132 research outputs found

    AMPA Receptor Activation Causes Silencing of AMPA Receptor-Mediated Synaptic Transmission in the Developing Hippocampus

    Get PDF
    Agonist-induced internalization of transmembrane receptors is a widespread biological phenomenon that also may serve as a mechanism for synaptic plasticity. Here we show that the agonist AMPA causes a depression of AMPA receptor (AMPAR) signaling at glutamate synapses in the CA1 region of the hippocampus in slices from developing, but not from mature, rats. This developmentally restricted agonist-induced synaptic depression is expressed as a total loss of AMPAR signaling, without affecting NMDA receptor (NMDAR) signaling, in a large proportion of the developing synapses, thus creating AMPAR silent synapses. The AMPA-induced AMPAR silencing is induced independently of activation of mGluRs and NMDARs, and it mimics and occludes stimulus-induced depression, suggesting that this latter form of synaptic plasticity is expressed as agonist-induced removal of AMPARs. Induction of long-term potentiation (LTP) rendered the developing synapses resistant to the AMPA-induced depression, indicating that LTP contributes to the maturation-related increased stability of these synapses. Our study shows that agonist binding to AMPARs is a sufficient triggering stimulus for the creation of AMPAR silent synapses at developing glutamate synapses

    Prognostic value and kinetics of circulating endothelial cells in patients with recurrent glioblastoma randomised to bevacizumab plus lomustine, bevacizumab single agent or lomustine single agent. A report from the Dutch Neuro-Oncology Group BELOB trial

    Get PDF
    Background:Angiogenesis is crucial for glioblastoma growth, and anti-vascular endothelial growth factor agents are widely used in recurrent glioblastoma patients. The number of circulating endothelial cells (CECs) is a surrogate marker for endothelial damage. We assessed their kinetics and explored their prognostic value in patients with recurrent glioblastoma.Methods:In this side study of the BELOB trial, 141 patients with recurrent glioblastoma were randomised to receive single-agent bevacizumab or lomustine, or bevacizumab plus lomustine. Before treatment, after 4 weeks and after 6 weeks of treatment, CECs were enumerated.Results:The number of CECs increased during treatment with bevacizumab plus lomustine, but not during treatment in the single-agent arms. In patients treated with lomustine single agent, higher absolute CEC numbers after 4 weeks (log 10 CEC hazard ratio (HR) 0.41, 95% CI 0.18-0.91) and 6 weeks (log 10 CEC HR 0.16, 95% CI 0.05-0.56) of treatment were associated with improved overall survival (OS). Absolute CEC numbers in patients receiving bevacizumab plus lomustine or bevacizumab single agent were not associated wit

    Riding on the Coat-Tails of Traditional Cultural Expressions

    Get PDF
    Matters related to the protection of traditional cultural expressions (‘TCEs’) or expressions of folklore (‘EoFs’) are sensitive and intricate as a blend of legal, economic, philosophical and anthropological considerations jostle to capture their core features. This results in disparate views surrounding what should qualify as TCEs or EoFs, who should be considered their ‘owner’ (assuming that ownership per se is conceptually compatible with these items), which is the most appropriate legal protection regime and how broad their scope of protection should be. Drawing from these various accounts on TCEs, this article focuses on the interaction between TCEs and EoFs originating on the European continent and the European Union (‘EU’) trade mark legislation. Specifically, this article examines whether the limitations of the effects of trade mark rights and of the absolute grounds of refusal, as developed by the case law of the Court of Justice of the European Union, are effective in preserving the cohesion of TCEs. This article advances the thesis that registration of TCEs and EoFs as trade marks generates an imbalance between the rights of the trade mark owner and the defences available to others under the EU trade mark law framework. Furthermore, such an imbalance is likely to hinder the unfettered circulation of TCEs and undermine their original meaning. Lastly, in some cases, trade mark registration of TCEs contributes to their appropriation and misappropriation. The article concludes that, de lege ferenda, the direct exclusion of TCEs as eligible subject matter for trade mark registration is preferable to seeking a post factum remedy

    Ubiquitous molecular substrates for associative learning and activity-dependent neuronal facilitation.

    Get PDF
    Recent evidence suggests that many of the molecular cascades and substrates that contribute to learning-related forms of neuronal plasticity may be conserved across ostensibly disparate model systems. Notably, the facilitation of neuronal excitability and synaptic transmission that contribute to associative learning in Aplysia and Hermissenda, as well as associative LTP in hippocampal CA1 cells, all require (or are enhanced by) the convergence of a transient elevation in intracellular Ca2+ with transmitter binding to metabotropic cell-surface receptors. This temporal convergence of Ca2+ and G-protein-stimulated second-messenger cascades synergistically stimulates several classes of serine/threonine protein kinases, which in turn modulate receptor function or cell excitability through the phosphorylation of ion channels. We present a summary of the biophysical and molecular constituents of neuronal and synaptic facilitation in each of these three model systems. Although specific components of the underlying molecular cascades differ across these three systems, fundamental aspects of these cascades are widely conserved, leading to the conclusion that the conceptual semblance of these superficially disparate systems is far greater than is generally acknowledged. We suggest that the elucidation of mechanistic similarities between different systems will ultimately fulfill the goal of the model systems approach, that is, the description of critical and ubiquitous features of neuronal and synaptic events that contribute to memory induction

    Plaatsspecifieke opslagbestrijding over twee jaar praktijprijp

    No full text
    In Wageningen wordt momenteel hard gewerkt aan een spuitmachine die plaatsspecifiek aardappelopslag uit een gewas kan verwijderen. Landbouwtechnisch ingenieur Ard Nieuwenhuizen heeft daarvoor samen met collega-technici een ingenieuze spuitmachine gemaakt. De eerste proefresultaten van het prototype zijn zeer hoopgevend. Over twee jaar kan de gebruikte techniek praktijkrijp zij

    Internetprogramma geeft inzicht in eigen Phytophthora-strategie. (Internet site gives insight in effectiveness of growers personal potato late blight control strategies)

    No full text
    Om telers te helpen met hun bestrijdingsstrategie is het Agrobiocon programma 'Visualisatie infectie Phytophthora' ontwikkeld. Uitleg van mede ontwikkelaar Geert Kessel van Plant Research International van Wageningen U

    Snel plantmonitoren met nieuwe cameratechniek (interview met Dr. V.G.A.A. Vleeshouwers)

    No full text
    De onderzoekers Henk Jalink en Rob van der Schoor van Wageningen UR hebben een innovatieve MIPS-LED camera ontwikkeld, waarmee collega-onderzoekers van de universiteit snel fotosynthese in planten kunnen vastleggen. Vivianne Vleeshouwers, is werkzaam bij Wageningen UR Plantenveredeling, en is een van de onderzoekers die de camera beproeft. Zij hoopt het apparaat te kunnen inzetten voor onderzoek naar phytophthoraresistentie in (nieuwe) aardappelrassen en wilde soorten

    Plaatsspecifieke opslagbestrijding over twee jaar praktijprijp

    No full text
    In Wageningen wordt momenteel hard gewerkt aan een spuitmachine die plaatsspecifiek aardappelopslag uit een gewas kan verwijderen. Landbouwtechnisch ingenieur Ard Nieuwenhuizen heeft daarvoor samen met collega-technici een ingenieuze spuitmachine gemaakt. De eerste proefresultaten van het prototype zijn zeer hoopgevend. Over twee jaar kan de gebruikte techniek praktijkrijp zij
    • …
    corecore