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

Spin-filtered Edge States with an Electrically Tunable Gap in a Two-Dimensional Topological Crystalline Insulator

Three-dimensional topological crystalline insulators were recently predicted and observed in the SnTe class of IV-VI semiconductors, which host metallic surface states protected by crystal symmetries. In this work, we study thin films of these materials and expose their potential for device applications. We demonstrate that thin films of SnTe and Pb(1-x)Sn(x)Se(Te) grown along the (001) direction are topologically nontrivial in a wide range of film thickness and carry conducting spin-filtered edge states that are protected by the (001) mirror symmetry via a topological invariant. Application of an electric field perpendicular to the film will break the mirror symmetry and generate a band gap in these edge states. This functionality motivates us to propose a novel topological transistor device, in which charge and spin transport are maximally entangled and simultaneously controlled by an electric field. The high on/off operation speed and coupling of spin and charge in such a device may lead to electronic and spintronic applications for topological crystalline insulators.Comment: 6 pages, 5 figures, minor changes made, accepted to Nature Material

Longitudinal Optogenetic Motor Mapping Revealed Structural and Functional Impairments and Enhanced Corticorubral Projection after Contusive Spinal Cord Injury in Mice

Current evaluation of impairment and repair after spinal cord injury (SCI) is largely dependent on behavioral assessment and histological analysis of injured tissue and pathways. Here, we evaluated whether transcranial optogenetic mapping of motor cortex could reflect longitudinal structural and functional damage and recovery after SCI. In Thy1-Channelrhodopsin2 transgenic mice, repeated motor mappings were made by recording optogenetically evoked electromyograms (EMGs) of a hindlimb at baseline and 1 day and 2, 4, and 6 weeks after mild, moderate, and severe spinal cord contusion. Injuries caused initial decreases in EMG amplitude, losses of motor map, and subsequent partial recoveries, all of which corresponded to injury severity. Reductions in map size were positively correlated with motor performance, as measured by Basso Mouse Scale, rota-rod, and grid walk tests, at different time points, as well as with lesion area at spinal cord epicenter at 6 weeks post-SCI. Retrograde tracing with Fluoro-Gold showed decreased numbers of cortico- and rubrospinal neurons, with the latter being negatively correlated with motor map size. Combined retro- and anterograde tracing and immunostaining revealed more neurons activated in red nucleus by cortical stimulation and enhanced corticorubral axons and synapses in red nucleus after SCI. Electrophysiological recordings showed lower threshold and higher amplitude of corticorubral synaptic response after SCI. We conclude that transcranial optogenetic motor mapping is sensitive and efficient for longitudinal evaluation of impairment and plasticity of SCI, and that spinal cord contusion induces stronger anatomical and functional corticorubral connection that may contribute to spontaneous recovery of motor function

Enhancement of third-order optical nonlinearities by conjugated polymer-bonded carbon nanotubes

This article may be downloaded for personal use only. Any other use requires prior permission of the author and AIP Publishing. This article appeared in Wei Feng, Wenhui Yi, Hongcai Wu, Masanori Ozaki, and Katsumi Yoshino, J. Appl. Phys. 98, 034301 (2005) and may be found at https://doi.org/10.1063/1.1954887