Orexin-1 receptor-cannabinoid CB1 receptor heterodimerization results in both ligand-dependent and -independent coordinated alterations of receptor localization and function

Following inducible expression in HEK293 cells, the human orexin-1 receptor was targeted to the cell surface but became internalized following exposure to the peptide agonist orexin A. By contrast, constitutive expression of the human cannabinoid CB1 receptor resulted in a predominantly punctate, intracellular distribution pattern consistent with spontaneous, agonistindependent internalization. Expression of the orexin-1 receptor in the presence of the CB1 receptor resulted in both receptors displaying the spontaneous internalization phenotype. Single cell fluorescence resonance energy transfer imaging indicated the two receptors were present as heterodimers/oligomers in intracellular vesicles. Addition of the CB1 receptor antagonist SR-141716A to cells expressing only the CB1 receptor resulted in re-localization of the receptor to the cell surface. Although SR-141716A has no significant affinity for the orexin-1 receptor, in cells co-expressing the CB1 receptor, the orexin-1 receptor was also re-localized to the cell surface by treatment with SR-141716A. Treatment of cells co-expressing the orexin-1 and CB1 receptors with the orexin-1 receptor antagonist SB-674042 also resulted in re-localization of both receptors to the cell surface. Treatment with SR-141716A resulted in decreased potency of orexin A to activate the mitogen-activated protein kinases ERK1/2 only in cells co-expressing the two receptors. Treatment with SB-674042 also reduced the potency of a CB1 receptor agonist to phosphorylate ERK1/2 only when the two receptors were co-expressed. These studies introduce an entirely novel pharmacological paradigm, whereby ligands modulate the function of receptors for which they have no significant inherent affinity by acting as regulators of receptor heterodimers

Competing interactions in artificial spin chains

The low-energy magnetic configurations of artificial frustrated spin chains are investigated using magnetic force microscopy and micromagnetic simulations. Contrary to most studies on two-dimensional artificial spin systems where frustration arises from the lattice geometry, here magnetic frustration originates from competing interactions between neighboring spins. By tuning continuously the strength and sign of these interactions, we show that different magnetic phases can be stabilized. Comparison between our experimental findings and predictions from the one-dimensional Anisotropic Next-Nearest-Neighbor Ising (ANNNI) model reveals that artificial frustrated spin chains have a richer phase diagram than initially expected. Besides the observation of several magnetic orders and the potential extension of this work to highly-degenerated artificial spin chains, our results suggest that the micromagnetic nature of the individual magnetic elements allows observation of metastable spin configurations.Comment: 5 pages, 4 figure

Longitudinal and Transverse Zeeman Ladders in the Ising-Like Chain Antiferromagnet BaCo2V2O8

We explore the spin dynamics emerging from the N\'eel phase of the chain compound antiferromagnet BaCo2V2O8. Our inelastic neutron scattering study reveals unconventional discrete spin excitations, so called Zeeman ladders, understood in terms of spinon confinement, due to the interchain attractive linear potential. These excitations consist in two interlaced series of modes, respectively with transverse and longitudinal polarization. The latter have no classical counterpart and are related to the zero-point fluctuations that weaken the ordered moment in weakly coupled quantum chains. Our analysis reveals that BaCo2V2O8, with moderate Ising anisotropy and sizable interchain interactions, remarkably fulfills the conditions necessary for the observation of these longitudinal excitations.Comment: 5 pages, 4 figures, 2 additional pages of supplemental material with 2 figures; Journal ref. added; 1 page erratum added at the end with 1 figur

Making the corona and the fast solar wind: a self-consistent simulation for the low-frequency Alfven waves from photosphere to 0.3AU

We show that the coronal heating and the fast solar wind acceleration in the coronal holes are natural consequence of the footpoint fluctuations of the magnetic fields at the photosphere, by performing one-dimensional magnetohydrodynamical simulation with radiative cooling and thermal conduction. We initially set up a static open flux tube with temperature 10^4K rooted at the photosphere. We impose transverse photospheric motions corresponding to the granulations with velocity = 0.7km/s and period between 20 seconds and 30 minutes, which generate outgoing Alfven waves. We self-consistently treat these waves and the plasma heating. After attenuation in the chromosphere by ~85% of the initial energy flux, the outgoing Alfven waves enter the corona and contribute to the heating and acceleration of the plasma mainly by the nonlinear generation of the compressive waves and shocks. Our result clearly shows that the initial cool and static atmosphere is naturally heated up to 10^6K and accelerated to 800km/s.Comment: 4 pages, 3 figures, ApJL, 632, L49, corrections of mistypes in eqs.(3) & (5), Mpeg movie for fig.1 (simulation result) is available at http://www-tap.scphys.kyoto-u.ac.jp/~stakeru/research/suzuki_200506.mp

Behavioral, electrophysiological and histopathological consequences of systemic manganese administration in MEMRI

Manganese (Mn2+)-enhanced magnetic resonance imaging (MEMRI) offers the possibility to generate longitudinal maps of brain activity in unrestrained and behaving animals. However, Mn2+ is a metabolic toxin and a competitive inhibitor for Ca2+, and therefore, a yet unsolved question in MEMRI studies is whether the concentrations of metal ion used may alter brain physiology. In the present work we have investigated the behavioral, electrophysiological and histopathological consequences of MnCl2 administration at concentrations and dosage protocols regularly used in MEMRI. Three groups of animals were sc injected with saline, 0.1 and 0.5 mmol/kg MnCl2, respectively. In vivo electrophysiological recordings in the hippocampal formation revealed a mild but detectable decrease in both excitatory postsynaptic potentials (EPSP) and population spike (PS) amplitude under the highest MnCl2 dose. The EPSP to PS ratio was preserved at control levels, indicating that neuronal excitability was not affected. Experiments of pair pulse facilitation demonstrated a dose dependent increase in the potentiation of the second pulse, suggesting presynaptic Ca2+ competition as the mechanism for the decreased neuronal response. Tetanization of the perforant path induced a long-term potentiation of synaptic transmission that was comparable in all groups, regardless of treatment. Accordingly, the choice accuracy tested on a hippocampal-dependent learning task was not affected. However, the response latency in the same task was largely increased in the group receiving 0.5 mmol/kg of MnCl2. Immunohistological examination of the hippocampus at the end of the experiments revealed no sign of neuronal toxicity or glial reaction. Although we show that MEMRI at 0.1 mmol/Kg MnCl2 may be safely applied to the study of cognitive networks, a detailed assessment of toxicity is strongly recommended for each particular study and Mn2+ administration protocol