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Now showing items 1 - 16 of 1424

  • Programmable Shape-Shifting Micelles**

    Miao-Ping Chien   Anthony M. Rush   Matthew P. Thompson   Nathan C. Gianneschi  

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  • Multiple sodium channels and their roles in electrogenesis within dorsal root ganglion neurons

    Anthony M. Rush   Theodore R. Cummins   Stephen G. Waxman  

    Dorsal root ganglion neurons express an array of sodium channel isoforms allowing precise control of excitability. An increasing body of literature indicates that regulation of firing behaviour in these cells is linked to their patterns of expression of specific sodium channel isoforms, which have been discovered to possess distinct biophysical characteristics. The pattern of expression of sodium channels differs in different subclasses of DRG neurons and is not fixed but, on the contrary, changes in response to a variety of disease insults. Moreover, modulation of channels by their environment has been found to play an important role in the response of these neurons to stimuli. In this review we illustrate how excitability can be finely tuned to provide contrasting firing templates in different subclasses of DRG neurons by selective deployment of various sodium channel isoforms, by plasticity of expression of these proteins, and by interactions of these sodium channel isoforms with each other and with other modulatory molecules.
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  • PGE2 increases the tetrodotoxin-resistant Nav1.9 sodium current in mouse DRG neurons via G-proteins

    Anthony M. Rush   Stephen G. Waxman  

    Inflammation caused by tissue damage results in pain, reflecting an increase in excitability of the primary afferent neurons innervating the area. There is some evidence to suggest that altered function of voltage-gated sodium channels is responsible for the hyperexcitability produced by inflammatory agents, possibly acting through G-proteins, but the role of different channel subtypes has not been fully explored. The tetrodotoxin-resistant (TTX-R) sodium channel Nav1.9 is expressed selectively in C- and A-fibre nociceptive-type units and is upregulated by G-protein activation. In this study, we examined the effects of the inflammatory agent prostaglandin-E2 (PGE2) on Nav1.9 current in both Nav1.8-null and wild-type (WT) mice and explored the role of specific G-proteins in modulation. PGE2 caused a twofold increase in Nav1.9 current (p < 0.05) in both systems. Steady-state activation was shifted in a hyperpolarizing direction by 6-8 mV and availability of channels by 12 mV. No differences in the activation and inactivation kinetics could be detected. The increase in current was blocked by pertussis toxin (PTX) but not cholera toxin (CTX), showing involvement of Gi/o. but not Gs subunits. Our data indicate that Nav1.9 current can be increased during inflammation via a G-protein dependent mechanism and suggest that this could contribute to the regulation of electrogenesis in dorsal root ganglia (DRG) neurons. Copyright 2004 Elsevier B.V. All rights reserved.
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  • Methods for arranging and packing nucleic acids for unusual resistance to nucleases and targeted delivery for gene therapy

    There are disclosed compositions and methods to render nucleic acids resistant to nuclease digestion while maintaining sequence selective hybridization competency. The approach relies on utilizing nucleic acids as the polar head group of a nucleic acid-polymer amphiphile in order to assemble well-defined, discrete micellar nanoparticles. Dense packing of nucleic acid in the micelle corona allows for hybridization of complementary oligonucleotides while prohibiting enzymatic degradation.
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  • Electrophysiological properties of two axonal sodium channels, Nav1.2 and Nav1.6, expressed in mouse spinal sensory neurones

    Anthony M. Rush   Sulayman D. Dib-Hajj   Stephen G. Waxman  

    Sodium channels Na(v)1.2 and Na(v)1.6 are both normally expressed along premyelinated and myelinated axons at different stages of maturation and are also expressed in a subset of demyelinated axons, where coexpression of Na(v)1.6 together with the Na+/Ca2+ exchanger is associated with axonal injury. It has been difficult to distinguish the currents produced by Na(v)1.2 and Na(v)1.6 in native neurones, and previous studies have not compared these channels within neuronal expression systems. In this study, we have characterized and directly compared Na(v)1.2 and Na(v)1.6 in a mammalian neuronal cell background and demonstrate differences in their properties that may affect neuronal behaviour. The Na(v)1.2 channel displays more depolarized activation and availability properties that may permit conduction of action potentials, even with depolarization. However, Na(v)1.2 channels show a greater accumulation of inactivation at higher frequencies of stimulation (20-100 Hz) than Na(v)1.6 and thus are likely to generate lower frequencies of firing. Na(v)1.6 channels produce a larger persistent current that may play a role in triggering reverse Na+/Ca2+ exchange, which can injure derayelinated axons where Na(v)1.6 and the Na+/Ca2+ exchanger are colocalized, while selective expression of Nav1.2 may support action potential electrogenesis, at least at lower frequencies, while producing a smaller persistent current.
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  • Differential modulation of sodium channel Nav1.6 by two members of the fibroblast growth factor homologous factor?2 subfamily

    Anthony M. Rush   Ellen K. Wittmack   Lynda Tyrrell   Joel A. Black   Sulayman D. Dib-Hajj   Stephen G. Waxman  

    Abstract FHF2A and FHF2B are two members of the fibroblast growth factor homologous factor 2 (FHF2) subfamily with distinct N termini. Using a generic antibody and electrophysiological methods, we previously showed that FHF2 is expressed in hippocampus and dorsal root ganglion (DRG) neurons and is colocalized with sodium channel Nav1.6 at sensory but not motor nodes of Ranvier, and that FHF2B associates with Nav1.6, causing an increase in current density and a small depolarizing shift in availability of channels. Using immunolabeling of adult rat tissue, we demonstrate that FHF2A is present within DRG but not in hippocampal or cerebellar neurons or at nodes of Ranvier in sciatic nerve, and that Nav1.6 and FHF2A are colocalized in nonmyelinated fibers. We also show that FHF2A binds directly to Nav1.6, and that the two proteins coimmunoprecipitate from transfected HEK293 cells. Because Nav1.6 has been associated with rapid firing rates, we examined the possible effects of FHF2B and the sister isoform, FHF2A, on electrophysiological properties of this channel in the DRG-derived ND7/23 cell line. We show that FHF2B inhibits accumulation of inactivation in response to trains of stimulation at high frequencies. In marked contrast, FHF2A causes an accumulation of inactivated channels at all frequencies tested due to a slowing of recovery from inactivation. Thus different FHF2 subfamily members have different functional effects on Nav1.6 and are differentially distributed in DRG neurons and their axons. This suggests that FHF2A and FHF2B may selectively alter firing behaviour of specific neuronal compartments via differential modulation of Nav1.6.
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  • SIU Scholarship: Dr. Anthony M. Kariuki

    Anthony M. Kariuki  

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  • SIU Scholarship: Dr. Anthony M. Kariuki

    Anthony M. Kariuki  

    The Société Internationale d'Urologie offers Training Scholarships for young doctors with basic surgical or urological qualifications. The SIU Scholarships involve training in a recognized Urological center of excellence located in the candidate's geographical region. These SIU-accredited centers provide an excellent environment for learning and, in many instances, hands-on experience, so that candidates may acquire knowledge and skills that they will be able to transfer to their own setting of practice. In this series of short communications, SIU Scholars write about the impact that these training opportunities faciliated by the SIU had on their quality of care and career development. Information about applying for an SIU Scholarship is available at http://www.siu-urology.org/. Anthony M
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  • SIU Scholarship: Dr. Anthony M. Kariuki

    Anthony M. Kariuki  

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  • Anthony M. Wachinski: Environmental Ion Exchange, Principles and Design. 2nd Edn

    Dyer   Alan  

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  • Anthony M. Wachinski: Environmental Ion Exchange, Principles and Design. 2nd Edn

    Dyer, Alan  

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  • The Cambridge Companion to Gandhi, by Judith M. Brown and Anthony Parel

    Ahmed   T.  

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  • The Cambridge Companion to Gandhi, by Judith M. Brown and Anthony Parel

    Ahmed, T.  

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  • The Tie Goes to Freedom: Justice Anthony M. Kennedy on Liberty.

    STONE   GEOFFREY R.  

    The article reviews the book "The Tie Goes to Freedom: Justice Anthony M. Kennedy on Liberty," by Helen J. Knowles.
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  • THE MATTER OF ANTHONY M. RAMUNNO, JR.

    ANTHONY M. RAMUNNO  

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  • Bougainville Before the Conflictby Anthony J. REGAN; Helga M. Griffin

    Review by: PAUL D\"ARCY  

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