Golgi localized β1-adrenergic receptors stimulate Golgi PI4P hydrolysis by PLCε to regulate cardiac hypertrophy.

Increased adrenergic tone resulting from cardiovascular stress leads to development of heart failure, in part, through chronic stimulation of β1 adrenergic receptors (βARs) on cardiac myocytes. Blocking these receptors is part of the basis for β-blocker therapy for heart failure. Recent data demonstrate that G protein-coupled receptors (GPCRs), including βARs, are activated intracellularly, although the biological significance is unclear. Here we investigated the functional role of Golgi βARs in rat cardiac myocytes and found they activate Golgi localized, prohypertrophic, phosphoinositide hydrolysis, that is not accessed by cell surface βAR stimulation. This pathway is accessed by the physiological neurotransmitter norepinephrine (NE) via an Oct3 organic cation transporter. Blockade of Oct3 or specific blockade of Golgi resident β1ARs prevents NE dependent cardiac myocyte hypertrophy. This clearly defines a pathway activated by internal GPCRs in a biologically relevant cell type and has implications for development of more efficacious β-blocker therapies

PLCε1 suppresses tumor growth by regulating murine T cell mobilization

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154282/1/cei13409.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154282/2/cei13409_am.pd

From laterally modulated two-dimensional electron gas towards artificial graphene

Cyclotron resonance has been measured in far-infrared transmission of GaAs/Al$_x$Ga$_{1-x}$As heterostructures with an etched hexagonal lateral superlattice. Non-linear dependence of the resonance position on magnetic field was observed as well as its splitting into several modes. Our explanation, based on a perturbative calculation, describes the observed phenomena as a weak effect of the lateral potential on the two-dimensional electron gas. Using this approach, we found a correlation between parameters of the lateral patterning and the created effective potential and obtain thus insights on how the electronic miniband structure has been tuned. The miniband dispersion was calculated using a simplified model and allowed us to formulate four basic criteria that have to be satisfied to reach graphene-like physics in such systems

G protein βγ subunits regulate cardiomyocyte hypertrophy through a perinuclear Golgi phosphatidylinositol 4-phosphate hydrolysis pathway.

We recently identified a novel GPCR-dependent pathway for regulation of cardiac hypertrophy that depends on Golgi phosphatidylinositol 4-phosphate (PI4P) hydrolysis by a specific isoform of phospholipase C (PLC), PLCε, at the nuclear envelope. How stimuli are transmitted from cell surface GPCRs to activation of perinuclear PLCε is not clear. Here we tested the role of G protein βγ subunits. Gβγ inhibition blocked ET-1-stimulated Golgi PI4P depletion in neonatal and adult ventricular myocytes. Blocking Gβγ at the Golgi inhibited ET-1-dependent PI4P depletion and nuclear PKD activation. Translocation of Gβγ to the Golgi stimulated perinuclear Golgi PI4P depletion and nuclear PKD activation. Finally, blocking Gβγ at the Golgi or PM blocked ET-1-dependent cardiomyocyte hypertrophy. These data indicate that Gβγ regulation of the perinuclear Golgi PI4P pathway and a separate pathway at the PM is required for ET-1-stimulated hypertrophy, and the efficacy of Gβγ inhibition in preventing heart failure maybe due in part to its blocking both these pathways

Fluctuations of the superconducting order parameter as an origin of the Nernst effect

We show that the strong Nernst signal observed recently in amorphous superconducting films far above the critical temperature is caused by the fluctuations of the superconducting order parameter. We demonstrate a striking agreement between our theoretical calculations and the experimental data at various temperatures and magnetic fields. Besides, the Nernst effect is interesting not only in the context of superconductivity. We discuss some subtle issues in the theoretical study of thermal phenomena that we have encountered while calculating the Nernst coefficient. In particular, we explain how the Nernst theorem (the third law of thermodynamics) imposes a strict constraint on the magnitude of the Nernst effect.Comment: 6 pages, 5 figures, extended versio

Information about the Integer Quantum Hall Transition Extracted from the Autocorrelation Function of Spectral Determinants

The Autocorrelation function of spectral determinants (ASD) is used to probe the sensitivity of a two-dimensional disordered electron gas to the system's size L. For weak magnetic fields ASD is shown to depend only trivially on L, which is a strong indication that all states are localized. From nontrivial dependence of ASD on L for infinite L at a Hall conductance of 1/2 e^2/h we deduce the existence of critical wave functions at this point, as long as the disorder strength does not exceed a critical value.Comment: 4 pages, one citation correcte

Breakdown of Fermi-liquid theory in a cuprate superconductor

The behaviour of electrons in solids is remarkably well described by Landau's Fermi-liquid theory, which says that even though electrons in a metal interact they can still be treated as well-defined fermions, called ``quasiparticles''. At low temperature, the ability of quasiparticles to transport heat is strictly given by their ability to transport charge, via a universal relation known as the Wiedemann-Franz law, which no material in nature has been known to violate. High-temperature superconductors have long been thought to fall outside the realm of Fermi-liquid theory, as suggested by several anomalous properties, but this has yet to be shown conclusively. Here we report on the first experimental test of the Wiedemann-Franz law in a cuprate superconductor, (Pr,Ce)$_2$CuO$_4$. Our study reveals a clear departure from the universal law and provides compelling evidence for the breakdown of Fermi-liquid theory in high-temperature superconductors.Comment: 7 pages, 3 figure

Transport Phenomena of Inversion Layers in High Magnetic Fields

The discovery of the quantum Hall effect in 1980 has demonstrated the importance of two- dimensional electronic systems for application and fundamental research. In this paper a review of some transport phenomena in such systems in high magnetic fields is given

Trace metals and micronutrients in bone tissues of the red fox Vulpes vulpes (L., 1758)

In this study we determined the levels of trace elements (zinc, copper, lead, cadmium and mercury) in three layers of bones of the hip joint (cartilage, compact bone and spongy bone) of 30 red foxes (Vulpes vulpes) from north-western Poland. Concentrations of Cu, Zn, Pb and Cd were determined by atomic absorption spectrophotometry (ICP-AES) in inductively coupled argon plasma using a Perkin-Elmer Optima 2000 DV. Determination of Hg concentration was performed by atomic absorption spectroscopy. In cartilage, compact bone and spongy bone samples from the red fox, median concentrations of the metals studied could be arranged in the following descending series: Zn > Cu > Pb > Cd > Hg, the values ranging from 142 to 0.002 mg/kg dw. There was a significant difference in Cu concentrations, among all the materials analyzed, with much more Cu found in spongy bone than in compact bone. Significant differences were also noted in the case of Hg concentrations in cartilage with compact bone and the spongy bone, and between concentrations of this metal in compact bone and spongy bone. In males, the concentration of Hg in spongy bone was greater than in females. Younger foxes had a higher concentration of this metal in cartilage than adults. The strongest synergistic relationships were observed in spongy bone between the Zn and Cu, Zn and Cd, as well as between Cu and Cd. Statistically significant antagonistic relationships were detected between zinc and lead in compact bone. In addition to monitoring studies conducted on the abiotic environment, an urgent need exists for long-term monitoring of concentrations of heavy metals with long-term effects on living organisms. An important addition is provided by biomonitoring studies on domesticated and free-living mammals, including Canidae