Sample records for kainate receptors kars

  1. Tonically Active Kainate Receptors (tKARs) : A Novel Mechanism Regulating Neuronal Function in the Brain


    Segerstråle, Mikael


    Fast excitatory transmission between neurons in the central nervous system is mainly mediated by L-glutamate acting on ligand gated (ionotropic) receptors. These are further categorized according to their pharmacological properties to AMPA (2-amino-3-(5-methyl-3-oxo-1,2- oxazol-4-yl)propanoic acid), NMDA (N-Methyl-D-aspartic acid) and kainate (KAR) subclasses. In the rat and the mouse hippocampus, development of glutamatergic transmission is most dynamic during the first postnatal weeks. This...

  2. Kainate receptors: multiple roles in neuronal plasticity. (United States)

    Sihra, Talvinder S; Flores, Gonzalo; Rodríguez-Moreno, Antonio


    Ionotropic glutamate receptors of the N-methyl-d-aspartate (NMDA)- and AMPA-type, as well as metabotropic glutamate receptors have been extensively invoked in plasticity. Until relatively recently, however, kainate-type receptors (KARs) had been the most elusive to study because of the lack of appropriate pharmacological tools to specifically address their roles. With the development of selective glutamate receptor antagonists, and knockout mice with specific KAR subunits deleted, the functions of KARs in neuromodulation and synaptic transmission, together with their involvement in some types of plasticity, have been extensively probed in the central nervous system. In this review, we summarize the findings related to the roles of KARs in short- and long-term forms of plasticity, primarily in the hippocampus, where KAR function and synaptic plasticity have received avid attention.

  3. Neto2 influences on kainate receptor pharmacology and function

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    Han, Liwei; Howe, James; Pickering, Darryl S


    Neuropilin tolloid-like protein 2 (Neto2) is an auxiliary subunit of kainate receptors (KARs). It specifically regulates KARs, e.g., slows desensitization and deactivation, increases the rate of recovery from desensitization, promotes modal gating and increases agonist sensitivity. Although...

  4. Kainate induces various domain closures in AMPA and kainate receptors

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    Venskutonyte, Raminta; Frydenvang, Karla; Hald, Helle


    Ionotropic glutamate receptors are key players in fast excitatory synaptic transmission within the central nervous system. These receptors have been divided into three subfamilies: the N-methyl-d-aspartic acid (NMDA), 2-amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic acid (AMPA) and kainate...... receptors. Kainate has previously been crystallized with the ligand binding domain (LBD) of AMPA receptors (GluA2 and GluA4) and kainate receptors (GluK1 and GluK2). Here, we report the structures of the kainate receptor GluK3 LBD in complex with kainate and GluK1 LBD in complex with kainate in the absence...... in the three kainate receptors, which is in contrast to the AMPA receptors where similar contacts are seen. It was revealed by patch clamp electrophysiology studies that kainate is a partial agonist at GluK1 with 36% efficacy compared to glutamate, which is in between the published efficacies of kainate at Glu...

  5. PSD-95 regulates synaptic kainate receptors at mouse hippocampal mossy fiber-CA3 synapses. (United States)

    Suzuki, Etsuko; Kamiya, Haruyuki


    Kainate-type glutamate receptors (KARs) are the third class of ionotropic glutamate receptors whose activation leads to the unique roles in regulating synaptic transmission and circuit functions. In contrast to AMPA receptors (AMPARs), little is known about the mechanism of synaptic localization of KARs. PSD-95, a major scaffold protein of the postsynaptic density, is a candidate molecule that regulates the synaptic KARs. Although PSD-95 was shown to bind directly to KARs subunits, it has not been tested whether PSD-95 regulates synaptic KARs in intact synapses. Using PSD-95 knockout mice, we directly investigated the role of PSD-95 in the KARs-mediated components of synaptic transmission at hippocampal mossy fiber-CA3 synapse, one of the synapses with the highest density of KARs. Mossy fiber EPSCs consist of AMPA receptor (AMPAR)-mediated fast component and KAR-mediated slower component, and the ratio was significantly reduced in PSD-95 knockout mice. The size of KARs-mediated field EPSP reduced in comparison with the size of the fiber volley. Analysis of KARs-mediated miniature EPSCs also suggested reduced synaptic KARs. All the evidence supports critical roles of PSD-95 in regulating synaptic KARs. Copyright © 2015 Elsevier Ireland Ltd and Japan Neuroscience Society. All rights reserved.

  6. Neto Auxiliary Subunits Regulate Interneuron Somatodendritic and Presynaptic Kainate Receptors to Control Network Inhibition

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    Megan S. Wyeth


    Full Text Available Although Netos are considered auxiliary subunits critical for kainate receptor (KAR function, direct evidence for their regulation of native KARs is limited. Because Neto KAR regulation is GluK subunit/Neto isoform specific, such regulation must be determined in cell-type-specific contexts. We demonstrate Neto1/2 expression in somatostatin (SOM-, cholecystokinin/cannabinoid receptor 1 (CCK/CB1-, and parvalbumin (PV-containing interneurons. KAR-mediated excitation of these interneurons is contingent upon Neto1 because kainate yields comparable effects in Neto2 knockouts and wild-types but fails to excite interneurons or recruit inhibition in Neto1 knockouts. In contrast, presynaptic KARs in CCK/CB1 interneurons are dually regulated by both Neto1 and Neto2. Neto association promotes tonic presynaptic KAR activation, dampening CCK/CB1 interneuron output, and loss of this brake in Neto mutants profoundly increases CCK/CB1 interneuron-mediated inhibition. Our results confirm that Neto1 regulates endogenous somatodendritic KARs in diverse interneurons and demonstrate Neto regulation of presynaptic KARs in mature inhibitory presynaptic terminals.

  7. Lessons from crystal structures of kainate receptors

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    Møllerud, Stine; Frydenvang, Karla Andrea; Pickering, Darryl S;


    synaptic transmission and modulate network excitability by regulating neurotransmitter release. Dysfunction of kainate receptors has been implicated in several neurological disorders such as epilepsy, schizophrenia and depression. Here we provide a review on the current understanding of kainate receptor...... structure and how they bind agonists, antagonists and ions. The first structure of the ligand-binding domain of the GluK1 subunit was reported in 2005, seven years after publication of the crystal structure of a soluble construct of the ligand-binding domain of the AMPA-type subunit GluA2. Today, a full...

  8. Lessons from crystal structures of kainate receptors. (United States)

    Møllerud, Stine; Frydenvang, Karla; Pickering, Darryl S; Kastrup, Jette Sandholm


    Kainate receptors belong to the family of ionotropic glutamate receptors. These receptors assemble from five subunits (GluK1-5) into tetrameric ion channels. Kainate receptors are located at both pre- and postsynaptic membranes in the central nervous system where they contribute to excitatory synaptic transmission and modulate network excitability by regulating neurotransmitter release. Dysfunction of kainate receptors has been implicated in several neurological disorders such as epilepsy, schizophrenia and depression. Here we provide a review on the current understanding of kainate receptor structure and how they bind agonists, antagonists and ions. The first structure of the ligand-binding domain of the GluK1 subunit was reported in 2005, seven years after publication of the crystal structure of a soluble construct of the ligand-binding domain of the AMPA-type subunit GluA2. Today, a full-length structure has been determined of GluK2 by cryo electron microscopy to 7.6 Å resolution as well as 84 high-resolution crystal structures of N-terminal domains and ligand-binding domains, including agonist and antagonist bound structures, modulatory ions and mutations. However, there are still many unanswered questions and challenges in front of us. This article is part of the Special Issue entitled 'Ionotropic glutamate receptors'.

  9. Activity-dependent upregulation of presynaptic kainate receptors at immature CA3-CA1 synapses. (United States)

    Clarke, Vernon R J; Molchanova, Svetlana M; Hirvonen, Teemu; Taira, Tomi; Lauri, Sari E


    Presynaptic kainate-type glutamate receptors (KARs) regulate glutamate release probability and short-term plasticity in various areas of the brain. Here we show that long-term depression (LTD) in the area CA1 of neonatal rodent hippocampus is associated with an upregulation of tonic inhibitory KAR activity, which contributes to synaptic depression and causes a pronounced increase in short-term facilitation of transmission. This increased KAR function was mediated by high-affinity receptors and required activation of NMDA receptors, nitric oxide (NO) synthetase, and postsynaptic calcium signaling. In contrast, KAR activity was irreversibly downregulated in response to induction of long-term potentiation in a manner that depended on activation of the TrkB-receptor of BDNF. Both tonic KAR activity and its plasticity were restricted to early stages of synapse development and were lost in parallel with maturation of the network due to ongoing BDNF-TrkB signaling. These data show that presynaptic KARs are targets for activity-dependent modulation via diffusible messengers NO and BDNF, which enhance and depress tonic KAR activity at immature synapses, respectively. The plasticity of presynaptic KARs in the developing network allows nascent synapses to shape their response to incoming activity. In particular, upregulation of KAR function after LTD allows the synapse to preferentially pass high-frequency afferent activity. This can provide a potential rescue from synapse elimination by uncorrelated activity and also increase the computational dynamics of the developing CA3-CA1 circuitry.

  10. Kainate receptor modulation by sodium and chloride. (United States)

    Plested, Andrew J R


    The kainate-type glutamate receptor displays strong modulation by monovalent anions and cations. This modulation is independent of permeation of the ion channel. Instead, structural, computational and biophysical evidence shows that receptor activity is controlled by binding of sodium and chloride ions at sites that stabilize active dimers of glutamate binding domains. Modulation by monovalent ions is a surprisingly general property across ion channel families. However, evidence of a physiological role for ion-dependent effects on glutamate receptors is lacking, perhaps reflecting the adventitious use of ions as structural components of the kainate receptor. "ergo, Hercules, vita humanior sine sale non quit degree […]" "Heaven known, a civilized life is impossible without salt" -Pliny the Elder, Natural History XXXI 88.

  11. Functional diversity and developmental changes in rat neuronal kainate receptors. (United States)

    Wilding, T J; Huettner, J E


    1. Whole-cell currents evoked by kainate and the GluR5-selective agonist (RS)-2-amino-3-(3-hydroxy-5-tertbutylisoxazol-4-yl)propanoic acid (ATPA) were used to compare the physiological properties of kainate receptors expressed by neurons from rat hippocampus, spinal cord and dorsal root ganglia. 2. In contrast to kainate, which evoked desensitizing currents with similar decay rates and steady-state components in all three cell types, responses to ATPA were distinctly different in the three cell populations. Currents evoked by ATPA displayed a significant steady-state component in hippocampal neurons, but decayed rapidly to baseline in dorsal root ganglion (DRG) cells. ATPA failed to evoke current in many of the spinal neurons. 3. ATPA caused steady-state desensitization in DRG cells with an IC50 of 41 nM. Recovery from desensitization of DRG cell receptors by ATPA was significantly slower than for any previously described agonist. In contrast, hippocampal kainate receptors recovered from desensitization by ATPA within a few seconds. 4. Half-maximal activation of kainate receptors in hippocampal neurons required 938 nM ATPA. In DRG cells treated with concanavalin A the EC50 for ATPA was 341 nM. ATPA evoked current in embryonic hippocampal neurons but with lower amplitude relative to kainate than in cultured postnatal neurons. 5. Collectively, these results highlight functional differences between neuronal kainate receptors that may reflect their distinct subunit composition and their diverse roles in synaptic transmission.

  12. Contribution of Aberrant GluK2-Containing Kainate Receptors to Chronic Seizures in Temporal Lobe Epilepsy

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    Angélique Peret


    Full Text Available Kainate is a potent neurotoxin known to induce acute seizures. However, whether kainate receptors (KARs play any role in the pathophysiology of temporal lobe epilepsy (TLE is not known. In TLE, recurrent mossy fiber (rMF axons form abnormal excitatory synapses onto other dentate granule cells that operate via KARs. The present study explores the pathophysiological implications of KARs in generating recurrent seizures in chronic epilepsy. In an in vitro model of TLE, seizure-like activity was minimized in mice lacking the GluK2 subunit, which is a main component of aberrant synaptic KARs at rMF synapses. In vivo, the frequency of interictal spikes and ictal discharges was strongly reduced in GluK2−/− mice or in the presence of a GluK2/GluK5 receptor antagonist. Our data show that aberrant GluK2-containing KARs play a major role in the chronic seizures that characterize TLE and thus constitute a promising antiepileptic target.

  13. The Structure of a High-Affinity Kainate Receptor: GluK4 Ligand-Binding Domain Crystallized with Kainate. (United States)

    Kristensen, Ole; Kristensen, Lise Baadsgaard; Møllerud, Stine; Frydenvang, Karla; Pickering, Darryl S; Kastrup, Jette Sandholm


    Ionotropic glutamate receptors play a key role in fast neurotransmission in the CNS and have been linked to several neurological diseases and disorders. One subfamily is the kainate receptors, which are grouped into low-affinity (GluK1-3) and high-affinity (GluK4-5) receptors based on their affinity for kainate. Although structures of the ligand-binding domain (LBD) of all low-affinity kainate receptors have been reported, no structures of the high-affinity receptor subunits are available. Here, we present the X-ray structure of GluK4-LBD with kainate at 2.05 Å resolution, together with thermofluor and radiolabel binding affinity data. Whereas binding-site residues in GluK4 are most similar to the AMPA receptor subfamily, the domain closure and D1-D2 interlobe contacts induced by kainate are similar to the low-affinity kainate receptor GluK1. These observations provide a likely explanation for the high binding affinity of kainate at GluK4-LBD.

  14. 3-Substituted phenylalanines as selective AMPA- and kainate receptor ligands

    DEFF Research Database (Denmark)

    Szymanska, Ewa; Pickering, Darryl S; Nielsen, Birgitte


    On the basis of X-ray structures of ionotropic glutamate receptor constructs in complex with amino acid-based AMPA and kainate receptor antagonists, a series of rigid as well as flexible biaromatic alanine derivatives carrying selected hydrogen bond acceptors and donors have been synthesized...... in order to investigate the structural determinants for receptor selectivity between AMPA and the GluR5 subtype of kainate receptors. Compounds selective for either GluR5 or AMPA receptors were identified. One particular substituent position appeared to be of special importance for control of ligand...... selectivity. Using molecular modeling the observed structure-activity relationships at AMPA and GluR5 receptors were deduced....

  15. Brain-derived neurotrophic factor controls activity-dependent maturation of CA1 synapses by downregulating tonic activation of presynaptic kainate receptors. (United States)

    Sallert, Marko; Rantamäki, Tomi; Vesikansa, Aino; Anthoni, Heidi; Harju, Kirsi; Yli-Kauhaluoma, Jari; Taira, Tomi; Castren, Eero; Lauri, Sari E


    Immature hippocampal synapses express presynaptic kainate receptors (KARs), which tonically inhibit glutamate release. Presynaptic maturation involves activity-dependent downregulation of the tonic KAR activity and consequent increase in release probability; however, the molecular mechanisms underlying this developmental process are unknown. Here, we have investigated whether brain derived neurotrophic factor (BDNF), a secreted protein implicated in developmental plasticity in several areas of the brain, controls presynaptic maturation by regulating KARs. Application of BDNF in neonate hippocampal slices resulted in increase in synaptic transmission that fully occluded the immature-type KAR activity in area CA1. Conversely, genetic ablation of BDNF was associated with delayed synaptic maturation and persistent presynaptic KAR activity, suggesting a role for endogenous BDNF in the developmental regulation of KAR function. In addition, our data suggests a critical role for BDNF TrkB signaling in fast activity-dependent regulation of KARs. Selective acute inhibition of TrkB receptors using a chemical-genetic approach prevented rapid change in synapse dynamics and loss of tonic KAR activity that is typically seen in response to induction of LTP at immature synapses. Together, these data show that BDNF-TrkB-dependent maturation of glutamatergic synapses is tightly associated with a loss of endogenous KAR activity. The coordinated action of these two receptor mechanisms has immediate physiological relevance in controlling presynaptic efficacy and transmission dynamics at CA3-CA1 synapses at a stage of development when functional contact already exists but transmission is weak.

  16. Presynaptic inhibition by kainate receptors converges mechanistically with presynaptic inhibition by adenosine and GABAB receptors. (United States)

    Partovi, Dara; Frerking, Matthew


    Kainate receptors are widely reported to regulate the release of neurotransmitter in the CNS, but the mechanisms involved remain controversial. Previous studies have found that the kainate receptor agonist ATPA, which selectively activates Glu(K5)-containing kainate receptors, depresses glutamate release at Schaffer-collateral synapses in the hippocampus. In the present study, we provide pharmacological evidence that this depressant effect is mediated by Glu(K5)-containing heteromers, but is distinct from a similar depressant effect engaged by the kainate receptor agonist domoate. The depressant effect of ATPA is insensitive to antagonists for GABA(A), GABA(B), and adenosine receptors, and is also unaffected by lowering the release probability by reducing extracellular calcium. However, the effect of ATPA is partly occluded by prior activation of GABA(B) receptors and completely occluded by prior activation of adenosine receptors, suggesting a mechanistic convergence of heteromeric Glu(K5) kainate receptor signaling with GABA(B) receptors and adenosine receptors. The effects of domoate are partially occluded by both adenosine and GABA(B) receptor agonists, indicating at least a partial convergence of Glu(K5)-lacking kainate receptor signaling with these other pathways. The depressant effect of ATPA is not blocked by inhibition of serine/threonine protein kinases. These results suggest that ATPA and domoate inhibit glutamate release through mechanisms that converge with those of classical metabotropic receptor agonists, although they do so through different receptors.

  17. Effects of the kainate receptor agonist ATPA on glutamatergic synaptic transmission and plasticity during early postnatal development. (United States)

    Sallert, Marko; Malkki, Hemi; Segerstråle, Mikael; Taira, Tomi; Lauri, Sari E


    Kainate type of glutamate receptors (KARs) modulate synaptic transmission in a developmentally regulated manner at several synapses in the brain. Previous studies have shown that KARs depress glutamatergic transmission at CA3-CA1 synapses in the hippocampus and these receptors are tonically active during early postnatal development. Here we use the GluR5 subunit specific agonist ATPA to further characterize the role of KARs in the modulation of synaptic transmission and plasticity in area CA1 during the first two weeks of life. We find that the depressant effect of ATPA on evoked fEPSPs/EPSCs is smaller in the neonate (P3-P6) than in the juvenile (P14-P18) rat CA1, due to endogenous activity of KAR in the neonate. Further, in the neonate but not juvenile CA1, ATPA downregulates action-potential independent transmission (mEPSCs) and its effects are dependent on protein kinase C activity. ATPA-induced depression of fEPSPs in the neonate occludes the presynaptic component of long-term depression (LTD). In contrast, at P14-P18, ATPA prevents LTD indirectly via GABAergic mechanisms. These data show that GluR5 signaling mechanisms are developmentally regulated and suggest distinct functional role for KARs in the modulation of synaptic transmission and plasticity at different stages of development.

  18. Stimulation of lateral hypothalamic kainate receptors selectively elicits feeding behavior. (United States)

    Hettes, Stacey R; Heyming, Theodore W; Stanley, B Glenn


    Glutamate and its receptor agonists, NMDA, AMPA, and KA, elicit feeding when microinjected into the lateral hypothalamus (LH) of satiated rats. However, determining the relative contributions of AMPA receptors (AMPARs) and KA receptors (KARs) to LH feeding mechanisms has been difficult due to a lack of receptor selective agonists and antagonists. Furthermore, LH injection of KA produces behavioral hyperactivity, questioning a role for KARs in feeding selective stimulation. In the present study, we used the KAR agonist, (RS)-2-amino-3-(3-hydroxy-5-tert-butylisoxazol-4-yl) propanoic acid (ATPA), which selectively binds the GluR5 subunit of KARs, to stimulate feeding, presumably via KAR activation. Using ATPA, we tested whether: (1) LH injection of ATPA elicits feeding, (2) prior treatment with the non-selective AMPA/KAR antagonist, CNQX, suppresses ATPA-elicited feeding, and (3) LH injection of ATPA elicits behavioral patterns specific for feeding. We found that injection of ATPA (0.1 and 1 nmol) elicited an intense feeding response (e.g., 4.8+/-1.6 g) that was blocked by LH pretreatment with CNQX, but was unaffected by pretreatment with the AMPAR selective antagonist, GYKI 52466. Furthermore, minute-by-minute behavioral analysis revealed that LH injection of ATPA increased time spent feeding to 55% of the initial test period with little or no effects on other behaviors at any time. In contrast, LH injection of KA similarly increased feeding but also produced intense locomotor activity. These data suggest that selective activation of LH KARs containing GluR5 subunit(s) is sufficient to elicit feeding.

  19. Distinct Subunit Domains Govern Synaptic Stability and Specificity of the Kainate Receptor

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    Christoph Straub


    Full Text Available Synaptic communication between neurons requires the precise localization of neurotransmitter receptors to the correct synapse type. Kainate-type glutamate receptors restrict synaptic localization that is determined by the afferent presynaptic connection. The mechanisms that govern this input-specific synaptic localization remain unclear. Here, we examine how subunit composition and specific subunit domains contribute to synaptic localization of kainate receptors. The cytoplasmic domain of the GluK2 low-affinity subunit stabilizes kainate receptors at synapses. In contrast, the extracellular domain of the GluK4/5 high-affinity subunit synergistically controls the synaptic specificity of kainate receptors through interaction with C1q-like proteins. Thus, the input-specific synaptic localization of the native kainate receptor complex involves two mechanisms that underlie specificity and stabilization of the receptor at synapses.

  20. Presynaptic kainate receptors that enhance the release of GABA on CA1 hippocampal interneurons. (United States)

    Cossart, R; Tyzio, R; Dinocourt, C; Esclapez, M; Hirsch, J C; Ben-Ari, Y; Bernard, C


    We report that kainate receptors are present on presynaptic GABAergic terminals contacting interneurons and that their activation increases GABA release. Application of kainate increased the frequency of miniature inhibitory postsynaptic currents recorded in CA1 interneurons. Local applications of glutamate but not of AMPA or NMDA also increased GABA quantal release. Application of kainate as well as synaptically released glutamate reduced the number of failures of GABAergic neurotransmission between interneurons. Thus, activation of presynaptic kainate receptors increases the probability of GABA release at interneuron-interneuron synapses. Glutamate may selectively control the communication between interneurons by increasing their mutual inhibition.

  1. Role of GluK1 kainate receptors in seizures, epileptic discharges, and epileptogenesis. (United States)

    Fritsch, Brita; Reis, Janine; Gasior, Maciej; Kaminski, Rafal M; Rogawski, Michael A


    Kainate receptors containing the GluK1 subunit have an impact on excitatory and inhibitory neurotransmission in brain regions, such as the amygdala and hippocampus, which are relevant to seizures and epilepsy. Here we used 2-amino-3-(3-hydroxy-5-tert-butylisoxazol-4-yl) propanoic acid (ATPA), a potent and selective agonist of kainate receptors that include the GluK1 subunit, in conjunction with mice deficient in GluK1 and GluK2 kainate receptor subunits to assess the role of GluK1 kainate receptors in provoking seizures and in kindling epileptogenesis. We found that systemic ATPA, acting specifically via GluK1 kainate receptors, causes locomotor arrest and forelimb extension (a unique behavioral characteristic of GluK1 activation) and induces myoclonic behavioral seizures and electrographic seizure discharges in the BLA and hippocampus. In contrast, the proconvulsant activity of systemic AMPA, kainate, and pentylenetetrazol is not mediated by GluK1 kainate receptors, and deletion of these receptors does not elevate the threshold for seizures in the 6 Hz model. ATPA also specifically activates epileptiform discharges in BLA slices in vitro via GluK1 kainate receptors. Olfactory bulb kindling developed similarly in wild-type, GluK1, and GluK2 knock-out mice, demonstrating that GluK1 kainate receptors are not required for epileptogenesis or seizure expression in this model. We conclude that selective activation of kainate receptors containing the GluK1 subunit can trigger seizures, but these receptors are not necessary for seizure generation in models commonly used to identify therapeutic agents for the treatment of epilepsy.

  2. High firing rate of neonatal hippocampal interneurons is caused by attenuation of afterhyperpolarizing potassium currents by tonically active kainate receptors. (United States)

    Segerstråle, Mikael; Juuri, Juuso; Lanore, Frédéric; Piepponen, Petteri; Lauri, Sari E; Mulle, Christophe; Taira, Tomi


    In the neonatal hippocampus, the activity of interneurons shapes early network bursts that are important for the establishment of neuronal connectivity. However, mechanisms controlling the firing of immature interneurons remain elusive. We now show that the spontaneous firing rate of CA3 stratum lucidum interneurons markedly decreases during early postnatal development because of changes in the properties of GluK1 (formerly known as GluR5) subunit-containing kainate receptors (KARs). In the neonate, activation of KARs by ambient glutamate exerts a tonic inhibition of the medium-duration afterhyperpolarization (mAHP) by a G-protein-dependent mechanism, permitting a high interneuronal firing rate. During development, the amplitude of the apamine-sensitive K+ currents responsible for the mAHP increases dramatically because of decoupling between KAR activation and mAHP modulation, leading to decreased interneuronal firing. The developmental shift in the KAR function and its consequences on interneuronal activity are likely to have a fundamental role in the maturation of the synchronous neuronal oscillations typical for adult hippocampal circuitry.

  3. Presynaptic regulation of the inhibitory transmission by GluR5-containing kainate receptors in spinal substantia gelatinosa. (United States)

    Xu, Hui; Wu, Long-Jun; Zhao, Ming-Gao; Toyoda, Hiroki; Vadakkan, Kunjumon I; Jia, Yongheng; Pinaud, Raphael; Zhuo, Min


    GluR5-containing kainate receptors (KARs) are known to be involved in nociceptive transmission. Our previous work has shown that the activation of presynaptic KARs regulates GABAergic and glycinergic synaptic transmission in cultured dorsal horn neurons. However, the role of GluR5-containing KARs in the modulation of inhibitory transmission in the spinal substantia gelatinosa (SG) in slices remains unknown. In the present study, pharmacological, electrophysiological and genetic methods were used to show that presynaptic GluR5 KARs are involved in the modulation of inhibitory transmission in the SG of spinal slices in vitro. The GluR5 selective agonist, ATPA, facilitated the frequency but not amplitude of spontaneous inhibitory postsynaptic currents (sIPSCs) in SG neurons. ATPA increased sIPSC frequency in all neurons with different firing patterns as delayed, tonic, initial and single spike patterns. The frequency of either GABAergic or glycinergic sIPSCs was significantly increased by ATPA. ATPA could also induce inward currents in all SG neurons recorded. The frequency, but not amplitude, of action potential-independent miniature IPSCs (mIPSCs) was also facilitated by ATPA in a concentration-dependent manner. However, the effect of ATPA on the frequency of either sIPSCs or mIPSCs was abolished in GluR5-/- mice. Deletion of the GluR5 subunit gene had no effect on the frequency or amplitude of mIPSCs in SG neurons. However, GluR5 antagonist LY293558 reversibly inhibited sIPSC and mIPSC frequencies in spinal SG neurons. Taken together, these results suggest that GluR5 KARs, which may be located at presynaptic terminals, contribute to the modulation of inhibitory transmission in the SG. GluR5-containing KARs are thus important for spinal sensory transmission/modulation in the spinal cord.

  4. Presynaptic regulation of the inhibitory transmission by GluR5-containing kainate receptors in spinal substantia gelatinosa

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    Pinaud Raphael


    Full Text Available Abstract GluR5-containing kainate receptors (KARs are known to be involved in nociceptive transmission. Our previous work has shown that the activation of presynaptic KARs regulates GABAergic and glycinergic synaptic transmission in cultured dorsal horn neurons. However, the role of GluR5-containing KARs in the modulation of inhibitory transmission in the spinal substantia gelatinosa (SG in slices remains unknown. In the present study, pharmacological, electrophysiological and genetic methods were used to show that presynaptic GluR5 KARs are involved in the modulation of inhibitory transmission in the SG of spinal slices in vitro. The GluR5 selective agonist, ATPA, facilitated the frequency but not amplitude of spontaneous inhibitory postsynaptic currents (sIPSCs in SG neurons. ATPA increased sIPSC frequency in all neurons with different firing patterns as delayed, tonic, initial and single spike patterns. The frequency of either GABAergic or glycinergic sIPSCs was significantly increased by ATPA. ATPA could also induce inward currents in all SG neurons recorded. The frequency, but not amplitude, of action potential-independent miniature IPSCs (mIPSCs was also facilitated by ATPA in a concentration-dependent manner. However, the effect of ATPA on the frequency of either sIPSCs or mIPSCs was abolished in GluR5-/- mice. Deletion of the GluR5 subunit gene had no effect on the frequency or amplitude of mIPSCs in SG neurons. However, GluR5 antagonist LY293558 reversibly inhibited sIPSC and mIPSC frequencies in spinal SG neurons. Taken together, these results suggest that GluR5 KARs, which may be located at presynaptic terminals, contribute to the modulation of inhibitory transmission in the SG. GluR5-containing KARs are thus important for spinal sensory transmission/modulation in the spinal cord.

  5. Role of desensitization and subunit expression for kainate receptor-mediated neurotoxicity in murine neocortical cultures

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    Jensen, J B; Schousboe, A; Pickering, D S


    ) toxicity mediated by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors, and (3) toxicity that can be mediated by kainate receptors when desensitization of the receptors is blocked. The indirect action at NMDA receptors was discovered because (5R, 10S)-(+)-5-methyl-10,11-dihydro-5H...... nedioxy-5H-2,3-benzodiazepine (GYKI 53655), a selective AMPA receptor antagonist, abolished the remaining toxicity. These results indicated that kainate- and domoate-mediated toxicity involves both the NMDA and the AMPA receptors. Pretreatment of the cultures with concanavalin A to prevent desensitization...

  6. Topiramate selectively protects against seizures induced by ATPA, a GluR5 kainate receptor agonist. (United States)

    Kaminski, Rafal M; Banerjee, Madhumita; Rogawski, Michael A


    Although the mechanism of action of topiramate is not fully understood, its anticonvulsant properties may result, at least in part, from an interaction with AMPA/kainate receptors. We have recently shown that topiramate selectively inhibits postsynaptic responses mediated by GluR5 kainate receptors. To determine if this action of topiramate is relevant to the anticonvulsant effects of the drug in vivo, we determined the protective activity of topiramate against seizures induced by intravenous infusion of various ionotropic glutamate receptor agonists in mice. Topiramate (25-100 mg/kg, i.p.) produced a dose-dependent elevation in the threshold for clonic seizures induced by infusion of ATPA, a selective agonist of GluR5 kainate receptors. Topiramate was less effective in protecting against clonic seizures induced by kainate, a mixed agonist of AMPA and kainate receptors. Topiramate did not affect clonic seizures induced by AMPA or NMDA. In contrast, the thresholds for tonic seizures induced by higher doses of these various glutamate receptor agonists were all elevated by topiramate. Unlike topiramate, carbamazepine elevated the threshold for AMPA- but not ATPA-induced clonic seizures. Our results are consistent with the possibility that the effects of topiramate on clonic seizure activity are due to functional blockade of GluR5 kainate receptors. Protection from tonic seizures may be mediated by other actions of the drug. Together with our in vitro cellular electrophysiological results, the present observations strongly support a unique mechanism of action of topiramate, which involves GluR5 kainate receptors.

  7. Stereostructure-activity studies on agonists at the AMPA and kainate subtypes of ionotropic glutamate receptors

    DEFF Research Database (Denmark)

    Johansen, Tommy N; Greenwood, Jeremy R; Frydenvang, Karla Andrea


    -methyl-4-isoxazolyl)propionic acid (AMPA) receptor subtype of ionotropic Glu receptors in the presence or absence of an agonist has provided important information about ligand-receptor interaction mechanisms. The availability of these binding domain crystal structures has formed the basis for rational...... design of ligands, especially for the AMPA and kainate subtypes of ionotropic Glu receptors. This mini-review will focus on structure-activity relationships on AMPA and kainate receptor agonists with special emphasis on stereochemical and three-dimensional aspects....

  8. Kainate receptors mediate signaling in both transient and sustained OFF bipolar cell pathways in mouse retina. (United States)

    Borghuis, Bart G; Looger, Loren L; Tomita, Susumu; Demb, Jonathan B


    A fundamental question in sensory neuroscience is how parallel processing is implemented at the level of molecular and circuit mechanisms. In the retina, it has been proposed that distinct OFF cone bipolar cell types generate fast/transient and slow/sustained pathways by the differential expression of AMPA- and kainate-type glutamate receptors, respectively. However, the functional significance of these receptors in the intact circuit during light stimulation remains unclear. Here, we measured glutamate release from mouse bipolar cells by two-photon imaging of a glutamate sensor (iGluSnFR) expressed on postsynaptic amacrine and ganglion cell dendrites. In both transient and sustained OFF layers, cone-driven glutamate release from bipolar cells was blocked by antagonists to kainate receptors but not AMPA receptors. Electrophysiological recordings from bipolar and ganglion cells confirmed the essential role of kainate receptors for signaling in both transient and sustained OFF pathways. Kainate receptors mediated responses to contrast modulation up to 20 Hz. Light-evoked responses in all mouse OFF bipolar pathways depend on kainate, not AMPA, receptors.

  9. [3H]ATPA: a high affinity ligand for GluR5 kainate receptors. (United States)

    Hoo, K; Legutko, B; Rizkalla, G; Deverill, M; Hawes, C R; Ellis, G J; Stensbol, T B; Krogsgaard-Larsen, P; Skolnick, P; Bleakman, D


    The pharmacological properties of [3H]ATPA ((RS)-2-amino-3(3-hydroxy-5-tert-butylisoxazol-4-yl)propanoic acid) are described. ATPA is a tert-butyl analogue of AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid) that has been shown to possess high affinity for the GluR5 subunit of kainate receptors. [3H]ATPA exhibits saturable, high affinity binding to membranes expressing human GluR5 (GluR5) kainate receptors (Kd approximately 13 nM). No specific binding was observed in membranes expressing GluR2 and GluR6 receptors. Several compounds known to interact with the GluR5 kainate receptor inhibited [3H]ATPA binding with potencies similar to those obtained for competition of [3H]kainate binding to GluR5. Saturable, high affinity [3H]ATPA binding (Kd approximately 4 nM) was also observed in DRG neuron (DRG) membranes isolated from neonatal rats. The rank order potency of compounds to inhibit [3H]ATPA binding in rat DRG and GluR5 membranes were in agreement. These finding demonstrate that [3H]ATPA can be used as a radioligand to examine the pharmacological properties of GluR5 containing kainate receptors.

  10. The GluK4 kainate receptor subunit regulates memory, mood, and excitotoxic neurodegeneration. (United States)

    Lowry, E R; Kruyer, A; Norris, E H; Cederroth, C R; Strickland, S


    Though the GluK4 kainate receptor subunit shows limited homology and a restricted expression pattern relative to other kainate receptor subunits, its ablation results in distinct behavioral and molecular phenotypes. GluK4 knockout mice demonstrated impairments in memory acquisition and recall in a Morris water maze test, suggesting a previously unreported role for kainate receptors in spatial memory. GluK4 knockout mice also showed marked hyperactivity and impaired pre-pulse inhibition, thereby mirroring two of the hallmark endophenotypes of patients with schizophrenia and bipolar disorder. Furthermore, we found that GluK4 is a key mediator of excitotoxic neurodegeneration: GluK4 knockout mice showed robust neuroprotection in the CA3 region of the hippocampus following intrahippocampal injection of kainate and widespread neuroprotection throughout the hippocampus following hypoxia-ischemia. Biochemical analysis of kainate- or sham-treated wild-type and GluK4 knockout hippocampal tissue suggests that GluK4 may act through the JNK pathway to regulate the molecular cascades that lead to excitotoxicity. Together, our findings suggest that GluK4 may be relevant to the understanding and treatment of human neuropsychiatric and neurodegenerative disorders.

  11. Pharmacology and crystal structure of novel 2,3-quinoxalinediones at kainate receptors

    DEFF Research Database (Denmark)

    Møllerud, Stine; Pallesen, Jakob Staun; Pasini, Diletta


    with the patho-physiology of CNS diseases such as epilepsy, schizophrenia and depression. Selective tool compounds are therefore needed to address the functional roles of different types of iGluRs. A few selective compounds that can discriminate between AMPA and kainate (KA) receptors are available. However...

  12. A pharmacological profile of the high-affinity GluK5 kainate receptor

    DEFF Research Database (Denmark)

    Møllerud, Stine; Kastrup, Jette Sandholm Jensen; Pickering, Darryl S


    Mouse GluK5 was expressed in Sf9 insect cells and radiolabelled with [3H]-kainate in receptor binding assays (Kd = 6.9 nM). Western immunoblotting indicated an Sf9 GluK5 band doublet corresponding to the glycosylated (128 kDa) and deglycosylated (111 kDa) protein, which was identical to the band...

  13. Kainate-type glutamate receptors modulating network activity in developing hippocampus


    Juuri, Juuso


    Kainate-type of ionotropic glutamate (KA) receptors are associated with the modulation of neuronal excitability, synaptic transmission, and activity of neuronal networks. They are believed to have an important role in the development of neuronal connections. In this thesis, the role of KA receptors in the early brain development was assessed by conducting in vitro electrophysiological recordings from individual neurons at CA3 region in acute slices of neonatal rodent hippocampi. It was f...

  14. Structural and pharmacological characterization of phenylalanine-based AMPA receptor antagonists at kainate receptors

    DEFF Research Database (Denmark)

    Venskutonyte, Raminta; Frydenvang, Karla; Valadés, Elena Antón


    . A new series of phenylalanine derivatives that target iGluRs was reported to bind AMPA receptors. Herein we report our studies of these compounds at the kainate receptors GluK1-3. Several compounds bind with micromolar affinity at GluK1 and GluK3, but do not bind GluK2. The crystal structure of the most...... potent compound in the ligand binding domain of GluK1 revealed different modes of binding to GluK1 and GluA2, due primarily to residues Ser741 (GluK1) and Met729 (GluA2). The compound was shown to be slightly more potent at GluK1 than at AMPA receptors and to induce a domain closure similar...

  15. Computational study of the evolutionary relationships of the ionotropic receptors NMDA, AMPA and kainate in four species of primates.


    Moreno-Pedraza, Francy Johanna; Grupo de Bioquímica Molecular Computacional y Bioinformática, Departamento de Bioquímica, Facultad de Ciencias. Pontificia Universidad Javeriana, Carrera 7 No. 43-82 Ed. 52, Bogotá,; Lareo, Leonardo René; Grupo de Bioquímica Molecular Computacional y Bioinformática, Departamento de Bioquímica, Facultad de Ciencias. Pontificia Universidad Javeriana, Carrera 7 No. 43-82 Ed. 52, Bogotá,; Reyes-Montaño, Edgar Antonio; Grupo de Investigación en Proteínas (GRIP) Departamento de Química, Universidad Nacional de Colombia, Ciudad Universitaria, Edificio 451, Bogotá


    Objective. To identify the influence of changes on the secondary structure and evolutionary relationship of NMDA, AMPA and kainate receptors in Homo sapiens, Pan troglodytes, Pongo pygmaeus and Macaca mulatta. Materials and methods. We identified 91 sequences for NMDA, AMPA and kainate receptors and analyzed with software for predicting secondary structure, phosphorylation sites, multiple alignments, selection of protein evolution models and phylogenetic prediction. Results. We found that s...

  16. Design, synthesis and structure-activity relationships of novel phenylalanine-based amino acids as kainate receptors ligands

    DEFF Research Database (Denmark)

    Szymańska, Ewa; Chałupnik, Paulina; Szczepańska, Katarzyna


    A new series of carboxyaryl-substituted phenylalanines was designed, synthesized and pharmacologically characterized in vitro at native rat ionotropic glutamate receptors as well as at cloned homomeric kainate receptors GluK1-GluK3. Among them, six compounds bound to GluK1 receptor subtypes with ...

  17. A pharmacological profile of the high-affinity GluK5 kainate receptor. (United States)

    Møllerud, Stine; Kastrup, Jette Sandholm; Pickering, Darryl S


    Mouse GluK5 was expressed in Sf9 insect cells and radiolabelled with [(3)H]-kainate in receptor binding assays (Kd=6.9nM). Western immunoblotting indicated an Sf9 GluK5 band doublet corresponding to the glycosylated (128kDa) and deglycosylated (111kDa) protein, which was identical to the band pattern of native rat brain GluK5. A pharmacological profile of the high-affinity kainate receptor GluK5 is described which is distinct from the profiles of other kainate receptors (GluK1-3). The 27 tested ligands generally show a preferential affinity to GluK1 over GluK5, the exceptions being: dihydrokainate, (S)-5-fluorowillardiine, (S)-glutamate and quisqualate, where the affinity is similar at GluK1 and GluK5. In contrast, quisqualate shows 40-fold higher affinity at GluK5 over GluK3 whereas (S)-1-(2'-amino-2'-caboxyethyl)thienol[3,4-d]pyrimidin-2,4-dione (NF1231), (RS)-2-amino-3-(5-tert-butyl-3-hydroxyisoxazol-4-yl)propionate (ATPA), dihydrokainate and (2S,4R)-4-methyl-glutamate (SYM2081) have higher affinity at GluK3 compared to GluK5. Since some studies have indicated that GluK5 is associated with various diseases in the central nervous system (e.g. schizophrenia, temporal lobe epilepsy, bipolar disorder), selective GluK5 ligands could have therapeutic potential. The distinct pharmacological profile of GluK5 suggests that it would be possible to design ligands with selectivity towards GluK5.

  18. Structure and affinity of two bicyclic glutamate analogues at AMPA and kainate receptors

    DEFF Research Database (Denmark)

    Møllerud, Stine; Pinto, Andrea; Marconi, Laura


    and depression. In order to understand the function of different types of iGluRs, selective agonists are invaluable as pharmacological tool compounds. Here, we report binding affinities of two bicyclic, conformationally restricted analogues of glutamate (CIP-AS and LM-12b) at AMPA (GluA2 and GluA3) and kainate...... receptor subunits (GluK1-3 and GluK5). Both CIP-AS and LM-12b were found to be GluK3-preferring agonists, with Ki of 6 and 22 nM, respectively, at recombinant GluK3 receptors. The detailed binding mode of CIP-AS and LM-12b in the ligand-binding domains of the AMPA receptor subunit GluA2 (GluA2-LBD...

  19. Target-cell specificity of kainate autoreceptor and Ca2+-store-dependent short-term plasticity at hippocampal mossy fiber synapses. (United States)

    Scott, Ricardo; Lalic, Tatjana; Kullmann, Dimitri M; Capogna, Marco; Rusakov, Dmitri A


    Presynaptic kainate receptors (KARs) modulate transmission between dentate granule cells and CA3 pyramidal neurons. Whether presynaptic KARs affect other synapses made by granule cell axons [mossy fibers (MFs)], on hilar mossy cells or interneurons, is not known. Nor is it known whether glutamate release from a single MF is sufficient to activate these receptors. Here, we monitor Ca(2+) in identified MF boutons traced from granule cell bodies. We show that a single action potential in a single MF activates both presynaptic KARs and Ca(2+) stores, contributing to use-dependent facilitation at MF-CA3 pyramidal cell synapses. Rapid local application of kainate to the giant MF bouton has no detectable effect on the resting Ca(2+) but facilitates action-potential-evoked Ca(2+) entry through a Ca(2+) store-dependent mechanism. Localized two-photon uncaging of the Ca(2+) store receptor ligand IP(3) directly confirms the presence of functional Ca(2+) stores at these boutons. In contrast, presynaptic Ca(2+) kinetics at MF synapses on interneurons or mossy cells are insensitive to KAR blockade, to local kainate application or to photolytic release of IP(3). Consistent with this, postsynaptic responses evoked by activation of a single MF show KAR-dependent paired-pulse facilitation in CA3 pyramidal cells, but not in interneurons or mossy cells. Thus, KAR-Ca(2+) store coupling acts as a synapse-specific, short-range autoreceptor mechanism.

  20. Assembly Stoichiometry of the GluK2/GluK5 Kainate Receptor Complex

    Directory of Open Access Journals (Sweden)

    Andreas Reiner


    Full Text Available Ionotropic glutamate receptors assemble as homo- or heterotetramers. One well-studied heteromeric complex is formed by the kainate receptor subunits GluK2 and GluK5. Retention motifs prevent trafficking of GluK5 homomers to the plasma membrane, but coassembly with GluK2 yields functional heteromeric receptors. Additional control over GluK2/GluK5 assembly seems to be exerted by the amino-terminal domains, which preferentially assemble into heterodimers as isolated domains. However, the stoichiometry of the full-length GluK2/GluK5 receptor complex has yet to be determined, as is the case for all non-NMDA glutamate receptors. Here, we address this question, using a single-molecule imaging technique that enables direct counting of the number of each GluK subunit type in homomeric and heteromeric receptors in the plasma membranes of live cells. We show that GluK2 and GluK5 assemble with 2:2 stoichiometry. This is an important step toward understanding the assembly mechanism, architecture, and functional consequences of heteromer formation in ionotropic glutamate receptors.

  1. Effects of pilocarpine and kainate-induced seizures on N-methyl-d-aspartate receptor gene expression in the rat hippocampus

    Energy Technology Data Exchange (ETDEWEB)

    Przewlocka, B.; Labuz, D.; Machelska, H.; Przewlocki, R.; Turchan, J.; Lason, W. [Department of Molecular Neuropharmacology, Institute of Pharmacology, Polish Academy of Sciences, 12 Smetna Street, 31-343 Krakow (Poland)


    The effects of pilocarpine- and kainate-induced seizures on N-methyl-d-aspartate receptor subunit-1 messenger RNA and [{sup 3}H]dizocilpine maleate binding were studied in the rat hippocampal formation. Pilocarpine- but not kainate-induced seizures decreased N-methyl-d-aspartate receptor subunit-1 messenger RNA level in dentate gyrus at 24 and 72 h after drug injection. Both convulsants decreased the messenger RNA level in CA1 pyramidal cells at 24 and 72 h, the effects of kainate being more profound. Kainate also decreased the N-methyl-d-aspartate receptor subunit-1 messenger RNA level in CA3 region after 24 and 72 h, whereas pilocarpine decreased the messenger RNA level at 72 h only. At 3 h after kainate, but not pilocarpine, an increased binding of [{sup 3}H]dizocilpine maleate in several apical dendritic fields of pyramidal cells was found. Pilocarpine reduced the [{sup 3}H]dizocilpine maleate binding in stratum lucidum only at 3 and 24 h after the drug injection. Pilocarpine but not kainate induced prolonged decrease in N-methyl-d-aspartate receptor subunit-1 gene expression in dentate gyrus. However, at the latest time measured, kainate had the stronger effect in decreasing both messenger RNA N-methyl-d-aspartate receptor subunit-1 and [{sup 3}H]dizocilpine maleate binding in CA1 and CA3 hippocampal pyramidal cells. The latter changes corresponded, however, to neuronal loss and may reflect higher neurotoxic potency of kainate.These data point to some differences in hippocampal N-methyl-d-aspartate receptor regulation in pilocarpine and kainate models of limbic seizures. Moreover, our results suggest that the N-methyl-d-aspartate receptor subunit-1 messenger RNA level is more susceptible to limbic seizures than is [{sup 3}H]dizocilpine maleate binding in the rat hippocampal formation. (Copyright (c) 1997 Elsevier Science B.V., Amsterdam. All rights reserved.)

  2. Neuroprotection of GluK1 kainate receptor agonist ATPA against ischemic neuronal injury through inhibiting GluK2 kainate receptor-JNK3 pathway via GABA(A) receptors. (United States)

    Lv, Qian; Liu, Yong; Han, Dong; Xu, Jing; Zong, Yan-Yan; Wang, Yao; Zhang, Guang-Yi


    It is well known that GluK2-containing kainate receptors play essential roles in seizure and cerebral ischemia-induced neuronal death, while GluK1-containing kainate receptors could increase tonic inhibition of post-synaptic pyramidal neurons. This research investigated whether GluK1 could inhibit activation of c-Jun N-terminal kinase 3 (JNK3) signaling pathway mediated by the GluK2 in cerebral ischemia-reperfusion. The results show that GluK1 activation by (RS)-2-amino-3-(3-hydroxy-5-tert-butylisoxazol-4-yl) propanoic acid (ATPA) at 1nmol per rat could inhibit the assembly of GluK2·Postsynaptic density 95·mixed lineage kinase 3 signaling module, activation of JNK3 and its downstream signal molecules. However, the inhibition of ATPA could be prevented by GluK1 antagonist NS3763, GluK1 antisense, and GABA(A) receptor antagonist bicuculline. In addition, ATPA played a neuroprotective role against cerebral ischemia. In sum, the findings indicate that activation of GluK1 by ATPA at specific dosages may promote GABA release, which then suppresses post-synaptic GluK2-JNK3 signaling-mediated cerebral ischemic injury via GABA(A)R.

  3. Differences in AMPA and Kainate Receptor Interactomes Facilitate Identification of AMPA Receptor Auxiliary Subunit GSG1L

    Directory of Open Access Journals (Sweden)

    Natalie F. Shanks


    Full Text Available AMPA receptor (AMPA-R complexes consist of channel-forming subunits, GluA1-4, and auxiliary proteins, including TARPs, CNIHs, synDIG1, and CKAMP44, which can modulate AMPA-R function in specific ways. The combinatorial effects of four GluA subunits binding to various auxiliary subunits amplify the functional diversity of AMPA-Rs. The significance and magnitude of molecular diversity, however, remain elusive. To gain insight into the molecular complexity of AMPA and kainate receptors, we compared the proteins that copurify with each receptor type in the rat brain. This interactome study identified the majority of known interacting proteins and, more importantly, provides candidates for additional studies. We validate the claudin homolog GSG1L as a newly identified binding protein and unique modulator of AMPA-R gating, as determined by detailed molecular, cellular, electrophysiological, and biochemical experiments. GSG1L extends the functional variety of AMPA-R complexes, and further investigation of other candidates may reveal additional complexity of ionotropic glutamate receptor function.

  4. Synaptic kainate receptors in interplay with INaP shift the sparse firing of dentate granule cells to a sustained rhythmic mode in temporal lobe epilepsy. (United States)

    Artinian, Julien; Peret, Angélique; Marti, Geoffrey; Epsztein, Jérôme; Crépel, Valérie


    Dentate granule cells, at the gate of the hippocampus, use coincidence detection of synaptic inputs to code afferent information under a sparse firing regime. In both human patients and animal models of temporal lobe epilepsy, mossy fibers sprout to form an aberrant glutamatergic network between dentate granule cells. These new synapses operate via long-lasting kainate receptor-mediated events, which are not present in the naive condition. Here, we report that in chronic epileptic rat, aberrant kainate receptors in interplay with the persistent sodium current dramatically expand the temporal window for synaptic integration. This introduces a multiplicative gain change in the input-output operation of dentate granule cells. As a result, their sparse firing is switched to an abnormal sustained and rhythmic mode. We conclude that synaptic kainate receptors dramatically alter the fundamental coding properties of dentate granule cells in temporal lobe epilepsy.

  5. Kainate Receptors in the Striatum: Implications for Excitotoxicity in Huntington’s Disease (United States)


    finding regarding the anatomical organization of caudal intralaminar Pf, which provides a massive feed - the basal ganglia is the demonstration of multiple...Trends Neurosci. 12, 366- Bonanno et a!., 1998). Future behavioural studies of 375. baclofen in animal models should help ascertain the Ainhardekar...Glutamand inhibitoryn raptor mese dephc pncipal Charara, A., Blankstein, E., Smith, Y., 1999. Presynaptic kainate tory and inhibitory transmission on rat

  6. Soman Induces Ictogenesis in the Amygdala and Interictal Activity in the Hippocampus That Are Blocked by a GluR5 Kainate Receptor Antagonist In Vitro (United States)


    damage, with long-term neu- ological and behavioral consequences (McDonough et al., 986; Brown and Brix , 1998; Bajgar et al., 2004). Nerve gent–induced...raga MF, Aroniadou-Anderjaska V, Li H (2004) The physiological role of kainate receptors in the amygdala. Mol Neurobiol 30:127–141. rown MA, Brix KA

  7. Phenobarbital but not diazepam reduces AMPA/Kainate receptor mediated currents and exerts opposite actions on initial seizures in the neonatal rat hippocampus

    Directory of Open Access Journals (Sweden)

    Romain eNardou


    Full Text Available Diazepam (DZP and phenobarbital (PB are extensively used as first and second line drugs to treat acute seizures in neonates and their actions are thought to be mediated by increasing the actions of GABAergic signals. Yet, their efficacy is variable with occasional failure or even aggravation of recurrent seizures questioning whether other mechanisms are not involved in their actions. We have now compared the effects of DZP and PB on ictal-like events (ILEs in an in vitro model of mirror focus (MF. Using the three-compartment chamber with the two immature hippocampi and their commissural fibers placed in 3 different compartments, kainate was applied to one hippocampus and PB or DZP to the contralateral one, either after one ILE or after many recurrent ILEs that produce an epileptogenic MF. We report that in contrast to PB, DZP aggravated propagating ILEs from the start and did not prevent the formation of MF. PB reduced and DZP increased the network driven Giant Depolarising Potentials suggesting that PB may exert additional actions that are not mediated by GABA signalling. In keeping with this, PB but not DZP reduced field potentials recorded in the presence of GABA and NMDA receptor antagonists. These effects are mediated by a direct action on AMPA/Kainate receptors since PB: i reduced AMPA/Kainate receptor mediated currents induced by focal applications of glutamate ; ii reduced the amplitude and the frequency of AMPA but not NMDA receptor mediated miniature EPSCs; iii augmented the number of AMPA receptor mediated EPSCs failures evoked by minimal stimulation. These effects persisted in MF. Therefore, PB exerts its anticonvulsive actions partly by reducing AMPA/Kainate receptors mediated EPSCs in addition to the pro-GABA effects. We suggest that PB may have advantage over DZP in the treatment of initial neonatal seizures since the additional reduction of glutamate receptors mediated signals may reduce the severity of neonatal seizures.

  8. Selective androgen receptor modulator RAD140 is neuroprotective in cultured neurons and kainate-lesioned male rats. (United States)

    Jayaraman, Anusha; Christensen, Amy; Moser, V Alexandra; Vest, Rebekah S; Miller, Chris P; Hattersley, Gary; Pike, Christian J


    The decline in testosterone levels in men during normal aging increases risks of dysfunction and disease in androgen-responsive tissues, including brain. The use of testosterone therapy has the potential to increase the risks for developing prostate cancer and or accelerating its progression. To overcome this limitation, novel compounds termed "selective androgen receptor modulators" (SARMs) have been developed that lack significant androgen action in prostate but exert agonist effects in select androgen-responsive tissues. The efficacy of SARMs in brain is largely unknown. In this study, we investigate the SARM RAD140 in cultured rat neurons and male rat brain for its ability to provide neuroprotection, an important neural action of endogenous androgens that is relevant to neural health and resilience to neurodegenerative diseases. In cultured hippocampal neurons, RAD140 was as effective as testosterone in reducing cell death induced by apoptotic insults. Mechanistically, RAD140 neuroprotection was dependent upon MAPK signaling, as evidenced by elevation of ERK phosphorylation and inhibition of protection by the MAPK kinase inhibitor U0126. Importantly, RAD140 was also neuroprotective in vivo using the rat kainate lesion model. In experiments with gonadectomized, adult male rats, RAD140 was shown to exhibit peripheral tissue-specific androgen action that largely spared prostate, neural efficacy as demonstrated by activation of androgenic gene regulation effects, and neuroprotection of hippocampal neurons against cell death caused by systemic administration of the excitotoxin kainate. These novel findings demonstrate initial preclinical efficacy of a SARM in neuroprotective actions relevant to Alzheimer's disease and related neurodegenerative diseases.

  9. Characterisation of the effects of ATPA, a GLU(K5) kainate receptor agonist, on GABAergic synaptic transmission in the CA1 region of rat hippocampal slices. (United States)

    Clarke, V R J; Collingridge, G L


    Kainate receptors are implicated in a variety of physiological and pathological processes in the CNS. Previously we demonstrated that (RS)-2-amino-3-(3-hydroxy-5-tert-butylisoxazol-4-yl)propanoic acid (ATPA), a selective agonist for the GLU(K5) subtype of kainate receptor, depresses monosynaptically evoked inhibitory postsynaptic potentials (IPSPs) in the CA1 region of the rat hippocampus. In the current study, we provide a more detailed characterisation of this effect. Firstly, our data demonstrate a rank order of potency of domoate>kainate>ATPA>alpha-amino-3-(3-hydroxy-5-methyl-4-isoxalolyl)propionic acid Secondly, we confirm that the effects of ATPA are not mediated indirectly via the activation of gamma-aminobutyric acid receptors (i.e. either GABA(A) or GABA(B)). Thirdly, we show that the small increase in conductance induced by ATPA is insufficient to account for the depression of monosynaptic inhibition. Fourthly, we show that the effects of ATPA on IPSPs are antagonised by the GLU(K5)-selective antagonist (3S, 4aR, 6S, 8aR)-6-(4-carboxyphenyl)methyl-1,2,3,4,4a,5,6,7,8,8a-decahydroisoquinoline-3-carboxylic acid (LY382884). However, LY382884 is less potent as an antagonist of the effects of ATPA on IPSPs compared to its depressant effect on EPSPs.

  10. Proteolytic fragments of laminin promote excitotoxic neurodegeneration by up-regulation of the KA1 subunit of the kainate receptor. (United States)

    Chen, Zu-Lin; Yu, Huaxu; Yu, Wei-Ming; Pawlak, Robert; Strickland, Sidney


    Degradation of the extracellular matrix (ECM) protein laminin contributes to excitotoxic cell death in the hippocampus, but the mechanism of this effect is unknown. To study this process, we disrupted laminin gamma1 (lamgamma1) expression in the hippocampus. Lamgamma1 knockout (KO) and control mice had similar basal expression of kainate (KA) receptors, but the lamgamma1 KO mice were resistant to KA-induced neuronal death. After KA injection, KA1 subunit levels increased in control mice but were unchanged in lamgamma1 KO mice. KA1 levels in tissue plasminogen activator (tPA)-KO mice were also unchanged after KA, indicating that both tPA and laminin were necessary for KA1 up-regulation after KA injection. Infusion of plasmin-digested laminin-1 into the hippocampus of lamgamma1 or tPA KO mice restored KA1 up-regulation and KA-induced neuronal degeneration. Interfering with KA1 function with a specific anti-KA1 antibody protected against KA-induced neuronal death both in vitro and in vivo. These results demonstrate a novel pathway for neurodegeneration involving proteolysis of the ECM and KA1 KA receptor subunit up-regulation.

  11. Role of AMPA and GluR5 kainate receptors in the development and expression of amygdala kindling in the mouse. (United States)

    Rogawski, M A; Kurzman, P S; Yamaguchi, S I; Li, H


    The role of AMPA and GluR5-containing kainate receptors in the development and expression of amygdala kindling was examined using the selective 2,3-benzodiazepine AMPA receptor antagonist GYKI 52466 [(1-(4-aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2, 3-benzodiazepine] and the decahydroisoquinoline mixed AMPA receptor and GluR5 kainate receptor antagonist LY293558 {(3S,4aR,6R, 8aR)-6-[2-(1(2)H-tetrazole-5-yl)ethyl]decahydroisoquinoline- 3-carboxy lic acid)}. Administration of GYKI 52466 (5-40 mg/kg, intraperitoneally) and LY293558 (10-40 mg/kg, intraperitoneally) prior to daily kindling stimulation in mice produced a dose-dependent suppression of the rate of development of behavioral kindled seizure activity and reduced the duration of the stimulation-induced electrographic afterdischarge. In drug-free stimulation sessions after the initial drug-treatment sessions, there was an acceleration in the rate of kindling development compared with the rate during the preceding drug-administration period; the "rebound" rate was also greater than the kindling rate in saline-treated control animals. In fully kindled animals, both GYKI 52466 and LY293558 produced a dose-dependent suppression of evoked seizures (ED(50), 19.3 and 16.7 mg/kg, respectively). Although AMPA receptors appear to be critical to the expression of kindled seizures, since kindling development progressed despite the suppression of behavioral seizure activity, AMPA receptors are less important to the kindling process. LY293558 was modestly less effective at suppressing behavioral seizures during kindling and was not superior to GYKI 52466 in retarding the overall extent of kindling development, indicating that GluR5 kainate receptors do not contribute to epileptogenesis in this model.

  12. Pharmacology and crystal structure of novel 2,3-quinoxalinediones at kainate receptors

    DEFF Research Database (Denmark)

    Møllerud, Stine; Pallesen, Jakob Staun; Pasini, Diletta


    , within the KA receptor family (GluK1-5) only compounds with selectivity towards GluK1 exist [1]. Thus, there is an unmet need for Tool compounds with selectivity towards the remaining KA receptor subunits. Here we report the pharmacology of a series of novel N1-substituted 2,3-quinoxalinediones, as well....... Functional electrophysiological (TEVC) experiments indeed showed these compounds to be antagonists at cloned, homomeric KA receptors. The structure and pharmacology will be valuable for design of new and more GluK3-selective quinoxalinedione analogues....

  13. Topiramate reduces excitability in the basolateral amygdala by selectively inhibiting GluK1 (GluR5) kainate receptors on interneurons and positively modulating GABAA receptors on principal neurons. (United States)

    Braga, Maria F M; Aroniadou-Anderjaska, Vassiliki; Li, He; Rogawski, Michael A


    Topiramate [2,3:4,5-bis-O-(1-methylethylidene)-beta-D-fructopyranose sulfamate] is a structurally novel antiepileptic drug that has broad efficacy in epilepsy, but the mechanisms underlying its therapeutic activity are not fully understood. We have found that topiramate selectively inhibits GluK1 (GluR5) kainate receptor-mediated excitatory postsynaptic responses in rat basolateral amygdala (BLA) principal neurons and protects against seizures induced by the GluK1 kainate receptor agonist (R,S)-2-amino-3-(3-hydroxy-5-tert-butylisoxazol-4-yl)propanoic acid (ATPA). Here, we demonstrate that topiramate also modulates inhibitory function in the BLA. Using whole-cell recordings in rat amygdala slices, we found that 0.3 to 10 microM topiramate 1) inhibited ATPA-evoked postsynaptic currents recorded from BLA interneurons; 2) suppressed ATPA-induced enhancement of spontaneous inhibitory postsynaptic currents (IPSCs) recorded from BLA pyramidal cells; and 3) blocked ATPA-induced suppression of evoked IPSCs, which is mediated by presynaptic GluK1 kainate receptors present on BLA interneurons. Topiramate (10 microM) had no effect on the AMPA [(R,S)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid]-induced enhancement of spontaneous activity of BLA neurons. Thus, although topiramate inhibits GluK1 kainate receptor-mediated enhancement of interneuron firing, it promotes evoked GABA release, leading to a net inhibition of circuit excitability. In addition, we found that topiramate (0.3-10 microM) increased the amplitude of evoked, spontaneous, and miniature IPSCs in BLA pyramidal neurons, indicating an enhancement of postsynaptic GABA(A) receptor responses. Taken together with our previous findings, we conclude that topiramate protects against hyperexcitability in the BLA by suppressing the GluK1 kainate receptor-mediated excitation of principal neurons by glutamatergic afferents, blocking the suppression of GABA release from interneurons mediated by presynaptic GluK1

  14. NMDA and AMPA/kainate glutamatergic receptors in the prelimbic medial prefrontal cortex modulate the elaborated defensive behavior and innate fear-induced antinociception elicited by GABAA receptor blockade in the medial hypothalamus. (United States)

    de Freitas, Renato Leonardo; Salgado-Rohner, Carlos José; Biagioni, Audrey Francisco; Medeiros, Priscila; Hallak, Jaime Eduardo Cecílio; Crippa, José Alexandre S; Coimbra, Norberto Cysne


    The aim of the present study was to investigate the involvement of N-methyl-d-aspartate (NMDA) and amino-3-hydroxy-5-methyl-isoxazole-4-proprionate (AMPA)/kainate receptors of the prelimbic (PL) division of the medial prefrontal cortex (MPFC) on the panic attack-like reactions evoked by γ-aminobutyric acid-A receptor blockade in the medial hypothalamus (MH). Rats were pretreated with NaCl 0.9%, LY235959 (NMDA receptor antagonist), and NBQX (AMPA/kainate receptor antagonist) in the PL at 3 different concentrations. Ten minutes later, the MH was treated with bicuculline, and the defensive responses were recorded for 10 min. The antagonism of NMDA receptors in the PL decreased the frequency and duration of all defensive behaviors evoked by the stimulation of the MH and reduced the innate fear-induced antinociception. However, the pretreatment of the PL cortex with NBQX was able to decrease only part of defensive responses and innate fear-induced antinociception. The present findings suggest that the NMDA-glutamatergic system of the PL is critically involved in panic-like responses and innate fear-induced antinociception and those AMPA/kainate receptors are also recruited during the elaboration of fear-induced antinociception and in panic attack-related response. The activation of the glutamatergic neurotransmission of PL division of the MPFC during the elaboration of oriented behavioral reactions elicited by the chemical stimulation of the MH recruits mainly NMDA receptors in comparison with AMPA/kainate receptors.

  15. Channel-opening kinetic mechanism for human wild-type GluK2 and the M867I mutant kainate receptor. (United States)

    Han, Yan; Wang, Congzhou; Park, Jae Seon; Niu, Li


    GluK2 is a kainate receptor subunit that is alternatively spliced at the C-terminus. Previous studies implicated GluK2 in autism. In particular, the methionine-to-isoleucine replacement at amino acid residue 867 (M867I) that can only occur in the longest isoform of the human GluK2 (hGluK2), as the disease (autism) mutation, is thought to cause gain-of-function. However, the kinetic properties of the wild-type hGluK2 and the functional consequence of this gain-of-function mutation at the molecular level are not well understood. To investigate whether the M867I mutation affects the channel properties of the human GluK2 kainate receptor, we have systematically characterized the rate and the equilibrium constants pertinent to channel opening and channel desensitization for this mutant and the wild-type hGluK2 receptor, along with the wild-type rat GluK2 kainate receptor (rGluK2) as the control. Our results show that the M867I mutation does not affect either the rate or the equilibrium constants of the channel opening but does slow down the channel desensitization rate by ~1.6-fold at saturating glutamate concentrations. It is possible that a consequence of this mutation on the desensitization rate is linked to facilitating the receptor trafficking and membrane expression, given the close proximity of M867 to the forward trafficking motif in the C-terminal sequence. By comparing the kinetic data of the wild-type human and rat GluK2 receptors, we also find that the human GluK2 has a ~3-fold smaller channel-opening rate constant but an identical channel-closing rate constant and thus a channel-opening probability of 0.85 vs 0.96 for rGluK2. Furthermore, the intrinsic equilibrium dissociation constant K(1) for hGluK2, like the EC(50) value, is ~2-fold lower than rGluK2. Our results therefore suggest that the human GluK2 is relatively a slowly activating channel but more sensitive to glutamate, as compared to the rat ortholog, despite the fact that the human and rat forms

  16. The GluR5 subtype of kainate receptor regulates excitatory synaptic transmission in areas CA1 and CA3 of the rat hippocampus. (United States)

    Vignes, M; Clarke, V R; Parry, M J; Bleakman, D; Lodge, D; Ornstein, P L; Collingridge, G L


    Activation of kainate receptors depresses excitatory synaptic transmission in the hippocampus. In the present study, we have utilised a GluR5 selective agonist, ATPA [(RS)-2-amino-3-(3-hydroxy-5-tert-butylisoxazol-4-yl)propanoic acid], and a GluR5 selective antagonist, LY294486 [(3SR,4aRS,6SR,8aRS)-6-([[(1H-tetrazol-5-y l)methyl]oxy]methyl)-1,2,3,4,4a,5,6,7,8,8a-decahydroisoquinoline-3 -carboxylic acid], to determine whether GluR5 subunits are involved in this effect. ATPA mimicked the presynaptic depressant effects of kainate in the CA1 region of the hippocampus. It depressed reversibly AMPA (alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid) receptor-mediated field excitatory postsynaptic potentials (field EPSPs) with an IC50 value of approximately 0.60 microM. The dual-component excitatory postsynaptic current (EPSC) and the pharmacologically isolated NMDA (N-methyl-D-aspartate) receptor-mediated EPSC were depressed to a similar extent by 2 microM ATPA (61 +/- 7% and 58 +/- 6%, respectively). Depressions were associated with an increase in the paired-pulse facilitation ratio suggesting a presynaptic locus of action. LY294486 (20 microM) blocked the effects of 2 microM ATPA on NMDA receptor-mediated EPSCs in a reversible manner. In area CA3, 1 microM ATPA depressed reversibly mossy fibre-evoked synaptic transmission (by 82 +/- 10%). The effects of ATPA were not accompanied by any changes in the passive properties of CA1 or CA3 neurones. However, in experiments where K+, rather than Cs+, containing electrodes were used, a small outward current was observed. These results show that GluR5 subunits comprise or contribute to a kainate receptor that regulates excitatory synaptic transmission in both the CA1 and CA3 regions of the hippocampus.

  17. Differences in AMPA and kainate receptor interactomes facilitate identification of AMPA receptor auxiliary subunit GSG1L

    National Research Council Canada - National Science Library

    Shanks, Natalie F; Savas, Jeffrey N; Maruo, Tomohiko; Cais, Ondrej; Hirao, Atsushi; Oe, Souichi; Ghosh, Anirvan; Noda, Yasuko; Greger, Ingo H; Yates, 3rd, John R; Nakagawa, Terunaga


    AMPA receptor (AMPA-R) complexes consist of channel-forming subunits, GluA1-4, and auxiliary proteins, including TARPs, CNIHs, synDIG1, and CKAMP44, which can modulate AMPA-R function in specific ways...

  18. Selective increases of AMPA, NMDA and kainate receptor subunit mRNAs in the hippocampus and orbitofrontal cortex but not in prefrontal cortex of human alcoholics

    Directory of Open Access Journals (Sweden)

    Zhe eJin


    Full Text Available Glutamate is the main excitatory transmitter in the human brain. Drugs that affect the glutamatergic signaling will alter neuronal excitability. Ethanol inhibits glutamate receptors. We examined the expression level of glutamate receptor subunit mRNAs in human post-mortem samples from alcoholics and compared the results to brain samples from control subjects. RNA from hippocampal dentate gyrus (HP-DG, orbitofrontal cortex (OFC, and dorso-lateral prefrontal cortex (DL-PFC samples from 21 controls and 19 individuals with chronic alcohol dependence were included in the study. Total RNA was assayed using quantitative RT-PCR. Out of the 16 glutamate receptor subunits, mRNAs encoding two AMPA (2-amino-3-(3-hydroxy-5-methyl-isoxazol-4-ylpropanoic acid receptor subunits GluA2 and GluA3; three kainate receptor subunits GluK2, GluK3 and GluK5 and five NMDA (N-methyl-D-aspartate receptor subunits GluN1, GluN2A, GluN2C, GluN2D and GluN3A were significantly increased in the HP-DG region in alcoholics. In the OFC, mRNA encoding the NMDA receptor subunit GluN3A was increased, whereas in the DL-PFC, no differences in mRNA levels were observed. Our laboratory has previously shown that the expression of genes encoding inhibitory GABA-A receptors is altered in the HP-DG and OFC of alcoholics (Jin et al., 2011. Whether the changes in one neurotransmitter system drives changes in the other or if they change independently is currently not known. The results demonstrate that excessive long-term alcohol consumption is associated with altered expression of genes encoding glutamate receptors in a brain region-specific manner. It is an intriguing possibility that genetic predisposition to alcoholism may contribute to these gene expression changes.

  19. Involvement of AMPA/kainate and GABAA receptors in topiramate neuroprotective effects against methylphenidate abuse sequels involving oxidative stress and inflammation in rat isolated hippocampus. (United States)

    Motaghinejad, Majid; Motevalian, Manijeh


    Abuses of methylphenidate (MPH) as psychostimulant cause neural damage of brain cells. Neuroprotective properties of topiramate (TPM) have been indicated in several studies but its exact mechanism of action remains unclear. The current study evaluates protective role of various doses of TPM and its mechanism of action in MPH induced oxidative stress and inflammation. The neuroprotective effects of various doses of TPM against MPH induced oxidative stress and inflammation were evaluated and then the action of TPM was studied in presence of domoic acid (DOM), as AMPA/kainate receptor agonist and bicuculline (BIC) as GABAA receptor antagonist, in isolated rat hippocampus. Open Field Test (OFT) was used to investigate motor activity changes. Oxidative, antioxidant and inflammatory factors were measured in isolated hippocampus. TPM (70 and 100mg/kg) decreased MPH induced motor activity disturbances and inhibit MPH induced oxidative stress and inflammation. On the other hand pretreatment of animals with DOM or BIC, inhibit this effect of TPM and potentiate MPH induced motor activity disturbances and increased lipid peroxidation, mitochondrial oxidized form of glutathione (GSSG) level, interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in isolated hippocampal cells and decreased reduced form of glutathione (GSH) level, superoxide dismutase, glutathione peroxidase and glutathione reductase activity. It seems that TPM can protect cells of hippocampus from oxidative stress and neuroinflammation and it could be partly by activation of GABAA receptor and inhibition of AMPA/kainite receptor.

  20. Insights into the mechanisms of ifosfamide encephalopathy: drug metabolites have agonistic effects on alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate receptors and induce cellular acidification in mouse cortical neurons. (United States)

    Chatton, J Y; Idle, J R; Vågbø, C B; Magistretti, P J


    Therapeutic value of the alkylating agent ifosfamide has been limited by major side effects including encephalopathy. Although the underlying biochemical processes of the neurotoxic side effects are still unclear, they could be attributed to metabolites rather than to ifosfamide itself. In the present study, the effects of selected ifosfamide metabolites on indices of neuronal activity have been investigated, in particular for S-carboxymethylcysteine (SCMC) and thiodiglycolic acid (TDGA). Because of structural similarities of SCMC with glutamate, the Ca(2+)(i) response of single mouse cortical neurons to SCMC and TDGA was investigated. SCMC, but not TDGA, evoked a robust increase in Ca(2+)(i) concentration that could be abolished by the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), but only partly diminished by the N-methyl-D-aspartate receptor antagonist 10,11-dihydro-5-methyl-5H-dibenzo[a,d]cyclohepten-5,10-imine (MK=801). Cyclothiazide (CYZ), used to prevent AMPA/kainate receptor desensitization, potentiated the response to SCMC. Because activation of AMPA/kainate receptors is known to induce proton influx, the intracellular pH (pH(i)) response to SCMC was investigated. SCMC caused a concentration-dependent acidification that was amplified by CYZ. Since H(+)/monocarboxylate transporter (MCT) activity leads to similar cellular acidification, we tested its potential involvement in the pH(i) response. Application of the lactate transport inhibitor quercetin diminished the pH(i) response to SCMC and TDGA by 43 and 51%, respectively, indicating that these compounds may be substrates of MCTs. Taken together, this study indicates that hitherto apparently inert ifosfamide metabolites, in particular SCMC, activate AMPA/kainate receptors and induce cellular acidification. Both processes could provide the biochemical basis of the observed ifosfamide-associated encephalopathy.

  1. Synthesis and in vitro pharmacology at AMPA and kainate preferring glutamate receptors of 4-heteroarylmethylidene glutamate analogues

    DEFF Research Database (Denmark)

    Valgeirsson, Jon; Christensen, Jeppe K; Kristensen, Anders S;


    2-Amino-3-[3-hydroxy-5-(2-thiazolyl)-4-isoxazolyl]propionic acid (1) is a potent AMPA receptor agonist with moderate affinity for native kainic acid (KA) receptors, whereas (S)-E-4-(2,2-dimethylpropylidene)glutamic acid (3) show high affinity for the GluR5 subtype of KA receptors and much lower...... affinity for the GluR2 subtype of AMPA receptors. As an attempt to develop new pharmacological tools for studies of GluR5 receptors, (S)-E-4-(2-thiazolylmethylene)glutamic acid (4a) was designed as a structural hybrid between 1 and 3. 4a was shown to be a potent GluR5 agonist and a high affinity ligand...

  2. Neuroprotection of GluR5-containing kainate receptor activation against ischemic brain injury through decreasing tyrosine phosphorylation of N-methyl-D-aspartate receptors mediated by Src kinase. (United States)

    Xu, Jie; Liu, Yong; Zhang, Guang-Yi


    Previous studies indicate that cerebral ischemia breaks the dynamic balance between excitatory and inhibitory inputs. The neural excitotoxicity induced by ionotropic glutamate receptors gain the upper hand during ischemia-reperfusion. In this paper, we investigate whether GluR5 (glutamate receptor 5)-containing kainate receptor activation could lead to a neuroprotective effect against ischemic brain injury and the related mechanism. The results showed that (RS)-2-amino-3-(3-hydroxy-5-tert-butylisoxazol-4-yl) propanoic acid (ATPA), a selective GluR5 agonist, could suppress Src tyrosine phosphorylation and interactions among N-methyl-D-aspartate (NMDA) receptor subunit 2A (NR2A), postsynaptic density protein 95 (PSD-95), and Src and then decrease NMDA receptor activation through attenuating tyrosine phosphorylation of NR2A and NR2B. More importantly, ATPA had a neuroprotective effect against ischemia-reperfusion-induced neuronal cell death in vivo. However, four separate drugs were found to abolish the effects of ATPA. These were selective GluR5 antagonist NS3763; GluR5 antisense oligodeoxynucleotides; CdCl(2), a broad spectrum blocker of voltage-gated calcium channels; and bicuculline, an antagonist of gamma-aminobutyric acid A (GABA(A)) receptor. GABA(A) receptor agonist muscimol could attenuate Src activation and interactions among NR2A, PSD-95 and Src, resulting the suppression of NMDA receptor tyrosine phosphorylation. Moreover, patch clamp recording proved that the activated GABA(A) receptor could inhibit NMDA receptor-mediated whole-cell currents. Taken together, the results suggest that during ischemia-reperfusion, activated GluR5 may facilitate Ca(2+)-dependent GABA release from interneurons. The released GABA can activate postsynaptic GABA(A) receptors, which then attenuates NMDA receptor tyrosine phosphorylation through inhibiting Src activation and disassembling the signaling module NR2A-PSD-95-Src. The final result of this process is that the pyramidal

  3. Neuroprotective effects of the allosteric agonist of metabotropic glutamate receptor 7 AMN082 on oxygen-glucose deprivation- and kainate-induced neuronal cell death. (United States)

    Domin, Helena; Jantas, Danuta; Śmiałowska, Maria


    Although numerous studies demonstrated a neuroprotective potency of unspecific group III mGluR agonists in in vitro and in vivo models of excitotoxicity, little is known about the protective role of group III mGlu receptor activation against neuronal cell injury evoked by ischemic conditions. The aim of the present study was to assess neuroprotective potential of the allosteric agonist of mGlu7 receptor, N,N'-Bis(diphenylmethyl)-1,2-ethanediamine dihydrochloride (AMN082) against oxygen-glucose deprivation (OGD)- and kainate (KA)-evoked neuronal cell damage in primary neuronal cultures, with special focus on its efficacy after delayed application. We demonstrated that in cortical neuronal cultures exposed to a 180 min OGD, AMN082 (0.01-1 µM) in a concentration- and time-dependent way attenuated the OGD-induced changes in the LDH release and MTT reduction assays. AMN082 (0.5 and 1 µM) produced also neuroprotective effects against KA-evoked neurotoxicity both in cortical and hippocampal cultures. Of particular importance was the finding that AMN082 attenuated excitotoxic neuronal injury after delayed application (30 min after OGD, or 30 min-1 h after KA). In both models of neurotoxicity, namely OGD- and KA-induced injury, the neuroprotective effects of AMN082 (1 µM) were reversed by the selective mGlu7 antagonist, 6-(4-Methoxyphenyl)-5-methyl-3-(4-pyridinyl)-isoxazolo[4,5-c]pyridin-4(5H)-one hydrochloride (MMPIP, 1 µM), suggesting the mGlu7-dependent mechanism of neuroprotective effects of AMN082. Next, we showed that AMN082 (0.5 and 1 µM) attenuated the OGD-induced increase in the number of necrotic nuclei as well inhibited the OGD-evoked calpain activation, suggesting the participation of these processes in the mechanism of AMN082-mediated protection. Additionally, we showed that protection evoked by AMN082 (1 µM) in KA model was connected with the inhibition of toxin-induced caspase-3 activity, and this effect was abolished by the mGlu7

  4. Selective Androgen Receptor Modulator RAD140 Is Neuroprotective in Cultured Neurons and Kainate-Lesioned Male Rats



    The decline in testosterone levels in men during normal aging increases risks of dysfunction and disease in androgen-responsive tissues, including brain. The use of testosterone therapy has the potential to increase the risks for developing prostate cancer and or accelerating its progression. To overcome this limitation, novel compounds termed “selective androgen receptor modulators” (SARMs) have been developed that lack significant androgen action in prostate but exert agonist effects in sel...

  5. Selective Androgen Receptor Modulator RAD140 Is Neuroprotective in Cultured Neurons and Kainate-Lesioned Male Rats


    Jayaraman, Anusha; Christensen, Amy; Moser, V. Alexandra; Vest, Rebekah S.; Miller, Chris P.; Hattersley, Gary; Pike, Christian J.


    The decline in testosterone levels in men during normal aging increases risks of dysfunction and disease in androgen-responsive tissues, including brain. The use of testosterone therapy has the potential to increase the risks for developing prostate cancer and or accelerating its progression. To overcome this limitation, novel compounds termed “selective androgen receptor modulators” (SARMs) have been developed that lack significant androgen action in prostate but exert agonist effects in sel...

  6. AMPA, NMDA and kainate glutamate receptor subunits are expressed in human peripheral blood mononuclear cells (PBMCs) where the expression of GluK4 is altered by pregnancy and GluN2D by depression in pregnant women. (United States)

    Bhandage, Amol K; Jin, Zhe; Hellgren, Charlotte; Korol, Sergiy V; Nowak, Krzysztof; Williamsson, Louise; Sundström-Poromaa, Inger; Birnir, Bryndis


    The amino acid glutamate opens cation permeable ion channels, the iGlu receptors. These ion channels are abundantly expressed in the mammalian brain where glutamate is the main excitatory neurotransmitter. The neurotransmitters and their receptors are being increasingly detected in the cells of immune system. Here we examined the expression of the 18 known subunits of the iGlu receptors families; α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), kainate, N-methyl-d-aspartate (NMDA) and delta in human peripheral blood mononuclear cells (PBMCs). We compared the expression of the subunits between four groups: men, non-pregnant women, healthy pregnant women and depressed pregnant women. Out of 18 subunits of the iGlu receptors, mRNAs for 11 subunits were detected in PBMCs from men and non-pregnant women; AMPA: GluA3, GluA4, kainate: GluK2, GluK4, GluK5, NMDA: GluN1, GluN2C, GluN2D, GluN3A, GluN3B, and delta: GluD1. In the healthy and the depressed pregnant women, in addition, the delta GluD2 subunit was identified. The mRNAs for GluK4, GluK5, GluN2C and GluN2D were expressed at a higher level than other subunits. Gender, pregnancy or depression during pregnancy altered the expression of GluA3, GluK4, GluN2D, GluN3B and GluD1 iGlu subunit mRNAs. The greatest changes recorded were the lower GluA3 and GluK4 mRNA levels in pregnant women and the higher GluN2D mRNA level in healthy but not in depressed pregnant women as compared to non-pregnant individuals. Using subunit specific antibodies, the GluK4, GluK5, GluN1, GluN2C and GluN2D subunit proteins were identified in the PBMCs. The results show expression of specific iGlu receptor subunit in the PBMCs and support the idea of physiology-driven changes of iGlu receptors subtypes in the immune cells. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Topiramate via NMDA, AMPA/kainate, GABAA and Alpha2 receptors and by modulation of CREB/BDNF and Akt/GSK3 signaling pathway exerts neuroprotective effects against methylphenidate-induced neurotoxicity in rats. (United States)

    Motaghinejad, Majid; Motevalian, Manijeh; Fatima, Sulail; Beiranvand, Tabassom; Mozaffari, Shiva


    Chronic abuse of methylphenidate (MPH) often causes neuronal cell death. Topiramate (TPM) carries neuroprotective effects, but its exact mechanism of action remains unclear. In the present study, the role of various doses of TPM and its possible mechanisms, receptors and signaling pathways involved against MPH-induced hippocampal neurodegeneration were evaluated in vivo. Thus, domoic acid (DOM) was used as AMPA/kainate receptor agonist, bicuculline (BIC) as GABAA receptor antagonist, ketamine (KET) as NMDA receptor antagonist, yohimbine (YOH) as α2 adrenergic receptor antagonist and haloperidol (HAL) was used as dopamine D2 receptor antagonist. Open field test (OFT) was used to investigate the disturbances in motor activity. Hippocampal neurodegenerative parameters were evaluated. Protein expressions of CREB/BDNF and Akt/GSK3 signaling pathways were also evaluated. Cresyl violet staining was performed to show and confirm the changes in the shape of the cells. TPM (70 and 100 mg/kg) reduced MPH-induced rise in lipid peroxidation, oxidized form of glutathione (GSSG), IL-1β and TNF-α levels, Bax expression and motor activity disturbances. In addition, TPM treatment increased Bcl-2 expression, the level of reduced form of glutathione (GSH) and the levels and activities of superoxide dismutase, glutathione peroxidase and glutathione reductase enzymes. TPM also inhibited MPH-induced hippocampal degeneration. Pretreatment of animals with DOM, BIC, KET and YOH inhibited TPM-induced neuroprotection and increased oxidative stress, neuroinflammation, neuroapoptosis and neurodegeneration while reducing CREB, BDNF and Akt protein expressions. Also pretreatment with DOM, BIC, KET and YOH inhibited TPM-induced decreases in GSK3. It can be concluded that the mentioned receptors by modulation of CREB/BDNF and Akt/GSK3 pathways, are involved in neuroprotection of TPM against MPH-induced neurodegeneration.

  8. Eestlased Karli sillal

    Index Scriptorium Estoniae


    16. XI etendas kunstirühmitus "Nervous Cowboys" Tšehhi pealinna Praha Karli sillal Eesti taassünnipäevale pühendatud performance'i "Eesti kui märk". Mööduvaid prahalasi küsitlesid Kiwa ja Jasper Zoova. Praha Eesti saatkonnas avati näitus xerox-tehnikas graafilistest lehtedest ja performance'ite videodokumentatsioonidest

  9. Eestlased Karli sillal

    Index Scriptorium Estoniae


    16. XI etendas kunstirühmitus "Nervous Cowboys" Tšehhi pealinna Praha Karli sillal Eesti taassünnipäevale pühendatud performance'i "Eesti kui märk". Mööduvaid prahalasi küsitlesid Kiwa ja Jasper Zoova. Praha Eesti saatkonnas avati näitus xerox-tehnikas graafilistest lehtedest ja performance'ite videodokumentatsioonidest

  10. AMPA/Kainate, NMDA, and Dopamine D1 Receptor Function in the Nucleus Accumbens Core: A Context-Limited Role in the Encoding and Consolidation of Instrumental Memory (United States)

    Hernandez, Pepe J.; Andrzejewski, Matthew E.; Sadeghian, Kenneth; Panksepp, Jules B.; Kelley, Ann E.


    Neural integration of glutamate- and dopamine-coded signals within the nucleus accumbens (NAc) is a fundamental process governing cellular plasticity underlying reward-related learning. Intra-NAc core blockade of NMDA or D1 receptors in rats impairs instrumental learning (lever-pressing for sugar pellets), but it is not known during which phase of…

  11. 77 FR 5291 - The Designation of Mevlut Kar, Also Known as Mivlut Kar, Also Known as Mavlut Kar, Also Known as... (United States)


    ... Designation of Mevlut Kar, Also Known as Mivlut Kar, Also Known as Mavlut Kar, Also Known as Mawlud Kar, Also Known as Meluvet Kar, Also Known as Mevlut Zikara, Also Known as Abdullah the Turk, Also Known as Mulfit Kar Iiyas Al Ubayda, Also Known as Abu Obeidah Al Turki, as a Specially Designated Global...

  12. Involvement of AMPA/Kainate Glutamate Receptor in the Extinction and Reinstatement of Morphine-Induced Conditioned Place Preference: A Behavioral and Molecular Study. (United States)

    Siahposht-Khachaki, Ali; Fatahi, Zahra; Yans, Asal; Khodagholi, Fariba; Haghparast, Abbas


    Glutamate receptors in mesolimbic areas such as the nucleus accumbens, ventral tegmental area, prefrontal cortex (PFC), and hippocampus (HIP) are a component of the mechanisms of drug-induced reward and can modulate the firing pattern of dopaminergic neurons in the reward system. In addition, several lines of study have indicated that cAMP response element-binding protein (CREB) and c-fos have important role in morphine-induced conditioned place preference (CPP) induced by drugs of abuse, such as morphine, cocaine, nicotine, and alcohol. Therefore, in the present study, we investigated the changes in phosphorylated CREB (p-CREB) and c-fos induction within the nucleus accumbens (NAc), HIP, and PFC after intracerebroventricular (ICV) administration of different doses of CNQX or vehicle during extinction period or reinstatement of morphine-induced CPP. In all groups, the CPP procedure was done; afterward, the conditioning scores were recorded by Ethovision software. After behavioral test recording, we dissected out the NAc, HIP, and PFC regions and measured the p-CREB/CREB ratio and c-fos level by Western blot analysis. Our results showed that administration of CNQX significantly shortened the extinction of morphine CPP. Besides, ICV microinjection of CNQX following extinction period decreased the reinstatement of morphine CPP in extinguished rats. In molecular section, in treatment group, all mentioned factors were dose-dependently decreased in comparison with vehicle group (DMSO) after ICV microinjection of different doses of CNQX but not in pre-extinction microinjection. These findings suggested that antagonism of AMPA receptor decreased p-CREB/CREB ratio and c-fos level in the PFC, NAc, and HIP. Modulation of the drug memory reconsolidation may be useful for faster extinction of drug-induced reward and attenuation of drug-seeking behavior.

  13. A Study of GluK1 Kainate Receptor Polymorphisms in Down Syndrome Reveals Allelic Non-Disjunction at 1173(C/T

    Directory of Open Access Journals (Sweden)

    Debarati Ghosh


    Full Text Available Mechanisms underlying Down syndrome (DS-related mental retardation (MR remain poorly understood. In trisomic offspring, non-disjunction may result in the reduction to homozygosity of a susceptibility allele inherited from a heterozygous parent. Accordingly, we sought evidence for allelic non-disjunction in the GluK1 gene that encodes the critical kainite-binding glutamate receptor subunit-5, maps to chromosome 21q22.1 in the DS critical region and is expressed in brain regions responsible for learning and memory. Three polymorphisms of GluK1 [522(A/C rs363538; 1173(C/T rs363430 and 2705(T/C rs363504] were genotyped in 86 DS patient families by means of PCR-coupled RFLP assays and evaluated with respect to allele frequency, heterozygosity, linkage disequilibrium, stage and parental origin of allelic non-disjunction. We report that the distribution of allele frequencies is in Hardy-Weinberg equilibrium. Moderate heterozygosity (0.339 and a major allele frequency of 0.78 render the 1173(C/T marker informative. Pair-wise comparisons reveal that 522(A/C-1173(C/T [χ2 = 31.2, df = 1, p = 0.0001; D’ = 0.42] and 1173(C/T-2705(T/C [χ2 = 18.3, df = 1, p = 0.0001; D’ = 0.34] are in significant linkage disequilibrium of weak magnitude. The estimated ratio of meiosis-I to meiosis-II errors arising from allelic non-disjunction of 1173(C/T is 4:1 in maternal cases and 2:1 in paternal cases. Studies including additional markers and patient samples are warranted to further substantiate present findings.

  14. Lessons from crystal structures of kainate receptors

    DEFF Research Database (Denmark)

    Møllerud, Stine; Frydenvang, Karla Andrea; Pickering, Darryl S


    structure and how they bind agonists, antagonists and ions. The first structure of the ligand-binding domain of the GluK1 subunit was reported in 2005, seven years after publication of the crystal structure of a soluble construct of the ligand-binding domain of the AMPA-type subunit GluA2. Today, a full......-length structure has been determined of GluK2 by cryo electron microscopy to 7.6 Å resolution as well as 84 high-resolution crystal structures of N-terminal domains and ligand-binding domains, including agonist and antagonist bound structures, modulatory ions and mutations. However, there are still many unanswered...

  15. Neuropeptide Y-stimulated [(35) S]GTPγs functional binding is reduced in the hippocampus after kainate-induced seizures in mice

    DEFF Research Database (Denmark)

    Elbrønd-Bek, Heidi; Olling, Janne Damm; Gøtzsche, Casper René;


    Kainate-induced seizures constitute a model of temporal lobe epilepsy where prominent changes are observed in the hippocampal neuropeptide Y (NPY) system. However, little is known about the functional state and signal transduction of the NPY receptor population resulting from kainate exposure. Thus......, in this study, we explored functional NPY receptor activity in the mouse hippocampus and neocortex after kainate-induced seizures using NPY-stimulated [(35) S]GTPγS binding. Moreover, we also studied levels of [(125) I]-peptide YY (PYY) binding and NPY, Y1, Y2, and Y5 receptor mRNA in these kainate-treated mice....... Functional NPY binding was unchanged up to 12 h post-kainate, but decreased significantly in all hippocampal regions after 24 h and 1 week. Similarly, a decrease in [(125) I]-PYY binding was found in the dentate gyrus (DG) 1 week post-kainate. However, at 2 h, 6 h, and 12 h, [(125) I]-PYY binding...

  16. Kar5p is required for multiple functions in both inner and outer nuclear envelope fusion in Saccharomyces cerevisiae. (United States)

    Rogers, Jason V; Rose, Mark D


    During mating in the budding yeast Saccharomyces cerevisiae, two haploid nuclei fuse via two sequential membrane fusion steps. SNAREs (i.e., soluble N-ethylmaleimide-sensitive factor attachment protein receptors) and Prm3p mediate outer nuclear membrane fusion, but the inner membrane fusogen remains unknown. Kar5p is a highly conserved transmembrane protein that localizes adjacent to the spindle pole body (SPB), mediates nuclear envelope fusion, and recruits Prm3p adjacent to the SPB. To separate Kar5p's functions, we tested localization, Prm3p recruitment, and nuclear fusion efficiency in various kar5 mutants. All domains and the conserved cysteine residues were essential for nuclear fusion. Several kar5 mutant proteins localized properly but did not mediate Prm3p recruitment; other kar5 mutant proteins localized and recruited Prm3p but were nevertheless defective for nuclear fusion, demonstrating additional functions beyond Prm3p recruitment. We identified one Kar5p domain required for SPB localization, which is dependent on the half-bridge protein Mps3p. Electron microscopy revealed a kar5 mutant that arrests with expanded nuclear envelope bridges, suggesting that Kar5p is required after outer nuclear envelope fusion. Finally, a split-GFP assay demonstrated that Kar5p localizes to both the inner and outer nuclear envelope. These insights suggest a mechanism by which Kar5p mediates inner nuclear membrane fusion.

  17. Presynaptic Adenosine Receptor-Mediated Regulation of Diverse Thalamocortical Short-Term Plasticity in the Mouse Whisker Pathway. (United States)

    Ferrati, Giovanni; Martini, Francisco J; Maravall, Miguel


    Short-term synaptic plasticity (STP) sets the sensitivity of a synapse to incoming activity and determines the temporal patterns that it best transmits. In "driver" thalamocortical (TC) synaptic populations, STP is dominated by depression during stimulation from rest. However, during ongoing stimulation, lemniscal TC connections onto layer 4 neurons in mouse barrel cortex express variable STP. Each synapse responds to input trains with a distinct pattern of depression or facilitation around its mean steady-state response. As a result, in common with other synaptic populations, lemniscal TC synapses express diverse rather than uniform dynamics, allowing for a rich representation of temporally varying stimuli. Here, we show that this STP diversity is regulated presynaptically. Presynaptic adenosine receptors of the A1R type, but not kainate receptors (KARs), modulate STP behavior. Blocking the receptors does not eliminate diversity, indicating that diversity is related to heterogeneous expression of multiple mechanisms in the pathway from presynaptic calcium influx to neurotransmitter release.

  18. Effect of curcumin on AMPA and kainate receptor-mediated calcium influx in cultured rat hippocampal neurons%姜黄素对AMPA/KA受体介导大鼠海马神经元钙内流的影响

    Institute of Scientific and Technical Information of China (English)

    杜鹏; 彭伟锋; 刘剑英; 林豪杰; 马昱; 汪昕; 范薇


    目的 探讨姜黄素对α-氨基-3-羧基-5-甲基异恶唑-4-丙酸(AMPA)/海人酸(KA)受体介导大鼠海马神经元钙内流的影响.方法 选用胚胎17dSD鼠分离海马,离体培养海马神经元,借助活体钙荧光染色和激光共聚焦钙成像技术观察100μmol/LKA刺激海马神经元内钙的变化,不同浓度(5、10、15、30、50 μmol/L)姜黄素预孵育海马神经元30min对100μmol/L KA刺激下细胞内钙变化的影响,15 μmol/L姜黄素对不同浓度(10、30、50、100、200、300 μmol/L)KA刺激海马神经元内钙变化的影响.应用钴染色技术观察(30、100 μmol/L KA)刺激后海马神经元钴阳性染色细胞变化.姜黄素预孵育30min对KA刺激导致钴阳性染色细胞变化的影响.结果 不同浓度姜黄素预孵育30 min均可以明显缓解100 μmol/L或30 μmol/L KA导致的细胞内钙升高程度.差异均有统计学意义(P<0.05),其中15 μmol/L姜黄素作用最为明显.30μmol/L或100 μmol/LKA刺激均可以引起海马神经元钴染色阳性细胞增加,15 μmol/L姜黄素预处理30 min后明显减少钴染色阳性细胞,差异有统计学意义(P<0.05),而其他浓度(5 μmol/L或30 μmol/L)姜黄素未见明显影响.结论 一定浓度的姜黄素可以影响AMPA/KA受体介导大鼠海马神经元钙内流.这可能是姜黄素抗癫痫作用的一个机制.%Objective To investigate the effect of curcumin on alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and kainate (KA) receptor-mediated calcium influx in cultured rat hippocampal neurons. Methods The hippocampal neurons from SD rat embryos (17 days old) were cultured for 9 days, and fluorescent calcium chelator and confocal microscopy calcium imaging were used to observe the changes in intracellular free calcium in the neurons following stimulation with 100 μmol/L KA. The effect of curcumin pretreatment at different concentrations (10, 30, 50, 100, 200 and 300 μmol/L) for 30 min on 100 μmol/L KA

  19. Ionotropic glutamate receptors & CNS disorders. (United States)

    Bowie, Derek


    Disorders of the central nervous system (CNS) are complex disease states that represent a major challenge for modern medicine. Although aetilogy is often unknown, it is established that multiple factors such as defects in genetics and/or epigenetics, the environment as well as imbalance in neurotransmitter receptor systems are all at play in determining an individual's susceptibility to disease. Gene therapy is currently not available and therefore, most conditions are treated with pharmacological agents that modify neurotransmitter receptor signaling. Here, I provide a review of ionotropic glutamate receptors (iGluRs) and the roles they fulfill in numerous CNS disorders. Specifically, I argue that our understanding of iGluRs has reached a critical turning point to permit, for the first time, a comprehensive re-evaluation of their role in the cause of disease. I illustrate this by highlighting how defects in AMPA receptor (AMPAR) trafficking are important to fragile X mental retardation and ectopic expression of kainate receptor (KAR) synapses contributes to the pathology of temporal lobe epilepsy. Finally, I discuss how parallel advances in studies of other neurotransmitter systems may allow pharmacologists to work towards a cure for many CNS disorders rather than developing drugs to treat their symptoms.

  20. Temperature- and concentration-dependence of kainate-induced y oscillation in rat hippocampal slices under submerged condition

    Institute of Scientific and Technical Information of China (English)

    Cheng-biao LU; Zhi-hua WANG; Yan-hong ZHOU; Martin VREUGDENHIL


    Aim:Fast neuronal network oscillation at the y frequency band (y oscillation:30-80 Hz) has been studied extensively in hippocampal slices under interface recording condition.The aim of this study is to establish a method for recording Y oscillation in submerged hippocampal slices that allows simultaneously monitoring Y oscillation and the oscillation-related intracellular events,such as intracellular Ca2+ concentration or mitochondrial membrane potentials.Methods:Horizontal hippocampal slices (thickness:300 pm) of adult rats were prepared and placed in a submerged or an interface chamber.Extracellular field recordings Were made in the CA3c pyramidal layer of the slices.Kainate,an AMPA/kainate receptor agonist,was applied via perfusion.Data analysis was performed off-line.Results:Addition of kainate (25-1000 nmol/L) induced Y oscillation in both the submerged and interface slices.Kainate increased the Y power in a concentration-dependent manner,but the duration of steady state oscillation was reduced at higher concentrations of kainate.Long-lasting Y oscillation was maintained at the concentrations of 100-300 nmol/L.Under submerged condition,Y oscillation was temperature-dependent,with the maximum power achieved at 29℃.The induction of Y oscillation under submerged condition also required a fast rate of perfusion (5-7 mL/min) and showed a fast dynamic during development and after the washout.Conclusion:The kainite-induced Y oscillation recorded in submerged rat hippocampal slices is useful for studying the intracellular events related to neuronal network activities and may represent a model to reveal the mechanisms underlying the normal neuronal synchronizations and diseased conditions.

  1. Comparison between spontaneous and kainate-induced gamma oscillations in the mouse hippocampus in vitro. (United States)

    Pietersen, Alexander N J; Patel, Nisha; Jefferys, John G R; Vreugdenhil, Martin


    Neuronal synchronization at gamma frequency, implicated in cognition, can be evoked in hippocampal slices by pharmacological activation. We characterized spontaneous small-amplitude gamma oscillations (SgammaO) recorded in area CA3 of mouse hippocampal slices and compared it with kainate-induced gamma oscillations (KgammaO). SgammaO had a lower peak frequency, a more sinusoidal waveform and was spatially less coherent than KgammaO, irrespective of oscillation amplitude. CA3a had the smallest oscillation power, phase-led CA3c by approximately 4 ms and had the highest SgammaO frequency in isolated subslices. During SgammaO CA3c neurons fired at the rebound of inhibitory postsynaptic potentials (IPSPs) that were associated with a current source in stratum lucidum, whereas CA3a neurons often fired from spikelets, 3-4 ms earlier in the cycle, and had smaller IPSPs. Kainate induced faster/larger IPSPs that were associated with an earlier current source in stratum pyramidale. SgammaO and KgammaO power were dependent on alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, gap junctions and gamma-aminobutyric acid (GABA)(A) receptors. SgammaO was suppressed by elevating extracellular KCl, blocking N-methyl-d-aspartate (NMDA) receptors or muscarinic receptors, or activating GluR5-containing kainate receptors. SgammaO was not affected by blocking metabotropic glutamate receptors or hyperpolarization-activated currents. The adenosine A(1) receptor antagonist 8-cyclopentyl-1,3-dimethoxyxanthine (8-CPT) and the CB1 cannabinoid receptor antagonist N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (AM251) increased SgammaO power, indicating that endogenous adenosine and/or endocannabinoids suppress or prevent SgammaO in vitro. SgammaO emerges from a similar basic network as KgammaO, but differs in involvement of somatically projecting interneurons and pharmacological modulation profile. These observations advocate

  2. Undifferentiated embryonic stem cells express ionotropic glutamate receptor mRNAs

    Directory of Open Access Journals (Sweden)

    Svenja ePachernegg


    Full Text Available Ionotropic glutamate receptors (iGluRs do not only mediate the majority of excitatory neurotransmission in the vertebrate CNS, but also modulate pre- and postnatal neurogenesis. Most of the studies on the developmental role of iGluRs are performed on neural progenitors and neural stem cells. We took a step back in our study by examining the role of iGluRs in the earliest possible cell type, embryonic stem cells (ESCs, by looking at the mRNA expression of the major iGluR subfamilies in undifferentiated mouse ESCs. For that, we used two distinct murine ES cell lines, 46C ESCs and J1 ESCs. Regarding 46C ESCs, we found transcripts of kainate receptors (GluK2 to GluK5, AMPA receptors (GluA1, GluA3, and GluA4, and NMDA receptors (GluN1, and GluN2A to GluN2D. Analysis of 46C-derived cells of later developmental stages, namely neuroepithelial precursor cells (NEPs and neural stem cells (NSCs, revealed that the mRNA expression of KARs is significantly upregulated in NEPs and, subsequently, downregulated in NSCs. However, we could not detect any protein expression of any of the KAR subunits present on the mRNA level either in ESCs, NEPs, or NSCs. Regarding AMPARs and NMDARs, GluN2A is weakly expressed at the protein level only in NSCs. Matching our findings for GluRs, all three cell types were found to weakly express pre- and postsynaptic markers of glutamatergic synapses only at the mRNA level. Finally, we performed patch-clamp recordings of 46C ESCs and could not detect any current upon iGluR agonist application. Similar to 46C ESCs, J1 ESCs express kainate receptors (GluK2 to GluK5, AMPA receptors (GluA3, and NMDA receptors (GluN1, and GluN2A to GluN2D at the mRNA level, but these transcripts are not translated into receptor proteins either. Thus, we conclude that ESCs do not contain functional iGluRs, although they do express an almost complete set of iGluR subunit mRNAs.

  3. Effects of AT1 receptor antagonism on kainate-induced seizures and concomitant changes in hippocampal extracellular noradrenaline, serotonin, and dopamine levels in Wistar-Kyoto and spontaneously hypertensive rats. (United States)

    Tchekalarova, Jana; Loyens, Ellen; Smolders, Ilse


    In the management of epilepsy, AT1 receptor antagonists have been suggested as an additional treatment strategy. A hyperactive brain angiotensin (Ang) II system and upregulated AT1 receptors are implicated in the cerebrovascular alterations in a genetic form of hypertension. Uncontrolled hypertension could also, in turn, be a risk factor for a seizure threshold decrease and development of epileptogenesis. The present study aimed to assess the effects of the selective AT1 receptor antagonist ZD7155 on kainic acid (KA)-induced status epilepticus (SE) development and accompanying changes in the hippocampal extracellular (EC) neurotransmitter levels of noradrenaline (NAD), serotonin (5-HT), and dopamine (DA) in spontaneously hypertensive rats (SHRs) and their parent strain Wistar-Kyoto (WKY) rats, since monoamines are well-known neurotransmitters involved in mechanisms of both epilepsy and hypertension. Status epilepticus was evoked in freely moving rats by a repetitive intraperitoneal (i.p.) administration of KA in subconvulsant doses. In the treatment group, ZD7155 (5mg/kg i.p.) was coadministered with the first KA injection. Spontaneously hypertensive rats exhibited higher susceptibility to SE than WKY rats, but the AT1 receptor antagonist did not alter the development of SE in SHRs or in WKY rats. In vivo microdialysis demonstrated significant KA-induced increases of the hippocampal NAD and DA levels in SHRs and of NAD, 5-HT, and DA in WKY rats. Although SHRs developed more severe seizures while receiving a lower dose of KA compared to WKY rats, AT1 receptor antagonism completely prevented all KA-induced increases of hippocampal monoamine levels in both rat strains without affecting seizure development per se. These results suggest a lack of direct relationship between KA-induced seizure susceptibility and adaptive changes of hippocampal NAD, 5-HT, and DA levels in the effects of ZD7155 in WKY rats and SHRs.

  4. Mitochondrial superoxide production and MnSOD activity following exposure to an agonist and antagonists of ionotropic receptors in rat brain

    Directory of Open Access Journals (Sweden)

    Radenović Lidija Lj.


    Full Text Available The involvement of NMDA and AMPA/kainate receptors in the induction of superoxide production in the rat brain was examined after intrahippocampal injection of kainate, a non-NMDA receptor agonist; kainate plus CNQX, a selective AMPA/kainate receptor antagonist; or kainate plus APV, a selective NMDA receptor antagonist. The measurements took place at different times in the ipsi- and contralateral hippocampus, forebrain cortex, striatum, and cerebellum homogenates. The used glutamate antagonists both ensured sufficient neuroprotection in the sense of lowering superoxide production and raising MnSOD levels, but in the mechanisms and time dynamics of their effects were different. Our findings suggest that NMDA and AMPA/kainate receptors are differentially involved in superoxide production. UDC 612.815 612.82.

  5. Atorvastatin enhances kainate-induced gamma oscillations in rat hippocampal slices. (United States)

    Li, Chengzhang; Wang, Jiangang; Zhao, Jianhua; Wang, Yali; Liu, Zhihua; Guo, Fang Li; Wang, Xiao Fang; Vreugdenhil, Martin; Lu, Cheng Biao


    Atorvastatin has been shown to affect cognitive functions in rodents and humans. However, the underlying mechanism is not fully understood. Because hippocampal gamma oscillations (γ, 20-80 Hz) are associated with cognitive functions, we studied the effect of atorvastatin on persistent kainate-induced γ oscillation in the CA3 area of rat hippocampal slices. The involvement of NMDA receptors and multiple kinases was tested before and after administration of atorvastatin. Whole-cell current-clamp and voltage-clamp recordings were made from CA3 pyramidal neurons and interneurons before and after atorvastatin application. Atorvastatin increased γ power by ~ 50% in a concentration-dependent manner, without affecting dominant frequency. Whereas atorvastatin did not affect intrinsic properties of both pyramidal neurons and interneurons, it increased the firing frequency of interneurons but not that of pyramidal neurons. Furthermore, whereas atorvastatin did not affect synaptic current amplitude, it increased the frequency of spontaneous inhibitory post-synaptic currents, but did not affect the frequency of spontaneous excitatory post-synaptic currents. The atorvastatin-induced enhancement of γ oscillations was prevented by pretreatment with the PKA inhibitor H89, the ERK inhibitor U0126, or the PI3K inhibitor wortmanin, but not by the NMDA receptor antagonist D-AP5. Taken together, these results demonstrate that atorvastatin enhanced the kainate-induced γ oscillation by increasing interneuron excitability, with an involvement of multiple intracellular kinase pathways. Our study suggests that the classical cholesterol-lowering agent atorvastatin may improve cognitive functions compromised in disease, via the enhancement of hippocampal γ oscillations.

  6. New insights from the use of pilocarpine and kainate models. (United States)

    Leite, J P; Garcia-Cairasco, N; Cavalheiro, E A


    Local or systemic administration of pilocarpine and kainate in rodents leads to a pattern of repetitive limbic seizures and status epilepticus, which can last for several hours. A latent period follows status epilepticus and precedes a chronic phase, which is characterized by the occurrence of spontaneous limbic seizures. These distinct features, in a single animal preparation, of an acute damage induced by status epilepticus, a silent interval between injury and the onset of spontaneous seizures, and a chronic epileptic state have allowed antiepileptic drug (AED) studies with different purposes, (a) in the acute phase, identification of compounds with efficacy against refractory status epilepticus and/or neuroprotection against damage induced by sustained seizures; (b) in the latent period, identification of agents with a potential for preventing epileptogenesis and/or against seizure-induced long-term behavioral deficits and (c) in the chronic phase, testing drugs effective against partial and secondarily generalized seizures. Studies on pilocarpine and kainate models have pointed out that some AEDs or other compounds exert an antiepileptogenic effect. The analogy of the latent phase of pilocarpine and kainate models with the acquisition of amygdala kindling should encourage testing of drugs that have proved to suppress the evolution of amygdala kindling. Drug testing in the chronic phase should not address only the suppression of secondarily generalized motor seizures. Most of current tools used to quantify spontaneous seizure events need to be coupled to electrophysiology and more sophisticated systems for recording and analyzing behavior.

  7. Synthesis and enantiopharmacology of new AMPA-kainate receptor agonists

    DEFF Research Database (Denmark)

    Conti, P; De Amici, M; De Sarro, G


    . The convulsant properties of all the compounds were evaluated in vivo on DBA/2 mice after icv injection. CIP-A showed a convulsant activity, measured as tonus and clonus seizures, 18-65 times higher than that produced by AMPA. It was also quite active after ip administration, since it induced seizures in mice...

  8. Synapse organization and modulation via C1q family proteins and their receptors in the central nervous system. (United States)

    Matsuda, Keiko


    Several C1q family members, related to the C1q complement component are extensively expressed in the central nervous system. Cbln1, which belongs to the Cbln subfamily of C1q proteins and released from cerebellar granule cells, plays an indispensable role in the synapse formation and function at parallel fiber-Purkinje cell synapses. This is achieved by formation of a trans-synaptic tripartite complex which is composed of one unit of the Cbln1 hexamer, monomeric neurexin (NRX) containing a splice site 4 insertion at presynaptic terminals and the postsynaptic GluD2 dimers. Recently an increasing number of soluble or transmembrane proteins have been identified to bind directly to the amino-terminal domains of iGluR and regulate the recruitment and function of iGluRs at synapses. Especially at mossy fiber (MF)-CA3 synapses in the hippocampus, postsynaptic kainate-type glutamate receptors (KARs) are involved in synaptic network activity through their characteristic channel kinetics. C1ql2 and C1ql3, which belong to the C1q-like subfamily of C1q proteins, are produced by MFs and serve as extracellular organizers to recruit functional postsynaptic KAR complexes at MF-CA3 synapses via binding to the amino-terminal domains of GluK2 and GluK4 KAR subunits. In addition, C1ql2 and C1ql3 directly bind to NRX3 containing sequences encoded by exon 25b insertion at splice site 5. In the present review, we highlighted the generality of the strategy by tripartite complex formation of the specific type of NRX and iGluR via C1q family members.

  9. Hippocampal N-methyl-d-aspartate and kainate binding in response to entorhinal cortex aspiration or 192 IgG-saporin lesions of the basal forebrain

    Energy Technology Data Exchange (ETDEWEB)

    Gallagher, M. [Curriculum in Neurobiology, University of North Carolina Chapel Hill, NC (United States); Gill, T.M. [Department of Psychology, University of North Carolina at Chapel Hill Chapel Hill, NC (United States); Shivers, A. [Department of Biology, University of North Carolina Chapel Hill, NC (United States); Nicolle, M.M. [Curriculum in Neurobiology, University of North Carolina Chapel Hill, NC (United States)


    Lesion models in the rat were used to examine the effects of removing innervation of the hippocampal formation on glutamate receptor binding in that system. Bilateral aspiration of the entorhinal cortex was used to remove the cortical innervation of the hippocampal formation and the dentate gyrus. The subcortical input to the hippocampus from cholinergic neurons of the basal forebrain was lesioned by microinjection of the immunotoxin 192 IgG-saporin into the medial septum and vertical limb of diagonal band. After a 30-day postlesion survival, the effects of these lesions on N-methyl-d-aspartate-displaceable [{sup 3}H]glutamate and [{sup 3}H]kainate binding in the hippocampus were quantified using in vitro autoradiography. The bilateral entorhinal lesion induced a sprouting response in the dentate gyrus, measured by an increase in the width of [{sup 3}H]kainate binding. It also induced an increase in the density of [{sup 3}H]kainate binding in CA3 stratum lucidum and an increase in N-methyl-d-aspartate binding throughout the hippocampus proper and the dentate gyrus. The selective lesion of cholinergic septal input did not have any effect on hippocampal [{sup 3}H]kainate binding and induced only a moderate decrease in N-methyl-d-aspartate binding that was not statistically reliable.The entorhinal and cholinergic lesions were used as in vivo models of the degeneration of hippocampal input that occurs in normal aging and Alzheimer's disease. The results from the present lesion study suggest that some, but not all, of the effects on hippocampal [{sup 3}H]kainate and N-methyl-d-aspartate binding induced by the lesions are consistent with the status of binding to these receptors in aging and Alzheimer's disease. Consistent with the effects of aging and Alzheimer's disease is an altered topography of [{sup 3}H]kainate binding after entorhinal cortex lesion and a modest decline in N-methyl-d-aspartate binding after lesions of the cholinergic septal input to

  10. Delayed cell death in the contralateral hippocampus following kainate injection into the CA3 subfield. (United States)

    Maglóczky, Z; Freund, T F


    A model of epileptic cell death has been developed employing unilateral injections of kainic acid, a glutamate agonist, into the CA3 subfield of the hippocampus. The contralateral hippocampus, where neuronal damage is induced by hyperactivity in afferent pathways, served as the model structure. The pattern of cell death in this model was shown earlier to correspond to the vulnerable regions in human temporal lobe epilepsy. In the present time-course study we demonstrated that the different subpopulations of vulnerable cells in the contralateral hippocampus of the rat degenerate at different times following kainate injection. Spiny calretinin-containing cells in the hilus and CA3 stratum lucidum disappear at 12-24 h, other types of hilar neurons and CA3c pyramidal cells show shrinkage and argyrophilia at two days, whereas CA1 pyramidal cells degenerate at three days postinjection. The majority of cells destined to die showed a transient expression of the heatshock protein 72, approximately one day (for hilar-CA3c) or two days (for CA1) before degeneration. Parvalbumin-immunoreactivity transiently disappeared from the soma and dendrites of interneurons between the first and the fourth day. The results suggest that seizure-induced cell death is delayed, therefore acute oedema, even if it occurs, is insufficient to kill neurons. The only exception is the population of calretinin-containing interneurons degenerating at 12-24 h. The further one day delay between hilar-CA3c and CA1 cell death is likely to be due to differences in the relative density of glutamate receptor types (kainate versus NMDA) and the source of afferent input of these subfields. Thus, simple pharmacotherapy targeting only one of the excitotoxic mechanisms (i.e. acute oedema of calretinin cells versus delayed death of hilar-CA3c and CA1 cells at different time points) is likely to fail.

  11. Zooplankton abundance in the River Kars, Northeast Turkey: Impact ...

    African Journals Online (AJOL)



    Nov 2, 2009 ... Turkey: Impact of environmental variables. H. Özbay1* and A. ... Key words: River Kars, zooplankton, running water, environmental factors. .... Fish preda- tion could ... is lack of the information about zooplankton diversity and.

  12. Tissue-type plasminogen activator is not required for kainate-induced motoneuron death in vitro. (United States)

    Vandenberghe, W; Van Den Bosch, L; Robberecht, W


    Spinal motoneurons are highly vulnerable to kainate both in vivo and in vitro. Tissue-type plasminogen activator (tPA) and plasmin have recently been shown to mediate kainate-induced neuronal death in the mouse hippocampus in vivo. The aim of the present study was to determine whether tPA also mediates the kainate-induced death of motoneurons in vitro. A motoneuron-enriched neuronal population was isolated from the ventral spinal cord of wild-type (WT) and tPA-deficient (tPA-/-) mouse embryos. WT and tPA-/- neurons were cultured on WT and tPA-/- spinal glial feeder layers, respectively. WT and tPA-/- co-cultures were morphologically indistinguishable. Expression of tPA in WT co-cultures was demonstrated using RT-PCR. WT and tPA-/- co-cultures were exposed to kainate for 24 h. The neurotoxic effect of kainate did not differ significantly between WT and tPA-/- cultures. The plasmin inhibitor alpha2-antiplasmin did not protect WT neurons against kainate-induced injury. These results indicate that the plasmin system is not a universal mediator of kainate-induced excitotoxicity.

  13. Presynaptic Adenosine Receptor-Mediated Regulation of Diverse Thalamocortical Short-Term Plasticity in the Mouse Whisker Pathway (United States)

    Ferrati, Giovanni; Martini, Francisco J.; Maravall, Miguel


    Short-term synaptic plasticity (STP) sets the sensitivity of a synapse to incoming activity and determines the temporal patterns that it best transmits. In “driver” thalamocortical (TC) synaptic populations, STP is dominated by depression during stimulation from rest. However, during ongoing stimulation, lemniscal TC connections onto layer 4 neurons in mouse barrel cortex express variable STP. Each synapse responds to input trains with a distinct pattern of depression or facilitation around its mean steady-state response. As a result, in common with other synaptic populations, lemniscal TC synapses express diverse rather than uniform dynamics, allowing for a rich representation of temporally varying stimuli. Here, we show that this STP diversity is regulated presynaptically. Presynaptic adenosine receptors of the A1R type, but not kainate receptors (KARs), modulate STP behavior. Blocking the receptors does not eliminate diversity, indicating that diversity is related to heterogeneous expression of multiple mechanisms in the pathway from presynaptic calcium influx to neurotransmitter release. PMID:26941610

  14. Switch in glutamate receptor subunit gene expression in CA1 subfield of hippocampus following global ischemia in rats.


    Pellegrini-Giampietro, D E; Zukin, R.S.; Bennett, M V; Cho, S; Pulsinelli, W. A.


    Severe, transient global ischemia of the brain induces delayed damage to specific neuronal populations. Sustained Ca2+ influx through glutamate receptor channels is thought to play a critical role in postischemic cell death. Although most kainate-type glutamate receptors are Ca(2+)-impermeable, Ca(2+)-permeable kainate receptors have been reported in specific kinds of neurons and glia. Recombinant receptors assembled from GluR1 and/or GluR3 subunits in exogenous expression systems are permeab...

  15. Ontogeny of Kainate-Induced Gamma Oscillations in the Rat CA3 Hippocampus in vitro


    Vera eTsintsadze; Marat eMinlebaev; Dimitry eSuchkov; Mark eCunningham; Rustem eKhazipov


    GABAergic inhibition, which is instrumental in the generation of hippocampal gamma oscillations, undergoes significant changes during development. However, the development of hippocampal gamma oscillations remains largely unknown. Here, we explored the developmental features of kainate-induced oscillations (KA-Os) in CA3 region of rat hippocampal slices. Up to postnatal day P5, the bath application of kainate failed to evoke any detectable oscillations. KA-Os emerged by the end of the first p...

  16. Ontogeny of kainate-induced gamma oscillations in the rat CA3 hippocampus in vitro


    Tsintsadze, Vera; Minlebaev, Marat; Suchkov, Dimitry; Mark O. Cunningham; Khazipov, Roustem


    International audience; GABAergic inhibition, which is instrumental in the generation of hippocampal gamma oscillations, undergoes significant changes during development. However, the development of hippocampal gamma oscillations remains largely unknown. Here, we explored the developmental features of kainate-induced oscillations (KA-Os) in CA3 region of rat hippocampal slices. Up to postnatal day P5, the bath application of kainate failed to evoke any detectable oscillations. KA-Os emerged b...

  17. L-(TH)glutamate binds to kainate-, NMDA- and AMPA-sensitive binding sites: an autoradiographic analysis

    Energy Technology Data Exchange (ETDEWEB)

    Monaghan, D.T.; Yao, D.; Cotman, C.W.


    The anatomical distribution of L-(TH)glutamate binding sites was determined in the presence of various glutamate analogues using quantitative autoradiography. The binding of L-(TH)glutamate is accounted for by the presence of 3 distinct binding sites when measured in the absence of CaS , Cl and Na ions. The anatomical distribution and pharmacological specificity of these binding sites correspond to that reported for the 3 excitatory amino acid binding sites selectively labelled by D-(TH)2-amino-5-phosphonopentanoate (D-(TH)AP5), (TH)kainate ((TH)KA) and (TH) -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid ((TH)AMPA) which are thought to be selective ligands for the N-methyl-D-aspartate (NMDA), KA and quisqualate (QA) receptors, respectively. (Auth.). 29 refs.; 1 figure; 1 table.

  18. Glutamate receptor-mediated toxicity in optic nerve oligodendrocytes (United States)

    Matute, Carlos; Sánchez-Gómez, M. Victoria; Martínez-Millán, Luis; Miledi, Ricardo


    In cultured oligodendrocytes isolated from perinatal rat optic nerves, we have analyzed the expression of ionotropic glutamate receptor subunits as well as the effect of the activation of these receptors on oligodendrocyte viability. Reverse transcription–PCR, in combination with immunocytochemistry, demonstrated that most oligodendrocytes differentiated in vitro express the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunits GluR3 and GluR4 and the kainate receptor subunits GluR6, GluR7, KA1 and KA2. Acute and chronic exposure to kainate caused extensive oligodendrocyte death in culture. This effect was partially prevented by the AMPA receptor antagonist GYKI 52466 and was completely abolished by the non-N-methyl-d-aspartate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), suggesting that both AMPA and kainate receptors mediate the observed kainate toxicity. Furthermore, chronic application of kainate to optic nerves in vivo resulted in massive oligodendrocyte death which, as in vitro, could be prevented by coinfusion of the toxin with CNQX. These findings suggest that excessive activation of the ionotropic glutamate receptors expressed by oligodendrocytes may act as a negative regulator of the size of this cell population. PMID:9238063

  19. Rapeseed oil and magnesium manipulations affect the seizure threshold to kainate in mice*

    Directory of Open Access Journals (Sweden)

    Pagès Nicole


    Full Text Available We have previously shown that the drop in N-methyl-D-aspartate (NMDA-induced seizure threshold caused by nutritional magnesium deprivation responded well to the w-3 polyunsaturated fatty acid (PUFA alpha-linolenate (ALA (5% rapeseed oil diet when compared to w-6 PUFA diet. In the present work, kainate-induced seizures are shown to be also exacerbated by magnesium deprivation. ALA diet better attenuates this seizure exacerbation when compared to the non-ALA diet. The reversion of the drop in kainate seizure threshold induced in these conditions by magnesium administration was, however, better under the non-ALA diet in comparison with the ALA diet. Taken as a whole, present data indicate that kainate like NMDA brain injury is attenuated by ALA diet. On the other hand, the relative failure of ALA diet to potentiate reversion induced by magnesium might suggest that magnesium and ALA protections are not additive.

  20. Neuroprotective effects of erythropoietin posttreatment against kainate-induced excitotoxicity in mixed spinal cultures. (United States)

    Yoo, Jong Yoon; Won, You Jin; Lee, Jong Hwan; Kim, Jong Uk; Sung, In Young; Hwang, Seung Jun; Kim, Mi Jung; Hong, Hea Nam


    Although the neuroprotective effects of erythropoietin (EPO) preconditioning are well known, the potential of postapplied EPO to protect neurons against excitotoxic injury has not been clearly established. Here we show that kainate (KA)-induced excitotoxicity, which plays a key role in secondary spinal cord injury, decreased neuron survival, inhibited neurite extension, and significantly reduced the expression of erythropoietin receptors (EpoR) in cultured spinal neurons. Posttreatment with EPO for 48 hr protected neurons against KA-induced injury, opposing KA-induced apoptosis and promoting regrowth of motoneuron neurites. These neuroprotective effects were paralleled by a restoration of EpoR expression. The importance of the EpoR signaling pathway was demonstrated using an EpoR blocking antibody, which neutralized the neuroprotective action of EPO posttreatment and prevented EPO-induced increases in EpoR expression. We also found that up-regulated EpoR stimulated the Janus kinase 2 (JAK2) pathway, which is known to facilitate neuronal growth and neurite regeneration. Although EPO posttreatment modestly attenuated KA-induced reactive gliosis in mixed neuron-glial cultures, blocking EpoR activity did not alter glial fibrillary acidic protein expression or astrocyte proliferation. In conclusion, 48 hr treatment with EPO following KA exposure induced EpoR-dependent protection against excitotoxic injury, demonstrating that preconditioning is not a prerequisite for neuroprotection by EPO. The neuroprotective effects of EPO posttreatment were mediated by an EpoR-dependent signaling pathway that possibly involves JAK2. The neuroprotective effect of EPO posttreatment against KA excitotoxicity appears to reflect direct effects on neurons and not indirect effects mediated by astrocytes.

  1. A subconvulsive dose of kainate selectively compromises astrocytic metabolism in the mouse brain in vivo

    DEFF Research Database (Denmark)

    Walls, Anne B; Eyjolfsson, Elvar M; Schousboe, Arne


    on cerebral metabolism and particularly that associated with astrocytes. We investigated astrocytic and neuronal metabolism in the cerebral cortex of adult mice after treatment with saline (controls), a subconvulsive or a mildly convulsive dose of kainate. A combination of [1,2-(13)C]acetate and [1-(13)C......]glutamine and an increase in the calculated astrocytic TCA cycle activity. In contrast, the convulsive dose led to decrements in the cortical content and (13)C labeling of glutamate, glutamine, GABA, and aspartate. Evidence is provided that astrocytic metabolism is affected by a subconvulsive dose of kainate, whereas...

  2. Kombatantu statuss asimetriskajā karā


    Dambis, Mārtiņš


    Bakalaura darbā „Kombatantu statuss asimetriskajā karā” pēta piemērojamo humanitāro tiesību regulējumu konfliktos, kam ir starptautisks raksturs, tomēr viena no pusēm nav uzskatāma par valsti un ignorē kara tiesības. Tiek analizēta ASV prakse tā saucamajā karā pret terorismu, jo ASV ir vistiešāk skāris jaunā tipa apdraudējums starptautiskajam mieram. Darbs strukturēts vispirms apskatot asimetriskā kara jēdzienu un humanitāro tiesību piemērošanas īpatnības šādā konfliktā. Darba otrā nodaļ...

  3. A new pyrrolyl-quinoxalinedione series of non-NMDA glutamate receptor antagonists: pharmacological characterization and comparison with NBQX and valproate in the kindling model of epilepsy. (United States)

    Löscher, W; Lehmann, H; Behl, B; Seemann, D; Teschendorf, H J; Hofmann, H P; Lubisch, W; Höger, T; Lemaire, H G; Gross, G


    Antagonists at the ionotropic non-NMDA [AMPA (amino-methyl proprionic acid)/kainate] type of glutamate receptors have been suggested to possess several advantages compared to NMDA (N-methyl-D-aspartate) receptor antagonists, particularly in terms of risk/benefit ratio, but the non-NMDA receptor antagonists available so far have not fulfilled this promise. From a large series of pyrrolyl-quinoxalinedione derivatives, we selected six new competitive non-NMDA receptor antagonists. The basis of selection was high potency and selectivity for AMPA and/or kainate receptors, high in vivo potency after systemic administration, and an acceptable ratio between neuroprotective or anticonvulsant effects and adverse effects. Pharmacological characteristics of these novel compounds are described in this study with special emphasis on their effects in the kindling model of temporal lobe epilepsy, the most common type of epilepsy in humans. In most experiments, NBQX and the major antiepileptic drug valproate were used for comparison with the novel compounds. The novel non-NMDA receptor antagonists markedly differed in their AMPA and kainate receptor affinities from NBQX. Thus, while NBQX essentially did not bind to kainate receptors at relevant concentrations, several of the novel compounds exhibited affinity to rat brain kainate receptors or recombinant kainate receptor subtypes in addition to AMPA receptors. One compound, LU 97175, bound to native high affinity kainate receptors and rat GluR5-GluR7 subunits, i.e. low affinity kainate binding sites, with much higher affinities than to AMPA receptors. All compounds potently blocked AMPA-induced cell death in vitro and, except LU 97175, AMPA-induced convulsions in vivo. In the kindling model, compounds with a high affinity for GluR7 (LU 97175) or compounds (LU 115455, LU 136541) which potently bind to AMPA receptors and low affinity kainate receptor subunits were potent anticonvulsants in the kindling model, whereas the AMPA

  4. Altkäemaksu vahendus (KarS § 296) kui vajaliku osavõtuga koosseis. Riigikohtu kriminaalkolleegiumi otsus 3-1-1-7-08 / Jaan Sootak

    Index Scriptorium Estoniae

    Sootak, Jaan, 1948-


    Riigikohtu kriminaalkolleegiumi otsusest 3-1-1-7-08. P. P. kaitsja vandeadvokaat Valentina Manjuki kassatsioon Viru Ringkonnakohtu 24. oktoobri 2007. a kohtuotsuse peale kriminaalasjas P. P. süüdistuses KarS § 296 lg 1 järgi

  5. Altkäemaksu vahendus (KarS § 296) kui vajaliku osavõtuga koosseis. Riigikohtu kriminaalkolleegiumi otsus 3-1-1-7-08 / Jaan Sootak

    Index Scriptorium Estoniae

    Sootak, Jaan, 1948-


    Riigikohtu kriminaalkolleegiumi otsusest 3-1-1-7-08. P. P. kaitsja vandeadvokaat Valentina Manjuki kassatsioon Viru Ringkonnakohtu 24. oktoobri 2007. a kohtuotsuse peale kriminaalasjas P. P. süüdistuses KarS § 296 lg 1 järgi

  6. Hyperexcitability and cell loss in kainate-treated hippocampal slice cultures

    DEFF Research Database (Denmark)

    Benedikz, Eirikur; Casaccia-Bonnefil, P; Stelzer, A


    Loss of hippocampal interneurons has been reported in patients with severe temporal lobe epilepsy and in animals treated with kainate. We investigated the relationship between KA induced epileptiform discharge and loss of interneurons in hippocampal slice cultures. Application of KA (1 micro......M) produced reversible epileptiform discharge without neurotoxicity. KA (5 microM), in contrast, produced irreversible epileptiform discharge and neurotoxicity, suggesting that the irreversible epileptiform discharge was required for the neuronal loss. Loss of CA3 pyramidal cells and parvalbumin...

  7. Neuropeptide Y-stimulated [(35) S]GTPγs functional binding is reduced in the hippocampus after kainate-induced seizures in mice

    DEFF Research Database (Denmark)

    Elbrønd-Bek, Heidi; Olling, Janne Damm; Gøtzsche, Casper René


    . Functional NPY binding was unchanged up to 12 h post-kainate, but decreased significantly in all hippocampal regions after 24 h and 1 week. Similarly, a decrease in [(125) I]-PYY binding was found in the dentate gyrus (DG) 1 week post-kainate. However, at 2 h, 6 h, and 12 h, [(125) I]-PYY binding...

  8. Glutamate Receptor Aptamers and ALS (United States)


    proposed, including oxidative stress, excitotoxicity, mitochondrial dysfunction, etc., the cause(s) of the disease, including the pathogenesis of the...GluR6-Selective Aptamers for Potential Autism Therapy This project is to develop RNA aptamers against a GluR6 kainate receptor mutant thought to be...involved in autism . Role: PI Department of Defense (PI: Niu) 4/1/09-3/30/14 Advanced Tech./Therapeutic Develop. Grant Developing Biostable

  9. NMDA and non-NMDA receptor gene expression following global brain ischemia in rats: effect of NMDA and non-NMDA receptor antagonists. (United States)

    Pellegrini-Giampietro, D E; Pulsinelli, W A; Zukin, R S


    Transient forebrain or global ischemia in rats induces selective and delayed damage of hippocampal CA1 neurons. In a previous study, we have shown that expression of GluR2, the kainate/alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunit that governs Ca2+ permeability, is preferentially reduced in CA1 at a time point preceding neuronal degeneration. Postischemic administration of the selective AMPA receptor antagonist, 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(f)quinoxaline (NBQX), protects CA1 neurons against delayed death. In this study we examined the effects of NBQX (at a neuroprotective dose) and of MK-801 (a selective NMDA receptor antagonist, not protective in this model) on kainate/AMPA receptor gene expression changes after global ischemia. We also examined the effects of transient forebrain ischemia on expression of the NMDA receptor subunit NMDAR1. In ischemic rats treated with saline, GluR2 and GluR3 mRNAs were markedly reduced in CA1 but were unchanged in CA3 or dentate gyrus. GluR1 and NMDAR1 mRNAs were not significantly changed in any region examined. Administration of NBQX or MK-801 did not alter the ischemia-induced changes in kainate/AMPA receptor gene expression. These findings suggest that NBQX affords neuroprotection by a direct blockade of kainate/AMPA receptors, rather than by a modification of GluR2 expression changes.

  10. Combined gene overexpression of neuropeptide Y and its receptor Y5 in the hippocampus suppresses seizures

    DEFF Research Database (Denmark)

    Gøtzsche, Casper René; Nikitidou, Litsa; Sørensen, Andreas;


    on kainate-induced motor seizures in rats. However, combined overexpression of Y5 receptors and neuropeptide Y exerted prominent suppression of seizures. This seizure-suppressant effect of combination gene therapy with Y5 receptors and neuropeptide Y was significantly stronger as compared to neuropeptide Y...

  11. Excitatory and inhibitory pathways modulate kainate excitotoxicity in hippocampal slice cultures

    DEFF Research Database (Denmark)

    Casaccia-Bonnefil, P; Benedikz, Eirikur; Rai, R;


    In organotypic hippocampal slice cultures, kainate (KA) specifically induces cell loss in the CA3 region while N-methyl-D-aspartate induces cell loss in the CA1 region. The sensitivity of slice cultures to KA toxicity appears only after 2 weeks in vitro which parallels the appearance of mossy...... fibers. KA toxicity is potentiated by co-application with the GABA-A antagonist, picrotoxin. These data suggest that the excitotoxicity of KA in slice cultures is modulated by both excitatory and inhibitory synapses....

  12. Molecular Characteristics of Membrane Glutamate Receptor-Ionophore Interaction. (United States)


    Neurochemical - Research , 1984, 9, 29-44. Chang, H.H., Michaelis, E.K. & Roy, S. Functional characteristics of . -Z L-glutamate, N-methyl-D-aspartate and kainate...receptors in isolated brain synaptic membranes. Neurochemical Research , 1984, 9, 901-913. Michaelis, E. K., Galton, N. and Early, S. L. Spider venous

  13. Molecular basis of Kar9-Bim1 complex function during mating and spindle positioning (United States)

    Manatschal, Cristina; Farcas, Ana-Maria; Degen, Miriam Steiner; Bayer, Mathias; Kumar, Anil; Landgraf, Christiane; Volkmer, Rudolf; Barral, Yves; Steinmetz, Michel O.


    The Kar9 pathway promotes nuclear fusion during mating and spindle alignment during metaphase in budding yeast. How Kar9 supports the different outcome of these two divergent processes is an open question. Here, we show that three sites in the C-terminal disordered domain of Kar9 mediate tight Kar9 interaction with the C-terminal dimerization domain of Bim1 (EB1 orthologue). Site1 and Site2 contain SxIP motifs; however, Site3 defines a novel type of EB1-binding site. Whereas Site2 and Site3 mediate Kar9 recruitment to microtubule tips, nuclear movement, and karyogamy, only Site2 functions in spindle positioning during metaphase. Site1 in turn plays an inhibitory role during mating. Additionally, the Kar9-Bim1 complex is involved in microtubule-independent activities during mating. Together, our data reveal how multiple and partially redundant EB1-binding sites provide a microtubule-associated protein with the means to modulate its biochemical properties to promote different molecular processes during cell proliferation and differentiation. PMID:27682587

  14. Pharmacological analysis of ionotropic glutamate receptor function in neuronal circuits of the zebrafish olfactory bulb.

    Directory of Open Access Journals (Sweden)

    Rico Tabor

    Full Text Available Although synaptic functions of ionotropic glutamate receptors in the olfactory bulb have been studied in vitro, their roles in pattern processing in the intact system remain controversial. We therefore examined the functions of ionotropic glutamate receptors during odor processing in the intact olfactory bulb of zebrafish using pharmacological manipulations. Odor responses of mitral cells and interneurons were recorded by electrophysiology and 2-photon Ca(2+ imaging. The combined blockade of AMPA/kainate and NMDA receptors abolished odor-evoked excitation of mitral cells. The blockade of AMPA/kainate receptors alone, in contrast, increased the mean response of mitral cells and decreased the mean response of interneurons. The blockade of NMDA receptors caused little or no change in the mean responses of mitral cells and interneurons. However, antagonists of both receptor types had diverse effects on the magnitude and time course of individual mitral cell and interneuron responses and, thus, changed spatio-temporal activity patterns across neuronal populations. Oscillatory synchronization was abolished or reduced by AMPA/kainate and NMDA receptor antagonists, respectively. These results indicate that (1 interneuron responses depend mainly on AMPA/kainate receptor input during an odor response, (2 interactions among mitral cells and interneurons regulate the total olfactory bulb output activity, (3 AMPA/kainate receptors participate in the synchronization of odor-dependent neuronal ensembles, and (4 ionotropic glutamate receptor-containing synaptic circuits shape odor-specific patterns of olfactory bulb output activity. These mechanisms are likely to be important for the processing of odor-encoding activity patterns in the olfactory bulb.

  15. Pharmacological and structural characterization of conformationally restricted (S)-glutamate analogues at ionotropic glutamate receptors

    DEFF Research Database (Denmark)

    Juknaite, Lina; Venskutonyte, Raminta; Assaf, Zeinab


    A2 and the kainate receptor GluK3. These structures show that CBG-IV interacts with the binding pocket in the same way as (S)-glutamate. The binding affinities reveal that CBG-IV has high affinity at the AMPA and kainate receptor subtypes. Appreciable binding affinity of CBG-IV was not observed......Conformationally restricted glutamate analogues have been pharmacologically characterized at AMPA and kainate receptors and the crystal structures have been solved of the ligand (2S,1'R,2'S)-2-(2'-carboxycyclobutyl)glycine (CBG-IV) in complex with the ligand binding domains of the AMPA receptor Glu...... at NMDA receptors, where the introduction of the carbocyclic ring is expected to lead to a steric clash with binding site residues. CBG-IV was demonstrated to be an agonist at both GluA2 and the kainate receptor GluK1. CBG-IV showed high affinity binding to GluK1 compared to GluA2, GluK2 and GluK3, which...

  16. Effects of Chronic Alcohol Exposure on Kainate Receptor-Mediated Neurotransmission in the Hippocampus (United States)


    Mexico REPORT NUMBER Albuquerque, New Mexico 87131-5041 E-Mail: fvalenzuela@ salud .unm. edu 9. SPONSORING /MONITORING 70. SPONSORING IMONITORING AGENCY...on a Separate Group of Rats (lights on from 0900 to 1700 hr). Rats received a Bioserv (Frenchtown, NJ) chocolate -flavored liquid diet that was based

  17. 海人藻酸受体的生理功能%Physiological function of kainate receptors

    Institute of Scientific and Technical Information of China (English)

    张云海; 胡国渊


    由于缺乏选择性药物,中枢神经系统内海人藻酸受体的生理功能长期未被阐明。近年来发现,2,3-苯二氮类化合物GYKI 52466和GYKI 53655是AMPA受体的选择性拮抗剂。应用重组受体技术,筛选出海人藻酸受体GluR5亚基的高选择性激动剂ATPA及拮抗剂LY294486、 LY293558和LY382884等。应用上述药物开展的生理学研究,证明海人藻酸受体在某些脑区具有介导兴奋性突触传递、参与突触可塑性的诱导机制以及调节神经递质释放等重要功能。

  18. Developement of the Potassium-Argon Laser Experiment (KArLE) for In Situ Geochronology (United States)

    Cohen, Barbara A.


    Absolute dating of planetary samples is an essential tool to establish the chronology of geological events, including crystallization history, magmatic evolution, and alteration. Thus far, radiometric geochronology of planetary samples has only been accomplishable in terrestrial laboratories on samples from dedicated sample return missions and meteorites. In situ instruments to measure rock ages have been proposed, but none have yet reached TRL 6, because isotopic measurements with sufficient resolution are challenging. We have begun work under the NASA Planetary Instrument Definition and Development Program (PIDDP) to develop the Potassium (K) - Argon Laser Experiment (KArLE), a novel combination of several flight-proven components that will enable accurate KAr isochron dating of planetary rocks. KArLE will ablate a rock sample, measure the K in the plasma state using laser-induced breakdown spectroscopy (LIBS), measure the liberated Ar using quadrupole mass spectrometry (QMS), and relate the two by measuring the volume of the abated pit using a optical methods such as a vertical scanning interferometer (VSI). Our preliminary work indicates that the KArLE instrument will be capable of determining the age of several kinds of planetary samples to 100 Myr, sufficient to address a wide range of geochronology problems in planetary science. Additional benefits derive from the fact that each KArLE component achieves analyses common to most planetary surface missions.

  19. Perampanel inhibition of AMPA receptor currents in cultured hippocampal neurons.

    Directory of Open Access Journals (Sweden)

    Chao-Yin Chen

    Full Text Available Perampanel is an aryl substituted 2-pyridone AMPA receptor antagonist that was recently approved as a treatment for epilepsy. The drug potently inhibits AMPA receptor responses but the mode of block has not been characterized. Here the action of perampanel on AMPA receptors was investigated by whole-cell voltage-clamp recording in cultured rat hippocampal neurons. Perampanel caused a slow (τ∼1 s at 3 µM, concentration-dependent inhibition of AMPA receptor currents evoked by AMPA and kainate. The rates of block and unblock of AMPA receptor currents were 1.5×105 M-1 s-1 and 0.58 s-1, respectively. Perampanel did not affect NMDA receptor currents. The extent of block of non-desensitizing kainate-evoked currents (IC50, 0.56 µM was similar at all kainate concentrations (3-100 µM, demonstrating a noncompetitive blocking action. Parampanel did not alter the trajectory of AMPA evoked currents indicating that it does not influence AMPA receptor desensitization. Perampanel is a selective negative allosteric AMPA receptor antagonist of high-affinity and slow blocking kinetics.

  20. Crystal structure of the Candida albicans Kar3 kinesin motor domain fused to maltose-binding protein

    Energy Technology Data Exchange (ETDEWEB)

    Delorme, Caroline; Joshi, Monika [Department of Biomedical and Molecular Sciences, Queen' s University, Kingston, ON, Canada K7L 3N6 (Canada); Allingham, John S., E-mail: [Department of Biomedical and Molecular Sciences, Queen' s University, Kingston, ON, Canada K7L 3N6 (Canada)


    Highlights: Black-Right-Pointing-Pointer The Candida albicans Kar3 motor domain structure was solved as a maltose-binding protein fusion. Black-Right-Pointing-Pointer The electrostatic surface and part of the ATPase pocket of the motor domain differs markedly from other kinesins. Black-Right-Pointing-Pointer The MBP-Kar3 interface highlights a new site for intramolecular or intermolecular interactions. -- Abstract: In the human fungal pathogen Candida albicans, the Kinesin-14 motor protein Kar3 (CaKar3) is critical for normal mitotic division, nuclear fusion during mating, and morphogenic transition from the commensal yeast form to the virulent hyphal form. As a first step towards detailed characterization of this motor of potential medical significance, we have crystallized and determined the X-ray structure of the motor domain of CaKar3 as a maltose-binding protein (MBP) fusion. The structure shows strong conservation of overall motor domain topology to other Kar3 kinesins, but with some prominent differences in one of the motifs that compose the nucleotide-binding pocket and the surface charge distribution. The MBP and Kar3 modules are arranged such that MBP interacts with the Kar3 motor domain core at the same site where the neck linker of conventional kinesins docks during the 'ATP state' of the mechanochemical cycle. This site differs from the Kar3 neck-core interface in the recent structure of the ScKar3Vik1 heterodimer. The position of MBP is also completely distinct from the Vik1 subunit in this complex. This may suggest that the site of MBP interaction on the CaKar3 motor domain provides an interface for the neck, or perhaps a partner subunit, at an intermediate state of its motile cycle that has not yet been observed for Kinesin-14 motors.

  1. The Potassium-Argon Laser Experiment (KArLE): In Situ Geochronology for Planetary Robotic Missions (United States)

    Cohen, Barbara


    The Potassium (K) - Argon (Ar) Laser Experiment (KArLE) will make in situ noble-gas geochronology measurements aboard planetary robotic landers and roverss. Laser-Induced Breakdown Spectroscopy (LIBS) is used to measure the K abun-dance in a sample and to release its noble gases; the evolved Ar is measured by mass spectrometry (MS); and rela-tive K content is related to absolute Ar abundance by sample mass, determined by optical measurement of the ablated volume. KArLE measures a whole-rock K-Ar age to 10% or better for rocks 2 Ga or older, sufficient to resolve the absolute age of many planetary samples. The LIBS-MS approach is attractive because the analytical components have been flight proven, do not require further technical development, and provide complementary measurements as well as in situ geochronology.

  2. Kar3Vik1 uses a minus-end directed powerstroke for movement along microtubules.

    Directory of Open Access Journals (Sweden)

    Julia Cope

    Full Text Available We have used cryo-electron microscopy (cryo-EM and helical averaging to examine the 3-D structure of the heterodimeric kinesin-14 Kar3Vik1 complexed to microtubules at a resolution of 2.5 nm. 3-D maps were obtained at key points in Kar3Vik1's nucleotide hydrolysis cycle to gain insight into the mechanism that this motor uses for retrograde motility. In all states where Kar3Vik1 maintained a strong interaction with the microtubule, we found, as observed by cryo-EM, that the motor bound with one head domain while the second head extended outwards. 3-D reconstructions of Kar3Vik1-microtubule complexes revealed that in the nucleotide-free state, the motor's coiled-coil stalk points toward the plus-end of the microtubule. In the ATP-state, the outer head is shown to undergo a large rotation that reorients the stalk ∼75° to point toward the microtubule minus-end. To determine which of the two heads binds to tubulin in each nucleotide state, we employed specific Nanogold®-labeling of Vik1. The resulting maps confirmed that in the nucleotide-free, ATP and ADP+Pi states, Kar3 maintains contact with the microtubule surface, while Vik1 extends away from the microtubule and tracks with the coiled-coil as it rotates towards the microtubule minus-end. While many previous investigations have focused on the mechanisms of homodimeric kinesins, this work presents the first comprehensive study of the powerstroke of a heterodimeric kinesin. The stalk rotation shown here for Kar3Vik1 is highly reminiscent of that reported for the homodimeric kinesin-14 Ncd, emphasizing the conservation of a mechanism for minus-end directed motility.

  3. Dose-Dependent Effect of Curcumin on Learning and Memory Deficit in Kainate-Epileptic Rats

    Directory of Open Access Journals (Sweden)

    Zahra Kiasalari


    Full Text Available Background & objectives : Epileptic seizures accompany disturbances in learning, memory, and cognitive skills. With regard to antiepileptic potential of curcumin and its beneficial effect on memory, the effect of its administration on learning and memory in kainate-epileptic rats was investigated.   Methods: Forty male rats were divided into sham, positive control ( valproate-treated epileptic, epileptic, and two curcumin-treated epileptic groups. Rat model of epilepsy was induced by unilateral intrahippocampal administration of 4 μg of kainate per rat. Rats received intraperitoneal injection of curcumin (50 and 100 mg/kg daily for 1 week before surgery. For evaluation of learning and memory, initial (IL and step-through latencies (STL were determined using passive avoidance test and alternation behavior percentage was obtained according to Y maze test.   Results: Regarding IL, there was no significant difference between the groups. In contrast, STL significantly decreased in curcumin-50-treated epileptic group (p<0.05 (a change from 263.1 to 184.5 s. However, this parameter significantly increased in curcumin-100-treated epileptic group as compared to epileptic group (p<0.01 (a change from 263.1 to 220.3 s. In addition, STL was also significantly higher in valproic acid-treated epileptic group versus epileptic group (p<0.05 (a change from 145.7 to 210.3 s. Alternation percentage was also significantly higher in curcumin-50- and curcumin-100-treated epileptic groups relative to epileptic group (p<0.05 (a change from 60.5 to 77.6 and 80.3%.   Conclusion: Curcumin could dose-dependently enhance the consolidation and recall in epileptic animals and could improve spatial memory in such animals.

  4. THE CONCEPT OF SEMANTIC PROSODY AND EXAMPLES FROM TURKISH: “aksettirmek, ...dan ibaret, ...nin teki, karşı karşıya, varsa yoksa”

    Directory of Open Access Journals (Sweden)

    Nihal Çalışkan


    Full Text Available This study introduces the concept of semantic prosody, and calls attention to the different aspects of it based on the examples taken form Turkish. Semantic prosody is a kind of hidden evaluative meaning whichcan not be identified at first sight, but can be revealed after a careful and detealid analysis of corpus data. Semantic prosodies can be both positive and negative, but previous reserchs show that negative prosodies are prevelant. The linguistic units subject to analysis were chosen depending on the author’s linguistic observations, and analysed based on the corpus data depending on the co-occurences and collocations. The corpus consulted in the study is the demo version of Turkish National Corpus. The node words are as follows: ““aksettirmek, ...dan ibaret, ...nin teki, karşı karşıya, varsa yoksa”.

  5. Combined K-Ar and 40Ar/39Ar dating of the upper Jaramillo reversal (United States)

    Guillou, Herve; Carracedo, Juan Carlos; Kissel, Catherine; Laj, Carlo; Nomade, Sebastien; Perez Torrado, Francisco Jose; Rodriguez Gonzalez, Alejandro; Wandres, Camille


    The Jaramillo subchron was first evidenced in 1966 (Doell and Dalrymple) through the Rhyolotic domes of the Valles Caldera, New Mexico (USA). 40Ar/39Ar studies achieved by Spell et McDougall (1992), Spell et Harrison (1993), Izett and Obradovich (1994) and Singer et al. (1994) defined the base of this subchron at 1053±6 ka, and the ceiling at 986±5 ka. Channell et al. (2009) delimited the age of the Jaramillo subchron by astronomic calibration (base 1071 ka, top 990 ka). To provide additional absolute ages on this geomagnetic period, which is critical to improve our knowledge of the earth magnetic field behaviour, we have carried out a study combining paleomagnetism and isotopic dating of a lava sequence from Tenerife island. This sequence of basaltic lava flows is some 500 m thick. The first 400 m present, based on field magnetometer measurements, normal polarity lavas, with dykes of normal and reverse polarity, passing at the top to reverse polarity lavas. Preliminary K-Ar ages bracketed this sequence between 1018 ± 18 ka and 978 ± 17 ka. Therefore, the upper Jaramillo reversal at least appeared to be potentially recorded in this sequence. A more detailed paleomagnetic study was then carried out to more precisely delimit the reversal itself (see Laj et al., session EMRP3.4). We have undertaken 40Ar/39Ar incremental heating and unspiked K-Ar experiments on groundmass from four transitionally magnetized flows. The first transitional flow is K-Ar dated at 993 ± 18 ka and 40Ar/39Ar dated at 991 ± 13 ka, the second at 981 ± 17 ka (K-Ar) and 1000 ± 13 ka (40Ar/39Ar), the third at 950 ± 17 ka (K-Ar) and 1000 ± 8 ka (40Ar/39Ar) and the fourth at 984 ± 17 ka (K-Ar) and 977 ± 12 (40Ar/39Ar). 40Ar/39Ar ages and K-Ar ages (relative to FCT 28.02 Ma) are indistinguishable at 2σ. The age of the upper boundary of the Jaramillo event calculated combining 40Ar/39Ar ages and K-Ar ages is 992 ± 6 ka, in agreement with previous estimates.

  6. Stereoselective effects of AMOA on non-NMDA receptors expressed in Xenopus oocytes

    DEFF Research Database (Denmark)

    Wahl, P; Nielsen, B; Krogsgaard-Larsen, P


    a nearly parallel shift to the right of the dose-response curve for kainate-induced currents. AMOA was found to have two different effects on AMPA receptors: 1) currents elicited by low concentrations of AMPA (6 microM) were inhibited by AMOA with an IC50 value of 160 +/- 19 microM and 2) currents elicited...

  7. The Potassium-Argon Laser Experiment (KarLE): In Situ Geochronology for Mars and Beyond (United States)

    Cohen, Barbara A.


    The search for life in the solar system depends upon discovering the right moments in planetary evolution: when habitable environments existed, when they declined, and when geologic processes operated to preserve traces of life after death. However, an incomplete knowledge of absolute Martian geochronology limits our ability to understand the timing of Martian evolutionary milestones, major climate changes, and stratigraphic epochs [1, 2]. Absolute dating relates these habitability markers to planetarywide geologic, atmospheric, and climate history places, and ties their occurrence to the history of the solar system, especially the Earth-Moon system and the timescale of evolution of life on Earth. KArLE is being developed to anchor the relative timeline of geological events to an absolute chronology that puts Mars into a wider solar system context. KArLE makes its measurements on rock samples that can be obtained by landers or rovers and inserted into a small, mechanically simple chamber. KArLE interrogates the samples using laser-induced breakdown spectrocopy (LIBS), mass spectrometry, and optical imaging. The KArLE experiment is flexible enough to accommodate any partner providing these instrument components, a creative approach that extends the ability of mission payloads to accomplish an additional highly-desirable science measurement for low cost and risk and minimal extra hardware.

  8. Electron spin resonance assay of ascorbyl radical generation in mouse hippocampal slices during and after kainate-induced seizures. (United States)

    Masumizu, Toshiki; Noda, Yasuko; Mori, Akitane; Packer, Lester


    As an index of oxidative status, we analyzed ascorbyl radical generation during and after kainate-induced seizures in mouse hippocampus, using an ESR spectrometer equipped with a special tissue-type quartz cell. A specific doublet ESR spectrum was observed after seizures, and the g value and the hyperfine coupling constant (hfcc) of the spectrum were identical with those of ascorbyl radical itself. Antiepileptic zonisamide inhibited the generation of ascorbyl radical accompanying the seizures.

  9. Effects of ionotropic glutamate receptor antagonists on rat dural artery diameter in an intravital microscopy model

    DEFF Research Database (Denmark)

    Chan, K Y; Gupta, S; de Vries, R;


    studies have shown that glutamate receptor antagonists affect the pathophysiology of migraine. This study investigated whether antagonists of NMDA (ketamine and MK801), AMPA (GYKI52466) and kainate (LY466195) glutamate receptors affected dural vasodilatation induced by alpha-CGRP, capsaicin......During migraine, trigeminal nerves may release calcitonin gene-related peptide (CGRP), inducing cranial vasodilatation and central nociception; hence, trigeminal inhibition or blockade of craniovascular CGRP receptors may prevent this vasodilatation and abort migraine headache. Several preclinical...

  10. Visualization of spatiotemporal energy dynamics of hippocampal neurons by mass spectrometry during a kainate-induced seizure.

    Directory of Open Access Journals (Sweden)

    Yuki Sugiura

    Full Text Available We report the use of matrix-assisted laser desorption/ionization (MALDI imaging mass spectrometry combined with capillary electrophoresis (CE mass spectrometry to visualize energy metabolism in the mouse hippocampus by imaging energy-related metabolites. We show the distribution patterns of ATP, ADP, and AMP in the hippocampus as well as changes in their amounts and distribution patterns in a murine model of limbic, kainate-induced seizure. As an acute response to kainate administration, we found massive and moderate reductions in ATP and ADP levels, respectively, but no significant changes in AMP levels--especially in cells of the CA3 layer. The results suggest the existence of CA3 neuron-selective energy metabolism at the anhydride bonds of ATP and ADP in the hippocampal neurons during seizure. In addition, metabolome analysis of energy synthesis pathways indicates accelerated glycolysis and possibly TCA cycle activity during seizure, presumably due to the depletion of ATP. Consistent with this result, the observed energy depletion significantly recovered up to 180 min after kainate administration. However, the recovery rate was remarkably low in part of the data-pixel population in the CA3 cell layer region, which likely reflects acute and CA3-selective neural death. Taken together, the present approach successfully revealed the spatiotemporal energy metabolism of the mouse hippocampus at a cellular resolution--both quantitatively and qualitatively. We aim to further elucidate various metabolic processes in the neural system.

  11. Distribution of neurotransmitter receptors and zinc in the pigeon (Columba livia) hippocampal formation: A basis for further comparison with the mammalian hippocampus. (United States)

    Herold, Christina; Bingman, Verner P; Ströckens, Felix; Letzner, Sara; Sauvage, Magdalena; Palomero-Gallagher, Nicola; Zilles, Karl; Güntürkün, Onur


    The avian hippocampal formation (HF) and mammalian hippocampus share a similar functional role in spatial cognition, but the underlying neuronal mechanisms allowing the functional similarity are incompletely understood. To understand better the organization of the avian HF and its transmitter receptors, we analyzed binding site densities for glutamatergic AMPA, NMDA, and kainate receptors; GABAA receptors; muscarinic M1 , M2 and nicotinic (nACh) acetylcholine receptors; noradrenergic α1 and α2 receptors; serotonergic 5-HT1A receptors; dopaminergic D1/5 receptors by using quantitative in vitro receptor autoradiography. Additionally, we performed a modified Timm staining procedure to label zinc. The regionally different receptor densities mapped well onto seven HF subdivisions previously described. Several differences in receptor expression highlighted distinct HF subdivisions. Notable examples include 1) high GABAA and α1 receptor expression, which rendered distinctive ventral subdivisions; 2) high α2 receptor expression, which rendered distinctive a dorsomedial subdivision; 3) distinct kainate, α2 , and muscarinic receptor densities that rendered distinctive the two dorsolateral subdivisions; and 4) a dorsomedial region characterized by high kainate receptor density. We further observed similarities in receptor binding densities between subdivisions of the avian and mammalian HF. Despite the similarities, we propose that 300 hundred million years of independent evolution has led to a mosaic of similarities and differences in the organization of the avian HF and mammalian hippocampus and that thinking about the avian HF in terms of the strict organization of the mammalian hippocampus is likely insufficient to understand the HF of birds.

  12. Aryl- and heteroaryl-substituted phenylalanines as AMPA receptor ligands

    DEFF Research Database (Denmark)

    Szymańska, Ewa; Chałupnik, Paulina; Johansen, Tommy Nørskov


    in radioligand binding assays at native rat ionotropic glutamate receptors. The most interesting compound in this series, (RS)-2-amino-3-(3'-hydroxy-5-(1H-pyrazol-4-yl)-[1,1'-biphenyl]-3-yl)propanoic acid 7e, showed the binding affinity of 4.6 µM for native AMPA receptors and almost 5-fold lower affinity...... with molecular modeling confirmed that aryl/heteroaryl-substituted phenylalanine analogues effectively bind to AMPA receptors with low micromolar affinity and high selectivity over native NMDA and kainate receptors. These properties make 7e a promising lead for the further development of new AMPA receptor...

  13. Prenatal Exposure to 1-Bromopropane Suppresses Kainate-Induced Wet Dog Shakes in Immature Rats. (United States)

    Fueta, Yukiko; Kanemitsu, Masanari; Egawa, Sumie; Ishidao, Toru; Ueno, Susumu; Hori, Hajime


    1-Bromopropane (1-BP) is used in degreasing solvents and spray adhesives. The adverse effects of 1-BP have been reported in human cases and adult animal models, and its developmental toxicity has also been reported, but its effects on developmental neurotoxicity have not been investigated in detail. We evaluated the effects in rat pups of prenatal exposure to 1-BP on behaviors such as scratching and wet dog shakes (WDS), which were induced by injection of kainate (KA). Pregnant Wistar rats were exposed to vaporized 1-BP with 700 ppm from gestation day 1 to day 20 (6 h/day). KA at doses of 0.1, 0.5, and 2.0 mg/kg were intraperitoneally injected into a control group and a 1-BP-exposed group of pups on postnatal day 14. There was no significant difference in scratching between the control and the prenatally 1-BP-exposed groups, while suppression of the occurrence ratio of WDS was observed at the low dose of 0.1 mg/kg of KA in the prenatally 1-BP-exposed pups. Our results suggest that prenatal exposure to 1-BP affects neurobehavioral responses in the juvenile period.


    Directory of Open Access Journals (Sweden)



    Full Text Available ÖzetKar yönetimi, finansal raporlama sürecinde yöneticilerin takdir yetkilerini kullanmaları sonucundaortaya çıkmaktadır. Birtakım işlemler yoluyla ya da Genel Kabul Görmüş Muhasebe İlkeleri’ndeki (GKGMİesnekliklerden faydalanılarak uygulanan kar yönetimi, finansal tablo kullanıcılarına yanıltıcı bilgi vermesinedeniyle son derece önemli bir konu haline gelmektedir. GKGMİ, işletmenin gerçek finansal durumunuyansıtabilmeleri açısından, muhasebe tercihlerini yaparken, yöneticilere, birçok seçenek sunmaktadır. Buseçenekler ise kar yönetimi uygulamalarına olanak sağlayabilmektedir. Çünkü yöneticiler, bunları,işletmenin veya kendi çıkarları doğrultusunda kullanabilmektedirler. Bu durum ise finansal raporlarıngerçeği yansıtmasına engel olacaktır. Bu çalışmanın amacı kar yönetimine, hile ile kar yönetimi arasındakifarklara ve kar yönetiminde kullanılan yöntemlere ilişkin bilgiler verilmektedir.AbstractEarnings management occurs when managers use their judgment in financial reporting process.Earnings management which is applied either through some transactions or by utilizing the flexibilitiesin the Generally Accepted Accounting Principles (GAAP, is crucial for financial statement users formisleading them. This study focuses on earnings management and the techniques applied. While managerswere making their accounting choices, GAAP provides them lots of alternatives to reveal the real financialstatement of the business. These accounting choices may enable earnings management. For managers mayexploit these choices for themselves or the business. And this situation will prevent financial reports toreveal the real statement of the business. This study focuses on earnings management, differences betweenearnings management and fraud, and earnings management techniques

  15. K-Ar ages for the Yahazudake volcanic rocks from southwest Kyushu, Japan; Kyushu nanseibu yahazudake kazanganrui no K-Ar nendai

    Energy Technology Data Exchange (ETDEWEB)

    Yokose, H.; Kikuchi, W. [Kumamoto Univ. (Japan)] Nagao, K. [Okayama Univ. (Japan)264000] Kodama, K. [Kochi Univ. (Japan)


    Many volcanic rocks, seemed to be erupted during the period from the Pliocene epoch to the Pleistocene epoch, are distributed abounding in Kyushu, Japan. In this study, K-Ar ages determination about the 4 samples which represents the Hisatsu volcanic rocks distributed around Yahazudake and rhyolite distributed in Gesujima placed in the southernmost extremity of Amakusa Shimojima, was conducted. And consideration of time/space distribution of the Hisatsu volcanic rocks upon collecting the data which were reported until now and the data obtained by the present K-Ar age determination, was done. In the result of the present measurement, the absolute age of the Hisatsu volcanic rocks distributed around Minamata-shi became clear. I was clarified that Yahazudake volcanic rocks consisted of andesite, which is comparatively lacking in potassium, were formed during about 100 thousand years from 1.98 to 2.08 Ma, and Ontake volcanic rocks which exists for the bottom erupted at about 2.15 Ma. And, the age value of 2.89 Ma was obtained from Ushibuka rhyolite distributed in Gesujima. 35 refs., 4 figs., 3 tabs.

  16. K/AR dating of clinoptilolite, mordenite, and associated clays from Yucca Mountains, Nevada

    Energy Technology Data Exchange (ETDEWEB)

    WoldeGabriel, G.


    Zeolites are abundant in the geologic record in both continental and marine environments. The purpose of the present study is to evaluate the utility of K-bearing zeolites for dating by the K/Ar method to determine the time of zeolite diagenesis at Yucca Mountain, Nevada (Fig. 1). At Yucca Mountain, K-rich clinoptilolite and possibly mordenite are the only potentially K/Ar dateable secondary minerals present in the zeolite-rich tuffs except for some illite/smectites ({ge}10% illite layers) associated with these minerals. Direct dating of K-rich clinoptilolite, the most abundant zeolite in the altered tuffs, is important to delineate zeolite chronology as part of the site characterization of Yucca Mountain.

  17. Discordant K-Ar and young exposure dates for the Windjana sandstone, Kimberley, Gale Crater, Mars (United States)

    Vasconcelos, P. M.; Farley, K. A.; Malespin, C. A.; Mahaffy, P.; Ming, D.; McLennan, S. M.; Hurowitz, J. A.; Rice, Melissa S.


    K-Ar and noble gas surface exposure age measurements were carried out on the Windjana sandstone, Kimberley region, Gale Crater, Mars, by using the Sample Analysis at Mars instrument on the Curiosity rover. The sandstone is unusually rich in sanidine, as determined by CheMin X-ray diffraction, contributing to the high K2O concentration of 3.09 ± 0.20 wt % measured by Alpha-Particle X-ray Spectrometer analysis. A sandstone aliquot heated to 915°C yielded a K-Ar age of 627 ± 50 Ma. Reheating this aliquot yielded no additional Ar. A second aliquot heated in the same way yielded a much higher K-Ar age of 1710 ± 110 Ma. These data suggest incomplete Ar extraction from a rock with a K-Ar age older than 1710 Ma. Incomplete extraction at 900°C is not surprising for a rock with a large fraction of K carried by Ar-retentive K-feldspar. Likely, variability in the exact temperature achieved by the sample from run to run, uncertainties in sample mass estimation, and possible mineral fractionation during transport and storage prior to analysis may contribute to these discrepant data. Cosmic ray exposure ages from 3He and 21Ne in the two aliquots are minimum values given the possibility of incomplete extraction. However, the general similarity between the 3He (57 ± 49 and 18 ± 32 Ma, mean 30 Ma) and 21Ne (2 ± 32 and 83 ± 24 Ma, mean 54 Ma) exposure ages provides no evidence for underextraction. The implied erosion rate at the Kimberley location is similar to that reported at the nearby Yellowknife Bay outcrop.

  18. Eesti Maanteemuuseumi välialad = Estonian Road Museum, outdoor areas / Ralf Lõoke, Karli Luik, Maarja Kask ; intervjueerinud Margit Mutso

    Index Scriptorium Estoniae

    Lõoke, Ralf, 1978-


    Arhitektid: Maarja Kask, Karli Luik, Ralf Lõoke, Pelle-Sten Viiburg (Salto AB). Näituse kujundajad: Malle Jürgenson, Tea Tammelaan, Krista Lepland (Laika, Belka & Strelka). Maarja Kask, Karli Luik ja Ralf Lõoke pälvisid Eesti Kultuurkapitali aastapreemia (2010) kõrgetasemelise panuse eest Eesti maa-arhitektuuri: Eesti Maanteemuuseumi välialad (kaasautor Pelle-Sten Viiburg), Sõmeru keskushoone (kaasautorid Kristiina Arusoo ja Margit Argus)

  19. Eesti Maanteemuuseumi välialad = Estonian Road Museum, outdoor areas / Ralf Lõoke, Karli Luik, Maarja Kask ; intervjueerinud Margit Mutso

    Index Scriptorium Estoniae

    Lõoke, Ralf, 1978-


    Arhitektid: Maarja Kask, Karli Luik, Ralf Lõoke, Pelle-Sten Viiburg (Salto AB). Näituse kujundajad: Malle Jürgenson, Tea Tammelaan, Krista Lepland (Laika, Belka & Strelka). Maarja Kask, Karli Luik ja Ralf Lõoke pälvisid Eesti Kultuurkapitali aastapreemia (2010) kõrgetasemelise panuse eest Eesti maa-arhitektuuri: Eesti Maanteemuuseumi välialad (kaasautor Pelle-Sten Viiburg), Sõmeru keskushoone (kaasautorid Kristiina Arusoo ja Margit Argus)

  20. Effects of Swimming Exercise on Learning and Memory in the Kainate-Lesion Model of Temporal Lobe Epilepsy (United States)

    Gorantla, Vasavi Rakesh; Pemminati, Sudhakar; Bond, Vernon; Meyers, Dewey G


    Introduction An aerobic exercise (Ex) augments neurogenesis and may ameliorate learning and memory deficits in the rat Kainic Acid (KA) model of temporal lobe epilepsy in the short-term but whether it reverses learning and memory deficits after a substantial period of delay remains unclear. Aim This study tests the hypothesis that aerobic Ex attenuates the learning and memory deficits associated with kainate seizures in the long-term. Materials and Methods A total of 60 rats were subjected to chemical lesioning using KA and to an Ex intervention consisting of a 30 days period of daily swimming for 15 min, immediately after KA lesioning (immediate exposure) or after a 60 days period of normal activity (delayed exposure). We evaluated spatial learning on a T-maze test, expressed as percentage of correct responses. We evaluated memory on a passive-avoidance test, expressed as time spent in a compartment in which the rats were previously exposed to an aversive stimulus. Results Ex increases the percentage of correct responses, percentage bias, and number of alternations, associated with the T-maze testing for the normal control, sham-operated control and kainate-lesioned animals after both immediate and delayed exposures to Ex. Ex decreased the time exposed to the aversive stimulus in the smaller compartment of the two-compartment passive-avoidance test, also for the normal control, sham-operated control and kainate-lesioned animals after both immediate and delayed exposures to Ex. Conclusion These findings suggest that, after temporal lobe epileptic seizures in rats, swimming exercise may attenuate the learning and memory deficits, even if the exercise treatment is delayed. PMID:28050361

  1. K-Ar age constrains on chemically weathered granitic basement rocks (saprolites) in Scandinavia (United States)

    Margreth, Annina; Fredin, Ola; Viola, Giulio; Knies, Jochen; Sørlie, Ronald; Lie, Jan-Erik; Margrethe Grandal, Else; Zwingmann, Horst; Vogt, Christoph


    Remnants of in-situ weathered bedrock, saprolite, are found in several locations in Scandinavia. Saprolites contain important information about past climate conditions and landscape evolution, although their age and genesis are commonly difficult to constrain. It is generally thought that clay-poor, coarse-grained (arêne) saprolites, mostly occurring as thin regolith blankets or in larger outcrops, formed in temperate climate during the Cenozoic, whereas clay-rich (argillic) saprolites, commonly restricted to small, fracture-bounded outcrops, formed in (sub-)tropical climate during the Mesozoic. Recent methodological and conceptual advances in K-Ar dating of illite-bearing fault rocks have been applied to date clay-rich saprolites. To test the K-Ar dating technique for saprolites, we first selected an offshore site in the Viking Graben of the North Sea, where weathered and fractured granitic basement highs have been drilled during petroleum exploration, and an abandoned kaolin mine in Southern Sweden. Both targets provide independent age control through the presence of overlying Mesozoic sedimentary rocks. Clay-rich saprolites occurring in fractured basement rocks were additionally sampled in a joint valley landscape on the southwestern coast of Norway, which can be regarded as the possible onland correlative to the offshore basement high. In order to offer a sound interpretation of the obtained K-Ar ages, the mineralogical and chemical composition of the saprolites requires a thorough characterization. Scanning electron microscopy of thin sections, integrated by XRD and XRF analysis, reveals the progressive transformation of primary granitic rock minerals into secondary clay minerals. The authigenesis of illite is particularly important to understand, since it is the only K-bearing clay mineral that can be dated by the K-Ar method. K-feldspars and mica are the common primary K-bearing minerals, from which illite can be formed. While progressive leaching of

  2. mRNAs coding for neurotransmitter receptors and voltage-gated sodium channels in the adult rabbit visual cortex after monocular deafferentiation (United States)

    Nguyen, Quoc-Thang; Matute, Carlos; Miledi, Ricardo


    It has been postulated that, in the adult visual cortex, visual inputs modulate levels of mRNAs coding for neurotransmitter receptors in an activity-dependent manner. To investigate this possibility, we performed a monocular enucleation in adult rabbits and, 15 days later, collected their left and right visual cortices. Levels of mRNAs coding for voltage-activated sodium channels, and for receptors for kainate/α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA), N-methyl-d-aspartate (NMDA), γ-aminobutyric acid (GABA), and glycine were semiquantitatively estimated in the visual cortices ipsilateral and contralateral to the lesion by the Xenopus oocyte/voltage-clamp expression system. This technique also allowed us to study some of the pharmacological and physiological properties of the channels and receptors expressed in the oocytes. In cells injected with mRNA from left or right cortices of monocularly enucleated and control animals, the amplitudes of currents elicited by kainate or AMPA, which reflect the abundance of mRNAs coding for kainate and AMPA receptors, were similar. There was no difference in the sensitivity to kainate and in the voltage dependence of the kainate response. Responses mediated by NMDA, GABA, and glycine were unaffected by monocular enucleation. Sodium channel peak currents, activation, steady-state inactivation, and sensitivity to tetrodotoxin also remained unchanged after the enucleation. Our data show that mRNAs for major neurotransmitter receptors and ion channels in the adult rabbit visual cortex are not obviously modified by monocular deafferentiation. Thus, our results do not support the idea of a widespread dynamic modulation of mRNAs coding for receptors and ion channels by visual activity in the rabbit visual system. PMID:9501250

  3. Conversion of K-Ar dates with modern constants : implications for recalculation of dates reported in Kawano and Ueda using constants reported by Steiger and Jager


    Iwata, Naoyoshi


    This report describes details of a procedure used to convert from K-Ar dates with old constants reported in the relevant literature to K-Ar dates with modern decay constants and the isotopic ratio of potassium reported by Steiger and Jager. Nearly 300 K-Ar dates published by Kawano and Ueda in the 1960s have been recalculated using this procedure. These data are useful for comparing dates reported by Kawano and Ueda to recently obtained K-Ar dates reported by others.

  4. Archaeogeophysical Studies in the Ruins of Kars-Ani (Turkey) in the 2009 Excavation Season (United States)

    Hoskan, Nihan; Ahmet Yuksel, Fethi; Gorucu, Ziya; Coruhlu, Yasar


    The Ani ancient city, which is at 48 km distance to Kars (Turkey), is founded at the banks of the Arpacay River flowing in the vicinity of Turkey - Armenia border and is in the borders of Mevcut Ocakli Village. Recent studies show that the first settlement in Ani ancient city could be in the 5th millenium B.C.(Chalcolithic Period) and moreover, there were some buildings built in the Iron and Bronze Period. In the early 9th century, Ashot Msaker, who was Bagratuni dynasty (806-827), declared their first capital city at Bagaran, some 40 km south of Ani, and then transferred it to Kars in the year 929. In 961, King Ashot III (953-977) transferred the capital city from Kars to Ani. Ani expanded during the reign of King Smbat II (977-989). Recent research shows that by the early 11th century the population of Ani was over 100,000. After capture of Ashot, Ani surrendered to Byzantine controlled in 1045. A Greek governor was installed in the city. In 1064 a Seljuk Turkish army, headed by Sultan Alparslan, attacked and captured Ani. Then the Georgians captured Ani in 1124, 1161 and 1174. By the 14th century Ani was ruled by the Turkish dynasties, namely Jalayrids and the Kara Koyunlu. After the Persian Safavids ruled Ani, it became part of the Turkish Ottoman Empire in 1579. A small town remained within its walls until 1650 A.C. and it was completely abandoned by the middle of the 18th century. Examples of Sasani, Arabic, Armenian, and Seljuk architecture can be found among the Ani ruins. Ani is home to the first Turkish mosque built in Anatolia, namely Ebul Menucehr. The mosque was erected by the members of the Seljuk Dynasty in 1072. The first archaeological excavations were conducted at Ani in 1892. Since then, several archaeological excavations have been done in Ani. In the 2009 excavation season, magnetic methods were applied in Ani ruins to find the exact locations of the ruins. Magnetic Gradient Measurements were taken in front of Ebul Menucehr Mosque. After

  5. El elemento sobrenatural en Anna Karénnina (Ana Karenina, 1835), de Clarence Brown


    Guiralt Gomar, Carmen


    Anna Karénina (Ana Karenina, 1935), de Clarence Brown, ha sido un largometraje generalmente menospreciado por los analíticos del medio fílmico, pues en torno a él existen múltiples prejuicios: vehículo para la estrella de Metro-Goldwyn-Mayer Greta Garbo, versión hollywoodiense poco fiel a la novela de Tolstoi, etc. Ahora bien, un estudio individual de la película revela importantes cuestiones relacionadas con su puesta en escena apenas reflexionadas. El resultado es una atmósfe...

  6. Differential patterns of synaptotagmin7 mRNA expression in rats with kainate- and pilocarpine-induced seizures.

    Directory of Open Access Journals (Sweden)

    Gordana Glavan

    Full Text Available Previous studies in rat models of neurodegenerative disorders have shown disregulation of striatal synaptotagmin7 mRNA. Here we explored the expression of synaptotagmin7 mRNA in the brains of rats with seizures triggered by the glutamatergic agonist kainate (10 mg/kg or by the muscarinic agonist pilocarpine (30 mg/kg in LiCl (3 mEq/kg pre-treated (24 h rats, in a time-course experiment (30 min-1 day. After kainate-induced seizures, synaptotagmin7 mRNA levels were transiently and uniformly increased throughout the dorsal and ventral striatum (accumbens at 8 and 12 h, but not at 24 h, followed at 24 h by somewhat variable upregulation within different parts of the cerebral cortex, amigdala and thalamic nuclei, the hippocampus and the lateral septum. By contrast, after LiCl/pilocarpine-induced seizures, there was a more prolonged increase of striatal Synaptotagmin7 mRNA levels (at 8, 12 and 24 h, but only in the ventromedial striatum, while in some other of the aforementioned brain regions there was a decline to below the basal levels. After systemic post-treatment with muscarinic antagonist scopolamine in a dose of 2 mg/kg the seizures were either extinguished or attenuated. In scopolamine post-treated animals with extinguished seizures the striatal synaptotagmin7 mRNA levels (at 12 h after the onset of seizures were not different from the levels in control animals without seizures, while in rats with attenuated seizures, the upregulation closely resembled kainate seizures-like pattern of striatal upregulation. In the dose of 1 mg/kg, scopolamine did not significantly affect the progression of pilocarpine-induced seizures or pilocarpine seizures-like pattern of striatal upregulation of synaptotagmin7 mRNA. In control experiments, equivalent doses of scopolamine per se did not affect the expression of synaptotagmin7 mRNA. We conclude that here described differential time course and pattern of synaptotagmin7 mRNA expression imply regional

  7. El universo plástico y sensorial de La mano (Wong Kar Wai, 2004

    Directory of Open Access Journals (Sweden)

    Melendo, Ana


    Full Text Available En español: Con el presente artículo, queremos mostrar cómo Wong Kar Wai, heredero de un cine muy vinculado a la modernidad cinematográfica, plantea en el cortometraje La mano (2004 temas como la soledad, la actitud melancólica o la necesidad de ensimismamiento. Estos, junto al estudio de la geometría, los colores saturados y las calidades pictóricas, y bajo el prisma de un realismo metafísico, dan lugar a situaciones ópticas, sonoras y táctiles puras. Es así como en el film del cineasta chino se ponen de manifiesto, a través de la presencia del fragmento corporal y la metonimia, las texturas, coloreadas y sonoras, que configuran los espacios sensoriomotrices del submundo en el que acontece la historia. In english: In this article, we show how Wong Kar Wai, heir to a filmography closely linked to cinematographic modernity, explores themes such as loneliness, melancholy, or self-absorption in his short film The Hand (2004. These themes, together with his study of geometry, saturated colours and pictorial qualities through the prism of metaphysical realism, give rise to purely optical, sonorous and tactile situations. In this way, the Chinese film director reveals, through the presence of a body fragment and metonymy, the colourful and sonorous textures that form the sensory-motor spaces of the underworld in which the story is set.

  8. Nuclear fusion occurs during mating in Candida albicans and is dependent on the KAR3 gene. (United States)

    Bennett, Richard J; Miller, Mathew G; Chua, Penelope R; Maxon, Mary E; Johnson, Alexander D


    It is now well established that mating can occur between diploid a and alpha cells of Candida albicans. There is, however, controversy over when, and with what efficiency, nuclear fusion follows cell fusion to create stable tetraploid a/alpha cells. In this study, we have analysed the mating process between C. albicans strains using both cytological and genetic approaches. Using strains derived from SC5314, we used a number of techniques, including time-lapse microscopy, to demonstrate that efficient nuclear fusion occurs in the zygote before formation of the first daughter cell. Consistent with these observations, zygotes micromanipulated from mating mixes gave rise to mononuclear tetraploid cells, even when no selection for successful mating was applied to them. Mating between different clinical isolates of C. albicans revealed that while all isolates could undergo nuclear fusion, the efficiency of nuclear fusion varied in different crosses. We also show that nuclear fusion in C. albicans requires the Kar3 microtubule motor protein. Deletion of the CaKAR3 gene from both mating partners had little or no effect on zygote formation but reduced the formation of stable tetraploids more than 600-fold, as determined by quantitative mating assays. These findings demonstrate that nuclear fusion is an active process that can occur in C. albicans at high frequency to produce stable, mononucleate mating products.

  9. Insights into the olfactory system of the ectoparasite Caligus rogercresseyi: molecular characterization and gene transcription analysis of novel ionotropic receptors. (United States)

    Núñez-Acuña, Gustavo; Valenzuela-Muñoz, Valentina; Marambio, Jorge Pino; Wadsworth, Simon; Gallardo-Escárate, Cristian


    Although various elements of the olfactory system have been elucidated in insects, it remains practically unstudied in crustaceans at a molecular level. Among crustaceans, some species are classified as ectoparasites that impact the finfish aquaculture industry. Thus, there is an urgent need to identify and comprehend the signaling pathways used by these in host recognition. The present study, through RNA-seq and qPCR analyses, found novel transcripts involved in the olfactory system of Caligus rogercresseyi, in addition to the transcriptomic patterns expressed during different stages of salmon lice development. From a transcriptomic library generated by Illumina sequencing, contigs that annotated for ionotropic receptors and other genes implicated in the olfactory system were identified and extracted. Full length mRNA was obtained for the ionotropic glutamate receptor 25, which had 3923 bp, and for the glutamate receptor ionotropic kainate 2, which had 2737 bp. Furthermore, two other transcripts identified as glutamate receptor, ionotropic kainate 2-like were found. In silico analysis was performed for the transcription expression from different stages of development in C. rogercresseyi, and clusters according to RPKM values were constructed. Gene transcription data were validated through qPCR assays in ionotropic receptors, and showed an expression of glutamate receptor 25 associated with the copepodid stage whereas adults, especially male adults, were associated with the kainate 2 and kainate 2-like transcripts. Additionally, gene transcription analysis of the ionotropic receptors showed an overexpression in response to the presence of masking compounds and immunostimulant in salmon diets. This response correlated to a reduction in sea lice infection following in vivo challenge. Diets with masking compounds showed a decrease of lice infestation of up to 25%. This work contributes to the available knowledge on chemosensory systems in this ectoparasite, providing

  10. Glycine activated ion channel subunits encoded by ctenophore glutamate receptor genes. (United States)

    Alberstein, Robert; Grey, Richard; Zimmet, Austin; Simmons, David K; Mayer, Mark L


    Recent genome projects for ctenophores have revealed the presence of numerous ionotropic glutamate receptors (iGluRs) in Mnemiopsis leidyi and Pleurobrachia bachei, among our earliest metazoan ancestors. Sequence alignments and phylogenetic analysis show that these form a distinct clade from the well-characterized AMPA, kainate, and NMDA iGluR subtypes found in vertebrates. Although annotated as glutamate and kainate receptors, crystal structures of the ML032222a and PbiGluR3 ligand-binding domains (LBDs) reveal endogenous glycine in the binding pocket, whereas ligand-binding assays show that glycine binds with nanomolar affinity; biochemical assays and structural analysis establish that glutamate is occluded from the binding cavity. Further analysis reveals ctenophore-specific features, such as an interdomain Arg-Glu salt bridge, present only in subunits that bind glycine, but also a conserved disulfide in loop 1 of the LBD that is found in all vertebrate NMDA but not AMPA or kainate receptors. We hypothesize that ctenophore iGluRs are related to an early ancestor of NMDA receptors, suggesting a common evolutionary path for ctenophores and bilaterian species, and suggest that future work should consider both glycine and glutamate as candidate neurotransmitters in ctenophore species.

  11. Preliminary assessment of clinoptilolite K/Ar results from Yucca Mountain, Nevada, USA: A potential high-level radioactive waste repository site

    Energy Technology Data Exchange (ETDEWEB)

    WoldeGabriel, G.; Broxton, D.E.; Bish, D.L.; Chipera, S.J. [Los Alamos National Lab., NM (United States)


    At Yucca Mountain, evidence for at least three distinct temporal groups of clinoptilolites can be delineated from the preliminary K/Ar dates (2 - 3 Ma; 4 - 5 Ma; 7 - 11 Ma). The older K/Ar dates that are similar to published illite/smectite ages (9-12 Ma) may be crystallization ages, whereas the younger dates probably represent continued diagenetic reactions of older clinoptilolites with percolating fluids. The K/Ar dates increase with depth, suggesting minimal argon loss in the deeper samples. internal consistency of the clinoptilolite K/Ar results at different levels within the drill holes suggest that dating of K-rich zeolites may provide useful information for assessing the zeolitization at Yucca Mountain. Variations in the K/Ar dates are probably related to Ar loss during dissolution of older clinoptilolites and to contamination by finely crystalline feldspars. 18 refs., 1 tab.

  12. Preliminary assessment of clinoptilolite K/Ar results from Yucca Mountain, Nevada: A potential high-level radioactive waste repository site

    Energy Technology Data Exchange (ETDEWEB)

    WoldeGabriel, G.; Bish, D.L.; Broxton, D.E.; Chipera, S.J.


    At Yucca Mountain, evidence for at least three distinct temporal groups of clinoptilolites can be delineated from the preliminary K/Ar dates (2--3 Ma; 4--5 Ma; 7--11 Ma). The older K/Ar dates that are similar to published illite/smectite ages (9--12 Ma) may be crystallization ages, whereas the younger dates probably represent continued diagenetic reactions of older clinoptilolites with percolating fluids. The K/Ar dates increase with depth, suggesting minimal argon loss in the deeper samples. Internal consistency of the clinoptilolite K/Ar results at different levels within the drill holes suggest that dating of K-rich zeolites may provide useful information for assessing the zeolitization at Yucca Mountain. Variations in the K/Ar dates are probably related to Ar loss during dissolution of older clinoptilolites and to contamination by finely crystalline feldspars.

  13. Novel Functional Properties of Drosophila CNS Glutamate Receptors

    Energy Technology Data Exchange (ETDEWEB)

    Li, Yan; Dharkar, Poorva; Han, Tae-Hee; Serpe, Mihaela; Lee, Chi-Hon; Mayer, Mark L.


    Phylogenetic analysis reveals AMPA, kainate, and NMDA receptor families in insect genomes, suggesting conserved functional properties corresponding to their vertebrate counterparts. However, heterologous expression of the Drosophila kainate receptor DKaiR1D and the AMPA receptor DGluR1A revealed novel ligand selectivity at odds with the classification used for vertebrate glutamate receptor ion channels (iGluRs). DKaiR1D forms a rapidly activating and desensitizing receptor that is inhibited by both NMDA and the NMDA receptor antagonist AP5; crystallization of the KaiR1D ligand-binding domain reveals that these ligands stabilize open cleft conformations, explaining their action as antagonists. Surprisingly, the AMPA receptor DGluR1A shows weak activation by its namesake agonist AMPA and also by quisqualate. Crystallization of the DGluR1A ligand-binding domain reveals amino acid exchanges that interfere with binding of these ligands. The unexpected ligand-binding profiles of insect iGluRs allows classical tools to be used in novel approaches for the study of synaptic regulation.

  14. Distribution and functional properties of glutamate receptors in the leech central nervous system. (United States)

    Dierkes, P W; Hochstrate, P; Schlue, W R


    1. The effect of kainate and other glutamatergic agonists on the membrane potential (Em), the intracellular Na+ activity (aNai), and the intracellular free Ca2+ concentration ([Ca2+]i) of identified leech neurons and neuropile glial cells was measured with conventional and ion-sensitive microelectrodes, as well as with the use of the iontophoretically injected fluorescent indicators sodium-binding benzofuran isophthalate and Fura-2. 2. In Retzius neurons, AE, L, 8, and 101 motoneurons, and in the unclassified 50 neurons (Leydig cells) and AP neurons, as well as in neuropile glial cells, bath application of 100 microM kainate evoked a marked membrane depolarization and an increase in aNai and [Ca2+]i. The kainate-induced aNai increase persisted in solutions with high Mg2+ concentration in which synaptic transmission is blocked. 3. A membrane depolarization as well as an increase in aNai and [Ca2+]i was also evoked by L-glutamate, quisqualate, and L-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA). The agonist-induced [Ca2+]i increase was inhibited by 6,7-dinitroquinoxaline-2,3-dione (DNQX). 4. In Ca(2+)-free solution, the kainate-induced [Ca2+]i increase was abolished in the neurons and in neuropile glial cells, whereas membrane depolarization and aNai increase were unchanged. In Na(+)-free solution, kainate had no effect on Em, aNai, or [Ca2+]i in the neurons. 5. In the mechanosensory T, P, and N neurons, kainate induced considerably smaller membrane depolarizations than in the other neurons or in neuropile glial cells, and it had no significant effect on aNai or [Ca2+]i. 6. It is concluded that in leech segmental ganglia the majority of the neurons and the neuropile glial cells, but probably not the mechanosensory neurons, possess glutamate receptors of the AMPA-kainate type. In the neurons, the [Ca2+]i increase caused by glutamatergic agonists is due to Ca2+ influx through voltage-dependent Ca2+ channels that are activated by the agonist

  15. Two modes of regulation of the fatty acid elongase ELOVL6 by the 3-ketoacyl-CoA reductase KAR in the fatty acid elongation cycle.

    Directory of Open Access Journals (Sweden)

    Tatsuro Naganuma

    Full Text Available Fatty acids (FAs are diverse molecules, and such diversity is important for lipids to exert their functions under several environmental conditions. FA elongation occurs at the endoplasmic reticulum and produces a variety of FA species; the FA elongation cycle consists of four distinct enzyme reactions. For this cycle to be driven efficiently, there must exist coordinated regulation of protein components of the FA elongation machinery. However, such regulation is poorly understood. In the present study, we performed biochemical analyses using the FA elongase ELOVL6 and the 3-ketoacyl-CoA reductase KAR, which catalyze the first and second steps of the FA elongation cycle, respectively. In vitro FA elongation assays using membrane fractions demonstrated that ELOVL6 activity was enhanced ∼10-fold in the presence of NADPH, although ELOVL6 itself did not require NADPH for its catalysis. On the other hand, KAR does use NADPH as a reductant in its enzyme reaction. Activity of purified ELOVL6 was enhanced by ∼3-fold in the presence of KAR. This effect was KAR enzyme activity-independent, since it was observed in the absence of NADPH and in the KAR mutant. However, ELOVL6 enzyme activity was further enhanced in a KAR enzyme activity-dependent manner. Therefore, KAR regulates ELOVL6 via two modes. In the first mode, KAR may induce conformational changes in ELOVL6 to become structure that can undergo catalysis. In the second mode, conversion of 3-ketoacyl-CoA to 3-hydroxyacyl-CoA by KAR may facilitate release of the product from the presumed ELOVL6-KAR complex.

  16. Application of K-Ar Dating to the Chronology of Young Volcanic Centers (United States)

    Lanphere, M. A.


    K-Ar dating and a derivative technique, 40Ar/39Ar dating, are methods of high-precision chronology applicable to young volcanic centers. Cascade volcanoes studied in detail by several USGS volcanologists, Duane Champion paleomagetist, and me include Mt. Baker, WA; Mt. Rainier, WA; Mt. Adams, WA; Mt. Hood, OR; Crater Lake, OR; and Medicine Lake, CA. For Mt. Adams using detailed geologic mapping by Hildreth and Fierstein and 74 K-Ar ages for 63 mapped units, Hildreth and Lanphere established a detailed chronology for the stratovolcano. Good agreement has been achieved for K-Ar ages and 40Ar/39Ar ages of rocks from Mt. Adams as young as 36 ka. A similar detailed chronology has been established for other Cascade volcanoes using andesites, in particular. These chronologies often take 10 years or more to develop. Major advantages of the 40Ar/39Ar technique are the ability to work with small sample sizes and the possibility to push the technique to very young ages. The Campanian Ignimbrite erupted from the Campi Flegrei crater near Naples, Italy is an example of the use of small samples. Nine incremental-heating ages were determined on samples of sanidine ranging in size from 47 mg to 67 mg. These samples yielded ages for the Campanian Ignimbrite ranging from 37.1 +/- 0.75 ka to 39.5 +/- 0.62 ka and averaging 38.1 +/- 0.8 ka. Other workers have proposed 40Ar/39Ar ages for the Campanian Ignimbrite of 37.1 +/- 0.4 ka and 39.3 +/- 0.1 ka. An example of the use of 40Ar/39Ar dating of very young samples is the Christian Era (CE) age of the Vesuvius eruption of year 79. Eight packets of sanidine weighing 213-296 mg from two localities, Casti Amanti in Pompeii and Villa Poppea in nearby Oplontis, yielded a weighted-mean incremental-heating age of 1924 +/- 66 years. The known age for the CE 79 eruption of Vesuvius is 1924 years. Earlier studies of Vesuvius by other workers yielded an 40Ar/39Ar age for the Villa Poppea locality of 1922 +/- 72 years.

  17. The Potassium-Argon Laser Experiment (KArLE): Design Concepts (United States)

    Cho, Y.; Cohen, B. A.


    The absolute ages of geologic events are fundamental information for understanding the timing and duration of surface processes on planetary bodies. Absolute ages can place a planet's history in the context of the solar system evolution. For example, "when was Mars warm and wet?" is one of the key questions of planetary science. If Mars was warm and wet until 3.7 billion years ago, for instance, it suggests that Mars was still warm and wet when life appeared on Earth. Mars history has been discussed so far based on crater chronology, but the current constraints for Martian chronology models come from the cratering history of the Moon [1]. Moreover, the lunar chronology model itself is fraught with uncertainty because our understanding of lunar chronology is constrained only in a few time periods and itself needs further investigation relating crater-counting ages to absolute ages [2]. Although sample return missions would provide highly accurate radiometric ages of returned samples, they are very expensive and technically challenging. In situ geochronology is highly valuable because they would have larger number of mission opportunities and the capability of iterative measurements for multiple rocks from multiple geologic units. The capability of flight instruments to perform in situ dating is required in the NASA Planetary Science Decadal Survey and the NASA Technology Roadmap. Beagle 2 is the only mission launched to date with the explicit aim to perform in situ potassium-argon (K-Ar) dating [3], but it did not happen because of the communication failure to the spacecraft. The first in situ K-Ar dating on Mars, using SAM and APXS measurements on the Cumberland mudstone [4], yielded an age of 4.21 +/- 0.35 Ga and validated the idea of K-Ar dating on other planets. However, the Curiosity method is not purposebuilt for dating and requires many assumptions that degrade its accuracy. To obtain more accurate and meaningful ages, multiple groups are developing dedicated

  18. Switch in glutamate receptor subunit gene expression in CA1 subfield of hippocampus following global ischemia in rats. (United States)

    Pellegrini-Giampietro, D E; Zukin, R S; Bennett, M V; Cho, S; Pulsinelli, W A


    Severe, transient global ischemia of the brain induces delayed damage to specific neuronal populations. Sustained Ca2+ influx through glutamate receptor channels is thought to play a critical role in postischemic cell death. Although most kainate-type glutamate receptors are Ca(2+)-impermeable, Ca(2+)-permeable kainate receptors have been reported in specific kinds of neurons and glia. Recombinant receptors assembled from GluR1 and/or GluR3 subunits in exogenous expression systems are permeable to Ca2+; heteromeric channels containing GluR2 subunits are Ca(2+)-impermeable. Thus, altered expression of GluR2 in development or following a neurological insult or injury to the brain can act as a switch to modify Ca2+ permeability. To investigate the molecular mechanism underlying delayed postischemic cell death, GluR1, GluR2, and GluR3 gene expression was examined by in situ hybridization in postischemic rats. Following severe, transient forebrain ischemia GluR2 gene expression was preferentially reduced in CA1 hippocampal neurons at a time point that preceded their degeneration. The switch in expression of kainate/AMPA receptor subunits coincided with the previously reported increase in Ca2+ influx into CA1 cells. Timing of the switch indicates that it may play a causal role in postischemic cell death.

  19. Maailma arhitektuurifestival = World Architecture Festival / Ingrid Ruudi ; kommenteerinud Maarja Kask, Karli Luik, Ralf Lõoke, Indrek Allmann, Martin Aunin

    Index Scriptorium Estoniae

    Ruudi, Ingrid, 1978-


    Barcelonas 2.-4. nov. 2011 toimunud 4. Maailma arhitektuurifestivalist (WAF). Muljeid jagavad II vooru pääsenud eesti arhitektid Maarja Kask, Karli Luik ja Ralf Lõoke AB-st Salto (Põhuteater, Sõmeru keskus), Martin Aunin (Must maja Nõmmel), Indrek Allmann AB-st Pluss (poolautonoomne saun). Üldvõitja - Media-ICT Barcelonas (Cloud 9 / Enric Ruiz-Geli)

  20. Maailma arhitektuurifestival = World Architecture Festival / Ingrid Ruudi ; kommenteerinud Maarja Kask, Karli Luik, Ralf Lõoke, Indrek Allmann, Martin Aunin

    Index Scriptorium Estoniae

    Ruudi, Ingrid, 1978-


    Barcelonas 2.-4. nov. 2011 toimunud 4. Maailma arhitektuurifestivalist (WAF). Muljeid jagavad II vooru pääsenud eesti arhitektid Maarja Kask, Karli Luik ja Ralf Lõoke AB-st Salto (Põhuteater, Sõmeru keskus), Martin Aunin (Must maja Nõmmel), Indrek Allmann AB-st Pluss (poolautonoomne saun). Üldvõitja - Media-ICT Barcelonas (Cloud 9 / Enric Ruiz-Geli)

  1. Preliminary K/Ar geochronology of the Crater Basalt volcanic field (CBVF, northern Patagonia

    Directory of Open Access Journals (Sweden)

    Z. Pécskay


    Full Text Available The Crater Basalt volcanic field is one of the Quaternary intraplate basaltic fields in northern Patagonia. A systematic geological, volcanological and geochronological study of CBVF indicates a multistage history of eruptions of basaltic volcanoes. K/Ar dating, using whole rock samples shows that the measured analytical ages are fully consistent with the available stratigraphic control. The radiometric ages fall into three distinct, internally consistent age groups, which give evidence that there were at least three major episodes of volcanic activity, at about 1.0 Ma, 0.6 Ma and 0.3 Ma ago. The age differences appear to be just significant, even although less than 10 % radiogenic argon was found in the isotope analysis of whole rock samples.

  2. General synthesis of β-alanine-containing spider polyamine toxins and discovery of nephila polyamine toxins 1 and 8 as highly potent inhibitors of ionotropic glutamate receptors. (United States)

    Lucas, Simon; Poulsen, Mette H; Nørager, Niels G; Barslund, Anne F; Bach, Tinna B; Kristensen, Anders S; Strømgaard, Kristian


    Certain spiders contain large pools of polyamine toxins, which are putative pharmacological tools awaiting further discovery. Here we present a general synthesis strategy for this class of toxins and prepare five structurally varied polyamine toxins. Electrophysiological testing at three ionotropic glutamate receptor subtypes reveals that two of these, Nephila polyamine toxins 1 (NPTX-1) and 8 (NPTX-8), comprise intriguing pharmacological activities by having subnanomolar IC(50) values at kainate receptors.

  3. Preliminary K/Ar geochronology of the Crater Basalt volcanic field (CBVF, northern Patagonia

    Directory of Open Access Journals (Sweden)

    Z. Pécskay


    Full Text Available The Crater Basalt volcanic field is one of the Quaternary intraplate basaltic fields in northern Patagonia. A systematic geological, volcanological and geochronological study of CBVF indicates a multistage history of eruptions of basaltic volcanoes. K/Ar dating, using whole rock samples shows that the measured analytical ages are fully consistent with the available stratigraphic control. The radiometric ages fall into three distinct, internally consistent age groups, which give evidence that there were at least three major episodes of volcanic activity, at about 1.0 Ma, 0.6 Ma and 0.3 Ma ago. The age differences appear to be just significant, even although less than 10 % radiogenic argon was found in the isotope analysis of whole rock samples.El campo volcánico del Basalto Cráter (CVBC constituye uno de los campos basálticos cuaternarios de intraplaca de la Patagonia septentrional. El estudio sistemático de la geología, volcanología y geocronología del CVBC muestra una historia eruptiva multiepisódica de volcanes basálticos. Las dataciones K-Ar realizadas sobre roca total son coherentes con el control estratigráfico. Las edades obtenidas para el Basalto Cráter permiten distinguir tres episodios diferentes, pero individualmente coherentes, de actividad volcánica, ocurridos hace ~1,0 Ma; 0,6 Ma y 0,3 Ma. Las diferencias de edad parecen ser significativas, aún cuando el contenido de argón radiogénico determinado en los análisis de roca total resultó menor al 10 %.

  4. K-Ar age of young volcanic rocks and excess argon--Binary mixing model and quantitative study of excess argon effect

    Institute of Scientific and Technical Information of China (English)


    A binary mixing model for excess argon is suggested in the note. According to this model and the data of excess argon component obtained in our experiment , a quantitative study of the effect of excess argon on real K-Ar age of young volcanic rocks is done. The result indicates that the effect of 5% excess argon component in samples on K-Ar age of the samples more than 2 Ma is less than 7.36% and can lead K-Ar age of 0.5 Ma samples to increase by 32.4%, while 1% excess argon component leads K-Ar age of 0.5 Ma samples to increase by 6.26%. Therefore, when pre-processed excess argon component is ≤1%, K-Ar age of the samples more than 0.5 Ma should be credible. On this basis we suggest a principal opinion for evaluation of previous K-Ar dating results and propose that the matrix is used to determine K-Ar age of young volcanic rocks. For the samples less than 0.2 Ma, in the case of high excess argon content, even if only 1% excess argon component exists in their matrix, it can also greatly affect their K-A age. Thus it must be careful to treat the dating result.

  5. Plasminogen mRNA induction in the mouse brain after kainate excitation: codistribution with plasminogen activator inhibitor-2 (PAI-2) mRNA. (United States)

    Sharon, Ronit; Abramovitz, Rene; Miskin, Ruth


    Plasminogen (Plg), which can be converted to the active protease plasmin by plasminogen activators, has been previously implicated in brain plasticity and in toxicity inflicted in hippocampal pyramidal neurons by kainate. Here we have localized Plg. mRNA through in situ hybridization in brain cryosections derived from normal adult mice or after kainate injection (i.p.). The results indicated that Plg mRNA was undetectable in the normal brain, but after kainate injection it was induced in neuronal cells in multiple, but specific areas, including layers II-III of the neocortex; the olfactory bulb, anterior olfactory nucleus, and the piriform cortex; the caudate/putamen and accumbens nucleus shell; throughout the amygdaloid complex; and in the CAI/CA3 subfields of the hippocampus. Interestingly, this distribution pattern coincided with what we have recently described for the plasminogen activator inhibitor-2 (PAI-2) mRNA, however differing from that of the plasminogen activator inhibitor-1 (PAI-1) mRNA, as also shown here. These results suggest that enhanced Plg gene expression could be involved in events associated with olfactory, striatal, and limbic structures. Furthermore, because PAI-2 is thought to intracellularly counteract cytotoxic events, our results raise the possibility that PAI-2 can act in the brain as an intracellular neuroprotector against potential plasmin-mediated toxicity.

  6. receptores

    Directory of Open Access Journals (Sweden)

    Salete Regina Daronco Benetti


    Full Text Available Se trata de un estudio etnográfico, que tuvo lo objetivo de interpretar el sistema de conocimiento y del significado atribuidos a la sangre referente a la transfusión sanguínea por los donadores y receptores de un banco de sangre. Para la colecta de las informaciones se observaron los participantes y la entrevista etnográfica se realizó el análisis de dominio, taxonómicos y temáticos. Los dominios culturales fueron: la sangre es vida: fuente de vida y alimento valioso; creencias religiosas: fuentes simbólicas de apoyos; donación sanguínea: un gesto colaborador que exige cuidarse, gratifica y trae felicidad; donación sanguínea: fuente simbólica de inseguridad; estar enfermo es una condición para realizar transfusión sanguínea; transfusión sanguínea: esperanza de vida; Creencias populares: transfusión sanguínea como riesgo para la salud; donadores de sangre: personas benditas; donar y recibir sangre: como significado de felicidad. Temática: “líquido precioso que origina, sostiene, modifica la vida, provoca miedo e inseguridad”.

  7. Volume Measurements of Laser-generated Pits for In Situ Geochronology using KArLE (Potassium-Argon Laser Experiment) (United States)

    French, R. A.; Cohen, B. A.; Miller, J. S.


    The Potassium-Argon Laser Experiment( KArLE), is composed of two main instruments: a spectrometer as part of the Laser-Induced Breakdown Spectroscopy (LIBS) method and a Mass Spectrometer (MS). The LIBS laser ablates a sample and creates a plasma cloud, generating a pit in the sample. The LIBS plasma is measured for K abundance in weight percent and the released gas is measured using the MS, which calculates Ar abundance in mols. To relate the K and Ar measurements, total mass of the ablated sample is needed but can be difficult to directly measure. Instead, density and volume are used to calculate mass, where density is calculated based on the elemental composition of the rock (from the emission spectrum) and volume is determined by pit morphology. This study aims to reduce the uncertainty for KArLE by analyzing pit volume relationships in several analog materials and comparing methods of pit volume measurements and their associated uncertainties.

  8. Glutamate-containing dipeptides do not modulate ligand binding at excitatory amino acid receptors. (United States)

    Baud, J; Fagg, G E


    Dipeptides of the structure X-Glu (e.g. X = Phe, Leu) have been proposed as allosteric modulators of excitatory amino acid receptors in rat brain membranes. Here we report that these dipeptides reduce the binding of L-[3H]Glu (predominantly N-methyl-D-aspartate-sensitive sites) and of [3H]kainate to postsynaptic density preparations isolated from rat brain. However, several observations indicate that the effects of these dipeptides are mediated not by allosteric modulation, but by free L-Glu liberated by the actions of a membrane-associated aminopeptidase. The absolute and relative potencies of the dipeptides are similar at all acidic amino acid binding sites examined to date, suggesting the involvement of a factor with similar activity at each site (e.g. L-Glu). N-Acetyl-Met-Glu is a weak inhibitor of L-Glu and kainate binding, and N-blocked peptides are known to be poor substrates of aminopeptidases. Bestatin, an inhibitor of aminopeptidases, decreases or abolishes the effects of substrate dipeptides on L-Glu and kainate receptor binding, while having no effect itself.

  9. Continued Development of in Situ Geochronology for Planetary Using KArLE (Potassium-Argon Laser Experiment) (United States)

    Devismes, D.; Cohen, B. A.


    Geochronology is a fundamental measurement for planetary samples, providing the ability to establish an absolute chronology for geological events, including crystallization history, magmatic evolution, and alteration events, and providing global and solar system context for such events. The capability for in situ geochronology will open up the ability for geochronology to be accomplished as part of lander or rover complement, on multiple samples rather than just those returned. An in situ geochronology package can also complement sample return missions by identifying the most interesting rocks to cache or return to Earth. The K-Ar radiometric dating approach to in situ dating has been validated by the Curiosity rover on Mars as well as several laboratories on Earth. Several independent projects developing in situ rock dating for planetary samples, based on the K-Ar method, are giving promising results. Among them, the Potassium (K)-Argon Laser Experiment (KArLE) at MSFC is based on techniques already in use for in planetary exploration, specifically, Laser-induced Breakdown Spectroscopy (LIBS, used on the Curiosity Chemcam), mass spectroscopy (used on multiple planetary missions, including Curiosity, ExoMars, and Rosetta), and optical imaging (used on most missions).

  10. Arctigenin reduces neuronal responses in the somatosensory cortex via the inhibition of non-NMDA glutamate receptors. (United States)

    Borbély, Sándor; Jócsák, Gergely; Moldován, Kinga; Sedlák, Éva; Preininger, Éva; Boldizsár, Imre; Tóth, Attila; Atlason, Palmi T; Molnár, Elek; Világi, Ildikó


    Lignans are biologically active phenolic compounds related to lignin, produced in different plants. Arctigenin, a dibenzylbutyrolactone-type lignan, has been used as a neuroprotective agent for the treatment of encephalitis. Previous studies of cultured rat cerebral cortical neurones raised the possibility that arctigenin inhibits kainate-induced excitotoxicity. The aims of the present study were: 1) to analyse the effect of arctigenin on normal synaptic activity in ex vivo brain slices, 2) to determine its receptor binding properties and test the effect of arctigenin on AMPA/kainate receptor activation and 3) to establish its effects on neuronal activity in vivo. Arctigenin inhibited glutamatergic transmission and reduced the evoked field responses. The inhibitory effect of arctigenin on the evoked field responses proved to be substantially dose dependent. Our results indicate that arctigenin exerts its effects under physiological conditions and not only on hyper-excited neurons. Furthermore, arctigenin can cross the blood-brain barrier and in the brain it interacts with kainate sensitive ionotropic glutamate receptors. These results indicate that arctigenin is a potentially useful new pharmacological tool for the inhibition of glutamate-evoked responses in the central nervous system in vivo.

  11. Isolation and Identification of Arcobacter spp. by Multiplex PCR from Water Sources in Kars Region. (United States)

    Çelik, Elif; Ünver, Ahmet


    This study was conducted to determine the prevalence of Arcobacter spp. in various water sources of stream, creek, pond, and drinking water in Kars and surrounding areas. A total of 113 water samples including 19 samples from creeks, 49 from streams, 10 from ponds, and 35 from drinking water samples collected from different regions were examined for presence of Arcobacter spp. by cultural methods. Arcobacter spp. were isolated from 14 (12.38 %) samples including 5 (26.31 %) creek and 9 (18.36 %) stream water samples and all were identified as Arcobacter butzleri by multiplex PCR. No agent was isolated from pond and drinking water samples. The results of this study demonstrated that creek and stream waters are contaminated by this agent showing high potential risk of Arcobacter species to be transmitted to humans and animals and in the contamination of food. It is concluded that water sources should also be considered as a factor not only carrying agents but also as a primary source of the infection.

  12. VALUASI EKONOMI BIODIVERSITY KARS: STUDI KASUS VALUASI EKONOMI KAWASAN KARS MAROS, SULAWESI SELATAN (Economic Valuation of Karst Biodiversity: A Case Study of Karst Region in Maros, South Sulawesi, Indonesia

    Directory of Open Access Journals (Sweden)

    Gustami Gustami


    Full Text Available ABSTRAK Studi ini bertujuan untuk menghitung nilai ekonomi total dari kawasan kars Maros Sulawesi Selatan. Studi berlokasi di Taman Wisata Alam bantimurung, Cagar Alam Karaenta, dan Taman Wisata Alam Gua Pattunang. Kegiatan ini merupakan kerjasama Kementerian Lingkungan Hidup dan Collaborative Environmental Project in Indonesia (CEPI dengan melibatkan Staf Bapedal Regional III Makassar, Pemda Maros, Universitas Muhammadiyah dan Universitas Hasanuddin Ujung Pandang. Pendekatan biaya perjalanan adalah yang pertama dikaji untuk menghitung nilai guna langsung dari kegiatan rekreasi. Penghitungan nilai tidak langsung keberadaan kawasan kars beserta hutannya yang didasarkan pada nilai dari fungsinya sebagai sumber air dan pencegah terjadinya banjir dan longsor. Nilai preservasi kawasan kars yang dinilai dengan menghitung keinginan membayar pengunjung untuk konservasi kupu-kupu dan kumbang,perbaikan lingkungan terutama yang berkaitan dengan kebersihan, keindahan dan kesejukan dengan jumlah kunjungan pertahun. Berdasarkan hasil analisis, nilai ekonomi total yang terdiri dari nilai guna langsung, nilai guna tidak langsung serta nilai bukan guna (non use value yang berupa nilai preservasi adalah Rp. 639,556,607,830,-. Walaupun kenyataannya masih banyak nilai ekonomi lain yang belum dikaji, namun studi ini telah mengungkapkan sebagian nilai ekonomi kawasan kars yang dimanfaatkan oleh masyarakat sekitar ataupun masyarakat di luar yang mengunjungi kawasan ini untuk menikmati fenomena “kars tropika klasik” Maros.   ABSTRACT The objective of this study is to assess total economic values of karst region in Maros, South Sulawesi, spesifically at Taman wisata alam Bantimurung, Cagar alam Karaenta, and Taman Wisata Alam Gua Pattunuang. This activity was a joint project between the Ministry of Environmental Republic of Indonesia and the Collaborative Environmental Project in Indonesia (CEPI involving staff of BAPEDAL Regional III, Makassar, local government of

  13. Retraction: Radenović L. Effect of 7-nitroindazole on superoxide production and MnSOD activity in the rat brain following kainate-induced neurotoxicity. Arch biol sci, 2008, 60(1:25-32. DOI: 10.2298/ABS0801025R

    Directory of Open Access Journals (Sweden)



    Full Text Available This is a notice of retraction of the article: Effect of 7-nitroindazole on superoxide production and MnSOD activity in the rat brain following kainate-induced neurotoxicity, published in the Archives of Biological Sciences in 2008, Vol. 60, Issue 1. The Editor-in-Chief has been informed that this paper plagiarizes an earlier paper: Radenovic L, Selakovic V, Kartelija G, Todorovic N, Nedeljkovic M. Differential effects of NMDA and AMPA/kainate receptor antagonists on superoxide production and MnSOD activity in rat brain following intrahippocampal injection. Brain Res Bull, 2004, 64(1:85-93. The results in the article being retracted were presented as findings obtained from novel research. Inspection of the results has revealed that they were part of research already presented in the original article without appropriate justification or cross-referencing. The Editor-in-Chief considered publishing a notice of redundancy specifying the elements published previously. However, since the original article had already been autoplagiarized by the same corresponding author in the same journal (retraction DOI:10.2298/ABS150318026E, the article is being retracted in accordance with the publishing ethics of the Archives of Biological Sciences in order to preserve the integrity of scientific research. We apologize to the journal's readers that it took so long to notice this error and instigate retraction of the paper. We request our readers to contact the editorial office and editors of the journal directly should similar cases occur in the future, so that the necessary action can be taken more promptly. Link to the retracted article 10.2298/ABS0801025R

  14. Development of calcium-permeable alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors in cultured neocortical neurons visualized by cobalt staining

    DEFF Research Database (Denmark)

    Jensen, J B; Schousboe, A; Pickering, D S


    The developmental expression of calcium (Ca2+)-permeable alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and kainate receptors in cultured neocortical neurons was evaluated by using cobalt uptake, a histochemical method that identifies cells expressing Ca2+-permeable, non-N-methyl......The developmental expression of calcium (Ca2+)-permeable alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and kainate receptors in cultured neocortical neurons was evaluated by using cobalt uptake, a histochemical method that identifies cells expressing Ca2+-permeable, non......-N-methyl-D-aspartate (non-NMDA) receptors. At a concentration of 500 microM, AMPA was found to stimulate cobalt uptake only late in development, resulting in staining of 2.7%+/-0.3% of the neurons maintained in culture for 12 days in vitro (DIV). When AMPA receptor desensitization was blocked with 50 microM cyclothiazide......, the developmental profile of cobalt uptake mediated by 25 microM AMPA changed dramatically. The cobalt staining now appeared in young cultures (5 DIV), and the percentage of stained cells increased from 3.4%+/-0.2% at 5 DIV to 21.7%+/-1.6% at 12 DIV. The effect of 200 microM kainate was similar to that seen with 25...

  15. Ablation of NMDA receptors enhances the excitability of hippocampal CA3 neurons.

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    Fumiaki Fukushima

    Full Text Available Synchronized discharges in the hippocampal CA3 recurrent network are supposed to underlie network oscillations, memory formation and seizure generation. In the hippocampal CA3 network, NMDA receptors are abundant at the recurrent synapses but scarce at the mossy fiber synapses. We generated mutant mice in which NMDA receptors were abolished in hippocampal CA3 pyramidal neurons by postnatal day 14. The histological and cytological organizations of the hippocampal CA3 region were indistinguishable between control and mutant mice. We found that mutant mice lacking NMDA receptors selectively in CA3 pyramidal neurons became more susceptible to kainate-induced seizures. Consistently, mutant mice showed characteristic large EEG spikes associated with multiple unit activities (MUA, suggesting enhanced synchronous firing of CA3 neurons. The electrophysiological balance between fast excitatory and inhibitory synaptic transmission was comparable between control and mutant pyramidal neurons in the hippocampal CA3 region, while the NMDA receptor-slow AHP coupling was diminished in the mutant neurons. In the adult brain, inducible ablation of NMDA receptors in the hippocampal CA3 region by the viral expression vector for Cre recombinase also induced similar large EEG spikes. Furthermore, pharmacological blockade of CA3 NMDA receptors enhanced the susceptibility to kainate-induced seizures. These results raise an intriguing possibility that hippocampal CA3 NMDA receptors may suppress the excitability of the recurrent network as a whole in vivo by restricting synchronous firing of CA3 neurons.

  16. Aspects of dopamine and acetylcholine release induced by glutamate receptors; Aspectos das liberacoes de dopamina e acetilcolina mediadas por receptores de glutamato

    Energy Technology Data Exchange (ETDEWEB)

    Paes, Paulo Cesar de Arruda


    The basal ganglia play an important role in the motor control of rats and humans. This control involves different neurotransmitters and the mutual control of these key elements has been subject to several studies. In this work we determined the role of glutamate on the release of radioactively labelled dopamine and acetylcholine from chopped striatal tissue in vitro. The values of Effective Concentration 50% for glutamate, NMDA, kainic, quisqualic acids and AMPA on the release of dopamine and acetylcholine were obtained. The inhibitory effects of magnesium, tetrodotoxin, MK-801, AP5 and MCPG, as well as the effects of glycin were evaluated. The results suggested that dopamine is influenced by the NMDA type glutamate receptor while acetylcholine seems to be influenced by NMDA, kainate and AMPA receptors. Tetrodotoxin experiments suggested that kainate receptors are both present in cholinergic terminals and cell bodies while AMPA and NMDA receptors are preferentially distributed in cell bodies. Magnesium effectively blocked the NMDA stimulation and unexpectedly also AMPA- and quisqualate-induced acetylcholine release. The latter could not be blocked by MCPG ruling out the participation of methabotropic receptors. MK-801 also blocked NMDA-receptors. Results point out the importance of the glutamic acid control of dopamine and acetylcholine release in striatal tissue. (author)

  17. (R-[11C]Verapamil PET studies to assess changes in P-glycoprotein expression and functionality in rat blood-brain barrier after exposure to kainate-induced status epilepticus

    Directory of Open Access Journals (Sweden)

    Lammertsma Adriaan A


    Full Text Available Abstract Background Increased functionality of efflux transporters at the blood-brain barrier may contribute to decreased drug concentrations at the target site in CNS diseases like epilepsy. In the rat, pharmacoresistant epilepsy can be mimicked by inducing status epilepticus by intraperitoneal injection of kainate, which leads to development of spontaneous seizures after 3 weeks to 3 months. The aim of this study was to investigate potential changes in P-glycoprotein (P-gp expression and functionality at an early stage after induction of status epilepticus by kainate. Methods (R-[11C]verapamil, which is currently the most frequently used positron emission tomography (PET ligand for determining P-gp functionality at the blood-brain barrier, was used in kainate and saline (control treated rats, at 7 days after treatment. To investigate the effect of P-gp on (R-[11C]verapamil brain distribution, both groups were studied without or with co-administration of the P-gp inhibitor tariquidar. P-gp expression was determined using immunohistochemistry in post mortem brains. (R-[11C]verapamil kinetics were analyzed with approaches common in PET research (Logan analysis, and compartmental modelling of individual profiles as well as by population mixed effects modelling (NONMEM. Results All data analysis approaches indicated only modest differences in brain distribution of (R-[11C]verapamil between saline and kainate treated rats, while tariquidar treatment in both groups resulted in a more than 10-fold increase. NONMEM provided most precise parameter estimates. P-gp expression was found to be similar for kainate and saline treated rats. Conclusions P-gp expression and functionality does not seem to change at early stage after induction of anticipated pharmacoresistant epilepsy by kainate.

  18. Kainate-enhanced release of D-(3H)aspartate from cerebral cortex and striatum: reversal by baclofen and pentobarbital

    Energy Technology Data Exchange (ETDEWEB)

    Potashner, S.J.; Gerard, D.


    A study was made of the actions of the excitant neurotoxin, kainic acid, on the uptake and the release of D-(2,3-3H)aspartate (D-ASP) in slices of guinea pig cerebral neocortex and striatum. The slices took up D-ASP, reaching concentrations of the amino acid in the tissue which were 14-23 times that in the medium. Subsequently, electrical stimulation of the slices evoked a Ca2+-dependent release of a portion of the D-ASP. Kainic acid (10(-5)-10(-3) M) produced a dose-dependent inhibition of D-ASP uptake. The electrically evoked release of D-ASP was increased 1.6-2.0 fold by 10(-5) and 10(-4)M kainic acid. The kainate-enlarged release was Ca2+-dependent. Dihydrokainic acid, an analogue of kainic acid with little excitatory or toxic action, did not increase D-ASP release but depressed D-ASP uptake. Attempts were made to block the action of kainic acid with baclofen and pentobarbital, compounds which depress the electrically evoked release of L-glutamate (L-GLU) and L-aspartate (L-ASP). Baclofen (4 X 10(-6)M), an antispastic drug, and pentobarbital (10(-4)M), an anesthetic agent, each inhibited the electrically evoked release of D-ASP and prevented the enhancement of the release above control levels usually produced by 10(-4)M kainic acid. It is proposed that 10(-5) and 10(-4)M kainic acid may enhance the synaptic release of L-GLU and L-ASP from neurons which use these amino acids as transmitters. This action is prevented by baclofen and pentobarbital. In view of the possibility that cell death in Huntington's disease could involve excessive depolarization of striatal and other cells by glutamate, baclofen might be effective in delaying the loss of neurons associated with this condition.

  19. K-Ar geochronology of the late cenozoic volcanic rocks of the Cordillera Occidental, southernmost Peru (United States)

    Tosdal, Richard M.; Farrar, Edward; Clark, Alan H.


    Twenty-four K-Ar radiometric ages are presented for late Cenozoic continental volcanic rocks of the Cordillera Occidental of southernmost Perú (lat. 16° 57'-17° 36'S). Rhyodacitic ignimbrite eruptions began in this transect during the Late Oligocene and continued episodically through the Miocene. The development of andesitic-dacitic strato volcanoes was initiated in the Pliocene and continues to the present. The earliest ignimbrite flows (25.3-22.7 Ma) are intercalated in the upper, coarsely-elastic member of the Moquegua Formation and demonstrate that this sedimentary unit accumulated in a trough, parallel to Andean tectonic trends, largely in the Oligocene. More voluminous ash-flow eruptions prevailed in the Early Miocene (22.8-17.6 Ma) and formed the extensively preserved Huaylillas Formation. This episode was coeval with a major phase of Andean uplift, and the pyroclastics overlie an erosional surface of regional extent incised into a Paleogene volcano-plutonic arc terrain. An age span of 14.2-8.9 Ma (mid-Late Miocene) is indicated for the younger Chuntacala Formation, which again comprises felsic ignimbrite flows, largely restricted to valleys incised into the pre-Huaylillas Formation lithologies, and, at lower altitudes, an extensive aggradational elastic facies. The youngest areally extensive ignimbrites, constituting the Sencca Formation, were extruded during the Late Miocene. In the earliest Pliocene, the ignimbrites were succeeded by more voluminous calcalkaline, intermediate flows which generated numerous large and small stratovolcanoes; these range in age from 5.3 to 1.6 Ma. Present-day, or Holocene, volcanism is restricted to several large stratovolcanoes which had begun their development during the Pleistocene (by 0.7 Ma). The late Oligocene/Early Miocene (ca. 22-23 Ma) reactivation of the volcanic arc coincided with a comparable increase in magmatic activity throughout much of the Cordilleras Occidental and Oriental of the Central Andes.

  20. ATPA induced GluR5-containing kainite receptor S-nitrosylation via activation of GluR5-Gq-PLC-IP(3)R pathway and signalling module GluR5·PSD-95·nNOS. (United States)

    Zhang, Hai-Jian; Li, Chong; Zhang, Guang-Yi


    GluR5-containing kainite receptor (GluR5-KAR) plays an important role in the pathophysiology of nervous system diseases, while S-nitrosylation exerts a variety of effects on biological systems. However, the mechanism of GluR5-KAR S-nitrosylation is still unclear up to now. Here our researches found that GluR5-KAR selective agonist ATPA stimulation activated the nonclassical GluR5-KAR-Gq-PLC-IP(3)R pathway and the signalling module GluR5·PSD-95·nNOS (the former is more important), led to Ca(2+) release from intracellular calcium stores endoplasmic reticulum (ER) to cytoplasm and extracellular calcium indrawal, respectively, which further resulted in nNOS activation and GluR5-KAR S-nitrosylation, and then inhibited GluR5-mediated whole-cell current attenuation and induced apoptosis in primary cultured hippocampal neurons. Clarification of the primary mechanisms of GluR5-KAR S-nitrosylation induced by ATPA and identification of critical cysteine for GluR5-2a S-nitrosylation (Cys231 and Cys804) open up a brand-new field for revealing downstream signalling pathway of GluR5-KAR and its molecular characteristics, exploring the pathogenesis of neurological diseases and searching for promising therapies.

  1. OLM interneurons are transiently recruited into field gamma oscillations evoked by brief kainate pressure ejections onto area CA1 in mice hippocampal slices. (United States)

    Kipiani, E


    Oscillations (30-100 Hz) are correlated with the cognitive functions of the brain. In the hippocampus interactions between perisomatic and trilaminar interneurons with pyramidal cells are thought to underlie generation of field gamma oscillations. In area CA3 OLM interneurons receive synaptic input in gamma range but generate action potential (AP) output in theta band and are involved in theta oscillations synchronized along the longitudinal axis of the hippocampus. In slice preparations of CA3 area the spike timing of OLM cells could be modulated by carbachole induced gamma oscillations, although their firing rates are limited to theta frequency. Normally, OLM interneurons are somatostatin positive cells. In this study we tested whether parvalbumin (PV) containing OLM interneurons in area CA1 limit AP output during kainate pressure ejection also to theta frequency. We used focal short applications of kainate in area CA1 to induce filed gamma oscillations with an average frequency of about 44.7+/-4.4 Hz. The duration of field gamma was on average 8.9+/-3.5 s. During such oscillations CA1 PV positive OLM interneurons of mice hippocampus received excitatory synaptic input at gamma frequency. Moreover, their AP output was in gamma range as well. Thus, we show that beside the somatostatin containing OLM interneurons, which generate theta rhythm there are PV containing OLM cells, which could synchronize the distal dendrites of CA1 pyramidal cells to the field gamma oscillations.

  2. Southern Brasilia Belt (SE Brazil): tectonic discontinuities, K-Ar data and evolution during the Neoproterozoic Brasiliano orogeny

    Energy Technology Data Exchange (ETDEWEB)

    Valeriano, Claudio Morrison de [Universidade do Estado, Rio de Janeiro, RJ (Brazil)]. E-mail:; Teixeira, Wilson [Sao Paulo Univ., SP (Brazil); Simoes, Luiz Sergio Amarante [UNESP, Sao Paulo, SP (Brazil); Heilbron, Monica [Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq), Brasilia, DF (Brazil)


    This paper focuses the tectonic evolution of the southern brasilia belt, with emphasis on the Furnas segment, along the 21 deg C S parallel. The uppermost structural unit (Passos Nappe - PN) comprises a highly deformed metasedimentary succession interpreted as a fragment of the Neoproterozoic passive margin of western Sao francisco craton. An inverted metamorphic gradient ranging from greensvhits to lower granulite facies of medium to high-pressure regime characterizes the PN as relict of a subduction zone. The External Domain display a complex imbrication of basement rocks (Archean Piumhi greenstones, a turbiditic gaywacke succession and a calc-alkaline granitoid suite) with undated siliciclast low-grade metasedimentary rocks. The Sao Francisco Craton (SFC) comprises pre-1.8 Ga basement rocks covered by anchimetamorphic Neoproterozoic carbonatic shallow marine platform deposits of the Bambui group. The Brasiliano thrust stacking generated a coarse clastic influx of molassic character on the foreland zone of Sao Francisco Craton, coeval with the exhumation of the External Domain thrust sheets. New K-Ar determinations on mineral separates are presented an interpreted among previous data. The SFC basement rocks display Paleo-to Meesoproterozoic cooling ages. The allochthonous units, in contrast, display K-Ar ages within the 560-675 Ma range. Brasiliano thrust stacking is therefore interpreted to have taken place onto a cold Sao Francisco craton foreland, in a thin-skinned style, as basement rocks were not heated enough to have their-K-ar systems reset during the allochthony. (author)

  3. K?Ar dating and geological significance of clastic sediments of the Paleocene Sepultura Formation, Baja California, México (United States)

    Téllez Duarte, Miguel Agustín.; López Martínez, Margarita


    At its type locality, the Paleocene Sepultura Formation consists of two members: a lower glauconitic-rich clastic section and an upper calcareous section. Three samples of authigenic glauconite pellets from two localities with good clastic sediment exposures were dated using K-Ar. At the type locality of Mesa La Sepultura, pellets from the middle of the clastic section yield a date of 60±1 Ma (weighted average of four experiments), and pellets from the top of the clastic unit give a date of 60±1 Ma (weighted average of two experiments). Pellets from the base of the section at La Mesa, 60 km distant, give a date of 59±1 Ma (one experiment). Dates obtained are in good agreement with those reported by biostratigraphy and confirm a Late Danian age. Our results differ from those reported elsewhere, in which low potassium content glauconites yield younger K-Ar ages than expected. An explanation for our observed agreement in ages could be related to the tectonic setting of forearc basins, where the low geothermal gradient prevents argon loss and reliable dates can be obtained.

  4. The selective activation of the glutamate receptor GluR5 by ATPA is controlled by serine 741. (United States)

    Nielsen, Mai Marie; Liljefors, Tommy; Krogsgaard-Larsen, Povl; Egebjerg, Jan


    Only a few agonists exhibit selectivity between the AMPA and the kainate subtypes of the glutamate receptor. The most commonly used kainate receptor preferring agonist, (S)-2-amino-3-(5-tert-butyl-3-hydroxy-4-isoxazolyl)propionic acid [(S)-ATPA], is an (R,S)-2-amino-3-(5-methyl-3-hydroxy-4-isoxazolyl)propionic acid (AMPA) derivative in which the methyl group at the 5-position of the isoxazole ring has been replaced by a tert-butyl group. When characterized by the two-electrode voltage clamp method in Xenopus laevis oocytes, ATPA exhibits at least 50-fold higher potency on the kainate receptor subtype, GluR5, compared with the AMPA receptors. Through mutagenesis studies of GluR5 and the AMPA receptor subtype, GluR1, we demonstrate that this pronounced selectivity for ATPA can be ascribed to Ser741 in GluR5 and Met722 in GluR1. Examination of other aliphatic substitutions at the 5-position of the isoxazole ring revealed that (R,S)-2-amino-3-(5-isopropyl-3-hydroxy-4-isoxazolyl)propionic acid (isopropyl-AMPA) displayed a 6-fold higher potency for GluR5 than for GluR1, whereas the analogs, propyl-AMPA and isobutyl-AMPA, did not exhibit significantly different potencies. Our study suggests that the GluR5 selectivity was a result not only of steric interference between the bulky tert-butyl group in ATPA and the methionine (Met722) in GluR1 but also a serine-dependent stabilization of the active conformation of GluR5 induced by ATPA. The stabilization was agonist-dependent and observed only for ATPA and isopropyl-AMPA, not for other AMPA analogs with bulky substitutions at the 5-position of the isoxazole ring.

  5. 40Ar/39Ar and K/Ar dating of low grade metamorphism: examples on metabasites from Central Chile (United States)

    Aguirre, L.; Feraud, G.; Fuentes, F.; Delbar, M.; Morata, D.


    Dating low to very low-grade burial metamorphic assemblages is often difficult because of (1) few mineral phases compositionally suitable to apply the 40Ar/39Ar and K-Ar methods, and (2) small amount in which these phases are commonly found. K-feldspar adularia, sericitic mica, and celadonite are the best known K-bearing secondary minerals. We present some successful attempts to analyse two distinct secondary phases from a same volcanic formation that allow to test the validity of the measured ages. These ages have been also compared with the crystallisation age of the volcanic rocks in which the secondary phases were lately developed. Adularia and sericite were selected from basic lava flows from a 3 to 13 km thick Cretaceous sequence from the Coastal Range of central Chile, at two different locations: the Bustamante Hill (west from Santiago), and the Cordón de Chacana, c. 80 km further north. Adularia came from a low-variance assemblage with pumpellyite, chlorite and low-albite contained in amygdules whereas sericite was present in milky-white strongly sericitized plagioclase crystals. While small clusters of rare fresh plagioclase grains from lava flows from Bustamante and Chacana displayed concordant plateau ages 119.4 ± 2.4 (2 sigma) and 118.7 ± 0.6 Ma, respectively, the adularia from the same formations gave sensibly younger ages around 94 Ma (high temperature steps), and 96.8 ± 0.2 Ma (plateau age) in Bustamante and Chacana, respectively. Sericite ages were measured in situ into single crystals of strongly transformed plagioclases. The relative proportion of sericite and plagioclase corresponding to each degasing step was monitored by measuring the Ca/K ratio (deduced from 37ArCa/39Ar_K). While intermediate ages were measured on some sericite of both sites (corresponding to a variable but permanent contribution of plagioclase on each step), a plateau age of 97.0 ± 1.6 Ma (concordant with adularia) could be obtained on a strongly sericitized plagioclase

  6. Anticonvulsant effects of carbamazepine on spontaneous seizures in rats with kainate-induced epilepsy: comparison of intraperitoneal injections with drug-in-food protocols. (United States)

    Grabenstatter, Heidi L; Clark, Suzanne; Dudek, F Edward


    The present study evaluated the effectiveness of intraperitoneal (IP) injections and oral administration of carbamazepine (CBZ) in food on the frequency of spontaneous motor seizures in rats with kainate-induced epilepsy. The purpose was to develop a convenient drug-in-food approach for continuous, long-term administration of potential antiepileptic drugs (AEDs). Single IP injections of CBZ (10-100 mg/kg) were compared to vehicle injections via six AED-versus-vehicle tests using a repeated-measures, crossover protocol. Similar protocols were used with CBZ-containing or control food pellets. CBZ significantly reduced motor seizure frequency at 30 and 100 mg/kg after single IP injections, and these doses completely blocked motor seizures during a 6-h postdrug epoch in 25% and 70% of the animals, respectively. Single administrations of 30 mg/kg and 100 mg/kg CBZ in food also significantly reduced motor seizures, and blocked seizures in 33% and 89% of the rats, respectively. CBZ administered in food three times per day (100 mg/kg x3 CBZ in food) continuously blocked nearly all motor seizures over a 5-day period, and completely suppressed motor seizures in 50% of the animals tested. CBZ strongly suppresses spontaneous motor seizures, and single doses of CBZ in food are as effective as IP injections in rats with kainate-induced epilepsy. CBZ administered regularly in food continuously blocks nearly all motor seizures, and may provide a relatively simple method to test AEDs in chronic models of epilepsy.

  7. Karštai rūkytų saliami dešrų kokybė


    Kaminskaitė, Donata


    Tyrimų objektu pasirinktos skirtingų Lietuvos mėsos įmonių, pagamintos karštai rūkytos aukščiausios rūšies saliami dešros. Atliktas juslinis tyrimas, kurio vertinimui taikytas „Juslinių savybių profilio testas ISO 13299:2003 Methodology – general guidance for establishing a sensory profile. Mėginių juslinių tyrimų intensyvumas vertintas, taikant nepertraukiamą tiesinę 150 mm skalę. (LST ISO 4121: 2004 Juslinė analizė. Metodika. Kiekybinių atsakų skalių taikymo nurodymai. Atliktas histomorfolo...

  8. European Islands, Development and the Cohesion Policy: A Case Study of Kökar, Åland Islands

    Directory of Open Access Journals (Sweden)

    Godfrey Baldacchino


    Full Text Available A European Union initiative is seeking ways of determining the development potential of Europe’s lagging regions, which include various islands. On the basis of the policy review, methodology and data collected by the ongoing EUROISLANDS project, this paper present Kökar (population: 262, the easternmost municipality of the Åland Islands, as a prototype archipelago that is seriously challenged by its size and multiple peripherality. It reviews the state of its social and transportation infrastructure, and of its human and financial capital. While the situation is serious, there are opportunities for branding, for developing associated economic activity, as well for appealing to a new wave of residents.

  9. K-Ar Geochronology of Mesozoic Mafic Dikes in Shandong Province, Eastern China:Implications for Crustal Extension

    Institute of Scientific and Technical Information of China (English)

    LIU Shen; HU Ruizhong; ZHAO Junhong; FENG Caixia


    Based on K-Ar isotope analyses, Mesozoic mafic (and alkali ultramafic) dikes from western and eastern Shandong Province, China, are dated at 88.2±1.70 Ma to 169.5±3.7 Ma with the majority of ages ranging from 90 Ma to 140 Ma. The emplacement of the dikes suggests a major Yanshanian (Cretaceous) crustal extension in Shandong province.Together with other available age data, this study suggests four periods of crustal extension at about 80 Ma, 100 Ma, 120 Ma and 140 Ma, respectively. Besides the effect of collapse of the Yanshanian orogenic belt on the emplacement of the mafic dikes in Shandong in the Cretaceous, the mantle plume and the extensive left-lateral advection and extension of the Tanlu fault also have controlled the crustal extension and the emplacement of the mafic dikes in eastern Shandong and western Shandong, respectively.

  10. Premedikasyonda Midazolam, Diazepam ve Plasebonun Anksiyolitik Etkilerinin Karşılaştırılması



    Premedikasyonda kullanılan midazolam, diazepam ve plasebonun anksiyeteyi gidermedeki etkilerini karşılaştırdığımız, /AS/ l-ll grubundan genel cerrahi operasyonuna alınacak 45 hasta çalışmaya alındı. Tüm olgulara bazal anksiete skorunu tespit etmek amacı ile "durumsal-sürekli anksiyete ölçeğini (State-Trait Anxiety Inventory-STAI) uyguladık. Tedavi öncesi anksiyeteyi belirlemek için de "Hamilton Anxiety Test (HAT)" ve Anksiyetenin Vizüel Analog Skalasını (AVAS) uygul...

  11. Induction of c-fos mRNA expression in an in vitro hippocampal slice model of adult rats after kainate but not gamma-aminobutyric acid or bicuculline treatment. (United States)

    Massamiri, T; Khrestchatisky, M; Ben-Ari, Y


    Levels of gene expression following in vitro treatment of rat hippocampal slices with kainate, gamma-aminobutyric acid (GABA), or bicuculline were measured by the reverse transcription-coupled polymerase chain reaction method. Following a short-term exposure to kainate, c-fos gene expression was induced by 12-fold in the adult, but not the newborn, hippocampus. Under the same experimental conditions, zifl268 and brain-derived neurotrophic factor (BDNF) gene expression were unchanged. Our results also demonstrate a lack of induction of c-fos, zifl268 and BDNF after short-time treatment of either adult or newborn hippocampal slices with GABA or bicuculline. The relevance of the differential induction of gene expression in the adult and newborn in an in vitro hippocampal slice model as compared to previously described in vivo models is discussed.

  12. In vitro autoradiography of ionotropic glutamate receptors in hippocampus and striatum of aged Long-Evans rats: relationship to spatial learning

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    Gallagher, M. [Curriculum in Neurobiology, University of North Carolina at Chapel Hill, Chapel Hill, NC (United States); Bizon, J.L. [Department of Psychology, University of North Carolina at Chapel Hill, Chapel Hill, NC (United States); Nicolle, M.M. [Curriculum in Neurobiology, University of North Carolina at Chapel Hill, Chapel Hill, NC (United States)


    Using in vitro autoradiography, we investigated [{sup 3}H]{alpha}-amino-3-hydroxy-5-methyl-4-isoxazolepropionate, [{sup 3}H]kainate and [{sup 3}H]N-methyl-d-aspartate binding in two forebrain regions, the hippocampus and striatum, of young (four months of age) and aged (24-25 months of age) Long-Evans rats that had previously been tested for spatial learning ability in the Morris water maze. Although there was substantial preservation of binding in the aged rats, reductions in binding were present in the aged rats that were specific to ligand and anatomical region. In the hippocampus of aged rats, [{sup 3}H]{alpha}-amino-3-hydroxy-5-methyl-4-isoxazolepropionate binding in CA1 and [{sup 3}H]kainate binding in CA3 were reduced. In contrast, N-methyl-d-aspartate binding was not significantly different between age groups. There was evidence of sprouting in the dentate gyrus molecular layer of aged rats, indicated by changes in the topography of [{sup 3}H]kainate binding. Binding density was analysed with respect to patch/matrix compartmentalization in the striatum. The most striking result was a large decrease in N-methyl-d-aspartate binding in aged rats that was not limited to any dorsal/ventral or patch/matrix area of the striatum. Additionally, [{sup 3}H]kainate binding in striatal matrix was modestly reduced in aged rats. Of these age effects, only N-methyl-d-aspartate binding in the striatum and [{sup 3}H]kainate binding in the CA3 region of the hippocampus were correlated with spatial learning, with lower binding in the aged rats associated with better spatial learning ability.Age-related alterations in ionotropic glutamate receptors differ with respect to the receptor subtype and anatomical region examined. The age effects were not neccessarily indicative of cognitive decline, as only two age-related binding changes were correlated with spatial learning. Interestingly, in these instances, lower binding in the aged rats was associated with preserved spatial


    Directory of Open Access Journals (Sweden)

    Kürşat ÖNCÜL


    Full Text Available Erzurum-Kars Region which is one of the first mentioned places in the studies of minstrel style poems in Turkey takes place in both written and oral works of almost all of the researchers with the saying “the place where the culture still exists and is being perpetuated”. That the historical, demographic and the geological position of the district enables the relationship between the narrator and the audience, which grounds the existence and the maintenance of this culture throughout the years, causes this utterance to become a classical. Yet in the last quarter of this century, the cultural structure of the region that changes in terms of culture, economy and sociology weakens the continuity of this tradition. That the institutions which are not adequately interested in the very latest improvements hasn’t met the expectations increases the minstrelsy’s disappointment; and moreover, the minstrels’ socio-economic straits are the order of the day instead of the art of minstrelsy itself. ÖZET Türkiye’deki âşık tarzı şiir geleneği çalışmalarında ilk olarak adı geçen yerlerden biri olan Erzurum-Kars bölgesi, “kültürün canlı bir şekilde yaşadığı ve yaşatıldığı” söylemiyle hemen bütün araştırıcıların sözlü ve yazılı ürünlerinde yer almaktadır. Bölgenin özellikle tarihî, demografik ve coğrafi konumunun yıllar boyunca geleneğin yaşaması ve yaşatılmasında temel olan anlatıcı, dinleyici ilişkisinin varlığına olanak tanıması, bu söylemin gelenekselleşmesine neden olmuştur. Ancak son çeyrek asırda kültürel, ekonomik ve sosyolojik açıdan değişen kültürel yapı geleneğin sürdürülebilirliğini zayıflatmıştır. Yaşanan gelişmelere yeterince ilgi göstermeyen kurumların âşıkların beklentilerini karşılayamaması hayal kırıklıklarını arttırmış ve âşıklık sanatından ziyade âşıkların sosyo ekonomik sıkıntıları gündemde yer edinmiştir.

  14. Antagonism of ionotropic glutamate receptors attenuates chemical ischemia-induced injury in rat primary cultured myenteric ganglia.

    Directory of Open Access Journals (Sweden)

    Elisa Carpanese

    Full Text Available Alterations of the enteric glutamatergic transmission may underlay changes in the function of myenteric neurons following intestinal ischemia and reperfusion (I/R contributing to impairment of gastrointestinal motility occurring in these pathological conditions. The aim of the present study was to evaluate whether glutamate receptors of the NMDA and AMPA/kainate type are involved in myenteric neuron cell damage induced by I/R. Primary cultured rat myenteric ganglia were exposed to sodium azide and glucose deprivation (in vitro chemical ischemia. After 6 days of culture, immunoreactivity for NMDA, AMPA and kainate receptors subunits, GluN(1 and GluA(1-3, GluK(1-3 respectively, was found in myenteric neurons. In myenteric cultured ganglia, in normal metabolic conditions, -AP5, an NMDA antagonist, decreased myenteric neuron number and viability, determined by calcein AM/ethidium homodimer-1 assay, and increased reactive oxygen species (ROS levels, measured with hydroxyphenyl fluorescein. CNQX, an AMPA/kainate antagonist exerted an opposite action on the same parameters. The total number and viability of myenteric neurons significantly decreased after I/R. In these conditions, the number of neurons staining for GluN1 and GluA(1-3 subunits remained unchanged, while, the number of GluK(1-3-immunopositive neurons increased. After I/R, -AP5 and CNQX, concentration-dependently increased myenteric neuron number and significantly increased the number of living neurons. Both -AP5 and CNQX (100-500 µM decreased I/R-induced increase of ROS levels in myenteric ganglia. On the whole, the present data provide evidence that, under normal metabolic conditions, the enteric glutamatergic system exerts a dualistic effect on cultured myenteric ganglia, either by improving or reducing neuron survival via NMDA or AMPA/kainate receptor activation, respectively. However, blockade of both receptor pathways may exert a protective role on myenteric neurons following and I

  15. Molecular Dynamics Investigation of gluazo, a Photo-Switchable Ligand for the Glutamate Receptor GluK2.

    Directory of Open Access Journals (Sweden)

    Yanan Guo

    Full Text Available Photochromic ligands (PCLs, defined as photoswitchable molecules that are able to endow native receptors with a sensitivity towards light, have become a promising photopharmacological tool for various applications in biology. In general, PCLs consist of a ligand of the target receptor covalently linked to an azobenzene, which can be reversibly switched between two configurations upon light illumination. Gluazo, as a PCL that targets excitatory amino acid receptors, in its dark-adapted trans iso-form was characterized to be a partial agonist of the kainate glutamate receptor GluK2. Application of UV light leads to the formation of the cis form, with remarkedly reduced affinity towards GluK2. The mechanism of the change of ligand affinity induced by the photoisomerization was unresolved. The presented computational study explains how the isomerization of such a PCL affects the structural changes in the target receptor that lead to its activation.

  16. CP-465,022, a selective noncompetitive AMPA receptor antagonist, blocks AMPA receptors but is not neuroprotective in vivo. (United States)

    Menniti, Frank S; Buchan, Alistair M; Chenard, Bertrand L; Critchett, Donald J; Ganong, Alan H; Guanowsky, Victor; Seymour, Patricia A; Welch, Willard M


    Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor inhibition has been hypothesized to provide neuroprotective efficacy after cerebral ischemia on the basis of the activity in experimental ischemia models of a variety of compounds with varying selectivity for AMPA over other glutamate receptor subtypes. CP-465,022 is a new, potent, and selective noncompetitive AMPA receptor antagonist. The present study investigated the ability of this compound to reduce neuronal loss after experimental cerebral ischemia to probe the neuroprotective potential of AMPA receptor inhibition. To demonstrate that CP-465,022 gains access to the brain, the effects of systemic administration of CP-465,022 were investigated on AMPA receptor-mediated electrophysiological responses in hippocampus and on chemically induced seizures in rats. The compound was then investigated for neuroprotective efficacy in rat global and focal ischemia models at doses demonstrated to be maximally effective in the electrophysiology and seizure models. CP-465,022 potently and efficaciously inhibited AMPA receptor-mediated hippocampal synaptic transmission and the induction of seizures. However, at comparable doses, CP-465,022 failed to prevent CA1 neuron loss after brief global ischemia or to reduce infarct volume after temporary middle cerebral artery occlusion. Given the high selectivity of CP-465,022 for AMPA over kainate and N-methyl-D-aspartate subtypes of glutamate receptors, the lack of neuroprotective efficacy of the compound calls into question the neuroprotective efficacy of AMPA receptor inhibition after ischemia.

  17. Protection from neuronal damage induced by combined oxygen and glucose deprivation in organotypic hippocampal cultures by glutamate receptor antagonists. (United States)

    Strasser, U; Fischer, G


    Organotypic hippocampal cultures were exposed to defined periods (30 and 60 min) of combined oxygen and glucose deprivation, mimicking transient ischemic conditions. The involvement of different glutamate receptors in individual hippocampal subfields (CA1, CA3 and dentate gyrus) was studied using antagonists of NMDA (dizocilpine) and AMPA/kainate receptors (CNQX and GYKI 52466). Staining with the fluorescent dye propidium iodide (PI) allowed detection of damaged cells. For quantitative determination of neuronal damage, fluorescence intensity was measured after a 22 h recovery period and was related to maximal fluorescence intensity measured after fixation and PI restaining of the cultures at the end of the experiment. Dizocilpine (10 microM), CNQX (100 microM) and GYKI 52466 (100 microM) provided complete protection in CA1, CA3 and dentate gyrus following the moderate ischemic insult, when the antagonists were present permanently. This indicates that none of the ionotropic glutamate receptor subtypes dominated toxicity in the most sensitive subpopulation of neurons. When applied only during the recovery period protection with dizocilpine (10 microM) or CNQX (100 microM) was drastically reduced by about 60% in the most sensitive area (CA1), but only slightly by 15% in CA3. Therefore the onset of irreversible damage seems to occur earlier in CA1 than in CA3. Blockade of AMPA/kainate receptors by GYKI 52466 (100 microM) offered no neuroprotection if the compound was applied only during the recovery period.(ABSTRACT TRUNCATED AT 250 WORDS)

  18. Biyodizel ve Karışımlarının Kullanıldığı bir Dizel Motorda Performans ve Emisyon Analizi

    Directory of Open Access Journals (Sweden)

    Ahmet Necati ÖZSEZEN


    Full Text Available Bu çalışmada, atık palmiye yağı kökenli biyodizel ve petrol kökenli dizel yakıtı (PKDY ile karışımlarının, bir dizel motordaki performans ve emisyon karakteristikleri üç boyutlu haritalar üzerinden analiz edilmiştir. Biyodizel ve karışımlarının performans ve emisyon karakterlerini belirlemek amacıyla, motor tam yük ve değişik devir testlerine tabi tutulmuştur. Analiz sonucunda, karışımdaki biyodizel oranı arttıkça PKDY'a göre özgül yakıt tüketiminde artış olduğu, motorun döndürme momentinde ise azalma meydana geldiği tespit edilmiştir. Emisyon analizi sonucunda ise, karışımdaki biyodizel oranı ile ilişkili olarak PKDY'a kıyasla yanmamış hidrokarbon (HC, karbon monoksit (CO ve duman koyuluğu emisyonlarında iyileşmeler olduğu, bununla birlikte karbon dioksit (CO2 ve azot oksit (NOx emisyonlarının motor devrine göre kararlı bir yapı sergilemediği belirlenmiştir.

  19. [Pēdējais karš. Atmiņa un traumas kominikācija] / Eva-Clarita Pettai

    Index Scriptorium Estoniae

    Pettai, Eva-Clarita, 1971-


    Arvustus: Pēdējais karš. Atmiņa un traumas kominikācija. Hrsg. von Mārtiņš Kaprāns, Vita Zelče. Latvijas Universitāte - Sociālo zinātņu fakultāte - Sociālo un politisko pētījumu institūts (Riga 2010)

  20. [Pēdējais karš. Atmiņa un traumas kominikācija] / Eva-Clarita Pettai

    Index Scriptorium Estoniae

    Pettai, Eva-Clarita, 1971-


    Arvustus: Pēdējais karš. Atmiņa un traumas kominikācija. Hrsg. von Mārtiņš Kaprāns, Vita Zelče. Latvijas Universitāte - Sociālo zinātņu fakultāte - Sociālo un politisko pētījumu institūts (Riga 2010)

  1. Cholesterol modulates open probability and desensitization of NMDA receptors (United States)

    Korinek, Miloslav; Vyklicky, Vojtech; Borovska, Jirina; Lichnerova, Katarina; Kaniakova, Martina; Krausova, Barbora; Krusek, Jan; Balik, Ales; Smejkalova, Tereza; Horak, Martin; Vyklicky, Ladislav


    NMDA receptors (NMDARs) are glutamate-gated ion channels that mediate excitatory neurotransmission in the CNS. Although these receptors are in direct contact with plasma membrane, lipid–NMDAR interactions are little understood. In the present study, we aimed at characterizing the effect of cholesterol on the ionotropic glutamate receptors. Whole-cell current responses induced by fast application of NMDA in cultured rat cerebellar granule cells (CGCs) were almost abolished (reduced to 3%) and the relative degree of receptor desensitization was increased (by seven-fold) after acute cholesterol depletion by methyl-β-cyclodextrin. Both of these effects were fully reversible by cholesterol repletion. By contrast, the responses mediated by AMPA/kainate receptors were not affected by cholesterol depletion. Similar results were obtained in CGCs after chronic inhibition of cholesterol biosynthesis by simvastatin and acute enzymatic cholesterol degradation to 4-cholesten-3-one by cholesterol oxidase. Fluorescence anisotropy measurements showed that membrane fluidity increased after methyl-β-cyclodextrin pretreatment. However, no change in fluidity was observed after cholesterol enzymatic degradation, suggesting that the effect of cholesterol on NMDARs is not mediated by changes in membrane fluidity. Our data show that diminution of NMDAR responses by cholesterol depletion is the result of a reduction of the open probability, whereas the increase in receptor desensitization is the result of an increase in the rate constant of entry into the desensitized state. Surface NMDAR population, agonist affinity, single-channel conductance and open time were not altered in cholesterol-depleted CGCs. The results of our experiments show that cholesterol is a strong endogenous modulator of NMDARs. Key points NMDA receptors (NMDARs) are tetrameric cation channels permeable to calcium; they mediate excitatory synaptic transmission in the CNS and their excessive activation can lead to

  2. Clay mineral provinces in tidal mud flats at Germany's North Sea coast with illite K-Ar ages potentially modified by biodegradation (United States)

    Brockamp, Olaf; Clauer, Norbert


    Mineralogical studies, chemical analyses and K-Ar dating were carried out on clay fractions from tidal mud flats along the Lower Saxony coast and its bays to identify material sources and sedimentary processes at this dynamic interface between air, land and sea. From the coast into the bays, sediments are enriched in fine-grained smectite relative to the coarser grained illite, chlorite and kaolinite, due to the weakening of the tidal current energy in the bays. In addition, the study area can be divided into two provinces on the basis of the illite K/Rb ratios and Mg contents. To the west [Schiermonnikoog, Dollart, Ley Bay up to Norderney island], longshore currents carry suspensions from the Belgian and Dutch coasts; to the east [from Langeoog island, Jade Bay to the Helgoland mud area] suspensions from the Elbe and Weser rivers are mixed with submarine reworked glacial sediments, whereas the portion of longshore current suspensions from the west decreases, becoming negligible in the Helgoland mud area off the Elbe and Weser estuaries. The illite K-Ar data vary considerably and fail as source indicators due to differential settling and mixing of the clay material and probably to Ar loss from illite by biodegradation during digestive processes. Only further offshore, outside the zone of dynamic sediment dispersion, do the K-Ar data fit provenance patterns.

  3. Spindle pole body-anchored Kar3 drives the nucleus along microtubules from another nucleus in preparation for nuclear fusion during yeast karyogamy. (United States)

    Gibeaux, Romain; Politi, Antonio Z; Nédélec, François; Antony, Claude; Knop, Michael


    Nuclear migration during yeast karyogamy, termed nuclear congression, is required to initiate nuclear fusion. Congression involves a specific regulation of the microtubule minus end-directed kinesin-14 motor Kar3 and a rearrangement of the cytoplasmic microtubule attachment sites at the spindle pole bodies (SPBs). However, how these elements interact to produce the forces necessary for nuclear migration is less clear. We used electron tomography, molecular genetics, quantitative imaging, and first principles modeling to investigate how cytoplasmic microtubules are organized during nuclear congression. We found that Kar3, with the help of its light chain, Cik1, is anchored during mating to the SPB component Spc72 that also serves as a nucleator and anchor for microtubules via their minus ends. Moreover, we show that no direct microtubule-microtubule interactions are required for nuclear migration. Instead, SPB-anchored Kar3 exerts the necessary pulling forces laterally on microtubules emanating from the SPB of the mating partner nucleus. Therefore, a twofold symmetrical application of the core principle that drives nuclear migration in higher cells is used in yeast to drive nuclei toward each other before nuclear fusion.

  4. Ionotropic glutamate receptor expression in preganglionic neurons of the rat inferior salivatory nucleus. (United States)

    Kim, M; Chiego, D J; Bradley, R M


    Glutamate receptor (GluR) subunit composition of inferior salivatory nucleus (ISN) neurons was studied by immunohistochemical staining of retrogradely labeled neurons. Preganglionic ISN neurons innervating the von Ebner or parotid salivary glands were labeled by application of a fluorescent tracer to the lingual-tonsilar branch of the glossopharyngeal nerve or the otic ganglion respectively. We used polyclonal antibodies to glutamate receptor subunits NR1, NR2A, NR2B, (NMDA receptor subunits) GluR1, GluR2, GluR3, GluR4 (AMPA receptor subunits), and GluR5-7, KA2 (kainate receptor subunits) to determine their expression in ISN neurons. The distribution of the NMDA, AMPA and kainate receptor subunits in retrogradely labeled ISN neurons innervating the von Ebner and parotid glands was qualitatively similar. The percentage of retrogradley labeled ISN neurons innervating the parotid gland expressing the GluR subunits was always greater than those innervating the von Ebner gland. For both von Ebner and parotid ISN neurons, NR2A subunit staining had the highest expression and the lowest expression of GluR subunit staining was NR2B for von Ebner ISN neurons and GluR1 for parotid ISN neurons. The percentage of NR2B and GluR4 expressing ISN neurons was significantly different between the two glands. The percentage of ISN neurons that expressed GluR receptor subunits ranged widely indicating that the distribution of GluR subunit expression differs amongst the ISN neurons. While ISN preganglionic neurons express all the GluR subunits, differences in the percentage of ISN neurons expression between neurons innervating the von Ebner and parotid glands may relate to the different functional roles of these glands.

  5. An alternating GluN1-2-1-2 subunit arrangement in mature NMDA receptors.

    Directory of Open Access Journals (Sweden)

    Morgane Riou

    Full Text Available NMDA receptors (NMDARs form glutamate-gated ion channels that play a critical role in CNS physiology and pathology. Together with AMPA and kainate receptors, NMDARs are known to operate as tetrameric complexes with four membrane-embedded subunits associating to form a single central ion-conducting pore. While AMPA and some kainate receptors can function as homomers, NMDARs are obligatory heteromers composed of homologous but distinct subunits, most usually of the GluN1 and GluN2 types. A fundamental structural feature of NMDARs, that of the subunit arrangement around the ion pore, is still controversial. Thus, in a typical NMDAR associating two GluN1 and two GluN2 subunits, there is evidence for both alternating 1/2/1/2 and non-alternating 1/1/2/2 arrangements. Here, using a combination of electrophysiological and cross-linking experiments, we provide evidence that functional GluN1/GluN2A receptors adopt the 1/2/1/2 arrangement in which like subunits are diagonal to one another. Moreover, based on the recent crystal structure of an AMPA receptor, we show that in the agonist-binding and pore regions, the GluN1 subunits occupy a "proximal" position, closer to the central axis of the channel pore than that of GluN2 subunits. Finally, results obtained with reducing agents that differ in their membrane permeability indicate that immature (intracellular and functional (plasma-membrane inserted pools of NMDARs can adopt different subunit arrangements, thus stressing the importance of discriminating between the two receptor pools in assembly studies. Elucidating the quaternary arrangement of NMDARs helps to define the interface between the subunits and to understand the mechanism and pharmacology of these key signaling receptors.

  6. Çok Etmenli Sistemlerde NetLogo İle Karınca Kolonisi Optimizasyonu

    Directory of Open Access Journals (Sweden)

    Mustafa Tüker


    Full Text Available Çok etmenli sistemler (ÇES, karmaşık optimizasyon problemlerinin modellenmesi ve çözülmesi için etkin bir yol sunarlar. Bu çalışmada, Gezgin Satıcı Problemi (GSP'ni çözmek için ÇES ve karınca kolonileri birlikte kullanılmıştır. Sistem benzetimi, etmen tabanlı bir programlama ortamı olan NetLogo ile gerçekleştirilmiştir. Problemin modellenmesi ve benzetimi için NetLogo'nun nasıl kullanılacağı kodlarla ayrıntılı olarak açıklanmıştır. Algoritma farklı düğüm sayıları için denenmiş ve elde edilen sonuçlar tartışılmıştır.

  7. Continued Development of In Situ Geochronology for Planetary Missions Using KArLE (Potassium-Argon-Laser Experiment) (United States)

    Devismes, Damien; Cohen, Barbara


    Since these techniques are very new and as they have never been used or this purpose. they will need to be replicated by several independent studies. These techniques may be very important if the optical imaging encounters difficulties, for example, if a sample is made of very dark or monochromatic material and in the case of very deep pits (>500 microns) Based on the preliminary results, the LIBS continuum technique is more appropriate to the large pits produced by long ablations The relationship may work best homogeneous samples, but the continuum is collected with every LIBS analysis so does not require any addition to the experimental suite of techniques. The integration of a QCMB in the ablation chamber may be a very interesting solution to determine the ablated mass. Even if it only measures a fraction of the total mass, its sensitivity should be able to weigh hundreds of nanograms accumulated on the crystal during ablation and relate it to the actual ablated mass. In the future. these options may help in situ K-Ar dating to give the age of the rock with the best accuracy and precision.

  8. Karşıt cinsel erkek üniversite öğrencilerinde riskli cinsel davranış


    KIYLIOĞLU, Levent


    Bu çalışmanın amacı, Türkiye’de yaşayan karşıt cinsel erkek üniversite öğrencilerinin riskli cinsel davranışlarının hangi değişkenler tarafından ve hangi oranlarda belirlendiğini ortaya koymaktır.Çalışmanın örneklemi Ankara Üniveristesi ve ODTÜ’de okuyan 382 öğrenciden oluşmuştur. Çalışmada demografik sorulara ek olarak Cinsel Heyecan Arama Ölçeği, Cinsel Risk Alma Ölçeği, Dinsel Tutum Ölçeği, AIDS Bilgi Ölçeği, AIDS’ten Korunmada Öz-Yeterlik Ölçeği, Bem Cinsiyet Rolü Envanteri kulla...

  9. The promoting role of an isolate of dark-septate fungus on its host plant Saussurea involucrata Kar. et Kir. (United States)

    Wu, Li-qin; Lv, Ya-li; Meng, Zhi-xia; Chen, Juan; Guo, Shun-Xing


    A dark-septate endophytic (DSE) fungus EF-37 was isolated from the roots of Saussurea involucrata Kar. et Kir., an endangered Chinese medicinal plant. The molecular identification of the fungus was based on internal transcribed spacer regions and the result showed that EF-37 was congeneric to Mycocentrospora. This study was conducted to clarify the influence of the root endophyte EF-37 on the host plant S. involucrata using material grown in a sterile culture bottle. After cultivation for 40 days, fungal hyphae were found to be branching repeatedly and forming "hyphae nets" in the epidermal layers. Significant differences were detected between the study groups in plant dry weight, plant height, root dry weight, shoot dry weight, and the number of hair root tips. There was a positive effect of endophyte EF-37 on plant root development, with results showing that cortical cells dissolved and formed aerate structures. There was a positive effect of endophyte EF-37 on plant growth, but chlorophyll fluorescence analysis showed that there were no significant differences between the study groups. In addition, analysis of the chemical composition of seedlings showed that the level of rutin was higher in plants cultivated with the EF-37 fungus compared to the controls. This study helps to establish a basis for germplasm conservation and for further investigation of the interaction between dark-septate fungi and this alpine plant.

  10. Noble Gas Analysis for Mars Robotic Missions: Evaluating K-Ar Age Dating for Mars Rock Analogs and Martian Shergottites (United States)

    Park, J.; Ming, D. W.; Garrison, D. H.; Jones, J. H.; Bogard, D. D.; Nagao, K.


    The purpose of this noble gas investigation was to evaluate the possibility of measuring noble gases in martian rocks and air by future robotic missions such as the Mars Science Laboratory (MSL). The MSL mission has, as part of its payload, the Sample Analysis at Mars (SAM) instrument, which consists of a pyrolysis oven integrated with a GCMS. The MSL SAM instrument has the capability to measure noble gas compositions of martian rocks and atmosphere. Here we suggest the possibility of K-Ar age dating based on noble gas release of martian rocks by conducting laboratory simulation experiments on terrestrial basalts and martian meteorites. We provide requirements for the SAM instrument to obtain adequate noble gas abundances and compositions within the current SAM instrumental operating conditions, especially, a power limit that prevents heating the furnace above approx.1100 C. In addition, Martian meteorite analyses from NASA-JSC will be used as ground truth to evaluate the feasibility of robotic experiments to constrain the ages of martian surface rocks.

  11. Profiling neurotransmitter receptor expression in the Ambystoma mexicanum brain. (United States)

    Reyes-Ruiz, Jorge Mauricio; Limon, Agenor; Korn, Matthew J; Nakamura, Paul A; Shirkey, Nicole J; Wong, Jamie K; Miledi, Ricardo


    Ability to regenerate limbs and central nervous system (CNS) is unique to few vertebrates, most notably the axolotl (Ambystoma sp.). However, despite the fact the neurotransmitter receptors are involved in axonal regeneration, little is known regarding its expression profile. In this project, RT-PCR and qPCR were performed to gain insight into the neurotransmitter receptors present in Ambystoma. Its functional ability was studied by expressing axolotl receptors in Xenopus laevis oocytes by either injection of mRNA or by direct microtransplantation of brain membranes. Oocytes injected with axolotl mRNA expressed ionotropic receptors activated by GABA, aspartate+glycine and kainate, as well as metabotropic receptors activated by acetylcholine and glutamate. Interestingly, we did not see responses following the application of serotonin. Membranes from the axolotl brain were efficiently microtransplanted into Xenopus oocytes and two types of native GABA receptors that differed in the temporal course of their responses and affinities to GABA were observed. Results of this study are necessary for further characterization of axolotl neurotransmitter receptors and may be useful for guiding experiments aimed at understanding activity-dependant limb and CNS regeneration.

  12. Kainate-induced epileptogenesis alters circular hole board learning strategy but not the performance of C57BL/6J mice. (United States)

    Hubens, Chantal J; Kaptein, Pascale S; ter Horst, Judith P; Voskuyl, Rob A; Schenk, Geert J


    Patients with mesial temporal lobe epilepsy (mTLE) frequently show cognitive deficits. However, the relation between mTLE and cognitive impairment is poorly understood. To gain more insight into epilepsy-associated alterations in cognitive performance, we studied the spatial learning of C57BL/6J mice five weeks after kainate-induced status epilepticus (SE). Typically, structural hippocampal rearrangements take place within five weeks after SE. Mice were monitored by exposing them to four tasks with a focus on spatial memory and anxiety: the circular hole board, modified hole board, novel object-placement task, and elevated plus maze. On the circular hole board, animals showed a higher preference for hippocampus-independent strategies after SE. In contrast, no change in strategy was seen on the modified hole board, but animals with SE were able to finish the task more often. Animals did not have an increased preference for a relocated object in the novel object-placement task but showed an increased locomotion after SE. No indications for altered anxiety were found when tested on the elevated plus maze following SE. These data suggest that the circular hole board is a well-suited paradigm to detect subtle SE-induced hippocampal deficits.

  13. Acute alterations of somatodendritic action potential dynamics in hippocampal CA1 pyramidal cells after kainate-induced status epilepticus in mice.

    Directory of Open Access Journals (Sweden)

    Daniel Minge

    Full Text Available Pathophysiological remodeling processes at an early stage of an acquired epilepsy are critical but not well understood. Therefore, we examined acute changes in action potential (AP dynamics immediately following status epilepticus (SE in mice. SE was induced by intraperitoneal (i.p. injection of kainate, and behavioral manifestation of SE was monitored for 3-4 h. After this time interval CA1 pyramidal cells were studied ex vivo with whole-cell current-clamp and Ca(2+ imaging techniques in a hippocampal slice preparation. Following acute SE both resting potential and firing threshold were modestly depolarized (2-5 mV. No changes were seen in input resistance or membrane time constant, but AP latency was prolonged and AP upstroke velocity reduced following acute SE. All cells showed an increase in AP halfwidth and regular (rather than burst firing, and in a fraction of cells the notch, typically preceding spike afterdepolarization (ADP, was absent following acute SE. Notably, the typical attenuation of backpropagating action potential (b-AP-induced Ca(2+ signals along the apical dendrite was strengthened following acute SE. The effects of acute SE on the retrograde spread of excitation were mimicked by applying the Kv4 current potentiating drug NS5806. Our data unveil a reduced somatodendritic excitability in hippocampal CA1 pyramidal cells immediately after acute SE with a possible involvement of both Na(+ and K(+ current components.

  14. Subregion-specific role of glutamate receptors in the nucleus accumbens on drug context-induced reinstatement of cocaine-seeking behavior in rats. (United States)

    Xie, Xiaohu; Lasseter, Heather C; Ramirez, Donna R; Ponds, KaiCee L; Wells, Audrey M; Fuchs, Rita A


    The functional integrity of the nucleus accumbens (NAC) core and shell is necessary for contextual cocaine-seeking behavior in the reinstatement animal model of drug relapse; however, the neuropharmacological mechanisms underlying this phenomenon are poorly understood. The present study evaluated the contribution of metabotropic glutamate receptor subtype 1 (mGluR1) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate receptor populations to drug context-induced reinstatement of cocaine-seeking behavior. Rats were trained to lever press for un-signaled cocaine infusions in a distinct context followed by extinction training in a different context. Cocaine-seeking behavior (non-reinforced active lever pressing) was then assessed in the previously cocaine-paired and extinction contexts after JNJ16259685 (mGluR1 antagonist: 0.0, 0.6, or 30 pg/0.3 µl/hemisphere) or CNQX (AMPA/kainate receptor antagonist: 0.0, 0.03, or 0.3 µg/0.3 µl /hemisphere) administration into the NAC core, medial or lateral NAC shell, or the ventral caudate-putamen (vCPu, anatomical control). JNJ16259685 or CNQX in the NAC core dose-dependently impaired contextual cocaine-seeking behavior relative to vehicle. Conversely, CNQX, but not JNJ16259685, in the lateral or medial NAC shell attenuated, whereas CNQX or JNJ16259685 in vCPu failed to inhibit, this behavior. The manipulations failed to alter instrumental behavior in the extinction context, general motor activity or food-reinforced instrumental behavior in control experiments. Thus, glutamate-mediated changes in drug context-induced motivation for cocaine involve distinct neuropharmacological mechanisms within the core and shell subregions of the NAC, with the stimulation of mGlu1 and AMPA/kainate receptors in the NAC core and the stimulation of AMPA/kainate, but not mGlu1, receptors in the NAC shell being necessary for this phenomenon.

  15. Preliminary Findings of Petrology and Geochemistry of The Aladaǧ Volcanic System and Surrounding Areas (Kars, Turkey) (United States)

    Duru, Olgun; Keskin, Mehmet


    Between the towns of Sarıkamış and Kaǧızman, NE Turkey, a medium-sized strato-volcano with satellite cones and domes on its slopes unconformably overlies the Erzurum-Kars Volcanic Plateau (EKVP) with a subhorizontal contact. It is called the Aladaǧ volcanic system (AVS). Dating results indicate that the AVS is Pliocene in age. The EKVP is known to be formed by a widespread volcanism between Middle Miocene to Pliocene. The young volcanism in E Turkey including the study area is linked to a collision between the Eurasia and Arabian continents, started almost 15 Ma ago. The EKVP lies over 2000 m above the sea level, and is deeply cut by the river Aras. On the slopes of the valley, one of the best volcano-stratigraphic transects of Eastern Anatolia, almost half a km thick, is exposed. That transect is composed of aphyric andesites-dacites, ignimbrites, tuffs, perlite and obsidian bands. Pyroclastic fall and surge-related pumice deposits are also widespread. Top of the plateau is composed of the andesitic to basaltic andesitic lavas containing plagioclase (Plg) and ortho/clino pyroxene (Opx/Cpx) phenocrysts set in glassy groundmass. In the northwest of the study area, an eroded stratovolcano, probably coeval with the plateau sequence is situated. It also consists of high-silica rhyolites and pyroclastic equivalents. The AVS is composed basically of intermediate lavas. The largest volcanic edifice of the Aladaǧ volcanic system, namely the Greater Aladaǧ stratovolcano reaches up to 3000 m height and includes a horseshoe shaped crater open to the North. Small volcanic cones and domes sit on the flanks of the Greater Aladaǧ volcano. The Aladaǧ lavas are divided into four sub-groups on the basis of their stratigraphic positions, mineral assemblages and textural properties. (1) The oldest products of the Greater Aladaǧ stratovolcano are andesitic and dasitic lavas. They directly sit on the EKVP. These are Plg and Opx/Cpx bearing lavas with porphric, vitrophyric

  16. K/Ar ages, magnetic stratigraphy and morphological evolution of La Gomera: implications for the Canary Islands hotspot evolution. (United States)

    Paris, R.; Guillou, H.; Carracedo, J. C.; Pérez Torrado, F. J.


    The Canary Islands are a group of seven volcanic islands, 100-700 km west of the Sahara continental margin. The spatial and chronological evolution of the canarian volcanism, from east to west, is due to the progression of the slow-moving african plate on a hotspot. La Gomera is located between the western shield-growing stage islands (La Palma, 1,7 Ma and El Hierro, 1,1 Ma) and the central "rejuvaneted stage" islands (Tenerife, 11,9 Ma and Gran Canaria, 14,5 Ma). After 23 K-Ar ages and paleomagnetism datas, we determine the main volcanic phases of La Gomera : (1) the submarine shield volcano (> 9,5 Ma), (2) the first subaeriel shield volcano (9,43-7,36 Ma), (3) the Vallehermoso stratovolcan, (4) the peripheral "planèzes" and domes forming series (6,67-1,94 Ma) and the Garajonay horizontal series (5,42-4,25 Ma). The stratovolcano and the horizontal series fill a 10 km wide depression that is supposed to be a giant landslide embayment. The scarps of this landslide correspond to the main discontinuity in the island structure. After 4 M.y. of very scarce volcanism, the whole structure of La Gomera is in relief inversion, with a radial pattern of deep barrancos. The erosion rates are lower during the hiatus (< 0,2 m/ka) than during the shield stage (0,2-0,9 m/ka), pointing out the fact that the volcanic construction rates and the erosion rates are strongly correlated. La Gomera is one of the best example of a hiatus stage of hotspot evolution. The volcanic load La Gomera and Tenerife may have delayed the western islands volcanism, favouring a dual-line.

  17. Mineralogical, chemical and K-Ar isotopic changes in Kreyenhagen Shale whole rocks and pyrolysis experimental maturation (United States)

    Clauer, Norbert; Lewan, Michael D.; Dolan, Michael P.; Chaudhuri, Sambhudas; Curtis, John B.


    Progressive maturation of the Eocene Kreyenhagen Shale from the San Joaquin Basin of California was studied by combining mineralogical and chemical analyses with K–Ar dating of whole rocks and pyrolysis of an immature outcrop sample. The K–Ar age decreases from 89.9 ± 3.9 and 72.4 ± 4.2 Ma for the outcrop whole rock and its <2 μm fraction, respectively, to 29.7 ± 1.5 and 21.0 ± 0.7 Ma for the equivalent materials buried to 5167 m. The natural maturation does not produce K–Ar ages in the historical sense, but rather K/Ar ratios of relative K and radiogenic 40Ar amounts resulting from a combined crystallization of authigenic and alteration of initial detrital K-bearing minerals of the rocks. The Al/K ratio of the naturally matured rocks is essentially constant for the entire depth sequence, indicating that there is no detectable variation in the crystallo-chemical organization of the K-bearing alumino-silicates with depth. No supply of K from outside of the rock volumes occurred, which indicates a closed-system behavior for it. Conversely, the content of the total organic carbon (TOC) content decreases significantly with burial, based on the progressive increasing Al/TOC ratio of the whole rocks. The initial varied mineralogy and chemistry of the rocks and their <2 μm fractions resulting from differences in detrital sources and depositional settings give scattered results that homogenize progressively during burial due to increased authigenesis, and concomitant increased alteration of the detrital material.

  18. The western Aeolian Islands volcanoes (South Tyrrhenian Sea): highlight on their eruptive history based on K-Ar dating. (United States)

    Leocat, E.; Gillot, P.-Y.; Peccerillo, A.


    The Aeolian Islands volcanoes are located in southern Tyrrhenian Sea on the northern continental margin of the Calabro-Peloritan basement. The Stromboli, Panarea and Vulcano volcanoes of the half eastern sector are well studied as they are still active and they represent high volcanic hazard. While stratigraphic studies were carried out on volcanoes of the western sector, radiometric ages are lacking to well understand their eruptive history. Therefore, new geochronological and geochemical data were obtained for Alicudi, Filicudi, Salina and Lipari western volcanoes. The aim is to establish a complete time framework of the volcanism and to study possible time-related variations of magma compositions. The 37 new ages were obtained using K-Ar Cassignol-Gillot technique that is suitable for dating Quaternary volcanic rocks. The new geochemical data consist of whole rock major and trace elements analysis on dated samples. Our new sets of data give evidence that the Aeolian Islands are young volcanoes emplaced within the last 300 ka. The oldest products outcrop at Filicudi, Salina and Lipari. Te first emerged activity of Alicudi volcano occurred 120 ka ago. While quiescence activity of at least 50 ka is recognized at Filicudi and Lipari, and potentially at Salina, the volcanic activity of Alicudi would have been relatively continuous. These whole volcanoes were active within the last 30 ka which has to be considered for volcanic hazard assessment. At the scale of each volcano, the degree of differentiation increase roughly through time, except at Filicudi where the ultimate products correspond to mafic magma. At the scale of the archipelago, this process increases from western Alicudi and Filicudi volcanoes, where andesitic magmas are the most evolved magmas, to central Salina and Lipari volcanoes, where rhyolitic magmas are emitted during explosive eruption. Moreover, pulses of magmatic activity would have occurred around 30-40 and 110-120 ka when the four volcanoes

  19. Estudio computacional de las relaciones evolutivas de los receptores ionotrópicos NMDA, AMPA y kainato en cuatro especies de primates

    Directory of Open Access Journals (Sweden)

    Francy Johanna Moreno-Pedraza


    Full Text Available Computational study of the evolutionary relationships of the ionotropic receptors NMDA, AMPA and kainate in four species ofprimates. Objective. To identify the influence of changes on the secondary structure and evolutionary relationship of NMDA, AMPA andkainate receptors in Homo sapiens, Pan troglodytes, Pongo pygmaeus and Macaca mulatta. Materials and methods. We identified 91sequences for NMDA, AMPA and kainate receptors and analyzed with software for predicting secondary structure, phosphorylation sites,multiple alignments, selection of protein evolution models and phylogenetic prediction. Results. We found that subunits GLUR5, NR2A,NR2C and NR3A showed structural changes in the C-terminal region and formation or loss of phosphorylation sites in this zone.Additionally the phylogenetic prediction suggests that the NMDA NR2 subunits are the closest to the ancestral node that gives rise to theother subunits. Conclusions. Changes in structure and phosphorylation sites in GLUR5, NR2A, NR2C and NR3A subunits suggestvariations in the interaction of the C-terminal region with kinase proteins and with proteins with PDZ domains, which could affect thetrafficking and anchoring of the subunits. On the other hand, the phylogenetic prediction suggests that the changes that occurred in the NR2subunits gave rise to the other subunits of glutamate ionotropic receptors, primarily because the NMDA and particularly the NR2D subunitsare the most closely related to the ancestral node that possibly gave rise to the iGluRs.

  20. Blockade of Ca2+-permeable AMPA/kainate channels decreases oxygen-glucose deprivation-induced Zn2+ accumulation and neuronal loss in hippocampal pyramidal neurons. (United States)

    Yin, Hong Z; Sensi, Stefano L; Ogoshi, Fumio; Weiss, John H


    Synaptic release of Zn2+ and its translocation into postsynaptic neurons probably contribute to neuronal injury after ischemia or epilepsy. Studies in cultured neurons have revealed that of the three major routes of divalent cation entry, NMDA channels, voltage-sensitive Ca2+ channels (VSCCs), and Ca2+-permeable AMPA/kainate (Ca-A/K) channels, Ca-A/K channels exhibit the highest permeability to exogenously applied Zn2+. However, routes through which synaptically released Zn2+ gains entry to postsynaptic neurons have not been characterized in vivo. To model ischemia-induced Zn2+ movement in a system approximating the in vivo situation, we subjected mouse hippocampal slice preparations to controlled periods of oxygen and glucose deprivation (OGD). Timm's staining revealed little reactive Zn2+ in CA1 and CA3 pyramidal neurons of slices exposed in the presence of O2 and glucose. However, 15 min of OGD resulted in marked labeling in both regions. Whereas strong Zn2+ labeling persisted if both the NMDA antagonist MK-801 and the VSCC blocker Gd3+ were present during OGD, the presence of either the Ca-A/K channel blocker 1-naphthyl acetyl spermine (NAS) or the extracellular Zn2+ chelator Ca2+ EDTA substantially decreased Zn2+ accumulation in pyramidal neurons of both subregions. In parallel experiments, slices were subjected to 5 min OGD exposures as described above, followed 4 hr later by staining with the cell-death marker propidium iodide. As in the Timm's staining experiments, substantial CA1 or CA3 pyramidal neuronal damage occurred despite the presence of MK-801 and Gd3+, whereas injury was decreased by NAS or by Ca2+ EDTA (in CA1).

  1. Three-dimensional structure of the ligand-binding core of GluR2 in complex with the agonist (S)-ATPA: implications for receptor subunit selectivity. (United States)

    Lunn, Marie-Louise; Hogner, Anders; Stensbøl, Tine B; Gouaux, Eric; Egebjerg, Jan; Kastrup, Jette S


    Two X-ray structures of the GluR2 ligand-binding core in complex with (S)-2-amino-3-(5-tert-butyl-3-hydroxy-4-isoxazolyl)propionic acid ((S)-ATPA) have been determined with and without Zn(2+) ions. (S)-ATPA induces a domain closure of ca. 21 degrees compared to the apo form. The tert-butyl moiety of (S)-ATPA is buried in a partially hydrophobic pocket and forces the ligand into the glutamate-like binding mode. The structures provide new insight into the molecular basis of agonist selectivity between AMPA and kainate receptors.

  2. Nuclear geochronology. Chapter 6: Sedimentary rocks dating by the Rubidium-Strontium (Rb/Sr) and Potassium-Argon (K/Ar) radiometric methods; Geocronologia nuclear. Capitulo 6: Datacao de rochas sedimentares pelos metodos radiometricos rubidio-estroncio (Rb/Sr) e potassio-argonio (K/Ar)

    Energy Technology Data Exchange (ETDEWEB)

    Thomaz Filho, Antonio [Universidade do Estado, Rio de Janeiro, RJ (Brazil). Inst. de Geociencias; Mizusaki, Ana Maria Pimentel [Rio Grande do Sul Univ., Porto Alegre, RS (Brazil). Inst. de Geociencias; Kawashita, Koji [Sao Paulo Univ., SP (Brazil). Inst. de Geociencias; Torquato, Joaquim Raul [Ceara Univ., Fortaleza, CE (Brazil). Dept. de Geologia


    The paper deals with the Rubidium/Strontium (Rb/Sr) and Potassium/Argon (K/Ar) radiometric methods application in the sedimentary rocks dating, including the methodology, the method restrictions and the ages meaning. The work concludes that the sedimentary rocks radiometric dating, by the Rb/Sr method is possible, furnishing results geologically significant. The {sup 87} Sr/{sup 86} Sr of marine carbonates has propitiated, mainly in the last years, the dating possibility of sedimentary rocks. The K/Ar radiometric method has been applied to determine the diagenetic events age of the sedimentary rocks, including its application in mesozoic and recent rocks, where the RB/Sr radiometric method presents some limitations 71 refs., 18 figs.

  3. An in-situ K-Ar isochron dating method for planetary landers using a spot-by-spot laser-ablation technique (United States)

    Cho, Yuichiro; Sugita, Seiji; Miura, Yayoi N.; Okazaki, Ryuji; Iwata, Naoyoshi; Morota, Tomokatsu; Kameda, Shingo


    Age is essential information for interpreting the geologic record on planetary surfaces. Although crater counting has been widely used to estimate the planetary surface ages, crater chronology in the inner solar system is largely built on radiometric age data from limited sites on the Moon. This has resulted in major uncertainty in planetary chronology. Because opportunities for sample-return missions are limited, in-situ geochronology measurements from one-way lander/rover missions are extremely valuable. Here we developed an in-situ isochron-based dating method using the K-Ar system, with K and Ar in a single rock sample extracted locally by laser ablation and measured using laser-induced breakdown spectroscopy (LIBS) and a quadrupole mass spectrometer (QMS), respectively. We built an experimental system combining flight-equivalent instruments and measured K-Ar ages for mineral samples with known ages (~1.8 Ga) and K contents (1-8 wt%); we achieved precision of 20% except for a mineral with low mechanical strength. Furthermore, validation measurements with two natural rocks (gneiss slabs) obtained K-Ar isochron ages and initial 40Ar consistent with known values for both cases. This result supports that our LIBS-MS approach can derive both isochron ages and contributions of non-in situ radiogenic 40Ar from natural rocks. Error assessments suggest that the absolute ages of key geologic events including the Noachian/Hesperian- and the Hesperian/Amazonian-transition can be dated with 10-20% errors for a rock containing ~1 wt% K2O, greatly reducing the uncertainty of current crater chronology models on Mars.

  4. Expression of Caenorhabditis elegans neurotransmitter receptors and ion channels in Xenopus oocytes (United States)

    Martínez-Torres, Ataúlfo; Miledi, Ricardo


    Injection of Caenorhabditis elegans polyA RNA into Xenopus laevis oocytes led to the expression of neurotransmitter receptors that generated some unique responses, including ionotropic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors as well as receptors that coupled to G proteins, such as those to octopamine, norepinephrine, and angiotensin, which activated the oocyte’s own phosphatidylinositol system and calcium-gated chloride channels. The oocytes also expressed chloride-conducting glutamate receptors, muscarinic acetylcholine receptors, and voltage-operated calcium channels. Unexpectedly, serotonin (5-hydroxytryptamine), dopamine, GABA, and kainate did not generate ionic currents, suggesting that the corresponding receptors were not expressed or were not functional in the oocytes. The use of X. laevis oocytes for expressing worm RNA demonstrates that there are many molecular components whose role remains to be clarified in the nematode. Among them are the nature of the endogenous agonists for the octopamine and angiotensin receptors and the subunits that compose the ionotropic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors and the norepinephrine receptors that couple to the phosphoinositide cascade. PMID:16549772

  5. Edades K/Ar de 54 rocas ígneas y metamórficas del occidente, centro y sur de México


    Jesús Solé; Juan Carlos Salinas; Enrique González Torres; José Eduardo Cendejas Cruz


    Se presenta un listado y se discuten las edades K/Ar de 54 muestras de rocas ígneas y metamórficas de varias localidades de México determinadas en el marco de un convenio entre el Consejo de Recursos Minerales (ahora Servicio Geológico Mexicano) y el Instituto de Geología de la Universidad Nacional Autónoma de México. Se analizaron rocas de los siguientes estados: Baja California Sur, Colima, Durango, Estado de México, Guerrero, Jalisco, Oaxaca, San Luis Potosí, Sinaloa y Zacatecas. Se report...

  6. White mica K-Ar geochronology of HP-UHP units in the Lago di Cignana area, western Alps, Italy: Tectonic implications for exhumation (United States)

    Gouzu, Chitaro; Yagi, Koshi; Thanh, Ngo Xuan; Itaya, Tetsumaru; Compagnoni, Roberto


    High-pressure and ultra-high pressure (HP-UHP) blueschist- and eclogite-facies metabasaltic and metasedimentary rocks occur in four different tectonic units near Lago di Cignana, western Alps. We have determined K-Ar ages for white micas (matrix phengite and paragonite) from the Lago di Cignana UHP unit (LCU; 39-41 Ma); the lower and upper units of the Zermatt-Saas meta-ophiolite (LU and UU; 37-38 Ma and 38-41 Ma respectively), and the Combin unit (CU; 36-40 Ma). These K-Ar ages overlap with single-grain Ar-Ar plateau ages (36-42 Ma) previously determined for phengites from LCU metasediments. Matrix white micas have been severely deformed during exhumation, and their chemistries differ from those of micas included in garnet. Although individual mica grains in the matrix could have experienced different degrees of deformation which have reset their K-Ar systems, "bulk" white mica separates provide the average age of all the individual grains in the separate. The similarity of ages determined for white micas from the LCU, LU, UU and CU units, regardless of rock type and mineral species, suggests that these four units were metamorphosed together as part of a single metamorphic sequence in the Piemonte-Liguria paleosubduction zone and were subsequently exhumed together. However, present-day structural relationship among those units and the limited occurrence of UHP minerals in LCU suggests that the exhumation of LCU was more rapid than that for LU, UU and CU. The age gaps between the youngest value of white mica K-Ar ages in each unit and the inferred timing of the metamorphic peak (U-Pb age: 44 Ma) is 5, 7, 6 and 8 Myr for LCU, LU, UU and CU, respectively. These intervals are considerably shorter than that determined for the Sanbagawa HP metamorphic belt of Southwest Japan (> 31 Myr). The short interval observed for the Lago di Cignana units that we have studied is consistent with the model of rapid exhumation of the UHP-bearing metamorphic domain, suggesting the

  7. Properties of GluR3 receptors tagged with GFP at the amino or carboxyl terminus (United States)

    Limon, Agenor; Reyes-Ruiz, Jorge Mauricio; Eusebi, Fabrizio; Miledi, Ricardo


    Anatomical visualization of neurotransmitter receptor localization is facilitated by tagging receptors, but this process can alter their functional properties. We have evaluated the distribution and properties of WT glutamate receptor 3 (GluR3) α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors (WT GluR3) and two receptors in which GFP was tagged to the amino terminus (GFP-GluR3) or to the carboxyl terminus (GluR3-GFP). Although the fluorescence in Xenopus oocytes was stronger in the vegetal hemisphere because of localization of internal structures (probable sites of production, storage or recycling of receptors), the insertion of receptors into the plasma membrane was polarized to the animal hemisphere. The fluorescence intensity of oocytes injected with GluR3-GFP RNA was approximately double that of oocytes injected with GFP-GluR3 RNA. Accordingly, GluR3-GFP oocytes generated larger kainate-induced currents than GFP-GluR3 oocytes, with similar EC50 values. Currents elicited by glutamate, or AMPA coapplied with cyclothiazide, were also larger in GluR3-GFP oocytes. The glutamate- to kainate-current amplitude ratios differed, with GluR3-GFP being activated more efficiently by glutamate than the WT or GFP-GluR3 receptors. This pattern correlates with the slower decay of glutamate-induced currents generated by GluR3-GFP receptors. These changes were not observed when GFP was tagged to the amino terminus, and these receptors behaved like the WT. The antagonistic effects of 6-nitro-7-sulfamoylbenzo[f]quinoxaline-2,3-dione (NBQX) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) were not altered in any of the tagged receptors. We conclude that GFP is a useful and convenient tag for visualizing these proteins. However, the effects of different sites of tag insertion on receptor characteristics must be taken into account in assessing the roles played by these receptor proteins. PMID:17881566

  8. Presynaptic adenosine receptor-mediated regulation of diverse thalamocortical short-term plasticity in the mouse whisker pathway

    Directory of Open Access Journals (Sweden)

    Giovanni eFerrati


    Full Text Available Short-term synaptic plasticity (STP sets the sensitivity of a synapse to incoming activity and determines the temporal patterns that it best transmits. In driver thalamocortical (TC synaptic populations, STP is dominated by depression during stimulation from rest. However, during ongoing stimulation, lemniscal TC connections onto layer 4 neurons in mouse barrel cortex express variable STP. Each synapse responds to input trains with a distinct pattern of depression or facilitation around its mean steady-state response. As a result, in common with other synaptic populations, lemniscal TC synapses express diverse rather than uniform dynamics, allowing for a rich representation of temporally varying stimuli. Here we show that this STP diversity is regulated presynaptically. Presynaptic adenosine receptors of the A1R type, but not kainate receptors, modulate STP behavior. Blocking the receptors does not eliminate diversity, indicating that diversity is related to heterogeneous expression of multiple mechanisms in the pathway from presynaptic calcium influx to neurotransmitter release.

  9. Optical control of endogenous receptors and cellular excitability using targeted covalent photoswitches. (United States)

    Izquierdo-Serra, Mercè; Bautista-Barrufet, Antoni; Trapero, Ana; Garrido-Charles, Aida; Díaz-Tahoces, Ariadna; Camarero, Nuria; Pittolo, Silvia; Valbuena, Sergio; Pérez-Jiménez, Ariadna; Gay, Marina; García-Moll, Alejandro; Rodríguez-Escrich, Carles; Lerma, Juan; de la Villa, Pedro; Fernández, Eduardo; Pericàs, Miquel À; Llebaria, Amadeu; Gorostiza, Pau


    Light-regulated drugs allow remotely photoswitching biological activity and enable plausible therapies based on small molecules. However, only freely diffusible photochromic ligands have been shown to work directly in endogenous receptors and methods for covalent attachment depend on genetic manipulation. Here we introduce a chemical strategy to covalently conjugate and photoswitch the activity of endogenous proteins and demonstrate its application to the kainate receptor channel GluK1. The approach is based on photoswitchable ligands containing a short-lived, highly reactive anchoring group that is targeted at the protein of interest by ligand affinity. These targeted covalent photoswitches (TCPs) constitute a new class of light-regulated drugs and act as prosthetic molecules that photocontrol the activity of GluK1-expressing neurons, and restore photoresponses in degenerated retina. The modularity of TCPs enables the application to different ligands and opens the way to new therapeutic opportunities.

  10. Y5 neuropeptide Y receptor overexpression in mice neither affects anxiety- and depression-like behaviours nor seizures but confers moderate hyperactivity

    DEFF Research Database (Denmark)

    Olesen, Mikkel V; Christiansen, Søren Hofman Oliveira; Gøtzsche, Casper René;


    , by testing effects of recombinant adeno-associated viral vector (rAAV) encoding Y5 (rAAV-Y5) in anxiety- and depression-like behaviour as well as in kainate-induced seizures in adult mice. The rAAV-Y5 vector injected into the hippocampus and amygdala induced a pronounced and sustained increase in Y5 receptor...... mRNA expression and functional Y5 receptor binding, but no significant effects were found with regard to anxiety- and depression-like behaviours or seizure susceptibility. Instead, rAAV-mediated Y5 receptor transgene overexpression resulted in moderate hyperactivity in the open field test....... These results do not support a potential role for single transgene overexpression of Y5 receptors for modulating anxiety-/depression-like behaviours or seizures in adult mice. Whether the induction of hyperactivity by rAAV-Y5 could be relevant for other conditions remains to be studied....

  11. Fosb gene products contribute to excitotoxic microglial activation by regulating the expression of complement C5a receptors in microglia. (United States)

    Nomaru, Hiroko; Sakumi, Kunihiko; Katogi, Atsuhisa; Ohnishi, Yoshinori N; Kajitani, Kosuke; Tsuchimoto, Daisuke; Nestler, Eric J; Nakabeppu, Yusaku


    The Fosb gene encodes subunits of the activator protein-1 transcription factor complex. Two mature mRNAs, Fosb and ΔFosb, encoding full-length FOSB and ΔFOSB proteins respectively, are formed by alternative splicing of Fosb mRNA. Fosb products are expressed in several brain regions. Moreover, Fosb-null mice exhibit depressive-like behaviors and adult-onset spontaneous epilepsy, demonstrating important roles in neurological and psychiatric disorders. Study of Fosb products has focused almost exclusively on neurons; their function in glial cells remains to be explored. In this study, we found that microglia express equivalent levels of Fosb and ΔFosb mRNAs to hippocampal neurons and, using microarray analysis, we identified six microglial genes whose expression is dependent on Fosb products. Of these genes, we focused on C5ar1 and C5ar2, which encode receptors for complement C5a. In isolated Fosb-null microglia, chemotactic responsiveness toward the truncated form of C5a was significantly lower than that in wild-type cells. Fosb-null mice were significantly resistant to kainate-induced seizures compared with wild-type mice. C5ar1 mRNA levels and C5aR1 immunoreactivity were increased in wild-type hippocampus 24 hours after kainate administration; however, such induction was significantly reduced in Fosb-null hippocampus. Furthermore, microglial activation after kainate administration was significantly diminished in Fosb-null hippocampus, as shown by significant reductions in CD68 immunoreactivity, morphological change and reduced levels of Il6 and Tnf mRNAs, although no change in the number of Iba-1-positive cells was observed. These findings demonstrate that, under excitotoxicity, Fosb products contribute to a neuroinflammatory response in the hippocampus through regulation of microglial C5ar1 and C5ar2 expression.

  12. Mineralogy and clinoptilolite K/Ar results from Yucca Mountain, Nevada, USA: A potential high-level radioactive waste repository site

    Energy Technology Data Exchange (ETDEWEB)

    WoldeGabriel, G.; Broxton, D.E.; Bish, D.L.; Chipera, S.J.


    The Yucca Mountain Site Characterization Project is investigating Yucca Mountain, Nevada, as a potential site for a high-level nuclear waste repository. An important aspect of this evaluation is to understand the geologic history of the site including the diagenetic processes that are largely responsible for the present-day chemical and physical properties of the altered tuffs. This study evaluates the use of K/Ar geochronology in determining the alteration history of the zeolitized portions of Miocene tuffs at Yucca Mountain. Clinoptilolite is not generally regarded as suitable for dating because of its open structure and large ion-exchange capacity. However, it is the most abundant zeolite at Yucca Mountain and was selected for this study to assess the feasibility of dating the zeolitization process and/or subsequent processes that may have affected the zeolites. In this study we examine the ability of this mineral to retain all or part of its K and radiogenic Ar during diagenesis and evaluate the usefulness of the clinoptilolite K/Ar dates for determining the history of alteration.

  13. Ortaöğretim On İkinci Sınıf Öğrencilerinin Matematik Dersine Karşı Tutumları

    Directory of Open Access Journals (Sweden)

    Esat AVCI


    Full Text Available Bu araştırma, ortaöğretim on ikinci sınıf öğrencilerinin matematik dersine karşı tutumlarını, cinsiyet,okul türü ve alan türüne göre incelemek amacıyla yapılmıştır. Araştırmanın örneklemini Mersin ili Tarsusilçesinde bulunan dört meslek lisesi, üç Anadolu lisesi, üç genel liseden 365 kız, 470 erkek toplam 835 onikinci sınıf öğrencisi oluşturmaktadır. Verilerin toplanmasında Aşkar (1986 tarafından geliştirilenMatematik Tutum Ölçeği kullanılmıştır. Verilerin analizinde aritmetik ortalama, standart sapma, t Testi veANOVA kullanılmıştır. Araştırmanın sonucunda, on ikinci sınıf öğrencilerinin matematik tutumlarındabazı değişkenlere göre anlamlı bir farklılık görülmüştür.

  14. The effect of prolonged storage on the virulence of isolates of Bacillus anthracis obtained from environmental and animal sources in the Kars Region of Turkey. (United States)

    Buyuk, Fatih; Sahin, Mitat; Cooper, Callum; Celebi, Ozgur; Saglam, Aliye Gulmez; Baillie, Les; Celik, Elif; Akca, Dogan; Otlu, Salih


    The stability of the plasmid-mediated virulence factors of Bacillus anthracis, a tripartite toxin located on pXO1 and an antiphagocytic capsule encoded by genes located on pXO2, following long-term storage was investigated. A collection of 159 isolates of B. anthracis were collected from the Kars region of Turkey between 2000 and 2013 and stored at -20°C in Brucella broth supplemented with 20% glycerine. A total of 142 isolates were recovered of which one failed to express a capsule upon primary culture. A further 35 isolates yielded a mixture of mucoid and non-mucoid colonies; the majority of which had lost the pXO2 plasmid as determined by PCR analysis. Results would suggest that pXO2 is more unstable than pXO1 and that this instability increases with the length of storage. It is possible that the pXO2-deficient isolates of B. anthracis described here could be developed into a vaccine to treat at risk animals in the Kars region as many animal vaccines are based upon pXO2 deficiency.

  15. Molecular cloning, chromosomal mapping, and functional expression of human brain glutamate receptors

    Energy Technology Data Exchange (ETDEWEB)

    Sun, W.; Ferrer-Montiel, A.V.; Schinder, A.F.; Montal, M. (Univ. of California, San Diego, La Jolla (United States)); McPherson, J.P. (Univ. of California, Irvine (United States)); Evans, G.A. (Salk Inst. for Biological Studies, La Jolla, CA (United States))


    A full-length cDNA clone encoding a glutamate receptor was isolated from a human brain cDNA library, and the gene product was characterized after expression in Xenopus oocytes. Degenerate PCR primers to conserved regions of published rat brain glutamate receptor sequences amplified a 1-kilobase fragment from a human brain cDNA library. This fragment was used as a probe for subsequent hybridization screening. Two clones were isolated that, based on sequence information, code for different receptors: a 3-kilobase clone, HBGR1, contains a full-length glutamate receptor cDNA highly homologous to the rat brain clone GluR1, and a second clone, HBGR2, contains approximately two-thirds of the coding region of a receptor homologous to rat brain clone GluR2. Southern and PCr analysis of a somatic cell-hybrid panel mapped HBGR1 to human chromosome 5q31.3-33.3 and mapped HBGR2 to chromosome 4q25-34.3. Xenopus oocytes injected with in vitro-synthesized HBGR1 cRNA expressed currents activated by glutamate receptor agonists. These results indicate that clone HBGR1 codes for a glutamate receptor of the kainate subtype cognate to members of the glutamate receptor family from rodent brain.

  16. Central phencyclidine (PCP) receptor binding is glutamate dependent: evidence for a PCP/excitatory amino acid receptor (EAAR) complex

    Energy Technology Data Exchange (ETDEWEB)

    Loo, P.; Braunwalder, A.; Lehmann, J.; Williams, M.


    PCP and other dissociative anesthetica block the increase in neuronal firing rate evoked by the EAAR agonist, N-methyl-Daspartate. NMDA and other EAAs such as glutamate (glu) have not been previously shown to affect PCP ligand binding. In the present study, using once washed rat forebrain membranes, 10 was found to increase the binding of (/sup 3/H)TCP, a PCP analog, to defined PCP recognition sites by 20%. Removal of glu and aspartate (asp) by extensive washing decreased TCP binding by 75-90%. In these membranes, 10 L-glu increased TCP binding 3-fold. This effect was stereospecific and evoked by other EAAs with the order of activity, L-glu > D-asp > L- asp > NMDA > D-glu > quisqualate. Kainate, GABA, NE, DA, 5-HT, 2-chloroadenosine, oxotremorine and histamine had no effect on TCP binding at concentrations up to 100 The effects of L-glu were attenuated by the NMDA-type receptor antagonist, 2-amino-7--phosphonoheptanoate (AP7; 10 mM). These findings indicate that EAAS facilitate TCP binding, possibly through NMDA-type receptors. The observed interaction between the PCP receptor and EAARs may reflect the existence of a macromolecular receptor complex similar to that demonstrated for the benzodiazepines and GABA.

  17. Ionotropic GABA and Glutamate Receptor Mutations and Human Neurologic Diseases. (United States)

    Yuan, Hongjie; Low, Chian-Ming; Moody, Olivia A; Jenkins, Andrew; Traynelis, Stephen F


    The advent of whole exome/genome sequencing and the technology-driven reduction in the cost of next-generation sequencing as well as the introduction of diagnostic-targeted sequencing chips have resulted in an unprecedented volume of data directly linking patient genomic variability to disorders of the brain. This information has the potential to transform our understanding of neurologic disorders by improving diagnoses, illuminating the molecular heterogeneity underlying diseases, and identifying new targets for therapeutic treatment. There is a strong history of mutations in GABA receptor genes being involved in neurologic diseases, particularly the epilepsies. In addition, a substantial number of variants and mutations have been found in GABA receptor genes in patients with autism, schizophrenia, and addiction, suggesting potential links between the GABA receptors and these conditions. A new and unexpected outcome from sequencing efforts has been the surprising number of mutations found in glutamate receptor subunits, with the GRIN2A gene encoding the GluN2A N-methyl-d-aspartate receptor subunit being most often affected. These mutations are associated with multiple neurologic conditions, for which seizure disorders comprise the largest group. The GluN2A subunit appears to be a locus for epilepsy, which holds important therapeutic implications. Virtually all α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor mutations, most of which occur within GRIA3, are from patients with intellectual disabilities, suggesting a link to this condition. Similarly, the most common phenotype for kainate receptor variants is intellectual disability. Herein, we summarize the current understanding of disease-associated mutations in ionotropic GABA and glutamate receptor families, and discuss implications regarding the identification of human mutations and treatment of neurologic diseases.

  18. Pharmacology of glutamate receptor antagonists in the kindling model of epilepsy. (United States)

    Löscher, W


    It is widely accepted that excitatory amino acid transmitters such as glutamate are involved in the initiation of seizures and their propagation. Most attention has been directed to synapses using NMDA receptors, but more recent evidence indicates potential roles for ionotropic non-NMDA (AMPA/kainate) and metabotropic glutamate receptors as well. Based on the role of glutamate in the development and expression of seizures, antagonism of glutamate receptors has long been thought to provide a rational strategy in the search for new, effective anticonvulsant drugs. Furthermore, because glutamate receptor antagonists, particularly those acting on NMDA receptors, protect effectively in the induction of kindling, it was suggested that they may have utility in epilepsy prophylaxis, for example, after head trauma. However, first clinical trials with competitive and uncompetitive NMDA receptor antagonists in patients with partial (focal) seizures, showed that these drugs lack convincing anticonvulsant activity but induce severe neurotoxic adverse effects in doses which were well tolerated in healthy volunteers. Interestingly, the only animal model which predicted the unfavorable clinical activity of competitive NMDA antagonists in patients with chronic epilepsy was the kindling model of temporal lobe epilepsy, indicating that this model should be used in the search for more effective and less toxic glutamate receptor antagonists. In this review, results from a large series of experiments on different categories of glutamate receptor antagonists in fully kindled rats are summarized and discussed. NMDA antagonists, irrespective whether they are competitive, high- or low-affinity uncompetitive, glycine site or polyamine site antagonists, do not counteract focal seizure activity and only weakly, if at all, attenuate propagation to secondarily generalized seizures in this model, indicating that once kindling is established, NMDA receptors are not critical for the expression of

  19. Quantitative Potassium Measurements with Laser-Induced Breakdown Spectroscopy Using Low-Energy Lasers: Application to In Situ K-Ar Geochronology for Planetary Exploration. (United States)

    Cho, Yuichiro; Horiuchi, Misa; Shibasaki, Kazuo; Kameda, Shingo; Sugita, Seiji


    In situ radiogenic isotope measurements to obtain the absolute age of geologic events on planets are of great scientific value. In particular, K-Ar isochrons are useful because of their relatively high technical readiness and high accuracy. Because this isochron method involves spot-by-spot K measurements using laser-induced breakdown spectroscopy (LIBS) and simultaneous Ar measurements with mass spectrometry, LIBS measurements are conducted under a high vacuum condition in which emission intensity decreases significantly. Furthermore, using a laser power used in previous planetary missions is preferable to examine the technical feasibility of this approach. However, there have been few LIBS measurements for K under such conditions. In this study, we measured K contents in rock samples using 30 mJ and 15 mJ energy lasers under a vacuum condition (10(-3 )Pa) to assess the feasibility of in situ K-Ar dating with lasers comparable to those used in NASA's Curiosity and Mars 2020 missions. We obtained various calibration curves for K using internal normalization with the oxygen line at 777 nm and continuum emission from the laser-induced plasma. Experimental results indicate that when K2O laser energy, with a detection limit of 88 ppm and 20% of error at 2400 ppm of K2O. Futhermore, the calibration curve based on the K 769 nm line intensity normalized with continuum emission yielded the best result for the 15 mJ laser, giving a detection limit of 140 ppm and 20% error at 3400 ppm K2O. Error assessments using obtained calibration models indicate that a 4 Ga rock with 3000 ppm K2O would be measured with 8% (30 mJ) and 10% (15 mJ) of precision in age when combined with mass spectrometry of (40)Ar with 10% of uncertainty. These results strongly suggest that high precision in situ isochron K-Ar dating is feasible with a laser used in previous and upcoming Mars rover missions.

  20. Characterisation of the effects of ATPA, a GLU(K5) receptor selective agonist, on excitatory synaptic transmission in area CA1 of rat hippocampal slices. (United States)

    Clarke, V R J; Collingridge, G L


    Kainate receptors are involved in a variety of synaptic functions in the CNS including the regulation of excitatory synaptic transmission. Previously we described the depressant action of the GLU(K5) selective agonist (RS)-2-amino-3-(3-hydroxy-5-tert-butylisoxazol-4-yl)propanoic acid (ATPA) on synaptic transmission in the Schaffer collateral-commissural pathway of rat hippocampal slices. In the present study we report several new features of the actions of ATPA at this synapse. Firstly, the effectiveness of ATPA is developmentally regulated. Secondly, the effects of ATPA decline during prolonged or repeated applications. Thirdly, the effects of ATPA are not mediated indirectly via activation of GABA(A), GABA(B), muscarinic or adenosine A(1) receptors. Fourthly, elevating extracellular Ca(2+) from 2 to 4 mM antagonises the effects of ATPA. Some differences between the actions of ATPA and kainate on synaptic transmission in the Schaffer collateral-commissural pathway are also noted.

  1. Temps, Espace et la Eeprésentation de la Subjectivité Dans les Films de Wong Kar-wai

    Directory of Open Access Journals (Sweden)



    Full Text Available Given the importance of the filmmaker Wong Kar-wai not only in the panorama of the cinema of Hong Kong, but in the contemporary cinematographic production as a whole, this paper proposes an analysis of his work concentrated on the problem of the identity of his characters. What we may call the «wongian subject” can be analyzed through various elements such as the tension between past, present and future, the relationship to public and private space, the changes of the perception of time and memory. Another important question that is analyzed is the relationship of the films with the social and political context of contemporary Hong Kong, because the topics of love, loneliness and alienation which invade the protagonists find relation in the transnational character of the Asian cinema and the fusion – often problematic – between Orient and Occident.

  2. Rejyonel anestezi sırasında midazolam ve deksmedetomidin\\'in sedatif etkilerinin karşılaştırılması


    Korkmaz, Mehmet; Gurbet, Alp; Şahin, Şükran; Pürcü, Özden Özkurt


    Amaç: Bu çalışmada, spinal anestezi altında artroskopik diz cerrahisi uygulanacak olgulara sedasyon amacıyla deksmedetomidin ve midazolam uygulamasının etkilerini karsılaştırmayı amaçladık. Gereç ve yöntem: Yaşları 18-65 yıl arasında değişen 50 olgu randomizasyon ile iki gruba ayrıldı: Grup M\\'deki ol­gulara midazolam 0.04 mg/kg intravenöz (iv) uygulandık­tan sonra Ramsay sedasyon skoru (RSS) 3-4 olacak şe­kilde 0,5 mg ek dozlarla işleme devam edild...

  3. Bazı Tıbbi ve Aromatik Bitkilerin Farklı Kirlilik Etmenlerine Karşı Fitoremediasyon Davranışları


    BAHTİYARCA BAĞDAT, Reyhan; EID, Ebrahem


    Tıbbi ve aromatik bitkiler koruyucu ve tedavi edici olarak kullanılmaktadır. Son zamanlarda, biyolojik çeşitliliğin korunması ve gelecek kuşaklara aktarılmasında önem kazanmışlardır. Civa, kadmiyum ve kurşun gibi ağır metallerin neden olduğu çevre kirliliği tüm dünyayı tehdit eder hale gelmiştir. Ağır ya da toksik metaller sudan beş kat daha yoğun ve hareketsiz olduklarından vücut tarafından sindirilemezler ancak besin zincirine geçebilirler. Zehirli endüstriyel atıklar sıvı gübrelerle karışa...

  4. Rb, Sr and strontium isotopic composition, K/Ar age and large ion lithophile trace element abundances in rocks and glasses from the Wanapitei Lake impact structure (United States)

    Winzer, S. R.; Lum, R. K. L.; Schuhmann, S.


    Shock metamorphosed rocks and shock-produced melt glasses from the Wanapitei Lake impact structure have been examined petrographically and by electron microprobe. Eleven clasts exhibiting varying degrees of shock metamorphism and eight impact-produced glasses have been analyzed for Rb, Sr and Sr isotopic composition. Five clasts and one glass have also been analyzed for large ion lithophile (LIL) trace element abundances including Li, Rb, Sr, and Ba and the REE's. The impact event forming the Wanapitei Lake structure occurred 37 m.y. ago based on K/Ar dating of glass and glassy whole-rock samples. Rb/Sr isotopic dating failed to provide a meaningful whole-rock or internal isochron. The isotopic composition of the glasses can be explained by impact-produced mixing and melting of metasediments.

  5. Sm-Nd, K-Ar and petrologic study of some kimberlites from eastern United States and their implication for mantle evolution (United States)

    Basu, A.R.; Rubury, E.; Mehnert, H.; Tatsumoto, M.


    We provide new data on Sm-Nd systematics, K-Ar dating and the major element chemistry of kimberlites from the eastern United States (mostly from central New York State) and their constituent mineral phases of olivine, clinopyroxene, garnet, phlogopite and perovskite. In addition, we report Nd-isotopes in a few kimberlites from South Africa, Lesotho and from the eastern part of China. The major element compositions of the New York dike rocks and of their constituent minerals including a xenolith of eclogite are comparable with those from the Kimberley area in South Africa. The K-Ar age of emplacement of the New York dikes is further established to be 143 Ma. We have analyzed the Nd-isotopic composition of the following kimberlites and related rocks: Nine kimberlite pipes from South Africa and Lesotho, two from southern India; one from the U.S.S.R., fifteen kimberlite pipes and related dike rocks from eastern and central U.S. and two pipes from the Shandong Province of eastern China. The age of emplacement of these kimberlites ranges from 1300 million years to 90 million years. The initial Nd-isotopic compositions of these kimberlitic rocks expressed as e{open}NdIwith respect to a chondritic bulk-earth growth-curve show a range between 0 and +4, with the majority of the kimberlites being in the range 0 to +2. This range is not matched by any other suite of mantle-derived igneous rocks. This result strengthens our earlier conclusion that kimberlitic liquids are derived from a relatively primeval and unique mantle reservoir with a nearly chondritic Sm/Nd ratio. ?? 1984 Springer-Verlag.

  6. Structural evolution of the Yeongwol thrust system, northeastern Okcheon fold-thrust belt, Korea: Insights from structural interpretations and SHRIMP U-Pb and K-Ar geochronology (United States)

    Jang, Yirang; Kwon, Sanghoon


    The NE-trending Okcheon Belt is a prominent fold-thrust belt preserved in the Korean Peninsula. In the Yeongwol area, the northeastern Okcheon Belt, the Cambrian-Ordovician (possibly to Silurian) Joseon Supergroup overlies the Carboniferous-Permian (possibly to early Triassic) Pyeongan Supergroup and/or Jurassic Bansong Group by N-S trending thrust faults, having highly connected traces in map view. To understand the structural geometry of these thrust faults and their evolution history, we have conducted structural analyses, together with SHRIMP U-Pb zircon and K-Ar illite age datings. The results show that (1) the thrusts in the Yeongwol area, carrying the lower Paleozoic strata over the upper Paleozoic or Mesozoic strata, are defined as the Yeongwol thrust system. The closed-loops map patterns of this system can further be interpreted by alternative duplex models in terms of a hinterland dipping duplex vs. a combination of major thrusts and connecting splays; (2) newly obtained SHRIMP U-Pb zircon ages from a dike and synorogenic sediments and K-Ar illite ages from fault gouges, together with previously reported evidences form the Yeongwol area, suggest multiple events after Permo-Triassic to early Neogene. The SHRIMP U-Pb detrital zircon ages from the lower Paleozoic rocks of the Yeongwol area can provide tectono-stratigraphic information of this area before the Permian. These further indicate the broader implications in that how detailed structural interpretations supported by the geochronological data can help to understand the tectonic evolution of the Okcheon Belt as well as the fold-thrust belts in general.

  7. Comparative 40Ar/39Ar and K-Ar dating of illite-type clay minerals: A tentative explanation for age identities and differences (United States)

    Clauer, Norbert; Zwingmann, Horst; Liewig, Nicole; Wendling, Raymond


    The 40K/40Ar (K-Ar) and 40Ar/39Ar dating methods are applied here to the same, very small, micrometric illite-type particles that crystallized under low-temperature (samples with a total of fifteen size fractions from advantages, such as the plateaus obtained by incremental step heating of the various size fractions, even if not translatable straight as ages of the illite populations; they allow identification of two generations of authigenic illite that formed at about 200 and 175 Ma, and one detrital generation. However, 40Ar/39Ar dating of clay minerals remains challenging as technical factors, such as the non-standardized encapsulation, may have potential unexpected effects. Both dating methods have their limitations: (1) K-Ar dating requires relatively large samples (ca. 10-20 mg) incurring potential sample homogeneity problems, with two aliquots required for K and Ar analysis for an age determination, also inducing a higher analytical uncertainty; (2) an identified drawback of 40Ar/39Ar dating is Ar recoil and therefore potential loss that occurs during neutronic creation of 39Ar from 39K, mostly in the finer mineral particles. If all the recoiled 39Ar is redistributed into adjacent grains/minerals, the final 40Ar/39Ar age of the analyzed size fraction remains theoretically identical, but it is not systematic in clay-type material. The finest grain sizes (e.g., convenient and straightforward use supported by a standardized and well-controlled technical approach. The present comparison of the two Ar-dating methods as applied to clay material shows that neither method is presently outdated, and that they are even of reciprocal use. Both methods have distinct application fields in clay geochronology and complementary application fields in clay crystallography.

  8. pkl1(+)and klp2(+): Two kinesins of the Kar3 subfamily in fission yeast perform different functions in both mitosis and meiosis. (United States)

    Troxell, C L; Sweezy, M A; West, R R; Reed, K D; Carson, B D; Pidoux, A L; Cande, W Z; McIntosh, J R


    We have identified Klp2p, a new kinesin-like protein (KLP) of the KAR3 subfamily in fission yeast. The motor domain of this protein is 61% identical and 71% similar to Pkl1p, another fission yeast KAR3 protein, yet the two enzymes are different in behavior and function. Pkl1p is nuclear throughout the cell cycle, whereas Klp2p is cytoplasmic during interphase. During mitosis Klp2p enters the nucleus where it forms about six chromatin-associated dots. In metaphase-arrested cells these migrate back and forth across the nucleus. During early anaphase they segregate with the chromosomes into two sets of about three, fade, and are replaced by other dots that form on the spindle interzone. Neither klp2(+) nor pkl1(+) is essential, and the double deletion is also wild type for both vegetative and sexual reproduction. Each deletion rescues different alleles of cut7(ts), a KLP that contributes to spindle formation and elongation. When either or both deletions are combined with a dynein deletion, vegetative growth is normal, but sexual reproduction fails: klp2 Delta,dhc1-d1 in karyogamy, pkl1 Delta,dhc1-d1 in multiple phases of meiosis, and the triple deletion in both. Deletion of Klp2p elongates a metaphase-arrested spindle, but pkl1 Delta shortens it. The anaphase spindle of klp2 Delta becomes longer than the cell, leading it to curl around the cell's ends. Apparently, Klp2p promotes spindle disassembly and contributes to the behavior of mitotic chromosomes.

  9. Kısmi ve Tam Dönümlü Spektral Metotların Karşılaştırması

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    İhsan Haluk Akın


    Full Text Available Bu çalışmada, yakın zamanda sunulmuş spektral modüler aritmetik işlemlerinin aritmetik karmaşıklığı üzerindeki bir analiz adım adım değerlendirme yöntemi ile karşılaştırılmıştır. Bilgisayar aritmetiğinde spektral yöntemlerin standart kullanımı çarpma ve indirgeme adımlarının spektrum ve zaman uzayında birbirinden ayrı olarak gerçekleştirilmesi gerektiğini belirtmektedir. Bu tarz bir prosedür ise açıkça tam dönümlü (ileri ve geri yönde DFT hesaplamalarına ihtiyaç duymaktadır. Öte yandan, bazı kısmı değerlerin işlem sırasında hesaplanması ile, yeni yöntemler indirgeme işlemi de dahil olmak üzere tüm verilerin tüm zamanlarda spektrumda tutulmasını gerektiren bir yaklaşımı benimsemişlerdir. Tüm bu yaklaşımların işlem süresi performanslarını karşılaştırdığımızda, tam dönümlü algoritmaların son zamanlarda önerilmiş yöntemlerden daha iyi performans gösterdiğini bu çalışmada göstermiş bulunmaktayız.

  10. Episodes of brittle deformation within the Dien Bien Phu Fault zone, Vietnam: Evidence from K-Ar age dating of authigenic illite (United States)

    Bui, Hoang Bac; Ngo, Xuan Thanh; Khuong, The Hung; Golonka, Jan; Nguyen, Tien Dung; Song, Yungoo; Itaya, Tetsumaru; Yagi, Koshi


    Constraining the timing of fault zone origin and movement history is of fundamental geotectonic importance to understand the evolution and processes of the brittle fault structures. The authors present in this paper authigenic illite K-Ar age data from the fault gouge samples, collected from the Dien Bien Phu Fault (DBPF) in the Dien Bien province, Vietnam as well as in a major strike-slip fault zone in South-East Asia; all of which played important roles in the structural formation and geotectonic development of northwestern Vietnam. The gouge fault samples were separated into four grain-size fractions (groups, from 26 to 29 Ma and 130 Ma. The timing of the fault movements is defined at 26 ± 0.24 Ma, 29 ± 0.61 Ma, 130.1 ± 1.27 Ma and 130.7 ± 1.29 Ma. This indicates that the Dien Bien Phu Fault underwent two movements, first in the Early Cretaceous, with an age of about 130 Ma and second in the Oligocene (Paleogene), with an age of about 26-29 Ma. The ductile deformation of the DBPF terminated during the Early Cretaceous. These studies also indicate slow exhumation of the Dien Bien granitoid complex during the Cretaceous times. The Oligocene ages indicate that the DBPF had been reactivated by the SE extrusion and clock-wise rotation of the Indochina block, caused by the collision of the Indian and Eurasian plates. This tectonic event led to the DBPF brittle-sinistral movement, causing the exhumation phase along the fault. This movement period (ca. 26-29 Ma) is coexistent with 600-700 km sinistral shearing along the Red River-Ailao Shan fault. This is the first report determining the absolute age constraints of multi-activated tectonic events, affecting the Dien Bien Phu Fault using the K-Ar dating method for the gouge samples.

  11. Godot Üzerine Bir Karşılaştırma A Comparison On Godot Summary

    Directory of Open Access Journals (Sweden)

    Halil ADIYAMAN


    kurguda değişiklik yapmaz. Fakat ayrıntıya baktığımızda Beckett eserini Godot’yu bekleme üzerine kurarken Atay, Godot’yu beklerken çok da gerekli bir unsur olarak ele almaz. Atay’a göre beklense de olur beklenmese de; Beckett’da ise Godot kesinlikle beklenmesi gereken bir unsur olarak ele alınır. Her an gelmesi beklenen Godot etrafa korku salmaktadır. Ne olduğu, ne getireceği, ne götüreceği, nasıl bir tip olduğu belli değildir. Atay’da ise insani özellikler gösteren bir varlık olarak çizilir. Portresi çizilebilen bir varlık olsa da Atay’ın Godot’u da muğlak bir yapı ortaya koyar. Mekân açısından farklı unsurlar içeren eserlerde ortak mekân yabancı bir kişinin mülkü üzerine kuruludur. Özel anlamda ise farklı kültür ve medeniyet unsurlarını içerisinde barındıran iki eserde mekânlar farklılaşır. Atay, betonlaşan çevreye kadar günümüz meselelerine değinir. Şahıs Kadrosunda ise isim değişiklikleri yapılmakla birlikte karakterlerin ruh dünyası ve olaylar karşısındaki tutumu korunmuştur.

  12. Role of glutamatergic receptors located in the nucleus raphe magnus on antinociceptive effect of morphine microinjected into the nucleus cuneiformis of rat. (United States)

    Haghparast, Abbas; Soltani-Hekmat, Ava; Khani, Abbas; Komaki, Alireza


    Neurons in the nucleus cuneiformis (CnF), located just ventrolateral to the periaqueductal gray, project to medullary nucleus raphe magnus (NRM), which is a key medullary relay for descending pain modulation and is critically involved in opioid-induced analgesia. Previous studies have shown that antinociceptive response of CnF-microinjected morphine can be modulated by the specific subtypes of glutamatergic receptors within the CnF. In this study, we evaluated the role of NMDA and kainate/AMPA receptors that are widely distributed within the NRM on morphine-induced antinociception elicited from the CnF. Hundred and five male Wistar rats weighing 250-300 g were used. Morphine (10, 20 and 40 microg) and NMDA receptor antagonist, MK-801 (10 microg) or kainate/AMPA receptor antagonist, DNQX (0.5 microg) in 0.5 microl saline were stereotaxically microinjected into the CnF and NRM, respectively. The latency of tail-flick response was measured at set intervals (2, 7, 12, 17, 22, 27 min after microinjection) by using an automated tail-flick analgesiometer. The results showed that morphine microinjection into the CnF dose-dependently causes increase in tail-flick latency (TFL). MK-801 microinjected into the NRM, just 1 min before morphine injection into the CnF, significantly attenuated antinociceptive effects of morphine. On the other hand, DNQX microinjected into the NRM, significantly increased TFL after local application of morphine into the CnF. We suggest that morphine related antinociceptive effect elicited from the CnF is mediated, in part, by NMDA receptor at the level of the NRM whereas kainite/AMPA receptor has a net inhibitory influence at the same pathway.

  13. Systemic administration of kainic acid induces selective time dependent decrease in [{sup 125}I]insulin-like growth factor I, [{sup 125}I]insulin-like growth factor II and [{sup 125}I]insulin receptor binding sites in adult rat hippocampal formation

    Energy Technology Data Exchange (ETDEWEB)

    Quirion, R. [Department of Pharmacology and Therapeutics, McGill University, Montreal (Canada); Chabot, J.-G.; Dore, S. [Douglas Hospital Research Center, Department of Psychiatry, McGill University, Montreal (Canada); Seto, D. [Department of Pharmacology and Therapeutics, McGill University, Montreal (Canada); Kar, S. [Douglas Hospital Research Center, Department of Psychiatry, McGill University, Montreal (Canada)


    Administration of kainic acid evokes acute seizure in hippocampal pathways that results in a complex sequence of functional and structural alterations resembling human temporal lobe epilepsy. The structural alterations induced by kainic acid include selective loss of neurones in CA1-CA3 subfields and the hilar region of the dentate gyrus followed by sprouting and permanent reorganization of the synaptic connections of the mossy fibre pathways. Although the neuronal degeneration and process of reactive synaptogenesis have been extensively studied, at present little is known about means to prevent pathological conditions leading to kainate-induced cell death. In the present study, to address the role of insulin-like growth factors I and II, and insulin in neuronal survival as well as synaptic reorganization following kainate-induced seizure, the time course alterations of the corresponding receptors were evaluated. Additionally, using histological preparations, the temporal profile of neuronal degeneration and hypertrophy of resident astroglial cells were also studied. [{sup 125}I]Insulin-like growth factor I binding was found to be decreased transiently in almost all regions of the hippocampal formation at 12 h following treatment with kainic acid. The dentate hilar region however, exhibited protracted decreases in [{sup 125}I]insulin-like growth factor I receptor sites throughout (i.e. 30 days) the study. [{sup 125}I]Insulin-like growth factor II receptor binding sites in the hippocampal formation were found to be differentially altered following systemic administration of kainic acid. A significant decrease in [{sup 125}I]insulin-like growth factor II receptor sites was observed in CA1 subfield and the pyramidal cell layer of the Ammon's horn at all time points studied whereas the hilar region and the stratum radiatum did not exhibit alteration at any time. A kainate-induced decrease in [{sup 125}I]insulin receptor binding was noted at all time points in the

  14. LTP requires a reserve pool of glutamate receptors independent of subunit type. (United States)

    Granger, Adam J; Shi, Yun; Lu, Wei; Cerpas, Manuel; Nicoll, Roger A


    Long-term potentiation (LTP) of synaptic transmission is thought to be an important cellular mechanism underlying memory formation. A widely accepted model posits that LTP requires the cytoplasmic carboxyl tail (C-tail) of the AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptor subunit GluA1. To find the minimum necessary requirement of the GluA1 C-tail for LTP in mouse CA1 hippocampal pyramidal neurons, we used a single-cell molecular replacement strategy to replace all endogenous AMPA receptors with transfected subunits. In contrast to the prevailing model, we found no requirement of the GluA1 C-tail for LTP. In fact, replacement with the GluA2 subunit showed normal LTP, as did an artificially expressed kainate receptor not normally found at these synapses. The only conditions under which LTP was impaired were those with markedly decreased AMPA receptor surface expression, indicating a requirement for a reserve pool of receptors. These results demonstrate the synapse's remarkable flexibility to potentiate with a variety of glutamate receptor subtypes, requiring a fundamental change in our thinking with regard to the core molecular events underlying synaptic plasticity.

  15. Stimulation of glutamate receptors in the ventral tegmental area is necessary for serotonin-2 receptor-induced increases in mesocortical dopamine release (United States)

    Pehek, E.A.; Hernan, A.E.


    Modulation of dopamine (DA) released by serotonin-2 (5-HT2) receptors has been implicated in the mechanism of action of antipsychotic drugs. The mesocortical DA system has been implicated particularly in the cognitive deficits observed in schizophrenia. Agonism at 5-HT2A receptors in the prefrontal cortex is associated with increases in cortical DA release. Evidence indicates that 5-HT2A receptors in the cortex regulate mesocortical DA release through stimulation of a “long-loop” feedback system from the PFC to the VTA and back. However, a causal role for VTA glutamate in the 5-HT2-induced increases in PFC DA has not been established. The present study does so by measuring 5-HT2 agonist-induced DA release in the cortex after infusions of glutamate antagonists into the VTA. Infusions of a combination of a NMDA (AP-5: 2-amino-5-phosphopentanoic acid) and an AMPA/kainate (CNQX: 6-cyano-7-nitroquinoxaline-2,3-dione) receptor antagonist into the VTA blocked the increases in cortical DA produced by administration of the 5-HT2 agonist DOI [(±)-2,5-Dimethoxy-4-iodoamphetamine] (2.5 mg/kg s.c.). These results demonstrate that stimulation of glutamate receptors in the VTA is necessary for 5-HT2 agonist-induced increases in cortical DA. PMID:25637799

  16. Dataciones radiometricas (14C y K/Ar del Teide y el Rift noroeste, Tenerife, Islas Canarias

    Directory of Open Access Journals (Sweden)

    Hansen, A.


    unstable slopes of Teide, it took place without any apparent response of the volcano; on the contrary, these eruptions seemed to progressively buttress and enhance the stability of Teide Volcano. Conversely, the occurrence of these flank eruptions, combined with the Pico Viejo and NW rift eruptions, poses a very high lava-flow risk to the now densely populated areas in north and west Tenerife, which have been almost entirely resurfaced during the past 20,000 years.El Teide, el edificio volcánico más alto del planeta (3.718 m sobre el nivel del mar, > 7 km desde el fondo oceánico después del Mauna Loa y Mauna Kea en las islas Hawaii, forma un complejo volcánico en el centro de la isla de Tenerife. Su actividad eruptiva reciente (últimos 20 Ka está asociada con la rama NO del rift triple (120" que ha configurado la etapa reciente de construcción de la isla. La mayoría de las erupciones de Tenerife en este período se han localizado en estas estructuras volcánicas, generando frecuentes y extensas coladas máficas y félsicas, muchas alcanzado la costa e invadiendo lo que es ahora una de las zonas más densamente pobladas de Tenerife y, probablemente, de cualquier isla oceánica del planeta. Sin embargo, y a pesar de los numerosos estudios y proyectos previos, falta aún información geológica básica para este importante sistema volcánico, en particular la datación de las diferentes erupciones que lo componen, con objeto de reconstruir el marco geocronológico indispensable para conocer su evolución y determinar científicamente los riesgos volcánicos, de perentoria necesidad habida cuenta de su naturaleza y entidad, y de la población potencialmente afectada. Nuevas dataciones de Carbono-14 y K/Ar aportan ahora importante información a este respecto. La mayoría de las erupciones de los últimos 20 Ka no están relacionadas con el estratovolcán Teide, que sólo ha tenido una hace 1.240 f 60 años -entre 663 y 943 AD una vez calibrada la edad-, sino con el

  17. The Role of GluK4 in Synaptic Plasticity and Affective Behavior in Mice (United States)

    Catches, Justin Samuel

    Kainate receptors (KARs) are glutamate-gated ion channels that signal through both ionotropic and metabotropic pathways (Contractor et al., 2011). Combinations of five KAR subunits (GluK1-5) form tetrameric receptors with GluK1, GluK2, and GluK3 able to form functional homomeric channels. The high-affinity subunits, GluK4 and GluK5, do not form homomeric channels but modify the properties of heteromeric receptors. Expression of the GluK4 receptor subunit in the forebrain is restricted to the CA3 region of the hippocampus and dentate gyrus regions where KARs modulate synaptic plasticity. In this study, ablation of Grik4, which encodes GluK4, in mice reduced KAR synaptic currents and altered activation properties of postsynaptic receptors but left two forms of presynaptic short-term plasticity intact. Disruption of both Grik4 and Grik5 caused complete loss of the postsynaptic ionotropic KAR current and impaired presynaptic frequency facilitation. Additionally, KAR surface expression was altered at pre- and postsynaptic sites at the MF synapse. Despite the loss of ionotropic signaling, KAR-mediated inhibition of the slow afterhyperpolarization current, which is dependent on metabotropic signaling, was intact in CA3 neurons. Long-term potentiation at the MF-CA3 synapse was reduced, likely through a loss of KAR modulation of excitability of the presynaptic MF axons. Genetic variants in the human GRIK4 gene alter the susceptibility for affective disorders (Bloss and Hunter, 2010). We found that ablation of Grik4 in mice resulted in reduced anxiety and an antidepressant-like phenotype. In the elevated zero-maze, a test for anxiety and risk taking behavior, and in two anxiogenic tests, marble-burying and novelty-induced suppression of feeding, anxiety-like behavior was consistently reduced in knockout animals. In the forced swim, a test of learned helplessness used to determine depression-like behavior, knockout mice demonstrated significantly less immobility suggesting

  18. Akademisyen Ücretlerine İlişkin Karşılaştırmalı Bir Analiz A Comparative Analysis Concerned With Academic Salaries

    Directory of Open Access Journals (Sweden)

    Hilmi SÜNGÜ


    retilen hizmetin kalitesinin geliştirilmesi ile emeğin karşılığında elde edilen kazanç doğrudan ilişkili olarak görülmektedir. Benzer statülere sahip ve birbirine eşit sayılabilecek görevlerde çalışan bireylere orantılı ücretler verilmesi örgütsel adaletin bir gereğidir. Ancak kamuda; hizmetlerin çeşitliliği, çalışan sayısının fazlalığı, kurum sayısının çok olması gibi nedenler ücret dengesinin sağlanmasını güçleştirmektedir. Karşılaştırmalı çalışmalarda ücret adaletsizliğinden en çok etkilenen gruplardan birinin akademisyenler olduğu görülmektedir. Gelir adaletsizliğini ortadan kaldırmak ve cumhuriyetin kuruluşunun 100 yılında, 2023 vizyonuna ilişkin belirlenen iddialı hedeflere ulaşabilmek için yetenekli bireyleri akademisyenliğe özendirmek gerekmektedir. Ancak ulusal bazda kamu çalışanları arasında bir karşılaştırma yapıldığında üniversitede görev yapmakta olan öğretim elemanlarının özellikle son yıllarda diğer çalışanlara oranla yıllık ücret artışlarından yeterince yararlanamadığı, bu durumun akademisyenlik mesleğinden uzaklaşmalara neden olduğu öne sürülmektedir. Uluslararası bazda yapılan karşılaştırma yapıldığında ise, Türkiye’deki kamu üniversitelerinde görev yapmakta olan akademisyenlerin aldıkları ücretin ortalamaların altında olduğuna işaret edilmektedir. Bu çalışmada Türkiye’de kamu üniversitelerinde görev yapmakta olan akademisyenlerin aylık ücretlerinin mevcut durumuna ve yıllar içindeki değişimine yer verilecek, üniversite öğretim elemanlarının aylık ücretleri ve diğer kamu çalışanları arasında bu açıdan yapılan karşılaştırmalarla birlikte, Türkiye ile diğer ülkelerdeki üniversitelerde görev yapan akademisyenlerin aylık ücretleri mevcut durumu tartışılmaktadır.

  19. A toolkit for orthogonal and in vivo optical manipulationof ionotropic glutamate receptors

    Directory of Open Access Journals (Sweden)

    Joshua Todd Levitz


    Full Text Available The ability to optically manipulate specific neuronal signaling proteins with genetic precision paves the way for the dissection of their roles in brain function, behavior, and disease. Chemical optogenetic control with photoswitchable tethered ligands (PTLs enables rapid, reversible and reproducible activation or block of specific neurotransmitter-gated receptors and ion channels in specific cells. In this study, we further engineered and characterized the light-activated GluK2 kainate receptor, LiGluR, to develop a toolbox of LiGluR variants. Low-affinity LiGluRs allow for efficient optical control of GluK2 while removing activation by native glutamate, whereas variant RNA edited versions enable the synaptic role of receptors with high and low Ca2+ permeability to be assessed and spectral variant photoswitches provide flexibility in illumination. Importantly, we establish that LiGluR works efficiently in the cortex of awake, adult mice using standard optogenetic techniques, thus opening the door to probing the role of specific synaptic receptors and cellular signals in the neural circuit operations of the mammalian brain in normal conditions and in disease. The principals developed in this study are widely relevant to the engineering and in vivo use of optically controllable proteins, including other neurotransmitter receptors.

  20. Expression of functional neurotransmitter receptors in Xenopus oocytes after injection of human brain membranes (United States)

    Miledi, Ricardo; Eusebi, Fabrizio; Martínez-Torres, Ataúlfo; Palma, Eleonora; Trettel, Flavia


    The Xenopus oocyte is a very powerful tool for studies of the structure and function of membrane proteins, e.g., messenger RNA extracted from the brain and injected into oocytes leads to the synthesis and membrane incorporation of many types of functional receptors and ion channels, and membrane vesicles from Torpedo electroplaques injected into oocytes fuse with the oocyte membrane and cause the appearance of functional Torpedo acetylcholine receptors and Cl− channels. This approach was developed further to transplant already assembled neurotransmitter receptors from human brain cells to the plasma membrane of Xenopus oocytes. Membranes isolated from the temporal neocortex of a patient, operated for intractable epilepsy, were injected into oocytes and, within a few hours, the oocyte membrane acquired functional neurotransmitter receptors to γ-aminobutyric acid, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, kainate, and glycine. These receptors were also expressed in the plasma membrane of oocytes injected with mRNA extracted from the temporal neocortex of the same patient. All of this makes the Xenopus oocyte a more useful model than it already is for studies of the structure and function of many human membrane proteins and opens the way to novel pathophysiological investigations of some human brain disorders. PMID:12237406

  1. N-methyl-D-aspartate receptor blockade is neuroprotective in experimental autoimmune optic neuritis. (United States)

    Sühs, Kurt-Wolfram; Fairless, Richard; Williams, Sarah K; Heine, Katrin; Cavalié, Adolfo; Diem, Ricarda


    Optic neuritis is a common clinical manifestation of the chronic inflammatory CNS disease multiple sclerosis that can result in persistent visual impairment caused by degeneration of optic nerve axons and apoptosis of retinal ganglion cells (RGCs). Using a model of experimental autoimmune encephalomyelitis with optic neuritis (Brown Norway rats), we show that administration of the N-methyl-D-aspartate (NMDA) receptor antagonists memantine or MK801 results in RGC protection, axon protection, and reduced demyelination of optic nerves. Calcium imaging revealed that RGC responses to glutamate stimulation predominantly occurred via NMDA receptors and were inhibited by memantine in a dose-dependent manner. In contrast, oligodendrocytes were mainly responsive through the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/kainate receptor. This suggests that NMDA receptor blockade protected RGCs directly and that the protection was independent of effects on oligodendrocytes. Moreover, increased RGC survival was observed before the onset of optic nerve demyelination--when RGC degeneration had already started. These results indicate an important pathophysiologic role for NMDA receptor-mediated glutamate toxicity during the induction phase of this disease model and highlight a potential target for therapeutic neuroprotection in human optic neuritis.

  2. Two-photon brightness of azobenzene photoswitches designed for glutamate receptor optogenetics. (United States)

    Carroll, Elizabeth C; Berlin, Shai; Levitz, Joshua; Kienzler, Michael A; Yuan, Zhe; Madsen, Dorte; Larsen, Delmar S; Isacoff, Ehud Y


    Mammalian neurotransmitter-gated receptors can be conjugated to photoswitchable tethered ligands (PTLs) to enable photoactivation, or photoantagonism, while preserving normal function at neuronal synapses. "MAG" PTLs for ionotropic and metabotropic glutamate receptors (GluRs) are based on an azobenzene photoswitch that is optimally switched into the liganding state by blue or near-UV light, wavelengths that penetrate poorly into the brain. To facilitate deep-tissue photoactivation with near-infrared light, we measured the efficacy of two-photon (2P) excitation for two MAG molecules using nonlinear spectroscopy. Based on quantitative characterization, we find a recently designed second generation PTL, L-MAG0460, to have a favorable 2P absorbance peak at 850 nm, enabling efficient 2P activation of the GluK2 kainate receptor, LiGluR. We also achieve 2P photoactivation of a metabotropic receptor, LimGluR3, with a new mGluR-specific PTL, D-MAG0460. 2P photoswitching is efficiently achieved using digital holography to shape illumination over single somata of cultured neurons. Simultaneous Ca(2+)-imaging reports on 2P photoswitching in multiple cells with high temporal resolution. The combination of electrophysiology or Ca(2+) imaging with 2P activation by optical wavefront shaping should make second generation PTL-controlled receptors suitable for studies of intact neural circuits.

  3. Updates of the KArLE Experiment: New Libs Calibration Under High Vacuum for the Quantification of Potassium in Basalt for In Situ Geochronology (United States)

    Devismes, D.; Cohen, B. A.; Li, Z.-H.; Miller, J. S.


    In planetary exploration, in situ absolute geochronology is one of the main important measurements that needs to be accomplished. Until now, on Mars, the age of the surface is only determined by crater density counting, which gives relative ages. These ages can have a lot of uncertainty as they depend on many parameters. More than that, the curves must be ties to absolute ages. Thus far, only the lost lander Beagle 2 was designed to conduct absolute geochronology measurements, though some recent attempts using MSL Curiosity show that this investigation is feasible and should be strongly encouraged for future flight. Experimental: The Potassium (K)-Argon Laser Experiment (KArLE) is being developed at MSFC through the NASA Planetary Instrument Definition and Development Program (PIDDP). The goal of this experiment is to provide in situ geochronology based on the K-Ar method. A laser ablates a rock under high vacuum, creating a plasma which is sensed by an optical spectrometer to do Laser Induced Breakdown Spectroscopy (LIBS). The ablated material frees gases, including radiogenic 40Ar,which is measured by a mass spectrometer (MS). As the potassium is a content and the 40Ar is a quantity, the ablated mass needed in order to relate them. The mass is given by the product of the ablated volume by the density of this material. So we determine the mineralogy of the ablated material with the LIBS spectra and images and calculate its density. The volume of the pit is measured by using microscopy. LIBS measurement of K under high vacuum: Three independant projects [1, 2, 3] including KArLE, are developing geochronological instruments based on this LA-LIBS-MS method. Despite several differences in their setup, all of them have validated the methods with analyses and ages. However, they all described difficulties with the LIBS measurements of K [3,4]. At ambient pressure, the quantification of K by LIBS on geological materials can be accurate [5]. However the protocol of the LA

  4. Karşılaştırmalı Edebiyat Bilimi ve Karşılaştırmalı Bir Metin Tahlili Örneği Comparative Literature Science and an Example of Comparative Text Examination

    Directory of Open Access Journals (Sweden)

    Timuçin AYKANAT


    Full Text Available When doing a scientific study, several methods are used to get usefull data. This methods become theoretical due to their capacity to answer the needs and their practicality. One of important theories atsicience is comparative literature.Comparative literature science, becouse of its being systemic,proved its efficacy to give right results and be practical to many field.Theory of comparative literarture, in almost every branch of sciencewithin the scientific discipline can be used without goingdiscrimination. On the other hand, large-scale interdisciplinary study ofgeological researches that allow them to think and is an approach thatmakes the vast perspective. For his reason, this theory can be used inclassical literature as it is used at modern literature.In this article, first, comparative literature is introduced. Then,introductory in formation about the composers of text that will becompared is given. As a third step, frequently used images in text suchas twillight, night and sleep examined according to how they areperceived in the context of mythology, traditional culture, mysticism,religion and literature. In the light of all these, 13 poems-that havecommon elements-of 6 poets from diffirent centuries but at the sameroad, are comparatively examined according to their from and content.In the context of all these the result of this article is that, thecommonality of tradition, perception and sensation is beyond timeperiods, and even reaches after centuries. Bilimsel bir çalışma yapılırken, sağlıklı ve işe yarar veriler elde edebilmek amacıyla çeşitli metotlar uygulanır. Bu metotlar uygulanabilirliği ve istenilene cevap verebilme ölçütleri bağlamında zaman süreci içerisinde kuramsallaşır. Bilim âleminde yer edinen önemli kuramlardan biri de karşılaştırmalı edebiyattır. Karşılaştırmalı edebiyat bilimi, kendinde var olan sistemlilik sâyesinde birçok alanda uygulanabilirliğini ve doğru sonuçları ortaya

  5. K-Ar age and geochemistry of the SW Japan Paleogene cauldron cluster: Implications for Eocene-Oligocene thermo-tectonic reactivation (United States)

    Imaoka, T.; Kiminami, K.; Nishida, K.; Takemoto, M.; Ikawa, T.; Itaya, T.; Kagami, H.; Iizumi, S.


    Systematic K-Ar dating and geochemical analyses of Paleogene cauldrons in the Sanin Belt of SW Japan have been made to explore the relationship between the timing of their formation and the Paleogene subduction history of SW Japan documented in the Shimanto accretionary complex. We also examine the magma sources and tectonics beneath the backarc region of SW Japan at the eastern plate boundary of Eurasia. Fifty-eight new K-Ar ages and 19 previously reported radiometric age data show that the cauldrons formed during Middle Eocene to Early Oligocene time (43-30 Ma), following a period of magmatic hiatus from 52 to 43 Ma. The hiatus coincides with absence of an accretionary prism in the Shimanto Belt. Resumption of the magmatism that formed the cauldron cluster in the backarc was concurrent with voluminous influx of terrigenous detritus to the trench, as a common tectono-thermal event within a subduction system. The cauldrons are composed of medium-K calc-alkaline basalts to rhyolites and their plutonic equivalents. These rocks are characterized by lower concentrations of large ion lithophile elements (LILE) including K 2O, Ba, Rb, Th, U and Li, lower (La/Yb) n ratios, lower initial Sr isotopic ratios (0.7037-0.7052) and higher ɛNd( T) values (-0.5 to +3.5) relative to Late Cretaceous to Early Paleogene equivalents. There are clear trends from enriched to depleted signatures with decreasing age, from the Late Cretaceous to the Paleogene. The same isotopic shift is also confirmed in lower crust-derived xenoliths, and is interpreted as mobilization of pre-existing enriched lithospheric mantle by upwelling depleted asthenosphere. Relatively elevated geothermal gradients are presumed to have prevailed over wide areas of the backarc and forearc of the SW Japan arc-trench system during the Eocene to Oligocene. Newly identified Late Eocene low silica adakites and high-Mg andesites in the Sanin Belt and Early Eocene A-type granites in the SW Korea Peninsula probably formed

  6. Otizm Spektrum Bozukluğu Olan Çocuklarda Karşılıklı Taklit Eğitimi

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    Gökhan Töret


    Full Text Available Bu çalışmada, son yıllarda ilgili araştırmalar çerçevesinde Otizm Spektrum Bozukluğu (OSB olan çocuklara taklit becerileri eğitiminde etkili olduğu bildirilen Karşılıklı Taklit Eğitimi’nin (Reciprocal Imitation Training; Ingersoll, 2008 incelenmesi amaçlanmıştır. Çalışmada, ilk olarak Karşılıklı Taklit Eğitimi’ne (KTE ilişkin kuramsal çerçeveye yer verilmiş; ikinci olarak, KTE teknikleri ve uygulama adımları tanıtılmıştır. Üçüncü olarak ise OSB olan çocukların taklit becerileri edinim veya kendiliğinden kullanım düzeyleri üzerinde KTE’nin etkililiğini inceleyen ilgili araştırma bulguları sunularak alanyazın çerçevesinde tartışılmıştır. Dördüncü ve son olarak, alanyazın doğrultusunda, Türkiye’de OSB olan çocuklara taklit becerileri öğretimine yönelik araştırma ve uygulama önerilerinde bulunulmuştur. The purpose of this study was to examine in the scope of the recent literature the Reciprocal Imitation Training (Ingersoll, 2008, which was suggested to be effective in teaching imitation skills to children with Autism Spectrum Disorders (ASD. Firstly, theoretical foundations of Reciprocal Imitation Training (RIT are explained; secondly, RIT techniques and its implementation steps are introduced. Thirdly, findings of the related research which examines effectiveness of RIT on acquisition or spontaneous use of imitation skills of children with ASD were discussed. Lastly, suggestions for practitioners and for research about teaching imitation skills to children with ASD in Turkey are made in the direction of the current literature.

  7. Arapça ve İngilizce bağlaçların karşıtsal çözümleme yöntemiyle incelenmesi




    Çalışmamızda dilbilimin bir dalı olan karşıtsal çözümleme yönteminden hareketle Arapça ve İngilizcedeki bağlaçları inceledik. Karşıtsal çözümlemenin tanımıyla giriş yaptığımız çalışmamızın birinci bölümünde Arapçadaki bağlaçları, ikinci bölümünde ise İngilizcedeki bağlaçları ele aldık. Üçüncü bölümde iki dilin bağlaçları arasındaki benzerlik ve farklılıkları tespit ettik; bu farklılıklardan hareketle yabancı dil olarak İngilizce öğrenmek isteyen Arap öğrencilerin öğrenim sürecinde karşılaşmas...

  8. Organik ve Konvansiyonel Tüplü Asma Fidanı Üretim Uygulamalarının Ekonomik Karşılaştırması


    Uysal, Hulya; ATEŞ, Fadime


    Bu çalışmanın amacı organik ve konvansiyonel tüplü asma fidanı üretim maliyet ve karını hesaplamaktır. 2013–2015 üretim döneminde Manisa Bağcılık Araştırma Enstitüsü seralarında yapılan bu çalışma ile tüplü organik ve konvansiyonel asma fidanlarının dekara üretim maliyetlerinin karşılaştırılması yapılmıştır. Dekar bazında üretim maliyeti organik tüplü asma fidanında 19016.03 TL, konvansiyonel tüplü asma fidanında 17144.47 TL olarak belirlenmiştir. Dekara net kar organik tüplü asma fidanı için...

  9. Role of glutamate receptors and nitric oxide on the effects of glufosinate ammonium, an organophosphate pesticide, on in vivo dopamine release in rat striatum. (United States)

    Faro, Lilian R F; Ferreira Nunes, Brenda V; Alfonso, Miguel; Ferreira, Vania M; Durán, Rafael


    The purpose of the present work was to assess the possible role of glutamatergic receptors and nitric oxide (NO) production on effects of glufosinate ammonium (GLA), an organophosphate pesticide structurally related to glutamate, on in vivo striatal dopamine release in awake and freely moving rats. For this, we used antagonists of NMDA (MK-801 and AP5) or AMPA/kainate (CNQX) receptors, or nitric oxide synthase (NOS) inhibitors (l-NAME and 7-NI), to study the effects of GLA on release of dopamine from rat striatum. So, intrastriatal infusion of 10mM GLA significantly increased dopamine levels (1035±140%, compared with basal levels) and administration of GLA to MK-801 (250μM) or AP5 (650μM) pretreated animals, produced increases in dopamine overflow that were ∼40% and ∼90% smaller than those observed in animals not pretreated with MK-801 or AP5. Administration of GLA to CNQX (500μM) pretreated animals produced an effect that was not significantly different from the one produced in animals not pretreated with CNQX. On the other hand, administration of GLA to l-NAME (100μM) or 7-NI (100μM) pretreated animals, produced increases in dopamine overflow that were ∼80% and ∼75% smaller than those observed in animals not pretreated with these inhibitors. In summary, GLA appears to act, at least in part, through an overstimulation of NMDA (and not AMPA/kainate) receptors with possible NO production to induce in vivo dopamine release. Administration of NMDA receptor antagonists and NOS inhibitors partially blocks the release of dopamine from rat striatum.

  10. Siblings in Kars, Turkey, with Uner Tan syndrome (quadrupedal locomotion, severe mental retardation, and no speech): a novel theory for the evolution of human bipedalism. (United States)

    Tan, Uner


    To investigate siblings from Kars (n  =  2), Turkey, with diagonal-sequence quadrupedal locomotion (QL), severe mental retardation, and no speech (Uner Tan syndrome, UTS), in relation to the evolutionary emergence of human bipedal locomotion (BL). Video recordings were made to assess gaits. Brain MRI scanning was performed to visualize the cerebro-cerebellar malformations. Genome-wide association analyses were performed in venous blood samples. One of the two men with UTS showed early-onset QL and late-onset BL without infantile hypotonia, the other consistent QL with infantile hypotonia. No homozygosity was found in the genetic analysis. The family lived under extremely poor socioeconomic conditions. Low socioeconomic status may be a triggering factor for the epigenetic emergence of UTS. The neural networks responsible for the ancestral diagonal-sequence QL, evolutionarily preserved since about 400 MYA, may be selected during locomotor development, under the influence of self-organizing processes during pre- and postnatal periods. The diagonal-sequence QL induced ipsilateral limb interference in UTS cases as in nonhuman primates. To overcome this condition, our ancestors would prefer the attractor BL. This novel theory for the evolution of human bipedalism was evaluated in light of dynamical systems theory.

  11. Apocalissi e rovine: The Road di Cormac McCarthy e In the mood for love di Wong KarWai

    Directory of Open Access Journals (Sweden)

    Elisabetta Trincherini


    Full Text Available This article aims to analyze Cormac McCarthy's novel, The Road, and Wong Kar-wai's film, In the Mood for Love, in an attempt to compare Eastern and Western societies. The comparison between the novel and the film – each a product (and a reflection of Western and Eastern cultures, respectively – should also be traced to the dystopian element of the narrations, conceived as a study of the concept of "otherness": namely, the hypothetical transcendence of one's own cultural limits. This comparative approach aims to connect two seemingly different plots: the novel is apocalyptic science fiction, the film a love story. The common ground between the two pieces and the connection point to dwell upon, however, is the contemplation of ruin: lingering on the contemplation of the downfall, in both works diverts from the core of their narrative. With the space-time continuum thus blocked, a parallel and split reality forms.

  12. Chemical, petrographic, and K-Ar age data to accompany reconnaissance geologic strip map from Kingman to south of Bill Williams Mountain, Arizona

    Energy Technology Data Exchange (ETDEWEB)

    Arney, B.; Goff, F.; Eddy, A.C.


    As part of a reconnaissance mapping project, 40 chemical analyses and 13 potassium-argon age dates were obtained for Tertiary volcanic and Precambrian granitic rocks between Kingman and Bill Williams Mountain, Arizona. The dated volcanic rocks range in age from 5.5 +- 0.2 Myr for basalt in the East Juniper Mountains to about 25 Myr for a biotite-pyroxene andesite. The date for Picacho Butte, a rhyodacite in the Mt. Floyd volcanic field, was 9.8 +- 0.07 Myr, making it the oldest rhyodacite dome in that volcanic field. Dated rocks in the Fort Rock area range from 20.7 to 24.3 Myr. No ages were obtained on the Precambrian rocks. Compositionally, the volcanic rocks analyzed range from alkali basalt to rhyolite, but many rocks on the western side of the map area are unusually potassic. The granites chosen for analysis include syenogranite from the Hualapai Mountains, a muscovite granite from the Picacho Butte area, and two other granites. The chemical and K-Ar age data and petrographic descriptions included in this report accompany the reconnaissance geologic strip map published as LA-9202-MAP by Goff, Eddy, and Arney. 9 refs., 4 figs., 2 tabs.

  13. Petrología y edad K/Ar de diques relacionados a la Formación Oncán, sierra de Ambargasta, Santiago del Estero Petrology and K/Ar age of dikes related to Oncán Formation, Santiago del Estero

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    MJ Correa


    Full Text Available Al noroeste de la sierra de Ambargasta, Santiago del Estero, en las cercanías de los puestos El Remanso y El Simbolar, aflora un enjambre de diques longitudinales de orientación predominante nordeste-sudoeste. La edad obtenida de 483±14 Ma (K/Ar roca total permite considerar a esta unidad como representativa de la culminación del magmatismo originado durante la aproximación y posterior colisión del terreno Pampia con el cratón del Río de La Plata. La presente contribución contiene además datos geoquímicos y petrográficos de esta litología, cuyas características permitieron correlacionarlos con el Pórfido Riodacítico Oncán. Poseen una composición granítica levemente peraluminosa y características geoquímicas similares a los granitoides más evolucionados de la sierra de Ambargasta.At the northwest of Ambargasta range, Santiago del Estero, near El Remanso and El Simbolar villages, a swarm of longitudinal dikes with a predominant NE trend crops out. The obtained age of 483±14 Ma (K/Ar WR, allows to consider this unit representative of the end of the magmatism originated during the approximation and subsequent collision of the Pampia terrane with the Río de La Plata craton. Geochemical and petrographic data allowed to correlate these rocks with the Oncán Rhyodacitic Porphyry. The studied rocks have a granitic composition, lightly peraluminous and geochemical characteristics similar to the highly evolved granitoids from the Sierra de Ambargasta.

  14. Potentiation of NMDA receptor-mediated transmission in striatal cholinergic interneurons

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    Manfred eOswald


    Full Text Available Pauses in the tonic firing of striatal cholinergic interneurons (CINs emerge during reward-related learning in response to conditioning of a neutral cue. We have previously reported that augmenting the postsynaptic response to cortical afferents in CINs is coupled to the emergence of a cell-intrinsic afterhyperpolarisation (AHP underlying pauses in tonic activity. Here we investigated in a bihemispheric rat-brain slice preparation the mechanisms of synaptic plasticity of excitatory afferents to CINs and the association with changes in the AHP. We found that high frequency stimulation (HFS of commissural corticostriatal afferents from the contralateral hemisphere induced a robust long-term depression (LTD of postsynaptic potentials (PSP in CINs. Depression of the PSP of smaller magnitude and duration was observed in response to HFS of the ipsilateral white matter or cerebral cortex. In Mg2+-free solution HFS induced NMDA receptor-dependent potentiation of the PSP, evident in both the maximal slope and amplitude of the PSP. The increase in maximal slope corroborates previous findings, and was blocked by antagonism of either D1-like dopamine receptors with SCH23390 or D2-like dopamine receptors with sulpiride during HFS in Mg2+-free solution. Potentiation of the slower PSP amplitude component was due to augmentation of the NMDA receptor-mediated potential as this was completely reversed on subsequent application of the NMDA receptor antagonist AP5. HFS similarly potentiated NMDA receptor currents isolated by blockade of AMPA/kainate receptors with CNQX. The plasticity-induced increase in the slow PSP component was directly associated with an increase in the subsequent AHP. Thus plasticity of cortical afferent synapses is ideally suited to influence the cue-induced firing dynamics of CINs, particularly through potentiation of NMDA receptor-mediated synaptic transmission.

  15. K/Ar chronologies of tephra units from the Middle Jurassic Sundance, and Late Early Cretaceous Mowry and Shell Creek Formations, Big Horn Basin, WY (United States)

    Jiang, H.; Meyer, E. E.; Johnson, G. D.


    The Middle Jurassic Sundance and Late Early Cretaceous Shell Creek and Mowry Formations of the Big Horn Basin, Wyoming, contain an extensive record of altered tephra. These tephra are likely related to contemporary volcanic activity in the Sierra Nevada and various Coast Range terranes to the west and provide valuable chronometric control on the sedimentary record within a portion of the Sevier-aged and later Cordilleran foreland basin. In addition, several of these altered tephra (bentonites) provide a valuable economic resource. Despite the prominence of these strata across the basin, few isotopic ages have been reported to date. Here we present new K/Ar ages on biotite phenocrysts from those tephra occurrences as a chronometric check on samples that contained zircons with significant Pb loss, that preclude more precise U/Pb age determinations. A bulk biotite sample extracted from an altered tuff in the Lower Sundance Formation gives an age of 167.5 × 5 Ma. This tuff occurs just above a dinosaur track-bearing peritidal sequence. Bulk biotite ages from the lower Shell Creek Formation give an age of 100.3 × 3 Ma and are statistically indistinguishable from biotite grains dated at 103.1 × 3 Ma extracted from the economically important 'Clay Spur' bentonite found at the top of the Mowry Shale. This work provides important new chronometric constraints on a portion of the Medial Jurassic to Late Early Cretaceous stratigraphy of the Big Horn Basin, Wyoming, and may be useful in understanding the regional tectonics that helped shape the development of the Sevier foreland basin and Western Interior Seaway.

  16. Time Evolution of the Basse Terre Island (Guadeloupe, French West Indies) Effusive Volcanism from New K-Ar Cassignol-Gillot Ages. (United States)

    Samper, A.; Quidelleur, X.; Mollex, D.; Komorowski, J. C.; Boudon, G.


    Radiometric dating and geochemistry of effusive volcanics have been combined with geomorphological observations in order to provide a general evolution model of the volcanic island of Basse Terre, Guadeloupe (French West Indies). More than forty new Cassignol-Gillot K-Ar ages distributed within the entire island, together with the twenty ages (Blanc, 1983; Carlut et al., 2000) previously obtained with the same technique, makes the Guadeloupe Island the best place to study the evolution of volcanic processes within the Lesser Antilles Arc. Dating was performed on the carefully separated groundmass in order to avoid K loss due to weathering and excess argon carried by mafic minerals. Ages obtained are relatively younger than previously thought on Basse Terre and range from a few ka to 2.79+-0.04 Ma. When available, the paleomagnetic polarity of the dated flows agree with the GPTS and a very good coherence of ages is observed for each massif. Our results demonstrate the general north to south migration of volcanism through time. It correlates with the main volcanic stages previously identified. The 2.75 Ma Basal Complex, the 1.81+-0.03 _ 1.15+-0.02 Ma Septentrional Chain, the 1.02+-0.02 Ma _ 0.606+-0.02 Ma Axial Chain, the 442+-6 _ 207+-28 ka Mateliane _ Sans Toucher Complex and the basaltic andesites and andesites although a few basalt and dacite have also been dated. All of them are characterized by low MgO values (geochemical characteristics similar to that of the central islands of the Lesser Antilles arc. Within Basse Terre, geochemical characteristics are relatively constant through time, indicating no major change of volcanic processes during the whole subaerial activity. Finally the detailed chronological framework now available provides new constraints for estimating rates of edification and destruction at the island scale and, more generally, to help better understand the evolution of the still active Guadeloupe island Soufriere volcano.

  17. Common variants in the regulative regions of GRIA1 and GRIA3 receptor genes are associated with migraine susceptibility

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    Gianfrancesco Fernando


    Full Text Available Abstract Background Glutamate is the principal excitatory neurotransmitter in the central nervous system which acts by the activation of either ionotropic (AMPA, NMDA and kainate receptors or G-protein coupled metabotropic receptors. Glutamate is widely accepted to play a major role in the path physiology of migraine as implicated by data from animal and human studies. Genes involved in synthesis, metabolism and regulation of both glutamate and its receptors could be, therefore, considered as potential candidates for causing/predisposing to migraine when mutated. Methods The association of polymorphic variants of GRIA1-GRIA4 genes which encode for the four subunits (GluR1-GluR4 of the alpha-amino-3- hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA receptor for glutamate was tested in migraineurs with and without aura (MA and MO and healthy controls. Results Two variants in the regulative regions of GRIA1 (rs2195450 and GRIA3 (rs3761555 genes resulted strongly associated with MA (P = 0.00002 and P = 0.0001, respectively, but not associated with MO, suggesting their role in cortical spreading depression. Whereas the rs548294 variant in GRIA1 gene showed association primarily with MO phenotype, supporting the hypothesis that MA and MO phenotypes could be genetically related. These variants modify binding sites for transcription factors altering the expression of GRIA1 and GRIA3 genes in different conditions. Conclusions This study represents the first genetic evidence of a link between glutamate receptors and migraine.

  18. Hâlit Ziya Uşaklıgil'in ''Kar Yağarken'' Adlı Öyküsüne Yapısalcı Bir Yaklaşım A Structuralist Approach to Hâlit Ziya Uşaklıgil's Short Story "Kar Yağarken" (While It Snows

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    Yavuz Sinan ULU


    Full Text Available 20th century is admitted era of structuralism in the human sciences. Firstly, structuralism emerged in range of linguistic and completed the process of acquisition of a scientific identity in this field. Sometimes structuralism was adopted as a method in expression of fact, sometimes it also was described as doctrin or common tendency of diffrent groups. Structuralism, founded by F. de Saussure, is interested in structures and it aspecially researches on general institutes making these structures on. Structuralism has a tendency to degradefhenomans up to some parts of these institutes. Structuralism theoryaims at determining and describing frame of components thosegenerating a narration and detecting every component’s function in thewhole part. According to structuralism, every single component isvaluable and these components are like keys those provide to cross intodeep structure from surface based upon simultaneity.This paper includes an analysis of the short story "Kar Yağarken"belonging to one of the most significant novelists of Turkish LiteratureHalit Ziya Uşaklıgil in the way of structuralism. This story occupied inBir Şi'r-i Hayal which published in 1914. Key element of Uşaklıgil'sstoryies is love of child. Writer opens the children's world of doors toreader with sensibility which wring the hearts. "Kar Yağarken" is alsosuch a story. In the story that is about pathetic lifestory of a lonelyfoundling by the name of Sermed, his dilemmas, rat race, dreams andlots of facts more are symbolized by the means of person, place, time,object, scent, and emotion profile. Child heart flourishing by a fury coatis represented by Sermed. 20. yüzyıl, insan bilimlerinde yapısalcılık çağı olarak adlandırılır. Yapısalcılık, ilk kez dilbilim sahasında kendini göstermiş ve bilimsel bir kimlik kazanım sürecini bu alanda tamamlamıştır. Yapısalcılık, bazen olguları ifadede bir yöntem olarak benimsenmiş bazen de öğreti veya

  19. Osmanlı Devleti’nde Mevlevî Olmayanların Sikke Giymesine Karşı Alınan Önlemler

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    Serdar Ösen


    giymiş bir sürü insanla karşılaşmıştır. Esat Paşa’nın karşılaşmış olduğu bu durum karşısında ne tür tedbirlere başvurduğu, Konya’da Mevlevî sikkesine gösterilmiş olan bu rağbetin sebepleri, Mevlevî olmayanların sikke giymelerinin yasaklanması ve sikke imal eden ustaların denetim altına alınmasına isteğine kadar giden sürecin detayları bu çalışmanın konusunu oluşturmaktadır.Le port du sikke par les personnes non-mawlawîs et les mesures prises par l’Etat ottoman en face de cette situationRésuméGénéralement connu comme une pièce de monnaie, le sikke a différentes significations telles que le style, le droit, l’attitude et la décence. Il signifie aussi le chapeau que les mawlawîs portent sur leurs têtes. Le sikke appelé aussi ‘kulâh-i mawlawî’, a pris des formes différentes depuis du début de la Mawlawiyya jusqu’au 19. siècle. Les styles et les formes du sikke étaient différents selon ceux qui le portaient. Le port du sikke était surtout une affaire de mérite et de droit car il est un symbole du niveau spirituel des individus qui ont franchi les étapes soufies avec patience et succès. Du fait de cette valeur significative, on le portait en ayant une cérémonie en présence du maitre.Pendant le règne du sultan Mahmut II, lorsque Esat Pacha a été nommé gouverneur de Konya, après avoir été le gouverneur d’Adana, il a rencontré, dans ses contrôles dans les rues, beaucoup de gens qui portaient le sikke. Notre étude va se pencher sur les mesures prises par Esad Pacha au sujet du problème, les causes du port du sikke par plusieurs personnes, son interdiction pour les gens non-mawlawîs et le contrôle de ses producteurs.

  20. (S)-2-Amino-3-(3-hydroxy-7,8-dihydro-6H-cyclohepta[d]isoxazol-4-yl)propionic acid, a potent and selective agonist at the GluR5 subtype of ionotropic glutamate receptors. Synthesis, modeling, and molecular pharmacology

    DEFF Research Database (Denmark)

    Brehm, Lotte; Greenwood, Jeremy R; Hansen, Kasper B


    We have previously described (RS)-2-amino-3-(3-hydroxy-7,8-dihydro-6H-cyclohepta[d]isoxazol-4-yl)propionic acid (4-AHCP) as a highly effective agonist at non-N-methyl-d-aspartate (non-NMDA) glutamate (Glu) receptors in vivo, which is more potent than (RS)-2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl......, activated cloned AMPA receptor subunits GluR1o, GluR3o, and GluR4o with EC(50) values in the range 4.5-15 microM and the coexpressed kainate-preferring subunits GluR6 + KA2 (EC(50) = 6.4 microM). Compound 6, but not 7, proved to be a very potent agonist (EC(50) = 0.13 microM) at the kainate-preferring GluR5...... subunit, equipotent with (S)-2-amino-3-(5-tert-butyl-3-hydroxyisothiazol-4-yl)propionic acid [(S)-Thio-ATPA, 4] and almost 4 times more potent than (S)-2-amino-3-(5-tert-butyl-3-hydroxyisoxazol-4-yl)propionic acid [(S)-ATPA, 3]. Compound 6 thus represents a new structural class of GluR5 agonists...

  1. Full domain closure of the ligand-binding core of the ionotropic glutamate receptor iGluR5 induced by the high affinity agonist dysiherbaine and the functional antagonist 8,9-dideoxyneodysiherbaine

    DEFF Research Database (Denmark)

    Frydenvang, Karla Andrea; Lash, L Leanne; Naur, Peter


    The prevailing structural model for ligand activation of ionotropic glutamate receptors posits that agonist efficacy arises from the stability and magnitude of induced domain closure in the ligand-binding core structure. Here we describe an exception to the correlation between ligand efficacy...... and domain closure. A weakly efficacious partial agonist of very low potency for homomeric iGluR5 kainate receptors, 8,9-dideoxy-neodysiherbaine (MSVIII-19), induced a fully closed iGluR5 ligand-binding core. The degree of relative domain closure, ~30 degrees , was similar to that we resolved...... to inter-domain hydrogen bonds residues Glu441 and Ser721 in the iGluR5-S1S2 structure. The weaker interactions of MSVIII-19 with iGluR5 compared to DH, together with altered stability of the inter-domain interaction, may be responsible for the apparent uncoupling of domain closure and channel opening...

  2. A Presynaptic Glutamate Receptor Subunit Confers Robustness to Neurotransmission and Homeostatic Potentiation

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    Beril Kiragasi


    Full Text Available Homeostatic signaling systems are thought to interface with other forms of plasticity to ensure flexible yet stable levels of neurotransmission. The role of neurotransmitter receptors in this process, beyond mediating neurotransmission itself, is not known. Through a forward genetic screen, we have identified the Drosophila kainate-type ionotropic glutamate receptor subunit DKaiR1D to be required for the retrograde, homeostatic potentiation of synaptic strength. DKaiR1D is necessary in presynaptic motor neurons, localized near active zones, and confers robustness to the calcium sensitivity of baseline synaptic transmission. Acute pharmacological blockade of DKaiR1D disrupts homeostatic plasticity, indicating that this receptor is required for the expression of this process, distinct from developmental roles. Finally, we demonstrate that calcium permeability through DKaiR1D is necessary for baseline synaptic transmission, but not for homeostatic signaling. We propose that DKaiR1D is a glutamate autoreceptor that promotes robustness to synaptic strength and plasticity with active zone specificity.

  3. Somatostatin receptors

    DEFF Research Database (Denmark)

    Møller, Lars Neisig; Stidsen, Carsten Enggaard; Hartmann, Bolette


    therefore been acknowledged to be a third endogenous ligand at SRIF receptors. This review goes through mechanisms of signal transduction, pharmacology, and anatomical distribution of SRIF receptors. Structurally, SRIF receptors belong to the superfamily of G protein-coupled (GPC) receptors, sharing....... The generation of knock-out (KO) mice, intended as a means to define the contributions made by individual receptor subtypes, necessarily marks but an approximation. Furthermore, we must now take into account the stunning complexity of receptor co-operation indicated by the observation of receptor homo......-peptides, receptor agonists and antagonists. Relatively long half lives, as compared to those of the endogenous ligands, have been paramount from the outset. Motivated by theoretical puzzles or the shortcomings of present-day diagnostics and therapy, investigators have also aimed to produce subtype...

  4. Germination induction of dormant Avena fatua caryopses by KAR(1) and GA(3) involving the control of reactive oxygen species (H2O2 and O2(·-)) and enzymatic antioxidants (superoxide dismutase and catalase) both in the embryo and the aleurone layers. (United States)

    Cembrowska-Lech, Danuta; Koprowski, Marek; Kępczyński, Jan


    Avena fatua L. caryopses did not germinate at 20 °C in darkness because they were dormant. However, they were able to germinate in the presence of karrikinolide (KAR1), a key bioactive compound present in smoke, and also in the presence of gibberellin A3 (GA3), a commonly known stimulator of seed germination. The aim of this study was to collect information on a possible relationship between the above regulators and abscisic acid (ABA), reactive oxygen species (ROS) and ROS scavenging antioxidants in the regulation of dormant caryopses germination. KAR1 and GA3 caused complete germination of dormant A. fatua caryopses. Hydrogen peroxide (H2O2), compounds generating the superoxide (O2(·-)), i.e. menadione (MN), methylviologen (MV) and an inhibitor of catalase activity, aminotriazole (AT), induced germination of dormant caryopses. KAR1, GA3, H2O2 and AT decreased ABA content in embryos. Furthermore, KAR1, GA3, H2O2, MN, MV and AT increased α-amylase activity in caryopses. The effect of KAR1 and GA3 on ROS (H2O2, O2(·-)) and activities of the superoxide dismutase (SOD) and catalase (CAT) were determined in caryopses, embryos and aleurone layers. SOD was represented by four isoforms and catalase by one. In situ localization of ROS showed that the effect of KAR1 and GA3 was associated with the localization of hydrogen peroxide mainly on the coleorhiza. However, the superoxide was mainly localized on the surface of the scutellum. Superoxide was also detected in the protruding radicle. Germination induction of dormant caryopses by KAR1 and GA3 was related to an increasing content of H2O2, O2(·-)and activities of SOD and CAT in embryos, thus ROS homeostasis was probably required for the germination of dormant caryopses. The above regulators increased the content of ROS in aleurone layers and decreased the activities of SOD and CAT, probably leading to the programmed cell death. The presented data provide new insights into the germination induction of A. fatua dormant

  5. Antik Yunan Dönemi Karşılaştırmalı Siyaset Biliminde Siyasal Sistem Sınıflandırmalarına Genel bir Bakış

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    Nihat YILMAZ


    Full Text Available Siyaset Biliminin bir alt disiplini olarak karşılaştırmalı siyaset biliminin popülaritesi günümüzde gittikçe artmaktadır. Bu disiplin, farklı ülkelerin siyasal sistemleri hakkında detaylı bilgiler vermesinden dolayı fazlaca önemsenmektedir. Günümüzde ilginin giderek arttığı böyle bir alanın tarihsel geçmişi ise oldukça eski dönemlere dayanmaktadır. karşılaştırmalı siyaset bilimi alanında yapılan ilk siyasal sistem sınıflandırmaları Antik Yunan döneminde ortaya çıkmıştır. Bundan dolayı bu makalede, batı siyasal düşüncesi içerisinde yer alan Antik Yunan dönemindeki siyasal sistem sınıflandırmalarının bazı düşünürler bağlamında incelenmesi amaçlanmaktadır. Makalede, öncelikle temel kavramlar olan karşılaştırmalı siyaset bilimi ve siyasal sistem kavramlarına değinilmekte ve daha sonra Antik Yunan dönemi siyasal sistem sınıflandırmaları Heredotos, Platon ve Aristoteles örnekleri ile incelenmektedir.

  6. Dating low-grade metamorphism and deformation of the Espinhaço Supergroup in the Chapada Diamantina (Bahia, NE Brazil: a K/Ar fine-fraction study

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    Annette Süssenberger

    Full Text Available This study focuses on the northernmost part of the Mesoproterozoic Espinhaço Supergroup that crops out in the Chapada Diamantina. The fine-fraction K/Ar dating obtained on slightly metamorphosed sediments of the siliciclastic Espinhaço Supergroup shows a polyphase deformation history that corresponds to the Brasiliano (Pan-African orogenic cycle. The isotopic results are interpreted to indicate three age domains coincident with three structurally different domains. Constrained by the Kübler Index ('illite crystallinity' and illite polytypism, the thermal conditions generated during the tectonic activity show a gradual trend from the craton margins to the interior from epizonal to diagenetic. The northern Chapada Diamantina is situated in the foreland of the Riacho do Pontal belt and comprises the sediments of the Espinhaço Supergroup northeast of the Irecê basin. The K/Ar ages for < 2 µm illite fractions range between 645 and 621 Ma [mean 637±9 Ma (2s] and for < 0.2 µm fraction range between 625 and 603 Ma [mean 614±9 Ma (2s]. Samples from the central Chapada Diamantina east of the Irecê basin are not affected by a Brasiliano deformation event and therefore, the N-S-trending structures are assumed to be older. The deformation of the southern Chapada Diamantina was established in conjunction with the formation of the Araçuai orogenesis and the inversion and reactivation of the Paramirim impactogen. The last stage of deformation in this area is recorded by the K/Ar fine-fraction dating between 470 and 460 Ma.

  7. The chemokine growth-related gene product β protects rat cerebellar granule cells from apoptotic cell death through α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptors (United States)

    Limatola, Cristina; Ciotti, Maria Teresa; Mercanti, Delio; Vacca, Fabrizio; Ragozzino, Davide; Giovannelli, Aldo; Santoni, Angela; Eusebi, Fabrizio; Miledi, Ricardo


    Cultured cerebellar granule neurons are widely used as a cellular model to study mechanisms of neuronal cell death because they undergo programmed cell death when switched from a culture medium containing 25 mM to one containing 5 mM K+. We have found that the growth-related gene product β (GROβ) partially prevents the K+-depletion-induced cell death, and that the neuroprotective action of GROβ on granule cells is mediated through the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) type of ionotropic glutamate receptors. GROβ-induced survival was suppressed by 6-cyano-7-nitroquinoxaline-2,3-dione, which is a specific antagonist of AMPA/kainate receptors; it was not affected by the inhibitor of N-methyl-d-aspartate receptors, 2-amino-5-phosphonopentanoic acid, and was comparable to the survival of granule cells induced by AMPA (10 μM) treatment. Moreover, GROβ-induced neuroprotection was abolished when granule cells were treated with antisense oligonucleotides specific for the AMPA receptor subunits, which significantly reduced receptor expression, as verified by Western blot analysis with subunit-specific antibodies and by granule cell electrophysiological sensitivity to AMPA. Our data demonstrate that GROβ is neurotrophic for cerebellar granule cells, and that this activity depends on AMPA receptors. PMID:10811878


    Directory of Open Access Journals (Sweden)

    Yağmur KERSE


    Full Text Available Consumer ethnocentrism that is evaluated of suitability on moral grounds of buying foreign a product by consumers is important for understanding their purchasing preferences. The aim of this study is to research the effect of country of origin and socio-psychologic factors consist of cultural openness, collectivism/individualism, conservatism on consumer ethnocentrism. In the study, data were gathered through a survey technique from consumers in the city center of Kars and these data were analysed by using SPSS 18. According to analysis, there are impact of country of origin, collectivism/individualism and conservatism on consumer ethnocentrism.

  9. Inhibition of calcium-permeable and calcium-impermeable AMPA receptors by perampanel in rat brain neurons. (United States)

    Barygin, Oleg I


    Perampanel is an antiepileptic drug that is used to treat partial-onset seizures and generalized tonic-clonic seizures. It is a highly selective AMPA receptor allosteric antagonist. However, published data on perampanel activity vary in different studies. In the present work we studied the inhibition of native calcium-permeable and calcium-impermeable AMPA receptors in rat brain neurons by perampanel using whole-cell patch clamp technique. We found that inhibitory activity and kinetics of perampanel action do not differ between calcium-permeable AMPA receptors of rat giant striatum interneurons and calcium-impermeable receptors of hippocampal CA1 pyramidal neurons (the IC50 value about 60nM). Also, perampanel caused the same inhibition of steady-state currents induced by kainate and glutamate. From the other side perampanel-induced inhibition was markedly reduced in the presence of cyclothiazide (IC50 value increased to 1.2±0.2μM). We demonstrated that perampanel competes with GYKI-52466 for binding site. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  10. Cooling age of the Birimian juvenile crust in West Africa. U-Pb, Rb-Sr and K-Ar data on the 2. 1 Ga granite-greenstone terrains from SW-Niger. Age de refroidissement de la croute juvenile birimienne d'Afrique de l'Ouest. Donnees U-Pb, Rb-Sr et K-Ar sur les formations a 2. 1 Ga du SW-Niger

    Energy Technology Data Exchange (ETDEWEB)

    Lama, C.; Dautel, D.; Zimmermann, J.L. (Centre National de la Recherche Scientifique (CNRS), 54 - Nancy (France). Centre de Recherches Petrographiques et Geochimiques); Barbey, P. (Nancy-1 Univ., 54 (France)); Cheilletz, A. (Centre National de la Recherche Scientifique (CNRS), 54 - Nancy (France). Centre de Recherches Petrographiques et Geochimiques Ecole Nationale Superieure de Geologie Appliquee et de Prospection Miniere, 54 - Nancy (France)); Pons, J. (Orleans Univ., 45 (France))


    A comparison between zircon U-Pb, whole-rock Rb-Sr and biotite-amphibole K-Ar data on Birimian granite-greenstone terrains from SW-Niger indicates that the youngest granitic plutons were emplaced at 2.115 [+-] 5 Ma and that both the plutons and the surrounding greenstones yield cooling ages around 2.118 Ma. The age similarity between the end of the plutonism and the cooling of plutons and surrounding greenstone further suggests rapid cooling at the end of the plutonic event and, thus, corroborates a model of greenstone metamorphism linked to the thermal effect of the plutons. (authors).

  11. Sammas number kaks / Karli Luik

    Index Scriptorium Estoniae

    Luik, Karli, 1977-


    Eesti Kunstiakadeemia uue hoone arhitektuurikonkursi võidutöö "Art Plaza" (Taani arhitektuuribürood Sea ja Effekt) muudetud joonistest. Kadunud on hoonesisene avar avalik ruum ja alles on jäänud tihedad, sügavad, kitsaste pimedate koridoridega korrused

  12. Sammas number kaks / Karli Luik

    Index Scriptorium Estoniae

    Luik, Karli, 1977-


    Eesti Kunstiakadeemia uue hoone arhitektuurikonkursi võidutöö "Art Plaza" (Taani arhitektuuribürood Sea ja Effekt) muudetud joonistest. Kadunud on hoonesisene avar avalik ruum ja alles on jäänud tihedad, sügavad, kitsaste pimedate koridoridega korrused

  13. Blushes All Around / Karlis Streips

    Index Scriptorium Estoniae

    Streips, Karlis


    Ameerika Ühendriikide diplomaatide saladokumente avaldanud veebisaidist WikiLeaks. Autor tunneb rõõmu, et siiani pole avalikustatud ühtegi dokumenti selle kohta, et Läti oleks illegaalsetest või kahtlastest toimingutest osa võtnud

  14. Tanzimat Hareketleri Karşısında Aşık Seyrani Ashik Seyrânî Against Tanzimat (Reform Movements

    Directory of Open Access Journals (Sweden)

    Eyüp AKMAN


    ılları arasında yaşamıştır. Aslen Kayseri Develilidir. Hayatı boyunca üç padişah dönemi görmüştür. Bunlar III. Selim, II. Mahmut ve Abdülmecit dönemleridir. Özellikle son iki padişah dönemi, gençlik ve olgunluk dönemine rastlar. Seyrânî, II. Mahmut döneminde hız kazanan, Abdülmecit döneminde Tanzimat ve Islahat fermanlarıyla resmiyet kazanan yenileşme ve batılılaşama hareketlerine karşı halkın duygularına tercüman olmuş, toplumda gördüğü sosyal aksaklıkları ve çarpıklıkları padişahtan bile çekinmeden pervasızca dile getirmiştir. Seyrani, klasik edebiyatta hiciv, halk edebiyatında taşlama adını alan türde oldukça başarılıdır. Bu durum biraz da onun mizacıyla alakalıdır. İstanbul’a mesleğini icra etmek için gelen Seyrani, devrin her aşığı gibi saray aşıklarının arasına katılmayı arzu etmiştir. Fakat bu arzusu gerçekleşmemiştir. Bundan dolayı olsa gerek saray erkanını özellikle sadrazamları keskin bir dille hicvetmiştir. Seyrani’nin saraya karşı bu kadar sert tavır almasına başka bir sebep olarak da Yeniçeri teşkilatının kaldırılmasını gösterebiliriz. Bektaşiliğe meyilli olan Seyrani de diğer Bektaşi şairleri gibi bu teşkilatın kaldırılmasını kabullenememiş bundan dolayı saraya menfi tavır almıştır. Seyrani’nin şiirlerinde on dokuzuncu yüzyılın sosyal, ekonomik hayatını bulmak mümkündür. Özellikle Tanzimat ve Islahat hareketleri neticesinde ülkenin düştüğü durum, saray tarafından lüzumu olmaksızın yapılan sınırsız harcamalar, halkın yeniliklere ayak uyduramaması, bizzat padişahların bir batılı gibi davranması, kadıların rüşvet alarak adalet mekanizmasının çökmesi onun şiirlerinde hicvedilmiştir. Bu araştırmamızda Tanzimat hareketleri ve bunların halka nasıl yansıdığı Seyrânî’nin şiirlerinden hareketle anlatılacak ve dönem hakkında bazı değerlendirmelerde bulunulacaktır.

  15. Petrological and geochemical constraints on the origin of mafic dykes intruding the composite Kaçkar Pluton from the eastern Blacksea magmatic arc, NE Turkey (United States)

    Aydin, Faruk; Oguz, Simge; Baser, Rasim; Uysal, Ibrahim; Sen, Cüneyt; Karsli, Orhan; Kandemir, Raif


    Geological, petrographical and geochemical data of mafic dykes intruding the composite Kaçkar Pluton from the eastern Blacksea magmatic arc (EBMA), NE Turkey, provide new insights into the nature of the metasomatizing agents in subcontinental lithospheric mantle beneath the region during the late Mesozoic-early Tertiary. Mafic dykes from the Çaykara and Hayrat (Trabzon), and also Ikizdere (Rize) areas from the northern margin of the EBMA consist of basalts, dolerites, lamprophyres (basic member) and lesser basaltic andesites and trachyandesites (evolved member). All dykes have no deformation and metamorphism. The outcrops of these dykes vary, with thickness from 0.2 to 10 m. and visible length from 3 to 20 m. In general, the mafic dykes dip steeply and cut directly across the Kaçkar Pluton, and show NW- and NE-trending, roughly parallel to the orientations of the EBMA main faults. Most of the dyke samples display subaphyric to porphyritic texture with phenocrysts of plagioclase (up to 10%), clinopyroxene (5-20%), amphibole (5-15%), and some contain variable amount of biotite (5-20%), lesser quartz (1-2%), and minor euhedral zircon, apatite and Fe-Ti oxides. The basic members of the mafic dykes have SiO2 of 44.1-51.9%, MgO of 4.5-12.1%, and TiO2 >mostly 0.8% (up to 2.3%) with K2O+Na2O of 1.3-6.6% with mostly subalkaline character. They are relatively high in mg-number (0.45-0.73) and transition metals (V=171-376 ppm, Co=22-45 ppm, Ni=3-148 ppm, and Sc=21-49 ppm). The evolved members of the dykes exhibit relatively higher SiO2 (57.1-60.2%) and K2O+Na2O (5.6-9.0%), and lower MgO (2.2-5.9%) and TiO2 (0.5-0.8%) contents than those from the basic dykes. Also, these samples have slightly low mg-number (0.41-0.65) and transition metals (V=99-172 ppm, Co=9-22 ppm, Ni=1-43 ppm, and Sc=9-20 ppm). In the Harker diagrams, all samples of the mafic dykes form a continuous array, and exhibit similar geochemical characteristics. In general, SiO2 inversely correlates with MgO, Fe

  16. Alüminyum ve bakırın yüksek devirli sürtünme karıştırma kaynağında takım pozisyonunun etkisi


    Çakır, Recep; Çelik, Sare


    Sürtünme karıştırma kaynağı (SKK) aynı veya farklı cins malzemelerin birleştirilmesinde kullanılan katı hal birleştirme yöntemidir. Bu yöntem, ilk olarak ergitme kaynak teknikleri ile birleştirilmesinde zorluklarla karşılaşılan alüminyum alaşımlarının birleştirilmesinde kullanılmış olmakla beraber günümüzde farklı malzeme çiftlerinin başarılı bir şekilde birleştirilmesine de olanak vermektedir. Bu çalışmada, alüminyum (AA1050) ve bakır levhalar, ısı girdisini arttırmak amacı ile yüksek takım ...

  17. İsviçre’deki Minare Karşıtı Referandum Afişlerinde İslamofobi’nin Söylemsel İnşası


    Çebi, Murat Sadullah


    Bu çalışmada, İsviçre’de 29 Kasım 2009 tarihinde ülke çapında düzenlenmiş olan minare referandumu öncesi yürütülen siyasal kampanya boyunca, minare karşıtlarının kullandığı propaganda afişlerinin söylemi içinde şifrelenen İslamofobiye ilişkin ideolojik anlamların inşası analiz edilmiştir. Minare karşıtı referandum afişlerinin metni ve söylemi içinde inşa edilen İslamofobiye ilişkin ideolojik anlamların kökenleri, doğası ve unsurları, çalışmanın temel araştırma sorunsalı olarak belirlenmiştir....

  18. Palaeomagnetism and K-Ar and 40Ar/39Ar ages in the Ali Sabieh area (Republic of Djibouti and Ethiopia): constraints on the mechanism of Aden ridge propagation into southeastern Afar during the last 10 Myr (United States)

    Audin, L.; Quidelleur, X.; Coulié, E.; Courtillot, V.; Gilder, S.; Manighetti, I.; Gillot, P.-Y.; Tapponnier, P.; Kidane, T.


    A new detailed palaeomagnetic study of Tertiary volcanics, including extensive K-Ar and 40Ar/39Ar dating, helps constrain the deformation mechanisms related to the opening processes of the Afar depression (Ethiopia and Djibouti). Much of the Afar depression is bounded by 30 Myr old flood basalts and floored by the ca 2 Myr old Stratoid basalts, and evidence for pre-2 Ma deformation processes is accessible only on its borders. K-Ar and 40Ar/39Ar dating of several mineral phases from rhyolitic samples from the Ali Sabieh block shows indistinguishable ages around 20 Myr. These ages can be linked to separation of this block in relation to continental breakup. Different amounts of rotation are found to the north and south of the Holhol fault zone, which cuts across the northern part of the Ali Sabieh block. The southern domain did not record any rotation for the last 8 Myr, whereas the northern domain experienced approximately 12 +/- 9° of clockwise rotation. We propose to link this rotation to the counter-clockwise rotation observed in the Danakil block since 7 Ma. This provides new constraints on the early phases of rifting and opening of the southern Afar depression in connection with the propagation of the Aden ridge. A kinematic model of propagation and transfer of extension within southern Afar is proposed, with particular emphasis on the previously poorly-known period from 10 to 4 Ma.

  19. İhracatın İthalatı Karşılama Oranlarının Parçalı Regresyonlarla Modellenmesi / Modeling with Piecewise Regression of Ratios of Export to Import


    Genç, Aşır; Erkan OKTAY; Ömer ALKAN


    Özet: İhracat ve ithalat, bir ülkenin dış ticaretini oluşturur. Dış ticaret istatistiklerinebakılarak ülkenin ekonomik durumu hakkında değerlendirme yapılabilmektedir. Buistatistiklerden biri de ihracatın ithalatı karşılama oranıdır. Bu çalışmada Türkiye'nin1923-2010 yılları arası ihracatın ithalatı karşılama oranlarının yıllık değişimleri parçalıregresyonlarla incelenmiştir. Verilerin dağılım grafiğine bakıldığında 1923-2010 yıllarıarası ihracatın ithalatı k...

  20. Reviews CD-ROM: Scientific American—The Amateur Scientist 3.0 Book: The New Resourceful Physics Teacher Equipment: DynaKar Book: The Fundamentals of Imaging Book: Teaching Secondary Physics Book: Novel Materials and Smart Applications Equipment: Cryptic disk Web Watch (United States)


    WE RECOMMEND Scientific American—The Amateur Scientist 3.0 Article collection spans the decades DynaKar DynaKar drives dynamics experiments The Fundamentals of Imaging Author covers whole imaging spectrum Teaching Secondary Physics Effective teaching is all in the approach Novel Materials and Smart Applications/Novel materials sample pack Resources kit samples smart materials WORTH A LOOK Cryptic disk Metal disk spins life into discussions about energy, surfaces and kinetics HANDLE WITH CARE The New Resourceful Physics Teacher Book brings creativity to physics WEB WATCH Apps for tablets and smartphones can aid physics teaching

  1. Electrophysiological effects of kainic acid on vasopressin-enhanced green fluorescent protein and oxytocin-monomeric red fluorescent protein 1 neurones isolated from the supraoptic nucleus in transgenic rats. (United States)

    Ohkubo, J; Ohbuchi, T; Yoshimura, M; Maruyama, T; Ishikura, T; Matsuura, T; Suzuki, H; Ueta, Y


    The supraoptic nucleus (SON) contains two types of magnocellular neurosecretory cells: arginine vasopressin (AVP)-producing and oxytocin (OXT)-producing cells. We recently generated and characterised two transgenic rat lines: one expressing an AVP-enhanced green fluorescent protein (eGFP) and the other expressing an OXT-monomeric red fluorescent protein 1 (mRFP1). These transgenic rats enable the visualisation of AVP or OXT neurones in the SON. In the present study, we compared the electrophysiological responses of AVP-eGFP and OXT-mRFP1 neurones to glutamic acid in SON primary cultures. Glutamate mediates fast synaptic transmission through three classes of ionotrophic receptors: the NMDA, AMPA and kainate receptors. We investigated the contributions of the three classes of ionotrophic receptors in glutamate-induced currents. Three different antagonists were used, each predominantly selective for one of the classes of ionotrophic receptor. Next, we focused on the kainate receptors (KARs). We examined the electrophysiological effects of kainic acid (KA) on AVP-eGFP and OXT-mRFP1 neurones. In current clamp mode, KA induced depolarisation and increased firing rates. These KA-induced responses were inhibited by the non-NMDA ionotrophic receptor antagonist 6-cyano-7-nitroquinoxaline-2,3(1H4H)-dione in both AVP-eGFP and OXT-mRFP1 neurones. In voltage clamp mode, the application of KA evoked inward currents in a dose-dependent manner. The KA-induced currents were significantly larger in OXT-mRFP1 neurones than in AVP-eGFP neurones. This significant difference in KA-induced currents was abolished by the GluK1-containing KAR antagonist UBP302. At high concentrations (250-500 μm), the specific GluK1-containing KAR agonist (RS)-2-amino-3-(3-hydroxy-5-tert-butylisoxazol-4-yl) propanoic acid (ATPA) induced significantly larger currents in OXT-mRFP1 neurones than in AVP-eGFP neurones. Furthermore, the difference between the AVP-eGFP and OXT-mRFP1 neurones in the ATPA currents

  2. Molecular lock regulates binding of glycine to a primitive NMDA receptor. (United States)

    Yu, Alvin; Alberstein, Robert; Thomas, Alecia; Zimmet, Austin; Grey, Richard; Mayer, Mark L; Lau, Albert Y


    The earliest metazoan ancestors of humans include the ctenophore Mnemiopsis leidyi The genome of this comb jelly encodes homologs of vertebrate ionotropic glutamate receptors (iGluRs) that are distantly related to glycine-activated NMDA receptors and that bind glycine with unusually high affinity. Using ligand-binding domain (LBD) mutants for electrophysiological analysis, we demonstrate that perturbing a ctenophore-specific interdomain Arg-Glu salt bridge that is notably absent from vertebrate AMPA, kainate, and NMDA iGluRs greatly increases the rate of recovery from desensitization, while biochemical analysis reveals a large decrease in affinity for glycine. X-ray crystallographic analysis details rearrangements in the binding pocket stemming from the mutations, and molecular dynamics simulations suggest that the interdomain salt bridge acts as a steric barrier regulating ligand binding and that the free energy required to access open conformations in the glycine-bound LBD is largely responsible for differences in ligand affinity among the LBD variants.

  3. Glutamate and GABA activate different receptors and Cl(-) conductances in crab peptide-secretory neurons. (United States)

    Duan, S; Cooke, I M


    Responses to rapid application of glutamic acid (Glu) and gamma-aminobutyric acid (GABA), 0.01-3 mM, were recorded by whole-cell patch clamp of cultured crab (Cardisoma carnifex) X-organ neurons. Responses peaked within 200 ms. Both Glu and GABA currents had reversal potentials that followed the Nernst Cl(-) potential when [Cl(-)](i) was varied. A Boltzmann fit to the normalized, averaged dose-response curve for Glu indicated an EC(50) of 0.15 mM and a Hill coefficient of 1.05. Rapid (t(1/2) approximately 1 s) desensitization occurred during Glu but not GABA application that required >2 min for recovery. Desensitization was unaffected by concanavalin A or cyclothiazide. N-methyl-D-aspartate, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, quisqualate, and kainate (to 1 mM) were ineffective, nor were Glu responses influenced by glycine (1 microM) or Mg(2+) (0-26 mM). Glu effects were imitated by ibotenic acid (0.1 mM). The following support the conclusion that Glu and GABA act on different receptors: 1) responses sum; 2) desensitization to Glu or ibotenic acid did not diminish GABA responses; 3) the Cl(-)-channel blockers picrotoxin and niflumic acid (0.5 mM) inhibited Glu responses by approximately 90 and 80% but GABA responses by approximately 50 and 20%; and 4) polyvinylpyrrolydone-25 (2 mM in normal crab saline) eliminated Glu responses but left GABA responses unaltered. Thus crab secretory neurons have separate receptors responsive to Glu and to GABA, both probably ionotropic, and mediating Cl(-) conductance increases. In its responses and pharmacology, this crustacean Glu receptor resembles Cl(-)-permeable Glu receptors previously described in invertebrates and differs from cation-permeable Glu receptors of vertebrates and invertebrates.

  4. Mechanisms of calcium influx into hippocampal spines: heterogeneity among spines, coincidence detection by NMDA receptors, and optical quantal analysis. (United States)

    Yuste, R; Majewska, A; Cash, S S; Denk, W


    Dendritic spines receive most excitatory inputs in the vertebrate brain, but their function is still poorly understood. Using two-photon calcium imaging of CA1 pyramidal neurons in rat hippocampal slices, we investigated the mechanisms by which calcium enters into individual spines in the stratum radiatum. We find three different pathways for calcium influx: high-threshold voltage-sensitive calcium channels, NMDA receptors, and an APV-resistant influx consistent with calcium-permeable AMPA or kainate receptors. These pathways vary among different populations of spines and are engaged under different stimulation conditions, with peak calcium concentrations reaching >10 microM. Furthermore, as a result of the biophysical properties of the NMDA receptor, the calcium dynamics of spines are exquisitely sensitive to the temporal coincidence of the input and output of the neuron. Our results confirm that individual spines are chemical compartments that can perform coincidence detection. Finally, we demonstrate that functional studies and optical quantal analysis of single, identified synapses is feasible in mammalian CNS neurons in brain slices.

  5. „Słownik wyrazów obcego a mniej jasnego pochodzenia…” Jana Karłowicza – wyrazem wiedzy i zamiłowań lituanistycznych autora

    Directory of Open Access Journals (Sweden)

    Kristina Rutkovska


    Full Text Available Dictionary of Foreign Words of the Less Known Origin by Jan Karłowicz – an Expression of Knowledge and Lithuanistic Tastes of Author The object of the description in the article is Lithuanian lexicon occurring in the Dictionary of foreign words of the less known origin (EWS composed by Jan Karłowicz, who was involved in the multifaceted research on the Lithuanian language and culture – he studied the Lithuanian dialect, local names, and initiated research on Lithuanian folklore. He also published materials from Lithuania (ethnographic descriptions, folklore and language descriptions of the Samogitian nobility in the Wisla, previously editing them and adding comments in the text to the Lithuanian vocabulary. His onomastic collections as well as the study About the Lithuanian Language have been rediscovered by Lithuanian linguists who devoted a separate study to them. Solid knowledge of comparative linguistics and his own experience in research the Lithuanian language and culture, work with Lithuanian printed materials, hand­written or derived from field studies in Lithuania, allowed him to use the knowledge and materials in very different ways. Next to words analyzed in the EWS, he included the words of Lithuanian origin and next – Slavic borrowings of Lithuanian dialects, thereby contributing indirectly to the study of foreign lexis in the Lithuanian dia­lects. A similar historic-linguistic interpretation was acceptable in those days when the methodology of etymological research was just developing and every manifestation of language was worth documenting. Karłowicz’s EWS is very important for researchers of the Baltic-Slavic border. He detected a significant part of the Lithuanian lexicon and, more broadly – regional lexicon in intensive Slavic-Lithuanian relations. The greater part of Lithuanianisms was recorded in the mid-nineteenth century, when peasants in Lithuania started massive convertions to the Polish language. At the

  6. Fenobarbital Uygulamasında Intravenöz ve Intraosseöz Yolların Karşılaştırılması


    Dündaröz, Ruşen; Çalışkaner, A.Zafer; Türkbay, Tümer; Sızlan, Ali; Değim, Tuncer; Gök, Faysal; Özışık, Tahir


    SüleymanDemirel Üniversitesi TIP FAKÜLTESİ DERGİSİ: 1999 Aralık; 6(4) Fenobarbital Uygulamasında Intravenöz ve Intraosseöz Yolların Karşılaştırılması Ruşen Dündaröz, Turner Türkbay, Ali Sızlan, Tuncer Değim, Faysal Gök, Tahir Özışık Özet Status epileptikus klasik olarak 30 dakikadan uzun süren jenaralize tonik-klonik nöbet olarak tarif edilir. Uzun süren nöbet aktivitesi irreversibl serebral hasar ile sonuçlanabilir. Üstelik, nöbet aktivitesinin uzun sürme...

  7. Use of combined Hartree–Fock–Roothaan theory in evaluation of lowest states of $K[Ar]4s^0 3d^1$ and $Cr^+ [Ar]4s^0 3d^5$ isoelectronic series over noninteger -Slater type orbitals

    Indian Academy of Sciences (India)

    I I Guseinov; M Erturk; E Sahin


    By using noninteger n-Slater type orbitals in combined Hartree–Fock–Roothaan method, self-consistent field calculations of orbital and lowest states energies have been performed for the isoelectronic series of open shell systems $K[Ar]4s^0 3d^1 ({}^2D) (Z = 19–30)$ and $Cr^+[Ar]4s^0 3d^5 ({}^6 S) (Z = 24–30)$. The results of the calculations for the orbital and total energies obtained by using minimal basis-sets of noninteger -Slater type orbitals are given in the tables. The results are compared with the extended-basis Hartree–Fock computations. The orbital and total energies are in good agreement with those presented in the literature. The results can be useful in the study of various properties of heavy atomic systems when the combined Hartree–Fock–Roothaan approach is employed.

  8. Bazı arpa genotiplerinin Drechslera teres f. maculata(Smed.-Pet., 1971)'ya karşı fide dönemi reaksiyonlarının belirlenmesi


    AKTAŞDOĞAN, Duygu; KARAKAYA, Aziz; ÇELİK OĞUZ, Arzu; MERT, Zafer; SAYİM, İsmail; ERGÜN, Namuk; AYDOĞAN, Sinan


    Üç arpa çeşidinin, 2 arpa çeşit adayının ve 20 ileri kademe arpa hattının Drechslera teres f. maculata (Smed.-Pet., 1971)'nın Sivas ve Eskişehir illerinden elde edilmiş iki izolatına karşı sera koşullarında fide dönemi reaksiyonları belirlenmiştir. Bülbül 89 çeşidi Sivas izolatına orta derecede hassas-hassas reaksiyon gösterirken Eskişehir izolatına orta derecede hassas reaksiyon göstermiştir. Avcı 2002 çeşidi her iki izolata da dayanıklı-orta derecede dayanıklı reaksiyon göstermiştir. Aydanh...

  9. Algumas idades Rb-Sr e K-Ar de rochas granitóides da região de Vilarinho da Castanheira-Foz do Sabor (Carrazeda de Anciães-Nordeste de Portugal)


    Silva, Antero Ferreira da; KAWASHITA,KOJI


    Neste trabalho apresentam-se algumas determinações isotópicas Rb/Sr e K/Ar de idades absolutas em rochas granitóides do antiforma de Alijó-Carviçais, correspondente à região es-sudeste de Carrazeda de Anciães (Vilarinho da Castanheira-Foz do Sabor). A rocha total de duas amostras dos granitos de Castedo-Cabanas de Cima e Zêdes-Cabeça Boa-Especiarias, indiferenciados localmente, proporcionaram as idades convencionais Rb/Sr de 361.1±23.8 e 404.7±22.3M.a., com razão inicial (87Sr/86S...

  10. K-Ar dating of late Mesozoic volcanism and geochemistry of volcanic gravels in the North Huaiyang Belt, Dabie orogen: Constraints on the stratigraphic framework and exhumation of the northern Dabie orthogneiss complex

    Institute of Scientific and Technical Information of China (English)


    Two eruption episodes are identified through systematic field investigations and K-Ar dating of the lateMesozoic volcanic rocks in the North Huaiyang belt (NHB),Dabie orogenic belt, of which the earlier volcanic suitetermed Maotanchang Fm. (Fm.) occurring at Jinzhai,Xianhualing and Maotanchang, etc., was erupted from 149Ma to 138 Ma. The other named Xiaotian Fm. mainly dis-tributed at Xiaotian, Shucheng, etc., was formed between132 Ma and 116 Ma. During the eruption gap of the two vol-canic suites deposited a volcano-sedimentary conglomeratelayer, which are composed of the multi-compositional gravels, including the North Dabie orthogneiss complex (NDOC),volcanic gravels, etc. These volcanic gravels in the con-glomerate layer show identical geochemical and isotopic compositions (87Sr/86Sr(t) =0.7084-0.7092, (Nd (t) = 21.8-24.4) to the Maotanchang Fm. volcanic rocks (87Sr/86Sr = 0.7086-0.7102, (Nd = 19.2-24.4), but significantly distinct from those of Xiaotian Fm. (87Sr/86Sr = 0.7076-0.7084, (Nd = 17.2 - 19.2). K-Ar dating results of its underlying andoverlying volcanic sequences indicate that the conglomerate layers were deposite d at ~135 Ma. This suggests that the NDOC was rapidly exhumed to the surface dur ing or shortly before ~135 Ma and became the important provenance of the late Me sozoic volcano-sedimentary basins in the NHB. In combination with the regional v olcano-sedimentary correlation, we divided the Mesozoic stratigraphic sequence i n the NHB from base to top into Fanghushan Fm. (>160 Ma), Yuantongshan Fm. (/mid dle- lower segment of Sanjianpu Fm.) (160-149 Ma), Maotanchang Fm. (/Zhougongsh an Fm./upper segment of Sanjianpu Fm./Fenghuangtai Fm.) (149-135 Ma) and Xiaoti an Fm. (/Baidafan Fm./Heshidu Fm.) (135-116 Ma).

  11. Cloning and Transformation of BCsp Gene of S.involucrata Kir.%天山雪莲根边缘细胞特异蛋白BCsp基因的克隆及转化

    Institute of Scientific and Technical Information of China (English)

    阴志刚; 祝建波


    根据石河子大学农业生物技术重点实验室天山雪莲cDNA文库单克隆测序结果,发现编号为123的单克隆具有1个843 bp的完整的ORF,编码281个氨基酸.Blastx分析表明该.DNA编码的蛋白与豌豆根边缘细胞特异蛋白具有很高的同源性,且具有相同的结构域,命名为 BCsp(暂无登录).以.DNA文库单克隆为模板,通过PCR克隆得到BCs p.以中间载体pUCCRNAi和植物表达载体pCAM2300-35S-Ocs为基础,成功构建了植物RNAi表达载体pCAB,转化天山雪莲愈伤组织获得转基因雪莲苗.%The monoclonal numbered 123 contain a 843 bp of the complete ORF encoding 281 amino acids under the result of S. involucrata Kar. et Kir. monoclonal cDNA library sequencing. The protein encoded from this cDNA was analyzed with Blastx software and it was highly homologous and had the same domain with the root border cell-specific protein of Pisum sativum , this cDNA was named BCsp. The BCsp gene was cloned from cDNA library by PCR. The plant siRNA expression vector pCAB was constructed based on the vectors pUCCRNAi and pCAM2300-35S-Ocs and thus it was made to express itself in plants. The transgenic S. involucrata Kar. et Kir. was obtained.

  12. Modern Dünya ve Ölüm : Batılının Ölüm Karşısında Tavırları

    Directory of Open Access Journals (Sweden)

    Adem Sağır


    Full Text Available Ariés’in çalışması aslında basit bir “ölüm sosyolojisi” demesidir. Philippe Ariés’in “ölüm” bağlamında hazırlamış olduğu ve ölümün toplumsal tarihini ele alan çalışması “Batılının Ölüm Karşısındaki Tavırları” geçmişten bugüne değişen ölüm biçimlerini odağa yerleştirmesi bakımından sosyolojik bir niteliğe sahiptir. Kitap, “evcilleştirilmiş ölüm, insanın kendi ölümü, senin ölümün ve yasaklanmış ölüm” başlıklarından oluşmaktadır. Bölümlerin her biri, Batı’nın geçmişten başlayarak ölüm karşısındaki takındığı tavrı betimlemektedir. Çalışmanın asıl bağlamı ise “yasaklanan ölüm” başlığında modern toplumun ölümü hayatından çıkartmak için verdiği çabanın resmedilmesidir.

  13. Mineralogical, chemical and K-Ar isotopic changes in Kreyenhagen Shale whole rocks and <2 μm clay fractions during natural burial and hydrous-pyrolysis experimental maturation (United States)

    Clauer, N.; Lewan, M. D.; Dolan, M. P.; Chaudhuri, S.; Curtis, J. B.


    Progressive maturation of the Eocene Kreyenhagen Shale from the San Joaquin Basin of California was studied by combining mineralogical and chemical analyses with K-Ar dating of whole rocks and bearing minerals of the rocks. The Al/K ratio of the naturally matured rocks is essentially constant for the entire depth sequence, indicating that there is no detectable variation in the crystallo-chemical organization of the K-bearing alumino-silicates with depth. No supply of K from outside of the rock volumes occurred, which indicates a closed-system behavior for it. Conversely, the content of the total organic carbon (TOC) content decreases significantly with burial, based on the progressive increasing Al/TOC ratio of the whole rocks. The initial varied mineralogy and chemistry of the rocks and their sources and depositional settings give scattered results that homogenize progressively during burial due to increased authigenesis, and concomitant increased alteration of the detrital material. Hydrous pyrolysis was intended to alleviate the problem of mineral and chemical variations in initially deposited rocks of naturally matured sequences. However, experiments on aliquots from thermally immature Kreyenhagen Shale outcrop sample did not mimic the results from naturally buried samples. Experiments conducted for 72 h at temperatures from 270 to 365 °C did not induce significant changes at temperatures above 310 °C in the mineralogical composition and K-Ar ages of the rock and heated the most at 365 °C for 216 h. This slight decrease in age outlines some loss of radiogenic 40Ar, together with losses of organic matter as oil, gas, and aqueous organic species. Large amounts of smectite layers in the illite-smectite mixed layers of the pyrolyzed outcrop source rock, the pore system is no longer wetted by water and smectite to illite conversion ceases. Experimental attempts to evaluate the smectite conversion to illite should preferentially use low-TOC rocks to avoid

  14. Cretaceous-Cenozoic tectonic history of the Jiaojia Fault and gold mineralization in the Jiaodong Peninsula, China: constraints from zircon U-Pb, illite K-Ar, and apatite fission track thermochronometry (United States)

    Deng, Jun; Wang, Changming; Bagas, Leon; Carranza, Emmanuel John M.; Lu, Yongjun


    The Jiaojia Fault (JJF) in the Jiaodong area of eastern China is an important NNE-trending structure that is subsidiary to the regional Tancheng-Lujiang (Tan-Lu) Fault Zone, and hosts >1200 t of gold reserves contained in disseminated and stockwork ore, dominantly in the footwall of the fault. We present new zircon U-Pb, apatite fission track, and illite K-Ar data along the JJF and have delineated its tectonic history focusing on its formation and reactivation. Zircon U-Pb dating shows that the Shangzhuang granite is a composite body with ages between 132 ± 1 and 127 ± 1 Ma. Illite K-Ar ages for the fault's gouge range from 83 ± 2 to 68 ± 2 Ma, and the measured apatite fission track ages for ores are between 55 and 21 Ma. Previous zircon U-Pb geochronology and structural studies suggest that the JJF was originally activated in the Jurassic during 160-150 Ma as a sinistral fault. The JJF was a normal fault in the Early Cretaceous due to NW-SE orientated tension and NE-SW compression, which lasted from 135 to 120 Ma. This was followed by sinistral strike-slip faulting due to NW-SE compression and NE-SW tension during 120-110 Ma, and it changed to normal displacement at ca. 110 Ma. Our apatite fission track data analysis and thermal modeling of representative samples suggest that there was a subsequent dextral reactivation of the fault at ca. 55 Ma. Previous age data of ca. 130-110 Ma for gold mineralization along the JJF coincides with the Early Cretaceous magmatism and is coeval with the transition from normal faulting to sinistral strike-slip faulting of the JJF in Early Cretaceous, which is interpreted to be due to changing direction of the subducting Pacific Plate.

  15. DCP-LA stimulates AMPA receptor exocytosis through CaMKII activation due to PP-1 inhibition. (United States)

    Kanno, Takeshi; Yaguchi, Takahiro; Nagata, Tetsu; Tanaka, Akito; Nishizaki, Tomoyuki


    The linoleic acid derivative 8-[2-(2-pentyl-cyclopropylmethyl)-cyclopropyl]-octanoic acid (DCP-LA) activated Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) by inhibiting protein phosphatase-1 (PP-1). DCP-LA induced a transient huge facilitation of synaptic transmission monitored from the CA1 region of rat hippocampal slices, which was largely inhibited by the CaMKII inhibitor KN-93. DCP-LA potentiated kainate-evoked whole-cell membrane currents for Xenopus oocytes expressing alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors composed of the GluR1, GluR3, GluR1/GluR2, GluR1/GluR3, and GluR1/GluR2/GluR3 subunits, and the potentiation was significantly inhibited by KN-93. A similar potentiation was still found with mutant GluR1 (S831A) receptor lacking CaMKII phosphorylation site. The GluR1 and GluR2 subunits formed AMPA receptors in the rat hippocampus, and DCP-LA increased expression of both the subunits on the plasma membrane. The DCP-LA action was blocked by KN-93 and the exocytosis inhibitor botulinum toxin type A, but not by the endocytosis inhibitor phenylarsine oxide. DCP-LA, thus, appears to activate CaMKII through PP-1 inhibition, that stimulates AMPA receptor exocytosis to increase expression of the receptors on the plasma membrane, responsible for potentiate AMPA receptor responses and facilitation of hippocampal synaptic transmission.

  16. Lipoxin Receptors

    Directory of Open Access Journals (Sweden)

    Mario Romano


    Full Text Available Lipoxins (LXs represent a class of arachidonic acid (AA metabolites that carry potent immunoregulatory and anti-inflammatory properties, LXA4 and LXB4 being the main components of this series. LXs are generated by cooperation between 5-lipoxygenase (LO and 12- or 15-LO during cell-cell interactions or by single cell types. LX epimers at carbon 15, the 15-epi-LXs, are formed by aspirin-acetylated cyclooxygenase-2 (COX-2 in cooperation with 5-LO. 15-epi-LXA4 is also termed aspirin-triggered LX (ATL. In vivo studies with stable LX and ATL analogs have established that these eicosanoids possess potent anti-inflammatory activities. A LXA4 receptor has been cloned. It belongs to the family of chemotactic receptors and clusters with formyl peptide receptors on chromosome 19. Therefore, it was initially denominated formyl peptide receptor like 1 (FPRL1. This receptor binds with high affinity and stereoselectivity LXA4 and ATL. It also recognizes a variety of peptides, synthetic, endogenously generated, or disease associated, but with lower affinity compared to LXA4. For this reason, this receptor has been renamed ALX. This review summarizes the current knowledge on ALX expression, signaling, and potential pathophysiological role. The involvement of additional recognition sites in LX bioactions is also discussed.

  17. K-Ar ages of igneous activity in the Amakusa area, Kumamoto prefecture: an investigation of Miocene magmatic activity in the Inner and Outer Zone of Kyushu, southwestern Japan; Kumamotoken Amakusa chiiki no kasei katsudo no K-Ar nendai to Kyushu naitai gaitai ni okeru chushinsei magma katsudo no renji no hikaku

    Energy Technology Data Exchange (ETDEWEB)

    Hamasaki, S. [Geological Survey of Japan, Tsukuba (Japan)


    The timing of igneous activity in the Amakusa area, the most southern part of the Inner Zone of Kyushu, was determined on two samples by K-Ar age dating (quartz porphyry: 16.7{+-}0.3 Ma, granodiorite: 14.6{+-}0.3 Ma). These and previous ages indicate that Miocene felsic igneous activity and continuous mafic igneous activity, composed of high Mg andesite, occurred between 19 and 14 Ms. Basalt activity took place at 10 and 7 Ma. The felsic and mafic igneous activity occurred intermittently at 1-3 m.y. intervals in the Amakusa area. Miocene igneous activity was protracted more than 5 m.y. in the Amakusa area and also elsewhere in the Inner Zone of Kyushu, for example, Tsushima (19-14 Ma), Goto (20-7 Ma) and Koshikijima (15-7 Ma). In contrast the ages of Miocene igneous activity in the Outer Zone of Kyushu extend for only about 2 m.y., around 15-13 Ma, which indicates that the range of Miocene magmatic activity in the Inner Zone of Kyushu was longer than that in the Outer Zone. It is possible that different styles of magmatic activity occurred during the Miocene in the Inner and Outer Zone of Kyushu, i.e. back-arc and fore-arc tectonic settings, respectively. In the back-arc area the upper lithosphere expanded, became thin and fractured as a result of being pulled by the subducted lithosphere. After that magma front the asthenosphere ascended intermittently along the cracks in the fractured upper lithosphere, which caused extensive and intermittent magmatic activity. This is one possible explanation why Miocene magmatic activity is protracted in the Inner Zone which was a back-arc area. The Miocene magmatic activity in the Tsushima and Goto area started at 20-18 Ma, which is almost the same time when the Sea of Japan opened. It maybe that a large amount of magmatic activity was associated with the opening of the Sea of Japan at about 20 Ma in the region of the Sea of Japan, Oki, Tsushima and Goto. Magmatic activity in the Goto and Koshikijima

  18. H/KDEL receptors mediate host cell intoxication by a viral A/B toxin in yeast (United States)

    Becker, Björn; Blum, Andrea; Gießelmann, Esther; Dausend, Julia; Rammo, Domenik; Müller, Nina C.; Tschacksch, Emilia; Steimer, Miriam; Spindler, Jenny; Becherer, Ute; Rettig, Jens; Breinig, Frank; Schmitt, Manfred J.


    A/B toxins such as cholera toxin, Pseudomonas exotoxin and killer toxin K28 contain a KDEL-like amino acid motif at one of their subunits which ensures retrograde toxin transport through the secretory pathway of a target cell. As key step in host cell invasion, each toxin binds to distinct plasma membrane receptors that are utilized for cell entry. Despite intensive efforts, some of these receptors are still unknown. Here we identify the yeast H/KDEL receptor Erd2p as membrane receptor of K28, a viral A/B toxin carrying an HDEL motif at its cell binding β-subunit. While initial toxin binding to the yeast cell wall is unaffected in cells lacking Erd2p, binding to spheroplasts and in vivo toxicity strongly depend on the presence of Erd2p. Consistently, Erd2p is not restricted to membranes of the early secretory pathway but extends to the plasma membrane where it binds and internalizes HDEL-cargo such as K28 toxin, GFPHDEL and Kar2p. Since human KDEL receptors are fully functional in yeast and restore toxin sensitivity in the absence of endogenous Erd2p, toxin uptake by H/KDEL receptors at the cell surface might likewise contribute to the intoxication efficiency of A/B toxins carrying a KDEL-motif at their cytotoxic A-subunit(s). PMID:27493088

  19. Presynaptic facilitation of glutamate release in the basolateral amygdala: a mechanism for the anxiogenic and seizurogenic function of GluK1 receptors. (United States)

    Aroniadou-Anderjaska, V; Pidoplichko, V I; Figueiredo, T H; Almeida-Suhett, C P; Prager, E M; Braga, M F M


    Kainate receptors containing the GluK1 subunit (GluK1Rs; previously known as GluR5 kainate receptors) are concentrated in certain brain regions, where they play a prominent role in the regulation of neuronal excitability, by modulating GABAergic and/or glutamatergic synaptic transmission. In the basolateral nucleus of the amygdala (BLA), which plays a central role in anxiety as well as in seizure generation, GluK1Rs modulate GABAergic inhibition via postsynaptic and presynaptic mechanisms. However, the role of these receptors in the regulation of glutamate release, and the net effect of their activation on the excitability of the BLA network are not well understood. Here, we show that in amygdala slices from 35- to 50-day-old rats, the GluK1 agonist (RS)-2-amino-3-(3-hydroxy-5-tert-butylisoxazol-4-yl) propanoic acid (ATPA) (300 nM) increased the frequency of spontaneous excitatory postsynaptic currents (sEPSCs) and miniature EPSCs (mEPSCs) recorded from BLA principal neurons, and decreased the rate of failures of evoked EPSCs. The GluK1 antagonist (S)-1-(2-amino-2-carboxyethyl)-3-(2-carboxybenzyl) pyrimidine-2,4-dione (UBP302) (25 or 30 μM) decreased the frequency of mEPSCs, reduced evoked field potentials, and increased the "paired-pulse ratio" of the field potential amplitudes. Taken together, these results suggest that GluK1Rs in the rat BLA are present on presynaptic terminals of principal neurons, where they mediate facilitation of glutamate release. In vivo bilateral microinjections of ATPA (250 pmol) into the rat BLA increased anxiety-like behavior in the open field test, while 2 nmol ATPA induced seizures. Similar intra-BLA injections of UBP302 (20 nmol) had anxiolytic effects in the open field and the acoustic startle response tests, without affecting pre-pulse inhibition. These results suggest that although GluK1Rs in the rat BLA facilitate both GABA and glutamate release, the facilitation of glutamate release prevails, and these receptors can have an

  20. Opioid Receptors. (United States)

    Stein, Christoph


    Opioids are the oldest and most potent drugs for the treatment of severe pain. Their clinical application is undisputed in acute (e.g., postoperative) and cancer pain, but their long-term use in chronic pain has met increasing scrutiny. This article reviews mechanisms underlying opioid analgesia and other opioid actions. It discusses the structure, function, and plasticity of opioid receptors; the central and peripheral sites of analgesic actions and side effects; endogenous and exogenous opioid receptor ligands; and conventional and novel opioid compounds. Challenging clinical situations, such as the tension between chronic pain and addiction, are also illustrated.

  1. Anticonvulsant effect of AMP by direct activation of adenosine A1 receptor. (United States)

    Muzzi, Mirko; Coppi, Elisabetta; Pugliese, Anna Maria; Chiarugi, Alberto


    Purinergic neurotransmission mediated by adenosine (Ado) type 1 receptors (A1Rs) plays pivotal roles in negative modulation of epileptic seizures, and Ado is thought to be a key endogenous anticonvulsant. Recent evidence, however, indicates that AMP, the metabolic precursor of Ado, also activate A1Rs. Here, we evaluated the antiepileptic effects of AMP adopting in vitro and in vivo models of epilepsy. We report that AMP reversed the increase in population spike (PS) amplitude and the decrease in PS latency induced by a Mg(2+)-free extracellular solution in CA1 neurons of mouse hippocampal slices. The AMP effects were inhibited by the A1R antagonist DPCPX, but not prevented by inhibiting conversion of AMP into Ado, indicating that AMP inhibited per se sustained hippocampal excitatory neurotransmission by directly activating A1Rs. AMP also reduced seizure severity and mortality in a model of audiogenic convulsion. Of note, the anticonvulsant effects of AMP were potentiated by preventing its conversion into Ado and inhibited by DPCPX. When tested in a model of kainate-induced seizure, AMP prolonged latency of convulsions but had no effects on seizure severity and mortality. Data provide the first evidence that AMP is an endogenous anticonvulsant acting at A1Rs.

  2. 5-Hydroxytryptamine1A receptor-activation hyperpolarizes pyramidal cells and suppresses hippocampal gamma oscillations via Kir3 channel activation. (United States)

    Johnston, April; McBain, Chris J; Fisahn, André


    Rhythmic cortical neuronal oscillations in the gamma frequency band (30-80 Hz, gamma oscillations) have been associated with cognitive processes such as sensory perception and integration, attention, learning, and memory. Gamma oscillations are disrupted in disorders for which cognitive deficits are hallmark symptoms such as schizophrenia and Alzheimer's disease.In vitro, various neurotransmitters have been found to modulate gamma oscillations. Serotonin(5-HT) has long been known to be important for both behavioural and cognitive functions such as learning and memory. Multiple 5-HT receptor subtypes are expressed in the CA3 region of the hippocampus and high doses of 5-HT reduce the power of induced gamma oscillations.Hypothesizing that 5-HT may have cell- and receptor subtype-specific modulatory effects, we investigated the receptor subtypes, cell types and cellular mechanisms engaged by 5-HT in the modulation of gamma oscillations in mice and rats. We found that 5-HT decreases the power of kainate-induced hippocampal gamma oscillations in both species via the 5-HT1A receptor subtype. Whole-cell patch clamp recordings demonstrated that this decrease was caused by a hyperpolarization of CA3 pyramidal cells and a reduction of their firing frequency, but not by alteration of inhibitory neurotransmission. Finally, our results show that the effect on pyramidal cells is mediated via the G protein-coupled receptor inwardly rectifying potassium channel Kir3.Our findings suggest this novel cellular mechanism as a potential target for therapies that are aimed at alleviating cognitive decline by helping the brain to maintain or re-establish normal gamma oscillation levels in neuropsychiatric and neurodegenerative disorders.

  3. Bilgisayar ortamında bireye uyarlanmış test stratejilerinin karşılaştırılması [A comparison of computerized adaptive testing strategies

    Directory of Open Access Journals (Sweden)

    Fatih KEZER


    Full Text Available Bu araştırmada, bilgisayar ortamında bireye uyarlanmış test (BOBUT yöntemi ile geleneksel kâğıt kalem test yönteminin karşılaştırılması ve BOBUT yöntemine ilişkin farklı stratejilerin karşılaştırılması amaçlanmıştır. Temel araştırma modelindeki araştırmanın verileri, Ankara Üniversitesi Yabancı Diller Yüksekokulu bünyesinde, hazırlık sınıfında öğrenim görmekte olan toplam 1166 öğrenciden toplanmıştır. Farklı stratejilerin karşılaştırılması amacıyla R programı ile simülatif veriler de oluşturulmuştur. Araştırmada veri toplama aracı olarak İngilizce Kelime Testi kullanılmıştır. BOBUT uygulamalarının yapılabilmesi için araştırmacı tarafından bir çevrimiçi ortam geliştirilmiştir. Araştırma sonucunda, çevrimiçi ortam kullanılarak yapılan bireye uyarlanmış test uygulamasında, kâğıt kalem testine göre madde sayılarında büyük oranda tasarruf sağlandığı saptanmıştır. Bireye uyarlanmış ve kâğıt kalem test uygulamalarından elde edilen yetenek parametreleri arasında da pozitif yönde yüksek korelâsyon katsayıları bulunmuştur. Farklı stratejiler ve kağıt kalem testinden elde edilen yetenek parametreleri arasında pozitif yönde yüksek korelasyon katsayıları bulunarak, araştırma kapsamında ele alınan 18 farklı strateji ile kağıt kalem testlerinin çok benzer yetenek parametrelerinin kestirildiği ortaya konmuştur. Aynı şekilde farklı stratejiler ile kestirilen yetenek parametrelerinin kendi aralarında pozitif yönde yüksek korelasyon katsayıları elde edilmiştir. Sonlandırma kuralları dikkate alındığında, farklı stratejilerden elde edilen yetenek kestirimlerinin gerek kağıt kalem testinden elde edilen yetenek parametreleri ile arasında gerekse kendi aralarında en düşük korelasyon katsayılarının sonlandırma kuralı olarak standart hatanın 0.50’den küçük olması durumunda elde edildiği saptanm

  4. Homojen Karışımlı Sıkıştırma Ateşlemeli (HCCI bir motorun tek-bölgeli modelleme yöntemi kullanılarak analizi

    Directory of Open Access Journals (Sweden)

    Halit Yaşar


    Full Text Available HCCI motorların modellenmesinde sıfır-boyutlu modeller yaygın olarak kullanılmaktadır. Bu modeller tek veya çok bölge içerebilirler. Bununla birlikte, en basit yaklaşım yanmış ve yanmamış gazı içeren tek bölge yaklaşımıdır. Bu tip sıfır-boyutlu modellerde yanma olayı Wiebe fonksiyonu ile modellenmektedir. Bu makalede, HCCI prensibine göre çalışan tek silindirli bir Ricardo Hydra motoru tek bölge yaklaşımı kullanılarak modellenmiştir. Analiz çalışmalarında SPICE (Simulated Petrol Internal Combustion Engine yazılımının modifiye edilmiş bir versiyonu olan TRICE yazılımı kullanılmıştır. Yanma analizlerinde, HCCI yanma modellerinde standart Wiebe fonksiyonu kullanımının maksimum silindir basıncının yüksek olarak tahmin edilmesi sonucunu doğurması nedeniyle, standart Wiebe fonksiyonunun modifiye edilmiş bir şekli olan Double-Wiebe fonksiyonu kullanılmıştır. Analizler, n-Heptan-Toluen karışımı için üç hava fazlalık katsayısı değerinde gerçekleştirilmiş ve elde edilen sonuçlar bir Avrupa Komisyonu Marie Curie destek programı (FP-6 projesi kapsamında Shell Araştırma Merkezine ait motor test laboratuvarında ölçülen deneysel verilerle karşılaştırılmıştır.

  5. Üç Boyutlu Sanal Dünyalarda Öğretim Materyalleri Geliştiren Tasarımcıların Karşılaştıkları Sorunlar

    Directory of Open Access Journals (Sweden)



    Full Text Available Özet: Üç boyutlu (3B sanal dünya platformlarının eğitim-öğretim sürecinde başarılı bir şekilde kullanılabilmesi ve yaygınlaşabilmesi için bu platformların sınırlılıklarının ve yaşanması muhtemel sorunlarının daha açık belirlenmesi gerekir. Bu araştırmanın amacı da; 3B sanal dünyalarda öğretim materyalleri geliştiren tasarımcıların karşılaştıkları sorunları belirlemeye çalışmaktır. Araştırmada öğretim tasarımcısı adayları (ÖTA bir eğitim-öğretim dönemi boyunca 3B Open Sim ortamında öğretim materyalleri tasarlamış ve geliştirmişlerdir. Süreçte veri toplama aracı olarak; yarı yapılandırılmış görüşme rehberi, tasarım görüntüleri ve iletişim ortamı olarak kullanılan Facebook kayıtları kullanılmıştır. Araştırmadan elde edilen veriler nitel araştırma yöntemleri kullanılarak betimlenmeye çalışılmıştır. Geliştirme sürecinde öğretim tasarımcısı adayları 3B Open Sim yazılımıyla ilgili yeterince Türkçe kaynak bulamadıklarını, teknik ve donanımsal sorunlarla karşılaştıklarını belirtmişlerdir. Anahtar sözcükler: Sanal dünyalar, 3B Open Simülatör (Open Sim, öğretim materyali, materyal tasarımı.

  6. The negative effects of alcohol hangover on high-anxiety phenotype rats are influenced by the glutamate receptors of the dorsal midbrain. (United States)

    Ezequiel Leite, L; Nobre, M J


    Alcoholism is a chronic disorder characterized by the appearance of a withdrawal syndrome following the abrupt cessation of alcohol intake that includes symptoms of physical and emotional disturbances, anxiety being the most prevalent symptom. In humans, it was shown that anxiety may increase the probability of relapse. In laboratory animals, however, the use of anxiety to predict alcohol preference has remained difficult. Excitatory amino acids as glutamate have been implicated in alcohol hangover and may be responsible for the seizures and anxiety observed during withdrawal. The dorsal periaqueductal gray (DPAG) is a midbrain region critical for the modulation/expression of anxiety- and fear-related behaviors and the propagation of seizures induced by alcohol withdrawal, the glutamate neurotransmission being one of the most affected. The present study was designed to evaluate whether low- (LA) and high-anxiety rats (HA), tested during the alcohol hangover phase, in which anxiety is the most prevalent symptom, are more sensitive to the reinforcing effects of alcohol when tested in a voluntary alcohol drinking procedure. Additionally, we were interested in investigating the main effects of reducing the excitatory tonus of the dorsal midbrain, after the blockade of the ionotropic glutamate receptors into the DPAG, on the voluntary alcohol intake of HA and LA motivated rats that were made previously experienced with the free operant response of alcohol drinking. For this purpose, we used local infusions of the N-metil D-Aspartato (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-kainate receptors antagonist DL-2-Amino-7-phosphonoheptanoic acid - DL-AP7 (10 nmol/0.2 μl) and l-glutamic acid diethyl ester - GDEE (160 nmol/0.2 μl), respectively. Alcohol intoxication was produced by 10 daily bolus intraperitonial (IP) injections of alcohol (2.0 g/kg). Peak-blood alcohol levels were determined by gas-chromatography analysis in order to assess blood

  7. Üreter taşlarının üreteroskopik tedavisinde pnömotik ve ultrasonik litotriptörlerin karşılaştırılması: Randomize ve prospektif bir çalışma

    National Research Council Canada - National Science Library

    ÜÇGÜL, Yusuf E; GÜRDAL, Mesut; KAYIGİL, Önder; AĞRAŞ, Koray; ALDEMİR, Mustafa


    ... litotriptörün üreter taşlarında kullanımının diğer litotriptörlerle karşılaştırıldığı prospektif çalışma bulunmamaktadır. Çalışmamızda üreter taşlarının tedavisinde...

  8. Expression of human epileptic temporal lobe neurotransmitter receptors in Xenopus oocytes: An innovative approach to study epilepsy (United States)

    Palma, Eleonora; Esposito, Vincenzo; Mileo, Anna Maria; Di Gennaro, Giancarlo; Quarato, Pierpaolo; Giangaspero, Felice; Scoppetta, Ciriaco; Onorati, Paolo; Trettel, Flavia; Miledi, Ricardo; Eusebi, Fabrizio


    Poly(A+) RNA was extracted from the temporal lobe (TL) of medically intractable epileptic patients which underwent surgical TL resection. Injection of this mRNA into Xenopus oocytes led to the expression of ionotropic receptors for γ-aminobutyric acid (GABA), kainate (KAI) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA). Membrane currents elicited by GABA inverted polarity at −15 mV, close to the oocyte's chloride equilibrium potential, were inhibited by bicuculline, and were potentiated by pentobarbital and flunitrazepam. These basic characteristics were also displayed by GABA currents elicited in oocytes injected with mRNAs isolated from human TL glioma (TLG) or from mouse TL. However, the GABA receptors expressed by the epileptic TL mRNA exhibited some unusual properties, consisting in a rapid current run-down after repetitive GABA applications and a large EC50 (125 μM). AMPA alone evoked very small or nil currents, whereas KAI induced larger currents. Nevertheless, upon cyclothiazide treatment, AMPA elicited substantial currents that, like the KAI currents, were inhibited by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). Furthermore, the glutamate receptor 5 (GluR5) agonist, ATPA, failed to evoke an obvious current although both RT-PCR and Western blot analyses showed GluR5 expression in the epileptic TL. Oocytes injected with mouse TL or human TLG mRNAs generated KAI and AMPA currents similar to those evoked in oocytes injected with epileptic TL mRNA but, in contrast to these, the mouse TL and human TLG oocytes were also responsive to ATPA. Our findings are in accord with the concept that both a depression of GABA inhibition and a dysfunction of the KAI-receptor system maintain a high neuronal excitability that results in epileptic seizures. PMID:12409614

  9. Regulated release of BDNF by cortical oligodendrocytes is mediated through metabotropic glutamate receptors and the PLC pathway

    Directory of Open Access Journals (Sweden)

    Issa P Bagayogo


    Full Text Available A number of studies suggest that OLGs (oligodendrocytes), the myelinating cells of the central nervous system, are also a source of trophic molecules, such as neurotrophins that may influence survival of proximate neurons. What is less clear is how the release of these molecules may be regulated. The present study investigated the effects of BDNF (brain-derived neurotrophic factor) derived from cortical OLGs on proximate neurons, as well as regulatory mechanisms mediating BDNF release. Initial work determined that BDNF derived from cortical OLGs increased the numbers of VGLUT1 (vesicular glutamate transporter 1)-positive glutamatergic cortical neurons. Furthermore, glutamate acting through metabotropic, and not AMPA/kainate or NMDA (N-methyl-d-aspartate), receptors increased BDNF release. The PLC (phospholipase C) pathway is a key mediator of metabotropic actions to release BDNF in astrocytes and neurons. Treatment of OLGs with the PLC activator m-3M3FBS [N-(3-trifluoromethylphenyl)-2,4,6-trimethylbenzenesulfonamide] induced robust release of BDNF. Moreover, release elicited by the metabotropic receptor agonist ACPD [trans-(1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid] was inhibited by the PLC antagonist U73122, the IP3 (inositol triphosphate 3) receptor inhibitor 2-APB (2-aminoethoxydiphenylborane) and the intracellular calcium chelator BAPTA/AM [1,2-bis-(o-aminophenoxy)ethane-N,N,N′,N′-tetra-acetic acid tetrakis(acetoxymethyl ester)]. Taken together, these results suggest that OLG lineage cells release BDNF, a molecule trophic for proximate neurons. BDNF release is regulated by glutamate acting through mGluRs (metabotropic glutamate receptors) and the PLC pathway. Thus glutamate and BDNF may be molecules that support neuron–OLG interactions in the cortex.

  10. Güvercin Destanları Üzerine Karşılaştırmalı Bir İnceleme A Comparisonal Research on Dove Episodes

    Directory of Open Access Journals (Sweden)

    Osman ERCİYAS


    örüşüne tercüman olmuş bu tür zenginlikler, bilimsel çalışmalar aracılığıyla ele alınıp değerlendirilmedikçe unutulmakta ve en önemli görevlerinden birisi olan yeni kuşaklara sesini duyurabilme işlevinden uzaklaşmaktadırlar. Filolojik yaklaşımların gerektirdiği şekilde izlenecek yöntemler, metinlere gerçek değerlerini iade etme noktasında evrensel özelliklere sahiptirler. Anadolu sahası Türk Halk Edebiyatı içerisinde yer alan önemli eserlerin birçoğu, fazlaca ilgi görmelerinden ötürü değişik yazarlarca kaleme alınmış ve eser nüshaları bağlamında bir zenginlik ortaya çıkmıştır. Söz konusu nüsha zenginliği ise, karşılaştırmalı metin çalışmalarını zorunlu hale getirmiştir. Bu çalışmaya konu edilen metin de söz konusu amaç doğrultusunda incelemeye alınmış ve farklı nüshaların karşılaştırılması yoluyla değerlendirilmiştir. Dinî-tasavvufî Türk Edebiyatının Anadolu’daki ilk örneklerinden sayılan ve Kirdeci Ali’ye ait olduğu düşünülen ‘Güvercin Destanı’, farklı araştırmacılar tarafından varyantlarıyla ortaya çıkarılmış ve yayımlanmıştır. Bu çalışmanın amacı, Atıf Efendi Kütüphanesi, Mehmet Zeki Pakalın Koleksiyonu 45/3 numaralı, Destanlar ve Gazeller isimli yazma eserin 1a, 1b ve 2a numaralı sayfalarında bulunan “Güvercin Destanı”nın (Gügercin Dasitanı bilinmeyen bir varyantını açığa çıkarmak, yayımlamak, değerlendirmek ve diğer varyantlarıyla karşılaştırarak aralarında bulunan benzerlik ve farklılıkları ortaya koymaktır.

  11. Beden Eğitimi Öğretmenlerinin Tükenmişlik Düzeylerinin Saptanması ve Karşılaştırılması


    Kelgökmen, Ali Haydar; Uzunöz, Fatma Saçlı; Demirhan, Gıyasettin


    Araştırmanın amacı, ilköğretim okullarında görev yapan beden eğitimi öğretmenlerinin tükenmişlik düzeylerini saptamak ve cinsiyet, medeni durum, mesleki hizmet yılı, haftalık ders yükü açısından karşılaştırmaktır. Araştırmaya, Ankara’da görev yapan 127 beden eğitimi öğretmeni katılmıştır. Veri toplama aracı olarak, Maslach Tükenmişlik Ölçeği (Maslach Burnout Inventory) (Maslach ve Jackson, 1981), verilerin analizinde ise tanımlayıcı istatistik, t-testi ve tek yönlü varyans analizi (ANOVA) kul...

  12. Taekwondo Hakemleri ile Antrenörlerinin Görev, Kişilik ve Saldırganlık Düzeylerinin Karşılaştırılması


    YILMAZ, Taner; ACET, MEHMET; IŞIK, Utku; ŞAHİN, Metin; CANBAZ, Muammer


    Bu çalışmanın amacı taekwondo hakemleri ile antrenörlerinin görev kişilik ve saldırganlık düzeylerinin karşılaştırılmasıdır. Çalışma verileri Antalya ilinde gerçekleştirilen taekwondo hakem ve antrenörleri seminerinde elde edilmiştir. Araştırma verileri görev kişilik ve saldırganlık ölçeği, eysenck kişilik anketi kısaltılmış formu, görev ve ego yönelimi ölçeği ile toplanmıştır. Araştırmanın örneklem grubu, taekwondo hakemi (n=88), taekwondo antrenörü (n=110), toplam 198 taekwondo hakem ve ant...

  13. K-Ar ages of clay-size concentrates from the mineralisation of the Pedroches Batholith, Spain, and evidence for Mesozoic hydrothermal activity associated with the break up of Pangaea

    Energy Technology Data Exchange (ETDEWEB)

    Halliday, A.N. (Scottish Universities Research and Reactor Centre, Glasgow (UK)); Mitchell, J.G. (Newcastle upon Tyne Univ. (UK). School of Physics)


    The K-Ar ages of 32 clay concentrates extracted from samples of ore, gangue and wallrock associated with mineralisation in the Pedroches Batholith lie in the range 119-285 Ma. Although some of the mineralisation is of Permian age more than half of the ages lie between 210 and 230 Ma and indicate a hydrothermal event at this (Triassic) time. A comparison with age data for mineralisation and certain anorogenic magmatism in other areas of the North Atlantic reveals a consistent pattern of a major event at ca. 230-210 Ma and a minor event at ca. 160 Ma with little Cretaceous or Tertiary activity. It is proposed that the ca. 230-210 Ma event was related to an initial rapid fracturing of the crust associated with the break up of Pangaea, which was related with an increase in the geothermal gradient and penetration of the deep crust by surface waters which returned via both new and rejuvenated fissure systems.

  14. Kastamonu’daki Tarihi Osmanlı Konağı’nda Tespit Edilen Zararlı Böceklere Karşı Fumigasyon Uygulaması




    Kastamonu ilinde bulunan kültürel değeri yüksek tarihi Kastamonu evleri ağaç malzemeden yapılmıştır. Bu ağaç malzemeler; çatı elemanları, kiriş, kolon, merdivenler, kapı ve pencere çerçeveleri ile mobilya ve diğer ahşap konstrüksiyonlardan oluşan kullanılmış kuru odunlardır. Bu çalışmanın amacı; Kastamonu’daki eski ahşap yapılardan biri olan Osmanlı Konağı’nda tahribat yapan böceklerin ve bu yapıları böceklere karşı koruyabilmek için, fümigasyon yönteminde kullanılan Alüminyum fosfitin etki d...

  15. Nitril Grubu Tasıyan Kaliks[4]aren ve Polimer Destekli Türevinin Sentezi ve Civa Taşıma Özelliklerinin Karşılaştırılması

    Directory of Open Access Journals (Sweden)

    Gülderen UYSAL AKKUŞ


    Full Text Available Bu çalışma 5,11,17,23-tetra-ter-bütil-25,27-bis(3siyanopropoksikaliks[4]aren (2 ve bunun birden fazla kaliksaren birimininin bir arada olduğu uygun polimerik yapısının sentezini ve ekstraksiyon özelliklerini içermektedir. Başlangıç maddesi olarak kullanılan p-ter-bütilkaliks[4]aren literatürdeki metotlara göre sentezlendi. Daha sonra bu bileşiğe literatürdeki metotlar uyarlanarak 2 nolu bileşik elde edildi. Polimerik yapı (3 bileşik 2 ile Merrifield reçinesinin reaksiyonuyla elde edildi. Son olarak bu bileşiklerin faz-transfer çalışmaları sıvı-sıvı ekstraksiyon metodu kullanılarak gerçekleştirildi. Ekstraksiyon sonuçlarından görülmektedir ki monomer 2 Hg+2 katyonuna karşı bir seçicilik göstermektedir. Halbuki, bunun polimeri (3 Ni2+ hariç seçilen metallerin hepsini iyi bir şekilde organik faza taşımaktadır.

  16. Building models for postmortem abnormalities in hippocampus of schizophrenics. (United States)

    Benes, Francine M


    Postmortem studies have suggested that there is abnormal GABAergic activity in the hippocampus in schizophrenia (SZ). In micro-dissected human hippocampal slices, a loss of interneurons and a compensatory upregulation of GABAA receptor binding activity on interneurons, but not PNs, has suggested that disinhibitory GABA-to-GABA connections are abnormal in stratum oriens (SO) of CA3/2, but not CA1, in schizophrenia. Abnormal expression changes in the expression of kainate receptor (KAR) subunits 5, 6 and 7, as well as an inwardly-rectifying hyperpolarization-activated cationic channel (Ih3; HCN3) may play important roles in regulating GABA cell activity at the SO CA3/2 locus. The exclusive neurons at this site are GABAergic interneurons; these cells also receive direct projections from the basolateral amygdala (BLA). When the BLA is stimulated by stereotaxic infusion of picrotoxin in rats, KARs influence axodendritic and presynaptic inhibitory mechanisms that regulate both inhibitory and disinhibitory interneurons in the SO-CA3/2 locus. The rat model described here was specifically developed to extend our understanding of these and other postmortem findings and has suggested that GABAergic abnormalities and possible disturbances in oscillatory rhythms may be related to a dysfunction of disinhibitory interneurons at the SO-CA3/2 site of schizophrenics.

  17. Distribution of Vesicular Glutamate Transporter 2 and Ionotropic Glutamate Receptors in the Auditory Ganglion and Cochlear Nuclei of Pigeons (Columba livia). (United States)

    Karim, M R; Atoji, Y


    Glutamate is a principal excitatory neurotransmitter in the auditory system. Our previous studies revealed localization of glutamate receptor mRNAs in the pigeon cochlear nuclei, suggesting the existence of glutamatergic input from the auditory nerve to the brainstem. This study demonstrated localization of mRNAs for vesicular glutamate transporter 2 (vGluT2) and ionotropic glutamate receptors (AMPA, kainate and NMDA) in the auditory ganglion (AG) and cochlear nuclei (magnocellular, angular and laminar nuclei). VGluT2 mRNA was intensely expressed in AG and intensely or moderately in the cochlear nuclei. The AG and cochlear nuclei showed intense-to-moderate mRNA signals for GluA2, GluA3, GluA4, GluK4 and GluN1. These results suggest that the pigeon AG neurons receives glutamatergic input from hair cells and in turn projects to the magnocellular and angular nuclei. Glutamate may play a pivotal role in the excitatory synapse transmission in the peripheral auditory pathway of birds.

  18. Excessive activation of ionotropic glutamate receptors induces apoptotic hair-cell death independent of afferent and efferent innervation (United States)

    Sheets, Lavinia


    Accumulation of excess glutamate plays a central role in eliciting the pathological events that follow intensely loud noise exposures and ischemia-reperfusion injury. Glutamate excitotoxicity has been characterized in cochlear nerve terminals, but much less is known about whether excess glutamate signaling also contributes to pathological changes in sensory hair cells. I therefore examined whether glutamate excitotoxicity damages hair cells in zebrafish larvae exposed to drugs that mimic excitotoxic trauma. Exposure to ionotropic glutamate receptor (iGluR) agonists, kainic acid (KA) or N-methyl-D-aspartate (NMDA), contributed to significant, progressive hair cell loss in zebrafish lateral-line organs. To examine whether hair-cell loss was a secondary effect of excitotoxic damage to innervating neurons, I exposed neurog1a morphants—fish whose hair-cell organs are devoid of afferent and efferent innervation—to KA or NMDA. Significant, dose-dependent hair-cell loss occurred in neurog1a morphants exposed to either agonist, and the loss was comparable to wild-type siblings. A survey of iGluR gene expression revealed AMPA-, Kainate-, and NMDA-type subunits are expressed in zebrafish hair cells. Finally, hair cells exposed to KA or NMDA appear to undergo apoptotic cell death. Cumulatively, these data reveal that excess glutamate signaling through iGluRs induces hair-cell death independent of damage to postsynaptic terminals. PMID:28112265

  19. Inhibition of glutamate receptors reduces the homocysteine-induced whole blood platelet aggregation but does not affect superoxide anion generation or platelet membrane fluidization. (United States)

    Karolczak, Kamil; Pieniazek, Anna; Watala, Cezary


    Homocysteine (Hcy) is an excitotoxic amino acid. It is potentially possible to prevent Hcy-induced toxicity, including haemostatic impairments, by antagonizing glutaminergic receptors. Using impedance aggregometry with arachidonate and collagen as platelet agonists, we tested whether the blockade of platelet NMDA (N-methyl-D-aspartate), AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) and kainate receptors with their inhibitors: MK-801 (dizocilpine hydrogen maleate, [5R,10S]-[+]-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine), CNQX (7-nitro-2,3-dioxo-1,4-dihydroquinoxaline-6-carbonitrile) and UBP-302 (2-{[3-[(2S)-2-amino-2-carboxyethyl]-2,6-dioxo-3,6-dihydropyrimidin 1(2H)-yl]methyl}benzoic acid) may hamper Hcy-dependent platelet aggregation. All the tested compounds significantly inhibited Hcy-augmented aggregation of blood platelets stimulated either with arachidonate or collagen. Hcy stimulated the generation of superoxide anion in whole blood samples in a concentration-dependent manner; however, this process appeared as independent on ionotropic glutamate receptors, as well as on NADPH oxidase and protein kinase C, and was not apparently associated with the extent of either arachidonate- or collagen-dependent platelet aggregation. Moreover, Hcy acted as a significant fluidizer of surface (more hydrophilic) and inner (more hydrophobic) regions of platelet membrane lipid bilayer, when used at the concentration range from 10 to 50 µmol/l. However, this effect was independent on the Hcy action through glutamate ionotropic receptors, since there was no effects of MK-801, CNQX or UBP-302 on Hcy-mediated membrane fluidization. In conclusion, Hcy-induced changes in whole blood platelet aggregation are mediated through the ionotopic excitotoxic receptors, although the detailed mechanisms underlying such interactions remain to be elucidated.

  20. apılan Sporun Karakteristiği Solunum Fonksiyonlarını Etkiler mi? Voleybol ve Judo Sporcularının Karşılaştırılması

    Directory of Open Access Journals (Sweden)

    Tuğba KOCAHAN


    Full Text Available Sporcular yapılan spora bağlı olarak farklı fizyolojik adaptasyonlar geliştirirler. Solunum fonksiyonları da bu adaptasyonlardan etkilenir. Çalışmamızın amacı karakteristiği birbirinden oldukça farklı olan voleybol ve judo sporunun solunum fonksiyonları üzerindeki etkisini karşılaştırmaktır. Çalışmaya ortalama yaşı 15,50±1,08 yıl olan 12 erkek voleybol sporcusu ile ortalama yaşı 15,10±1.37 yıl olan 10 erkek judo sporcusu dahil edildi. Sporcuların solunum fonksiyonları spirometre ile test edildi. Sporcuların forced expiratory volume-zorlu ekspiratuar hacim (FEV, forced expiratory volume in one second-bir saniyedeki zorlu ekspiratuar hacim (FEV1, forced vital capasity- zorlu vital kapasite (FVC, forced ekspiratuary volume-zorlu ekspiraturar volüm/ forced vital capasity-zorlu vital kapasite yüzdesi (FEV1/FVC%, peak expiratory flow- tepe akım hızı (PEF, forced expiratory volume at %25- %25’deki zorlu ekspiratuar hacim (FEV25, forced expiratory volume at %50- %50’deki zorlu ekspiratuar hacim (FEV50, forced expiratory volume at %75- %75’deki zorlu ekspiratuar hacim (FEV75 değerleri kaydedildi ve SPSS istatistiksel analiz programı kullanılarak veriler karşılaştırıldı. Sporcuların yaşları arasında anlamlı bir fark bulunamamıştır (p>0,05. Boy ve kilo değerleri arasında anlamlı bir fark mevcut olsa da söz konusu bu fark BKI (Beden Kitle İndeksi için geçerli değildir (p>0,05. Spirometrik değişkenlerden FEV1/FVC% haricindeki tüm değerler voleybol sporcularında daha yüksek belirlenmiştir ve iki grup arasındaki değişkenler arasındaki farkın tamamı anlamlılık düzeyine ulaşmıştır (p<0,05. Voleybol sporunda, judo sporuna kıyasla solunum sistemi üzerine düşen yükün daha fazla olması bu sporcuların solunum fonksiyonlarının judo sporcularından yüksek çıkmasına sebep olmuştur. Bu çalışma ile yapılan sporun karakteristiğinin solunum sistemi

  1. Isolation and Homologous Genetic Transformation of DFR in Saussurea involucrata Kir.%新疆雪莲DFR基因的分离及同源遗传转化

    Institute of Scientific and Technical Information of China (English)

    覃建兵; 唐亚萍; 曾卫军


    二氢黄酮醇4-还原酶(dihydroflavonol 4-reductase,DFR)是植物重要的次生代谢产物花青素生物合成途径中的关键酶.运用RT-PCR和RACE技术从新疆雪莲(Saussurea involucrata Kir.)中克隆得到DFR基因(GenBank登录号为JN092126).DFR基因的cDNA全长序列含有1个1 029 bp的开放阅读框(ORF),编码343个氨基酸,该基因推断的蛋白与水母雪莲DFR基因推断的蛋白高度同源,相似性达到92%;以不同物种中DFR氨基酸序列进行比对分析,推断的蛋白含有与NADPH特异结合的结构域.将该基因运用农杆菌介导的叶片转化法进行同源转化,将含有转DFR基因的愈伤组织进行悬浮培养,紫外分光光度法测定愈伤组织的总黄酮含量,结果表明转基因愈伤组织的总黄酮含量明显高于非转基因愈伤组织的含量.该研究为提高新疆雪莲药用化学成分黄酮类物质及实现新疆雪莲花青素的人工生物合成的研究奠定基础,对解决天山雪莲资源匮乏提供参考.%The dihydroflavonol-4-reductase (DFR) is an important enzyme in plant secondary metabolites and catalyzes the key step in the biosynthesis of anthocyanins. DFR gene ( GenBank Accession JN092126) was cloned from Saussurea involucrata Kar. et Kir. by RT-PCR and RACE. The cDNA sequence of DFR was consisted of 1 029 bp open reading frame ( ORF) encoding 343 amino acid, the deduced DFR protein has high homolo-gy with S. medusa (92% identity). Homology analysis showed that deduced DFR protein has the special domain regioselectivity towards NADPH. DFR gene of S. involucrata was under the control of the cauliflower mosaic virus (CaMV) 35S promoter, homologous transformation was conducted using an Agrobacter-ium rihizogenes-mediated transformation system. The results of UV spectrophotometry showed that Sinvolucrata callus after suspension culture had an obviously higher average content of total flavonoids than non-transgenic callus. This study will improve the

  2. K-Ar dating and delta O-18-delta D characterization of nanometric illite from Ordovician K-bentonites of the Appalachians: illitization and the Acadian-Alleghenian tectonic activity (United States)

    Clauer, Norbert; Fallick, Anthony E.; Eberl, Dennis D.; Honty, Miroslav; Huff, Warren D.; Auberti, Amelie


    Nanometric (2 diagram that illitization occurred in all fractions by simultaneous nucleation and crystal growth, except for one sample. In that sample, a period of growth without nucleation was detected on top of the nucleation and growth episode. The K-Ar ages organize into two isochrons, the first at 319.9 ± 2.0 Ma with an initial 40Ar/36Ar ratio of 271 ± 66 Ma, and the second at 284.9 ± 1.2 Ma with an initial 40Ar/36Ar ratio of 310 ± 44. One data point above the older isochron and three between the two isochrons suggest a detrital contamination for the former separate and a possible further generation of nanoparticles for the three others. The samples with the older crystallization age consist of illite and illite-rich mixed-layers, and those with the younger age contain smectite-rich mixed-layers without illite, or illite-enriched illite-smectite mixed-layers. The K-Ar ages fit the age trends published previously for similar K-bentonites with regional age patterns between 240 and 270 Ma in the southwestern region, between 270 and 300 Ma in the central zone and the southern Appalachians, and between 315 and 370 Ma in the northernmost. Each of the two generations of illite crystals yields very consistent δ18O (V-SMOW) values at 17 ± 1‰ for the older and at 21 ± 1‰ for the younger. If crystallization temperatures of the nanometric illite were between 100 and 200 °C, as suggested by microthermometric determinations, the hydrothermal fluids had δ18O values of 4 ± 1‰ in the Dalton district and of 8 ± 1‰ in the Lafayette, Trenton, and Dirtseller districts at 100 °C, and of 11 ± 1 and 15 ± 1‰ in the same locations at 200 °C, probably because the water-rock isotope exchanges at elevated temperature occurred in rock-dominated systems. The δ18O of the fluids remained unchanged during local crystal growth, but varied depending on the geographic location of the samples and timing of illitization. The δD (V-SMOW) values of the different size

  3. Marrubium lutescens Boiss. ve M. cephalanthum Boiss. & Noë subsp. akdaghicum (Lamiaceae' un Gövde ve Yaprak Özelliklerinin Anatomik Olarak Karşılaştırılması

    Directory of Open Access Journals (Sweden)

    Meltem TUYLU


    Full Text Available Çalışmada; Lamiaceae familyasındaki Marrubium L. cinsinin iki taksonu olan   Marrubium lutescens Boiss. ve M. cephalanthum Boiss. & Noë subsp. akdaghicum’ da gövde ve yaprak, anatomik olarak incelenerek cinsin taksonomik problemlerinin çözümüne katkı amaçlanmıştır. Işık mikroskobu için iki tip preperasyon yapılmıştır. Parafin içerisindeki gövde ve yaprak örnekleri Safranin-Fast Green ile boyandıktan sonra, epon içerisindeki yarı ince kesitler ise Toluidine blue ile boyandıktan sonra ışık mikroskobunda incelenerek fotoğrafları çekilmiştir. Her iki taksonda gövde; köşeli, kalın kutikulalı, tek sıralı epidermis ile çevrilidir. Köşelerde, epidermisin altında 2-3 sıralı lamellar kollenkima bulunmaktadır. Yaprak; M. lutescens' te bifasiyal iken M. cephalanthum’ da unifasiyaldir. Küçük iletim demetleri kollateraldir ve yaprak amfistomatiktir. Gövdelerde ve yaprakların alt ve üst yüzeyinde örtü ve salgı tüyleri bulunmaktadır. Anatomik sonuçlar karşılaştırıldığında, iki taksonun birbirine yakın oldukları anlaşılmıştır.

  4. K-Ar dating, whole-rock and Sr-Nd isotope geochemistry of calc-alkaline volcanic rocks around the Gümüşhane area: implications for post-collisional volcanism in the Eastern Pontides, Northeast Turkey (United States)

    Aslan, Zafer; Arslan, Mehmet; Temizel, İrfan; Kaygusuz, Abdullah


    Volcanic rocks from the Gümüşhane area in the southern part of the Eastern Pontides (NE Turkey) consist mainly of andesitic lava flows associated with tuffs, and rare basaltic dykes. The K-Ar whole-rock dating of these rocks range from 37.62 ± 3.33 Ma (Middle Eocene) to 30.02 ± 2.84 Ma (Early Oligocene) for the andesitic lava flows, but are 15.80 ± 1.71 Ma (Middle Miocene) for the basaltic dykes. Petrochemically, the volcanic rocks are dominantly medium-K calc-alkaline in composition and show enrichment of large ion lithophile elements, as well as depletion of high field strength elements, thus revealing that volcanic rocks evolved from a parental magmas derived from an enriched mantle source. Chondrite-normalized rare-earth element patterns of the volcanic rocks are concave upwards with low- to-medium enrichment (LaCN/LuCN = 3.39 to 12.56), thereby revealing clinopyroxene- and hornblende-dominated fractionations for andesitic-basaltic rocks and tuffs, respectively. The volcanic rocks have low initial 87Sr/86Sr ratios (0.70464 to 0.70494) and ɛNd(i) values (+1.11 to +3.08), with Nd-model ages (TDM) of 0.68 to 1.02 Ga, suggesting an enriched lithospheric mantle source of Proterozoic age. Trace element and isotopic data, as well as the modelling results, show that fractional crystallization and minor assimilation played an important role in the evolution of the volcanic rocks studied. The Eocene to Miocene volcanism in the region has resulted from lithospheric delamination and the associated convective thinning of the mantle, which led to the partial melting of the subduction-metasomatized lithospheric mantle.

  5. Monzonitoid magmatism of the copper-porphyritic Lazurnoe deposit (South Primor'e): U-Pb and K-Ar geochronology and peculiarities of ore-bearing magma genesis by the data of isotopic-geochemical studies (United States)

    Sakhno, V. G.; Kovalenko, S. V.; Alenicheva, A. A.


    Magmatic rocks from the copper-porphyritic Lazurnoe deposit (Central Primor'e) have been studied. It has been found that rocks from the Lazurnyi massif are referred to gabbro-monzodiorites, monzodiorites, and monzo-granodiorites formed during two magmatic phases of different ages. The earlier phase is represented by gabbro-monzodiorites and diorites of the North Stock, and the later one, by gabbro-monzodiorites and monzo-grano-diorites of the South Stock. On the basis of isotopic dating by the U-Pb (SHRIMP) method for zircon and by the K-Ar method for hornblendes and biotites, the age of magmatic rocks is determined at 110 ± 4 for the earlier phase and at 103.5 ± 1.5 for the later one. Examination of the isotopic composition for Nd, Sr, Pb, Hf, δ18O, and REE spectra has shown that melts of the first phase are contaminated with crustal rocks and they are typical for a high degree of secondary alterations. Potassiumfeldspar, biotite, propylitic alterations, and sulfidization are manifested in these rocks. The rocks of the later stage of magmatism are characteristic for a primitive composition of isotopes and the absence of secondary alterations. They carry the features of adakite specifics that allows us to consider them derivatives of mantle generation under high fluid pressure. The intrusion of fluid-saturated melts of the second phase into the magmatic source of the first phase caused both an alteration pattern of rocks and copper-porphyritic mineralization. Isotopes of sulfur and oxygen allow us to consider the ore component to be of magmatic origin.

  6. Deri Materyalinden ve Dokuma Kumaştan Tasarlanan Ceketlerin Üretim Süreçlerinin Karşılaştırılması

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    Emine Utkun


    Full Text Available Deri ve deri ürünleri sektörü, 1990'lı yıllarda dağılan Doğu Bloku ülkelerinden gelen talep ve yoğun bavul ticareti neticesinde üretim ve ihracat açısından önemli bir gelişme göstermiştir. Bu süreç, sektörde büyük yatırımların yapılmasına ve dolayısıyla kapasite artışına neden olmuştur. Deri konfeksiyon sektörü dokuma kumaş konfeksiyon sektöründen çeşitli noktalarda farklılıklar göstermektedir. Bu durum, deri konfeksiyonunda hammadde olarak kullanılan işlenmiş derinin, dokuma kumaşlara göre ebat, kalınlık, homojenlik gibi biyolojik, kimyasal ve fiziksel farklılıklarından kaynaklanmaktadır. Derinin, doğal yapısı gereği farklı bölgeleri farklı özellikler göstermektedir. Bu çalışmada deri materyalinden ve dokuma kumaştan tasarlanmış ceketlerin farklı üretim süreçleri incelenmiş ve karşılaştırılmıştır.

  7. Mogan Gölü’ndeki bazı balık türlerinde vitellogenin proteininin elektroforetik karşılaştırılması

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    Göktuğ Gül


    Full Text Available Öz: Bu çalışma, balıkçılık ve rekreasyon alanı olarak kullanılan Mogan Gölü’nde (Ankara - Türkiye Ocak-Mayıs 2013 ayları arasında yürütülmüştür. Gölde yaşayan balık türlerinden Cyprinus carpio, Carassius gibelio, Tinca tinca ve Esox lucius türlerinin erkek ve dişi bireylerinin kan plazmasında elektroforetik SDS-Page (Sodyum Dodesil Sülfat Poliakrilamid Jel Elektroforezi metodu ile vitellogenin (VTG proteini araştırılmış ve türler arası karşılaştırma yapılmıştır. Bu metot için Biometra marka dikey elektroforez cihazı kullanılmıştır. Üreme döneminde C. carpio, T. tinca ve E. Lucius’un erkek bireylerinde vitellogenin proteini saptanmıştır. Göl ortamındaki çeşitli kirleticilerin bu sonuçlar üzerinde etkili olduğu düşünülmektedir. Bu çalışmada elde edilen bulgulara göre kullanılan testin iyi bir biyo-belirteç olduğu anlaşılmıştır.Anahtar kelimeler: Vitellogenin, elektroforez, Cyprinus carpio, Carassius gibelio, Tinca tinca, Esox lucius

  8. The androgen receptor and estrogen receptor

    NARCIS (Netherlands)

    Oosterkamp, H.M.; Bernards, R.A.


    The androgen receptor (AR) and the estrogen receptors (ER) are members of the nuclear receptor (NR) family. These NRs are distinguished from the other transcription factors by their ability to control gene expression upon ligand binding (steroids, retinoids, thyroid hormone, vitamin D, fatty acids,

  9. Kafkasya Muhacirlerinin Suriye Vilayetine İskânı ve Karşılaşılan Zorluklar The Settlement of Caucasian Refugees to Syria Province and the Hardships Encountered

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    ı-RusSavaşı sonucunda Osmanlı Devleti savaşı kaybetti. Savaş neticesindeOsmanlı Devleti Balkan coğrafyası’nda büyük bir toprak parçasıkaybetti. Bundan dolayı daha önce Balkan Coğrafyasına iskân edilenKafkasya muhacirleri yeniden muhacir konumuna düştü. HemKafkasya hem de Rumeli’den gelen göçmenlere yeni iskân bölgesi olarakSuriye Vilayeti uygun görüldü. Suriye Vilayetine gönderilen göçmenlerorada büyük zorluklarla karşılaştı. Doğal şartlar yönünden Suriye’ninhavasına ve suyuna uyum problemi yaşadılar. Buna bakımsızlıktankaynaklanan salgın hastalıklarda eklenince, muhacirlerin yarıya yakınıyaşamını kaybetti. Bunun dışında, bölgedeki Dürzî ve Bedevi Arapaşiretleri ile muhacirler arasında yaşanan toplumsal çatışmalar daeklenince muhacirler büyük sıkıntılarla karşılaştı.Muhacirler, Suriye Vilayetine iskânından yaklaşık otuz yıl sonrabölgenin sosyo-kültürel ve iklim şartlarına uyum sağladılar. Muhacirler,Suriye Vilayetine uyum sağladıktan sonra kendilerine saldırılardabulunan Bedevi ve Dürzîlere karşı daha güçlü hale geldiler.Osmanlı Devleti imkânlarının çok üstünde olan muhacir iskânıkonusunda bütün imkânlarını seferber etti. Buna rağmen istenmeyenolayların yaşanmasına engel olamadı.

  10. GLP-1 Receptor Agonists (United States)

    ... in Balance › GLP-1 Receptor Agonists Fact Sheet GLP-1 Receptor Agonists May, 2012 Download PDFs English Espanol Editors Silvio ... are too high or too low. What are GLP-1 receptor agonist medicines? GLP-1 receptor agonist medicines, also called ...

  11. Protection from inorganic mercury effects on the in vivo dopamine release by ionotropic glutamate receptor antagonists and nitric oxide synthase inhibitors. (United States)

    Vidal, Lucía; Durán, Rafael; Faro, Lilian F; Campos, Francisco; Cervantes, Rosa C; Alfonso, Miguel


    The possible role of ionotropics glutamate receptors on the HgCl(2)-induced dopamine (DA) release from rat striatum was investigated by using in vivo brain microdialysis technique after administration of selective NMDA and AMPA/Kainate receptors antagonists dizocilpine (MK-801), D (-)-2-amino-5-phoshonopentanoic acid (AP5), and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). Moreover, we have also studied the effects of nitric oxide synthase (NOS) inhibitors L-nitro-arginine methyl ester (L-NAME) and 7-nitro-indazol (7-NI) on HgCl(2)-induced DA release. Intraestriatal infusion of 1mM HgCl(2) increased striatal DA to 1717.2+/-375.4% respect to basal levels. Infusion of 1mM HgCl(2) in 400 microM MK-801 pre-treated animals produced an increase on striatal DA levels 61% smaller than that induced in non-pre-treated animals. In the case of AP5, this treatment reduced 92% the increase produced by HgCl(2) as compared to non-pre-treated rats. Nevertheless, the administration of CNQX did not produce any effect on HgCl(2)-induced dopamine release. Intrastriatal infusion of 1mM HgCl(2) in 100 microM L-NAME pre-treated animals produced an increase on extracellular DA levels 82% smaller than produced by HgCl(2) alone. In addition, the pre-treatment with 7-NI reduced 90% the increase produced by infusion of HgCl(2) alone in rats. Thus, HgCl(2)-induced DA release could be produced at last in part, by overstimulation of NMDA receptors with NO production, since administration of NMDA receptor antagonists and NOS inhibitors protected against HgCl(2) effects on DA release.

  12. Effects of the abused solvent toluene on recombinant N-methyl-D-aspartate and non-N-methyl-D-aspartate receptors expressed in Xenopus oocytes. (United States)

    Cruz, S L; Mirshahi, T; Thomas, B; Balster, R L; Woodward, J J


    Previous studies have shown that toluene, which is commonly abused, depresses neuronal activity and causes behavioral effects in both animals and man similar to those observed for ethanol. In this study, the oocyte expression system was used to test the hypothesis that toluene, like ethanol, inhibits the function of ionotropic glutamate receptors. Oocytes were injected with mRNA for specific N-methyl-D-aspartate (NMDA) or non-NMDA subunits and currents were recorded using conventional two-electrode voltage clamp. To enhance the low water solubility of toluene, drug solutions were prepared by mixing toluene with alkamuls (ethoxylated castor oil) at a 1:1 ratio (v:v) and diluting this mixture to the appropriate concentration with barium-containing normal frog Ringer solution. Alkamuls, up to 0.1%, had no significant effects on membrane leak currents or on NMDA-induced currents. Toluene, up to approximately 9 mM, had only minor effects on membrane leak currents but dose-dependently inhibited NMDA-mediated currents in oocytes. The inhibition of NMDA receptor currents by toluene was rapid, reversible and the potency for toluene's effects was subunit dependent. The NR1/2B subunit combination was the most sensitive with an IC50 value for toluene-induced inhibition of 0.17 mM. The NR1/2A and NR1/2C receptors were 6- and 12-fold less sensitive with IC50 values of 1.4 and 2.1 mM, respectively. In contrast, toluene up to approximately 9 mM did not inhibit kainate-induced currents in oocytes expressing GluR1, GluR1(+)R2 or GluR6 subunits. These results suggest that some of the effects of toluene on neuronal activity and behavior may be mediated by inhibition of NMDA receptors.

  13. Eğitimle İlgili Sapan Değer İçeren Veri Kümelerinde En Küçük Kareler ve Robust M Tahmin Edicilerin Karşılaştırılması

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    Orkun Coşkuntuncel


    Full Text Available Eğitim araştırmalarında regresyon katsayılarını tahmin etmek için en çok kullanılan yöntem klasik yöntem olarak da bilinen en küçük kareler (EKK tahmin edicisidir. Ancak bu yöntem gözlenen verilerdeki sapan değerlere karşı çok hassastır. Bu çalışmanın amacı, eğitim araştırmalarında ortaya çıkabilen, sapan değer(lere sahip verilerde adı geçen problemlere karşı daha dayanıklı olan robust M regresyon tahmin edicisinin performansını incelemektir. Bunun için, Öğrenci Seçme Sınavı (ÖSS puanları bağımlı değişken, orta öğretim ders başarı puanları (OÖBP ise bağımsız değişken olarak ele alınarak, bağımsız değişkenlerin bağımlı değişkeni ne derece yordadığı iki farklı regresyon yöntemine dayalı olarak (En Küçük Kareler (EKK ve robust M regresyon kestirimi belirlenmiş ve sonuçlar karşılaştırılmıştır.

  14. Adenosine A3 receptor activation is neuroprotective against retinal neurodegeneration. (United States)

    Galvao, Joana; Elvas, Filipe; Martins, Tiago; Cordeiro, M Francesca; Ambrósio, António Francisco; Santiago, Ana Raquel


    Death of retinal neural cells, namely retinal ganglion cells (RGCs), is a characteristic of several retinal neurodegenerative diseases. Although the role of adenosine A3 receptor (A3R) in neuroprotection is controversial, A3R activation has been reported to afford protection against several brain insults, with few studies in the retina. In vitro models (retinal neural and organotypic cultures) and animal models [ischemia-reperfusion (I-R) and partial optic nerve transection (pONT)] were used to study the neuroprotective properties of A3R activation against retinal neurodegeneration. The A3R selective agonist (2-Cl-IB-MECA, 1 μM) prevented apoptosis (TUNEL(+)-cells) induced by kainate and cyclothiazide (KA + CTZ) in retinal neural cultures (86.5 ± 7.4 and 37.2 ± 6.1 TUNEL(+)-cells/field, in KA + CTZ and KA + CTZ + 2-Cl-IB-MECA, respectively). In retinal organotypic cultures, 2-Cl-IB-MECA attenuated NMDA-induced cell death, assessed by TUNEL (17.3 ± 2.3 and 8.3 ± 1.2 TUNEL(+)-cells/mm(2) in NMDA and NMDA+2-Cl-IB-MECA, respectively) and PI incorporation (ratio DIV4/DIV2 3.3 ± 0.3 and 1.3 ± 0.1 in NMDA and NMDA+2-Cl-IB-MECA, respectively) assays. Intravitreal 2-Cl-IB-MECA administration afforded protection against I-R injury decreasing the number of TUNEL(+) cells by 72%, and increased RGC survival by 57%. Also, intravitreal administration of 2-Cl-IB-MECA inhibited apoptosis (from 449.4 ± 37.8 to 207.6 ± 48.9 annexin-V(+)-cells) and RGC loss (from 1.2 ± 0.6 to 8.1 ± 1.7 cells/mm) induced by pONT. This study demonstrates that 2-Cl-IB-MECA is neuroprotective to the retina, both in vitro and in vivo. Activation of A3R may have great potential in the management of retinal neurodegenerative diseases characterized by RGC death, as glaucoma and diabetic retinopathy, and ischemic diseases.

  15. “Gülün Adı ve Benim Adım Kırmızı” Adlı Romanlara Karşılaştırmalı Bir Yaklaşım A Comparative Approach to the novels “Name of the Rose and My Name Is Red”

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    Elmas ŞAHİN


    similarapproaches or re-interpretations of the original text are closely relatedto comparative literature.In this context, The novels of the Italian writer Umberto Eco's Name of the Rose, from author of our time, (1980 and Orhan Pamuk's My Name is Red (1998 from our modern writer enter to field of literature in different geographies, but have similar themes in the terms of the content and form, they are synchronic samples for comparative literatureThe works Name of the Rose and My Name is Red in this study, using the text-oriented analysis method will be compared in terms of essence and form. Both of these works, by considered similar species, subject matter and motifs, examined in intertextual size, will be resolved by their similarities and differences by the method of comparative literature. Özellikle son yıllarda dünya edebiyatına duyulan ilgi dolayısıyla kültürel çalışmaların da etkisi ile karşılaştırmalı edebiyat popüler bir disiplin olarak karşımıza çıkar. Günümüzde eleştiri ve kültürel çalışmalarla başa baş gitmeye başlayan karşılaştırmalı çalışmaların; ulusal edebiyatları uluslar arası boyutlara taşıyarak; gerek kuram ve gerekse uygulamada dünya edebiyatlarının bir noktada buluşmasına zemin hazırladıkları görülür.Bir eserin başka bir eser yada eserlerle ortak konu ve motif bağlamında benzer ve farklılıklarıyla mukayese edilmesi anlamına gelen ″Karşılaştırmalı edebiyat″ terimi, her ne kadar 19. yüzyılda akademik bir disiplin olarak ortaya çıksa da, ″karşılaştırmalı″ (comparative teriminin çıkış noktasının, Platon ve Aristotales'in klasik çağı ile başladığını söylemek yanlış olmaz. Platon ve Aristotale’in şiir ile felsefeyi karşılaştırarak başladıkları karşılaştırmalı söylemler, Horace, Longinus, Dryden, Arnold; Sanctis, Goethe ve Cuiver ile gelişerek 20. yüzyılda akademik boyutta üst seviyeye ulaşır.Batıda Rene Wellek'in The Crisis of Comparative

  16. Differential expression of glutamate receptors in avian neural pathways for learned vocalization. (United States)

    Wada, Kazuhiro; Sakaguchi, Hironobu; Jarvis, Erich D; Hagiwara, Masatoshi


    Learned vocalization, the substrate for human language, is a rare trait. It is found in three distantly related groups of birds-parrots, hummingbirds, and songbirds. These three groups contain cerebral vocal nuclei for learned vocalization not found in their more closely related vocal nonlearning relatives. Here, we cloned 21 receptor subunits/subtypes of all four glutamate receptor families (AMPA, kainate, NMDA, and metabotropic) and examined their expression in vocal nuclei of songbirds. We also examined expression of a subset of these receptors in vocal nuclei of hummingbirds and parrots, as well as in the brains of dove species as examples of close vocal nonlearning relatives. Among the 21 subunits/subtypes, 19 showed higher and/or lower prominent differential expression in songbird vocal nuclei relative to the surrounding brain subdivisions in which the vocal nuclei are located. This included relatively lower levels of all four AMPA subunits in lMAN, strikingly higher levels of the kainite subunit GluR5 in the robust nucleus of the arcopallium (RA), higher and lower levels respectively of the NMDA subunits NR2A and NR2B in most vocal nuclei and lower levels of the metabotropic group I subtypes (mGluR1 and -5) in most vocal nuclei and the group II subtype (mGluR2), showing a unique expression pattern of very low levels in RA and very high levels in HVC. The splice variants of AMPA subunits showed further differential expression in vocal nuclei. Some of the receptor subunits/subtypes also showed differential expression in hummingbird and parrot vocal nuclei. The magnitude of differential expression in vocal nuclei of all three vocal learners was unique compared with the smaller magnitude of differences found for nonvocal areas of vocal learners and vocal nonlearners. Our results suggest that evolution of vocal learning was accompanied by differential expression of a conserved gene family for synaptic transmission and plasticity in vocal nuclei. They also suggest

  17. İki Şair: Hâfız–Fuzûli Karşılaştırması Two Poets: The Comparison Between Hafız and Fuzuli

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    Hamdi BİRGÖREN


    is going to be seen thatmore comprehensive studies are needed. Klasik Türk edebiyatından bahseden kaynaklar, İran edebiyatının Türk edebiyatına etkisinden söz etmektedirler. Bu etkinin ne boyutlarda olduğunun anlaşılabilmesi için çok yönlü karşılaştırmalara ihtiyaç vardır. Ancak derinlemesine bir araştırma yapmadan Firdevsî, Feridüddin Attar, Nizamî-i Gencevî, Mevlânâ, Sadî, Ömer Hayyam, Hâfız-ı Şîrâzî, Molla Câmî gibi isimleri saymak bile bu etkiye ışık tutacak mahiyettedir. Bu isimlerden Firdevsî’nin Şehnâme, Attar’ın Tezkiretü’l-evliyâ ve Mantıku’t-tayr, Mevlânâ’nın Mesnevî, Sadî’nin Bostan ve Gülistan, Molla Câmî’nin Bahâristan ve Ömer Hayyam’ın rubaileriyle Türk şairleri üzerinde etkili olduğu bilinmekte diğer şairlerin hangi alanda ne kadar etki ettiği pek bilinmemektedir. Bu etkinin anlaşılmasına katkı sağlamak amacıyla biz de Hâfız ile Fuzûlî Divanlarını birkaç açıdan karşılaştırmak istiyoruz.İran edebiyatının büyük gazel şairi Hâfız-ı Şîrâzî ile Türk edebiyatının büyük şairi Fuzûlî arasındaki etkileşimi anlamak için öncelikle bu şairlerin içinde bulundukları sosyal ve siyasi şartlara bir göz atmak yerinde olur sanırız. Sonra bu şairlerin hayatlarına ve edebi şahsiyetlerine değinerek şiirdeki başarılarından söz etmek istiyoruz.Hâfız 14. yüzyılda yaşamış büyük bir İran şairi, Fuzûlî ise 16. yüzyıl Türk edebiyatının büyük şairlerinden biridir. Elbette iki ayrı edebiyatın iki büyük ismini bütün özellikleriyle bir makale çerçevesinde karşılaştırma imkânı olmadığının farkındayız. Bu sebeple genel bir değerlendirmede bulunabilmek için şiirlerinin bazı yönlerine değinecek ve örnek olmak üzere şairlerin birer gazelini ve nesre çevrilmiş biçimini vereceğiz.Yaşadıkları çağlar, kullandıkları diller ve işledikleri konular göz önüne alındığında daha kapsamlı

  18. Zihin Kuramı: Otizm Spektrum Bozukluğu Olan ve Normal Gelişen Çocukların Performanslarının Karşılaştırılması

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    Full Text Available Nedensel karşılaştırma deseni kullanılarak planlanan bu araştırmada, otizm spektrum bozukluğu (OSB olan ve normal gelişen (NG çocukların, zihin kuramı performansları ve bu alandaki performansların genel dil ve kronolojik yaşla ilişkisi incelenmiştir. Araştırma grubunu, Türkçe Erken Dil Gelişimi Testi (TEDİL ifade edici dil eşdeğer yaşları en az 4 olan 30 OSB olan ve 30 NG çocuk oluşturmuştur. OSB olan ve NG çocuklar ortalama sözce uzunluğuna (OSU göre eşleştirilmişlerdir. Zihin kuramı becerileri bir grup işlemle değerlendirilmiştir. Araştırma sonuçları, dilde OSU’ ya göre eşleştirilen OSB olan çocuklarla NG çocukların zihin kuramı performanslarının benzer olduğunu, her iki grupta da dilin, zihin kuramı ile ilişkili olduğunu ancak NG çocuklarda dile ek olarak kronolojik yaşın da zihin kuramı ile ilişkili olduğunu göstermiştir. This study examined the theory of mind (ToM performance and the relationship between language, chronological age and theory of mind in children with autism spectrum disorders (ASD and in typically developing (TD children by utilizing the ex-post-facto design. The participants were 30 children with ASD and 30 TD children whose Test of Early Language Development (TELD - Turkish Version expressive language age scores were at least 4 years old. Children with ASD and TD children were matched on mean length of utterance (MLU. ToM ability was assessed on a battery of tasks that have developmental sequence. The findings revealed that the children with ASD and TD children who were matched according to MLU, performed similarly on ToM tasks. Besides language was related to the performance on ToM tasks in children with ASD and in TD children whereas also chronological age is related to the performance on ToM tasks in TD children.

  19. New K-Ar ages from La Montagne massif, Réunion Island (Indian Ocean), supporting two geomagnetic events in the time period 2.2-2.0 Ma (United States)

    Quidelleur, X.; Holt, J. W.; Salvany, T.; Bouquerel, H.


    We present new radiometric ages obtained at the type locality in La Réunion Island where palaeomagnetic records of the Réunion events have first been identified. Seven dated lava flows from the Rivière Saint Denis section, which recorded a reverse-to-normal transition, display ages from 2.12 +/- 0.03 to 2.17 +/- 0.03 Ma, with a mean age of 2.15 +/- 0.02 Ma. Two significantly younger flows from this section, interpreted here as valley fill flows from trace elements compositions and Pb isotopic data, have been dated at 2.06 +/- 0.03 and 2.08 +/- 0.03 Ma. Within the Grande Chaloupe section, where a normal-to-reverse transition is recorded, two coherent ages of 2.05 +/- 0.03 and 2.03 +/- 0.03 Ma have been obtained. When a direct comparison was possible, our new K-Ar ages performed on separated groundmass show a rather good coherence with previous ages from La Réunion Island. When considered with continuous palaeomagnetic sedimentary records in the 2.2-2.0 Ma interval, these new results suggest that two distinct events are recorded in La Montagne lava flows at La Réunion Island, with ages of 2.15 +/- 0.02 and 2.04 +/- 0.02 Ma. Following recent nomenclature, the former is the Réunion event s.s., while the latter can be related to the Huckleberry Ridge event. Globally distributed volcanic and sedimentary records show that the first (Réunion s.s.; RU-1) is associated with a large dipole intensity decrease at 2.15 +/- 0.02 Ma, and hence is recorded in many sequences. On the other hand, the dipole intensity decrease was not as pronounced at 2.04 +/- 0.02 Ma, when the Huckleberry Ridge (RU-2) palaeomagnetic event occurred. Consequently, it is not present as a full directional change in many sections worldwide, but rather appears as a geomagnetic excursion during an episode of increased secular variation. Finally, the use of the Réunion event for magnetostratigraphic studies is recommended, while the clear identification of the Huckleberry Ridge excursion might often

  20. Chemoenzymatic synthesis of new 2,4-syn-functionalized (S)-glutamate analogues and structure-activity relationship studies at ionotropic glutamate receptors and excitatory amino acid transporters. (United States)

    Assaf, Zeinab; Larsen, Anja P; Venskutonytė, Raminta; Han, Liwei; Abrahamsen, Bjarke; Nielsen, Birgitte; Gajhede, Michael; Kastrup, Jette S; Jensen, Anders A; Pickering, Darryl S; Frydenvang, Karla; Gefflaut, Thierry; Bunch, Lennart


    In the mammalian central nervous system, (S)-glutamate (Glu) is released from the presynaptic neuron where it activates a plethora of pre- and postsynaptic Glu receptors. The fast acting ionotropic Glu receptors (iGluRs) are ligand gated ion channels and are believed to be involved in a vast number of neurological functions such as memory and learning, synaptic plasticity, and motor function. The synthesis of 14 enantiopure 2,4-syn-Glu analogues 2b-p is accessed by a short and efficient chemoenzymatic approach starting from readily available cyclohexanone 3. Pharmacological characterization at the iGluRs and EAAT1-3 subtypes revealed analogue 2i as a selective GluK1 ligand with low nanomolar affinity. Two X-ray crystal structures of the key analogue 2i in the ligand-binding domain (LBD) of GluA2 and GluK3 were determined. Partial domain closure was seen in the GluA2-LBD complex with 2i comparable to that induced by kainate. In contrast, full domain closure was observed in the GluK3-LBD complex with 2i, similar to that of GluK3-LBD with glutamate bound.

  1. Regulation of GABA(A and glutamate receptor expression, synaptic facilitation and long-term potentiation in the hippocampus of prion mutant mice.

    Directory of Open Access Journals (Sweden)

    Alejandra Rangel

    Full Text Available BACKGROUND: Prionopathies are characterized by spongiform brain degeneration, myoclonia, dementia, and periodic electroencephalographic (EEG disturbances. The hallmark of prioniopathies is the presence of an abnormal conformational isoform (PrP(sc of the natural cellular prion protein (PrP(c encoded by the Prnp gene. Although several roles have been attributed to PrP(c, its putative functions in neuronal excitability are unknown. Although early studies of the behavior of Prnp knockout mice described minor changes, later studies report altered behavior. To date, most functional PrP(c studies on synaptic plasticity have been performed in vitro. To our knowledge, only one electrophysiological study has been performed in vivo in anesthetized mice, by Curtis and coworkers. They reported no significant differences in paired-pulse facilitation or LTP in the CA1 region after Schaffer collateral/commissural pathway stimulation. METHODOLOGY/PRINCIPAL FINDINGS: Here we explore the role of PrP(c expression in neurotransmission and neural excitability using wild-type, Prnp -/- and PrP(c-overexpressing mice (Tg20 strain. By correlating histopathology with electrophysiology in living behaving mice, we demonstrate that both Prnp -/- mice but, more relevantly Tg20 mice show increased susceptibility to KA, leading to significant cell death in the hippocampus. This finding correlates with enhanced synaptic facilitation in paired-pulse experiments and hippocampal LTP in living behaving mutant mice. Gene expression profiling using Illumina microarrays and Ingenuity pathways analysis showed that 129 genes involved in canonical pathways such as Ubiquitination or Neurotransmission were co-regulated in Prnp -/- and Tg20 mice. Lastly, RT-qPCR of neurotransmission-related genes indicated that subunits of GABA(A and AMPA-kainate receptors are co-regulated in both Prnp -/- and Tg20 mice. CONCLUSIONS/SIGNIFICANCE: Present results demonstrate that PrP(c is necessary for the

  2. Computertomografiangiografi af hjernens og halsens kar

    DEFF Research Database (Denmark)

    Langkilde, Annika Reynberg; Stavngaard, Trine; Cortsen, Marie;


    Due to the high temporal and spatial resolution in multislice computed tomography it is possible to perform high-quality computer tomography angiography (CTA) of the cerebral and cervical vessels. Compared to digital subtraction angiography (DSA), a method that is still considered to be the golden...... standard, CTA is faster and can be performed using a minimal invasive technique. In this paper we outline the clinical indications for performing CTA (aneurysms, stroke, vasospasms, arterio-venous malformations, dissection). Examples of scan protocols are given both for angiography of the cerebral vessels...... alone and for angiography of the cervical and cerebral vessels in combination. Postprocessing methods for evaluating the images in 2D and 3D are described. Finally CTA is compared to other modalities (DSA, magnetic resonance angiography and Doppler ultrasound)....

  3. Maksukorralduse uurimata imidž / Karlis Goldstein

    Index Scriptorium Estoniae

    Goldstein, Karlis


    Uurimusest maksukorralduse imago tõstmise, maksude kogumise ja nende kasutamise vahele seoste tekitamise vajalikkusest. Avalike allikate funktsioonidest maksukorralduse maine käsitlemisel ning trükimeedia ja erakondade programmilistest hinnangutest. Lisa: Autori CV. Tabelid: Ajalehtedes kasutatud maksuteemaliste sõnade positiivsus (jaanuar 2002-aprill 2005); Erakondade programmides kasutatud maksuteemaliste sõnade positiivsus; Küsimustiku tulemused üksikute sõnade kaupa

  4. Stress og hjerte-kar-sygdom

    DEFF Research Database (Denmark)

    Ebstrup, Jeanette Frost; Jørgensen, Torben


    Risk factors of cardiovascular disease (CVD) have been studied intensely since the 1950s. Results on stress as a risk factor for CVD have been inconsistent, but mainly positive. The risk is mediated through lifestyle, but more direct physiological mechanisms (e.g. autonomous nervous system...... and hypothalamic-pituitary-adrenal axis) are also found. Personality and general coping resources influence stress-appraisal, stress-coping and stress-response. Future studies should integrate stress as a cause (stressor), as a subjective reaction (perception), and as a physiological reaction in the same...

  5. Stress og hjerte-kar-sygdom

    DEFF Research Database (Denmark)

    Ebstrup, Jeanette Frost; Jørgensen, Torben


    Risk factors of cardiovascular disease (CVD) have been studied intensely since the 1950s. Results on stress as a risk factor for CVD have been inconsistent, but mainly positive. The risk is mediated through lifestyle, but more direct physiological mechanisms (e.g. autonomous nervous system...... and hypothalamic-pituitary-adrenal axis) are also found. Personality and general coping resources influence stress-appraisal, stress-coping and stress-response. Future studies should integrate stress as a cause (stressor), as a subjective reaction (perception), and as a physiological reaction in the same...

  6. Attempts of whole-rock K/Ar dating of mesozoic volcanic and hypabissal igneous rocks from the Central Subbetic (Southern Spain: A case of differential Argon loss related to very low-grade metamorphism

    Directory of Open Access Journals (Sweden)

    Sanz de Galdeano, C.


    Full Text Available 12 samples of basic intrusives within Triassic rocks «ophites» and 11 samples of volcanic and associated intrusives within Jurassic to Early Cretaceous sequences of the Subbetic Zone were subjected to whole-rock K/Ar dating in combination with chemical/petrological analysis. Satisfactory results were obtained only from a number of samples of volcanic rocks, however, analytical ages commonly agree, within about 10 relative percent, with those deduced from stratigraphic location. «Ophite» samples, on the other hand, may reveal considerably lower analytic ages than the volcanics and show much stronger scattering, even among samples collected within a small area. It is argued that the inferred loss of Ar results from very-low-grade alpine metamorphic alteration, which affected the «ophites» more intensely than the higher volcanic rocks. Other post-emplacement chemical changes, such as the degree of secondary oxidation of Fe, are also distintive among the two groups of samples, and are to some extent consistent with the above view in that the alteration environment of the ophites should have produced conditions for more penetrative fluid-rock interactions and homogeneous recrystallization. Overall, the magmatic activity from which the ophitic rocks originated might have started in the Late Triassic and continued in the Lower Jurassic. 80th, the «ophites» and the volcanics are though to be the result of magmatic events Collowing tensional to transtensive crustal movements affecting the external basins of the Betic Cordilleras Crom Late Triassic to Early Cretaceous times.Doce muestras de cuerpos básicos intrusivos en rocas triásicas («ofitas» y 11 muestras de volcanitas y rocas intrusivas asociadas en secuencias jurásico-cretáceas de la zona Subbética han sido objeto de datación radiométrica K/Ar (roca total en combinación con análisis químico-petrográfico. Las edades analíticas obtenidas son 's

  7. İki farklı Co-Cr HBP alaşımının mekanik özelliklerinin karşılaştırılması

    Directory of Open Access Journals (Sweden)

    Cem Kurtoglu


    Full Text Available

    Purpose: The purpose of this study was to compare the mechanical properties of two different removable partial denture alloys that are commonly used in Çukurova University Faculty of Dentistry.

    Material and Methods: Using two different Co-Cr alloys; Magnum H60 (MESA, Travagliato, Italy and Biosil F (Degussa Dental, GmbH, Hanau, Germany ten tensile test specimens were prepared for each group according to the ADA specification number 14. Specimens were loaded to crack. Ultimate tensile strength and percent elongation of two groups were compared using Mann Whitney U test (α=0.05. Crack surfaces were investigated using a stereomicroskop.

    Results: A statistically significant difference was found between ultimate tensile strength of Magnum H60 (828 ± 17.3 MPa and Biosil F (782 ± 51.6 (α =0.01. Percent elongation of Magnum H60 and Biosil F were found as 6.77 ± 1.62 and 6.32 ± 2.38, respectively. No significant difference was found among the two groups when the percent elongation was compared (α =0.496. Stereomicroscope images that are taken from the crack surfaces of both groups show similarities. Porotic structures and cracks that formed during solidification of the alloys can be seen on crack surfaces.

    Conclusion: Both of the Co-Cr removable partial denture alloys tested in the current study seem capable of serving in the mouth for a long time.


    Amaç: Bu çalışmanın amacı Çukurova Üniversitesi Diş Hekimliği Fakültesi’nde sıklıkla kullanılmakta olan iki farklı hareketli bölümlü protez alaşımının mekanik özelliklerini karşılaştırmaktır.

    Gereç ve Yöntem: Magnum H60 (MESA, Travagliato, İtalya ve Biosil F (Degussa Dental, GmbH, Hanau, Almanya olmak üzere iki farklı Co-Cr alaşımı kullanılarak her grup için 10

  8. Acetylcholine receptor antibody (United States)

    ... page: // Acetylcholine receptor antibody To use the sharing features on this page, please enable JavaScript. Acetylcholine receptor antibody is a protein found in the blood ...

  9. The combination of glutamate receptor antagonist MK-801 with tamoxifen and its active metabolites potentiates their antiproliferative activity in mouse melanoma K1735-M2 cells

    Energy Technology Data Exchange (ETDEWEB)

    Ribeiro, Mariana P.C. [Center for Neuroscience and Cell Biology, University of Coimbra, 3000-354 Coimbra (Portugal); Laboratory of Biochemistry, Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra (Portugal); Nunes-Correia, Isabel [Center for Neuroscience and Cell Biology, Flow Cytometry Unit, University of Coimbra, 3000-354 Coimbra (Portugal); Santos, Armanda E., E-mail: [Center for Neuroscience and Cell Biology, University of Coimbra, 3000-354 Coimbra (Portugal); Laboratory of Biochemistry, Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra (Portugal); Custódio, José B.A. [Center for Neuroscience and Cell Biology, University of Coimbra, 3000-354 Coimbra (Portugal); Laboratory of Biochemistry, Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra (Portugal)


    Recent reports suggest that N-methyl-D-aspartate receptor (NMDAR) blockade by MK-801 decreases tumor growth. Thus, we investigated whether other ionotropic glutamate receptor (iGluR) antagonists were also able to modulate the proliferation of melanoma cells. On the other hand, the antiestrogen tamoxifen (TAM) decreases the proliferation of melanoma cells, and is included in combined therapies for melanoma. As the efficacy of TAM is limited by its metabolism, we investigated the effects of the NMDAR antagonist MK-801 in combination with TAM and its active metabolites, 4-hydroxytamoxifen (OHTAM) and endoxifen (EDX). The NMDAR blockers MK-801 and memantine decreased mouse melanoma K1735-M2 cell proliferation. In contrast, the NMDAR competitive antagonist APV and the AMPA and kainate receptor antagonist NBQX did not affect cell proliferation, suggesting that among the iGluR antagonists only the NMDAR channel blockers inhibit melanoma cell proliferation. The combination of antiestrogens with MK-801 potentiated their individual effects on cell biomass due to diminished cell proliferation, since it decreased the cell number and DNA synthesis without increasing cell death. Importantly, TAM metabolites combined with MK-801 promoted cell cycle arrest in G1. Therefore, the data obtained suggest that the activity of MK-801 and antiestrogens in K1735-M2 cells is greatly enhanced when used in combination. - Highlights: • MK-801 and memantine decrease melanoma cell proliferation. • The combination of MK-801 with antiestrogens inhibits melanoma cell proliferation. • These combinations greatly enhance the effects of the compounds individually. • MK-801 combined with tamoxifen active metabolites induces cell cycle arrest in G1. • The combination of MK-801 and antiestrogens is an innovative strategy for melanoma.

  10. Androgen receptor abnormalities

    NARCIS (Netherlands)

    A.O. Brinkmann (Albert); G.G.J.M. Kuiper (George); C. Ris-Stalpers (Carolyn); H.C.J. van Rooij (Henri); G. Romalo (G.); G. Trifiro (Gianluca); E. Mulder (Eppo); L. Pinsky (L.); H.U. Schweikert (H.); J. Trapman (Jan)


    markdownabstract__Abstract__ The human androgen receptor is a member of the superfamily of steroid hormone receptors. Proper functioning of this protein is a prerequisite for normal male sexual differentiation and development. The cloning of the human androgen receptor cDNA and the elucidation of t

  11. Mammalian Sweet Taste Receptors

    National Research Council Canada - National Science Library

    Nelson, Greg; Hoon, Mark A; Chandrashekar, Jayaram; Zhang, Yifeng; Ryba, Nicholas J.P; Zuker, Charles S


    ... and information coding, and have focused on the isolation and characterization of genes encoding sweet and bitter taste receptors. The identification of taste receptors generates powerful molecular tools to investigate not only the function of taste receptor cells, but also the logic of taste coding. For example, defining the size and diversity of the re...

  12. [Melatonin receptor agonist]. (United States)

    Uchiyama, Makoto


    Melatonin is a hormone secreted by the pineal gland and is involved in the regulation of human sleep-wake cycle and circadian rhythms. The melatonin MT1 and MT2 receptors located in the suprachiasmatic nucleus in the hypothalamus play a pivotal role in the sleep-wake regulation. Based on the fact that MT1 receptors are involved in human sleep onset process, melatonin receptor agonists have been developed to treat insomnia. In this article, we first reviewed functions of melatonin receptors with special reference to MT1 and MT2, and properties and clinical application of melatonin receptor agonists as hypnotics.

  13. Dopamine receptors and hypertension. (United States)

    Banday, Anees Ahmad; Lokhandwala, Mustafa F


    Dopamine plays an important role in regulating renal function and blood pressure. Dopamine synthesis and dopamine receptor subtypes have been shown in the kidney. Dopamine acts via cell surface receptors coupled to G proteins; the receptors are classified via pharmacologic and molecular cloning studies into two families, D1-like and D2-like. Two D1-like receptors cloned in mammals, the D1 and D5 receptors (D1A and D1B in rodents), are linked to adenylyl cyclase stimulation. Three D2-like receptors (D2, D3, and D4) have been cloned and are linked mainly to adenylyl cyclase inhibition. Activation of D1-like receptors on the proximal tubules inhibits tubular sodium reabsorption by inhibiting Na/H-exchanger and Na/K-adenosine triphosphatase activity. Reports exist of defective renal dopamine production and/or dopamine receptor function in human primary hypertension and in genetic models of animal hypertension. In humans with essential hypertension, renal dopamine production in response to sodium loading is often impaired and may contribute to hypertension. A primary defect in D1-like receptors and an altered signaling system in proximal tubules may reduce dopamine-mediated effects on renal sodium excretion. The molecular basis for dopamine receptor dysfunction in hypertension is being investigated, and may involve an abnormal posttranslational modification of the dopamine receptor.

  14. Köyceğiz Gölü ve Dalyan Kanallarında Kıyı Kenar Çizgisinin UA ve CBS Teknikleri ile Belirlenmesi, Alanda Karşılaşılan Sorunlar

    Directory of Open Access Journals (Sweden)

    Serdar SELİM


    Full Text Available Köyceğiz-Dalyan Havzası, sahip olduğu doğal-kültürel varlık ve değerleri sebebiyle 1988 yılında ülkemizin ilk Özel Çevre Koruma Bölgesi (ÖÇKB olarak ilan edilmiştir. Yöre; su ve kıyı ekosistemini oluşturan Köyceğiz Gölü, Dalyan Kanalları, Dalyan Lagün Ağzı ve İztuzu kıyısı ile uluslararası ölçekte önem taşımaktadır. Ancak havzada kıyı kenar çizgisi henüz net bir şekilde ortaya konulmuş değildir. Bu durum kıyı kullanımlarında sorunlara ve kıyı alanları üzerine baskılara neden olmaktadır. Bu çalışmada, Köyceğiz Gölü ve Dalyan Kanallarında uzaktan algılama (UA ve coğrafi bilgi sistemleri (CBS kullanılarak, 3621 sayılı Kıyı Kanunu ile Kıyı Kanunun Uygulanmasına Dair Yönetmelik çerçevesinde kıyı kenar çizgisi tespit edilmiştir. Kıyı çizgisi ve kıyı kenar çizgisinin tespitinde, alana ait temel toprak haritalarının, ortofotoların ve güncel uydu verilerinin jeoreferanslama ve sayısallaştırma işlemleri gerçekleştirilmiş, haritalar çakıştırılmış ve arazi kontrolleri ile karşılaştırılmıştır. Sonuç olarak, herkesin eşit ve serbest olarak yararlanmasına açık olan Köyceğiz Gölü, Dalyan Kanalları ve İztuzu kıyısında ‘Kıyıda ve sahil şeridinde planlama ve uygulama yapılabilmesi için kıyı kenar çizgisinin tespiti zorunludur’ kanun hükmünün henüz uygulanmadığı görülmüştür. Yapılan analizlerde ulusal kıyı mevzuatına aykırı kullanımlar tespit edilmiştir. Uzaktan algılama ve coğrafi bilgi sistemleri teknikleriyle bölgede kıyı çizgisi ve kıyı kenar çizgisi tespit edilerek bu çalışmanın bölge kıyılarındaki planlama kararlarında belirleyici olması hedeflenmiştir. 

  15. Otizm Spektrum Bozukluğu Olan ve Normal Gelişim Gösteren Çocuklarda Anne-Çocuk Etkileşiminin Karşılaştırılması

    Directory of Open Access Journals (Sweden)

    Yasemin Doğan


    Full Text Available Bu araştırmada otizm spektrum bozukluğu (OSB olan çocuğa sahip (n=34 annelerin ve normal gelişim gösteren (NG çocuğa sahip (n=28 annelerin ebeveyn-çocuk etkileşimi sırasında sergiledikleri etkileşimsel davranışları karşılaştırılmıştır. Araştırma kapsamında çalışma grubunda yer alan annelerin serbest oyun bağlamında çocukları ile etkileşimlerinin video kayıtları alınmıştır. Kayıtlar anne davranışları için oluşturulan beş kategori ve annelerin çocuklarına sunduğu pekiştireçlerin analizi ile incelenmiştir. Anne etkileşimsel davranışları kategorileri; yönlendirici olma, başarı odaklı olma, yanıtlayıcı olma, sıcak olma ve etkileşimsizliktir. Araştırma bulguları OSB‟li çocuğu olan annelerin NG‟li çocuğu olan annelere oranla daha fazla yönlendirici vedaha az yanıtlayıcı etkileşimsel davranışlar sergiledikleri yönündedir. Araştırma bulguları erken çocukluk döneminde OSB‟li çocuğu olan ve NG‟li çocuğu olan annelerin çocuklarına yönelik etkileşimsel davranışları bağlamında tartışılmış ve ileride yapılacak araştırmalara yönelik önerilere yer verilmiştir. This study compares the interactional behaviors of mothers of children with autism spectrum disorders (n=34 and mothers of typically developing children (n=28 through mother-child dyads. Participating mothers and their children were recorded while playing in an unstructured environment. Data were analyzed using five distinct mother interactional behavior categories and mother reinforcements used during the interactions. Mother interactional behaviors were: Directiveness, achievement orientation, responsivity, warmth and un-engagement. Study results were discussed in regard to the interactional behaviors of mothers of children with ASD and TD with their children and suggestions for future research were provided .

  16. Üniversite Öğrencilerinin ‘‘Topluluk Karşısında Konuşma’’ İle İlgili Çeşitli Görüşleri Some Opinions of the University Students Related to “Giving a Speech in Front of Public”

    Directory of Open Access Journals (Sweden)

    Akif ARSLAN


    Full Text Available This study aims to determine various opinions of university students related to the skill of making a speech in front of the public.With this aim 500 university students, attending different departments at Ağrı İbrahim Çecen University, were administered a questionnaire developed by the researcher, and the data of research are gathered. As a result of this study, it is determined that many of the students want to give a speech in front of the public but because of various reasons such as not to have adequacy in Turkish, acquiring Turkish as a second language, the fear of giving wrong or inadequate knowledge, audience’s sarcastic reactions, lack of self-confidence, shy personality, accent problems, worry of not being understood etc. even if they have the chance, they do not speak in front of the public or they avoid the duties required giving speech in front of the public. It is also identified that the students in this study are of the idea that this skill is not improved at educational institutions because of some reasons such as only successful students’ being given the right of the speech, the activities in front of the public’s being limited to some official ceremonies, crowded classroom, students not being given right to speak as required and teachers speaking mostly, fear of students from teacher’s reaction and ignoring speaking skills because of focusing on centrally given examinations. In this study, after the students’ psychological and physical characteristics, getting nervous, sweating, fear of being criticized, forgetting what to say, fear of getting dizzy, and blushing, sweating, trembling, headache, stumbling, trilling, heart beat speeding up, swallowing words respectively are determined it is also mentioned what should be done in order to decrease the level of excitement that occurs in front of public. Çalışmanın amacı üniversite öğrencilerinin topluluk karşısında konuşma becerisi ile ilgili çeşitli g

  17. GABA receptor imaging

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jong Doo [Yonsei University College of Medicine, Seoul (Korea, Republic of)


    GABA is primary an inhibitory neurotransmitter that is localized in inhibitory interneurons. GABA is released from presynaptic terminals and functions by binding to GABA receptors. There are two types of GABA receptors, GABA{sub A}-receptor that allows chloride to pass through a ligand gated ion channel and GABA{sub B}-receptor that uses G-proteins for signaling. The GABA{sub A}-receptor has a GABA binding site as well as a benzodiazepine binding sites, which modulate GABA{sub A}-receptor function. Benzodiazepine GABAA receptor imaging can be accomplished by radiolabeling derivates that activates benzodiazepine binding sites. There has been much research on flumazenil (FMZ) labeled with {sup 11}C-FMZ, a benzodiazepine derivate that is a selective, reversible antagonist to GABAA receptors. Recently, {sup 18}F-fluoroflumazenil (FFMZ) has been developed to overcome {sup 11}C's short half-life. {sup 18}F-FFMZ shows high selective affinity and good pharmacodynamics, and is a promising PET agent with better central benzodiazepine receptor imaging capabilities. In an epileptic focus, because the GABA/benzodiazepine receptor amount is decreased, using '1{sup 1}C-FMZ PET instead of {sup 18}F-FDG, PET, restrict the foci better and may also help find lesions better than high resolution MR. GABA{sub A} receptors are widely distributed in the cerebral cortex, and can be used as an viable neuronal marker. Therefore it can be used as a neuronal cell viability marker in cerebral ischemia. Also, GABA-receptors decrease in areas where neuronal plasticity develops, therefore, GABA imaging can be used to evaluate plasticity. Besides these usages, GABA receptors are related with psychological diseases, especially depression and schizophrenia as well as cerebral palsy, a motor-related disorder, so further in-depth studies are needed for these areas.

  18. A new agonist of the erythropoietin receptor, Epobis, induces neurite outgrowth and promotes neuronal survival

    DEFF Research Database (Denmark)

    Pankratova, Stanislava; Gu, Bing; Kiryushko, Darya


    study shows that the Epobis peptide specifically binds to EPOR and induces neurite outgrowth from primary neurons in an EPOR-expression dependent manner. Furthermore, Epobis promoted the survival of hippocampal and cerebellar neuronal cultures after kainate treatment and KCl deprivation, respectively...

  19. Dopamine D4 receptor activation increases hippocampal gamma oscillations by enhancing synchronization of fast-spiking interneurons.

    Directory of Open Access Journals (Sweden)

    Richard Andersson

    Full Text Available BACKGROUND: Gamma oscillations are electric activity patterns of the mammalian brain hypothesized to serve attention, sensory perception, working memory and memory encoding. They are disrupted or altered in schizophrenic patients with associated cognitive deficits, which persist in spite of treatment with antipsychotics. Because cognitive symptoms are a core feature of schizophrenia it is relevant to explore signaling pathways that potentially regulate gamma oscillations. Dopamine has been reported to decrease gamma oscillation power via D1-like receptors. Based on the expression pattern of D4 receptors (D4R in hippocampus, and pharmacological effects of D4R ligands in animals, we hypothesize that they are in a position to regulate gamma oscillations as well. METHODOLOGY/PRINCIPAL FINDINGS: To address this hypothesis we use rat hippocampal slices and kainate-induced gamma oscillations. Local field potential recordings as well as intracellular recordings of pyramidal cells, fast-spiking and non-fast-spiking interneurons were carried out. We show that D4R activation with the selective ligand PD168077 increases gamma oscillation power, which can be blocked by the D4R-specific antagonist L745,870 as well as by the antipsychotic drug Clozapine. Pyramidal cells did not exhibit changes in excitatory or inhibitory synaptic current amplitudes, but inhibitory currents became more coherent with the oscillations after application of PD168077. Fast-spiking, but not non-fast spiking, interneurons, increase their action potential phase-coupling and coherence with regard to ongoing gamma oscillations in response to D4R activation. Among several possible mechanisms we found that the NMDA receptor antagonist AP5 also blocks the D4R mediated increase in gamma oscillation power. CONCLUSIONS/SIGNIFICANCE: We conclude that D4R activation affects fast-spiking interneuron synchronization and thereby increases gamma power by an NMDA receptor-dependent mechanism. This

  20. Chicken NK cell receptors. (United States)

    Straub, Christian; Neulen, Marie-Luise; Sperling, Beatrice; Windau, Katharina; Zechmann, Maria; Jansen, Christine A; Viertlboeck, Birgit C; Göbel, Thomas W


    Natural killer cells are innate immune cells that destroy virally infected or transformed cells. They recognize these altered cells by a plethora of diverse receptors and thereby differ from other lymphocytes that use clonally distributed antigen receptors. To date, several receptor families that play a role in either activating or inhibiting NK cells have been identified in mammals. In the chicken, NK cells have been functionally and morphologically defined, however, a conclusive analysis of receptors involved in NK cell mediated functions has not been available. This is partly due to the low frequencies of NK cells in blood or spleen that has hampered their intensive characterization. Here we will review recent progress regarding the diverse NK cell receptor families, with special emphasis on novel families identified in the chicken genome with potential as chicken NK cell receptors. Copyright © 2013 Elsevier Ltd. All rights reserved.

  1. LU 73068, a new non-NMDA and glycine/NMDA receptor antagonist: pharmacological characterization and comparison with NBQX and L-701,324 in the kindling model of epilepsy. (United States)

    Potschka, H; Löscher, W; Wlaź, P; Behl, B; Hofmann, H P; Treiber, H J; Szabo, L


    The aim of this study was to assess whether a drug which combines an antagonistic action at both NMDA and non-NMDA receptors offers advantages for treatment of epileptic seizures compared to drugs which antagonize only one of these ionotropic glutamate receptors. The novel glutamate receptor antagonist LU 73068 (4,5-dihydro-1-methyl-4-oxo-7-trifluoromethylimidazo[1,2a]quinoxal ine-2-carbonic acid) binds with high affinity to both the glycine site of the NMDA receptor (Ki 185 nM) and to the AMPA receptor (Ki 158 nM). Furthermore, binding experiments with recombinant kainate receptor subunits showed that LU 73068 binds to several of these subunits, particularly to rGluR7 (Ki 104 nM) and rGluR5 (Ki 271 nM). In comparison, the prototype non-NMDA receptor antagonist NBQX (2,3-dihydroxy-6-nitro-7-sulphamoyl-benzo[f]quinoxaline) binds with high affinity to AMPA receptors only. Both NBQX and LU 73068 were about equieffective after i.p. injection in mice to block lethal convulsions induced by AMPA or NMDA. In the rat amygdala kindling model of temporal lobe epilepsy, LU 73068 dose-dependently increased the focal seizure threshold (afterdischarge threshold, ADT). When rats were stimulated with a current 20% above the individual control ADT, LU 73068 completely blocked seizures with an ED50 of 4.9 mg kg(-1). Up to 20 mg kg(-1), only moderate adverse effects, e.g. slight ataxia, were observed. NBQX, 10 mg kg(-1), and the glycine/NMDA site antagonist L-701,324 (7-chloro-4-hydroxy-3-(3-phenoxy)phenyl-quinoline-2(1H)one), 2.5 or 5 mg kg(-1), exerted no anticonvulsant effects in kindled rats when administered alone, but combined treatment with both drugs resulted in a significant ADT increase. The data indicate that combination of glycine/NMDA and non-NMDA receptor antagonism in a single drug is an effective means of developing a potent and effective anticonvulsant agent.

  2. Novel cannabinoid receptors


    Brown, A J


    Cannabinoids have numerous physiological effects. In the years since the molecular identification of the G protein-coupled receptors CB1 and CB2, the ion channel TRPV1, and their corresponding endogenous ligand systems, many cannabinoid-evoked actions have been shown conclusively to be mediated by one of these specific receptor targets. However, there remain several examples where these classical cannabinoid receptors do not explain observed pharmacology. Studies using mice genetically delete...

  3. Therapeutic androgen receptor ligands


    Allan, George F.; Sui, Zhihua


    In the past several years, the concept of tissue-selective nuclear receptor ligands has emerged. This concept has come to fruition with estrogens, with the successful marketing of drugs such as raloxifene. The discovery of raloxifene and other selective estrogen receptor modulators (SERMs) has raised the possibility of generating selective compounds for other pathways, including androgens (that is, selective androgen receptor modulators, or SARMs).

  4. AMPA receptor ligands

    DEFF Research Database (Denmark)

    Strømgaard, Kristian; Mellor, Ian


    Alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors (AMPAR), subtype of the ionotropic glutamate receptors (IGRs), mediate fast synaptic transmission in the central nervous system (CNS), and are involved in many neurological disorders, as well as being a key player in the f......Alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors (AMPAR), subtype of the ionotropic glutamate receptors (IGRs), mediate fast synaptic transmission in the central nervous system (CNS), and are involved in many neurological disorders, as well as being a key player...

  5. Spreading depression induces expression of calcium-independent protein kinase C subspecies in ischaemia-sensitive cortical layers: regulation by N-methyl-D-aspartate receptors and glucocorticoids. (United States)

    Koponen, S; Keinänen, R; Roivainen, R; Hirvonen, T; Närhi, M; Chan, P H; Koistinaho, J


    Spreading depression is a wave of sustained depolarization challenging the energy metabolism of the cells without causing irreversible damage. In the ischaemic brain, sreading depression-like depolarization contributes to the evolution of ischaemia to infarction. The depolarization is propagated by activation of N-methyl-D-aspartate receptors, but changes in signal transduction downstream of the receptors are not known. Because protein phosphorylation is a general mechanism whereby most cellular processes are regulated, and inhibition of N-methyl-D-aspartate receptors or protein kinase C is neuroprotective, the expression of protein kinase C subspecies in spreading depression was examined. Cortical treatment with KCl induced an upregulation of protein kinase Cdelta and zeta messenger RNA at 4 and 8 h, whereas protein kinase Calpha, beta, gamma and epsilon did not show significant changes. The gene induction was the strongest in layers 2 and 3, and was followed by an increased number of protein kinase Cdelta-immunoreactive neurons. Protein kinase Cdelta and zeta inductions were inhibited by pretreatment with an N-methyl-D-aspartate receptor antagonist, dizocilpine maleate, which also blocked spreading depression propagation, and with dexamethasone, which acted without blocking the propagation. Quinacrine, a phospholipase A2 inhibitor, reduced only protein kinase C5 induction. In addition, N(G)(-nitro-L-arginine methyl ester, a nitric oxide synthase inhibitor, did not influence protein kinase Cdelta or zeta induction, whereas 6-nitro-7-sulphamoylbenzo[f]quinoxaline-2,3-dione, an alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate/kainate receptor antagonist, and the cyclo-oxygenase inhibitors indomethacin and diclophenac tended to increase gene expression. The data show that cortical spreading depression induces Ca2(+)-independent protein kinase C subspecies delta and zeta, but not Ca(2+)-dependent subspecies, through activation of N-methyl-D-aspartate receptors and

  6. Altered gamma oscillations during pregnancy through loss of δ subunit-containing GABA(A) receptors on parvalbumin interneurons. (United States)

    Ferando, Isabella; Mody, Istvan


    Gamma (γ) oscillations (30-120 Hz), an emergent property of neuronal networks, correlate with memory, cognition and encoding. In the hippocampal CA3 region, locally generated γ oscillations emerge through feedback between inhibitory parvalbumin-positive basket cells (PV+BCs) and the principal (pyramidal) cells. PV+BCs express δ-subunit-containing GABA(A)Rs (δ-GABA(A)Rs) and NMDA receptors (NMDA-Rs) that balance the frequency of γ oscillations. Neuroactive steroids (NS), such as the progesterone-derived (3α,5α)-3-hydroxy-pregnan-20-one (allopregnanolone; ALLO), modulate the expression of δ-GABA(A)Rs and the tonic conductance they mediate. Pregnancy produces large increases in ALLO and brain-region-specific homeostatic changes in δ-GABA(A)Rs expression. Here we show that in CA3, where most PV+ interneurons (INs) express δ-GABA(A)Rs, expression of δ-GABA(A)Rs on INs diminishes during pregnancy, but reverts to control levels within 48 h postpartum. These anatomical findings were corroborated by a pregnancy-related increase in the frequency of kainate-induced CA3 γ oscillations in vitro that could be countered by the NMDA-R antagonists D-AP5 and PPDA. Mimicking the typical hormonal conditions during pregnancy by supplementing 100 nM ALLO lowered the γ frequencies to levels found in virgin or postpartum mice. Our findings show that states of altered NS levels (e.g., pregnancy) may provoke perturbations in γ oscillatory activity through direct effects on the GABAergic system, and underscore the importance of δ-GABA(A)Rs homeostatic plasticity in maintaining constant network output despite large hormonal changes. Inaccurate coupling of NS levels to δ-GABA(A)R expression may facilitate abnormal neurological and psychiatric conditions such as epilepsy, post-partum depression, and post-partum psychosis, thus providing insights into potential new treatments.

  7. Altered gamma oscillations during pregnancy through loss of δ subunit-containing GABAA receptors on parvalbumin interneurons

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    Isabella eFerando


    Full Text Available Gamma (γ oscillations (30-120 Hz, an emergent property of neuronal networks, correlate with memory, cognition and encoding. In the hippocampal CA3 region, locally generated γ oscillations emerge through feedback between inhibitory parvalbumin-positive basket cells (PV+BCs and the principal (pyramidal cells. PV+BCs express δ-subunit-containing GABAARs (-GABAARs and NMDA receptors (NMDA-Rs that balance the frequency of γ oscillations. Neuroactive steroids (NS, such as the progesterone-derived (3α,5α-3-hydroxy-pregnan-20-one (allopregnanolone; ALLO, modulate the expression of δ-GABAARs and the tonic conductance they mediate. Pregnancy produces large increases in ALLO and brain-region-specific homeostatic changes in δ-GABAARs expression. Here we show that in CA3, where most PV+ interneurons (INs express δ-GABAARs, expression of δ-GABAARs on INs diminishes during pregnancy, but reverts to control levels within 48 hours postpartum. These anatomical findings were corroborated by a pregnancy-related increase in the frequency of kainate-induced CA3 γ oscillations in vitro that could be countered by the NMDA-R antagonists D-AP5 and PPDA. Mimicking the typical hormonal conditions during pregnancy by supplementing 100 nM ALLO lowered the γ frequencies to levels found in virgin or postpartum mice. Our findings show that states of altered NS levels (e.g., pregnancy may provoke perturbations in γ oscillatory activity through direct effects on the GABAergic system, and underscore the importance of δ-GABAARs homeostatic plasticity in maintaining constant network output despite large hormonal changes. Inaccurate coupling of NS levels to δ-GABAAR expression may facilitate abnormal neurological and psychiatric conditions such as epilepsy, post-partum depression, and post-partum psychosis, thus providing insights into potential new treatments.

  8. GLYX-13, a NMDA Receptor Glycine-Site Functional Partial Agonist, Induces Antidepressant-Like Effects Without Ketamine-Like Side Effects (United States)

    Burgdorf, Jeffrey; Zhang, Xiao-lei; Nicholson, Katherine L; Balster, Robert L; David Leander, J; Stanton, Patric K; Gross, Amanda L; Kroes, Roger A; Moskal, Joseph R


    Recent human clinical studies with the NMDA receptor (NMDAR) antagonist ketamine have revealed profound and long-lasting antidepressant effects with rapid onset in several clinical trials, but antidepressant effects were preceded by dissociative side effects. Here we show that GLYX-13, a novel NMDAR glycine-site functional partial agonist, produces an antidepressant-like effect in the Porsolt, novelty induced hypophagia, and learned helplessness tests in rats without exhibiting substance abuse-related, gating, and sedative side effects of ketamine in the drug discrimination, conditioned place preference, pre-pulse inhibition and open-field tests. Like ketamine, the GLYX-13-induced antidepressant-like effects required AMPA/kainate receptor activation, as evidenced by the ability of NBQX to abolish the antidepressant-like effect. Both GLYX-13 and ketamine persistently (24 h) enhanced the induction of long-term potentiation of synaptic transmission and the magnitude of NMDAR-NR2B conductance at rat Schaffer collateral-CA1 synapses in vitro. Cell surface biotinylation studies showed that both GLYX-13 and ketamine led to increases in both NR2B and GluR1 protein levels, as measured by Western analysis, whereas no changes were seen in mRNA expression (microarray and qRT-PCR). GLYX-13, unlike ketamine, produced its antidepressant-like effect when injected directly into the medial prefrontal cortex (MPFC). These results suggest that GLYX-13 produces an antidepressant-like effect without the side effects seen with ketamine at least in part by directly modulating NR2B-containing NMDARs in the MPFC. Furthermore, the enhancement of ‘metaplasticity' by both GLYX-13 and ketamine may help explain the long-lasting antidepressant effects of these NMDAR modulators. GLYX-13 is currently in a Phase II clinical development program for treatment-resistant depression. PMID:23303054

  9. Fulfilling the need for knowledge via distance education: A university program proposalUzaktan eğitim ile bilgi ihtiyacının karşılanması: Bir üniversite programı önerisi

    Directory of Open Access Journals (Sweden)

    Mehmet Cüneyt Birkök


    Full Text Available The ongoing social transformation process and the developments in science and technology concurrently raised the importance of knowledge at any range. Technical educators happen to lose knowledge because of forgetting after their graduation, their knowledge grows obsolete and they need to learn the new acquirements which turn out at the same time. In this research, the effect of a distance education based program which is lead by universities in corresponding to the requirements of knowledge is examined.First of all, in this study, in order to confirm the subject, an employee oriented pre-research is done. After that, a technical educators based questionnaire is surveyed which is concerning the distance education to the technical educators and their need of knowledge. In this research, it is observed that in this period of time, the employees need to gain knowledge continuously and this requirment can be covered by such distance education lead by universities.According to the results of the survey, technical teachers need to be informed and reminded of their earlier knowledge which they received through different educational programmes but forgot in the course of time. The information need of technical teachers must be provided via internet education supported with face to face trainings. Universities must meet the technical teachers’ need of information by organizing educational programmes. A program prepared for this reason, will fulfill the emptiness in our system of technical education, thus presenting important contribution to social development and bringing up qualified staff which the industry is in need. This sort of program must be put in process without delay with the association of all official and private institutions. Özet:Bu araştırmada üniversitelerce yürütülecek uzaktan eğitime dayalı bir programın, teknik öğretmenlerin bilgi ihtiyaçlarının karşılanmasına etkisinin ne düzeyde olacağı incelenmektedir

  10. Seçici Özellikteki Farklı Besiyerlerinin bazı Mayaların Meyveli Yoğurttan Geri Kazanımları Amacı ile Karşılaştırılmaları (İngilizce)


    Ergül, Şule Şenses; Özbaş, Z. Yeşim


    Bu çalışmada, yapay olarak aşılanan meyveli yoğurt örneklerinden bazı mayaların izolasyonu için kullanılabilecek farklı besiyerleri karşılaştırılmıştır. Bu amaçla, kontrol besiyeri olarak malt extract agar ve beş farklı seçici besiyeri kullanılmıştır. Bu besiyerleri; malt extract yeast extract %50 fructose glucose agar, malt extract yeast extract %40 sucrose agar, malt extract yeast extract glucose %0.8 peptone agar, malt extract yeast extract glucose %0.1 peptone agar and potato dextrose %50...

  11. Retraction: Radenović L, Selaković V. Mitochondrial superoxide production and MnSOD activity following exposure to an agonist and antagonists of ionotropic receptors in rat brain, Arch Biol Sci. 2005; 57(1:1-10, DOI:10.2298/ABS0501001R

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    Full Text Available This is a notice of retraction of the article: Mitochondrial superoxide production and MnSOD activity following exposure to an agonist and antagonists of ionotropic glutamate receptors in rat brain, published in the Archives of Biological Sciences in 2005, Vol. 57, Issue 1. The Editor-in-Chief has been informed that this paper plagiarizes an earlier paper: Radenović L, Selaković V, Kartelija G, Todorović N, Nedeljković M. Differential effects of NMDA and AMPA/kainate receptor antagonists on superoxide production and MnSOD activity in rat brain following intrahippocampal injection. Brain Res Bull, 2004, 64(1:85-93. This claim is correct and almost the entire paper is a verbatim copy of the earlier one. After confirmation of this fact, the Editor-in-Chief of the Archives of Biological Sciences has decided to retract the paper immediately. We apologize to the readers of the journal that it took so many years to notice this error and to retract the paper. We request readers of the journal to directly get in touch with the editorial office and the editors of the journal for similar cases in the future, so that they can be handled promptly. Link to the retracted article 10.2298/ABS0501001R

  12. U/Pb (SHRIMP), {sup 207}Pb/{sup 206}Pb, Rb/Sr, Sm/Nd e K/Ar geochronology of granite-greenstone terrains of Gaviao Block: implications for the Proterozoic and Archean evolution of Sao Francisco Craton, Brazil; Geocronologia U/Pb (SHRIMP), {sup 207}Pb/{sup 206}Pb, Rb/Sr, Sm/Nd e K/Ar dos terrenos granito-greenstone do Bloco do Gaviao: implicacoes para a evolucao arqueana e proterozoica do craton do Sao Francisco, Brasil

    Energy Technology Data Exchange (ETDEWEB)

    Leal, Luiz Rogerio Bastos


    The Gaviao Block (GB) in the northern portion of the Sao Francisco Craton-Northeast of Brazil, constitutes one of the oldest Archean fragments of the South American Platform Archean crust. GB underwent several events of juvenile accretion and reworking of continental crust along its evolutionary history, notably between the Archean and the Paleoproterozoic. {sup 207}Pb/{sup 206}Pb isotopic analyses were carried out in two zircons populations from strongly migmatized TTG terranes found in the proximity of Brumado: the first population (7 crystals) is taken as representative of the crystallization period of the TTG terranes at 3300 {+-} 45 Ma; the second (2 crystals) represents the age of the first even of metamorphism/migmatization at 2910 {+-} 10 Ma. {sup 207} Pb/{sup 206} Pb analyses in zircons from an outcrop of non-migmatized TTG in the area yielded a 3202 {+-} 15 Ma age (4 crystals), interpreted to be the crystallization period of the gneiss protolith. Sm/Nd analyses on the TTG rocks of the Brumado region yielded T{sub DM} model ages varying between 3.26 and 3.36 Ga and {epsilon}{sub Nd}{sup (t)} between -3.5 and +0.7. These data suggest the occurrence of juvenile accretions to the continental crust during the Archean, with differential involvement of crustal materials. The geochemical data of rare earth elements corresponding to the TTG terranes revealed moderate LRRE contents (La{sub N}=83,5), low HREE contents (La{sub N}=2,5) and a fairly fractionated pattern (La/Yb){sub N}=34, besides lack of negative Eu anomaly, showing that these rocks have similar compositions to those TTG terranes of cratonic continents, as well as some Archean rocks from CSF (e.g. Sete Voltas, Boa Vista). Finally, the youngest ages present in GB rocks (ca. 1.2-0.45 Ga) represent the role played by tectono thermal events, which produced partial or total rejuvenation of the Rb/Sr and K/Ar isotopic systems during the Espinhaco and Brasiliano cycles. In particular, K/Ar ages illustrate the

  13. “Cihanda Türk” Ve “Şarkımız” Şiirlerinin Varlıkbilim Açısından / Ontolojik Açıdan Karşılaştırılması Ontological Comparison Of “Cihanda Türk” And “Şarkimiz” Poems

    Directory of Open Access Journals (Sweden)



    orplagiarism, parallel these concepts are closer. Gustave Lanson’a göre, en özgün yazarların bile kişiliği geçmiş nesillerin ve edebi akımların sentezi olarak dörtte üç oranında ödünçleme ögelerden oluştuğu için her şairin yahut yazarın ufkunda başka şair ve yazarlar ile kendinden önce yazılmış edebi metinler vardır. Mitolojik bağlamda, bir söz söylediğinde bunun kendinden önce söylenmediğini bilme olanağına sahip tek kişi Hz. Adem yahut eşi Hz. Havva’dır. Uygarlık, insanlığın ulaştığı en büyük fikir sentezi olarak tanımlanır. Kendisinden zengin kültür ve uygarlıklarla karşılaşmayan ve bunlardan yararlanmayan kültürlerin gelişmesi ve uygarlık düzeyine yükselmesi nasıl mümkün değilse; bir yazarın öteki yazarlar ile karşı karşıya gelmemesi, onları keşfedip kendine mal etmemesi de mümkün değildir. Bu ilişkiler ağı içinden, yazarlık (metnimiz bağlamında şairlik da bir yazarın ulaştığı en büyük fikir sentezidir, çıkarımına ve tanımına ulaşabiliriz.Yazarların birbirlerinden etkilenmeleri doğal olduğu kadar üzerinde durulmaya değecek kertede ilginçtir ve karşılaştırmalı edebiyatın en önemli çalışma alanıdır. Bu yazıda Bekir Sıtkı Erdoğan’ın Cihanda Türk adlı şiiri ile Necip Fazıl Kısakürek’in Şarkımız adlı şiirleri ontolojik açıdan karşılaştırılmıştır. Makalemizde karşılaştırmalı edebiyatın kısa tarihi verildikten ve ontolojik yönteme göre edebi eserdeki varlık tabakaları özetlendikten sonra geçilen karşılaştırmada önce şiirlerin yayın serüveni üzerinde durularak, sahih bir metne ulaşılmaya çalışılmış; devamında edebi eserde varlık tabakaları olarak iç içe geçmiş olan ses tabakaları, anlam tabakaları, farklı şematik görüşler tabakları, alınyazısı tabakaları ayrıştırılmaya çalışılarak değerlendirmeler yapılmıştır. Sonuç başlığında ise aklama yahut karalama amacı g

  14. Osmanlı Devleti’nde Cadı Avı Var mıydı? (Karşılaştırmalı Bir İnceleme

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    Cem Doğan


    Full Text Available AbstractWitchcraft, namely putting a spell on someone in a general meaning is a traditionally ritual of early pagan societies. In the middle ages, thousands of people was sentenced to torture or death by accusing witchcraft and wondering and harming people around. As we look at the Ottoman Empire, we will see that there were some people who were accused by being a witch and exiled, or burned after their deaths by opening their graves. This study discusses the place of witchcraft and witches in the Western tradition and examines the trials of witchcraft both in Western and Ottoman societies. In addition to this, the attitude of the Ottoman State to witchcraft and witches also to be held.ÖzetCadılık yani genel anlamıyla düşünüldüğünde kötü emellerle büyü yapma geleneği, aslen erken dönem pagan toplumlarında görülen bir âdettir. Ortaçağ Avrupa’sında da engizisyon tarafından büyücülükle ve geceleri dolaşarak insanlara kötülük etmekle suçlanan binlerce kişi, “cadı” oldukları iddiasıyla işkenceye ve ölüme mahkûm edilmiştir. Osmanlı Devletine baktığımızda ise yine cadılıkla suçlanan ve bu nedenle yer değiştirme, öldükten sonra mezarı açılarak yakılma gibi birtakım cezalara çarptırılan kişilerin var olduğunu görürüz. Bu çalışmada, cadılığın ve cadıların Batı geleneğindeki yeri ve cadılığa ilişkin görülen davalar incelenmiş ve Osmanlı’da cadılığa ve devletin cadılara yönelik tutumu tetkik edilmiş ve Osmanlı toplumu ile Batı toplumlarında Cadılığı yaklaşım ile ilgili karşılaştırmalı bir inceleme yapılmıştır.La chasse aux sorcières dans l'Empire ottomanRésuméLa sorcellerie, à savoir faire de la magie dans un but négatif, était à l’origine une tradition des sociétés païennes de l’âge classique. Dans l’Europe médiévale, des milliers de personnes, accusées de sorcellerie du fait qu’elles sortaient la nuit pour faire de

  15. Öğretmenlerin Öğretim Stilleri Tercihleri:Türkiye-ABD Karşılaştırılması Teachers' Teaching Style Preferences: A Comparison of Turkey and the USA

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    ğretim stilleri tercihlerini karşılaştırmak olarak belirlenmiştir. Çalışmada, Türkiye’deki öğretmenlere (N=283 Grasha (1996 tarafından geliştirilen ve Üredi (2006 tarafından Türkçeye uyarlanan “Öğretim Stilleri Envanteri”, ABD’deki öğretmenlere (N=229 envanterin özgün formu uygulanmıştır. Araştırmada ilişkisel tarama modeli kullanılmıştır. Verilerin çözümlenmesinde frekans, yüzde dağılımları verilmiş ve ki-kare testi yapılmıştır. Bulgular ABD ve Türkiye’deki öğretmenlerin öğretim stilleri tercihlerinin istatistiksel olarak anlamlı farklılıklar gösterdiğini ortaya koymuştur. ABD’de en fazla tercih edilen öğretim stilinin temsilci/kolaylaştırıcı/uzman, en az tercih edilen öğretim stilinin ise uzman/otorite olduğu belirlenmiştir. Türkiye’de ise kolaylaştırıcı/kişisel model/uzman en fazla tercih edilen öğretim stili iken kişisel model/uzman/otorite en az tercih edilen öğretim stili olmuştur. Türkiye’deki öğretmenlerin yaygın olarak tercih ettiği öğretim stilinin hümanist yaklaşıma uygun olması olumlu bir sonuç olarak görülmüş ancak otorite/uzman öğretim stilinin de ikinci sırada tercih edilmesi dikkat çekici bulunmuştur. Bu bulgu, Türk Eğitim Sisteminde bir geçiş dönemi yaşandığı, yeniden yapılanma çalışmaları ile öğretmenlerin öğretmen merkezli öğretim anlayışından öğrenci merkezli eğitim anlayışına yöneldikleri biçiminde yorumlanmıştır.

  16. İmplant destekli overdenture ve klasik tam protezlerin hasta memnuniyeti açısından karşılaştırılması

    Directory of Open Access Journals (Sweden)

    Ceyda Ozcakir Tomruk


    dentures, implant-retained overdentures, satisfaction.



    Amaç: Bu çalışmanın amacı, klasik tam protez ve implant destekli tam protez kullanan hastaların memnuniyetlerini değerlendirmek ve demografik özelliklerin memnuniyet üzerine etkisini incelemekti.

    Gereç ve Yöntem: Çalışmaya, 2011 yılında Yeditepe Üniversitesi Diş Hekimliği Fakültesi’nde, alt-üst klasik tam protez ve üst klasik-alt implant destekli tam protez uygulanan, 27’si kadın ve 15’i erkek, toplam 42 hasta dahil edildi. Hastalara, sosyodemografik özelliklerini (cinsiyet, yaş, ömedeni durum, öğrenim durumu, gelir düzeyi içeren ve protezlerinin memnuniyetini değerlendiren anket formları dağıtıldı. Cevapların, memnun değilim/memnunum/çok memnunum şeklinde verilmesi istendi. Niteliksel verilerin karşılaştırılmasında Ki-Kare testi ve Fisher’s Exact Ki-Kare testi kullanıldı. Anlamlılık p<0,05 düzeyinde değerlendirildi.

    Bulgular: %64,3’ü kadın ve %35,7’si erkek olan toplam 42 hastanın yaş ortalaması 62,26 idi. İmplant destekli protez kullanan lise ve üzeri eğitim düzeyindeki hastaların oranının, klasik tam protezler kullananlardan anlamlı şekilde yüksek olduğu görüldü. Bu hastaların temizlenebilirlikten çok memnun olma düzeylerinin ise klasik tam protez kullanan hastalardan yüksek olduğu belirlendi (p=0,039. İmplant destekli protez kullanan hastalar ile klasik tam protez kullanan hastaların estetik, çiğneme, konuşma, tutuculuk ve rahatlık memnuniyet düzeyleri arasında istatistiksel olarak anlamlı bir farklılık bulunmadı.

    Sonuç: Yapılan çalışmada, demografik faktörlerin her iki protez tipinin memnuniyeti üzerine etkisi olmadığı, yalnızca klasik tam protez hastalarının implant destekli tam protez hastalarına kıyasla, temizlenebilirlik a

  17. Job satisfaction and social comparison levels of teachers working for state schoolsDevlet okullarında görev yapan öğretmenlerin iş doyumu ve sosyal karşılaştırma düzeylerinin incelenmesi

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    Serpil Kılıç


    Full Text Available The main purpose of this study is to determine primary and secondary level teachers’ job satisfaction and social comparison levels. In line with this general aim, the relationship between the teachers’ personal data and job satisfaction and social comparison levels were researched. The research sampling was 185 teachers composed of 105 female and 81 male participants. Research data were gathered through Minnesota Job Satisfaction and Social Comparison questionnaires, respectively. According to the research findings, there is no statistically meaningful difference between the teachers’ gender, position at the school, experience in teaching and their job satisfaction and social comparison levels. However, the research shows that school level, teachers’ marital status and age have affected the teachers’ job satisfaction levels. Accordingly, primary teachers’ general job satisfaction level is higher than secondary level teachers’ general job satisfaction level. Single teachers’ external job satisfaction level is also higher than married teachers’ external job satisfaction level. General job satisfaction level is  the highest with the teachers at the age of 20-25, but it is  the lowest with the teachers at the age of 31-35.  There is also a significant correlation between teachers ‘educational level and their social comparison levels. Besides, it has been found out that there is positive correlation between teachers’ job satisfaction and social comparison levels. ÖzetBu araştırmanın amacı, ilköğretim ve ortaöğretimde görevli öğretmenlerin iş doyum ve sosyal karşılaştırma düzeylerinin tespit edilmesidir. Bu genel amaca paralel olarak, öğretmenlerin kişisel özellikleri ile iş doyum ve sosyal karşılaştırma düzeyleri arasındaki ilişki incelenmiştir. Araştırma örneklemi 104’ü kadın, 81’i erkek olmak üzere toplam 185 öğretmenden oluşmaktadır. Araştırma verileri Minnesota i

  18. [The LDL receptor family]. (United States)

    Meilinger, Melinda


    The members of the LDL receptor family are structurally related endocytic receptors. Our view on these receptors has considerably changed in recent years. Not only have new members of the family been identified, but also several interesting observations have been published concerning the biological function of these molecules. The LDL receptor family members are able to bind and internalize a plethora of ligands; as a consequence, they play important roles in diverse physiological processes. These receptors are key players in the lipoprotein metabolism, vitamin homeostasis, Ca2+ homeostasis, cell migration, and embryonic development. Until recently, LDL receptor family members were thought to be classic endocytic receptors that provide cells with metabolites on one hand, while regulating the concentration of their ligands in the extracellular fluids on the other hand. However, recent findings indicate that in addition to their cargo transport function, LDL receptor family members can act as signal transducers, playing important roles in the development of the central nervous system or the skeleton. Better understanding of physiological and pathophysiological functions of these molecules may open new avenues for the treatment or prevention of many disorders.

  19. Glutamate receptor agonists

    DEFF Research Database (Denmark)

    Vogensen, Stine Byskov; Greenwood, Jeremy R; Bunch, Lennart;


    The neurotransmitter (S)-glutamate [(S)-Glu] is responsible for most of the excitatory neurotransmission in the central nervous system. The effect of (S)-Glu is mediated by both ionotropic and metabotropic receptors. Glutamate receptor agonists are generally a-amino acids with one or more...... stereogenic centers due to strict requirements in the agonist binding pocket of the activated state of the receptor. By contrast, there are many examples of achiral competitive antagonists. The present review addresses how stereochemistry affects the activity of glutamate receptor ligands. The review focuses...... mainly on agonists and discusses stereochemical and conformational considerations as well as biostructural knowledge of the agonist binding pockets, which is useful in the design of glutamate receptor agonists. Examples are chosen to demonstrate how stereochemistry not only determines how the agonist...

  20. [Glutamate receptors genes polymorphism and the risk of paranoid schizophrenia in Russians and tatars from the Republic of Bashkortostan]. (United States)

    Gareeva, A E; Khusnutdinova, E K


    Schizophrenia is a severe mental disorder that affects about 1% of the world population, leading to disability and social exclusion. Glutamatergic neurotransmission is a violation of one of the main hypotheses put forward to explain the neurobiological mechanisms of schizophrenia. Post mortem studies have found changes in the degree of affinity glutamate receptors, their transcription, and altered expression of their subunits in the prefrontal cortex, hippocampus, and thalamus in patients with schizophrenia. As a result of genetic studies of gene family encoding ionotropic AMPA and kainate glutamate receptors in schizophrenia, ambiguous results were received. The association of polymorphic variants of genes GRIA2 and GRIK2 with paranoid schizophrenia and response to therapy with haloperidol in Russian and Tatar of the Republic of Bashkortostan was conducted in the present study. DNA samples of 257 patients with paranoid schizophrenia and of 349 healthy controls of Russian and Tatar ethnic group living in the Republic of Bashkortostan were involved into the present study. In the result of the present study: (1) high risk genetic markers of paranoid schizophrenia (PSZ) were obtained: in Russians-GR4IA2*CCC (OR = 9.60) and in Tatars-GRIK2*ATG (OR = 3.5), GRIK2*TGG (OR = 3.12) (2) The following low risk genetic markers of PSZ were revealed: in Tatars-GRIA2*T/T (rs43025506) of GRIA2 gene (OR = 0.34); in Russians.- GRIA2*CCT (OR = 0.481). (3) Genetic markers of low haloperido! treatment efficacy in respect of negative and positive symptoms GRIK2*T/T (rs2227281) of GRIK2 gene and GRAL42*C/C in Russians, GRIK2*A/A (rs995640) of GRIK2 gene in Tatars. (4) Genetic markers of low haloperidol treatment efficacy in respect of positive symptoms GRL42*C/C in Russians. The results of the present study support the hypothesis of the involvement of glutamate receptor genes in schizophrenia pathway. Considerable inter-ethnic'diversity of genetic risk factors for this disease was

  1. Glutamate Receptors in the Central Nucleus of the Amygdala Mediate Cisplatin-Induced Malaise and Energy Balance Dysregulation through Direct Hindbrain Projections. (United States)

    Alhadeff, Amber L; Holland, Ruby A; Nelson, Alexandra; Grill, Harvey J; De Jonghe, Bart C


    Cisplatin chemotherapy is used commonly to treat a variety of cancers despite severe side effects such as nausea, vomiting, and anorexia that compromise quality of life and limit treatment adherence. The neural mechanisms mediating these side effects remain elusive despite decades of clinical use. Recent data highlight the dorsal vagal complex (DVC), lateral parabrachial nucleus (lPBN), and central nucleus of the amygdala (CeA) as potential sites of action in mediating the side effects of cisplatin. Here, results from immunohistochemical studies in rats identified a population of cisplatin-activated DVC neurons that project to the lPBN and a population of cisplatin-activated lPBN calcitonin gene-related peptide (CGRP, a marker for glutamatergic neurons in the lPBN) neurons that project to the CeA, outlining a neuroanatomical circuit that is activated by cisplatin. CeA gene expressions of AMPA and NMDA glutamate receptor subunits were markedly increased after cisplatin treatment, suggesting that CeA glutamate receptor signaling plays a role in mediating cisplatin side effects. Consistent with gene expression results, behavioral/pharmacological data showed that CeA AMPA/kainate receptor blockade attenuates cisplatin-induced pica (a proxy for nausea/behavioral malaise in nonvomiting laboratory rodents) and that CeA NMDA receptor blockade attenuates cisplatin-induced anorexia and body weight loss in addition to pica, demonstrating that glutamate receptor signaling in the CeA is critical for the energy balance dysregulation caused by cisplatin treatment. Together, these data highlight a novel circuit and CGRP/glutamatergic mechanism through which cisplatin-induced malaise and energy balance dysregulation are mediated. To treat cancer effectively, patients must follow prescribed chemotherapy treatments without interruption, yet most cancer treatments produce side effects that devastate quality of life (e.g., nausea, vomiting, anorexia, weight loss). Although hundreds of

  2. Opiate receptors: an introduction. (United States)

    Carmody, J J


    Current status of opiate receptors and their agonists is reviewed--basic aspects of receptor theory, the importance of stereospecificity in drug-receptor interactions and the role of 'second messengers' in drug action. The three classes of endogenous opioids, originating from three distinct genes, are discussed: pro-opiomelanocortin, giving rise to beta-endorphin, ACTH and various MSHs; pro-enkephalin, giving methionine enkephalin and leucine enkephalin; and prodynorphin; their anatomical distribution and the main classes of receptors with which they interact, the mu-receptor, with a high affinity for met-enkephalin and beta-endorphin (as well as morphine and dynorphin A); the delta-receptor for which the primary ligand is leu-enkephalin; and the kappa-receptor which is the main target for the dynorphins. Functional roles for endogenous opioids are considered. Essentially they are inhibitory to target neurones, depressing motor reflexes, baroreflexes and nociception. They also have roles in the response to physical and psychological stress.

  3. Mandibular tam protez ölçü modellerinin üç boyutlu bir ölçüm yöntemiyle karşılaştırılması

    Directory of Open Access Journals (Sweden)

    Ali Kemal Ozdemir


    >Key Words: Complete denture impression technique, 3-Dimensional measurement system



    Amaç: Bu çalışmanın amacı çeşitli ölçü maddeleriyle alınan mandibular alveolar kret ölçülerinin stabilitesinin üç boyutlu bir ölçüm yöntemiyle değerlendirilmesidir.

    Gereç ve Yöntem: Bu çalışmada 14 dişsiz hastadan alınan ölçüler kullanıldı. Hastalar iki gruba ayrıldı. Son ölçü maddesi olarak birinci grupta çinko-oksid öjenol (ZOE, ikinci grupta polivinilsiloksan (PVS kullanılarak alınan ölçülerden ana modeller elde edildi. Ana modeller üzerinden modifiye şahsi kaşık hazırlanarak hastalardan ölçü alçısı ile yeniden ölçüler alındı. Elde edilen modeller üzerinde sınır çizgileri tahmini olarak çizildi ve alveol kret üzerinde 14 referans noktası belirlendi. Ana modellerin fotoğrafları alındı (Nikon E2/E2s ve 3 boyutlu görüntüleri elde edildi. Alveolar kret yüksekliği, protezin oturduğu alanın büyüklüğü ve çevresel sınır çizgilerinin uzunluğu 3 boyutlu görüntüler üzerinde ölçüldü.

    Bulgular: Bu çalışmada ölçü alçısıyla elde edilen modellerdeki ölçüm değerlerinin diğerlerinden yüksek olduğu görüldü. Ölçü alçısıyla bundan düşük değerlerde ölçüm değerleri gösteren çinko-oksid öjenol ölçü modelleri arasında istatistiksel olarak anlamlı bir fark bulunamadı (p>0.05. Buna karşılık polivinilsiloksan ile elde edilen modellerin ölçüm değerlerinde alveolar kret yüksekliği istatistiksel olarak anlamlı bir azalma gösterdi (p< 0.05.

    Sonuç: Ölçü maddesinin alveolar muköz membran üzerindeki etkileri membranın özelliklerine ve şahsi kaşık dizaynına bağlı kalmaktadır. Bu yüzden desteksiz rezidüel kretlere sahip mandibular tam protez hastalarında ölçü maddesinin ve ölçü tekniğinin seçimi oldukça önemlidir. Mandibular

  4. Serotonin receptors in hippocampus. (United States)

    Berumen, Laura Cristina; Rodríguez, Angelina; Miledi, Ricardo; García-Alcocer, Guadalupe


    Serotonin is an ancient molecular signal and a recognized neurotransmitter brainwide distributed with particular presence in hippocampus. Almost all serotonin receptor subtypes are expressed in hippocampus, which implicates an intricate modulating system, considering that they can be localized as autosynaptic, presynaptic, and postsynaptic receptors, even colocalized within the same cell and being target of homo- and heterodimerization. Neurons and glia, including immune cells, integrate a functional network that uses several serotonin receptors to regulate their roles in this particular part of the limbic system.

  5. Serotonin Receptors in Hippocampus

    Directory of Open Access Journals (Sweden)

    Laura Cristina Berumen


    Full Text Available Serotonin is an ancient molecular signal and a recognized neurotransmitter brainwide distributed with particular presence in hippocampus. Almost all serotonin receptor subtypes are expressed in hippocampus, which implicates an intricate modulating system, considering that they can be localized as autosynaptic, presynaptic, and postsynaptic receptors, even colocalized within the same cell and being target of homo- and heterodimerization. Neurons and glia, including immune cells, integrate a functional network that uses several serotonin receptors to regulate their roles in this particular part of the limbic system.

  6. Dopamine receptor and hypertension. (United States)

    Zeng, Chunyu; Eisner, Gilbert M; Felder, Robin A; Jose, Pedro A


    Dopamine plays an important role in the pathogenesis of hypertension by regulating epithelial sodium transport and reactive oxygen and by interacting with vasopressin, renin-angiotensin, and the sympathetic nervous system. Decreased renal dopamine production and/or impaired dopamine receptor function have been reported in hypertension. Disruption of any of the dopamine receptors (D(1), D(2), D(3), D(4), and D(5)) results in hypertension. In this paper, we review the mechanisms by which hypertension develops when dopamine receptor function is perturbed.

  7. Serotonin Receptors in Hippocampus (United States)

    Berumen, Laura Cristina; Rodríguez, Angelina; Miledi, Ricardo; García-Alcocer, Guadalupe


    Serotonin is an ancient molecular signal and a recognized neurotransmitter brainwide distributed with particular presence in hippocampus. Almost all serotonin receptor subtypes are expressed in hippocampus, which implicates an intricate modulating system, considering that they can be localized as autosynaptic, presynaptic, and postsynaptic receptors, even colocalized within the same cell and being target of homo- and heterodimerization. Neurons and glia, including immune cells, integrate a functional network that uses several serotonin receptors to regulate their roles in this particular part of the limbic system. PMID:22629209

  8. Recognition receptors in biosensors

    CERN Document Server

    Zourob, Mohammed


    This book presents a significant and up-to-date review of the various recognition receptors, their immobilization, and an overview of the used surface characterization techniques. It includes more than 150 illustrations that help explain the ideas presented.

  9. Somatostatin receptor skintigrafi

    DEFF Research Database (Denmark)

    Rasmussen, Karin; Nielsen, Jørn Theil; Rehling, Michael


    Somatostatin receptor scintigraphy (SRS) is a very valuable imaging technique for visualisation of a diversity of neuroendocrine tumours. The sensitivity for localisation of carcinoid tumours is high, but somewhat lower for other neuroendocrine tumours. The methodology, multiple clinical aspects...

  10. Update on Melatonin Receptors. IUPHAR Review. : Melatonin Receptors


    Jockers, Ralf; Delagrange, Philippe; Dubocovich, Margarita ,; Markus, Regina ,; Renault, Nicolas; Tosini, Gianluca; Cecon, Erika; Zlotos, Darius Paul


    International audience; Melatonin receptors are seven transmembrane-spanning proteins belonging to the G protein-coupled receptor super-family. In mammals, two melatonin receptor subtypes exit MT1 and MT2 encoded by the MTNR1A and MTNR1B genes, respectively. The current review provides an update on melatonin receptors by the corresponding sub-committee of the International Union of Basic and Clinical Pharmacology. We will highlight recent developments of melatonin receptor ligands, including ...

  11. Serotonin Receptors in Hippocampus


    Laura Cristina Berumen; Angelina Rodríguez; Ricardo Miledi; Guadalupe García-Alcocer


    Serotonin is an ancient molecular signal and a recognized neurotransmitter brainwide distributed with particular presence in hippocampus. Almost all serotonin receptor subtypes are expressed in hippocampus, which implicates an intricate modulating system, considering that they can be localized as autosynaptic, presynaptic, and postsynaptic receptors, even colocalized within the same cell and being target of homo- and heterodimerization. Neurons and glia, including immune cells, integrate a fu...

  12. Receptors for enterovirus 71


    Yamayoshi, Seiya; Fujii, Ken; Koike, Satoshi


    Enterovirus 71 (EV71) is one of the major causative agents of hand, foot and mouth disease (HFMD). Occasionally, EV71 infection is associated with severe neurological diseases, such as acute encephalitis, acute flaccid paralysis and cardiopulmonary failure. Several molecules act as cell surface receptors that stimulate EV71 infection, including scavenger receptor B2 (SCARB2), P-selectin glycoprotein ligand-1 (PSGL-1), sialylated glycan, heparan sulfate and annexin II (Anx2). SCARB2 plays crit...

  13. Adenosine receptor neurobiology: overview. (United States)

    Chen, Jiang-Fan; Lee, Chien-fei; Chern, Yijuang


    Adenosine is a naturally occurring nucleoside that is distributed ubiquitously throughout the body as a metabolic intermediary. In the brain, adenosine functions as an important upstream neuromodulator of a broad spectrum of neurotransmitters, receptors, and signaling pathways. By acting through four G-protein-coupled receptors, adenosine contributes critically to homeostasis and neuromodulatory control of a variety of normal and abnormal brain functions, ranging from synaptic plasticity, to cognition, to sleep, to motor activity to neuroinflammation, and cell death. This review begun with an overview of the gene and genome structure and the expression pattern of adenosine receptors (ARs). We feature several new developments over the past decade in our understanding of AR functions in the brain, with special focus on the identification and characterization of canonical and noncanonical signaling pathways of ARs. We provide an update on functional insights from complementary genetic-knockout and pharmacological studies on the AR control of various brain functions. We also highlight several novel and recent developments of AR neurobiology, including (i) recent breakthrough in high resolution of three-dimension structure of adenosine A2A receptors (A2ARs) in several functional status, (ii) receptor-receptor heterodimerization, (iii) AR function in glial cells, and (iv) the druggability of AR. We concluded the review with the contention that these new developments extend and strengthen the support for A1 and A2ARs in brain as therapeutic targets for neurologic and psychiatric diseases.

  14. Imidazoline receptors ligands

    Directory of Open Access Journals (Sweden)

    Agbaba Danica


    Full Text Available Extensive biochemical and pharmacological studies have determined three different subtypes of imidazoline receptors: I1-imidazoline receptors (I1-IR involved in central inhibition of sympathicus that produce hypotensive effect; I2-imidazoline receptors (I2-IR modulate monoamine oxidase B activity (MAO-B; I3-imidazoline receptors (I3-IR regulate insulin secretion from pancreatic β-cells. Therefore, the I1/I2/I3 imidazoline receptors are selected as new, interesting targets for drug design and discovery. Novel selective I1/I2/I3 agonists and antagonists have been recently developed. In the present review, we provide a brief update to the field of imidazoline research, highlighting some of the chemical diversity and progress made in the 2D-QSAR, 3D-QSAR and quantitative pharmacophore development studies of I1-IR and I2-IR imidazoline receptor ligands. Theoretical studies of I3-IR ligands are not yet performed because of insufficient number of synthesized I3-IR ligands.

  15. Tasvir Anlamı İçeren Birleşik Eylemlerin İngilizce Çeviri Eserlerde Aldığı Karşılılıklar English Equivalents of Descriptive Compound Verbs in Translated Literary Works

    Directory of Open Access Journals (Sweden)


    Full Text Available Descriptive verbs are one of the pre-eminent constructions revealing the structure productivity of our language. The forms describing verbs depict variety of structures. Descriptive verbs, semi-descriptive verbs and the other type including two conjugated forms areparticularly selected to display the capacity of narration in manyliterary works. These forms are particularly preferred because of thefrequency of their use in the works in question. The main focus in thepresent study is to analyse English equivalents of these verbs in thetranslated versions of the works in terms of meaning and structure andto point out whether they are able to carry out the same literary value.In spite of the fact that Turkish and English belong to the totallydifferent language families we could utter the existence of descriptiveverbs in both. Considering these structural variations, what forms andexpressions English holds for the demonstative verbs in accordancewith the bulk sample of translated works is questioned. Many novelstranslated to English are analysed and the structures are classified. Themodel expressions exemplifying the target structure are taken frommany works of our literature. As a result, modal verbs and almost thesame type of adverbials and prepositional phrases are used to providemore or less their translated equivalences. Dilimizin yapı açısından ne kadar zengin olduğunu gösteren oluşumlardan biri tasvir eylemleridir. Eylemi tasvir eden yapılar yapısal olarak çok çeşitlilik gösterir. Bu çalışmada birçok farklı yapıyı barındıran bu birleşik oluşumlardan sadece tasvir eylemleri, yarı tasvir eylemleri ve iki çekimli eylem gibi türleri seçilmiştir. Bu üç yapı, eserlerin incelenmesi esnasında kullanım sıklığı açısından öne çıkmış ve çalışma konusu olarak tercih edilmişlerdir. Bu çalışmadaki asıl amaç, hedef yapıyı içeren bu eylemlerin İngilizceye çevrilmiş eserlerdeki anlatım ve yapı kar

  16. Blister fluid T lymphocytes during toxic epidermal necrolysis are functional cytotoxic cells which express human natural killer (NK) inhibitory receptors (United States)

    Le Cleach, L; Delaire, S; Boumsell, L; Bagot, M; Bourgault-Villada, I; Bensussan, A; Roujeau, J C


    Toxic epidermal necrolysis (TEN) is a rare life-threatening adverse drug reaction characterized by a massive destruction of the epidermis. Immunohistological studies of skin biopsies of TEN showed infiltrates of predominantly CD8+ T lymphocytes even though other authors reported a prominent involvement of cells of the monocyte-macrophage lineage. The aim of this study was to characterize phenotypically and functionally the cells present in the cutaneous blister fluid of four patients with TEN. We first determined that lymphocytes were predominant in blister fluid obtained early, while monocytes/macrophages later became the most important population. We then showed that this lymphocyte population, mainly CD3+CD8+, corresponded to a peculiar cell subset as they expressed cutaneous leucocyte antigen, killer inhibitory receptors KIR/KAR and failed to express CD28 molecule. Functionally, we determined that blister T lymphocytes had a cytotoxic T lymphocyte (CTL)- and NK-like cytotoxicity. The role of this cytotoxic lymphocyte population present at the site of lesions during TEN remains to be understood. PMID:10606987

  17. D-aspartate and NMDA, but not L-aspartate, block AMPA receptors in rat hippocampal neurons

    DEFF Research Database (Denmark)

    Gong, Xiang-Qun; Frandsen, Anne; Lu, Wei-Yang;


    -independent in the tested voltage range (-80 to +60 mV). 3 The estimated EC50 of the L-glutamate-induced AMPAR current was increased in the presence of D-aspartate, while the estimated maximum L-glutamate-induced AMPAR current was not changed. D-aspartate concentration-dependently shifted the dose-response curve of kainate...

  18. Üstün Yetenekli Çocukları Belirlemede Öğretmen Öncelikleri: İkili Karşılaştırma Yöntemiyle Bir Ölçekleme Çalışması

    Directory of Open Access Journals (Sweden)

    Eren Halil Özberk


    Full Text Available Bu çalışmanın amacı üstün yetenekli çocukları belirlemede öğretmen önceliklerinin tespit edilmesidir. Bu doğrultuda alanyazına ve uzman görüşüne dayalı olarak üstün yetenekli bireylere ait özellikler belirlenmiş, ardından bu öğrencileri seçmede en önemli referans kaynağı olan öğretmenlere bu kriterler sunularak onların görüşlerine göre ölçekleme yöntemi ile önem dereceleri tespit edilmiş ve bu önem derecelerinin öğretmenlerin demografik özelliklerine göre nasıl değişkenlik gösterdiği incelenmiştir. Bu amaçla ölçekleme çalışmasında üstün yetenekli öğrencilerin özellikleri yedi ifade altında toplanmıştır. Araştırmada Ankara ili merkez ilçelerinde bulunan 785 öğretmenden bu 7 özelliği ikili karşılaştırma yaparak sıralamaları istenmiştir. Yapılan ölçekleme işlemi sonunda öğretmenlerin üstün yetenekli çocukları belirlemede ilk önce tercih ettiği özellik, çevreye ve sosyal olaylara karşı duyarlı olması, son tercih ettiği özellik ise arkadaş çevresinde liderlik özelliğine sahip olması olmuştur. Öğretmenlerin demografik özelliklerine göre önem sıralamasında ise üstün yetenekli çocukları belirlemede ilk tercih edilen özellik, çevreye ve sosyal olaylara karşı duyarlı olması olmuştur. The aim of the research is to determine teacher priorities on identifying gifted children. The study is based on the principle of comparison of seven different specifications which were determined by literature and professionals majored in gifted education according to the judgments of the primary and secondary school teachers using pairwise comparison method according to various demographic variable. In that particular scaling study, specifications of gifted children have been summarized in seven statements. These seven statements have been asked 785 teachers in Ankara province to compare by using pairwise comparison. As a result of scaling study

  19. Ionotropic crustacean olfactory receptors.

    Directory of Open Access Journals (Sweden)

    Elizabeth A Corey

    Full Text Available The nature of the olfactory receptor in crustaceans, a major group of arthropods, has remained elusive. We report that spiny lobsters, Panulirus argus, express ionotropic receptors (IRs, the insect chemosensory variants of ionotropic glutamate receptors. Unlike insects IRs, which are expressed in a specific subset of olfactory cells, two lobster IR subunits are expressed in most, if not all, lobster olfactory receptor neurons (ORNs, as confirmed by antibody labeling and in situ hybridization. Ligand-specific ORN responses visualized by calcium imaging are consistent with a restricted expression pattern found for other potential subunits, suggesting that cell-specific expression of uncommon IR subunits determines the ligand sensitivity of individual cells. IRs are the only type of olfactory receptor that we have detected in spiny lobster olfactory tissue, suggesting that they likely mediate olfactory signaling. Given long-standing evidence for G protein-mediated signaling in activation of lobster ORNs, this finding raises the interesting specter that IRs act in concert with second messenger-mediated signaling.

  20. Sürtünme Karıştırma Kaynak Yöntemiyle Birleştirilen Farklı Tipteki Alüminyum Bağlantıların Tahribatlı ve Tahribatsız Muayenesi

    Directory of Open Access Journals (Sweden)

    Furkan SARSILMAZ


    Full Text Available Bu çalışmada farklı kimyasal ve mekanik özelliklere sahip AA 5754 (AlMg3 ile AA 5083 (AlMg4,5Mn0,7 alüminyum alaşım levhaları, günümüzde yeni geliştirilen sürtünme karıştırma kaynak (SKK yöntemiyle birleştirilmiştir. Çalışmada farklı devir ve ilerleme hızlarının, kaynaklı bağlantıların mekanik özelliklerini belirlemek amacıyla tahribatlı (çekme, çentik darbe, ve yorulma ve tahribatsız (floroskopik testler uygulanmıştır. Tahribatlı testler sonucunda farklı kaynak dönme ve ilerleme hızlarının, bağlantının mekanik test sonuçlarını etkilediği belirlenmiştir. Tahribatsız test sonucunda ise düşük devir sayısının ve yüksek ilerleme hızının, kaynak bölgesinde yetersiz birleşme meydana getirmesiyle, dikiş boyunca bölgesel porozite, tünel ve boşluklu bölgelerin oluştuğu görülmüştür. En iyi mekanik test sonucunu, 1400 devir dönme hızı ve 250 mm/dak ilerleme hızı işlem parametresi ile birleştirilen numune sergilemiştir. Anahtar Kelimeler: Sürtünme Karıştırma Kaynağı, Alüminyum Alaşımları, Tahribatlı Ve Tahribatsız Muayene, Kaynak Bölgesi

  1. Presynaptic P2 receptors? (United States)

    Stone, T W; O'Kane, E M; Nikbakht, M R; Ross, F M


    Although the emphasis in ATP research has been on postjunctional receptors, there is also evidence for presynaptic receptors regulating transmitter release in the autonomic nervous system. Recent work has attempted to identify similar mechanisms in the central nervous system. Some of the existing results can be explained by the metabolism of nucleotides to adenosine or adenosine 5'-monophosphate (AMP). However, studies of presynaptic effects using sensitive electrophysiological tests such as paired-pulse interactions indicate that nucleotides can act at presynaptic sites, but that their effects may be mediated by a release of adenosine. Results are also described which indicate that, under some conditions, nucleotides can mediate phenomena such as long-term potentiation, which probably involves a significant presynaptic element. In part these effects may involve a nucleotide-induced release of adenosine and the simultaneous activation of P1 and P2 receptors.

  2. Human presynaptic receptors. (United States)

    Schlicker, Eberhard; Feuerstein, Thomas


    Presynaptic receptors are sites at which transmitters, locally formed mediators or hormones inhibit or facilitate the release of a given transmitter from its axon terminals. The interest in the identification of presynaptic receptors has faded in recent years and it may therefore be justified to give an overview of their occurrence in the autonomic and central nervous system; this review will focus on presynaptic receptors in human tissues. Autoreceptors are presynaptic receptors at which a given transmitter restrains its further release, though in some instances may also increase its release. Inhibitory autoreceptors represent a typical example of a negative feedback; they are tonically activated by the respective endogenous transmitter and/or are constitutively active. Autoreceptors also play a role under pathophysiological conditions, e.g. by limiting the massive noradrenaline release occurring during congestive heart failure. They can be used for therapeutic purposes; e.g., the α2-adrenoceptor antagonist mirtazapine is used as an antidepressant and the inverse histamine H3 receptor agonist pitolisant has been marketed as a new drug for the treatment of narcolepsy in 2016. Heteroreceptors are presynaptic receptors at which transmitters from adjacent neurons, locally formed mediators (e.g. endocannabinoids) or hormones (e.g. adrenaline) can inhibit or facilitate transmitter release; they may be subject to an endogenous tone. The constipating effect of the sympathetic nervous system or of the antihypertensive drug clonidine is related to the activation of inhibitory α2-adrenoceptors on postganglionic parasympathetic neurons. Part of the stimulating effect of adrenaline on the sympathetic nervous system during stress is related to its facilitatory effect on noradrenaline release via β2-adrenoceptors.

  3. Biomimetic Receptors and Sensors

    Directory of Open Access Journals (Sweden)

    Franz L. Dickert


    Full Text Available In biomimetics, living systems are imitated to develop receptors for ions, molecules and bioparticles. The most pertinent idea is self-organization in analogy to evolution in nature, which created the key-lock principle. Today, modern science has been developing host-guest chemistry, a strategy of supramolecular chemistry for designing interactions of analytes with synthetic receptors. This can be realized, e.g., by self-assembled monolayers (SAMs or molecular imprinting. The strategies are used for solid phase extraction (SPE, but preferably in developing recognition layers of chemical sensors.

  4. Beyond the Receptor

    Institute of Scientific and Technical Information of China (English)

    Russell Jones


    @@ Had this Special Issue on plant hormones been published 5 years ago,it is likely that details about biosynthetic pathways would have taken center stage.As articles in this issue show,however,the field of plant hormone research has progressed rapidly and is now moving beyond the search for receptors.Progress in research on the mechanism of action of plant hormones has been rapid;receptors for the main classes of hormones have been identified;and the search is on for players downstream in signal-transduction chains.

  5. Assays for calcitonin receptors

    Energy Technology Data Exchange (ETDEWEB)

    Teitelbaum, A.P.; Nissenson, R.A.; Arnaud, C.D.


    The assays for calcitonin receptors described focus on their use in the study of the well-established target organs for calcitonin, bone and kidney. The radioligand used in virtually all calcitonin binding studies is /sup 125/I-labelled salmon calcitonin. The lack of methionine residues in this peptide permits the use of chloramine-T for the iodination reaction. Binding assays are described for intact bone, skeletal plasma membranes, renal plasma membranes, and primary kidney cell cultures of rats. Studies on calcitonin metabolism in laboratory animals and regulation of calcitonin receptors are reviewed.

  6. Chemokine Receptors and Transplantation

    Institute of Scientific and Technical Information of China (English)

    Jinquan Tan; Gang Zhou


    A complex process including both the innate and acquired immune responses results in allograft rejection. Some chemokine receptors and their ligands play essential roles not only for leukocyte migration into the graft but also in facilitating dendritic and T cell trafficking between lymph nodes and the transplant in the early and late stage of the allogeneic response. This review focuses on the impact of these chemoattractant proteins on transplant outcome and novel diagnostic and therapeutic approaches for antirejection therapy based on targeting of chemokine receptors and/or their ligands. Cellular & Molecular Immunology.

  7. Angiotensin type 2 receptor (AT2R) and receptor Mas

    DEFF Research Database (Denmark)

    Villela, Daniel; Leonhardt, Julia; Patel, Neal


    The angiotensin type 2 receptor (AT2R) and the receptor Mas are components of the protective arms of the renin-angiotensin system (RAS), i.e. they both mediate tissue protective and regenerative actions. The spectrum of actions of these two receptors and their signalling mechanisms display striking...

  8. Hfc-134a Ve Alternatifi Soğutkanların (Hfo-1234yf Ve Hfo-1234ze) Soğutma Çevrimi Performansı Açısından Karşılaştırması


    Arif Emre ÖZGÜR


    Bu çalışmada, alternatif soğutucu akışkanlar olarak günümüzde ön plana çıkan, HFO-1234yf ve HFO- 1234ze’nin, bir buhar sıkıştırmalı mekanik soğutma çevriminin etkinliğine ve ekserji verimine olan etkileri teorik olarak incelenmiştir. HFO-1234yf ve HFO-1234ze soğutkanları, HFC-134a soğutucu akışkanlarına alternatif olarak önerildiği için bu üç akışkanın, aynı çevrim ve çalışma aralıklarında, çevrim etkinliğine ve çevrimin ekserji verimine etkileri karşılaştırmalı olarak sunulmuştur ve bu akışk...

  9. Haşim Bey Mecmuasının “Makam Ve Tonalite Karşılaştırması” Yönünden İncelenmesi The Analysis Of Haşim Bey’s Anthology For “Comparison Of Maqam And Tonality”

    Directory of Open Access Journals (Sweden)

    Gökhan YALÇIN


    Full Text Available The first printed source contains Western music theory knowledgeis the second edition of “Mecmûa-i Kârhâ ve Nakışhâ ve Şarkıyât”known as “Hâşim Bey Mecmuası” is published by Hasim Bey in 1864.Another feature of this book is in the description of the Turkish musicmaqams, Hasim Bey compared maqams with Western music tonalsequences and identified them. This comparison is completely rejectedby some musicologists, has been considered by some as the first. In therelated researchs, it is confirmed that the translation of Hasim Bey’santhology has been done but the analysis of the chapter about Westernmusic theory has not been done. The aim of this study is theexamination relevant departments of the Western music in Hasim Bey’santhology and to reveal what are the similarities in the comparison ofTurkish music maqams with Western music tonal sequences.According to the findings, the similarities are classified "accordingto the tonic note”, according to the progress and behaviour”, "accordingto the used alterative markings" and "similar in all aspects". Theharmonic analysis of the maqamic polyphonic works composed in thesame period and latter has been done and according to the the usedharmony the tonalities were also in good agreement with similarities ofHasim Bey’s. Furthermore, as a theory book in this anthology thecomparison is used as a method to introduce and teach the tonalities orto introduce and teach the maqams. Afterwards, it is seen that this kindof works are used as a method especially for teaching the Westernmusic notes. 1864’te Haşim Bey tarafından yayınlanan ve “Hâşim Bey Mecmuası” olarak bilinen “Mecmûa-i Kârhâ ve Nakışhâ ve Şarkıyât” adlı eserinin ikinci baskısı Batı müzik teorisi bilgileri içeren ilk basılı kaynaktır. Bu kitabın başka bir özelliği de Türk müziği makamlarının tarifinde Haşim Bey’in makamları Batı müziği tonal dizileri ile karşılaştırmış ve

  10. İlköğretim 7.Sınıf Öğrencilerinin Yazılarındaki Söz Dizimi İle Edebî Dilin Söz Diziminin Karşılaştırılması



    Bu tezde, ilköğretim 7.sımf öğrencilerinin yazılarındaki söz dizimi ile edebî dilin söz dizimi karşılaştmlmıştır. Edebî dili temsilen Yakup Kadri Karaosmanoğlu seçilmiştir. GİRİŞ bölümünde, problem ortaya konmuş, çalışmanın amacı ve yöntemi belirtilmiştir. BİRİNCİ BÖLÜM’de dilbilimcilerimizin söz dizimi hakkındaki görüşleri özetlenerek değerlendirilmiş söz dizimi üzerine yazılmış kitaplar ve çalışmalardan hareketle terim ve kavramlar açıklanmıştır. Ayrıca Yakup Kadri Karaosmanoğlu’nun h...

  11. Characterization of melanocortin receptors. (United States)

    Goetz, Aaron S; Ignar, Diane M


    This unit describes a Scintillation Proximity Assay (SPA) for the measurement of ligand binding to melanocortin receptors (MCRs) using membranes prepared from cell lines stably expressing recombinant MCRs. It provides a facile method for determining the affinity of compounds at MC1R, MC3R, MC4R, or MC5R.

  12. P2-purinerge receptorer

    DEFF Research Database (Denmark)

    Solgaard, Marie; Jørgensen, Niklas Rye


    and by osteoclasts, and agonist binding affects cell proliferation, differentiation, activity and apoptosis. With increasing knowledge of the function and role of these receptors in bone biology, they will undoubtedly be a future target for the design of new drugs which can be used for treatment of metabolic bone...

  13. Meeting report: nuclear receptors

    DEFF Research Database (Denmark)

    Tuckermann, Jan; Bourguet, William; Mandrup, Susanne


    The biannual European Molecular Biology Organization (EMBO) conference on nuclear receptors was organized by Beatrice Desvergne and Laszlo Nagy and took place in Cavtat near Dubrovnik on the Adriatic coast of Croatia September 25-29, 2009. The meeting brought together researchers from all over...

  14. Glutamate receptor ligands

    DEFF Research Database (Denmark)

    Guldbrandt, Mette; Johansen, Tommy N; Frydenvang, Karla Andrea;


    Homologation and substitution on the carbon backbone of (S)-glutamic acid [(S)-Glu, 1], as well as absolute stereochemistry, are structural parameters of key importance for the pharmacological profile of (S)-Glu receptor ligands. We describe a series of methyl-substituted 2-aminoadipic acid (AA......-ray crystallographic analyses, chemical correlation, and CD spectral analyses. The effects of the individual stereoisomers at ionotropic and metabotropic (S)-Glu receptors (iGluRs and mGluRs) were characterized. Compounds with S-configuration at the alpha-carbon generally showed mGluR2 agonist activity of similar...... limited effect on pharmacology. Structure-activity relationships at iGluRs in the rat cortical wedge preparation showed a complex pattern, some compounds being NMDA receptor agonists [e.g., EC(50) =110 microM for (2S,5RS)-5-methyl-AA (6a,b)] and some compounds showing NMDA receptor antagonist effects [e...

  15. Ginkgolides and glycine receptors

    DEFF Research Database (Denmark)

    Jaracz, Stanislav; Nakanishi, Koji; Jensen, Anders A.


    Ginkgolides from the Ginkgo biloba tree are diterpenes with a cage structure consisting of six five-membered rings and a unique tBu group. They exert a variety of biological properties. In addition to being antagonists of the platelet activating factor receptor (PAFR), it has recently been shown...

  16. Androgen receptor mutations

    NARCIS (Netherlands)

    A.O. Brinkmann (Albert); G.W. Jenster (Guido); C. Ris-Stalpers (Carolyn); J.A.G.M. van der Korput (J. A G M); H.T. Brüggenwirth (Hennie); A.L.M. Boehmer (Annemie); J. Trapman (Jan)


    textabstractMale sexual differentiation and development proceed under direct control of androgens. Androgen action is mediated by the intracellular androgen receptor, which belongs to the superfamily of ligand-dependent transcription factors. At least three pathological situations are associated wit

  17. Metformin and insulin receptors

    Energy Technology Data Exchange (ETDEWEB)

    Vigneri, R.; Gullo, D.; Pezzino, V.

    The authors evaluated the effect of metformin (N,N-dimethylbiguanide), a biguanide known to be less toxic than phenformin, on insulin binding to its receptors, both in vitro and in vivo. Specific /sup 125/I-insulin binding to cultured IM-9 human lymphocytes and MCF-7 human breast cancer cells was determined after preincubation with metformin. Specific /sup 125/I-insulin binding to circulating monocytes was also evaluated in six controls, eight obese subjects, and six obese type II diabetic patients before and after a short-term treatment with metformin. Plasma insulin levels and blood glucose were also measured on both occasions. Metformin significantly increased insulin binding in vitro to both IM-9 lymphocytes and MCF-7 cells; the maximum increment was 47.1% and 38.0%, respectively. Metformin treatment significantly increased insulin binding in vivo to monocytes of obese subjects and diabetic patients. Scatchard analysis indicated that the increased binding was mainly due to an increase in receptor capacity. Insulin binding to monocytes of normal controls was unchanged after metformin as were insulin levels in all groups; blood glucose was significantly reduced after metformin only in diabetic patients. These data indicate that metformin increases insulin binding to its receptors in vitro and in vivo. The effect in vivo is observed in obese subjects and in obese type II diabetic patients, paralleling the clinical effectiveness of this antidiabetic agent, and is not due to receptor regulation by circulating insulin, since no variation in insulin levels was recorded.

  18. Increased glutamate receptor and transporter expression in the cerebral cortex and striatum of gcdh-/- mice: possible implications for the neuropathology of glutaric acidemia type I.

    Directory of Open Access Journals (Sweden)

    Valeska Lizzi Lagranha

    Full Text Available We determined mRNA expression of the ionotropic glutamate receptors NMDA (NR1, NR2A and NR2B subunits, AMPA (GluR2 subunit and kainate (GluR6 subunit, as well as of the glutamate transporters GLAST and GLT1 in cerebral cortex and striatum of wild type (WT and glutaryl-CoA dehydrogenase deficient (Gchh-/- mice aged 7, 30 and 60 days. The protein expression levels of some of these membrane proteins were also measured. Overexpression of NR2A and NR2B in striatum and of GluR2 and GluR6 in cerebral cortex was observed in 7-day-old Gcdh-/-. There was also an increase of mRNA expression of all NMDA subunits in cerebral cortex and of NR2A and NR2B in striatum of 30-day-old Gcdh-/- mice. At 60 days of life, all ionotropic receptors were overexpressed in cerebral cortex and striatum of Gcdh-/- mice. Higher expression of GLAST and GLT1 transporters was also verified in cerebral cortex and striatum of Gcdh-/- mice aged 30 and 60 days, whereas at 7 days of life GLAST was overexpressed only in striatum from this mutant mice. Furthermore, high lysine intake induced mRNA overexpression of NR2A, NR2B and GLAST transcripts in striatum, as well as of GluR2 and GluR6 in both striatum and cerebral cortex of Gcdh-/- mice. Finally, we found that the protein expression of NR2A, NR2B, GLT1 and GLAST were significantly greater in cerebral cortex of Gcdh-/- mice, whereas NR2B and GLT1 was similarly enhanced in striatum, implying that these transcripts were translated into their products. These results provide evidence that glutamate receptor and transporter expression is higher in Gcdh-/- mice and that these alterations may be involved in the pathophysiology of GA I and possibly explain, at least in part, the vulnerability of striatum and cerebral cortex to injury in patients affected by GA I.

  19. Anti-nociceptive effect induced by intrathecal injection of ATPA, an effect enhanced and prolonged by concanavalin A. (United States)

    Wu, Dong-Chuan; Zhou, Ning; Yu, Long-Chuan


    The present study investigated the effect of intrathecal injection of (RS)-2-alpha-amino-3-(3-hydroxy-5-tbutylisoxazol-4-yl) propanoic acid (ATPA), a selective agonist to kainate receptor, on nociception in rats. Intrathecal administration of 1, 4 and 10 nmol of ATPA induced dose-dependent increases in the hindpaw withdrawal latency (HWL) to thermal and mechanical stimulation in rats. Pretreatment with intrathecal injection of 300 microg of concanavalin A (ConA) to block the desensitization of kainate receptors enhanced and prolonged the anti-nociceptive effect induced by intrathecal injection of ATPA. The results suggest that the pre-synaptic kainate receptor in the primary afferent terminals is involved in the transmission of nociceptive information in dorsal horn of the spinal cord in rats. Furthermore, blocking the desensitization of kainate receptor enhanced and prolonged the ATPA-induced anti-nociceptive effects.

  20. Levamisole receptors: a second awakening (United States)

    Martin, Richard J.; Robertson, Alan P.; Buxton, Samuel K.; Beech, Robin N.; Charvet, Claude L.; Neveu, Cedric


    Levamisole and pyrantel are old (1965) but useful anthelmintics that selectively activate nematode acetylcholine ion-channel receptors; they are used to treat roundworm infections in humans and animals. Interest in their actions has surged, giving rise to new knowledge and technical advances, including an ability to reconstitute receptors that reveal more details of modes of action/resistance. We now know that the receptors are plastic and may form diverse species-dependent subtypes of receptor with different sensitivities to individual cholinergic anthelmintics. Understanding the biology of the levamisole receptors is expected to inform other studies on anthelmintics (ivermectin and emodepside) that act on ion-channels. PMID:22607692

  1. Histamine H3-receptor isoforms. (United States)

    Bakker, R A


    Increasing evidence supports a role for HA as a neurotransmitter and neuromodulator in various brain functions, including emotion, cognition, and feeding. The recent cloning of the histamine H3 receptor allowed for the subsequent cloning of a variety of H3 receptor isoforms from different species as well as the H4 receptor. As a result a wide variety of H3-receptor isoforms are now known that display differential brain expression patterns and signalling properties. These recent discoveries are discussed in view of the growing interest of the H3 receptor as a target for the development of potential therapeutics.

  2. Virally encoded 7TM receptors

    DEFF Research Database (Denmark)

    Rosenkilde, M M; Waldhoer, M; Lüttichau, H R


    A number of herpes- and poxviruses encode 7TM G-protein coupled receptors most of which clearly are derived from their host chemokine system as well as induce high expression of certain 7TM receptors in the infected cells. The receptors appear to be exploited by the virus for either immune evasion...... in various parts of the viral life cyclus. Most of the receptors encoded by human pathogenic virus are still orphan receptors, i.e. the endogenous ligand is unknown. In the few cases where it has been possible to characterize these receptors pharmacologically, they have been found to bind a broad spectrum...... expression of this single gene in certain lymphocyte cell lineages leads to the development of lesions which are remarkably similar to Kaposi's sarcoma, a human herpesvirus 8 associated disease. Thus, this and other virally encoded 7TM receptors appear to be attractive future drug targets....

  3. Receptor tyrosine kinases in carcinogenesis. (United States)

    Zhang, Xiao-Ying; Zhang, Pei-Ying


    Receptor tyrosine kinases (RTKs) are cell surface glycoproteins with enzymatic activity involved in the regulation of various important functions. In all-important physiological functions including differentiation, cell-cell interactions, survival, proliferation, metabolism, migration and signaling these receptors are the key players of regulation. Additionally, mutations of RTKs or their overexpression have been described in many human cancers and are being explored as a novel avenue for a new therapeutic approach. Some of the deregulated RTKs observed to be significantly affected in cancers included vascular endothelial growth factor receptor, epidermal growth factor receptor, fibroblast growth factor receptor, RTK-like orphan receptor 1 (ROR1) and the platelet-derived growth factor receptor. These deregulated RTKs offer attractive possibilities for the new anticancer therapeutic approach involving specific targeting by monoclonal antibodies as well as kinase. The present review aimed to highlight recent perspectives of RTK ROR1 in cancer.


    Michalek, Krzysztof; Morshed, Syed A.; Latif, Rauf; Davies, Terry F.


    Thyrotropin receptor autoantibodies (TSHR-Abs) of the stimulating variety are the hallmark of Graves’ disease. The presence of immune defects leading to synthesis of TSHR-Abs causes hyperthyroidism and is associated with other extrathyroidal manifestations. Further characterization of these antibodies has now been made possible by the generation of monoclonal antibodies with this unique stimulating capacity as well as similar TSHR-Abs not associated with hyperthyroidism. Their present classification divides TSHR-Abs into stimulating, blocking (competing with TSH binding) and neutral (no signaling). Recent studies using monoclonal TSHR-Abs has revealed that stimulating and blocking antibodies bind to the receptor using mostly conformational epitopes, whilst neutral antibodies utilize exclusively linear peptides. Subtle differences in epitopes for stimulating and blocking antibodies account for the diversity of their biological actions. Recently non-classical signaling elicited by neutral antibodies has also been described, raising the need for a new classification of TSHR-Abs. PMID:19332151

  5. Ligand-Receptor Interactions

    CERN Document Server

    Bongrand, Pierre


    The formation and dissociation of specific noncovalent interactions between a variety of macromolecules play a crucial role in the function of biological systems. During the last few years, three main lines of research led to a dramatic improvement of our understanding of these important phenomena. First, combination of genetic engineering and X ray cristallography made available a simultaneous knowledg of the precise structure and affinity of series or related ligand-receptor systems differing by a few well-defined atoms. Second, improvement of computer power and simulation techniques allowed extended exploration of the interaction of realistic macromolecules. Third, simultaneous development of a variety of techniques based on atomic force microscopy, hydrodynamic flow, biomembrane probes, optical tweezers, magnetic fields or flexible transducers yielded direct experimental information of the behavior of single ligand receptor bonds. At the same time, investigation of well defined cellular models raised the ...

  6. The interleukin-4 receptor: signal transduction by a hematopoietin receptor. (United States)

    Keegan, A D; Pierce, J H


    Over the last several years, the receptors for numerous cytokines have been molecularly characterized. Analysis of their amino acid sequences shows that some of these receptors bear certain motifs in their extracellular domains that define a family of receptors called the Hematopoietin receptor superfamily. Significant advances in characterizing the structure, function, and mechanisms of signal transduction have been made for several members of this family. The purpose of this review is to discuss the recent advances made for one of the family members, the interleukin (IL) 4 receptor. Other receptor systems have recently been reviewed elsewhere. The IL-4 receptor consists of, at the minimum, the cloned 140 kDa IL-4-binding chain with the potential for associating with other chains. The IL-4 receptor transduces its signal by activating a tyrosine kinase that phosphorylates cellular substrates, including the receptor itself, and the 170 kDa substrate called 4PS. Phosphorylated 4PS interacts with the SH2 domain of the enzyme PI-3'-kinase and increases its enzymatic activity. These early events in the IL-4 receptor initiated signaling pathway may trigger a series of signals that will ultimately lead to an IL-4 specific biologic outcome.

  7. [Lipoprotein receptors. Old acquaintances and newcomers]. (United States)

    Ducobu, J


    Lipoprotein receptors are plasma membrane proteins of high affinity which interact with circulating lipoprotein particles. The well characterized LDL receptor continues to be analysed and some new findings on its intracellular mechanisms of action have emerged. New lipoprotein receptors have recently been described: the chylomicron remnant receptor or LDL-related protein (LRP), the lipolysis stimulated receptor (LSR), the very low density lipoprotein receptor (VLDLR), the HDL receptor (HDLR) and the scavenger receptor (SR). The molecular details of the receptors will facilitate the development of new therapeutic means to improve receptor-mediated clearance of lipoproteins.

  8. Similarity of Bovine Rotavirus Receptor and Human Rotavirus Receptor

    Institute of Scientific and Technical Information of China (English)

    苏琦华; 訾自强; 潘菊芬; 徐燕


    The monoclonal antibody against bovine rotavirus (BRV) receptor (BRV-R-mAb) was used to explore the similarity between the receptors of BRV and human rotavirus (HRV). ELISA, dot immunobinding assay, cell protection assay, solid-phase assay and immunohistochemistry method were applied. BRV-R-mAb bound both anti-BRV IgG and anti-HRV IgG respectively and could protect MA 104 cells against BRV and HRV challenges. Immunohistochemistry test showed that there were rotavirus receptors on the surfaces of foetal intestinal, tracheal mucosa and MA 104 cells membrane. We purified the rotavirus receptors on MA 104 ceils, which could bind both BRV and HRV in vitro. It is concluded that BRV receptor and HRV receptor are homogenous proteins and can be recognized by both BRV and HRV.

  9. Melatonin Receptor Genes in Vertebrates

    Directory of Open Access Journals (Sweden)

    Hua Dong Yin


    Full Text Available Melatonin receptors are members of the G protein-coupled receptor (GPCR family. Three genes for melatonin receptors have been cloned. The MT1 (or Mel1a or MTNR1A and MT2 (or Mel1b or MTNR1B receptor subtypes are present in humans and other mammals, while an additional melatonin receptor subtype, Mel1c (or MTNR1C, has been identified in fish, amphibians and birds. Another melatonin related orphan receptor, GPR50, which does not bind melatonin, is found exclusively in mammals. The hormone melatonin is secreted primarily by the pineal gland, with highest levels occurring during the dark period of a circadian cycle. This hormone acts systemically in numerous organs. In the brain, it is involved in the regulation of various neural and endocrine processes, and it readjusts the circadian pacemaker, the suprachiasmatic nucleus. This article reviews recent studies of gene organization, expression, evolution and mutations of melatonin receptor genes of vertebrates. Gene polymorphisms reveal that numerous mutations are associated with diseases and disorders. The phylogenetic analysis of receptor genes indicates that GPR50 is an outgroup to all other melatonin receptor sequences. GPR50 may have separated from a melatonin receptor ancestor before the split between MTNR1C and the MTNR1A/B ancestor.

  10. Malzeme Taşıma Odaklı Planlama için Üretim Sistemlerindeki Tezgah Yerleşim Düzenlerinin Benzetim Analizi ile Karşılaştırılması

    Directory of Open Access Journals (Sweden)

    Mehmet AKSARAYLI


    Full Text Available Günümüzde işletmeler üretim maliyetlerini azaltmak ve verimliliklerinin artırmak için uygun tesis planları yapmak zorundadırlar. Çalışma, üretim sistemlerindeki tesis içi yerleşim problemlerinin çözümüne ulaşmakta kullanılan temel tezgâh yerleşim şekilleri ve ürüne göre yerleşim için önerilen yeni bir yaklaşımı birbirleriyle karşılaştıran bir çalışmadır. Çalışmada özellikle tezgâhlar arasındaki malzeme taşıma süreleri ve bu sürelerin toplam üretim süresi içerisindeki oranları ile ilgilenilmiştir. Buna ek olarak, incelenen tüm tezgâh yerleşim şekillerine göre benzetim modelleri sonucunda elde edilen tezgâhların kullanım yüzdeleri ve ürünlerin üretim miktarları da bu çalışma kapsamında aktarılmıştır. Çalışmada ilk olarak tesis planlamasında kullanılan temel yerleşim şekilleri için bir üretim sistemi tanımlanmıştır. Daha sonra tanımlanan üretim sistemi, her bir yerleşim şekli için tezgâh yerleşimi yapılmıştır. Ardından ürüne göre yerleşim şekli için önerilen yaklaşım aktarılarak üretim sistemi için tezgâh yerleşimi yapılmıştır. Daha sonra tezgâh yerleşim şekilleri "PROMODEL" benzetim yazılımı ortamına aktarılmıştır. Son olarak yapılan analizler ile farklı tezgâh yerleşim şekillerinin malzeme taşıma süreleri ve toplam üretim süresi içerisindeki oranları karşılaştırılmış ve analizlerden elde edilen sonuçlar yorumlanarak aktarılmıştır.

  11. Sağlık İletişiminde Korku Öğesinin Kullanımı: Sigara Paketlerinde Kullanılan Sigara Karşıtı Görsellerin Göstergebilimsel Analizi

    Directory of Open Access Journals (Sweden)

    Aslıhan Ardıç Çobaner


    Full Text Available Sağlık iletişiminde sağlıkla ilgili kampanyalarda ve özellikle de riskli davranışın değiştirilmesi ve bireyleri sağlığa zararlı davranışlarından vazgeçirmek amacıyla hazırlanan içeriklerde korku öğesinin (fear appeal kullanımına sık rastlanmaktadır. Bu çalışmanın amacı, sigara içme davranışını azaltmak için sigara paketlerinin üzerinde yer alan sigara karşıtı görsellerde korku öğesinin kullanımını, iletilerin neler olduğunu ve anlamın nasıl oluştuğunu göstergebilimsel analiz yöntemini kullanarak ortaya koymaktır. Bu çalışma, Türkiye’de sigara paketleri üzerinde kullanılan on dört görseli kapsamaktadır. Çalışmanın sonucunda, sigara paketleri üzerinde yer alan görsellerde korku öğesinin farklı düzeylerde kullanıldığı ortaya konulmuş ve korku öğesinin tıbbi paradigma içerisinde “sağlık” ve “sağlıklı olma” mitleri ile sağlık-hastalık, hayat-ölüm, kadınlık-erkeklik, gençlik-yaşlılık gibi karşıtlıklarla pekiştirildiği tespit edilmiştir.Ayrıca analiz sonuçları, görsel metinlerde sigara içmenin “bireysel bir davranış” ve bir “bağımlılık” olarak çerçevelendiğini de ortaya koymuştur. Korku öğesinin kullanımında beklenen tutum ve davranış değişikliğini sağlamak için bireylerin toplumsal olarak da desteklenmeleri gerekmektedir. Dolayısıyla bu çalışma bireyin ve toplumun sağlığı için bireysel çabaların yanında; politika geliştirme süreçlerine katılımın ve insanların kendi sağlıklarına dair farkındalıklarını ve öz-yeterliliklerini arttıran sağlık iletişimi faaliyetlerinin önemini de vurgulamaktadır.

  12. Türkiye ve Almanya’daki Coğrafya Öğretim Programlarının Karşılaştırılması / Comparisons of Geography Teaching Programs in Turkey and Germany

    Directory of Open Access Journals (Sweden)

    Mehmet Fatih KAYA


    Full Text Available Bu çalışmada; Türkiye’de 2005, Almanya’da ise 2004 yılından itibaren liselerde uygulanmaya başlanan Coğrafya Öğretim Programları karşılaştırılmıştır. Bu araştırma, lise Coğrafya Öğretim Programları’nın hedef, içerik, öğretme-öğrenme ve değerlendirme süreçlerini tespit etmeye yönelik bir araştırma şeklinde tasarlanmıştır. Araştırma nitel bir desene sahiptir. Araştırmanın evrenini Türkiye ve Almanya’da lise Coğrafya Öğretim Programları oluşturmaktadır. Örneklemini ise Türkiye’deki lise 9. sınıflar, Almanya’da ise nüfus miktarı ve yoğunluğu en fazla olan Nordhrhein-Westfalen eyaletindeki lise 9. sınıflar teşkil etmektedir. Coğrafya Öğretim Programları içerik analizine uygun olarak incelenmiş ve elde edilen bulgular doğrultusunda programlar; hedef, içerik, öğretme-öğrenme süreci ve değerlendirme süreci açısından karşılaştırılmıştır. Yaptığımız araştırmada şu sorulara cevap aranmıştır: Türkiye ve Almanya’daki Coğrafya Öğretim Programı’nın benzer ve farklılıkları nelerdir? Türkiye ve Almanya’daki Coğrafya Öğretim Programı’nın hedef, içerik, öğretme-öğrenme süreci ve değerlendirme süreci açısından olumlu ve olumsuz yönleri nelerdir? Her iki programın da benzerlik göstermekle birlikte birtakım farklılıkları da içerdiği tespit edilmiştir. Elde edilen bulgular ışığında araştırmacılara, öğretmenlere ve program geliştirme uzmanlarına bazı önerilerde bulunulmuştur.

  13. Ameliyat sonrası gelişen karın içi yapışıklıkların önlenmesinde metilen mavisinin etkinliğinin değerlendirilmesi (deneysel çalışma

    Directory of Open Access Journals (Sweden)

    Erkan Hazar


    Full Text Available Amaç. İntestinal tıkanıklıkların önemli bir nedeni ameliyat sonrası yapışıklıklardır. Bu çalışmanın amacı, metilen mavisinin ameliyat sonrası yapışıklıkları önleyici etkilerini araştırmaktır. Yöntem. Matür 40 adet sıçan kullanılıp, ameliyat öncesi sıçanlar rastgele olarak her biri 10 sıçandan oluşan 4 gruba ayrıldı; 1’inci gruba çekum ön duvarında 0,5cm’lik alan 15 no lu bistüri ile travmatize edilerek, 2’nci gruba çekum ön duvarda 1cm’lik alana bistüri ile tam kat kesildi ve kapatıldı. Bu iki gruba karın içerisine 2mL SF konuldu; 3’üncü gruba çekum ön duvarında 0,5cm’lik alan 15no’lu bistüri ile travmatize edilerek, IV. Grup’a çekum ön duvarda 1cm’lik alana bistüri ile tam kat kesildi ve kapatıldı. Bu iki gruba da karın içerisine %1’lik metilen mavisinden 2mL konuldu. Ameliyat sonrası 14’üncü günde çekumdan histopatolojik inceleme için biyopsi alınarak fıbrozis, neovaskülarizasyon, ve inflamasyon dereceleri incelendi. Bulgular. Fibrozis bakımından; 2 ve 4’üncü gruplar tamamen pozitif (+, 1’inci grubun %80’i negatif (- olarak değerlendirildi. İnflamatuar cevap için hastaların %25’i negatif (-, %75’i pozitif (+’tir. İkinci grup için tamamı %100’ü pozitiftir (+. Neovaskülarizasyon bakımından, tüm hastaların %35’i negatif (- %65’i pozitif (+’tir. Her gruptan en az bir hasta negatifken en çok 1’inci grupta %70 negatif (- hasta vardır. Mezotel hücre proliferasyonu bakımından, hastaların %27,5’i negatif,%62,5’i pozitif(+’tir. Grup 1’de negatiflik(- oranı %80, Grup 3’te pozitiflik oranı %90, Grup 4 için deneklerin tamamı pozitiftir. Sonuç. Metilen mavisinin fıbrozisi, neovaskülarizasyonu ve inflamasyonu azaltmadığı, mezotel hücre proliferasyonunu azalttığı görüldü. Bu bulgular, metilen mavisinin mezotel hücre proliferasyonunu azaltarak ameliyat sonrası yapışıklıkları

  14. Veri Madenciliğinde Kümeleme Teknikleri Üzerine Bir Çalışma: K-Means ve K-Medoids Kümeleme Algoritmalarının Karşılaştırılması

    Directory of Open Access Journals (Sweden)

    Güncel SARIMAN


    Full Text Available Günümüzde bilişim alanındaki gelişmeler sayesinde kullanıcılar daha gelişmiş bilgisayar teknolojilerine hakim olmaktadır ve bu gelişmeler beraberinde sayısal verilerin birikmesine neden olmaktadır. Bilişim teknolojileri biriken verileri saklayabilir. Tüm bu saklanan verilerin anlamlandırılması için veri madenciliği kullanılmaktadır. Veri madenciliği, verilerden önceden bilinmeyen anlamlı bilgileri tanımlama ya da tahmin etme tekniklerini içermektedir. Veri madenciliğinde verileri ortak özellikleri ile gruplamak için kümeleme algoritmaları yardımıyla ilginç desenler bulunabilir. Bu çalışmada UCI Machine Learning Repository veritabanından “Flags” veri seti alınarak k-means ve k-medoids bölümlemeli kümeleme algoritmalarıyla ülkelerin özelliklerine göre kümelere ayrılması hedeflenmiştir. Uygulama Asp.Net ile web ara yüzünde geliştirilerek internet ortamında kullanıcılara sunulmuştur. Çalışmanın sonunda veri seti K-Means ve K-Medoids algoritmalarıyla çalıştırılmış ve elde edilen analiz sonuçları karşılaştırılmalı olarak incelenmiş ve kullanım yerlerine yönelik öneriler sunulmuştur

  15. Pemikiran Teologi Ash‘Arîyah Dalam Irshâd Al-‘Aql Al-Salîm Ilâ Mazâyâ Al-Kitâb Al-Karîm Karya Abû Al-Su‘ud

    Directory of Open Access Journals (Sweden)

    Husni Mubarok


    Full Text Available This article explores theological thought of al-Ash‘arî in Abû al-Su‘ûd’s work Irshâd al-‘Aql al-Salîm ilâ Mazâyâ al-Kitâb al-Karîm. The study finds an interesting fact that when interpreting the Quranic verses on theological matters, Abû al-Su‘ûd tended to affiliate to Ash‘arîyah. However, Abû al-Su‘ûd firmly stated that he referred most to al-Kashshâf of al-Zamakhsharî in his exegetical works. It has been widely known that al-Zamakhsharî was one of prominent proponents of Mu‘tazilah. The article emphasizes a number of theological issues discussed by Abû al-Su‘ûd in his tafsîr such as God’s free will, anthropomorphism, and God’s justice. There have been three steps to analyze theological thoughts of Ash‘arîyah mentioned in Abû al-Su‘ûd’s work, are: firstly, grouping the most Quranic verses on theological realm referred by mutakallimîn. Secondly, explaining the views of each school (madhhab of Islamic theology. Thirdly, discussing the assessments and interpretation of Abû al-Su‘ûd on theological verses and comparing them to al-Zamakhsharî’s interpretation. Based on these three steps the author will analyze the Ash‘arîyah theological pattern adhered by Abû al-Su‘ûd.

  16. Seçmen Tercihinde Imaj Faktörü: Siyasal Parti ve Aday İmajı Karşılaştırmasına Yönelik Bir Alan Arştırması

    Directory of Open Access Journals (Sweden)

    Esra Aydın Kılıç


    Full Text Available Normal 0 false false false EN-US X-NONE X-NONE “Seçmen Tercihinde Imaj Faktörü: Siyasal Parti ve Aday İmajı Karşılaştırmasına İlişkin Bir Alan Arştırması”  adlıbuaraştırma partiimajı veadayimajınınseçmenlerin tercihleri üzerindekietkisiniincelemek amacıylayapılmıştır.Ankara’nın beş ilçesinden seçilen üçer mahallede tesadüfiörnekleme yöntemiilebelirlenen 546kişinin parti ve aday imajı ve bunları oluşturan unsurlar üzerindeki görüşleri anket tekniğinden yararlanılarak belirlenmiştir. /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin-top:0cm; mso-para-margin-right:0cm; mso-para-margin-bottom:10.0pt; mso-para-margin-left:0cm; line-height:115%; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin;}

  17. Flavivirus Entry Receptors: An Update

    Directory of Open Access Journals (Sweden)

    Manuel Perera-Lecoin


    Full Text Available Flaviviruses enter host cells by endocytosis initiated when the virus particles interact with cell surface receptors. The current model suggests that flaviviruses use at least two different sets of molecules for infectious entry: attachment factors that concentrate and/or recruit viruses on the cell surface and primary receptor(s that bind to virions and direct them to the endocytic pathway. Here, we present the currently available knowledge regarding the flavivirus receptors described so far with specific attention to C-type lectin receptors and the phosphatidylserine receptors, T-cell immunoglobulin and mucin domain (TIM and TYRO3, AXL and MER (TAM. Their role in flavivirus attachment and entry as well as their implication in the virus biology will be discussed in depth.

  18. Angiotensin II receptors in testes

    Energy Technology Data Exchange (ETDEWEB)

    Millan, M.A.; Aguilera, G.


    Receptors for angiotensin II (AII) were identified and characterized in testes of rats and several primate species. Autoradiographic analysis of the binding of 125I-labeled (Sar1,Ile8)AII to rat, rhesus monkey, cebus monkey, and human testicular slide-mounted frozen sections indicated specific binding to Leydig cells in the interstitium. In rat collagenase-dispersed interstitial cells fractionated by Percoll gradient, AII receptor content was parallel to that of hCG receptors, confirming that the AII receptors are in the Leydig cells. In rat dispersed Leydig cells, binding was specific for AII and its analogs and of high affinity (Kd, 4.8 nM), with a receptor concentration of 15 fmol/10(6) cells. Studies of AII receptors in rat testes during development reveals the presence of high receptor density in newborn rats which decreases toward the adult age (4934 +/- 309, 1460 +/- 228, 772 +/- 169, and 82 +/- 12 fmol/mg protein at 5, 15, 20, and 30 days of age, respectively) with no change in affinity. At all ages receptors were located in the interstitium, and the decrease in binding was parallel to the decrease in the interstitial to tubular ratio observed with age. AII receptor properties in membrane-rich fractions from prepuberal testes were similar in the rat and rhesus monkey. Binding was time and temperature dependent, reaching a plateau at 60 min at 37 C, and was increased by divalent cations, EGTA, and dithiothreitol up to 0.5 mM. In membranes from prepuberal monkey testes, AII receptors were specific for AII analogs and of high affinity (Kd, 4.2 nM) with a receptor concentration of 7599 +/- 1342 fmol/mg protein. The presence of AII receptors in Leydig cells in rat and primate testes in conjunction with reports of the presence of other components of the renin-angiotensin system in the testes suggests that the peptide has a physiological role in testicular function.

  19. Uncompetitive antagonism of AMPA receptors

    DEFF Research Database (Denmark)

    Andersen, Trine F; Tikhonov, Denis B; Bølcho, Ulrik;


    Philanthotoxins are uncompetitive antagonists of Ca2+-permeable AMPA receptors presumed to bind to the pore-forming region, but a detailed molecular mechanism for this interaction is missing. Here a small library of novel philanthotoxins was designed and synthesized using a solid-phase strategy. ...... polyamine toxins antagonize the AMPA receptor ion channel and provide the basis for rational development of uncompetitive antagonists of AMPA receptors....

  20. GABAρ1/GABAAα1 receptor chimeras to study receptor desensitization (United States)

    Martínez-Torres, Ataúlfo; Demuro, Angelo; Miledi, Ricardo


    γ-Aminobutyrate type C (GABAC) receptors are ligand-gated ion channels that are expressed preponderantly in the vertebrate retina and are characterized, among other things, by a very low rate of desensitization and resistance to the specific GABAA antagonist bicuculline. To examine which structural elements determine the nondesensitizing character of the human homomeric ρ1 receptor, we used a combination of gene chimeras and electrophysiology of receptors expressed in Xenopus oocytes. Two chimeric genes were constructed, made up of portions of the ρ1-subunit and of the α1-subunit of the GABAA receptor. When expressed in Xenopus oocytes, one chimeric gene (ρ1/α1) formed functional homooligomeric receptors that were fully resistant to bicuculline and were blocked by the specific GABAC antagonist (1,2,5,6-tetrahydropyridine-4-yl)methylphosphinic acid and by zinc. Moreover, these chimeric receptors had a fast-desensitizing component, even faster than that of heterooligomeric GABAA receptors, in striking contrast to the almost nil desensitization of wild-type ρ1 (wt ρ1) receptors. To see whether the fast-desensitizing characteristic of the chimera was determined by the amino acids forming the ion channels, we replaced the second transmembrane segment (TM2) of ρ1 by that of the α1-subunit of GABAA. Although the α1-subunit forms fast-desensitizing receptors when coexpressed with other GABAA subunits, the sole transfer of the α1TM2 segment to ρ1 was not sufficient to form desensitizing receptors. All this suggests that the slow-desensitizing trait of ρ1 receptors is determined by a combination of several interacting domains along the molecule. PMID:10725369

  1. Renal dopamine receptors and hypertension. (United States)

    Hussain, Tahir; Lokhandwala, Mustafa F


    Dopamine has been recognized as an important modulator of central as well as peripheral physiologic functions in both humans and animals. Dopamine receptors have been identified in a number of organs and tissues, which include several regions within the central nervous system, sympathetic ganglia and postganglionic nerve terminals, various vascular beds, the heart, the gastrointestinal tract, and the kidney. The peripheral dopamine receptors influence cardiovascular and renal function by decreasing afterload and vascular resistance and promoting sodium excretion. Within the kidney, dopamine receptors are present along the nephron, with highest density on proximal tubule epithelial cells. It has been reported that there is a defective dopamine receptor, especially D(1) receptor function, in the proximal tubule of various animal models of hypertension as well as in humans with essential hypertension. Recent reports have revealed the site of and the molecular mechanisms responsible for the defect in D(1) receptors in hypertension. Moreover, recent studies have also demonstrated that the disruption of various dopamine receptor subtypes and their function produces hypertension in rodents. In this review, we present evidence that dopamine and dopamine receptors play an important role in regulating renal sodium excretion and that defective renal dopamine production and/or dopamine receptor function may contribute to the development of various forms of hypertension.

  2. Leptin and its receptors. (United States)

    Wada, Nobuhiro; Hirako, Satoshi; Takenoya, Fumiko; Kageyama, Haruaki; Okabe, Mai; Shioda, Seiji


    Leptin is mainly produced in the white adipose tissue before being secreted into the blood and transported across the blood-brain barrier. Leptin binds to a specific receptor (LepR) that has numerous subtypes (LepRa, LepRb, LepRc, LepRd, LepRe, and LepRf). LepRb, in particular, is expressed in several brain nuclei, including the arcuate nucleus, the paraventricular nucleus, and the dorsomedial, lateral and ventromedial regions of the hypothalamus. LepRb is also co-expressed with several neuropeptides, including proopiomelanocortin, neuropeptide Y, galanin, galanin-like peptide, gonadotropin-releasing hormone, tyrosine hydroxylase and neuropeptide W. Functionally, LepRb induces activation of the JAK2/ERK, /STAT3, /STAT5 and IRS/PI3 kinase signaling cascades, which are important for the regulation of energy homeostasis and appetite in mammals. In this review, we discuss the structure, genetics and distribution of the leptin receptors, and their role in cell signaling mechanisms.

  3. Axonal GABAA receptors. (United States)

    Trigo, Federico F; Marty, Alain; Stell, Brandon M


    Type A GABA receptors (GABA(A)Rs) are well established as the main inhibitory receptors in the mature mammalian forebrain. In recent years, evidence has accumulated showing that GABA(A)Rs are prevalent not only in the somatodendritic compartment of CNS neurons, but also in their axonal compartment. Evidence for axonal GABA(A)Rs includes new immunohistochemical and immunogold data: direct recording from single axonal terminals; and effects of local applications of GABA(A)R modulators on action potential generation, on axonal calcium signalling, and on neurotransmitter release. Strikingly, whereas presynaptic GABA(A)Rs have long been considered inhibitory, the new studies in the mammalian brain mostly indicate an excitatory action. Depending on the neuron that is under study, axonal GABA(A)Rs can be activated by ambient GABA, by GABA spillover, or by an autocrine action, to increase either action potential firing and/or transmitter release. In certain neurons, the excitatory effects of axonal GABA(A)Rs persist into adulthood. Altogether, axonal GABA(A)Rs appear as potent neuronal modulators of the mammalian CNS.

  4. Discoidin Domain Receptor 1 (United States)

    Song, Sunmi; Shackel, Nicholas A.; Wang, Xin M.; Ajami, Katerina; McCaughan, Geoffrey W.; Gorrell, Mark D.


    Discoidin domain receptor 1 (DDR1) is a receptor tyrosine kinase that binds and is activated by collagens. Transcriptional profiling of cirrhosis in human liver using a DNA array and quantitative PCR detected elevated mRNA expression of DDR1 compared with that in nondiseased liver. The present study characterized DDR1 expression in cirrhotic and nondiseased human liver and examined the cellular effects of DDR1 expression. mRNA expression of all five isoforms of DDR1 was detected in human liver, whereas DDR1a demonstrated differential expression in liver with hepatitis C virus and primary biliary cirrhosis compared with nondiseased liver. In addition, immunoblot analysis detected shed fragments of DDR1 more readily in cirrhotic liver than in nondiseased liver. Inasmuch as DDR1 is subject to protease-mediated cleavage after prolonged interaction with collagen, this differential expression may indicate more intense activation of DDR1 protein in cirrhotic compared with nondiseased liver. In situ hybridization and immunofluorescence localized intense DDR1 mRNA and protein expression to epithelial cells including hepatocytes at the portal-parenchymal interface and the luminal aspect of the biliary epithelium. Overexpression of DDR1a altered hepatocyte behavior including increased adhesion and less migration on extracelular matrix substrates. DDR1a regulated extracellular expression of matrix metalloproteinases 1 and 2. These data elucidate DDR1 function pertinent to cirrhosis and indicate the importance of epithelial cell–collagen interactions in chronic liver injury. PMID:21356365

  5. Trace amine-associated receptors are olfactory receptors in vertebrates. (United States)

    Liberles, Stephen D


    The mammalian nose is a powerful chemosensor, capable of detecting and distinguishing a myriad of chemicals. Sensory neurons in the olfactory epithelium contain two types of chemosensory G protein-coupled receptors (GPCRs): odorant receptors (ORs), which are encoded by the largest gene family in mammals, and trace amine-associated receptors (TAARs), a smaller family of receptors distantly related to biogenic amine receptors. Do TAARs play a specialized role in olfaction distinct from that of ORs? Genes encoding TAARs are found in diverse vertebrates, from fish to mice to humans. Like OR genes, each Taar gene defines a unique population of canonical sensory neurons dispersed in a single zone of the olfactory epithelium. Ligands for mouse TAARs include a number of volatile amines, several of which are natural constituents of mouse urine, a rich source of rodent social cues. One chemical, 2-phenylethylamine, is reported to be enriched in the urine of stressed animals, and two others, trimethylamine and isoamylamine, are enriched in male versus female urine. Furthermore, isoamylamine has been proposed to be a pheromone that induces puberty acceleration in young female mice. These data raise the possibility that some TAARs are pheromone receptors in the nose, a hypothesis consistent with recent data suggesting that the olfactory epithelium contains dedicated pheromone receptors, separate from pheromone receptors in the vomeronasal organ. Future experiments will clarify the roles of TAARs in olfaction.

  6. GABAB receptors modulate NMDA receptor calcium signals in dendritic spines. (United States)

    Chalifoux, Jason R; Carter, Adam G


    Metabotropic GABA(B) receptors play a fundamental role in modulating the excitability of neurons and circuits throughout the brain. These receptors influence synaptic transmission by inhibiting presynaptic release or activating postsynaptic potassium channels. However, their ability to directly influence different types of postsynaptic glutamate receptors remains unresolved. Here we examine GABA(B) receptor modulation in layer 2/3 pyramidal neurons from the mouse prefrontal cortex. We use two-photon laser-scanning microscopy to study synaptic modulation at individual dendritic spines. Using two-photon optical quantal analysis, we first demonstrate robust presynaptic modulation of multivesicular release at single synapses. Using two-photon glutamate uncaging, we then reveal that GABA(B) receptors strongly inhibit NMDA receptor calcium signals. This postsynaptic modulation occurs via the PKA pathway and does not affect synaptic currents mediated by AMPA or NMDA receptors. This form of GABA(B) receptor modulation has widespread implications for the control of calcium-dependent neuronal function.

  7. Possible Relevance of Receptor-Receptor Interactions between Viral- and Host-Coded Receptors for Viral-Induced Disease

    Directory of Open Access Journals (Sweden)

    Luigi F. Agnati


    Full Text Available It has been demonstrated that some viruses, such as the cytomegalovirus, code for G-protein coupled receptors not only to elude the immune system, but also to redirect cellular signaling in the receptor networks of the host cells. In view of the existence of receptor-receptor interactions, the hypothesis is introduced that these viral-coded receptors not only operate as constitutively active monomers, but also can affect other receptor function by interacting with receptors of the host cell. Furthermore, it is suggested that viruses could also insert not single receptors (monomers, but clusters of receptors (receptor mosaics, altering the cell metabolism in a profound way. The prevention of viral receptor-induced changes in host receptor networks may give rise to novel antiviral drugs that counteract viral-induced disease.

  8. Sensory receptors in monotremes. (United States)

    Proske, U; Gregory, J E; Iggo, A


    This is a summary of the current knowledge of sensory receptors in skin of the bill of the platypus, Ornithorhynchus anatinus, and the snout of the echidna, Tachyglossus aculeatus. Brief mention is also made of the third living member of the monotremes, the long-nosed echidna, Zaglossus bruijnii. The monotremes are the only group of mammals known to have evolved electroreception. The structures in the skin responsible for the electric sense have been identified as sensory mucous glands with an expanded epidermal portion that is innervated by large-diameter nerve fibres. Afferent recordings have shown that in both platypuses and echidnas the receptors excited by cathodal (negative) pulses and inhibited by anodal (positive) pulses. Estimates give a total of 40,000 mucous sensory glands in the upper and lower bill of the platypus, whereas there are only about 100 in the tip of the echidna snout. Recording of electroreceptor-evoked activity from the brain of the platypus have shown that the largest area dedicated to somatosensory input from the bill, S1, shows alternating rows of mechanosensory and bimodal neurons. The bimodal neurons respond to both electrosensory and mechanical inputs. In skin of the platypus bill and echidna snout, apart from the electroreceptors, there are structures called push rods, which consist of a column of compacted cells that is able to move relatively independently of adjacent regions of skin. At the base of the column are Merkel cell complexes, known to be type I slowly adapting mechanoreceptors, and lamellated corpuscles, probably vibration receptors. It has been speculated that the platypus uses its electric sense to detect the electromyographic activity from moving prey in the water and for obstacle avoidance. Mechanoreceptors signal contact with the prey. For the echidna, a role for the electrosensory system has not yet been established during normal foraging behaviour, although it has been shown that it is able to detect the presence

  9. Coronavirus spike-receptor interactions

    NARCIS (Netherlands)

    Mou, H.


    Coronaviruses cause important diseases in humans and animals. Coronavirus infection starts with the virus binding with its spike proteins to molecules present on the surface of host cells that act as receptors. This spike-receptor interaction is highly specific and determines the virus’ cell, tissue

  10. Hydrocarbon Receptor Pathway in Dogs

    NARCIS (Netherlands)

    Steenbeek, F.G. van; Spee, B.; Penning, L.C.; Kummeling, A.; Gils, I.H.M.; Grinwis, G.C.M.; Leenen, D. van; Holstege, F.C.P.; Vos-Loohuis, M.; Rothuizen, J.; Leegwater, P.A.J.


    The aryl hydrocarbon receptor (AHR) mediates biological responses to toxic chemicals. An unexpected role for AHR in vascularization was suggested when mice lacking AHR displayed impaired closure of the ductus venosus after birth, as did knockout mice for aryl hydrocarbon receptor interacting protein

  11. Hydrocarbon Receptor Pathway in Dogs

    NARCIS (Netherlands)

    Steenbeek, F.G. van; Spee, B.; Penning, L.C.; Kummeling, A.; Gils, I.H.M.; Grinwis, G.C.M.; Leenen, D. van; Holstege, F.C.P.; Vos-Loohuis, M.; Rothuizen, J.; Leegwater, P.A.J.

    The aryl hydrocarbon receptor (AHR) mediates biological responses to toxic chemicals. An unexpected role for AHR in vascularization was suggested when mice lacking AHR displayed impaired closure of the ductus venosus after birth, as did knockout mice for aryl hydrocarbon receptor interacting

  12. Purinergic Receptors in Thrombosis and Inflammation

    National Research Council Canada - National Science Library

    Hechler, Béatrice; Gachet, Christian


    .... Beyond platelets, these 3 receptors, along with the P2Y2, P2Y6, and P2X7 receptors, constitute the main P2 receptors mediating the proinflammatory effects of nucleotides, which play important roles...

  13. Dopamine Receptors and Parkinson's Disease

    Directory of Open Access Journals (Sweden)

    Shin Hisahara


    Full Text Available Parkinson's disease (PD is a progressive extrapyramidal motor disorder. Pathologically, this disease is characterized by the selective dopaminergic (DAergic neuronal degeneration in the substantia nigra. Correcting the DA deficiency in PD with levodopa (L-dopa significantly attenuates the motor symptoms; however, its effectiveness often declines, and L-dopa-related adverse effects emerge after long-term treatment. Nowadays, DA receptor agonists are useful medication even regarded as first choice to delay the starting of L-dopa therapy. In advanced stage of PD, they are also used as adjunct therapy together with L-dopa. DA receptor agonists act by stimulation of presynaptic and postsynaptic DA receptors. Despite the usefulness, they could be causative drugs for valvulopathy and nonmotor complication such as DA dysregulation syndrome (DDS. In this paper, physiological characteristics of DA receptor familyare discussed. We also discuss the validity, benefits, and specific adverse effects of pharmaceutical DA receptor agonist.

  14. Opioids and their peripheral receptors

    Directory of Open Access Journals (Sweden)

    Francesco Amato


    Full Text Available The inflammation of peripheral tissues leads the primary afferent neurons, in particular at the cell bodies level located in the DRG (dorsal root ganglia, to an increased synthesis of opioid receptors: determining an “up-regulation”. After that opioid receptors are transported at the level of the nociceptive terminals, they are incorporated into the neuronal membrane becoming functional receptors. The above receptor proteins bind to opioid produced by immune cells or the exogenous ones. This leads to a direct or indirect suppression of the Ca2+ currents induced by TRPV1 or the currents of the Na+, resulting in neuronal reduced excitability and in transmitted signals decrease. The observation that the immune system is able to modulate the pain by ligands that interact with the opioid receptors located on sensory neurons, may have broad implications for the development of innovative and safer pain drugs.

  15. Ryanodine receptor channelopathies (United States)

    Betzenhauser, Matthew J.


    Ryanodine receptors (RyR) are intracellular Ca2+-permeable channels that provide the sarcoplasmic reticulum Ca2+ release required for skeletal and cardiac muscle contractions. RyR1 underlies skeletal muscle contraction, and RyR2 fulfills this role in cardiac muscle. Over the past 20 years, numerous mutations in both RyR isoforms have been identified and linked to skeletal and cardiac diseases. Malignant hyperthermia, central core disease, and catecholaminergic polymorphic ventricular tachycardia have been genetically linked to mutations in either RyR1 or RyR2. Thus, RyR channelopathies are both of interest because they cause significant human diseases and provide model systems that can be studied to elucidate important structure–function relationships of these ion channels. PMID:20179962

  16. The evolution of vertebrate opioid receptors


    Stevens, Craig W.


    The proteins that mediate the analgesic and other effects of opioid drugs and endogenous opioid peptides are known as opioid receptors. Opioid receptors consist of a family of four closely-related proteins belonging to the large superfamily of G-protein coupled receptors. The three types of opioid receptors shown unequivocally to mediate analgesia in animal models are the mu (MOR), delta (DOR), and kappa (KOR) opioid receptor proteins. The role of the fourth member of the opioid receptor fami...

  17. High-resolution immunogold localization of AMPA type glutamate receptor subunits at synaptic and non-synaptic sites in rat hippocampus. (United States)

    Baude, A; Nusser, Z; Molnár, E; McIlhinney, R A; Somogyi, P


    The cellular and subcellular localization of the GluRA, GluRB/C and GluRD subunits of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) type glutamate receptor was determined in the rat hippocampus using polyclonal antipeptide antibodies in immunoperoxidase and immunogold procedures. For the localization of the GluRD subunit a new polyclonal antiserum was developed using the C-terminal sequence of the protein (residues 869-881), conjugated to carrier protein and absorbed to colloidal gold for immunization. The purified antibodies immunoprecipitated about 25% of 3[H]AMPA binding activity from the hippocampus, cerebellum or whole brain, but very little from neocortex. These antibodies did not precipitate a significant amount of 3[H]kainate binding activity. The antibodies also recognize the GluRD subunit, but not the other AMPA receptor subunits, when expressed in transfected COS-7 cells and only when permeabilized with detergent, indicating an intracellular epitope. All subunits were enriched in the neuropil of the dendritic layers of the hippocampus and in the molecular layer of the dentate gyrus. The cellular distribution of the GluRD subunit was studied more extensively. The strata radiatum, oriens and the dentate molecular layer were more strongly immunoreactive than the stratum lacunosum moleculare, the stratum lucidum and the hilus. However, in the stratum lucidum of the CA3 area and in the hilus the weakly reacting dendrites were surrounded by immunopositive rosettes, shown in subsequent electron microscopic studies to correspond to complex dendritic spines. In the stratum radiatum, the weakly reacting apical dendrites contrasted with the surrounding intensely stained neuropil. The cell bodies of pyramidal and granule cells were moderately reactive. Some non-principal cells and their dendrites in the pyramidal cell layer and in the alveus also reacted very strongly for the GluRD subunit. At the subcellular level, silver intensified immunogold

  18. Stimulus intensity, cell excitation and the N-methyl-D-aspartate receptor component of sensory responses in the rat spinal cord in vivo. (United States)

    Chizh, B A; Cumberbatch, M J; Herrero, J F; Stirk, G C; Headley, P M


    responses. When background activity of neurones was enhanced by continuous activation of C-fibres with cutaneous application of mustard oil, ketamine was less effective against superimposed noxious pinch responses. Ongoing background activity was affected in parallel with evoked responses. When background discharge of the cells was maintained at a stable level with continuous ejection of kainate, neither the N-methyl-D-aspartate antagonists nor thyrotrophin-relasing hormone affected the responses to noxious pinch or heat, although responses to exogenous N-methyl-D-aspartate were still blocked. The wind-up of the electrical responses was, however, reduced by ketamine irrespective of the level of background activity. The results indicate that under these conditions in vivo, N-methyl-D-aspartate receptors mediate ongoing low-frequency background activity rather than phasic high-frequency nociceptive responses. The effects of N-methyl-D-aspartate antagonists and positive modulators on nociceptive responses are evidently indirect, being secondary to changes in background synaptic excitation. These results cannot be explained simply in relation to the voltage-dependence of N-methyl-D-aspartate receptor-mediated activity; other factors, such as modulation by neuropeptides, must be involved.

  19. Estrogen-related receptor β (ERRβ) - renaissance receptor or receptor renaissance? (United States)

    Divekar, Shailaja D; Tiek, Deanna M; Fernandez, Aileen; Riggins, Rebecca B


    Estrogen-related receptors (ERRs) are founding members of the orphan nuclear receptor (ONR) subgroup of the nuclear receptor superfamily. Twenty-seven years of study have yet to identify cognate ligands for the ERRs, though they have firmly placed ERRα and ERRγ at the intersection of cellular metabolism and oncogenesis. The pace of discovery for novel functions of ERRβ, however, has until recently been somewhat slower than that of its family members. ERRβ has also been largely ignored in summaries and perspectives of the ONR literature. Here, we provide an overview of established and emerging knowledge of ERRβ in mouse, man, and other species, highlighting unique aspects of ERRβ biology that set it apart from the other two estrogen-related receptors, with a focus on the impact of alternative splicing on the structure and function of this receptor.

  20. Stargazin Modulation of AMPA Receptors

    Directory of Open Access Journals (Sweden)

    Sana A. Shaikh


    Full Text Available Fast excitatory synaptic signaling in the mammalian brain is mediated by AMPA-type ionotropic glutamate receptors. In neurons, AMPA receptors co-assemble with auxiliary proteins, such as stargazin, which can markedly alter receptor trafficking and gating. Here, we used luminescence resonance energy transfer measurements to map distances between the full-length, functional AMPA receptor and stargazin expressed in HEK293 cells and to determine the ensemble structural changes in the receptor due to stargazin. In addition, we used single-molecule fluorescence resonance energy transfer to study the structural and conformational distribution of the receptor and how this distribution is affected by stargazin. Our nanopositioning data place stargazin below the AMPA receptor ligand-binding domain, where it is well poised to act as a scaffold to facilitate the long-range conformational selection observations seen in single-molecule experiments. These data support a model of stargazin acting to stabilize or select conformational states that favor activation.

  1. Cytokine receptors and hematopoietic differentiation. (United States)

    Robb, L


    Colony-stimulating factors and other cytokines signal via their cognate receptors to regulate hematopoiesis. In many developmental systems, inductive signalling determines cell fate and, by analogy with this, it has been postulated that cytokines, signalling via their cognate receptors, may play an instructive role in lineage specification in hematopoiesis. An alternative to this instructive hypothesis is the stochastic or permissive hypothesis. The latter proposes that commitment to a particular hematopoietic lineage is an event that occurs independently of extrinsic signals. It predicts that the role of cytokines is to provide nonspecific survival and proliferation signals. In this review, we look at the role of cytokine receptor signalling in hematopoiesis and consider the evidence for both hypotheses. Data from experiments that genetically manipulate receptor gene expression in vitro or in vivo are reviewed. Experiments in which cytokine receptors were installed in multipotential cells showed that, in some cases, stimulation with the cognate ligand could lead to alterations in lineage output. The creation of genetically manipulated mouse strains demonstrated that cytokine receptors are required for expansion and survival of single lineages but did not reveal a role in lineage commitment. We conclude that hematopoietic differentiation involves mainly stochastic events, but that cytokine receptors also have some instructive role.

  2. Vascular dopamine-I receptors. (United States)

    Yasunari, K; Kohno, M; Yokokawa, K; Horio, T; Kano, H; Takeda, T


    The modulation of dopamine DA1 receptors of cultured rat renal arterial smooth muscle cells by phorbol ester, glucocorticoid and sodium chloride was studied. The extent of [3H]Sch-23390 binding to phorbol ester-treated cell was increased without any change in the dissociation constant (Kd). At a concentration of 10 nmol/l, the synthetic glucocorticoid dexamethasone increased maximum receptor binding (Bmax) but had no effect on the Kd. 100 mmol/l sodium chloride did not change Bmax, but increased the Kd for DA1 receptor. The production of cAMP in response to DA1 receptor stimulation was enhanced without any change of the adenylate cyclase activity. The glucocorticoid effect on DA1 of arterial smooth muscle cells became apparent after hours of incubation in the presence of the steroid and was significantly inhibited by cycloheximide (10 micrograms/ml) and by the glucocorticoid receptor antagonist RU-38486, indicating that the effect required protein synthesis through glucocorticoid receptors. Treatment of cells with 1 mumol/l dexamethasone for 24 h increased basal and DA1-stimulated adenylate cyclase activity. Basal adenylate cyclase was decreased by sodium chloride in a dose-dependent manner. These results suggest differential control of DA1 receptors on vascular smooth muscle cells by protein kinase C, glucocorticoid or sodium chloride.

  3. Kurumsal Yönetimin Finansal Raporlama Kalitesindeki Rolü: Borsa İstanbul Üzerine Karşılaştırmalı Bir Uygulama (The Role Of Corporate Governance On The Quality Of Financial Reporting: A Comparative Study On Borsa Istanbul

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    Mahmut KARĞIN


    Full Text Available Corporate governance is sum of the principles to manage businesses by an understanding that assure all of the stakeholders’ rights. The theoretical expectation is that financial reporting quality of businesses that follow the corporate governance principles increases. The purpose of this study is to investigate the impact of corporate governance on the financial reporting quality. Therefore the quality of financial reports of listed and non-listed firms in Borsa Istanbul Corporate Governance Index (XKURY is compared with each other in terms of earnings persistence. As a result of the study, it’s seen that earnings of firms traded in XKURY are more persistent than others. It is concluded that their financial reports are more qualified. Kurumsal yönetim, işletmelerin tüm paydaşlarının haklarının korunduğu bir anlayışla yönetilmesine dayalı ilkeler bütünüdür. Kurumsal yönetim ilkelerine uyan işletmelerde finansal raporların kalitesinin artması, teorik olarak beklenen bir durumdur. Bu çalışmanın amacı, kurumsal yönetimin finansal raporlama kalitesi üzerindeki etkisinin araştırılmasıdır. Bu amaçla çalışmada Borsa İstanbul Kurumsal Yönetim Endeksi (XKURY’nde işlem gören firmalar ile bu endekste yer almayan firmaların finansal raporlama kaliteleri, karların sürekliliği açısından karşılaştırılmıştır. Çalışma sonucunda, teorik beklentilere uygun olarak XKURY’de işlem gören firmaların karlarının daha sürekli olduğu dolayısıyla finansal raporlarının daha kaliteli olduğu sonucuna ulaşılmıştır.

  4. Comparison of some physical and physiological characteristics of the male sedentaries, male handball players and male wrestlers whose ages were between 13 and 1513- 15 yaş arasındaki güreşçiler hentbolcular ve sedanterlerin bazı fiziksel ve fizyolojik parametrelerinin karşılaştırılması

    Directory of Open Access Journals (Sweden)

    Ömer Alıcı


    Full Text Available The study aimed at the comparison of some physical and physiological characteristics of the male sedentaries, male handball players and male wrestlers whose ages were between 13 and 15.77 male individuals (sedentaries=26, handball players=26 and wrestler=25 participated voluntarily. Height, weight and BMI values of the subjects were measured and tests for right and left hand grip strengths, leg and back strength, 20m sprint test, 30 sec sit-up, push-up, sit-reach (flexibility, respiratory function (FVC, VC, FEV1, PEF and counter movement jump (anaerobic power  were performed.As a result; it was found out that those who did sports in adolescent period had higher physical and physiological parameters than sedentaries. ÖzetBu çalışmanın amacı, 13-15 yaş erkek sedanter, hentbolcu ve güreşçilerin bazı fiziksel ve fizyolojik özelliklerinin karşılaştırılmasıdır.Araştırmaya 77 erkek sporcu ve öğrenci (sedanter=26, hentbolcu=26 ve güreşçi=25 gönüllü olarak katılmıştır. Çalışmaya katılan deneklerin boy, vücut ağırlığı, beden kitle indeksi (BKİ ölçülmüş ve sağ ve sol el-pençe kuvvetleri, sırt-bacak kuvveti, 20 m. sürat, 30 sn. mekik, 30 sn. şınav, otur-uzan (esneklik, solunum fonksiyon (FVC, VC, FEV1, PEF değerleri ve dikey sıçrama (anaerobik güç testleri uygulanmıştır.Sonuç olarak; adölesan dönemdeki spor yapan bireylerin fiziksel ve fizyolojik parametrelerinin aynı yaştaki sedanter bireylerden daha yüksek olduğu tespit edilmiştir.

  5. 等待或拒绝唯有时间--时间在王家卫电影意义生成过程中的作用分析%Waiting and Refusing Depend on Plot Time:Analysis of Time Effect in the Process of Meaning Generation in Wong Kar Wai’s Film

    Institute of Scientific and Technical Information of China (English)

    王冬冬; 林梓浩