205 research outputs found

    Mechanisms Of Autonomic Control By The Insular Cortex In The Rat

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    The insular cortex (IC) has been proposed to act as visceral sensory and autonomic cortex. The mechanism of control by the IC, however, is not clear. The nature of insular cortical function in hypertension is also unknown.;Middle cerebral artery occlusion (MCAO) in Wistar rats has been shown to cause cortical infarction, including the IC, resulting in increases in sympathetic nerve discharge (SND). MCAO in the urethane anesthetized spontaneously hypertensive rat (SHR) resulted in decreases in arterial pressure (AP) and SND.;To determine if the autonomic effects of MCAO in the SHR and Wistar rat are due to insular damage, a lesion of the IC was made, using an excitotoxic amino acid. Increases in SND were observed in Wistar rats and decreases in SHR\u27s, similar to that seen following MCAO.;Systematic D,L homocysteate (DLH) injections into the IC of propofol-anesthetized Wistar rats resulted in a significant increase in AP and a significant decrease in HR and SND. DLH and lidocaine injections into the IC of conscious Wistar rats both resulted in a significant increase in AP. It was concluded that the IC of conscious Wistar rats has a tonic inhibitory output, while neural excitation is capable of eliciting pressor responses. The IC of SHR appeared to exert no tonic influence on AP.;Previous studies have shown sympathetic nerve responses to C stimulation are mediated by uncharacterized synapses within the lateral hypothalamic area (LHA) and ventrolateral medulla (VLM). Glutamate antagonist injection into the ipsilateral VLM blocked IC and LHA sympathetic responses. A non-NMDA receptor antagonist also blocked IC and LHA sympathetic responses, while an NMDA antagonist was ineffective.;Glutamate antagonist injection into the ipsilateral LHA blocked IC sympathetic nerve responses. NMDA antagonist injection also inhibited IC sympathetic responses, while the non-NMDA antagonist had no effect.;These studies provide the most conclusive evidence that the IC is critical to the autonomic disruptions following stroke. The IC may also play a role in the pathogenesis of hypertension. The IC appears to have a tonic sympatho-inhibitory influence in normotensive animals, though a sympatho-excitatory response is possible. The IC sympathetic effects are mediated by an NMDA glutamatergic synapse in the LHA and a non-NMDA synapse in the VLM

    The acoustic impedance of liquid helium-three

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    Measurements of the transverse acoustic resistance of liquid helium-3 have been made at pressures between 0.3 bar and 28.0 bar in the temperature range 0.015 Kelvin to 1.0 Kelvin using a helium-3/helium-4 dilution refrigerator. The method involved observation of the decay of a series of echos generated in a piezoelectric rod immersed in the liquid, one end of the rod being excited by a resonant cavity. The frequency of this cavity was 242 MHz in the greater proportion of this work but similar measurements were also made at 1048 MHz. The measurements at the lower frequency have confirmed the existence of the collective oscillation known as transverse zero sound in liquid helium-3 at higher pressures, as predicted by the Landau Theory of a Fermi liquid. This has enabled an estimate to be made of the magnitude of the symmetrical Landau parameter, F2S. The result obtained was in agreement with those of other experimenters who have used a variety of methods to determine F2S. A similar experimental technique has been used to study the longitudinal acoustic resistance of liquid helium-3 in order to investigate the anomalously high value of F2S indicated by previous measurements of this phenomenon. These measurements, both transverse and longitudinal, have mainly been carried out on pure helium-3 (ie. better than 99.9997 per cent) but some data have been obtained for the transverse acoustic resistance of helium-3 in which a small amount of helium-4 (about 1%) was present. These results enabled the determination of the acoustic resistance of an assembly of non-interacting Fermions.<p

    Multiadaptive Galerkin Methods for ODEs III: A Priori Error Estimates

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    The multiadaptive continuous/discontinuous Galerkin methods mcG(q) and mdG(q) for the numerical solution of initial value problems for ordinary differential equations are based on piecewise polynomial approximation of degree q on partitions in time with time steps which may vary for different components of the computed solution. In this paper, we prove general order a priori error estimates for the mcG(q) and mdG(q) methods. To prove the error estimates, we represent the error in terms of a discrete dual solution and the residual of an interpolant of the exact solution. The estimates then follow from interpolation estimates, together with stability estimates for the discrete dual solution

    tert-Butyl 6-methyl-2-oxo-4-[4-(trifluoro­meth­oxy)anilino]cyclo­hex-3-ene-1-carboxyl­ate

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    In the title compound, C19H22F3NO4, the dihedral angle between the benzene ring and the conjugated part of the enaminone ring is 42.5 (1)°. The ester substituent makes a dihedral angle of 81.3 (2)° with this latter moiety. The crystal structure is held together by strong N—H⋯O and weak C—H⋯O inter­molecular inter­actions. The enaminone ring is disordered over two orientations with relative occupancies of 0.794 (4) and 0.206 (4)

    N-methyl-D-aspartate receptors mediate the phosphorylation and desensitization of muscarinic receptors in cerebellar granule neurons.

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    Changes in synaptic strength mediated by ionotropic glutamate N-methyl-D-asparate (NMDA) receptors is generally considered to be the molecular mechanism underlying memory and learning. NMDA receptors themselves are subject to regulation through signaling pathways that are activated by G-protein-coupled receptors (GPCRs). In this study we investigate the ability of NMDA receptors to regulate the signaling of GPCRs by focusing on the G(q/11)-coupled M(3)-muscarinic receptor expressed endogenously in mouse cerebellar granule neurons. We show that NMDA receptor activation results in the phosphorylation and desensitization of M(3)-muscarinic receptors through a mechanism dependent on NMDA-mediated calcium influx and the activity of calcium-calmodulin-dependent protein kinase II. Our study reveals a complex pattern of regulation where GPCRs (M(3)-muscarinic) and NMDA receptors can feedback on each other in a process that is likely to influence the threshold value of signaling networks involved in synaptic plasticity

    3-(4-Chloro­anilino)-2,5-dimethyl­cyclo­hex-2-en-1-one

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    In the title compound, C14H16ClNO, the dihedral angle between the benzene ring and the conjugated part of the cyclo­hexene ring is 61.7 (2)°. Part of the cyclo­hexene ring and one of the attached methyl groups are disordered over two orientations with occupancies of 0.602 (7) and 0.398 (7). In addition, the crystal studied was a racemic twin [Flack parameter = 0.58 (4)]. In the crystal, the mol­ecules are linked into chains in the b-axis direction by inter­molecular N—H⋯O hydrogen bonds. C—H⋯O and C—H⋯Cl inter­actions are also observed

    Prospective observational study of implantable cardioverter-defibrillators in primary prevention of sudden cardiac death: study design and cohort description

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    BACKGROUND: Primary-prevention implantable cardioverter-defibrillators (ICDs) reduce total mortality in patients with severe left ventricular systolic function. However, only a minority of patients benefit from these devices. We designed the Prospective Observational Study of Implantable Cardioverter-Defibrillators (PROSE-ICD) to identify risk factors and enhance our understanding of the biological mechanisms that predispose to arrhythmic death in patients undergoing ICD implantation for primary prevention of sudden death. METHODS AND RESULTS: This is a multicenter prospective cohort study with a target enrollment of 1200 patients. The primary end point is ICD shocks for adjudicated ventricular tachyarrhythmias. The secondary end point is total mortality. All patients undergo a comprehensive evaluation including history and physical examination, signal-averaged electrocardiograms, and blood sampling for genomic, proteomic, and metabolomic analyses. Patients are evaluated every 6 months and after every known ICD shock for additional electrocardiographic and blood sampling. As of December 2011, a total of 1177 patients have been enrolled with more nonwhite and female patients compared to previous randomized trials. A total of 143 patients have reached the primary end point, whereas a total of 260 patients died over an average follow-up of 59 months. The PROSE-ICD study represents a real-world cohort of individuals with systolic heart failure receiving primary-prevention ICDs. CONCLUSIONS: Extensive electrophysiological and structural phenotyping as well as the availability of serial DNA and serum samples will be important resources for evaluating novel metrics for risk stratification and identifying patients at risk for arrhythmic sudden death. CLINICAL TRIAL REGISTRATION: URL: http://clinicaltrials.gov/ Unique Identifier: NCT00733590.This work was supported in part by the Donald W. Reynolds Cardiovascular Foundation and NIH R01 HL091062 (to G.F.T.).S
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