions and elevate Ca2+ influx in ventricular myocytes. Bimolecular fluorescence complementation experiments reveal that the βAR agonist, isoproterenol (ISO), promotes enhanced CaV 1.2-CaV 1.2 physical interactions. Super-resolution nanoscopy and dynamic channel tracking indicate that these interactions are expedited by enhanced spatial proximity between channels, resulting in the appearance of CaV 1.2 'super-clusters' along the z-lines of ISO-stimulated cardiomyocytes. The mechanism that leads to super-cluster formation involves rapid, dynamic augmentation of sarcolemmal CaV 1.2 channel abundance after ISO application. Optical and electrophysiological single channel recordings confirm that these newly inserted channels are functional and contribute to overt co-operative gating behaviour of CaV 1.2 channels in ISO stimulated myocytes. The results of the present study reveal a new facet of βAR-mediated regulation of CaV 1.2 channels in the heart and support the novel concept that a pre-synthesized pool of sub-sarcolemmal CaV 1.2 channel-containing vesicles/endosomes resides in cardiomyocytes and can be mobilized to the sarcolemma to tune excitation-contraction coupling to meet metabolic and/or haemodynamic demands

Self-consistent symmetries in the proton-neutron Hartree-Fock-Bogoliubov approach

Symmetry properties of densities and mean fields appearing in the nuclear Density Functional Theory with pairing are studied. We consider energy functionals that depend only on local densities and their derivatives. The most important self-consistent symmetries are discussed: spherical, axial, space-inversion, and mirror symmetries. In each case, the consequences of breaking or conserving the time-reversal and/or proton-neutron symmetries are discussed and summarized in a tabulated form, useful in practical applications.Comment: 26 RevTex pages, 1 eps figure, 9 tables, submitted to Physical Review

Algebro-Geometric Solutions of the Boussinesq Hierarchy

We continue a recently developed systematic approach to the Bousinesq (Bsq) hierarchy and its algebro-geometric solutions. Our formalism includes a recursive construction of Lax pairs and establishes associated Burchnall-Chaundy curves, Baker-Akhiezer functions and Dubrovin-type equations for analogs of Dirichlet and Neumann divisors. The principal aim of this paper is a detailed theta function representation of all algebro-geometric quasi-periodic solutions and related quantities of the Bsq hierarchy.Comment: LaTeX, 48 page

Neurology

Contains reports on seven research projects.U. S. Public Health Service (B-3055-3,U. S. Public Health Service (B-3090-3)U. S. Public Health Service (38101-22)Office of Naval Research (Nonr-1841 (70))Air Force (AF33(616)-7588)Air Force (AFAOSR 155-63)Army Chemical Corps (DA-18-108-405-Cml-942)National Institutes of Health (Grant MH-04734-03

Elliptic Solitons and Groebner Bases

We consider the solution of spectral problems with elliptic coefficients in the framework of the Hermite ansatz. We show that the search for exactly solvable potentials and their spectral characteristics is reduced to a system of polynomial equations solvable by the Gr\"obner bases method and others. New integrable potentials and corresponding solutions of the Sawada-Kotera, Kaup-Kupershmidt, Boussinesq equations and others are found.Comment: 18 pages, no figures, LaTeX'2

Dynamical Tide in Solar-Type Binaries

Circularization of late-type main-sequence binaries is usually attributed to turbulent convection, while that of early-type binaries is explained by resonant excitation of g modes. We show that the latter mechanism operates in solar-type stars also and is at least as effective as convection, despite inefficient damping of g modes in the radiative core. The maximum period at which this mechanism can circularize a binary composed of solar-type stars in 10 Gyr is as low as 3 days, if the modes are damped by radiative diffusion only and g-mode resonances are fixed; or as high as 6 days, if one allows for evolution of the resonances and for nonlinear damping near inner turning points. Even the larger theoretical period falls short of the observed transition period by a factor two.Comment: 17 pages, 2 postscript figures, uses aaspp4.sty. Submitted to Ap

Elevated carbon dioxide and ozone alter productivity and ecosystem carbon content in northern temperate forests

Three young northern temperate forest communities in the north‐central United States were exposed to factorial combinations of elevated carbon dioxide ( CO 2 ) and tropospheric ozone (O 3 ) for 11 years. Here, we report results from an extensive sampling of plant biomass and soil conducted at the conclusion of the experiment that enabled us to estimate ecosystem carbon (C) content and cumulative net primary productivity ( NPP ). Elevated CO 2 enhanced ecosystem C content by 11%, whereas elevated O 3 decreased ecosystem C content by 9%. There was little variation in treatment effects on C content across communities and no meaningful interactions between CO 2 and O 3 . Treatment effects on ecosystem C content resulted primarily from changes in the near‐surface mineral soil and tree C, particularly differences in woody tissues. Excluding the mineral soil, cumulative NPP was a strong predictor of ecosystem C content ( r 2  = 0.96). Elevated CO 2 enhanced cumulative NPP by 39%, a consequence of a 28% increase in canopy nitrogen (N) content (g N m −2 ) and a 28% increase in N productivity ( NPP /canopy N). In contrast, elevated O 3 lowered NPP by 10% because of a 21% decrease in canopy N, but did not impact N productivity. Consequently, as the marginal impact of canopy N on NPP (∆ NPP /∆N) decreased through time with further canopy development, the O 3 effect on NPP dissipated. Within the mineral soil, there was less C in the top 0.1 m of soil under elevated O 3 and less soil C from 0.1 to 0.2 m in depth under elevated CO 2 . Overall, these results suggest that elevated CO 2 may create a sustained increase in NPP , whereas the long‐term effect of elevated O 3 on NPP will be smaller than expected. However, changes in soil C are not well‐understood and limit our ability to predict changes in ecosystem C content.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/108065/1/gcb12564.pd

Entanglement in a quantum annealing processor

Entanglement lies at the core of quantum algorithms designed to solve problems that are intractable by classical approaches. One such algorithm, quantum annealing (QA), provides a promising path to a practical quantum processor. We have built a series of scalable QA processors consisting of networks of manufactured interacting spins (qubits). Here, we use qubit tunneling spectroscopy to measure the energy eigenspectrum of two- and eight-qubit systems within one such processor, demonstrating quantum coherence in these systems. We present experimental evidence that, during a critical portion of QA, the qubits become entangled and that entanglement persists even as these systems reach equilibrium with a thermal environment. Our results provide an encouraging sign that QA is a viable technology for large-scale quantum computing.Comment: 13 pages, 8 figures, contact corresponding author for Supplementary Informatio

Elevated carbon dioxide and ozone alter productivity and ecosystem carbon content in northern temperate forests

Three young northern temperate forest communities in the north-central United States were exposed to factorial combinations of elevated carbon dioxide (CO2) and tropospheric ozone (O3) for 11 years. Here, we report results from an extensive sampling of plant biomass and soil conducted at the conclusion of the experiment that enabled us to estimate ecosystem carbon (C) content and cumulative net primary productivity (NPP). Elevated CO2 enhanced ecosystem C content by 11%, whereas elevated O3 decreased ecosystem C content by 9%. There was little variation in treatment effects on C content across communities and no meaningful interactions between CO2 and O3. Treatment effects on ecosystem C content resulted primarily from changes in the near-surface mineral soil and tree C, particularly differences in woody tissues. Excluding the mineral soil, cumulative NPP was a strong predictor of ecosystem C content (r2 = 0.96). Elevated CO2 enhanced cumulative NPP by 39%, a consequence of a 28% increase in canopy nitrogen (N) content (g N m−2) and a 28% increase in N productivity (NPP/canopy N). In contrast, elevated O3 lowered NPP by 10% because of a 21% decrease in canopy N, but did not impact N productivity. Consequently, as the marginal impact of canopy N on NPP (ΔNPP/ΔN) decreased through time with further canopy development, the O3 effect on NPP dissipated. Within the mineral soil, there was less C in the top 0.1 m of soil under elevated O3 and less soil C from 0.1 to 0.2 m in depth under elevated CO2. Overall, these results suggest that elevated CO2 may create a sustained increase in NPP, whereas the long-term effect of elevated O3 on NPP will be smaller than expected. However, changes in soil C are not well-understood and limit our ability to predict changes in ecosystem C content