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

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Romain eNardou

2011-07-01

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.

Type II and III Taste Bud Cells Preferentially Expressed Kainate Glutamate Receptors in Rats.

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Lee, Sang-Bok; Lee, Cil-Han; Kim, Se-Nyun; Chung, Ki-Myung; Cho, Young-Kyung; Kim, Kyung-Nyun

2009-12-01

Glutamate-induced cobalt uptake reveals that non-NMDA glutamate receptors (GluRs) are present in rat taste bud cells. Previous studies involving glutamate induced cobalt staining suggest this uptake mainly occurs via kainate type GluRs. It is not known which of the 4 types of taste bud cells express subunits of kainate GluR. Circumvallate and foliate papillae of Sprague-Dawley rats (45~60 days old) were used to search for the mRNAs of subunits of non-NMDA GluRs using RT-PCR with specific primers for GluR1-7, KA1 and KA2. We also performed RT-PCR for GluR5, KA1, PLCbeta2, and NCAM/SNAP 25 in isolated single cells from taste buds. Taste epithelium, including circumvallate or foliate papilla, express mRNAs of GluR5 and KA1. However, non-taste tongue epithelium expresses no subunits of non-NMDA GluRs. Isolated single cell RT-PCR reveals that the mRNAs of GluR5 and KA1 are preferentially expressed in Type II and Type III cells over Type I cells.

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

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

2014-01-01

, 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...

The dextromethorphan analog dimemorfan attenuates kainate-induced seizures via σ1 receptor activation: comparison with the effects of dextromethorphan

OpenAIRE

Shin, Eun-Joo; Nah, Seung-Yeol; Kim, Won-Ki; Ko, Kwang Ho; Jhoo, Wang-Kee; Lim, Yong-Kwang; Cha, Joo Young; Chen, Chieh-Fu; Kim, Hyoung-Chun

2005-01-01

In a previous study, we demonstrated that a dextromethorphan analog, dimemorfan, has neuroprotective effects.Dextromethorphan and dimemorfan are high-affinity ligands at σ1 receptors. Dextromethorphan has moderate affinities for phencyclidine sites, while dimemorfan has very low affinities for such sites, suggesting that these sites are not essential for the anticonvulsant actions of dimemorfan.Kainate (KA) administration (10 mg kg−1, i.p.) produced robust convulsions lasting 4–6 h in rats. P...

Quantum chemical study of agonist-receptor vibrational interactions for activation of the glutamate receptor.

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Kubo, M; Odai, K; Sugimoto, T; Ito, E

2001-06-01

To understand the mechanism of activation of a receptor by its agonist, the excitation and relaxation processes of the vibrational states of the receptor should be examined. As a first approach to this problem, we calculated the normal vibrational modes of agonists (glutamate and kainate) and an antagonist (6-cyano-7-nitroquinoxaline-2,3-dione: CNQX) of the glutamate receptor, and then investigated the vibrational interactions between kainate and the binding site of glutamate receptor subunit GluR2 by use of a semiempirical molecular orbital method (MOPAC2000-PM3). We found that two local vibrational modes of kainate, which were also observed in glutamate but not in CNQX, interacted through hydrogen bonds with the vibrational modes of GluR2: (i) the bending vibration of the amine group of kainate, interacting with the stretching vibration of the carboxyl group of Glu705 of GluR2, and (ii) the symmetric stretching vibration of the carboxyl group of kainate, interacting with the bending vibration of the guanidinium group of Arg485. We also found collective modes with low frequency at the binding site of GluR2 in the kainate-bound state. The vibrational energy supplied by an agonist may flow from the high-frequency local modes to the low-frequency collective modes in a receptor, resulting in receptor activation.

Zinc movement in the brain under kainate-induced seizures.

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Takeda, Atsushi; Hirate, Maki; Tamano, Haruna; Oku, Naoto

2003-05-01

On the basis of the evidence that elimination of 65Zn from the brain of epilepsy (EL) mice is facilitated by induction of seizures, zinc movement in the brain was studied in mice injected with kainate (12 mg/kg x 3), which exhibited status epilepticus within 120 min after the last injection of kainate. Zinc concentrations in the brain were determined 24 h after the last injection of kainate. Zinc concentrations in the hippocampus, amygdala and cerebral cortex, in which zinc-containing glutamatergic neuron terminals exist, were significantly decreased by the treatment with kainate, while that in the cerebellum was not decreased. Timm's stain in the brain was extensively attenuated 24 h after the last injection of kainate. These results indicate that zinc homeostasis in the brain is affected by kainate-induced seizures. In the hippocampus of rats injected with kainate (10 mg/kg), furthermore, the release of zinc and glutamate into the extracellular fluid was studied using in vivo microdialysis. The levels of zinc and glutamate in the perfusate were increased along with seizure severity after injection of kainate. It is likely that zinc concentration in the synaptic vesicles is decreased by the excess excitation of glutamatergic neurons. The present study suggests that the excessive release of zinc and glutamate from the neuron terminals under kainate-induced seizures is associated with the loss of zinc from the brain.

Selective kainate receptor (GluK1) ligands structurally based upon1H-Cyclopentapyrimidin-2,4(1H,3H)-dione: synthesis, molecular modeling, and pharmacological and biostructural characterization

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Venskutonyte, Raminta; Butini, Stefania; Coccone, Salvatore Sanna

2011-01-01

The physiological function of kainate receptors (GluK1- GluK5) in the central nervous system is not fully understood yet. With the aim of developing potent and selective GluK1 ligands, we have synthesized a series of new thiophene-based GluK1 agonists (6a-c) and antagonists (7a-d). Pharmacologica...

Evidence for a Specific Integrative Mechanism for Episodic Memory Mediated by AMPA/kainate Receptors in a Circuit Involving Medial Prefrontal Cortex and Hippocampal CA3 Region.

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de Souza Silva, Maria A; Huston, Joseph P; Wang, An-Li; Petri, David; Chao, Owen Yuan-Hsin

2016-07-01

We asked whether episodic-like memory requires neural mechanisms independent of those that mediate its component memories for "what," "when," and "where," and if neuronal connectivity between the medial prefrontal cortex (mPFC) and the hippocampus (HPC) CA3 subregion is essential for episodic-like memory. Unilateral lesion of the mPFC was combined with unilateral lesion of the CA3 in the ipsi- or contralateral hemispheres in rats. Episodic-like memory was tested using a task, which assesses the integration of memories for "what, where, and when" concomitantly. Tests for novel object recognition (what), object place (where), and temporal order memory (when) were also applied. Bilateral disconnection of the mPFC-CA3 circuit by N-methyl-d-aspartate (NMDA) lesions disrupted episodic-like memory, but left the component memories for object, place, and temporal order, per se, intact. Furthermore, unilateral NMDA lesion of the CA3 plus injection of (6-cyano-7-nitroquinoxaline-2,3-dione) (CNQX) (AMPA/kainate receptor antagonist), but not AP-5 (NMDA receptor antagonist), into the contralateral mPFC also disrupted episodic-like memory, indicating the mPFC AMPA/kainate receptors as critical for this circuit. These results argue for a selective neural system that specifically subserves episodic memory, as it is not critically involved in the control of its component memories for object, place, and time. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Elimination of zinc-65 from the brain under kainate-induced seizures.

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Takeda, Atsushi; Hirate, Maki; Oku, Naoto

2004-04-01

On the basis of the previous evidence that 65Zn concentrations in the brain of EL (epilepsy) mice was affected by induction of seizures, 65Zn movement in the brain was quantitatively evaluated in ddY mice treated with kainate. Six days after intravenous injection of 65ZnCl2, mice were intraperitoneally injected with kainate (10 mg/kg x 6 times in 2 weeks). Myoclonic jerks were observed during treatment with kainate. Twenty days after 65Zn injection, 65Zn distribution in the brain was compared between the kainite-treated and control mice. 65Zn distribution in the brain of the kainate-treated mice was overall lower than in the control mice. 65Zn concentration was significantly decreased in the frontal cortex, hippocampal CA1, thalamus and hypothalamus by treatment with kainate. These results demonstrate that kainate-induced seizures are linked to decreased zinc concentrations in the brain.

Neto2 influences on kainate receptor pharmacology and function

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

2016-01-01

the mechanism of Neto2 modulation is still unclear, gain-of-function results from the characterization of GluK1-GluA2 chimeras indicate that the GluK1 sequences included in these chimeras (part or all of the TMD and part of the linkers between the TMDs and LBD) play a key role in Neto2 modulation of KAR...

Different structural requirements for functional ion pore transplantation suggest different gating mechanisms of NMDA and kainate receptors.

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Villmann, Carmen; Hoffmann, Jutta; Werner, Markus; Kott, Sabine; Strutz-Seebohm, Nathalie; Nilsson, Tanja; Hollmann, Michael

2008-10-01

Although considerable progress has been made in characterizing the physiological function of the high-affinity kainate (KA) receptor subunits KA1 and KA2, no homomeric ion channel function has been shown. An ion channel transplantation approach was employed in this study to directly test if homomerically expressed KA1 and KA2 pore domains are capable of conducting currents. Transplantation of the ion pore of KA1 or KA2 into GluR6 generated perfectly functional ion channels that allowed characterization of those electrophysiological and pharmacological properties that are determined exclusively by the ion pore of KA1 or KA2. This demonstrates for the first time that KA1 and KA2 ion pore domains are intrinsically capable of conducting ions even in homomeric pore assemblies. NMDA receptors, similar to KA1- or KA2-containing receptors, function only as heteromeric complexes. They are composed of NR1 and NR2 subunits, which both are non-functional when expressed homomerically. In contrast to NR1, the homomeric NR2B ion pore failed to translate ligand binding into pore opening when transplanted into GluR6. Similarly, heteromeric coexpression of the ion channel domains of both NR1 and NR2 inserted into GluR6 failed to produce functional channels. Therefore, we conclude that the mechanism underlying the ion channel opening in the obligatorily heterotetrameric NMDA receptors differs significantly from that in the facultatively heterotetrameric alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate and KA receptors.

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

International Nuclear Information System (INIS)

Gallagher, M.; Gill, T.M.; Shivers, A.; Nicolle, M.M.

1997-01-01

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 [ 3 H]glutamate and [ 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 [ 3 H]kainate binding. It also induced an increase in the density of [ 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 [ 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 [ 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 [ 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 the hippocampus. (Copyright (c) 1997

AMPA/kainate glutamate receptors contribute to inflammation, degeneration and pain related behaviour in inflammatory stages of arthritis

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Bonnet, Cleo S; Williams, Anwen S; Gilbert, Sophie J; Harvey, Ann K; Evans, Bronwen A; Mason, Deborah J

2015-01-01

Objectives Synovial fluid glutamate concentrations increase in arthritis. Activation of kainate (KA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptors (GluRs) increase interleukin-6 (IL-6) release and cause arthritic pain, respectively. We hypothesised that AMPA and KA GluRs are expressed in human arthritis, and that intra-articular NBQX (AMPA/KA GluR antagonist) prevents pain and pathology in antigen-induced arthritis (AIA). Methods GluR immunohistochemistry was related to synovial inflammation and degradation in osteoarthritis (OA) and rheumatoid arthritis (RA). A single intra-articular NBQX injection was given at induction, and knee swelling and gait of AIA and AIA+NBQX rats compared over 21 days, before imaging, RT-qPCR, histology and immunohistochemistry of joints. Effects of NBQX on human primary osteoblast (HOB) activity were determined. Results AMPAR2 and KA1 immunolocalised to remodelling bone, cartilage and synovial cells in human OA and RA, and rat AIA. All arthritic tissues showed degradation and synovial inflammation. NBQX reduced GluR abundance, knee swelling (parthritis. PMID:24130267

High Concentrations of Tranexamic Acid Inhibit Ionotropic Glutamate Receptors.

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Lecker, Irene; Wang, Dian-Shi; Kaneshwaran, Kirusanthy; Mazer, C David; Orser, Beverley A

2017-07-01

The antifibrinolytic drug tranexamic acid is structurally similar to the amino acid glycine and may cause seizures and myoclonus by acting as a competitive antagonist of glycine receptors. Glycine is an obligatory co-agonist of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptors. Thus, it is plausible that tranexamic acid inhibits NMDA receptors by acting as a competitive antagonist at the glycine binding site. The aim of this study was to determine whether tranexamic acid inhibits NMDA receptors, as well as α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid and kainate subtypes of ionotropic glutamate receptors. Tranexamic acid modulation of NMDA, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, and kainate receptors was studied using whole cell voltage-clamp recordings of current from cultured mouse hippocampal neurons. Tranexamic acid rapidly and reversibly inhibited NMDA receptors (half maximal inhibitory concentration = 241 ± 45 mM, mean ± SD; 95% CI, 200 to 281; n = 5) and shifted the glycine concentration-response curve for NMDA-evoked current to the right. Tranexamic acid also inhibited α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (half maximal inhibitory concentration = 231 ± 91 mM; 95% CI, 148 to 314; n = 5 to 6) and kainate receptors (half maximal inhibitory concentration = 90 ± 24 mM; 95% CI, 68 to 112; n = 5). Tranexamic acid inhibits NMDA receptors likely by reducing the binding of the co-agonist glycine and also inhibits α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid and kainate receptors. Receptor blockade occurs at high millimolar concentrations of tranexamic acid, similar to the concentrations that occur after topical application to peripheral tissues. Glutamate receptors in tissues including bone, heart, and nerves play various physiologic roles, and tranexamic acid inhibition of these receptors may contribute to adverse drug effects.

USHA P KAR

Indian Academy of Sciences (India)

Volume 42 Issue 2 June 2017 pp 333-344 Review. Regulation of dynamin family proteins by post-translational modifications · USHA P KAR HIMANI ... Volume 43 Issue 1 March 2018 pp 139-148 Article. Tetrahymena dynamin-related protein 6 self-assembles independent of membrane association · USHA P KAR HIMANI ...

Kainate-induced network activity in the anterior cingulate cortex.

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Shinozaki, R; Hojo, Y; Mukai, H; Hashizume, M; Murakoshi, T

2016-06-14

Anterior cingulate cortex (ACC) plays a pivotal role in higher order processing of cognition, attention and emotion. The network oscillation is considered an essential means for integration of these CNS functions. The oscillation power and coherence among related areas are often dis-regulated in several psychiatric and pathological conditions with a hemispheric asymmetric manner. Here we describe the network-based activity of field potentials recorded from the superficial layer of the mouse ACC in vitro using submerged type recordings. A short activation by kainic acid administration to the preparation induced populational activities ranging over several frequency bands including theta (3-8Hz), alpha (8-12Hz), beta (13-30Hz), low gamma (30-50Hz) and high gamma (50-80Hz). These responses were repeatable and totally abolished by tetrodotoxin, and greatly diminished by inhibitors of ionotropic and metabotropic glutamate receptors, GABAA receptor or gap-junctions. These observations suggest that the kainate-induced network activity can be a useful model of the network oscillation in the ACC circuit. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

The dextromethorphan analog dimemorfan attenuates kainate-induced seizures via σ1 receptor activation: comparison with the effects of dextromethorphan

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Shin, Eun-Joo; Nah, Seung-Yeol; Kim, Won-Ki; Ko, Kwang Ho; Jhoo, Wang-Kee; Lim, Yong-Kwang; Cha, Joo Young; Chen, Chieh-Fu; Kim, Hyoung-Chun

2005-01-01

In a previous study, we demonstrated that a dextromethorphan analog, dimemorfan, has neuroprotective effects. Dextromethorphan and dimemorfan are high-affinity ligands at σ1 receptors. Dextromethorphan has moderate affinities for phencyclidine sites, while dimemorfan has very low affinities for such sites, suggesting that these sites are not essential for the anticonvulsant actions of dimemorfan. Kainate (KA) administration (10 mg kg−1, i.p.) produced robust convulsions lasting 4–6 h in rats. Pre-treatment with dimemorfan (12 or 24 mg kg−1) reduced seizures in a dose-dependent manner. Dimemorfan pre-treatment also attenuated the KA-induced increases in c-fos/c-jun expression, activator protein (AP)-1 DNA-binding activity, and loss of cells in the CA1 and CA3 fields of the hippocampus. These effects of dimemorfan were comparable to those of dextromethorphan. The anticonvulsant action of dextromethorphan or dimemorfan was significantly counteracted by a selective σ1 receptor antagonist BD 1047, suggesting that the anticonvulsant action of dextromethorphan or dimemorfan is, at least in part, related to σ1 receptor-activated modulation of AP-1 transcription factors. We asked whether dimemorfan produces the behavioral side effects seen with dextromethorphan or dextrorphan (a phencyclidine-like metabolite of dextromethorphan). Conditioned place preference and circling behaviors were significantly increased in mice treated with phencyclidine, dextrorphan or dextromethorphan, while mice treated with dimemorfan showed no behavioral side effects. Our results suggest that dimemorfan is equipotent to dextromethorphan in preventing KA-induced seizures, while it may lack behavioral effects, such as psychotomimetic reactions. PMID:15723099

Kainate receptors in the rat hippocampus: A distribution and time course of changes in response to unilateral lesions of the entorhinal cortex

International Nuclear Information System (INIS)

Ulas, J.; Monaghan, D.T.; Cotman, C.W.

1990-01-01

The response of kainate receptors to deafferentation and subsequent reinnervation following unilateral entorhinal cortex lesions was studied in the rat hippocampus using quantitative in vitro autoradiography. The binding levels of [3H]kainic acid (KA) and changes in the distribution of KA sites were investigated in the dentate gyrus molecular layer (ML) and in various terminal zones in the CA1 field at 1, 3, 7, 14, 21, 30, and 60 d postlesion. The data from both the ipsilateral and contralateral hippocampus were compared with those from unoperated controls. The first changes in KA receptor distribution were observed 21 d postlesion when the dense band of KA receptors occupying the inner one-third of the ML expanded into the denervated outer two-thirds of the ipsilateral ML. The spreading of the KA receptor field into previously unoccupied zones continued 30 and 60 d postlesion. At these time points, the zone enriched in [3H]KA binding sites became significantly (on average 50%) wider than in unoperated controls. No changes were observed in either the distribution or binding levels in other hippocampal areas or in the contralateral hippocampus at any studied time point. Saturation analysis of binding in the ipsilateral ML 60 d postlesion revealed changes in the maximum number of receptor sites (Bmax) without changes in KA receptor affinity (Kd). The data suggest that the elevation of the [3H]KA binding in the outer two-thirds of the ML reflects an increase in the number of both low and high affinity receptor binding sites. The pattern of KA receptor redistribution was similar to the well-characterized pattern of sprouting of commissural/associational systems from the inner one-third into the outer two-thirds of the ML after entorhinal lesions

Glufosinate ammonium induces convulsion through N-methyl-D-aspartate receptors in mice.

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Matsumura, N; Takeuchi, C; Hishikawa, K; Fujii, T; Nakaki, T

2001-05-18

Glufosinate ammonium, a broad-spectrum herbicide, causes convulsion in rodents and humans. Because of the structural similarities between glufosinate and glutamate, the convulsion induced by glufosinate ammonium may be ascribed to glutamate receptor activation. Three N-methyl-D-asparate (NMDA) receptor antagonists, dizocilpine, LY235959, and Compound 40, and an alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)/kainate receptor antagonist, NBQX, were coadministrated with glufosinate ammonium (80 mg/kg, intraperitoneally) in mice. Statistical analyses showed that the NMDA receptor antagonists markedly inhibited the convulsions, while the AMPA/kainate receptor antagonist had no effect on the convulsion. These results suggest that the convulsion caused by glufosinate ammonium is mediated through NMDA receptors.

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

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Walls, Anne B; Eyjolfsson, Elvar M; Schousboe, Arne; Sonnewald, Ursula; Waagepetersen, Helle S

2014-08-01

Despite the well-established use of kainate as a model for seizure activity and temporal lobe epilepsy, most studies have been performed at doses giving rise to general limbic seizures and have mainly focused on neuronal function. Little is known about the effect of lower doses of kainate 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]glucose was injected and subsequent nuclear magnetic resonance spectroscopy of cortical extracts was employed to distinctively map astrocytic and neuronal metabolism. The subconvulsive dose of kainate led to an instantaneous increase in the cortical lactate content, a subsequent reduction in the amount of [4,5-(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 a higher dose is required to affect neuronal metabolism. The cerebral glycogen content was dose-dependently reduced by kainate supporting a role for glycogen during seizure activity.

Kar5p is required for multiple functions in both inner and outer nuclear envelope fusion in Saccharomyces cerevisiae.

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Rogers, Jason V; Rose, Mark D

2014-12-02

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. Copyright © 2015 Rogers and Rose.

Medicinal Chemistry of Competitive Kainate Receptor Antagonists

Science.gov (United States)

2010-01-01

Kainic acid (KA) receptors belong to the group of ionotropic glutamate receptors and are expressed throughout in the central nervous system (CNS). The KA receptors have been shown to be involved in neurophysiological functions such as mossy fiber long-term potentiation (LTP) and synaptic plasticity and are thus potential therapeutic targets in CNS diseases such as schizophrenia, major depression, neuropathic pain and epilepsy. Extensive effort has been made to develop subtype-selective KA receptor antagonists in order to elucidate the physiological function of each of the five subunits known (GluK1−5). However, to date only selective antagonists for the GluK1 subunit have been discovered, which underlines the strong need for continued research in this area. The present review describes the structure−activity relationship and pharmacological profile for 10 chemically distinct classes of KA receptor antagonists comprising, in all, 45 compounds. To the medicinal chemist this information will serve as reference guidance as well as an inspiration for future effort in this field. PMID:22778857

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

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Zhe eJin

2014-01-01

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.

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

2005-01-01

1 The amino acid, D-aspartate, exists in the mammalian brain and is an agonist at the N-methyl-D-aspartate (NMDA) subtype of ionotropic glutamate receptors. Here, for the first time, we studied the actions of D-aspartate on alpha-amino-3-hydroxyl-5-methyl-4-isoxazolepropionate receptors (AMPARs......) in acutely isolated rat hippocampal neurons. 2 In the presence of the NMDA receptor channel blocker, MK801, D-aspartate inhibited kainate-induced AMPAR current in hippocampal neurons. The inhibitory action of D-aspartate on kainate-induced AMPAR current was concentration-dependent and was voltage......-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...

Novel Functional Properties of Drosophila CNS Glutamate Receptors

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

2016-12-01

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.

Increased NMDA and AMPA receptor densities in the anterior cingulate cortex in schizophrenia

International Nuclear Information System (INIS)

Zavitsanou, K.; Huang, X.-F.

2002-01-01

Full text: The anterior cingulate cortex (ACC) is a brain area of potential importance to our understanding of the pathophysiology of schizophrenia. Since a disturbed balance between excitatory and inhibitory activity is suggested to occur in the ACC in schizophrenia, the present study has focused on the analysis of binding of [ 3 H]MK801, [ 3 H]AMPA and [ 3 H]kainate, radioligands which respectively label the NMDA, AMPA and kainate receptors of the ionotropic glutamate receptor family in the ACC of 10 schizophrenia patients and 10 matched controls, using quantitative autoradiography. AMPA receptor densities were higher in cortical layer II whereas NMDA receptor densities were higher in cortical layers II-III in the ACC of both control and schizophrenia group. In contrast, kainate receptors displayed the highest density in cortical layer V. [ 3 H]AMPA binding was significantly increased by 25% in layer II in the schizophrenia group as compared to the control group. Similarly, a significant 17% increase of [ 3 H]MK801 binding was observed in layers II-III in the schizophrenia group. No statistically significant differences were observed for [ 3 H] kainate binding between the two groups. These results suggest that ionotropic glutamate receptors are differentially altered in the ACC of schizophrenia. The increase in [ 3 H]AMPA and [ 3 H]MK801 binding points to a postsynaptic compensation for impaired glutamatergic neurotransmission in the ACC in schizophrenia. Such abnormality could lead to an imbalance between the excitatory and inhibitory neurotransmission in this brain area that may contribute to the emergence of some schizophrenia symptoms. Copyright (2002) Australian Neuroscience Society

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

2014-01-01

Despite the well-established use of kainate as a model for seizure activity and temporal lobe epilepsy, most studies have been performed at doses giving rise to general limbic seizures and have mainly focused on neuronal function. Little is known about the effect of lower doses of kainate on cere...

The Role of GluK4 in Synaptic Plasticity and Affective Behavior in Mice

Science.gov (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

The effect of Vitamin E on learning and memory deficits in intrahippocampal kainate-induced temporal lobe epilepsy in rats.

Science.gov (United States)

Kiasalari, Zahra; Khalili, Mohsen; Shafiee, Samaneh; Roghani, Mehrdad

2016-01-01

Since temporal lobe epilepsy (TLE) is associated with learning and memory impairment, we investigated the beneficial effect of Vitamin E on the impaired learning and memory in the intrahippocampal kainate model of TLE in rats. Rats were divided into sham, Vitamin E-treated sham, kainate, and Vitamin E-treated kainate. Intrahippocampal kainate was used for induction of epilepsy. Vitamin E was injected intraperitoneal (i.p.) at a dose of 200 mg/kg/day started 1 week before surgery until 1 h presurgery. Initial and step-through latencies in the passive avoidance test and alternation behavior percentage in Y-maze were finally determined in addition to measurement of some oxidative stress markers. Kainate injection caused a higher severity and rate of seizures and deteriorated learning and memory performance in passive avoidance paradigm and spontaneous alternation as an index of spatial recognition memory in Y-maze task. Intrahippocampal kainate also led to the elevation of malondialdehyde (MDA) and nitrite and reduced activity of superoxide dismutase (SOD). Vitamin E pretreatment significantly attenuated severity and incidence rate of seizures, significantly improved retrieval and recall in passive avoidance, did not ameliorate spatial memory deficit in Y-maze, and lowered MDA and enhanced SOD activity. Vitamin E improves passive avoidance learning and memory and part of its beneficial effect is due to its potential to mitigate hippocampal oxidative stress.

Neuropeptide Y Y1 receptor hippocampal overexpression via viral vectors is associated with modest anxiolytic-like and proconvulsant effects in mice

DEFF Research Database (Denmark)

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

2012-01-01

overexpression was found to be associated with modest anxiolytic-like effect in the open field and elevated plus maze tests, but no effect was seen on depression-like behavior using the tail suspension and forced swim tests. However, the rAAV-Y1 vector modestly aggravated kainate-induced seizures. These data...... in the hippocampus of adult mice and tested the animals in anxiety- and depression-like behavior. Hippocampal Y1 receptors have been suggested to mediate seizure-promoting effect, so the effects of rAAV-induced Y1 receptor overexpression were also tested in kainate-induced seizures. Y1 receptor transgene...

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

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Paes, Paulo Cesar de Arruda

2002-07-01

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)

Aspects of dopamine and acetylcholine release induced by glutamate receptors

International Nuclear Information System (INIS)

Paes, Paulo Cesar de Arruda

2002-01-01

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)

Interactions of neurotoxins with non-NMDA glutamate receptors: an autoradiographic study

International Nuclear Information System (INIS)

Kuenig, G.; Niedermeyer, B.; Krause, F.; Hartmann, J.; Deckert, J.; Heinsen, H.; Beckmann, H.; Riederer, P.; Ransmayr, G.

1994-01-01

Neurotoxic substances are discussed to cause neurode-generation by acting as excitotoxins on glutamate receptors. We investigated the properties of L-beta-oxalyl-amino-alanine (L-BOAA) and 3,4,6-trihydroxyphenlyalanine (6-OH-Dopa) at the alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) glutamate receptor and that of L-BOAA and domoic acid at the kainate glutamate receptor in human hippocampus. (3 H)AMPA binding in hippocampal subfields was inhibited by L-BOAA and 6-OH-Dopa with mean IC50-values in the low micromolar range. (3H)Kainate binding was inhibited by L-BOAA with similar potency as (3H)AMPA binding and by domoic acid with mean IC50-values in the low nanomolar range. These results support the notion that symptoms like anterograde amnesia and epileptic seizures seen in domoic acid intoxication and limbic symptoms, e.g. cognitive and mood impairment observed in neurolathyrism may be caused by excitotoxic action on non-NMDA receptors. The potent interaction of 6-OH-Dopa with the AMPA-receptor may point to a possible dopaminergic-glutamatergic interaction in the development of neurodegenerative diseases like Parkinson's and Huntington's disease. (author)

Glufosinate ammonium stimulates nitric oxide production through N-methyl D-aspartate receptors in rat cerebellum.

Science.gov (United States)

Nakaki, T; Mishima, A; Suzuki, E; Shintani, F; Fujii, T

2000-09-01

Glufosinate ammonium, a structural analogue of glutamate, is an active herbicidal ingredient. The neuronal activities of this compound were investigated by use of a microdialysis system that allowed us to measure nitric oxide production in the rat cerebellum in vivo. Kainate (0.3-30 nmol/10 microliter), N-methyl-D-aspartate (NMDA) (3-300 nmol/10 microliter) and glufosinate ammonium (30-3000 nmol/10 microliter), which were administered through the microdialysis probe at a rate of 1 microliter/min for 10 min, stimulated nitric oxide production. The glufosinate ammonium-elicited increase in nitric oxide production was suppressed by an inhibitor of nitric oxide synthase and was antagonized by NMDA receptor antagonists, but not by a kainate/(+/-)-alphaamino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor antagonist. These results suggest that glufosinate ammonium stimulates nitric oxide production through NMDA receptors.

Arctigenin reduces neuronal responses in the somatosensory cortex via the inhibition of non-NMDA glutamate receptors.

Science.gov (United States)

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

2016-07-01

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. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

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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

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.

Science.gov (United States)

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

2017-11-01

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 GABA A receptor antagonist, ketamine (KET) as NMDA receptor antagonist, yohimbine (YOH) as α 2 adrenergic receptor antagonist and haloperidol (HAL) was used as dopamine D 2 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.

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

Index Scriptorium Estoniae

Sootak, Jaan, 1948-

2008-01-01

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

Eestlased Karli sillal

Index Scriptorium Estoniae

1999-01-01

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

K/Ar dating of diagenetic illites

International Nuclear Information System (INIS)

Mizusaki, A.M.P.; Anjos, S.M.C. dos; Costa, M.G.F. da; Silva, O.B. da; Kawashita, K.

1990-01-01

Ascertaining the potassium/argon (K/Ar) age of diagenetic illites yields important information for hydrocarbon exploration since the growth of this mineral in the pores of sandstone reservoir and oil migration are interlinked events in the diagenetic evolution of rocks. Illite growth ceases as soon as hydrocarbons completely fill in rock pores, displacing interstitial water. By providing an estimate of the period when the illite formed, K/Ar dating can indirectly tells us when hydrocarbons entered the reservoir. Samples of oil-saturated sandstones collected from Carboniferous reservoirs of the Solimoes Basin reveal a diagenetic evolution consisting predominantly of quartz, calcite, and illite overgrowths. In the present study, illite was mechanically separated by repeating a series of ultrasonic baths and ultrasonic probes followed by high-speed centrifuging. Resultant fractions were analyzed by X-ray diffractometry to measure the illite content of each sample. The separated illite material was found to be composed of illite and ordered mixed layer illite-smectite with 80% illite layers. Separated fractions were dated radiometrically by the K/Ar method. Preliminary results indicate an average age of some 200 m.y., which marks the end of the diagenetic development of the illites of this area. (author)

The GABAA receptor agonist THIP is neuroprotective in organotypic hippocampal slice cultures

DEFF Research Database (Denmark)

Kristensen, Bjarne Winther; Noraberg, Jens; Zimmer, Jens

2003-01-01

The potential neuroprotective effects of the GABA(A) receptor agonists THIP (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol) and muscimol, and the selective GluR5 kainate receptor agonist ATPA ((RS)-2-amino-3-(3-hydroxy-5-tert-butylisoxazol-4-yl)propanoic acid), which activates GABAergic interneu......The potential neuroprotective effects of the GABA(A) receptor agonists THIP (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol) and muscimol, and the selective GluR5 kainate receptor agonist ATPA ((RS)-2-amino-3-(3-hydroxy-5-tert-butylisoxazol-4-yl)propanoic acid), which activates GABAergic...... interneurons, were examined in hippocampal slice cultures exposed to N-methyl-D-aspartate (NMDA). The NMDA-induced excitotoxicity was quantified by densitometric measurements of propidium iodide (PI) uptake. THIP (100-1000 microM) was neuroprotective in slice cultures co-exposed to NMDA (10 microM) for 48 h......, while muscimol (100-1000 microM) and ATPA (1-3 microM) were without effect. The results demonstrate that direct GABA(A) agonism can mediate neuroprotection in the hippocampus in vitro as previously suggested in vivo....

Biochemical characterization of an autoradiographic method for studying excitatory amino acid receptors using L-[3H]glutamate

International Nuclear Information System (INIS)

Cincotta, M.; Summers, R.J.; Beart, P.M.

1989-01-01

A method was developed for radiolabeling excitatory amino acid receptors of rat brain with L-[ 3 H]glutamate. Effective labeling of glutamate receptors in slide-mounted 10-microns sections was obtained using a low incubation volume (0.15 ml) and rapid washing: a procedure where high ligand concentrations were achieved with minimal waste. Saturation experiments using [ 3 H]glutamate revealed a single binding site of micromolar affinity. The Bmax was trebled in the presence of Ca2+ (2.5 mM) and Cl- (20 mM) with no change in the Kd. Binding was rapid, saturable, stereospecific, and sensitive to glutamate receptor agonists. The proportions of [ 3 H]glutamate binding sensitive to N-methyl-D-aspartate (NMDA), kainate, and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) were 34, 54, and 51%, respectively. NMDA inhibited binding at a distinct subset of L-[ 3 H]glutamate sites, whereas AMPA and kainate competed for some common sites. Labeling of sections with L-[ 3 H]glutamate in the presence of the selective agonists allowed autoradiographic visualization of glutamate receptor subtypes in brain tissue

Dopamine modulation of avoidance behavior in Caenorhabditis elegans requires the NMDA receptor NMR-1.

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Melvin Baidya

Full Text Available The nematode C. elegans utilizes a relatively simple neural circuit to mediate avoidance responses to noxious stimuli such as the volatile odorant octanol. This avoidance behavior is modulated by dopamine. cat-2 mutant animals that are deficient in dopamine biosynthesis have an increased response latency to octanol compared to wild type animals, and this defect can be fully restored with the application of exogenous dopamine. Because this avoidance behavior is mediated by glutamatergic signaling between sensory neurons and premotor interneurons, we investigated the genetic interactions between dopaminergic signaling and ionotropic glutamate receptors. cat-2 mutant animals lacking either the GLR-1 or GLR-2 AMPA/kainate receptors displayed an increased response latency to octanol, which could be restored via exogenous dopamine. However, whereas cat-2 mutant animals lacking the NMR-1 NMDA receptor had increased response latency to octanol they were insensitive to exogenous dopamine. Mutants that lacked both AMPA/kainate and NMDA receptors were also insensitive to exogenous dopamine. Our results indicate that dopamine modulation of octanol avoidance requires NMR-1, consistent with NMR-1 as a potential downstream signaling target for dopamine.

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

Directory of Open Access Journals (Sweden)

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.

Identification of Checkpoint Genes Involved in the kar3 Cell Cycle Arrest

National Research Council Canada - National Science Library

Shanks, Robert

2001-01-01

...) including Cik1p and Vik1p. We have explored the roles of these KAPs in mejosis. Cik1p is essential for meiosis, while Vik1p has a very minor role. These data are consistent with Cik1p and Kar3p acting together to perform the essential role of Kar3p in meiosis. We have also localized Kar3p, Cik1p,and Vik1p during meiosis.

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 Toft

2012-01-01

We recently demonstrated that recombinant adeno-associated viral vector-induced hippocampal overexpression of neuropeptide Y receptor, Y2, exerts a seizure-suppressant effect in kindling and kainate-induced models of epilepsy in rats. Interestingly, additional overexpression of neuropeptide Y...

Expression and localization of ionotropic glutamate receptor subunits in the goldfish retina--an in situ hybridization and immunocytochemical study

NARCIS (Netherlands)

Vandenbranden, C. A.; Kamphuis, W.; Nunes Cardozo, B.; Kamermans, M.

2000-01-01

The expression and distribution of AMPA, kainate and NMDA glutamate receptor subunits was studied in the goldfish retina. For the immunocytochemical localization of the AMPA receptor antisera against GluR2, GluR2/3 and GluR4 were used, and for in situ hybridization rat specific probes for GluR1 and

Cell cycle-dependent regulation of kainate-induced inward currents in microglia

International Nuclear Information System (INIS)

Yamada, Jun; Sawada, Makoto; Nakanishi, Hiroshi

2006-01-01

Microglia are reported to have α-amino-hydroxy-5-methyl-isoxazole-4-propionate/kainate (KA) types. However, only small population of primary cultured rat microglia (approximately 20%) responded to KA. In the present study, we have attempted to elucidate the regulatory mechanism of responsiveness to KA in GMIR1 rat microglial cell line. When the GMIR1 cells were plated at a low density in the presence of granulocyte macrophage colony-stimulating factor, the proliferation rate increased and reached the peak after 2 days in culture and then gradually decreased because of density-dependent inhibition. At cell proliferation stage, approximately 80% of the GMIR1 cells exhibited glutamate (Glu)- and KA-induced inward currents at cell proliferation stage, whereas only 22.5% of the cells showed responsiveness to Glu and KA at cell quiescent stage. Furthermore, the mean amplitudes of inward currents induced by Glu and KA at cell proliferation stage (13.8 ± 3.0 and 8.4 ± 0.6 pA) were significantly larger than those obtained at cell quiescent stage (4.7 ± 0.8 and 6.2 ± 1.2 pA). In the GMIR1 cells, KA-induced inward currents were markedly inhibited by (RS)-3-(2-carboxybenzyl) willardiine (UBP296), a selective antagonist for KA receptors. The KA-responsive cells also responded to (RS)-2-amino-3-(3-hydroxy-5-tert-butylisoxazol-4-yl) propanoic acid (ATPA), a selective agonist for GluR5, in both GMIR1 cells and primary cultured rat microglia. Furthermore, mRNA levels of the KA receptor subunits, GluR5 and GluR6, at the cell proliferation stage were significantly higher than those at the cell quiescent stage. Furthermore, the immunoreactivity for GluR6/7 was found to increase in activated microglia in the post-ischemic hippocampus. These results strongly suggest that microglia have functional KA receptors mainly consisting of GluR5 and GluR6, and the expression levels of these subunits are closely regulated by the cell cycle mechanism

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

International Nuclear Information System (INIS)

Gallagher, M.; Bizon, J.L.; Nicolle, M.M.

1996-01-01

Using in vitro autoradiography, we investigated [ 3 H]α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate, [ 3 H]kainate and [ 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, [ 3 H]α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate binding in CA1 and [ 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 [ 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, [ 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 [ 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 learning, suggesting a compensatory reduction

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

International Nuclear Information System (INIS)

Delorme, Caroline; Joshi, Monika; Allingham, John S.

2012-01-01

Highlights: ► The Candida albicans Kar3 motor domain structure was solved as a maltose-binding protein fusion. ► The electrostatic surface and part of the ATPase pocket of the motor domain differs markedly from other kinesins. ► 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.

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: allinghj@queensu.ca [Department of Biomedical and Molecular Sciences, Queen' s University, Kingston, ON, Canada K7L 3N6 (Canada)

2012-11-30

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.

(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

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Lammertsma Adriaan A

2011-01-01

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.

(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

International Nuclear Information System (INIS)

Syvänen, Stina; Luurtsema, Gert; Molthoff, Carla FM; Windhorst, Albert D; Huisman, Marc C; Lammertsma, Adriaan A; Voskuyl, Rob A; Lange, Elizabeth C de

2011-01-01

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. (R)-[ 11 C]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)-[ 11 C]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)-[ 11 C]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). All data analysis approaches indicated only modest differences in brain distribution of (R)-[ 11 C]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. P-gp expression and functionality does not seem to change at early stage after induction of anticipated pharmacoresistant epilepsy by kainate

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.

A new potential AED, carisbamate, substantially reduces spontaneous motor seizures in rats with kainate-induced epilepsy

Science.gov (United States)

Grabenstatter, Heidi L.; Dudek, F. Edward

2010-01-01

Purpose Animal models with spontaneous epileptic seizures may be useful in the discovery of new antiepileptic drugs (AEDs). The purpose of the present study was to evaluate the efficacy of carisbamate on spontaneous motor seizures in rats with kainate-induced epilepsy. Methods Repeated, low-dose (5 mg/kg), intraperitoneal injections of kainate were administered every hour until each male Sprague-Dawley rat had experienced convulsive status epilepticus for at least 3 h. Five 1-month trials (n= 8–10 rats) assessed the effects of 0.3, 1, 3, 10 and 30 mg/kg carisbamate on spontaneous seizures. Each trial involved six AED-versus-vehicle tests comprised of carisbamate or 10% solutol-HS-15 treatments administered as intraperitoneal injections on alternate days with a recovery day between each treatment day. Results Carisbamate significantly reduced motor seizure frequency at doses of 10 and 30 mg/kg, and caused complete seizure cessation during the 6-h post-drug epoch in 7 of 8 animals at 30 mg/kg. The effects of carisbamate (0.3–30 mg/kg) on spontaneous motor seizures appeared dose dependent. Conclusions These data support the hypothesis that a repeated-measures, cross-over protocol in animal models with spontaneous seizures is an effective method for testing AEDs. Carisbamate reduced the frequency of spontaneous motor seizures in a dose-dependent manner, and was more effective than topiramate at reducing seizures in rats with kainate-induced epilepsy. PMID:18494790

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

Energy Technology Data Exchange (ETDEWEB)

Syvänen, Stina [Division of Pharmacology, LACDR, Leiden University, P.O. Box 9502, 2300 RA Leiden (Netherlands); Luurtsema, Gert [Department of Nuclear Medicine & Molecular Imaging, Groningen University Medical Center, P.O. Box 30.001 9700 RB Groningen (Netherlands); Molthoff, Carla FM; Windhorst, Albert D; Huisman, Marc C; Lammertsma, Adriaan A [Department of Nuclear Medicine & PET Research, VU University Medical Center, P.O. Box 7057, 1007 MB, Amsterdam (Netherlands); Voskuyl, Rob A [Division of Pharmacology, LACDR, Leiden University, P.O. Box 9502, 2300 RA Leiden (Netherlands); Epilepsy Institute of The Netherlands Foundation (SEIN), P.O. Box 21, 2100 AA, Heemstede (Netherlands); Lange, Elizabeth C de [Division of Pharmacology, LACDR, Leiden University, P.O. Box 9502, 2300 RA Leiden (Netherlands)

2011-01-03

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. (R)-[{sup 11}C]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)-[{sup 11}C]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)-[{sup 11}C]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). All data analysis approaches indicated only modest differences in brain distribution of (R)-[{sup 11}C]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. P-gp expression and functionality does not seem to change at early stage after induction of anticipated pharmacoresistant epilepsy by kainate.

Excitatory and inhibitory pathways modulate kainate excitotoxicity in hippocampal slice cultures

DEFF Research Database (Denmark)

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

1993-01-01

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....

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

DEFF Research Database (Denmark)

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

2017-01-01

, 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....

Cyto- and receptor architecture of area 32 in human and macaque brains.

Science.gov (United States)

Palomero-Gallagher, Nicola; Zilles, Karl; Schleicher, Axel; Vogt, Brent A

2013-10-01

Human area 32 plays crucial roles in emotion and memory consolidation. It has subgenual (s32), pregenual (p32), dorsal, and midcingulate components. We seek to determine whether macaque area 32 has subgenual and pregenual subdivisions and the extent to which they are comparable to those in humans by means of NeuN immunohistochemistry and multireceptor analysis of laminar profiles. The macaque has areas s32 and p32. In s32, layer IIIa/b neurons are larger than those of layer IIIc. This relationship is reversed in p32. Layer Va is thicker and Vb thinner in s32. Area p32 contains higher kainate, benzodiazepine (BZ), and serotonin (5-HT)1A but lower N-methyl-D-aspartate (NMDA) and α2 receptor densities. Most differences were found in layers I, II, and VI. Together, these differences support the dual nature of macaque area 32. Comparative analysis of human and macaque s32 and p32 supports equivalences in cyto- and receptor architecture. Although there are differences in mean areal receptor densities, there are considerable similarities at the layer level. Laminar receptor distribution patterns in each area are comparable in the two species in layers III-Va for kainate, NMDA, γ-aminobutyric acid (GABA)B , BZ, and 5-HT1A receptors. Multivariate statistical analysis of laminar receptor densities revealed that human s32 is more similar to macaque s32 and p32 than to human p32. Thus, macaque 32 is more complex than hitherto known. Our data suggest a homologous neural architecture in anterior cingulate s32 and p32 in human and macaque brains. © 2013 Wiley Periodicals, Inc.

Hyperexcitability and cell loss in kainate-treated hippocampal slice cultures

DEFF Research Database (Denmark)

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

1993-01-01

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......-like immunoreactive (PV-I) interneurons preceded loss of somatostatin-like immunoreactive (SS-I) interneurons suggesting a different time course of KA neurotoxicity in these subpopulations of interneurons....

Kainate toxicity in energy-compromised rat hippocampal slices: differences between oxygen and glucose deprivation.

Science.gov (United States)

Schurr, A; Rigor, B M

1993-06-18

The effects of kainate (KA) on the recovery of neuronal function in rat hippocampal slices after hypoxia or glucose deprivation (GD) were investigated and compared to those of (R,S)-alpha-amino-3-hydroxy-5-methyl-4- isoxazoleproprionate (AMPA). KA and AMPA were found to be more toxic than either N-methyl-D-aspartate (NMDA), quinolinate, or glutamate, both under normal conditions and under states of energy deprivation. Doses as low as 1 microM KA or AMPA were sufficient to significantly reduce the recovery rate of neuronal function in slices after a standardized period of hypoxia or GD. The enhancement of hypoxic neuronal damage by both agonists could be partially blocked by the antagonist kynurenate, by the NMDA competitive antagonist AP5, and by elevating [Mg2+] in or by omitting Ca2+ from the perfusion medium. The AMPA antagonist glutamic acid diethyl ester was ineffective in preventing the enhanced hypoxic neuronal damage by either KA or AMPA. The antagonist of the glycine modulatory site on the NMDA receptor, 7-chlorokynurenate, did not block the KA toxicity but was able to block the toxicity of AMPA. 2,3-Dihydroxyquinoxaline completely blocked the KA- and AMPA-enhanced hypoxic neuronal damage. The KA-enhanced, GD-induced neuronal damage was prevented by Ca2+ depletion and partially antagonized by kynurenate but not by AP5 or elevated [Mg2+]. The results of the present study indicate that the KA receptor is involved in the mechanism of neuronal damage induced by hypoxia and GD, probably allowing Ca2+ influx and subsequent intracellular Ca2+ overload.(ABSTRACT TRUNCATED AT 250 WORDS)

Single Chondrule K/Ar ages of Mexican Meteorites Using ID-TIMS.

Science.gov (United States)

Hernandez, M.; Sole, J.

2007-05-01

We have determined the K/Ar ages of two H5 ordinary meteorites: Cosina and Nuevo Mercurio, neither dated until this study. We analyzed several single chondrules - weighing few milligrams - of each meteorite. Ages were obtained by using very precise K content determined by isotope dilution mass spectrometry. The K content in chondrules ranges between 650 and 1400 ppm. The 40Ar was measured by static vacuum noble gas mass spectrometry. Samples were fused with an infrared CO2 laser. Chondrule ages vary from 3.66 to 4.59 Ga for Cosina and from 4.20 to 4.87 Ga for Nuevo Mercurio. A comparison between our data and the published K/Ar ages of H and L whole rocks shows that dates obtained from single chondrules are older than those obtained from whole rocks and seem to preserve older events not evidenced in the WR ages. This implies that chondrules can preserve K/Ar ages very close to U-Pb crystallization ages.

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

1998-01-01

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...

Development of the Potassium-Argon Laser Experiment (KArLE) Instrument for In Situ Geochronology

Science.gov (United States)

Cohen, Barbara A.; Li, Z.-H.; Miller, J. S.; Brinckerhoff, W. B.; Clegg, S. M.; Mahaffy, P. R.; Swindle, T. D.; Wiens, R. C.

2012-01-01

Absolute dating of planetary samples is an essential tool to establish the chronology of geological events, including crystallization history, magmatic evolution, and alteration. Traditionally, geochronology has only been accomplishable on samples from dedicated sample return missions or meteorites. The capability for in situ geochronology is highly desired, because it will allow one-way planetary missions to perform dating of large numbers of samples. The success of an in situ geochronology package will not only yield data on absolute ages, but can also complement sample return missions by identifying the most interesting rocks to cache and/or return to Earth. In situ dating instruments have been proposed, but none have yet reached TRL 6 because the required high-resolution isotopic measurements are very challenging. Our team is now addressing this challenge by developing the Potassium (K) - Argon Laser Experiment (KArLE) under the NASA Planetary Instrument Definition and Development Program (PIDDP), building on previous work to develop a K-Ar in situ instrument [1]. KArLE uses a combination of several flight-proven components that enable accurate K-Ar isochron dating of planetary rocks. KArLE will ablate a rock sample, determine 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 the volume of the ablated pit using an optical method 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.

Update on Development of the Potassium-Argon Laser Experiment (KArLE) Instrument for In Situ Geochronology

Science.gov (United States)

Cohen, Barbara A.; Li, Z.-H.; Miller, J. S.; Brinckerhoff, W. B.; Clegg, S. M.; Mahaffy, P. R.; Swindle, T. D.; Wiens, R. C.

2013-01-01

Absolute dating of planetary samples is an essential tool to establish the chronology of geological events, including crystallization history, magmatic evolution, and alteration. We are addressing this challenge by developing the Potassium (K) -- Argon Laser Experiment (KArLE), building on previous work to develop a K-Ar in situ instrument. KArLE ablates a rock sample, determines the K in the plasma state using laser-induced breakdown spectroscopy (LIBS), measures the liberated Ar using quadrupole mass spectrometry (QMS), and relates the two by the volume of the ablated pit using laser confocal microscopy (LCM). Our goal is for the KArLE instrument to be capable of determining the age of several kinds of planetary samples to address a wide range of geochronolgy problems in planetary science.

Co-induction of p75(NTR) and the associated death executor NADE in degenerating hippocampal neurons after kainate-induced seizures in the rat.

Science.gov (United States)

Yi, Jung-Sun; Lee, Soon-Keum; Sato, Taka-Aki; Koh, Jae-Young

2003-08-21

Zinc induces in cultured cortical neurons both p75(NTR) and p75(NTR)-associated death executor (NADE), which together contribute to caspase-dependent neuronal apoptosis. Since zinc neurotoxicity may contribute to neuronal death following seizures, we examined whether p75(NTR) and NADE are co-induced also in rat hippocampal neurons degenerating after seizures. Staining of brain sections with a zinc-specific fluorescent dye (N-(6-methoxy-8-quinolyl)-p-carboxybenzoylsulphonamide) and acid fuchsin revealed zinc accumulation in degenerating neuronal cell bodies in CA1 and CA3 of hippocampus 24 h after kainate injection. Both anti-p75(NTR) and anti-NADE immunoreactivities appeared in zinc-accumulating/degenerating neurons in both areas. Intraventricular injection of CaEDTA, without altering the severity or time course of kainate-induced seizures, markedly attenuated the induction of p75(NTR)/NADE in hippocampus, which correlated with the decrease of caspase-3 activation and zinc accumulation/cell death. The present study has demonstrated that p75(NTR) and NADE are co-induced in neurons degenerating after kainate-induced seizures in rats, likely in a zinc-dependent manner.

Properties of GluR3 receptors tagged with GFP at the amino or carboxyl terminus.

Science.gov (United States)

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

2007-09-25

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) alpha-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 EC(50) 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.

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

DEFF Research Database (Denmark)

Møllerud, Stine; Pinto, Andrea; Marconi, Laura

2017-01-01

Ionotropic glutamate receptors (iGluRs) are involved in most of the fast excitatory synaptic transmission in the central nervous system. These receptors are important for learning and memory formation, but are also involved in the development of diseases such as Alzheimer’s disease, epilepsy...

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

African Journals Online (AJOL)

PRECIOUS

2009-11-02

Nov 2, 2009 ... Turkey: Impact of environmental variables. H. Özbay1* and ... in the river. Key words: River Kars, zooplankton, running water, environmental factors. ..... tergestina (Branchiopoda: Onychopoda) in Guanabara Bay, Brazil. Braz.

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

International Nuclear Information System (INIS)

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

1992-01-01

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

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)

1998-05-05

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.

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

Science.gov (United States)

Cohen, Barbara

2016-01-01

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.

Illite K-Ar dating of fault breccia samples from ONKALO underground research facility, Olkiluoto, Eurajoki, SW Finland

International Nuclear Information System (INIS)

Maenttaeri, I.; Mattila, J.; Zwingmann, H.; Todd, A.J.

2007-08-01

Illite K-Ar age determinations were done on five fault breccia samples from the ONKALO underground research facility, Olkiluoto, Eurajoki, S-W Finland. The XRD, SEM, and TEM studies and K-Ar analyses were done in John deLaeter Center in Mass Spectrometry at Curtin University, Perth, Western Australia. The <2 micron grain size fractions contain illite, chlorite, dickite, and quartz. All fractions had minor contamination phases comprising mainly of quartz but traces of K-feldspar contamination could be identified in all samples. The authigenic illite shows variable K concentrations. The illite contents of the ONK-PL68 and ONK-PL87 samples are the smallest. The K-Ar ages for the <2 micron fractions vary from ∼0.55 Ga to 1.38 Ga. The sample ONKPL68 yields a K-Ar age of 912 ± 18 Ma corresponding to a Neoproterozoic-Tonian age. This age can be roughly temporally linked with late events related to Sveconorwegian orogeny. Sample ONK-PL87 has a K-Ar age of 550 ± 11 Ma corresponding to a Neoproterozoic - Lower Cambrian age. The samples ONK-PL522 and ONK-PL901 sampled from the storage hall fault show identical K-Ar ages of 1385 ± 27 Ma and 1373 ± 27 Ma, respectively. These correspond to a Mesoproterozoic-Ectasian age related to Subjotnian or Postjotnian events. ONK-PL960 yields a K-Ar age of 1225 ± 24 Ma corresponding to a Mesoproterozoic-Ectasian age. This age agrees well with the ages from Postjotnian diabase dykes in W Finland. The 2-3 % detrital K-feldspar contamination in clay fractions increases the age. Especially for the youngest sample ONK-PL87, the effect may be geologically meaningful as after the correction the age clearly indicates Caledonian events. Moreover, the age for the low K sample ONKPL901 shifts to indicate Postjotnian diabase age. (orig.)

In Situ Dating Experiments of Igneous Rocks Using the KArLE Instrument: A Case Study for Approximately 380 Ma Basaltic Rocks

Science.gov (United States)

Cho, Yuichiro; Cohen, Barbara A.

2018-01-01

We report new K-Ar isochron data for two approximately 380 Ma basaltic rocks, using an updated version of the Potassium-Argon Laser Experiment (KArLE). These basalts have K contents comparable to lunar KREEP basalts or igneous lithologies found by Mars rovers, whereas previous proof-of-concept studies focused primarily on more K-rich rocks. We continue to measure these analogue samples to show the advancing capability of in situ K-Ar geochronology. KArLE is applicable to other bodies including the Moon or asteroids.

K-Ar ages of the Auckland geomagnetic excursions

International Nuclear Information System (INIS)

Mochizuki, Nobutatsu; Tsunakawa, Hideo; Shibuya, Hidetoshi; Tagami, Takahiro; Ozawa, Ayako; Cassidy, John; Smith, E.M.

2004-01-01

K-Ar age determinations were made on two monogenetic volcanoes in the Auckland volcanic field, New Zealand, which have recorded the Auckland geomagnetic excursions. For the Wiri volcano with the north-down intermediate paleomagnetic direction, five samples gave a weighted mean age of 27±5 (1σ) ka. For the Hampton Park volcano with the west-up intermediate direction, three samples gave a weighted mean of 55±5(1σ) ka. Since these two K-Ar ages are distinguished at 2σ level, it is inferred that at least two geomagnetic excursions can be recognized in Auckland. The age of the Hampton Park is barely distinguished from the established age range of the Laschamp excursion (39-45 ka) at 2σ level. The age of the Wiri coincides with the age of c. 30 ka in which excursions have been found from sedimentary and volcanic records. The reported excursions from volcanic rocks show a VGP cluster in the central to northern Pacific region which is distinct from the VGP paths or clusters during polarity reversals. (author)

Profiling neurotransmitter receptor expression in the Ambystoma mexicanum brain.

Science.gov (United States)

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

2013-03-22

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. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Kars ilinde örgün eğitimin gelişimi ve mevcut durumu

OpenAIRE

DEMİR, MUCİP

2016-01-01

Doğu Anadolu Bölgesinin Kars Erzurum bölümünde yer alan Kars İli ortalama irtifası 2000 metre civarında olan ve birçok yeri volkanik materyallerle örtülü Kars Platosu üzerinde bulunmaktadır. Mevcut topografik koşulların etkisiyle sert karasal iklimin görüldüğü ilde başta nüfus olmak üzere diğer beşeri faaliyetler bu coğrafik faktörlerin yoğun etkisiyle şekillenmektedir. İlde halen 300.000 civarında bulunan nüfus il dışına doğru meydana gelen göçlerle azalış eğilimi göstermektedir. 373 ilko...

Radial symmetry in a chimeric glutamate receptor pore

Science.gov (United States)

Wilding, Timothy J.; Lopez, Melany N.; Huettner, James E.

2014-02-01

Ionotropic glutamate receptors comprise two conformationally different A/C and B/D subunit pairs. Closed channels exhibit fourfold radial symmetry in the transmembrane domain (TMD) but transition to twofold dimer-of-dimers symmetry for extracellular ligand binding and N-terminal domains. Here, to evaluate symmetry in open pores we analysed interaction between the Q/R editing site near the pore loop apex and the transmembrane M3 helix of kainate receptor subunit GluK2. Chimeric subunits that combined the GluK2 TMD with extracellular segments from NMDA receptors, which are obligate heteromers, yielded channels made up of A/C and B/D subunit pairs with distinct substitutions along M3 and/or Q/R site editing status, in an otherwise identical homotetrameric TMD. Our results indicate that Q/R site interaction with M3 occurs within individual subunits and is essentially the same for both A/C and B/D subunit conformations, suggesting that fourfold pore symmetry persists in the open state.

Erratum Aldosterone synthase C-344T, angiotensin II type 1 receptor ...

Indian Academy of Sciences (India)

Aldosterone synthase C-344T, angiotensin II type 1 receptor A1166C and 11-β hydroxysteroid dehydrogenase G534A gene polymorphisms and essential hypertension in the population of Odisha, India. Manisha Patnaik, Pallabi Pati, Surendra N. Swain, Manoj K. Mohapatra, Bhagirathi Dwibedi, Shantanu K. Kar.

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

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Francy Johanna Moreno-Pedraza

2010-12-01

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.

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

International Nuclear Information System (INIS)

Quirion, R.; Chabot, J.-G.; Dore, S.; Seto, D.; Kar, S.

1997-01-01

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. [ 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 [ 125 I]insulin-like growth factor I receptor sites throughout (i.e. 30 days) the study. [ 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 [ 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 [ 125 I]insulin receptor binding was noted at all time points in the molecular layer of the

Role of glutamatergic receptors located in the nucleus raphe magnus on antinociceptive effect of morphine microinjected into the nucleus cuneiformis of rat.

Science.gov (United States)

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

2007-10-29

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.

Loss of function of Saccharomyces cerevisiae kinesin-related CIN8 and KIP1 is suppressed by KAR3 motor domain mutations.

Science.gov (United States)

Hoyt, M A; He, L; Totis, L; Saunders, W S

1993-09-01

The kinesin-related products of the CIN8 and KIP1 genes of Saccharomyces cerevisiae redundantly perform an essential function in mitosis. The action of either gene-product is required for an outwardly directed force that acts upon the spindle poles. We have selected mutations that suppress the temperature-sensitivity of a cin8-temperature-sensitive kip1-delta strain. The extragenic suppressors analyzed were all found to be alleles of the KAR3 gene. KAR3 encodes a distinct kinesin-related protein whose action antagonizes Cin8p/Kip1p function. All seven alleles analyzed were altered within the region of KAR3 that encodes the putative force-generating (or "motor") domain. These mutations also suppressed the inviability associated with the cin8-delta kip1-delta genotype, a property not shared by a deletion of KAR3. Other properties of the suppressing alleles revealed that they were not null for function. Six of the seven were unaffected for the essential karyogamy and meiosis properties of KAR3 and the seventh was dominant for the suppressing trait. Our findings suggest that despite an antagonistic relationship between Cin8p/Kip1p and Kar3p, aspects of their mitotic roles may be similar.

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

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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.

TRADITION OF KARS MINSTREL ACCORDING TO THE TYPE OF FOLK POET IN DEDE KORKUT STORIES DEDE KORKUT HİKÂYELERİNDEKİ OZAN TİPİ BAĞLAMINDA KARS ÂŞIKLIK GELENEĞİ

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Cengiz GÖKŞEN

2011-12-01

Full Text Available The Dede Korkut stories are one of the most important commonvalues of Turkish World. Although this work had been written thehundreds of years later that the Turks accepted Islam religion, it hasmany elements of Turkish culture that belongs to pre-islamic period. Thecustom of being a poet, which is a type of musician, is one of theTurkish culture of pre-islamic age. The poets were not only musicianswho had ability of music, but also they have the ability of a religiousperson, a doctor or a witch. After a while, by the effects of Islamicculture, these poets had left their places to the minstrels(=Aşık. Kars andits neighbourhood is one of the place that the custom of minstrel hasperformed mostly. There has been many common elements between thetype of poets in the Dede Korkut Stories and in the living tradition ofminstrel of Kars. In this study, the similarities between the Dede KorkutStories and Kars minstrel tadition, and the reason of these had been triedto be defineted. Dede Korkut Hikâyeleri Türk Dünyasının en önemli ortakdeğerlerinden biridir. Bu eser, Türklerin İslam dinini kabul etmesindenyüzlerce yıl sonra yazıya geçirilmiş olmasına rağmen, İslamiyet öncesiTürk kültür hayatına ait birçok unsur taşımaktadır. İslamiyet öncesiTürk kültürünün müzisyen sanatçı tipi olan ozan’lık geleneği bunlardanbiridir. Müzisyenlik yanında, din adamlığı, büyücülük, hekimlik gibi bilgive becerilere de sahip olan ozanlar İslamiyet’in de etkisiyle bir süre sonrayerlerini âşıklara bırakmışlardır Âşıklık geleneğinin ülkemizde en canlıyaşadığı yerlerden biri Kars ve çevresidir. Yaşayan Kars âşıklık geleneğiiçinde Dede Korkut Hikâyelerindeki ozan tipi ve ozanlık geleneğiyle ortakbirçok unsur bulunmaktadır. Bu çalışmada Dede Korkut Hikâyelerindekiozanlık geleneğiyle Kars âşıklık geleneğindeki benzerlikler ve bunlarınsebepleri tespit edilmeye çalışılmıştır.

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

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Zahra Kiasalari

2014-09-01

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.

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

International Nuclear Information System (INIS)

WoldeGabriel, G.

1993-01-01

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 (≥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

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

2002-07-01

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

The laser microprobe dating drives K-Ar geochronology into a new milestone at the end of 20th century

International Nuclear Information System (INIS)

Mu Zhiguo; Gao Yongjun

2001-01-01

K-Ar age dating method is facing a serious challenge to its application due to that both Ar loss and Ar excess are widespread found even though it has been undergoing 50 years. In the latest few years of the 20th century, studies on K-Ar geochronology have been pushing on a new step as a sign of method perfected and precision enhanced. High precision and high resolution 40 Ar/ 39 Ar dating, can use in both micro-area and a single grain, extends dating limit into the historical realm. Applied range of K-Ar geochronology is getting bigger and bigger due to fine analytical techniques while solved geological problems are getting wider and wider

K-Ar geochronology of the Kulu-Mandi Belt, NW Himalaya, India

International Nuclear Information System (INIS)

Mehta, P.K.; Rex, D.C.

1977-01-01

The K-Ar dates of micas and whole rock amphibolites from the Kulu-Mandi Belt define two distinct groups, (1) 20 to 75 m. y., and (2) 277 to 366 m. y. Our data together with the other available K-Ar and Rb-Sr mineral and whole rock data, enable us to confirm three major events in the Himalaya, the Late Precambrian-Cambrian Assyntian (Cadomian) Orogenic cycle, the Late Palaeozoic Hercynian Magmatic-Epeirogenic cycle and the Late Cretaceous-Teritiary Himalayan Orogenic cycle. The mineral dating is significant for delineating different phases of the last i.e. the Himalayan Oregeny. The radiometric data, so far to hand, indicate that the main activity of the young, Himalayan metamorphism was probably around 50 to 70 m. y. (Late Cretaceous-Eocene) and this was followed by a major uplift during the 10 to 25 m. y. (Mid. Miocene) time, which was responsible for thrusting and formation of nappe structures in the Himalaya. (orig.) [de

Adeno-associated viral vector-induced overexpression of neuropeptide Y Y2 receptors in the hippocampus suppresses seizures

DEFF Research Database (Denmark)

Woldbye, David Paul Drucker; Ängehagen, Mikael; Gøtzsche, Casper René

2010-01-01

Gene therapy using recombinant adeno-associated viral vectors overexpressing neuropeptide Y in the hippocampus exerts seizure-suppressant effects in rodent epilepsy models and is currently considered for clinical application in patients with intractable mesial temporal lobe epilepsy. Seizure...... recombinant adeno-associated viral vectors. In two temporal lobe epilepsy models, electrical kindling and kainate-induced seizures, vector-based transduction of Y2 receptor complementary DNA in the hippocampus of adult rats exerted seizure-suppressant effects. Simultaneous overexpression of Y2...... and neuropeptide Y had a more pronounced seizure-suppressant effect. These results demonstrate that overexpression of Y2 receptors (alone or in combination with neuropeptide Y) could be an alternative strategy for epilepsy treatment....

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

Index Scriptorium Estoniae

Lõoke, Ralf, 1978-

2011-01-01

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)

Regulation of GABA and benzodiazepine receptors following neurotoxin-induced striatal and medial forebrain bundle lesions

International Nuclear Information System (INIS)

Pan, H.S.I.

1985-01-01

GABA, a major inhibitory transmitter, is used by many projection neurons of the striatum. To investigate the role of GABA in striatal function, the GABA receptor complex was studied after lesions of the striatum or the nigrostriatal neurons. Quantitative receptor autoradiography using thaw-mounted tissue slices was developed for the study of GABA and benzodiazepine (BDZ) receptors. With the technique established, binding to GABA and BDZ receptors after unilateral striatal kainate lesions was examined. Subsequently, changes in GABA and BDZ receptors were studied following the destruction of dopaminergic nigrostriatal cells by unilateral 6-hydroxydopamine lesion of the medial forebrain bundle. In summary, quantitative receptor autoradiography allowed the detection of GABA and BDZ receptor changes in multiple small areas in each lesioned brain. This technique made it feasible to carry out kinetic saturation, and competition studies using less than 1 mg of tissue. The data suggest that dopamine is functionally inhibitory on striatopallidal neurons but is functionally excitatory on striatoentopeduncular and striatonigral cells which in turn inhibit the thalamus. This quantitative autoradiographic technique can be generalized to study other transmitter receptors and can be combined with 2-deoxyglucose uptake studies

K-Ar age of molybdenum mineralization in the east-central Kitakami Mountains, northern Honshu, Japan

International Nuclear Information System (INIS)

Ishihara, Shunso; Shibata, Ken; Uchiumi, Shigeru

1989-01-01

Three K-Ar ages were determined on rocks and minerals from the mineralized areas in the east-central part of the Kitakami Cretaceous granitic terrain, where a Paleogene mineralization age was reported recently on molybdenite by the Re-Os method. The present result showed an early Cretaceous age of 114±4 Ma for the same molybdenite deposit. A rather large discrepancy was found between the Re-Os ages for molybdenite and the K-Ar and Rb-Sr ages for silicate minerals from the same ore deposits of Mesozoic-Cenozoic ages in the Circum-Pacific region, indicating that the Re-Os method needs further examination. (author)

(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

2003-01-01

)propionic acid (AMPA) but inactive at NMDA receptors. However, 4-AHCP was found to be much weaker than AMPA as an inhibitor of [(3)H]AMPA binding and to have limited effect in a [(3)H]kainic acid binding assay using rat cortical membranes. To shed light on the mechanism(s) underlying this quite enigmatic......, 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...

KARS İLİNDE ÖRGÜN EĞİTİMİN GELİŞİMİ VE MEVCUT DURUMU

OpenAIRE

DEMİR, MUCİP

2016-01-01

Doğu Anadolu Bölgesinin Kars Erzurum bölümünde yer alan Kars İli ortalama irtifası 2000 metre civarında olan ve birçok yeri volkanik materyallerle örtülü Kars Platosu üzerinde bulunmaktadır. Mevcut topografik koşulların etkisiyle sert karasal iklimin görüldüğü ilde başta nüfus olmak üzere diğer beşeri faaliyetler bu coğrafik faktörlerin yoğun etkisiyle şekillenmektedir. İlde halen 300.000 civarında bulunan nüfus il dışına doğru meydana gelen göçlerle azalış eğilimi göstermektedir.373 ilkokul,...

K-Ar age of the Tertiary volcanic rocks in the Tohoku area, Japan

International Nuclear Information System (INIS)

Konda, Tadashi; Ueda, Yoshio.

1980-01-01

The absolute age of the Tertiary volcanic rocks in Tohoku area has been estimated by K-Ar method. The results are: (1) in case of the volcanic rocks of Monzen-Aikawa stage, 32.8 - 38.5 m.y.B.P., (2) in case of the volcanic rocks of Nozaki-Daijima stage, 22.0 - 25.1 m.y.B.P., (3) in case of the volcanic rocks of Nishikurosawa stage, 15.5 - 16.5 m.y.B.P., (4) in case of the volcanic rocks of Onnagawa stage, 12.6 - 14.8 m.y.B.P., (5) in case of the volcanic rocks of Funakawa stage, 9.6 - 11.3 m.y.B.P., and (6) in case of the volcanic rocks of Kitaura stage, 6.9 - 9.0 m.y.B.P. The samples used are such as biotite and whole rocks. The eruption periods in Tertiary volcanic activities presumed by K-Ar method are geologically significant. In the measurements made on the same system of samples under same conditions, there was difference in the K-Ar ages between the Monzen-Aikawa and the Nozaki-Daijima stages, and it was significantly noteworthy. It is indicated that the volcanic rock activities in the former stage had took place before those in the latter stage. In the Tohoku arc of northern Japan, the simultaneity in initial volcanic activities is not seen in the direction across the arc. (J.P.N.)

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

Science.gov (United States)

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

2013-09-15

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. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

U-Pb and K-Ar isotopic dating of Sinec (Rimavica) granites (Kohut zone of veporides)

International Nuclear Information System (INIS)

Bibikova, E.V.; Grachema, T.V.; Makarov, V.A.

1988-01-01

New results of radiometric dating of Sinec (Rimavica) granites by U-Pb and K-Ar method are presented. The K-Ar method (muscovite and biotite) gives the age of 94 m.y., which can be interpreted by tectonics. The U-Pb dating of zircons gave a concordant age of 350±5 m.y., which is a more reliable age than the one obtained from the same samples by Rb-Sr isochrone. The increased age of the Sinec (Rimavica) granites determined by the Sb-Sr method could be caused by the supply of radiogenic Sr from the surrounding older metamorphic rocks to the granites during retrograde metamorphism synchronous with granite autometasomatism. (author). 3 figs., 2 tabs., 15 refs

K-Ar and Rb-Sr dating results of the Malyshevsky leucogranite massif (eastern slope of the Middle Urals)

International Nuclear Information System (INIS)

Smirnov, V.N.; Ivanov, K.S.; Ronkin, Yu.L.; Levin, V.Ya.; Bushlyakov, I.N.; Lepikhina, O.P.; Popova, O.Yu.

2005-01-01

The age of leucogranites and minerals forming the Malyshevsky massif was identified by the methods of K-Ar- and Rb-Sr dating for refining the sequence of magmatic complexes formation on the eastern slope of the Middle Urals. The obtained isotope age values, i.e. 229-277 mln. years (K-Ar) and 277.1±1.1 mln. years (Rb-Sr), permit considering the age of 277 mln. years as the period of the leucogranites formation and of the associated molybdenum mineralization [ru

Neurosteroid modulation of neuronal excitability and synaptic transmission in the rat medial vestibular nuclei.

Science.gov (United States)

Grassi, Silvarosa; Frondaroli, Adele; Dieni, Cristina; Dutia, Mayank B; Pettorossi, Vito E

2007-07-01

In rat brainstem slices, we investigated the influence of the neurosteroids tetrahydrodeoxycorticosterone (THDOC) and allopregnanolone (ALLO) on the synaptically driven and spontaneous activity of vestibular neurons, by analysing their effects on the amplitude of the field potentials evoked in the medial vestibular nuclei (MVN) by vestibular afferent stimulation and on the spontaneous firing rate of MVN neurons. Furthermore, the interaction with gamma-aminobutyric acid (GABA) and glutamate receptors was analysed by using specific antagonists for GABA(A) (bicuculline), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/ kainate [2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo(f)quinoxaline-7-sulphonamide disodium salt (NBQX)], N-methyl-D-aspartate (NMDA) [D-(-)-2-amino-5-phosphonopentanoic acid (AP-5)] and group I metabotropic glutamate receptors (mGlu-I) [(R,S)-1-aminoindan-1,5-dicarboxylic acid (AIDA)] receptors. THDOC and ALLO evoked two opposite long-lasting effects, consisting of either a potentiation or a reduction of field potential and firing rate, which showed early and late components, occurring in conjunction or separately after neurosteroid application. The depressions depended on GABA(A) receptors, as they were abolished by bicuculline, while early potentiation involved glutamate AMPA/kainate receptors, as NBQX markedly reduced the incidence of early firing rate enhancement and, in the case of ALLO, even provoked depression. This suggests that THDOC and ALLO enhance the GABA(A) inhibitory influence on the MVN neurons and facilitate the AMPA/kainate facilitatory one. Conversely, a late potentiation effect, which was still induced after glutamate and GABA(A) receptor blockade, might involve a different mechanism. We conclude that the modulation of neuronal activity in the MVN by THDOC and ALLO, through their actions on GABA(A) and AMPA/kainate receptors, may have a physiological role in regulating the vestibular system function under normal

Revisions of K/Ar ages for the Hadar hominid site, Ethiopia

Energy Technology Data Exchange (ETDEWEB)

Walter, R.C.; Aronson, J.L. (Case Western Reserve Univ., Cleveland, OH (USA). Dept. of Geology)

1982-03-11

Conventional K/Ar age measurements are reported for two volcanic units from the hominid-bearing Hadar Formation. These ages represent revision of previously published ages for the BKT-2 tephra and the Kadada Moumou basalt. BKT-2 is revised from 2.65 to 2.9 Myr BP and the Kadada Moumou basalt is revised from 3.0 to 3.6 Myr BP.

Glutamate requires NMDA receptors to modulate alpha2 adrenoceptor in medulla oblongata cultured cells of newborn rats.

Science.gov (United States)

Marinho da Silva, Sergio; Carrettiero, Daniel C; Chadi, Débora R F

2014-04-03

α2 Adrenoceptors (α2-ARs) are important in regulating the central control of blood pressure in medulla oblongata. However, it is unclear how this receptor is modulated by different receptors, especially the glutamatergic. In the present study, we studied the influence of ionotropic glutamatergic receptors over the α2-ARs in cultured cells of the medulla oblongata of newborn rats. For this purpose, the protein level of the α2-ARs was assessed after administration to the cultured cells of glutamate (glu), the agonists NMDA and kainate (KA), the NMDA receptor antagonist MK801 and the KA receptor antagonist DNQX. Results indicate that the α2-AR protein levels were increased after the treatments with glu and NMDA, and the addition of MK801 to this treatment thwarted this increase. Notwithstanding the fact that KA did not alter the receptor protein level, the combined treatment of DNQX with glu prevented the α2-AR protein modulation. In conclusion, the present study suggests that ionotropic glutamatergic receptors could be related to the α2-AR protein regulation in the medulla oblongata. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Hayıt (Vitex agnus-castus), Çam ve Karışım Çiçek Balının Bazı Kalite Kriterleri Açısından Karşılaştırılması

OpenAIRE

UÇAK KOÇ, Aytül; KARACAOĞLU, Mete; DOĞAN, Mustafa

2017-01-01

Bu araştırma, Aydın yöresinde üretilen hayıt balının bazı kalite parametrelerinin belirlenerek, çam ve karışım çiçek balları ile karşılaştırılması amacıyla gerçekleştirilmiştir. Çalışmada, Aydın ili sınırları içinde üretilmiş ve yeni hasat edilmiş hayıt balı, çam balı ve yöre arıcılarının Orta Anadolu’da ürettiği karışım çiçek ballarının bazı kimyasal parametreleri belirlenmiştir. Üç bal grubunda her bir özelliğe ait veriler basit varyans analizi (ANOVA) ile değerlendirilmiştir. Tüm özellikle...

Isochron reassessment of K-Ar dating from the West Carpathian crystalline complex

International Nuclear Information System (INIS)

Burchart, J.; Cambel, B.; Kral, J.

1987-01-01

Published K-Ar ages from the West Carpathian crystalline complex show an extreme dispersion of values. Therefore agreement of model data with Harper's (1970) isochron models was confronted and verified. On the basis of this analysis only a few numbers -isochron data which have real importance from the point of view of geological conditions - can be presented: 1. 394±24 m.y. -amphiboles, Male Karpaty Mts.; 2. 265±18 m.y. - amphiboles, gemerides; 3. 302±40 m.y. - biotites, core mountains; 4. 94±18 m.y. - biotites, veporides. Only isochron K-Ar ages of amphiboles approximate the time of their recrystallization. Isochron ages of biotites belong to the category of cooling ages and they represent the period since transition through isotherm of ca. 270 degC. The results of muscovite and feldspar dating cannot be interpreted by Harper's models. A substantial part of analyzed material is represented by analyses of whole rocks which are inapplicable to geochronological purposes. (author). 15 figs., 4 tabs., 53 refs

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

2003-01-01

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...

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

2003-01-01

(S)-Glutamic acid (Glu), the major excitatory neurotransmitter in the central nervous system, operates through ionotropic as well as metabotropic receptors and is considered to be involved in certain neurological disorders and degenerative brain diseases that are currently without any satisfactory...

Problems in the K-Ar dating of Quaternary volcanic rocks younger than 1 Ma

International Nuclear Information System (INIS)

Takaoka, Nobuo

1989-01-01

The assumption that the 40 Ar/ 36 Ar ratio of Ar trapped in volcanic rocks at eruption is atmospheric often gives a large systematic error in the K-Ar dating of Quaternary volcanic rocks younger than 1 Ma. There are two possible sources of error, the existence of excess Ar and mass-fractionated, initial Ar. The major source of excess Ar is supposed to be magma. The 40 Ar/ 36 Ar ratio for magmatic Ar in the North-East Japan arc is tentatively estimated to be 340±10 from measurements of Ar in large phenocrysts separated from Quaternary volcanic rocks. Separation of phenocrysts is the most effective to decrease the systematic error caused by excess Ar. The mass-fractionation of initial Ar should give the 38 Ar/ 36 Ar ratio which was changed from the atmospheric ratio. This can be checked by determining the 38 Ar/ 36 Ar ratio in samples. Since the systematic error caused by the mass-fractionated, initial Ar increases greatly with the increasing atmospheric Ar correction, it is important to correct the result for the mass-fractionation. Correction formulae are given. The error sources other than those mentioned above are uncertainty in the blank correction and instabilities in the sensitivity of spectrometer and the Ar isotopic ratio measurement. In order to increase accuracy of the K-Ar age obtained, to check the systematic errors by measuring samples together with standard samples is of great importance in the K-Ar dating of very young volcanic rocks. (author)

Low-frequency stimulation in anterior nucleus of thalamus alleviates kainate-induced chronic epilepsy and modulates the hippocampal EEG rhythm.

Science.gov (United States)

Wang, Yi; Liang, Jiao; Xu, Cenglin; Wang, Ying; Kuang, Yifang; Xu, Zhenghao; Guo, Yi; Wang, Shuang; Gao, Feng; Chen, Zhong

2016-02-01

High-frequency stimulation (HFS) of the anterior nucleus of thalamus (ANT) is a new and alternative option for the treatment of intractable epilepsy. However, the responder rate is relatively low. The present study was designed to determine the effect of low-frequency stimulation (LFS) in ANT on chronic spontaneous recurrent seizures and related pathological pattern in intra-hippocampal kainate mouse model. We found that LFS (1 Hz, 100 μs, 300 μA), but not HFS (100 Hz, 100 μs, 30 μA), in bilateral ANT significantly decreased the frequency of spontaneous recurrent seizures, either non-convulsive focal seizures or tonic-clonic generalized seizures. The anti-epileptic effect persisted for one week after LFS cessation, which manifested as a long-term inhibition of the frequency of seizures with short (20-60 s) and intermediate duration (60-120 s). Meanwhile, LFS decreased the frequency of high-frequency oscillations (HFOs) and interictal spikes, two indicators of seizure severity, whereas HFS increased the HFO frequency. Furthermore, LFS decreased the power of the delta band and increased the power of the gamma band of hippocampal background EEG. In addition, LFS, but not HFS, improved the performance of chronic epileptic mice in objection-location task, novel objection recognition and freezing test. These results provide the first evidence that LFS in ANT alleviates kainate-induced chronic epilepsy and cognitive impairment, which may be related to the modulation of the hippocampal EEG rhythm. This may be of great therapeutic significance for clinical treatment of epilepsy with deep brain stimulation. Copyright © 2015 Elsevier Inc. All rights reserved.

K/Ar age dating of Oshnaviyeh plutonic complex

International Nuclear Information System (INIS)

Ghalamghash, J.; Vosoughi Abedini, M.; Bellon, H.; Emami, M.H.; Pourmafi, M.; Rashid, H.

2003-01-01

Oshnaviyeh plutonic complex, the western member of Urumiyeh-Golpayehgan intrusive plutons is located in northern part of Sanandaj-Sirjan zon. Oshnaviyeh plutonic complex, exposing in an area of about 700 km 2 , comprises 10 plutons that can be divided into three suites, i.e.,diorite,granite,and alkali syenite-alkali granite. Dioritic bodies are the oldest intrusive rocks of the region, which on the basis of the field study, their relative age of emplacement is estimated to be post-Jurassic and pre-miocene. However, with respect to the age of other similar intrusive bodies in Naghadeh area, they are most likely of post early cretaceous-pre miocene age. Hybrid intrusive rocks, occurring at the contact of dioritic and granitic rocks may suggest a simultaneous emplacement of both magmas. Syntetic pluton from alkali syenite-alkali granite has intruded dioritic and granitic rocks, in contrast, flourine bearing alkali granite pluton from this suite shows no contact with other igneous rocks in the area. K-Ar age determinations obtained on amphibole specimens from diorite suite are 91.9±2.3, 94.1±2.3 and 100±2.4 Ma, and on biotite specimens from granite suite are 100±1.5 to 98.9±1.5 Ma. Chronology study using same method on arfvedsonite specimens from syenite pluton shows 78.9±3.1, 79.6±1.9 and 81.7±2.0 Ma and on K-fled par samples of flourine bearing alkali granite pluton from the alkali syenite-alkali granite suite presents 76±3.4 and 77.1±1.8. Therefore, based on field evidence and K/Ar age dating, Oshnaviyeh plutonic complex presumably formed during two episodes: granite and diorite suites formed simultaneously at about 100 Ma, then plutons of alkali syenite-alkali granite suite emplaced at about 80 Ma

Transcriptome analyzis of germinatiing maize kernels exposed to smoke-water and active compound KAR1

Czech Academy of Sciences Publication Activity Database

Soós, V.; Sebestyén, E.; Juhász, A.; Light, M. E.; Kohout, Ladislav; Szalai, G.; Tandori, J.; van Staden, J.; Balázs, E.

2010-01-01

Roč. 10, č. 236 (2010), s. 1-15 ISSN 1471-2229 Institutional research plan: CEZ:AV0Z40550506 Keywords : smoke compound * transcriptome * KAR1 * butenolide Subject RIV: CC - Organic Chemistry Impact factor: 4.085, year: 2010

40Ar/39Ar and K-Ar dating of altered glassy volcanic rocks: the Dabi Volcanics, P.N.G

International Nuclear Information System (INIS)

Walker, D.A.; McDougall, I.

1982-01-01

K-Ar and 40 Ar/ 39 Ar ages have been determined for altered submarine tholeiitic and boninite (high-Mg andesite) lavas from the Dabi Volcanics, Cape Vogel Peninsula, Papua New Guinea. 40 Ar/ 39 Ar whole rock total fusion and plateau ages identify a Late Paleocene age for the tholeiitic lavas (58.9 +- 1.1 Ma), and also for the boninitic lavas (58.8 +- 0.8 Ma). Apparent K-Ar ages for the same samples range from 27.2 +- 0.7 to 63.9 +- 4.5 Ma, and young K-Ar ages for glassy boninites are probably due to variable radiogenic 40 Ar( 40 Ar*) loss. These new ages effectively reconcile previously ambiguous age data for the Dabi Volcanics, and indicate contemporaneous tholeiitic and boninitic volcanism occurring in southeast PNG during the Late Paleocene. Smectites, developed as alteration products after glass in oceanic lavas commonly do not retain 39 Ar during or subsequent to irradiation, but in some cases may contain 40 Ar*. The results are discussed. (author)

Cell-specific cre recombinase expression allows selective ablation of glutamate receptors from mouse horizontal cells.

Directory of Open Access Journals (Sweden)

Sebastian Ströh

Full Text Available In the mouse retina, horizontal cells form an electrically coupled network and provide feedback signals to photoreceptors and feedforward signals to bipolar cells. Thereby, horizontal cells contribute to gain control at the first visual synapse and to the antagonistic organization of bipolar and ganglion cell receptive fields. However, the nature of horizontal cell output remains a matter of debate, just as the exact contribution of horizontal cells to center-surround antagonism. To facilitate studying horizontal cell function, we developed a knockin mouse line which allows ablating genes exclusively in horizontal cells. This knockin line expresses a Cre recombinase under the promoter of connexin57 (Cx57, a gap junction protein only expressed in horizontal cells. Consistently, in Cx57+/Cre mice, Cre recombinase is expressed in almost all horizontal cells (>99% and no other retinal neurons. To test Cre activity, we crossbred Cx57+/Cre mice with a mouse line in which exon 11 of the coding sequence for the ionotropic glutamate receptor subunit GluA4 was flanked by two loxP sites (GluA4fl/fl. In GluA4fl/fl:Cx57+/Cre mice, GluA4 immunoreactivity was significantly reduced (∼ 50% in the outer retina where horizontal cells receive photoreceptor inputs, confirming the functionality of the Cre/loxP system. Whole-cell patch-clamp recordings from isolated horizontal cell somata showed a reduction of glutamate-induced inward currents by ∼ 75%, suggesting that the GluA4 subunit plays a major role in mediating photoreceptor inputs. The persistent current in GluA4-deficient cells is mostly driven by AMPA and to a very small extent by kainate receptors as revealed by application of the AMPA receptor antagonist GYKI52466 and concanavalin A, a potentiator of kainate receptor-mediated currents. In summary, the Cx57+/Cre mouse line provides a versatile tool for studying horizontal cell function. GluA4fl/fl:Cx57+/Cre mice, in which horizontal cells receive less

Cell-Specific Cre Recombinase Expression Allows Selective Ablation of Glutamate Receptors from Mouse Horizontal Cells

Science.gov (United States)

Janssen-Bienhold, Ulrike; Schultz, Konrad; Cimiotti, Kerstin; Weiler, Reto; Willecke, Klaus; Dedek, Karin

2013-01-01

In the mouse retina, horizontal cells form an electrically coupled network and provide feedback signals to photoreceptors and feedforward signals to bipolar cells. Thereby, horizontal cells contribute to gain control at the first visual synapse and to the antagonistic organization of bipolar and ganglion cell receptive fields. However, the nature of horizontal cell output remains a matter of debate, just as the exact contribution of horizontal cells to center-surround antagonism. To facilitate studying horizontal cell function, we developed a knockin mouse line which allows ablating genes exclusively in horizontal cells. This knockin line expresses a Cre recombinase under the promoter of connexin57 (Cx57), a gap junction protein only expressed in horizontal cells. Consistently, in Cx57+/Cre mice, Cre recombinase is expressed in almost all horizontal cells (>99%) and no other retinal neurons. To test Cre activity, we crossbred Cx57+/Cre mice with a mouse line in which exon 11 of the coding sequence for the ionotropic glutamate receptor subunit GluA4 was flanked by two loxP sites (GluA4fl/fl). In GluA4fl/fl:Cx57+/Cre mice, GluA4 immunoreactivity was significantly reduced (∼50%) in the outer retina where horizontal cells receive photoreceptor inputs, confirming the functionality of the Cre/loxP system. Whole-cell patch-clamp recordings from isolated horizontal cell somata showed a reduction of glutamate-induced inward currents by ∼75%, suggesting that the GluA4 subunit plays a major role in mediating photoreceptor inputs. The persistent current in GluA4-deficient cells is mostly driven by AMPA and to a very small extent by kainate receptors as revealed by application of the AMPA receptor antagonist GYKI52466 and concanavalin A, a potentiator of kainate receptor-mediated currents. In summary, the Cx57+/Cre mouse line provides a versatile tool for studying horizontal cell function. GluA4fl/fl:Cx57+/Cre mice, in which horizontal cells receive less excitatory input

Structural, K-Ar and 40Ar-39Ar age studies of adularia K-feldspars from the Lizard Complex, England

International Nuclear Information System (INIS)

Halliday, A.N.; Mitchell, J.G.

1976-01-01

Conventional K-Ar analyses of fifteen adularia feldspars from the Lizard Complex yield ages between 181+-2 Ma and 220+-3 Ma (with one exception from Holseer Cove yielding an age of 156+-3 Ma). The feldspars are dominantly monoclinic but most contain a minor but constant proportion of triclinic material with variable triclinicity. An inverse correlation exists between triclinicity and K-Ar age interpreted as representing argon loss related to the structural state. Extrapolation of the data to zero triclinicity indicates a true age of 210-220 Ma. 40 Ar- 39 Ar stepwise degassing analyses yield plateau ages related to the K-Ar ages and not the crystallization age. The results can be explained in terms of postcrystallization Al-Si ordering resulting in argon loss from lattice sites which under normal diffusion conditions requires a range of activation energies. The Holseer Cove sample is monoclinic and an 40 Ar- 39 Ar stepheating analysis suggests a later crystallization at 160-170 Ma. Neither primary crystallization nor spontaneous ordering through time explain the origin of the triclinic adularia. It is suggested that ordering has been induced by the passage of low-temperature alkaline solutions at a subsequent point in geological time. Argon loss by ordering could explain the low ages found using both K-Ar and 40 Ar- 39 Ar stepheating methods when applied to feldspars in general. The 210-220 Ma, and 160-170 Ma hydrothermal events affected much of southwest England and are probably related to major geotectonic movements in western Europe. (Auth.)

The use of Rb-Sr and K-Ar dating methods as a stratigraphic tool applied to sedimentary rocks and minerals

International Nuclear Information System (INIS)

Bonhomme, M.G.

1982-01-01

Rb-Sr and K-Ar methods can be used for direct numerical chronostratigraphy of sediments using the clay silicates they contain. The interpretation of the ages calculated depends on the satisfaction of the following requirements: (1) The series studied must include diagenetic clay sediments. Coarsely-detrital or slightly-metamorphic formations must be excluded. Studies in progress concerning decarbonatation may lead to the application of direct dating of sediments being extended to carbonate sediments. (2) Careful mineralogical study of the clay minerals must prove early diagenetic recrystallization or new formation. This part of the study must precede any isotopic work. (3) The isotopic study must involve the use of both Rb-Sr and K-Ar methods. The extreme sensibility of the K-Ar isotopic system to late diagenesis helps to choose between early or late diagenesis: a younger K-Ar age may generally be regarded as that of the late diagenesis, whereas the Rb-Sr age may be that of the early diagenesis. (4) The initial 87 Sr/ 86 Sr isotopic ratio is not always a reliable criterion, owing to the effects of the dilution of the radiogenic 87 Sr by the great amounts of primary Sr contained in carbonates. (5) The regularly-decreasing succession of isotopic ages must follow the stratigraphic succession. When this condition is satisfied, there is a high probability that the calculated ages are indeed those of the deposition dates. (Auth.)

Caffeine and an adenosine A(2A) receptor antagonist prevent memory impairment and synaptotoxicity in adult rats triggered by a convulsive episode in early life.

Science.gov (United States)

Cognato, Giana P; Agostinho, Paula M; Hockemeyer, Jörg; Müller, Christa E; Souza, Diogo O; Cunha, Rodrigo A

2010-01-01

Seizures early in life cause long-term behavioral modifications, namely long-term memory deficits in experimental animals. Since caffeine and adenosine A(2A) receptor (A(2A)R) antagonists prevent memory deficits in adult animals, we now investigated if they also prevented the long-term memory deficits caused by a convulsive period early in life. Administration of kainate (KA, 2 mg/kg) to 7-days-old (P7) rats caused a single period of self-extinguishable convulsions which lead to a poorer memory performance in the Y-maze only when rats were older than 90 days, without modification of locomotion or anxiety-like behavior in the elevated-plus maze. In accordance with the relationship between synaptotoxicity and memory dysfunction, the hippocampus of these adult rats treated with kainate at P7 displayed a lower density of synaptic proteins such as SNAP-25 and syntaxin (but not synaptophysin), as well as vesicular glutamate transporters type 1 (but not vesicular GABA transporters), with no changes in PSD-95, NMDA receptor subunits (NR1, NR2A, NR2B) or alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate receptor subunits (GluR1, GluR2) compared with controls. Caffeine (1 g/L) or the A(2A)R antagonist, KW6002 (3 mg/kg) applied in the drinking water from P21 onwards, prevented these memory deficits in P90 rats treated with KA at P7, as well as the accompanying synaptotoxicity. These results show that a single convulsive episode in early life causes a delayed memory deficit in adulthood accompanied by a glutamatergic synaptotoxicity that was prevented by caffeine or adenosine A(2A)R antagonists.

K-Ar age of bronzite-andesite from Choshi, Chiba Prefecture, Japan

International Nuclear Information System (INIS)

Tatsumi, Yoshiyuki; Ishizaka, Kyoichi

1979-01-01

The authors have forwarded the study on the activity period of Setouchi volcanic rocks and the research on Sanukitoid which characterizes it. It was already mentioned that the activity period of Setouchi volcanic rocks is only the middle period of Mid-cainozoic era, and that Setouchi volcanic rocks can be treated as one rock region. In this paper, the K-Ar age of bronzite-andesite in Choshi, Chiba Prefecture, is reported, which the authors think as the eastern end of Setouchi volcanic rock region. The outline of the geological features in the vicinity of Choshi is explained. The rock samples for the measurement were collected in May, 1978, in the reconstruction site of the fishing port. The rock samples were fresh, and the effects of degeneration, wathering and others were not observed. The K-Ar age of these bronzite-andesite was determined by Teledyne Isotopes Co. in commission. The determination of K and Ar was carried out on all rock samples twice respectively. The isotopic age of the bronzite-andesite in Choshi was 11.8 +- 0.6 m.y., and it was produced by the volcanic activity in the middle period of Mid-cainozoic era, same as the volcanic rocks of Setouchi. It is considered that the eastern end of Setouchi volcanic rock region is Choshi according to the results of chemical properties and isotopic age. (Kako, I.)

Regional elevation history from Ribeira belt based in K-Ar dating

International Nuclear Information System (INIS)

Zimbres, E.; Kawashita, K.; Motoki, A.

1990-01-01

The Ribeira orogenic belt, Brazilian cycle in metamorphism, has biotite K-Ar ages becoming young from the border (600 Ma) to the central axis (450 Ma), these ages are not related to rock type nor intrusive phase, but to occurrence area. The fact suggests that this wide-ranging age distribution is not due to later thermal events, e.g. post tectonic intrusion, but to slow cooling on the axis zone. The climax metamorphic condition have been estimated as 675 sup(0)C and 4 to 5 kb (18 km's depth). This temperature is much higher than that of biotite argon retention (310 sup(0)C). These data indicate that the biotite K-Ar clock have been set fairly after the climax during regional uplift at a depth much shallower that the metamorphism. Biotite clock setting depth (310 sup(0)C) is calculated as 7.5 km, using geothermal gradient of 30 sup(0)C/km. In this connection, uplift of 11.5 km from 600 Ma to 450 Ma (rate of 77 m/m.y.) is estimated. Fission track datings in apatite (110 Ma), combined with a present geothermal gradient (25 sup(0)C/km) indicate uplift of 3.5 km from 450 Ma to 110 Ma (16 m/m.y.) and 4 km from 110 Ma to the present (35 m/m.y.). (author)

Changes in flip/flop splicing of astroglial AMPA receptors in human temporal lobe epilepsy.

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Seifert, Gerald; Schröder, Wolfgang; Hinterkeuser, Stefan; Schumacher, Thekla; Schramm, Johannes; Steinhäuser, Christian

2002-01-01

Recent data suggested a role for glial cells in epilepsy. This study sought to identify and functionally characterize AMPA receptors expressed by astrocytes in human hippocampal tissue resected from patients with intractable temporal lobe epilepsy. Patch-clamp and fast application methods were combined to investigate astrocytes in situ and after fresh isolation from the stratum radiatum of the hippocampal CA1 subfield. Relying on presurgical and histopathologic analysis, we divided human specimens into two groups, Ammon's horn sclerosis (AHS) and lesion-associated epilepsy. Fast application of glutamate and kainate evoked receptor currents in all cells studied. Reversal-potential analysis revealed an intermediate Ca2+ permeability of the receptor channels that did not vary between the two groups of patients. However, preapplication of the AMPA receptor-specific modulator, cyclothiazide, disclosed differences in flip-flop splicing. This treatment considerably enhanced the receptor conductance, with potentiation being significantly stronger in cells from AHS specimens compared with lesion-associated cells, suggesting upregulation of AMPA receptor flip splice variants in astrocytes of the sclerotic tissue. Compelling evidence has been accumulated showing direct and rapid signaling between neurons and glial cells. Our data suggest that in AHS patients, neuronally released glutamate will lead to an enhanced and prolonged depolarization of astrocytes, which might be involved in seizure generation and spread in this particular condition of human temporal lobe epilepsy.

Dating of retrograde metamorphism in Western Carpathians by K-Ar analysis of muscovites

International Nuclear Information System (INIS)

Cambel, B.; Korikovskij, S.P.; Krasivskaya, I.S.; Arakelyants, M.M.

1986-01-01

Using the K-Ar isotope dating method of muscovites it was found that many retrogradely metamorphosed rocks are the results of Variscan retrograde metamorphism and are not pre-Cambrian or Alpine metamorphites (diaphthorites). Samples for dating were taken from the Western Carpathian crystalline formation. The content of radiogenic argon was determined by mass spectrometry using the method of isotope dilution. (M.D.)

Disrupted Co-activation of Interneurons and Hippocampal Network after Focal Kainate Lesion

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Lim-Anna Sieu

2017-11-01

Full Text Available GABAergic interneurons are known to control activity balance in physiological conditions and to coordinate hippocampal networks during cognitive tasks. In temporal lobe epilepsy interneuron loss and consecutive network imbalance could favor pathological hypersynchronous epileptic discharges. We tested this hypothesis in mice by in vivo unilateral epileptogenic hippocampal kainate lesion followed by in vitro recording of extracellular potentials and patch-clamp from GFP-expressing interneurons in CA3, in an optimized recording chamber. Slices from lesioned mice displayed, in addition to control synchronous events, larger epileptiform discharges. Despite some ipsi/contralateral and layer variation, interneuron density tended to decrease, average soma size to increase. Their membrane resistance decreased, capacitance increased and contralateral interneuron required higher current intensity to fire action potentials. Examination of synchronous discharges of control and larger amplitudes, revealed that interneurons were biased to fire predominantly with the largest population discharges. Altogether, these observations suggest that the overall effect of reactive cell loss, hypertrophy and reduced contralateral excitability corresponds to interneuron activity tuning to fire with larger population discharges. Such cellular and network mechanisms may contribute to a runaway path toward epilepsy.

Stress state and movement potential of the Kar-e-Bas fault zone, Fars, Iran

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Sarkarinejad, Khalil; Zafarmand, Bahareh

2017-08-01

The Kar-e-Bas or Mengharak basement-inverted fault is comprised of six segments in the Zagros foreland folded belt of Iran. In the Fars region, this fault zone associated with the Kazerun, Sabz-Pushan and Sarvestan faults serves as a lateral transfer zone that accommodates the change in shortening direction from the western central to the eastern Zagros. This study evaluates the recent tectonic stress regime of the Kar-e-Bas fault zone based on inversion of earthquake focal mechanism data, and quantifies the fault movement potential of this zone based on the relationship between fault geometric characteristics and recent tectonic stress regimes. The trend and plunge of σ 1 and σ 3 are S25°W/04°-N31°E/05° and S65°E/04°-N60°W/10°, respectively, with a stress ratio of Φ = 0.83. These results are consistent with the collision direction of the Afro-Arabian continent and the Iranian microcontinent. The near horizontal plunge of maximum and minimum principle stresses and the value of stress ratio Φ indicate that the state of stress is nearly strike-slip dominated with little relative difference between the value of two principal stresses, σ 1 and σ 2. The obliquity of the maximum compressional stress into the fault trend reveals a typical stress partitioning of thrust and strike-slip motion in the Kar-e-Bas fault zone. Analysis of the movement potential of this fault zone shows that its northern segment has a higher potential of fault activity (0.99). The negligible difference between the fault-plane dips of the segments indicates that their strike is a controlling factor in the changes in movement potential.

K-Ar age estimate for the KBS Tuff, East Turkana, Kenya

International Nuclear Information System (INIS)

McDougall, I.; Maier, R.; Sutherland-Hawkes, P.; Gleadow, A.J.W.

1980-01-01

Stone tools and numerous vertebrate fossils including hominids, have been found in close stratigraphic proximity to the KBS Tuff, whose age has been the subject of much debate. Concordant K-Ar ages, averaging 1.89 +- 0.01 Myr, are reported on anorthoclase phenocrysts from 13 pumice clasts collected from within the KBS Tuff or its correlatives. It is believed that this age is the best estimate currently available for the time of formation of this important marker horizon within the East Turkana Basin. (author)

New K-Ar ages of the Martel Inlet Group, king George Island, South Shetland Islands, Antarctica

International Nuclear Information System (INIS)

Soliani Junior, E.; Kawashita, K.

1986-01-01

This paper presents twelve new K-Ar whole rocks ages of the Martel Inlet Group that crops out in the Keller Peninsula region, in the Admiralty Bay, King George Island. That lithostratigraphic unit has been considered the oldest one know in the area and it is the result of several volcanic and volcanoclastic episodes occurred probably during the Upper Jurassic. As the group is mainly represented by lithologies that show low-grade metamorphic changes and metasomatic evidences, as well as other alteration processes, it has been difficult to obtain that expected age, specially using the K-Ar method. A significant number of time values concentrated between 40 and 50 Ma, independently of the unit's position in the strategraphic context, could be suggesting an important tectono-thermal event that affected the area setting the isotopic results by re-heating and/or by chemical processes. (author) [pt

/sup 40/Ar//sup 39/Ar and K-Ar dating of altered glassy volcanic rocks: the Dabi Volcanics, P. N. G

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Walker, D.A. (Australian National Univ., Canberra. Dept. of Geology); McDougall, I. (Australian National Univ., Canberra. Research School of Earth Sciences)

1982-11-01

K-Ar and /sup 40/Ar//sup 39/Ar ages have been determined for altered submarine tholeiitic and boninite (high-Mg andesite) lavas from the Dabi Volcanics, Cape Vogel Peninsula, Papua New Guinea. /sup 40/Ar//sup 39/Ar whole rock total fusion and plateau ages identify a Late Paleocene age for the tholeiitic lavas (58.9 +- 1.1 Ma), and also for the boninitic lavas (58.8 +- 0.8 Ma). Apparent K-Ar ages for the same samples range from 27.2 +- 0.7 to 63.9 +- 4.5 Ma, and young K-Ar ages for glassy boninites are probably due to variable radiogenic /sup 40/Ar(/sup 40/Ar*) loss. These new ages effectively reconcile previously ambiguous age data for the Dabi Volcanics, and indicate contemporaneous tholeiitic and boninitic volcanism occurring in southeast PNG during the Late Paleocene. Smectites, developed as alteration products after glass in oceanic lavas commonly do not retain /sup 39/Ar during or subsequent to irradiation, but in some cases may contain /sup 40/Ar*. The results are discussed.

Archaeogeophysical Studies in the Ruins of Kars-Ani (Turkey) in the 2009 Excavation Season

Science.gov (United States)

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

2010-05-01

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

K-Ar ages of some metamorphic rocks of Oban massif and their implications for the tectonothermal evolution of Southeastern Nigeria

International Nuclear Information System (INIS)

Ekwueme, B.N.; Itaya, Tetsumaru; Yabe, Hisatomo

2000-01-01

The following K-Ar ages have been obtained on mineral separates from some metamorphic rocks in the Oban massif: amphibolites (592-930 Ma), banded gneisses (492-538 Ma), granodioritic gneiss (502 Ma), schists (514-519 Ma) and charnockite (481 Ma). Comparison of these ages with previous dates obtained by the Rb-Sr whole rock method and the Pb-Pb evaporation technique on single zircon throws light on the cooling history and orogenic events in the Oban massif. The banded gneiss in the Oban massif yields a zircon age of 1932±5 Ma, indicating that it was emplaced during the early Proterozoic (Eburnean orogeny). The K-Ar age of 492-538 Ma suggests that these rocks were metamorphosed during the Pan-African orogeny. This age is similar to the Rb-Sr isochron age of 510±10 Ma earlier suggested to be the age of migmatization in the Oban massif. The amphibolite yielded Rb-Sr isochron ages of 784±31 Ma and 1313±37 Ma. The age of 1313±37 Ma fits into the Kibaran event. The K-Ar hornblende age of 930±37 Ma on the same amphibolite strongly suggests that this amphibolite belongs to an event older than Pan-African (600±150 Ma) and has not been reset perfectly by the Pan-African event. The migmatitic schists in the Oban massif yielded a Rb-Sr isochron age of 527±16 Ma which has been interpreted as the age of its migmatization. One sample of this schist, however, gave a model age of 676±24 Ma. The K-Ar ages for the Oban massif schists (514-519 Ma) are close to the Rb-Sr isochron age of ca. 527 Ma and confirm that a metamorphic event occurred in the area at this time. This was followed by final cooling at 515±10 Ma. Charnockite in the Oban area has yielded a zircon age of 584±20 Ma, which is Pan-African. The age possibly dates the time of formation of the charnockites. The K-Ar age (481 Ma) obtained in this study is approximately 100 Ma younger than the zircon age and possibly dates the subsequent cooling of the charnockite through hornblende blocking temperature. (author)

Rb/Sr and K/Ar determinations of Monguba and Pendanga rocks,Ceara

International Nuclear Information System (INIS)

Torquato, J.R.F.; Pedreira, L.H.; Kawashita, K.; Barbosa, H.S.P.

1986-01-01

In this paper we describe the petrography and geochronology of rocks from two quarries near the City of Fortaleza/Ceara. One, the Pedreira Monguba, is formed, basically, by rocks of the granitic to monzogranitic type. Its isochrone age is 672 +- 46 m.y. with an initial ratio of 0.7036 +- 0.0005. Datinfs of biotite by the K/Ar method gave values of 522+- 19m.y. for the consolidation of the region. For comparison with the other components of the same morphologic unit, the Massif of Maranguape, we designed a reference isochrone with all values available from the literature (for granite, gneisses and migmatites) and obtained a straight line parallel to the first, but with a higher initial ratio of 0.709, demonstrating the strong influence of the Brasiliano Cycle in this region. The other quarry, Pedreira Pendanga, is composed of gneisses and migmatized gneisses and forms an open chemical system. It was possible, however, to verify that its age is equal or greater than 2150+- 71 m.y. and that all of its rocks have suffered strong metamorphism during the Brasiliano Cycle as in shown by the K/Ar ages of biotites of 541+- 3 m.y. A discussion of sampling problems is given and the influence of a granitic intrusion on the chemical opening of the system is evidenced. (author) [pt

Biyodizel ve Karışımlarının Kullanıldığı bir Dizel Motorda Performans ve Emisyon Analizi

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Ahmet Necati ÖZSEZEN

2009-02-01

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.

Radiation-related retrograde hydrogen isotope and K-Ar exchange in clay minerals

International Nuclear Information System (INIS)

Halter, C.; Pagel, M.; Sheppard, S.M.F.; Weber, F.; Clauer, N.

1987-01-01

Hydrogen and oxygen isotope studies have been widely applied to characterize the origin of fluids during ore-foaming processes. The primary isotope record, however, may be disturbed by retrograde exchange reactions, thus complicating the interpretation of the data. The susceptibility of minerals to retrograde isotope and chemical exchange is variable, reflecting differences in the mechanism and rate of isotope exchange. Results are presented on deuterium depletion, K/Ar ages and H 2 O + content of illites associated with uranium mineralization from the Athabasca basin (Canada). (author)

Modulation of GABA receptors expressed in Xenopus oocytes by 13-L-hydroxylinoleic acid and food additives.

Science.gov (United States)

Aoshima, H; Tenpaku, Y

1997-12-01

To study the effects of 13-L-hydroxylinoleic acid (LOH) and food additives on gamma-aminobutyric acid (GABA) receptors, ionotropic GABA receptors were expressed in Xenopus oocytes by injecting mRNAs prepared from rat whole brain. LOH, which was prepared by reduction of 13-L-hydroperoxylinoleic acid (LOOH), inhibited the response of GABA receptors in the presence of high concentrations of GABA. LOH also inhibited nicotinic acetylcholine, glycine, and kainate receptors, while it had little effect on NMDA receptors expressed in Xenopus oocytes. However, LOH potentiated the response of GABA receptors as well as LOOH in the presence of low concentrations of GABA, possibly increasing the affinity of GABA for the receptors, while linoleic acid did not. Since some modification of the compounds seemed to change their effects on GABA receptors, the responses of GABA receptors elicited by 10 microM GABA were measured in the presence of compounds with various kinds of functional groups or the structural isomers of pentanol. Potentiation of GABA receptors depended strongly on the species of functional groups and also depended on the structure of the isomers. Then effects of various kinds of food additives on GABA receptors were also examined; perfumes such as alcohols or esters potentiated the responses strongly, while hexylamine, nicotinamide, or caffeine inhibited the responses, mainly in a competitive manner, and vanillin inhibited the responses noncompetitively. These results suggest the possibility that production of LOOH and LOH, or intake of much of some food additives, modulates the neural transmission in the brain, especially through ionotropic GABA receptors and changes the frame of the human mind, as alcohol or tobacco does.

Comparison of germination responses of Anigozanthos flavidus (Haemodoraceae), Gyrostemon racemiger and Gyrostemon ramulosus (Gyrostemonaceae) to smoke-water and the smoke-derived compounds karrikinolide (KAR1) and glyceronitrile.

Science.gov (United States)

Downes, Katherine S; Light, Marnie E; Pošta, Martin; Kohout, Ladislav; van Staden, Johannes

2013-03-01

A major germination-promoting chemical in smoke-water is 3-methyl-2H-furo[2,3-c]pyran-2-one (karrikinolide, KAR(1)). However, not all species that germinate in response to smoke-water are responsive to KAR(1), such as Tersonia cyathiflora (Gyrostemonaceae). In this study, a test was made of whether two Gyrostemon species (Gyrostemonaceae) that have previously been shown to respond to smoke-water, respond to KAR(1). If not, then the smoke-derived chemical that stimulates germination of these species is currently unknown. Recently, glyceronitrile was isolated from smoke-water and promoted the germination of certain Anigozanthos species (Haemodoraceae). Whether this chemical promotes Gyrostemon racemiger germination is also examined. Furthermore, an investigation was carried out into whether these species germinate in response to smoke-water derived from burning cellulose alone. Gyrostemon racemiger and G. ramulosus seeds were buried after collection and retrieved in autumn the following year when dormancy was alleviated and seeds had become responsive to smoke-water. Anigozanthos flavidus seeds were after-ripened at 35 °C to alleviate dormancy. Gyrostemon and Anigozanthos seeds were then tested with 'Seed Starter' smoke-water, KAR(1), glyceronitrile and cellulose-derived smoke-water. Although Gyrostemon racemiger, G. ramulosus and A. flavidus were all stimulated to germinate by 'Seed Starter' smoke-water, none of these species responded to KAR(1). Gyrostemon racemiger germination was not promoted by glyceronitrile. This is in contrast to A. flavidus, where glyceronitrile, at concentrations of 1-500 µm, promoted germination, although seedling growth was inhibited at ≥400 µm. Maximum A. flavidus germination occurred at glyceronitrile concentrations of 25-300 µm. Some Gyrostemon germination was promoted by cellulose-derived smoke-water. KAR(1) and glyceronitrile, chemicals in smoke-water that are known to stimulate germination in other species, did not promote the

XIX-wieczne badania ludoznawcze na obszarze Łotwy w świetle korespondencji Stefanii Ulanowskiej do Jana Karłowicza

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Dorota Krystyna Rembiszewska

2014-12-01

Full Text Available 19th century ethnological research on the territory of Latvia in view of correspondence of Stefania Ulanowska to Jan Karłowicz Letters, which are the basis of the article, are a part of Jan Karlowicz’s (a 19th century ethnographer, lexicographer heritage kept in the historical archive in Vilnius. They are evidence of correspondence between Jan Karłowicz and Stefania Ulanowska, the author of Łotysze Inflant Polskich, a w szczególności z gminy wielońskiej powiatu rzeżyckiego since October 1889 until January 1890 during Ulanowska’s stay in the village of Wielony, now Viļāni (Latvia. The correspondence is a source of rich material including information about Ulanowska that has not been published so far as well as data of Latgale’s and its inhabitants’ past. Moreover, it is a unique evidence of scientific peregrinations. These letters have their contribution in ethnographic research on the former territory of Poland as they show circumstances and methods of exploration used in the 19th century. At the same time they can be an interesting gloss for research over Latgalian dialects as far as names of material culture are concerned.   XIX-wieczne badania ludoznawcze na obszarze Łotwy w świetle korespondencji Stefanii Ulanowskiej do Jana Karłowicza Listy, stanowiące podstawę omówienia, pochodzą ze spuścizny Jana Karłowicza (XIX-wiecznego etnografa, leksykografa przechowywanej w litewskim archiwum historycznym w Wilnie. Są one świadectwem korespondencji prowadzonej przez Jana Karłowicza i Stefanię Ulanowską – m.in. autorkę Łotyszy Inflant Polskich, a w szczególności z gminy wielońskiej powiatu rzeżyckiego, od października 1889 r. do stycznia 1890 r. podczas pobytu badaczki w miejscowości Wielony, obecnie Viļāni (Łotwa. Korespondencja ta dostarcza dość bogatego materiału, zawierającego informacje dotychczas niedrukowane na temat Ulanowskiej. Przynosi także sporo danych z przeszłości Łatgalii i jej

K-Ar ages of alkaline rock from Southern Brazil and Eastern Paraguay: compilation and adaptation of new decay constants

International Nuclear Information System (INIS)

Sonoki, I.K.; Garda, G.M.

1990-01-01

A compilation of 295 geochronological data of 52 alkaline occurrences from Southern Brazil and Eastern Paraguay is presented. These data, mostly available in previous publications, were recalculated, using the new constants recommended by STEIGER and JAEGER (1977) for the K-Ar method. The estimated analytical error of the age determined using experimental parameters is also indicated (COX and DALRYMPLE, 1967). This paper aims, specifically, at making ages published prior to 1977 compatible with recent data, allowing, for example, comparisons between ages obtained from a single alkaline massif or from neighbouring massifs. By calculating K-Ar ages using the constants recommended by STEIGER and JAEGER (op. cit.), there occurs an increase of 2.1 to 2.4% in the value of the age calculated with the previous constants. (author) [pt

K-Ar geology, geochemistry and geochronology from the Maria River region dikes, Parana State southeastern part, Brazil

International Nuclear Information System (INIS)

Silva Junior, Renato Oliveira da; Dall'Agnol, Roberto; Oliveira, Elson Paiva de

1996-01-01

The paper synthesizes the geological, petrographical, geochemical and geochronological data from the Maria River region dikes, situated at the southeastern part of the Para State, Brazil. It identifies five groups of dikes and determines the age of these dikes, through the Potassium-Argon (K-Ar) methodology

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

Science.gov (United States)

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

2014-01-01

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.

A compilation of 40Ar-39 and K-Ar ages: report 25

International Nuclear Information System (INIS)

Hunt, P.A.; Roddick, J.C.

1996-01-01

Twenty-three 40 Ar- 39 Ar age determinations (including two potassium-argon analyses) carried out by the Geological Survey of Canada are reported. Each age determination is accompanied by a description of the rock and mineral concentrate used; brief interpretative comments regarding the geological significance of each age are also provided where possible. The experimental procedures employed are described in outline. An index of all Geological Survey of Canada K-Ar age determinations published in this format has been prepared using NTS quadrangles as the primary reference. (author). 6 refs., 2 tabs., 1 fig

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

Science.gov (United States)

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

2013-02-01

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.

Rb-Sr and K-Ar isotopic evidence for neoproterozoic (Pan-African) granulite metamorphism from the basement of Mumbai offshore basin, India

International Nuclear Information System (INIS)

Rathore, S.S.; Vijan, A.R.; Singh, M.P.; Misra, K.N.; Prabhu, B.N.

2000-01-01

Precambrian basement from well HBM-1 in the Heera oil field of Mumbai offshore basin has been dated by Rb-Sr and K-Ar methods. Five granulitic basement samples from three conventional drill cores have yielded Rb-Sr isochron age of 502±25 Ma with an initial Sr ratio of 0.70855±0.00013. This age has been interpreted as the time of granulite facies metamorphism of the basement rocks in the region. Two whole rock samples from the basement of this well have yielded mutually concordant K-Ar ages of 505±16 Ma and 507±17 Ma. The K-Ar ages are significantly similar to Rb-Sr age obtained from this well, suggesting complete isotopic reequilibration around 500 Ma ago. The time of secondary thermal heating around 500 Ma ago in the basement of Heera field coincides with the widespread neoproterozoic (Pan-African) thermo-tectonic event extending from the Arabian Peninsula and eastern Africa covering Madagascar, southern India. Sri Lanka and East Antarctica. This study widens the limit of the Pan-African zone, which hitherto was thought to be confined to the western part (presently southern part) of the Indian subcontinent, towards further east. (author)

The Plio-Quaternary Volcanic Evolution of Gran Canaria Based on new Unspiked K-Ar ages and Magnetostratigraphy

Science.gov (United States)

Guillou, H.; Carracedo, J.; Perez Torrado, F.

2003-12-01

The combined use of radioisotopic dating, magnetostratigraphy and field geology is a powerful tool to provide reliable chronological frameworks of volcanic edifices. This approach has been used to investigate the last two stages of the volcanic evolution of Gran Canaria. Fifty samples were dated using the unspiked K-Ar method and had their magnetic polarity measured both in the field and in laboratory. Ages were compared to their stratigraphic positions and magnetic polarities before accepting their validity. The unspiked K-Ar chronology constrains the timing of lateral collapses, eruption rates and the contemporaneity of different volcano-magmatic stages at Gran Canaria. Our new data set modifies significantly the previous chronological framework of Gran Canaria, especially between 4 and 2.8 Ma. Based on these new ages, we can bracket the age of the multiple lateral collapses of the Roque Nublo stratovolcano flanks between 3.5 and 3.1 Ma .This time interval corresponds to a main period of volcanic quiescence. Calculated eruptive rates during the stratovolcano edification are about 0.1 km3/kyr which is significantly lower than the published estimates. The dating also reveals that the two main last stages are not separated by a major time gap, but that the early stages of the rift forming eruption and the vanishing activity of the Roque Nublo strato-volcano were contemporaneous for at least 600 kyrs. These results support that our combined approach provides a rapid first-pass and reliable geochronology. Nevertheless, this chronology can be amplified and made more precise where necessary through detailed Ar-Ar incremental-heating methods. Samples which should be investigated using this method are the oldest and youngest K-Ar dated flows of each volcanic stage, and samples from stratigraphic sections that hold potential to study the behaviour of the earth's magnetic field during reversals (Gauss-Gilbert transition, Olduvai and Reunion events).

Synthesis and pharmacological characterization of the selective GluK1 radioligand (S)-2-amino-3-(6-[3H]-2,4-dioxo-3,4-dihydrothieno[3,2-d]pyrimidin-1(2H)-yl)propanoic acid ([3H]-NF608)

Czech Academy of Sciences Publication Activity Database

Alcaide, A.; Marconi, L.; Marek, Aleš; Haym, I.; Nielsen, B.; Mollerud, S.; Jensen, M.; Conti, P.; Pickering, D. S.; Bunch, L.

2016-01-01

Roč. 7, č. 11 (2016), s. 2136-2144 ISSN 2040-2503 Institutional support: RVO:61388963 Keywords : 2,4-syn-functionalized (S)-glutamate analogs * ionotropic glutamate receptors * kainate receptor Subject RIV: CC - Organic Chemistry Impact factor: 2.608, year: 2016 http://pubs.rsc.org/en/content/articlehtml/2016/md/c6md00339g

Rb/Sr and K/Ar dating of Slovakia's rocks, its possibilities and interpretation

International Nuclear Information System (INIS)

Cambel, B.; Bagdasaryan, G.P.; Gukasyan, P.Kh.; Veselskij, I.

1979-01-01

Nuclear geochronological data are evaluated and summarized into histograms. On the basis of an evaluation, the results are compared obtained using various methods (K/Ar, Rb/Sr and U-Th-Pb) and the age of rocks in West Carpathians determined. It is pointed out that the age determination is dependent on the geochemical state of the studied minerals and rocks. The obtained results confirm the palaeozoic age of the majority of rocks of West Carpathians. Direct nuclear geochronological evidence of precambrium rocks has not yet been obtained. (author)

Differential alterations of cortical glutamatergic binding sites in senile dementia of the Alzheimer type

International Nuclear Information System (INIS)

Chalmers, D.T.; Dewar, D.; Graham, D.I.; Brooks, D.N.; McCulloch, J.

1990-01-01

Involvement of cortical glutamatergic mechanisms in senile dementia of the Alzheimer type (SDAT) has been investigated with quantitative ligand-binding autoradiography. The distribution and density of Na(+)-dependent glutamate uptake sites and glutamate receptor subtypes--kainate, quisqualate, and N-methyl-D-aspartate--were measured in adjacent sections of frontal cortex obtained postmortem from six patients with SDAT and six age-matched controls. The number of senile plaques was determined in the same brain region. Binding of D-[3H]aspartate to Na(+)-dependent uptake sites was reduced by approximately 40% throughout SDAT frontal cortex relative to controls, indicating a general loss of glutamatergic presynaptic terminals. [3H]Kainate receptor binding was significantly increased by approximately 70% in deep layers of SDAT frontal cortex compared with controls, whereas this binding was unaltered in superficial laminae. There was a positive correlation (r = 0.914) between kainate binding and senile plaque number in deep cortical layers. Quisqualate receptors, as assessed by 2-amino-3-hydroxy-5-[3H]methylisoxazole-4-propionic acid binding, were unaltered in SDAT frontal cortex compared with controls. There was a small reduction (25%) in N-methyl-D-aspartate-sensitive [3H]glutamate binding only in superficial cortical layers of SDAT brains relative to control subjects. [3H]Glutamate binding in SDAT subjects was unrelated to senile plaque number in superficial cortical layers (r = 0.104). These results indicate that in the presence of cortical glutamatergic terminal loss in SDAT plastic alterations occur in some glutamate receptor subtypes but not in others

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

Index Scriptorium Estoniae

Pettai, Eva-Clarita, 1971-

2012-01-01

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)

K-Ar geochronology of the Survey Pass, Ambler River and Eastern Baird Mountains quadrangles, southwestern Brooks Range, Alaska

Science.gov (United States)

Turner, Donald L.; Forbes, R.B.; Mayfield, C.F.

1978-01-01

We report 76 previously unpublished K-Ar mineral ages from 47 metamorphic and igneous rocks in the southwestern Brooks Range. The pattern of radiometric ages is complex, reflecting the complex geologic history of this area. Local and regional radiometric evidence suggests that the southern Brooks Range schist belt has, at least in part, undergone a late Precambrian metamorphism and that the parent sedimentary and igneous rocks for the metamorphic rocks dated as late Precambrian are at least this old (Precambrian Z). This schist terrane experienced a major thermal event in mid-Cretaceous time, causing widespread resetting of nearly all K-Ar mica ages. A series of apparent ages intermediate between late Precambrian and mid-Cretaceous are interpreted as indicating varying amounts of partial argon loss from older rocks during the Cretaceous event. The schist belt is characterized by dominant metasediments and subordinate metabasites and metafelsites. Blueschists occur within the schist belt from the Chandalar quadrangle westward to the Baird Mountains quadrangle, but geologic evidence does not support the existence of a fossil subduction zone.

Seizures beget seizures in temporal lobe epilepsies: the boomerang effects of newly formed aberrant kainatergic synapses.

Science.gov (United States)

Ben-Ari, Yehezkel; Crepel, Valérie; Represa, Alfonso

2008-01-01

Do temporal lobe epilepsy (TLE) seizures in adults promote further seizures? Clinical and experimental data suggest that new synapses are formed after an initial episode of status epilepticus, however their contribution to the transformation of a naive network to an epileptogenic one has been debated. Recent experimental data show that newly formed aberrant excitatory synapses on the granule cells of the fascia dentate operate by means of kainate receptor-operated signals that are not present on naive granule cells. Therefore, genuine epileptic networks rely on signaling cascades that differentiate them from naive networks. Recurrent limbic seizures generated by the activation of kainate receptors and synapses in naive animals lead to the formation of novel synapses that facilitate the emergence of further seizures. This negative, vicious cycle illustrates the central role of reactive plasticity in neurological disorders.

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

Directory of Open Access Journals (Sweden)

Melendo, Ana

2012-04-01

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.

Molecular and serological investigation of border disease virus infection in sheep in the Kars District of Turkey

Directory of Open Access Journals (Sweden)

Volkan Yilmaz

2014-01-01

Full Text Available This study is a serological and virological examination of the border disease virus (BDV in sheep at 1–5 years of age from private small scale production units of less than 20 sheep per unit, in the Kars District of Turkey. For this purpose, blood sera from 460 sheep were tested for antibodies against BDV using a commercial enzyme-linked immunosorbent assay (ELISA. Since BDV causes persistent infection, antigen-ELISA was also performed for this agent. Seropositivity rate was detected to be 74.57%. In addition, the BDV antigen was detected in one sample of seronegative sera (0.85%. Reverse transcription polymerase chain reaction (RT-PCR technique was used to determine the presence of pestivirus nucleic acid by using 5’UTR primer pair. Pestivirus nucleic acid was found in 2 of 117 seronegative samples (1.71% by RT-PCR. The results suggest that the infection was spreading in private small scale production units. Furthermore, recommendations for the control of BDV infection are presented. This study is the first molecular and serological study to determine viroprevalence and seroprevalence of BDV infection in sheep in the Kars District of Turkey.

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

Index Scriptorium Estoniae

Ruudi, Ingrid, 1978-

2011-01-01

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)

Plio-Pleistocene basanitic and melilititic series of the Bohemian Massif: K-Ar ages, major/trace element and Sr–Nd isotopic data

Czech Academy of Sciences Publication Activity Database

Ulrych, Jaromír; Ackerman, Lukáš; Balogh, K.; Hegner, E.; Jelínek, E.; Pécskay, Z.; Přichystal, A.; Upton, B. G. J.; Zimák, J.; Foltýnová, R.

2013-01-01

Roč. 73, č. 4 (2013), s. 429-450 ISSN 0009-2819 Institutional support: RVO:67985831 Keywords : Bohemian Massif * Plio-Pleistocene * Basanite * Melilitite * K-Ar age * Magmatism * Sr–Nd isotopes Subject RIV: DD - Geochemistry Impact factor: 1.397, year: 2013

Glutamatergic induction of CREB phosphorylation and Fos expression in primary cultures of the suprachiasmatic hypothalamus in vitro is mediated by co-ordinate activity of NMDA and non-NMDA receptors.

Science.gov (United States)

Schurov, I L; McNulty, S; Best, J D; Sloper, P J; Hastings, M H

1999-01-01

Exposure of Syrian hamsters to light 1 h after lights-off rapidly (10 min) induced nuclear immunoreactivity (-ir) to the phospho-Ser133 form of the Ca2+/cAMP response element (CRE) binding protein (pCREB) in the retinorecipient zone of the suprachiasmatic nuclei (SCN). Light also induced nuclear Fos-ir in the same region of the SCN after 1 h. The glutamatergic N-methyl-D-aspartate (NMDA) receptor blocker MK801 attenuated the photic induction of both factors. To investigate glutamatergic regulation of pCREB and Fos further, tissue blocks and primary cultures of neonatal hamster SCN were examined by Western blotting and immunocytochemistry in vitro. On Western blots of SCN tissue, the pCREB-ir signal at 45 kDa was enhanced by glutamate or a mixture of glutamatergic agonists (NMDA, amino-methyl proprionic acid (AMPA), and Kainate (KA)), whereas total CREB did not change. Glutamate or the mixture of agonists also induced a 56 kDa band identified as Fos protein in SCN tissue. In dissociated cultures of SCN, glutamate caused a rapid (15 min) induction of nuclear pCREB-ir and Fos-ir (after 60 min) exclusively in neurones, both GABA-ir and others. Treatment with NMDA alone had no effect on pCREB-ir. AMPA alone caused a slight increase in pCREB-ir. However, kainate alone or in combination with NMDA and AMPA induced nuclear pCREB-ir equal to that induced by glutamate. The effects of glutamate on pCREB-ir and Fos-ir were blocked by antagonists of both NMDA (MK801) and AMPA/KA (NBQX) receptors. In the absence of extracellular Mg2+, MK801 blocked glutamatergic induction of Fos-ir. However, the AMPA/KA receptor antagonist was no longer effective at blocking glutamatergic induction of either Fos-ir or pCREB-ir, consistent with the model that glutamate regulates gene expression in the SCN by a co-ordinate action through both NMDA and AMPA/KA receptors. Glutamatergic induction of nuclear pCREB-ir in GABA-ir neurones was blocked by KN-62 an inhibitor of Ca2+/Calmodulin (Ca

K-Ar cooling age profile from Joinville massif (PR and SC, Brazil) and Dom Feliciano belt (SC, Brazil) - Tectonics entanglement

International Nuclear Information System (INIS)

Siga Junior, O.; Basei, M.A.S.; Kawashita, K.

1990-01-01

A K-Ar cooling age profile using different minerals from metamorphic rocks of the Joinville Massif and Dom Feliciano Belt is presented. Three main geochronological domains are distinguishable, from NW to SE: 1) Northern part of the Joinville Massif (NJM); 2) Southern part of the Joinville Massif (SJM) and 3) Dom Feliciano Belt (DBF). Geochronological domains 1 and 3 yielded K-Ar values in the range 800-500 Ma and 700-500 Ma, respectively, which show a clear influence of the Brasiliano Cycle. The granulite terrain comprising the SMJ exhibits ages older than 1700 Ma, indicating that this area was cool during the Late Proterozoic Brasiliano Cycle. The SJM and NJM limit is marked by a rapid Transition from Early Proterozoic ages in the SJM to Late Proterozoic ages in the NJM. On the other hand the contact between the SJM and DFB is interpreted as a thrust at a high, relatively cool crustal level. (author)

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

International Nuclear Information System (INIS)

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

1993-11-01

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

The tectonic significance of K/Ar illite fine-fraction ages from the San Luis Formation (Eastern Sierras Pampeanas, Argentina)

Science.gov (United States)

Wemmer, Klaus; Steenken, André; Müller, Stefan; de Luchi, Mónica G. López; Siegesmund, Siegfried

2011-04-01

The Sierra de San Luis forms the southern tip of the Eastern Sierras Pampeanas in central Argentina. Two narrow belts of low-grade phyllites and quartz arenites, i.e. the San Luis Formation, have accommodated part of the strain-related differential exhumation of the medium- to high-grade metamorphic domains that constitute to the basement complex of the sierra. Eleven phyllite samples were subjected to the K/Ar fine-fraction dating technique. Results are interpreted in relation to the Kübler index of the illites, which indicate epimetamorphic conditions for the majority of the samples. Obtained ages between 330 and 290 Ma cover a period of compressional tectonics in the late Mississippian (Visean/Serpukhovian boundary) followed by the subsidence during the formation of the Paganzo Basin in the provinces of La Rioja and San Luis. These tectonic movements are coincident with the Toco orogeny in northern Chile and southern Bolivia. This suggests that the older K/Ar ages document the compressional stage and that younger ages record the cooling of the basement during the subsequent extensional uplift of the basement.

K-Ar dating: incomplete extraction of radiogenic argon from alkali feldspar - a comment

International Nuclear Information System (INIS)

Baksi, A.K.

1984-01-01

In a recent paper, McDowell (1983) discussed the difficulties involved in obtaining accurate K-Ar ages on alkali feldspar samples. These difficulties primarily stem from the fact that the feldspars melt at high temperatures and lack structural volatiles which could flush out all of the 40 Ar* from the viscous melt at temperatures below 1600 0 C. Evidently, if feldspar samples could be satisfactorily melted at lower temperatures by the use of a suitable flux, complete release of 40 Ar* should occur. McDowell (1983) also commented on the lack of a suitable feldspar standard sample for argon dating work. This comment will briefly address these two problems. (Auth.)

6061 Alüminyum Alaşımının Sürtünme Karıştırma Kaynak Yöntemi ile Kaynak Edilebilirliğinin İncelenmesi

Directory of Open Access Journals (Sweden)

İlker EKER

2009-02-01

Full Text Available Bu çalışmada sürtünme karıştırma kaynağı yöntemiyle birleştirilen alüminyum döküm levhaların kaynak bölgelerinin değişen parametrelerle mikrosertlik ve mekanik özellikleri incelenmiştir. Kaynak süresince karıştırıcı ucun devir sayısı ve kaynak ilerleme hızı değişken parametreler olarak alınmıştır. Alüminyum alaşımlı levhaların kaynağında SAE 8620 malzeme numaralı sementasyon çeliğinden imal edilmiş karıştırıcı uç kullanılmıştır. Karıştırıcı ucun devir hızı sabitken kaynak ilerleme hızı dört farklı değerde seçilmiştir. Kaynaklı birleştirmelere metalografik ve mekanik testler yapılarak işlem parametrelerinin etkileri araştırılmıştır.

Tectono-metamorphic evolution of high-P/T and low-P/T metamorphic rocks in the Tia Complex, southern New England Fold Belt, eastern Australia: Insights from K-Ar chronology

Science.gov (United States)

Fukui, Shiro; Tsujimori, Tatsuki; Watanabe, Teruo; Itaya, Tetsumaru

2012-10-01

The Tia Complex in the southern New England Fold Belt is a poly-metamorphosed Late Paleozoic accretionary complex. It consists mainly of high-P/low-T type pumpellyite-actinolite facies (rare blueschist facies) schists, phyllite and serpentinite (T = 300 °C and P = 5 kbar), and low-P/high-T type amphibolite facies schist and gneiss (T = 600 °C and P Tia granodiorite). White mica and biotite K-Ar ages distinguish Carboniferous subduction zone metamorphism and Permian granitic intrusions, respectively. The systematic K-Ar age mapping along a N-S traverse of the Tia Complex exhibits a gradual change. The white mica ages become younger from the lowest-grade zone (339 Ma) to the highest-grade zone (259 Ma). In contrast, Si content of muscovite changes drastically only in the highest-grade zone. The regional changes of white mica K-Ar ages and chemical compositions of micas indicate argon depletion from precursor high-P/low-T type phengitic white mica during the thermal overprinting and recrystallization by granitoids intrusions. Our new K-Ar ages and available geological data postulate a model of the eastward rollback of a subduction zone in Early Permian. The eastward shift of a subduction zone system and subsequent magmatic activities of high-Mg andesite and adakite might explain formation of S-type granitoids (Hillgrove suite) and coeval low-P/high-T type metamorphism in the Tia Complex.

El universo plástico y sensorial de la mano (Wong Kar Wai, 2004

Directory of Open Access Journals (Sweden)

Ana MELENDO CRUZ

2014-10-01

Full Text Available 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

A compilation of {sup 40}Ar-{sup 39} and K-Ar ages: report 25

Energy Technology Data Exchange (ETDEWEB)

Hunt, P A [Geological Survey of Canada, Ottawa, ON (Canada); Roddick, J C

1997-12-31

Twenty-three {sup 40}Ar-{sup 39}Ar age determinations (including two potassium-argon analyses) carried out by the Geological Survey of Canada are reported. Each age determination is accompanied by a description of the rock and mineral concentrate used; brief interpretative comments regarding the geological significance of each age are also provided where possible. The experimental procedures employed are described in outline. An index of all Geological Survey of Canada K-Ar age determinations published in this format has been prepared using NTS quadrangles as the primary reference. (author). 6 refs., 2 tabs., 1 fig.

Modulation of [3H]-glutamate binding by serotonin in the rat hippocampus: An autoradiographic study

International Nuclear Information System (INIS)

Mennini, T.; Miari, A.

1991-01-01

Serotonin (5-HT) added in vitro increased [ 3 H]-glutamate specific binding in the rat hippocampus, reaching statistical significance in layers rich in N-Methyl-D-Aspartate sensitive glutamate receptors. This effect was explained by a significant increase in the apparent affinity of [ 3 H]-glutamate when 5-HT is added in vitro. Two days after lesion of serotonergic afferents to the hippocampus with 5,7- Dihydroxytryptamine [ 3 H]-glutamate binding was significantly decreased in the CA3 region and stratum lacunosum moleculare of the hippocampus, this reduction being reversed by in vitro addition of 10 μM 5-HT. The decrease observed is due to a significant reduction of quisqualate-insensitive (radiatum CA3) and kainate receptors (strata oriens, radiatum, pyramidal of CA3). Five days after lesion [ 3 H]-glutamate binding increased significantly in the CA3 region of the hippocampus but was not different from sham animals in the other hippocampal layers. Two weeks after lesion [ 3 H]-glutamate binding to quisqualate-insensitive receptors was increased in all the hippocampal layers, while kainate and quisqualate-sensitive receptors were not affected. These data are consistent with the possibility that 5-HT is a direct positive modulator of glutamate receptor subtypes

Investigation into the metamorphic Nappes of the Central Scandinavian Caledonides on the basis of Rb-Sr and K-Ar age determination

International Nuclear Information System (INIS)

Reymer, A.P.S.

1979-01-01

This study concerns age determinations on several rock units of metamorphic nappes in the central Scandinavian Caledonides. Rb-Sr analyses on whole-rocks and minerals (biotite, muscovite/phengite, feldspars, garnet) were made as well as K-Ar determinations on biotite, muscovite/phengite, amphibole and feldspar. (Auth.)

Nootropic agents enhance the recruitment of fast GABAA inhibition in rat neocortex.

Science.gov (United States)

Ling, Douglas S F; Benardo, Larry S

2005-07-01

It is widely believed that nootropic (cognition-enhancing) agents produce their therapeutic effects by augmenting excitatory synaptic transmission in cortical circuits, primarily through positive modulation of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate receptors (AMPARs). However, GABA-mediated inhibition is also critical for cognition, and enhanced GABA function may be likewise therapeutic for cognitive disorders. Could nootropics act through such a mechanism as well? To address this question, we examined the effects of nootropic agents on excitatory and inhibitory postsynaptic currents (EPSCs and IPSCs) recorded from layer V pyramidal cells in acute slices of somatosensory cortex. Aniracetam, a positive modulator of AMPA/kainate receptors, increased the peak amplitude of evoked EPSCs and the amplitude and duration of polysynaptic fast IPSCs, manifested as a greater total charge carried by IPSCs. As a result, the EPSC/IPSC ratio of total charge was decreased, representing a shift in the excitation-inhibition balance that favors inhibition. Aniracetam did not affect the magnitude of either monosynaptic IPSCs (mono-IPSCs) recorded in the presence of excitatory amino acid receptor antagonists, or miniature IPSCs (mIPSCs) recorded in the presence of tetrodotoxin. However, the duration of both mono-IPSCs and mIPSCs was prolonged, suggesting that aniracetam also directly modulates GABAergic transmission. Cyclothiazide, a preferential modulator of AMPAR function, enhanced the magnitude and duration of polysynaptic IPSCs, similar to aniracetam, but did not affect mono-IPSCs. Concanavalin A, a kainate receptor modulator, had little effect on EPSCs or IPSCs, suggesting there was no contribution from kainate receptor activity. These findings indicate that AMPAR modulators strengthen inhibition in neocortical pyramidal cells, most likely by altering the kinetics of AMPARs on synaptically connected interneurons and possibly by modulating GABA(A) receptor responses

K/Ar hornblende ages from the higher Himalaya: implications for India-Asia collision and Himalayan metamorphosis

International Nuclear Information System (INIS)

Sorkhabi, R.B.; Stump, A.K.; Jain, A.K.; Manickavasagam, R.M.; Nishimura Susumu

1993-01-01

Two amphibolite samples from the Higher Himalayan Crystalline (HHC) belt from the Suru Valley, Zanskar, have yielded Eocene K/Ar hornblende cooling ages between 40 and 45 Ma, thus indicating much older peak metamorphic conditions in northern parts of the Indian Plate. These ages are in conformity with almost identical ages from metamorphic complexes across the Nanga Parbat syntaxis in Pakistan and reveal a 65 to 70-Ma collision phase of the Indian indentor in the NW-Himalaya. (author). 21 refs., 2 figs

Translational approach for gene therapy in epilepsy

DEFF Research Database (Denmark)

Ledri, Litsa Nikitidou; Melin, Esbjörn; Christiansen, Søren H.

2016-01-01

clinical trial for gene therapy of temporal lobe epilepsy was explored: We investigated (i) whether the post intrahippocampal kainate-induced status epilepticus (SE) model of chronic epilepsy in rats could be clinically relevant; and (ii) whether a translationally designed neuropeptide Y (NPY)/Y2 receptor...

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.

Science.gov (United States)

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

2015-03-15

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

Amaç ve Beklenti Karşısında Karşılaştırmalı Edebiyatın Tanı(MSal Krizine İlişkin Birtakım Tartışmalı Saptamalar Some Argumentative Determinations Regarding Diagnostic/Definitional Crisis Of Comparative Literature In Terms Of Accordance With Its Purpose And Expectation

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Abdulhakim TUĞLUK

2013-09-01

Full Text Available Comparison which possesses the characteristics of critic in linewith its purposes and ambitions keeps on its actuality and differenceperception because of its argumentative position within the science ofliterature. “Comparative Literature Science” which has become effectivein literature argumentations in recent years in Turkey has not beenable to make its identity and conceptual entity acceptable, yet. Not onlythe uncertainties in the definition, but also some problems in practicekeep the questions against comparative literature in a certain level.There are also some uncertainties whether it is a method or a science initself as well as the acceptability of it by national men of literature.Comparison, which is seen as easy to do at first in terms of feasibility,shows itself as a complex process when the literal and aestheticmissions attributed by the concept to it are taken into consideration.This complexity becomes a crisis in which there are many questionswhen it is faced with diagnostic and definitive problems. On the otherhand, West-centered perception of the comparative literature and itsinternational face embracing the concept of „world literature‟(Weltliteratur make global scale expectations committed by the conceptmore argumentative rather than meeting these expectations. In thisstudy, the main starting point is gaining a certain point of view to theidentity confusion of comparative literature and establishing a generalargumentation basis. The purpose of this study is revealing somecomplex points in theory and practice considering existential problemsof comparative literature and bringing some expansion to somehandicaps regarding essence of the comparative literature. Amaç ve hedefleri doğrultusunda bir eleştiri türü niteliği taşıyan karşılaştırma, edebiyat bilimi içerisindeki tartışmalı konumu nedeniyle güncelliğini ve farklılık algısını sürdürmektedir. Türkiye‟de, son yıllarda, edebi tart

Bidirectional modulation of hippocampal gamma (20-80 Hz) frequency activity in vitro via alpha(α)- and beta(β)-adrenergic receptors (AR).

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Haggerty, D C; Glykos, V; Adams, N E; Lebeau, F E N

2013-12-03

Noradrenaline (NA) in the hippocampus plays an important role in memory function and has been shown to modulate different forms of synaptic plasticity. Oscillations in the gamma frequency (20-80 Hz) band in the hippocampus have also been proposed to play an important role in memory functions and, evidence from both in vitro and in vivo studies, has suggested this activity can be modulated by NA. However, the role of different NA receptor subtypes in the modulation of gamma frequency activity has not been fully elucidated. We have found that NA (30 μM) exerts a bidirectional control on the magnitude of kainate-evoked (50-200 nM) gamma frequency oscillations in the cornu Ammonis (CA3) region of the rat hippocampus in vitro via activation of different receptor subtypes. Activation of alpha-adrenergic receptors (α-AR) reduced the power of the gamma frequency oscillation. In contrast, activation of beta-adrenergic receptors (β-AR) caused an increase in the power of the gamma frequency oscillations. Using specific agonists and antagonists of AR receptor subtypes we demonstrated that these effects are mediated specifically via α1A-AR and β1-AR subtypes. NA activated both receptor subtypes, but the α1A-AR-mediated effect predominated, resulting in a reversible suppression of gamma frequency activity. These results suggest that NA is able to differentially modulate on-going gamma frequency oscillatory activity that could result in either increased or decreased information flow through the hippocampus. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

The distribution of excitatory amino acid receptors on acutely dissociated dorsal horn neurons from postnatal rats.

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Arancio, O; Yoshimura, M; Murase, K; MacDermott, A B

1993-01-01

Excitatory amino acid receptor distribution was mapped on acutely dissociated neurons from postnatal rat spinal cord dorsal horn. N-methyl D-aspartate, quisqualate and kainate were applied to multiple locations along the somal and dendritic surfaces of voltage-clamped neurons by means of a pressure application system. To partially compensate for the decrement of response amplitude due to current loss between the site of activation on the dendrite and the recording electrode at the soma, a solution containing 0.15 M KCl was applied on the cell bodies and dendrites of some cells to estimate an empirical length constant. In the majority of the cells tested, the dendritic membrane had regions of higher sensitivity to excitatory amino acid agonists than the somatic membrane, with dendritic response amplitudes reaching more than seven times those at the cell body. A comparison of the relative changes in sensitivity between each combination of two of the three excitatory amino acid agonists along the same dendrite showed different patterns of agonist sensitivity along the dendrite in the majority of the cells. These data were obtained from dorsal horn neurons that had developed and formed synaptic connections in vivo. They demonstrate that in contrast to observations made on ventral horn neurons, receptor density for all the excitatory amino acid receptors on dorsal horn neurons, including the N-methyl-D-aspartate receptor, are generally higher on the dendrites than on the soma. Further, these results are similar to those obtained from dorsal horn neurons grown in culture.

Changes in calcium and iron levels in the brains of rats during kainate induced epilepsy

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Ren, Min-Qin; Ong, Wei-Yi; Makjanic, Jagoda; Watt, Frank

1999-10-01

Epilepsy is a recurrent disorder of cerebral function characterised by sudden brief attacks of altered consciousness, motor activity or sensory phenomena, and affects approximately 1% of the population. Kainic acid injection induces neuronal degeneration in rats, is associated with glial hypertrophy and proliferation in the CA3-CA4 fields of hippocampal complex, and is a model for temporal lobe epilepsy. In this study we have applied Nuclear Microscopy to the investigation of the elemental changes within the hippocampus and the cortex areas of the rat brain following kainate injection. Analyses of unstained freeze dried tissue sections taken at 1 day and 1, 2, 3 and 4 weeks following injection were carried out using the Nuclear Microscopy facility at the Research Centre for Nuclear Microscopy, National University of Singapore. Quantitative analysis and elemental mapping indicates that there are significant changes in the calcium levels and distributions in the hippocampus as early as 1 day following injection. Preliminary results indicate a rapid increase in cellular calcium. High levels of calcium can activate calcium dependent proteins and phospholipases. Activation of phospholipase A 2 can be harmful to surrounding neurons through free radical damage. In addition to observed increases in calcium, there was evidence of increases in iron levels. This is consistent with measurements in other degenerative brain disorders, and may signal a late surge in free radical production.

Changes in calcium and iron levels in the brains of rats during kainate induced epilepsy

International Nuclear Information System (INIS)

Ren, M.-Q.; Ong, W.-Y.; Makjanic, Jagoda; Watt, Frank

1999-01-01

Epilepsy is a recurrent disorder of cerebral function characterised by sudden brief attacks of altered consciousness, motor activity or sensory phenomena, and affects approximately 1% of the population. Kainic acid injection induces neuronal degeneration in rats, is associated with glial hypertrophy and proliferation in the CA3-CA4 fields of hippocampal complex, and is a model for temporal lobe epilepsy. In this study we have applied Nuclear Microscopy to the investigation of the elemental changes within the hippocampus and the cortex areas of the rat brain following kainate injection. Analyses of unstained freeze dried tissue sections taken at 1 day and 1, 2, 3 and 4 weeks following injection were carried out using the Nuclear Microscopy facility at the Research Centre for Nuclear Microscopy, National University of Singapore. Quantitative analysis and elemental mapping indicates that there are significant changes in the calcium levels and distributions in the hippocampus as early as 1 day following injection. Preliminary results indicate a rapid increase in cellular calcium. High levels of calcium can activate calcium dependent proteins and phospholipases. Activation of phospholipase A 2 can be harmful to surrounding neurons through free radical damage. In addition to observed increases in calcium, there was evidence of increases in iron levels. This is consistent with measurements in other degenerative brain disorders, and may signal a late surge in free radical production

New K-Ar ages of volcanic rocks and associated mineralization in Canada Honda district, San Luis, Argentina

International Nuclear Information System (INIS)

Urbina, N.E.; Oggier, F.P

2001-01-01

New K-Ar ages in the Late Tertiary gold-bearing volcanic belt of the Sierras Pampeanas of San Luis, Argentina are presented. At Canada Honda district, an age of 8.49±0.2 Ma yielded by Cerro del Valle andesite indicates that the dome emplacement postdates the Diente Verde eruptive event. An even younger age of 7.3±0.2 Ma was obtained for illite from hydrothermal alteration at La Reynela mineralization which is hosted by Cerro del Valle andesite (au)

Ipsilateral feeding-specific circuits between the nucleus accumbens shell and the lateral hypothalamus: regulation by glutamate and GABA receptor subtypes.

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Urstadt, Kevin R; Kally, Peter; Zaidi, Sana F; Stanley, B Glenn

2013-04-01

The nucleus accumbens shell (AcbSh) and the lateral hypothalamus (LH) are both involved in the control of food intake. Activation of GABA(A) receptors or blockade of AMPA and kainate receptors within the AcbSh induces feeding, as does blockade of GABA(A) receptors or activation of NMDA receptors in the LH. Further, evidence suggests that feeding induced via the AcbSh can be suppressed by LH inhibition. However, it is unclear if this suppression is specific to feeding. Adult male Sprague-Dawley rats with 3 intracranial guide cannulas, one unilaterally into the AcbSh and two bilaterally into the LH, were used to explore this issue. DNQX (1.25 μg) or muscimol (100 ng) infused into the AcbSh unilaterally elicited feeding, and this elicited intake was suppressed by bilateral LH injection of d-AP5 (2 μg) or muscimol (25 ng). The effectiveness of d-AP5 or muscimol infusion into either the LH site ipsilateral or contralateral to the AcbSh injection was compared. Ipsilateral LH injection of d-AP5 or muscimol was significantly more effective than contralateral injection in suppressing food intake initiated by AcbSh injection of DNQX or muscimol. These results add to the prior evidence that inhibition of the LH through pharmacological modulation of NMDA or GABA(A) receptors specifically suppresses feeding initiated by AcbSh inhibition, and that these two regions communicate via an ipsilateral circuit to specifically regulate feeding. Copyright © 2012 Elsevier Ltd. All rights reserved.

Legacy K/Ar and 40Ar/39Ar geochronologic data from the Alaska-Aleutian Range batholith of south-central Alaska

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Koeneman, Lisa L.; Wilson, Frederic H.

2018-04-06

Sample descriptions and analytical data for more than 200 K/Ar and 40Ar/39Ar analyses from rocks of the Alaska-Aleutian Range batholith of south-central Alaska are reported here. Samples were collected over a period of 20 years by Bruce R. Reed and Marvin A. Lanphere (both U.S. Geological Survey) as part of their studies of the batholith.

Effect of intrathecal non-NMDA EAA receptor antagonist LY293558 in rats: a new class of drugs for spinal anesthesia.

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Von Bergen, Nicholas H; Subieta, Alberto; Brennan, Timothy J

2002-07-01

Excitatory amino acid receptors are important for both sensory and motor function in the spinal cord. We studied the effects of intrathecal LY293558, a competitive non-N-methyl-D-aspartate excitatory amino acid receptor antagonist, on motor and sensory function in rats to determine whether drugs blocking these receptors could potentially be used as alternative agents to local anesthetics for spinal anesthesia. Rats were tested before and 15-240 min after intrathecal injection of 5 nmol (in 10 microl) LY293558. Sensory function was tested at the hind paw using withdrawal response to pin prick and withdrawal to pinch with sharp forceps. Motor performance (ambulation, placing reflex, and Rotorod time), blood pressure, and heart rate were also evaluated. Some tests were repeated the next day. Responses after LY293558 were compared to injection of 40 microl bupivacaine, 0.75%. Pin-prick responses at the forepaw, chest, abdomen, hind leg, and hind paw were also examined after intrathecal LY293558. Intrathecal LY293558 blocked both sensory and motor responses through 180 min; complete recovery was present the following day. No change in blood pressure or heart rate occurred. The effects of LY293558 were more pronounced and sustained than those of bupivacaine. Segmental blockade of the response to pin prick was present after LY293558. Drugs like LY293558 that block alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA)/kainate receptors may be an alternative to local anesthetics for spinal anesthesia in humans.

Glutamate modulation of GABA transport in retinal horizontal cells of the skate

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Kreitzer, Matthew A; Andersen, Kristen A; Malchow, Robert Paul

2003-01-01

Transport of the amino acid GABA into neurons and glia plays a key role in regulating the effects of GABA in the vertebrate retina. We have examined the modulation of GABA-elicited transport currents of retinal horizontal cells by glutamate, the likely neurotransmitter of vertebrate photoreceptors. Enzymatically isolated external horizontal cells of skate were examined using whole-cell voltage-clamp techniques. GABA (1 mm) elicited an inward current that was completely suppressed by the GABA transport inhibitors tiagabine (10 μm) and SKF89976-A (100 μm), but was unaffected by 100 μm picrotoxin. Prior application of 100 μm glutamate significantly reduced the GABA-elicited current. Glutamate depressed the GABA dose-response curve without shifting the curve laterally or altering the voltage dependence of the current. The ionotropic glutamate receptor agonists kainate and AMPA also reduced the GABA-elicited current, and the effects of glutamate and kainate were abolished by the ionotropic glutamate receptor antagonist 6-cyano-7-nitroquinoxaline. NMDA neither elicited a current nor modified the GABA-induced current, and metabotropic glutamate analogues were also without effect. Inhibition of the GABA-elicited current by glutamate and kainate was reduced when extracellular calcium was removed and when recording pipettes contained high concentrations of the calcium chelator BAPTA. Caffeine (5 mm) and thapsigargin (2 nm), agents known to alter intracellular calcium levels, also reduced the GABA-elicited current, but increases in calcium induced by depolarization alone did not. Our data suggest that glutamate regulates GABA transport in retinal horizontal cells through a calcium-dependent process, and imply a close physical relationship between calcium-permeable glutamate receptors and GABA transporters in these cells. PMID:12562999

A reconnaissance Rb-Sr, Sm-Nd, U-Pb, and K-Ar study of some host rocks and ore minerals in the West Shasta Cu- Zn district, California ( USA).

Science.gov (United States)

Kistler, R.W.; McKee, E.H.; Futa, K.; Peterman, Z.E.; Zartman, R.E.

1985-01-01

The Copley Greenstone, Balaklala Rhyolite, and Mule Mountain stock in the West Shasta Cu-Zn district, California, have Rb-Sr, Sm-Nd, U-Pb, and K-Ar systematics that indicate they are a cogenetic suite of ensimatic island-arc rocks about 400 Ma. Pervasive alteration and mineralization of these rocks, for the most part, was syngenetic and the major component of the mineralizing fluid was Devonian seawater. K-Ar ages of quarz-sericite concentrates from ore horizons and Rb-Sr systematics of a few rock and ore specimens record a later thermal and mineralizing event in the district of about 260 Ma. Contamination of some rocks with pelagic sediments is indicated by the Sm-Nd data. -Authors

Transmitter receptors reveal segregation of the arcopallium/amygdala complex in pigeons (Columba livia).

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Herold, Christina; Paulitschek, Christina; Palomero-Gallagher, Nicola; Güntürkün, Onur; Zilles, Karl

2018-02-15

At the beginning of the 20th century it was suggested that a complex group of nuclei in the avian posterior ventral telencephalon is comparable to the mammalian amygdala. Subsequent findings, however, revealed that most of these structures share premotor characteristics, while some indeed constitute the avian amygdala. These developments resulted in 2004 in a change of nomenclature of these nuclei, which from then on were named arcopallial or amygdala nuclei and referred to as the arcopallium/amygdala complex. The structural basis for the similarities between avian and mammalian arcopallial and amygdala subregions is poorly understood. Therefore, we analyzed binding site densities for glutamatergic AMPA, NMDA and kainate, GABAergic GABA A , muscarinic M 1 , M 2 and nicotinic acetylcholine (nACh; α 4 β 2 subtype), noradrenergic α 1 and α 2 , serotonergic 5-HT 1A and dopaminergic D 1/5 receptors using quantitative in vitro receptor autoradiography combined with a detailed analysis of the cyto- and myelo-architecture. Our approach supports a segregation of the pigeon's arcopallium/amygdala complex into the following subregions: the arcopallium anterius (AA), the arcopallium ventrale (AV), the arcopallium dorsale (AD), the arcopallium intermedium (AI), the arcopallium mediale (AM), the arcopallium posterius (AP), the nucleus posterioris amygdalopallii pars basalis (PoAb) and pars compacta (PoAc), the nucleus taeniae amgygdalae (TnA) and the area subpallialis amygdalae (SpA). Some of these subregions showed further subnuclei and each region of the arcopallium/amygdala complex are characterized by a distinct multi-receptor density expression. Here we provide a new detailed map of the pigeon's arcopallium/amygdala complex and compare the receptor architecture of the subregions to their possible mammalian counterparts. © 2017 Wiley Periodicals, Inc.

K-Ar geochronology of mafic dyke swarms from the meridional part of Sao Francisco craton and implications on tectonic context

International Nuclear Information System (INIS)

Teixeira, W.; Kawashita, K.; Pecchio, M.; Tame, N.R.

1988-01-01

The southern region of the Sao Francisco Craton is made up of gneissic-granitoid terranes (mainly of amphibolite facies) associated with supracrustals, which can be separed into two crustal provinces, the oldest formed during the Archean (3-2-2.6 Ga.), and the youngest in the Early Proterozoic (2.4-2.0 Ga.). Mafic dyke swarms inject the basement complexes in the area west of Belo Horizonte city, but not the Late proterozoic Bambui sedimentary cover. These dykes show NNW, NW, WNW, NNE and ENE trends and are of anorogenic character. Most dykes are tholeiitic in composition. Metamorphic recrystallization at greenschist to amphibolite facies as well as minor hidrothermal and/or deuteric transformations are characteristics in the majority of the these dykes. About sixty K/Ar determinations have been performed on plagioclases, amphiboles and whole rocks. They are interpretated combining the use of K/Ar diagrams and histogram, and according to the crustal evolution proposed for the craton. The available radiometric data suggest that the main period of mafic intrusions took place in the Early proterozoic as supported by the apparent ages on amphiboles. However, the beginning of the Middle Proterozoic (1.7-1.5 Ga.) probably corresponds to a period of tensional tectonics as well. On the other hand, most ages obtained on plagioclases and whole rocks, can be associated with Late Proterozoic processes of argon gain or loss. The results are tectonicaly associated with crustal rifting of the continental mass. This two radiometric groupings are characteristic for the evolution of the Early proterozoic crustal provine and of the Mid-Proterozoic intracratonic Espinhaco System respectively. The youngest Late Proterozoic apparent ages associated with the reflections of the contemporaneous evolution of the Braziliano marginal mobile belt which is also suggested by the partial resetting of the K/Ar ages of basement rocks within the eastern part of the Sao Francisco Craton. (author) [pt

Mutual enhancement of central neurotoxicity induced by ketamine followed by methamphetamine

International Nuclear Information System (INIS)

Ke, J.-J.; Chen, H.-I.; Jen, C.J.; Kuo, Y.-M.; Cherng, C.G.; Tsai, Y.-P.N.; Ho, M.-C.; Tsai, C.-W.; Lung Yu

2008-01-01

We hereby report that repeated administration of ketamine (350 mg/kg in total) and methamphetamine (30 mg/kg in total) causes specific glutamatergic and dopaminergic neuron deficits, respectively, in adult mouse brain. Acute ketamine did not affect basal body temperature or the later methamphetamine-induced hyperthermia. However, pretreatment with repeated doses of ketamine aggravated methamphetamine-induced dopaminergic terminal loss as evidenced by a drastic decrease in the levels of dopamine, 3,4-dihydroxyphenylacetic acid, and dopamine transporter density as well as poor gait balance performance. In contrast, methamphetamine-induced serotonergic depletion was not altered by ketamine pretreatment. Likewise, the subsequent treatment with methamphetamine exacerbated the ketamine-induced glutamatergic damage as indicated by reduced levels of the vesicular glutamate transporter in hippocampus and striatum and poor memory performance in the Morris water maze. Finally, since activation of the D1 and AMPA/kainate receptors has been known to be involved in the release of glutamate and dopamine, we examined the effects of co-administration of SCH23390, a D1 antagonist, and CNQX, an AMPA/kainate antagonist. Intraventricular CNQX infusion abolished ketamine's potentiation of methamphetamine-induced dopamine neurotoxicity, while systemic SCH23390 mitigated methamphetamine's potentiation of ketamine-induced glutamatergic toxicity. We conclude that repeated doses of ketamine potentiate methamphetamine-induced dopamine neurotoxicity via AMPA/kainate activation and that conjunctive use of methamphetamine aggravates ketamine-induced glutamatergic neurotoxicity possibly via D1 receptor activation

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

International Nuclear Information System (INIS)

Valeriano, Claudio Morrison de; Teixeira, Wilson; Simoes, Luiz Sergio Amarante; Heilbron, Monica

2000-01-01

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)

K-Ar age for alunite-bearing rock from the Iwato gold deposit, Kagoshima Prefecture, southern Japan

International Nuclear Information System (INIS)

Togashi, Yukio; Shibata, Ken

1984-01-01

K-Ar age determination was made on a whole rock sample of the alunite-bearing silicified rock from the Iwato gold deposit, Kagoshima Prefecture, southern Japan. The sample is from one of the Nansatsu-type gold deposits, whose mineralization is characterized by the occurrence of leaching-type massive silicified rocks with gold dissemination. The result, 4.15 +- 0.78 Ma, is interpreted to be the age of the mineralization at the Iwato gold deposit. It also suggests that the Nansatsu-type deposits were formed in close association with andesitic volcanism in the early Pliocene age. (author)

Effects of neonatal. gamma. -ray irradiation on rat hippocampus: Pt. 2; Development of excitatory amino acid binding sites

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Dessi, F; Represa, A; Ben-Ari, Y [Institut National de la Sante et de la Recherche Medicale (INSERM), 75 - Paris (France)

1991-01-01

In the rat, neonatal irradiation produces a destruction of denate granule cells and prevents the development of the mossy fibre-CA3 pyramidal cell synapse. The developmental increase of high affinity kainate binding sites in the stratum lucidum was reduced on the irradiated side as compared with the control side. This suggests that a proportion of high affinity kainate binding sites is associated with mossy fibres. In contrast, the development profile of N-methyl-D-aspartate binding sites, which are associated with associational and commissural synapses in CA3, was not affected by irradiation. The role that afferent fibres may play in the development of pyramidal cells is discussed in connection with the modulatory effects of glutamate receptors on the development of neurons. (author).

K/Ar dating of the Eastern Rhodope Paleogene magmatism

Energy Technology Data Exchange (ETDEWEB)

Lilov, P.; Yanev, Y.; Marchev, P.

1987-12-01

Paleogene magmatic rocks from the Eastern Rhodope Mountains have seldom been an object of radiogeochronological studies and very few data are available from the geological literature. Until now their dating relied heavily on paleontological data from fossil-bearing sediments, alternating with the lava flows. However, there are also many cross bodies (extrusions, dikes and intrusions) as well as volcanic areas of no sediments or of fossil-free sediments which require the combined use of both methods. This paper aims at characterizing geochronologically the Eastern Rhodope Paleogene volcanism. The K/Ar method was used to date reference volcanoes (mostly with well-defined positions in the Paleogene sequence) associated with the various phases of volcanic activity, as well as some separate intrusive bodies. Nomenclature of volcanics followed the classification of the Soviet Petrographic Commission and that of Peccerillo and Taylor as supplemented by Marchey. The paper characterizes only two of the three main volcanic districts, the Momcilgrad-Arda and the Borovica districts. The third one, Susica district, has restricted exposures near the state boundary between Bulgari and Greece and was excluded from the study. The results obtained are compared with the geochronological scales proposed by Odin and Cavelier and Pomerol which correlate radiogeochronological and paleontological data (nannoplancton data included).

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.

Vitamin E-Mediated Modulation of Glutamate Receptor Expression in an Oxidative Stress Model of Neural Cells Derived from Embryonic Stem Cell Cultures

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Afifah Abd Jalil

2017-01-01

Full Text Available Glutamate is the primary excitatory neurotransmitter in the central nervous system. Excessive concentrations of glutamate in the brain can be excitotoxic and cause oxidative stress, which is associated with Alzheimer’s disease. In the present study, the effects of vitamin E in the form of tocotrienol-rich fraction (TRF and alpha-tocopherol (α-TCP in modulating the glutamate receptor and neuron injury markers in an in vitro model of oxidative stress in neural-derived embryonic stem (ES cell cultures were elucidated. A transgenic mouse ES cell line (46C was differentiated into a neural lineage in vitro via induction with retinoic acid. These cells were then subjected to oxidative stress with a significantly high concentration of glutamate. Measurement of reactive oxygen species (ROS was performed after inducing glutamate excitotoxicity, and recovery from this toxicity in response to vitamin E was determined. The gene expression levels of glutamate receptors and neuron-specific enolase were elucidated using real-time PCR. The results reveal that neural cells derived from 46C cells and subjected to oxidative stress exhibit downregulation of NMDA, kainate receptor, and NSE after posttreatment with different concentrations of TRF and α-TCP, a sign of neurorecovery. Treatment of either TRF or α-TCP reduced the levels of ROS in neural cells subjected to glutamate-induced oxidative stress; these results indicated that vitamin E is a potent antioxidant.

K-Ar ages, paleomagnetism, and geochemistry of the South Auckland volcanic field, North Island, New Zealand

International Nuclear Information System (INIS)

Briggs, R.M.; Okada, T.; Itaya, T.; Shibuya, H.; Smith, I.E.M.

1994-01-01

The South Auckland volcanic field is one of the Pliocene-Quaternary intraplate basaltic fields in northern North Island. It consists of at least 97 monogenetic volcanic centres covering an area of c. 300 km 2 , 38 km south of Auckland. Fifty-nine of the volcanic centres are characterised by mainly magmatic or effusive activity that constructed scoria cones and lava flows, while 38 are mainly phreatomagmatic or explosive that produced tuff rings and maars. Rock types consist of basanites, hawaiites, nepheline hawaiites, transitional basalts, and ol-tholeiitic basalts, with relatively minor amounts of nephelinites, alkali basalts, Q-tholeiitic basalts, and nepheline mugearites. Forty-three new K-Ar ages are presented, which range from 0.51 to 1.59 Ma, and show two peaks of activity at 0.6 and 1.3 Ma. Paleomagnetic determinations at 26 selected sites agree well with the paleomagnetic reversal time scale and support the K-Ar age data. Age data from each of the volcanic fields of Okete, Ngatutura, South Auckland, and Auckland, which constitute the Auckland intraplate basaltic province, show that they have developed within a time span of 0.3-1.1 Ma. After activity ceased in any particular field, a new field then developed 35-38 km to the north. These consistent time/space patterns indicate the possibility of a mantle source migrating northwards at c. 5 cm/yr. There is no correlation of rock composition with time, which is consistent with observations in the Northland intraplate province, but is not consistent with the formerly invoked rising diapir model. (author). 30 refs., 8 figs., 3 tabs

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

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Godfrey Baldacchino

2010-05-01

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.

Facilitation of granule cell epileptiform activity by mossy fiber-released zinc in the pilocarpine model of temporal lobe epilepsy.

Science.gov (United States)

Timofeeva, Olga; Nadler, J Victor

2006-03-17

Recurrent mossy fiber synapses in the dentate gyrus of epileptic brain facilitate the synchronous firing of granule cells and may promote seizure propagation. Mossy fiber terminals contain and release zinc. Released zinc inhibits the activation of NMDA receptors and may therefore oppose the development of granule cell epileptiform activity. Hippocampal slices from rats that had experienced pilocarpine-induced status epilepticus and developed a recurrent mossy fiber pathway were used to investigate this possibility. Actions of released zinc were inferred from the effects of chelation with 1 mM calcium disodium EDTA (CaEDTA). When granule cell population bursts were evoked by mossy fiber stimulation in the presence of 6 mM K(+) and 30 microM bicuculline, CaEDTA slowed the rate at which evoked bursting developed, but did not change the magnitude of the bursts once they had developed fully. The effects of CaEDTA were then studied on the pharmacologically isolated NMDA receptor- and AMPA/kainate receptor-mediated components of the fully developed bursts. CaEDTA increased the magnitude of NMDA receptor-mediated bursts and reduced the magnitude of AMPA/kainate receptor-mediated bursts. CaEDTA did not affect the granule cell bursts evoked in slices from untreated rats by stimulating the perforant path in the presence of bicuculline and 6 mM K(+). These results suggest that zinc released from the recurrent mossy fibers serves mainly to facilitate the recruitment of dentate granule cells into population bursts.

Sm-Nd, Rb-Sr and K-Ar age constraints of the El Molle and Barroso plutons, western Sierra de San Luis, Argentina

International Nuclear Information System (INIS)

Sato, A.M.; Gonzalez, P.D; Petronilho, L.A; Llambias, E.J.; Varela, R; Basei, M.A.S

2001-01-01

Within the Early Paleozoic Famatinian orogeny of Southern Sierras Pampeanas (Sierra de San Luis and Sierra de Cordoba), the post-orogenic granitoids are characterized by circular intrusions. The published Rb-Sr and K-Ar ages from plutons in the Sierra de San Luis range between 408 and 320 Ma (see synthesis in Llambias et al., 1998). The El Molle and Barroso plutons (Sims et al., 1997; Gonzalez and Sato, 2000) are the two main exposures of a post-orogenic intrusive complex located in the western area of the Sierra de San Luis basement. They also exhibit an overall circular map view of almost 8 km in diameter, and are emplaced in a metamorphic complex developed through pre-Famatinian (Proterozoic? to Early Paleozoic) to Famatinian (Early Paleozoic) orogenies (Gonzalez and Llambias, 1998; von Gosen and Prozzi, 1998). We are carrying out isotopic datings of the El Molle and Barroso plutons in order to contribute to the understanding of the magmatic and metamorphic evolution of the final stages of the Famatinian orogenic cycle in the Sierra de San Luis. The first results of the Sm-Nd, Rb-Sr and K-Ar dates are here presented (au)

Elma Bahçelerinde Bazı Önemli Zararlılara Karşı Azadirachtin ve Kaolin Uygulamalarının Etkisi

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Nazım KÜÇÜKBALLI

2018-02-01

Full Text Available Elma bahçelerinde ekonomik kayıplara neden olan birçok hastalık, zararlı ve yabancıot türü bulunmaktadır. Zararlılar içinde elma içkurdu, kırmızıörümcekler ve yaprakbitleri ana zararlılar arasında yer almaktadır. Elma üretiminin yoğun yapıldığı Isparta ilinde özellikle yağışlı geçen yıllarda yılda 20 kezden daha fazla ilaçlama yapıldığı bilinmektedir. Bu çalışmada söz konusu zararlılara karşı çevre ve yararlılara fazla etkisi olmadığı bilinen azadirachtin ve kaolinin etkisi 2015 yılında incelenmiştir. Denemeler Süleyman Demirel Üniversitesi, Ziraat Fakültesi bünyesinde bulunan 5 ve 2 dekarlık iki elma bahçesinde yürütülmüştür. Her bahçe dört parsele ayrılmış ve her bir parsele kaolin, azadirachtin (neem, karşılaştırma ilacı olarak chlorpyrifos-ethyl ve Kontrol parseline de su püskürtme şeklinde uygulanmıştır. Denemeler tesadüf blokları deneme desenine göre kurulmuş olup, her tekerrürde 8 ağaç olacak şekilde 6 tekerrürlü olarak düzenlenmiştir. Her hafta, her bir ağaçtan 40 yaprak örneği alınarak Tetranychus urticae, Pananychus ulmi, Aphis pomi ve Dysaphis plantaginea sayımları yapılmıştır. Elma içkurdu zararı ise hasat zamanında ağaç üzerinde ve yere düşen meyvelerde bulaşma oranına göre belirlenmiştir. Çalışma sonucunda yaprakbitine karşı en etkili Chlorpyrifos-ethyl bulunmuş, bunu kaolin ve neem izlemiştir. Preparatlar kırmızıörümceklere karşı benzer etki gösterirken elma içkurdu bulaşma oranları sırasıyla, kontrol parselinde %49.99, kaolin parselinde %42.27, neem parselinde %41.20 ve chlorpyrifos-ethyl parselinde %31.23 olmuştur.

Synthesis and enantiopharmacology of new AMPA-kainate receptor agonists

DEFF Research Database (Denmark)

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

1999-01-01

. 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...... at doses as low as 3.2 nmol/mouse. On the basis of the above-reported results we prepared and tested the enantiomers of CIP-A and CIP-B, obtained by reacting (S)-3,4-didehydroproline and (R)-3,4-didehydroproline, respectively, with ethoxycarbonylformonitrile oxide. In all the tests the S-form, CIP...

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

Science.gov (United States)

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

2017-08-01

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 K 2 O laser energy, with a detection limit of 88 ppm and 20% of error at 2400 ppm of K 2 O. 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 K 2 O. Error assessments using obtained calibration models indicate that a 4 Ga rock with 3000 ppm K 2 O 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.

Palaeomagnetism and K-Ar age of Mesozoic and Cenozoic igneous rocks from Antarctica

International Nuclear Information System (INIS)

Valencio, D.A.; Mendia, J.E.; Vilas, J.F.

1979-01-01

A new analysis of palaeomagnetic data for igneous rocks from Deception Island, 25 de Mayo Island (King George Island) and Cape Spring, are given. K-Ar age determinations indicate that most of the igneous samples from 25 de Mayo Island included in the palaeomagnetic study are of Late Mesozoic/Early Tertiary age. The significance of these palaeomagnetic-radiometric data on the hypothesis of oroclinal bending of the Antarctic Peninsula and on the apparent polar movement of Antarctica is discussed. The positions of palaeomagnetic poles for the Andean igneous complex indicate that there has not been any apparent post-Late Cretaceous/Early Tertiary oroclinal bending in the Antarctic Peninsula from 74 0 S to 62 0 S. A comparison of the positions of palaeomagnetic poles for Antarctica and Australia suggests that the direction of apparent polar movement relative to Antarctica reversed after the Miocene. (Auth.)

Ion Channels and Zinc: Mechanisms of Neurotoxicity and Neurodegeneration

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Deborah R. Morris

2012-01-01

Full Text Available Ionotropic glutamate receptors, such as NMDA, AMPA and kainate receptors, are ligand-gated ion channels that mediate much of the excitatory neurotransmission in the brain. Not only do these receptors bind glutamate, but they are also regulated by and facilitate the postsynaptic uptake of the trace metal zinc. This paper discusses the role of the excitotoxic influx and accumulation of zinc, the mechanisms responsible for its cytotoxicity, and a number of disorders of the central nervous system that have been linked to these neuronal ion channels and zinc toxicity including ischemic brain injury, traumatic brain injury, and epilepsy.

New K-Ar ages of altered rocks from Paramillos Sur and Norte: Interpretation of the results; Nuevas edades K-Ar de las rocas alteradas de Paramillos Sur y Norte: Interpretacion de los resultados

Energy Technology Data Exchange (ETDEWEB)

Koukharsky, Magdalena; Brodtkorb, Alejo [Buenos Aires Univ. (Argentina). Facultad de Ciencias Exactas y Naturales; Munizaga, Francisco [Chile Univ., Santiago (Chile). Dept. de Geologia

1998-07-01

The whole-rock K-Ar dates from porphyry copper prospects of Paramillos Sur (phyllic and potasic alteration zones) and Paramillos Norte (propilitic zone) are reported. Radiometric data yielded 17,8 {+-} 0,9 Ma, 15,8 {+-} 1,0 Ma and 15,2 {+-} 0,5 Ma in Paramillos Sur, and 17,3 {+-} 0,7 Ma in Paramillos Norte, which can be added to an previously reported age of 16,4 {+-} 0,3 Ma. These data are in agreement with isotopic ages from non altered or non mineralized magmatic rocks of the region. When the isotopic ages and petrographic characteristics of the dated rocks are considered, two alteration-mineralization events are suggested for Paramillos Sur prospect. However this possibility needs to be confirmed by means of future studies, in view of the reduced interval between these events when compared with the analytical errors. (author)

Çok Etmenli Sistemlerde NetLogo İle Karınca Kolonisi Optimizasyonu

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Mustafa Tüker

2013-02-01

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.

New K-Ar constraints on the onset of subsidence in the Canning Basin, Western Australia

International Nuclear Information System (INIS)

Shaw, R.D.; Tyler, I.M.; Griffin, T.J.; Webb, A.

1992-01-01

Structural mapping and reconnaissance K-Ar studies have helped to delineate and date the latest deformational stages (D4 and D5) in the King Leopold Orogen, to the north of the Canning Basin. The dates have been determined for schists selected from both contractional shear zones and from rocks metamorphosed to the lower greenschist facies during the final phase of basement deformation. These dates imply that the basement-deforming event started in the latest Precambrian to earliest Cambrian (ca 560 Ma), and that tectonism recurred in the latest Cambrian to earliest Ordovician (ca 500 Ma). The final contractional deformation is slightly older than the oldest-known sedimentary rocks in the basin (latest Tremadoc), and helps to define the time that basin subsidence started. 23 refs., 3 tabs., 2 figs

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

Science.gov (United States)

2012-05-01

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

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

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Nihat YILMAZ

2014-01-01

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.

Glutamatergic mechanisms for speed control and network operation in the rodent locomotor CPG

DEFF Research Database (Denmark)

Talpalar, Adolfo E.; Kiehn, Ole

2010-01-01

in mammals have produced conflicting results regarding the necessity and role of the different ionotropic glutamate receptors (GluRs) in the CPG function. Here, we use electrophysiological and pharmacological techniques in the in vitro neonatal mouse lumbar spinal cord to investigate the role of a broad...... mechanisms acting at various network levels. AMPA and kainate receptors are necessary for generating the highest locomotor frequencies. For coordination, NMDARs are more important than non-NMDARs for conveying the rhythmic signal from the network to the motor neurons during long-lasting and steady locomotor...

Discordant K-Ar ages between hornblende and biotite from the Tanzawa tonalitic pluton in the southern Fossa Magna, central Japan

International Nuclear Information System (INIS)

Sato, Kohei; Shibata, Ken; Uchiumi, Shigeru

1986-01-01

K-Ar ages were determined for hornblende and biotite in three tonalites from the Tanzawa pluton in the southern Fossa Magna, central Japan. The two minerals show discordant ages of 10.1 and 10.7 Ma for hornblende and 4.6 - 5.1 Ma for biotite. The age data and field evidence indicate that the pluton was emplaced in the Tanzawa Group in Middle Miocene time and its slow cooling (ca. 50 deg C/Ma in average) resulted in younger ages of boitites than hornblendes due to lower closure temperature for biotite. (author)

Mobilā reklāma kā mobilo priekšapmaksas sarunu karšu reklāmas komunikācijas instruments: Y paaudzes radītās iespējas

OpenAIRE

Daudze, Anita

2009-01-01

Bakalaura darba temats ir „Mobilā reklāma kā mobilo priekšapmaksas sarunu karšu reklāmas komunikācijas instruments: Y paaudzes radītās iespējas”. Pētījuma problēma ir mobilās reklāmas piemērotība komunikācijai ar Y paaudzes pārstāvjiem – mobilo priekšapmaksas sarunu karšu lietotājiem. Darba teorētiskais pamatojums balstīts uz Y paaudzes jēdziena izpratni, mobilā telefona kā reklāmas komunikācijas kanāla aplūkošanu, kā arī mobilā mārketinga un reklāmas pamatprincipu izklāstu. Darbā izman...

Anticonvulsant effect of AMP by direct activation of adenosine A1 receptor.

Science.gov (United States)

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

2013-12-01

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. © 2013.

The Use of Adenosine Agonists to Treat Nerve Agent-Induced Seizure and Neuropathology

Science.gov (United States)

2016-09-01

not be cited for purposes of advertisement . REPORT DOCUMENTATION PAGE Form Approved OMB No. 0704-0188 Public reporting burden for this...survivability. That was an important step to clinical relevancy as it was feared that ADO’s depression of cardiovascular output would exacerbate...kainate, adenosine and neuropeptide Y receptors. Neurochemical Research. 28: 1501-1515. 23. Bjorness, T. E. & R. W. Greene . 2009. Adenosine and sleep

Münih’te Tüketime Sunulan Koyun ve Keçi Peynirlerinde İnek Sütü Karışımının Enzim-İmmünolojik Sandwich-EIA Testi ile Araştırılması

Directory of Open Access Journals (Sweden)

Özer Ergün

2015-02-01

Full Text Available Münih piyasasında market ve dükkanlarda satışa sunulan yerli veya ithal koyun keçi peynirlerinden 48 adet toplanmış ve Enzim-immünolojik Sandwich-EIA testi ile inek sütü karışımı yönünden incelenmiştir. Numunelerin 27 tanesinde (%56’da inek sütü karışımı tespit edilmiş olup uygulanan testin hassasiyeti %1’dir.

Batı Karadeniz Bölgesi Düzce Ekolojik Koşulları Altında Bazı Ekmeklik Buğday Çeşitlerinin Yaprak Hastalıklarına Karşı Reaksiyonlarının Belirlenmesi

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Nedim Altın

2017-07-01

Full Text Available Bu çalışma, Batı Karadeniz Bölgesi Düzce ili ekolojik koşulları altında 19 adet ekmeklik buğday çeşidinin doğal enfeksiyon koşullarında yaprak hastalıklarına karşı reaksiyonlarının belirlenmesi amacıyla yürütülmüştür. Deneme tesadüf blokları deneme desenine uygun olarak 4 tekerrürlü olarak kurulmuş ve ekim işlemi 17.11.2015 tarihinde yapılmıştır. Hastalık gözlemleri ile ilgili çalışmalar; Septoria tritici etmeninin neden olduğu septorya yaprak lekesi hastalığı için süt olum dönemi başlangıcında, Puccinia striiformis etmeninin neden olduğu Sarı Pas hastalığı için çiçeklenme dönemi sonunda, Puccinia recondita etmeninin neden olduğu Kahverengi Pas için süt olum dönemi başlangıcında yapılmıştır. Tarla koşullarında doğal bulaşıklığa göre yapılan değerlendirme sonucunda hastalık oranları belirlenmiştir. Belirlenen hastalık şiddetine göre, septorya yaprak lekesi hastalığına karşı en hassas çeşidin % 60 hastalık şiddeti ile “Bereket”, en tolerant çeşidin ise %14 ile “Aslı” olduğu, Sarı Pas hastalığına karşı en hassas çeşidin %45,4 ile “Tekirdağ”, en tolerant çeşidin %0,6 ile “Midas” olduğu ve Kahverengi Pas hastalığına karşı ise en hassas çeşidin %22 ile “Tahirova” en tolerant çeşidin ise %0,2 ile “Midas” olduğu belirlenmiştir. Çalışma sonucunda elde edilen verilere göre septorya yaprak lekesi hastalığına karşı Aldane, Aslı, Konya 2002, Köprü, Masaccio ve Tosunbey, Sarı Pas hastalığına karşı Aslı, Esperia, Kate A1, Karasunya Odeska, Masaccio ve Midas, Kahverengi Pas hastalığına karşı ise Aldane, Aslı, Bereket, Köprü, Masaccio, Midas ve Tekirdağ çeşitlerinin ileride yapılacak ıslah çalışmaları için ümitvar olduğu görülmüştür.

K-Ar chronological study of the quaternary volcanic activity in Shin-etsu Highland

International Nuclear Information System (INIS)

Kaneko, Takayuki; Shimizu, Satoshi; Itaya, Tetsumaru.

1989-01-01

In order to clarify the temporal and spatial patterns in arc volcanism, 55 K-Ar ages of volcanic rocks from 17 volcanoes in Shin-etsu Highland, central Japan were determined. In addition, life spans, volume of erupted materials and eruption rates of each volcano were estimated. Graphical analysis demonstrates that volume of ejecta varies proportionately with both life span and eruption rate, and that there is no significant correlation between eruption rate and distance from the volcanic front. The life span of each volcano in this Highland is less than 0.6 m.y. In the central Shiga and southern Asama area, the volcanism started at 1 Ma and is still active. However the former had a peak in the activity at around 0.5 Ma, while the latter is apparently most intense at present. Northern Kenashi area has the volcanism without peak in 1.7 - 0.2 Ma, though the activity within a volcanic cluster or chain in central Japan lasts generally for 1 m.y. or less with a peak. (author)

From the immortal regulator to the wanna-be dictator: the specters of the father in Saatleri Ayarlama Enstitüsü and kar

OpenAIRE

Aslan, Adile

2012-01-01

This study brings two texts of modern Turkish literature together, Saatleri Ayarlama Enstitüsü [The Clock-Setting Institute] and Kar (Snow) in order to show their dialogue with each other through the issues of modernization/westernization, the father complex, East-West division. Close textual analysis shows that the former is a model for the latter, which Orhan Pamuk develops in accordance with the changes in narrative techniques, developments in literary movements and unfolding of events in ...

Estrogen receptor and progesterone receptor status of breast cancer patients of eastern India: A multi-institutional study.

Science.gov (United States)

Chatterjee, Koushik; Bhaumik, Gautam; Chattopadhyay, Bhargab

2018-01-01

There is a paucity of any significant data on the estrogen receptor (ER) and progesterone receptor (PR) status of breast cancer patients from the eastern part of India. This study aims to document the ER and PR status of breast cancer patients in the eastern Indian population, as catered by two premier tertiary care hospitals in Kolkata. All breast cancer patients registered between January 1, 2013 and December 31, 2015, in the Departments of Oncology, of IPGMER and SSKM Hospitals and R. G. Kar Medical College and Hospital, Kolkata, who had at least undergone a core biopsy or surgery, were analyzed retrospectively for documentation of their ER and PR status, using the 2010 American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) interpretation guidelines. Over a period of 3 years, a total of 927 patients were included for the study. A total of 825 (89%) patients had their ER and PR data available for evaluation. ER and PR positive was seen in 312 (37.82%) patients, ER and PR negative in 399 (48.36%) patients, ER positive and PR negative in 71 (8.6%) patients, and ER negative and PR positive results was found in 43 (5.21%) patients. This is the first multi-institutional documentation of ER and PR status from eastern India, having a modest number of patients and one of the earliest documentations using the latest ASCO/CAP interpretation guidelines. These findings resemble the data from the south and also reiterate the fact that majority of the Indian breast cancer patients are still ER and PR negative in spite of the changes in the interpretation guidelines.

Glutamate as a neurotransmitter in the brain: review of physiology and pathology.

Science.gov (United States)

Meldrum, B S

2000-04-01

Glutamate is the principal excitatory neurotransmitter in brain. Our knowledge of the glutamatergic synapse has advanced enormously in the last 10 years, primarily through application of molecular biological techniques to the study of glutamate receptors and transporters. There are three families of ionotropic receptors with intrinsic cation permeable channels [N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and kainate]. There are three groups of metabotropic, G protein-coupled glutamate receptors (mGluR) that modify neuronal and glial excitability through G protein subunits acting on membrane ion channels and second messengers such as diacylglycerol and cAMP. There are also two glial glutamate transporters and three neuronal transporters in the brain. Glutamate is the most abundant amino acid in the diet. There is no evidence for brain damage in humans resulting from dietary glutamate. A kainate analog, domoate, is sometimes ingested accidentally in blue mussels; this potent toxin causes limbic seizures, which can lead to hippocampal and related pathology and amnesia. Endogenous glutamate, by activating NMDA, AMPA or mGluR1 receptors, may contribute to the brain damage occurring acutely after status epilepticus, cerebral ischemia or traumatic brain injury. It may also contribute to chronic neurodegeneration in such disorders as amyotrophic lateral sclerosis and Huntington's chorea. In animal models of cerebral ischemia and traumatic brain injury, NMDA and AMPA receptor antagonists protect against acute brain damage and delayed behavioral deficits. Such compounds are undergoing testing in humans, but therapeutic efficacy has yet to be established. Other clinical conditions that may respond to drugs acting on glutamatergic transmission include epilepsy, amnesia, anxiety, hyperalgesia and psychosis.

Dopamine D4 receptor activation increases hippocampal gamma oscillations by enhancing synchronization of fast-spiking interneurons.

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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

Morphology and kainate-receptor immunoreactivity of identified neurons within the entorhinal cortex projecting to superior temporal sulcus in the cynomolgus monkey

Science.gov (United States)

Good, P. F.; Morrison, J. H.; Bloom, F. E. (Principal Investigator)

1995-01-01

Projections of the entorhinal cortex to the hippocampus are well known from the classical studies of Cajal (Ramon y Cajal, 1904) and Lorente de No (1933). Projections from the entorhinal cortex to neocortical areas are less well understood. Such connectivity is likely to underlie the consolidation of long-term declarative memory in neocortical sites. In the present study, a projection arising in layer V of the entorhinal cortex and terminating in a polymodal association area of the superior temporal gyrus has been identified with the use of retrograde tracing. The dendritic arbors of neurons giving rise to this projection were further investigated by cell filling and confocal microscopy with computer reconstruction. This analysis demonstrated that the dendritic arbor of identified projection neurons was largely confined to layer V, with the exception of a solitary, simple apical dendrite occasionally ascending to superficial laminae but often confined to the lamina dissecans (layer IV). Finally, immunoreactivity for glutamate-receptor subunit proteins GluR 5/6/7 of the dendritic arbor of identified entorhinal projection neurons was examined. The solitary apical dendrite of identified entorhinal projection neurons was prominently immunolabeled for GluR 5/6/7, as was the dendritic arbor of basilar dendrites of these neurons. The restriction of the large bulk of the dendritic arbor of identified entorhinal projection neurons to layer V implies that these neurons are likely to be heavily influenced by hippocampal output arriving in the deep layers of the entorhinal cortex. Immunoreactivity for GluR 5/6/7 throughout the dendritic arbor of such neurons indicates that this class of glutamate receptor is in a position to play a prominent role in mediating excitatory neurotransmission within hippocampal-entorhinal circuits.

Neurotransmitter modulation of extracellular H+ fluxes from isolated retinal horizontal cells of the skate

Science.gov (United States)

Molina, Anthony J A; Verzi, Michael P; Birnbaum, Andrea D; Yamoah, Ebenezer N; Hammar, Katherine; Smith, Peter J S; Malchow, Robert Paul

2004-01-01

Self-referencing H+-selective microelectrodes were used to measure extracellular H+ fluxes from horizontal cells isolated from the skate retina. A standing H+ flux was detected from quiescent cells, indicating a higher concentration of free hydrogen ions near the extracellular surface of the cell as compared to the surrounding solution. The standing H+ flux was reduced by removal of extracellular sodium or application of 5-(N-ethyl-N-isopropyl) amiloride (EIPA), suggesting activity of a Na+–H+ exchanger. Glutamate decreased H+ flux, lowering the concentration of free hydrogen ions around the cell. AMPA/kainate receptor agonists mimicked the response, and the AMPA/kainate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) eliminated the effects of glutamate and kainate. Metabotropic glutamate agonists were without effect. Glutamate-induced alterations in H+ flux required extracellular calcium, and were abolished when cells were bathed in an alkaline Ringer solution. Increasing intracellular calcium by photolysis of the caged calcium compound NP-EGTA also altered extracellular H+ flux. Immunocytochemical localization of the plasmalemma Ca2+–H+-ATPase (PMCA pump) revealed intense labelling within the outer plexiform layer and on isolated horizontal cells. Our results suggest that glutamate modulation of H+ flux arises from calcium entry into cells with subsequent activation of the plasmalemma Ca2+–H+-ATPase. These neurotransmitter-induced changes in extracellular pH have the potential to play a modulatory role in synaptic processing in the outer retina. However, our findings argue against the hypothesis that hydrogen ions released by horizontal cells normally act as the inhibitory feedback neurotransmitter onto photoreceptor synaptic terminals to create the surround portion of the centre-surround receptive fields of retinal neurones. PMID:15272044

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

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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.

Tempe Üretiminde Asetik ve Laktik Asit Ölçümleri İçin Kullanılan İki Metodun Karşılaştırılması

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Günnur Tuncel

2015-02-01

Full Text Available Soya fasulyesinin ıslatma aşamasında fermantasyona uğraması tempenin daha kaliteli olmasına neden olmaktadır. Böyle bir fermantasyonda meydana gelen Laktik ve Asetik asit miktarlarının ölçülmesinde çeşitli yöntemler kullanılmaktadır. Araştırmada bu asitler tek olarak ve karıştırılarak HPLC ve Enzimatik yöntemle ölçülmüş ve sonuçlar karşılaştırılmıştır. HPLC yöntemi ile mevcut Laktik ve Asetik asit miktarlarının %40’ı belirlenebilmiş, enzimatik yöntemde ise bu %70’e kadar çıkmıştır.

U-Pb, Pb-Pb, and K-Ar isotopic study and petrography of uraniferous phosphate-bearing rocks in the Thelon Formation, Dubawnt Group, Northwest Territories, Canada

International Nuclear Information System (INIS)

Miller, A.R.; Cumming, G.L.; Krstic, D.

1989-01-01

The Thelon Formation, uppermost unit of the Dubawnt Group, overlies a regionally extensive paleoweathered zone developed on a wide range of lithochronological units including formations in the lower Dubawnt Group. Authigenic uraniferous phosphate minerals, fluorapatite and goyazite, cementing Thelon conglomerate - sandstone and filling fractures in the underlying paleoweathered zone, were dated in an attempt to better constrain the age of Thelon sedimentation and diagenesis. The oldest age, 1720 ± 6 Ma, derived from phosphate-cemented sediments, is interpreted as a minimum age for diagenesis and therefore brackets initial Thelon sedimentation between emplacement of fluorite-bearing granites at 1753 Ma and authigenic phosphate cementation at 1720 Ma. Additional ages of 1685 ± 4 and 1647 Ma are interpreted as remobilization or subsequent cementation events. K-Ar ages on illite, 1386 ± 37 and 1266 ± 31 Ma, from the paleoweathered zone and basal conglomerate, respectively, are significantly younger than ages derived from coexisting phosphate. These K-Ar ages recorded hydrothermal events that may be related to processes associated with unconformity-type uranium mineralization at approximately 1400-1300 Ma. Ages from the Thelon Basin permit geochronologic correlations with the Athabasca and Hornby basins, long correlated on the basis of similarities in sedimentation, stratigraphy, and tectonic setting

K/Ar dating of Neogene volcanic activity in Hungary: Experimental technique, experiences and methods of chronological studies

International Nuclear Information System (INIS)

Balogh, Kadosa

1985-01-01

Construction and essential parameters of an argon extraction line and magnetic mass spectrometer for K/Ar dating are descibed. Experiences of chronoligical studies on Miocene intermediate and acid lavas and tuffs as well as on Pliocene basalts are summarized. Great attention is paid to the ascertainment of the geological reliability of radiometric ages. Experiences concerning the frequency, character and reason of geological errors for the different rock types are reviewed and methods of sample selection used for the recognition of unreliable ages are outlined. The isochron methods are used mostly for dating Pliocene basalts. The limitations of the pure mathematical treatment of the experimental data are pointed out and geological interpretation of the isochron ages is discussed. The uncertainty of error estimation of isotopic ratio and potassium concentration measurements is emphasized. (author)

K-Ar dating celadonite: A contribution to timing of a very low-grade metamorphism in the Central Andes of Chile

International Nuclear Information System (INIS)

Belmar, M; Schmidt, S.; Frey, M

2001-01-01

Clay minerals have been used in several studies to date very low-grade metamorphism processes and hydrothermal episodes. The technique of using the K-Ar isotopic dating was demonstrated by many authors (e.g. Hunziker et al., 1986; Clauer et al., 1995; Kirschner et al 1995; Zhao et al., 1997; Glasmacher et al., 2001). White mica and illitic materials of different size are usually analysed, whereasceladonite mineral with high potassium content has been low developed and few data are published. Successful dating of continental Andean celadonite could mean that is possible to date the very low-grade metamorphism (zeolites facies) in which celadonites are very often observed (au)

The K-Ar ages and their stratigraphic interpretation of the Cheju Island volcanics, Korea

International Nuclear Information System (INIS)

Tamanyu, Shiroh

1990-01-01

K-Ar datings were performed on the 5 volcanic rock samples of the Cheju Island Korea. The results of these datings are as follows. Hallasan trachyte; 0.07±0.01 Ma, Paeknoktam Hawaiite; 0.47±0.07 Ma, Hallasan Hawaiite; 0.52±0.03 Ma, Sogwip'o Hawaiite; 0.55±0.04 Ma, P'yosonri Alkali Basalt; 0.31±0.04 Ma. Among them, only Paeknoktam Hawaiite seems to be grown older by the excess Argon. But, all other ages can be interpreted respectively as the essential ages of their eruptions. Based on these newly obtained age data and previously reported age data, the volcanism of this island can be roughly divided into three stages as follows. I stage; early Pleistocene basic-intermediate volcanism. II stage; middle Pleistocene basic volcanism. III stage; late Pleistocene-Holocene basic-intermediate volcanism. And also, the age of Sogwip'o Formation which is famous of bearing the index molluscan fossil; Turritella saishuensis Yokoyama, must be correlated to early Pleistocene. (author)

K-Ar geochronology and palaeomagnetism of volcanic rocks in the lesser Antilles island arc

International Nuclear Information System (INIS)

Briden, J.C.; Rex, D.C.; Faller, A.M.; Tomblin, J.F.

1979-01-01

K-Ar age determinations on rocks and minerals from 95 locations in the Lesser Antilles. An age range of 38 - 10 million years was found for the outer arc (Limestone Caribbees) but less than 7.7 million years in the inner arc (Volcanic Caribbees). From Martinique southwards the two arcs are superimposed. These age ranges fit between discontinuities in sea floor spreading in the North Atlantic at about 38 and 9 million years and a causal connection between spreading change and relocation of arc volcanicity is suggested. Paleomagnetic directions at 108 localities in 10 islands fall into normal and reversed groups with 6 sites intermediate and 5 indeterminate. The mean dipole axis is within 2% of the present rotation axis. The data generally agrees with the established geomagnetic polarity time scale but there is some suggestion of a normal polarity event at about 1.18 million years. The paleomagnetic data suggest that in the past 10 million years the Lesser Antilles have not changed their latitude or geographical orientation and the geomagnetic field has averaged that of a central axial dipole. (author)

K-Ar dating on acidic rocks from the Western Aizu District, Fukushima Prefecture

International Nuclear Information System (INIS)

Shimada, Ikuro; Ueda, Yoshio

1979-01-01

K-Ar age determinations were carried out on twelve samples of various acidic rocks (six volcanic rocks, two pyroclastics and four granitic rocks) which were obtained from the western part of Aizu district. The district studied is one of the important acidic petrographic provinces in the Green tuff region of Northeast Japan, and is widely covered by the acidic volcanic rocks and pyroclastics of Neogene period. The ages of six volcanic rocks range from 8 to 23 m.y., and they are generally correlated to the stratigraphic units of the Neogene in Northeast Japan. Dating results on four granitic rocks from the Tagokura granitic body showed the age range of 39 to 65 m.y., corresponding to the Late Cretaceous to Eocene. A sample of dacitic welded tuff from the Miyako River area gave an age of 44 m.y. It is pointed out that the welded tuff may be correlated to the Late Cretaceous to Paleogene acidic igneous rocks such as Nohi rhyolites, Asahi rhyolites, Tagawa acidic rocks and others, on the basis of the age and lithofacies of the rock. However, further geological and geochronological data are necessary to settle the problem. (author)

40Ar/39Ar and K-Ar age constraints on the timing of regional deformation, south coast of New South Wales, Lachlan Fold Belt: problems and implications

International Nuclear Information System (INIS)

Fergusson, C.L.; Phillips, D.

2001-01-01

Four slate samples from subduction complex rocks exposed on the south coast of New South Wales, south of Batemans Bay, were analysed by K-Ar and 40 Ar/ 39 Ar step-heating methods, One sample contains relatively abundant detrital muscovite flakes that are locally oblique to the regional cleavage in the rock, whereas the remaining samples appear to contain sparse detrital muscovite. Separates of detrital muscovite yielded plateau ages of 505 + 3 Ma and 513 + 3 Ma indicating that inheritance has not been eliminated by metamorphism and recrystallisation. Step-heating analyses of whole-rock chips from all four slate samples produced discordant apparent age spectra with 'saddle shapes' following young apparent ages at the lowest temperature increments. Elevated apparent ages associated with the highest temperature steps are attributed to the presence of variable quantities of detrital muscovite ( 40 Ar/ 39 Ar integrated ages of ca 455Ma, which are some 15-30 million years older than K-Ar ages for the same samples. These discrepancies suggest that the slates have also been affected by recoil loss/redistribution of 39 Ar, Ieading to anomalously old 40 Ar/ 39 Ar ages. Two other samples, from slaty tectonic melange and intensely cleaved slate, yielded average 40 Ar/ 39 Ar integrated ages of ca 424Ma, which are closer to associated mean K-Ar ages of 423 + 4Ma and 409 + 16Ma, respectively. Taking into account the potential influences of recoil loss/redistribution of 39 Ar and inheritance, the results from the latter samples suggest a maximum age of ca 440 Ma for deformation/metamorphism. The current results indicate that recoil and inheritance problems may also have affected whole-rock 40 Ar/ 39 Ar data reported from other regions of the Lachlan Fold Belt. Therefore, until these effects are adequately quantified, models for the evolution of the Lachlan Fold Belt, that are based on such whole-rock 40 Ar/ 39 Ar data, should be treated with caution. Copyright (2001) Geological

Bazı Dondurma Karışımlarının Isıl İletkenliklerinin Sıcaklıkla Değişiminin Belirlenmesi

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Seher Kumcuoğlu

2015-02-01

Full Text Available Bu çalışmada geleneksel ürünlerimizden olan ve modern bir işletmede sürekli sistemde üretilen Maraş usulü ve kaymaklı dondurma karışımlarının  -30 °C ile +30°C sıcaklık aralığındaki  ısıl iletkenlik değerleri çizgisel ısı kaynaklı prob yöntemi kullanılarak deneysel olarak belirlenmiştir. Kalibrasyon materyali olarak % 0.3 agar içeren saf su  kullanılmıştır. Optimum ölçüm koşulları; değişik elektriksel akım, işlem süreleri ve örnek boyutları kullanılarak tespit edilmiştir. Örneklerin donmuş durumlarındaki ısıl iletkenlik değerlerinin donmamış durumlarına ait ısıl iletkenlik değerlerinden daha yüksek olduğu belirlenmiştir.  Maraş usulü dondurma karışımının ısıl iletkenliği 25 °C’de 0.494 W/m.K, –30 °C’de 1.051 W/m.K; kaymaklı dondurma karışımının ısıl iletkenliği ise 25 °C’de 0.452 W/m.K, –30 °C’de 0.993 W/m.K  olarak ölçülmüştür. Örneklerin ısıl iletkenlik değerlerinin bileşim ve sıcaklıkla değişim gösterdiği saptanmıştır.

New K-Ar ages of altered rocks from Paramillos Sur and Norte: Interpretation of the results

International Nuclear Information System (INIS)

Koukharsky, Magdalena; Brodtkorb, Alejo; Munizaga, Francisco

1998-01-01

The whole-rock K-Ar dates from porphyry copper prospects of Paramillos Sur (phyllic and potasic alteration zones) and Paramillos Norte (propilitic zone) are reported. Radiometric data yielded 17,8 ± 0,9 Ma, 15,8 ± 1,0 Ma and 15,2 ± 0,5 Ma in Paramillos Sur, and 17,3 ± 0,7 Ma in Paramillos Norte, which can be added to an previously reported age of 16,4 ± 0,3 Ma. These data are in agreement with isotopic ages from non altered or non mineralized magmatic rocks of the region. When the isotopic ages and petrographic characteristics of the dated rocks are considered, two alteration-mineralization events are suggested for Paramillos Sur prospect. However this possibility needs to be confirmed by means of future studies, in view of the reduced interval between these events when compared with the analytical errors. (author)

K-AR chronology of the ultimate activity of Piton des Neiges volcano, Reunion Island, Indian Ocean

International Nuclear Information System (INIS)

Gillot, P.Y.; Nativel, P.; Paris-11 Univ., 91 - Orsay

1982-01-01

Potassium-argon measurements were made on 17 samples from the ultimate stage of activity of the Piton des Neiges volcano, which corresponds to a differentiated series with lavas varying from basalt to quartz trachyte. Samples were selected as a function of their stratographic position and their representativity of magmatic evolution. The technology used to date young volcanic rocks (Pleistocene) by K-Ar is described and discussed because of its reliability in the analysis of modern lavas and because of the agreement of the results with the available stratigraphic control. The data, together with those previously obtained by McDougall, yield ages ranging between 330.000 and 30.000 years, with two mainly effusive periods separated by a phase of instability of chiefly explosive volcanism around 190.000 to 150.000 years ago. A rough correlation between the chemical evolution of the lavas and time is established. (orig./ME)

K-Ar ages of the low-grade metamorphic rocks in the Altar massif, Northwest Sonora, Mexico

International Nuclear Information System (INIS)

Hayama, Yoshikazu; Shibata, Ken; Takeda, Hideo.

1984-01-01

The K-Ar ages of low-grade regional metamorphism, granodiorite intrusion and its contact metamorphism were studied in the Altar massif of Northwest Sonora, Mexico. The results gave the ages of 55 Ma for metamorphic hornblende and 15 to 17 Ma for mica of metamorphic rocks and granodiorite. About the meaning of these discordant ages and the too young ages of 15 to 17 Ma against the previously presented data, we pointed out the following two possibilities; 1) the contact effect of the Miocene granodiorite on the regional metamorphic rocks of the Laramide phase, 2) both regional metamorphism and granodiorite intrusion took place during the Laramide phase, whereas the young ages, 15 to 17 Ma, show the time of temperature release after the low-angle thrust movement, which is well known in the hinterland of the Sevier orogenic belt in Nevada and Utah. (author)

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

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Kristina Rutkovska

2016-12-01

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

K-Ar ages of the Nyuto-Takakura volcanic products, southern part of the Sengan geothermal area, northeast Japan

International Nuclear Information System (INIS)

Suto, Shigeru; Uto, Kozo; Uchiumi, Shigeru

1990-01-01

The K-Ar age determination of the volcanic rocks from the Nyuto-Takakura volcano group, northeast Japan, was carried out. Nyuto-Takakura volcanoes are situated in the southern part of the Sengan geothermal area. And the Young Volcanic Rocks in the area were already divided into the Early stage volcanics (erupted in Matsuyama reversed epoch or more older epoch) and the Later stage volcanics (erupted in Brunhes normal epoch) by accumulated paleomagnetic and K-Ar age data. The results in this study are as follows; Nyuto Volcano: 0.63±0.06, 0.36±0.07 Ma, Sasamoriyama Volcano: 0.09±0.07, 0.3±0.3 Ma, Marumori Lava Dome: 0.4±0.3, 0.31±0.12 Ma, Mikadoyama Lava Dome: <1 Ma, Takakurayama-Kotakakurayama volcano: 1.4±0.5, 1.0±0.4, <0.4 Ma. The determinated ages are concordant with the volcanic stratigraphy and the paleomagnetic data. Nyuto Volcano, Sasamoriyama Volcano, Marumori Lava Dome, Mikadoyama Lava Dome and upper part of the Takakurayama-Kotakakurayama Volcano are interpreted to be erupted in Brunhes normal epoch. The volcanic rocks from the lower part of the Takakurayama-Kotakakurayama volcano show normal magnetic polarity, so they are interpreted to be erupted in Jaramillo normal polarity event. The Early stage volcanics and the Later stage volcanics in the studied area are tend to be distributed in the central part and the outer part of the area, respectively. But the determinated ages in this study show that there is no simple migration of the eruption center of the volcanic rocks from the central part to the peripheral part. There is no geothermal manifestation or alteration area around the Sasamoriyama Volcano and the Marumori Lava Dome, which are the youngest volcanoes in the studied area. So it is concluded that there is no direct correlation between the eruption age of the nearest volcano and the geothermal activity. (author)

Geleneksel Mağazalar ile İnternetten Alışverişte Değer Algısı ve Satınalma Niyeti: Bir Karşılaştırma

OpenAIRE

Kaya, İsmail; Özen, Hilal

2012-01-01

ÖzetGünümüzde geleneksel dağıtım kanalları, internetten alışverişin getirdiği bazı tehditlerle karşı karşıya görünmektedirler. Müşterilerin değer algılarının bu iki kanal arasında anlamlı derecede farklılık gösterebilme ihtimali, tüketicilerin alışverişlerini birinden diğerine kaydırma ihtimalini de beraberinde getirmektedir. Temelde, geleneksel mağazalar ve sanal mağazaların tüketicilerinin değer algılamaları itibariyle ele alındığı bu çalışmada, özelde, değer algılamasının satın alma niyeti...

Phanerozoic polyphase orogenies recorded in the northeastern Okcheon Belt, Korea from SHRIMP U-Pb detrital zircon and K-Ar illite geochronologies

Science.gov (United States)

Jang, Yirang; Kwon, Sanghoon; Song, Yungoo; Kim, Sung Won; Kwon, Yi Kyun; Yi, Keewook

2018-05-01

We present the SHRIMP U-Pb detrital zircon and K-Ar illite 1Md/1M and 2M1 ages, suggesting new insight into the Phanerozoic polyphase orogenies preserved in the northeastern Okcheon Belt, Korea since the initial basin formation during Neoproterozoic rifting through several successive contractional orogens. The U-Pb detrital zircon ages from the Early Paleozoic strata of the Taebaeksan Zone suggest a Cambrian maximum deposition age, and are supported by trilobite and conodont biostratigraphy. Although the age spectra from two sedimentary groups, the Yeongwol and Taebaek Groups, show similar continuous distributions from the Late Paleoproterozoic to Early Paleozoic ages, a Grenville-age hiatus (1.3-0.9 Ga) in the continuous stratigraphic sequence from the Taebaek Group suggests the existence of different peripheral clastic sources along rifted continental margin(s). In addition, we present the K-Ar illite 1Md/1M ages of the fault gouges, which confirm fault formation/reactivation during the Late Cretaceous to Early Paleogene (ca. 82-62 Ma) and the Early Miocene (ca. 20-18 Ma). The 2M1 illite ages, at least those younger than the host rock ages, provide episodes of deformation, metamorphism and hydrothermal effects related to the tectonic events during the Devonian (ca.410 Ma) and Permo-Triassic (ca. 285-240 Ma). These results indicate that the northeastern Okcheon Belt experienced polyphase orogenic events, namely the Okcheon (Middle Paleozoic), Songrim (Late Paleozoic to Early Mesozoic), Daebo (Middle Mesozoic) and Bulguksa (Late Mesozoic to Early Cenozoic) Orogenies, reflecting the Phanerozoic tectonic evolution of the Korean Peninsula along the East Asian continental margin.

K-Ar ages of basalts from the Higashi-Matsuura district, northwestern Kyushu, Japan and regional geochronology of the Cenozoic alkaline volcanic rocks in eastern Asia

International Nuclear Information System (INIS)

Nakamura, Eizo; Campbell, I.H.; McDougall, I.

1986-01-01

Seven new K-Ar age determinations are presented on whole rock samples from alkaline and tholeiitic basalts of the Higashi-Matsuura district, northwestern Kyushu, Japan. Ages obtained range from 2.92 ± 0.03 Ma to 3.01 ± 0.04 Ma; these ages are essentially identical within analytical errors and yield an average age of 2.98 ± 0.03 Ma (Late Pliocene). When combined on an isochron type diagram the six Higashi-Matsuura samples give an age of 3.00 ± 0.03 Ma with the composition of nonradiogenic 40 Ar/ 36 Ar = 294.2 ± 2.0. The excellent age agreement of samples with different K contents and petrographic characteristics provides strong evidence that the tholeiitic and alkaline basalts were erupted for an extremely short period in the Higashi-Matsuura district. A basalt from Ogawashima Island yields a K-Ar age of 3.58 ± 0.04 Ma. This study and previously reported data support the hypothesis that alkaline volcanic activity in southwestern Japan commenced some 10 Ma ago and continued intermittently until recent times. Systematic variations of age and distribution of Cenozoic alkaline basalts are recognized in northeastern China, Korea and southwestern Japan. It is suggested that these variations are related to the initiation of 'mantle plumes' resulting from convection in the mantle wedge caused or controlled by subduction of the Kula and Pacific plates. (author)

Alternative Splicing of AMPA subunits in Prefrontal Cortical Fields of Cynomolgus Monkeys following Chronic Ethanol Self-Administration

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Glen eAcosta

2012-01-01

Full Text Available Functional impairment of the orbital and medial prefrontal cortex underlies deficits in executive control that characterize addictive disorders, including alcohol addiction. Previous studies indicate that alcohol alters glutamate neurotransmission and one substrate of these effects may be through the reconfiguration of the subunits constituting ionotropic glutamate receptor (iGluR complexes. Glutamatergic transmission is integral to cortico-cortical and cortico-subcortical communication and alcohol-induced changes in the abundance of the receptor subunits and/or their splice variants may result in critical functional impairments of prefrontal cortex in alcohol dependence. To this end, the effects of chronic ethanol self-administration on glutamate receptor ionotropic AMPA (GRIA subunit variant and kainate (GRIK subunit mRNA expression were studied in the orbitofrontal cortex (OFC, dorsolateral prefrontal cortex (DLPFC and anterior cingulate cortex (ACC of male cynomolgus monkeys. In DLPFC, total AMPA splice variant expression and total kainate receptor subunit expression were significantly decreased in alcohol drinking monkeys. Expression levels of GRIA3 flip and flop and GRIA4 flop mRNAs in this region were positively correlated with daily ethanol intake and blood ethanol concentrations averaged over the six months prior to necropsy. In OFC, AMPA subunit splice variant expression was reduced in the alcohol treated group. GRIA2 flop mRNA levels in this region were positively correlated with daily ethanol intake and blood ethanol concentrations averaged over the six months prior to necropsy. Results from these studies provide further evidence of transcriptional regulation of iGluR subunits in the primate brain following chronic alcohol self-administration. Additional studies examining the cellular localization of such effects in the framework of primate prefrontal cortical circuitry are warranted.

K-Ar ages of the Hiruzen volcano group and the Daisen volcano

International Nuclear Information System (INIS)

Tsukui, Masashi; Nishido, Hirotsugu; Nagao, Keisuke.

1985-01-01

Seventeen volcanic rocks of the Hiruzen volcano group and the Daisen volcano, in southwest Japan, were dated by the K-Ar method to clarify the age of volcanic activity in this region and the evolution of these composite volcanoes. The eruption ages of the Hiruzen volcano group were revealed to be about 0.9 Ma to 0.5 Ma, those of the Daisen volcano to be about 1 Ma to very recent. These results are consistent with geological and paleomagnetic data of previous workers. Effusion of lavas in the area was especially vigorous at 0.5+-0.1 Ma. It was generally considered that the Hiruzen volcano group had erupted during latest Pliocene to early Quaternary and it is older than the Daisen volcano, mainly from their topographic features. However, their overlapping eruption ages and petrographical similarities of the lavas of the Hiruzen volcano group and the Daisen volcano suggest that they may be included in the Daisen volcano in a broad sense. The aphyric andesite, whose eruption age had been correlated to Wakurayama andesite (6.34+-0.19 Ma) in Matsue city and thought to be the basement of the Daisen volcano, was dated to be 0.46+-0.04 Ma. It indicates that petrographically similar aphyric andesite erupted sporadically at different time and space in the San'in district. (author)

2-arylureidobenzoic acids

DEFF Research Database (Denmark)

Valgeirsson, Jon; Nielsen, Elsebet Ø; Peters, Dan

2003-01-01

A series of 2-arylureidobenzoic acids (AUBAs) was prepared by a short and effective synthesis, and the pharmacological activity at glutamate receptors was evaluated in vitro and in vivo. The compounds showed noncompetitive antagonistic activity at the kainate receptor subtype GluR5. The most potent...... on the benzoic acid moiety (ring A), whereas ring B tolerated a variety of substituents, but with a preference for lipophilic substituents. The most potent compounds had a 4-chloro substituent on ring A and 3-chlorobenzene (6b), 2-naphthalene (8h), or 2-indole (8k) as ring B and had IC(50) values of 1.3, 1...

In vivo microdialysis studies on the effects of decortication and excitotoxic lesions on kainic acid-induced calcium fluxes, and endogenous amino acid release, in the rat striatum

Energy Technology Data Exchange (ETDEWEB)

Butcher, S.P.; Lazarewicz, J.W.; Hamberger, A.

1987-11-01

The in vivo effects of kainate (1 mM) on fluxes of /sup 45/Ca2+, and endogenous amino acids, were examined in the rat striatum using the brain microdialysis technique. Kainate evoked a rapid decrease in dialysate /sup 45/Ca2+, and an increase in the concentration of amino acids in dialysates in Ca2+-free dialysates. Taurine was elevated six- to 10-fold, glutamate two- to threefold, and aspartate 1.5- to twofold. There was also a delayed increase in phosphoethanolamine, whereas nonneuroactive amino acids were increased only slightly. The kainic acid-evoked reduction in dialysate /sup 45/Ca2+ activity was attenuated in striata lesioned previously with kainate, suggesting the involvement of intrinsic striatal neurons in this response. The increase in taurine concentration induced by kainate was slightly smaller under these conditions. Decortication did not affect the kainate-evoked alterations in either dialysate /sup 45/Ca2+ or amino acids. These data suggest that kainate does not release acidic amino acids from their transmitter pools located in corticostriatal terminals.

Metabotropic action of postsynaptic kainate receptors triggers hippocampal long-term potentiation

Czech Academy of Sciences Publication Activity Database

Petrovič, Miloš; da Silva, S. V.; Clement, J. P.; Vyklický ml., Ladislav; Mulle, C.; González-González, I. M.; Henley, J. M.

2017-01-01

Roč. 20, č. 4 (2017), s. 529-539 ISSN 1097-6256 R&D Projects: GA ČR(CZ) GA17-02300S Institutional support: RVO:67985823 Keywords : hippocampus * long-term potentiation * membrane proteins Subject RIV: FH - Neurology OBOR OECD: Neuroscience s (including psychophysiology Impact factor: 17.839, year: 2016

An N-methyl-D-aspartate receptor mediated large, low-frequency, spontaneous excitatory postsynaptic current in neonatal rat spinal dorsal horn neurons.

Science.gov (United States)

Thomson, L M; Zeng, J; Terman, G W

2006-09-01

Examples of spontaneous oscillating neural activity contributing to both pathological and physiological states are abundant throughout the CNS. Here we report a spontaneous oscillating intermittent synaptic current located in lamina I of the neonatal rat spinal cord dorsal horn. The spontaneous oscillating intermittent synaptic current is characterized by its large amplitude, slow decay time, and low-frequency. We demonstrate that post-synaptic N-methyl-D-aspartate receptors (NMDARs) mediate the spontaneous oscillating intermittent synaptic current, as it is inhibited by magnesium, bath-applied d-2-amino-5-phosphonovalerate (APV), or intracellular MK-801. The NR2B subunit of the NMDAR appears important to this phenomenon, as the NR2B subunit selective NMDAR antagonist, alpha-(4-hydroxphenyl)-beta-methyl-4-benzyl-1-piperidineethanol tartrate (ifenprodil), also partially inhibited the spontaneous oscillating intermittent synaptic current. Inhibition of spontaneous glutamate release by the AMPA/kainate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) or the mu-opioid receptor agonist [D-Ala2, N-Me-Phe4, Gly5] enkephalin-ol (DAMGO) inhibited the spontaneous oscillating intermittent synaptic current frequency. Marked inhibition of spontaneous oscillating intermittent synaptic current frequency by tetrodotoxin (TTX), but not post-synaptic N-(2,6-dimethylphenylcarbamoylmethyl)triethylammonium bromide (QX-314), suggests that the glutamate release important to the spontaneous oscillating intermittent synaptic current is dependent on active neural processes. Conversely, increasing dorsal horn synaptic glutamate release by GABAA or glycine inhibition increased spontaneous oscillating intermittent synaptic current frequency. Moreover, inhibiting glutamate transporters with threo-beta-benzyloxyaspartic acid (DL-TBOA) increased spontaneous oscillating intermittent synaptic current frequency and decay time. A possible functional role of this spontaneous NMDAR

Alpha-Adrenoceptor Antagonists Improve Memory by Activating -methyl-D-Aspartate-Induced Ion Currents in the Rat Hippocampus

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Chang Hee Kim

2015-12-01

Full Text Available Purpose: Alpha1 (α1-adrenoceptor antagonists are widely used to treat lower urinary tract symptoms. These drugs not only act on peripheral tissues, but also cross the blood-brain barrier and affect the central nervous system. Therefore, α1-adrenoceptor antagonists may enhance brain functions. In the present study, we investigated the effects of tamsulosin, an α1-adrenoceptor antagonist, on short-term memory, as well as spatial learning and memory, in rats. Methods: The step-down avoidance test was used to evaluate short-term memory, and an eight-arm radial maze test was used to evaluate spatial learning and memory. TUNEL (terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling staining was performed in order to evaluate the effect of tamsulosin on apoptosis in the hippocampal dentate gyrus. Patch clamp recordings were used to evaluate the effect of tamsulosin on ionotropic glutamate receptors, such as N-methyl-D-aspartate (NMDA, amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA, and kainate receptors, in hippocampal CA1 neurons. Results: Tamsulosin treatment improved short-term memory, as well as spatial learning and memory, without altering apoptosis. The amplitudes of NMDA-induced ion currents were dose-dependently increased by tamsulosin. However, the amplitudes of AMPA- and kainate-induced ion currents were not affected by tamsulosin. Conclusions: Tamsulosin enhanced memory function by activating NMDA receptor-mediated ion currents in the hippocampus without initiating apoptosis. The present study suggests the possibility of using tamsulosin to enhance memory under normal conditions, in addition to its use in treating overactive bladder.

Synaptic impairment in layer 1 of the prefrontal cortex induced by repeated stress during adolescence is reversed in adulthood

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Ignacio eNegron-Oyarzo

2015-11-01

Full Text Available Chronic stress is a risk factor for the development of psychiatric disorders, some of which involve dysfunction of the prefrontal cortex (PFC. There is a higher prevalence of these chronic stress-related psychiatric disorders during adolescence, when the PFC has not yet fully matured. In the present work we studied the effect of repeated stress during adolescence on synaptic function in the PFC in adolescence and adulthood. To this end, adolescent Sprague-Dawley rats were subjected to seven consecutive days of restraint stress. Afterward, both synaptic transmission and short- and long-term synaptic plasticity were evaluated in layer 1 of medial-PFC (mPFC slices from adolescent and adult rats. We found that repeated stress significantly reduced the amplitude of evoked field excitatory postsynaptic potential (fEPSP in the mPFC. Isolation of excitatory transmission reveled that lower-amplitude fEPSPs were associated with a reduction in AMPA/kainate receptor-mediated transmission. We also found that repeated stress significantly decreased long-term depression (LTD. Interestingly, AMPA/kainate receptor-mediated transmission and LTD were recovered in adult animals that experienced a three-week stress-free recovery period. The data indicates that the changes in synaptic transmission and plasticity in the mPFC induced by repeated stress during adolescence are reversed in adulthood after a stress-free period.

Swiss Albino Farelerde Fenpiroksimat (Akarisit’ın Teşvik Ettiği Biyokimyasal Değişime Karşı Fındığın Koruyucu Rolü

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Kültiğin ÇAVUŞOĞLU

2017-02-01

Full Text Available Özet. Fenpiroksimat Tetranychidae, Eriophyiidae ve Tarsonemidae ailelerindeki önemli fitofag akarlarına karşı mücadelede kullanılan pirazol bir akarisittir. Bu çalışmanın amacı, Swiss albino farelerde seçilen biyokimyasal parametreler üzerine Fenpiroksimat akarisitinin toksisitesini değerlendirmek ve bu biyokimyasal değişimlere karşı fındığın koruyucu rolünü araştırmaktır. Fareler rastgele bir (1 kontrol ve üç (3 uygulama olmak üzere toplam dört (4 gruba ayrılmıştır. Deneysel periyodun sonunda, tüm fareler hafif eter anestezisi altında bayıltılmış, biyokimyasal analiz ve ölçümler için kan örnekleri ile karaciğer ve böbrek dokuları elde edilmiştir. Serum Aspartat Aminotransferaz (AST, Alanin Aminotransferaz (ALT, Kan Üre Nitrojen (BUN ve kreatinin seviyeleri ölçülmüş, elde edilen dokularda ise Malondialdehit (MDA ve Glutatyon (GSH seviyeleri analiz edilmiştir. Sonuçta, kontrol grubu ile karşılaştırıldığında Fenpiroksimat uygulanan farelerde GSH seviyelerinde önemli bir azalma (p<0.05, AST, ALT, BUN, kreatinin ve MDA seviyelerinde ise önemli bir artış (p<0.05 görülmüştür. Fenpiroksimat uygulama grubu ile karşılaştırıldığında, Fenpiroksimat ile birlikte fındık uygulaması GSH seviyelerinde tekrar önemli bir artışa (p<0.05, AST, ALT, BUN, kreatinin ve MDA seviyelerinde ise önemli bir azalmaya (p<0.05 neden olmuştur. Sonuç olarak, fındık ile beslemenin Fenpiroksimat tarafından teşvik edilen biyokimyasal hasara karşı önemli bir koruma sağladığı söylenebilir.Anahtar Kelimeler: Albino fare, fenpiroksimat, oksidatif stres, serum parametresi Abstract. Fenpyroximate is a pyrazole acaricide with selective activity against important phytophagous mites in the families’ Tetranychidae, Eriophyiidae, and Tarsonemidae. The goal of this study was to evaluate the toxicity of Fenpyroximate acaricide on selected biochemical parameters in Swiss albino mice. And

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.

1983-06-01

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.

Arctigenin reduces neuronal responses in the somatosensory cortex via the inhibition of non-NMDA glutamate receptors

OpenAIRE

Borbély, S; Jocsak, Gergely; Moldovan, Kinga; Sedlak, Lucie; Preininger, Eva; Boldizsar, Imre; Toth, Attila; Atlason, Palmi T; Molnar, Elek; Vilagi, Ildiko

2016-01-01

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) t...

K-Ar ages of rocks from Lago Alumine, Rucachoroi and Quillen, North Patagonian Andes, Neuquen, Republica Argentina

International Nuclear Information System (INIS)

Latorre, Carlos O.; Vattuone, M.E; Linares, Enrique; Leal, Pablo R

2001-01-01

This study presents new K-Ar ages of granitic rocks from the Patagonian Batholit in the North Patagonian Andes (38 o 00'- 39 o 30' SL), from localities near Alumine lake and from Norquinco lake to Quillen valley, in the Neuquen Province, Argentine. The granitic rocks of Patagonia had been recognized as Upper Paleozoic to Middle Jurassic batholits and as Late Jurassic to Tertiary batholiths (Rapela and Pankhurst, 1992). Geochronologically, Rapela and Kay (1988) had distinguished Early Cretaceous (140 to 120 Ma) and Late Cretaceous (110 to 75 Ma ) magmatic episodes based in potassium-argon data. For the granitic rocks of the area of Paso Icalma, Moquehue and the Rahue granodiorites, Cingolani et al. (1991) presented Rb-Sr whole rock isochron ages of 70±10 Ma, 209±13 Ma and 237±37 Ma, respectively, and Varela et al. (1994), with the same method, cited an age of 285±5 Ma for the Rahue granodiorites and diorites (au)

Geotectonic structural interpretation of the basement complex at the eastern border of the Espinhaco ridge, in Guanhaes and Gouveia region, based on an integration of their U/Pb and K/Ar geochronology united

International Nuclear Information System (INIS)

Teixeira, W.; Salvador, E.D.; Siga Junior, O.; Sato, K.; Dossin, I.A.; Dossin, T.M.

1990-01-01

The basement complex at the eastern border of the Espinhaco ridge is composed of predominantly gneissic rocks which were subjected to migmatization and granitization. Overall the area shows complex tectonic evolution with recurrence of tectonomagmatic and metamorphic events as supported by geological, geochronological and structural studies. The Rb/Sr geochronology carried out on the basement rocks and metavolcanics from the Espinhaco interpreted together with the published U-Pb, Rb-Sr and K-Ar data defines the following scenario for the Precambrian crustal evolution. 1. Primary origin of a sialic crust at 2.97-2.84 Ga. ago as supported by U-Pb zircon ages. 2. Crustal reworking of the Archean crust and subordinate juvenile accretion from upper mantle during the 2.2-2.OGa. period, as suggested by the isochrons. 3. Recurrence of Middle Proterozoic events over the basement rocks (gneisses and charnockites) and metavolcanics of the Espinhaco as showed by isochrons. 4. Development of Late Proterozoic migmatization over the basement rocks (0.75 Ga., R.I.= 0.787) is association with Collisional tectonics and resetting of K-Ar mineral systems. (author)

Tüketici Fiyat Endeksinin Uyarlamalı Ağa Dayalı Bulanık Çıkarım Sistemi ile Kestirimi / Consumer Price Index Forecast with Adaptive Neuro Fuzzy Inference System

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Serenay VAROL

2016-04-01

Full Text Available Son yıllarda zaman serisi tahmini için birçok alternatif yöntem önerilmiştir. Uyarlamalı ağa dayalı bulanık çıkarım sistemi (ANFIS öngörü problemi için literatürde en çok uygulanan bulanık çıkarım sistemidir. Bu çalışmada tüketici fiyat endeksinin kestiriminde ANFIS’in performansı incelenmiştir. Çalışmanın sonucunda ANFIS yöntemi ile ilgilenilen zaman aralığındaki tüketici fiyat endeksinin kestiriminde ulaşılan sonuçlar yorumlanmıştır. / Alternative methods have been proposed for time series prediction in last years. Adaptive neuro fuzzy inference system (ANFIS is the most used fuzzy inference system in literature for prediction problem. In this study, the performance of ANFIS in forecasting consumer price index is examined, and the results of the consumer price index estimation in time period, on which ANFIS method is applied, are interpreted.

“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

2013-09-01

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

Evidence for a role of glutamate as an efferent transmitter in taste buds

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Anderson Catherine B

2010-06-01

Full Text Available Abstract Background Glutamate has been proposed as a transmitter in the peripheral taste system in addition to its well-documented role as an umami taste stimulus. Evidence for a role as a transmitter includes the presence of ionotropic glutamate receptors in nerve fibers and taste cells, as well as the expression of the glutamate transporter GLAST in Type I taste cells. However, the source and targets of glutamate in lingual tissue are unclear. In the present study, we used molecular, physiological and immunohistochemical methods to investigate the origin of glutamate as well as the targeted receptors in taste buds. Results Using molecular and immunohistochemical techniques, we show that the vesicular transporters for glutamate, VGLUT 1 and 2, but not VGLUT3, are expressed in the nerve fibers surrounding taste buds but likely not in taste cells themselves. Further, we show that P2X2, a specific marker for gustatory but not trigeminal fibers, co-localizes with VGLUT2, suggesting the VGLUT-expressing nerve fibers are of gustatory origin. Calcium imaging indicates that GAD67-GFP Type III taste cells, but not T1R3-GFP Type II cells, respond to glutamate at concentrations expected for a glutamate transmitter, and further, that these responses are partially blocked by NBQX, a specific AMPA/Kainate receptor antagonist. RT-PCR and immunohistochemistry confirm the presence of the Kainate receptor GluR7 in Type III taste cells, suggesting it may be a target of glutamate released from gustatory nerve fibers. Conclusions Taken together, the results suggest that glutamate may be released from gustatory nerve fibers using a vesicular mechanism to modulate Type III taste cells via GluR7.

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

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MOREIRA MACEDO, Ludmila

2006-12-01

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.

In situ dating on Mars: A new approach to the K-Ar method utilizing cosmogenic argon

Science.gov (United States)

Cassata, William S.

2014-01-01

Cosmogenic argon isotopes are produced in feldspars via nuclear reactions between cosmic rays and Ca and K atoms within the lattice. These cosmogenic isotopes can be used as proxies for K and Ca, much like nuclear reactor-derived 39Ar and 37Ar are used as proxies for K and Ca, respectively, in 40Ar/39Ar geochronology. If Ca and K are uniformly distributed, then the ratio of radiogenic 40Ar (40Ar*) to cosmogenic 38Ar or 36Ar (38Arcos or 36Arcos) is proportional to the difference between the radioisotopic and exposure ages, as well as the K/Ca ratio of the degassing phase. Thus cosmogenic, radiogenic, and trapped Ar isotopes, all of which can be measured remotely and are stable over geologic time, are sufficient to generate an isochron-like diagram from which the isotopic composition of the trapped component may be inferred. Such data also provide a means to assess the extent to which the system has remained closed with respect to 40Ar*, thereby mitigating otherwise unquantifiable uncertainties that complicate the conventional K-Ar dating method.

Transition of neogene arc volcanism in central-western Hokkaido, viewed from K-Ar ages, style of volcanic activity, and bulk rock chemistry

Energy Technology Data Exchange (ETDEWEB)

Hirose, Wataru; Iwasaki, Miyuki; Nakagawa, Mitsuhiro [Hokkaido Univ., Sapporo (Japan)

2000-02-01

Spatial and temporal variations in late Cenozoic volcanism of southwestern Hokkaido at the northern end of NE-Japan arc have been clarified by 261 K-Ar and 76 FT ages including 49 newly determined K-Ar ages, volcanic stratigraphy, physical volcanology and whole-rock geochemistry. Arc volcanism characterized by rocks with low-Ti and Nb, and by across-arc increase in K{sub 2}O content in these rocks has continued at least since 12 Ma. Based on volcanic stratigraphy, physical volcanology and whole-rock geochemistry, volcanism after 12 Ma can be subdivided into 4 stages, 12-5, 5-1.7, and 1.7-0 Ma. The volcanism from 12 Ma to 5 Ma extended northward widely compared with distribution of Quaternary arc volcanism (1.7-0 Ma). This suggests that the arc trench junction between Kuril and NE-Japan arc's trenches was located about 100 km northward from the present position. Since around 5 Ma until 1.7 Ma, different type of volcanism under local extension field, characterized by a group of monogenetic volcanoes of alkali basalt and shield volcanoes of calc-alkaline andesite, had occurred at northern end of the volcanic region (Takikawa-Mashike region). During and after this volcanism, the northern edge of arc volcanism in the area has migrated southward. This suggests that the trench junction has migrated about 100 km southward since {approx}5 Ma. The quaternary arc volcanism (1.7-0 Ma) has been restricted at the southern part of the region. The volcanism since 12 Ma might be influenced by oblique subduction of Pacific plate beneath Kuril arc, resulting in the formation of local back arc basin at the junction and to southward migration of the trench junction. (author)

The neuropharmacology of L-theanine(N-ethyl-L-glutamine): a possible neuroprotective and cognitive enhancing agent.

Science.gov (United States)

Nathan, Pradeep J; Lu, Kristy; Gray, M; Oliver, C

2006-01-01

L-theanine (N-ethyl-L-glutamine) or theanine is a major amino acid uniquely found in green tea. L-theanine has been historically reported as a relaxing agent, prompting scientific research on its pharmacology. Animal neurochemistry studies suggest that L-theanine increases brain serotonin, dopamine, GABA levels and has micromolar affinities for AMPA, Kainate and NMDA receptors. In addition has been shown to exert neuroprotective effects in animal models possibly through its antagonistic effects on group 1 metabotrophic glutamate receptors. Behavioural studies in animals suggest improvement in learning and memory. Overall, L-theanine displays a neuropharmacology suggestive of a possible neuroprotective and cognitive enhancing agent and warrants further investigation in animals and humans.

Asetonitril-Su İkili Karışımlarında Piroksikam ve Tenoksikam'ın Potansiyometrik pKa Tayini

OpenAIRE

Çubuk Demiralay, Ebru; Yılmaz, Hülya

2012-01-01

İyonlaşma sabiti (pKa) çözünebilirlik sınırlaması olmaksızın doğru tahmin edilebilen parametrelerden birisidir. Sunulan bu çalışmada, piroksikam ve tenoksikamın asit- baz davranışı çalışılmıştır. Potansiyometrik metot kullanılarak, piroksikam ve tenoksikamın pKa değerleri asetonitril-su ikili karışımlarının farklı yüzdelerinde tayin edilmiştir (asetonitril içeriği hacimce % 30 ile 45 arasında). Bu bileşiklerin sudaki pKa değerleri mol kesri ve Yasuda-Shedlovsky eşitlikleri kullanarak hesaplan...

Augsnes un zemes kvalitātes novērtējuma karšu digitizēšana

OpenAIRE

Stalīdzāns, Didzis

2014-01-01

Maģistra darba mērķis ir nodrošināt augšņu agroķīmiskās izpētes izstrādes procesa kartogrāfiskā materiāla lietošanas efektivitātes pieaugumu. Maģistra darbā tiek aprakstīts līdzšinējais augšņu agroķīmiskās izstrādes process Valsts augu aizsardzības dienestā un digitālo augšņu karšu izmantošanas iespējas. Pamatojoties uz darbā veiktās izpētes rezultātiem ir definēta problēma: augšņu agroķīmiskās kartes nav pieejamas telpisko datu formātā. Problēmas risinājumam tiek piedāvātas projekta alternat...

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

Directory of Open Access Journals (Sweden)

Hilmi SÜNGÜ

2013-09-01

�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.

Enhanced pre-synaptic glutamate release in deep-dorsal horn contributes to calcium channel alpha-2-delta-1 protein-mediated spinal sensitization and behavioral hypersensitivity

Directory of Open Access Journals (Sweden)

Dickenson Anthony H

2009-02-01

Full Text Available Abstract Nerve injury-induced expression of the spinal calcium channel alpha-2-delta-1 subunit (Cavα2δ1 has been shown to mediate behavioral hypersensitivity through a yet identified mechanism. We examined if this neuroplasticity modulates behavioral hypersensitivity by regulating spinal glutamatergic neurotransmission in injury-free transgenic mice overexpressing the Cavα2δ1 proteins in neuronal tissues. The transgenic mice exhibited hypersensitivity to mechanical stimulation (allodynia similar to the spinal nerve ligation injury model. Intrathecally delivered antagonists for N-methyl-D-aspartate (NMDA and α-amino-3-hydroxyl-5-methylisoxazole-4-propionic acid (AMPA/kainate receptors, but not for the metabotropic glutamate receptors, caused a dose-dependent allodynia reversal in the transgenic mice without changing the behavioral sensitivity in wild-type mice. This suggests that elevated spinal Cavα2δ1 mediates allodynia through a pathway involving activation of selective glutamate receptors. To determine if this is mediated by enhanced spinal neuronal excitability or pre-synaptic glutamate release in deep-dorsal horn, we examined wide-dynamic-range (WDR neuron excitability with extracellular recording and glutamate-mediated excitatory postsynaptic currents with whole-cell patch recording in deep-dorsal horn of the Cavα2δ1 transgenic mice. Our data indicated that overexpression of Cavα2δ1 in neuronal tissues led to increased frequency, but not amplitude, of miniature excitatory post synaptic currents mediated mainly by AMPA/kainate receptors at physiological membrane potentials, and also by NMDA receptors upon depolarization, without changing the excitability of WDR neurons to high intensity stimulation. Together, these findings support a mechanism of Cavα2δ1-mediated spinal sensitization in which elevated Cavα2δ1 causes increased pre-synaptic glutamate release that leads to reduced excitation thresholds of post-synaptic dorsal

Enhanced pre-synaptic glutamate release in deep-dorsal horn contributes to calcium channel alpha-2-delta-1 protein-mediated spinal sensitization and behavioral hypersensitivity

Science.gov (United States)

Nguyen, David; Deng, Ping; Matthews, Elizabeth A; Kim, Doo-Sik; Feng, Guoping; Dickenson, Anthony H; Xu, Zao C; Luo, Z David

2009-01-01

Nerve injury-induced expression of the spinal calcium channel alpha-2-delta-1 subunit (Cavα2δ1) has been shown to mediate behavioral hypersensitivity through a yet identified mechanism. We examined if this neuroplasticity modulates behavioral hypersensitivity by regulating spinal glutamatergic neurotransmission in injury-free transgenic mice overexpressing the Cavα2δ1 proteins in neuronal tissues. The transgenic mice exhibited hypersensitivity to mechanical stimulation (allodynia) similar to the spinal nerve ligation injury model. Intrathecally delivered antagonists for N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxyl-5-methylisoxazole-4-propionic acid (AMPA)/kainate receptors, but not for the metabotropic glutamate receptors, caused a dose-dependent allodynia reversal in the transgenic mice without changing the behavioral sensitivity in wild-type mice. This suggests that elevated spinal Cavα2δ1 mediates allodynia through a pathway involving activation of selective glutamate receptors. To determine if this is mediated by enhanced spinal neuronal excitability or pre-synaptic glutamate release in deep-dorsal horn, we examined wide-dynamic-range (WDR) neuron excitability with extracellular recording and glutamate-mediated excitatory postsynaptic currents with whole-cell patch recording in deep-dorsal horn of the Cavα2δ1 transgenic mice. Our data indicated that overexpression of Cavα2δ1 in neuronal tissues led to increased frequency, but not amplitude, of miniature excitatory post synaptic currents mediated mainly by AMPA/kainate receptors at physiological membrane potentials, and also by NMDA receptors upon depolarization, without changing the excitability of WDR neurons to high intensity stimulation. Together, these findings support a mechanism of Cavα2δ1-mediated spinal sensitization in which elevated Cavα2δ1 causes increased pre-synaptic glutamate release that leads to reduced excitation thresholds of post-synaptic dorsal horn neurons to innocuous

[Glutamate receptors genes polymorphism and the risk of paranoid schizophrenia in Russians and tatars from the Republic of Bashkortostan].

Science.gov (United States)

Gareeva, A E; Khusnutdinova, E K

2014-01-01

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

K-Ar ages of Early Miocene arc-type volcanoes in northern New Zealand

International Nuclear Information System (INIS)

Hayward, B.W.; Black, P.M.; Smith, I.E.M.; Ballance, P.F.; Itaya, T.; Doi, M.; Takagi, M.; Bergman, S.; Adams, C.J.; Herzer, R.H.; Robertson, D.J.

2001-01-01

Understanding the temporal and spatial development of the Early Miocene Northland Volcanic Arc is critical to interpreting the patterns of volcanic activity in northern New Zealand through the Late Cenozoic. The northwesterly trending arc is considered to have developed above a southwest-dipping subduction system. The distribution of its constituent eruptive centres is described in terms of an eastern belt that extends along the eastern side of Northland and a complementary broad western belt which includes subaerial and submarine volcanic edifices. Critical examination of all 216 K-Ar ages available, including 180 previously unpublished ages, and their assessment against tectonic, lithostratigraphic, seismic stratigraphic, and biostratigraphic constraints, leads us to deduce a detailed chronology of periods of activity for the various Early (and Middle) Miocene arc-type volcanic complexes and centres of northern New Zealand: Waipoua Shield Volcano Complex (19-18 Ma, Altonian); Kaipara Volcanic Complex (23-16 Ma, Waitakian-Altonian); Manukau Volcanic Complex (c. 23-15.5 Ma, Waitakian-Clifdenian); North Cape Volcanic Centre (23-18 Ma, Waitakian-Altonian); Whangaroa Volcanic Complex (22.5-17.5 Ma, Waitakian-Altonian); Taurikura Volcanic Complex (22-15.5 Ma, Otaian-Clifdenian); Parahaki Dacites (22.5-18 Ma, Waitakian-Altonian); Kuaotunu Volcanic Complex (18.5-11 Ma, Altonian-Waiauan). In general, volcanic activity does not show geographic migration with time, and the western (25-15.5 Ma) and eastern (23-11 Ma) belts appear to have developed concurrently. (author). 123 refs., 9 figs., 1 tab

The combination of glutamate receptor antagonist MK-801 with tamoxifen and its active metabolites potentiates their antiproliferative activity in mouse melanoma K1735-M2 cells

International Nuclear Information System (INIS)

Ribeiro, Mariana P.C.; Nunes-Correia, Isabel; Santos, Armanda E.; Custódio, José B.A.

2014-01-01

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

Successive reactivation of older structures under variable heat flow conditions evidenced by K-Ar fault gouge dating in Sierra de Ambato, northern Argentine broken foreland

Science.gov (United States)

Nóbile, Julieta C.; Collo, Gilda; Dávila, Federico M.; Martina, Federico; Wemmer, Klaus

2015-12-01

The Argentine broken foreland has been the subject of continuous research to determine the uplift and exhumation history of the region. High-elevation mountains are the result of N-S reverse faults that disrupted a W-E Miocene Andean foreland basin. In the Sierra de Ambato (northern Argentine broken foreland) the reverse faults offset Neogene sedimentary rocks (Aconquija Fm., ˜9 Ma) and affect the basement comprising Paleozoic metamorphic rocks that have been dated at ˜477-470 Ma. In order to establish a chronology of these faults affecting the previous continuous basin we date the formation age of clay minerals associated with fault gouge using the K-Ar dating technique. Clay mineral formation is a fundamental process in the evolution of faults under the brittle regime (history with a minimum age of ˜360 Ma and a last clay minerals forming event at ˜220 Ma. Moreover, given the progression of apparent ages decreasing from coarse to fine size fractions (˜360-311 Ma for 2-1 μm grain size fraction, ˜326-286 Ma for 1-0.2 μm and ˜291-219 Ma of <0.2 μm), we modeled discrete deformation events at ˜417 Ma (ending of the Famatinian cycle), ˜317-326 Ma (end of Gondwanic orogeny), and ˜194-279 Ma (Early Permian - Jurassic deformation). According to our data, the Neogene reactivation would not have affected the K-Ar system neither generated a significant clay minerals crystallization in the fault gouge, although an exhumation of more than 2 Km is recorded in this period from stratigraphic data.

A pharmacological profile of the high-affinity GluK5 kainate receptor

DEFF Research Database (Denmark)

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

2016-01-01

-hydroxyisoxazol-4-yl)propionate (ATPA), dihydrokainate and (2 S,4 R)−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...

An arid episod in the climatic evolution of the Atakor mountains (Hoggar) about 1.5 m.y. (K/Ar datations). Its signification in the paleoclimatic context during the Plio-Pleistocene of Africa

International Nuclear Information System (INIS)

Rognon, Pierre; Gourinard, Yves; Bandet, Y.

1981-01-01

Nine K/Ar datations of some basaltic lavas from the Atakor mountains allow to date, for the first time, an arid period at 1.5 m.y. +- 0.1. This arid period takes place after the drying of the Plio-Pleistocene tropical lakes and after the first cool Pluvial, during an important turning phase of the geomorphologic and climatic evolution. These environmental changes are similar to those pointed out in Eastern Africa [fr

GLYX-13, a NMDA receptor glycine-site functional partial agonist, induces antidepressant-like effects without ketamine-like side effects.

Science.gov (United States)

Burgdorf, Jeffrey; Zhang, Xiao-lei; Nicholson, Katherine L; Balster, Robert L; Leander, J David; Stanton, Patric K; Gross, Amanda L; Kroes, Roger A; Moskal, Joseph R

2013-04-01

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.

Gating characteristics control glutamate receptor distribution and trafficking in vivo.

Science.gov (United States)

Petzoldt, Astrid G; Lee, Yü-Hien; Khorramshahi, Omid; Reynolds, Eric; Plested, Andrew J R; Herzel, Hanspeter; Sigrist, Stephan J

2014-09-08

Glutamate-releasing synapses dominate excitatory release in the brain. Mechanisms governing their assembly are of major importance for circuit development and long-term plasticity underlying learning and memory. AMPA/Kainate-type glutamate receptors (GluRs) are tetrameric ligand-gated ion channels that open their ion-conducting pores in response to binding of the neurotransmitter. Changes in subunit composition of postsynaptic GluRs are highly relevant for plasticity and development of glutamatergic synapses [1-4]. To date, posttranslational modifications, mostly operating via the intracellular C-terminal domains (CTDs) of GluRs, are presumed to be the major regulator of trafficking [5]. In recent years, structural and electrophysiological analyses have improved our understanding of GluR gating mechanism [6-11]. However, whether conformational changes subsequent to glutamate binding may per se be able to influence GluR trafficking has remained an unaddressed question. Using a Drosophila system allowing for extended visualization of GluR trafficking in vivo, we here provide evidence that mutations changing the gating behavior alter GluR distribution and trafficking. GluR mutants associated with reduced charge transfer segregated from coexpressed wild-type GluRs on the level of individual postsynaptic densities. Segregation was lost upon blocking of evoked glutamate release. Photobleaching experiments suggested increased mobility of mutants with reduced charge transfer, which accumulated prematurely during early steps of synapse assembly, but failed to further increase their level in accordance with assembly of the presynaptic scaffold. In summary, gating characteristics seem to be a new variable for the understanding of GluR trafficking relevant to both development and plasticity. Copyright © 2014 Elsevier Ltd. All rights reserved.

Preliminary study of geotectonic evolution of the southern region of Sao Francisco (MG, Brazil) craton: an interpretation based on Rb-Sr, K-Ar, Pb-Pb and fission track data

International Nuclear Information System (INIS)

Teixeira, W.; Fonseca, A.C.; Poupeau, G.; Padilha, A.V.; Zapparolli, L.H.; Kawashita, K.; Khoury, M.C.

1985-01-01

The results obtained from isotopic dating techniques (Rb-Sr, K-Ar, Pb-Pb and fission tracks) applied to samples from the southern region of Sao Francisco craton (Mg, Brazil) are discussed. Rb-Sr and Pb-Pb ages, in total rock, allowed the determination of crust enlargement, with eventual modifications of the pre-existing crust, during the Late Archean period (3000 to 2600 million years) and the Inferior Proterozoic period (2400 to 2100 m.y.). Three main cooling periods of time were determined by K-Ar dating of mica, amphiboles and total rock at the craton border: 2200 to 1700 m.y., 1300 to 1100 m.y. and 900 to 400 m.y. related, respectively, to superposition of three cycles: Transamazonico, Uruacuano and Brasiliano. Cooling below 110 0 C, detected by the fission track method applied to apatites, pointed out an age of 850 m.y. at the internal parts and 550 m.y. at the craton periphery, thus showing a progressive action of Brazilian marginal movable zones in the studied region. The application of these two techniques together enabled the evaluation of the rocks cooling shape. Cooling of these samples was complex between 2700 and 2200 m.y. and slow from 2000 m.y. onwards. The integrated treatment of data from the various dating techniques is of great importance to know the geotectonic evolution of ancient polycyclic sites. (C.L.B.) [pt

Glutamate Receptors in the Central Nucleus of the Amygdala Mediate Cisplatin-Induced Malaise and Energy Balance Dysregulation through Direct Hindbrain Projections.

Science.gov (United States)

Alhadeff, Amber L; Holland, Ruby A; Nelson, Alexandra; Grill, Harvey J; De Jonghe, Bart C

2015-08-05

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

Glutamate Receptors in the Central Nucleus of the Amygdala Mediate Cisplatin-Induced Malaise and Energy Balance Dysregulation through Direct Hindbrain Projections

Science.gov (United States)

Alhadeff, Amber L.; Holland, Ruby A.; Nelson, Alexandra; Grill, Harvey J.

2015-01-01

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. SIGNIFICANCE STATEMENT 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

40Ar/39Ar and K/Ar whole rock age constraints on the timing of regional deformation, South Coast of New South Wales, Lachlan Fold Belt, Southeastern Australia: problems and implications

International Nuclear Information System (INIS)

Phillips, D.; Fergusson, C.L.

1999-01-01

Full text: Subduction complex rocks are well exposed on the south coast of New South Wales around Batemans Bay. Farther south in the Narooma and Bermagui region, Offier et al (1998) have determined two 40 Ar/ 39 Ar ages of 450 ± 3 Ma and 445 ± 2 Ma. They argued that these ages constrain the timing of intense underplating-related deformation and we have undertaken farther work, from an area south of Batemans Bay, to test this suggestion. The 40 Ar/ 39 Ar method applied to fine-grained, low temperature metamorphic rocks, such as slates, is beset by the problem of recoil loss and/or redistribution of 39 Ar during the irradiation process. Another problem is the difficulty of distinguishing between the contributions to 40 Ar/ 39 Ar spectra from illite/muscovite grown during the cleavage-producing deformation and detrital muscovite/illite. In the current study, four slate samples, with variable contents of detrital white mica, were analysed by both the K-Ar and 40 Ar/ 39 Ar step-heating methods. A separate of detrital white mica from one slate sample yields a plateau age of 500 ± 2 Ma. This result indicates that inheritance has not been eliminated by metamorphism as is commonly assumed and that the 40 Ar/ 39 Ar ages provide only a maximum estimate for the timing of deformation. 40 Ar/ 39 Ar analyses of state chips yield discordant, saddle-shaped age spectra, with minimum, within-saddle' ages of ca. 420 Ma. Two slate samples give identical 40 Ar/ 39 Ar integrated ages of 455 ± 2 Ma. One sample contains relatively abundant detrital bedding-parallel mica flakes that are locally oblique to the regional cleavage in the rock. The 40 Ar/ 39 Ar ages are some 20 Ma older than K-Ar ages for these same samples, suggesting that recoil loss of 39 Ar may also have affected these slates. Both recoil loss of 39 Ar and inherited white micas will yield elevated apparent ages, thus providing only maximum ages for the cleavage-producing deformation. Two other samples from slaty tectonic

Structural and K/Ar Illite geochronological constraints on the brittle deformation history of the Olkiluoto Region, Southwest Finland

International Nuclear Information System (INIS)

Viola, G.; Zwingmann, H.; Todd, A.; Raven, M.

2011-07-01

Sveconorwegian orogeny whereas younger extension, almost coaxial with the latter, is interpreted as the result of the late Sveconorwegian orogenic collapse at the Meso- Neoproterozoic boundary. In order to add absolute time constraints to the conceptual model of the structural evolution of the Olkiluoto region, selected fault gouge samples were collected for K/Ar dating of authigenic and synkinematic illite. The new K/Ar ages range in total from 561.3 ± 11.2 Ma (Neoproterozoic-Ediacaran) to 1451.7 ± 29.3 Ma (Mesoproterozoic-Calymmian). Structural analysis of the dated fault cores made it possible to assign tight time constraints to several of the faulting episodes, thus strengthening the structural model produced by the study. (orig.)

Effect of endurance training on seizure susceptibility, behavioral changes and neuronal damage after kainate-induced status epilepticus in spontaneously hypertensive rats.

Science.gov (United States)

Tchekalarova, J; Shishmanova, M; Atanasova, D; Stefanova, M; Alova, L; Lazarov, N; Georgieva, K

2015-11-02

The therapeutic efficacy of regular physical exercises in an animal model of epilepsy and depression comorbidity has been confirmed previously. In the present study, we examined the effects of endurance training on susceptibility to kainate (KA)-induced status epilepticus (SE), behavioral changes and neuronal damage in spontaneously hypertensive rats (SHRs). Male SHRs were randomly divided into two groups. One group was exercised on a treadmill with submaximal loading for four weeks and the other group was sedentary. Immediately after the training period, SE was evoked in half of the sedentary and trained rats by KA, while the other half of the two groups received saline. Basal systolic (SP), diastolic (DP) and mean arterial pressure (MAP) of all rats were measured at the beginning and at the end of the training period. Anxiety, memory and depression-like behaviour were evaluated a month after SE. The release of 5-HT in the hippocampus was measured using a liquid scintillation method and neuronal damage was analyzed by hematoxylin and eosin staining. SP and MAP of exercised SHRs decreased in comparison with the initial values. The increased resistance of SHRs to KA-induced SE was accompanied by an elongated latent seizure-free period, improved object recognition memory and antidepressant effect after the training program. While the anticonvulsant and positive behavioral effects of endurance training were accompanied by an increase of 5-HT release in the hippocampus, it did not exert neuroprotective activity. Our results indicate that prior exercise is an effective means to attenuate KA-induced seizures and comorbid behavioral changes in a model of hypertension and epilepsy suggesting a potential influence of hippocampal 5-HT on a comorbid depression. However, this beneficial impact does not prevent the development of epilepsy and concomitant brain damage. Copyright © 2015 Elsevier B.V. All rights reserved.

Updates of the KArLE Experiment: New Libs Calibration Under High Vacuum for the Quantification of Potassium in Basalt for In Situ Geochronology

Science.gov (United States)

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

2014-01-01

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

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

International Nuclear Information System (INIS)

Lama, C.; Dautel, D.; Zimmermann, J.L.; Cheilletz, A.; Pons, J.

1994-01-01

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)

The 40Ar/39Ar and K/Ar dating of lavas from the Hilo 1-km core hole, Hawaii Scientific Drilling Project

Science.gov (United States)

Sharp, W.D.; Turrin, B.D.; Renne, P.R.; Lanphere, M.A.

1996-01-01

Mauna Kea lava flows cored in the HilIo hole range in age from <200 ka to about 400 ka based on 40Ar/39Ar incremental heating and K-Ar analyses of 16 groundmass samples and one coexisting plagioclase. The lavas, all subaerially deposited, include a lower section consisting only of tholeiitic basalts and an upper section of interbedded alkalic, transitional tholeiitic, and tholeiitic basalts. The lower section has yielded predominantly complex, discordant 40Ar/39Ar age spectra that result from mobility of 40Ar and perhaps K, the presence of excess 40Ar, and redistribution of 39Ar by recoil. Comparison of K-Ar ages with 40Ar/39Ar integrated ages indicates that some of these samples have also lost 39Ar. Nevertheless, two plateau ages of 391 ?? 40 and 400 ?? 26 ka from deep in the hole, combined with data from the upper section, show that the tholeiitic section accumulated at an average rate of about 7 to 8 m/kyr and has an mean recurrence interval of 0.5 kyr/flow unit. Samples from the upper section yield relatively precise 40Ar/39Ar plateau and isotope correlation ages of 326 ?? 23, 241 ?? 5, 232 ?? 4, and 199 ?? 9 ka for depths of -415.7 m to -299.2 m. Within their uncertainty, these ages define a linear relationship with depth, with an average accumulation rate of 0.9 m/kyr and an average recurrence interval of 4.8 kyr/flow unit. The top of the Mauna Kea sequence at -280 m must be older than the plateau age of 132 ?? 32 ka, obtained for the basal Mauna Loa flow in the corehole. The upward decrease in lava accumulation rate is a consequence of the decreasing magma supply available to Mauna Kea as it rode the Pacific plate away from its magma source, the Hawaiian mantle plume. The age-depth relation in the core hole may be used to test and refine models that relate the growth of Mauna Kea to the thermal and compositional structure of the mantle plume.

Kars ilinde şeker pancarı üretiminin beşeri ve ekonomik önemi, sürdürülebilirliği

OpenAIRE

DEMİR, MUCİP

2017-01-01

Türkiye’nin kuzeydoğusunda yer alan Kars İlinin büyük kısmı ortalama irtifası 2000 metre civarında bulunan ve volkanik malzemelerle örtülmüş plato sahasında yer almaktadır. İldeki genel morfolojik ve jeolojik özellikler nedeniyle kışları oldukça soğuk, karlı, yazları serin ve yağışlı sert karasal iklim görülmekte bu nedenle bitkisel üretim faaliyetleri yerine daha çok hayvancılık faaliyetleri yapılmaktadır. İlde şeker pancarı üretimi daha çok ilin kuzeyindeki Akyaka ve Arpaçay ilçelerinde...

Characterization of glutamate-induced formation of N- acylphosphatidylethanolamine and N-acylethanolamine in cultured neocortical neurons

DEFF Research Database (Denmark)

Hansen, Harald S.; Lauritzen, L.; Strand, A.M.

1997-01-01

) assay). The increase in NAPE and NAE could be detected earlier than the neuronal death. Neither cyclic AMP, cyclic GMP, nitric oxide, protein kinase C, nor peroxidation appears to be involved in the formation of NAPE and NAE, as assessed by the use of different pharmacological agents. Exposure to 5 m...... receptors as seen by the inhibitory action of the NMDA-selective receptor antagonists D(-)-2-amino-5-phosphonovalerate and N- (1-(2-thienyl)-cyclohexyl)piperidine and the lack of effect of the a-amino- 3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)/kainate-receptor antagonist 6-cyano-7-nitro......-quinoxaline-2,3-dione (CNQX). In 6-day-old cultures, exposure to NMDA (100 µM for 24 h) induced a linear increase in the formation of NAPE and NAE as well as a 40-50% neuronal death, as measured by a decrease in cellular formazan formation [3-(4,5-dimethylthiazol-2-yl)- 2,5-diphenyltetrazolium bromide (MTT...

Hrob nemlčí pevněji nežli Vy : (Dopisy Jiřího Karáska, Arnošta Procházky, Jiřiny Böhmové a Antonína Trýba)

Czech Academy of Sciences Publication Activity Database

Färber, Vratislav (ed.)

2007-01-01

Roč. 18, č. 4 (2007), s. 163-170 ISSN 0862-6928 R&D Projects: GA ČR GA405/05/2152 Institutional research plan: CEZ:AV0Z90560517 Keywords : Kamil Fiala * Jiří Karásek ze Lvovic * Arnošt Procházka * Jiřina Böhmová * Antnoní Trýb Subject RIV: AJ - Letters, Mass-media, Audiovision

AA2024 Alüminyum Alaşımının Sürtünme Karıştırma Kaynağında Farklı Parametrelerin Mekanik Özelliklere Etkisinin İncelenmesi

Directory of Open Access Journals (Sweden)

Aydın ŞIK

2010-02-01

Full Text Available Bu çalışmada, genel özelliği hafifliği, işlenebilirliği, yüksek korozyon dayancı, yüksek dayanıma sahip olmasından dolayı kullanım alanı olarak özellikle uçak gövdelerinde ve kanatlarda ve otomotiv endüstrilerinde kullanılan AA2024 alaşımı sürtünme karıştırma kaynağı yöntemi ile birleştirilerek, oluşan bağlantıların yorulma, sertlik, eğme ve çekme deneyleri incelenmiştir. 4 mm kalınlığındaki levhaların kaynak esnasında kaynak ilerleme hızı ve karıştırıcı ucun dönme devri değişken parametreler olarak belirlenmiştir. Bu parametreler; 20 mm omuz genişliği, devir sayısı 1000 dev/dak, 1500 dev/dak, 2500 dev/dak ve ilerleme hızları 120 mm/dak ve 200 mm/ dak olarak alınmıştır.

Majanduskaristusõigus karistusõiguse revisjoni raames / Marko Kairjak

Index Scriptorium Estoniae

Kairjak, Marko, 1983-

2014-01-01

Kelmuse (KarS § 209), investeerimiskelmuse (KarS § 211) ning äriühingu varalise seisundi ja muude kontrollitavate asjaolude kohta ebaõigete andmete esitamise (KarS § 381) koosseisus tehtud muudatustest karistusseadustikus. Pankrotiavalduse esitamise kohustuse täitmata jätmise (KarS § 3851) dekriminaliseerimise põhjused

Marmara Bölgesi'nde Arpa açık rastığı (Ustilago nuda hordei “Jens.â€? Rostr. Schaffn.)'na karşı arpa çeşit ve hatlarının reaksiyonlarının tespiti üzerinde araştırmalar.

OpenAIRE

Gümüştekin, H.; Akın, K.

2008-01-01

Arpa çeşit ve hatlarının, arpa açık rastık hastalığı (Ustilago nuda hordei “Jens.â€? Rostr. Schaffn.)'na karşı göstermiş olduğu reaksiyonları tespit etmek amacı ile bu çalışma 1994 yılında başlamıştır. 1994 Yılında 14 arpa çeşit ve hattı, 1995 yılında 23 arpa çeşit ve hattı kullanılmıştır. Denemelerde kullanılan 37 çeşit ve hattan 27'si hastalığa karşı dayanıklı (R) bulunurken, 10'u hassas (S) bulunmuştur.

The effects of conformational constraints and steric bulk in the amino acid moiety of philanthotoxins on AMPAR antagonism

DEFF Research Database (Denmark)

Jørgensen, Malene; Olsen, Christian A; Mellor, Ian R

2005-01-01

, establishing general protocols for philanthotoxin solution- and solid-phase synthesis (39-90% and 42-54% overall yields, respectively). The analogues were tested for their ability to antagonize kainate-induced currents of 2-amino-3-(3-hydroxy-5-methyl-4-isoxazoyl)propanoic acid receptors (AMPAR) expressed...... in Xenopus oocytes from rat brain mRNA. This showed that steric bulk in the amino acid moiety is well tolerated and suggests that binding to AMPAR does not involve the alpha-NHCO group as a donor in hydrogen bonding.......Philanthotoxin-343 (PhTX-343), a synthetic analogue of wasp toxin PhTX-433, is a noncompetitive antagonist at ionotropic receptors (e.g., AChR or iGluR). To determine possible effects of variations of the amino acid side chain, a library consisting of seventeen PhTX-343 analogues was prepared. Thus...

Orman Kanunu’nun 16’ncı maddesi uygulamalarında alınan bedellerin hesaplanma yaklaşımının değer belirleme yöntemleriyle karşılaştırmalı irdelenmesi

Directory of Open Access Journals (Sweden)

Prof.Dr. Kenan Ok

2017-07-01

Full Text Available Orman alanlarında sıklıkla maden çıkarılmak istenmektedir. Bu istek, madencilik üretimini artırırken ormancılık üretimlerini azaltmaktadır. Refah ekonomisinin klasik sorunu olan, sektörler arası tahsis kararları, ülkemiz ormancılık uygulamaları içerisinde, arazi izin ve ağaçlandırma bedellerinin belirlenmesi sorunu şeklinde görülmektedir. Bu çalışmanın amacı, Orman Genel Müdürlüğünün (OGM Orman Kanunu’nun 16’ncı maddesi gereği verdiği izinlerde talep ettiği bedelleri hesaplama yaklaşımı ile evrensel değer belirleme yöntemlerini karşılaştırmalı olarak irdelemektir. Bu amaçla, seçilen gerçek bir olayın verileri örnek alınarak OGM’nin ilgili yönetmeliğinin kabul ettiği değer hesapları yapılmıştır. Bu hesaplama yaklaşımı ile evrensel değer belirleme yaklaşımları karşılaştırılmış ve yönetmelikle ortaya konan yaklaşımın kısmen maliyetlere dayalı bir bakış içerdiği, pazar fiyatları, toplumsal tercihler ve transfer edilen faydalarla ilgilenmediği görülmüştür. Buna ek olarak, yönetmelikle ortaya konan yaklaşımın temel bileşenlerinin, bilimsel bulgular yerine idari kararlara dayalı olarak kurgulandığı saptanmıştır.

Chronic ketamine reduces the peak frequency of gamma oscillations in mouse prefrontal cortex ex vivo

Directory of Open Access Journals (Sweden)

James M. McNally

2013-09-01

Full Text Available Abnormalities in EEG gamma band oscillations (GBO, 30-80 Hz serve as a prominent biomarker of schizophrenia (Sz, associated with positive, negative and cognitive symptoms. Chronic, subanesthetic administration of antagonists of N-methyl-D-aspartate receptors (NMDAR, such as ketamine, elicits behavioral effects and alterations in cortical interneurons similar to those observed in Sz. However, the chronic effects of ketamine on neocortical GBO are poorly understood. Thus, here we examine the effects of chronic (5 daily i.p. injections application of ketamine (5 and 30 mg/kg and the more specific NMDAR antagonist, MK-801 (0.02, 0.5, and 2 mg/kg, on neocortical GBO ex vivo. Oscillations were generated by focal application of the glutamate receptor agonist, kainate, in coronal brain slices containing the prelimbic cortex. This region constitutes the rodent analogue of the human dorsolateral prefrontal cortex, a brain region strongly implicated in Sz-pathophysiology. Here we report the novel finding that chronic ketamine elicits a reduction in the peak oscillatory frequency of kainate-elicited oscillations (from 47 to 40 Hz at 30 mg/kg. Moreover, the power of GBO in the 40-50 Hz band was reduced. These findings are reminiscent of both the reduced resonance frequency and power of cortical oscillations observed in Sz clinical studies. Surprisingly, MK-801 had no significant effect, suggesting care is needed when equating Sz-like behavioral effects elicited by different NMDAR antagonists to alterations in GBO activity. We conclude that chronic ketamine in the mouse mimics GBO abnormalities observed in Sz patients. Use of this ex vivo slice model may be useful in testing therapeutic compounds which rescue these GBO abnormalities.

Hayata ve Vücut Dokunulmazlığına Karşı İşlenen Suçlarda Kadın Suçluluğu ve Dindarlık İlişkisi / Female Criminality and Religiosity in the Homicide and Assault Crimes

Directory of Open Access Journals (Sweden)

Fatma Kenevir

2017-06-01

Full Text Available Abstract        This study consists of the results of the research conducted with convicted female prisoners who committed crimes against the immunity and body immunity in Ankara (Sincan, İzmir (Şakran and İstanbul (Bakırköy women's closed prisons. The scope of the research includes women convicted of crimes against life and body immunity, who are more religious than prisoners convicted of theft, drugs etc. In this respect, the factors that lead to the criminality of women, who were convicted of murder or attempt murder, convicted of wounding offenses and who defined themselves as religious, are determined. Another aim is to demonstrate the crime and victim relationship, how convicts explain criminal actions to themselves and their surroundings and how they justify themselves. Questionnaires and semi-structured interview techniques were used as a method. In this direction, the findings obtained from the results of the questionnaire conducted with 151 women convicts were evaluated by descriptive statistical method and the results of semi-structured interviews with 8 women were included in the results. These types of explanations, included in neutralization techniques, are: commitment to values, the role of the victim, and rejection of responsibility. In the first place, the victim sees the situation as a matter of honor and explains the guilt involved with their beliefs / beliefs. Secondly, the violence (domestic problems that is experienced is said to be the result, as in the opposite party deserves it. In the third place, the victim rejects the responsibility, indicating that the mental illness or depression is the result of suicide. Öz      Bu çalışma, Ankara (Sincan, İzmir (Şakran ve İstanbul (Bakırköy kadın kapalı ceza infaz kurumlarında bulunan hayata ve vücut dokunulmazlığına karşı suç işlemiş hükümlü kadın mahkûmlarla yapılan araştırma sonuçlarından oluşmaktadır. Araştırmanın kapsam

Developing a chronostratigraphic tool for climatic archives: absolute dating (K/Ar and 40Ar/39Ar) and paleo-magnetism applied to lavas

International Nuclear Information System (INIS)

Sasco, Romain

2015-01-01

The understanding of climatic mechanisms and rapid climate changes requires a high-resolution, robust, and precise timescale which allows long-distance and multi-archives correlations.An appropriate tool to construct such a timescale is provided by the Earth magnetic field (EMF). The EMF is independent from climatic variations and its past evolution, global at the surface of the Earth, is recorded by most of the geological/climatic archives. Sedimentary sequences provide continuous records of relative intensities of the EMF on timescales usually based on ice core age models or orbital tuning. Lavas, though discontinuously emitted through time, record the absolute intensity of the EMF during their cooling at the surface of the Earth. Lavas are dated using 2 complementary methods: 40 Ar/ 39 Ar and K-Ar, both independent from climatic parameters. Lavas have therefore the potential to deliver tie-points (age - paleo-intensity couples) enabling the time calibration of sedimentary sequences and their transfer onto absolute intensity scale and chronological time scale. This timescale can then be transferred to other climatic archives. The present study focusses on the last 200 ka with lavas sampled from young volcanoes of Ardeche (South Massif Central, France) and recent phases of volcanism in the Canary Islands. Lava flows from Ardeche provided un-exploitable paleo-intensity results and ages with large uncertainties. Therefore, they failed to provide suitable tie-points. However, our geochronological results evidence how crucial the combination of both the K-Ar and 40 Ar/ 39 Ar methods is to test the accuracy and geological meaning of the ages. Ardeche lavas have abundant mantellic and crustal xenoliths, potential carriers of excess 40 Ar*. Our study suggests that the argon excess is located in sites that decrepitate at low temperature (≤600 C). Because 40 Ar/ 39 Ar ages are not affected by excess 40 Ar*, they provide reliable results. The new age dataset indicates

Receptor-receptor interactions within receptor mosaics. Impact on neuropsychopharmacology.

Science.gov (United States)

Fuxe, K; Marcellino, D; Rivera, A; Diaz-Cabiale, Z; Filip, M; Gago, B; Roberts, D C S; Langel, U; Genedani, S; Ferraro, L; de la Calle, A; Narvaez, J; Tanganelli, S; Woods, A; Agnati, L F

2008-08-01

Future therapies for diseases associated with altered dopaminergic signaling, including Parkinson's disease, schizophrenia and drug addiction or drug dependence may substantially build on the existence of intramembrane receptor-receptor interactions within dopamine receptor containing receptor mosaics (RM; dimeric or high-order receptor oligomers) where it is believed that the dopamine D(2) receptor may operate as the 'hub receptor' within these complexes. The constitutive adenosine A(2A)/dopamine D(2) RM, located in the dorsal striato-pallidal GABA neurons, are of particular interest in view of the demonstrated antagonistic A(2A)/D(2) interaction within these heteromers; an interaction that led to the suggestion and later demonstration that A(2A) antagonists could be used as novel anti-Parkinsonian drugs. Based on the likely existence of A(2A)/D(2)/mGluR5 RM located both extrasynaptically on striato-pallidal GABA neurons and on cortico-striatal glutamate terminals, multiple receptor-receptor interactions within this RM involving synergism between A(2A)/mGluR5 to counteract D(2) signaling, has led to the proposal of using combined mGluR5 and A(2A) antagonists as a future anti-Parkinsonian treatment. Based on the same RM in the ventral striato-pallidal GABA pathways, novel strategies for the treatment of schizophrenia, building on the idea that A(2A) agonists and/or mGluR5 agonists will help reduce the increased dopaminergic signaling associated with this disease, have been suggested. Such treatment may ensure the proper glutamatergic drive from the mediodorsal thalamic nucleus to the prefrontal cortex, one which is believed to be reduced in schizophrenia due to a dominance of D(2)-like signaling in the ventral striatum. Recently, A(2A) receptors also have been shown to counteract the locomotor and sensitizing actions of cocaine and increases in A(2A) receptors have also been observed in the nucleus accumbens after extended cocaine self-administration, probably

Kannatanu nõusolek kui õigusvastasust välistav asjaolu vägivallategude kontekstis / Allar Nisu

Index Scriptorium Estoniae

Nisu, Allar, 1987-

2015-01-01

Kannatanu nõusolekust kui õigusvastasust välistavast asjaolust ja nõusoleku kehtivuse eeldustest. Kannatanu nõusolekust kehalise väärkohtlemise (KarS § 121), raske tervisekahjustuse tekitamise (KarS § 118) ja tapmise (KarS § 113) valguses

The C1q complement family of synaptic organizers: not just complementary.

Science.gov (United States)

Yuzaki, Michisuke

2017-08-01

Molecules that regulate formation, differentiation, and maintenance of synapses are called synaptic organizers. Recently, various 'C1q family' proteins have been shown to be released from neurons, and serve as a new class of synaptic organizers. Cbln1 and C1ql1 proteins regulate the formation and maintenance of parallel fiber-Purkinje cell and climbing fiber-Purkinje cell synapses, respectively, in the cerebellum. Cbln1 also modulates the function of postsynaptic delta2 glutamate receptors to regulate synaptic plasticity. C1ql2 and C1ql3, released from mossy fibers, determine the synaptic localization of postsynaptic kainate receptors in the hippocampus. C1ql3 also regulates the formation of synapses between the basolateral amygdala and the prefrontal cortex. These findings indicate the diverse functions of C1q family proteins in various brain regions. Copyright © 2017 Elsevier Ltd. All rights reserved.

Mõningatest karistusõiguslikest inimese surma põhjustamise, vabaduse võtmise ja kuriteo varjamisega seotud probleemidest : Riigikohtu kriminaalkolleegiumi otsus asjas 3-1-1-57-10 / Erkki Hirsnik

Index Scriptorium Estoniae

Hirsnik, Erkki, 1982-

2011-01-01

Riigikohtu lahendist 3-1-1-57-10: Andres Rannamehe kaitsja vandeadvokaat Veljo Viiloli, Elina Vainovi kaitsja vandeadvokaat Sirje Musta, kannatanute A. M.-i ja A. M.-i esindaja vandeadvokaat Mart Sikuti ning Lõuna Ringkonnaprokuratuuri kassatsioonid Tartu Ringkonnakohtu 8. aprilli 2010. a kohtuotsuse peale kriminaalasjas Andres Rannamehe süüditunnistamises KarS § 117 lg 1, § 118 p 1 ja § 136 lg 1, Edgar Mengeli süüditunnistamises KarS § 121, Elina Vainovi süüditunnistamises KarS § 209 lg 1 järgi ja õigeksmõistmises KarS § 306 lg 1 ja § 307 lg 1 järgi ning Margit Vilgo õigeksmõistmises KarS § 306 lg 1 ja § 307 lg 1 järgi

Isobolographic analysis of the mechanisms of action of anticonvulsants from a combination effect.

Science.gov (United States)

Matsumura, Nobuko; Nakaki, Toshio

2014-10-15

The nature of the pharmacodynamic interactions of drugs is influenced by the drugs׳ mechanisms of action. It has been hypothesized that drugs with different mechanisms are likely to interact synergistically, whereas those with similar mechanisms seem to produce additive interactions. In this review, we describe an extensive investigation of the published literature on drug combinations of anticonvulsants, the nature of the interaction of which has been evaluated by type I and II isobolographic analyses and the subthreshold method. The molecular targets of antiepileptic drugs (AEDs) include Na(+) and Ca(2+) channels, GABA type-A receptor, and glutamate receptors such as NMDA and AMPA/kainate receptors. The results of this review indicate that the nature of interactions evaluated by type I isobolographic analyses but not by the two other methods seems to be consistent with the above hypothesis. Type I isobolographic analyses may be used not only for evaluating drug combinations but also for predicting the targets of new drugs. Copyright © 2014 Elsevier B.V. All rights reserved.

Distinct roles for key karyogamy proteins during yeast nuclear fusion.

Science.gov (United States)

Melloy, Patricia; Shen, Shu; White, Erin; Rose, Mark D

2009-09-01

During yeast mating, cell fusion is followed by the congression and fusion of the two nuclei. Proteins required for nuclear fusion are found at the surface (Prm3p) and within the lumen (Kar2p, Kar5p, and Kar8p) of the nuclear envelope (NE). Electron tomography (ET) of zygotes revealed that mutations in these proteins block nuclear fusion with different morphologies, suggesting that they act in different steps of fusion. Specifically, prm3 zygotes were blocked before formation of membrane bridges, whereas kar2, kar5, and kar8 zygotes frequently contained them. Membrane bridges were significantly larger and occurred more frequently in kar2 and kar8, than in kar5 mutant zygotes. The kinetics of NE fusion in prm3, kar5, and kar8 mutants, measured by live-cell fluorescence microscopy, were well correlated with the size and frequency of bridges observed by ET. However the kar2 mutant was defective for transfer of NE lumenal GFP, but not diffusion within the lumen, suggesting that transfer was blocked at the NE fusion junction. These observations suggest that Prm3p acts before initiation of outer NE fusion, Kar5p may help dilation of the initial fusion pore, and Kar2p and Kar8p act after outer NE fusion, during inner NE fusion.

40Ar/39Ar laster fusion and K-Ar ages from Lathrop Wells, Nevada, and Cima, California: The age of the latest volcanic activity in the Yucca Mountain area

International Nuclear Information System (INIS)

Turrin, B.D.; Champion, D.E.

1991-01-01

K-Ar and 40 Ar/ 39 Ar ages from the Lathrop Wells volcanic center, Nevada, and from the Cima volcanic field, California, indicate that the recently reported 20-ka age estimate for the Lathrop Wells volcanic center is incorrect. Instead, an age of 119 ± 11 to 141 ± 10 ka is indicated for the Lathrop Wells volcanic center. This age corrected is concordant with the ages determined by two independent isotopic geochronometric techniques and with the stratigraphy of surficial deposits in the Yucca Mountain region. In addition, paleomagnetic data and radiometric age data indicate only two volcanic events at the Lathrop Wells volcanic center that are probably closely linked in time, not as many as five as recently reported. 32 refs., 2 figs., 2 tabs

K-Ar age data and geochemistry of the Kiwitahi Volcanics, western Hauraki Rift, North Island, New Zealand

Energy Technology Data Exchange (ETDEWEB)

Black, P M [Department of Geology, Auckland University, Auckland (New Zealand); Briggs, R M [Department of Earth Sciences, Waikato University, Hamilton (New Zealand); Itaya, T [Hiruzen Research Institute, Okayama University of Science, Okayama (Japan); Dewes, E R [Department of Earth Sciences, Waikato University, Hamilton (New Zealand); Dunbar, H M [Department of Earth Sciences, Waikato University, Hamilton (New Zealand); Kawasaki, K [Hiruzen Research Institute, Okayama University of Science, Okayama (Japan); Kuschel, E [Department of Geology, Auckland University, Auckland (New Zealand); Smith, I E.M. [Department of Geology, Auckland University, Auckland (New Zealand)

1992-07-01

The Kiwitahi Volcanics of late Miocene age crop out in a number of localities situated along the western side of the Hauraki Rift in northern North Island, New Zealand. They extend from Waiheke Island in the north to Te Tapui in the south. From 19 new K-Ar ages presented here and geochemical data from volcanics at each locality, it is suggested that the Kiwitahi Volcanics should be informally subdivided into five groups: (1) an oldest group of agglomerates and volcanic breccias at northeastern Waiheke, containing pyroxene and hornblende andesites with an age range of 14.4-16.02 Ma; (2) a volcanic centre at Stony Batter (6.85-8.34 Ma) comprised of olivine basaltic andesites which should be assigned to the geochemically and temporally similar Ti Point Volcanics; (3) a group including the andesitic breccias at Ness Valley and the volcanic centres of Miranda (pyroxene basaltic andesite, pyroxene and hornblende andesite, hornblende dacite) and Pukekamaka (hornblende andesites), all within the age range 10.22-12.96 Ma; (4) a separate group at Tahuna (6.36-6.80 Ma) consisting of pyroxene basaltic andesites and pyroxene andesites; and (5) a southern group of Maungatapu, Ruru, Maungakawa, and Te Tapui (5.52-6.23 Ma), forming eroded cones of olivine basaltic andesites, pyroxene basaltic andesites, and pyroxene andesites. The Kiwitahi Volcanics of late Miocene age crop out in a number of localities situated along the western side of the Hauraki Rift in northern North Island, New Zealand. They extend from Waiheke Island in the north to Te Tapui in the south. From 19 new K-Ar ages presented here and geochemical data from volcanics at each locality, it is suggested that the Kiwitahi Volcanics should be informally subdivided into five groups: (1) an oldest group of agglomerates and volcanic breccias at northeastern Waiheke, containing pyroxene and hornblende andesites with an age range of 14.4-16.02 Ma; (2) a volcanic centre at Stony Batter (6.85-8.34 Ma) comprised of olivine

K-Ar age data and geochemistry of the Kiwitahi Volcanics, western Hauraki Rift, North Island, New Zealand

International Nuclear Information System (INIS)

Black, P.M.; Briggs, R.M.; Itaya, T.; Dewes, E.R.; Dunbar, H.M.; Kawasaki, K.; Kuschel, E.; Smith, I.E.M.

1992-01-01

The Kiwitahi Volcanics of late Miocene age crop out in a number of localities situated along the western side of the Hauraki Rift in northern North Island, New Zealand. They extend from Waiheke Island in the north to Te Tapui in the south. From 19 new K-Ar ages presented here and geochemical data from volcanics at each locality, it is suggested that the Kiwitahi Volcanics should be informally subdivided into five groups: (1) an oldest group of agglomerates and volcanic breccias at northeastern Waiheke, containing pyroxene and hornblende andesites with an age range of 14.4-16.02 Ma; (2) a volcanic centre at Stony Batter (6.85-8.34 Ma) comprised of olivine basaltic andesites which should be assigned to the geochemically and temporally similar Ti Point Volcanics; (3) a group including the andesitic breccias at Ness Valley and the volcanic centres of Miranda (pyroxene basaltic andesite, pyroxene and hornblende andesite, hornblende dacite) and Pukekamaka (hornblende andesites), all within the age range 10.22-12.96 Ma; (4) a separate group at Tahuna (6.36-6.80 Ma) consisting of pyroxene basaltic andesites and pyroxene andesites; and (5) a southern group of Maungatapu, Ruru, Maungakawa, and Te Tapui (5.52-6.23 Ma), forming eroded cones of olivine basaltic andesites, pyroxene basaltic andesites, and pyroxene andesites. The Kiwitahi Volcanics of late Miocene age crop out in a number of localities situated along the western side of the Hauraki Rift in northern North Island, New Zealand. They extend from Waiheke Island in the north to Te Tapui in the south. From 19 new K-Ar ages presented here and geochemical data from volcanics at each locality, it is suggested that the Kiwitahi Volcanics should be informally subdivided into five groups: (1) an oldest group of agglomerates and volcanic breccias at northeastern Waiheke, containing pyroxene and hornblende andesites with an age range of 14.4-16.02 Ma; (2) a volcanic centre at Stony Batter (6.85-8.34 Ma) comprised of olivine

Coenzyme Q10 instilled as eye drops on the cornea reaches the retina and protects retinal layers from apoptosis in a mouse model of kainate-induced retinal damage.

Science.gov (United States)

Lulli, Matteo; Witort, Ewa; Papucci, Laura; Torre, Eugenio; Schipani, Christian; Bergamini, Christian; Dal Monte, Massimo; Capaccioli, Sergio

2012-12-17

To evaluate if coenzyme Q10 (CoQ10) can protect retinal ganglion cells (RGCs) from apoptosis and, when instilled as eye drops on the cornea, if it can reach the retina and exert its antiapoptotic activity in this area in a mouse model of kainate (KA)-induced retinal damage. Rat primary or cultured RGCs were subjected to glutamate (50 μM) or chemical hypoxia (Antimycin A, 200 μM) or serum withdrawal (FBS, 0.5%) in the presence or absence of CoQ10 (10 μM). Cell viability was evaluated by light microscopy and fluorescence-activated cell sorting analyses. Apoptosis was evaluated by caspase 3/7 activity and mitochondrion depolarization tetramethylrhodamine ethyl ester analysis. CoQ10 transfer to the retina following its instillation as eye drops on the cornea was quantified by HPLC. Retinal protection by CoQ10 (10 μM) eye drops instilled on the cornea was then evaluated in a mouse model of KA-induced excitotoxic retinal cell apoptosis by cleaved caspase 3 immunohistofluorescence, caspase 3/7 activity assays, and quantification of inhibition of RGC loss. CoQ10 significantly increased viable cells by preventing RGC apoptosis. Furthermore, when topically applied as eye drops to the cornea, it reached the retina, thus substantially increasing local CoQ10 concentration and protecting retinal layers from apoptosis. The ability of CoQ10 eye drops to protect retinal cells from apoptosis in the mouse model of KA-induced retinal damage suggests that topical CoQ10 may be evaluated in designing therapies for treating apoptosis-driven retinopathies.

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

2007-01-01

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.

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

2012-09-01

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

Birinci basamak Helikobakter pilori eradikasyon tedavisinde 7 ve 14 günlük lansoprazol, amoksisilin, metronidazol protokolünün karşılaştırılması

OpenAIRE

UYGUN, Ahmet; KANTARCIOĞLU, Murat; POLAT, Zülfikar; KİLCİLER, Güldem; GÜLŞEN, Mustafa

2010-01-01

Giriş ve Amaç: Ülkemizde günümüzde birinci basamak Helikobakter pilori eradikasyon tedavisinde protokollerin süresi ve eradikasyon oranları konusunda tartışmalar sürmektedir. Bu çalışmadaki amacımız; nonülser dispepsili Helikobakter pilori pozitif hastalarda lansoprazol, amoksisilin, metronidazol'den oluşan 7 ve 14 günlük tedavi protokollerinin eradikasyon oranlarını karşılaştırmaktır. Gereç ve Yöntem: Çalışmaya Helikobakter pilori pozitif nonülser dispepsili 180 hasta (84 kadın,...

Neuromodulation by Mg2+ and polyamines of excitatory amino acid currents in rodent neurones in culture.

Science.gov (United States)

Kumamoto, E

1996-12-01

Excitatory amino-acid currents in rodent central neurones are mediated by the activation of glutamate receptors. Ionotropic types of the receptors are divided into alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA), kainate and N-methyl-D-aspartate (NMDA) receptors, and the former two are collectively called non-NMDA receptors. The NMDA receptor is modulated by a number of endogenous neuromodulators including Mg2+, polyamines, glycine and protons in extracellular solutions. Although it has been generally thought that each of the neuromodulators acts on a distinct site in the NMDA receptor, recent studies have revealed that these actions may be not necessarily independent of each other. The NMDA receptor response is not only inhibited but also potentiated by Mg2+, and the latter action is due to an interaction of a Mg2+ site with either glycine- or proton-binding site. In the presence of polyamines, a tonic inhibition by protons of the NMDA receptor response is relieved, resulting in a potentiation of the response. Alternatively, it has been recently revealed that there are some subtypes of non-NMDA receptors which are negatively modulated by polyamines in either extra- or intra cellular solutions. The difference in polyamine sensitivity among non-NMDA receptors is attributed to a distinction in their constituted subunits. The inhibition of non-NMDA receptor by intracellular polyamines results in inward rectification of the current-voltage relation which is not seen for polyamine-insensitive ones. This polyamine action is not mimicked by intracellular Mg2+.

Neonatal domoic acid decreases in vivo binding of [11C]yohimbine to α2 adrenoceptors in adult rat brain

DEFF Research Database (Denmark)

Thomsen, Majken; Lillethorup, Thea Pinholt; Jakobsen, Steen

day 8-14 with saline or one of two low sub-convulsive doses, 20µg/kg [DOM20] or 60µg/kg [DOM60] of DOM, an AMPA/kainate receptor agonist. The behaviour of the rats was observed in an open field test, a social interaction test and the forced swim test at day 50, 75 and 98, respectively. At ~120 days...... of age 3-4 rats per group were injected with [11C]yohimbine, an α2 adrenergic receptor antagonist and scanned in a micro positron emission tomography (PET) scanner. DOM60 spent more time in the periphery during the open field test and less time struggling in the forced swim test compared to the saline...... treated rats. microPET data revealed that DOM60 rats had a 40-47 % reduction in [11C]yohimbine binding in limbic and cortical brain regions relative to saline treated rats. We conclude that neonatal administration of DOM combined with the potential stress associated with behavioural testing results...

Altered gamma oscillations during pregnancy through loss of δ subunit-containing GABAA receptors on parvalbumin interneurons

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Isabella eFerando

2013-09-01

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.

Somatostatin receptors

DEFF Research Database (Denmark)

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

2003-01-01

functional units, receptors co-operate. The total receptor apparatus of individual cell types is composed of different-ligand receptors (e.g. SRIF and non-SRIF receptors) and co-expressed receptor subtypes (e.g. sst(2) and sst(5) receptors) in characteristic proportions. In other words, levels of individual......-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...

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

International Nuclear Information System (INIS)

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

1985-04-01

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

K-Ar and Ar-Ar dating of the Palaeozoic metamorphic complex from the Mid-Bosnian Schist Mts., Central Dinarides, Bosnia and Hercegovina

International Nuclear Information System (INIS)

Pamic, J.; Balogh, K.; Hrvatovic, H.; Balen, D.; Palinkas, L.; Jurkovic, I.

2004-01-01

K-Ar and Ar-Ar whole rock and mineral ages are presented for 25 samples of metamorphic rocks from the Mid-Bosnian Schist Mts., representing one of the largest allochthonous Palaeozoic terranes incorporated within the Internal Dinarides. Four main age groups can be distinguished: 1) Variscan (∼ 343 Ma), 2) post-Variscan (288-238 Ma), 3) Early Cretaceous (mainly 121-92 Ma), and 4) Eocene (59--35 Ma) ages. Apart from this, an Oligocene (31 Ma) age was obtained on Alpine vein hyalophane. The radiometric dating indicates a polyphase metamorphic evolution of the Palaeozoic formations and suggests a pre-Carboniferous age of the volcano-sedimentary protoliths, an Early Carboniferous age of Variscan metamorphism and deformation, post-Variscan volcanism, an Early Cretaceous metamorphic overprint related to out-of-sequence thrusting of the Palaeozoic complex, and an Eocene and Oligocene metamorphic overprint related to the main Alpine compressional deformation and subsequent strike-slip faulting, and uplift of the metamorphic core. Accordingly, the Mid-Bosnian Schist Mts. can be correlated in its multistage geodynamic evolution with some Palaeozoic tectonostratigraphic units from the Austroalpine domain in the Eastern Alps. (author)

Süüteod elu ja tervise vastu / Jaan Sootak

Index Scriptorium Estoniae

Sootak, Jaan, 1948-

2014-01-01

Raske tervisekahjustuse tunnustes tehtud täiendusi ning lisandunud kakluses osalemise koosseisu (KarS § 1191) ja kehalise väärkohtlemise kooseisus (KarS § 121) tehtud muudatusi karistusseadustikus

Binding of L-glutamic acid to non-receptor materials

International Nuclear Information System (INIS)

Periyasamy, S.; Ito, M.; Chiu, T.H.

1986-01-01

[ 3 H]L-glutamic acid ([ 3 H]Glu) binding to microfuge tubes, glass fiber filters, and glass tubes was studied in 4 buffers (50 mM, pH 7.4 at 4 0 C). Binding assays were done at 0-4 0 C. Binding to these materials was negligible in the absence of external force, but was increased by suction or centrifugation in Tris-HCl or Tris-citrate buffer. The force-induced binding was much less or was eliminated in Tris-acetate or HEPES-KOH buffer. [ 3 H]Glu binding to microfuge tubes was inhibited by L- but not D- isomers of glutamate and aspartate. DL-2-amino-7-phosphonoheptanoic acid was without effect. Other compounds that showed low to moderate inhibitory activity were N-methyl-D-aspartate, quisqualate, L-glutamic acid diethyl ester. N-methyl-L-aspartate, kainate, and 2-amino-4-phosphonobutyrate. Binding was inhibited by denatured P 2 membrane preparation in Tris-acetate buffer was used. It is suggested that Tris-acetate or HEPES-KOH buffer should be used in the glutamate binding assay

“Cihanda Türk” Ve “Şarkımız” Şiirlerinin Varlıkbilim Açısından / Ontolojik Açıdan Karşılaştırılması Ontological Comparison Of “Cihanda Türk” And “Şarkimiz” Poems

Directory of Open Access Journals (Sweden)

Salim DURUKOĞLU

2013-09-01

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

Helicobacter pylori eradikasyon tedavisinde 7 ve 14 günlük lansoprazol, amoksisilin, klaritromisin protokolünün karşılaştırılması

OpenAIRE

UYGUN, Ahmet; TÜZÜN, Ahmet; YEŞİLOVA, Zeki; ASLAN, Murat; ATEŞ, Yüksel; POLAT, Zülfikar; ERDİL, Ahmet; BAĞCI, Sait; GÜNHAN, Ömer; GÜLŞEN, Mustafa; DAĞALP, Kemal

2015-01-01

Giriş ve amaç: Günümüzde birinci basamak Helicobacter pylori (Hp) eradikasyon tedavisinde protokollerin süresi ve eradikasyon oranları konusunda tartışmalar sürmektedir. Bu çalışmadaki amacımız; nonülser dispepsili Hp pozitif hastalarda lansoprazol, klaritromisin ve amoksisilin'den oluşan 7 ve 14 günlük tedavi protokollerinin eradikasyon oranları nı karşılaştırmaktır. Gereç ve yöntem: Çalışmaya Hp pozitif nonülser dispepsili 188 hasta (92 kadın, 96 erkek, ortalama yaş 44.8 yıl) alı...

Organize Sanayi Bölgelerinde Faaliyet Gösteren Firmaların Karşılaştıkları İhracat Engelleri: Mersin Tarsus Organize Sanayi Bölgesinde Bir Uygulama

Directory of Open Access Journals (Sweden)

Eda YAŞA ÖZELTÜRKAY

2014-09-01

Full Text Available Dış ticaret faaliyetleri, ülke ekonomileri açısından çok önemli bir yere sahiptir. Bu ekonomik katılımlardan yararlanılırken çeşitli güçlüklerle de karşılaşılabilinmektedir. Dış ticaret faaliyetlerini yürüten işletmeler açısından maliyet çok önemli bir unsurdur. Hükümetlerin bu unsuru göz önüne alarak gerçekleştirmiş olduğu maliyet azaltıcı alt yapı faaliyetlerinden biri de organize sanayi bölgeleridir. Bu çalışma Mersin-Tarsus Organize Sanayi Bölgesinde faaliyet gösteren ve ihracat yapan firmalara ihracat yaparken karşılaşmış oldukları engelleri belirlemek amacıyla uygulanmıştır. 108 firmaya gönderilen anket formlarından 49 tanesi değerlendirmeye uygun olarak geri dönmüştür. Tanımlayıcı bir araştırma olan bu çalışmada literatüre dayalı araştırma soruları oluşturulmuştur. Çalışmadaki verilerin analizinde faktör analizi, güvenilirlik analizi ve tanımlayıcı istatistikî analizlerden faydalanılmıştır. Faktör analizi sonucu, değişkenler yedi alt başlık altında toplanmıştır: firmanın kendi yetersizlikleri, dış pazar ortamına ilişkin engeller, finansal engeller, bilgi eksikliği, bürokratik engeller, kültürel farklılıklar ve ulaşım maliyetleri ve destek eksiklikleri.

Organize Sanayi Bölgelerinde Faaliyet Gösteren Firmaların Karşılaştıkları İhracat Engelleri: Mersin Tarsus Organize Sanayi Bölgesinde Bir Uygulama

Directory of Open Access Journals (Sweden)

Eda YAŞA ÖZELTÜRKAY

2014-12-01

Full Text Available Dış ticaret faaliyetleri, ülke ekonomileri açısından çok önemli bir yere sahiptir. Bu ekonomik katılımlardan yararlanılırken çeşitli güçlüklerle de karşılaşılabilinmektedir. Dış ticaret faaliyetlerini yürüten işletmeler açısından maliyet çok önemli bir unsurdur. Hükümetlerin bu unsuru göz önüne alarak gerçekleştirmiş olduğu maliyet azaltıcı alt yapı faaliyetlerinden biri de organize sanayi bölgeleridir. Bu çalışma Mersin-Tarsus Organize Sanayi Bölgesinde faaliyet gösteren ve ihracat yapan firmalara ihracat yaparken karşılaşmış oldukları engelleri belirlemek amacıyla uygulanmıştır. 108 firmaya gönderilen anket formlarından 49 tanesi değerlendirmeye uygun olarak geri dönmüştür. Tanımlayıcı bir araştırma olan bu çalışmada literatüre dayalı araştırma soruları oluşturulmuştur. Çalışmadaki verilerin analizinde faktör analizi, güvenilirlik analizi ve tanımlayıcı istatistikî analizlerden faydalanılmıştır. Faktör analizi sonucu, değişkenler yedi alt başlık altında toplanmıştır: firmanın kendi yetersizlikleri, dış pazar ortamına ilişkin engeller, finansal engeller, bilgi eksikliği, bürokratik engeller, kültürel farklılıklar ve ulaşım maliyetleri ve destek eksiklikleri.

Effect of lanthanum on rooting of in vitro regenerated shoots of Saussurea involucrata Kar. et Kir.

Science.gov (United States)

Guo, Bin; Xu, Ling-Ling; Guan, Zhen-Jun; Wei, Ya-Hui

2012-06-01

In present study, the effect of lanthanum (La) on the rooting of regenerated shoots of Saussurea involucrata Kar. et Kir was analyzed. Rooting occurred from regenerated shoots inoculated on a medium supplemented with La, the plant rooting hormone indole-3-acetic acid (IAA), or both La and IAA together. The highest rooting efficiency (96%), root number/shoot (8.5), and root length (63 mm) were recorded in shoots cultured on medium containing 2.5 μM IAA combined with 100 μM La(3+). In order to elucidate the mechanism of rooting enhancement by La, we examined dynamic changes in antioxidant enzyme activities in plant tissue over time in culture. We found that the activities of peroxidase (POX) and superoxide dismutase (SOD) were significantly higher in plant tissue cultured in IAA plus La than in La or IAA alone. At the same time, the highest H(2)O(2) content was detected in plant tissue in the presence of 2.5 μM IAA plus 100 μM La(3+). In light of these data and previous results, we speculate that La enhanced IAA-induced rooting by acting as a mild abiotic stress to stimulate POX and SOD activities in plant cells. Then, IAA reacted with oxygen and POX to form the ternary complex enzyme-IAA-O(2) that dissociated into IAA radicals and O(2)(-). Subsequently, IAA-induced O(2)(-) readily converted to hydroxyl radical (HO·) via SOD-catalyzed dismutation. Finally, cell wall loosening and cell elongation occurred as a consequence of HO-dependent scission of wall components, leading to root growth. The treatment of IAA combined with La resulted in the highest plantlet survival (80%) compared to single treatments with IAA or La alone. These data suggest that rare earth elements enhance root morphogenesis and the growth of S. involucrata.

Insulin receptors

International Nuclear Information System (INIS)

Kahn, C.R.; Harrison, L.C.

1988-01-01

This book contains the proceedings on insulin receptors. Part A: Methods for the study of structure and function. Topics covered include: Method for purification and labeling of insulin receptors, the insulin receptor kinase, and insulin receptors on special tissues

Mõned menetlusõiguslikud tähelepanekud. Riigikohtu kriminaalkolleegiumi otsus 3-1-1-22-10 / Oliver Nääs

Index Scriptorium Estoniae

Nääs, Oliver, 1986-

2010-01-01

Riigikohtu lahendist 3-1-1-22-10: Tarmo Silla (Sild) kaitsja vandeadvokaat Üllar Talviste, Villu Reiljani kaitsja vandeadvokaat Aivar Pilve ja Aivo Pärna kaitsja vandeadvokaat Maria Mägi-Rohtmetsa kassatsioonid Tallinna Ringkonnakohtu 20. novembri 2009. a kohtuotsuse peale kriminaalasjas Tarmo Silla süüdistuses KarS § 295 lg 1, Villu Reiljani süüdistuses KarS § 293 lg 2 p-de 2 ja 4 ning Aivo Pärna süüdistuses KarS § 297 lg 1 järgi

Üldohtlik viis, kahe või enama isiku tapmine ja omakasu motiiv kui mõrva tunnused. Riigikohtu kriminaalkolleegiumi otsus asjas 3-1-1-36-09 / Elina Elkind

Index Scriptorium Estoniae

Elkind, Elina, 1982-

2009-01-01

Riigikohtu lahendist 3-1-1-36-09: Nikolai Galkovski kaitsja vandeadvokaat Anatoli Jaroslavski, Andrei Grišini kaitsja vandeadvokaat Leonid Olovjanišnikovi, Aleksandr Semjonovi kaitsja vandeadvokaat Oleg Nišajevi ja Dmitri Štšerbakovi kaitsja vandeadvokaat Toomas Alpi kassatsioonid Tallinna Ringkonnakohtu 24. novembri 2008. a kohtuotsuse peale kriminaalasjas Andrei Grišini süüdistuses KarS § 114 p-de 2, 3 ja 5 ja § 22 lg-te 2 ja 3, Dmitri Štšerbakovi süüdistuses KarS § 114 p-de 2, 3 ja 5, Aleksandr Semjonovi süüdistuses KarS § 114 p-de 2, 3 ja 5 ning Nikolai Galkovski süüdistuses KarS § 257, § 114 p-de 2, 3 ja 5 ja § 22 lg 3 järgi

Seeds of Brassicaceae weeds have an inherent or inducible response to the germination stimulant karrikinolide.

Science.gov (United States)

Long, Rowena L; Stevens, Jason C; Griffiths, Erin M; Adamek, Markus; Gorecki, Marta J; Powles, Stephen B; Merritt, David J

2011-10-01

Karrikinolide (KAR(1)) is a smoke-derived chemical that can trigger seeds to germinate. A potential application for KAR(1) is for synchronizing the germination of weed seeds, thereby enhancing the efficiency of weed control efforts. Yet not all species germinate readily with KAR(1), and it is not known whether seemingly non-responsive species can be induced to respond. Here a major agronomic weed family, the Brassicaceae, is used to test the hypothesis that a stimulatory response to KAR(1) may be present in physiologically dormant seeds but may not be expressed under all circumstances. Seeds of eight Brassicaceae weed species (Brassica tournefortii, Raphanus raphanistrum, Sisymbrium orientale, S. erysimoides, Rapistrum rugosum, Lepidium africanum, Heliophila pusilla and Carrichtera annua) were tested for their response to 1 µm KAR(1) when freshly collected and following simulated and natural dormancy alleviation, which included wet-dry cycling, dry after-ripening, cold and warm stratification and a 2 year seed burial trial. Seven of the eight Brassicaceae species tested were stimulated to germinate with KAR(1) when the seeds were fresh, and the remaining species became responsive to KAR(1) following wet-dry cycling and dry after-ripening. Light influenced the germination response of seeds to KAR(1), with the majority of species germinating better in darkness. Germination with and without KAR(1) fluctuated seasonally throughout the seed burial trial. KAR(1) responses are more complex than simply stating whether a species is responsive or non-responsive; light and temperature conditions, dormancy state and seed lot all influence the sensitivity of seeds to KAR(1), and a response to KAR(1) can be induced. Three response types for generalizing KAR(1) responses are proposed, namely inherent, inducible and undetected. Given that responses to KAR(1) were either inherent or inducible in all 15 seed lots included in this study, the Brassicaceae may be an ideal target for

Riigikohtu kriminaalkolleegiumi 24. aprilli 2009. a otsus kriminaalasjas 3-1-1-10-09 / Margus Mõttus

Index Scriptorium Estoniae

Mõttus, Margus

2009-01-01

Riigikohtu otsusest 3-1-1-10-09: Livio Karro kaitsjate A. Pilve ja R. Otsa, Margus Nei kaitsja T. Pilve, Vladimir Kudrjavtsevi kaitsja A. Lubergi, M. Loorpuu kaitsja T. Ploomipuu, R. Väinoja kaitsja H. Tombergi ja K. Kaunispaiga kaitsja A. Gorkini kassatsioonid kriminaalasjas L. Karro süüdistuses KarS § 294 lg 2 p-de 1 ja 3; § 294 lg 2 p-de 1 ja 3 ja § 22 lg 2 ning § 296 lg 2 p-de 1 ja 2 järgi, M. Nei ja V. Kudrjavtsevi süüdistuses KarS § 294 lg 2 p 3 järgi, R. Väinoja süüdistuses KarS § 298 lg 1 järgi ja K. Kaunispaiga süüdistuses KarS § 298 lg 1 ja § 22 lg 2 järgi

High-resolution immunogold localization of AMPA type glutamate receptor subunits at synaptic and non-synaptic sites in rat hippocampus.

Science.gov (United States)

Baude, A; Nusser, Z; Molnár, E; McIlhinney, R A; Somogyi, P

1995-12-01

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

Devital dişlerin ıntrakoronal ağartmasında kullanılan iki farklı materyalin klinik etkinliğinin karşılaştırılması

OpenAIRE

Keçeci, Diljin

2009-01-01

SüleymanDemirel Üniversitesi TIP FAKÜLTESİ DERGİSİ: 2006 Eylül; 13(3) Devital dişlerin ıntrakoronal ağartmasında kullanılan iki farklı materyalin klinik etkinliğinin karşılaştırılması Diljin Keçeci Devital diş renklenmeleri diş dizisinde kolayca ayırt edilebildiği için özellikle ön dişlerde estetik sorunlara yol açmaktadır. Bu çalışmada kanal tedavisi uygulanmış veya travmaya maruz kalmış, ön dişlerde ortaya çıkan renklenmelerin ağartılması amacıyla bir sodyum perborat (Starbrite, Dentr...

The interleukin-4 receptor: signal transduction by a hematopoietin receptor.

Science.gov (United States)

Keegan, A D; Pierce, J H

1994-02-01

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.

Electron transfer from H2 and Ar to stored multiply charged argon ions produced by synchrotron radiation

International Nuclear Information System (INIS)

Kravis, S.D.; Church, D.A.; Johnson, B.M.; Meron, M.; Jones, K.W.; Levin, J.C.; Sellin, I.A.; Azuma, Y.; Berrah-Mansour, N.; Berry, H.G.; Druetta, M.

1992-01-01

The rate coefficients for electron transfer from Ar and H 2 to Ar q+ ions (3≤q≤6) have been measured using an ion-storage technique in a Penning ion trap. The ions were produced in the trap by K-shell photoionization of Ar atoms, using broadband synchrotron x-ray radiation. K-electron removal resulted in vacancy cascading, yielding a distribution of argon-ion charge states peaked near Ar 4+ . The stored ion gas had an initial temperature near 480 K. The basic data determining the rate coefficients k(Ar q+ ) are the storage time constants of each charge state in the trap, in the presence of a measured pressure of target gas. The results of the measurements (in units of 10 -9 cm 3 s -1 ) are k(Ar 3+ ,H 2 )=4.3(0.7), k(Ar 3+ ,Ar)=1.6(0.2), k(Ar 4+ ,H 2 )=5.2(0.6), k(Ar 4+ ,Ar)=2.5(0.3), k(Ar 5+ ,H 2 )=5.9(0.7), k(Ar 5+ ,Ar)=2.9(0.3), k(Ar 6+ ,H 2 )=8.5(1.2), and k(Ar 6+ ,Ar)=2.5(0.3)

İzmir Merkez İlçelerindeki Akvaryum İşletmelerinin Genel Profilinin Çıkarılması Üzerine Bir Araştırma.

Directory of Open Access Journals (Sweden)

Müge A. Hekimoğlu

2015-12-01

Full Text Available Bu araştırmada, İzmir merkez ilçelerindeki akvaryum işletmelerinin profili çıkarılarak, genel durumları hakkında değerlendirmeler amaçlanmıştır. Çalışmada öncelikle, İzmir`deki mevcut akvaryum işletmelerinin sayısal durumunun tespiti yapılıp; işletmelerin pazarladıkları ürünler belirlenmiş ve gelecekteki pazar durumu hakkında tahminde bulunulmuştur. İzmir ilinde yer alan akvaryum işletmeleriyle doğrudan görüşmeler yoluyla gerçekleştirilen araştırmanın orijinal verileri hazırlanmıştır. Anket çalışmasına temel oluşturan İzmir ilinde bulunan akvaryum işletmeleri ana kitle olarak kabul edilerek tam sayım yöntemi kullanılmıştır. Anket sonuçları SPSS ( The Statistical Package for The Social Sciences paket programı yardımıyla değerlendirilmiştir. Çalışmada belirlenen tüm akvaryum işletmelerinden %65’nin halen faaliyette olduğu, %35’inin ise kapandığı tespit edilmiştir. Halen çalışan akvaryum işletmelerinin %38,2`si Konak, %23,5`u Bornova, %17,6’sı Karşıyaka ve %21,6`sı Buca ve Narlıdere’de bulunmaktadır. Bugüne kadar bu işletmelerin % 82`si üniversiteden danışmanlık almışlardır. Bu akvaryum işletmelerinin %94`ü şahıs işletmesi ve %6’sı ticaret ortaklığıdır, bunun yanında bu işletmelerde çalışanların %94`ü erkek ve çalışanların %59`u lise mezunudur. Araştırma sonunda akvaryumcuların sorunları belirlenerek çözüm önerileri ortaya konulmaya çalışılmıştır

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)

1984-05-01

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.

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

International Nuclear Information System (INIS)

Halliday, A.N.; Mitchell, J.G.

1984-01-01

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. (orig.)

The LDL receptor.

Science.gov (United States)

Goldstein, Joseph L; Brown, Michael S

2009-04-01

In this article, the history of the LDL receptor is recounted by its codiscoverers. Their early work on the LDL receptor explained a genetic cause of heart attacks and led to new ways of thinking about cholesterol metabolism. The LDL receptor discovery also introduced three general concepts to cell biology: receptor-mediated endocytosis, receptor recycling, and feedback regulation of receptors. The latter concept provides the mechanism by which statins selectively lower plasma LDL, reducing heart attacks and prolonging life.

Nd and Sr isotopes and K-Ar ages of the Ulreungdo alkali volcanic rocks in the East Sea, South Korea

International Nuclear Information System (INIS)

Kim Kyuhan; Jang Sunkyung; Tanaka, Tsuyoshi; Nagao, Keisuke

1999-01-01

Temporal geochemical and isotopical variations in the Ulreundgo alkali volcanic rocks provide important constraints on the origin and evolution of the volcanic rocks in relation to backarc basin tectonism. We determined the K-Ar ages, major and trace element contents, and Nd and Sr isotopic rations of the alkali volcanic rocks. The activities of Ulreungdo volcanoes can be divided, on the basis of radiometric ages and field occurrences, into five stages, though their activities range from 1.4 Ma to 0.01 Ma with short volcanic hiatus (ca. 0.05-0.3 Ma). The Nd-Sr isotopic data for Ulreungdo volcanic rocks enable us to conclude that: (1) the source materials of Ulreungdo volcanics are isotopically heterogeneous in composition, which is explained by the mixing of mantle derived magma and continental crustal source rocks. There is no systematic isotopic variations with eruption stages. Particularly, some volcanic rocks of stage 2 and 3 have extremely wide initial 87 Sr/ 86 Sr isotopic variations ranging from 0.7038 to 0.7092, which are influenced by seawater alterations; (2) the Ulreungdo volcanic rocks show EMI characteristic, while volcanic rocks from the Jejudo, Yeong-il and Jeon-gok areas have slightly depleted mantle source characteristics; (3) the trachyandesite of the latest eruption stage was originated from the mantle source materials which differ from other stages. A schematic isotopic evolution model for alkali basaltic magma is presented in the Ulreungdo volcanic island of the backarc basin of Japanese island arc system. (author)

Autecology of Astragalus arpilobus Kar. & Kir, a promised species for restoration of the winter rangelands in the northeast of Iran

Directory of Open Access Journals (Sweden)

M. Jankju

2016-04-01

Full Text Available Studying the autecology of range plants provides the basic information on their ecological requirements, cultivation methods and the interactions with the prevailing environment. Such information is necessary for a proper range management. Some ecological characteristics of Astragalus arpilobus Kar. & Kir., were studied in the winter rangelands of Northern Khorasan province. It was naturally growing in Jargalan, Bojnourd, where the altitudinal range varied 500-600 a.s.l, slope 20-100%, and the average annual rainfall 236.85 mm. Soil properties were: loamy texture, average organic matter, low fertility, pH 7.32 and EC 2.30 ds.m-1. A. aripilobus started vegetative growth at the early March, flowering during early May, seed production during June, and terminated its yearly growth at early July. The highest nutritive values and forage quality were at the beginning of growth, which was gradually decreased towards the end of growth season. Crude protein (CP, and ash were decreased whereas acid detergent fiber (ADF, natural detergent fiber (NDF, and dry matter (DM increased by the growing season. Seeds were easily established within pots; however, seed germination rate was low (24%, which by sand paper scarification was increased up to 51%. In conclusion, feasibility of seedling establishment, high nutritive value, and concurrence of plant phenology with the time of maximum need to fodder, by livestocks, propose A. arpilobus as a promising forage plant species for restoration of the winter rangelands in Northern Khorasan province.

U-Pb and K-Ar geochronology from the Cerro Empexa Formation, 1st and 2nd Regions, Precordillera, northern Chile

International Nuclear Information System (INIS)

Tomlinson, A.J; Martin, M.W; Blanco, N.; Perez de Arce, C

2001-01-01

The Cerro Empexa Formation (Galli, 1957) is a regionally distributed andesitic volcanic and continental sedimentary unit exposed in the Precordillera of the 1st and 2nd Regions of northern Chile. The formation has generally been considered to lie within the Lower or 'mid' Cretaceous, however, this assignment is based on scant, unreliable geochronologic data. Furthermore, there are conflicting interpretations as to whether the unit predates or postdates the first major Mesozoic shortening event affecting northern Chile. Because of the formation's presumed mid-Cretaceous age and its stratigraphic position over older back-arc sedimentary successions, the unit has been interpreted to represent products of the first eastward jump in the Andean magmatic arc from the arc's initial position in the Cordillera de la Costa (Scheuber and Reutter, 1992). In this paper we present the results of mapping and field observations that indicate exposures previously assigned to the Cerro Empexa Formation include two andesitic volcanic units separated by a major unconformity. The Cerro Empexa Formation proper lies above this unconformity. We also present U-Pb zircon and K-Ar geochronology that indicate the Cerro Empexa Formation is latest Cretaceous in its lower levels, and integrate our data with previously reported 40 Ar/ 39 Ar and fission-track data in the Cerros de Montecristo area (Maksaev, 1990; Maksaev and Zentilli, 1999) to show that 1800±600 m of rocks were deposited within ca. 2.5 m.y (au)

Sürtünme Karıştırma Kaynak Yöntemiyle Birleştirilen Farklı Tipteki Alüminyum Bağlantıların Tahribatlı ve Tahribatsız Muayenesi

Directory of Open Access Journals (Sweden)

Furkan SARSILMAZ

2009-04-01

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

Larinks kanserli hastalarda serum CA 72-4, CA 19-9, CEA ve kombine tümör marker seviyelerinin karşılaştırılması ve prognostik değerleri

OpenAIRE

Altaş, Enver; Kızıltunç, Ahmet; Karaşen, R.Murat; Öztürk, Aziz; Sütbeyaz, Yavuz; Gündoğdu, Cemal

2009-01-01

SüleymanDemirel Üniversitesi TIP FAKÜLTESİ DERGİSİ: 1997 Haziran; 4(3) Larinks kanserli hastalarda serum CA 72-4, CA 19-9, CEA ve kombine tümör marker seviyelerinin karşılaştırılması ve prognostik değerleri Enver Altaş Ahmet Kızıltunç R. Murat Karaşen Aziz Öztürk Yavuz Sütbeyaz Cemal Gündoğdu ÖzetLarinks kanserli hastaların tedavi etkinliklerinin takibinde çeşitli klinik ve laboratuvar tetkikleri kullanılmaktadır. Tümör markerleri de bu tetkiklerden birisidir. Ancak, CA 19-9 (Carbohydr...

β-Adrenergic receptor-mediated suppression of interleukin 2 receptors in human lymphocytes

International Nuclear Information System (INIS)

Feldman, R.D.; Hunninghake, G.W.; McArdle, W.L.

1987-01-01

Adrenergic receptor agonists are know to attenuate the proliferative response of human lymphocytes after activation; however, their mechanism of action is unknown. Since expression of interleukin 2 (IL-2) receptors is a prerequisite for proliferation, the effect of β-adrenergic receptor agonists on lymphocyte IL-2 receptors was studied on both mitogen-stimulated lymphocytes and IL-2-dependent T lymphocyte cell lines. In both cell types the β-adrenergic receptor agonist isoproterenol blocked the expression of IL-2 receptors, as determined with the IL-2 receptor anti-TAC antibody. To determine the effect of β-adrenergic agonists on expression of the high affinity IL-2 receptors, [ 125 I]IL-2 binding studies were performed at concentrations selective for high affinity sites. No significant effect of β-adrenergic agonists on high affinity IL-2 receptor sites could be detected. The data demonstrate that β-adrenergic receptor agonists down-regulate IL-2 receptors primarily affecting low affinity sites

Isotopegeochemical investigations and dating on minerals and fossils from sedimentary rocks: 1. Glauconites from Jura, Molasse and Helveticum (K-Ar, Rb-Sr), 2. 87Sr/86Sr-Isotope stratigraphy on marine and limnetic micro- and macro-fossils, 3. Primary minerals from tertiary bentonites and tuffs (U-Pb, K-Ar)

International Nuclear Information System (INIS)

Fischer, H.

1988-01-01

Glauconite investigations: the main problem in dating glauconites lies in the identification of authigenic minerals which have not been influenced by post-sedimentary processes. The age determination on glauconites from the three different tectonic units: the Jura mountains, the molasse basin and the Helvetic nappes, yield inconsistent results. Up to 35% too young K-Ar ''ages'' of glauconites from limestones from the Helvetic nappes can be traced to partial Ar loss caused by sediment-lithification and tectonic events. Sr-isotope stratigraphy: multiple analyses of recent samples from the Mediterranean Sea and from the North Atlantic show that the 87 Sr/ 86 Sr isotope ratios correspond well. In a stratigraphic ideal section from the Upper marine molasse a resolution of 206 Pb/ 238 U method zircons from the Fish Canyon Tuff were measured and yielded ages of 28.49±0.10, 24.46±0.11 and 28.46±0.13 Ma. These values correspond well with the published mean value of zircon and apatite fission track age of 28.4±0.7 Ma. Thus, the U-Pb method for dating young volcanic minerals seems to be suitable. However, the published mean value (''solid state age'') of Naeser et al. (1981) is higher than the published (''gas age'') mean value of 27.2±0.7 Ma based on biotite, sanidine, hornblende and plagioclase. (author) figs., tabs., refs

Quantitative receptor radioautography in the study of receptor-receptor interactions in the nucleus tractus solitarii

Directory of Open Access Journals (Sweden)

Fior-Chadi D.R.

1998-01-01

Full Text Available The nucleus tractus solitarii (NTS in the dorsomedial medulla comprises a wide range of neuropeptides and biogenic amines. Several of them are related to mechanisms of central blood pressure control. Angiotensin II (Ang II, neuropeptide Y (NPY and noradrenaline (NA are found in the NTS cells, as well as their receptors. Based on this observation we have evaluated the modulatory effect of these peptide receptors on a2-adrenoceptors in the NTS. Using quantitative receptor radioautography, we observed that NPY and Ang II receptors decreased the affinity of a2-adrenoceptors for their agonists in the NTS of the rat. Cardiovascular experiments agreed with the in vitro data. Coinjection of a threshold dose of Ang II or of the NPY agonists together with an ED50 dose of adrenergic agonists such as NA, adrenaline and clonidine counteracted the depressor effect produced by the a2-agonist in the NTS. The results provide evidence for the existence of an antagonistic interaction between Ang II at1 receptors and NPY receptor subtypes with the a2-adrenoceptors in the NTS. This receptor interaction may reduce the transduction over the a2-adrenoceptors which can be important in central cardiovascular regulation and in the development of hypertension

Neonatal domoic acid decreases in vivo binding of [11C]yohimbine to α2 adrenoceptors in adult rat brain

DEFF Research Database (Denmark)

Thomsen, Majken; Lillethorup, Thea Pinholt; Jakobsen, Steen

-quantitative analysis. MicroPET images were analyzed using PMOD software and registered to an average Sprague-Dawley rat MRI brain atlas to acquire data in limbic and cortical regions of interest. Results: In behavioural testing DOM60, and to a lesser extent DOM20 rats, spent more time in the periphery during the open......-Dawley rats (n=6-7 per group) were injected (s.c.) daily from postnatal day 8-14 with saline or one of two low sub-convulsive doses, 20µg/kg [DOM20] or 60µg/kg [DOM60] of DOM, an AMPA/kainate receptor agonist. The behaviour of the rats was observed in an open field test, a social interaction test...... and the forced swim test at day 50, 75 and 98, respectively. At ~120 days of age 3-4 rats per group were injected with [11C]yohimbine, an α2 adrenergic receptor antagonist, and scanned in a Mediso micro positron emission tomography (PET) scanner, to measure α2 adrenoceptor binding. The volume of distribution (VT...

Characterization of neuronal intrinsic properties and synaptic transmission in layer I of anterior cingulate cortex from adult mice

Directory of Open Access Journals (Sweden)

Li Xiang-Yao

2012-07-01

Full Text Available Abstract The neurons in neocortex layer I (LI provide inhibition to the cortical networks. Despite increasing use of mice for the study of brain functions, few studies were reported about mouse LI neurons. In the present study, we characterized intrinsic properties of LI neurons of the anterior cingulate cortex (ACC, a key cortical area for sensory and cognitive functions, by using whole-cell patch clamp recording approach. Seventy one neurons in LI and 12 pyramidal neurons in LII/III were recorded. Although all of the LI neurons expressed continuous adapting firing characteristics, the unsupervised clustering results revealed five groups in the ACC, including: Spontaneous firing neurons; Delay-sAHP neurons, Delay-fAHP neurons, and two groups of neurons with ADP, named ADP1 and ADP2, respectively. Using pharmacological approaches, we found that LI neurons received both excitatory (mediated by AMPA, kainate and NMDA receptors, and inhibitory inputs (which were mediated by GABAA receptors. Our studies provide the first report characterizing the electrophysiological properties of neurons in LI of the ACC from adult mice.

XMRV: usage of receptors and potential co-receptors

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Gaddam Durga

2011-09-01

Full Text Available Abstract Background XMRV is a gammaretrovirus first identified in prostate tissues of Prostate Cancer (PC patients and later in the blood cells of patients with Chronic Fatigue Syndrome (CFS. Although XMRV is thought to use XPR1 for cell entry, it infects A549 cells that do not express XPR1, suggesting usage of other receptors or co-receptors. Methods To study the usage of different receptors and co- receptors that could play a role in XMRV infection of lymphoid cells and GHOST (GFP- Human osteosarcoma cells expressing CD4 along with different chemokine receptors including CCR1, CCR2, etc., were infected with XMRV. Culture supernatants and cells were tested for XMRV replication using real time quantitative PCR. Results Infection and replication of XMRV was seen in a variety of GHOST cells, LNCaP, DU145, A549 and Caski cell lines. The levels of XMRV replication varied in different cell lines showing differential replication in different cell lines. However, replication in A549 which lacks XPR1 expression was relatively higher than DU145 but lower than, LNCaP. XMRV replication varied in GHOST cell lines expressing CD4 and each of the co- receptors CCR1-CCR8 and bob. There was significant replication of XMRV in CCR3 and Bonzo although it is much lower when compared to DU145, A549 and LNCaP. Conclusion XMRV replication was observed in GHOST cells that express CD4 and each of the chemokine receptors ranging from CCR1- CCR8 and BOB suggesting that infectivity in hematopoietic cells could be mediated by use of these receptors.

GABA receptor imaging

Energy Technology Data Exchange (ETDEWEB)

Lee, Jong Doo [Yonsei University College of Medicine, Seoul (Korea, Republic of)

2007-04-15

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.

GABA receptor imaging

International Nuclear Information System (INIS)

Lee, Jong Doo

2007-01-01

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 A -receptor that allows chloride to pass through a ligand gated ion channel and GABA B -receptor that uses G-proteins for signaling. The GABA A -receptor has a GABA binding site as well as a benzodiazepine binding sites, which modulate GABA 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 11 C-FMZ, a benzodiazepine derivate that is a selective, reversible antagonist to GABAA receptors. Recently, 18 F-fluoroflumazenil (FFMZ) has been developed to overcome 11 C's short half-life. 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 1 C-FMZ PET instead of 18 F-FDG, PET, restrict the foci better and may also help find lesions better than high resolution MR. GABA 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

The two-state dimer receptor model: a general model for receptor dimers.

Science.gov (United States)

Franco, Rafael; Casadó, Vicent; Mallol, Josefa; Ferrada, Carla; Ferré, Sergi; Fuxe, Kjell; Cortés, Antoni; Ciruela, Francisco; Lluis, Carmen; Canela, Enric I

2006-06-01

Nonlinear Scatchard plots are often found for agonist binding to G-protein-coupled receptors. Because there is clear evidence of receptor dimerization, these nonlinear Scatchard plots can reflect cooperativity on agonist binding to the two binding sites in the dimer. According to this, the "two-state dimer receptor model" has been recently derived. In this article, the performance of the model has been analyzed in fitting data of agonist binding to A(1) adenosine receptors, which are an example of receptor displaying concave downward Scatchard plots. Analysis of agonist/antagonist competition data for dopamine D(1) receptors using the two-state dimer receptor model has also been performed. Although fitting to the two-state dimer receptor model was similar to the fitting to the "two-independent-site receptor model", the former is simpler, and a discrimination test selects the two-state dimer receptor model as the best. This model was also very robust in fitting data of estrogen binding to the estrogen receptor, for which Scatchard plots are concave upward. On the one hand, the model would predict the already demonstrated existence of estrogen receptor dimers. On the other hand, the model would predict that concave upward Scatchard plots reflect positive cooperativity, which can be neither predicted nor explained by assuming the existence of two different affinity states. In summary, the two-state dimer receptor model is good for fitting data of binding to dimeric receptors displaying either linear, concave upward, or concave downward Scatchard plots.

3He/4He ratio, noble gas abundance and K-Ar dating of diamonds - an attempt to search for the records of early terrestrial history

International Nuclear Information System (INIS)

Ozima, M.; Zashu, S.; Nitoh, O.

1983-01-01

The 3 He/ 4 He ratios measured in 27 Southern Africa diamond stones, four from Premier Mine and the rest of unidentified origin, range from 4.2 x 10 -8 to 3.2 x 10 -4 , with three stones above 1 x 10 -4 . We conclude that the initial helium isotopic ratio ( 3 He/ 4 He) 0 in the earth was significantly higher than that of the planetary helium-A ( 3 He/ 4 He = 1.42 x 10 -4 ), but close to the solar helium ( 3 He/ 4 He = approx. 4 x 10 -4 ). The apparent K-Ar ages for the twelve diamonds of unidentified origin show enormously old age, indicating excess argon-40. 3 He/ 4 He evolution in diamonds suggests that the diamonds with the high 3 He/ 4 He ratio (> 2 x 10 -4 ) may be as old as the earth. Noble gas elemental abundance in the diamonds relative to the air noble gas abundance shows monotonic decrease with a decreasing mass number. This paper discusses the implications of these observations on the early solar system and the origin of diamonds. (author)

U/Pb (SHRIMP), 207Pb/206Pb, 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

International Nuclear Information System (INIS)

Leal, Luiz Rogerio Bastos

1998-01-01

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. 207 Pb/ 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. 207 Pb/ 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 DM model ages varying between 3.26 and 3.36 Ga and ε Nd (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 N =83,5), low HREE contents (La N =2,5) and a fairly fractionated pattern (La/Yb) 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 effect of younger regional cooling episodes related to the

Karrikins delay soybean seed germination by mediating abscisic acid and gibberellin biogenesis under shaded conditions

Science.gov (United States)

Meng, Yongjie; Chen, Feng; Shuai, Haiwei; Luo, Xiaofeng; Ding, Jun; Tang, Shengwen; Xu, Shuanshuan; Liu, Jianwei; Liu, Weiguo; Du, Junbo; Liu, Jiang; Yang, Feng; Sun, Xin; Yong, Taiwen; Wang, Xiaochun; Feng, Yuqi; Shu, Kai; Yang, Wenyu

2016-01-01

Karrikins (KAR) are a class of signal compounds, discovered in wildfire smoke, which affect seed germination. Currently, numerous studies have focused on the model plant Arabidopsis in the KAR research field, rather than on crops. Thus the regulatory mechanisms underlying KAR regulation of crop seed germination are largely unknown. Here, we report that KAR delayed soybean seed germination through enhancing abscisic acid (ABA) biosynthesis, while impairing gibberellin (GA) biogenesis. Interestingly, KAR only retarded soybean seed germination under shaded conditions, rather than under dark and white light conditions, which differs from in Arabidopsis. Phytohormone quantification showed that KAR enhanced ABA biogenesis while impairing GA biosynthesis during the seed imbibition process, and subsequently, the ratio of active GA4 to ABA was significantly reduced. Further qRT-PCR analysis showed that the transcription pattern of genes involved in ABA and GA metabolic pathways are consistent with the hormonal measurements. Finally, fluridone, an ABA biogenesis inhibitor, remarkably rescued the delayed-germination phenotype of KAR-treatment; and paclobutrazol, a GA biosynthesis inhibitor, inhibited soybean seed germination. Taken together, these evidences suggest that KAR inhibit soybean seed germination by mediating the ratio between GA and ABA biogenesis. PMID:26902640

Karrikins delay soybean seed germination by mediating abscisic acid and gibberellin biogenesis under shaded conditions.

Science.gov (United States)

Meng, Yongjie; Chen, Feng; Shuai, Haiwei; Luo, Xiaofeng; Ding, Jun; Tang, Shengwen; Xu, Shuanshuan; Liu, Jianwei; Liu, Weiguo; Du, Junbo; Liu, Jiang; Yang, Feng; Sun, Xin; Yong, Taiwen; Wang, Xiaochun; Feng, Yuqi; Shu, Kai; Yang, Wenyu

2016-02-23

Karrikins (KAR) are a class of signal compounds, discovered in wildfire smoke, which affect seed germination. Currently, numerous studies have focused on the model plant Arabidopsis in the KAR research field, rather than on crops. Thus the regulatory mechanisms underlying KAR regulation of crop seed germination are largely unknown. Here, we report that KAR delayed soybean seed germination through enhancing abscisic acid (ABA) biosynthesis, while impairing gibberellin (GA) biogenesis. Interestingly, KAR only retarded soybean seed germination under shaded conditions, rather than under dark and white light conditions, which differs from in Arabidopsis. Phytohormone quantification showed that KAR enhanced ABA biogenesis while impairing GA biosynthesis during the seed imbibition process, and subsequently, the ratio of active GA4 to ABA was significantly reduced. Further qRT-PCR analysis showed that the transcription pattern of genes involved in ABA and GA metabolic pathways are consistent with the hormonal measurements. Finally, fluridone, an ABA biogenesis inhibitor, remarkably rescued the delayed-germination phenotype of KAR-treatment; and paclobutrazol, a GA biosynthesis inhibitor, inhibited soybean seed germination. Taken together, these evidences suggest that KAR inhibit soybean seed germination by mediating the ratio between GA and ABA biogenesis.

Citation and quantitative analysis for articles of scientific- research journal of “SALAMAT KAR- E- IRAN”, Tehran University of Medical Sciences

Directory of Open Access Journals (Sweden)

A.A. Farshad

2011-12-01

Full Text Available Background and aimsNowadays study on journals is a common work. Thus, for the first time scientific- research journal of “SALAMAT KAR- E- IRAN” has considered to be study.MethodsImportant qualitative indices in studying articles were selected at first (such as distribution of study type, number of studies and balance between subjects, then based on original documents of all volumes, they were analyzed (by Microsoft Excel 2010 software and results were calculated via descriptive statistics methods. ResultsResults from survey and evaluation of 12 published volumes (106 articles showed that the majority of articles were about ergonomics and safety issues. However, in some other subjects there was no article at all. Majority of them have cited the English references. Consensus was a method that has used more than the other sampling methods. Research articles conducted by Male authors were five times more than articles written by females and; Total team corporation coefficient was calculated to be 0.62. Conclusion it was concluded that there was no proper distribution between subjects of articles. English references have cited more than Persian references because of a lack in Persian references or infirmity of a comprehensive indexing system. Considering the methodological point of view the majority of studies were of observational. However, interventional and high level studies can be performed in this field, conditions and facilities must be provided in order to achieve a higher quality and quantity of studies.

Receptor oligomerization in family B1 of G-protein-coupled receptors

DEFF Research Database (Denmark)

Roed, Sarah Norklit; Ørgaard, Anne; Jørgensen, Rasmus

2012-01-01

, the glucagon receptor, and the receptors for parathyroid hormone (PTHR1 and PTHR2). The dysregulation of several family B1 receptors is involved in diseases, such as diabetes, chronic inflammation, and osteoporosis which underlines the pathophysiological importance of this GPCR subfamily. In spite of this......, investigation of family B1 receptor oligomerization and especially its pharmacological importance is still at an early stage. Even though GPCR oligomerization is a well-established phenomenon, there is a need for more investigations providing a direct link between these interactions and receptor functionality......The superfamily of the seven transmembrane G-protein-coupled receptors (7TM/GPCRs) is the largest family of membrane-associated receptors. GPCRs are involved in the pathophysiology of numerous human diseases, and they constitute an estimated 30-40% of all drug targets. During the last two decades...

Activation of glucocorticoid receptors increases 5-HT2A receptor levels

DEFF Research Database (Denmark)

Trajkovska, Viktorija; Kirkegaard, Lisbeth; Krey, Gesa

2009-01-01

an effect of GR activation on 5-HT2A levels, mature organotypic hippocampal cultures were exposed to corticosterone with or without GR antagonist mifepristone and mineralocorticoid receptor (MR) antagonist spironolactone. In GR under-expressing mice, hippocampal 5-HT2A receptor protein levels were decreased......Major depression is associated with both dysregulation of the hypothalamic pituitary adrenal axis and serotonergic deficiency, not the least of the 5-HT2A receptor. However, how these phenomena are linked to each other, and whether a low 5-HT2A receptor level is a state or a trait marker...... of depression is unknown. In mice with altered glucocorticoid receptor (GR) expression we investigated 5-HT2A receptor levels by Western blot and 3H-MDL100907 receptor binding. Serotonin fibre density was analyzed by stereological quantification of serotonin transporter immunopositive fibers. To establish...

Nd and Sr isotopes and K-Ar ages of the Ulreungdo alkali volcanic rocks in the East Sea, South Korea

Energy Technology Data Exchange (ETDEWEB)

Kim Kyuhan; Jang Sunkyung [Ewha Womans Univ., Seoul (Korea); Tanaka, Tsuyoshi; Nagao, Keisuke

1999-07-01

Temporal geochemical and isotopical variations in the Ulreundgo alkali volcanic rocks provide important constraints on the origin and evolution of the volcanic rocks in relation to backarc basin tectonism. We determined the K-Ar ages, major and trace element contents, and Nd and Sr isotopic rations of the alkali volcanic rocks. The activities of Ulreungdo volcanoes can be divided, on the basis of radiometric ages and field occurrences, into five stages, though their activities range from 1.4 Ma to 0.01 Ma with short volcanic hiatus (ca. 0.05-0.3 Ma). The Nd-Sr isotopic data for Ulreungdo volcanic rocks enable us to conclude that: (1) the source materials of Ulreungdo volcanics are isotopically heterogeneous in composition, which is explained by the mixing of mantle derived magma and continental crustal source rocks. There is no systematic isotopic variations with eruption stages. Particularly, some volcanic rocks of stage 2 and 3 have extremely wide initial {sup 87}Sr/{sup 86}Sr isotopic variations ranging from 0.7038 to 0.7092, which are influenced by seawater alterations; (2) the Ulreungdo volcanic rocks show EMI characteristic, while volcanic rocks from the Jejudo, Yeong-il and Jeon-gok areas have slightly depleted mantle source characteristics; (3) the trachyandesite of the latest eruption stage was originated from the mantle source materials which differ from other stages. A schematic isotopic evolution model for alkali basaltic magma is presented in the Ulreungdo volcanic island of the backarc basin of Japanese island arc system. (author)

Seçici Özellikteki Farklı Besiyerlerinin bazı Mayaların Meyveli Yoğurttan Geri Kazanımları Amacı ile Karşılaştırılmaları (İngilizce)

OpenAIRE

Şule Şenses Ergül; Z. Yeşim Özbaş

2015-01-01

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...

Gβ promotes pheromone receptor polarization and yeast chemotropism by inhibiting receptor phosphorylation.

Science.gov (United States)

Ismael, Amber; Tian, Wei; Waszczak, Nicholas; Wang, Xin; Cao, Youfang; Suchkov, Dmitry; Bar, Eli; Metodiev, Metodi V; Liang, Jie; Arkowitz, Robert A; Stone, David E

2016-04-12

Gradient-directed cell migration (chemotaxis) and growth (chemotropism) are processes that are essential to the development and life cycles of all species. Cells use surface receptors to sense the shallow chemical gradients that elicit chemotaxis and chemotropism. Slight asymmetries in receptor activation are amplified by downstream signaling systems, which ultimately induce dynamic reorganization of the cytoskeleton. During the mating response of budding yeast, a model chemotropic system, the pheromone receptors on the plasma membrane polarize to the side of the cell closest to the stimulus. Although receptor polarization occurs before and independently of actin cable-dependent delivery of vesicles to the plasma membrane (directed secretion), it requires receptor internalization. Phosphorylation of pheromone receptors by yeast casein kinase 1 or 2 (Yck1/2) stimulates their internalization. We showed that the pheromone-responsive Gβγ dimer promotes the polarization of the pheromone receptor by interacting with Yck1/2 and locally inhibiting receptor phosphorylation. We also found that receptor phosphorylation is essential for chemotropism, independently of its role in inducing receptor internalization. A mathematical model supports the idea that the interaction between Gβγ and Yck1/2 results in differential phosphorylation and internalization of the pheromone receptor and accounts for its polarization before the initiation of directed secretion. Copyright © 2016, American Association for the Advancement of Science.

Karrikins delay soybean seed germination by mediating abscisic acid and gibberellin biogenesis under shaded conditions

OpenAIRE

Meng, Yongjie; Chen, Feng; Shuai, Haiwei; Luo, Xiaofeng; Ding, Jun; Tang, Shengwen; Xu, Shuanshuan; Liu, Jianwei; Liu, Weiguo; Du, Junbo; Liu, Jiang; Yang, Feng; Sun, Xin; Yong, Taiwen; Wang, Xiaochun

2016-01-01

Karrikins (KAR) are a class of signal compounds, discovered in wildfire smoke, which affect seed germination. Currently, numerous studies have focused on the model plant Arabidopsis in the KAR research field, rather than on crops. Thus the regulatory mechanisms underlying KAR regulation of crop seed germination are largely unknown. Here, we report that KAR delayed soybean seed germination through enhancing abscisic acid (ABA) biosynthesis, while impairing gibberellin (GA) biogenesis. Interest...

Glucocorticoid receptor modulators.

Science.gov (United States)

Meijer, Onno C; Koorneef, Lisa L; Kroon, Jan

2018-06-01

The glucocorticoid hormone cortisol acts throughout the body to support circadian processes and adaptation to stress. The glucocorticoid receptor is the target of cortisol and of synthetic glucocorticoids, which are used widely in the clinic. Both agonism and antagonism of the glucocorticoid receptor may be beneficial in disease, but given the wide expression of the receptor and involvement in various processes, beneficial effects are often accompanied by unwanted side effects. Selective glucocorticoid receptor modulators are ligands that induce a receptor conformation that allows activation of only a subset of downstream signaling pathways. Such molecules thereby combine agonistic and antagonistic properties. Here we discuss the mechanisms underlying selective receptor modulation and their promise in treating diseases in several organ systems where cortisol signaling plays a role. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Üstün Yetenekli Çocukları Belirlemede Öğretmen Öncelikleri: İkili Karşılaştırma Yöntemiyle Bir Ölçekleme Çalışması

Directory of Open Access Journals (Sweden)

Eren Halil Özberk

2016-08-01

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

Angiotensin type 2 receptor (AT2R) and receptor Mas

DEFF Research Database (Denmark)

Villela, Daniel; Leonhardt, Julia; Patel, Neal

2015-01-01

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 striki...

K/Ar and 40Ar/39Ar dating of emerald mineralizations from Brazil. Evidence of Transamazonian (2 Ga) and Brazilian (650 - 500 Ma) ages. Influence of phlogopite crystallo-chemistry on argon retention

International Nuclear Information System (INIS)

Ribeiro-Althoff, A.M.

1997-01-01

The emerald deposits of Brazil are always found within basic and ultra-basic formations which have been metasomatized by hydrothermal fluids, and transformed into phlogopitites. Two types of deposits may be distinguished: one associated with pegmatites, the other with shear zones. In both cases the precipitation of emerald is contemporaneous with that of phlogopite. The age of these has been determined by dating of the latter, using K-Ar and 40 Ar/ 39 Ar methods. Deposits associated with pegmatite have ages between 2.0 et 1.9 Ga (Carnaiba, Socoto), and between 650 et 500 Ma (Pombos, Juca, Pirenoplis, Capoeirana, Coqui). The Santa Terezinha deposit, associated with a shear zone where pegmatites are absent, gives an age of formation of 520 Ma. These results show that brazilian emeralds were formed during two distinct orogenic periods: the Transamazonian (2.0 Ga), in the Sao Francisco craton, and the Brasilian (650 - 500 Ma)

A search for presynaptic inhibitory histamine receptors in guinea-pig tissues: Further H3 receptors but no evidence for H4 receptors.

Science.gov (United States)

Petri, Doris; Schlicker, Eberhard

2016-07-01

The histamine H4 receptor is coupled to Gi/o proteins and expressed on inflammatory cells and lymphoid tissues; it was suggested that this receptor also occurs in the brain or on peripheral neurones. Since many Gi/o protein-coupled receptors, including the H3 receptor, serve as presynaptic inhibitory receptors, we studied whether the sympathetic neurones supplying four peripheral tissues and the cholinergic neurones in the hippocampus from the guinea-pig are equipped with release-modulating H4 and H3 receptors. For this purpose, we preincubated tissue pieces from the aorta, atrium, renal cortex and vas deferens with (3)H-noradrenaline and hippocampal slices with (3)H-choline and determined the electrically evoked tritium overflow. The stimulation-evoked overflow in the five superfused tissues was inhibited by the muscarinic receptor agonist oxotremorine, which served as a positive control, but not affected by the H4 receptor agonist 4-methylhistamine. The H3 receptor agonist R-α-methylhistamine inhibited noradrenaline release in the peripheral tissues without affecting acetylcholine release in the hippocampal slices. Thioperamide shifted the concentration-response curve of histamine in the aorta and the renal cortex to the right, yielding apparent pA2 values of 8.0 and 8.1, respectively, which are close to its affinity at other H3 receptors but higher by one log unit than its pKi at the H4 receptor of the guinea-pig. In conclusion, histamine H4 receptors could not be identified in five experimental models of the guinea-pig that are suited for the detection of presynaptic inhibitory receptors whereas H3 receptors could be shown in the peripheral tissues but not in the hippocampus. This article is part of the Special Issue entitled 'Histamine Receptors'. Copyright © 2015 Elsevier Ltd. All rights reserved.

Real-Time G-Protein-Coupled Receptor Imaging to Understand and Quantify Receptor Dynamics

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María S. Aymerich

2011-01-01

Full Text Available Understanding the trafficking of G-protein-coupled receptors (GPCRs and their regulation by agonists and antagonists is fundamental to develop more effective drugs. Optical methods using fluorescent-tagged receptors and spinning disk confocal microscopy are useful tools to investigate membrane receptor dynamics in living cells. The aim of this study was to develop a method to characterize receptor dynamics using this system which offers the advantage of very fast image acquisition with minimal cell perturbation. However, in short-term assays photobleaching was still a problem. Thus, we developed a procedure to perform a photobleaching-corrected image analysis. A study of short-term dynamics of the long isoform of the dopamine type 2 receptor revealed an agonist-induced increase in the mobile fraction of receptors with a rate of movement of 0.08 μm/s For long-term assays, the ratio between the relative fluorescence intensity at the cell surface versus that in the intracellular compartment indicated that receptor internalization only occurred in cells co-expressing G protein-coupled receptor kinase 2. These results indicate that the lateral movement of receptors and receptor internalization are not directly coupled. Thus, we believe that live imaging of GPCRs using spinning disk confocal image analysis constitutes a powerful tool to study of receptor dynamics.

Knock-In Mice with NOP-eGFP Receptors Identify Receptor Cellular and Regional Localization.

Science.gov (United States)

Ozawa, Akihiko; Brunori, Gloria; Mercatelli, Daniela; Wu, Jinhua; Cippitelli, Andrea; Zou, Bende; Xie, Xinmin Simon; Williams, Melissa; Zaveri, Nurulain T; Low, Sarah; Scherrer, Grégory; Kieffer, Brigitte L; Toll, Lawrence

2015-08-19

The nociceptin/orphanin FQ (NOP) receptor, the fourth member of the opioid receptor family, is involved in many processes common to the opioid receptors including pain and drug abuse. To better characterize receptor location and trafficking, knock-in mice were created by inserting the gene encoding enhanced green fluorescent protein (eGFP) into the NOP receptor gene (Oprl1) and producing mice expressing a functional NOP-eGFP C-terminal fusion in place of the native NOP receptor. The NOP-eGFP receptor was present in brain of homozygous knock-in animals in concentrations somewhat higher than in wild-type mice and was functional when tested for stimulation of [(35)S]GTPγS binding in vitro and in patch-clamp electrophysiology in dorsal root ganglia (DRG) neurons and hippocampal slices. Inhibition of morphine analgesia was equivalent when tested in knock-in and wild-type mice. Imaging revealed detailed neuroanatomy in brain, spinal cord, and DRG and was generally consistent with in vitro autoradiographic imaging of receptor location. Multicolor immunohistochemistry identified cells coexpressing various spinal cord and DRG cellular markers, as well as coexpression with μ-opioid receptors in DRG and brain regions. Both in tissue slices and primary cultures, the NOP-eGFP receptors appear throughout the cell body and in processes. These knock-in mice have NOP receptors that function both in vitro and in vivo and appear to be an exceptional tool to study receptor neuroanatomy and correlate with NOP receptor function. The NOP receptor, the fourth member of the opioid receptor family, is involved in pain, drug abuse, and a number of other CNS processes. The regional and cellular distribution has been difficult to determine due to lack of validated antibodies for immunohistochemical analysis. To provide a new tool for the investigation of receptor localization, we have produced knock-in mice with a fluorescent-tagged NOP receptor in place of the native NOP receptor. These

Receptor assay

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Kato, K; Ibayashi, H [Kyushu Univ., Fukuoka (Japan). Faculty of Medicine

1975-05-01

This paper summarized present status and problems of analysis of hormone receptor and a few considerations on clinical significance of receptor abnormalities. It was pointed that in future clinical field quantitative and qualitative analysis of receptor did not remain only in the etiological discussion, but that it was an epoch-making field of investigation which contained the possiblity of artificial change of sensitivity of living body on drugs and the development connected directly with treatment of various diseases.

Bazı Şekerlemeler ve Yapay Toz İçeceklerdeki Diazo Boyar Madde Olan Sunset Yellow FCF ile Tartrazin Miktar Tayinlerinin Voltametrik ve Spektrofotometrik Metod Karşılaştırması

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Nejat Altıniğne

2015-02-01

Full Text Available Bazı şekerlemeler ve toz içeceklere katımlı olan sunset yellow FCF ve tartrazin boyar maddelerin analizleri, voltametrik (DPP ve spektrofotometrik metotlarla yapılarak karşılaştırılmıştır. Şekerlemelerde ve sentetik toz içeceklerde boyar maddenin yalnız bir tanesi bulunduğunda, doğru, hassas ve güvenli sonuçlar elde edilebilmektedir. Uygulanan her iki metodun korelasyon sayısı r= 0.995 ve tayin sınıfları 0.8 mg/ml olarak saptanmıştır. Bu çalışma nitel ve nicel tayinlerin, spektrofotometrik metot yanında voltametri metoduyla da yapılabildiğini göstermiştir.

Calcitonin and calcitonin receptor-like receptors: common themes with family B GPCRs?

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Barwell, James; Gingell, Joseph J; Watkins, Harriet A; Archbold, Julia K; Poyner, David R; Hay, Debbie L

2012-05-01

The calcitonin receptor (CTR) and calcitonin receptor-like receptor (CLR) are two of the 15 human family B (or Secretin-like) GPCRs. CTR and CLR are of considerable biological interest as their pharmacology is moulded by interactions with receptor activity-modifying proteins. They also have therapeutic relevance for many conditions, such as osteoporosis, diabetes, obesity, lymphatic insufficiency, migraine and cardiovascular disease. In light of recent advances in understanding ligand docking and receptor activation in both the family as a whole and in CLR and CTR specifically, this review reflects how applicable general family B GPCR themes are to these two idiosyncratic receptors. We review the main functional domains of the receptors; the N-terminal extracellular domain, the juxtamembrane domain and ligand interface, the transmembrane domain and the intracellular C-terminal domain. Structural and functional findings from the CLR and CTR along with other family B GPCRs are critically appraised to gain insight into how these domains may function. The ability for CTR and CLR to interact with receptor activity-modifying proteins adds another level of sophistication to these receptor systems but means careful consideration is needed when trying to apply generic GPCR principles. This review encapsulates current thinking in the realm of family B GPCR research by highlighting both conflicting and recurring themes and how such findings relate to two unusual but important receptors, CTR and CLR. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

Sınıflandırma Problemlerinin Karşılaştırılmasında ANFIS ve Basamak Korelasyon Sinir Ağının Kullanımı

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Nilgün ŞENGÖZ

2016-11-01

Full Text Available Yapılan bu çalışmada, sınıflandırma problemleri üzerinde durulmuştur. Bu çalışma farklı yapıda olan 3 adet veri kümesinin (Tohum, Arazi Uydu Görüntüleme ve Kırmızı Şarap Kalite Değerlendirme incelenmesi ve aynı algoritmaların bu verilere uygulanması itibariyle hem başarı performansı olarak hem de zaman bakımından aralarındaki ilişkiyi gözler önüne sermektedir. Tohum verisi için yapılan karşılaştırmada Uyarlamalı ağ tabanlı bulanık çıkarım sistemi (Adaptive-Network Based Fuzzy Inference Systems-ANFIS  ile Basamak Korelasyon Sinir Ağı BKSA (Cascade Correlation Neural Network-CCNN test performans yüzdeleri %86.41 ve %88.06 olup, işlem zamanı yönünden bakıldığında ise BKSA  0.59 saniye gibi kısa bir süre içerisinde sınıflandırma yapmıştır.  Arazi Uydu Görüntüleme veri kümesinde ise test performans yüzdeleri ANFIS de %100, BKSA da ise %99.92 olmaktadır. Verinin algoritma içerisinde yaptığı işlem süreleri ise ANFIS 800 saniye, BKSA 72 saniyede tüm sınıflandırma işlemini tamamlamıştır. Son veri kümemiz ise Kırmızı Şarap Kalite değerlendirmedir ve test performans olarak bakıldığında ANFIS %99.975, BKSA ise %99.862 gibi birbirleri arasında çokta anlamlı bir fark oluşturmadığı açıkça görünmektedir. İşlem zamanı bakımından ANFIS 85.271 saniye ile BKSA metoduna göre çok hantal kalmaktadır.

Molecular modeling of ligand-receptor interactions in the OR5 olfactory receptor.

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Singer, M S; Shepherd, G M

1994-06-02

Olfactory receptors belong to the superfamily of seven transmembrane domain, G protein-coupled receptors. In order to begin analysis of mechanisms of receptor activation, a computer model of the OR5 olfactory receptor has been constructed and compared with other members of this superfamily. We have tested docking of the odor molecule lyral, which is known to activate the OR5 receptor. The results point to specific ligand-binding residues on helices III through VII that form a binding pocket in the receptor. Some of these residues occupy sequence positions identical to ligand-binding residues conserved among other superfamily members. The results provide new insights into possible molecular mechanisms of odor recognition and suggest hypotheses to guide future experimental studies using site-directed mutagenesis.

Receptor downregulation and desensitization enhance the information processing ability of signalling receptors

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Resat Haluk

2007-11-01

Full Text Available Abstract Background In addition to initiating signaling events, the activation of cell surface receptors also triggers regulatory processes that restrict the duration of signaling. Acute attenuation of signaling can be accomplished either via ligand-induced internalization of receptors (endocytic downregulation or via ligand-induced receptor desensitization. These phenomena have traditionally been viewed in the context of adaptation wherein the receptor system enters a refractory state in the presence of sustained ligand stimuli and thereby prevents the cell from over-responding to the ligand. Here we use the epidermal growth factor receptor (EGFR and G-protein coupled receptors (GPCR as model systems to respectively examine the effects of downregulation and desensitization on the ability of signaling receptors to decode time-varying ligand stimuli. Results Using a mathematical model, we show that downregulation and desensitization mechanisms can lead to tight and efficient input-output coupling thereby ensuring synchronous processing of ligand inputs. Frequency response analysis indicates that upstream elements of the EGFR and GPCR networks behave like low-pass filters with the system being able to faithfully transduce inputs below a critical frequency. Receptor downregulation and desensitization increase the filter bandwidth thereby enabling the receptor systems to decode inputs in a wider frequency range. Further, system-theoretic analysis reveals that the receptor systems are analogous to classical mechanical over-damped systems. This analogy enables us to metaphorically describe downregulation and desensitization as phenomena that make the systems more resilient in responding to ligand perturbations thereby improving the stability of the system resting state. Conclusion Our findings suggest that in addition to serving as mechanisms for adaptation, receptor downregulation and desensitization can play a critical role in temporal information

Modulating Estrogen Receptor-related Receptor-α Activity Inhibits Cell Proliferation*

OpenAIRE

Bianco, Stéphanie; Lanvin, Olivia; Tribollet, Violaine; Macari, Claire; North, Sophie; Vanacker, Jean-Marc

2009-01-01

High expression of the estrogen receptor-related receptor (ERR)-α in human tumors is correlated to a poor prognosis, suggesting an involvement of the receptor in cell proliferation. In this study, we show that a synthetic compound (XCT790) that modulates the activity of ERRα reduces the proliferation of various cell lines and blocks the G1/S transition of the cell cycle in an ERR...

Receptor binding properties and antinociceptive effects of chimeric peptides consisting of a micro-opioid receptor agonist and an ORL1 receptor antagonist.

Science.gov (United States)

Kawano, Susumu; Ito, Risa; Nishiyama, Miharu; Kubo, Mai; Matsushima, Tomoko; Minamisawa, Motoko; Ambo, Akihiro; Sasaki, Yusuke

2007-07-01

Receptor binding properties and antinociceptive activities of chimeric peptides linked by spacers were investigated. The peptides consisted of the micro-opioid receptor ligand dermorphin (Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH(2)) or its analog YRFB (Tyr-D-Arg-Phe-betaAla-NH(2)) linked to the ORL1 receptor ligand Ac-Arg-Tyr-Tyr-Arg-Ile-Lys-NH(2) (Ac-RYYRIK-NH(2)). All chimeric peptides were found to possess high receptor binding affinities for both micro-opioid and ORL1 receptors in mouse brain membranes although their binding affinities for both receptors in spinal membranes were significantly lower. Among them, chimeric peptide 2, which consists of dermorphin and Ac-RYYRIK-NH(2) connected by a long spacer, had the highest binding affinity towards both receptors. In the tail-flick test following intrathecal (i.t.) administration to mice, all chimeric peptides showed potent and dose-dependent antinociceptive activities with an ED(50) of 1.34-4.51 (pmol/mouse), nearly comparable to dermorphin alone (ED(50); 1.08 pmol/mouse). In contrast to their micro-opioid receptor binding profiles, intracerebroventricular (i.c.v.) administration of the chimeric peptides resulted in much less potent antinociceptive activity (ED(50) 5.55-100peptides, and the regulation of mu-opioid receptor-mediated antinociception in brain. The present chimeric peptides may be useful as pharmacological tools for studies on micro-opioid receptor/ORL1 receptor heterodimers.

Glutamate receptor agonists

DEFF Research Database (Denmark)

Vogensen, Stine Byskov; Greenwood, Jeremy R; Bunch, Lennart

2011-01-01

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...

Regulation of neurosteroid biosynthesis by neurotransmitters and neuropeptides

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Jean-Luc eDo-Rego

2012-01-01

Full Text Available The enzymatic pathways leading to the synthesis of bioactive steroids in the brain are now almost completely elucidated in various groups of vertebrates and, during the last decade, the neuronal mechanisms involved in the regulation of neurosteroid production have received increasing attention. This report reviews the current knowledge concerning the effects of neurotransmitters, peptide hormones and neuropeptides on the biosynthesis of neurosteroids. Anatomical studies have been carried out to visualize the neurotransmitter- or neuropeptide-containing fibers contacting steroid-synthesizing neurons as well as the neurotransmitter, peptide hormones or neuropeptide receptors expressed in these neurons. Biochemical experiments have been conducted to investigate the effects of neurotransmitters, peptide hormones or neuropeptides on neurosteroid biosynthesis, and to characterize the type of receptors involved. Thus, it has been found that glutamate, acting through kainate and/or AMPA receptors, rapidly inactivates P450arom, and that melatonin produced by the pineal gland and eye inhibits the biosynthesis of 7-hydroxypregnenolone (7-OH-5P, while prolactin produced by the adenohypophysis enhances the formation of 7-OH-5P. It has also been demonstrated that the biosynthesis of neurosteroids is inhibited by GABA, acting through GABAA receptors, and neuropeptide Y, acting through Y1 receptors. In contrast, it has been shown that the octadecaneuropetide ODN, acting through central-type benzodiazepine receptors, the triakontatetraneuropeptide TTN, acting though peripheral-type benzodiazepine receptors, and vasotocine, acting through V1a-like receptors, stimulate the production of neurosteroids. Since neurosteroids are implicated in the control of various neurophysiological and behavioral processes, these data suggest that some of the neurophysiological effects exerted by neurotransmitters and neuropeptides may be mediated via the regulation

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

1998-07-01

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

Cocaine Inhibits Dopamine D2 Receptor Signaling via Sigma-1-D2 Receptor Heteromers

Science.gov (United States)

Navarro, Gemma; Moreno, Estefania; Bonaventura, Jordi; Brugarolas, Marc; Farré, Daniel; Aguinaga, David; Mallol, Josefa; Cortés, Antoni; Casadó, Vicent; Lluís, Carmen; Ferre, Sergi

2013-01-01

Under normal conditions the brain maintains a delicate balance between inputs of reward seeking controlled by neurons containing the D1-like family of dopamine receptors and inputs of aversion coming from neurons containing the D2-like family of dopamine receptors. Cocaine is able to subvert these balanced inputs by altering the cell signaling of these two pathways such that D1 reward seeking pathway dominates. Here, we provide an explanation at the cellular and biochemical level how cocaine may achieve this. Exploring the effect of cocaine on dopamine D2 receptors function, we present evidence of σ1 receptor molecular and functional interaction with dopamine D2 receptors. Using biophysical, biochemical, and cell biology approaches, we discovered that D2 receptors (the long isoform of the D2 receptor) can complex with σ1 receptors, a result that is specific to D2 receptors, as D3 and D4 receptors did not form heteromers. We demonstrate that the σ1-D2 receptor heteromers consist of higher order oligomers, are found in mouse striatum and that cocaine, by binding to σ1 -D2 receptor heteromers, inhibits downstream signaling in both cultured cells and in mouse striatum. In contrast, in striatum from σ1 knockout animals these complexes are not found and this inhibition is not seen. Taken together, these data illuminate the mechanism by which the initial exposure to cocaine can inhibit signaling via D2 receptor containing neurons, destabilizing the delicate signaling balance influencing drug seeking that emanates from the D1 and D2 receptor containing neurons in the brain. PMID:23637801

Function of the cytoplasmic tail of human calcitonin receptor-like receptor in complex with receptor activity-modifying protein 2

Energy Technology Data Exchange (ETDEWEB)

Kuwasako, Kenji, E-mail: kuwasako@fc.miyazaki-u.ac.jp [Frontier Science Research Center, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692 (Japan); Kitamura, Kazuo; Nagata, Sayaka; Hikosaka, Tomomi [Division of Circulation and Body Fluid Regulation, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692 (Japan); Kato, Johji [Frontier Science Research Center, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692 (Japan)

2010-02-12

Receptor activity-modifying protein 2 (RAMP2) enables calcitonin receptor-like receptor (CRLR) to form an adrenomedullin (AM)-specific receptor. Here we investigated the function of the cytoplasmic C-terminal tail (C-tail) of human (h)CRLR by co-transfecting its C-terminal mutants into HEK-293 cells stably expressing hRAMP2. Deleting the C-tail from CRLR disrupted AM-evoked cAMP production or receptor internalization, but did not affect [{sup 125}I]AM binding. We found that CRLR residues 428-439 are required for AM-evoked cAMP production, though deleting this region had little effect on receptor internalization. Moreover, pretreatment with pertussis toxin (100 ng/mL) led to significant increases in AM-induced cAMP production via wild-type CRLR/RAMP2 complexes. This effect was canceled by deleting CRLR residues 454-457, suggesting Gi couples to this region. Flow cytometric analysis revealed that CRLR truncation mutants lacking residues in the Ser/Thr-rich region extending from Ser{sup 449} to Ser{sup 467} were unable to undergo AM-induced receptor internalization and, in contrast to the effect on wild-type CRLR, overexpression of GPCR kinases-2, -3 and -4 failed to promote internalization of CRLR mutants lacking residues 449-467. Thus, the hCRLR C-tail is crucial for AM-evoked cAMP production and internalization of the CRLR/RAMP2, while the receptor internalization is dependent on the aforementioned GPCR kinases, but not Gs coupling.

Prostaglandin Receptor Signaling in Disease

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Toshiyuki Matsuoka

2007-01-01

Full Text Available Prostanoids, consisting of the prostaglandins (PGs and the thromboxanes (TXs, are a group of lipid mediators formed in response to various stimuli. They include PGD2, PGE2, PGF2α, PGI2, and TXA2. They are released outside of the cells immediately after synthesis, and exert their actions by binding to a G-protein coupled rhodopsin-type receptor on the surface of target cells. There are eight types of the prostanoid receptors conserved in mammals from mouse to human. They are the PGD receptor (DP, four subtypes of the PGE receptor (EP1, EP2, EP3, and EP4, the PGF receptor (FP, PGI receptor (IP, and TXA receptor (TP. Recently, mice deficient in each of these prostanoid receptors were generated and subjected to various experimental models of disease. These studies have revealed the roles of PG receptor signaling in various pathological conditions, and suggest that selective manipulation of the prostanoid receptors may be beneficial in treatment of the pathological conditions. Here we review these recent findings of roles of prostanoid receptor signaling and their therapeutic implications.

Receptor Autoradiography Protocol for the Localized Visualization of Angiotensin II Receptors.

Science.gov (United States)

Linares, Andrea; Couling, Leena E; Carrera, Eduardo J; Speth, Robert C

2016-06-07

This protocol describes receptor binding patterns for Angiotensin II (Ang II) in the rat brain using a radioligand specific for Ang II receptors to perform receptor autoradiographic mapping. Tissue specimens are harvested and stored at -80 °C. A cryostat is used to coronally section the tissue (brain) and thaw-mount the sections onto charged slides. The slide-mounted tissue sections are incubated in (125)I-SI-Ang II to radiolabel Ang II receptors. Adjacent slides are separated into two sets: 'non-specific binding' (NSP) in the presence of a receptor saturating concentration of non-radiolabeled Ang II, or an AT1 Ang II receptor subtype (AT1R) selective Ang II receptor antagonist, and 'total binding' with no AT1R antagonist. A saturating concentration of AT2 Ang II receptor subtype (AT2R) antagonist (PD123319, 10 µM) is also present in the incubation buffer to limit (125)I-SI-Ang II binding to the AT1R subtype. During a 30 min pre-incubation at ~22 °C, NSP slides are exposed to 10 µM PD123319 and losartan, while 'total binding' slides are exposed to 10 µM PD123319. Slides are then incubated with (125)I-SI-Ang II in the presence of PD123319 for 'total binding', and PD123319 and losartan for NSP in assay buffer, followed by several 'washes' in buffer, and water to remove salt and non-specifically bound radioligand. The slides are dried using blow-dryers, then exposed to autoradiography film using a specialized film and cassette. The film is developed and the images are scanned into a computer for visual and quantitative densitometry using a proprietary imaging system and a spreadsheet. An additional set of slides are thionin-stained for histological comparisons. The advantage of using receptor autoradiography is the ability to visualize Ang II receptors in situ, within a section of a tissue specimen, and anatomically identify the region of the tissue by comparing it to an adjacent histological reference section.

Expression of GABAergic receptors in mouse taste receptor cells.

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Margaret R Starostik

Full Text Available BACKGROUND: Multiple excitatory neurotransmitters have been identified in the mammalian taste transduction, with few studies focused on inhibitory neurotransmitters. Since the synthetic enzyme glutamate decarboxylase (GAD for gamma-aminobutyric acid (GABA is expressed in a subset of mouse taste cells, we hypothesized that other components of the GABA signaling pathway are likely expressed in this system. GABA signaling is initiated by the activation of either ionotropic receptors (GABA(A and GABA(C or metabotropic receptors (GABA(B while it is terminated by the re-uptake of GABA through transporters (GATs. METHODOLOGY/PRINCIPAL FINDINGS: Using reverse transcriptase-PCR (RT-PCR analysis, we investigated the expression of different GABA signaling molecules in the mouse taste system. Taste receptor cells (TRCs in the circumvallate papillae express multiple subunits of the GABA(A and GABA(B receptors as well as multiple GATs. Immunocytochemical analyses examined the distribution of the GABA machinery in the circumvallate papillae. Both GABA(A-and GABA(B- immunoreactivity were detected in the peripheral taste receptor cells. We also used transgenic mice that express green fluorescent protein (GFP in either the Type II taste cells, which can respond to bitter, sweet or umami taste stimuli, or in the Type III GAD67 expressing taste cells. Thus, we were able to identify that GABAergic receptors are expressed in some Type II and Type III taste cells. Mouse GAT4 labeling was concentrated in the cells surrounding the taste buds with a few positively labeled TRCs at the margins of the taste buds. CONCLUSIONS/SIGNIFICANCE: The presence of GABAergic receptors localized on Type II and Type III taste cells suggests that GABA is likely modulating evoked taste responses in the mouse taste bud.

AMPA receptor ligands

DEFF Research Database (Denmark)

Strømgaard, Kristian; Mellor, Ian

2004-01-01

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...... in the formation of memory. Hence, ligands affecting AMPARs are highly important for the study of the structure and function of this receptor, and in this regard polyamine-based ligands, particularly polyamine toxins, are unique as they selectively block Ca2+ -permeable AMPARs. Indeed, endogenous intracellular...

A2A-D2 receptor-receptor interaction modulates gliotransmitter release from striatal astrocyte processes.

Science.gov (United States)

Cervetto, Chiara; Venturini, Arianna; Passalacqua, Mario; Guidolin, Diego; Genedani, Susanna; Fuxe, Kjell; Borroto-Esquela, Dasiel O; Cortelli, Pietro; Woods, Amina; Maura, Guido; Marcoli, Manuela; Agnati, Luigi F

2017-01-01

Evidence for striatal A2A-D2 heterodimers has led to a new perspective on molecular mechanisms involved in schizophrenia and Parkinson's disease. Despite the increasing recognition of astrocytes' participation in neuropsychiatric disease vulnerability, involvement of striatal astrocytes in A2A and D2 receptor signal transmission has never been explored. Here, we investigated the presence of D2 and A2A receptors in isolated astrocyte processes prepared from adult rat striatum by confocal imaging; the effects of receptor activation were measured on the 4-aminopyridine-evoked release of glutamate from the processes. Confocal analysis showed that A2A and D2 receptors were co-expressed on the same astrocyte processes. Evidence for A2A-D2 receptor-receptor interactions was obtained by measuring the release of the gliotransmitter glutamate: D2 receptors inhibited the glutamate release, while activation of A2A receptors, per se ineffective, abolished the effect of D2 receptor activation. The synthetic D2 peptide VLRRRRKRVN corresponding to the receptor region involved in electrostatic interaction underlying A2A-D2 heteromerization abolished the ability of the A2A receptor to antagonize the D2 receptor-mediated effect. Together, the findings are consistent with heteromerization of native striatal astrocytic A2A-D2 receptors that via allosteric receptor-receptor interactions could play a role in the control of striatal glutamatergic transmission. These new findings suggest possible new pathogenic mechanisms and/or therapeutic approaches to neuropsychiatric disorders. © 2016 International Society for Neurochemistry.

Systemic injection of kainic acid: Gliosis in olfactory and limbic brain regions quantified with [3H]PK 11195 binding autoradiography

International Nuclear Information System (INIS)

Altar, C.A.; Baudry, M.

1990-01-01

Neurodegenerative diseases may result from excessive stimulation of excitatory amino acid receptors by endogenous ligands. Because neuronal degeneration is associated with glial proliferation and hypertrophy, the degenerative changes throughout rat brain following the systemic administration of kainic acid (12 mg/kg) were mapped with quantitative autoradiography of [3H]PK 11195. This radioligand binds to a mitochondrial benzodiazepine binding site (MBBS) on microglia and astrocytes. Analysis of eight horizontal and four coronal brain levels revealed up to 16-fold increases in [3H]PK 11195 binding from 1 to 5 weeks but not 1 day after kainate injection. Increases in [3H]PK 11195 binding were predominantly in ventral limbic brain regions and olfactory projections to neocortical areas, with the olfactory cortex greater than subiculum/CA1 greater than anterior olfactory nucleus, medial thalamic nucleus, and piriform cortex greater than cingulate cortex and rostral hippocampus greater than dentate gyrus, septum, and amygdala greater than entorhinal cortex and temporal cortex. Little or no enhancement of [3H]PK 11195 binding was observed in numerous regions including the caudate-putamen, substantia nigra, nucleus accumbens, olfactory tubercle, cerebellum, thalamic nuclei, choroid plexus, medulla, parietal or occipital cortex, or pons. A 2-fold greater extent of neurodegeneration was obtained in ventral portions of the olfactory bulb, entorhinal cortex, temporal cortex, and dentate gyrus compared with the dorsal portions of these structures. The pattern of increase in [3H]PK 11195 binding closely matched the patterns of neuronal degeneration reported following parenteral kainate injection. These findings strengthen the notion that quantitative autoradiography of [3H]PK 11195 is a valuable tool to quantify the extent of neuronal degeneration

Bumetanide is not capable of terminating status epilepticus but enhances phenobarbital efficacy in different rat models.

Science.gov (United States)

Töllner, Kathrin; Brandt, Claudia; Erker, Thomas; Löscher, Wolfgang

2015-01-05

In about 20-40% of patients, status epilepticus (SE) is refractory to standard treatment with benzodiazepines, necessitating second- and third-line treatments that are not always successful, resulting in increased mortality. Rat models of refractory SE are instrumental in studying the changes underlying refractoriness and to develop more effective treatments for this severe medical emergency. Failure of GABAergic inhibition is a likely cause of the development of benzodiazepine resistance during SE. In addition to changes in GABAA receptor expression, trafficking, and function, alterations in Cl(-) homeostasis with increased intraneuronal Cl(-) levels may be involved. Bumetanide, which reduces intraneuronal Cl(-) by inhibiting the Cl(-) intruding Na(+), K(+), Cl(-) cotransporter NKCC1, has been reported to interrupt SE induced by kainate in urethane-anesthetized rats, indicating that this diuretic drug may be an interesting candidate for treatment of refractory SE. In this study, we evaluated the effects of bumetanide in the kainate and lithium-pilocarpine models of SE as well as a model in which SE is induced by sustained electrical stimulation of the basolateral amygdala. Unexpectedly, bumetanide alone was ineffective to terminate SE in both conscious and anesthetized adult rats. However, it potentiated the anticonvulsant effect of low doses of phenobarbital, although this was only seen in part of the animals; higher doses of phenobarbital, particularly in combination with diazepam, were more effective to terminate SE than bumetanide/phenobarbital combinations. These data do not suggest that bumetanide, alone or in combination with phenobarbital, is a valuable option in the treatment of refractory SE in adult patients. Copyright © 2014 Elsevier B.V. All rights reserved.

N-glycosylation of the β2 adrenergic receptor regulates receptor function by modulating dimerization.

Science.gov (United States)

Li, Xiaona; Zhou, Mang; Huang, Wei; Yang, Huaiyu

2017-07-01

N-glycosylation is a common post-translational modification of G-protein-coupled receptors (GPCRs). However, it remains unknown how N-glycosylation affects GPCR signaling. β 2 adrenergic receptor (β 2 AR) has three N-glycosylation sites: Asn6, Asn15 at the N-terminus, and Asn187 at the second extracellular loop (ECL2). Here, we show that deletion of the N-glycan did not affect receptor expression and ligand binding. Deletion of the N-glycan at the N-terminus rather than Asn187 showed decreased effects on isoproterenol-promoted G-protein-dependent signaling, β-arrestin2 recruitment, and receptor internalization. Both N6Q and N15Q showed decreased receptor dimerization, while N187Q did not influence receptor dimerization. As decreased β 2 AR homodimer accompanied with reduced efficiency for receptor function, we proposed that the N-glycosylation of β 2 AR regulated receptor function by influencing receptor dimerization. To verify this hypothesis, we further paid attention to the residues at the dimerization interface. Studies of Lys60 and Glu338, two residues at the receptor dimerization interface, exhibited that the K60A/E338A showed decreased β 2 AR dimerization and its effects on receptor signaling were similar to N6Q and N15Q, which further supported the importance of receptor dimerization for receptor function. This work provides new insights into the relationship among glycosylation, dimerization, and function of GPCRs. Peptide-N-glycosidase F (PNGase F, EC 3.2.2.11); endo-β-N-acetylglucosaminidase A (Endo-A, EC 3.2.1.96). © 2017 Federation of European Biochemical Societies.

Prognostic Value of Estrogen Receptor alpha and Progesterone Receptor Conversion in Distant Breast Cancer Metastases

NARCIS (Netherlands)

Hoefnagel, Laurien D. C.; Moelans, Cathy B.; Meijer, S. L.; van Slooten, Henk-Jan; Wesseling, Pieter; Wesseling, Jelle; Westenend, Pieter J.; Bart, Joost; Seldenrijk, Cornelis A.; Nagtegaal, Iris D.; Oudejans, Joost; van der Valk, Paul; van Gils, Carla H.; van der Wall, Elsken; van Diest, Paul J.

2012-01-01

BACKGROUND: Changes in the receptor profile of primary breast cancers to their metastases (receptor conversion) have been described for the estrogen receptor alpha (ER alpha) and progesterone receptor (PR). The purpose of this study was to evaluate the impact of receptor conversion for ER alpha and

Microarray-Based Determination of Estrogen Receptor, Progesterone Receptor, and HER2 Receptor Status in Breast Cancer

NARCIS (Netherlands)

Roepman, Paul; Horlings, Hugo M.; Krijgsman, Oscar; Kok, Marleen; Bueno-de-Mesquita, Jolien M.; Bender, Richard; Linn, Sabine C.; Glas, Annuska M.; van de Vijver, Marc J.

2009-01-01

Purpose: The level of estrogen receptor (ER), progesterone receptor (PR), and HER2 aids in the determination of prognosis and treatment of breast cancer. Immunohistochemistry is currently the predominant method for assessment, but differences in methods and interpretation can substantially affect

The Orphan Nuclear Receptor TR4 Is a Vitamin A-activated Nuclear Receptor

Energy Technology Data Exchange (ETDEWEB)

Zhou, X. Edward; Suino-Powell, Kelly M.; Xu, Yong; Chan, Cee-Wah; Tanabe, Osamu; Kruse, Schoen W.; Reynolds, Ross; Engel, James Douglas; Xu, H. Eric (Michigan-Med); (Van Andel)

2015-11-30

Testicular receptors 2 and 4 (TR2/4) constitute a subgroup of orphan nuclear receptors that play important roles in spermatogenesis, lipid and lipoprotein regulation, and the development of the central nervous system. Currently, little is known about the structural features and the ligand regulation of these receptors. Here we report the crystal structure of the ligand-free TR4 ligand binding domain, which reveals an autorepressed conformation. The ligand binding pocket of TR4 is filled by the C-terminal half of helix 10, and the cofactor binding site is occupied by the AF-2 helix, thus preventing ligand-independent activation of the receptor. However, TR4 exhibits constitutive transcriptional activity on multiple promoters, which can be further potentiated by nuclear receptor coactivators. Mutations designed to disrupt cofactor binding, dimerization, or ligand binding substantially reduce the transcriptional activity of this receptor. Importantly, both retinol and retinoic acid are able to promote TR4 to recruit coactivators and to activate a TR4-regulated reporter. These findings demonstrate that TR4 is a ligand-regulated nuclear receptor and suggest that retinoids might have a much wider regulatory role via activation of orphan receptors such as TR4.

Soman- or kainic acid-induced convulsions decrease muscarinic receptors but not benzodiazepine receptors

International Nuclear Information System (INIS)

Churchill, L.; Pazdernik, T.L.; Cross, R.S.; Nelson, S.R.; Samson, F.E.

1990-01-01

[3H]Quinuclidinyl benzilate (QNB) binding to muscarinic receptors decreased in the rat forebrain after convulsions induced by a single dose of either soman, a potent inhibitor of acetylcholinesterase, or kainic acid, an excitotoxin. A Rosenthal plot revealed that the receptors decreased in number rather than affinity. When the soman-induced convulsions were blocked, the decrease in muscarinic receptors at 3 days was less extensive than when convulsions occurred and at 10 days they approached control levels in most of the brain areas. The most prominent decrements in QNB binding were in the piriform cortex where the decline in QNB binding is probably related to the extensive convulsion-associated neuropathology. The decrements in QNB binding after convulsions suggest that the convulsive state leads to a down-regulation of muscarinic receptors in some brain areas. In contrast to the decrease in QNB binding after convulsions, [3H]flunitrazepam binding to benzodiazepine receptors did not change even in the piriform cortex where the loss in muscarinic receptors was most prominent. Thus, it appears that those neuronal processes that bear muscarinic receptors are more vulnerable to convulsion-induced change than those with benzodiazepine receptors

Cooperative ethylene receptor signaling

OpenAIRE

Liu, Qian; Wen, Chi-Kuang

2012-01-01

The gaseous plant hormone ethylene is perceived by a family of five ethylene receptor members in the dicotyledonous model plant Arabidopsis. Genetic and biochemical studies suggest that the ethylene response is suppressed by ethylene receptor complexes, but the biochemical nature of the receptor signal is unknown. Without appropriate biochemical measures to trace the ethylene receptor signal and quantify the signal strength, the biological significance of the modulation of ethylene responses ...

Radiolabelled GLP-1 receptor antagonist binds to GLP-1 receptor-expressing human tissues

International Nuclear Information System (INIS)

Waser, Beatrice; Reubi, Jean Claude

2014-01-01

Radiolabelled glucagon-like peptide 1 (GLP-1) receptor agonists have recently been shown to successfully image benign insulinomas in patients. For the somatostatin receptor targeting of tumours, however, it was recently reported that antagonist tracers were superior to agonist tracers. The present study therefore evaluated various forms of the 125 iodinated-Bolton-Hunter (BH)-exendin(9-39) antagonist tracer for the in vitro visualization of GLP-1 receptor-expressing tissues in rats and humans and compared it with the agonist tracer 125 I-GLP-1(7-36)amide. Receptor autoradiography studies with 125 I-GLP-1(7-36)amide agonist or 125 I-BH-exendin(9-39) antagonist radioligands were performed in human and rat tissues. The antagonist 125 I-BH-exendin(9-39) labelled at lysine 19 identifies all human and rat GLP-1 target tissues and GLP-1 receptor-expressing tumours. Binding is of high affinity and is comparable in all tested tissues in its binding properties with the agonist tracer 125 I-GLP-1(7-36)amide. For comparison, 125 I-BH-exendin(9-39) with the BH labelled at lysine 4 did identify the GLP-1 receptor in rat tissues but not in human tissues. The GLP-1 receptor antagonist exendin(9-39) labelled with 125 I-BH at lysine 19 is an excellent GLP-1 radioligand that identifies human and rat GLP-1 receptors in normal and tumoural tissues. It may therefore be the molecular basis to develop suitable GLP-1 receptor antagonist radioligands for in vivo imaging of GLP-1 receptor-expressing tissues in patients. (orig.)

Effect of neoadjuvant chemotherapy on low-density lipoprotein (LDL) receptor and LDL receptor-related protein 1 (LRP-1) receptor in locally advanced breast cancer

International Nuclear Information System (INIS)

Pires, L.A.; Hegg, R.; Freitas, F.R.; Tavares, E.R.; Almeida, C.P.; Baracat, E.C.; Maranhão, R.C.

2012-01-01

Low-density lipoprotein (LDL) receptors are overexpressed in most neoplastic cell lines and provide a mechanism for the internalization and concentration of drug-laden nanoemulsions that bind to these receptors. The aim of the present study was to determine whether the administration of standard chemotherapeutic schemes can alter the expression of LDL and LDL receptor-related protein 1 (LRP-1) receptors in breast carcinoma. Fragments of tumoral and normal breast tissue from 16 consecutive volunteer women with breast cancer in stage II or III were obtained from biopsies before the beginning of neoadjuvant chemotherapy and after chemotherapy, from fragments excised during mastectomy. Tissues were analyzed by immunohistochemistry for both receptors. Because complete response to treatment was achieved in 4 patients, only the tumors from 12 were analyzed. Before chemotherapy, there was overexpression of LDL receptor in the tumoral tissue compared to normal breast tissue in 8 of these patients. LRP-1 receptor overexpression was observed in tumors of 4 patients. After chemotherapy, expression of both receptors decreased in the tumors of 6 patients, increased in 4 and was unchanged in 2. Nonetheless, even when chemotherapy reduced receptors expression, the expression was still above normal. The fact that chemotherapy does not impair LDL receptors expression supports the use of drug carrier systems that target neoplastic cells by the LDL receptor endocytic pathway in patients on conventional chemotherapy

Radiolabelled GLP-1 receptor antagonist binds to GLP-1 receptor-expressing human tissues

Energy Technology Data Exchange (ETDEWEB)

Waser, Beatrice; Reubi, Jean Claude [University of Berne, Division of Cell Biology and Experimental Cancer Research, Institute of Pathology, PO Box 62, Berne (Switzerland)

2014-06-15

Radiolabelled glucagon-like peptide 1 (GLP-1) receptor agonists have recently been shown to successfully image benign insulinomas in patients. For the somatostatin receptor targeting of tumours, however, it was recently reported that antagonist tracers were superior to agonist tracers. The present study therefore evaluated various forms of the {sup 125}iodinated-Bolton-Hunter (BH)-exendin(9-39) antagonist tracer for the in vitro visualization of GLP-1 receptor-expressing tissues in rats and humans and compared it with the agonist tracer {sup 125}I-GLP-1(7-36)amide. Receptor autoradiography studies with {sup 125}I-GLP-1(7-36)amide agonist or {sup 125}I-BH-exendin(9-39) antagonist radioligands were performed in human and rat tissues. The antagonist {sup 125}I-BH-exendin(9-39) labelled at lysine 19 identifies all human and rat GLP-1 target tissues and GLP-1 receptor-expressing tumours. Binding is of high affinity and is comparable in all tested tissues in its binding properties with the agonist tracer {sup 125}I-GLP-1(7-36)amide. For comparison, {sup 125}I-BH-exendin(9-39) with the BH labelled at lysine 4 did identify the GLP-1 receptor in rat tissues but not in human tissues. The GLP-1 receptor antagonist exendin(9-39) labelled with {sup 125}I-BH at lysine 19 is an excellent GLP-1 radioligand that identifies human and rat GLP-1 receptors in normal and tumoural tissues. It may therefore be the molecular basis to develop suitable GLP-1 receptor antagonist radioligands for in vivo imaging of GLP-1 receptor-expressing tissues in patients. (orig.)

Dengue virus receptor

OpenAIRE

Hidari, Kazuya I.P.J.; Suzuki, Takashi

2011-01-01

Dengue virus is an arthropod-borne virus transmitted by Aedes mosquitoes. Dengue virus causes fever and hemorrhagic disorders in humans and non-human primates. Direct interaction of the virus introduced by a mosquito bite with host receptor molecule(s) is crucial for virus propagation and the pathological progression of dengue diseases. Therefore, elucidation of the molecular mechanisms underlying the interaction between dengue virus and its receptor(s) in both humans and mosquitoes is essent...

Repeated blockade of mineralocorticoid receptors, but not of glucocorticoid receptors impairs food rewarded spatial learning

NARCIS (Netherlands)

Douma, B. R.; Korte, S. M.; Buwalda, B.; La Fleur, S. E.; Bohus, B.; Luiten, P. G.

1998-01-01

Corticosteroids from the adrenal cortex influence a variety of behaviours including cognition, learning and memory. These hormones act via two intracellular receptors, the mineralo-corticoid receptor (MR) and the glucocorticoid receptor (GR). These two receptor types display a high concentration and

Repeated blockade of mineralocorticoid receptors, but not of glucocorticoid receptors impairs food rewarded spatial learning

NARCIS (Netherlands)

Douma, BRK; Korte, SM; Buwalda, B; la Fleur, SE; Bohus, B; Luiten, PGM

Corticosteroids from the adrenal cortex influence a variety of behaviours including cognition, learning and memory. These hormones act via two intracellular receptors, the mineralo-corticoid receptor (MR) and the glucocorticoid receptor (GR). These two receptor types display a high concentration and

Functional relevance of G-protein-coupled-receptor-associated proteins, exemplified by receptor-activity-modifying proteins (RAMPs).

Science.gov (United States)

Fischer, J A; Muff, R; Born, W

2002-08-01

The calcitonin (CT) receptor (CTR) and the CTR-like receptor (CRLR) are close relatives within the type II family of G-protein-coupled receptors, demonstrating sequence identity of 50%. Unlike the interaction between CT and CTR, receptors for the related hormones and neuropeptides amylin, CT-gene-related peptide (CGRP) and adrenomedullin (AM) require one of three accessory receptor-activity-modifying proteins (RAMPs) for ligand recognition. An amylin/CGRP receptor is revealed when CTR is co-expressed with RAMP1. When complexed with RAMP3, CTR interacts with amylin alone. CRLR, initially classed as an orphan receptor, is a CGRP receptor when co-expressed with RAMP1. The same receptor is specific for AM in the presence of RAMP2. Together with human RAMP3, CRLR defines an AM receptor, and with mouse RAMP3 it is a low-affinity CGRP/AM receptor. CTR-RAMP1, antagonized preferentially by salmon CT-(8-32) and not by CGRP-(8-37), and CRLR-RAMP1, antagonized by CGRP-(8-37), are two CGRP receptor isotypes. Thus amylin and CGRP interact specifically with heterodimeric complexes between CTR and RAMP1 or RAMP3, and CGRP and AM interact with complexes between CRLR and RAMP1, RAMP2 or RAMP3.

Pathophysiological consequences of receptor mistraffic: Tales from the platelet P2Y12 receptor.

Science.gov (United States)

Cunningham, Margaret R; Aungraheeta, Riyaad; Mundell, Stuart J

2017-07-05

Genetic variations in G protein-coupled receptor (GPCR) genes can disrupt receptor function in a wide variety of human genetic diseases, including platelet bleeding disorders. Platelets are critical for haemostasis with inappropriate platelet activation leading to the development of arterial thrombosis, which can result in heart attack and stroke whilst decreased platelet activity is associated with an increased risk of bleeding. GPCRs expressed on the surface of platelets play key roles in regulating platelet activity and therefore function. Receptors include purinergic receptors (P2Y 1 and P2Y 12 ), proteinase-activated receptor (PAR1 and PAR4) and thromboxane receptors (TPα), among others. Pharmacological blockade of these receptors forms a powerful therapeutic tool in the treatment and prevention of arterial thrombosis. With the advance of genomic technologies, there has been a substantial increase in the identification of naturally occurring rare and common GPCR variants. These variants include single-nucleotide polymorphisms (SNPs) and insertion or deletions that have the potential to alter GPCR expression or function. A number of defects in platelet GPCRs that disrupt receptor function have now been characterized in patients with mild bleeding disorders. This review will focus on rare, function-disrupting variants of platelet GPCRs with particular emphasis upon mutations in the P2Y 12 receptor gene that affect receptor traffic to modulate platelet function. Further this review will outline how the identification and characterization of function-disrupting GPCR mutations provides an essential link in translating our detailed understanding of receptor traffic and function in cell line studies into relevant human biological systems. Copyright © 2017. Published by Elsevier B.V.

Vägivald ja abitusseisund kui seksuaalsüütegude koosseisutunnused / Elina Elkind

Index Scriptorium Estoniae

Elkind, Elina, 1982-

2008-01-01

Kommentaar Riigikohtu kriminaalkolleegiumi otsustele 3-1-1-25-07 (Aivar Koppeli kaitsja vandeadvokaat Veljo Viiloli kassatsioon Tallinna Ringkonnakohtu 8. veebruari 2007. a kohtuotsuse peale kriminaalasjas Aivar Koppeli süüdistuses KarS § 142 lg 2 p 1 järgi) ja 3-1-1-59-07 (Sergei Volkovi ja Sergei Štšurikovi kaitsja vandeadvokaat Oleg Nišajevi kassatsioonid Tallinna Ringkonnakohtu 30. aprilli 2007. a kohtuotsuse peale kriminaalasjas Sergei Volkovi ja Sergei Štšurikovi süüdistuses KarS § 120; § 121 ja § 141 lg 2 p 2 järgi)

The effects of glycemic control on seizures and seizure-induced excitotoxic cell death

Directory of Open Access Journals (Sweden)

Schauwecker Paula

2012-08-01

Full Text Available Abstract Background Epilepsy is the most common neurological disorder after stroke, affecting more than 50 million persons worldwide. Metabolic disturbances are often associated with epileptic seizures, but the pathogenesis of this relationship is poorly understood. It is known that seizures result in altered glucose metabolism, the reduction of intracellular energy metabolites such as ATP, ADP and phosphocreatine and the accumulation of metabolic intermediates, such as lactate and adenosine. In particular, it has been suggested that the duration and extent of glucose dysregulation may be a predictor of the pathological outcome of status. However, little is known about neither the effects of glycemic control on brain metabolism nor the effects of managing systemic glucose concentrations in epilepsy. Results In this study, we examined glycemic modulation of kainate-induced seizure sensitivity and its neuropathological consequences. To investigate the relationship between glycemic modulation, seizure susceptibility and its neuropathological consequences, C57BL/6 mice (excitotoxin cell death resistant were subjected to hypoglycemia or hyperglycemia, followed by systemic administration of kainic acid to induce seizures. Glycemic modulation resulted in minimal consequences with regard to seizure severity but increased hippocampal pathology, irrespective of whether mice were hypoglycemic or hyperglycemic prior to kainate administration. Moreover, we found that exogenous administration of glucose following kainic acid seizures significantly reduced the extent of hippocampal pathology in FVB/N mice (excitotoxin cell death susceptible following systemic administration of kainic acid. Conclusion These findings demonstrate that modulation of the glycemic index can modify the outcome of brain injury in the kainate model of seizure induction. Moreover, modulation of the glycemic index through glucose rescue greatly diminishes the extent of seizure

Acetylcholine receptor antibody

Science.gov (United States)

... medlineplus.gov/ency/article/003576.htm Acetylcholine receptor antibody To use the sharing features on this page, please enable JavaScript. Acetylcholine receptor antibody is a protein found in the blood of ...

Cerrahi Adezyonun Önlenmesi için Yeni Bir Yaklaşım: Nanolifli Cerrahi Adezyon Bariyerleri

OpenAIRE

ŞAFAK, Şerife; KARACA, Esra; ÖZALP, R. Gözde

2017-01-01

Adezyonlar; seröz zarı ile çevrili olan organların, yaralanmalarını takiben aralarında meydana gelen anormal birleşmelerdir. Karın içi operasyonları, karın zarı iltihabı, çikolata kisti, radyasyon ve kanser gibi nedenlerle organlar birbirlerine ya da karın duvarına yapışabilirler. Adezyonlar; bağırsak tıkanıklıklarının yanı sıra kronik karın ağrısına ve kısırlığa da neden olmaktadır. Adezyon oluşumu ve komplikasyonlarının tedavisi ise, ciddi iş gücü ve ekonomik kayıplara yol açmaktadır. Karın...

L-glutamate Receptor In Paramecium

Science.gov (United States)

Bernal-Martínez, Juan; Ortega-Soto, Arturo

2004-09-01

Behavioral, electrophysiological and biochemical experiments were performed in order to establish the presence of a glutamate receptor in the ciliate Paramecium. It was found that an AMPA/KA receptor is functionally expressed in Paramecium and that this receptor is immunologically and fillogenetically related to the AMPA/KA receptor present in vertebrates.

Do receptors get pregnant too? Adrenergic receptor alterations in human pregnancy.

Science.gov (United States)

Smiley, R M; Finster, M

1996-01-01

In this review we discuss adrenergic receptor number and function during pregnancy, with emphasis on evidence that pregnancy results in specific receptor alterations from the nonpregnant state. Changes in adrenergic receptor function or distribution in vascular smooth muscle may be in part responsible for the decreased vascular responsiveness seen in human pregnancy, and the lack of the normal alterations may be a part of the syndromes of gestational hypertension, including preeclampsia-eclampsia. The onset of labor may be influenced by adrenergic modulation, and receptor or postreceptor level molecular alterations may trigger or facilitate normal or preterm labor. Human studies are emphasized when possible to assess the role of adrenergic signal transduction regulation in the physiology and pathophysiology of normal and complicated human pregnancy.

Melatonin Receptor Genes in Vertebrates

Directory of Open Access Journals (Sweden)

Hua Dong Yin

2013-05-01

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.

Clinical and Genomic Crosstalk between Glucocorticoid Receptor and Estrogen Receptor α In Endometrial Cancer

Directory of Open Access Journals (Sweden)

Jeffery M. Vahrenkamp

2018-03-01

Full Text Available Summary: Steroid hormone receptors are simultaneously active in many tissues and are capable of altering each other’s function. Estrogen receptor α (ER and glucocorticoid receptor (GR are expressed in the uterus, and their ligands have opposing effects on uterine growth. In endometrial tumors with high ER expression, we surprisingly found that expression of GR is associated with poor prognosis. Dexamethasone reduced normal uterine growth in vivo; however, this growth inhibition was abolished in estrogen-induced endometrial hyperplasia. We observed low genomic-binding site overlap when ER and GR are induced with their respective ligands; however, upon simultaneous induction they co-occupy more sites. GR binding is altered significantly by estradiol with GR recruited to ER-bound loci that become more accessible upon estradiol induction. Gene expression responses to co-treatment were more similar to estradiol but with additional regulated genes. Our results suggest phenotypic and molecular interplay between ER and GR in endometrial cancer. : Estrogen receptor α (ER and glucocorticoid receptor (GR are expressed in the uterus and have differential effects on growth. Vahrenkamp et al. find that expression of both receptors is associated with poor outcome in endometrial cancer and that simultaneous induction of ER and GR leads to molecular interplay between the receptors. Keywords: estrogen receptor, glucocorticoid receptor, endometrial cancer

Depolarization-induced release of [(3)H]D-aspartate from GABAergic neurons caused by reversal of glutamate transporters

DEFF Research Database (Denmark)

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

2000-01-01

if glutamate in addition to gamma-aminobutyric acid (GABA) could be released from these cultures. The neurons were preloaded with [(3)H]D-aspartate and subsequently its release was followed during depolarization induced by a high potassium concentration or the alpha-amino-3-hydroxy-5-methyl-4......-isoxazolepropionic acid (AMPA) receptor agonists, AMPA and kainate. Depolarization of the neurons with 55 mM potassium increased the release of [(3)H]D-aspartate by more than 10-fold. When the non-specific calcium-channel blockers cobalt or lanthanum were included in the stimulation buffer with potassium......, the release of [(3)H]D-aspartate was decreased by about 40%. These results indicated that some of the released [(3)H]D-aspartate might originate from a vesicular pool. When AMPA was applied to the neurons, the release of [(3)H]D-aspartate was increased 2-fold and could not be prevented or decreased...

Receptor binding radiotracers for the angiotensin II receptor: radioiodinated [Sar1, Ile8]angiotensin II

International Nuclear Information System (INIS)

Gibson, R.E.; Beauchamp, H.T.; Fioravanti, C.; Brenner, N.; Burns, H.D.

1994-01-01

The potential for imaging the angiotensin II receptor was evaluated using the radioiodinated peptide antagonist [ 125 I][Sar 1 , Ile 8 ]angiotensin II. The radioligand provides a receptor-mediated signal in several tissues in rat (kidneys, adrenal and liver). The receptor-mediated signal of 3% ID/g kidney cortex should be sufficient to permit imaging, at least via SPECT. The radiotracer is sensitive to reductions in receptor concentration and can be used to define in vivo dose-occupancy curves of angiotensin II receptor ligands. Receptor-mediated images of [ 123 I][Sar 1 , Ile 8 ]angiotensin II were obtained in the rat kidney and Rhesus monkey liver. (author)

40 CFR 52.870 - Identification of plan.

Science.gov (United States)

2010-07-01

... FR 1420 K.A.R. 28-19-23 Hydrocarbon Emissions—Stationary Sources 12/27/72 11/8/73, 38 FR 30876 K.A.R... Operations 10/7/91 6/23/92, 57 FR 27936 K.A.R. 28-19-77 Chemical Processing Facilities That Operate Alcohol... published 3/2/76. (7) Analysis and Recommendations Concerning Designation of Air Quality Maintenance Areas...

The lactate receptor, G-protein-coupled receptor 81/hydroxycarboxylic acid receptor 1

DEFF Research Database (Denmark)

Morland, Cecilie; Lauritzen, Knut Huso; Puchades, Maja

2015-01-01

We have proposed that lactate is a “volume transmitter” in the brain and underpinned this by showing that the lactate receptor, G-protein-coupled receptor 81 (GPR81, also known as HCA1 or HCAR1), which promotes lipid storage in adipocytes, is also active in the mammalian brain. This includes......, energy metabolism, and energy substrate availability, including a glucose- and glycogen-saving response. HCAR1 may contribute to optimizing the cAMP concentration. For instance, in the prefrontal cortex, excessively high cAMP levels are implicated in impaired cognition in old age, fatigue, stress...

Adenosine receptor desensitization and trafficking.

Science.gov (United States)

Mundell, Stuart; Kelly, Eamonn

2011-05-01

As with the majority of G-protein-coupled receptors, all four of the adenosine receptor subtypes are known to undergo agonist-induced regulation in the form of desensitization and trafficking. These processes can limit the ability of adenosine receptors to couple to intracellular signalling pathways and thus reduce the ability of adenosine receptor agonists as well as endogenous adenosine to produce cellular responses. In addition, since adenosine receptors couple to multiple signalling pathways, these pathways may desensitize differentially, while the desensitization of one pathway could even trigger signalling via another. Thus, the overall picture of adenosine receptor regulation can be complex. For all adenosine receptor subtypes, there is evidence to implicate arrestins in agonist-induced desensitization and trafficking, but there is also evidence for other possible forms of regulation, including second messenger-dependent kinase regulation, heterologous effects involving G proteins, and the involvement of non-clathrin trafficking pathways such as caveolae. In this review, the evidence implicating these mechanisms is summarized for each adenosine receptor subtype, and we also discuss those issues of adenosine receptor regulation that remain to be resolved as well as likely directions for future research in this field. Copyright © 2010 Elsevier B.V. All rights reserved.

Cocaine Disrupts Histamine H3 Receptor Modulation of Dopamine D1 Receptor Signaling: σ1-D1-H3 Receptor Complexes as Key Targets for Reducing Cocaine's Effects

Science.gov (United States)

Moreno, Estefanía; Moreno-Delgado, David; Navarro, Gemma; Hoffmann, Hanne M.; Fuentes, Silvia; Rosell-Vilar, Santi; Gasperini, Paola; Rodríguez-Ruiz, Mar; Medrano, Mireia; Mallol, Josefa; Cortés, Antoni; Casadó, Vicent; Lluís, Carme; Ferré, Sergi; Ortiz, Jordi; Canela, Enric

2014-01-01

The general effects of cocaine are not well understood at the molecular level. What is known is that the dopamine D1 receptor plays an important role. Here we show that a key mechanism may be cocaine's blockade of the histamine H3 receptor-mediated inhibition of D1 receptor function. This blockade requires the σ1 receptor and occurs upon cocaine binding to σ1-D1-H3 receptor complexes. The cocaine-mediated disruption leaves an uninhibited D1 receptor that activates Gs, freely recruits β-arrestin, increases p-ERK 1/2 levels, and induces cell death when over activated. Using in vitro assays with transfected cells and in ex vivo experiments using both rats acutely treated or self-administered with cocaine along with mice depleted of σ1 receptor, we show that blockade of σ1 receptor by an antagonist restores the protective H3 receptor-mediated brake on D1 receptor signaling and prevents the cell death from elevated D1 receptor signaling. These findings suggest that a combination therapy of σ1R antagonists with H3 receptor agonists could serve to reduce some effects of cocaine. PMID:24599455

Receptor studies in biological psychiatry

International Nuclear Information System (INIS)

Fujiwara, Yutaka

1992-01-01

Recent advances in the pharmacological treatment of endogenous psychosis have led to the development of biological studies in psychiatry. Studies on neurotransmitter receptors were reviewed in order to apply positron-emission tomograph (PET) for biological psychiatry. The dopamine (DA) hypothesis for schizophrenia was advanced on the basis of the observed effects of neuroleptics and methamphetamine, and DA(D 2 ) receptor supersensitivity measured by PET and receptor binding in the schizophrenic brain. The clinical potencies of neuroleptics for schizophrenia were correlated with their abilities to inhibit the D 2 receptor, and not other receptors. The σ receptor was expected to be a site of antipsychotic action. However, the potency of drugs action on it was not correlated with clinical efficacy. Haloperidol binds with high affinity to the σ receptor, which may mediate acute dystonia, an extrapyramidal side effect of neuroleptics. Behavioral and neurochemical changes induced by methamphetamine treatment were studied as an animal model of schizophrenia, and both a decrease of D 2 receptor density and an increase of DA release were detected. The monoamine hypothesis for manic-depressive psychosis was advanced on the basis of the effect of reserpine, monoamine oxidase inhibitor and antidepressants. 3 H-clonidine binding sites were increased in platelet membranes of depressive patients, 3 H-imipramine binding sites were decreased. The GABA A receptor is the target site for the action of anxiolytics and antiepileptics such as benzodiazepines and barbiturates. Recent developments in molecular biology techniques have revealed the structure of receptor proteins, which are classified into two receptor families, the G-protein coupled type (D 2 ) and the ion-channel type (GABA A ). (J.P.N.)

Arrestin scaffolds NHERF1 to the P2Y12 receptor to regulate receptor internalization.

Science.gov (United States)

Nisar, Shaista P; Cunningham, Margaret; Saxena, Kunal; Pope, Robert J; Kelly, Eamonn; Mundell, Stuart J

2012-07-13

We have recently shown in a patient with mild bleeding that the PDZ-binding motif of the platelet G protein-coupled P2Y(12) receptor (P2Y(12)R) is required for effective receptor traffic in human platelets. In this study we show for the first time that the PDZ motif-binding protein NHERF1 exerts a major role in potentiating G protein-coupled receptor (GPCR) internalization. NHERF1 interacts with the C-tail of the P2Y(12)R and unlike many other GPCRs, NHERF1 interaction is required for effective P2Y(12)R internalization. In vitro and prior to agonist stimulation P2Y(12)R/NHERF1 interaction requires the intact PDZ binding motif of this receptor. Interestingly on receptor stimulation NHERF1 no longer interacts directly with the receptor but instead binds to the receptor via the endocytic scaffolding protein arrestin. These findings suggest a novel model by which arrestin can serve as an adaptor to promote NHERF1 interaction with a GPCR to facilitate effective NHERF1-dependent receptor internalization.

A candidate pheromone receptor and two odorant receptors of the hawkmoth Manduca sexta.

Science.gov (United States)

Patch, Harland M; Velarde, Rodrigo A; Walden, Kimberly K O; Robertson, Hugh M

2009-05-01

In this study, we cloned and characterized three Manduca sexta odorant receptors (ORs). One receptor is a putative pheromone receptor expressed exclusively in a cell associated with male-specific type-I trichoid sensilla. We describe the results of real-time PCR (RT-PCR) and quantitative real-time PCR (qRT-PCR) experiments that show MsextaOR1 is expressed only in male antennae. In situ hybridization labels a single cell associated with type-1 trichoid sensilla, which houses two neurons that have been previously determined to respond to the major components of the pheromone blend. The second receptor, MsextaOR2, was discovered using degenerate primers designed to conserved motifs of a unique group ORs that share as much as 88% identity. Comparison of RT-PCR, qRT-PCR, and in situ hybridization results with those of ORs in the Drosophila melanogaster Or83b subfamily shows a strong sequence and expression pattern similarity. The third receptor, MsextaOR3, was found by 5'-end sequencing of a normalized and subtracted cDNA library from male M. sexta antennae. RT-PCR and qRT-PCR show that this receptor is expressed only in male and female antennae. These are the first ORs, including a putative pheromone receptor, to be described from M. sexta.

Upper Triassic mafic dykes of Lake Nyos, Cameroon (West Africa) I: K-Ar age evidence within the context of Cameroon Line magmatism, and the tectonic significance

Science.gov (United States)

Aka, Festus Tongwa; Hasegawa, Takeshi; Nche, Linus Anye; Asaah, Asobo Nkengmatia Elvis; Mimba, Mumbfu Ernestine; Teitchou, Isidore; Ngwa, Caroline; Miyabuchi, Yasuo; Kobayashi, Tetsuo; Kankeu, Boniface; Yokoyama, Tetsuya; Tanyileke, Gregory; Ohba, Takeshi; Hell, Joseph Victor; Kusakabe, Minoru

2018-05-01

The hydrodynamic fragmentation that formed Lake Nyos in northwest Cameroon did not only make it the most unpopular lake in the world from a gas disaster perspective, it also opened a rare and formidable window through which much of the geology of Cameroon can be studied in a single locality. The Cambrian quartz monzonite cliff excavated by the maar-forming explosion and exposed in its northeastern shore is intruded by mafic dykes, two of which we dated. Even though close to one another, the dykes are different in composition. The alkaline dyke yields a slightly older (Carnian) K-Ar fedspar age of 231.1 ± 4.8 Ma, while the sub alkaline dyke yields an age of 224.8 ± 4.7 Ma (Norian). Based on radioisotopic age data available over the last 48 years (347 data) for the Cameroon Line magmatism comprising eruptives and volcano-plutonic complexes, the Nyos dykes are way older than the Cameroon Line, and even pre-date the Lower Cretaceous initiation of west Gondwana fragmentation in Equatorial Atlantic domain. They would therefore not have been directly linked to the formation of the Cameroon Line. Alternatively, they might be associated with the development of intra-continental rift systems in West Central Africa that pre-dated west Gondwana breakup to form the Atlantic Ocean.

Kafkasya Muhacirlerinin Suriye Vilayetine İskânı ve Karşılaşılan Zorluklar The Settlement of Caucasian Refugees to Syria Province and the Hardships Encountered

Directory of Open Access Journals (Sweden)

Oktay KIZILKAYA

2013-03-01

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.

Rb-Sr and K-Ar age of globular phyllosilicates and biostratigraphy of the Riphean deposits of the Olenek Uplift (North Siberia)

Science.gov (United States)

Zaitseva, T. S.; Gorokhov, I. M.; Semikhatov, M. A.; Ivanovskaya, T. A.; Kuznetsov, A. B.; Dorzhieva, O. V.

2017-11-01

This work presents results of the complex mineralogical, geochemical, and isotope-geochronological investigation of globular dioctahedral 2: 1 phyllosilicates (GPS) of the illite-glauconite series from the Riphean sequences of the Olenek Uplift. It is established that GPS (glauconite, Al-glauconite, Fe-illite) in deposits of the Arymass, Debengda, and Khaipakh formations are represented by mixed-layer varieties of two types: (1) with relatively low (cell of minerals varies from 9.18 to 9.72 Å. The Rb-Sr age dating of GPS was first carried out in combination with the calculation of theoretical pattern of the cation distribution in the mineral structure and comparison of the calculation results obtained with the Mössbauer and IR spectroscopy data. This approach is based on the assumption that development and evolution of isotope systems in GPS are synchronous with the evolution of the crystalline structure of the mineral at various stages of the geological and geochemical history of the development of sedimentary units. Analysis of the obtained data allows us to state that the structural features of the Riphean GPS from the Olenek section reflect the early diagenetic stages of the formation of the minerals studied. The 87Sr/86Sr initial ratios in the studied sediments are consistent with the range of variations in this ratio in the Middle Riphean Ocean (0.7049-0.7061). The Rb-Sr and K-Ar ages of the GPS of the Arymass (1305 ± 8 and 1302 Ma, respectively), Debengda (1265 ± 12 and 1284 ± 22 Ma), and Khaipakh (1172 ± 18 and 1112 ± 24 Ma) formations in the Olenek Uplift section are close to the accumulation time of corresponding deposits and, correspondingly, have significance for stratigraphic correlations.

Transcriptional targets shared by estrogen receptor- related receptors (ERRs) and estrogen receptor (ER) alpha, but not by ERbeta.

Science.gov (United States)

Vanacker, J M; Pettersson, K; Gustafsson, J A; Laudet, V

1999-01-01

The physiological activities of estrogens are thought to be mediated by specific nuclear receptors, ERalpha and ERbeta. However, certain tissues, such as the bone, that are highly responsive to estrogens only express a low level of these receptors. Starting from this apparent contradiction, we have evaluated the potentials of two related receptors ERRalpha and ERRbeta to intervene in estrogen signaling. ERalpha, ERRalpha and ERRbeta bind to and activate transcription through both the classical estrogen response element (ERE) and the SF-1 response element (SFRE). In contrast, ERbeta DNA-binding and transcriptional activity is restricted to the ERE. Accordingly, the osteopontin gene promoter is stimulated through SFRE sequences, by ERRalpha as well as by ERalpha, but not by ERbeta. Analysis of the cross-talk within the ER/ERR subgroup of nuclear receptors thus revealed common targets but also functional differences between the two ERs. PMID:10428965

Flavivirus Entry Receptors: An Update

Directory of Open Access Journals (Sweden)

Manuel Perera-Lecoin

2013-12-01

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.

Pharmacological characterization of receptor-activity-modifying proteins (RAMPs) and the human calcitonin receptor.

Science.gov (United States)

Armour, S L; Foord, S; Kenakin, T; Chen, W J

1999-12-01

Receptor-activity-modifying proteins (RAMPs) are a family of single transmembrane domain proteins shown to be important for the transport and ligand specificity of the calcitonin gene-related peptide (CGRP) receptor. In this report, we describe the analysis of pharmacological properties of the human calcitonin receptor (hCTR) coexpressed with different RAMPs with the use of the Xenopus laevis melanophore expression system. We show that coexpression of RAMP3 with human calcitonin receptor changed the relative potency of hCTR to human calcitonin (hCAL) and rat amylin. RAMP1 and RAMP2, in contrast, had little effect on the change of hCTR potency to hCAL or rat amylin. When coexpressed with RAMP3, hCTR reversed the relative potency by a 3.5-fold loss in sensitivity to hCAL and a 19-fold increase in sensitivity to rat amylin. AC66, an inverse agonist, produced apparent simple competitive antagonism of hCAL and rat amylin, as indicated by linear Schild regressions. The potency of AC66 was changed in the blockade of rat amylin but not hCAL responses with RAMP3 coexpression. The mean pK(B) for AC66 to hCAL was 9.4 +/- 0.3 without RAMP3 and 9.45 +/- 0.07 with RAMP3. For the antagonism of AC66 to rat amylin, the pK(B) was 9.25 +/- 0.15 without RAMP3 and 8.2 +/- 0.35 with RAMP3. The finding suggests that RAMP3 might modify the active states of calcitonin receptor in such a way as to create a new receptor phenotype that is "amylin-like." Irrespective of the physiological association of the new receptor species, the finding that a coexpressed membrane protein can completely change agonist and antagonist affinities for a receptor raises implications for screening in recombinant receptor systems.

Serotonin 5-HT4 receptors and forebrain cholinergic system: receptor expression in identified cell populations.

Science.gov (United States)

Peñas-Cazorla, Raúl; Vilaró, M Teresa

2015-11-01

Activation of serotonin 5-HT4 receptors has pro-cognitive effects on memory performance. The proposed underlying neurochemical mechanism is the enhancement of acetylcholine release in frontal cortex and hippocampus elicited by 5-HT4 agonists. Although 5-HT4 receptors are present in brain areas related to cognition, e.g., hippocampus and cortex, the cellular localization of the receptors that might modulate acetylcholine release is unknown at present. We have analyzed, using dual label in situ hybridization, the cellular localization of 5-HT4 receptor mRNA in identified neuronal populations of the rat basal forebrain, which is the source of the cholinergic innervation to cortex and hippocampus. 5-HT4 receptor mRNA was visualized with isotopically labeled oligonucleotide probes, whereas cholinergic, glutamatergic, GABAergic and parvalbumin-synthesizing neurons were identified with digoxigenin-labeled oligonucleotide probes. 5-HT4 receptor mRNA was not detected in the basal forebrain cholinergic cell population. In contrast, basal forebrain GABAergic, parvalbumin synthesizing, and glutamatergic cells contained 5-HT4 receptor mRNA. Hippocampal and cortical glutamatergic neurons also express this receptor. These results indicate that 5-HT4 receptors are not synthesized by cholinergic cells, and thus would be absent from cholinergic terminals. In contrast, several non-cholinergic cell populations within the basal forebrain and its target hippocampal and cortical areas express these receptors and are thus likely to mediate the enhancement of acetylcholine release elicited by 5-HT4 agonists.

Stargazin Modulation of AMPA Receptors

Directory of Open Access Journals (Sweden)

Sana A. Shaikh

2016-10-01

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.

Photo-antagonism of the GABAA receptor.

Science.gov (United States)

Mortensen, Martin; Iqbal, Favaad; Pandurangan, Arun P; Hannan, Saad; Huckvale, Rosemary; Topf, Maya; Baker, James R; Smart, Trevor G

2014-07-29

Neurotransmitter receptor trafficking is fundamentally important for synaptic transmission and neural network activity. GABAA receptors and inhibitory synapses are vital components of brain function, yet much of our knowledge regarding receptor mobility and function at inhibitory synapses is derived indirectly from using recombinant receptors, antibody-tagged native receptors and pharmacological treatments. Here we describe the use of a set of research tools that can irreversibly bind to and affect the function of recombinant and neuronal GABAA receptors following ultraviolet photoactivation. These compounds are based on the competitive antagonist gabazine and incorporate a variety of photoactive groups. By using site-directed mutagenesis and ligand-docking studies, they reveal new areas of the GABA binding site at the interface between receptor β and α subunits. These compounds enable the selected inactivation of native GABAA receptor populations providing new insight into the function of inhibitory synapses and extrasynaptic receptors in controlling neuronal excitation.

Scavenger receptors in homeostasis and immunity.

Science.gov (United States)

Canton, Johnathan; Neculai, Dante; Grinstein, Sergio

2013-09-01

Scavenger receptors were originally identified by their ability to recognize and to remove modified lipoproteins; however, it is now appreciated that they carry out a striking range of functions, including pathogen clearance, lipid transport, the transport of cargo within the cell and even functioning as taste receptors. The large repertoire of ligands recognized by scavenger receptors and their broad range of functions are not only due to the wide range of receptors that constitute this family but also to their ability to partner with various co-receptors. The ability of individual scavenger receptors to associate with different co-receptors makes their responsiveness extremely versatile. This Review highlights recent insights into the structural features that determine the function of scavenger receptors and the emerging role that these receptors have in immune responses, notably in macrophage polarization and in the pathogenesis of diseases such as atherosclerosis and Alzheimer's disease.

Central alpha2 adrenergic receptors in the rat cerebral cortex: repopulation kinetics and receptor reserve

International Nuclear Information System (INIS)

Adler, C.H.

1986-01-01

The alpha 2 adrenergic receptor subtype is thought to play a role in the mechanism of action of antidepressant and antihypertensive drugs. This thesis has attempted to shed light on the regulation of central alpha 2 adrenergic receptors in the rat cerebral cortex. Repopulation kinetics analysis allows for the determination of the rate of receptor production, rate constant of degradation, and half-life of the receptor. This analysis was carried out using both radioligand binding and functional receptor assays at various times following the irreversible inactivation of central alpha 2 adrenergic receptors by in vivo administration of N-ethoxycarbonyl-2-ethyoxy-1,2-dihydroquinoline (EEDQ). Both alpha 2 agonist and antagonist ligand binding sites recovered with a t/sub 1/2/ equal to approximately 4 days. The function of alpha 2 adrenergic autoreceptors, which inhibit stimulation-evoked release of 3 H-norepinephrine ( 3 H-NE) and alpha 2 adrenergic heteroreceptors which inhibit stimulation-evoked release of 3 H-serotonin ( 3 H-5-HT) were assayed. The t/sub 1/2/ for recovery of maximal autoreceptor and heteroreceptor function was 2.4 days and 4.6 days, respectively. The demonstration of a receptor reserve is critical to the interpretation of past and future studies of the alpha 2 adrenergic receptor since it demonstrates that: (1) alterations in the number of alpha 2 adrenergic receptor binding sites cannot be extrapolated to the actual function of the alpha 2 adrenergic receptor; and (2) alterations in the number of alpha 2 receptors is not necessarily accompanied by a change in the maximum function being studied, but may only result in shifting of the dose-response curve

Identifying the receptor subtype selectivity of retinoid X and retinoic acid receptors via quantum mechanics.

Science.gov (United States)

Tsuji, Motonori; Shudo, Koichi; Kagechika, Hiroyuki

2017-03-01

Understanding and identifying the receptor subtype selectivity of a ligand is an important issue in the field of drug discovery. Using a combination of classical molecular mechanics and quantum mechanical calculations, this report assesses the receptor subtype selectivity for the human retinoid X receptor (hRXR) and retinoic acid receptor (hRAR) ligand-binding domains (LBDs) complexed with retinoid ligands. The calculated energies show good correlation with the experimentally reported binding affinities. The technique proposed here is a promising method as it reveals the origin of the receptor subtype selectivity of selective ligands.

Interaction of epidermal growth factor receptors with the cytoskeleton is related to receptor clustering

NARCIS (Netherlands)

van Belzen, N.; Spaargaren, M.; Verkleij, A. J.; Boonstra, J.

1990-01-01

Recently it has been established that cytoskeleton-associated epidermal growth factor (EGF) receptors are predominantly of the high-affinity class and that EGF induces a recruitment of low-affinity receptors to the cytoskeleton. The nature of this EGF-induced receptor-cytoskeleton interaction,

Toll-like receptors and NOD-like receptors in rheumatic diseases.

LENUS (Irish Health Repository)

McCormack, William J

2012-02-01

The past 10 years have seen the description of families of receptors that drive proinflammatory cytokine production in infection and tissue injury. Two major classes have been examined in the context of inflammatory joint disease--the Toll-like receptors (TLRs) and NOD-like receptors (NLRs). TLRs such as TLR2 and TLR4 are being implicated in the pathology of rheumatoid arthritis, ankylosing spondylitis, lyme arthritis and osteoarthritis. Nalp3 has been identified as a key NLR for IL-1beta production and has been shown to have a particular role in gout. These findings present new therapeutic opportunities, possibly allowing for the replacement of biologics with small molecule inhibitors.

Olfactory Receptor Database: a sensory chemoreceptor resource

OpenAIRE

Skoufos, Emmanouil; Marenco, Luis; Nadkarni, Prakash M.; Miller, Perry L.; Shepherd, Gordon M.

2000-01-01

The Olfactory Receptor Database (ORDB) is a WWW-accessible database that has been expanded from an olfactory receptor resource to a chemoreceptor resource. It stores data on six classes of G-protein-coupled sensory chemoreceptors: (i) olfactory receptor-like proteins, (ii) vomeronasal receptors, (iii) insect olfactory receptors, (iv) worm chemoreceptors, (v) taste papilla receptors and (vi) fungal pheromone receptors. A complementary database of the ligands of these receptors (OdorDB) has bee...

Molecular characterization of opioid receptors

Energy Technology Data Exchange (ETDEWEB)

Howard, A.D.

1986-01-01

The aim of this research was to purify and characterize active opioid receptors and elucidate molecular aspects of opioid receptor heterogeneity. Purification to apparent homogeneity of an opioid binding protein from bovine caudate was achieved by solubilization in the non-ionic detergent, digitonin, followed by sequential chromatography on the opiate affinity matrix, ..beta..-naltrexylethylenediamine-CH-Sepharose 4B, and on the lectine affinity matrix, wheat germ agglutinin-agarose. Polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate (SDS-PAGE) followed by autoradiography revealed that radioiodinated purified receptor gave a single band. Purified receptor preparations showed a specific activity of 12,000-15,000 fmol of opiate bound per mg of protein. Radioiodinated human beta-endorphin (/sup 125/I-beta-end/sub H/) was used as a probe to investigate the ligand binding subunits of mu and delta opioid receptors. /sup 125/I-beta-end/sub H/ was shown to bind to a variety of opioid receptor-containing tissues with high affinity and specificity with preference for mu and delta sites, and with little, if any, binding to kappa sites. Affinity crosslinking techniques were employed to covalently link /sup 125/I-beta-end/sub H/ to opioid receptors, utilizing derivatives of bis-succinimidyl esters that are bifunctional crosslinkers with specificities for amino and sulfhydryl groups. This, and competition experiments with high type-selective ligands, permitted the assignment of two labeled peptides to their receptor types, namely a peptide of M/sub r/ = 65,000 for mu receptors and one of M/sub r/ = 53,000 for delta receptors.

Lipid raft integrity affects GABAA receptor, but not NMDA receptor modulation by psychopharmacological compounds.

Science.gov (United States)

Nothdurfter, Caroline; Tanasic, Sascha; Di Benedetto, Barbara; Uhr, Manfred; Wagner, Eva-Maria; Gilling, Kate E; Parsons, Chris G; Rein, Theo; Holsboer, Florian; Rupprecht, Rainer; Rammes, Gerhard

2013-07-01

Lipid rafts have been shown to play an important role for G-protein mediated signal transduction and the function of ligand-gated ion channels including their modulation by psychopharmacological compounds. In this study, we investigated the functional significance of the membrane distribution of NMDA and GABAA receptor subunits in relation to the accumulation of the tricyclic antidepressant desipramine (DMI) and the benzodiazepine diazepam (Diaz). In the presence of Triton X-100, which allowed proper separation of the lipid raft marker proteins caveolin-1 and flotillin-1 from the transferrin receptor, all receptor subunits were shifted to the non-raft fractions. In contrast, under detergent-free conditions, NMDA and GABAA receptor subunits were detected both in raft and non-raft fractions. Diaz was enriched in non-raft fractions without Triton X-100 in contrast to DMI, which preferentially accumulated in lipid rafts. Impairment of lipid raft integrity by methyl-β-cyclodextrine (MβCD)-induced cholesterol depletion did not change the inhibitory effect of DMI at the NMDA receptor, whereas it enhanced the potentiating effect of Diaz at the GABAA receptor at non-saturating concentrations of GABA. These results support the hypothesis that the interaction of benzodiazepines with the GABAA receptor likely occurs outside of lipid rafts while the antidepressant DMI acts on ionotropic receptors both within and outside these membrane microdomains.

Internalization of G-protein-coupled receptors: Implication in receptor function, physiology and diseases.

Science.gov (United States)

Calebiro, Davide; Godbole, Amod

2018-04-01

G protein-coupled receptors (GPCRs) are the largest family of membrane receptors and mediate the effects of numerous hormones and neurotransmitters. The nearly 1000 GPCRs encoded by the human genome regulate virtually all physiological functions and are implicated in the pathogenesis of prevalent human diseases such as thyroid disorders, hypertension or Parkinson's disease. As a result, 30-50% of all currently prescribed drugs are targeting these receptors. Once activated, GPCRs induce signals at the cell surface. This is often followed by internalization, a process that results in the transfer of receptors from the plasma membrane to membranes of the endosomal compartment. Internalization was initially thought to be mainly implicated in signal desensitization, a mechanism of adaptation to prolonged receptor stimulation. However, several unexpected functions have subsequently emerged. Most notably, accumulating evidence indicates that internalization can induce prolonged receptor signaling on intracellular membranes, which is apparently required for at least some biological effects of hormones like TSH, LH and adrenaline. These findings reveal an even stronger connection between receptor internalization and signaling than previously thought. Whereas new studies are just beginning to reveal an important physiological role for GPCR signaling after internalization and ways to exploit it for therapeutic purposes, future investigations will be required to explore its involvement in human disease. Copyright © 2018 Elsevier Ltd. All rights reserved.

Effect of the non-NMDA receptor antagonist GYKI 52466 on the microdialysate and tissue concentrations of amino acids following transient forebrain ischaemia.

Science.gov (United States)

Arvin, B; Lekieffre, D; Graham, J L; Moncada, C; Chapman, A G; Meldrum, B S

1994-04-01

The effect of the non-N-methyl-D-aspartate (non-NMDA) receptor antagonist 1-(4-aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine hydrochloride (GYKI 52466) on ischaemia-induced changes in the microdialysate and tissue concentrations of glutamate, aspartate, and gamma-aminobutyric acid (GABA) was studied in rats. Twenty minutes of four-vessel occlusion resulted in a transient increase in microdialysate levels of glutamate, aspartate, and GABA in striatum, cortex, and hippocampus. Administration of GYKI 52466 (10 mg/kg bolus + 10 mg/kg/60 min intravenously starting 20 min before onset of ischaemia) inhibited ischaemia-induced increases in microdialysate glutamate and GABA in striatum without affecting the increases in hippocampus or cortex. Twenty minutes of four-vessel occlusion resulted in immediate small decreases and larger delayed (72 h) decreases in tissue levels of glutamate and aspartate. Transient increases in tissue levels of GABA were shown in all three structures at the end of the ischaemic period. At 72 h, after the ischaemic period, significantly reduced GABA levels were observed in striatum and hippocampus. GYKI 52466, given under identical conditions as above, augmented the ischaemia-induced decrease in striatal tissue levels of glutamate and aspartate, without significantly affecting the decreases in hippocampus and cortex. Twenty minutes of ischaemia resulted in a large increase in microdialysate dopamine in striatum. GYKI 52466 failed to inhibit this increase. Kainic acid (500 microM infused through the probe for 20 min) caused increases in microdialysate glutamate and aspartate in the striatum. GYKI 52466 (10 mg/kg bolus + 10 mg/kg/60 min) completely inhibited the kainic acid-induced glutamate release. In conclusion, the action of the non-NMDA antagonist, GYKI 52466, in the striatum is different from that in the cortex and hippocampus. The inhibition by GYKI 52466 of ischaemia-induced and kainate-induced increases in microdialysate

The Cannabinoid Receptor CB1 Modulates the Signaling Properties of the Lysophosphatidylinositol Receptor GPR55*

Science.gov (United States)

Kargl, Julia; Balenga, Nariman; Parzmair, Gerald P.; Brown, Andrew J.; Heinemann, Akos; Waldhoer, Maria

2012-01-01

The G protein-coupled receptor (GPCR) 55 (GPR55) and the cannabinoid receptor 1 (CB1R) are co-expressed in many tissues, predominantly in the central nervous system. Seven transmembrane spanning (7TM) receptors/GPCRs can form homo- and heteromers and initiate distinct signaling pathways. Recently, several synthetic CB1 receptor inverse agonists/antagonists, such as SR141716A, AM251, and AM281, were reported to activate GPR55. Of these, SR141716A was marketed as a promising anti-obesity drug, but was withdrawn from the market because of severe side effects. Here, we tested whether GPR55 and CB1 receptors are capable of (i) forming heteromers and (ii) whether such heteromers could exhibit novel signaling patterns. We show that GPR55 and CB1 receptors alter each others signaling properties in human embryonic kidney (HEK293) cells. We demonstrate that the co-expression of FLAG-CB1 receptors in cells stably expressing HA-GPR55 specifically inhibits GPR55-mediated transcription factor activation, such as nuclear factor of activated T-cells and serum response element, as well as extracellular signal-regulated kinases (ERK1/2) activation. GPR55 and CB1 receptors can form heteromers, but the internalization of both receptors is not affected. In addition, we observe that the presence of GPR55 enhances CB1R-mediated ERK1/2 and nuclear factor of activated T-cell activation. Our data provide the first evidence that GPR55 can form heteromers with another 7TM/GPCR and that this interaction with the CB1 receptor has functional consequences in vitro. The GPR55-CB1R heteromer may play an important physiological and/or pathophysiological role in tissues endogenously co-expressing both receptors. PMID:23161546

Mechanism of A2 adenosine receptor activation. I. Blockade of A2 adenosine receptors by photoaffinity labeling

International Nuclear Information System (INIS)

Lohse, M.J.; Klotz, K.N.; Schwabe, U.

1991-01-01

It has previously been shown that covalent incorporation of the photoreactive adenosine derivative (R)-2-azido-N6-p-hydroxy-phenylisopropyladenosine [(R)-AHPIA] into the A1 adenosine receptor of intact fat cells leads to a persistent activation of this receptor, resulting in a reduction of cellular cAMP levels. In contrast, covalent incorporation of (R)-AHPIA into human platelet membranes, which contain only stimulatory A2 adenosine receptors, reduces adenylate cyclase stimulation via these receptors. This effect of (R)-AHPIA is specific for the A2 receptor and can be prevented by the adenosine receptor antagonist theophylline. Binding studies indicate that up to 90% of A2 receptors can be blocked by photoincorporation of (R)-AHPIA. However, the remaining 10-20% of A2 receptors are sufficient to mediate an adenylate cyclase stimulation of up to 50% of the control value. Similarly, the activation via these 10-20% of receptors occurs with a half-life that is only 2 times longer than that in control membranes. This indicates the presence of a receptor reserve, with respect to both the extent and the rate of adenylate cyclase stimulation. These observations require a modification of the models of receptor-adenylate cyclase coupling

The First Fifteen Years of Steroid Receptor Research in Zebrafish; Characterization and Functional Analysis of the Receptors

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Marcel J. M. Schaaf

2017-07-01

Full Text Available Steroid hormones regulate a wide range of processes in our body, and their effects are mediated by steroid receptors. In addition to their physiological role, these receptors mediate the effects of endocrine disrupting chemicals (EDCs and are widely used targets for dugs involved in the treatment of numerous diseases, ranging from cancer to inflammatory disorders. Over the last fifteen years, the zebrafish has increasingly been used as an animal model in steroid receptor research. Orthologues of all human steroid receptor genes appear to be present in zebrafish. All zebrafish steroid receptors have been characterized in detail, and their expression patterns have been analyzed. Functional studies have been performed using morpholino knockdown of receptor expression and zebrafish lines carrying mutations in one of their steroid receptor genes. To investigate the activity of the receptors in vivo, specific zebrafish reporter lines have been developed, and transcriptomic studies have been carried out to identify biomarkers for steroid receptor action. In this review, an overview of research on steroid receptors in zebrafish is presented, and it is concluded that further exploitation of the possibilities of the zebrafish model system will contribute significantly to the advancement of steroid receptor research in the next decade.

How calcium makes endocytic receptors attractive

DEFF Research Database (Denmark)

Andersen, Christian B F; Moestrup, Søren K

2014-01-01

of the receptor. Endosomal acidification and calcium efflux lead to the essential ligand-receptor affinity switch and separation. Recent data, including crystal structures of receptor-ligand complexes, now reveal how calcium, in different types of domain scaffolds, functions in a common way as a removable...... 'lynchpin' that stabilizes favorable positioning of ligand-attractive receptor residues. In addition to explaining how calcium depletion can cause ligand-receptor dissociation, the new data add further insight into how acidification contributes to dissociation through structural changes that affect...... the receptor calcium sites....

Radiosequence analysis of the human progestin receptor charged with [3H]promegestone. A comparison with the glucocorticoid receptor

International Nuclear Information System (INIS)

Stroemstedt, P.E.B.; Berkenstam, A.; Joernvall, H.G.; Gustafsson, J.A.; Carlstedt-Duke, J.

1990-01-01

Partially purified preparations of the human progestin receptor and the human and rat glucocorticoid receptor proteins were covalently charged with the synthetic progestin, [ 3 H]promegestone, by photoaffinity labeling. After labeling, the denaturated protein was cleaved and the mixture of peptides subjected to radiosequence analysis as previously described for the rat glucocorticoid receptor protein. The radioactivity labels identified, corresponded to Met-759 and Met-909 after photoaffinity labeling of the human progestin receptor, and Met-622 and Cys-754 after labeling of the rat glucocorticoid receptor. The residues labeled in the glucocorticoid receptor are the same as those previously reported to bind triamcinolone actonide. The corresponding residues were also labeled in the human glucocorticoid receptor. Met-759 of the progestin receptor and Met-622 of the rat glucocorticoid receptor are positioned within a segment with an overall high degree of sequence similarity and are equivalent. However, Met-909 (progestin receptor) and Cys-754 (glucocorticoid receptor) do not occur within equivalent segments of the two proteins. Thus, although the two classes of steroid hormone share a common structure within the A-ring, there are subtle differences in their interaction with the two separate receptor proteins

Toll-like receptors in neonatal sepsis.

LENUS (Irish Health Repository)

O'Hare, Fiona M

2013-06-01

Toll-like receptors are vital transmembrane receptors that initiate the innate immune response to many micro-organisms. The discovery of these receptors has improved our understanding of host-pathogen interactions, and these receptors play an important role in the pathogenesis of multiple neonatal conditions such as sepsis and brain injury. Toll-like receptors, especially TLRs 2 and 4, are associated with necrotizing enterocolitis, periventricular leukomalacia and sepsis.

Labeled receptor ligands for spect

International Nuclear Information System (INIS)

Kung, H.F.

1989-01-01

Receptor specific imaging agents for single photon emission computed tomography (SPECT) can potentially be useful in the understanding of basic biochemistry and pharmacology of receptors. SPECT images may also provide tools for evaluation of density and binding kinetics of a specific receptor, information important for diagnosis and patient management. Basic requirements for receptor imaging agents are: (a) they are labeled with short-lived isotopes, (b) they show high selectivity and specific uptake, (c) they exhibit high target/background ratio, and (d) they can be modeled to obtain quantitative information. Several good examples of CNS receptor specific ligands labeled with I-123 have been developed, including iodoQNB, iodoestrogen iodobenzadiazepine, iodobenazepine, iodobenzamides for muscarinic, estrogen benzadiazepine, D-1 and D-2 dopamine receptors. With the advent of newer and faster SPECT imaging devices, it may be feasible to quantitate the receptor density by in vivo imaging techniques. These new brain imaging agents can provide unique diagnostic information, which may not be available through other imaging modalities, such as CT and MRI

The alpha-fetoprotein third domain receptor binding fragment: in search of scavenger and associated receptor targets.

Science.gov (United States)

Mizejewski, G J

2015-01-01

Recent studies have demonstrated that the carboxyterminal third domain of alpha-fetoprotein (AFP-CD) binds with various ligands and receptors. Reports within the last decade have established that AFP-CD contains a large fragment of amino acids that interact with several different receptor types. Using computer software specifically designed to identify protein-to-protein interaction at amino acid sequence docking sites, the computer searches identified several types of scavenger-associated receptors and their amino acid sequence locations on the AFP-CD polypeptide chain. The scavenger receptors (SRs) identified were CD36, CD163, Stabilin, SSC5D, SRB1 and SREC; the SR-associated receptors included the mannose, low-density lipoprotein receptors, the asialoglycoprotein receptor, and the receptor for advanced glycation endproducts (RAGE). Interestingly, some SR interaction sites were localized on the AFP-derived Growth Inhibitory Peptide (GIP) segment at amino acids #480-500. Following the detection studies, a structural subdomain analysis of both the receptor and the AFP-CD revealed the presence of epidermal growth factor (EGF) repeats, extracellular matrix-like protein regions, amino acid-rich motifs and dimerization subdomains. For the first time, it was reported that EGF-like sequence repeats were identified on each of the three domains of AFP. Thereafter, the localization of receptors on specific cell types were reviewed and their functions were discussed.

Modulating Estrogen Receptor-related Receptor-α Activity Inhibits Cell Proliferation*

Science.gov (United States)

Bianco, Stéphanie; Lanvin, Olivia; Tribollet, Violaine; Macari, Claire; North, Sophie; Vanacker, Jean-Marc

2009-01-01

High expression of the estrogen receptor-related receptor (ERR)-α in human tumors is correlated to a poor prognosis, suggesting an involvement of the receptor in cell proliferation. In this study, we show that a synthetic compound (XCT790) that modulates the activity of ERRα reduces the proliferation of various cell lines and blocks the G1/S transition of the cell cycle in an ERRα-dependent manner. XCT790 induces, in a p53-independent manner, the expression of the cell cycle inhibitor p21waf/cip1 at the protein, mRNA, and promoter level, leading to an accumulation of hypophosphorylated Rb. Finally, XCT790 reduces cell tumorigenicity in Nude mice. PMID:19546226

Functionally biased signalling properties of 7TM receptors - opportunities for drug development for the ghrelin receptor

DEFF Research Database (Denmark)

Sivertsen, B; Holliday, N; Madsen, A N

2013-01-01

UNLABELLED: The ghrelin receptor is a 7 transmembrane (7TM) receptor involved in a variety of physiological functions including growth hormone secretion, increased food intake and fat accumulation as well as modulation of reward and cognitive functions. Because of its important role in metabolism...... and energy expenditure, the ghrelin receptor has become an important therapeutic target for drug design and the development of anti-obesity compounds. However, none of the compounds developed so far have been approved for commercial use. Interestingly, the ghrelin receptor is able to signal through several...... review, we have described how ligands and mutations in the 7TM receptor may bias the receptors to favour either one G-protein over another or to promote G-protein independent signalling pathways rather than G-protein-dependent pathways. For the ghrelin receptor, both agonist and inverse agonists have...

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.

Isotopic ages of rocks along the Median Tectonic Line in the Yoshino area, Nara Prefecture

International Nuclear Information System (INIS)

Shibata, Ken; Sugiyama, Yuichi; Uchiumi, Shigeru; Takagi, Hideo.

1988-01-01

K-Ar, Rb-Sr and fission-track age determinations were carried out on rocks along the Median Tectonic Line (MTL) in the Yoshino area, Nara Prefecture. K-Ar ages on th Ryoke granitic rocks range from 35.3 to 75.9 Ma. Within about 1000 m of MTL the ages decrease toward MTL, probably caused by the hydrothermal alteration associated with cataclasis. The Takamiyama acidic rocks give a K-Ar age of 12.8 Ma. The cooling rate of the granitic rocks, calculated from K-Ar ages and closure temperatures of minerals, is 23 - 27degC/Ma. K-Ar ages for muscovites from pelitic schists in the Sambagawa belt are 62.3 - 69.4 Ma, whereas K-Ar whole-rock ages for phyllites in the Shimanto belt are 57.1 - 76.7 Ma; decrease in age is not observed even near MTL. Rb-Sr ages for muscovites from the schists are 70.4 and 72.5 Ma, which are assumed to indicate the time of metamorphism. The phyllites give a Rb-Sr whole-rock isochron age of 77.1±6.1 Ma, which is interpreted to represent the time of diagenesis or weak metamorphism. Fission-track ages for zircons from the Ryoke granitic rocks range from 37.0 to 68.2 Ma and decrease toward MTL. Fission-track ages of zircon are generally close to K-Ar ages of K-feldspar for the same rocks. From this fact the closure temperature for zircon is estimated to be lower than 200degC. The fine fractions (<2μm) separated from MTL fault gouges at Michaya and Takamiyama give K-Ar ages of 36.7 and 18.3 Ma, respectively. These ages probably represent the time of hydrothermal alteration following the major fault movement of MTL associated with cataclasis. (author)

Dynamics of the actin cytoskeleton mediates receptor cross talk: An emerging concept in tuning receptor signaling

Science.gov (United States)

Mattila, Pieta K.; Batista, Facundo D.

2016-01-01

Recent evidence implicates the actin cytoskeleton in the control of receptor signaling. This may be of particular importance in the context of immune receptors, such as the B cell receptor, where dysregulated signaling can result in autoimmunity and malignancy. Here, we discuss the role of the actin cytoskeleton in controlling receptor compartmentalization, dynamics, and clustering as a means to regulate receptor signaling through controlling the interactions with protein partners. We propose that the actin cytoskeleton is a point of integration for receptor cross talk through modulation of protein dynamics and clustering. We discuss the implication of this cross talk via the cytoskeleton for both ligand-induced and low-level constitutive (tonic) signaling necessary for immune cell survival. PMID:26833785

DMPD: Toll-like receptor 3: a link between toll-like receptor, interferon and viruses. [Dynamic Macrophage Pathway CSML Database

Lifescience Database Archive (English)

Full Text Available 15031527 Toll-like receptor 3: a link between toll-like receptor, interferon and virus... (.csml) Show Toll-like receptor 3: a link between toll-like receptor, interferon and viruses. PubmedID 1503...1527 Title Toll-like receptor 3: a link between toll-like receptor, interferon and virus

Korduv pisivargus ja süstemaatiline vargus. Riigikohtu kriminaalkolleegiumi otsus asjas 3-1-1-36-07 / Jaan Sootak

Index Scriptorium Estoniae

Sootak, Jaan, 1948-

2008-01-01

Kommentaar Riigikohtu lahendile 3-1-1-36-07 (Ivailo Siimani kaitsja vandeadvokaadi vanemabi Andres Veski ja Margo Küti kaitsja vandeadvokaat Anu Pärteli kassatsioonid Tartu Ringkonnakohtu 13. veebruari 2007. a kohtuotsuse peale kriminaalasjas Ivailo Siimani süüdistuses KarS § 199 lg 2 p-de 4, 7 ja 8; § 263 p-de 1 ja 4 järgi ning Margo Küti süüdistuses KarS § 200 lg 2 p 7, § 199 lg 2 p-de 4, 7, 8, § 263 p-de 1, 2, 3 ja § 25 lg-te 1 ja 2 ning § 209 lg 2 p 1 järgi)

Andrographolide regulates epidermal growth factor receptor and transferrin receptor trafficking in epidermoid carcinoma (A-431) cells

Science.gov (United States)

Tan, Y; Chiow, KH; Huang, D; Wong, SH

2010-01-01

Background and purpose: Andrographolide is the active component of Andrographis paniculata, a plant used in both Indian and Chinese traditional medicine, and it has been demonstrated to induce apoptosis in different cancer cell lines. However, not much is known about how it may affect the key receptors implicated in cancer. Knowledge of how andrographolide affects receptor trafficking will allow us to better understand new mechanisms by which andrographolide may cause death in cancer cells. Experimental approach: We utilized the well-characterized epidermal growth factor receptor (EGFR) and transferrin receptor (TfR) expressed in epidermoid carcinoma (A-431) cells as a model to study the effect of andrographolide on receptor trafficking. Receptor distribution, the total number of receptors and surface receptors were analysed by immunofluorescence, Western blot as well as flow-cytometry respectively. Key results: Andrographolide treatment inhibited cell growth, down-regulated EGFRs on the cell surface and affected the degradation of EGFRs and TfRs. The EGFR was internalized into the cell at an increased rate, and accumulated in a compartment that co-localizes with the lysosomal-associated membrane protein in the late endosomes. Conclusion and implications: This study sheds light on how andrographolide may affect receptor trafficking by inhibiting receptor movement from the late endosomes to lysosomes. The down-regulation of EGFR from the cell surface also indicates a new mechanism by which andrographolide may induce cancer cell death. PMID:20233216

In vivo studies of opiate receptors

International Nuclear Information System (INIS)

Frost, J.J.; Dannals, R.F.; Duelfer, T.; Burns, H.D.; Ravert, H.T.; Langstroem, B.; Balasubramanian, V.; Wagner, H.N. Jr.

1984-01-01

To study opiate receptors noninvasively in vivo using positron emission tomography, techniques for preferentially labeling opiate receptors in vivo can be used. The rate at which receptor-bound ligand clears from the brain in vivo can be predicted by measuring the equilibrium dissociation constant (KD) at 37 degrees C in the presence of 100 mM sodium chloride and 100 microM guanyl-5'-imidodiphosphate, the drug distribution coefficient, and the molecular weight. A suitable ligand for labeling opiate receptors in vivo is diprenorphine, which binds to mu, delta, and kappa receptors with approximately equal affinity in vitro. However, in vivo diprenorphine may bind predominantly to one opiate receptor subtype, possibly the mu receptor. To predict the affinity for binding to the opiate receptor, a Hansch correlation was determined between the 50% inhibitory concentration for a series of halogen-substituted fentanyl analogs and electronic, lipophilic, and steric parameters. Radiochemical methods for the synthesis of carbon-11-labeled diprenorphine and lofentanil are presented

In vivo studies of opiate receptors

Energy Technology Data Exchange (ETDEWEB)

Frost, J.J.; Dannals, R.F.; Duelfer, T.; Burns, H.D.; Ravert, H.T.; Langstroem, B.; Balasubramanian, V.; Wagner, H.N. Jr.

1984-01-01

To study opiate receptors noninvasively in vivo using positron emission tomography, techniques for preferentially labeling opiate receptors in vivo can be used. The rate at which receptor-bound ligand clears from the brain in vivo can be predicted by measuring the equilibrium dissociation constant (KD) at 37 degrees C in the presence of 100 mM sodium chloride and 100 microM guanyl-5'-imidodiphosphate, the drug distribution coefficient, and the molecular weight. A suitable ligand for labeling opiate receptors in vivo is diprenorphine, which binds to mu, delta, and kappa receptors with approximately equal affinity in vitro. However, in vivo diprenorphine may bind predominantly to one opiate receptor subtype, possibly the mu receptor. To predict the affinity for binding to the opiate receptor, a Hansch correlation was determined between the 50% inhibitory concentration for a series of halogen-substituted fentanyl analogs and electronic, lipophilic, and steric parameters. Radiochemical methods for the synthesis of carbon-11-labeled diprenorphine and lofentanil are presented.

Differential trafficking of AMPA receptors following activation of NMDA receptors and mGluRs

Directory of Open Access Journals (Sweden)

Sanderson Thomas M

2011-07-01

Full Text Available Abstract The removal of AMPA receptors from synapses is a major component of long-term depression (LTD. How this occurs, however, is still only partially understood. To investigate the trafficking of AMPA receptors in real-time we previously tagged the GluA2 subunit of AMPA receptors with ecliptic pHluorin and studied the effects of NMDA receptor activation. In the present study we have compared the effect of NMDA receptor and group I mGluR activation, using GluA2 tagged with super ecliptic pHluorin (SEP-GluA2 expressed in cultured hippocampal neurons. Surprisingly, agonists of the two receptors, which are both able to induce chemical forms of LTD, had clearly distinct effects on AMPA receptor trafficking. In agreement with our previous work we found that transient NMDA receptor activation results in an initial decrease in surface GluA2 from extrasynaptic sites followed by a delayed reduction in GluA2 from puncta (putative synapses. In contrast, transient activation of group I mGluRs, using DHPG, led to a pronounced but more delayed decrease in GluA2 from the dendritic shafts. Surprisingly, there was no average change in the fluorescence of the puncta. Examination of fluorescence at individual puncta, however, indicated that alterations did take place, with some puncta showing an increase and others a decrease in fluorescence. The effects of DHPG were, like DHPG-induced LTD, prevented by treatment with a protein tyrosine phosphatase (PTP inhibitor. The electrophysiological correlate of the effects of DHPG in the SEP-GluA2 infected cultures was a reduction in mEPSC frequency with no change in amplitude. The implications of these findings for the initial mechanisms of expression of both NMDA receptor- and mGluR-induced LTD are discussed.

Characterization of melanocortin receptor ligands on cloned brain melanocortin receptors and on grooming behavior in the rat

NARCIS (Netherlands)

Gispen, W.H.; Adan, R.A.H.; Szklarczyk, A.W.; Oosterom, J.; Brakkee, J.H.; Nijenhuis, W.A.; Schaaper, W.M.; Meloen, R.H.

1999-01-01

Since the melanocortin MC3 and melanocortin MC4 receptors are the main melanocortin receptor subtypes expressed in rat brain, we characterized the activity and affinity of nine melanocortin receptor ligands using these receptors in vitro, as well as their activity in a well-defined

A bioluminescence resonance energy transfer 2 (BRET2) assay for monitoring seven transmembrane receptor and insulin receptor crosstalk

DEFF Research Database (Denmark)

Sanni, Samra Joke; Kulahin, Nikolaj; Jorgensen, Rasmus

2017-01-01

The angiotensin AT1 receptor is a seven transmembrane (7TM) receptor, which mediates the regulation of blood pressure. Activation of angiotensin AT1 receptor may lead to impaired insulin signaling indicating crosstalk between angiotensin AT1 receptor and insulin receptor signaling pathways....... To elucidate the molecular mechanisms behind this crosstalk, we applied the BRET2 technique to monitor the effect of angiotensin II on the interaction between Rluc8 tagged insulin receptor and GFP2 tagged insulin receptor substrates 1, 4, 5 (IRS1, IRS4, IRS5) and Src homology 2 domain-containing protein (Shc......). We demonstrate that angiotensin II reduces the interaction between insulin receptor and IRS1 and IRS4, respectively, while the interaction with Shc is unaffected, and this effect is dependent on Gαq activation. Activation of other Gαq-coupled 7TM receptors led to a similar reduction in insulin...

The repertoire of olfactory C family G protein-coupled receptors in zebrafish: candidate chemosensory receptors for amino acids

Directory of Open Access Journals (Sweden)

Ngai John

2006-12-01

Full Text Available Abstract Background Vertebrate odorant receptors comprise at least three types of G protein-coupled receptors (GPCRs: the OR, V1R, and V2R/V2R-like receptors, the latter group belonging to the C family of GPCRs. These receptor families are thought to receive chemosensory information from a wide spectrum of odorant and pheromonal cues that influence critical animal behaviors such as feeding, reproduction and other social interactions. Results Using genome database mining and other informatics approaches, we identified and characterized the repertoire of 54 intact "V2R-like" olfactory C family GPCRs in the zebrafish. Phylogenetic analysis – which also included a set of 34 C family GPCRs from fugu – places the fish olfactory receptors in three major groups, which are related to but clearly distinct from other C family GPCRs, including the calcium sensing receptor, metabotropic glutamate receptors, GABA-B receptor, T1R taste receptors, and the major group of V2R vomeronasal receptor families. Interestingly, an analysis of sequence conservation and selective pressure in the zebrafish receptors revealed the retention of a conserved sequence motif previously shown to be required for ligand binding in other amino acid receptors. Conclusion Based on our findings, we propose that the repertoire of zebrafish olfactory C family GPCRs has evolved to allow the detection and discrimination of a spectrum of amino acid and/or amino acid-based compounds, which are potent olfactory cues in fish. Furthermore, as the major groups of fish receptors and mammalian V2R receptors appear to have diverged significantly from a common ancestral gene(s, these receptors likely mediate chemosensation of different classes of chemical structures by their respective organisms.

Intracellular insulin-receptor dissociation and segregation in a rat fibroblast cell line transfected with a human insulin receptor gene

International Nuclear Information System (INIS)

Levy, J.R.; Olefsky, J.M.

1988-01-01

The cellular processing of insulin and insulin receptors was studied using a rat fibroblast cell line that had been transfected with a normal human insulin receptor gene, expressing approximately 500 times the normal number of native fibroblasts insulin receptors. These cells bind and internalize insulin normally. Biochemically assays based on the selective precipitation by polyethylene glycol of intact insulin-receptor complexes but not of free intracellular insulin were developed to study the time course of intracellular insulin-receptor dissociation. Fibroblasts were incubated with radiolabeled insulin at 4 0 C, and internalization of insulin-receptor complexes was initiated by warming the cells to 37 0 C. Within 2 min, 90% of the internalized radioactivity was composed of intact insulin-receptor complexes. The dissociation of insulin from internalized insulin-receptor complexes was markedly inhibited by monensin and chloroquine. Furthermore, chloroquine markedly increased the number of cross-linkable intracellular insulin-receptor complexes, as analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis autoradiography. These findings suggest that acidification of intracellular vesicles is responsible for insulin-receptor dissociation. Physical segregation of dissociated intracellular insulin from its receptor was monitored. The results are consistent with the view that segregation of insulin and receptor occurs 5-10 min after initiation of dissociation. These studies demonstrate the intracellular itinerary of insulin-receptor complexes, including internalization, dissociation of insulin from the internalized receptor within an acidified compartment, segregation of insulin from the receptor, and subsequent ligand degradation

Functional ET(A)-ET(B) Receptor Cross-talk in Basilar Artery In Situ From ET(B) Receptor Deficient Rats.

Science.gov (United States)

Yoon, SeongHun; Gariepy, Cheryl E; Yanagisawa, Masashi; Zuccarello, Mario; Rapoport, Robert M

2016-03-01

The role of endothelin (ET)(A)-ET(B) receptor cross-talk in limiting the ET(A) receptor antagonist inhibition of ET-1 constriction is revealed by the partial or complete dependency of the ET(A) receptor antagonist inhibition on functional removal of the ET(B) receptor. Although functional removal of the ET(B) receptor is generally accomplished with ET(B) receptor antagonist, a novel approach using rats containing a naturally occurring deletion mutation in the ET(B) receptor [rescued "spotting lethal" (sl) rats; ET(B)(sl/sl)] demonstrated increased ET(A) receptor antagonist inhibition of ET-1 constriction in vena cava. We investigated whether this deletion mutation was also sufficient to remove the ET(B) receptor dependency of the ET(A) receptor antagonist inhibition of ET-1 constriction in the basilar artery. Consistent with previous reports, ET-1 plasma levels were elevated in ET(B)(sl/sl) as compared with ET(B)(+/+) rats. ET(B) receptor antagonist failed to relax the ET-1 constricted basilar artery from ET(B)(+/+) and ET(B)(sl/sl) rats. Relaxation to combined ET(A) and ET(B) receptor antagonist was greater than relaxation to ET(A) receptor antagonist in the basilar artery from ET(B)(+/+) and, unexpectedly, ET(B)(sl/sl) rats. These findings confirm the presence of ET(A)-ET(B) receptor cross-talk in the basilar artery. We speculate that mutant ET(B) receptor expression produced by alternative splicing may be sufficient to allow cross-talk.

Subtype selective kainic acid receptor agonists

DEFF Research Database (Denmark)

Bunch, Lennart; Krogsgaard-Larsen, Povl

2009-01-01

(S)-Glutamic acid (Glu) is the major excitatory neurotransmitter in the mammalian central nervous system, activating the plethora of glutamate receptors (GluRs). In broad lines, the GluRs are divided into two major classes: the ionotropic Glu receptors (iGluRs) and the metabotropic Glu receptors (m......GluRs). Within the iGluRs, five subtypes (KA1, KA2, iGluR5-7) show high affinity and express full agonist activity upon binding of the naturally occurring amino acid kainic acid (KA). Thus these receptors have been named the KA receptors. This review describes all-to our knowledge-published KA receptor agonists...

Hypoxia increases pulmonary arterial thromboxane receptor internalization independent of receptor sensitization.

Science.gov (United States)

Fediuk, J; Sikarwar, A S; Lizotte, P P; Hinton, M; Nolette, N; Dakshinamurti, S

2015-02-01

Persistent Pulmonary Hypertension of the Newborn (PPHN) is characterized by sustained vasospasm and an increased thromboxane:prostacyclin ratio. Thromboxane (TP) receptors signal via Gαq to mobilize IP3 and Ca(2+), causing pulmonary arterial constriction. We have previously reported increased TP internalization in hypoxic pulmonary arterial (PA) myocytes. Serum-deprived PA myocytes were grown in normoxia (NM) or hypoxia (HM) for 72 h. TP localization was visualized in agonist-naïve and -challenged NM and HM by immunocytochemistry. Pathways for agonist-induced TP receptor internalization were determined by inhibiting caveolin- or clathrin-mediated endocytosis, and caveolar fractionation. Roles of actin and tubulin in TP receptor internalization were assessed using inhibitors of tubulin, actin-stabilizing or -destabilizing agents. PKA, PKC or GRK activation and inhibition were used to determine the kinase responsible for post-agonist receptor internalization. Agonist-naïve HM had decreased cell surface TP, and greater TP internalization after agonist challenge. TP protein did not sort with caveolin-rich fractions. Inhibition of clathrin prevented TP internalization. Both actin-stabilizing and -destabilizing agents prevented TP endocytosis in NM, while normalizing TP internalization in HM. Velocity of TP internalization was unaffected by PKA activity, but PKC activation normalized TP receptor internalization in HM. GRK inhibition had no effect. We conclude that in hypoxic myocytes, TP is internalized faster and to a greater extent than in normoxic controls. Internalization of the agonist-challenged TP requires clathrin, dynamic actin and is sensitive to PKC activity. TP receptor trafficking and signaling in hypoxia are pivotal to understanding increased vasoconstrictor sensitivity. Copyright © 2014 Elsevier Ltd. All rights reserved.

Toll-like receptor 2 or toll-like receptor 4 deficiency does not modify lupus in MRLlpr mice.

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Simon J Freeley

Full Text Available Systemic lupus erythematosus is an autoimmune disease with a high morbidity and nephritis is a common manifestation. Previous studies in murine lupus models have suggest a role for Toll-like receptor 2 and 4. We examined the role of these molecules in MRL lpr mice which is one of the most established and robust murine models. We compared disease parameters in Toll-like receptor 2 or Toll-like receptor 4 deficient mice with their littermate controls. We found no difference in the severity of glomerulonephritis as assessed by histology, serum creatinine and albuminuria when Toll-like receptor 2 or Toll-like receptor 4 deficient MRLlpr mice were compared with Toll-like receptor sufficient controls. We also found similar levels of anti-dsDNA and anti-ssDNA antibodies. These results show that Toll-like receptor 2 and Toll-like receptor 4 do not play a significant role in MRLlpr mice, and therefore they may not be important in human lupus.

Involvement of direct inhibition of NMDA receptors in the effects of sigma-receptor ligands on glutamate neurotoxicity in vitro.

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Nishikawa, H; Hashino, A; Kume, T; Katsuki, H; Kaneko, S; Akaike, A

2000-09-15

This study was performed to examine the roles of the N-methyl-D-aspartate (NMDA) receptor/phencyclidine (PCP) channel complex in the protective effects of sigma-receptor ligands against glutamate neurotoxicity in cultured cortical neurons derived from fetal rats. A 1-h exposure of cultures to glutamate caused a marked loss of viability, as determined by Trypan blue exclusion. This acute neurotoxicity of glutamate was prevented by NMDA receptor antagonists. Expression of sigma(1) receptor mRNA in cortical cultures was confirmed by reverse transcription polymerase chain reaction (RT-PCR). sigma Receptor ligands with affinity for NMDA receptor channels including the PCP site, such as (+)-N-allylnormetazocine ((+)-SKF10,047), haloperidol, and R(-)-N-(3-phenyl-1-propyl)-1-phenyl-2-aminopropane ((-)-PPAP), prevented glutamate neurotoxicity in a concentration-dependent manner. In contrast, other sigma-receptor ligands without affinity for NMDA receptors, such as carbetapentane and R(+)-3-(3-hydroxyphenyl)-N-propylpiperidine ((+)-3-PPP), did not show neuroprotective effects. Putative endogenous sigma receptor ligands such as pregnenolone, progesterone, and dehydroepiandrosterone did not affect glutamate neurotoxicity. The protective effects of (+)-SKF10,047, haloperidol, and (-)-PPAP were not affected by the sigma(1) receptor antagonist rimcazole. These results suggested that a direct interaction with NMDA receptors but not with sigma receptors plays a crucial role in the neuroprotective effects of sigma receptor ligands with affinity for NMDA receptors.