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  1. Involvement of intracellular Zn2+ signaling in LTP at perforant pathway-CA1 pyramidal cell synapse.

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    Tamano, Haruna; Nishio, Ryusuke; Takeda, Atsushi

    2017-07-01

    Physiological significance of synaptic Zn 2+ signaling was examined at perforant pathway-CA1 pyramidal cell synapses. In vivo long-term potentiation (LTP) at perforant pathway-CA1 pyramidal cell synapses was induced using a recording electrode attached to a microdialysis probe and the recording region was locally perfused with artificial cerebrospinal fluid (ACSF) via the microdialysis probe. Perforant pathway LTP was not attenuated under perfusion with CaEDTA (10 mM), an extracellular Zn 2+ chelator, but attenuated under perfusion with ZnAF-2DA (50 μM), an intracellular Zn 2+ chelator, suggesting that intracellular Zn 2+ signaling is required for perforant pathway LTP. Even in rat brain slices bathed in CaEDTA in ACSF, intracellular Zn 2+ level, which was measured with intracellular ZnAF-2, was increased in the stratum lacunosum-moleculare where perforant pathway-CA1 pyramidal cell synapses were contained after tetanic stimulation. These results suggest that intracellular Zn 2+ signaling, which originates in internal stores/proteins, is involved in LTP at perforant pathway-CA1 pyramidal cell synapses. Because the influx of extracellular Zn 2+ , which originates in presynaptic Zn 2+ release, is involved in LTP at Schaffer collateral-CA1 pyramidal cell synapses, synapse-dependent Zn 2+ dynamics may be involved in plasticity of postsynaptic CA1 pyramidal cells. © 2017 Wiley Periodicals, Inc.

  2. Activation of functional α7-containing nAChRs in hippocampal CA1 pyramidal neurons by physiological levels of choline in the presence of PNU-120596.

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    Bopanna I Kalappa

    2010-11-01

    trigger action potentials.1 The majority of hippocampal CA1 pyramidal neurons express functional α7-containing nAChRs. In the absence of PNU-120596, a positive allosteric modulator of α7 nAChRs, a lack of responsiveness of some hippocampal CA1 pyramidal neurons to focal application of 0.5-1 mM choline does not imply a lack of expression of functional α7-containing nAChRs in these neurons. Rather, it may indicate a lack of detection of α7-containing nAChR-mediated currents by patch-clamp electrophysiology. 2 PNU-120596 can serve as a powerful tool for detection and enhancement of responsiveness of low densities of functional α7-containing nAChRs such as those present in hippocampal CA1 pyramidal neurons. 3 In the presence of PNU-120596, physiological concentrations of choline activate functional CA1 pyramidal α7-containing nAChRs and produce step-like currents that cause repetitive step-like depolarizations, occasionally triggering bursts of action potentials in CA1 pyramidal neurons. Therefore, the results of this study suggest that in the presence of PNU-120596 and possibly other positive allosteric modulators, endogenous choline may persistently activate CA1 pyramidal α7-containing nAChRs, enhance the excitability of CA1 pyramidal neurons and thus act as a potent therapeutic agent with potential neuroprotective and cognition-enhancing properties.

  3. Quantitative assessment of CA1 local circuits: knowledge base for interneuron-pyramidal cell connectivity.

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    Bezaire, Marianne J; Soltesz, Ivan

    2013-09-01

    In this work, through a detailed literature review, data-mining, and extensive calculations, we provide a current, quantitative estimate of the cellular and synaptic constituents of the CA1 region of the rat hippocampus. Beyond estimating the cell numbers of GABAergic interneuron types, we calculate their convergence onto CA1 pyramidal cells and compare it with the known input synapses on CA1 pyramidal cells. The convergence calculation and comparison are also made for excitatory inputs to CA1 pyramidal cells. In addition, we provide a summary of the excitatory and inhibitory convergence onto interneurons. The quantitative knowledge base assembled and synthesized here forms the basis for data-driven, large-scale computational modeling efforts. Additionally, this work highlights specific instances where the available data are incomplete, which should inspire targeted experimental projects toward a more complete quantification of the CA1 neurons and their connectivity. Copyright © 2013 Wiley Periodicals, Inc.

  4. Muscarinic Long-Term Enhancement of Tonic and Phasic GABAA Inhibition in Rat CA1 Pyramidal Neurons

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    Domínguez, Soledad; Fernández de Sevilla, David; Buño, Washington

    2016-01-01

    Acetylcholine (ACh) regulates network operation in the hippocampus by controlling excitation and inhibition in rat CA1 pyramidal neurons (PCs), the latter through gamma-aminobutyric acid type-A receptors (GABAARs). Although, the enhancing effects of ACh on GABAARs have been reported (Dominguez et al., 2014, 2015), its role in regulating tonic GABAA inhibition has not been explored in depth. Therefore, we aimed at determining the effects of the activation of ACh receptors on responses mediated by synaptic and extrasynaptic GABAARs. Here, we show that under blockade of ionotropic glutamate receptors ACh, acting through muscarinic type 1 receptors, paired with post-synaptic depolarization induced a long-term enhancement of tonic GABAA currents (tGABAA) and puff-evoked GABAA currents (pGABAA). ACh combined with depolarization also potentiated IPSCs (i.e., phasic inhibition) in the same PCs, without signs of interactions of synaptic responses with pGABAA and tGABAA, suggesting the contribution of two different GABAA receptor pools. The long-term enhancement of GABAA currents and IPSCs reduced the excitability of PCs, possibly regulating plasticity and learning in behaving animals. PMID:27833531

  5. Human limbic encephalitis serum enhances hippocampal mossy fiber-CA3 pyramidal cell synaptic transmission.

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    Lalic, Tatjana; Pettingill, Philippa; Vincent, Angela; Capogna, Marco

    2011-01-01

    Limbic encephalitis (LE) is a central nervous system (CNS) disease characterized by subacute onset of memory loss and epileptic seizures. A well-recognized form of LE is associated with voltage-gated potassium channel complex antibodies (VGKC-Abs) in the patients' sera. We aimed to test the hypothesis that purified immunoglobulin G (IgG) from a VGKC-Ab LE serum would excite hippocampal CA3 pyramidal cells by reducing VGKC function at mossy-fiber (MF)-CA3 pyramidal cell synapses. We compared the effects of LE and healthy control IgG by whole-cell patch-clamp and extracellular recordings from CA3 pyramidal cells of rat hippocampal acute slices. We found that the LE IgG induced epileptiform activity at a population level, since synaptic stimulation elicited multiple population spikes extracellularly recorded in the CA3 area. Moreover, the LE IgG increased the rate of tonic firing and strengthened the MF-evoked synaptic responses. The synaptic failure of evoked excitatory postsynaptic currents (EPSCs) was significantly lower in the presence of the LE IgG compared to the control IgG. This suggests that the LE IgG increased the release probability on MF-CA3 pyramidal cell synapses compared to the control IgG. Interestingly, α-dendrotoxin (120 nm), a selective Kv1.1, 1.2, and 1.6 subunit antagonist of VGKC, mimicked the LE IgG-mediated effects. This is the first functional demonstration that LE IgGs reduce VGKC function at CNS synapses and increase cell excitability. Wiley Periodicals, Inc. © 2010 International League Against Epilepsy.

  6. The GLP-1 Receptor Agonist Exendin-4 and Diazepam Differentially Regulate GABAA Receptor-Mediated Tonic Currents in Rat Hippocampal CA3 Pyramidal Neurons.

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    Sergiy V Korol

    Full Text Available Glucagon-like peptide-1 (GLP-1 is a metabolic hormone that is secreted in a glucose-dependent manner and enhances insulin secretion. GLP-1 receptors are also found in the brain where their signalling affects neuronal activity. We have previously shown that the GLP-1 receptor agonists, GLP-1 and exendin-4 enhanced GABA-activated synaptic and tonic currents in rat hippocampal CA3 pyramidal neurons. The hippocampus is the centre for memory and learning and is important for cognition. Here we examined if exendin-4 similarly enhanced the GABA-activated currents in the presence of the benzodiazepine diazepam. In whole-cell recordings in rat brain slices, diazepam (1 μM, an allosteric positive modulator of GABAA receptors, alone enhanced the spontaneous inhibitory postsynaptic current (sIPSC amplitude and frequency by a factor of 1.3 and 1.6, respectively, and doubled the tonic GABAA current normally recorded in the CA3 pyramidal cells. Importantly, in the presence of exendin-4 (10 nM plus diazepam (1 μM, only the tonic but not the sIPSC currents transiently increased as compared to currents recorded in the presence of diazepam alone. The results suggest that exendin-4 potentiates a subpopulation of extrasynaptic GABAA receptors in the CA3 pyramidal neurons.

  7. Novel nootropic dipeptide Noopept increases inhibitory synaptic transmission in CA1 pyramidal cells.

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    Kondratenko, Rodion V; Derevyagin, Vladimir I; Skrebitsky, Vladimir G

    2010-05-31

    Effects of newly synthesized nootropic and anxiolytic dipeptide Noopept on inhibitory synaptic transmission in hippocampal CA1 pyramidal cells were investigated using patch-clamp technique in whole-cell configuration. Bath application of Noopept (1 microM) significantly increased the frequency of spike-dependant spontaneous IPSCs whereas spike-independent mIPSCs remained unchanged. It was suggested that Noopept mediates its effect due to the activation of inhibitory interneurons terminating on CA1 pyramidal cells. Results of current clamp recording of inhibitory interneurons residing in stratum radiatum confirmed this suggestion. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

  8. Transient increase in Zn2+ in hippocampal CA1 pyramidal neurons causes reversible memory deficit.

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    Atsushi Takeda

    Full Text Available The translocation of synaptic Zn(2+ to the cytosolic compartment has been studied to understand Zn(2+ neurotoxicity in neurological diseases. However, it is unknown whether the moderate increase in Zn(2+ in the cytosolic compartment affects memory processing in the hippocampus. In the present study, the moderate increase in cytosolic Zn(2+ in the hippocampus was induced with clioquinol (CQ, a zinc ionophore. Zn(2+ delivery by Zn-CQ transiently attenuated CA1 long-term potentiation (LTP in hippocampal slices prepared 2 h after i.p. injection of Zn-CQ into rats, when intracellular Zn(2+ levels was transiently increased in the CA1 pyramidal cell layer, followed by object recognition memory deficit. Object recognition memory was transiently impaired 30 min after injection of ZnCl(2 into the CA1, but not after injection into the dentate gyrus that did not significantly increase intracellular Zn(2+ in the granule cell layer of the dentate gyrus. Object recognition memory deficit may be linked to the preferential increase in Zn(2+ and/or the preferential vulnerability to Zn(2+ in CA1 pyramidal neurons. In the case of the cytosolic increase in endogenous Zn(2+ in the CA1 induced by 100 mM KCl, furthermore, object recognition memory was also transiently impaired, while ameliorated by co-injection of CaEDTA to block the increase in cytosolic Zn(2+. The present study indicates that the transient increase in cytosolic Zn(2+ in CA1 pyramidal neurons reversibly impairs object recognition memory.

  9. Transient increase in Zn2+ in hippocampal CA1 pyramidal neurons causes reversible memory deficit.

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    Takeda, Atsushi; Takada, Shunsuke; Nakamura, Masatoshi; Suzuki, Miki; Tamano, Haruna; Ando, Masaki; Oku, Naoto

    2011-01-01

    The translocation of synaptic Zn(2+) to the cytosolic compartment has been studied to understand Zn(2+) neurotoxicity in neurological diseases. However, it is unknown whether the moderate increase in Zn(2+) in the cytosolic compartment affects memory processing in the hippocampus. In the present study, the moderate increase in cytosolic Zn(2+) in the hippocampus was induced with clioquinol (CQ), a zinc ionophore. Zn(2+) delivery by Zn-CQ transiently attenuated CA1 long-term potentiation (LTP) in hippocampal slices prepared 2 h after i.p. injection of Zn-CQ into rats, when intracellular Zn(2+) levels was transiently increased in the CA1 pyramidal cell layer, followed by object recognition memory deficit. Object recognition memory was transiently impaired 30 min after injection of ZnCl(2) into the CA1, but not after injection into the dentate gyrus that did not significantly increase intracellular Zn(2+) in the granule cell layer of the dentate gyrus. Object recognition memory deficit may be linked to the preferential increase in Zn(2+) and/or the preferential vulnerability to Zn(2+) in CA1 pyramidal neurons. In the case of the cytosolic increase in endogenous Zn(2+) in the CA1 induced by 100 mM KCl, furthermore, object recognition memory was also transiently impaired, while ameliorated by co-injection of CaEDTA to block the increase in cytosolic Zn(2+). The present study indicates that the transient increase in cytosolic Zn(2+) in CA1 pyramidal neurons reversibly impairs object recognition memory.

  10. Serotonin-mediated modulation of Na+/K+ pump current in rat hippocampal CA1 pyramidal neurons.

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    Zhang, Li Nan; Su, Su Wen; Guo, Fang; Guo, Hui Cai; Shi, Xiao Lu; Li, Wen Ya; Liu, Xu; Wang, Yong Li

    2012-01-19

    The aim of this study was to investigate whether serotonin (5-hydroxytryptamine, 5-HT) can modulate Na+/K+ pump in rat hippocampal CA1 pyramidal neurons. 5-HT (0.1, 1 mM) showed Na+/K+ pump current (Ip) densities of 0.40 ± 0.04, 0.34 ± 0.03 pA/pF contrast to 0.63 ± 0.04 pA/pF of the control of 0.5 mM strophanthidin (Str), demonstrating 5-HT-induced inhibition of Ip in a dose-dependent manner in hippocampal CA1 pyramidal neurons. The effect was partly attenuated by ondasetron, a 5-HT3 receptor (5-HT3R) antagonist, not by WAY100635, a 5-HT1AR antagonist, while 1-(3-Chlorophenyl) biguanide hydrochloride (m-CPBG), a 5-HT3R specific agonist, mimicked the effect of 5-HT on Ip. 5-HT inhibits neuronal Na+/K+ pump activity via 5-HT3R in rat hippocampal CA1 pyramidal neurons. This discloses novel mechanisms for the function of 5-HT in learning and memory, which may be a useful target to benefit these patients with cognitive disorder.

  11. Pyramidal neurons in the septal and temporal CA1 field of the human and hedgehog tenrec hippocampus.

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    Liagkouras, Ioannis; Michaloudi, Helen; Batzios, Christos; Psaroulis, Dimitrios; Georgiadis, Marios; Künzle, Heinz; Papadopoulos, Georgios C

    2008-07-07

    The present study examines comparatively the cellular density of disector-counted/Nissl-stained CA1 pyramidal neurons and the morphometric characteristics (dendritic number/length, spine number/density and Sholl-counted dendritic branch points/20 microm) of the basal and apical dendritic systems of Golgi-impregnated CA1 neurons, in the septal and temporal hippocampus of the human and hedgehog tenrec brain. The obtained results indicate that in both hippocampal parts the cellular density of the CA1 pyramidal neurons is lower in human than in tenrec. However, while the human pyramidal cell density is higher in the septal hippocampal part than in the temporal one, in the tenrec the density of these cells is higher in the temporal part. The dendritic tree of the CA1 pyramidal cells, more developed in the septal than in temporal hippocampus in both species studied, is in general more complex in the human hippocampus. The basal and the apical dendritic systems exhibit species related morphometric differences, while dendrites of different orders exhibit differences in their number and length, and in their spine density. Finally, in both species, as well as hippocampal parts and dendritic systems, changes of dendritic morphometric features along ascending dendritic orders fluctuate in a similar way, as do the number of dendritic branch points in relation to the distance from the neuron soma.

  12. Functional characterization of the beta-adrenergic receptor subtypes expressed by CA1 pyramidal cells in the rat hippocampus.

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    Hillman, Kristin L; Doze, Van A; Porter, James E

    2005-08-01

    Recent studies have demonstrated that activation of the beta-adrenergic receptor (AR) using the selective beta-AR agonist isoproterenol (ISO) facilitates pyramidal cell long-term potentiation in the cornu ammonis 1 (CA1) region of the rat hippocampus. We have previously analyzed beta-AR genomic expression patterns of 17 CA1 pyramidal cells using single cell reverse transcription-polymerase chain reaction, demonstrating that all samples expressed the beta2-AR transcript, with four of the 17 cells additionally expressing mRNA for the beta1-AR subtype. However, it has not been determined which beta-AR subtypes are functionally expressed in CA1 for these same pyramidal neurons. Using cell-attached recordings, we tested the ability of ISO to increase pyramidal cell action potential (AP) frequency in the presence of subtype-selective beta-AR antagonists. ICI-118,551 [(+/-)-1-[2,3-(dihydro-7-methyl-1H-inden-4-yl)oxy]-3-[(1-methylethyl)amino]-2-butanol] and butoxamine [alpha-[1-(t-butylamino)ethyl]-2,5-dimethoxybenzyl alcohol) hydrochloride], agents that selectively block the beta2-AR, produced significant parallel rightward shifts in the concentration-response curves for ISO. From these curves, apparent equilibrium dissociation constant (K(b)) values of 0.3 nM for ICI-118,551 and 355 nM for butoxamine were calculated using Schild regression analysis. Conversely, effective concentrations of the selective beta1-AR antagonists CGP 20712A [(+/-)-2-hydroxy-5-[2-([2-hydroxy-3-(4-[1-methyl-4-(trifluoromethyl)-1H-imidazol-2-yl]phenoxy)propyl]amino)ethoxy]-benzamide methanesulfonate] and atenolol [4-[2'-hydroxy-3'-(isopropyl-amino)propoxy]phenylacetamide] did not significantly affect the pyramidal cell response to ISO. However, at higher concentrations, atenolol significantly decreased the potency for ISO-mediated AP frequencies. From these curves, an apparent atenolol K(b) value of 3162 nM was calculated. This pharmacological profile for subtype-selective beta-AR antagonists

  13. Acupuncture attenuates cognitive deficits and increases pyramidal neuron number in hippocampal CA1 area of vascular dementia rats.

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    Li, Fang; Yan, Chao-Qun; Lin, Li-Ting; Li, Hui; Zeng, Xiang-Hong; Liu, Yi; Du, Si-Qi; Zhu, Wen; Liu, Cun-Zhi

    2015-04-28

    Decreased cognition is recognized as one of the most severe and consistent behavioral impairments in dementia. Experimental studies have reported that acupuncture may improve cognitive deficits, relieve vascular dementia (VD) symptoms, and increase cerebral perfusion and electrical activity. Multi-infarction dementia was modeled in rats with 3% microemboli saline suspension. Two weeks after acupuncture at Zusanli (ST36), all rats were subjected to a hidden platform trial to test their 3-day spatial memory using the Morris water maze test. To estimate the numbers of pyramidal neuron, astrocytes, and synaptic boutons in hippocampal CA1 area, we adopted an unbiased stereology method to accurately sample and measure the size of cells. We found that acupuncture at ST36 significantly decreased the escape latency of VD rats. In addition, acupuncture significantly increased the pyramidal neuron number in hippocampal CA1 area (P area in any of the groups (P > 0.05). These findings suggest that acupuncture may improve cognitive deficits and increase pyramidal neuron number of hippocampal CA1 area in VD rats.

  14. ERK1/2 Activation Is Necessary for BDNF to Increase Dendritic Spine Density in Hippocampal CA1 Pyramidal Neurons

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    Alonso, Mariana; Medina, Jorge H.; Pozzo-Miller, Lucas

    2004-01-01

    Brain-derived neurotrophic factor (BDNF) is a potent modulator of synaptic transmission and plasticity in the CNS, acting both pre- and postsynaptically. We demonstrated recently that BDNF/TrkB signaling increases dendritic spine density in hippocampal CA1 pyramidal neurons. Here, we tested whether activation of the prominent ERK (MAPK) signaling…

  15. Removal of area CA3 from hippocampal slices induces postsynaptic plasticity at Schaffer collateral synapses that normalizes CA1 pyramidal cell discharge.

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    Dumas, Theodore C; Uttaro, Michael R; Barriga, Carolina; Brinkley, Tiffany; Halavi, Maryam; Wright, Susan N; Ferrante, Michele; Evans, Rebekah C; Hawes, Sarah L; Sanders, Erin M

    2018-05-05

    Neural networks that undergo acute insults display remarkable reorganization. This injury related plasticity is thought to permit recovery of function in the face of damage that cannot be reversed. Previously, an increase in the transmission strength at Schaffer collateral to CA1 pyramidal cell synapses was observed after long-term activity reduction in organotypic hippocampal slices. Here we report that, following acute preparation of adult rat hippocampal slices and surgical removal of area CA3, input to area CA1 was reduced and Schaffer collateral synapses underwent functional strengthening. This increase in synaptic strength was limited to Schaffer collateral inputs (no alteration to temporoammonic synapses) and acted to normalize postsynaptic discharge, supporting a homeostatic or compensatory response. Short-term plasticity was not altered, but an increase in immunohistochemical labeling of GluA1 subunits was observed in the stratum radiatum (but not stratum moleculare), suggesting increased numbers of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors and a postsynaptic locus of expression. Combined, these data support the idea that, in response to the reduction in presynaptic activity caused by removal of area CA3, Schaffer collateral synapses undergo a relatively rapid increase in functional efficacy likely supported by insertion of more AMPARs, which maintains postsynaptic excitability in CA1 pyramidal neurons. This novel fast compensatory plasticity exhibits properties that would allow it to maintain optimal network activity levels in the hippocampus, a brain structure lauded for its ongoing experience-dependent malleability. Copyright © 2018 Elsevier B.V. All rights reserved.

  16. Mechanism underlying unaltered cortical inhibitory synaptic transmission in contrast with enhanced excitatory transmission in CaV2.1 knockin migraine mice

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    Vecchia, Dania; Tottene, Angelita; van den Maagdenberg, Arn M.J.M.; Pietrobon, Daniela

    2014-01-01

    Familial hemiplegic migraine type 1 (FHM1), a monogenic subtype of migraine with aura, is caused by gain-of-function mutations in CaV2.1 (P/Q-type) calcium channels. In FHM1 knockin mice, excitatory neurotransmission at cortical pyramidal cell synapses is enhanced, but inhibitory neurotransmission at connected pairs of fast-spiking (FS) interneurons and pyramidal cells is unaltered, despite being initiated by CaV2.1 channels. The mechanism underlying the unaltered GABA release at cortical FS interneuron synapses remains unknown. Here, we show that the FHM1 R192Q mutation does not affect inhibitory transmission at autapses of cortical FS and other types of multipolar interneurons in microculture from R192Q knockin mice, and investigate the underlying mechanism. Lowering the extracellular [Ca2+] did not reveal gain-of-function of evoked transmission neither in control nor after prolongation of the action potential (AP) with tetraethylammonium, indicating unaltered AP-evoked presynaptic calcium influx at inhibitory autapses in FHM1 KI mice. Neither saturation of the presynaptic calcium sensor nor short duration of the AP can explain the unaltered inhibitory transmission in the mutant mice. Recordings of the P/Q-type calcium current in multipolar interneurons in microculture revealed that the current density and the gating properties of the CaV2.1 channels expressed in these interneurons are barely affected by the FHM1 mutation, in contrast with the enhanced current density and left-shifted activation gating of mutant CaV2.1 channels in cortical pyramidal cells. Our findings suggest that expression of specific CaV2.1 channels differentially sensitive to modulation by FHM1 mutations in inhibitory and excitatory cortical neurons underlies the gain-of-function of excitatory but unaltered inhibitory synaptic transmission and the likely consequent dysregulation of the cortical excitatory–inhibitory balance in FHM1. PMID:24907493

  17. Housing under the pyramid reduces susceptibility of hippocampal CA3 pyramidal neurons to prenatal stress in the developing rat offspring.

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    Murthy, Krishna Dilip; George, Mitchel Constance; Ramasamy, Perumal; Mustapha, Zainal Arifin

    2013-12-01

    Mother-offspring interaction begins before birth. The foetus is particularly vulnerable to environmental insults and stress. The body responds by releasing excess of the stress hormone cortisol, which acts on glucocorticoid receptors. Hippocampus in the brain is rich in glucocorticoid receptors and therefore susceptible to stress. The stress effects are reduced when the animals are placed under a model wooden pyramid. The present study was to first explore the effects of prenatal restraint-stress on the plasma corticosterone levels and the dendritic arborisation of CA3 pyramidal neurons in the hippocampus of the offspring. Further, to test whether the pyramid environment would alter these effects, as housing under a pyramid is known to reduce the stress effects, pregnant Sprague Dawley rats were restrained for 9 h per day from gestation day 7 until parturition in a wire-mesh restrainer. Plasma corticosterone levels were found to be significantly increased. In addition, there was a significant reduction in the apical and the basal total dendritic branching points and intersections of the CA3 hippocampal pyramidal neurons. The results thus suggest that, housing in the pyramid dramatically reduces prenatal stress effects in rats.

  18. Bursting response to current-evoked depolarization in rat CA1 pyramidal neurons is correlated with lucifer yellow dye coupling but not with the presence of calbindin-D28k

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    Baimbridge, K.G.; Peet, M.J.; McLennan, H.; Church, J.

    1991-01-01

    Calbindin-D28k (CaBP) immunohistochemistry has been combined with electrophysiological recording and Lucifer Yellow (LY) cell identification in the CA1 region of the rat hippocampal formation. CaBP is shown to be contained within a distinct sub-population of CA1 pyramidal cells which is equivalent to the superficial layer described by Lorente de No (1934). The neurogenesis of these CaBP-positive neurons occurs 1-2 days later than the CaBP-negative neurons in the deep pyramidal cell layer, as shown by 3H-thymidine autoradiography. No correlation could be found between the presence or absence of CaBP and the type of electrophysiological response to current-evoked depolarizing pulses. The latter could be separated into bursting or non-bursting types, and the bursting-type response was nearly always found to be associated with the presence of LY dye coupling. Furthermore, when dye coupling involved three neurons, a characteristic pattern was observed which may represent the coupling of phenotypically identical neurons into distinct functional units within the CA1 pyramidal cell layer. In this particular case the three neurons were all likely to be CaBP-positive

  19. CA1 Pyramidal Cell Theta-Burst Firing Triggers Endocannabinoid-Mediated Long-Term Depression at Both Somatic and Dendritic Inhibitory Synapses

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    Younts, Thomas J.; Chevaleyre, Vivien

    2013-01-01

    Endocannabinoids (eCBs) are retrograde lipid messengers that, by targeting presynaptic type 1 cannabinoid receptors (CB1Rs), mediate short- and long-term synaptic depression of neurotransmitter release throughout the brain. Short-term depression is typically triggered by postsynaptic, depolarization-induced calcium rises, whereas long-term depression is induced by synaptic activation of Gq/11 protein-coupled receptors. Here we report that a physiologically relevant pattern of postsynaptic activity, in the form of theta-burst firing (TBF) of hippocampal CA1 pyramidal neurons, can trigger long-term depression of inhibitory transmission (iLTD) in rat hippocampal slices. Paired recordings between CA1 interneurons and pyramidal cells, followed by post hoc morphological reconstructions of the interneurons' axon, revealed that somatic and dendritic inhibitory synaptic inputs equally expressed TBF-induced iLTD. Simultaneous recordings from neighboring pyramidal cells demonstrated that eCB signaling triggered by TBF was highly restricted to only a single, active cell. Furthermore, pairing submaximal endogenous activation of metabotropic glutamate or muscarinic acetylcholine receptors with submaximal TBF unmasked associative iLTD. Although CB1Rs are also expressed at Schaffer-collateral excitatory terminals, long-term plasticity under various recording conditions was spared at these synapses. Consistent with this observation, TBF also shifted the balance of excitation and inhibition in favor of excitatory throughput, thereby altering information flow through the CA1 circuit. Given the near ubiquity of burst-firing activity patterns and CB1R expression in the brain, the properties described here may be a general means by which neurons fine tune the strength of their inputs in a cell-wide and cell-specific manner. PMID:23966696

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

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    Fumiaki Fukushima

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

  1. Complementary theta resonance filtering by two spatially segregated mechanisms in CA1 hippocampal pyramidal neurons.

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    Hu, Hua; Vervaeke, Koen; Graham, Lyle J; Storm, Johan F

    2009-11-18

    Synaptic input to a neuron may undergo various filtering steps, both locally and during transmission to the soma. Using simultaneous whole-cell recordings from soma and apical dendrites from rat CA1 hippocampal pyramidal cells, and biophysically detailed modeling, we found two complementary resonance (bandpass) filters of subthreshold voltage signals. Both filters favor signals in the theta (3-12 Hz) frequency range, but have opposite location, direction, and voltage dependencies: (1) dendritic H-resonance, caused by h/HCN-channels, filters signals propagating from soma to dendrite when the membrane potential is close to rest; and (2) somatic M-resonance, caused by M/Kv7/KCNQ and persistent Na(+) (NaP) channels, filters signals propagating from dendrite to soma when the membrane potential approaches spike threshold. Hippocampal pyramidal cells participate in theta network oscillations during behavior, and we suggest that that these dual, polarized theta resonance mechanisms may convey voltage-dependent tuning of theta-mediated neural coding in the entorhinal/hippocampal system during locomotion, spatial navigation, memory, and sleep.

  2. Reproductive experience modified dendritic spines on cortical pyramidal neurons to enhance sensory perception and spatial learning in rats.

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    Chen, Jeng-Rung; Lim, Seh Hong; Chung, Sin-Cun; Lee, Yee-Fun; Wang, Yueh-Jan; Tseng, Guo-Fang; Wang, Tsyr-Jiuan

    2017-01-27

    Behavioral adaptations during motherhood are aimed at increasing reproductive success. Alterations of hormones during motherhood could trigger brain morphological changes to underlie behavioral alterations. Here we investigated whether motherhood changes a rat's sensory perception and spatial memory in conjunction with cortical neuronal structural changes. Female rats of different statuses, including virgin, pregnant, lactating, and primiparous rats were studied. Behavioral test showed that the lactating rats were most sensitive to heat, while rats with motherhood and reproduction experience outperformed virgin rats in a water maze task. By intracellular dye injection and computer-assisted 3-dimensional reconstruction, the dendritic arbors and spines of the layer III and V pyramidal neurons of the somatosensory cortex and CA1 hippocampal pyramidal neurons were revealed for closer analysis. The results showed that motherhood and reproductive experience increased dendritic spines but not arbors or the lengths of the layer III and V pyramidal neurons of the somatosensory cortex and CA1 hippocampal pyramidal neurons. In addition, lactating rats had a higher incidence of spines than pregnant or primiparous rats. The increase of dendritic spines was coupled with increased expression of the glutamatergic postsynaptic marker protein (PSD-95), especially in lactating rats. On the basis of the present results, it is concluded that motherhood enhanced rat sensory perception and spatial memory and was accompanied by increases in dendritic spines on output neurons of the somatosensory cortex and CA1 hippocampus. The effect was sustained for at least 6 weeks after the weaning of the pups.

  3. Synaptically evoked Ca2+ release from intracellular stores is not influenced by vesicular zinc in CA3 hippocampal pyramidal neurones.

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    Evstratova, Alesya; Tóth, Katalin

    2011-12-01

    The co-release of neuromodulatory substances in combination with classic neurotransmitters such as glutamate and GABA from individual presynaptic nerve terminals has the capacity to dramatically influence synaptic efficacy and plasticity. At hippocampal mossy fibre synapses vesicular zinc is suggested to serve as a cotransmitter capable of regulating calcium release from internal stores in postsynaptic CA3 pyramidal cells. Here we investigated this possibility using combined intracellular ratiometric calcium imaging and patch-clamp recording techniques. In acute hippocampal slices a brief train of mossy fibre stimulation produced a large, delayed postsynaptic Ca(2+) wave that was spatially restricted to the proximal apical dendrites of CA3 pyramidal cells within stratum lucidum. This calcium increase was sensitive to intracellularly applied heparin indicating reliance upon release from internal stores and was triggered by activation of both group I metabotropic glutamate and NMDA receptors. Importantly, treatment of slices with the membrane-impermeant zinc chelator CaEDTA did not influence the synaptically evoked postsynaptic Ca(2+) waves. Moreover, mossy fibre stimulus evoked postsynaptic Ca(2+) signals were not significantly different between wild-type and zinc transporter 3 (ZnT3) knock-out animals. Considered together our data do not support a role for vesicular zinc in regulating mossy fibre evoked Ca(2+) release from CA3 pyramidal cell internal stores.

  4. 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.

  5. Amyloid-beta induced CA1 pyramidal cell loss in young adult rats is alleviated by systemic treatment with FGL, a neural cell adhesion molecule-derived mimetic peptide.

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    Nicola J Corbett

    Full Text Available Increased levels of neurotoxic amyloid-beta in the brain are a prominent feature of Alzheimer's disease. FG-Loop (FGL, a neural cell adhesion molecule-derived peptide that corresponds to its second fibronectin type III module, has been shown to provide neuroprotection against a range of cellular insults. In the present study impairments in social recognition memory were seen 24 days after a 5 mg/15 µl amyloid-beta(25-35 injection into the right lateral ventricle of the young adult rat brain. This impairment was prevented if the animal was given a systemic treatment of FGL. Unbiased stereology was used to investigate the ability of FGL to alleviate the deleterious effects on CA1 pyramidal cells of the amyloid-beta(25-35 injection. NeuN, a neuronal marker (for nuclear staining was used to identify pyramidal cells, and immunocytochemistry was also used to identify inactive glycogen synthase kinase 3beta (GSK3β and to determine the effects of amyloid-beta(25-35 and FGL on the activation state of GSK3β, since active GSK3β has been shown to cause a range of AD pathologies. The cognitive deficits were not due to hippocampal atrophy as volume estimations of the entire hippocampus and its regions showed no significant loss, but amyloid-beta caused a 40% loss of pyramidal cells in the dorsal CA1 which was alleviated partially by FGL. However, FGL treatment without amyloid-beta was also found to cause a 40% decrease in CA1 pyramidal cells. The action of FGL may be due to inactivation of GSK3β, as an increased proportion of CA1 pyramidal neurons contained inactive GSK3β after FGL treatment. These data suggest that FGL, although potentially disruptive in non-pathological conditions, can be neuroprotective in disease-like conditions.

  6. Biphasic somatic A-type K channel downregulation mediates intrinsic plasticity in hippocampal CA1 pyramidal neurons.

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    Sung-Cherl Jung

    2009-08-01

    Full Text Available Since its original description, the induction of synaptic long-term potentiation (LTP has been known to be accompanied by a lasting increase in the intrinsic excitability (intrinsic plasticity of hippocampal neurons. Recent evidence shows that dendritic excitability can be enhanced by an activity-dependent decrease in the activity of A-type K(+ channels. In the present manuscript, we examined the role of A-type K(+ channels in regulating intrinsic excitability of CA1 pyramidal neurons of the hippocampus after synapse-specific LTP induction. In electrophysiological recordings we found that LTP induced a potentiation of excitability which was accompanied by a two-phased change in A-type K(+ channel activity recorded in nucleated patches from organotypic slices of rat hippocampus. Induction of LTP resulted in an immediate but short lasting hyperpolarization of the voltage-dependence of steady-state A-type K(+ channel inactivation along with a progressive, long-lasting decrease in peak A-current density. Blocking clathrin-mediated endocytosis prevented the A-current decrease and most measures of intrinsic plasticity. These results suggest that two temporally distinct but overlapping mechanisms of A-channel downregulation together contribute to the plasticity of intrinsic excitability. Finally we show that intrinsic plasticity resulted in a global enhancement of EPSP-spike coupling.

  7. Sustained increase of spontaneous input and spike transfer in the CA3-CA1 pathway following long term potentiation in vivo

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    Oscar eHerreras

    2012-10-01

    Full Text Available Long term potentiation (LTP is commonly used to study synaptic plasticity but the associated changes in the spontaneous activity of individual neurons or the computational properties of neural networks in vivo remain largely unclear. The multisynaptic origin of spontaneous spikes makes difficult estimating the impact of a particular potentiated input. Accordingly, we adopted an approach that isolates pathway-specific postsynaptic activity from raw local field potentials (LFPs in the rat hippocampus in order to study the effects of LTP on ongoing spike transfer between cell pairs in the CA3-CA1 pathway. CA1 Schaffer-specific LFPs elicited by spontaneous clustered firing of CA3 pyramidal cells involved a regular succession of elementary micro-field-EPSPs (gamma-frequency that fired spikes in CA1 units. LTP increased the amplitude but not the frequency of these ongoing excitatory quanta. Also, the proportion of Schaffer-driven spikes in both CA1 pyramidal cells and interneurons increased in a cell-specific manner only in previously connected CA3-CA1 cell pairs, i.e., when the CA3 pyramidal cell had shown pre-LTP significant correlation with firing of a CA1 unit and potentiated spike-triggered average of Schaffer LFPs following LTP. Moreover, LTP produced subtle reorganization of presynaptic CA3 cell assemblies. These findings show effective enhancement of pathway specific ongoing activity which leads to increased spike transfer in potentiated segments of a network. These indicate that plastic phenomena induced by external protocols may intensify spontaneous information flow across specific channels as proposed in transsynaptic propagation of plasticity and synfire chain hypotheses that may be the substrate for different types of memory involving multiple brain structures.

  8. Enhancement of synchronized activity between hippocampal CA1 neurons during initial storage of associative fear memory.

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    Liu, Yu-Zhang; Wang, Yao; Shen, Weida; Wang, Zhiru

    2017-08-01

    Learning and memory storage requires neuronal plasticity induced in the hippocampus and other related brain areas, and this process is thought to rely on synchronized activity in neural networks. We used paired whole-cell recording in vivo to examine the synchronized activity that was induced in hippocampal CA1 neurons by associative fear learning. We found that both membrane potential synchronization and spike synchronization of CA1 neurons could be transiently enhanced after task learning, as observed on day 1 but not day 5. On day 1 after learning, CA1 neurons showed a decrease in firing threshold and rise times of suprathreshold membrane potential changes as well as an increase in spontaneous firing rates, possibly contributing to the enhancement of spike synchronization. The transient enhancement of CA1 neuronal synchronization may play important roles in the induction of neuronal plasticity for initial storage and consolidation of associative memory. The hippocampus is critical for memory acquisition and consolidation. This function requires activity- and experience-induced neuronal plasticity. It is known that neuronal plasticity is largely dependent on synchronized activity. As has been well characterized, repetitive correlated activity of presynaptic and postsynaptic neurons can lead to long-term modifications at their synapses. Studies on network activity have also suggested that memory processing in the hippocampus may involve learning-induced changes of neuronal synchronization, as observed in vivo between hippocampal CA3 and CA1 networks as well as between the rhinal cortex and the hippocampus. However, further investigation of learning-induced synchronized activity in the hippocampus is needed for a full understanding of hippocampal memory processing. In this study, by performing paired whole-cell recording in vivo on CA1 pyramidal cells (PCs) in anaesthetized adult rats, we examined CA1 neuronal synchronization before and after associative fear

  9. Enhanced sensitivity to ethanol-induced inhibition of LTP in CA1 pyramidal neurons of socially isolated C57BL/6J mice: role of neurosteroids

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    Giuseppe eTalani

    2011-10-01

    Full Text Available Ethanol (EtOH–induced impairment of long-term potentiation (LTP in the rat hippocampus is prevented by the 5α-reductase inhibitor finasteride, suggesting that this effect of EtOH is dependent on the increased local release of neurosteroids such as 3α,5α-THP that promote GABA–mediated transmission. Given that social isolation (SI in rodents is associated with altered plasma and brain levels of such neurosteroids as well as with an enhanced neurosteroidogenic action of EtOH, we examined whether the inhibitory effect of EtOH on LTP at CA3-CA1 hippocampal excitatory synapses is altered in C57BL/6J mice subjected to SI for 6 weeks in comparison with group-housed (GH animals. Extracellular recording of fEPSPs as well as patch-clamp analysis were performed in hippocampal slices prepared from both SI and GH mice. Consistent with previous observations, recording of fEPSPs revealed that the extent of LTP induced in the CA1 region of SI mice was significantly reduced compared with that in GH animals. EtOH (40 mM inhibited LTP in slices from SI mice but not in those from GH mice, and this effect of EtOH was abolished by co-application of 1 µM finasteride. Current-clamp analysis of CA1 pyramidal neurons revealed a decrease in action potential frequency and an increase in the intensity of injected current required to evoke the first action potential in SI mice compared with GH mice, indicative of a decrease in neuronal excitability associated with SI. Together, our data suggest that SI results in reduced levels of neuronal excitability and synaptic plasticity in the hippocampus. Furthermore, the increased sensitivity to the neurosteroidogenic effect of EtOH associated with SI likely accounts for the greater inhibitory effect of EtOH on LTP in SI mice. The increase in EtOH sensitivity induced by SI may be important for the changes in the effects of EtOH on anxiety and on learning and memory associated with the prolonged stress attributable to social

  10. Somal and dendritic development of human CA3 pyramidal neurons from midgestation to middle childhood: a quantitative Golgi study.

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    Lu, Dahua; He, Lixin; Xiang, Wei; Ai, Wei-Min; Cao, Ye; Wang, Xiao-Sheng; Pan, Aihua; Luo, Xue-Gang; Li, Zhiyuan; Yan, Xiao-Xin

    2013-01-01

    The CA3 area serves a key relay on the tri-synaptic loop of the hippocampal formation which supports multiple forms of mnemonic processing, especially spatial learning and memory. To date, morphometric data about human CA3 pyramidal neurons are relatively rare, with little information available for their pre- and postnatal development. Herein, we report a set of developmental trajectory data, including somal growth, dendritic elongation and branching, and spine formation, of human CA3 pyramidal neurons from midgestation stage to middle childhood. Golgi-impregnated CA3 pyramidal neurons in fetuses at 19, 20, 26, 35, and 38 weeks of gestation (GW) and a child at 8 years of age (Y) were analyzed by Neurolucida morphometry. Somal size of the impregnated CA3 cells increased age-dependently among the cases. The length of the apical and basal dendrites of these neurons increased between 26 GW to 38 GW, and appeared to remain stable afterward until 8 Y. Dendritic branching points increased from 26 GW to 38 GW, with that on the apical dendrites slightly reduced at 8 Y. Spine density on the apical and basal dendrites increased progressively from 26 GW to 8 Y. These data suggest that somal growth and dendritic arborization of human CA3 pyramidal neurons occur largely during the second to third trimester. Spine development and likely synaptogenesis on CA3 pyramidal cells progress during the third prenatal trimester and may continue throughout childhood. Copyright © 2012 Wiley Periodicals, Inc.

  11. Detection of zinc translocation into apical dendrite of CA1 pyramidal neuron after electrical stimulation.

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    Suh, Sang Won

    2009-02-15

    Translocation of the endogenous cation zinc from presynaptic terminals to postsynaptic neurons after brain insult has been implicated as a potential neurotoxic event. Several studies have previously demonstrated that a brief electrical stimulation is sufficient to induce the translocation of zinc from presynaptic vesicles into the cytoplasm (soma) of postsynaptic neurons. In the present work I have extended those findings in three ways: (i) providing evidence that zinc translocation occurs into apical dendrites, (ii) presenting data that there is an apparent translocation into apical dendrites when only a zinc-containing synaptic input is stimulated, and (iii) presenting data that there is no zinc translocation into apical dendrite of ZnT3 KO mice following electrical stimulation. Hippocampal slices were preloaded with the "trappable" zinc fluorescent probe, Newport Green. After washout, a single apical dendrite in the stratum radiatum of hippocampal CA1 area was selected and focused on. Burst stimulation (100Hz, 500microA, 0.2ms, monopolar) was delivered to either the adjacent Schaffer-collateral inputs (zinc-containing) or to the adjacent temporo-ammonic inputs (zinc-free) to the CA1 dendrites. Stimulation of the Schaffer collaterals increased the dendritic fluorescence, which was blocked by TTX, low-Ca medium, or the extracellular zinc chelator, CaEDTA. Stimulation of the temporo-ammonic pathway caused no significant rise in the fluorescence. Genetic depletion of vesicular zinc by ZnT3 KO showed no stimulation-induced apical dendrite zinc rise. The present study provides evidence that synaptically released zinc translocates into postsynaptic neurons through the apical dendrites of CA1 pyramidal neurons during physiological synaptic activity.

  12. Local Optogenetic Induction of Fast (20-40 Hz Pyramidal-Interneuron Network Oscillations in the In Vitro and In Vivo CA1 Hippocampus: Modulation by CRF and Enforcement of Perirhinal Theta Activity

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    Julien eDine

    2016-04-01

    Full Text Available The neurophysiological processes that can cause theta-to-gamma frequency range (4-80 Hz network oscillations in the rhinal cortical-hippocampal system and the potential connectivity-based interactions of such forebrain rhythms are a topic of intensive investigation. Here, using selective Channelrhodopsin-2 (ChR2 expression in mouse forebrain glutamatergic cells, we were able to locally, temporally precisely, and reliably induce fast (20-40 Hz field potential oscillations in hippocampal area CA1 in vitro (at 25°C and in vivo (i.e., slightly anaesthetized NEX-Cre-ChR2 mice. As revealed by pharmacological analyses and patch-clamp recordings from pyramidal cells and GABAergic interneurons in vitro, these light-triggered oscillations can exclusively arise from sustained suprathreshold depolarization (~200 ms or longer and feedback inhibition of CA1 pyramidal neurons, as being mandatory for prototypic pyramidal-interneuron network (P-I oscillations. Consistently, the oscillations comprised rhythmically occurring population spikes (generated by pyramidal cells and their frequency increased with increasing spectral power. We further demonstrate that the optogenetically driven CA1 oscillations, which remain stable over repeated evocations, are impaired by the stress hormone corticotropin-releasing factor (CRF, 125 nM in vitro and, even more remarkably, found that they are accompanied by concurrent states of enforced theta activity in the memory-associated perirhinal cortex (PrC in vivo. The latter phenomenon most likely derives from neurotransmission via a known, but poorly studied excitatory CA1PrC pathway. Collectively, our data provide evidence for the existence of a prototypic (CRF-sensitive P-I gamma rhythm generator in area CA1 and suggest that CA1 P-I oscillations can rapidly up-regulate theta activity strength in hippocampus-innervated rhinal networks, at least in the PrC.

  13. Local Optogenetic Induction of Fast (20-40 Hz) Pyramidal-Interneuron Network Oscillations in the In Vitro and In Vivo CA1 Hippocampus: Modulation by CRF and Enforcement of Perirhinal Theta Activity.

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    Dine, Julien; Genewsky, Andreas; Hladky, Florian; Wotjak, Carsten T; Deussing, Jan M; Zieglgänsberger, Walter; Chen, Alon; Eder, Matthias

    2016-01-01

    The neurophysiological processes that can cause theta-to-gamma frequency range (4-80 Hz) network oscillations in the rhinal cortical-hippocampal system and the potential connectivity-based interactions of such forebrain rhythms are a topic of intensive investigation. Here, using selective Channelrhodopsin-2 (ChR2) expression in mouse forebrain glutamatergic cells, we were able to locally, temporally precisely, and reliably induce fast (20-40 Hz) field potential oscillations in hippocampal area CA1 in vitro (at 25°C) and in vivo (i.e., slightly anesthetized NEX-Cre-ChR2 mice). As revealed by pharmacological analyses and patch-clamp recordings from pyramidal cells and GABAergic interneurons in vitro, these light-triggered oscillations can exclusively arise from sustained suprathreshold depolarization (~200 ms or longer) and feedback inhibition of CA1 pyramidal neurons, as being mandatory for prototypic pyramidal-interneuron network (P-I) oscillations. Consistently, the oscillations comprised rhythmically occurring population spikes (generated by pyramidal cells) and their frequency increased with increasing spectral power. We further demonstrate that the optogenetically driven CA1 oscillations, which remain stable over repeated evocations, are impaired by the stress hormone corticotropin-releasing factor (CRF, 125 nM) in vitro and, even more remarkably, found that they are accompanied by concurrent states of enforced theta activity in the memory-associated perirhinal cortex (PrC) in vivo. The latter phenomenon most likely derives from neurotransmission via a known, but poorly studied excitatory CA1→PrC pathway. Collectively, our data provide evidence for the existence of a prototypic (CRF-sensitive) P-I gamma rhythm generator in area CA1 and suggest that CA1 P-I oscillations can rapidly up-regulate theta activity strength in hippocampus-innervated rhinal networks, at least in the PrC.

  14. The effect of propofol on CA1 pyramidal cell excitability and GABAA-mediated inhibition in the rat hippocampal slice.

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    Albertson, T E; Walby, W F; Stark, L G; Joy, R M

    1996-05-24

    An in vitro paired-pulse orthodromic stimulation technique was used to examine the effects of propofol on excitatory afferent terminals, CA1 pyramidal cells and recurrent collateral evoked inhibition in the rat hippocampal slice. Hippocampal slices 400 microns thick were perfused with oxygenated artificial cerebrospinal fluid, and electrodes were placed in the CA1 region to record extracellular field population spike (PS) or excitatory postsynaptic potential (EPSP) responses to stimulation of Schaffer collateral/commissural fibers. Gamma-aminobutyric acid (GABA)-mediated recurrent inhibition was measured using a paired-pulse technique. The major effect of propofol (7-28 microM) was a dose and time dependent increase in the intensity and duration of GABA-mediated inhibition. This propofol effect could be rapidly and completely reversed by exposure to known GABAA antagonists, including picrotoxin, bicuculline and pentylenetetrazol. It was also reversed by the chloride channel antagonist, 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS). It was not antagonized by central (flumazenil) or peripheral (PK11195) benzodiazepine antagonists. Reversal of endogenous inhibition was also noted with the antagonists picrotoxin and pentylenetetrazol. Input/output curves constructed using stimulus propofol caused only a small enhancement of EPSPs at higher stimulus intensities but had no effect on PS amplitudes. These studies are consistent with propofol having a GABAA-chloride channel mechanism causing its effect on recurrent collateral evoked inhibition in the rat hippocampal slice.

  15. Activation of CRH receptor type 1 expressed on glutamatergic neurons increases excitability of CA1 pyramidal neurons by the modulation of voltage-gated ion channels

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    Stephan eKratzer

    2013-07-01

    Full Text Available Corticotropin-releasing hormone (CRH plays an important role in a substantial number of patients with stress-related mental disorders, such as anxiety disorders and depression. CRH has been shown to increase neuronal excitability in the hippocampus, but the underlying mechanisms are poorly understood. The effects of CRH on neuronal excitability were investigated in acute hippocampal brain slices. Population spikes (PS and field excitatory postsynaptic potentials (fEPSP were evoked by stimulating Schaffer-collaterals and recorded simultaneously from the somatic and dendritic region of CA1 pyramidal neurons. CRH was found to increase PS amplitudes (mean  Standard error of the mean; 231.8  31.2% of control; n=10 while neither affecting fEPSPs (104.3 ± 4.2%; n=10 nor long-term potentiation (LTP. However, when Schaffer-collaterals were excited via action potentials (APs generated by stimulation of CA3 pyramidal neurons, CRH increased fEPSP amplitudes (119.8 ± 3.6%; n=8 and the magnitude of LTP in the CA1 region. Experiments in slices from transgenic mice revealed that the effect on PS amplitude is mediated exclusively by CRH receptor 1 (CRHR1 expressed on glutamatergic neurons. The effects of CRH on PS were dependent on phosphatase-2B, L- and T-type calcium channels and voltage-gated potassium channels but independent on intracellular Ca2+-elevation. In patch-clamp experiments, CRH increased the frequency and decay times of APs and decreased currents through A-type and delayed-rectifier potassium channels. These results suggest that CRH does not affect synaptic transmission per se, but modulates voltage-gated ion currents important for the generation of APs and hence elevates by this route overall neuronal activity.

  16. Ischemic damage in hippocampal CA1 is dependent on glutamate release and intact innervation from CA3

    DEFF Research Database (Denmark)

    Benveniste, H; Jørgensen, M B; Sandberg, M

    1989-01-01

    The removal of glutamatergic afferents to CA1 by destruction of the CA3 region is known to protect CA1 pyramidal cells against 10 min of transient global ischemia. To investigate further the pathogenetic significance of glutamate, we measured the release of glutamate in intact and CA3-lesioned CA...

  17. Long term potentiation, but not depression, in interlamellar hippocampus CA1.

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    Sun, Duk-Gyu; Kang, Hyeri; Tetteh, Hannah; Su, Junfeng; Lee, Jihwan; Park, Sung-Won; He, Jufang; Jo, Jihoon; Yang, Sungchil; Yang, Sunggu

    2018-03-26

    Synaptic plasticity in the lamellar CA3 to CA1 circuitry has been extensively studied while interlamellar CA1 to CA1 connections have not yet received much attention. One of our earlier studies demonstrated that axons of CA1 pyramidal neurons project to neighboring CA1 neurons, implicating information transfer along a longitudinal interlamellar network. Still, it remains unclear whether long-term synaptic plasticity is present within this longitudinal CA1 network. Here, we investigate long-term synaptic plasticity between CA1 pyramidal cells, using in vitro and in vivo extracellular recordings and 3D holography glutamate uncaging. We found that the CA1-CA1 network exhibits NMDA receptor-dependent long-term potentiation (LTP) without direction or layer selectivity. By contrast, we find no significant long-term depression (LTD) under various LTD induction protocols. These results implicate unique synaptic properties in the longitudinal projection suggesting that the interlamellar CA1 network could be a promising structure for hippocampus-related information processing and brain diseases.

  18. Intrinsic excitability changes induced by acute treatment of hippocampal CA1 pyramidal neurons with exogenous amyloid β peptide

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    Scullion, Sarah; Brown, Jon T.; Randall, Andrew D.

    2015-01-01

    ABSTRACT Accumulation of beta‐amyloid (Aβ) peptides in the human brain is a canonical pathological hallmark of Alzheimer's disease (AD). Recent work in Aβ‐overexpressing transgenic mice indicates that increased brain Aβ levels can be associated with aberrant epileptiform activity. In line with this, such mice can also exhibit altered intrinsic excitability (IE) of cortical and hippocampal neurons: these observations may relate to the increased prevalence of seizures in AD patients. In this study, we examined what changes in IE are produced in hippocampal CA1 pyramidal cells after 2–5 h treatment with an oligomeric preparation of synthetic human Aβ 1–42 peptide. Whole cell current clamp recordings were compared between Aβ‐(500 nM) and vehicle‐(DMSO 0.05%) treated hippocampal slices obtained from mice. The soluble Aβ treatment did not produce alterations in sub‐threshold intrinsic properties, including membrane potential, input resistance, and hyperpolarization activated “sag”. Similarly, no changes were noted in the firing profile evoked by 500 ms square current supra‐threshold stimuli. However, Aβ 500 nM treatment resulted in the hyperpolarization of the action potential (AP) threshold. In addition, treatment with Aβ at 500 nM depressed the after‐hyperpolarization that followed both a single AP or 50 Hz trains of a number of APs between 5 and 25. These data suggest that acute exposure to soluble Aβ oligomers affects IE properties of CA1 pyramidal neurons differently from outcomes seen in transgenic models of amyloidopathy. However, in both chronic and acute models, the IE changes are toward hyperexcitability, reinforcing the idea that amyloidopathy and increased incidence in seizures might be causally related in AD patients. © 2014 The Authors Hippocampus Published by Wiley Periodicals, Inc. PMID:25515596

  19. Spontaneous release from mossy fiber terminals inhibits Ni2+-sensitive T-type Ca2+ channels of CA3 pyramidal neurons in the rat organotypic hippocampal slice.

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    Reid, Christopher A; Xu, Shenghong; Williams, David A

    2008-01-01

    Mossy fibers (axons arising from dentate granule cells) form large synaptic contacts exclusively onto the proximal apical dendrites of CA3 pyramidal neurons. They can generate large synaptic currents that occur in close proximity to the soma. These properties mean that active conductance in the proximal apical dendrite could have a disproportionate influence on CA3 pyramidal neuron excitability. Ni(2+)-sensitive T-type Ca(2+) channels are important modulators of dendritic excitability. Here, we use an optical approach to determine the contribution of Ni(2+) (100 microM)-sensitive Ca(2+) channels to action potential (AP) elicited Ca(2+) flux in the soma, proximal apical and distal apical dendrites. At resting membrane potentials Ni(2+)-sensitive Ca(2+) channels do not contribute to the Ca(2+) signal in the proximal apical dendrite, but do contribute in the other cell regions. Spontaneous release from mossy fiber terminals acting on 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX)-sensitive postsynaptic channels underlies a tonic inhibition of Ni(2+)-sensitive channels. Chelating Zn(2+) with CaEDTA blocks CNQX-sensitive changes in Ca(2+) flux implicating a mechanistic role of this ion in T-type Ca(2+) channel block. To test if this inhibition influenced excitability, progressively larger depolarizing pulses were delivered to CA3 pyramidal neurons. CNQX significantly reduced the size of the depolarizing step required to generate APs and increased the absolute number of APs per depolarizing step. This change in AP firing was completely reversed by the addition of Ni(2+). This mechanism may reduce the impact of T-type Ca(2+) channels in a region where large synaptic events are common.

  20. Distinguishing linear vs. nonlinear integration in CA1 radial oblique dendrites: it’s about time

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    José Francisco eGómez González

    2011-11-01

    Full Text Available It was recently shown that multiple excitatory inputs to CA1 pyramidal neuron dendrites must be activated nearly simultaneously to generate local dendritic spikes and superlinear responses at the soma; even slight input desynchronization prevented local spike initiation (Gasparini, 2006;Losonczy, 2006. This led to the conjecture that CA1 pyramidal neurons may only express their nonlinear integrative capabilities during the highly synchronized sharp waves and ripples that occur during slow wave sleep and resting/consummatory behavior, whereas during active exploration and REM sleep (theta rhythm, inadequate synchronization of excitation would lead CA1 pyramidal cells to function as essentially linear devices. Using a detailed single neuron model, we replicated the experimentally observed synchronization effect for brief inputs mimicking single synaptic release events. When synapses were driven instead by double pulses, more representative of the bursty inputs that occur in vivo, we found that the tolerance for input desynchronization was increased by more than an order of magnitude. The effect depended mainly on paired pulse facilitation of NMDA receptor-mediated responses at Schaffer collateral synapses. Our results suggest that CA1 pyramidal cells could function as nonlinear integrative units in all major hippocampal states.

  1. THE KINETICS OF MULTIBRANCH INTEGRATION ON THE DENDRITIC ARBOR OF CA1 PYRAMIDAL NEURONS

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    Sunggu eYang

    2014-05-01

    Full Text Available The process by which synaptic inputs separated in time and space are integrated by the dendritic arbor to produce a sequence of action potentials is among the most fundamental signal transformations that takes place within the central nervous system. Some aspects of this complex process, such as integration at the level of individual dendritic branches, have been extensively studied. But other aspects, such as how inputs from multiple branches are combined, and the kinetics of that integration have not been systematically examined. Using a 3D digital holographic photolysis technique to overcome the challenges posed by the complexities of the 3D anatomy of the dendritic arbor of CA1 pyramidal neurons for conventional photolysis, we show that integration on a single dendrite is fundamentally different from that on multiple dendrites. Multibranch integration occurring at oblique and basal dendrites allows somatic action potential firing of the cell to faithfully follow the driving stimuli over a significantly wider frequency range than what is possible with single branch integration. However, multibranch integration requires greater input strength to drive the somatic action potentials. This tradeoff between sensitivity and kinetics may explain the puzzling report of the predominance of multibranch, rather than single branch, integration from in vivo recordings during presentation of visual stimuli.

  2. Epitaxial growth of lithium fluoride on the (1 1 1) surface of CaF 2

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    Klumpp, St; Dabringhaus, H.

    1999-08-01

    Growth of lithium fluoride by molecular beam epitaxy on the (1 1 1) surface of calcium fluoride crystals was studied by TEM and LEED for crystal temperatures from 400 to 773 K and impinging lithium fluoride fluxes from 3×10 11 to 3×10 14 cm -2 s -1. Growth starts, usually, at the steps on the (1 1 1) surface of CaF 2. For larger step distances and at later growth stages also growth on the terraces between the steps is found. Preferably, longish, roof-like crystallites are formed, which can be interpreted by growth of LiF(2 0 1¯)[0 1 0] parallel to CaF 2(1 1 1)[ 1¯ 0 1]. To a lesser extent square crystallites, i.e. growth with LiF(0 0 1), and, rarely, three-folded pyramidal crystallites, i.e. growth with LiF(1 1 1) parallel to CaF 2(1 1 1), are observed. While the pyramidal crystallites show strict epitaxial orientation with LiF[ 1¯ 0 1]‖CaF 2[ 1¯ 0 1] and LiF[ 1¯ 0 1]‖CaF 2[11], only about 80% of the square crystallites exhibit an epitaxial alignment, where LiF[1 0 0]‖CaF 2[ 1¯ 0 1] is preferred to LiF[1 1 0]‖CaF 2[ 1¯ 0 1]. The epitaxial relationships are discussed on the basis of theoretically calculated adsorption positions of the lithium fluoride monomer and dimer on the terrace and at the steps of the CaF 2(1 1 1) surface.

  3. Estradiol pretreatment ameliorates impaired synaptic plasticity at synapses of insulted CA1 neurons after transient global ischemia

    Science.gov (United States)

    Takeuchi, Koichi; Yang, Yupeng; Takayasu, Yukihiro; Gertner, Michael; Hwang, Jee-Yeon; Aromolaran, Kelly; Bennett, Michael V.L.; Zukin, R. Suzanne

    2015-01-01

    Global ischemia in humans or induced experimentally in animals causes selective and delayed neuronal death in pyramidal neurons of the hippocampal CA1. The ovarian hormone estradiol administered before or immediately after insult affords histological protection in experimental models of focal and global ischemia and ameliorates the cognitive deficits associated with ischemic cell death. However, the impact of estradiol on the functional integrity of Schaffer collateral to CA1 (Sch-CA1) pyramidal cell synapses following global ischemia is not clear. Here we show that long term estradiol treatment initiated 14 days prior to global ischemia in ovariectomized female rats acts via the IGF-1 receptor to protect the functional integrity of CA1 neurons. Global ischemia impairs basal synaptic transmission, assessed by the input/output relation at Sch-CA1 synapses, and NMDA receptor (NMDAR)-dependent long term potentiation (LTP), assessed at 3 days after surgery. Presynaptic function, assessed by fiber volley and paired pulse facilitation, is unchanged. To our knowledge, our results are the first to demonstrate that estradiol at near physiological concentrations enhances basal excitatory synaptic transmission and ameliorates deficits in LTP at synapses onto CA1 neurons in a clinically-relevant model of global ischemia. Estradiol-induced rescue of LTP requires the IGF-1 receptor, but not the classical estrogen receptors (ER)-α or β. These findings support a model whereby estradiol acts via the IGF-1 receptor to maintain the functional integrity of hippocampal CA1 synapses in the face of global ischemia. PMID:25463028

  4. Computational modeling reveals dendritic origins of GABA(A-mediated excitation in CA1 pyramidal neurons.

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    Naomi Lewin

    Full Text Available GABA is the key inhibitory neurotransmitter in the adult central nervous system, but in some circumstances can lead to a paradoxical excitation that has been causally implicated in diverse pathologies from endocrine stress responses to diseases of excitability including neuropathic pain and temporal lobe epilepsy. We undertook a computational modeling approach to determine plausible ionic mechanisms of GABA(A-dependent excitation in isolated post-synaptic CA1 hippocampal neurons because it may constitute a trigger for pathological synchronous epileptiform discharge. In particular, the interplay intracellular chloride accumulation via the GABA(A receptor and extracellular potassium accumulation via the K/Cl co-transporter KCC2 in promoting GABA(A-mediated excitation is complex. Experimentally it is difficult to determine the ionic mechanisms of depolarizing current since potassium transients are challenging to isolate pharmacologically and much GABA signaling occurs in small, difficult to measure, dendritic compartments. To address this problem and determine plausible ionic mechanisms of GABA(A-mediated excitation, we built a detailed biophysically realistic model of the CA1 pyramidal neuron that includes processes critical for ion homeostasis. Our results suggest that in dendritic compartments, but not in the somatic compartments, chloride buildup is sufficient to cause dramatic depolarization of the GABA(A reversal potential and dominating bicarbonate currents that provide a substantial current source to drive whole-cell depolarization. The model simulations predict that extracellular K(+ transients can augment GABA(A-mediated excitation, but not cause it. Our model also suggests the potential for GABA(A-mediated excitation to promote network synchrony depending on interneuron synapse location - excitatory positive-feedback can occur when interneurons synapse onto distal dendritic compartments, while interneurons projecting to the perisomatic

  5. Use of Colchicine in Cortical Area 1 of the Hippocampus Impairs Transmission of Non-Motivational Information by the Pyramidal Cells

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    Nosaibeh Riahi Zaniani

    2013-11-01

    Full Text Available Colchicine, a potent neurotoxin derived from plants, has been recently introduced as a degenerative toxin of small pyramidal cells in the cortical area 1 of the hippocampus (CA1. In this study, the effect of the alkaloid in CA1 on the behaviors in the conditioning task was measured. Injections of colchicine (1,5 μg/rat, intra-CA1 was performed in the male Wistar rats, while the animals were settled and cannulated in a stereotaxic apparatus. In the control group solely injection of saline (1 μl/rat, intra-CA1 was used. One week later, all the animals passed the saline conditioning task using a three-day schedule of an unbiased paradigm. They were administered saline (1 ml/kg, s.c. twice a day throughout the conditioning phase. To evaluate the possible effects of cell injury by the toxin on the pyramidal cells, both the motivational signals while in the conditioning box and the non-motivational locomotive signs of the treated and control rats were measured. Based on the present study the alkaloid caused no change in the score of place conditioning, but affected both the sniffing and grooming behaviors in the group that received colchicine. However, the alkaloid did not show the significant effect on the rearing or compartment entering in the rats. According to the findings, the intra-CA1 injection of colchicine may impair the neuronal transmission of non-motivational information by the pyramidal cells in the dorsal hippocampus.

  6. Disinhibition mediates a form of hippocampal long-term potentiation in area CA1.

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    Jake Ormond

    Full Text Available The hippocampus plays a central role in memory formation in the mammalian brain. Its ability to encode information is thought to depend on the plasticity of synaptic connections between neurons. In the pyramidal neurons constituting the primary hippocampal output to the cortex, located in area CA1, firing of presynaptic CA3 pyramidal neurons produces monosynaptic excitatory postsynaptic potentials (EPSPs followed rapidly by feedforward (disynaptic inhibitory postsynaptic potentials (IPSPs. Long-term potentiation (LTP of the monosynaptic glutamatergic inputs has become the leading model of synaptic plasticity, in part due to its dependence on NMDA receptors (NMDARs, required for spatial and temporal learning in intact animals. Using whole-cell recording in hippocampal slices from adult rats, we find that the efficacy of synaptic transmission from CA3 to CA1 can be enhanced without the induction of classic LTP at the glutamatergic inputs. Taking care not to directly stimulate inhibitory fibers, we show that the induction of GABAergic plasticity at feedforward inhibitory inputs results in the reduced shunting of excitatory currents, producing a long-term increase in the amplitude of Schaffer collateral-mediated postsynaptic potentials. Like classic LTP, disinhibition-mediated LTP requires NMDAR activation, suggesting a role in types of learning and memory attributed primarily to the former and raising the possibility of a previously unrecognized target for therapeutic intervention in disorders linked to memory deficits, as well as a potentially overlooked site of LTP expression in other areas of the brain.

  7. Selective decline of neurotrophin and neurotrophin receptor genes within CA1 pyramidal neurons and hippocampus proper: Correlation with cognitive performance and neuropathology in mild cognitive impairment and Alzheimer's disease.

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    Ginsberg, Stephen D; Malek-Ahmadi, Michael H; Alldred, Melissa J; Che, Shaoli; Elarova, Irina; Chen, Yinghua; Jeanneteau, Freddy; Kranz, Thorsten M; Chao, Moses V; Counts, Scott E; Mufson, Elliott J

    2017-09-09

    Hippocampal CA1 pyramidal neurons, a major component of the medial temporal lobe memory circuit, are selectively vulnerable during the progression of Alzheimer's disease (AD). The cellular mechanism(s) underlying degeneration of these neurons and the relationship to cognitive performance remains largely undefined. Here, we profiled neurotrophin and neurotrophin receptor gene expression within microdissected CA1 neurons along with regional hippocampal dissections from subjects who died with a clinical diagnosis of no cognitive impairment (NCI), mild cognitive impairment (MCI), or AD using laser capture microdissection (LCM), custom-designed microarray analysis, and qPCR of CA1 subregional dissections. Gene expression levels were correlated with cognitive test scores and AD neuropathology criteria. We found a significant downregulation of several neurotrophin genes (e.g., Gdnf, Ngfb, and Ntf4) in CA1 pyramidal neurons in MCI compared to NCI and AD subjects. In addition, the neurotrophin receptor transcripts TrkB and TrkC were decreased in MCI and AD compared to NCI. Regional hippocampal dissections also revealed select neurotrophic gene dysfunction providing evidence for vulnerability within the hippocampus proper during the progression of dementia. Downregulation of several neurotrophins of the NGF family and cognate neurotrophin receptor (TrkA, TrkB, and TrkC) genes correlated with antemortem cognitive measures including the Mini-Mental State Exam (MMSE), a composite global cognitive score (GCS), and Episodic, Semantic, and Working Memory, Perceptual Speed, and Visuospatial domains. Significant correlations were found between select neurotrophic expression downregulation and neuritic plaques (NPs) and neurofibrillary tangles (NFTs), but not diffuse plaques (DPs). These data suggest that dysfunction of neurotrophin signaling complexes have profound negative sequelae within vulnerable hippocampal cell types, which play a role in mnemonic and executive dysfunction

  8. Inward rectifier K+ channel and T-type Ca2+ channel contribute to enhancement of GABAergic transmission induced by β1-adrenoceptor in the prefrontal cortex.

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    Luo, Fei; Zheng, Jian; Sun, Xuan; Tang, Hua

    2017-02-01

    The functions of prefrontal cortex (PFC) are sensitive to norepinephrine (NE). Endogenously released NE influences synaptic transmission through activation of different subtypes of adrenergic receptors in PFC including α 1 , α 2 , β 1 or β 2 -adrenoceptor. Our recent study has revealed that β 1 -adrenoceptor (β 1 -AR) activation modulates glutamatergic transmission in the PFC, whereas the roles of β 1 -AR in GABAergic transmission are elusive. In the current study, we probed the effects of the β 1 -AR agonist dobutamine (Dobu) on GABAergic transmission onto pyramidal neurons in the PFC of juvenile rats. Dobu increased both the frequency and amplitude of miniature IPSCs (mIPSCs). Ca 2+ influx through T-type voltage-gated Ca 2+ channel was required for Dobu-enhanced mIPSC frequency. We also found that Dobu facilitated GABA release probability and the number of releasable vesicles through regulating T-type Ca 2+ channel. Dobu depolarized GABAergic fast-spiking (FS) interneurons with no effects on the firing rate of action potentials (APs) of interneurons. Dobu-induced depolarization of FS interneurons required inward rectifier K + channel (Kir). Our results suggest that Dobu increase GABA release via inhibition of Kir, which further depolarizes FS interneurons resulting in Ca 2+ influx via T-type Ca 2+ channel. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Kv2 Channel Regulation of Action Potential Repolarization and Firing Patterns in Superior Cervical Ganglion Neurons and Hippocampal CA1 Pyramidal Neurons

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    Liu, Pin W.

    2014-01-01

    Kv2 family “delayed-rectifier” potassium channels are widely expressed in mammalian neurons. Kv2 channels activate relatively slowly and their contribution to action potential repolarization under physiological conditions has been unclear. We explored the function of Kv2 channels using a Kv2-selective blocker, Guangxitoxin-1E (GxTX-1E). Using acutely isolated neurons, mixed voltage-clamp and current-clamp experiments were done at 37°C to study the physiological kinetics of channel gating and action potentials. In both rat superior cervical ganglion (SCG) neurons and mouse hippocampal CA1 pyramidal neurons, 100 nm GxTX-1E produced near-saturating block of a component of current typically constituting ∼60–80% of the total delayed-rectifier current. GxTX-1E also reduced A-type potassium current (IA), but much more weakly. In SCG neurons, 100 nm GxTX-1E broadened spikes and voltage clamp experiments using action potential waveforms showed that Kv2 channels carry ∼55% of the total outward current during action potential repolarization despite activating relatively late in the spike. In CA1 neurons, 100 nm GxTX-1E broadened spikes evoked from −70 mV, but not −80 mV, likely reflecting a greater role of Kv2 when other potassium channels were partially inactivated at −70 mV. In both CA1 and SCG neurons, inhibition of Kv2 channels produced dramatic depolarization of interspike voltages during repetitive firing. In CA1 neurons and some SCG neurons, this was associated with increased initial firing frequency. In all neurons, inhibition of Kv2 channels depressed maintained firing because neurons entered depolarization block more readily. Therefore, Kv2 channels can either decrease or increase neuronal excitability depending on the time scale of excitation. PMID:24695716

  10. Schaffer collateral inputs to CA1 excitatory and inhibitory neurons follow different connectivity rules.

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    Kwon, Osung; Feng, Linqing; Druckmann, Shaul; Kim, Jinhyun

    2018-05-04

    Neural circuits, governed by a complex interplay between excitatory and inhibitory neurons, are the substrate for information processing, and the organization of synaptic connectivity in neural network is an important determinant of circuit function. Here, we analyzed the fine structure of connectivity in hippocampal CA1 excitatory and inhibitory neurons innervated by Schaffer collaterals (SCs) using mGRASP in male mice. Our previous study revealed spatially structured synaptic connectivity between CA3-CA1 pyramidal cells (PCs). Surprisingly, parvalbumin-positive interneurons (PVs) showed a significantly more random pattern spatial structure. Notably, application of Peters' Rule for synapse prediction by random overlap between axons and dendrites enhanced structured connectivity in PCs, but, by contrast, made the connectivity pattern in PVs more random. In addition, PCs in a deep sublayer of striatum pyramidale appeared more highly structured than PCs in superficial layers, and little or no sublayer specificity was found in PVs. Our results show that CA1 excitatory PCs and inhibitory PVs innervated by the same SC inputs follow different connectivity rules. The different organizations of fine scale structured connectivity in hippocampal excitatory and inhibitory neurons provide important insights into the development and functions of neural networks. SIGNIFICANCE STATEMENT Understanding how neural circuits generate behavior is one of the central goals of neuroscience. An important component of this endeavor is the mapping of fine-scale connection patterns that underlie, and help us infer, signal processing in the brain. Here, using our recently developed synapse detection technology (mGRASP and neuTube), we provide detailed profiles of synaptic connectivity in excitatory (CA1 pyramidal) and inhibitory (CA1 parvalbumin-positive) neurons innervated by the same presynaptic inputs (CA3 Schaffer collaterals). Our results reveal that these two types of CA1 neurons follow

  11. Characterization of altered intrinsic excitability in hippocampal CA1 pyramidal cells of the Aβ-overproducing PDAPP mouse☆

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    Kerrigan, T.L.; Brown, J.T.; Randall, A.D.

    2014-01-01

    Transgenic mice that accumulate Aβ peptides in the CNS are commonly used to interrogate functional consequences of Alzheimer's disease-associated amyloidopathy. In addition to changes to synaptic function, there is also growing evidence that changes to intrinsic excitability of neurones can arise in these models of amyloidopathy. Furthermore, some of these alterations to intrinsic properties may occur relatively early within the age-related progression of experimental amyloidopathy. Here we report a detailed comparison between the intrinsic excitability properties of hippocampal CA1 pyramidal neurones in wild-type (WT) and PDAPP mice. The latter is a well-established model of Aβ accumulation which expresses human APP harbouring the Indiana (V717F) mutation. At the age employed in this study (9–10 months) CNS Abeta was elevated in PDAPP mice but significant plaque pathology was absent. PDAPP mice exhibited no differences in subthreshold intrinsic properties including resting potential, input resistance, membrane time constant and sag. When CA1 cells of PDAPP mice were given depolarizing stimuli of various amplitudes they initially fired at a higher frequency than WT cells. Commensurate with this, PDAPP cells exhibited a larger fast afterdepolarizing potential. PDAPP mice had narrower spikes but action potential threshold, rate of rise and peak were not different. Thus not all changes seen in our previous studies of amyloidopathy models were present in PDAPP mice; however, narrower spikes, larger ADPs and the propensity to fire at higher frequencies were consistent with our prior work and thus may represent robust, cross-model, indices of amyloidopathy. This article is part of a Special Issue entitled ‘Neurodevelopment Disorder’. PMID:24055500

  12. [The effect of enzymatic treatment using proteases on properties of persistent sodium current in CA1 pyramidal neurons of rat hippocampus].

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    Lun'ko, O O; Isaiev, D S; Maxymiuk, O P; Kryshtal', O O; Isaieva, O V

    2014-01-01

    We investigated the effect of proteases, widely used for neuron isolation in electrophysiological studies, on the amplitude and kinetic characteristics of persistent sodium current (I(NaP)) in hippocampal CA1 pyramidal neurons. Properties of I(NaP) were studied on neurons isolated by mechanical treatment (control group) and by mechanical and enzymatic treatment using pronase E (from Streptomyces griseus) or protease type XXIII (from Aspergillus oryzae). We show that in neurons isolated with pronase E kinetic of activation and density of I(NaP) was unaltered. Enzymatic treatment with protease type XXIII did not alter I(NaP) activation but result in significant decrease in I(NaP) density. Our data indicates that enzymatic treatment using pronase E for neuron isolation is preferable for investigation of I(NaP).

  13. Optogenetic activation of CA1 pyramidal neurons at the dorsal and ventral hippocampus evokes distinct brain-wide responses revealed by mouse fMRI.

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    Norio Takata

    Full Text Available The dorsal and ventral hippocampal regions (dHP and vHP are proposed to have distinct functions. Electrophysiological studies have revealed intra-hippocampal variances along the dorsoventral axis. Nevertheless, the extra-hippocampal influences of dHP and vHP activities remain unclear. In this study, we compared the spatial distribution of brain-wide responses upon dHP or vHP activation and further estimate connection strengths between the dHP and the vHP with corresponding extra-hippocampal areas. To achieve this, we first investigated responses of local field potential (LFP and multi unit activities (MUA upon light stimulation in the hippocampus of an anesthetized transgenic mouse, whose CA1 pyramidal neurons expressed a step-function opsin variant of channelrhodopsin-2 (ChR2. Optogenetic stimulation increased hippocampal LFP power at theta, gamma, and ultra-fast frequency bands, and augmented MUA, indicating light-induced activation of CA1 pyramidal neurons. Brain-wide responses examined using fMRI revealed that optogenetic activation at the dHP or vHP caused blood oxygenation level-dependent (BOLD fMRI signals in situ. Although activation at the dHP induced BOLD responses at the vHP, the opposite was not observed. Outside the hippocampal formation, activation at the dHP, but not the vHP, evoked BOLD responses at the retrosplenial cortex (RSP, which is in line with anatomical evidence. In contrast, BOLD responses at the lateral septum (LS were induced only upon vHP activation, even though both dHP and vHP send axonal fibers to the LS. Our findings suggest that the primary targets of dHP and vHP activation are distinct, which concurs with attributed functions of the dHP and RSP in spatial memory, as well as of the vHP and LS in emotional responses.

  14. Regulation of hippocampus-dependent memory by the zinc finger protein Zbtb20 in mature CA1 neurons.

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    Ren, Anjing; Zhang, Huan; Xie, Zhifang; Ma, Xianhua; Ji, Wenli; He, David Z Z; Yuan, Wenjun; Ding, Yu-Qiang; Zhang, Xiao-Hui; Zhang, Weiping J

    2012-10-01

    The mammalian hippocampus harbours neural circuitry that is crucial for associative learning and memory. The mechanisms that underlie the development and regulation of this complex circuitry are not fully understood. Our previous study established an essential role for the zinc finger protein Zbtb20 in the specification of CA1 field identity in the developing hippocampus. Here, we show that conditionally deleting Zbtb20 specifically in mature CA1 pyramidal neurons impaired hippocampus-dependent memory formation, without affecting hippocampal architecture or the survival, identity and basal excitatory synaptic activity of CA1 pyramidal neurons. We demonstrate that mature CA1-specific Zbtb20 knockout mice exhibited reductions in long-term potentiation (LTP) and NMDA receptor (NMDAR)-mediated excitatory post-synaptic currents. Furthermore, we show that activity-induced phosphorylation of ERK and CREB is impaired in the hippocampal CA1 of Zbtb20 mutant mice. Collectively, these results indicate that Zbtb20 in mature CA1 plays an important role in LTP and memory by regulating NMDAR activity, and activation of ERK and CREB.

  15. Membrane voltage fluctuations reduce spike frequency adaptation and preserve output gain in CA1 pyramidal neurons in a high conductance state

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    Fernandez, Fernando R.; Broicher, Tilman; Truong, Alan; White, John A.

    2011-01-01

    Modulating the gain of the input-output function of neurons is critical for processing of stimuli and network dynamics. Previous gain control mechanisms have suggested that voltage fluctuations play a key role in determining neuronal gain in vivo. Here we show that, under increased membrane conductance, voltage fluctuations restore Na+ current and reduce spike frequency adaptation in rat hippocampal CA1 pyramidal neurons in vitro. As a consequence, membrane voltage fluctuations produce a leftward shift in the f-I relationship without a change in gain, relative to an increase in conductance alone. Furthermore, we show that these changes have important implications for the integration of inhibitory inputs. Due to the ability to restore Na+ current, hyperpolarizing membrane voltage fluctuations mediated by GABAA-like inputs can increase firing rate in a high conductance state. Finally, our data show that the effects on gain and synaptic integration are mediated by voltage fluctuations within a physiologically relevant range of frequencies (10–40 Hz). PMID:21389243

  16. Temporal dynamics of distinct CA1 cell populations during unconscious state induced by ketamine.

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    Hui Kuang

    2010-12-01

    Full Text Available Ketamine is a widely used dissociative anesthetic which can induce some psychotic-like symptoms and memory deficits in some patients during the post-operative period. To understand its effects on neural population dynamics in the brain, we employed large-scale in vivo ensemble recording techniques to monitor the activity patterns of simultaneously recorded hippocampal CA1 pyramidal cells and various interneurons during several conscious and unconscious states such as awake rest, running, slow wave sleep, and ketamine-induced anesthesia. Our analyses reveal that ketamine induces distinct oscillatory dynamics not only in pyramidal cells but also in at least seven different types of CA1 interneurons including putative basket cells, chandelier cells, bistratified cells, and O-LM cells. These emergent unique oscillatory dynamics may very well reflect the intrinsic temporal relationships within the CA1 circuit. It is conceivable that systematic characterization of network dynamics may eventually lead to better understanding of how ketamine induces unconsciousness and consequently alters the conscious mind.

  17. Estrogen induces rapid decrease in dendritic thorns of CA3 pyramidal neurons in adult male rat hippocampus

    International Nuclear Information System (INIS)

    Tsurugizawa, Tomokazu; Mukai, Hideo

    2005-01-01

    Modulation of hippocampal synaptic plasticity by estrogen has been attracting much attention. Thorns of thorny excrescences of CA3 hippocampal neurons are post-synaptic regions whose presynaptic partners are mossy fiber terminals. Here we demonstrated the rapid effect of estradiol on the density of thorns of thorny excrescences, by imaging Lucifer Yellow-injected CA3 neurons in adult male rat hippocampal slices. The application of 1 nM estradiol induced rapid decrease in the density of thorns on pyramidal neurons within 2 h. The estradiol-mediated decrease in the density of thorns was blocked by CNQX (AMPA receptor antagonist) and PD98059 (MAP kinase inhibitor), but not by MK-801 (NMDA receptor antagonist). ERα agonist PPT induced the same suppressive effect as that induced by estradiol on the density of thorns, but ERβ agonist DPN did not affect the density of thorns. Note that a 1 nM estradiol treatment did not affect the density of spines in the stratum radiatum and stratum oriens. A search for synaptic ERα was performed using purified RC-19 antibody. The localization of ERα (67 kDa) in the CA3 mossy fiber terminals and thorns was demonstrated using immunogold electron microscopy. These results imply that estradiol drives the signaling pathway including ERα and MAP kinase

  18. NMDA receptor content of synapses in stratum radiatum of the hippocampal CA1 area.

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    Racca, C; Stephenson, F A; Streit, P; Roberts, J D; Somogyi, P

    2000-04-01

    Glutamate receptors activated by NMDA (NMDARs) or AMPA (AMPARs) are clustered on dendritic spines of pyramidal cells. Both the AMPAR-mediated postsynaptic responses and the synaptic AMPAR immunoreactivity show a large intersynapse variability. Postsynaptic responses mediated by NMDARs show less variability. To assess the variability in NMDAR content and the extent of their coexistence with AMPARs in Schaffer collateral-commissural synapses of adult rat CA1 pyramidal cells, electron microscopic immunogold localization of receptors has been used. Immunoreactivity of NMDARs was detected in virtually all synapses on spines, but AMPARs were undetectable, on average, in 12% of synapses. A proportion of synapses had a very high AMPAR content relative to the mean content, resulting in a distribution more skewed toward larger values than that of NMDARs. The variability of synaptic NMDAR content [coefficient of variation (CV), 0.64-0.70] was much lower than that of the AMPAR content (CV, 1.17-1.45). Unlike the AMPAR content, the NMDAR content showed only a weak correlation with synapse size. As reported previously for AMPARs, the immunoreactivity of NMDARs was also associated with the spine apparatus within spines. The results demonstrate that the majority of the synapses made by CA3 pyramidal cells onto spines of CA1 pyramids express both NMDARs and AMPARs, but with variable ratios. A less-variable NMDAR content is accompanied by a wide variability of AMPAR content, indicating that the regulation of expression of the two receptors is not closely linked. These findings support reports that fast excitatory transmission at some of these synapses is mediated by activation mainly of NMDARs.

  19. Alterations of in vivo CA1 network activity in Dp(16)1Yey Down syndrome model mice.

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    Raveau, Matthieu; Polygalov, Denis; Boehringer, Roman; Amano, Kenji; Yamakawa, Kazuhiro; McHugh, Thomas J

    2018-02-27

    Down syndrome, the leading genetic cause of intellectual disability, results from an extra-copy of chromosome 21. Mice engineered to model this aneuploidy exhibit Down syndrome-like memory deficits in spatial and contextual tasks. While abnormal neuronal function has been identified in these models, most studies have relied on in vitro measures. Here, using in vivo recording in the Dp(16)1Yey model, we find alterations in the organization of spiking of hippocampal CA1 pyramidal neurons, including deficits in the generation of complex spikes. These changes lead to poorer spatial coding during exploration and less coordinated activity during sharp-wave ripples, events involved in memory consolidation. Further, the density of CA1 inhibitory neurons expressing neuropeptide Y, a population key for the generation of pyramidal cell bursts, were significantly increased in Dp(16)1Yey mice. Our data refine the 'over-suppression' theory of Down syndrome pathophysiology and suggest specific neuronal subtypes involved in hippocampal dysfunction in these model mice. © 2018, Raveau et al.

  20. Contextual Learning Requires Functional Diversity at Excitatory and Inhibitory Synapses onto CA1 Pyramidal Neurons

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    Dai Mitsushima

    2015-01-01

    Full Text Available Although the hippocampus is processing temporal and spatial information in particular context, the encoding rule creating memory is completely unknown. To examine the mechanism, we trained rats on an inhibitory avoidance (IA task, a hippocampus-dependent rapid one-trial contextual learning paradigm. By combining Herpes virus-mediated in vivo gene delivery with in vitro patch-clamp recordings, I reported contextual learning drives GluR1-containing AMPA receptors into CA3-CA1 synapses. The molecular event is required for contextual memory, since bilateral expression of delivery blocker in CA1 successfully blocked IA learning. Moreover, I found a logarithmic correlation between the number of delivery blocking cells and learning performance. Considering that one all-or-none device can process 1-bit of data per clock (Nobert Wiener 1961, the logarithmic correlation may provides evidence that CA1 neurons transmit essential data of contextual information. Further, I recently reported critical role of acetylcholine as an intrinsic trigger of learning-dependent synaptic plasticity. IA training induced ACh release in CA1 that strengthened not only AMPA receptor-mediated excitatory synapses, but also GABAA receptor-mediated inhibitory synapses on each CA1 neuron. More importantly, IA-trained rats showed individually different excitatory and inhibitory synaptic inputs with wide variation on each CA1 neuron. Here I propose a new hypothesis that the diversity of synaptic inputs on CA1 neurons may depict cell-specific outputs processing experienced episodes after training.

  1. Changes in inhibitory CA1 network in dual pathology model of epilepsy.

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    Ouardouz, Mohamed; Carmant, Lionel

    2012-01-01

    The combination of two precipitating factors appears to be more and more recognized in patients with temporal lobe epilepsy. Using a two-hit rat model, with a neonatal freeze lesion mimicking a focal cortical malformation combined with hyperthermia-induced seizures mimicking febrile seizures, we have previously reported an increase of inhibition in CA1 pyramidal cells at P20. Here, we investigated the changes affecting excitatory and inhibitory drive onto CA1 interneurons to better define the changes in CA1 inhibitory networks and their paradoxical role in epileptogenesis, using electrophysiological recordings in CA1 hippocampus from rat pups (16-20 d old). We investigated interneurons in CA1 hippocampal area located in stratum oriens (Or) and at the border of strata lacunosum and moleculare (L-M). Our results revealed an increase of the excitatory drive to both types of interneurons with no change in the inhibitory drive. The mechanisms underlying the increase of excitatory synaptic currents (EPSCs) in both types of interneurons are different. In Or interneurons, the amplitude of spontaneous and miniature EPSCs increased, while their frequency was not affected suggesting changes at the post-synaptic level. In L-M interneurons, the frequency of spontaneous EPSCs increases, but the amplitude is not affected. Analyses of miniature EPSCs showed no changes in both their frequency and amplitude. We concluded that L-M interneurons increase in excitatory drive is due to a change in Shaffer collateral axon excitability. The changes described here in CA1 inhibitory network may actually contribute to the epileptogenicity observed in this dual pathology model by increasing pyramidal cell synchronization.

  2. Streptozotocin Inhibits Electrophysiological Determinants of Excitatory and Inhibitory Synaptic Transmission in CA1 Pyramidal Neurons of Rat Hippocampal Slices: Reduction of These Effects by Edaravone

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    Ting Ju

    2016-12-01

    Full Text Available Background: Streptozotocin (STZ has served as an agent to generate an Alzheimer's disease (AD model in rats, while edaravone (EDA, a novel free radical scavenger, has recently emerged as an effective treatment for use in vivo and vitro AD models. However, to date, these beneficial effects of EDA have only been clearly demonstrated within STZ-induced animal models of AD and in cell models of AD. A better understanding of the mechanisms of EDA may provide the opportunity for their clinical application in the treatment of AD. Therefore, the purpose of this study was to investigate the underlying mechanisms of STZ and EDA as assessed upon electrophysiological alterations in CA1 pyramidal neurons of rat hippocampal slices. Methods: Through measures of evoked excitatory postsynaptic currents (eEPSCs, AMPAR-mediated eEPSCs (eEPSCsAMPA, evoked inhibitory postsynaptic currents (eIPSCs, evoked excitatory postsynaptic current paired pulse ratio (eEPSC PPR and evoked inhibitory postsynaptic current paired pulse ratio (eIPSC PPR, it was possible to investigate mechanisms as related to the neurotoxicity of STZ and reductions in these effects by EDA. Results: Our results showed that STZ (1000 µM significantly inhibited peak amplitudes of eEPSCs, eEPSCsAMPA and eIPSCs, while EDA (1000 µM attenuated these STZ-induced changes at holding potentials ranging from -60mV to +40 mV for EPSCs and -60mV to +20 mV for IPSCs. Our work also indicated that mean eEPSC PPR were substantially altered by STZ, effects which were partially restored by EDA. In contrast, no significant effects upon eIPSC PPR were obtained in response to STZ and EDA. Conclusion: Our data suggest that STZ inhibits glutamatergic transmission involving pre-synaptic mechanisms and AMPAR, and that STZ inhibits GABAergic transmission by post-synaptic mechanisms within CA1 pyramidal neurons. These effects are attenuated by EDA.

  3. Carbamazepine and oxcarbazepine, but not eslicarbazepine, enhance excitatory synaptic transmission onto hippocampal CA1 pyramidal cells through an antagonist action at adenosine A1 receptors.

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    Booker, Sam A; Pires, Nuno; Cobb, Stuart; Soares-da-Silva, Patrício; Vida, Imre

    2015-06-01

    This study assessed the anticonvulsant and seizure generation effects of carbamazepine (CBZ), oxcarbazepine (OXC) and eslicarbazepine (S-Lic) in wild-type mice. Electrophysiological recordings were made to discriminate potential cellular and synaptic mechanisms underlying anti- and pro-epileptic actions. The anticonvulsant and pro-convulsant effects were evaluated in the MES, the 6-Hz and the Irwin tests. Whole-cell patch-clamp recordings were used to investigate the effects on fast excitatory and inhibitory synaptic transmission in hippocampal area CA1. The safety window for CBZ, OXC and eslicarbazepine (ED50 value against the MES test and the dose that produces grade 5 convulsions in all mice), was 6.3, 6.0 and 12.5, respectively. At high concentrations the three drugs reduced synaptic transmission. CBZ and OXC enhanced excitatory postsynaptic currents (EPSCs) at low, therapeutically-relevant concentrations. These effects were associated with no change in inhibitory postsynaptic currents (IPSCs) resulting in altered balance between excitation and inhibition. S-Lic had no effect on EPSC or IPSC amplitudes over the same concentration range. The CBZ mediated enhancement of EPSCs was blocked by DPCPX, a selective antagonist, and occluded by CCPA, a selective agonist of the adenosine A1 receptor. Furthermore, reduction of endogenous adenosine by application of the enzyme adenosine deaminase also abolished the CBZ- and OXC-induced increase of EPSCs, indicating that the two drugs act as antagonists at native adenosine receptors. In conclusion, CBZ and OXC possess pro-epileptic actions at clinically-relevant concentrations through the enhancement of excitatory synaptic transmission. S-Lic by comparison has no such effect on synaptic transmission, explaining its lack of seizure exacerbation. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Cortical synaptic transmission in CaV2.1 knockin mice with the S218L missense mutation which causes a severe familial hemiplegic migraine syndrome in humans.

    Directory of Open Access Journals (Sweden)

    Dania eVecchia

    2015-02-01

    Full Text Available Familial hemiplegic migraine type 1 (FHM1 is caused by gain-of-function mutations in CaV2.1 (P/Q-type Ca2+ channels. Knockin (KI mice carrying the FHM1 R192Q missense mutation show enhanced cortical excitatory synaptic transmission at pyramidal cell synapses but unaltered cortical inhibitory neurotransmission at fast-spiking interneuron synapses. Enhanced cortical glutamate release was shown to cause the facilitation of cortical spreading depression (CSD in R192Q KI mice. It, however, remains unknown how other FHM1 mutations affect cortical synaptic transmission. Here, we studied neurotransmission in cortical neurons in microculture from KI mice carrying the S218L mutation, which causes a severe FHM syndrome in humans and an allele-dosage dependent facilitation of experimental CSD in KI mice, which is larger than that caused by the R192Q mutation. We show gain-of-function of excitatory neurotransmission, due to increased action-potential evoked Ca2+ influx and increased probability of glutamate release at pyramidal cell synapses, but unaltered inhibitory neurotransmission at multipolar interneuron synapses in S218L KI mice. In contrast with the larger gain-of-function of neuronal CaV2.1 current in homozygous than heterozygous S218L KI mice, the gain-of-function of evoked glutamate release, the paired-pulse ratio and the Ca2+ dependence of the EPSC were all similar in homozygous and heterozygous S218L KI mice, suggesting compensatory changes in the homozygous mice. Furthermore, we reveal a unique feature of S218L KI cortical synapses which is the presence of a fraction of mutant CaV2.1 channels being open at resting potential. Our data suggest that, while the gain-of-function of evoked glutamate release may explain the facilitation of CSD in heterozygous S218L KI mice, the further facilitation of CSD in homozygous S218L KI mice is due to other CaV2.1-dependent mechanisms, that likely include Ca2+ influx at voltages sub-threshold for action

  5. Input-Timing-Dependent Plasticity in the Hippocampal CA2 Region and Its Potential Role in Social Memory.

    Science.gov (United States)

    Leroy, Felix; Brann, David H; Meira, Torcato; Siegelbaum, Steven A

    2017-08-30

    Input-timing-dependent plasticity (ITDP) is a circuit-based synaptic learning rule by which paired activation of entorhinal cortical (EC) and Schaffer collateral (SC) inputs to hippocampal CA1 pyramidal neurons (PNs) produces a long-term enhancement of SC excitation. We now find that paired stimulation of EC and SC inputs also induces ITDP of SC excitation of CA2 PNs. However, whereas CA1 ITDP results from long-term depression of feedforward inhibition (iLTD) as a result of activation of CB1 endocannabinoid receptors on cholecystokinin-expressing interneurons, CA2 ITDP results from iLTD through activation of δ-opioid receptors on parvalbumin-expressing interneurons. Furthermore, whereas CA1 ITDP has been previously linked to enhanced specificity of contextual memory, we find that CA2 ITDP is associated with enhanced social memory. Thus, ITDP may provide a general synaptic learning rule for distinct forms of hippocampal-dependent memory mediated by distinct hippocampal regions. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Zinc-mediated transactivation of TrkB potentiates the hippocampal mossy fiber-CA3 pyramid synapse.

    Science.gov (United States)

    Huang, Yang Z; Pan, Enhui; Xiong, Zhi-Qi; McNamara, James O

    2008-02-28

    The receptor tyrosine kinase, TrkB, is critical to diverse functions of the mammalian nervous system in health and disease. Evidence of TrkB activation during epileptogenesis in vivo despite genetic deletion of its prototypic neurotrophin ligands led us to hypothesize that a non-neurotrophin, the divalent cation zinc, can transactivate TrkB. We found that zinc activates TrkB through increasing Src family kinase activity by an activity-regulated mechanism independent of neurotrophins. One subcellular locale at which zinc activates TrkB is the postsynaptic density of excitatory synapses. Exogenous zinc potentiates the efficacy of the hippocampal mossy fiber (mf)-CA3 pyramid synapse by a TrkB-requiring mechanism. Long-term potentiation of this synapse is impaired by deletion of TrkB, inhibition of TrkB kinase activity, and by CaEDTA, a selective chelator of zinc. The activity-dependent activation of synaptic TrkB in a neurotrophin-independent manner provides a mechanism by which this receptor can regulate synaptic plasticity.

  7. Nootropic dipeptide noopept enhances inhibitory synaptic transmission in the hippocampus.

    Science.gov (United States)

    Povarov, I S; Kondratenko, R V; Derevyagin, V I; Ostrovskaya, R U; Skrebitskii, V G

    2015-01-01

    Application of nootropic agent Noopept on hippocampal slices from Wistar rats enhanced the inhibitory component of total current induced by stimulation of Shaffer collaterals in CA1 pyramidal neurons, but did not affect the excitatory component. A direct correlation between the increase in the amplitude of inhibitory current and agent concentration was found. The substance did not affect the release of inhibitory transmitters from terminals in the pyramidal neurons, which indicated changes in GABAergic interneurons.

  8. Abnormal cortical synaptic transmission in CaV2.1 knockin mice with the S218L missense mutation which causes a severe familial hemiplegic migraine syndrome in humans

    Science.gov (United States)

    Vecchia, Dania; Tottene, Angelita; van den Maagdenberg, Arn M.J.M.; Pietrobon, Daniela

    2015-01-01

    Familial hemiplegic migraine type 1 (FHM1) is caused by gain-of-function mutations in CaV2.1 (P/Q-type) Ca2+ channels. Knockin (KI) mice carrying the FHM1 R192Q missense mutation show enhanced cortical excitatory synaptic transmission at pyramidal cell synapses but unaltered cortical inhibitory neurotransmission at fast-spiking interneuron synapses. Enhanced cortical glutamate release was shown to cause the facilitation of cortical spreading depression (CSD) in R192Q KI mice. It, however, remains unknown how other FHM1 mutations affect cortical synaptic transmission. Here, we studied neurotransmission in cortical neurons in microculture from KI mice carrying the S218L mutation, which causes a severe FHM syndrome in humans and an allele-dosage dependent facilitation of experimental CSD in KI mice, which is larger than that caused by the R192Q mutation. We show gain-of-function of excitatory neurotransmission, due to increased action-potential evoked Ca2+ influx and increased probability of glutamate release at pyramidal cell synapses, but unaltered inhibitory neurotransmission at multipolar interneuron synapses in S218L KI mice. In contrast with the larger gain-of-function of neuronal CaV2.1 current in homozygous than heterozygous S218L KI mice, the gain-of-function of evoked glutamate release, the paired-pulse ratio and the Ca2+ dependence of the excitatory postsynaptic current were similar in homozygous and heterozygous S218L KI mice, suggesting compensatory changes in the homozygous mice. Furthermore, we reveal a unique feature of S218L KI cortical synapses which is the presence of a fraction of mutant CaV2.1 channels being open at resting potential. Our data suggest that, while the gain-of-function of evoked glutamate release may explain the facilitation of CSD in heterozygous S218L KI mice, the further facilitation of CSD in homozygous S218L KI mice is due to other CaV2.1-dependent mechanisms, that likely include Ca2+ influx at voltages sub-threshold for action

  9. Galantamine Prevents Long-Lasting Suppression of Excitatory Synaptic Transmission in CA1 Pyramidal Neurons of Soman-Challenged Guinea Pigs

    Science.gov (United States)

    Alexandrova, E. A.; Alkondon, M.; Aracava, Y.; Pereira, E. F. R.; Albuquerque, E. X.

    2014-01-01

    Galantamine, a drug currently approved for treatment of Alzheimer's disease, has recently emerged as an effective pretreatment against the acute toxicity and delayed cognitive deficits induced by organophosphorus (OP) nerve agents, including soman. Since cognitive deficits can result from impaired glutamatergic transmission in the hippocampus, the present study was designed to test the hypothesis that hippocampal glutamatergic transmission declines following an acute exposure to soman and that this effect can be prevented by galantamine. To test this hypothesis, spontaneous excitatory postsynaptic currents (EPSCs) were recorded from CA1 pyramidal neurons in hippocampal slices obtained at 1 h, 24 h, or 6-9 days after guinea pigs were injected with: (i) 1xLD50 soman (26.3 μg/kg, s.c.); (ii) galantamine (8 mg/kg, i.m.) followed 30 min later by 1xLD50 soman, (iii) galantamine (8 mg/kg, i.m.), or (iv) saline (0.5 ml/kg, i.m.). In soman-injected guinea pigs that were not pretreated with galantamine, the frequency of EPSCs was significantly lower than that recorded from saline-injected animals. There was no correlation between the severity of soman-induced acute toxicity and the magnitude of soman-induced reduction of EPSC frequency. Pretreatment with galantamine prevented the reduction of EPSC frequency observed at 6-9 days after the soman challenge. Prevention of soman-induced long-lasting reduction of hippocampal glutamatergic synaptic transmission may be an important determinant of the ability of galantamine to counter cognitive deficits that develop long after an acute exposure to the nerve agent. PMID:25064080

  10. Pyramidal cell-interneuron interactions underlie hippocampal ripple oscillations.

    Science.gov (United States)

    Stark, Eran; Roux, Lisa; Eichler, Ronny; Senzai, Yuta; Royer, Sebastien; Buzsáki, György

    2014-07-16

    High-frequency ripple oscillations, observed most prominently in the hippocampal CA1 pyramidal layer, are associated with memory consolidation. The cellular and network mechanisms underlying the generation, frequency control, and spatial coherence of the rhythm are poorly understood. Using multisite optogenetic manipulations in freely behaving rodents, we found that depolarization of a small group of nearby pyramidal cells was sufficient to induce high-frequency oscillations, whereas closed-loop silencing of pyramidal cells or activation of parvalbumin- (PV) or somatostatin-immunoreactive interneurons aborted spontaneously occurring ripples. Focal pharmacological blockade of GABAA receptors abolished ripples. Localized PV interneuron activation paced ensemble spiking, and simultaneous induction of high-frequency oscillations at multiple locations resulted in a temporally coherent pattern mediated by phase-locked interneuron spiking. These results constrain competing models of ripple generation and indicate that temporally precise local interactions between excitatory and inhibitory neurons support ripple generation in the intact hippocampus. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. Target-specific M1 inputs to infragranular S1 pyramidal neurons

    Science.gov (United States)

    Fanselow, Erika E.; Simons, Daniel J.

    2016-01-01

    The functional role of input from the primary motor cortex (M1) to primary somatosensory cortex (S1) is unclear; one key to understanding this pathway may lie in elucidating the cell-type specific microcircuits that connect S1 and M1. Recently, we discovered that a subset of pyramidal neurons in the infragranular layers of S1 receive especially strong input from M1 (Kinnischtzke AK, Simons DJ, Fanselow EE. Cereb Cortex 24: 2237–2248, 2014), suggesting that M1 may affect specific classes of pyramidal neurons differently. Here, using combined optogenetic and retrograde labeling approaches in the mouse, we examined the strengths of M1 inputs to five classes of infragranular S1 neurons categorized by their projections to particular cortical and subcortical targets. We found that the magnitude of M1 synaptic input to S1 pyramidal neurons varies greatly depending on the projection target of the postsynaptic neuron. Of the populations examined, M1-projecting corticocortical neurons in L6 received the strongest M1 inputs, whereas ventral posterior medial nucleus-projecting corticothalamic neurons, also located in L6, received the weakest. Each population also possessed distinct intrinsic properties. The results suggest that M1 differentially engages specific classes of S1 projection neurons, thereby regulating the motor-related influence S1 exerts over subcortical structures. PMID:27334960

  12. Prenatal nicotine and maternal deprivation stress de-regulate the development of CA1, CA3, and dentate gyrus neurons in hippocampus of infant rats.

    Directory of Open Access Journals (Sweden)

    Hong Wang

    Full Text Available Adverse experiences by the developing fetus and in early childhood are associated with profound effects on learning, emotional behavior, and cognition as a whole. In this study we investigated the effects of prenatal nicotine exposure (NIC, postnatal maternal deprivation (MD or the combination of the two (NIC+MD to determine if hippocampal neuron development is modulated by exposure to drugs of abuse and/or stress. Growth of rat offspring exposed to MD alone or NIC+MD was repressed until after weaning. In CA1 but not CA3 of postnatal day 14 (P14 pups, MD increased pyramidal neurons, however, in dentate gyrus (DG, decreased granule neurons. NIC had no effect on neuron number in CA1, CA3 or DG. Unexpectedly, NIC plus MD combined caused a synergistic increase in the number of CA1 or CA3 neurons. Neuron density in CA regions was unaffected by treatment, but in the DG, granule neurons had a looser packing density after NIC, MD or NIC+MD exposure. When septotemporal axes were analyzed, the synergism of stress and drug exposure in CA1 and CA3 was associated with rostral, whereas MD effects were predominantly associated with caudal neurons. TUNEL labeling suggests no active apoptosis at P14, and doublecortin positive neurons and mossy fibers were diminished in NIC+MD relative to controls. The laterality of the effect of nicotine and/or maternal deprivation in right versus left hippocampus was also analyzed and found to be insiginificant. We report for the first time that early life stressors such as postnatal MD and prenatal NIC exposure, when combined, may exhibit synergistic consequences for CA1 and CA3 pyramidal neuron development, and a potential antagonistic influence on developing DG neurons. These results suggest that early stressors may modulate neurogenesis, apoptosis, or maturation of glutamatergic neurons in the hippocampus in a region-specific manner during critical periods of neurodevelopment.

  13. Serotonergic modulation of hippocampal pyramidal cells in euthermic, cold-acclimated, and hibernating hamsters

    Science.gov (United States)

    Horrigan, D. J.; Horwitz, B. A.; Horowitz, J. M.

    1997-01-01

    Serotonergic fibers project to the hippocampus, a brain area previously shown to have distinctive changes in electroencephalograph (EEG) activity during entrance into and arousal from hibernation. The EEG activity is generated by pyramidal cells in both hibernating and nonhibernating species. Using the brain slice preparation, we characterized serotonergic responses of these CA1 pyramidal cells in euthermic, cold-acclimated, and hibernating Syrian hamsters. Stimulation of Shaffer-collateral/commissural fibers evoked fast synaptic excitation of CA1 pyramidal cells, a response monitored by recording population spikes (the synchronous generation of action potentials). Neuromodulation by serotonin (5-HT) decreased population spike amplitude by 54% in cold-acclimated animals, 80% in hibernating hamsters, and 63% in euthermic animals. The depression was significantly greater in slices from hibernators than from cold-acclimated animals. In slices from euthermic animals, changes in extracellular K+ concentration between 2.5 and 5.0 mM did not significantly alter serotonergic responses. The 5-HT1A agonist 8-hydroxy-2(di-n-propylamino)tetralin mimicked serotonergic inhibition in euthermic hamsters. Results show that 5-HT is a robust neuromodulator not only in euthermic animals but also in cold-acclimated and hibernating hamsters.

  14. Pyramids of QTLs enhance host-plant resistance and Bt-mediated resistance to leaf-chewing insects in soybean.

    Science.gov (United States)

    Ortega, María A; All, John N; Boerma, H Roger; Parrott, Wayne A

    2016-04-01

    QTL-M and QTL-E enhance soybean resistance to insects. Pyramiding these QTLs with cry1Ac increases protection against Bt-tolerant pests, presenting an opportunity to effectively deploy Bt with host-plant resistance genes. Plant resistance to leaf-chewing insects minimizes the need for insecticide applications, reducing crop production costs and pesticide concerns. In soybean [Glycine max (L.) Merr.], resistance to a broad range of leaf-chewing insects is found in PI 229358 and PI 227687. PI 229358's resistance is conferred by three quantitative trait loci (QTLs): M, G, and H. PI 227687's resistance is conferred by QTL-E. The letters indicate the soybean Linkage groups (LGs) on which the QTLs are located. This study aimed to determine if pyramiding PI 229358 and PI 227687 QTLs would enhance soybean resistance to leaf-chewing insects, and if pyramiding these QTLs with Bt (cry1Ac) enhances resistance against Bt-tolerant pests. The near-isogenic lines (NILs): Benning(ME), Benning(MGHE), and Benning(ME+cry1Ac) were developed. Benning(ME) and Benning(MGHE) were evaluated in detached-leaf and greenhouse assays with soybean looper [SBL, Chrysodeixis includens (Walker)], corn earworm [CEW, Helicoverpa zea (Boddie)], fall armyworm [FAW, Spodoptera frugiperda (J.E. Smith)], and velvetbean caterpillar [VBC, Anticarsia gemmatalis (Hübner)]; and in field-cage assays with SBL. Benning(ME+cry1Ac) was tested in detached-leaf assays against SBL, VBC, and Southern armyworm [SAW, Spodoptera eridania (Cramer)]. In the detached-leaf assay, Benning(ME) showed the strongest antibiosis against CEW, FAW, and VBC. In field-cage conditions, Benning(ME) and Benning(MGHE) suffered 61 % less defoliation than Benning. Benning(ME+cry1Ac) was more resistant than Benning(ME) and Benning (cry1Ac) against SBL and SAW. Agriculturally relevant levels of resistance in soybean can be achieved with just two loci, QTL-M and QTL-E. ME+cry1Ac could present an opportunity to protect the durability of Bt

  15. Transmitter release modulation in nerve terminals of rat neocortical pyramidal cells by intracellular calcium buffers

    Science.gov (United States)

    Ohana, Ora; Sakmann, Bert

    1998-01-01

    Dual whole-cell voltage recordings were made from synaptically connected layer 5 (L5) pyramidal neurones in slices of the young (P14-P16) rat neocortex. The Ca2+ buffers BAPTA or EGTA were loaded into the presynaptic neurone via the pipette recording from the presynaptic neurone to examine their effect on the mean and the coefficient of variation (c.v.) of single fibre EPSP amplitudes, referred to as unitary EPSPs. The fast Ca2+ buffer BAPTA reduced unitary EPSP amplitudes in a concentration dependent way. With 0.1 mm BAPTA in the pipette, the mean EPSP amplitude was reduced by 14 ± 2.8% (mean ±s.e.m., n = 7) compared with control pipette solution, whereas with 1.5 mm BAPTA, the mean EPSP amplitude was reduced by 72 ± 1.5% (n = 5). The concentration of BAPTA that reduced mean EPSP amplitudes to one-half of control was close to 0.7 mm. Saturation of BAPTA during evoked release was tested by comparing the effect of loading the presynaptic neurone with 0.1 mm BAPTA at 2 and 1 mm[Ca2+]o. Reducing [Ca2+]o from 2 to 1 mm, thereby reducing Ca2+ influx into the terminals, decreased the mean EPSP amplitude by 60 ± 2.2% with control pipette solution and by 62 ± 1.9% after loading with 0.1 mm BAPTA (n = 7). The slow Ca2+ buffer EGTA at 1 mm reduced mean EPSP amplitudes by 15 ± 2.5% (n = 5). With 10 mm EGTA mean EPSP amplitudes were reduced by 56 ± 2.3% (n = 4). With both Ca2+ buffers, the reduction in mean EPSP amplitudes was associated with an increase in the c.v. of peak EPSP amplitudes, consistent with a reduction of the transmitter release probability as the major mechanism underlying the reduction of the EPSP amplitude. The results suggest that in nerve terminals of thick tufted L5 pyramidal cells the endogenous mobile Ca2+ buffer is equivalent to less than 0.1 mm BAPTA and that at many release sites of pyramidal cell terminals the Ca2+ channel domains overlap, a situation comparable with that at large calyx-type terminals in the brainstem. PMID:9782165

  16. Effects of FK506 on Hippocampal CA1 Cells Following Transient Global Ischemia/Reperfusion in Wistar Rat

    Directory of Open Access Journals (Sweden)

    Zahra-Nadia Sharifi

    2012-01-01

    Full Text Available Transient global cerebral ischemia causes loss of pyramidal cells in CA1 region of hippocampus. In this study, we investigated the neurotrophic effect of the immunosuppressant agent FK506 in rat after global cerebral ischemia. Both common carotid arteries were occluded for 20 minutes followed by reperfusion. In experimental group 1, FK506 (6 mg/kg was given as a single dose exactly at the time of reperfusion. In the second group, FK506 was administered at the beginning of reperfusion, followed by its administration intraperitoneally (IP 6, 24, 48, and 72 hours after reperfusion. FK506 failed to show neurotrophic effects on CA1 region when applied as a single dose of 6 mg/kg. The cell number and size of the CA1 pyramidal cells were increased, also the number of cell death decreased in this region when FK506 was administrated 48 h after reperfusion. This work supports the possible use of FK506 in treatment of ischemic brain damage.

  17. Ammonia inhibits long-term potentiation via neurosteroid synthesis in hippocampal pyramidal neurons.

    Science.gov (United States)

    Izumi, Y; Svrakic, N; O'Dell, K; Zorumski, C F

    2013-03-13

    Neurosteroids are a class of endogenous steroids synthesized in the brain that are believed to be involved in the pathogenesis of neuropsychiatric disorders and memory impairment. Ammonia impairs long-term potentiation (LTP), a synaptic model of learning, in the hippocampus, a brain region involved in memory acquisition. Although mechanisms underlying ammonia-mediated LTP inhibition are not fully understood, we previously found that the activation of N-methyl-d-aspartate receptors (NMDARs) is important. Based on this, we hypothesize that metabolic stressors, including hyperammonemia, promote untimely NMDAR activation and result in neural adaptations that include the synthesis of allopregnanolone (alloP) and other GABA-potentiating neurosteroids that dampen neuronal activity and impair LTP and memory formation. Using an antibody against 5α-reduced neurosteroids, we found that 100 μM ammonia acutely enhanced neurosteroid immunostaining in pyramidal neurons in the CA1 region of rat hippocampal slices. The enhanced staining was blocked by finasteride, a selective inhibitor of 5α-reductase, a key enzyme required for alloP synthesis. Finasteride also overcame LTP inhibition by 100 μM ammonia, as did picrotoxin, an inhibitor of GABA-A receptors. These results indicate that GABA-enhancing neurosteroids, synthesized locally within pyramidal neurons, contribute significantly to ammonia-mediated synaptic dysfunction. These results suggest that the manipulation of neurosteroid synthesis could provide a strategy to improve cognitive function in individuals with hyperammonemia. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

  18. Can astronomy enhance UNESCO World Heritage recognition? The paradigm of 4th Dynasty Egyptian pyramids

    Science.gov (United States)

    Belmonte, Juan Antonio

    2015-08-01

    The pyramids of Egypt, notably those of the 4th Dinasty as Giza, have always be considered an unmistikable part of human world heritage as the only surviving wonders of the Ancient World. Their majesty, technical hability and innovative character have always beeen considered as representative of ancient Egyptian ingenuity. However, past and present fringe theories about the pyramids and astronomy have always polluted the role of our discipline in the design, construction and symbolism of these impressive monuments. This is indeed unfear. Fortunately, things have started to change in the last couple of decades and now astronomy is interpreted as a neccessary tool for the correct interpretation of the astral eschatology present in the 5th and 6th Dynasty Texts of the Pyramids. Although the pyramid complexes of the 4th Dynasty are mute, there is however recent research showing that a strong astral symbolism could be hidden in many aspects of the complex architecture and in the design of these exceptional monuments. This idea comes from several hints obtained not only from planning and construction, but also from epigraphy and the analysis of celestial and local landscapes. Chronology also plays a most relevant role on this. The pyramid complexes of the 4th Dynasty at Meidum, Dahshur, Giza and Abu Rowash -- all of which enjoy UNESCO World Heritage recognition -- willl be scrutinized. As a consequence, we will show how astronomy can certainly enhance the face value of these extraordinary monuments as a definitive proof of the ancient Egyptian quest for Ma'at, i.e. their perennial obsesion for Cosmic Order.

  19. The cradle of pyramids in satellite images

    OpenAIRE

    Sparavigna, Amelia Carolina

    2011-01-01

    We propose the use of image processing to enhance the Google Maps of some archaeological areas of Egypt. In particular we analyse that place which is considered the cradle of pyramids, where it was announced the discovery of a new pyramid by means of an infrared remote sensing.

  20. Influx of extracellular Zn(2+) into the hippocampal CA1 neurons is required for cognitive performance via long-term potentiation.

    Science.gov (United States)

    Takeda, A; Suzuki, M; Tempaku, M; Ohashi, K; Tamano, H

    2015-09-24

    Physiological significance of synaptic Zn(2+) signaling was examined in the CA1 of young rats. In vivo CA1 long-term potentiation (LTP) was induced using a recording electrode attached to a microdialysis probe and the recording region was locally perfused with artificial cerebrospinal fluid (ACSF) via the microdialysis probe. In vivo CA1 LTP was inhibited under perfusion with CaEDTA and ZnAF-2DA, extracellular and intracellular Zn(2+) chelators, respectively, suggesting that the influx of extracellular Zn(2+) is required for in vivo CA1 LTP induction. The increase in intracellular Zn(2+) was chelated with intracellular ZnAF-2 in the CA1 1h after local injection of ZnAF-2DA into the CA1, suggesting that intracellular Zn(2+) signaling induced during learning is blocked with intracellular ZnAF-2 when the learning was performed 1h after ZnAF-2DA injection. Object recognition was affected when training of object recognition test was performed 1h after ZnAF-2DA injection. These data suggest that intracellular Zn(2+) signaling in the CA1 is required for object recognition memory via LTP. Surprisingly, in vivo CA1 LTP was affected under perfusion with 0.1-1μM ZnCl2, unlike the previous data that in vitro CA1 LTP was enhanced in the presence of 1-5μM ZnCl2. The influx of extracellular Zn(2+) into CA1 pyramidal cells has bidirectional action in CA1 LTP. The present study indicates that the degree of extracellular Zn(2+) influx into CA1 neurons is critical for LTP and cognitive performance. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  1. Enhanced photovoltaic performance of inverted pyramid-based nanostructured black-silicon solar cells passivated by an atomic-layer-deposited Al2O3 layer.

    Science.gov (United States)

    Chen, Hong-Yan; Lu, Hong-Liang; Ren, Qing-Hua; Zhang, Yuan; Yang, Xiao-Feng; Ding, Shi-Jin; Zhang, David Wei

    2015-10-07

    Inverted pyramid-based nanostructured black-silicon (BS) solar cells with an Al2O3 passivation layer grown by atomic layer deposition (ALD) have been demonstrated. A multi-scale textured BS surface combining silicon nanowires (SiNWs) and inverted pyramids was obtained for the first time by lithography and metal catalyzed wet etching. The reflectance of the as-prepared BS surface was about 2% lower than that of the more commonly reported upright pyramid-based SiNW BS surface over the whole of the visible light spectrum, which led to a 1.7 mA cm(-2) increase in short circuit current density. Moreover, the as-prepared solar cells were further passivated by an ALD-Al2O3 layer. The effect of annealing temperature on the photovoltaic performance of the solar cells was investigated. It was found that the values of all solar cell parameters including short circuit current, open circuit voltage, and fill factor exhibit a further increase under an optimized annealing temperature. Minority carrier lifetime measurements indicate that the enhanced cell performance is due to the improved passivation quality of the Al2O3 layer after thermal annealing treatments. By combining these two refinements, the optimized SiNW BS solar cells achieved a maximum conversion efficiency enhancement of 7.6% compared to the cells with an upright pyramid-based SiNWs surface and conventional SiNx passivation.

  2. Estradiol attenuates ischemia-induced death of hippocampal neurons and enhances synaptic transmission in aged, long-term hormone-deprived female rats.

    Directory of Open Access Journals (Sweden)

    Tomoko Inagaki

    Full Text Available Transient global forebrain ischemia causes selective, delayed death of hippocampal CA1 pyramidal neurons, and the ovarian hormone 17β-estradiol (E2 reduces neuronal loss in young and middle-aged females. The neuroprotective efficacy of E2 after a prolonged period of hormone deprivation is controversial, and few studies examine this issue in aged animals given E2 treatment after induction of ischemia.The present study investigated the neuroprotective effects of E2 administered immediately after global ischemia in aged female rats (15-18 months after 6 months of hormone deprivation. We also used electrophysiological methods to assess whether CA1 synapses in the aging hippocampus remain responsive to E2 after prolonged hormone withdrawal. Animals were ovariohysterectomized and underwent 10 min global ischemia 6 months later. A single dose of E2 (2.25 µg infused intraventricularly after reperfusion significantly increased cell survival, with 45% of CA1 neurons surviving vs 15% in controls. Ischemia also induced moderate loss of CA3/CA4 pyramidal cells. Bath application of 1 nM E2 onto brain slices derived from non-ischemic aged females after 6 months of hormone withdrawal significantly enhanced excitatory transmission at CA1 synapses evoked by Schaffer collateral stimulation, and normal long-term potentiation (LTP was induced. The magnitude of LTP and of E2 enhancement of field excitatory postsynaptic potentials was indistinguishable from that recorded in slices from young rats.The data demonstrate that 1 acute post-ischemic infusion of E2 into the brain ventricles is neuroprotective in aged rats after 6 months of hormone deprivation; and 2 E2 enhances synaptic transmission in CA1 pyramidal neurons of aged long-term hormone deprived females. These findings provide evidence that the aging hippocampus remains responsive to E2 administered either in vivo or in vitro even after prolonged periods of hormone withdrawal.

  3. Astrocytic Ca2+ signals are required for the functional integrity of tripartite synapses

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    Tanaka Mika

    2013-01-01

    Full Text Available Abstract Background Neuronal activity alters calcium ion (Ca2+ dynamics in astrocytes, but the physiologic relevance of these changes is controversial. To examine this issue further, we generated an inducible transgenic mouse model in which the expression of an inositol 1,4,5-trisphosphate absorbent, “IP3 sponge”, attenuates astrocytic Ca2+ signaling. Results Attenuated Ca2+ activity correlated with reduced astrocytic coverage of asymmetric synapses in the hippocampal CA1 region in these animals. The decreased astrocytic ‘protection’ of the synapses facilitated glutamate ‘spillover’, which was reflected by prolonged glutamate transporter currents in stratum radiatum astrocytes and enhanced N-methyl-D-aspartate receptor currents in CA1 pyramidal neurons in response to burst stimulation. These mice also exhibited behavioral impairments in spatial reference memory and remote contextual fear memory, in which hippocampal circuits are involved. Conclusions Our findings suggest that IP3-mediated astrocytic Ca2+ signaling correlates with the formation of functional tripartite synapses in the hippocampus.

  4. Opposite effects of glucocorticoid receptor activation on hippocampal CA1 dendritic complexity in chronically stressed and handled animals

    NARCIS (Netherlands)

    Alfarez, D.N.; Karst, H.; Velzing, E.H.; Joëls, M.; Krugers, H.J.

    2008-01-01

    Remodeling of synaptic networks is believed to contribute to synaptic plasticity and long-term memory performance, both of which are modulated by chronic stress. We here examined whether chronic stress modulates dendritic complexity of hippocampal CA1 pyramidal cells, under conditions of basal as

  5. Estrogen levels regulate the subcellular distribution of phosphorylated Akt in hippocampal CA1 dendrites.

    Science.gov (United States)

    Znamensky, Vladimir; Akama, Keith T; McEwen, Bruce S; Milner, Teresa A

    2003-03-15

    In addition to genomic pathways, estrogens may regulate gene expression by activating specific signal transduction pathways, such as that involving phosphatidylinositol 3-kinase (PI3-K) and the subsequent phosphorylation of Akt (protein kinase B). The Akt pathway regulates various cellular events, including the initiation of protein synthesis. Our previous studies showed that synaptogenesis in hippocampal CA1 pyramidal cell dendritic spines is highest when brain estrogen levels are highest. To address the role of Akt in this process, the subcellular distribution of phosphorylated Akt immunoreactivity (pAkt-I) in the hippocampus of female rats across the estrous cycle and male rats was analyzed by light microscopy (LM) and electron microscopy (EM). By LM, the density of pAkt-I in stratum radiatum of CA1 was significantly higher in proestrus rats (or in estrogen-supplemented ovariectomized females) compared with diestrus, estrus, or male rats. By EM, pAkt-I was found throughout the shafts and in select spines of stratum radiatum dendrites. Quantitative ultrastructural analysis identifying pAkt-I with immunogold particles revealed that proestrus rats compared with diestrus, estrus, and male rats contained significantly higher pAkt-I associated with (1) dendritic spines (both cytoplasm and plasmalemma), (2) spine apparati located within 0.1 microm of dendritic spine bases, (3) endoplasmic reticula and polyribosomes in the cytoplasm of dendritic shafts, and (4) the plasmalemma of dendritic shafts. These findings suggest that estrogens may regulate spine formation in CA1 pyramidal neurons via Akt-mediated signaling events.

  6. Thermoluminescence of pyramid stones

    International Nuclear Information System (INIS)

    Gomaa, M.A.; Eid, A.M.

    1982-01-01

    It is the aim of the present study to investigate some thermoluminescence properties of pyramid stones. Using a few grammes of pyramid stones from Pyramids I and II, the TL glow peaks were observed at 250 and 310 0 C, respectively. The TL glow peaks of samples annealed at 600 0 C, then exposed to 60 Co γ-rays were observed at 120, 190 and 310 0 C, respectively. The accumulated dose of natural samples is estimated to be around 310 Gray (31 krad). By assuming an annual dose is 1 mGy, the estimated age of pyramid stones is 0.31 M year. (author)

  7. Thermoluminescence of pyramid stones

    Energy Technology Data Exchange (ETDEWEB)

    Gomaa, M A; Eid, A M [Atomic Energy Establishment, Cairo (Egypt)

    1982-01-01

    It is the aim of the present study to investigate some thermoluminescence properties of pyramid stones. Using a few grammes of pyramid stones from Pyramids I and II, the TL glow peaks were observed at 250 and 310/sup 0/C, respectively. The TL glow peaks of samples annealed at 600/sup 0/C, then exposed to /sup 60/Co ..gamma..-rays were observed at 120, 190 and 310/sup 0/C, respectively. The accumulated dose of natural samples is estimated to be around 310 Gray (31 krad). By assuming an annual dose is 1 mGy, the estimated age of pyramid stones is 0.31 M year.

  8. Loss of protohaem IX farnesyltransferase in mature dentate granule cells impairs short-term facilitation at mossy fibre to CA3 pyramidal cell synapses.

    Science.gov (United States)

    Booker, Sam A; Campbell, Graham R; Mysiak, Karolina S; Brophy, Peter J; Kind, Peter C; Mahad, Don J; Wyllie, David J A

    2017-03-15

    Neurodegenerative disorders can exhibit dysfunctional mitochondrial respiratory chain complex IV activity. Conditional deletion of cytochrome c oxidase, the terminal enzyme in the respiratory electron transport chain of mitochondria, from hippocampal dentate granule cells in mice does not affect low-frequency dentate to CA3 glutamatergic synaptic transmission. High-frequency dentate to CA3 glutamatergic synaptic transmission and feedforward inhibition are significantly attenuated in cytochrome c oxidase-deficient mice. Intact presynaptic mitochondrial function is critical for the short-term dynamics of mossy fibre to CA3 synaptic function. Neurodegenerative disorders are characterized by peripheral and central symptoms including cognitive impairments which have been associated with reduced mitochondrial function, in particular mitochondrial respiratory chain complex IV or cytochrome c oxidase activity. In the present study we conditionally removed a key component of complex IV, protohaem IX farnesyltransferase encoded by the COX10 gene, in granule cells of the adult dentate gyrus. Utilizing whole-cell patch-clamp recordings from morphologically identified CA3 pyramidal cells from control and complex IV-deficient mice, we found that reduced mitochondrial function did not result in overt deficits in basal glutamatergic synaptic transmission at the mossy-fibre synapse because the amplitude, input-output relationship and 50 ms paired-pulse facilitation were unchanged following COX10 removal from dentate granule cells. However, trains of stimuli given at high frequency (> 20 Hz) resulted in dramatic reductions in short-term facilitation and, at the highest frequencies (> 50 Hz), also reduced paired-pulse facilitation, suggesting a requirement for adequate mitochondrial function to maintain glutamate release during physiologically relevant activity patterns. Interestingly, local inhibition was reduced, suggesting the effect observed was not restricted to synapses

  9. Network state-dependent inhibition of identified hippocampal CA3 axo-axonic cells in vivo

    Science.gov (United States)

    Tukker, John J; Klausberger, Thomas; Somogyi, Peter

    2015-01-01

    Hippocampal sharp waves are population discharges initiated by an unknown mechanism in pyramidal cell networks of CA3. Axo-axonic cells (AACs) regulate action potential generation through GABAergic synapses on the axon initial segment. We found that CA3 AACs in anesthetized rats and AACs in freely moving rats stopped firing during sharp waves, when pyramidal cells fire most. AACs fired strongly and rhythmically around the peak of theta oscillations, when pyramidal cells fire at low probability. Distinguishing AACs from other parvalbumin-expressing interneurons by their lack of detectable SATB1 transcription factor immunoreactivity, we discovered a somatic GABAergic input originating from the medial septum that preferentially targets AACs. We recorded septo-hippocampal GABAergic cells that were activated during hippocampal sharp waves and projected to CA3. We hypothesize that inhibition of AACs, and the resulting subcellular redistribution of inhibition from the axon initial segment to other pyramidal cell domains, is a necessary condition for the emergence of sharp waves promoting memory consolidation. PMID:24141313

  10. Chronic Loss of CA2 Transmission Leads to Hippocampal Hyperexcitability.

    Science.gov (United States)

    Boehringer, Roman; Polygalov, Denis; Huang, Arthur J Y; Middleton, Steven J; Robert, Vincent; Wintzer, Marie E; Piskorowski, Rebecca A; Chevaleyre, Vivien; McHugh, Thomas J

    2017-05-03

    Hippocampal CA2 pyramidal cells project into both the neighboring CA1 and CA3 subfields, leaving them well positioned to influence network physiology and information processing for memory and space. While recent work has suggested unique roles for CA2, including encoding position during immobility and generating ripple oscillations, an interventional examination of the integrative functions of these connections has yet to be reported. Here we demonstrate that CA2 recruits feedforward inhibition in CA3 and that chronic genetically engineered shutdown of CA2-pyramidal-cell synaptic transmission consequently results in increased excitability of the recurrent CA3 network. In behaving mice, this led to spatially triggered episodes of network-wide hyperexcitability during exploration accompanied by the emergence of high-frequency discharges during rest. These findings reveal CA2 as a regulator of network processing in hippocampus and suggest that CA2-mediated inhibition in CA3 plays a key role in establishing the dynamic excitatory and inhibitory balance required for proper network function. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Storyline and Associations Pyramid as Methods of Creativity Enhancement: Comparison of Effectiveness in 5-Year-Old Children

    Science.gov (United States)

    Smogorzewska, Joanna

    2012-01-01

    This article presents the results of a study comparing the originality, the length, the number of neologisms and the syntactic complexity of fairy tales created with "Storyline" and "Associations Pyramid." Both methods were developed to enhance children's language abilities and their creative thinking. One hundred twenty eight 5-year-old children…

  12. Tris-hydroxymethyl-aminomethane enhances capsaicin-induced intracellular Ca2+ influx through transient receptor potential V1 (TRPV1 channels

    Directory of Open Access Journals (Sweden)

    Satoshi Murakami

    2016-02-01

    Full Text Available Non-selective transient receptor potential vanilloid (TRPV cation channels are activated by various insults, including exposure to heat, acidity, and the compound capsaicin, resulting in sensations of pain in the skin, visceral organs, and oral cavity. Recently, TRPV1 activation was also demonstrated in response to basic pH elicited by ammonia and intracellular alkalization. Tris-hydroxymethyl aminomethane (THAM is widely used as an alkalizing agent; however, the effects of THAM on TRPV1 channels have not been defined. In this study, we characterized the effects of THAM-induced TRPV1 channel activation in baby hamster kidney cells expressing human TRPV1 (hTRPV1 and the Ca2+-sensitive fluorescent sensor GCaMP2 by real-time confocal microscopy. Notably, both capsaicin (1 μM and pH 6.5 buffer elicited steep increases in the intracellular Ca2+ concentration ([Ca2+]i, while treatment with THAM (pH 8.5 alone had no effect. However, treatment with THAM (pH 8.5 following capsaicin application elicited a profound, long-lasting increase in [Ca2+]i that was completely inhibited by the TRPV1 antagonist capsazepine. Taken together, these results suggest that hTRPV1 pre-activation is required to provoke enhanced, THAM-induced [Ca2+]i increases, which could be a mechanism underlying pain induced by basic pH.

  13. Activation of pyramidal neurons in mouse medial prefrontal cortex enhances food seeking behavior while reducing impulsivity in the absence of an effect on food intake

    Directory of Open Access Journals (Sweden)

    Daniel McAllister Warthen

    2016-03-01

    Full Text Available The medial prefrontal cortex (mPFC is involved in a wide range of executive cognitive functions, including reward evaluation, decision-making, memory extinction, mood, and task switching. Manipulation of the mPFC has been shown to alter food intake and food reward valuation, but whether exclusive stimulation of mPFC pyramidal neurons, which form the principle output of the mPFC, is sufficient to mediate food rewarded instrumental behavior is unknown. We sought to determine the behavioral consequences of manipulating mPFC output by exciting pyramidal neurons in mouse mPFC during performance of a panel of behavioral assays, focusing on food reward. We found that increasing mPFC pyramidal cell output using Designer Receptors Exclusively Activated by Designer Drugs (DREADD enhanced performance in instrumental food reward assays that assess food seeking behavior, while sparing effects in affect and food intake. Specifically, activation of mPFC pyramidal neurons enhanced operant responding for food reward, reinstatement of palatable food seeking, and suppression of impulsive responding for food reward. Conversely, activation of mPFC pyramidal neurons had no effect on unconditioned food intake, social interaction, or behavior in an open field. Furthermore, we found that behavioral outcome is influenced by the degree of mPFC activation, with a low drive sufficient to enhance operant responding and a higher drive required to alter impulsivity. Additionally, we provide data demonstrating that DREADD stimulation involves a nitric oxide synthase dependent pathway, similar to endogenous muscarinic M3 receptor stimulation, a finding that provides novel mechanistic insight into an increasingly widespread method of remote neuronal control.

  14. Constitutive expression of CaPLA1 conferred enhanced growth and grain yield in transgenic rice plants.

    Science.gov (United States)

    Park, Ki Youl; Kim, Eun Yu; Seo, Young Sam; Kim, Woo Taek

    2016-03-01

    Phospholipids are not only important components of cell membranes, but participate in diverse processes in higher plants. In this study, we generated Capsicum annuum phospholipiase A1 (CaPLA1) overexpressing transgenic rice (Oryza sativa L.) plants under the control of the maize ubiquitin promoter. The T4 CaPLA1-overexpressing rice plants (Ubi:CaPLA1) had a higher root:shoot mass ratio than the wild-type plants in the vegetative stage. Leaf epidermal cells from transgenic plants had more cells than wild-type plants. Genes that code for cyclin and lipid metabolic enzymes were up-regulated in the transgenic lines. When grown under typical paddy field conditions, the transgenic plants produced more tillers, longer panicles and more branches per panicle than the wild-type plants, all of which resulted in greater grain yield. Microarray analysis suggests that gene expressions that are related with cell proliferation, lipid metabolism, and redox state were widely altered in CaPLA1-overexpressing transgenic rice plants. Ubi:CaPLA1 plants had a reduced membrane peroxidation state, as determined by malondialdehyde and conjugated diene levels and higher peroxidase activity than wild-type rice plants. Furthermore, three isoprenoid synthetic genes encoding terpenoid synthase, hydroxysteroid dehydrogenase and 3-hydroxy-3-methyl-glutaryl-CoA reductase were up-regulated in CaPLA1-overexpressing plants. We suggest that constitutive expression of CaPLA1 conferred increased grain yield with enhanced growth in transgenic rice plants by alteration of gene activities related with cell proliferation, lipid metabolism, membrane peroxidation state and isoprenoid biosynthesis.

  15. Adrenergic Modulation Regulates the Dendritic Excitability of Layer 5 Pyramidal Neurons In Vivo

    Directory of Open Access Journals (Sweden)

    Christina Labarrera

    2018-04-01

    Full Text Available Summary: The excitability of the apical tuft of layer 5 pyramidal neurons is thought to play a crucial role in behavioral performance and synaptic plasticity. We show that the excitability of the apical tuft is sensitive to adrenergic neuromodulation. Using two-photon dendritic Ca2+ imaging and in vivo whole-cell and extracellular recordings in awake mice, we show that application of the α2A-adrenoceptor agonist guanfacine increases the probability of dendritic Ca2+ events in the tuft and lowers the threshold for dendritic Ca2+ spikes. We further show that these effects are likely to be mediated by the dendritic current Ih. Modulation of Ih in a realistic compartmental model controlled both the generation and magnitude of dendritic calcium spikes in the apical tuft. These findings suggest that adrenergic neuromodulation may affect cognitive processes such as sensory integration, attention, and working memory by regulating the sensitivity of layer 5 pyramidal neurons to top-down inputs. : Labarrera et al. show that noradrenergic neuromodulation can be an effective way to regulate the interaction between different input streams of information processed by an individual neuron. These findings may have important implications for our understanding of how adrenergic neuromodulation affects sensory integration, attention, and working memory. Keywords: cortical layer 5 pyramidal neuron, dendrites, norepinephrine, HCN, Ih, Ca2+ spike, apical tuft, guanfacine, ADHD, somatosensory cortex

  16. Electrophysiological and Morphological Characterization of Chrna2 Cells in the Subiculum and CA1 of the Hippocampus: An Optogenetic Investigation

    Directory of Open Access Journals (Sweden)

    Heather Nichol

    2018-02-01

    Full Text Available The nicotinic acetylcholine receptor alpha2 subunit (Chrna2 is a specific marker for oriens lacunosum-moleculare (OLM interneurons in the dorsal CA1 region of the hippocampus. It was recently shown using a Chrna2-cre mice line that OLM interneurons can modulate entorhinal cortex and CA3 inputs and may therefore have an important role in gating, encoding, and recall of memory. In this study, we have used a combination of electrophysiology and optogenetics using Chrna2-cre mice to determine the role of Chrna2 interneurons in the subiculum area, the main output region of the hippocampus. We aimed to assess the similarities between Chrna2 subiculum and CA1 neurons in terms of the expression of interneuron markers, their membrane properties, and their inhibitory input to pyramidal neurons. We found that subiculum and CA1 dorsal Chrna2 cells similarly expressed the marker somatostatin and had comparable membrane and firing properties. The somas of Chrna2 cells in both regions were found in the deepest layer with axons projecting superficially. However, subiculum Chrna2 cells displayed more extensive projections with dendrites which occupied a significantly larger area than in CA1. The post-synaptic responses elicited by Chrna2 cells in pyramidal cells of both regions revealed comparable inhibitory responses elicited by GABAA receptors and, interestingly, GABAB receptor mediated components. This study provides the first in-depth characterization of Chrna2 cells in the subiculum, and suggests that subiculum and CA1 Chrna2 cells are generally similar and may play comparable roles in both sub-regions.

  17. A study on radiation energy of Pyramidal shape 1- Effect of housing within a Pyramid model on cancer growth and some blood parameters of mice

    International Nuclear Information System (INIS)

    El-Abiad, N.M.; Lotfi, S.A.; El Hadary, A.A.; Nagi, G.A.

    2010-01-01

    A study of solid tumor growth retardation by impaling the pyramid energy radiation in a pyramidal model shape was carried out. The great Pyramid of Egypt has evoked a keen interest since 1920, both for its architectural, marvel and mystical significance. Its strange thing (via shaping of razers, longer shelf life of vegetables, alerted states of consciousnesses, sleeping in hum and, wound healing). Power energy radiations are said to occur within a pyramid constructed in the exact geometric properties of Giza pyramid. The effect of housing in two different pyramidal shapes on cancer growth and some blood physiological indices in mice infected with cancer were observed. The results obtained that housing in pyramid shape cage significantly reduced the development of cancer, significant increase in liver enzymes activity and α feto proteins, however, no effect was observed in levels of thyroid hormones concentration when compared with their matched value in ordinary 2 inverted pyramid cages. It could be concluded that the radiation energy of pyramidal shapes might improve certain biochemical and physiological indices leading to tumor growth retardation

  18. Recurrent synapses and circuits in the CA3 region of the hippocampus: an associative network.

    Directory of Open Access Journals (Sweden)

    Richard eMiles

    2014-01-01

    Full Text Available In the CA3 region of the hippocampus, pyramidal cells excite other pyramidal cells and interneurons. The axons of CA3 pyramidal cells spread throughout most of the region to form an associative network. These connections were first drawn by Cajal and Lorente de No. Their physiological properties were explored to understand epileptiform discharges generated in the region. Synapses between pairs of pyramidal cells involve one or few release sites and are weaker than connections made by mossy fibres on CA3 pyramidal cells. Synapses with interneurons are rather effective, as needed to control unchecked excitation. We examine contributions of recurrent synapses to epileptiform synchrony, to the genesis of sharp waves in the CA3 region and to population oscillations at theta and gamma frequencies. Recurrent connections in CA3, as other associative cortices, have a lower connectivity spread over a larger area than in primary sensory cortices. This sparse, but wide-ranging connectivity serves the functions of an associative network, including acquisition of neuronal representations as activity in groups of CA3 cells and completion involving the recall from partial cues of these ensemble firing patterns.

  19. caGrid 1.0: a Grid enterprise architecture for cancer research.

    Science.gov (United States)

    Oster, Scott; Langella, Stephen; Hastings, Shannon; Ervin, David; Madduri, Ravi; Kurc, Tahsin; Siebenlist, Frank; Covitz, Peter; Shanbhag, Krishnakant; Foster, Ian; Saltz, Joel

    2007-10-11

    caGrid is the core Grid architecture of the NCI-sponsored cancer Biomedical Informatics Grid (caBIG) program. The current release, caGrid version 1.0, is developed as the production Grid software infrastructure of caBIG. Based on feedback from adopters of the previous version (caGrid 0.5), it has been significantly enhanced with new features and improvements to existing components. This paper presents an overview of caGrid 1.0, its main components, and enhancements over caGrid 0.5.

  20. Prolonged sojourn of developing pyramidal cells in the intermediate zone of the hippocampus and their settling in the stratum pyramidale

    International Nuclear Information System (INIS)

    Altman, J.; Bayer, S.A.

    1990-01-01

    In radiograms of rat embryos that received a single dose of [3H]thymidine between days E16 and E20 and were killed 24 hours after the injection, the heavily labeled cells (those that ceased to multiply soon after the injection) form a horizontal layer in the intermediate zone of the hippocampus, called the inferior band. The fate of these heavily labeled cells was traced in radiograms of the dorsal hippocampus in embryos that received [3H]thymidine on day E18 and were killed at different intervals thereafter. Two hours after injection the labeled proliferative cells are located in the Ammonic neuroepithelium. The heavily labeled cells that leave the neuroepithelium and aggregate in the inferior band 1 day after the injection become progressively displaced toward the stratum pyramidale 2-3 days later, and penetrate the stratum pyramidale of the CA1 region on the 4th day. In the stratum pyramidale of the CA3 region, farther removed from the Ammonic neuroepithelium, the heavily labeled cells are still sojourning in the intermediate zone 4 days after labeling. Observations in methacrylate sections suggest that two morphogenetic features of the developing hippocampus may contribute to the long sojourn of young pyramidal cells in the intermediate zone: the way in which the stratum pyramidale forms and the way in which the alveolar channels develop. The stratum pyramidale of the CA1 region forms before that of the CA3 region, which is the reverse of the neurogenetic gradient in the production of pyramidal cells. We hypothesize that this is so because the pyramidal cells destined to settle in the CA3 region, which will be contacted by granule cells axons (the mossy fibers), have to await the formation of the granular layer on days E21-E22

  1. A role for CA3 in social recognition memory.

    Science.gov (United States)

    Chiang, Ming-Ching; Huang, Arthur J Y; Wintzer, Marie E; Ohshima, Toshio; McHugh, Thomas J

    2018-02-02

    Social recognition memory is crucial for survival across species, underlying the need to correctly identify conspecifics, mates and potential enemies. In humans the hippocampus is engaged in social and episodic memory, however the circuit mechanisms of social memory in rodent models has only recently come under scrutiny. Work in mice has established that the dorsal CA2 and ventral CA1 regions play critical roles, however a more comprehensive comparative analyses of the circuits and mechanisms required has not been reported. Here we employ conditional genetics to examine the differential contributions of the hippocampal subfields to social memory. We find that the deletion of NMDA receptor subunit 1 gene (NR1), which abolishes NMDA receptor synaptic plasticity, in CA3 pyramidal cells led to deficits in social memory; however, mice lacking the same gene in DG granule cells performed indistinguishable from controls. Further, we use conditional pharmacogenetic inhibition to demonstrate that activity in ventral, but not dorsal, CA3 is necessary for the encoding of a social memory. These findings demonstrated CA3 pyramidal cell plasticity and transmission contribute to the encoding of social stimuli and help further identify the distinct circuits underlying the role of the hippocampus in social memory. Copyright © 2018 Elsevier B.V. All rights reserved.

  2. Pyramidal cells in V1 of African rodents are bigger more branched and more spiny than those in primates.

    Directory of Open Access Journals (Sweden)

    Guy eElston

    2014-02-01

    Full Text Available Pyramidal cells are characterised by markedly different sized dendritic trees, branching patterns and spine density across the cortical mantle. Moreover, pyramidal cells have been shown to differ in structure among homologous cortical areas in different species; however, most of these studies have been conducted in primates. Whilst pyramidal cells have been quantified in a few cortical areas in some other species there are, as yet, no uniform comparative data on pyramidal cell structure in a homologous cortical area among species in different Orders. Here we studied layer III pyramidal cells in V1 of three species of rodents, the greater cane rat, highveld gerbil and four-striped mouse, by the same methodology used to sample data from layer III pyramidal cells in primates. The data reveal markedly different trends between rodents and primates: there is an appreciable increase in the size, branching complexity and number of spines in the dendritic trees of pyramidal cells with increasing size of V1 in the brain in rodents, whereas there is relatively little difference in primates. Moreover, pyramidal cells in rodents are larger, more branched and more spinous than those in primates. For example, the dendritic trees of pyramidal cells in V1 of the cane rat are nearly three times larger, and have more than ten times the number of spines in their basal dendritic trees, than those in V1 of the macaque (7900 and 600, respectively, which has a V1 40 times the size that of the cane rat. It remains to be determined to what extent these differences may result from developmental differences or reflect evolutionary and/or processing specializations.

  3. Juvenile Hippocampal CA2 Region Expresses Aggrecan

    Directory of Open Access Journals (Sweden)

    Asako Noguchi

    2017-05-01

    Full Text Available Perineuronal nets (PNNs are distributed primarily around inhibitory interneurons in the hippocampus, such as parvalbumin-positive interneurons. PNNs are also present around excitatory neurons in some brain regions and prevent plasticity in these neurons. A recent study demonstrated that PNNs also exist around mouse hippocampal pyramidal cells, which are the principle type of excitatory neurons, in the CA2 subregion and modulate the excitability and plasticity of these neurons. However, the development of PNNs in the CA2 region during postnatal maturation was not fully investigated. This study found that a main component of PNNs, aggrecan, existed in the pyramidal cell layer of the putative CA2 subarea prior to the appearance of the CA2 region, which was defined by the CA2 marker protein regulator of G protein signaling 14 (RGS14. We also found that aggrecan immunoreactivity was more evident in the anterior sections of the CA2 area than the posterior sections, which suggests that the function of CA2 PNNs varies along the anterior-posterior axis.

  4. Distal axotomy enhances retrograde presynaptic excitability onto injured pyramidal neurons via trans-synaptic signaling.

    Science.gov (United States)

    Nagendran, Tharkika; Larsen, Rylan S; Bigler, Rebecca L; Frost, Shawn B; Philpot, Benjamin D; Nudo, Randolph J; Taylor, Anne Marion

    2017-09-20

    Injury of CNS nerve tracts remodels circuitry through dendritic spine loss and hyper-excitability, thus influencing recovery. Due to the complexity of the CNS, a mechanistic understanding of injury-induced synaptic remodeling remains unclear. Using microfluidic chambers to separate and injure distal axons, we show that axotomy causes retrograde dendritic spine loss at directly injured pyramidal neurons followed by retrograde presynaptic hyper-excitability. These remodeling events require activity at the site of injury, axon-to-soma signaling, and transcription. Similarly, directly injured corticospinal neurons in vivo also exhibit a specific increase in spiking following axon injury. Axotomy-induced hyper-excitability of cultured neurons coincides with elimination of inhibitory inputs onto injured neurons, including those formed onto dendritic spines. Netrin-1 downregulation occurs following axon injury and exogenous netrin-1 applied after injury normalizes spine density, presynaptic excitability, and inhibitory inputs at injured neurons. Our findings show that intrinsic signaling within damaged neurons regulates synaptic remodeling and involves netrin-1 signaling.Spinal cord injury can induce synaptic reorganization and remodeling in the brain. Here the authors study how severed distal axons signal back to the cell body to induce hyperexcitability, loss of inhibition and enhanced presynaptic release through netrin-1.

  5. Transition Dynamics of a Dentate Gyrus-CA3 Neuronal Network during Temporal Lobe Epilepsy

    Directory of Open Access Journals (Sweden)

    Liyuan Zhang

    2017-07-01

    Full Text Available In temporal lobe epilepsy (TLE, the variation of chemical receptor expression underlies the basis of neural network activity shifts, resulting in neuronal hyperexcitability and epileptiform discharges. However, dynamical mechanisms involved in the transitions of TLE are not fully understood, because of the neuronal diversity and the indeterminacy of network connection. Hence, based on Hodgkin–Huxley (HH type neurons and Pinsky–Rinzel (PR type neurons coupling with glutamatergic and GABAergic synaptic connections respectively, we propose a computational framework which contains dentate gyrus (DG region and CA3 region. By regulating the concentration range of N-methyl-D-aspartate-type glutamate receptor (NMDAR, we demonstrate the pyramidal neuron can generate transitions from interictal to seizure discharges. This suggests that enhanced endogenous activity of NMDAR contributes to excitability in pyramidal neuron. Moreover, we conclude that excitatory discharges in CA3 region vary considerably on account of the excitatory currents produced by the excitatory pyramidal neuron. Interestingly, by changing the backprojection connection, we find that glutamatergic type backprojection can promote the dominant frequency of firings and further motivate excitatory counterpropagation from CA3 region to DG region. However, GABAergic type backprojection can reduce firing rate and block morbid counterpropagation, which may be factored into the terminations of TLE. In addition, neuronal diversity dominated network shows weak correlation with different backprojections. Our modeling and simulation studies provide new insights into the mechanisms of seizures generation and connectionism in local hippocampus, along with the synaptic mechanisms of this disease.

  6. Transition Dynamics of a Dentate Gyrus-CA3 Neuronal Network during Temporal Lobe Epilepsy.

    Science.gov (United States)

    Zhang, Liyuan; Fan, Denggui; Wang, Qingyun

    2017-01-01

    In temporal lobe epilepsy (TLE), the variation of chemical receptor expression underlies the basis of neural network activity shifts, resulting in neuronal hyperexcitability and epileptiform discharges. However, dynamical mechanisms involved in the transitions of TLE are not fully understood, because of the neuronal diversity and the indeterminacy of network connection. Hence, based on Hodgkin-Huxley (HH) type neurons and Pinsky-Rinzel (PR) type neurons coupling with glutamatergic and GABAergic synaptic connections respectively, we propose a computational framework which contains dentate gyrus (DG) region and CA3 region. By regulating the concentration range of N-methyl-D-aspartate-type glutamate receptor (NMDAR), we demonstrate the pyramidal neuron can generate transitions from interictal to seizure discharges. This suggests that enhanced endogenous activity of NMDAR contributes to excitability in pyramidal neuron. Moreover, we conclude that excitatory discharges in CA3 region vary considerably on account of the excitatory currents produced by the excitatory pyramidal neuron. Interestingly, by changing the backprojection connection, we find that glutamatergic type backprojection can promote the dominant frequency of firings and further motivate excitatory counterpropagation from CA3 region to DG region. However, GABAergic type backprojection can reduce firing rate and block morbid counterpropagation, which may be factored into the terminations of TLE. In addition, neuronal diversity dominated network shows weak correlation with different backprojections. Our modeling and simulation studies provide new insights into the mechanisms of seizures generation and connectionism in local hippocampus, along with the synaptic mechanisms of this disease.

  7. Au nanoparticle-decorated silicon pyramids for plasmon-enhanced hot electron near-infrared photodetection

    Science.gov (United States)

    Qi, Zhiyang; Zhai, Yusheng; Wen, Long; Wang, Qilong; Chen, Qin; Iqbal, Sami; Chen, Guangdian; Xu, Ji; Tu, Yan

    2017-07-01

    The heterojunction between metal and silicon (Si) is an attractive route to extend the response of Si-based photodiodes into the near-infrared (NIR) region, so-called Schottky barrier diodes. Photons absorbed into a metallic nanostructure excite the surface plasmon resonances (SPRs), which can be damped non-radiatively through the creation of hot electrons. Unfortunately, the quantum efficiency of hot electron detectors remains low due to low optical absorption and poor electron injection efficiency. In this study, we propose an efficient and low-cost plasmonic hot electron NIR photodetector based on a Au nanoparticle (Au NP)-decorated Si pyramid Schottky junction. The large-area and lithography-free photodetector is realized by using an anisotropic chemical wet etching and rapid thermal annealing (RTA) of a thin Au film. We experimentally demonstrate that these hot electron detectors have broad photoresponsivity spectra in the NIR region of 1200-1475 nm, with a low dark current on the order of 10-5 A cm-2. The observed responsivities enable these devices to be competitive with other reported Si-based NIR hot electron photodetectors using perfectly periodic nanostructures. The improved performance is attributed to the pyramid surface which can enhance light trapping and the localized electric field, and the nano-sized Au NPs which are beneficial for the tunneling of hot electrons. The simple and large-area preparation processes make them suitable for large-scale thermophotovoltaic cell and low-cost NIR detection applications.

  8. Excitatory Synaptic Drive and Feedforward Inhibition in the Hippocampal CA3 Circuit Are Regulated by SynCAM 1.

    Science.gov (United States)

    Park, Kellie A; Ribic, Adema; Laage Gaupp, Fabian M; Coman, Daniel; Huang, Yuegao; Dulla, Chris G; Hyder, Fahmeed; Biederer, Thomas

    2016-07-13

    Select adhesion proteins control the development of synapses and modulate their structural and functional properties. Despite these important roles, the extent to which different synapse-organizing mechanisms act across brain regions to establish connectivity and regulate network properties is incompletely understood. Further, their functional roles in different neuronal populations remain to be defined. Here, we applied diffusion tensor imaging (DTI), a modality of magnetic resonance imaging (MRI), to map connectivity changes in knock-out (KO) mice lacking the synaptogenic cell adhesion protein SynCAM 1. This identified reduced fractional anisotropy in the hippocampal CA3 area in absence of SynCAM 1. In agreement, mossy fiber refinement in CA3 was impaired in SynCAM 1 KO mice. Mossy fibers make excitatory inputs onto postsynaptic specializations of CA3 pyramidal neurons termed thorny excrescences and these structures were smaller in the absence of SynCAM 1. However, the most prevalent targets of mossy fibers are GABAergic interneurons and SynCAM 1 loss unexpectedly reduced the number of excitatory terminals onto parvalbumin (PV)-positive interneurons in CA3. SynCAM 1 KO mice additionally exhibited lower postsynaptic GluA1 expression in these PV-positive interneurons. These synaptic imbalances in SynCAM 1 KO mice resulted in CA3 disinhibition, in agreement with reduced feedforward inhibition in this network in the absence of SynCAM 1-dependent excitatory drive onto interneurons. In turn, mice lacking SynCAM 1 were impaired in memory tasks involving CA3. Our results support that SynCAM 1 modulates excitatory mossy fiber inputs onto both interneurons and principal neurons in the hippocampal CA3 area to balance network excitability. This study advances our understanding of synapse-organizing mechanisms on two levels. First, the data support that synaptogenic proteins guide connectivity and can function in distinct brain regions even if they are expressed broadly

  9. Expression of Kv3.1b potassium channel is widespread in macaque motor cortex pyramidal cells: A histological comparison between rat and macaque.

    Science.gov (United States)

    Soares, David; Goldrick, Isabelle; Lemon, Roger N; Kraskov, Alexander; Greensmith, Linda; Kalmar, Bernadett

    2017-06-15

    There are substantial differences across species in the organization and function of the motor pathways. These differences extend to basic electrophysiological properties. Thus, in rat motor cortex, pyramidal cells have long duration action potentials, while in the macaque, some pyramidal neurons exhibit short duration "thin" spikes. These differences may be related to the expression of the fast potassium channel Kv3.1b, which in rat interneurons is associated with generation of thin spikes. Rat pyramidal cells typically lack these channels, while there are reports that they are present in macaque pyramids. Here we made a systematic, quantitative comparison of the Kv3.1b expression in sections from macaque and rat motor cortex, using two different antibodies (NeuroMab, Millipore). As our standard reference, we examined, in the same sections, Kv3.1b staining in parvalbumin-positive interneurons, which show strong Kv3.1b immunoreactivity. In macaque motor cortex, a large sample of pyramidal neurons were nearly all found to express Kv3.1b in their soma membranes. These labeled neurons were identified as pyramidal based either by expression of SMI32 (a pyramidal marker), or by their shape and size, and lack of expression of parvalbumin (a marker for some classes of interneuron). Large (Betz cells), medium, and small pyramidal neurons all expressed Kv3.1b. In rat motor cortex, SMI32-postive pyramidal neurons expressing Kv3.1b were very rare and weakly stained. Thus, there is a marked species difference in the immunoreactivity of Kv3.1b in pyramidal neurons, and this may be one of the factors explaining the pronounced electrophysiological differences between rat and macaque pyramidal neurons. © 2017 The Authors The Journal of Comparative Neurology Published by Wiley Periodicals, Inc.

  10. CaMKK2 Inhibition in Enhancing Bone Fracture Healing

    Science.gov (United States)

    2016-05-01

    AWARD NUMBER: W81XWH-13-1-0188 TITLE: CaMKK2 Inhibition in Enhancing Bone Fracture Healing PRINCIPAL INVESTIGATOR: Uma Sankar, Ph.D...Enhancing Bone Fracture Healing 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-13-1-0188 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Uma Sankar 5d...accelerated fracture healing . We generated unilateral mid-shaft fractures using a three-point bending method (first described for use in rats by Bonnarens and

  11. Calcium current activation kinetics in isolated pyramidal neurones of the Ca1 region of the mature guinea-pig hippocampus.

    Science.gov (United States)

    Kay, A R; Wong, R K

    1987-11-01

    1. Neurones were isolated from the CA1 region of the guinea-pig hippocampus and subjected to the whole-cell mode of voltage clamping, to determine the kinetics of voltage-gated Ca2+ channel activation. 2. Isolated neurones had an abbreviated morphology, having lost most of the distal dendritic tree during the isolation procedure. The electrical compactness of the cells facilitates voltage clamp analysis. 3. Block of sodium and potassium currents revealed a persistent current activated on depolarization above -40 mV, which inactivated slowly when the intracellular medium contained EGTA. The current was blocked by Co2+ and Cd2+, augmented by increases in Ca2+ and could be carried by Ba2+, suggesting that the current is borne by Ca2+. 4. Steady-state activation of the Ca2+ current was found to be well described by the Boltzman equation raised to the second power. 5. The open channel's current-voltage (I-V) relationship rectified in the inward direction and was consistent with the constant-field equation. 6. The kinetics of Ca2+ current onset followed m2 kinetics throughout the range of its activation. Tail current kinetics were in accord with this model. A detailed Hodgkin-Huxley model was derived, defining the activation of this current. 7. The kinetics of the currents observed in this regionally and morphologically defined class of neurones were consistent with the existence of a single kinetic class of channels.

  12. Exciton binding energy in a pyramidal quantum dot

    Indian Academy of Sciences (India)

    A ANITHA

    2018-03-27

    Mar 27, 2018 ... screening function on exciton binding energy in a pyramid-shaped quantum dot of ... tures may generate unique properties and they show .... where Ee is the ground-state energy of the electron in ... Figure 1. The geometry of the pyramidal quantum dot. base and H is the height of the pyramid which is taken.

  13. Hippocampal deletion of BDNF gene attenuates gamma oscillations in area CA1 by up-regulating 5-HT3 receptor.

    Directory of Open Access Journals (Sweden)

    Ying Huang

    2011-01-01

    Full Text Available Pyramidal neurons in the hippocampal area CA3 express high levels of BDNF, but how this BDNF contributes to oscillatory properties of hippocampus is unknown.Here we examined carbachol-induced gamma oscillations in hippocampal slices lacking BDNF gene in the area CA3. The power of oscillations was reduced in the hippocampal area CA1, which coincided with increases in the expression and activity of 5-HT3 receptor. Pharmacological block of this receptor partially restored power of gamma oscillations in slices from KO mice, but had no effect in slices from WT mice.These data suggest that BDNF facilitates gamma oscillations in the hippocampus by attenuating signaling through 5-HT3 receptor. Thus, BDNF modulates hippocampal oscillations through serotonergic system.

  14. CAMKII activation is not required for maintenance of learning-induced enhancement of neuronal excitability.

    Directory of Open Access Journals (Sweden)

    Ori Liraz

    Full Text Available Pyramidal neurons in the piriform cortex from olfactory-discrimination trained rats show enhanced intrinsic neuronal excitability that lasts for several days after learning. Such enhanced intrinsic excitability is mediated by long-term reduction in the post-burst after-hyperpolarization (AHP which is generated by repetitive spike firing. AHP reduction is due to decreased conductance of a calcium-dependent potassium current, the sI(AHP. We have previously shown that learning-induced AHP reduction is maintained by persistent protein kinase C (PKC and extracellular regulated kinase (ERK activation. However, the molecular machinery underlying this long-lasting modulation of intrinsic excitability is yet to be fully described. Here we examine whether the CaMKII, which is known to be crucial in learning, memory and synaptic plasticity processes, is instrumental for the maintenance of learning-induced AHP reduction. KN93, that selectively blocks CaMKII autophosphorylation at Thr286, reduced the AHP in neurons from trained and control rat to the same extent. Consequently, the differences in AHP amplitude and neuronal adaptation between neurons from trained rats and controls remained. Accordingly, the level of activated CaMKII was similar in pirifrom cortex samples taken form trained and control rats. Our data show that although CaMKII modulates the amplitude of AHP of pyramidal neurons in the piriform cortex, its activation is not required for maintaining learning-induced enhancement of neuronal excitability.

  15. Pyramid shape of polymer solar cells: a simple solution to triple efficiency

    International Nuclear Information System (INIS)

    Xia, Yuxin; Hou, Lintao; Ma, Kaijie; Wang, Biao; Xiong, Kang; Liu, Pengyi; Liao, Jihai; Wen, Shangsheng; Wang, Ergang

    2013-01-01

    Pyramid-shaped polymer solar cells fabricated on flexible substrates were investigated. Effective light trapping can be realized due to light reflection in all 360° directions, and 100% space utilization is achieved when assembled into arrays. The power conversion efficiency is enhanced by 200% ([60]PCBM as the acceptor) and 260% ([70]PCBM as the acceptor) with a dihedral angle of 30° between the opposite sides of the pyramid compared with a planar device, and a high V oc of 3.5 V in series connection is obtained. Considering the material utilization, an angle of 90° for pyramid-shaped polymer solar cells is proposed. Pyramid-shaped polymer solar cells are particularly suitable for installation on roof of vehicles and houses, which have limited surface area. (paper)

  16. Fast gamma oscillations are generated intrinsically in CA1 without the involvement of fast-spiking basket cells.

    Science.gov (United States)

    Craig, Michael T; McBain, Chris J

    2015-02-25

    Information processing in neuronal networks relies on the precise synchronization of ensembles of neurons, coordinated by the diverse family of inhibitory interneurons. Cortical interneurons can be usefully parsed by embryonic origin, with the vast majority arising from either the caudal or medial ganglionic eminences (CGE and MGE). Here, we examine the activity of hippocampal interneurons during gamma oscillations in mouse CA1, using an in vitro model where brief epochs of rhythmic activity were evoked by local application of kainate. We found that this CA1 KA-evoked gamma oscillation was faster than that in CA3 and, crucially, did not appear to require the involvement of fast-spiking basket cells. In contrast to CA3, we also found that optogenetic inhibition of pyramidal cells in CA1 did not significantly affect the power of the oscillation, suggesting that excitation may not be essential for gamma genesis in this region. We found that MGE-derived interneurons were generally more active than CGE interneurons during CA1 gamma, although a group of CGE-derived interneurons, putative trilaminar cells, were strongly phase-locked with gamma oscillations and, together with MGE-derived axo-axonic and bistratified cells, provide attractive candidates for being the driver of this locally generated, predominantly interneuron-driven model of gamma oscillations. Copyright © 2015 the authors 0270-6474/15/353616-09$15.00/0.

  17. The Pyramidal Capacitated Vehicle Routing Problem

    DEFF Research Database (Denmark)

    Lysgaard, Jens

    This paper introduces the Pyramidal Capacitated Vehicle Routing Problem (PCVRP) as a restricted version of the Capacitated Vehicle Routing Problem (CVRP). In the PCVRP each route is required to be pyramidal in a sense generalized from the Pyramidal Traveling Salesman Problem (PTSP). A pyramidal...

  18. The pyramidal capacitated vehicle routing problem

    DEFF Research Database (Denmark)

    Lysgaard, Jens

    2010-01-01

    This paper introduces the pyramidal capacitated vehicle routing problem (PCVRP) as a restricted version of the capacitated vehicle routing problem (CVRP). In the PCVRP each route is required to be pyramidal in a sense generalized from the pyramidal traveling salesman problem (PTSP). A pyramidal...

  19. Comparison between basal and apical dendritic spines in estrogen-induced rapid spinogenesis of CA1 principal neurons in the adult hippocampus

    International Nuclear Information System (INIS)

    Murakami, Gen; Tsurugizawa, Tomokazu; Hatanaka, Yusuke; Komatsuzaki, Yoshimasa; Tanabe, Nobuaki; Mukai, Hideo; Hojo, Yasushi; Kominami, Shiro; Yamazaki, Takeshi; Kimoto, Tetsuya; Kawato, Suguru

    2006-01-01

    Modulation of hippocampal synaptic plasticity by estrogen has been attracting much attention. Here, we demonstrated the rapid effect of 17β-estradiol on the density and morphology of spines in the stratum oriens (s.o., basal side) and in the stratum lacunosum-moleculare (s.l.m., apical side) by imaging Lucifer Yellow-injected CA1 neurons in adult male rat hippocampal slices, because spines in s.o. and s.l.m. have been poorly understood as compared with spines in the stratum radiatum. The application of 1 nM estradiol-induced a rapid increase in the density of spines of pyramidal neurons within 2 h. This increase by estradiol was blocked by Erk MAP kinase inhibitor and estrogen receptor inhibitor in both regions. Effect of blockade by agonists of AMPA receptors and NMDA receptors was different between s.o. and s.l.m. In both regions, ERα agonist PPT induced the same enhancing effect of spinogenesis as that induced by estradiol

  20. Using Pyramids Effects as a method of nuclear and radiation protection

    International Nuclear Information System (INIS)

    Abdullayev, I.E.

    2011-01-01

    Results most of experiments fixed that When radioactive waste is placed inside the pyramids, there is a decrease in their level of radioactivity Based on result of these experiments we suggest - Using Pyramids Effects as a method of nuclear and radiation protection. Explanation of this method based on 3 factors. (2 of them - internal factors, 1 of them - external factor) Factor I. Based o the Theory of the Pyramids Effects we know, that Pyramid construction separate the normal geomagnetic field of the Earth to 2 parts, which have difference vise verse physical characteristics. Cause of the energetic barrier of side of Pyramid, internal space of the Pyramid isolate from the influence of the external normal geomagnetic field of Earth. Therefore, internal space of the Pyramid is fulfilling only by the attractive power of the Earth (pic.1)

  1. Inhibiting the Activity of CA1 Hippocampal Neurons Prevents the Recall of Contextual Fear Memory in Inducible ArchT Transgenic Mice.

    Directory of Open Access Journals (Sweden)

    Masanori Sakaguchi

    Full Text Available The optogenetic manipulation of light-activated ion-channels/pumps (i.e., opsins can reversibly activate or suppress neuronal activity with precise temporal control. Therefore, optogenetic techniques hold great potential to establish causal relationships between specific neuronal circuits and their function in freely moving animals. Due to the critical role of the hippocampal CA1 region in memory function, we explored the possibility of targeting an inhibitory opsin, ArchT, to CA1 pyramidal neurons in mice. We established a transgenic mouse line in which tetracycline trans-activator induces ArchT expression. By crossing this line with a CaMKIIα-tTA transgenic line, the delivery of light via an implanted optrode inhibits the activity of excitatory CA1 neurons. We found that light delivery to the hippocampus inhibited the recall of a contextual fear memory. Our results demonstrate that this optogenetic mouse line can be used to investigate the neuronal circuits underlying behavior.

  2. Exogenous hydrogen sulfide eliminates spatial memory retrieval impairment and hippocampal CA1 LTD enhancement caused by acute stress via promoting glutamate uptake.

    Science.gov (United States)

    He, Jin; Guo, Ruixian; Qiu, Pengxin; Su, Xingwen; Yan, Guangmei; Feng, Jianqiang

    2017-05-14

    Acute stress impairs the hippocampus-dependent spatial memory retrieval, and its synaptic mechanisms are associated with hippocampal CA1 long-term depression (LTD) enhancement in the adult rats. Endogenous hydrogen sulfide (H 2 S) is recognized as a novel gasotransmitter and has the neural protective roles. However, very little attention has been paid to understanding the effects of H 2 S on spatial memory retrieval impairment. We observed the protective effects of NaHS (a donor of H 2 S) against spatial memory retrieval impairment caused by acute stress and its synaptic mechanisms. Our results showed that NaHS abolished spatial memory retrieval impairment and hippocampal CA1 LTD enhancement caused by acute stress, but not by glutamate transporter inhibitor l-trans-pyrrolidine-2,4-dicarboxylic (tPDC), indicating that the activation of glutamate transporters is necessary for exogenous H 2 S to exert its roles. Moreover, NaHS restored the decreased glutamate uptake in the hippocampal CA1 synaptosomal fraction caused by acute stress. Dithiothreitol (DTT, a disulfide reducing agent) abolished a decrease in the glutamate uptake caused by acute stress, and NaHS eradicated the decreased glutamate uptake caused by 5,5'-dithio-bis(2-nitrobenzoic)acid (DTNB, a thiol oxidizing agent), collectively, revealing that exogenous H 2 S increases glutamate uptake by reducing disulfide bonds of the glutamate transporters. Additionally, NaHS inhibited the increased expression level of phosphorylated c-Jun-N-terminal kinase (JNK) in the hippocampal CA1 region caused by acute stress. The JNK inhibitor SP600125 eliminated spatial memory retrieval impairment, hippocampal CA1 LTD enhancement and the decreased glutamate uptake caused by acute stress, indicating that exogenous H 2 S exerts these roles by inhibiting the activation of JNK signaling pathway. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  3. The Formation and Characterization of GaN Hexagonal Pyramids

    Science.gov (United States)

    Zhang, Shi-Ying; Xiu, Xiang-Qian; Lin, Zeng-Qin; Hua, Xue-Mei; Xie, Zi-Li; Zhang, Rong; Zheng, You-Dou

    2013-05-01

    GaN with hexagonal pyramids is fabricated using the photo-assisted electroless chemical etching method. Defective areas of the GaN substrate are selectively etched in a mixed solution of KOH and K2S2O8 under ultraviolet illumination, producing submicron-sized pyramids. Hexagonal pyramids on the etched GaN with well-defined {101¯1¯} facets and very sharp tips are formed. High-resolution x-ray diffraction shows that etched GaN with pyramids has a higher crystal quality, and micro-Raman spectra reveal a tensile stress relaxation in GaN with pyramids compared with normal GaN. The cathodoluminescence intensity of GaN after etching is significantly increased by three times, which is attributed to the reduction in the internal reflection, high-quality GaN with pyramids and the Bragg effect.

  4. Pyramiding of transgenic Pm3 alleles in wheat results in improved powdery mildew resistance in the field.

    Science.gov (United States)

    Koller, Teresa; Brunner, Susanne; Herren, Gerhard; Hurni, Severine; Keller, Beat

    2018-04-01

    The combined effects of enhanced total transgene expression level and allele-specificity combination in transgenic allele-pyramided Pm3 wheat lines result in improved powdery mildew field resistance without negative pleiotropic effects. Allelic Pm3 resistance genes of wheat confer race-specific resistance to powdery mildew (Blumeria graminis f. sp. tritici, Bgt) and encode nucleotide-binding domain, leucine-rich repeat (NLR) receptors. Transgenic wheat lines overexpressing alleles Pm3a, b, c, d, f, and g have previously been generated by transformation of cultivar Bobwhite and tested in field trials, revealing varying degrees of powdery mildew resistance conferred by the transgenes. Here, we tested four transgenic lines each carrying two pyramided Pm3 alleles, which were generated by crossbreeding of lines transformed with single Pm3 alleles. All four allele-pyramided lines showed strongly improved powdery mildew resistance in the field compared to their parental lines. The improved resistance results from the two effects of enhanced total transgene expression levels and allele-specificity combinations. In contrast to leaf segment tests on greenhouse-grown seedlings, no allelic suppression was observed in the field. Plant development and yield scores of the pyramided lines were similar to the mean scores of the corresponding parental lines, and thus, the allele pyramiding did not cause any negative effects. On the contrary, in pyramided line, Pm3b × Pm3f normal plant development was restored compared to the delayed development and reduced seed set of parental line Pm3f. Allele-specific RT qPCR revealed additive transgene expression levels of the two Pm3 alleles in the pyramided lines. A positive correlation between total transgene expression level and powdery mildew field resistance was observed. In summary, allele pyramiding of Pm3 transgenes proved to be successful in enhancing powdery mildew field resistance.

  5. Enhanced radiative Auger emission from lithiumlike 20Ca17+

    International Nuclear Information System (INIS)

    Bernstein, E.M.; Clark, M.W.; Tanis, J.A.; Graham, W.G.; Morgan, T.J.; Stoeckli, M.P.; Berkner, K.H.; Schlachter, A.S.; Stearns, J.W.

    1991-01-01

    Radiative Auger emission (RAE) from lithiumlike 20 Ca 17+ projectiles excited in collisions with He has been measured. The intensity of RAE photons relative to K α X-ray emission is enhanced by a factor of 10-17 compared with theoretical calculations for ions with few electron vacancies. The enhancement of RAE for Ca 17+ is consistent with the results reported previously for lithiumlike 16 S 13+ and 23 V 20+ and indicates a systematic dependence on Z. Both the enhancement and the relative RAE transition rate increase with Z. (orig.)

  6. Control of recollection by slow gamma dominating mid-frequency gamma in hippocampus CA1

    Science.gov (United States)

    Dvorak, Dino; Radwan, Basma; Sparks, Fraser T.; Talbot, Zoe Nicole

    2018-01-01

    Behavior is used to assess memory and cognitive deficits in animals like Fmr1-null mice that model Fragile X Syndrome, but behavior is a proxy for unknown neural events that define cognitive variables like recollection. We identified an electrophysiological signature of recollection in mouse dorsal Cornu Ammonis 1 (CA1) hippocampus. During a shocked-place avoidance task, slow gamma (SG) (30–50 Hz) dominates mid-frequency gamma (MG) (70–90 Hz) oscillations 2–3 s before successful avoidance, but not failures. Wild-type (WT) but not Fmr1-null mice rapidly adapt to relocating the shock; concurrently, SG/MG maxima (SGdom) decrease in WT but not in cognitively inflexible Fmr1-null mice. During SGdom, putative pyramidal cell ensembles represent distant locations; during place avoidance, these are avoided places. During shock relocation, WT ensembles represent distant locations near the currently correct shock zone, but Fmr1-null ensembles represent the formerly correct zone. These findings indicate that recollection occurs when CA1 SG dominates MG and that accurate recollection of inappropriate memories explains Fmr1-null cognitive inflexibility. PMID:29346381

  7. Intraoperative tractography and neuronavigation of the pyramidal tract

    International Nuclear Information System (INIS)

    Nimsky, C.; Ganslandt, O.; Weigel, D.; Keller, B. von; Stadlbauer, A.; Akutsu, H.; Hammen, T.; Buchfelder, M.

    2008-01-01

    Diffusion tensor imaging (DTI) based fiber tracking was applied to visualize the course of the pyramidal tract in the surgical field by microscope-based navigation. In 70 patients with lesions adjacent to the pyramidal tract, DTI data were integrated in a navigational setup. Diffusion data (b=0) were rigidly registered with standard T1-weighted 3-D images. Fiber tracking was performed applying a tensor-deflection algorithm using a multiple volume of interest approach as seed regions for tracking. fMRI data identifying the motor gyrus were applied as selection criteria to define the fibers of interest. After tracking, a 3-D object was generated representing the pyramidal tract. In selected cases, the intraoperative image data (1.5 T intraoperative MRI) were used to update the navigation system. In all patients the pyramidal tract could be visualized in the operative field applying the heads-up display of the operating microscope. In 8 patients (11%) a new or aggravated postoperative paresis could be observed, which was transient in 5 of them; thus, only in 3 patients (4.2%) was there a new permanent neurological deficit. Intraoperative imaging depicted a shifting of the pyramidal tract which amounted up to 15 mm; even the direction of shifting was variable and could not be predicted before surgery, so that mathematical models trying to predict brain shift behaviour are of restricted value only. DTI fiber tracking data can be reliably integrated into navigational systems providing intraoperative visualization of the pyramidal tract. This technique allowed the resection of lesions adjacent to the pyramidal tract with low morbidity. (author)

  8. Cell type-specific genetic and optogenetic tools reveal hippocampal CA2 circuits.

    Science.gov (United States)

    Kohara, Keigo; Pignatelli, Michele; Rivest, Alexander J; Jung, Hae-Yoon; Kitamura, Takashi; Suh, Junghyup; Frank, Dominic; Kajikawa, Koichiro; Mise, Nathan; Obata, Yuichi; Wickersham, Ian R; Tonegawa, Susumu

    2014-02-01

    The formation and recall of episodic memory requires precise information processing by the entorhinal-hippocampal network. For several decades, the trisynaptic circuit entorhinal cortex layer II (ECII)→dentate gyrus→CA3→CA1 and the monosynaptic circuit ECIII→CA1 have been considered the primary substrates of the network responsible for learning and memory. Circuits linked to another hippocampal region, CA2, have only recently come to light. Using highly cell type-specific transgenic mouse lines, optogenetics and patch-clamp recordings, we found that dentate gyrus cells, long believed to not project to CA2, send functional monosynaptic inputs to CA2 pyramidal cells through abundant longitudinal projections. CA2 innervated CA1 to complete an alternate trisynaptic circuit, but, unlike CA3, projected preferentially to the deep, rather than to the superficial, sublayer of CA1. Furthermore, contrary to existing knowledge, ECIII did not project to CA2. Our results allow a deeper understanding of the biology of learning and memory.

  9. Top-down cellular pyramids

    Energy Technology Data Exchange (ETDEWEB)

    Wu, A Y; Rosenfeld, A

    1983-10-01

    A cellular pyramid is an exponentially tapering stack of arrays of processors (cells), where each cell is connected to its neighbors (siblings) on its own level, to a parent on the level above, and to its children on the level below. It is shown that in some situations, if information flows top-down only, from fathers to sons, then a cellular pyramid may be no faster than a one-level cellular array; but it may be possible to use simpler cells in the pyramid case. 23 references.

  10. David Macaulay's Pyramid.

    Science.gov (United States)

    Frew, Andrew W.

    1997-01-01

    Integrating literature and mathematics can be meaningful using David Macaulay's "Pyramid." This article provides an annotated bibliography of picture books, fiction, folk tales, nonfiction, videotapes, audio books, and CD-ROMs for grades 1-12 to support a unit on Egypt. Describes related math activities; and highlights a catalog of…

  11. RUN1 and REN1 Pyramiding in Grapevine (Vitis vinifera cv. Crimson Seedless) Displays an Improved Defense Response Leading to Enhanced Resistance to Powdery Mildew (Erysiphe necator)

    Science.gov (United States)

    Agurto, Mario; Schlechter, Rudolf O.; Armijo, Grace; Solano, Esteban; Serrano, Carolina; Contreras, Rodrigo A.; Zúñiga, Gustavo E.; Arce-Johnson, Patricio

    2017-01-01

    Fungal pathogens are the cause of the most common diseases in grapevine and among them powdery mildew represents a major focus for disease management. Different strategies for introgression of resistance in grapevine are currently undertaken in breeding programs. For example, introgression of several resistance genes (R) from different sources for making it more durable and also strengthening the plant defense response. Taking this into account, we cross-pollinated P09-105/34, a grapevine plant carrying both RUN1 and REN1 pyramided loci of resistance to Erysiphe necator inherited from a pseudo-backcrossing scheme with Muscadinia rotundifolia and Vitis vinifera ‘Dzhandzhal Kara,’ respectively, with the susceptible commercial table grape cv. ‘Crimson Seedless.’ We developed RUN1REN1 resistant genotypes through conventional breeding and identified them by marker assisted selection. The characterization of defense response showed a highly effective defense mechanism against powdery mildew in these plants. Our results reveal that RUN1REN1 grapevine plants display a robust defense response against E. necator, leading to unsuccessful fungal establishment with low penetration rate and poor hypha development. This resistance mechanism includes reactive oxygen species production, callose accumulation, programmed cell death induction and mainly VvSTS36 and VvPEN1 gene activation. RUN1REN1 plants have a great potential as new table grape cultivars with durable complete resistance to E. necator, and are valuable germplasm to be included in grape breeding programs to continue pyramiding with other sources of resistance to grapevine diseases. PMID:28553300

  12. Cell-specific expression of calcineurin immunoreactivity within the rat basolateral amygdala complex and colocalization with the neuropeptide Y Y1 receptor.

    Science.gov (United States)

    Leitermann, Randy J; Sajdyk, Tammy J; Urban, Janice H

    2012-10-01

    Neuropeptide Y (NPY) produces potent anxiolytic effects via activation of NPY Y1 receptors (Y1r) within the basolateral amygdaloid complex (BLA). The role of NPY in the BLA was recently expanded to include the ability to produce stress resilience and long-lasting reductions in anxiety-like behavior. These persistent behavioral effects are dependent upon activity of the protein phosphatase, calcineurin (CaN), which has long been associated with shaping long-term synaptic signaling. Furthermore, NPY-induced reductions in anxiety-like behavior persist months after intra-BLA delivery, which together indicate a form of neuronal plasticity had likely occurred. To define a site of action for NPY-induced CaN signaling within the BLA, we employed multi-label immunohistochemistry to determine which cell types express CaN and if CaN colocalizes with the Y1r. We have previously reported that both major neuronal cell populations in the BLA, pyramidal projection neurons and GABAergic interneurons, express the Y1r. Therefore, this current study evaluated CaN immunoreactivity in these cell types, along with Y1r immunoreactivity. Antibodies against calcium-calmodulin kinase II (CaMKII) and GABA were used to identify pyramidal neurons and GABAergic interneurons, respectively. A large population of CaN immunoreactive cells displayed Y1r immunoreactivity (90%). Nearly all (98%) pyramidal neurons displayed CaN immunoreactivity, while only a small percentage of interneurons (10%) contained CaN immunoreactivity. Overall, these anatomical findings provide a model whereby NPY could directly regulate CaN activity in the BLA via activation of the Y1r on CaN-expressing, pyramidal neurons. Importantly, they support BLA pyramidal neurons as prime targets for neuronal plasticity associated with the long-term reductions in anxiety-like behavior produced by NPY injections into the BLA. Copyright © 2012 Elsevier B.V. All rights reserved.

  13. Urban public health: is there a pyramid?

    Science.gov (United States)

    Su, Meirong; Chen, Bin; Yang, Zhifeng; Cai, Yanpeng; Wang, Jiao

    2013-01-28

    Early ecologists identified a pyramidal trophic structure in terms of number, biomass and energy transfer. In 1943, the psychologist Maslow put forward a pyramid model to describe layers of human needs. It is indicated that the pyramid principle is universally applicable in natural, humanistic and social disciplines. Here, we report that a pyramid structure also exists in urban public health (UPH). Based on 18 indicators, the UPH states of four cities (Beijing, Tokyo, New York, and London) are compared from the point of view of five aspects, namely physical health, living conditions, social security, environmental quality, and education and culture. A pyramid structure was found in each city when focusing on 2000-2009 data. The pyramid of Beijing is relatively similar to that of Tokyo, and the pyramids of New York and London are similar to each other. A general development trend in UPH is proposed and represented by different pyramid modes. As a basic conjecture, the UPH pyramid model can be verified and developed with data of more cities over a longer period, and be used to promote healthy urban development.

  14. Design and Preparation of a Micro-Pyramid Structured Thin Film for Broadband Infrared Antireflection

    Directory of Open Access Journals (Sweden)

    Shaobo Ge

    2018-05-01

    Full Text Available A micro-pyramid structured thin film with a broad-band infrared antireflection property is designed and fabricated by using the single-point diamond turning (SPDT technique and combined with nano-imprint lithography (NIL. A structure with dimensions of 10 μm pitch and 5 μm height is transferred from the copper mold to the silicon nitride optical film by using NIL and proportional inductively-coupled plasma (ICP etching. Reflectance of the micro-optical surface is reduced below 1.0% over the infrared spectral range (800–2500 nm. A finite-difference-time-domain (FDTD analysis indicates that this micro-structure can localize photons and enhance the absorption inside the micro-pyramid at long wavelengths. As described above, the micro-pyramid array has been integrated in an optical film successfully. Distinguishing from the traditional micro-optical components, considering the effect of refraction and diffraction, it is a valuable and flexible method to take account of the interference effect of optical film.

  15. 4-containing GABA receptors at the hippocampal CA1 spines is a biomarker for resilience to food restriction-evoked excessive exercise and weight loss of adolescent female rats

    Science.gov (United States)

    Aoki, Chiye; Wable, Gauri; Chowdhury, Tara G.; Sabaliauskas, Nicole A.; Laurino, Kevin; Barbarich-Marsteller, Nicole C.

    2014-01-01

    Anorexia nervosa (AN) is a psychiatric illness characterized by restricted eating and an intense fear of gaining weight. Most individuals with AN are females, diagnosed first during adolescence, 40% to 80% of whom exhibit excessive exercise, and an equally high number with a history of anxiety disorder. We sought to determine the cellular basis for individual differences in AN vulnerability by using an animal model, activity-based anorexia (ABA), that is induced by combining food restriction (FR) with access to a running wheel that allows voluntary exercise. Previously, we showed that by the 4th day of FR, the ABA group of adolescent female rats exhibit > 500% greater levels of non-synaptic α4βδ−GABAARs at the plasma membrane of hippocampal CA1 pyramidal cell spines, relative to the levels found in age-matched controls that are not FR and without wheel access. Here, we show that the ABA group exhibits individual differences in body weight loss, with some losing nearly 30%, while others lose only 15%. The individual differences in weight loss are ascribable to individual differences in wheel activity that both precedes and concurs with days of FR. Moreover, the increase in activity during FR correlates strongly and negatively with α4βδ−GABAAR levels (R= - 0.9, p<0.01). This negative correlation is evident within 2 days of FR, before body weight loss approaches life-threatening levels for any individual. These findings suggest that increased shunting inhibition by α4βδ−GABAARs in spines of CA1 pyramidal neurons may participate in the protection against the ABA-inducing environmental factors of severe weight loss by suppressing excitability of the CA1 pyramidal neurons which, in turn, is related indirectly to suppression of excessive exercise. The data also indicate that, although exercise has many health benefits, it can be maladaptive to individuals with low levels of α4βδ−GABAARs in the CA1, particularly when combined with FR. PMID:24444828

  16. Long term delivery of pulsed magnetic fields does not alter visual discrimination learning or dendritic spine density in the mouse CA1 pyramidal or dentate gyrus neurons [v2; ref status: indexed, http://f1000r.es/2gk

    Directory of Open Access Journals (Sweden)

    Matthew Sykes

    2013-12-01

    Full Text Available Repetitive transcranial magnetic stimulation (rTMS is thought to facilitate brain plasticity. However, few studies address anatomical changes following rTMS in relation to behaviour. We delivered 5 weeks of daily pulsed rTMS stimulation to adult ephrin-A2-/- and wildtype (C57BI/6j mice (n=10 per genotype undergoing a visual learning task and analysed learning performance, as well as spine density, in the dentate gyrus molecular and CA1 pyramidal cell layers in Golgi-stained brain sections. We found that neither learning behaviour, nor hippocampal spine density was affected by long term rTMS. Our negative results highlight the lack of deleterious side effects in normal subjects and are consistent with previous studies suggesting that rTMS has a bigger effect on abnormal or injured brain substrates than on normal/control structures.

  17. Urban Public Health: Is There a Pyramid?

    Directory of Open Access Journals (Sweden)

    Meirong Su

    2013-01-01

    Full Text Available Early ecologists identified a pyramidal trophic structure in terms of number, biomass and energy transfer. In 1943, the psychologist Maslow put forward a pyramid model to describe layers of human needs. It is indicated that the pyramid principle is universally applicable in natural, humanistic and social disciplines. Here, we report that a pyramid structure also exists in urban public health (UPH. Based on 18 indicators, the UPH states of four cities (Beijing, Tokyo, New York, and London are compared from the point of view of five aspects, namely physical health, living conditions, social security, environmental quality, and education and culture. A pyramid structure was found in each city when focusing on 2000–2009 data. The pyramid of Beijing is relatively similar to that of Tokyo, and the pyramids of New York and London are similar to each other. A general development trend in UPH is proposed and represented by different pyramid modes. As a basic conjecture, the UPH pyramid model can be verified and developed with data of more cities over a longer period, and be used to promote healthy urban development.

  18. Functional optical probing of the hippocampal trisynaptic circuit in vitro: network dynamics, filter properties, and polysynaptic induction of CA1 LTP.

    Science.gov (United States)

    Stepan, Jens; Dine, Julien; Eder, Matthias

    2015-01-01

    Decades of brain research have identified various parallel loops linking the hippocampus with neocortical areas, enabling the acquisition of spatial and episodic memories. Especially the hippocampal trisynaptic circuit [entorhinal cortex layer II → dentate gyrus (DG) → cornu ammonis (CA)-3 → CA1] was studied in great detail because of its seemingly simple connectivity and characteristic structures that are experimentally well accessible. While numerous researchers focused on functional aspects, obtained from a limited number of cells in distinct hippocampal subregions, little is known about the neuronal network dynamics which drive information across multiple synapses for subsequent long-term storage. Fast voltage-sensitive dye imaging in vitro allows real-time recording of activity patterns in large/meso-scale neuronal networks with high spatial resolution. In this way, we recently found that entorhinal theta-frequency input to the DG most effectively passes filter mechanisms of the trisynaptic circuit network, generating activity waves which propagate across the entire DG-CA axis. These "trisynaptic circuit waves" involve high-frequency firing of CA3 pyramidal neurons, leading to a rapid induction of classical NMDA receptor-dependent long-term potentiation (LTP) at CA3-CA1 synapses (CA1 LTP). CA1 LTP has been substantially evidenced to be essential for some forms of explicit learning in mammals. Here, we review data with particular reference to whole network-level approaches, illustrating how activity propagation can take place within the trisynaptic circuit to drive formation of CA1 LTP.

  19. Relevance of the pyramidal syndrome in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Álvarez, N; Díez, L; Avellaneda, C; Serra, M; Rubio, M Á

    Pyramidal signs (hyperreflexia, spasticity, Babinski sign) are essential for the diagnosis of amyotrophic lateral sclerosis (ALS). However, these signs are not always present at onset and may vary over time, besides which their role in disease evolution is controversial. Our goal was to describe which pyramidal signs were present and how they evolved in a cohort of patients with ALS, as well as their role in prognosis. Retrospective analysis of prospectively collected patients diagnosed with ALS in our centre from 1990 to 2015. Of a total of 130 patients with ALS, 34 (26.1%) patients showed no pyramidal signs at the first visit while 15 (11.5%) had a complete pyramidal syndrome. Of those patients without initial pyramidal signs, mean time of appearance of the first signs was 4.5 months. Babinski sign was positive in 64 (49.2%) patients, hyperreflexia in 90 (69.2%) and 22 (16.9%) patients had spasticity. Pyramidal signs tended to remain unchanged over time, although they seem to appear at later stages or even disappear with time in some patients. We found no association between survival and the presence of changes to pyramidal signs, although decreased spasticity was associated with greater clinical deterioration (ALSFR scale) (P<.001). A quarter of patients with ALS initially showed no pyramidal signs and in some cases they even disappear over time. These data support the need for tools that assess the pyramidal tract. Copyright © 2016 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

  20. INSTABILITY MODELING OF FINANCIAL PYRAMIDS

    OpenAIRE

    Girdzijauskas, Stasys; Moskaliova, Vera

    2005-01-01

    The financial structures that make use of money flow for “easy money” or cheating purpose are called financial pyramids. Recently financial pyramids intensively penetrates IT area. It is rather suitable way of the fraud. Money flow modeling and activity analysis of such financial systems allows identifying financial pyramids and taking necessary means of precautions. In the other hand even investing companies that function normally when market conditions changes (e.g. interest rates) eventual...

  1. Npas4 Is a Critical Regulator of Learning-Induced Plasticity at Mossy Fiber-CA3 Synapses during Contextual Memory Formation.

    Science.gov (United States)

    Weng, Feng-Ju; Garcia, Rodrigo I; Lutzu, Stefano; Alviña, Karina; Zhang, Yuxiang; Dushko, Margaret; Ku, Taeyun; Zemoura, Khaled; Rich, David; Garcia-Dominguez, Dario; Hung, Matthew; Yelhekar, Tushar D; Sørensen, Andreas Toft; Xu, Weifeng; Chung, Kwanghun; Castillo, Pablo E; Lin, Yingxi

    2018-03-07

    Synaptic connections between hippocampal mossy fibers (MFs) and CA3 pyramidal neurons are essential for contextual memory encoding, but the molecular mechanisms regulating MF-CA3 synapses during memory formation and the exact nature of this regulation are poorly understood. Here we report that the activity-dependent transcription factor Npas4 selectively regulates the structure and strength of MF-CA3 synapses by restricting the number of their functional synaptic contacts without affecting the other synaptic inputs onto CA3 pyramidal neurons. Using an activity-dependent reporter, we identified CA3 pyramidal cells that were activated by contextual learning and found that MF inputs on these cells were selectively strengthened. Deletion of Npas4 prevented both contextual memory formation and this learning-induced synaptic modification. We further show that Npas4 regulates MF-CA3 synapses by controlling the expression of the polo-like kinase Plk2. Thus, Npas4 is a critical regulator of experience-dependent, structural, and functional plasticity at MF-CA3 synapses during contextual memory formation. Copyright © 2018 Elsevier Inc. All rights reserved.

  2. Pyramiding for Resistance Durability: Theory and Practice.

    Science.gov (United States)

    Mundt, Chris

    2018-04-12

    Durable disease resistance is a key component of global food security, and combining resistance genes into "pyramids" is an important way to increase durability of resistance. The mechanisms by which pyramids impact durability are not well known. The traditional view of resistance pyramids considers the use of major resistance gene (R-gene) combinations deployed against pathogens that are primarily asexual. Interestingly, published examples of the successful use of pyramids in the traditional sense are rare. In contrast, most published descriptions of durable pyramids in practice are for cereal rusts, and tend to indicate an association between durability and cultivars combining major R-genes with incompletely expressed, adult plant resistance genes. Pyramids have been investigated experimentally for a diversity of pathogens, and many reduce disease levels below that of the single best gene. Resistance gene combinations have been identified through phenotypic reactions, molecular markers, and challenge against effector genes. As resistance genes do not express equally in all genetic backgrounds, however, a combination of genetic information and phenotypic analyses provide the ideal scenario for testing of putative pyramids. Not all resistance genes contribute equally to pyramids, and approaches have been suggested to identify the best genes and combinations of genes for inclusion. Combining multiple resistance genes into a single plant genotype quickly is a challenge that is being addressed through alternative breeding approaches, as well as through genomics tools such as resistance gene cassettes and gene editing. Experimental and modeling tests of pyramid durability are in their infancy, but have promise to help direct future studies of pyramids. Several areas for further work on resistance gene pyramids are suggested.

  3. Pyramid Comet Sampler, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — Based on the sampling requirements, we propose an Inverted Pyramid sampling system. Each face of the pyramid includes a cutting blade which is independently actuated...

  4. Capsicum annuum homeobox 1 (CaHB1) is a nuclear factor that has roles in plant development, salt tolerance, and pathogen defense

    Energy Technology Data Exchange (ETDEWEB)

    Oh, Sang-Keun; Yoon, Joonseon [Department of Plant Science, College of Agriculture and Life Sciences, Seoul National University, Seou1 151-742 (Korea, Republic of); Choi, Gyung Ja [Screening Division, Korea Research Institute of Chemical Technology, Daejeon 305-600 (Korea, Republic of); Jang, Hyun A; Kwon, Suk-Yoon [Korea Research Institute of Bioscience and Biotechnology, Yusung, Daejeon 305-600 (Korea, Republic of); Choi, Doil, E-mail: doil@snu.ac.kr [Department of Plant Science, College of Agriculture and Life Sciences, Seoul National University, Seou1 151-742 (Korea, Republic of)

    2013-12-06

    Highlights: •The CaHB1 is a nuclear factor, belonging to HD-Zip proteins. •SA and ET, as signal molecules, modulate CaHB1-mediated responses. •Overexpression of CaHB1 in tomato resulted in a thicker cell wall. •CaHB1-transgenic tomato confers resistance to Phytophthora infestans. •CaHB1 enhanced tolerance to saline stress in tomato. -- Abstract: Homeodomain-leucine zipper (HD-Zip) family proteins are unique to plants, but little is known about their role in defense responses. CaHB1 is a nuclear factor in peppers, belonging to subfamily II of HD-Zip proteins. Here, we determined the role of CaHB1 in the defense response. CaHB1 expression was induced when pepper plants were challenged with Phytophthora capsici, a plant pathogen to which peppers are susceptible, or environmental stresses such as drought and salt stimuli. CaHB1 was also highly expressed in pepper leaves following application of SA, whereas ethephon and MeJA had a moderate effect. To further investigate the function of CaHB1 in plants, we performed gain-of-function study by overexpression of CaHB1 in tomato. CaHB1-transgenic tomatoes showed significant growth enhancement including increased leaf thickness and enlarged cell size (1.8-fold larger than control plants). Microscopic analysis revealed that leaves from CaHB1-transgenic plants had thicker cell walls and cuticle layers than those from controls. Moreover, CaHB1-transgenic plants displayed enhanced resistance against Phytophthora infestans and increased tolerance to salt stress. Additionally, RT-PCR analysis of CaHB1-transgenic tomatoes revealed constitutive up-regulation of multiple genes involved in plant defense and osmotic stress. Therefore, our findings suggest roles for CaHB1 in development, salt stress, and pathogen defense.

  5. Capsicum annuum homeobox 1 (CaHB1) is a nuclear factor that has roles in plant development, salt tolerance, and pathogen defense

    International Nuclear Information System (INIS)

    Oh, Sang-Keun; Yoon, Joonseon; Choi, Gyung Ja; Jang, Hyun A; Kwon, Suk-Yoon; Choi, Doil

    2013-01-01

    Highlights: •The CaHB1 is a nuclear factor, belonging to HD-Zip proteins. •SA and ET, as signal molecules, modulate CaHB1-mediated responses. •Overexpression of CaHB1 in tomato resulted in a thicker cell wall. •CaHB1-transgenic tomato confers resistance to Phytophthora infestans. •CaHB1 enhanced tolerance to saline stress in tomato. -- Abstract: Homeodomain-leucine zipper (HD-Zip) family proteins are unique to plants, but little is known about their role in defense responses. CaHB1 is a nuclear factor in peppers, belonging to subfamily II of HD-Zip proteins. Here, we determined the role of CaHB1 in the defense response. CaHB1 expression was induced when pepper plants were challenged with Phytophthora capsici, a plant pathogen to which peppers are susceptible, or environmental stresses such as drought and salt stimuli. CaHB1 was also highly expressed in pepper leaves following application of SA, whereas ethephon and MeJA had a moderate effect. To further investigate the function of CaHB1 in plants, we performed gain-of-function study by overexpression of CaHB1 in tomato. CaHB1-transgenic tomatoes showed significant growth enhancement including increased leaf thickness and enlarged cell size (1.8-fold larger than control plants). Microscopic analysis revealed that leaves from CaHB1-transgenic plants had thicker cell walls and cuticle layers than those from controls. Moreover, CaHB1-transgenic plants displayed enhanced resistance against Phytophthora infestans and increased tolerance to salt stress. Additionally, RT-PCR analysis of CaHB1-transgenic tomatoes revealed constitutive up-regulation of multiple genes involved in plant defense and osmotic stress. Therefore, our findings suggest roles for CaHB1 in development, salt stress, and pathogen defense

  6. A Backward Pyramid Oriented Optical Flow Field Computing Method for Aerial Image

    Directory of Open Access Journals (Sweden)

    LI Jiatian

    2016-09-01

    Full Text Available Aerial image optical flow field is the foundation for detecting moving objects at low altitude and obtaining change information. In general,the image pyramid structure is embedded in numerical procedure in order to enhance the convergence globally. However,more often than not,the pyramid structure is constructed using a bottom-up approach progressively,ignoring the geometry imaging process.In particular,when the ground objects moving it will lead to miss optical flow or the optical flow too small that could hardly sustain the subsequent modeling and analyzing issues. So a backward pyramid structure is proposed on the foundation of top-level standard image. Firstly,down sampled factors of top-level image are calculated quantitatively through central projection,which making the optical flow in top-level image represent the shifting threshold of the set ground target. Secondly,combining top-level image with its original,the down sampled factors in middle layer are confirmed in a constant proportion way. Finally,the image of middle layer is achieved by Gaussian smoothing and image interpolation,and meanwhile the pyramid is formed. The comparative experiments and analysis illustrate that the backward pyramid can calculate the optic flow field in aerial image accurately,and it has advantages in restraining small ground displacement.

  7. Enhancement of Mechanical Properties of Extruded Mg-9Al-1Zn-1MM-0.7CaO-0.3Mn Alloy Through Pre-aging Treatment

    Science.gov (United States)

    Jeong, Seok Hoan; Kim, Yong Joo; Kong, Kyung Ho; Cho, Tae Hee; Kim, Young Kyun; Lim, Hyun Kyu; Kim, Won Tae; Kim, Do Hyang

    2018-03-01

    The effect of pre-aging treatment before extrusion has been investigated in Mg-9.0Al-1.0Zn-1MM-0.7CaO-0.3Mn alloy. The as-cast microstructure consists of α-Mg dendrite with secondary solidification phase particles, (Mg, Al)2Ca, β-Mg17Al12 and Al11RE3 at the inter-dendritic region. After extrusion, β-Mg17Al12 precipitates are present, but higher density and more homogeneous distribution in pre-aged alloy. In addition, μm-scale banded bulk β-Mg17Al12 particles are generated during extrusion. Al11RE3 particles are broken into small particles, and are aligned along the extrusion direction. (Mg, Al)2Ca particles are only slightly elongated along the extrusion direction, providing stronger particle stimulated nucleation (PSN) effect by severe deformation during extrusion. The mechanical properties can be significantly enhanced by introducing pre-aging treatment, i.e. β-Mg17Al12 precipitates provide grain refining and strengthening effects and (Mg, Al)2Ca particles provide PSN effect.

  8. Pyramid solar micro-grid

    Science.gov (United States)

    Huang, Bin-Juine; Hsu, Po-Chien; Wang, Yi-Hung; Tang, Tzu-Chiao; Wang, Jia-Wei; Dong, Xin-Hong; Hsu, Hsin-Yi; Li, Kang; Lee, Kung-Yen

    2018-03-01

    A novel pyramid solar micro-grid is proposed in the present study. All the members within the micro-grid can mutually share excess solar PV power each other through a binary-connection hierarchy. The test results of a 2+2 pyramid solar micro-grid consisting of 4 individual solar PV systems for self-consumption are reported.

  9. A computational simulation of long-term synaptic potentiation inducing protocol processes with model of CA3 hippocampal microcircuit.

    Science.gov (United States)

    Świetlik, D; Białowąs, J; Kusiak, A; Cichońska, D

    2018-01-01

    An experimental study of computational model of the CA3 region presents cog-nitive and behavioural functions the hippocampus. The main property of the CA3 region is plastic recurrent connectivity, where the connections allow it to behave as an auto-associative memory. The computer simulations showed that CA3 model performs efficient long-term synaptic potentiation (LTP) induction and high rate of sub-millisecond coincidence detection. Average frequency of the CA3 pyramidal cells model was substantially higher in simulations with LTP induction protocol than without the LTP. The entropy of pyramidal cells with LTP seemed to be significantly higher than without LTP induction protocol (p = 0.0001). There was depression of entropy, which was caused by an increase of forgetting coefficient in pyramidal cells simulations without LTP (R = -0.88, p = 0.0008), whereas such correlation did not appear in LTP simulation (p = 0.4458). Our model of CA3 hippocampal formation microcircuit biologically inspired lets you understand neurophysiologic data. (Folia Morphol 2018; 77, 2: 210-220).

  10. Methylphenidate enhances NMDA-receptor response in medial prefrontal cortex via sigma-1 receptor: a novel mechanism for methylphenidate action.

    Directory of Open Access Journals (Sweden)

    Chun-Lei Zhang

    Full Text Available Methylphenidate (MPH, commercially called Ritalin or Concerta, has been widely used as a drug for Attention Deficit Hyperactivity Disorder (ADHD. Noteworthily, growing numbers of young people using prescribed MPH improperly for pleasurable enhancement, take high risk of addiction. Thus, understanding the mechanism underlying high level of MPH action in the brain becomes an important goal nowadays. As a blocker of catecholamine transporters, its therapeutic effect is explained as being due to proper modulation of D1 and α2A receptor. Here we showed that higher dose of MPH facilitates NMDA-receptor mediated synaptic transmission via a catecholamine-independent mechanism, in layer V∼VI pyramidal cells of the rat medial prefrontal cortex (PFC. To indicate its postsynaptic action, we next found that MPH facilitates NMDA-induced current and such facilitation could be blocked by σ1 but not D1/5 and α2 receptor antagonists. And this MPH eliciting enhancement of NMDA-receptor activity involves PLC, PKC and IP3 receptor mediated intracellular Ca(2+ increase, but does not require PKA and extracellular Ca(2+ influx. Our additional pharmacological studies confirmed that higher dose of MPH increases locomotor activity via interacting with σ1 receptor. Together, the present study demonstrates for the first time that MPH facilitates NMDA-receptor mediated synaptic transmission via σ1 receptor, and such facilitation requires PLC/IP3/PKC signaling pathway. This novel mechanism possibly explains the underlying mechanism for MPH induced addictive potential and other psychiatric side effects.

  11. Differential regulation of the excitability of prefrontal cortical fast-spiking interneurons and pyramidal neurons by serotonin and fluoxetine.

    Directory of Open Access Journals (Sweden)

    Ping Zhong

    2011-02-01

    Full Text Available Serotonin exerts a powerful influence on neuronal excitability. In this study, we investigated the effects of serotonin on different neuronal populations in prefrontal cortex (PFC, a major area controlling emotion and cognition. Using whole-cell recordings in PFC slices, we found that bath application of 5-HT dose-dependently increased the firing of FS (fast spiking interneurons, and decreased the firing of pyramidal neurons. The enhancing effect of 5-HT in FS interneurons was mediated by 5-HT₂ receptors, while the reducing effect of 5-HT in pyramidal neurons was mediated by 5-HT₁ receptors. Fluoxetine, the selective serotonin reuptake inhibitor, also induced a concentration-dependent increase in the excitability of FS interneurons, but had little effect on pyramidal neurons. In rats with chronic fluoxetine treatment, the excitability of FS interneurons was significantly increased, while pyramidal neurons remained unchanged. Fluoxetine injection largely occluded the enhancing effect of 5-HT in FS interneurons, but did not alter the reducing effect of 5-HT in pyramidal neurons. These data suggest that the excitability of PFC interneurons and pyramidal neurons is regulated by exogenous 5-HT in an opposing manner, and FS interneurons are the major target of Fluoxetine. It provides a framework for understanding the action of 5-HT and antidepressants in altering PFC network activity.

  12. Climbing the Needs Pyramids

    Directory of Open Access Journals (Sweden)

    J. C. Lomas

    2013-08-01

    Full Text Available Abraham Maslow’s theory of human adult motivation is often represented by a pyramid image showing two proposals: First, the five needs stages in emergent order of hierarchical ascension and second, a percentage of the adult population suggested to occupy each needs tier. Specifically, Maslow proposed that adults would be motivated to satisfy their unfilled needs until they reached the hierarchy’s apex and achieved self-transcendence. Yet how adults can purposefully ascend Maslow’s pyramid through satisfying unfilled needs remains elusive. This brief article challenges this on the theory’s 70th anniversary by presenting a new image of the needs hierarchy, based on ecological design principles to support adults’ purposeful endeavors to climb the needs pyramid.

  13. Investigation of the Great Pyramid of Giza.

    Science.gov (United States)

    Peace, Nigel; And Others

    1997-01-01

    Describes an activity in which geometry and trigonometry are studied using pyramids. Identical model pyramids are constructed from card stock, along with pyramids of different proportions and cuboids to use as controls. Also includes an investigation of some apparently non-scientific claims. (DDR)

  14. Renal pyramid echogenicity in ureteropelvic junction obstruction: correlation between altered echogenicity and differential renal function

    Energy Technology Data Exchange (ETDEWEB)

    Chavhan, Govind; Daneman, Alan; Lim, Ruth; Traubici, Jeffrey [University of Toronto, Department of Diagnostic Imaging, The Hospital for Sick Children, Toronto (Canada); Moineddin, Rahim [University of Toronto, Department of Family and Community Medicine, Toronto (Canada); Langlois, Valerie [University of Toronto, Division of Nephrology, Department of Pediatrics, Hospital for Sick Children, Toronto (Canada)

    2008-10-15

    Improvement in resolution and use of high-frequency transducers in US has enabled visualization of previously unreported changes in medullary pyramid echogenicity in children with obstructive hydronephrosis. To determine whether these unreported changes in echogenicity and morphology of the renal pyramids in ureteropelvic junction (UPJ) obstruction correlate with differential renal function (DRF) of the kidney as determined by technetium-99m mercaptoacetyltriglycine ({sup 99m}Tc-MAG3) scan. Renal sonograms in 60 children with UPJ obstruction were retrospectively reviewed. Children were divided into three groups based on the echogenicity of the pyramids: (1) normal echogenicity of the pyramids, (2) increased echogenicity of the pyramids with maintained corticomedullary differentiation (CMD), and (3) loss of CMD. DRF, as determined by {sup 99m}Tc-MAG3 scan, of the obstructed kidney of {>=}45% was considered normal and of {<=}44% was considered abnormal based on a published study correlating histological changes with DRF. Fisher's exact test was performed for assessing the association between DRF and altered echogenicity of the pyramids. In group 1, which consisted of 13 patients with normal pyramids on US, DRF was normal in 11 and abnormal in two. In group 2, which consisted of 33 patients with echogenic pyramids and preserved CMD, DRF was normal in 15 and abnormal in 18. In group 3, which consisted of 14 patients with complete loss of CMD, DRF was normal in 2 and abnormal in 12. There was a strong correlation between abnormal pyramids and DRF (P=0.0009). The risk ratio (RR) of DRF becoming abnormal for those kidneys with abnormal echogenicity of the pyramids with preserved CMD (group 2) compared to normal pyramid echogenicity (group 1) was 1.56 (95% CI 1.088-2.236). The RR of DRF becoming abnormal for those kidneys with loss of CMD (group 3) compared to normal pyramid echogenicity (group 1) was 5.571 (95% CI 1.530-20.294). We observed that in obstructed kidneys

  15. Modulation of local field potentials by high-frequency stimulation of afferent axons in the hippocampal CA1 region.

    Science.gov (United States)

    Yu, Ying; Feng, Zhouyan; Cao, Jiayue; Guo, Zheshan; Wang, Zhaoxiang; Hu, Na; Wei, Xuefeng

    2016-03-01

    Modulation of the rhythmic activity of local field potentials (LFP) in neuronal networks could be a mechanism of deep brain stimulation (DBS). However, exact changes of LFP during the periods of high-frequency stimulation (HFS) of DBS are unclear because of the interference of dense stimulation artifacts with high amplitudes. In the present study, we investigated LFP changes induced by HFS of afferent axons in the hippocampal CA1 region of urethane-anesthetized rats by using a proper algorithm of artifact removal. Afterward, the LFP changes in the frequency bands of [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text] and [Formula: see text] rhythms were studied by power spectrum analysis and coherence analysis for the recorded signals collected in the pyramidal layer and in the stratum radiatum of CA1 region before, during and after 1-min long 100 and 200[Formula: see text]Hz HFS. Results showed that the power of LFP rhythms in higher-frequency band ([Formula: see text] rhythm) increased in the pyramidal layer and the power of LFP rhythms in lower-frequency bands ([Formula: see text], [Formula: see text] and [Formula: see text] rhythms) decreased in the stratum radiatum during HFS. The synchronization of [Formula: see text] rhythm decreased and the synchronization of [Formula: see text] rhythm increased during HFS in the stratum radiatum. These results suggest that axonal HFS could modulate LFP rhythms in the downstream brain areas with a plausible underlying mechanism of partial axonal blockage induced by HFS. The study provides new evidence to support the mechanism of DBS modulating rhythmic activity of neuronal populations.

  16. Imaging a Pyramid Interior by ERT-3D Methods, Preliminar Results at El Castillo Pyramid, Chichen Itza, Mexico

    Science.gov (United States)

    Chavez, R. E.; Tejero, A.; Cifuentes, G.; HernaNdez-Quintero, J. E.; Garcia-Serrano, A.

    2016-12-01

    The well known Pyramid El Castillo, located in the archaeological site of Chichen Itza, in the Yucatan Peninsula is the emblematic structure of this archaeological site and elected as one of the man-made world seven wonders. The archaeological team that restored this structure during the 1920's discovered a smaller pyramid inside this prehispanic body, which corresponded to an older Mayan period. The possibility of finding other constructive periods inside this edifice should be important to reconstruct the Mayan history. Previous geophysical studies carried out by us in 2014, employed novel Electrical Resistivity Tomography (ERT) arrays that surrounded the pyramids surface with flat electrodes to obtain a 3D image of the subsoil. At that time, a low resistivity body was found beneath the pyramid, which was associated to a sinkhole filled with sweet water. Employing the same technique, a series of flat electrodes were deployed on each body conforming the pyramid, a total of 10 bodies were covered, employing a different number of electrodes trying to keep the distance between each electrode constant ( 3 m). Each body was treated as a single observation cube, where the apparent resistivity data measured was later inverted. A precise topographic control for each electrode was realized and introduced in the inversion process. 45,000 observation points within the pyramid were obtained. Initially, each working cube corresponding to a given pyramid's body was inverted. A composition of each inversion was assembled to form the resistivity distribution within the pyramid using a smooth interpolation method. A high resistivity anomaly was found towards the northern portion of the model that could be associated to the main stairway of the inner pyramid. The cavity detected during the 2014 survey was observed as a low resistivity anomaly found at the pyramid's base. At the moment, we are assembling the full observed resistivity data as a single file to compute an integrated

  17. Altered Intrinsic Pyramidal Neuron Properties and Pathway-Specific Synaptic Dysfunction Underlie Aberrant Hippocampal Network Function in a Mouse Model of Tauopathy.

    Science.gov (United States)

    Booth, Clair A; Witton, Jonathan; Nowacki, Jakub; Tsaneva-Atanasova, Krasimira; Jones, Matthew W; Randall, Andrew D; Brown, Jonathan T

    2016-01-13

    The formation and deposition of tau protein aggregates is proposed to contribute to cognitive impairments in dementia by disrupting neuronal function in brain regions, including the hippocampus. We used a battery of in vivo and in vitro electrophysiological recordings in the rTg4510 transgenic mouse model, which overexpresses a mutant form of human tau protein, to investigate the effects of tau pathology on hippocampal neuronal function in area CA1 of 7- to 8-month-old mice, an age point at which rTg4510 animals exhibit advanced tau pathology and progressive neurodegeneration. In vitro recordings revealed shifted theta-frequency resonance properties of CA1 pyramidal neurons, deficits in synaptic transmission at Schaffer collateral synapses, and blunted plasticity and imbalanced inhibition at temporoammonic synapses. These changes were associated with aberrant CA1 network oscillations, pyramidal neuron bursting, and spatial information coding in vivo. Our findings relate tauopathy-associated changes in cellular neurophysiology to altered behavior-dependent network function. Dementia is characterized by the loss of learning and memory ability. The deposition of tau protein aggregates in the brain is a pathological hallmark of dementia; and the hippocampus, a brain structure known to be critical in processing learning and memory, is one of the first and most heavily affected regions. Our results show that, in area CA1 of hippocampus, a region involved in spatial learning and memory, tau pathology is associated with specific disturbances in synaptic, cellular, and network-level function, culminating in the aberrant encoding of spatial information and spatial memory impairment. These studies identify several novel ways in which hippocampal information processing may be disrupted in dementia, which may provide targets for future therapeutic intervention. Copyright © 2016 Booth, Witton et al.

  18. Large variability in synaptic N-methyl-D-aspartate receptor density on interneurons and a comparison with pyramidal-cell spines in the rat hippocampus.

    Science.gov (United States)

    Nyíri, G; Stephenson, F A; Freund, T F; Somogyi, P

    2003-01-01

    Pyramidal cells receive input from several types of GABA-releasing interneurons and innervate them reciprocally. Glutamatergic activation of interneurons involves both alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-D-aspartate (NMDA) type glutamate receptors expressed in type I synapses, mostly on their dendritic shafts. On average, the synaptic AMPA receptor content is several times higher on interneurons than in the spines of pyramidal cells. To compare the NMDA receptor content of synapses, we used a quantitative postembedding immunogold technique on serial electron microscopic sections, and analysed the synapses on interneuron dendrites and pyramidal cell spines in the CA1 area. Because all NMDA receptors contain the obligatory NR1 subunit, receptor localisation was carried out using antibodies recognising all splice variants of the NR1 subunit. Four populations of synapse were examined: i). on spines of pyramidal cells in stratum (str.) radiatum and str. oriens; ii). on parvalbumin-positive interneuronal dendritic shafts in str. radiatum; iii). on randomly found dendritic shafts in str. oriens and iv). on somatostatin-positive interneuronal dendritic shafts and somata in str. oriens. On average, the size of the synapses on spines was about half of those on interneurons. The four populations of synapse significantly differed in labelling for the NR1 subunit. The median density of NR1 subunit labelling was highest on pyramidal cell spines. It was lowest in the synapses on parvalbumin-positive dendrites in str. radiatum, where more than half of these synapses were immunonegative. In str. oriens, synapses on interneurons had a high variability of receptor content; some dendrites were similar to those in str. radiatum, including the proximal synapses of somatostatin-positive cells, whereas others had immunoreactivity for the NR1 subunit similar to or higher than synapses on pyramidal cell spines. These results show that synaptic NMDA

  19. Virtual Reality Tumor Resection: The Force Pyramid Approach.

    Science.gov (United States)

    Sawaya, Robin; Bugdadi, Abdulgadir; Azarnoush, Hamed; Winkler-Schwartz, Alexander; Alotaibi, Fahad E; Bajunaid, Khalid; AlZhrani, Gmaan A; Alsideiri, Ghusn; Sabbagh, Abdulrahman J; Del Maestro, Rolando F

    2017-09-05

    The force pyramid is a novel visual representation allowing spatial delineation of instrument force application during surgical procedures. In this study, the force pyramid concept is employed to create and quantify dominant hand, nondominant hand, and bimanual force pyramids during resection of virtual reality brain tumors. To address 4 questions: Do ergonomics and handedness influence force pyramid structure? What are the differences between dominant and nondominant force pyramids? What is the spatial distribution of forces applied in specific tumor quadrants? What differentiates "expert" and "novice" groups regarding their force pyramids? Using a simulated aspirator in the dominant hand and a simulated sucker in the nondominant hand, 6 neurosurgeons and 14 residents resected 8 different tumors using the CAE NeuroVR virtual reality neurosurgical simulation platform (CAE Healthcare, Montréal, Québec and the National Research Council Canada, Boucherville, Québec). Position and force data were used to create force pyramids and quantify tumor quadrant force distribution. Force distribution quantification demonstrates the critical role that handedness and ergonomics play on psychomotor performance during simulated brain tumor resections. Neurosurgeons concentrate their dominant hand forces in a defined crescent in the lower right tumor quadrant. Nondominant force pyramids showed a central peak force application in all groups. Bimanual force pyramids outlined the combined impact of each hand. Distinct force pyramid patterns were seen when tumor stiffness, border complexity, and color were altered. Force pyramids allow delineation of specific tumor regions requiring greater psychomotor ability to resect. This information can focus and improve resident technical skills training. Copyright © 2017 by the Congress of Neurological Surgeons

  20. The Effect of Rosa Damascena Extract on Expression of Neurotrophic Factors in the CA1 Neurons of Adult Rat Hippocampus Following Ischemia

    Directory of Open Access Journals (Sweden)

    Seyedeh Farzaneh Moniri

    2018-01-01

    Full Text Available Ischemic stroke is an important cause of death and disability in the world. Brain ischemia causes damage to brain cell, and among brain neurons, pyramidal neurons of the hippocampal CA1 region are more susceptive to ischemic injury. Recent findings suggest that neurotrophic factors protect against ischemic cell death. A dietary component of Rosa damascene extract possibly is associated with expression of neurotrophic factors mRNA following ischemia, so it can have therapeutic effect on cerebral ischemia. The present study attempts to evaluate the neuroprotective effect of Rosa damascene extract on adult rat hippocampal neurons following ischemic brain injury. Forty-eight adult male Wistar rats (weighing 250±20 gr and ages 10-12 weeks used in this study, animals randomly were divided into 6 groups including Control, ischemia/ reperfusion (IR, vehicle and three treated groups (IR+0.5, 1, 2 mg/ml extract. Global ischemia was induced by bilateral common carotid arteries occlusion for 20 minutes. The treatment was done by different doses of Rosa damascena extract for 30 days. After 30 days cell death and gene expression in neurons of the CA1 region of the hippocampus were evaluated by Nissl staining and real time PCR assay. We found a significant decrease in NGF, BDNF and NT3 mRNA expression in neurons of CA1 region of the hippocampus in ischemia group compared to control group (P<0.0001. Our results also revealed that the number of dark neurons significantly increases in ischemia group compared to control group (P<0.0001. Following treatment with Rosa damascene extract reduced the number of dark neurons that was associated with NGF, NT3, and BDNF mRNA expression. All doses level had positive effects, but the most effective dose of Rosa damascena extract was 1 mg/ml. Our results suggest that neuroprotective activity of Rosa damascena can enhance hippocampal CA1 neuronal survival after global ischemia.

  1. Chronic Ca2+ influx through voltage-dependent Ca2+ channels enhance delayed rectifier K+ currents via activating Src family tyrosine kinase in rat hippocampal neurons.

    Science.gov (United States)

    Yang, Yoon-Sil; Jeon, Sang-Chan; Kim, Dong-Kwan; Eun, Su-Yong; Jung, Sung-Cherl

    2017-03-01

    Excessive influx and the subsequent rapid cytosolic elevation of Ca 2+ in neurons is the major cause to induce hyperexcitability and irreversible cell damage although it is an essential ion for cellular signalings. Therefore, most neurons exhibit several cellular mechanisms to homeostatically regulate cytosolic Ca 2+ level in normal as well as pathological conditions. Delayed rectifier K + channels (I DR channels) play a role to suppress membrane excitability by inducing K + outflow in various conditions, indicating their potential role in preventing pathogenic conditions and cell damage under Ca 2+ -mediated excitotoxic conditions. In the present study, we electrophysiologically evaluated the response of I DR channels to hyperexcitable conditions induced by high Ca 2+ pretreatment (3.6 mM, for 24 hours) in cultured hippocampal neurons. In results, high Ca 2+ -treatment significantly increased the amplitude of I DR without changes of gating kinetics. Nimodipine but not APV blocked Ca 2+ -induced I DR enhancement, confirming that the change of I DR might be targeted by Ca 2+ influx through voltage-dependent Ca 2+ channels (VDCCs) rather than NMDA receptors (NMDARs). The VDCC-mediated I DR enhancement was not affected by either Ca 2+ -induced Ca 2+ release (CICR) or small conductance Ca 2+ -activated K + channels (SK channels). Furthermore, PP2 but not H89 completely abolished I DR enhancement under high Ca 2+ condition, indicating that the activation of Src family tyrosine kinases (SFKs) is required for Ca 2+ -mediated I DR enhancement. Thus, SFKs may be sensitive to excessive Ca 2+ influx through VDCCs and enhance I DR to activate a neuroprotective mechanism against Ca 2+ -mediated hyperexcitability in neurons.

  2. Maternal mobile phone exposure alters intrinsic electrophysiological properties of CA1 pyramidal neurons in rat offspring.

    Science.gov (United States)

    Razavinasab, Moazamehosadat; Moazzami, Kasra; Shabani, Mohammad

    2016-06-01

    Some studies have shown that exposure to electromagnetic field (EMF) may result in structural damage to neurons. In this study, we have elucidated the alteration in the hippocampal function of offspring Wistar rats (n = 8 rats in each group) that were chronically exposed to mobile phones during their gestational period by applying behavioral, histological, and electrophysiological tests. Rats in the EMF group were exposed to 900 MHz pulsed-EMF irradiation for 6 h/day. Whole cell recordings in hippocampal pyramidal cells in the mobile phone groups did show a decrease in neuronal excitability. Mobile phone exposure was mostly associated with a decrease in the number of action potentials fired in spontaneous activity and in response to current injection in both male and female groups. There was an increase in the amplitude of the afterhyperpolarization (AHP) in mobile phone rats compared with the control. The results of the passive avoidance and Morris water maze assessment of learning and memory performance showed that phone exposure significantly altered learning acquisition and memory retention in male and female rats compared with the control rats. Light microscopy study of brain sections of the control and mobile phone-exposed rats showed normal morphology.Our results suggest that exposure to mobile phones adversely affects the cognitive performance of both female and male offspring rats using behavioral and electrophysiological techniques. © The Author(s) 2014.

  3. The influence of phospho-tau on dendritic spines of cortical pyramidal neurons in patients with Alzheimer’s disease

    Science.gov (United States)

    Merino-Serrais, Paula; Benavides-Piccione, Ruth; Blazquez-Llorca, Lidia; Kastanauskaite, Asta; Rábano, Alberto; Avila, Jesús

    2013-01-01

    The dendritic spines on pyramidal cells represent the main postsynaptic elements of cortical excitatory synapses and they are fundamental structures in memory, learning and cognition. In the present study, we used intracellular injections of Lucifer yellow in fixed tissue to analyse over 19 500 dendritic spines that were completely reconstructed in three dimensions along the length of the basal dendrites of pyramidal neurons in the parahippocampal cortex and CA1 of patients with Alzheimer’s disease. Following intracellular injection, sections were immunostained for anti-Lucifer yellow and with tau monoclonal antibodies AT8 and PHF-1, which recognize tau phosphorylated at Ser202/Thr205 and at Ser396/404, respectively. We observed that the diffuse accumulation of phospho-tau in a putative pre-tangle state did not induce changes in the dendrites of pyramidal neurons, whereas the presence of tau aggregates forming intraneuronal neurofibrillary tangles was associated with progressive alteration of dendritic spines (loss of dendritic spines and changes in their morphology) and dendrite atrophy, depending on the degree of tangle development. Thus, the presence of phospho-tau in neurons does not necessarily mean that they suffer severe and irreversible effects as thought previously but rather, the characteristic cognitive impairment in Alzheimer’s disease is likely to depend on the relative number of neurons that have well developed tangles. PMID:23715095

  4. PYRAMID LAKE RENEWEABLE ENERGY PLAN

    Energy Technology Data Exchange (ETDEWEB)

    HIGH DESERT GEOCULTURE, LLC

    2009-06-06

    The Pyramid Lake Renewable Energy Plan covers these areas: energy potential (primarily focusing on geothermal resource potential, but also more generally addressing wind energy potential); renewable energy market potential; transmission system development; geothermal direct use potential; and business structures to accomplish the development objectives of the Pyramid Lake Paiute Tribe.

  5. The relativistic titls of Giza pyramids' entrance-passages

    Science.gov (United States)

    Aboulfotouh, H.

    The tilts of Giza pyramids' entrance-passages have never been considered as if they were the result of relativistic mathematical equations, and never been thought to encode the Earth's obliquity parameters. This paper presents an attempt to retrieve the method of establishing the equations that the pyramids' designer used to quantify the entrance-passages' tilts of these architectonic masterpieces. It proves that the pyramids' designer was able to include the geographic, astronomical and time parameters in one relativistic equation, encoding the date of the design of the Giza pyramids in the tilt of the entrance passage of the great pyramid.

  6. The Effect of Single Pyramidal Neuron Firing Within Layer 2/3 and Layer 4 in Mouse V1.

    Science.gov (United States)

    Meyer, Jochen F; Golshani, Peyman; Smirnakis, Stelios M

    2018-01-01

    The influence of cortical cell spiking activity on nearby cells has been studied extensively in vitro . Less is known, however, about the impact of single cell firing on local cortical networks in vivo . In a pioneering study, Kwan and Dan (Kwan and Dan, 2012) reported that in mouse layer 2/3 (L2/3), under anesthesia , stimulating a single pyramidal cell recruits ~2.1% of neighboring units. Here we employ two-photon calcium imaging in layer 2/3 of mouse V1, in conjunction with single-cell patch clamp stimulation in layer 2/3 or layer 4, to probe, in both the awake and lightly anesthetized states , how (i) activating single L2/3 pyramidal neurons recruits neighboring units within L2/3 and from layer 4 (L4) to L2/3, and whether (ii) activating single pyramidal neurons changes population activity in local circuit. To do this, it was essential to develop an algorithm capable of quantifying how sensitive the calcium signal is at detecting effectively recruited units ("followers"). This algorithm allowed us to estimate the chance of detecting a follower as a function of the probability that an epoch of stimulation elicits one extra action potential (AP) in the follower cell. Using this approach, we found only a small fraction (layer-2/3 or layer-4 pyramidal neurons produces few (<1% of local units) reliable single-cell followers in L2/3 of mouse area V1, either under light anesthesia or in quiet wakefulness: instead, single cell stimulation was found to elevate aggregate population activity in a weak but highly distributed fashion.

  7. Mobile Money Empowering People Living at Bottom of Pyramid and Boosting Socio-Economic Development in a Big Way

    Directory of Open Access Journals (Sweden)

    Agrawal Reena

    2016-06-01

    Full Text Available Hardly anyone would disagree that mobile money is an engine of financial inclusion and has the potential to outreach millions of people, living at the bottom of pyramid and those living in remote areas. The current study was taken up to investigate the impact of mobile money access on the people living at the bottom of pyramid. The aim was to: (1 understand the concept of mobile money, (2 explore the relevance of mobile money in economic growth, (3 capture the growth of mobile money worldwide, (4 explore the socio – economic impact of mobile money and (4 discuss vital insights for traditional financial institutions and policy makers. The study revealed that mobile money had positive impact on financial inclusion. It also enhanced the economic opportunities for the large unbanked population living at the bottom of pyramid. The increase in the mobile penetration and use of mobile internet, among the people living at the bottom of pyramid in the developing countries, clearly reflect at the potential of mobile money, in bringing the financially excluded in the economic mainstream and thus help in sustainable socio-economic development.

  8. Space Station view of the Pyramids at Giza

    Science.gov (United States)

    2002-01-01

    One of the world's most famous archaeological sites has been photographed in amazing detail by the astronauts onboard Space Station Alpha. This image, taken 15 August, 2001, represents the greatest detail of the Giza plateau captured from a human-occupied spacecraft (approximate 7 m resolution). Afternoon sun casts shadows that help the eye make out the large pyramids of Khufu, Khafre and Menkaure. Sets of three smaller queens' pyramids can be seen to the east of the Pyramid of Khufu and south of the Pyramid of Menkaure. The light-colored causeway stretching from the Mortuary Temple at the Pyramid of Khafre to the Valley Temple near the Sphinx (arrow) can also be seen. Because it is not tall enough to cast a deep shadow, the Sphinx itself cannot readily be distinguished. Although some commercial satellites, such as IKONOS, have imaged the Pyramids at Giza in greater detail (1 m resolution), this image highlights the potential of the International Space Station as a remote sensing platform. A commercial digital camera without space modifications was used to obtain this picture. Similarly, a variety of remote sensing instruments developed for use on aircraft can potentially be used from the Space Station. Currently, all photographs of Earth taken by astronauts from the Space Shuttle and Space Station are released to the public for scientific and educational benefit and can be accessed on the World Wide Web through the NASA-JSC Gateway to Astronaut Photography of Earth (http://eol/jsc.nasa.gov/sseop). Image ISS003-ESC-5120 was provided by the Earth Sciences and Image Analysis Laboratory at Johnson Space Center (http://eol.jsc.nasa.gov).

  9. Neuropathic Pain Causes Pyramidal Neuronal Hyperactivity in the Anterior Cingulate Cortex

    Directory of Open Access Journals (Sweden)

    Ruohe Zhao

    2018-04-01

    Full Text Available The anterior cingulate cortex (ACC is thought to be important for acute pain perception as well as the development of chronic pain after peripheral nerve injury. Nevertheless, how ACC neurons respond to sensory stimulation under chronic pain states is not well understood. Here, we used an in vivo two-photon imaging technique to monitor the activity of individual neurons in the ACC of awake, head restrained mice. Calcium imaging in the dorsal ACC revealed robust somatic activity in layer 5 (L5 pyramidal neurons in response to peripheral noxious stimuli, and the degree of evoked activity was correlated with the intensity of noxious stimulation. Furthermore, the activation of ACC neurons occurred bilaterally upon noxious stimulation to either contralateral or ipsilateral hind paws. Notably, with nerve injury-induced neuropathic pain in one limb, L5 pyramidal neurons in both sides of the ACC showed enhanced activity in the absence or presence of pain stimuli. These results reveal hyperactivity of L5 pyramidal neurons in the bilateral ACC during the development of neuropathic pain.

  10. Activity of pyramidal I and II slip in Mg alloys as revealed by texture development

    Science.gov (United States)

    Zecevic, Miroslav; Beyerlein, Irene J.; Knezevic, Marko

    2018-02-01

    Due to the geometry of the hexagonal close-packed (HCP) lattice, there are two types of pyramidal slip modes: { 10 1 bar 1 } 〈 11 2 bar 3 bar 〉 or type I and { 1 bar 1 bar 22 } 〈 11 2 bar 3 〉 or type II in HCP crystalline materials. Here we use crystal plasticity to examine the importance of crystallographic slip by pyramidal type I and type II on texture evolution. The study is applied to an Mg-4%Li alloy. An elastic-plastic polycrystal model is employed to elucidate the reorientation tendencies of these two slip modes in rolling of a textured polycrystal. Comparisons with experimental texture measurements indicate that both pyramidal I and II type slip were active during rolling deformation, with pyramidal I being the dominant mode. A single-slip-mode analysis is used to identify the orientations that prefer pyramidal I vs. II type slip when acting alone in a crystal. The analysis applies not only to Mg-4%Li, but identifies the key texture components in HCP crystals that would help distinguish the activity of pyramidal I from pyramidal II slip in rolling deformation.

  11. Physiological and Pathological Roles of CaMKII-PP1 Signaling in the Brain

    Directory of Open Access Journals (Sweden)

    Norifumi Shioda

    2017-12-01

    Full Text Available Ca2+/calmodulin (CaM-dependent protein kinase II (CaMKII, a multifunctional serine (Ser/threonine (Thr protein kinase, regulates diverse activities related to Ca2+-mediated neuronal plasticity in the brain, including synaptic activity and gene expression. Among its regulators, protein phosphatase-1 (PP1, a Ser/Thr phosphatase, appears to be critical in controlling CaMKII-dependent neuronal signaling. In postsynaptic densities (PSDs, CaMKII is required for hippocampal long-term potentiation (LTP, a cellular process correlated with learning and memory. In response to Ca2+ elevation during hippocampal LTP induction, CaMKIIα, an isoform that translocates from the cytosol to PSDs, is activated through autophosphorylation at Thr286, generating autonomous kinase activity and a prolonged Ca2+/CaM-bound state. Moreover, PP1 inhibition enhances Thr286 autophosphorylation of CaMKIIα during LTP induction. By contrast, CaMKII nuclear import is regulated by Ser332 phosphorylation state. CaMKIIδ3, a nuclear isoform, is dephosphorylated at Ser332 by PP1, promoting its nuclear translocation, where it regulates transcription. In this review, we summarize physio-pathological roles of CaMKII/PP1 signaling in neurons. CaMKII and PP1 crosstalk and regulation of gene expression is important for neuronal plasticity as well as survival and/or differentiation.

  12. The effects of black garlic ethanol extract on the spatial memory and estimated total number of pyramidal cells of the hippocampus of monosodium glutamate-exposed adolescent male Wistar rats.

    Science.gov (United States)

    Hermawati, Ery; Sari, Dwi Cahyani Ratna; Partadiredja, Ginus

    2015-09-01

    Monosodium glutamate (MSG) is believed to exert deleterious effects on various organs, including the hippocampus, likely via the oxidative stress pathway. Garlic (Alium sativum L.), which is considered to possess potent antioxidant activity, has been used as traditional remedy for various ailments since ancient times. We have investigated the effects of black garlic, a fermented form of garlic, on spatial memory and estimated the total number of pyramidal cells of the hippocampus in adolescent male Wistar rats treated with MSG. Twenty-five rats were divided into five groups: C- group, which received normal saline; C+ group, which was exposed to 2 mg/g body weight (bw) of MSG; three treatment groups (T2.5, T5, T10), which were treated with black garlic extract (2.5, 5, 10 mg/200 g bw, respectively) and MSG. The spatial memory test was carried out using the Morris water maze (MWM) procedure, and the total number of pyramidal cells of the hippocampus was estimated using the physical disector design. The groups treated with black garlic extract were found to have a shorter path length than the C- and C+ groups in the escape acquisition phase of the MWM test. The estimated total number of pyramidal cells in the CA1 region of the hippocampus was higher in all treated groups than that of the C+ group. Based on these results, we conclude that combined administration of black garlic and MSG may alter the spatial memory functioning and total number of pyramidal neurons of the CA1 region of the hippocampus of rats.

  13. Influence of Deposition Pressure on the Properties of Round Pyramid Textured a-Si:H Solar Cells for Maglev.

    Science.gov (United States)

    Lee, Jaehyeong; Choi, Wonseok; Lee, Kyuil; Lee, Daedong; Kang, Hyunil

    2016-05-01

    HIT (Heterojunction with Intrinsic Thin-layer) photovoltaic cells is one of the highest efficiencies in the commercial solar cells. The pyramid texturization for reducing surface reflectance of HIT solar cells silicon wafers is widely used. For the low leakage current and high shunt of solar cells, the intrinsic amorphous silicon (a-Si:H) on substrate must be uniformly thick of pyramid structure. However, it is difficult to control the thickness in the traditional pyramid texturing process. Thus, we textured the intrinsic a-Si:H thin films with the round pyramidal structure by using HNO3, HF, and CH3COOH solution. The characteristics of round pyramid a-Si:H solar cells deposited at pressure of 500, 1000, 1500, and 2000 mTorr by PECVD (Plasma Enhanced Chemical Vapor Deposition) was investigated. The lifetime, open circuit voltage, fill factor and efficiency of a-Si:H solar cells were investigated with respect to various deposition pressure.

  14. Marker-assisted pyramiding of brown planthopper (Nilaparvata lugens Stål) resistance genes Bph1 and Bph2 on rice chromosome 12.

    Science.gov (United States)

    Sharma, Prem N; Torii, Akihide; Takumi, Shigeo; Mori, Naoki; Nakamura, Chiharu

    2004-01-01

    Brown planthopper (BPH) (Nilaparvata lugens Stål) is a significant insect pest of rice (Oryza sativa L.). We constructed a gene-pyramided japonica line, in which two BPH resistance genes Bph1 and Bph2 on the long arm of chromosome 12 independently derived from two indica resistance lines were combined through the recombinant selection. The gene-pyramiding was achieved based on the previously constructed high-resolution linkage maps of the two genes. Two co-dominant and four dominant PCR-based markers flanking the loci were used to select for a homozygous recombinant line in a segregating population that was derived from a cross between the parental homozygous single-gene introgression lines. BPH bioassay showed that the resistance level of the pyramided line was equivalent to that of the Bph1-single introgression line, which showed a higher level of resistance than the Bph2-single introgression line. The pyramid line should provide a useful experimental means for studying the fine structure of the chromosomal region covering these two major BPH resistance genes.

  15. Enhancement of acetylcholine-induced desensitization of guinea-pig ileal longitudinal muscle in Ca2+-free conditions.

    Science.gov (United States)

    Horio, S; Nagare, T; Moritoki, H

    1999-10-01

    1. To determine the role of cellular Ca2+ in desensitization, acetylcholine(ACh)-induced desensitization was studied under Ca2+-free condition in guinea-pig ileal longitudinal muscle. 2. Pretreatment of the tissue with 10(-4) M ACh (desensitizing treatment) in normal Tyrode solution caused desensitization of the responses both to ACh and histamine. The desensitizing treatment performed in Ca2+-free solution enhanced desensitization of the responses to ACh and histamine significantly. 3. The desensitizing treatment with ACh caused suppression of the responses to high K+ (tonic component) and Bay K 8644. The desensitizing treatment performed in Ca2+-free solution potentiated the suppression of the responses to high K+ and Bay K 8644 significantly. 4. ACh-induced desensitization was enhanced significantly in the presence of a protein kinase C inhibitor, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine(H-7, 10(-4) M) to a similar extent as desensitization obtained under Ca2+-free condition, but not in the presence of a non-specific and less potent kinase inhibitor, N-(2-guanidinoethyl)-5-isoquinolinesulfonamide hydrochloride (HA1004, 10(-4) M). 5. These results suggested that voltage-gated Ca2+ channels were involved in ACh-induced desensitization and that intracellular Ca2+, which was increased during the stimulation with ACh, inhibited desensitization through the activation of protein kinase C. This kinase could have activated or protected Ca2+ channels during the desensitization process to reduce desensitization.

  16. Egyptian pyramid or Aztec pyramid: How should we describe the industrial architecture of automotive supply chains in Europe?

    OpenAIRE

    Vincent FRIGANT (GREThA, CNRS, UMR 5113)

    2011-01-01

    This article questions a terminology that is frequently used to describe automotive supply chains’ industrial architecture. Since vertical disintegration became a trend in the 1980s, this architecture has been represented using the image of the pyramid. Implicitly, authors have had the image of an Egyptian pyramid in mind, one that is pointed at the top and broad at the base. We will demonstrate that even if pyramids are an appropriate image, in the auto industry the Aztec variant, with its s...

  17. On the astronomical orientation of the IV dynasty Egyptian pyramids and the dating of the second Giza pyramid

    OpenAIRE

    Magli, Giulio

    2003-01-01

    The data on the astronomical orientation of the IV dynasty Egyptian pyramids are re-analyzed and it is shown that such data suggest an inverse chronology between the `first` and the `second` Giza pyramid.

  18. Low concentrations of the solvent dimethyl sulphoxide alter intrinsic excitability properties of cortical and hippocampal pyramidal cells.

    Directory of Open Access Journals (Sweden)

    Francesco Tamagnini

    Full Text Available Dimethylsulfoxide (DMSO is a widely used solvent in biology. It has many applications perhaps the most common of which is in aiding the preparation of drug solutions from hydrophobic chemical entities. Recent studies have suggested that this molecule may be able to induce apoptosis in neural tissues urging caution regarding its introduction into humans, for example as part of stem cell transplants. Here we have used in vitro electrophysiological methods applied to murine brain slices to examine whether a few hours treatment with 0.05% DMSO (a concentration regarded by many as innocuous alters intrinsic excitability properties of neurones. We investigated pyramidal neurones in two distinct brain regions, namely area CA1 of the hippocampus and layer 2 of perirhinal cortex. In the former there was no effect on resting potential but input resistance was decreased by DMSO pre-treatment. In line with this action potential count for any level of depolarizing current stimulus was reduced by ∼25% following DMSO treatment. Ih-mediated "sag" was also increased in CA1 pyramids and action potential waveform analysis demonstrated that DMSO treatment moved action potential threshold towards resting potential. In perirhinal cortex a decreased action potential output for various depolarizing current stimuli was also seen. In these cells action potential threshold was unaltered by DMSO but a significant increase in action potential width was apparent. These data indicate that pre-treatment with this widely employed solvent can elicit multifaceted neurophysiological changes in mammalian neurones at concentrations below those frequently encountered in the published literature.

  19. Neutron investigation of Ru-doped Nd1/2Ca1/2MnO3. Comparison with Cr-doped Nd1/2Ca1/2MnO3

    International Nuclear Information System (INIS)

    Moritomo, Yutaka; Nonobe, Toshihiko; Machida, Akihiko; Ohoyama, Kenji

    2002-01-01

    Lattice and magnetic properties are investigated for 3% Ru- and Cr-doped Nd 1/2 Ca 1/2 MnO 3 . The parent Nd 1/2 Ca 1/2 MnO 3 is a charge-ordered insulator (T CO =250K). With decreasing temperature below ≅210K, these compounds are separated into two perovskite phases, that is, the long-c and short-c phases. The long-c region shows a ferromagnetic transition at T C ≅210K for the Ru-doped compound and ≅130K for the Cr-doped compound, while the short-c region shows antiferromagnetic transition at T N ≅150K for Ru and ≅110K for Cr. We discuss the origin of the enhanced T C for the Ru-doped compound in terms of the effective one-electron bandwidth W of the e g -band. (author)

  20. Analysis of deterioration of rocky material which conform the sculptured serpents of the Tenayuca pyramid

    International Nuclear Information System (INIS)

    Mendoza A, D.; Martinez C, G.; Rodriguez L, V.

    2004-01-01

    This work presents the results about the characterization of rocky materials samples proceeding from heads of snakes that adorn the pyramid of Tenayuca, Mexico. Analysis of these samples, that show deterioration presence was performance through Scanning Electron Microscopy (SEM), Energy Dispersive X-ray Spectroscopy (EDS) and X-ray Diffraction (XRD). Several morphological structures such as granular, tubular, acicular growths and fibers were observed, some of they could be associate to salt migration. It was possible to identify different crystalline phases associated with albite (NaAlSi 3 O 8 ), anorthite [(Ca,Na)(Si,Al) 4 O 8 ], ferroactinolite [(Ca,Na,K) 2 Fe 5 Si 8 O 22 (OH) 2 ], gypsum (CaSO 4 2H 2 O), quartz (SiO 2 ) and thenardite (Na 2 SO 4 ). (Author) 10 refs., 2 tabs., 12 figs

  1. Imaging the Cheops Pyramid

    CERN Document Server

    Bui, H D

    2012-01-01

    In this book Egyptian Archeology  and Mathematics meet. The author is an expert in theories and applications in Solid Mechanics and Inverse Problems, a former professor at Ecole Polytechnique and now works with Electricité de France on maintenance operations on nuclear power plants. In the Autumn of 1986, after the end of the operation on the King’s chamber conducted under the Technological and Scientific Sponsorship of EDF, to locate a cavity, he was called to solve a mathematical inverse problem, to find the unknown tomb of the King and the density structure of the whole pyramid based on measurements of microgravity made inside and outside of the pyramid. This book recounts the various search operations on the pyramid of Cheops made at the request of the Egyptian and French authorities in 1986-1987. After the premature end of the Cheops operation in the Autumn of 1986, following the fiasco of unsuccessful drillings in the area suspected by both architects G. Dormion and J.P. Goidin and microgravity aus...

  2. Transient Receptor Potential Vanilloid 4 Activation-Induced Increase in Glycine-Activated Current in Mouse Hippocampal Pyramidal Neurons

    Directory of Open Access Journals (Sweden)

    Mengwen Qi

    2018-02-01

    Full Text Available Background/Aims: Glycine plays an important role in regulating hippocampal inhibitory/ excitatory neurotransmission through activating glycine receptors (GlyRs and acting as a co-agonist of N-methyl-d-aspartate-type glutamate receptors. Activation of transient receptor potential vanilloid 4 (TRPV4 is reported to inhibit hippocampal A-type γ-aminobutyric acid receptor, a ligand-gated chloride ion channel. GlyRs are also ligand-gated chloride ion channels and this paper aimed to explore whether activation of TRPV4 could modulate GlyRs. Methods: Whole-cell patch clamp recording was employed to record glycine-activated current (IGly and Western blot was conducted to assess GlyRs subunits protein expression. Results: Application of TRPV4 agonist (GSK1016790A or 5,6-EET increased IGly in mouse hippocampal CA1 pyramidal neurons. This action was blocked by specific antagonists of TRPV4 (RN-1734 or HC-067047 and GlyR (strychnine, indicating that activation of TRPV4 increases strychnine-sensitive GlyR function in mouse hippocampal pyramidal neurons. GSK1016790A-induced increase in IGly was significantly attenuated by protein kinase C (PKC (BIM II or D-sphingosine or calcium/calmodulin-dependent protein kinase II (CaMKII (KN-62 or KN-93 antagonists but was unaffected by protein kinase A or protein tyrosine kinase antagonists. Finally, hippocampal protein levels of GlyR α1 α2, α3 and β subunits were not changed by treatment with GSK1016790A for 30 min or 1 h, but GlyR α2, α3 and β subunits protein levels increased in mice that were intracerebroventricularly (icv. injected with GSK1016790A for 5 d. Conclusion: Activation of TRPV4 increases GlyR function and expression, and PKC and CaMKII signaling pathways are involved in TRPV4 activation-induced increase in IGly. This study indicates that GlyRs may be effective targets for TRPV4-induced modulation of hippocampal inhibitory neurotransmission.

  3. Sonographic findings in primary diseases of renal pyramids

    International Nuclear Information System (INIS)

    Rao, B.K.

    1987-01-01

    Primary pathologic processes involving the renal pyramids such as papillary necrosis, drug-induced necrosis or calcinosis, cysts, neoplasms, and medullary nephrocalcinosis are rare. Thirty-four patients with primary renal pyramid diseases underwent US evaluation for altered morphology; a 5-MHz transducer was used. In 20 patients site-specific changes in the pyramid (e.g., papillary necrosis at the apex, small cysts at the base in medullary cystic disease, tubular calcification in MSK, corticomedullary hyperechogenicity in oxalosis) were noted on US. Sonographic delineation of the site and pattern of pathologic changes in the renal pyramid may help to identify specific diseases

  4. Npas4 Is a Critical Regulator of Learning-Induced Plasticity at Mossy Fiber-CA3 Synapses during Contextual Memory Formation

    DEFF Research Database (Denmark)

    Weng, Feng-Ju; Garcia, Rodrigo I; Lutzu, Stefano

    2018-01-01

    Synaptic connections between hippocampal mossy fibers (MFs) and CA3 pyramidal neurons are essential for contextual memory encoding, but the molecular mechanisms regulating MF-CA3 synapses during memory formation and the exact nature of this regulation are poorly understood. Here we report...... pyramidal cells that were activated by contextual learning and found that MF inputs on these cells were selectively strengthened. Deletion of Npas4 prevented both contextual memory formation and this learning-induced synaptic modification. We further show that Npas4 regulates MF-CA3 synapses by controlling...... the expression of the polo-like kinase Plk2. Thus, Npas4 is a critical regulator of experience-dependent, structural, and functional plasticity at MF-CA3 synapses during contextual memory formation....

  5. Phosphorylation of Ser1928 mediates the enhanced activity of the L-type Ca2+ channel Cav1.2 by the β2-adrenergic receptor in neurons.

    Science.gov (United States)

    Qian, Hai; Patriarchi, Tommaso; Price, Jennifer L; Matt, Lucas; Lee, Boram; Nieves-Cintrón, Madeline; Buonarati, Olivia R; Chowdhury, Dhrubajyoti; Nanou, Evanthia; Nystoriak, Matthew A; Catterall, William A; Poomvanicha, Montatip; Hofmann, Franz; Navedo, Manuel F; Hell, Johannes W

    2017-01-24

    The L-type Ca 2+ channel Ca v 1.2 controls multiple functions throughout the body including heart rate and neuronal excitability. It is a key mediator of fight-or-flight stress responses triggered by a signaling pathway involving β-adrenergic receptors (βARs), cyclic adenosine monophosphate (cAMP), and protein kinase A (PKA). PKA readily phosphorylates Ser 1928 in Ca v 1.2 in vitro and in vivo, including in rodents and humans. However, S1928A knock-in (KI) mice have normal PKA-mediated L-type channel regulation in the heart, indicating that Ser 1928 is not required for regulation of cardiac Ca v 1.2 by PKA in this tissue. We report that augmentation of L-type currents by PKA in neurons was absent in S1928A KI mice. Furthermore, S1928A KI mice failed to induce long-term potentiation in response to prolonged theta-tetanus (PTT-LTP), a form of synaptic plasticity that requires Ca v 1.2 and enhancement of its activity by the β 2 -adrenergic receptor (β 2 AR)-cAMP-PKA cascade. Thus, there is an unexpected dichotomy in the control of Ca v 1.2 by PKA in cardiomyocytes and hippocampal neurons. Copyright © 2017, American Association for the Advancement of Science.

  6. Incorporating IGCC and CaO sorption-enhanced process for power generation with CO2 capture

    International Nuclear Information System (INIS)

    Chen, Shiyi; Xiang, Wenguo; Wang, Dong; Xue, Zhipeng

    2012-01-01

    Highlights: ► CaO sorption-enhanced process is incorporated with IGCC for CO 2 capture. ► IGCC–CCS is simplified using CaO sorption-enhanced process. ► The electricity efficiency is around 31–33% and CO 2 capture efficiency exceeds 95%. ► Parameters such as sorption pressure influence the system performance. -- Abstract: Integrated gasification combined cycle (IGCC) is a power generation technology to convert solid fuels into electricity. IGCC with CCS is regarded as a promising option to mitigate CO 2 emission. In this paper, the CaO sorption-enhanced process is incorporated downstream with coal gasification to produce a hydrogen-rich stream for electricity production and CO 2 separation. A WGS-absorber substitutes the high- and low-temperature water–gas shift reactors and desulfurization units in conventional IGCC–CCS to produce a hydrogen-rich stream, which is sent onto a gas turbine. CaO is used as the sorbent to enhance hydrogen production and for CO 2 capture. Regeneration of CaO is completed via calcination in a regenerator vessel. The IGCC with CaO sorption-enhanced process is modeled and simulated using Aspen Plus software. Two commercial available gasification technologies, Shell and Texaco, are integrated with the sorption-enhanced process. The results showed IGCC with CaO sorption-enhanced process has a satisfactory system performance. Even though the net electricity efficiency is not as high as expected, just around 30–33%, the system has a high CO 2 capture efficiency ∼97% and low pollutant emissions. Moreover, compared with conventional IGCC–CCS, the schematic diagram of the IGCC–CCS process is simplified. Parameters that affect the plant performance are analyzed in the sensitive analysis, including WGS-absorber temperature, H 2 O/CO ratio, pressure, etc. Some challenges to the system are also discussed.

  7. Involvement of intracellular free Ca2+ in enhanced release of herpes simplex virus by hydrogen peroxide

    Directory of Open Access Journals (Sweden)

    Ogawa Yuzo

    2006-08-01

    Full Text Available Abstract Background It was reported that elevation of the intracellular concentration of free Ca2+ ([Ca2+]i by a calcium ionophore increased the release of herpes simplex virus type 1 (HSV-1. Freely diffusible hydrogen peroxide (H2O2 is implied to alter Ca2+ homeostasis, which further enhances abnormal cellular activity, causing changes in signal transduction, and cellular dysfunction. Whether H2O2 could affect [Ca2+]i in HSV-1-infected cells had not been investigated. Results H2O2 treatment increased the amount of cell-free virus and decreased the proportion of viable cells. After the treatment, an elevation in [Ca2+]i was observed and the increase in [Ca2+]i was suppressed when intracellular and cytosolic Ca2+ were buffered by Ca2+ chelators. In the presence of Ca2+ chelators, H2O2-mediated increases of cell-free virus and cell death were also diminished. Electron microscopic analysis revealed enlarged cell junctions and a focal disintegration of the plasma membrane in H2O2-treated cells. Conclusion These results indicate that H2O2 can elevate [Ca2+]i and induces non-apoptotic cell death with membrane lesions, which is responsible for the increased release of HSV-1 from epithelial cells.

  8. Lindane blocks GABAA-mediated inhibition and modulates pyramidal cell excitability in the rat hippocampal slice.

    Science.gov (United States)

    Joy, R M; Walby, W F; Stark, L G; Albertson, T E

    1995-01-01

    An in vitro paired-pulse orthodromic stimulation technique was used to examine the effects of lindane on excitatory afferent terminals, CA1 pyramidal cells and recurrent collateral evoked inhibition in the rat hippocampal slice. This was done to establish simultaneous effects on a simple neural network and to develop procedures for more detailed analyses of the effects of lindane. Hippocampal slices 400 microns thick were perfused with oxygenated artificial cerebrospinal fluid. Electrodes were placed in the CA1 region to record extracellular population spike (PS) or excitatory postsynaptic potential (EPSP) responses to stimulation of Schaffer collateral/commissural (SC/C) fibers. Gamma-aminobutyric acid (GABA)-mediated recurrent inhibition was measured using a paired-pulse technique. Perfusion with lindane produced both time and dose dependent changes in a number of the responses measured. The most striking effect produced by lindane was the loss of GABAA-mediated recurrent collateral inhibition. This tended to occur rapidly, often before changes in EPSP or PS responses could be detected. With longer exposures to lindane, repetitive discharge of pyramidal cells developed resulting in multiple PSs to single stimuli. Lindane (50 microM) also completely reversed the effects of the injectable anesthetic, propofol, a compound known to potentiate GABAA-mediated inhibition via a direct action on the GABAA receptor-chloride channel complex. An analysis of input/output relationships at varying stimulus intensities showed that lindane increased EPSP and PS response amplitudes at any given stimulus intensity resulting in a leftward shift in the EPSP amplitude/stimulus intensity, PS amplitude/stimulus intensity and PS amplitude/EPSP amplitude relationships. This effect was most noticeable with low intensity stimuli and became progressively less so as stimulus intensities approached those yielding maximal responses. In addition lindane significantly increased paired pulse

  9. [Pyramidal syndrome in lateral amyotrophic sclerosis: clinico-morphological analysis].

    Science.gov (United States)

    Musaeva, L S; Zavalishin, I A; Gulevskaia, T S

    2003-01-01

    Retrospective clinical analysis with a special focus on pyramidal syndrome expression in the disease course as well as morphological study of brain and spinal structures in all levels of cortical-spinal projection (from brain motor cortex to spinal lumbar segments) have been conducted for 11 section cases of lateral amyotrophic sclerosis (LAS), sporadic type. Two groups of patients were studied: with pronounced pyramidal syndrome (spasticity, hyperreflexia, etc)--7 cases and with some signs of pyramidal deficiency (anisoreflexia, stability of peritoneal reflexes)--4 cases. Pyramidal syndrome in LAS is considered as an emergence of current neurodegenerative process, embracing a significant part of upper motor neurons of both precentral convolution and its axons along the whole length of cerebrospinal axis in the form of cytoplasmic inclusions and axonal spheroids. A presence of pathomorphological changes in other upper segmental structures of motor control reveals their role in pyramidal deficiency. Comparative analysis showed that expression of pyramidal syndrome signs and its correlation to atrophic paresis appearances is specifically determined by the severity of upper and lower motor neurons lesions. With regard to morphological changes in CNS structures, the peculiarities of some pyramidal syndrome appearances in LAS are analyzed.

  10. TRH regulates action potential shape in cerebral cortex pyramidal neurons.

    Science.gov (United States)

    Rodríguez-Molina, Víctor; Patiño, Javier; Vargas, Yamili; Sánchez-Jaramillo, Edith; Joseph-Bravo, Patricia; Charli, Jean-Louis

    2014-07-07

    Thyrotropin releasing hormone (TRH) is a neuropeptide with a wide neural distribution and a variety of functions. It modulates neuronal electrophysiological properties, including resting membrane potential, as well as excitatory postsynaptic potential and spike frequencies. We explored, with whole-cell patch clamp, TRH effect on action potential shape in pyramidal neurons of the sensorimotor cortex. TRH reduced spike and after hyperpolarization amplitudes, and increased spike half-width. The effect varied with dose, time and cortical layer. In layer V, 0.5µM of TRH induced a small increase in spike half-width, while 1 and 5µM induced a strong but transient change in spike half-width, and amplitude; after hyperpolarization amplitude was modified at 5µM of TRH. Cortical layers III and VI neurons responded intensely to 0.5µM TRH; layer II neurons response was small. The effect of 1µM TRH on action potential shape in layer V neurons was blocked by G-protein inhibition. Inhibition of the activity of the TRH-degrading enzyme pyroglutamyl peptidase II (PPII) reproduced the effect of TRH, with enhanced spike half-width. Many cortical PPII mRNA+ cells were VGLUT1 mRNA+, and some GAD mRNA+. These data show that TRH regulates action potential shape in pyramidal cortical neurons, and are consistent with the hypothesis that PPII controls its action in this region. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. HERC 1 ubiquitin ligase mutation affects neocortical, CA3 hippocampal and spinal cord projection neurons. An ultrastructural study

    Directory of Open Access Journals (Sweden)

    Rocío eRuiz

    2016-04-01

    Full Text Available The spontaneous mutation tambaleante is caused by the Gly483Glu substitution in the highly conserved N terminal RCC1-like domain of the HERC1 protein, which leads to the increase of mutated protein levels responsible for cerebellar Purkinje cell death by autophagy. Until now, Purkinje cells have been the only central nervous neurons reported as being targeted by the mutation, and their degeneration elicits an ataxic syndrome in adult mutant mice. However, the ultrastructural analysis performed here demonstrates that signs of autophagy, such as autophagosomes, lysosomes, and altered mitochondria, are present in neocortical pyramidal, CA3 hippocampal pyramidal, and spinal cord motor neurons. The main difference is that the reduction in the number of neurons affected in the tambaleante mutation in the neocortex, the hippocampus, and the spinal cord is not so evident as the dramatic loss of cerebellar Purkinje cells. Interestingly, signs of autophagy are absent in both interneurons and neuroglia cells. Affected neurons have in common that they are projection neurons which receive strong and varied synaptic inputs, and possess the highest degree of neuronal activity. Therefore, because the integrity of the ubiquitin-proteasome system is essential for protein degradation and, hence, for normal protein turnover, it could be hypothesized that the deleterious effects of the misrouting of these pathways would depend directly on the neuronal activity.

  12. Formation of Various Pyramidal Structures on Monocrystalline Silicon Surface and Their Influence on the Solar Cells

    Directory of Open Access Journals (Sweden)

    Yangang Han

    2013-01-01

    Full Text Available Texturization is a useful method to enhance the optical absorption of monocrystalline silicon wafers by light-trapping effect in solar cell processing. In present study, a series of textured wafers with various pyramid sizes ranging from 200 nm to 10 μm were fabricated by modified wet-chemical method and characterized. The results show that there is little difference in the reflectance with the pyramid sizes from 1 to 10 μm, which is consistent with the ray-tracing simulation results. However, the light-trapping function of the 200 nm sample below the geometrical optics limit is much weaker. The solar cells fabricated from the 1 μm samples own the highest power conversion efficiency of 18.17% due to a better coverage of metal finger lines than the larger ones, and the 200 nm samples have the lowest efficiency of 10.53%.

  13. Teacher Acquisition of Functional Analysis Methods Using Pyramidal Training

    Science.gov (United States)

    Pence, Sacha T.; St. Peter, Claire C.; Giles, Aimee F.

    2014-01-01

    Pyramidal training involves an experienced professional training a subset of individuals who, in turn, train additional individuals. Pyramidal training is effective for training a variety of behavior-analytic skills with direct-care staff, parents, and teachers. As teachers' roles in behavioral assessment increase, pyramidal training may be…

  14. Structural basis for the differential effects of CaBP1 and calmodulin on CaV1.2 calcium-dependent inactivation

    Science.gov (United States)

    Findeisen, Felix; Minor, Daniel L.

    2010-01-01

    Calcium-binding protein 1 (CaBP1), a calmodulin (CaM) homolog, endows certain voltage-gated calcium channels (CaVs) with unusual properties. CaBP1 inhibits CaV1.2 calcium-dependent inactivation (CDI) and introduces calcium-dependent facilitation (CDF). Here, we show that the ability of CaBP1 to inhibit CaV1.2 CDI and induce CDF arises from interaction between the CaBP1 N-lobe and interlobe linker residue Glu94. Unlike CaM, where functional EF hands are essential for channel modulation, CDI inhibition does not require functional CaBP1 EF-hands. Furthermore, CaBP1-mediated CDF has different molecular requirements than CaM-mediated CDF. Overall, the data show that CaBP1 comprises two structural modules having separate functions: similar to CaM, the CaBP1 C-lobe serves as a high-affinity anchor that binds the CaV1.2 IQ domain at a site that overlaps with the Ca2+/CaM C-lobe site, whereas the N-lobe/linker module houses the elements required for channel modulation. Discovery of this division provides the framework for understanding how CaBP1 regulates CaVs. PMID:21134641

  15. Structural basis for the differential effects of CaBP1 and calmodulin on Ca(V)1.2 calcium-dependent inactivation.

    Science.gov (United States)

    Findeisen, Felix; Minor, Daniel L

    2010-12-08

    Calcium-binding protein 1 (CaBP1), a calmodulin (CaM) homolog, endows certain voltage-gated calcium channels (Ca(V)s) with unusual properties. CaBP1 inhibits Ca(V)1.2 calcium-dependent inactivation (CDI) and introduces calcium-dependent facilitation (CDF). Here, we show that the ability of CaBP1 to inhibit Ca(V)1.2 CDI and induce CDF arises from interaction between the CaBP1 N-lobe and interlobe linker residue Glu94. Unlike CaM, where functional EF hands are essential for channel modulation, CDI inhibition does not require functional CaBP1 EF hands. Furthermore, CaBP1-mediated CDF has different molecular requirements than CaM-mediated CDF. Overall, the data show that CaBP1 comprises two structural modules having separate functions: similar to CaM, the CaBP1 C-lobe serves as a high-affinity anchor that binds the Ca(V)1.2 IQ domain at a site that overlaps with the Ca²+/CaM C-lobe site, whereas the N-lobe/linker module houses the elements required for channel modulation. Discovery of this division provides the framework for understanding how CaBP1 regulates Ca(V)s. Copyright © 2010 Elsevier Ltd. All rights reserved.

  16. Turmeric (Curcuma longa L.) extract may prevent the deterioration of spatial memory and the deficit of estimated total number of hippocampal pyramidal cells of trimethyltin-exposed rats.

    Science.gov (United States)

    Yuliani, Sapto; Mustofa; Partadiredja, Ginus

    2018-01-01

    Protection of neurons from degeneration is an important preventive strategy for dementia. Much of the dementia pathology implicates oxidative stress pathways. Turmeric (Curcuma longa L.) contains curcuminoids which has anti-oxidative and neuro-protective effects. These effects are considered to be similar to those of citicoline which has been regularly used as one of standard medications for dementia. This study aimed at investigating the effects of turmeric rhizome extract on the hippocampus of trimethyltin (TMT)-treated Sprague-Dawley rats. The rats were divided randomly into six groups, i.e., a normal control group (N); Sn group, which was given TMT chloride; Sn-Cit group, which was treated with citicoline and TMT chloride; and three Sn-TE groups, which were treated with three different dosages of turmeric rhizome extract and TMT chloride. Morris water maze test was carried out to examine the spatial memory. The estimated total number of CA1 and CA2-CA3 pyramidal cells was calculated using a stereological method. The administration of turmeric extract at a dose of 200 mg/kg bw has been shown to prevent the deficits in the spatial memory performance and partially inhibit the reduction of the number of CA2-CA3 regions pyramidal neurons. TMT-induced neurotoxic damage seemed to be mediated by the generation of reactive oxygen species and reactive nitrogen species. Turmeric extract might act as anti inflammatory as well as anti-oxidant agent. The effects of turmeric extract at a dose of 200 mg/kg bw seem to be comparable to those of citicoline.

  17. Layer- and column-specific knockout of NMDA receptors in pyramidal neurons of the mouse barrel cortex.

    Directory of Open Access Journals (Sweden)

    Rachel Aronoff

    2007-11-01

    Full Text Available Viral vectors injected into the mouse brain offer the possibility for localized genetic modifications in a highly controlled manner. Lentivector injection into mouse neocortex transduces cells within a diameter of approximately 200µm, which closely matches the lateral scale of a column in barrel cortex. The depth and volume of the injection determines which cortical layer is transduced. Furthermore, transduced gene expression from the lentivector can be limited to predominantly pyramidal neurons by using a 1.3kb fragment of the αCaMKII promoter. This technique therefore allows genetic manipulation of a specific cell type in defined columns and layers of the neocortex. By expressing Cre recombinase from such a lentivector in gene-targeted mice carrying a floxed gene, highly specific genetic lesions can be induced. Here, we demonstrate the utility of this approach by specifically knocking out NMDA receptors (NMDARs in pyramidal neurons in the somatosensory barrel cortex of gene-targeted mice carrying floxed NMDAR 1 genes. Neurons transduced with lentivector encoding GFP and Cre recombinase exhibit not only reductions in NMDAR 1 mRNA levels, but reduced NMDAR-dependent currents and pairing-induced synaptic potentiation. This technique for knockout of NMDARs in a cell type, column- and layer-specific manner in the mouse somatosensory cortex may help further our understanding of the functional roles of NMDARs in vivo during sensory perception and learning.

  18. Assessment of energy credits for the enhancement of the Egyptian Green Pyramid Rating System

    International Nuclear Information System (INIS)

    Abdel Aleem, Shady H.E.; Zobaa, Ahmed F.; Abdel Mageed, Hala M.

    2015-01-01

    Energy is one of the most important categories in the Green Building Rating Systems all over the world. Green Building is a building that meets the energy requirements of the present with low energy consumption and investment costs without infringing on the rights of forthcoming generations to find their own needs. Despite having more than a qualified rating system, it is clear that each system has different priorities and needs on the other. Accordingly, this paper proposes a methodology using the Analytic Hierarchy Process (AHP) for assessment of the energy credits through studying and comparing four of the common global rating systems, the British Building Research Establishment Environmental Assessment Method (BREEAM), the American Leadership in Energy and Environmental Design (LEED), the Australian Green Stars (GS), and the PEARL assessment system of the United Arab Emirates, in order to contribute to the enhancement of the Egyptian Green Pyramid Rating System (GPRS). The results show the mandatory and optional energy credits that should be considered with their proposed weights according to the present and future needs of green Egypt. The results are compared to data gathered through desk studies and results extracted from recent questionnaires. - Highlights: • The Egyptian rating system is underway but not on track. • The main objective is the enhancement of the Egyptian rating system. • We propose a methodology for assessment of the energy credits. • The results show the optional energy credits with their optimal weights. • The results show the mandatory energy credits that should be considered.

  19. Extracellular Ca(2+)-dependent enhancement of cytocidal potency of zoledronic acid in human oral cancer cells.

    Science.gov (United States)

    Inoue, Sayaka; Arai, Naoya; Tomihara, Kei; Takashina, Michinori; Hattori, Yuichi; Noguchi, Makoto

    2015-08-15

    Direct antitumor effects of bisphosphonates (BPs) have been demonstrated in various cancer cells in vitro. However, the effective concentrations of BPs are typically much higher than their clinically relevant concentrations. Oral cancers frequently invade jawbone and may lead to the release of Ca(2+) in primary lesions. We investigated the effects of the combined application of zoledronic acid (ZA) and Ca(2+) on proliferation and apoptosis of oral cancer cells. Human oral cancer cells, breast cancer cells, and colon cancer cells were treated with ZA at a wide range of concentrations in different Ca(2+) concentration environments. Under a standard Ca(2+) concentration (0.6mM), micromolar concentrations of ZA were required to inhibit oral cancer cell proliferation. Increasing extracellular Ca(2+) concentrations greatly enhanced the potency of the ZA cytocidal effect. The ability of Ca(2+) to enhance the cytocidal effects of ZA was negated by the Ca(2+)-selective chelator EGTA. In contrast, the cytocidal effect of ZA was less pronounced in breast and colon cancer cells regardless of whether extracellular Ca(2+) was elevated. In oral cancer cells incubated with 1.6mM Ca(2+), ZA up-regulated mitochondrial Bax expression and increased mitochondrial Ca(2+) uptake. This was associated with decreased mitochondrial membrane potential and increased release of cytochrome c. We suggest that ZA can specifically produce potent cytocidal activity in oral cancer cells in an extracellular Ca(2+)-dependent manner, implying that BPs may be useful for treatment of oral squamous cell carcinoma with jawbone invasion leading to the hypercalcemic state. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. Effect of housing rats within a pyramid on stress parameters.

    Science.gov (United States)

    Bhat, Surekha; Rao, Guruprasad; Murthy, K Dilip; Bhat, P Gopalakrishna

    2003-11-01

    The Giza pyramids of Egypt have been the subject of much research. Pyramid models with the same base to height ratio as of the Great Pyramid of Giza, when aligned on a true north-south axis, are believed to generate, transform and transmit energy. Research done with such pyramid models has shown that they induced greater relaxation in human subjects, promoted better wound healing in rats and afforded protection against stress-induced neurodegnerative changes in mice. The present study was done to assess the effects of housing Wistar rats within the pyramid on the status of oxidative damage and antioxidant defense in their erythrocytes and cortisol levels in their plasma. Rats were housed in cages under standard laboratory conditions. Cages were left in the open (normal control), under a wooden pyramid model (experimental rats) or in a cubical box of comparable dimensions (6 hr/day for 14 days). Erythrocyte malondialdehyde and plasma cortisol levels were significantly decreased in rats kept within the pyramid as compared to the normal control and those within the square box. Erythrocyte reduced glutathione levels, erythrocyte glutathione peroxidase and superoxide dismutase activities were significantly increased in the rats kept in the pyramid as compared to the other two groups. There was no significant difference in any of the parameters between the normal control and rats kept in the square box. The results showed that exposure of adult female Wistar rats to pyramid environment reduces stress oxidative stress and increases antioxidant defense in them.

  1. Effect of Ca{sup 2+} substitution on impedance and electrical conduction mechanism of Ba{sub 1−x}Ca{sub x}Zr{sub 0.1}Ti{sub 0.9}O{sub 3} (0.00≤x≤0.20) ceramics

    Energy Technology Data Exchange (ETDEWEB)

    Mondal, Tanusree [Functional Ceramics Laboratory, Department of Applied Physics, Indian Institute of Technology (ISM), Dhanbad 826004 (India); Das, Sayantani [Department of Physics, University of Calcutta, 92, Acharya Prafulla Chandra Road, Kolkata 700009 (India); Badapanda, T. [Department of Physics, C.V. Raman College of Engineering, Bhubaneswar, Odisha 7520544 (India); Sinha, T.P. [Department of Physics, Bose Institute, 93/1, Acharya Prafulla Chandra Road, Kolkata 700009 (India); Sarun, P.M., E-mail: sarun.res@gmail.com [Functional Ceramics Laboratory, Department of Applied Physics, Indian Institute of Technology (ISM), Dhanbad 826004 (India)

    2017-03-01

    The Ca modified Ba{sub 1−x}Ca{sub x}Zr{sub 0.1}Ti{sub 0.9}O{sub 3} (BCZT) system for x=0.00–0.20 is synthesized by the high-temperature conventional solid state reaction method. The morphotropic phase boundary (MPB) between the tetragonal and cubic structure is obtained at room temperature for the composition x=0.15. The doping of Ca facilitates the enhancement of the homogeneity of microstructure and growth of the grain size. The phase transition is also confirmed by Raman spectroscopy. In order to explore the effect of Ca concentration variation on the conduction mechanism of BaZr{sub 0.1}Ti{sub 0.9}O{sub 3} (BZT) ceramic, the frequency dependent ac impedance spectroscopy technique is used at various temperatures. The effect of Ca doping on the electrical properties of BZT is clearly noticeable. The resistance of the grain (bulk) and the grain boundary is increased as a consequence of the increase in the activation energy of Ca substituted BZT samples. The enhanced resistivity of the Ca substituted BZT ceramics is explained in terms of the decrease in the mobility of the charge carriers associated with the lattice distortion. The electric modulus analysis reveals the enhanced capacitance of BCZT ceramics which is in good agreement with the results obtained from complex impedance analysis.

  2. Graphene oxide-Ag nanoparticles-pyramidal silicon hybrid system for homogeneous, long-term stable and sensitive SERS activity

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Jia [School of Physics and Electronics, Shandong Normal University, Jinan 250014 (China); Xu, Shicai [Shandong Provincial Key Laboratory of Biophysics, College of Physics and Electronic Information, Dezhou University, Dezhou 253023 (China); Liu, Xiaoyun; Li, Zhe; Hu, Litao; Li, Zhen; Chen, Peixi; Ma, Yong [School of Physics and Electronics, Shandong Normal University, Jinan 250014 (China); Jiang, Shouzhen, E-mail: jiang_sz@126.com [School of Physics and Electronics, Shandong Normal University, Jinan 250014 (China); Shandong Provincial Key Laboratory of Optics and Photonic Device, Jinan 250014 (China); Ning, Tingyin [School of Physics and Electronics, Shandong Normal University, Jinan 250014 (China); Shandong Provincial Key Laboratory of Optics and Photonic Device, Jinan 250014 (China)

    2017-02-28

    Highlights: • We directly grown AgNPs on substrate by annealing method in the quartz tube. Compare with spin-coating Ag nanoparticles solution method, we got more uniform distribution of AgNPs and the AgNPs better adsorption on the substrate. • We use a simple and lost-cost method to obtain the pyramidal silicon (PSi). The PSi possessing well-separated pyramid arrays can make contribution to the homogeneity and sensitivity of the substrate. • In our work, graphene oxide (GO) film is uniformly deposited on AgNPs and PSi by using a spin-coating method. The GO films endow the hybrid system a good stability and enhance the homogeneity and sensitivity of the substrate. - Abstract: In our work, few layers graphene oxide (GO) were directly synthesized on Ag nanoparticles (AgNPs) by spin-coating method to fabricate a GO-AgNPs hybrid structure on a pyramidal silicon (PSi) substrate for surface-enhanced Raman scattering (SERS). The GO-AgNPs-PSi substrate showed excellent Raman enhancement effect, the minimum detected concentration for Rhodamine 6G (R6G) can reach 10{sup −12} M, which is one order of magnitude lower than the AgNPs-PSi substrate and two order of magnitude lower than the GO-AgNPs-flat-Si substrate. The linear fit calibration curve with error bars is presented and the value of R{sup 2} of 612 and 773 cm{sup −1} can reach 0.986 and 0.980, respectively. The excellent linear response between the Raman intensity and R6G concentrations prove that the prepared GO-AgNPs-PSi substrates can serve as good SERS substrate for molecule detection. The maximum deviations of SERS intensities from 20 positions of the GO-AgNPs-PSi substrate are less than 8%, revealing the high homogeneity of the SERS substrate. The excellent homogeneity of the enhanced Raman signals can be attributed to well-separated pyramid arrays of PSi, the uniform morphology of AgNPs and multi-functions of GO layer. Besides, the uniform GO film can effectively protect AgNPs from oxidation and endow

  3. Effects of neonatal. gamma. -ray irradiation on rat hippocampus: Pt. 1; Postnatal maturation of hippocampal cells

    Energy Technology Data Exchange (ETDEWEB)

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

    1991-01-01

    The axons of dentate granule cells, the mossy fibres, establish synaptic contacts with the thorny excrescences of the apical dendrite of CA3 pyramidal neurons. Dentate granule cells develop postnatally in rats, whereas the CA3 pyramidal cells are generated before birth. In the present studies, using unilateral neonatal {gamma}-ray irradiation to destroy the granule cells in one hemisphere, we have studied the effect of mossy fibre deprivation on the development of their targets. We show that such ''degranulation'' prevents the normal development of giant thorny excrescences, suggesting that the development of thorny excrescences in CA3 pyramidal neurons is under the control of mossy fibres. In contrast, irradiation of the hippocampus of the neonatal rat does not affect the development of the dendritic arborization of CA3 pyramidal cells and their non-mossy dendritic spines. (author).

  4. A new class of morphological pyramids for multiresolution image analysis

    NARCIS (Netherlands)

    Roerdink, Jos B.T.M.; Asano, T; Klette, R; Ronse, C

    2003-01-01

    We study nonlinear multiresolution signal decomposition based on morphological pyramids. Motivated by a problem arising in multiresolution volume visualization, we introduce a new class of morphological pyramids. In this class the pyramidal synthesis operator always has the same form, i.e. a

  5. Pyramidal cell development: postnatal spinogenesis, dendritic growth, axon growth, and electrophysiology.

    Directory of Open Access Journals (Sweden)

    Guy eElston

    2014-08-01

    Full Text Available Here we review recent findings related to postnatal spinogenesis, dendritic and axon growth, pruning and electrophysiology of neocortical pyramidal cells in the developing primate brain. Pyramidal cells in sensory, association and executive cortex grow dendrites, spines and axons at different rates, and vary in the degree of pruning. Of particular note is the fact that pyramidal cells in primary visual area (V1 prune more spines than they grow during postnatal development, whereas those in inferotemporal (TEO and TE and granular prefrontal cortex (gPFC; Brodmann’s area 12 grow more than they prune. Moreover, pyramidal cells in TEO, TE and the gPFC continue to grow larger dendritic territories from birth into adulthood, replete with spines, whereas those in V1 become smaller during this time. The developmental profile of intrinsic axons also varies between cortical areas: those in V1, for example, undergo an early proliferation followed by pruning and local consolidation into adulthood, whereas those in area TE tend to establish their territory and consolidate it into adulthood with little pruning. We correlate the anatomical findings with the electrophysiological properties of cells in the different cortical areas, including membrane time constant, depolarizing sag, duration of individual action potentials, and spike-frequency adaptation. All of the electrophysiological variables ramped up before 7 months of age in V1, but continued to ramp up over a protracted period of time in area TE. These data suggest that the anatomical and electrophysiological profiles of pyramidal cells vary among cortical areas at birth, and continue to diverge into adulthood. Moreover, the data reveal that the use it or lose it notion of synaptic reinforcement may speak to only part of the story, use it but you still might lose it may be just as prevalent in the cerebral cortex.

  6. Exogenous progesterone exacerbates running response of adolescent female mice to repeated food restriction stress by changing α4-GABAA receptor activity of hippocampal pyramidal cells.

    Science.gov (United States)

    Wable, G S; Chen, Y-W; Rashid, S; Aoki, C

    2015-12-03

    Adolescent females are particularly vulnerable to mental illnesses with co-morbidity of anxiety, such as anorexia nervosa (AN). We used an animal model of AN, called activity-based anorexia (ABA), to investigate the neurobiological basis of vulnerability to repeated, food restriction (FR) stress-evoked anxiety. Twenty-one of 23 adolescent female mice responded to the 1st FR with increased wheel-running activity (WRA), even during the limited period of food access, thereby capturing AN's symptoms of voluntary FR and over-exercise. Baseline WRA was an excellent predictor of FR-elicited WRA (severity of ABA, SOA), with high baseline runners responding to FR with minimal SOA (i.e., negative correlation). Nine gained resistance to ABA following the 1st FR. Even though allopregnanolone (3α-OH-5α-pregnan-20-one, THP), the metabolite of progesterone (P4), is a well-recognized anxiolytic agent, subcutaneous P4 to these ABA-resistant animals during the 2nd FR was exacerbative, evoking greater WRA than the counterpart resistant group that received oil vehicle, only. Moreover, P4 had no WRA-reducing effect on animals that remained ABA-vulnerable. To explain the sensitizing effect of P4 upon the resistant mice, we examined the relationship between P4 treatment and levels of the α4 subunit of GABAARs at spines of pyramidal cells of the hippocampal CA1, a parameter previously shown to correlate with resistance to ABA. α4 levels at spine membrane correlated strongly and negatively with SOA during the 1st ABA (prior to P4 injection), confirming previous findings. α4 levels were greater among P4-treated animals that had gained resistance than of vehicle-treated resistant animals or of the vulnerable animals with or without P4. We propose that α4-GABAARs play a protective role by counterbalancing the ABA-induced increase in excitability of CA1 pyramidal neurons, and although exogenous P4's metabolite, THP, enhances α4 expression, especially among those that can gain resistance

  7. Aging-related impairments of hippocampal mossy fibers synapses on CA3 pyramidal cells.

    Science.gov (United States)

    Villanueva-Castillo, Cindy; Tecuatl, Carolina; Herrera-López, Gabriel; Galván, Emilio J

    2017-01-01

    The network interaction between the dentate gyrus and area CA3 of the hippocampus is responsible for pattern separation, a process that underlies the formation of new memories, and which is naturally diminished in the aged brain. At the cellular level, aging is accompanied by a progression of biochemical modifications that ultimately affects its ability to generate and consolidate long-term potentiation. Although the synapse between dentate gyrus via the mossy fibers (MFs) onto CA3 neurons has been subject of extensive studies, the question of how aging affects the MF-CA3 synapse is still unsolved. Extracellular and whole-cell recordings from acute hippocampal slices of aged Wistar rats (34 ± 2 months old) show that aging is accompanied by a reduction in the interneuron-mediated inhibitory mechanisms of area CA3. Several MF-mediated forms of short-term plasticity, MF long-term potentiation and at least one of the critical signaling cascades necessary for potentiation are also compromised in the aged brain. An analysis of the spontaneous glutamatergic and gamma-aminobutyric acid-mediated currents on CA3 cells reveal a dramatic alteration in amplitude and frequency of the nonevoked events. CA3 cells also exhibited increased intrinsic excitability. Together, these results demonstrate that aging is accompanied by a decrease in the GABAergic inhibition, reduced expression of short- and long-term forms of synaptic plasticity, and increased intrinsic excitability. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Phospholipid mediated activation of calcium dependent protein kinase 1 (CaCDPK1 from chickpea: a new paradigm of regulation.

    Directory of Open Access Journals (Sweden)

    Ajay Kumar Dixit

    Full Text Available Phospholipids, the major structural components of membranes, can also have functions in regulating signaling pathways in plants under biotic and abiotic stress. The effects of adding phospholipids on the activity of stress-induced calcium dependent protein kinase (CaCDPK1 from chickpea are reported here. Both autophosphorylation as well as phosphorylation of the added substrate were enhanced specifically by phosphatidylcholine and to a lesser extent by phosphatidic acid, but not by phosphatidylethanolamine. Diacylgylerol, the neutral lipid known to activate mammalian PKC, stimulated CaCDPK1 but at higher concentrations. Increase in V(max of the enzyme activity by these phospholipids significantly decreased the K(m indicating that phospholipids enhance the affinity towards its substrate. In the absence of calcium, addition of phospholipids had no effect on the negligible activity of the enzyme. Intrinsic fluorescence intensity of the CaCDPK1 protein was quenched on adding PA and PC. Higher binding affinity was found with PC (K(½ = 114 nM compared to PA (K(½ = 335 nM. We also found that the concentration of PA increased in chickpea plants under salt stress. The stimulation by PA and PC suggests regulation of CaCDPK1 by these phospholipids during stress response.

  9. Multiple C-terminal tail Ca(2+)/CaMs regulate Ca(V)1.2 function but do not mediate channel dimerization.

    Science.gov (United States)

    Kim, Eun Young; Rumpf, Christine H; Van Petegem, Filip; Arant, Ryan J; Findeisen, Felix; Cooley, Elizabeth S; Isacoff, Ehud Y; Minor, Daniel L

    2010-12-01

    Interactions between voltage-gated calcium channels (Ca(V)s) and calmodulin (CaM) modulate Ca(V) function. In this study, we report the structure of a Ca(2+)/CaM Ca(V)1.2 C-terminal tail complex that contains two PreIQ helices bridged by two Ca(2+)/CaMs and two Ca(2+)/CaM-IQ domain complexes. Sedimentation equilibrium experiments establish that the complex has a 2:1 Ca(2+)/CaM:C-terminal tail stoichiometry and does not form higher order assemblies. Moreover, subunit-counting experiments demonstrate that in live cell membranes Ca(V)1.2s are monomers. Thus, contrary to previous proposals, the crystallographic dimer lacks physiological relevance. Isothermal titration calorimetry and biochemical experiments show that the two Ca(2+)/CaMs in the complex have different properties. Ca(2+)/CaM bound to the PreIQ C-region is labile, whereas Ca(2+)/CaM bound to the IQ domain is not. Furthermore, neither of lobes of apo-CaM interacts strongly with the PreIQ domain. Electrophysiological studies indicate that the PreIQ C-region has a role in calcium-dependent facilitation. Together, the data show that two Ca(2+)/CaMs can bind the Ca(V)1.2 tail simultaneously and indicate a functional role for Ca(2+)/CaM at the C-region site.

  10. Neuroprotective effect of olive oil in the hippocampus CA1 neurons following ischemia: Reperfusion in mice

    Directory of Open Access Journals (Sweden)

    M Zamani

    2013-01-01

    Full Text Available Introduction: Transient global ischemia induces selective, delayed neuronal death of pyramidal neurons in the hippocampal CA1. Oxidative Stress is considered to be involved in a number of human diseases including ischemia. Preliminary studies confirmed reduction of cell death in brain following treatment with antioxidants. Aim: According to this finding, we study the relationship between consumption of olive oil on cell death and memory disorder in brain ischemia. We studied the protective effect of olive oil against ischemia-reperfusion. Material and Methods: Experimental design includes three groups: Intact (n = 8, ischemic control (n = 8 and treatment groups with olive oil (n = 8. The mice treated with olive oil as pre-treatment for a week. Then, ischemia induced by common carotid artery ligation and following the reduction of inflammation [a week after ischemia], the mice post-treated with olive oil. Nissl staining applied for counting necrotic cells in hippocampus CA1. Tunnel kit was used to quantify apoptotic cell death while to short term memory scale, we apply y-maze and shuttle box tests and for detection the rate of apoptotic and treated cell, we used western blotting test for bax and bcl2 proteins. Results: High rate of apoptosis was seen in ischemic group that significantly associated with short-term memory loss. Cell death was significantly lower when mice treated with olive oil. The memory test results were adjusted with cell death results and bax and bcl2 expression in all groups′ comparison. Ischemia for 15 min induced cell death in hippocampus with more potent effect on CA1. Conclusion: Olive oil intake significantly reduced cell death and decreased memory loss.

  11. High density micro-pyramids with silicon nanowire array for photovoltaic applications

    International Nuclear Information System (INIS)

    Rahman, Tasmiat; Navarro-Cía, Miguel; Fobelets, Kristel

    2014-01-01

    We use a metal assisted chemical etch process to fabricate silicon nanowire arrays (SiNWAs) onto a dense periodic array of pyramids that are formed using an alkaline etch masked with an oxide layer. The hybrid micro-nano structure acts as an anti-reflective coating with experimental reflectivity below 1% over the visible and near-infrared spectral regions. This represents an improvement of up to 11 and 14 times compared to the pyramid array and SiNWAs on bulk, respectively. In addition to the experimental work, we optically simulate the hybrid structure using a commercial finite difference time domain package. The results of the optical simulations support our experimental work, illustrating a reduced reflectivity in the hybrid structure. The nanowire array increases the absorbed carrier density within the pyramid by providing a guided transition of the refractive index along the light path from air into the silicon. Furthermore, electrical simulations which take into account surface and Auger recombination show an efficiency increase for the hybrid structure of 56% over bulk, 11% over pyramid array and 8.5% over SiNWAs. (paper)

  12. Nanopore fabricated in pyramidal HfO2 film by dielectric breakdown method

    Science.gov (United States)

    Wang, Yifan; Chen, Qi; Deng, Tao; Liu, Zewen

    2017-10-01

    The dielectric breakdown method provides an innovative solution to fabricate solid-state nanopores on insulating films. A nanopore generation event via this method is considered to be caused by random charged traps (i.e., structural defects) and high electric fields in the membrane. Thus, the position and number of nanopores on planar films prepared by the dielectric breakdown method is hard to control. In this paper, we propose to fabricate nanopores on pyramidal HfO2 films (10-nm and 15-nm-thick) to improve the ability to control the location and number during the fabrication process. Since the electric field intensity gets enhanced at the corners of the pyramid-shaped film, the probability of nanopore occurrence at vertex and edge areas increases. This priority of appearance provides us chance to control the location and number of nanopores by monitoring a sudden irreversible discrete increase in current. The experimental results showed that the probability of nanopore occurrence decreases in an order from the vertex area, the edge area to the side face area. The sizes of nanopores ranging from 30 nm to 10 nm were obtained. Nanopores fabricated on the pyramid-shaped HfO2 film also showed an obvious ion current rectification characteristic, which might improve the nanopore performance as a biomolecule sequencing platform.

  13. Biofilm exopolymers control microbialite formation at thermal springs discharging into the alkaline Pyramid Lake, Nevada, USA

    Science.gov (United States)

    Arp, Gernot; Thiel, Volker; Reimer, Andreas; Michaelis, Walter; Reitner, Joachim

    1999-07-01

    Calcium carbonate precipitation and microbialite formation at highly supersaturated mixing zones of thermal spring waters and alkaline lake water have been investigated at Pyramid Lake, Nevada. Without precipitation, pure mixing should lead to a nearly 100-fold supersaturation at 40°C. Physicochemical precipitation is modified or even inhibited by the properties of biofilms, dependent on the extent of biofilm development and the current precipitation rate. Mucus substances (extracellular polymeric substances, EPS, e.g., of cyanobacteria) serve as effective Ca 2+-buffers, thus preventing seed crystal nucleation even in a highly supersaturated macroenvironment. Carbonate is then preferentially precipitated in mucus-free areas such as empty diatom tests or voids. After the buffer capacity of the EPS is surpassed, precipitation is observed at the margins of mucus areas. Hydrocarbon biomarkers extracted from (1) a calcifying Phormidium-biofilm, (2) the stromatolitic carbonate below, and (3) a fossil `tufa' of the Pleistocene pinnacles, indicate that the cyanobacterial primary producers have been subject to significant temporal changes in their species distribution. Accordingly, the species composition of cyanobacterial biofilms does not appear to be relevant for the formation of microbial carbonates in Pyramid Lake. The results demonstrate the crucial influence of mucus substances on carbonate precipitation in highly supersaturated natural environments.

  14. Enhancement of information transmission with stochastic resonance in hippocampal CA1 neuron models: effects of noise input location.

    Science.gov (United States)

    Kawaguchi, Minato; Mino, Hiroyuki; Durand, Dominique M

    2007-01-01

    Stochastic resonance (SR) has been shown to enhance the signal to noise ratio or detection of signals in neurons. It is not yet clear how this effect of SR on the signal to noise ratio affects signal processing in neural networks. In this paper, we investigate the effects of the location of background noise input on information transmission in a hippocampal CA1 neuron model. In the computer simulation, random sub-threshold spike trains (signal) generated by a filtered homogeneous Poisson process were presented repeatedly to the middle point of the main apical branch, while the homogeneous Poisson shot noise (background noise) was applied to a location of the dendrite in the hippocampal CA1 model consisting of the soma with a sodium, a calcium, and five potassium channels. The location of the background noise input was varied along the dendrites to investigate the effects of background noise input location on information transmission. The computer simulation results show that the information rate reached a maximum value for an optimal amplitude of the background noise amplitude. It is also shown that this optimal amplitude of the background noise is independent of the distance between the soma and the noise input location. The results also show that the location of the background noise input does not significantly affect the maximum values of the information rates generated by stochastic resonance.

  15. Evaluation of the Green Egyptian Pyramid

    OpenAIRE

    Ammar, Mohamed Gamal

    2012-01-01

    In January 2009 was established the Egyptian Council for evaluating green building, then the Board issue a primary version of the Egyptian pyramid in 2010, and as a result of economic, social and political changes that happened in Egypt after the Arab spring period, the study of regional experiences of neighboring countries in Africa and Asia in the development of evaluation system for green buildings of global systems that can contribute to the development of the Egyptian pyramid to promote ...

  16. Tiling a Pyramidal Polycube with Dominoes

    Directory of Open Access Journals (Sweden)

    Olivier Bodini

    2007-05-01

    Full Text Available The notion of pyramidal polycubes, namely the piling-up of bricks of a non-increasing size, generalizes in ℝ n the concept of trapezoidal polyominoes. In the present paper, we prove that n-dimensional dominoes can tile a pyramidal polycube if and only if the latter is balanced, that is, if the number of white cubes is equal to the number of black ones for a chessboard-like coloration, generalizing the result of [BC92] when n=2

  17. SFPQ associates to LSD1 and regulates the migration of newborn pyramidal neurons in the developing cerebral cortex.

    Science.gov (United States)

    Saud, K; Cánovas, J; Lopez, C I; Berndt, F A; López, E; Maass, J C; Barriga, A; Kukuljan, M

    2017-04-01

    The development of the cerebral cortex requires the coordination of multiple processes ranging from the proliferation of progenitors to the migration and establishment of connectivity of the newborn neurons. Epigenetic regulation carried out by the COREST/LSD1 complex has been identified as a mechanism that regulates the development of pyramidal neurons of the cerebral cortex. We now identify the association of the multifunctional RNA-binding protein SFPQ to LSD1 during the development of the cerebral cortex. In vivo reduction of SFPQ dosage by in utero electroporation of a shRNA results in impaired radial migration of newborn pyramidal neurons, in a similar way to that observed when COREST or LSD1 expressions are decreased. Diminished SFPQ expression also associates to decreased proliferation of progenitor cells, while it does not affect the acquisition of neuronal fate. These results are compatible with the idea that SFPQ, plays an important role regulating proliferation and migration during the development of the cerebral cortex. Copyright © 2016 ISDN. Published by Elsevier Ltd. All rights reserved.

  18. Tunneling and propping : a justification for pyramidal ownership

    NARCIS (Netherlands)

    Riyanto, Y.E.; Toolsema-Veldman, Linda

    2004-01-01

    This paper presents a formal model of tunneling and propping in a pyramidal ownership structure. Tunneling refers to controlling shareholders shifting resources from one firm to another in the same pyramid. Propping is tunneling that is done to save the receiving firm from bankruptcy. We compare the

  19. Transient Receptor Potential Canonical (TRPC)/Orai1-dependent Store-operated Ca2+ Channels

    Science.gov (United States)

    Sabourin, Jessica; Bartoli, Fiona; Antigny, Fabrice; Gomez, Ana Maria; Benitah, Jean-Pierre

    2016-01-01

    Store-operated Ca2+ entry (SOCE) has emerged as an important mechanism in cardiac pathology. However, the signals that up-regulate SOCE in the heart remain unexplored. Clinical trials have emphasized the beneficial role of mineralocorticoid receptor (MR) signaling blockade in heart failure and associated arrhythmias. Accumulated evidence suggests that the mineralocorticoid hormone aldosterone, through activation of its receptor, MR, might be a key regulator of Ca2+ influx in cardiomyocytes. We thus assessed whether and how SOCE involving transient receptor potential canonical (TRPC) and Orai1 channels are regulated by aldosterone/MR in neonatal rat ventricular cardiomyocytes. Molecular screening using qRT-PCR and Western blotting demonstrated that aldosterone treatment for 24 h specifically increased the mRNA and/or protein levels of Orai1, TRPC1, -C4, -C5, and stromal interaction molecule 1 through MR activation. These effects were correlated with a specific enhancement of SOCE activities sensitive to store-operated channel inhibitors (SKF-96365 and BTP2) and to a potent Orai1 blocker (S66) and were prevented by TRPC1, -C4, and Orai1 dominant negative mutants or TRPC5 siRNA. A mechanistic approach showed that up-regulation of serum- and glucocorticoid-regulated kinase 1 mRNA expression by aldosterone is involved in enhanced SOCE. Functionally, 24-h aldosterone-enhanced SOCE is associated with increased diastolic [Ca2+]i, which is blunted by store-operated channel inhibitors. Our study provides the first evidence that aldosterone promotes TRPC1-, -C4-, -C5-, and Orai1-mediated SOCE in cardiomyocytes through an MR and serum- and glucocorticoid-regulated kinase 1 pathway. PMID:27129253

  20. Tunneling and propping : A justification for pyramidal ownership

    NARCIS (Netherlands)

    Riyanto, Y.E.; Toolsema-Veldman, Linda

    2008-01-01

    This paper links existence of the pyramidal ownership structure to tunneling and propping. Tunneling refers to a transfer of resources from a lower-level firm to a higher-level firm in the pyramidal chain, whereas propping concerns a transfer in the opposite direction intended to bail out the

  1. Content-adaptive pyramid representation for 3D object classification

    DEFF Research Database (Denmark)

    Kounalakis, Tsampikos; Boulgouris, Nikolaos; Triantafyllidis, Georgios

    2016-01-01

    In this paper we introduce a novel representation for the classification of 3D images. Unlike most current approaches, our representation is not based on a fixed pyramid but adapts to image content and uses image regions instead of rectangular pyramid scales. Image characteristics, such as depth...... and color, are used for defining regions within images. Multiple region scales are formed in order to construct the proposed pyramid image representation. The proposed method achieves excellent results in comparison to conventional representations....

  2. The Effect of N-acetyl-cysteine on Memory Retrieval and the Number of Intact Neurons of Hippocampal CA1 Area in Streptozotocin-induced Alzheimeric Male Rats

    Directory of Open Access Journals (Sweden)

    Niloufar Darbandi

    2018-01-01

    Full Text Available Abstract Background: Alzheimer is a neurodegenerative disease wich caused memory impairment, reduced cognitive functions, intellectual ability and behavior changes. In this study, the effect of N-acetyl-cysteine (NAC as a strong antioxidant on memory deficiency and number of CA1 pyramidal neurons in Streptozotocine (STZ - induced Alzheimeric rats were studied. Materials and Methods: 32 Male Wistar rats were divided into four groups: sham group, streptozotocin group, treated group with streptozotocin plus N-acetyl-cysteine, and treated group with N-acetyl-cysteine alone. Intracerebroventricular (ICV administration of STZ was done in the first and the third day of surgery and i.p injection of N-acetyl-cysteine was done in the fourth of surgery. After the memory test, the animals were killed and their brains were fixed and density of intact neurons in the CA1 area of the hippocampus was investigated. Statistical analysis was performed with software SPSS, ANOVA and Prisme software. The level of statistical significance was set at p 0.05. Conclusion: N-acetyl-cysteine improved memory retrieval and hippocampal CA1 area intact neurons in streptozotocin-induced Alzheimeric male rats.

  3. Ih tunes theta/gamma oscillations and cross-frequency coupling in an in silico CA3 model.

    Directory of Open Access Journals (Sweden)

    Samuel A Neymotin

    Full Text Available Ih channels are uniquely positioned to act as neuromodulatory control points for tuning hippocampal theta (4-12 Hz and gamma (25 Hz oscillations, oscillations which are thought to have importance for organization of information flow. contributes to neuronal membrane resonance and resting membrane potential, and is modulated by second messengers. We investigated oscillatory control using a multiscale computer model of hippocampal CA3, where each cell class (pyramidal, basket, and oriens-lacunosum moleculare cells, contained type-appropriate isoforms of . Our model demonstrated that modulation of pyramidal and basket allows tuning theta and gamma oscillation frequency and amplitude. Pyramidal also controlled cross-frequency coupling (CFC and allowed shifting gamma generation towards particular phases of the theta cycle, effected via 's ability to set pyramidal excitability. Our model predicts that in vivo neuromodulatory control of allows flexibly controlling CFC and the timing of gamma discharges at particular theta phases.

  4. A possible explanation of the void discovered in the pyramid of Khufu on the basis of the pyramid texts

    OpenAIRE

    Magli, Giulio

    2017-01-01

    A recent exploration has shown the presence of a significant void in the pyramid of Khufu at Giza. A possible explanation of this space, interpreted as a chamber connected to the lower north channel and aimed to contain a specific funerary equipment is tentatively proposed. According to the Pyramid Texts, this equipment might consist of a Iron throne, actually a wooden throne endowed with meteoritic Iron sheets.

  5. Degeneration of pyramidal tract of MRI (magnetic resonance imaging)

    International Nuclear Information System (INIS)

    Yamagami, Tatsuhito; Harada, Noboru; Gotoh, Yasunobu; Imataka, Kiyoharu; Kinuta, Yuji; Okumura, Teizo; Niijima, Kyo; Taki, Waro; Kikuchi, Haruhiko.

    1988-01-01

    MRI (magnetic resonance imaging) examinaion was performed on cases of hemiplegia and hemiparesis. These included seven cases of intracerebral hemorrhage, four cases of subarachnoid hemorrhage, one case of cerebral infarct, and two cases of head trauma. The pyramidal tract in the brain stem was studied in five patients with complete hemiplegia and in nine with incomplete hemiparesis. The scanner of the MRI was a resistive type operating at a field of 0.2 Tesla. The inversion recovery (IR) and saturation recovery (SR) techniques were utilized. The pyramidal tract at the level of the midbrain and the pons was recognized as a low intensity area on the T 1 image (IR 1500/43) in the cases of complete hemiplegia. However, it was recognized as a high intensity area on the SR image (SR 1000/60) and the T 2 image (SR 2000/100). No abnormal signal intensity was found in the cases of incomplete hemiparesis. A low intensity area on the T 1 image and a high intensity area on the T 2 image were recognized in the ventral portion of the midbrain and the pons on the affected side. These findings indicate a degeneration of the pyramidal tract at the level of the brain stem in patients with complete hemiplegia. (author)

  6. Multiresolution, Multi-Scale Target Identification and Tracking using the Anisotropic Diffusion Pyramid

    National Research Council Canada - National Science Library

    Acton, Scott

    1998-01-01

    ...: the anisotropic diffusion pyramid and the morphological pyramid. Coarse-to-fine target searches are implemented within the image pyramids, providing a lOOX improvement in computational expense over standard correlation-based approaches...

  7. Distinct roles of two ceramide synthases, CaLag1p and CaLac1p, in the morphogenesis of Candida albicans

    DEFF Research Database (Denmark)

    Cheon, Seon Ah; Bal, Jyotiranjan; Song, Yunkyoung

    2012-01-01

    p) and Lac1p (CaLac1p) are functionally distinct. Lack of CaLag1p, but not CaLac1p, caused severe defects in the growth and hyphal morphogenesis of C. albicans. Deletion of CaLAG1 decreased expression of the hypha-specific HWP1 and ECE1 genes. Moreover, overexpression of CaLAG1 induced pseudohyphal...... growth in this organism under non-hypha-inducing conditions, suggesting that CaLag1p is necessary for relaying signals to induce hypha-specific gene expression. Analysis of ceramide and sphingolipid composition revealed that CaLag1p predominantly synthesizes ceramides with C24:0/C26:0 fatty acid moieties...

  8. A role for progesterone and α4-containing GABAA receptors of hippocampal pyramidal cells in the exacerbated running response of adolescent female mice to repeated food restriction stress

    Science.gov (United States)

    Wable, Gauri; Chen, Yi-Wen; Rashid, Shannon; Aoki, Chiye

    2015-01-01

    Adolescent females are particularly vulnerable to mental illnesses with comorbidity of anxiety, such as anorexia nervosa (AN). We used an animal model of AN, called activity-based anorexia (ABA), to investigate the neurobiological basis of vulnerability to repeated, food restriction (FR) stress-evoked anxiety. Twenty-one of 23 adolescent female mice responded to the 1st FR with increased wheel running activity (WRA), even during the limited period of food access, thereby capturing AN's symptoms of voluntary FR and over-exercise. Baseline WRA was an excellent predictor of FR-elicited WRA (severity of ABA, SOA), with high baseline-runners responding to FR with minimal SOA (i.e., negative correlation). Nine gained resistance to ABA following the 1st FR. Even though allopregnanolone (3α-OH-5α-pregnan-20-one, THP), the metabolite of progesterone (P4), is a well-recognized anxiolytic agent, subcutaneous P4 to these ABA-resistant animals during the 2nd FR was exacerbative, evoking greater WRA than the counterpart resistant group that received oil vehicle, only. Moreover, P4 had no WRA-reducing effect on animals that remained ABA-vulnerable. To explain the sensitizing effect of P4 upon the resistant mice, we examined the relationship between P4 treatment and levels of the α4 subunit of GABAARs at spines of pyramidal cells of the hippocampal CA1, a parameter previously shown to correlate with resistance to ABA. α4 levels at spine membrane correlated strongly and negatively with SOA during the 1st ABA (prior to P4 injection), confirming previous findings. α4 expression levels were greater among P4-treated animals that had gained resistance than of vehicle-treated resistant animals or of the vulnerable animals with or without P4. We propose that α4-GABAARs play a protective role by counterbalancing the ABA-induced increase in excitability of CA1 pyramidal neurons, and although exogenous P4's metabolite, THP, enhances α4 expression, especially among those that can gain

  9. Growth of GaN single crystals by a Ca- and Ba-added Na flux method

    Science.gov (United States)

    Ukegawa, H.; Konishi, Y.; Fujimori, T.; Miyoshi, N.; Imade, M.; Yoshimura, M.; Kitaoka, Y.; Sasaki, T.; Mori, Y.

    2011-02-01

    GaN substrates are desirable for fabricating ultra-violet LEDs and LDs, and high-power and high-frequency transistors. High-quality GaN single crystals can be obtained by using Na flux method, but the growth habit of bulk crystals must be controlled. In this study, we investigated the effects of additives (Ca, Ba) on the growth habit and impurity concentration in the crystals. The aspect ratio (c/a) of the crystals was increased by increasing the amount of additives, showing that the growth habit could be changed from the pyramidal shape to the prism shape. Ba concentration was below the detection limit (1x1015 atoms/cm3).

  10. Essential Roles for ARID1B in Dendritic Arborization and Spine Morphology of Developing Pyramidal Neurons

    Science.gov (United States)

    Ka, Minhan; Chopra, Divyan A.; Dravid, Shashank M.

    2016-01-01

    De novo truncating mutations in ARID1B, a chromatin-remodeling gene, cause Coffin–Siris syndrome, a developmental disorder characterized by intellectual disability and speech impairment; however, how the genetic elimination leads to cognitive dysfunction remains unknown. Thus, we investigated the neural functions of ARID1B during brain development. Here, we show that ARID1B regulates dendritic differentiation in the developing mouse brain. We knocked down ARID1B expression in mouse pyramidal neurons using in utero gene delivery methodologies. ARID1B knockdown suppressed dendritic arborization of cortical and hippocampal pyramidal neurons in mice. The abnormal development of dendrites accompanied a decrease in dendritic outgrowth into layer I. Furthermore, knockdown of ARID1B resulted in aberrant dendritic spines and synaptic transmission. Finally, ARID1B deficiency led to altered expression of c-Fos and Arc, and overexpression of these factors rescued abnormal differentiation induced by ARID1B knockdown. Our results demonstrate a novel role for ARID1B in neuronal differentiation and provide new insights into the origin of cognitive dysfunction associated with developmental intellectual disability. SIGNIFICANCE STATEMENT Haploinsufficiency of ARID1B, a component of chromatin remodeling complex, causes intellectual disability. However, the role of ARID1B in brain development is unknown. Here, we demonstrate that ARID1B is required for neuronal differentiation in the developing brain, such as in dendritic arborization and synapse formation. Our findings suggest that ARID1B plays a critical role in the establishment of cognitive circuitry by regulating dendritic complexity. Thus, ARID1B deficiency may cause intellectual disability via abnormal brain wiring induced by the defective differentiation of cortical neurons. PMID:26937011

  11. Effect of 1,25(OH)2 vitamin D3 and ionized Ca2+ on 45Ca uptake by primary cultures of aortic myocytes of spontaneously hypertensive and Wistar Kyoto normotensive rats

    International Nuclear Information System (INIS)

    Bukoski, R.D.; Xue, H.; McCarron, D.A.

    1987-01-01

    The effect of several regulators of whole animal Ca 2+ homeostasis on 45 Ca uptake by primary cultures of aortic myocytes isolated from spontaneously hypertensive (SHR) and normotensive Wistar Kyoto (WKY) rats was examined. Exposure of confluent cells to 1.0, 1.25 or 1.50 mM ionized Ca 2+ in serum-free medium for seven days resulted in increased 45 Ca uptake at the higher concentrations of Ca 2+ in cells of the SHR but not the WKY. 1,25 (OH)2 vitamin D3 (1 ng/ml) for 7 days caused enhanced influx in cells from both the SHR and WKY while parathyroid hormone (1-34) (1 ng/ml) was without effect. The data indicate that humoral factors that serve to regulate whole animal Ca 2+ homeostasis may also play a role in the regulation of Ca 2+ metabolism of the vascular smooth muscle cell

  12. Chelation of hippocampal zinc enhances long-term potentiation and synaptic tagging/capture in CA1 pyramidal neurons of aged rats: implications to aging and memory.

    Science.gov (United States)

    Shetty, Mahesh Shivarama; Sharma, Mahima; Sajikumar, Sreedharan

    2017-02-01

    Aging is associated with decline in cognitive functions, prominently in the memory consolidation and association capabilities. Hippocampus plays a crucial role in the formation and maintenance of long-term associative memories, and a significant body of evidence shows that impairments in hippocampal function correlate with aging-related memory loss. A number of studies have implicated alterations in hippocampal synaptic plasticity, such as long-term potentiation (LTP), in age-related cognitive decline although exact mechanisms underlying are not completely clear. Zinc deficiency and the resultant adverse effects on cognition have been well studied. However, the role of excess of zinc in synaptic plasticity, especially in aging, is not addressed well. Here, we have investigated the hippocampal zinc levels and the impairments in synaptic plasticity, such as LTP and synaptic tagging and capture (STC), in the CA1 region of acute hippocampal slices from 82- to 84-week-old male Wistar rats. We report increased zinc levels in the hippocampus of aged rats and also deficits in the tetani-induced and dopaminergic agonist-induced late-LTP and STC. The observed deficits in synaptic plasticity were restored upon chelation of zinc using a cell-permeable chelator. These data suggest that functional plasticity and associativity can be successfully established in aged neural networks by chelating zinc with cell-permeable chelating agents. © 2016 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  13. The ebola virus interferon antagonist VP24 directly binds STAT1 and has a novel, pyramidal fold.

    Science.gov (United States)

    Zhang, Adrianna P P; Bornholdt, Zachary A; Liu, Tong; Abelson, Dafna M; Lee, David E; Li, Sheng; Woods, Virgil L; Saphire, Erica Ollmann

    2012-02-01

    Ebolaviruses cause hemorrhagic fever with up to 90% lethality and in fatal cases, are characterized by early suppression of the host innate immune system. One of the proteins likely responsible for this effect is VP24. VP24 is known to antagonize interferon signaling by binding host karyopherin α proteins, thereby preventing them from transporting the tyrosine-phosphorylated transcription factor STAT1 to the nucleus. Here, we report that VP24 binds STAT1 directly, suggesting that VP24 can suppress at least two distinct branches of the interferon pathway. Here, we also report the first crystal structures of VP24, derived from different species of ebolavirus that are pathogenic (Sudan) and nonpathogenic to humans (Reston). These structures reveal that VP24 has a novel, pyramidal fold. A site on a particular face of the pyramid exhibits reduced solvent exchange when in complex with STAT1. This site is above two highly conserved pockets in VP24 that contain key residues previously implicated in virulence. These crystal structures and accompanying biochemical analysis map differences between pathogenic and nonpathogenic viruses, offer templates for drug design, and provide the three-dimensional framework necessary for biological dissection of the many functions of VP24 in the virus life cycle.

  14. The ebola virus interferon antagonist VP24 directly binds STAT1 and has a novel, pyramidal fold.

    Directory of Open Access Journals (Sweden)

    Adrianna P P Zhang

    2012-02-01

    Full Text Available Ebolaviruses cause hemorrhagic fever with up to 90% lethality and in fatal cases, are characterized by early suppression of the host innate immune system. One of the proteins likely responsible for this effect is VP24. VP24 is known to antagonize interferon signaling by binding host karyopherin α proteins, thereby preventing them from transporting the tyrosine-phosphorylated transcription factor STAT1 to the nucleus. Here, we report that VP24 binds STAT1 directly, suggesting that VP24 can suppress at least two distinct branches of the interferon pathway. Here, we also report the first crystal structures of VP24, derived from different species of ebolavirus that are pathogenic (Sudan and nonpathogenic to humans (Reston. These structures reveal that VP24 has a novel, pyramidal fold. A site on a particular face of the pyramid exhibits reduced solvent exchange when in complex with STAT1. This site is above two highly conserved pockets in VP24 that contain key residues previously implicated in virulence. These crystal structures and accompanying biochemical analysis map differences between pathogenic and nonpathogenic viruses, offer templates for drug design, and provide the three-dimensional framework necessary for biological dissection of the many functions of VP24 in the virus life cycle.

  15. Involvement of the putative Ca²⁺-permeable mechanosensitive channels, NtMCA1 and NtMCA2, in Ca²⁺ uptake, Ca²⁺-dependent cell proliferation and mechanical stress-induced gene expression in tobacco (Nicotiana tabacum) BY-2 cells.

    Science.gov (United States)

    Kurusu, Takamitsu; Yamanaka, Takuya; Nakano, Masataka; Takiguchi, Akiko; Ogasawara, Yoko; Hayashi, Teruyuki; Iida, Kazuko; Hanamata, Shigeru; Shinozaki, Kazuo; Iida, Hidetoshi; Kuchitsu, Kazuyuki

    2012-07-01

    To gain insight into the cellular functions of the mid1-complementing activity (MCA) family proteins, encoding putative Ca²⁺-permeable mechanosensitive channels, we isolated two MCA homologs of tobacco (Nicotiana tabacum) BY-2 cells, named NtMCA1 and NtMCA2. NtMCA1 and NtMCA2 partially complemented the lethality and Ca²⁺ uptake defects of yeast mutants lacking mechanosensitive Ca²⁺ channel components. Furthermore, in yeast cells overexpressing NtMCA1 and NtMCA2, the hypo-osmotic shock-induced Ca²⁺ influx was enhanced. Overexpression of NtMCA1 or NtMCA2 in BY-2 cells enhanced Ca²⁺ uptake, and significantly alleviated growth inhibition under Ca²⁺ limitation. NtMCA1-overexpressing BY-2 cells showed higher sensitivity to hypo-osmotic shock than control cells, and induced the expression of the touch-inducible gene, NtERF4. We found that both NtMCA1-GFP and NtMCA2-GFP were localized at the plasma membrane and its interface with the cell wall, Hechtian strands, and at the cell plate and perinuclear vesicles of dividing cells. NtMCA2 transcript levels fluctuated during the cell cycle and were highest at the G1 phase. These results suggest that NtMCA1 and NtMCA2 play roles in Ca²⁺-dependent cell proliferation and mechanical stress-induced gene expression in BY-2 cells, by regulating the Ca²⁺ influx through the plasma membrane.

  16. Sigma-1 receptor chaperones at the ER-mitochondrion interface regulate Ca(2+) signaling and cell survival.

    Science.gov (United States)

    Hayashi, Teruo; Su, Tsung-Ping

    2007-11-02

    Communication between the endoplasmic reticulum (ER) and mitochondrion is important for bioenergetics and cellular survival. The ER supplies Ca(2+) directly to mitochondria via inositol 1,4,5-trisphosphate receptors (IP3Rs) at close contacts between the two organelles referred to as mitochondrion-associated ER membrane (MAM). We found here that the ER protein sigma-1 receptor (Sig-1R), which is implicated in neuroprotection, carcinogenesis, and neuroplasticity, is a Ca(2+)-sensitive and ligand-operated receptor chaperone at MAM. Normally, Sig-1Rs form a complex at MAM with another chaperone, BiP. Upon ER Ca(2+) depletion or via ligand stimulation, Sig-1Rs dissociate from BiP, leading to a prolonged Ca(2+) signaling into mitochondria via IP3Rs. Sig-1Rs can translocate under chronic ER stress. Increasing Sig-1Rs in cells counteracts ER stress response, whereas decreasing them enhances apoptosis. These results reveal that the orchestrated ER chaperone machinery at MAM, by sensing ER Ca(2+) concentrations, regulates ER-mitochondrial interorganellar Ca(2+) signaling and cell survival.

  17. PDGF-induced migration of synthetic vascular smooth muscle cells through c-Src-activated L-type Ca2+ channels with full-length CaV1.2 C-terminus.

    Science.gov (United States)

    Guo, Xiaoguang; Kashihara, Toshihide; Nakada, Tsutomu; Aoyama, Toshifumi; Yamada, Mitsuhiko

    2018-06-01

    In atherosclerosis, vascular smooth muscle cells (VSMC) migrate from the media toward the intima of the arteries in response to cytokines, such as platelet-derived growth factor (PDGF). However, molecular mechanism underlying the PDGF-induced migration of VSMCs remains unclear. The migration of rat aorta-derived synthetic VSMCs, A7r5, in response to PDGF was potently inhibited by a Ca V 1.2 channel inhibitor, nifedipine, and a Src family tyrosine kinase (SFK)/Abl inhibitor, bosutinib, in a less-than-additive manner. PDGF significantly increased Ca V 1.2 channel currents without altering Ca V 1.2 protein expression levels in A7r5 cells. This reaction was inhibited by C-terminal Src kinase, a selective inhibitor of SFKs. In contractile VSMCs, the C-terminus of Ca V 1.2 is proteolytically cleaved into proximal and distal C-termini (PCT and DCT, respectively). Clipped DCT is noncovalently reassociated with PCT to autoinhibit the channel activity. Conversely, in synthetic A7r5 cells, full-length Ca V 1.2 (Ca V 1.2FL) is expressed much more abundantly than truncated Ca V 1.2. In a heterologous expression system, c-Src activated Ca V 1.2 channels composed of Ca V 1.2FL but not truncated Ca V 1.2 (Ca V 1.2Δ1763) or Ca V 1.2Δ1763 plus clipped DCT. Further, c-Src enhanced the coupling efficiency between the voltage-sensing domain and activation gate of Ca V 1.2FL channels by phosphorylating Tyr1709 and Tyr1758 in PCT. Compared with Ca V 1.2Δ1763, c-Src could more efficiently bind to and phosphorylate Ca V 1.2FL irrespective of the presence or absence of clipped DCT. Therefore, in atherosclerotic lesions, phenotypic switching of VSMCs may facilitate pro-migratory effects of PDGF on VSMCs by suppressing posttranslational Ca V 1.2 modifications.

  18. Depolarization-dependent 45Ca uptake by synaptosomes of rat cerebral cortex is enhanced by L-triiodothyronine

    International Nuclear Information System (INIS)

    Mason, G.A.; Walker, C.H.; Prange, A.J. Jr.

    1990-01-01

    Depolarization-induced release of neurotransmitters and other secretions from nerve endings is triggered by the rapid entry of Ca++ through voltage-sensitive channels. Calcium entry is thought to occur in two distinct phases or processes: a fast-phase response to an action potential, which initiates release; and a slow phase associated with extended stimulation of the neuron. Thyroid hormones are sequestered by nerve terminals and can produce changes in behaviour and mood. They may therefore be involved in modulating central synaptic transmission. We studied the effects of L-triiodothyronine (T3), L-thyroxine (T4), reverse T3 (rT3) and D-T3 on depolarization-induced uptake of 45Ca by synaptosomes from euthyroid and hypothyroid rats. T3, but not T4, rT3, or D-T3 significantly enhanced depolarization-induced 45Ca uptake at physiologically relevant (1 to 10 nmol/L) concentrations. The stimulatory effect of 10 nmol/L T3 on depolarization-induced uptake after 2 seconds (21%) was greater than after 5 (10%) or 30 (8%) seconds, indicating that T3 enhanced primarily the fast-phase process. There was no effect of T3 or other hormones tested on nondepolarization-induced 45Ca uptake. Preincubation of synaptosomes with T3 prior to depolarization did not enhance the effect of T3; in fact, preincubations of 30 seconds or more resulted in diminished T3 effects. Preincubation of synaptosomes for 15 seconds with D-T3 or the addition of D-T3 and T3 together reduced the effect of T3. We found no difference in the effect of T3 on 45Ca uptake by synaptosomes from euthyroid and hypothyroid rats. These results suggest a novel mechanism of action of thyroid hormones in the brain

  19. Enhanced magnetoresistance in La0.7Ca0.3Mn03/Nd0.7Ca0.3Mn03 epitaxial multilayers

    International Nuclear Information System (INIS)

    Sharma, Himanshu; Khan, Md. S.; Tomy, C.V.; Jain, Sourabh; Tulapurkar, Ashwin

    2014-01-01

    Magnanite multilayers of La 0.7 Ca 0.3 MnO 3 /Nd 0.7 Ca 0.5 MnO 3 have been fabricated on SrTiO 3 (100) substrate using Nd 0.7 Ca 0.5 MnO 3 as the spacer layers. An enhanced magnetoresistance (MR) of more than 80% is observed in the multilayers compared with LCMO thin film (∼50%). Result suggests that the interface strains between LCMO and NCMO layers may have influences on the transport properties and a suitable film structure could be used to increase the large low field magnetoresistance. (author)

  20. The force pyramid: a spatial analysis of force application during virtual reality brain tumor resection.

    Science.gov (United States)

    Azarnoush, Hamed; Siar, Samaneh; Sawaya, Robin; Zhrani, Gmaan Al; Winkler-Schwartz, Alexander; Alotaibi, Fahad Eid; Bugdadi, Abdulgadir; Bajunaid, Khalid; Marwa, Ibrahim; Sabbagh, Abdulrahman Jafar; Del Maestro, Rolando F

    2017-07-01

    OBJECTIVE Virtual reality simulators allow development of novel methods to analyze neurosurgical performance. The concept of a force pyramid is introduced as a Tier 3 metric with the ability to provide visual and spatial analysis of 3D force application by any instrument used during simulated tumor resection. This study was designed to answer 3 questions: 1) Do study groups have distinct force pyramids? 2) Do handedness and ergonomics influence force pyramid structure? 3) Are force pyramids dependent on the visual and haptic characteristics of simulated tumors? METHODS Using a virtual reality simulator, NeuroVR (formerly NeuroTouch), ultrasonic aspirator force application was continually assessed during resection of simulated brain tumors by neurosurgeons, residents, and medical students. The participants performed simulated resections of 18 simulated brain tumors with different visual and haptic characteristics. The raw data, namely, coordinates of the instrument tip as well as contact force values, were collected by the simulator. To provide a visual and qualitative spatial analysis of forces, the authors created a graph, called a force pyramid, representing force sum along the z-coordinate for different xy coordinates of the tool tip. RESULTS Sixteen neurosurgeons, 15 residents, and 84 medical students participated in the study. Neurosurgeon, resident and medical student groups displayed easily distinguishable 3D "force pyramid fingerprints." Neurosurgeons had the lowest force pyramids, indicating application of the lowest forces, followed by resident and medical student groups. Handedness, ergonomics, and visual and haptic tumor characteristics resulted in distinct well-defined 3D force pyramid patterns. CONCLUSIONS Force pyramid fingerprints provide 3D spatial assessment displays of instrument force application during simulated tumor resection. Neurosurgeon force utilization and ergonomic data form a basis for understanding and modulating resident force

  1. Novel Au/CaIn{sub 2}S{sub 4} nanocomposites with plasmon-enhanced photocatalytic performance under visible light irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Li, Jie; Meng, Suci, E-mail: mengsc@ujs.edu.cn; Wang, Tianyong; Xu, Qing; Shao, Leqiang; Jiang, Deli, E-mail: dlj@ujs.edu.cn; Chen, Min

    2017-02-28

    Highlights: • Au/CaIn{sub 2}S{sub 4} nanocomposites were fabricated by a simple photoreduction process. • The nanocomposites shown plasmon-enhanced visible light photocatalytic activity. • The enhanced activity was mainly due to improved separation of charge carriers. • The superoxide radicals and holes are the two main photoactive species. - Abstract: A series of Au/CaIn{sub 2}S{sub 4} nanocomposites with different Au contents were prepared by a simple photoreduction process. Under visible light irradiation, the as-prepared Au/CaIn{sub 2}S{sub 4} nanocomposites exhibited plasmon-enhanced photocatalytic activity for the degradation of methylene blue (MB) compared to that of bare CaIn{sub 2}S{sub 4}. The sample with 4 wt% Au hybridized CaIn{sub 2}S{sub 4} exhibited the highest photocatalytic efficiency for MB degradation compared with those of the other nanocomposites. The mechanism for improving the photocatalytic performance of the Au/CaIn{sub 2}S{sub 4} nanocomposites was proposed by using the photoluminescence measurement and electrochemical analyses. The enhanced photocatalytic performance could be attributed to the high separation efficiency of the photogenerated electron-hole pairs. This work could provide a new insight into the fabrication of CaIn{sub 2}S{sub 4}-based plasmonic photocatalysts with enhanced performance.

  2. Gene pyramiding as a Bt resistance management strategy: How ...

    African Journals Online (AJOL)

    Reports on the emergence of insect resistance to Bacillus thuringiensis delta endotoxins have raised doubts on the sustainability of Bt-toxin based pest management technologies. Corporate industry has responded to this challenge with innovations that include gene pyramiding among others. Pyramiding entails stacking ...

  3. Control of Excitation/Inhibition Balance in a Hippocampal Circuit by Calcium Sensor Protein Regulation of Presynaptic Calcium Channels.

    Science.gov (United States)

    Nanou, Evanthia; Lee, Amy; Catterall, William A

    2018-05-02

    Activity-dependent regulation controls the balance of synaptic excitation to inhibition in neural circuits, and disruption of this regulation impairs learning and memory and causes many neurological disorders. The molecular mechanisms underlying short-term synaptic plasticity are incompletely understood, and their role in inhibitory synapses remains uncertain. Here we show that regulation of voltage-gated calcium (Ca 2+ ) channel type 2.1 (Ca V 2.1) by neuronal Ca 2+ sensor (CaS) proteins controls synaptic plasticity and excitation/inhibition balance in a hippocampal circuit. Prevention of CaS protein regulation by introducing the IM-AA mutation in Ca V 2.1 channels in male and female mice impairs short-term synaptic facilitation at excitatory synapses of CA3 pyramidal neurons onto parvalbumin (PV)-expressing basket cells. In sharp contrast, the IM-AA mutation abolishes rapid synaptic depression in the inhibitory synapses of PV basket cells onto CA1 pyramidal neurons. These results show that CaS protein regulation of facilitation and inactivation of Ca V 2.1 channels controls the direction of short-term plasticity at these two synapses. Deletion of the CaS protein CaBP1/caldendrin also blocks rapid depression at PV-CA1 synapses, implicating its upregulation of inactivation of Ca V 2.1 channels in control of short-term synaptic plasticity at this inhibitory synapse. Studies of local-circuit function revealed reduced inhibition of CA1 pyramidal neurons by the disynaptic pathway from CA3 pyramidal cells via PV basket cells and greatly increased excitation/inhibition ratio of the direct excitatory input versus indirect inhibitory input from CA3 pyramidal neurons to CA1 pyramidal neurons. This striking defect in local-circuit function may contribute to the dramatic impairment of spatial learning and memory in IM-AA mice. SIGNIFICANCE STATEMENT Many forms of short-term synaptic plasticity in neuronal circuits rely on regulation of presynaptic voltage-gated Ca 2+ (Ca V

  4. Efficacy and connectivity of intracolumnar pairs of layer 2/3 pyramidal cells in the barrel cortex of juvenile rats

    Science.gov (United States)

    Feldmeyer, Dirk; Lübke, Joachim; Sakmann, Bert

    2006-01-01

    Synaptically coupled layer 2/3 (L2/3) pyramidal neurones located above the same layer 4 barrel (‘barrel-related’) were investigated using dual whole-cell voltage recordings in acute slices of rat somatosensory cortex. Recordings were followed by reconstructions of biocytin-filled neurones. The onset latency of unitary EPSPs was 1.1 ± 0.4 ms, the 20–80% rise time was 0.7 ± 0.2 ms, the average amplitude was 1.0 ± 0.7 mV and the decay time constant was 15.7 ± 4.5 ms. The coefficient of variation (c.v.) of unitary EPSP amplitudes decreased with increasing EPSP peak and was 0.33 ± 0.18. Bursts of APs in the presynaptic pyramidal cell resulted in EPSPs that, over a wide range of frequencies (5–100 Hz), displayed amplitude depression. Anatomically the barrel-related pyramidal cells in the lower half of layer 2/3 have a long apical dendrite with a small terminal tuft, while pyramidal cells in the upper half of layer 2/3 have shorter and often more ‘irregularly’ shaped apical dendrites that branch profusely in layer 1. The number of putative excitatory synaptic contacts established by the axonal collaterals of a L2/3 pyramidal cell with a postsynaptic pyramidal cell in the same column varied between 2 and 4, with an average of 2.8 ± 0.7 (n = 8 pairs). Synaptic contacts were established predominantly on the basal dendrites at a mean geometric distance of 91 ± 47 μm from the pyramidal cell soma. L2/3-to-L2/3 connections formed a blob-like innervation domain containing 2.8 mm of the presynaptic axon collaterals with a bouton density of 0.3 boutons per μm axon. Within the supragranular layers of its home column a single L2/3 pyramidal cell established about 900 boutons suggesting that 270 pyramidal cells in layer 2/3 are innervated by an individual pyramidal cell. In turn, a single pyramidal cell received synaptic inputs from 270 other L2/3 pyramidal cells. The innervation domain of L2/3-to-L2/3 connections superimposes almost exactly with that of L4-to-L2

  5. The FINUT healthy lifestyles guide: Beyond the food pyramid.

    Science.gov (United States)

    Gil, Angel; Ruiz-Lopez, Maria Dolores; Fernandez-Gonzalez, Miguel; Martinez de Victoria, Emilio

    2014-05-01

    The WHO has proposed that health be promoted and protected through the development of an environment that enables sustainable actions at individual, community, national, and global levels. Indeed, food-based dietary guidelines, i.e., food pyramids, have been developed in numerous countries to disseminate nutritional information to the general population. However, wider recommendations are needed, with information on an active healthy lifestyle, not just healthy eating. The objective of the present work is to propose a three-dimensional pyramid as a new strategy for promoting adequate nutrition and active healthy lifestyles in a sustainable way. Indeed, the Iberoamerican Nutrition Foundation (FINUT) pyramid of healthy lifestyles has been designed as a tetrahedron, with its 3 lateral faces corresponding to the facets of food and nutrition, physical activity and rest, and education and hygiene. Each lateral face is divided into 2 triangles. These faces show the following: 1) food-based guidelines and healthy eating habits as related to a sustainable environment; 2) recommendations for rest and physical activity and educational, social, and cultural issues; and 3) selected hygiene and educational guidelines that, in conjunction with the other 2 faces, would contribute to better health for people in a sustainable planet. The new FINUT pyramid is addressed to the general population of all ages and should serve as a guide for living a healthy lifestyle within a defined social and cultural context. It includes an environmental and sustainability dimension providing measures that should contribute to the prevention of noncommunicable chronic diseases. © 2014 American Society for Nutrition.

  6. [The finut healthy lifestyles guide: beyond the food pyramid].

    Science.gov (United States)

    Gil, Angel; Ruiz-Lopez, Maria Dolores; Fernandez-Gonzalez, Miguel; Martinez de Victoria, Emilio

    2015-05-01

    The World Health Organization has proposed that health be promoted and protected through the development of an environment that enables sustainable actions at individual, community, national and global levels. Indeed, food-based dietary guidelines, i.e., food pyramids, have been developed in numerous countries to disseminate nutritional information to the general population. However, wider recommendations are needed, with information on an active, healthy lifestyle, not just healthy eating. The objective of the present work is to propose a three-dimensional pyramid as a new strategy for promoting adequate nutrition and active healthy lifestyles in a sustainable way. Indeed, the Iberomerican Nutrition Foundation (FINUT) pyramid of healthy lifestyles has been designed as a tetrahedron, its three lateral faces corresponding to the binomials food and nutrition, physical activity and rest, and education and hygiene. Each lateral face is divided into two triangles. These faces show the following: 1. food-based guidelines and healthy eating habits as related to a sustainable environment; 2. recommendations for rest and physical activity and educational, social and cultural issues; 3. selected hygiene and educational guidelines that, in conjunction with the other two faces, would contribute to better health and provide measures to promote environmental sustainability. The new FINUT pyramid is addressed to the general population of all ages and should serve as a guide for living a healthy lifestyle within a defined social and cultural context. It includes an environmental and sustainability dimension providing measures that should contribute to the prevention of non-communicable chronic diseases. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

  7. The Heeger & Bergen Pyramid Based Texture Synthesis Algorithm

    Directory of Open Access Journals (Sweden)

    Thibaud Briand

    2014-11-01

    Full Text Available This contribution deals with the Heeger-Bergen pyramid-based texture analysis/synthesis algorithm. It brings a detailed explanation of the original algorithm tested on many characteristic examples. Our analysis reproduces the original results, but also brings a minor improvement concerning non-periodic textures. Inspired by visual perception theories, Heeger and Bergen proposed to characterize a texture by its first-order statistics of both its color and its responses to multiscale and multi-orientation filters, namely the steerable pyramid. The Heeger-Bergen algorithm consists in the following procedure: starting from a white noise image, histogram matchings are performed to the noise alternatively in both the image domain and steerable pyramid domain, so that the corresponding histograms match the ones of the input texture.

  8. PGC-1α accelerates cytosolic Ca2+ clearance without disturbing Ca2+ homeostasis in cardiac myocytes

    International Nuclear Information System (INIS)

    Chen, Min; Wang, Yanru; Qu, Aijuan

    2010-01-01

    Energy metabolism and Ca 2+ handling serve critical roles in cardiac physiology and pathophysiology. Peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α) is a multi-functional coactivator that is involved in the regulation of cardiac mitochondrial functional capacity and cellular energy metabolism. However, the regulation of PGC-1α in cardiac Ca 2+ signaling has not been fully elucidated. To address this issue, we combined confocal line-scan imaging with off-line imaging processing to characterize calcium signaling in cultured adult rat ventricular myocytes expressing PGC-1α via adenoviral transduction. Our data shows that overexpressing PGC-1α improved myocyte contractility without increasing the amplitude of Ca 2+ transients, suggesting that myofilament sensitivity to Ca 2+ increased. Interestingly, the decay kinetics of global Ca 2+ transients and Ca 2+ waves accelerated in PGC-1α-expressing cells, but the decay rate of caffeine-elicited Ca 2+ transients showed no significant change. This suggests that sarcoplasmic reticulum (SR) Ca 2+ -ATPase (SERCA2a), but not Na + /Ca 2+ exchange (NCX) contribute to PGC-1α-induced cytosolic Ca 2+ clearance. Furthermore, PGC-1α induced the expression of SERCA2a in cultured cardiac myocytes. Importantly, overexpressing PGC-1α did not disturb cardiac Ca 2+ homeostasis, because SR Ca 2+ load and the propensity for Ca 2+ waves remained unchanged. These data suggest that PGC-1α can ameliorate cardiac Ca 2+ cycling and improve cardiac work output in response to physiological stress. Unraveling the PGC-1α-calcium handing pathway sheds new light on the role of PGC-1α in the therapy of cardiac diseases.

  9. A plant EPF-type zinc-finger protein, CaPIF1, involved in defence against pathogens.

    Science.gov (United States)

    Oh, Sang-Keun; Park, Jeong Mee; Joung, Young Hee; Lee, Sanghyeob; Chung, Eunsook; Kim, Soo-Yong; Yu, Seung Hun; Choi, Doil

    2005-05-01

    SUMMARY To understand better the defence responses of plants to pathogen attack, we challenged hot pepper plants with bacterial pathogens and identified transcription factor-encoding genes whose expression patterns were altered during the subsequent hypersensitive response. One of these genes, CaPIF1 (Capsicum annuum Pathogen-Induced Factor 1), was characterized further. This gene encodes a plant-specific EPF-type protein that contains two Cys(2)/His(2) zinc fingers. CaPIF1 expression was rapidly and specifically induced when pepper plants were challenged with bacterial pathogens to which they are resistant. In contrast, challenge with a pathogen to which the plants are susceptible only generated weak CaPIF1 expression. CaPIF1 expression was also strongly induced in pepper leaves by the exogenous application of ethephon, an ethylene-releasing compound, and salicylic acid, whereas methyl jasmonate had only moderate effects. CaPIF1 localized to the nuclei of onion epidermis when expressed as a CaPIF1-smGFP fusion protein. Transgenic tobacco plants over-expressing CaPIF1 driven by the CaMV 35S promoter showed increased resistance to challenge with a tobacco-specific pathogen or non-host bacterial pathogens. These plants also showed constitutive up-regulation of multiple defence-related genes. Moreover, virus-induced silencing of the CaPIF1 orthologue in Nicotiana benthamiana enhanced susceptibility to the same host or non-host bacterial pathogens. These observations provide evidence that an EPF-type Cys(2)/His(2) zinc-finger protein plays a crucial role in the activation of the pathogen defence response in plants.

  10. Characterization of the porcine FBX07 gene: the first step towards generation of a pig model for Parkinsonian pyramidal syndrome

    DEFF Research Database (Denmark)

    Larsen, Knud; Bendixen, Christian

    2012-01-01

    Parkinsonian pyramidal syndrome, also named pallido-pyramidal syndrome (PKPS), is the combination of early-onset progressive Parkinsonism with pyramidal tract signs. FBXO7, an F-box protein, is a component of modular E3 ubiquitin protein ligases called SCFs (SKP1, cullin, F-box proteins), which...

  11. Oxygen chain disorder and compensation by Ca in Y(1-2-3) cuprates

    International Nuclear Information System (INIS)

    Suryanarayanan, R.; Ouhammou, L.; Das, A.; Leelaprute, S.

    1994-01-01

    Several M dopants such as Al, Fe, and Co at the Cu site destroy the superconductivity of YBa 2 Cu 3 O 6+z . However, superconductivity is restored by substituting Ca at the Y site. Arguments are developed to show that the oxygen chain disorder is not the only cause for destroying the superconductivity. A universal relation seems to exist between the net hole density as a result of Ca substitution and Tc. To stabilize the perovskite structure of YSr 2 Cu 3 O 6+z , it is necessary to substitute Cu by certain elements. Examples are given on Ti and Re substitution. Again, Ca cosubstitution increases Tc. Further, the irreversibility line is enhanced by Ca, indicating improved pinning in these materials in spite of the oxygen disorder. 16 refs., 4 figs., 1 tab

  12. The FINUT Healthy Lifestyles Guide: Beyond the Food Pyramid 1 2 3

    OpenAIRE

    Gil, Angel; Ruiz-Lopez, Maria Dolores; Fernandez-Gonzalez, Miguel; Martinez de Victoria, Emilio

    2014-01-01

    The WHO has proposed that health be promoted and protected through the development of an environment that enables sustainable actions at individual, community, national, and global levels. Indeed, food-based dietary guidelines, i.e., food pyramids, have been developed in numerous countries to disseminate nutritional information to the general population. However, wider recommendations are needed, with information on an active healthy lifestyle, not just healthy eating. The objective of the pr...

  13. Behavior-Dependent Activity and Synaptic Organization of Septo-hippocampal GABAergic Neurons Selectively Targeting the Hippocampal CA3 Area.

    Science.gov (United States)

    Joshi, Abhilasha; Salib, Minas; Viney, Tim James; Dupret, David; Somogyi, Peter

    2017-12-20

    Rhythmic medial septal (MS) GABAergic input coordinates cortical theta oscillations. However, the rules of innervation of cortical cells and regions by diverse septal neurons are unknown. We report a specialized population of septal GABAergic neurons, the Teevra cells, selectively innervating the hippocampal CA3 area bypassing CA1, CA2, and the dentate gyrus. Parvalbumin-immunopositive Teevra cells show the highest rhythmicity among MS neurons and fire with short burst duration (median, 38 ms) preferentially at the trough of both CA1 theta and slow irregular oscillations, coincident with highest hippocampal excitability. Teevra cells synaptically target GABAergic axo-axonic and some CCK interneurons in restricted septo-temporal CA3 segments. The rhythmicity of their firing decreases from septal to temporal termination of individual axons. We hypothesize that Teevra neurons coordinate oscillatory activity across the septo-temporal axis, phasing the firing of specific CA3 interneurons, thereby contributing to the selection of pyramidal cell assemblies at the theta trough via disinhibition. VIDEO ABSTRACT. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  14. Negative modulation of presynaptic activity by zinc released from Schaffer collaterals.

    Science.gov (United States)

    Takeda, Atsushi; Fuke, Sayuri; Tsutsumi, Wataru; Oku, Naoto

    2007-12-01

    The role of zinc in excitation of Schaffer collateral-CA1 pyramidal cell synapses is poorly understood. Schaffer collaterals stained with ZnAF-2 or ZnAF-2DA, a membrane-impermeable or a membrane-permeable zinc indicator, respectively, were treated by tetanic stimulation (200 Hz, 1 sec). Extracellular and intracellular ZnAF-2 signals were increased in the stratum radiatum of the CA1, in which Schaffer collateral synapses exist. Both the increases were completely blocked in the presence of 1 mM CaEDAT, a membrane-impermeable zinc chelator, suggesting that 1 mM CaEDTA is effective for chelating zinc released from Schaffer collaterals. The role of Schaffer collateral zinc in presynaptic activity was examined by using FM4-64, a fluorescent indicator for vesicular exocytosis. The decrease in FM4-64 signal during tetanic stimulation (10 Hz, 180 sec) was enhanced in Schaffer collaterals in the presence of 1 mM CaEDTA but suppressed in the presence of 5 microM ZnC1(2), suggesting that zinc released from Schaffer collaterals suppresses presynaptic activity during tetanic stimulation. When Schaffer collateral synapses stained with calcium orange AM, a membrane-permeable calcium indicator, were regionally stimulated with 1 mM glutamate, calcium orange signal was increased in the CA1 pyramidal cell layer. This increase was enhanced in the presence of CaEDTA and attenuated in the presence of zinc. These results suggest that zinc attenuates excitation of Schaffer collateral synapses elicited with glutamate via suppression of presynaptic activity. (c) 2007 Wiley-Liss, Inc.

  15. Fabrication of micromirrors with pyramidal shape using anisotropic etching of silicon

    OpenAIRE

    Moktadir, Z.; Vijaya Prakash, G.; Trupke, M.; Koukharenko, E.; Kraft, M.; Baumberg, J.J.; Eriksson, S.; Hinds, E.A.

    2005-01-01

    Gold micro-mirrors have been formed in silicon in an inverted pyramidal shape. The pyramidal structures are created in the (100) surface of a silicon wafer by anisotropic etching in potassium hydroxide. High quality micro-mirrors are then formed by sputtering gold onto the smooth silicon (111) faces of the pyramids. These mirrors show great promise as high quality optical devices suitable for integration into MOEMS systems.

  16. Cerebellar ataxia by enhanced Cav2.1 currents is alleviated by Ca2+-dependent K-channel activators in Cacna1aS218l mutant mice

    NARCIS (Netherlands)

    Z. Gao (Zhenyu); B. Todorov (Boyan); C.F. Barrett (Curtis); S. van Dorp (Stijn); M.D. Ferrari (Michel); M. Dichgans (Martin); C.I. de Zeeuw (Chris); F.E. Hoebeek (Freek)

    2012-01-01

    textabstractMutations in the CACNA1A gene are associated with neurological disorders, such as ataxia, hemiplegic migraine, and epilepsy. These mutations affect the pore-forming α1A-subunit of CaV2.1 channels and thereby either decrease or increase neuronal Ca2+ influx. A decreased CaV2.1-mediated

  17. THE DIGITAL VON FAHRENHEID PYRAMID

    Directory of Open Access Journals (Sweden)

    M. Bura

    2017-08-01

    Full Text Available 3D Scanners Lab from Digital Humanities Laboratory at the University of Warsaw initiated the scientific project, the purpose of which was to call attention to systematically penetrated and devastated pyramid-shaped tomb from the XVIII/XIX century, of family von Fahrenheid in Rapa in Banie Mazurskie commune (NE Poland. By conducting a series of non-invasive studies, such as 3D inventory using terrestrial laser scanning (TLS, thermal imaging, georadar measurements (around and inside the tomb and anthropological research of mummified remains as well - the complete dataset was collected. Through the integration of terrestrial (TLS and airborne laser scanning (ALS authors managed to analyse the surroundings of Fahrenheid pyriamid and influence of some objects (like trees on the condition and visibility of the Pyramids in the landscape.

  18. Inclinations of Egyptian pyramids and finding of the divine essence

    OpenAIRE

    GRIGORIEV STANISLAV ARKADIEVICH

    2015-01-01

    The aim of this research is discovery of astronomical reasons in orientation of slopes of Egyptian pyramids used as tombs for pharaohs of Ancient Egypt. The article contains results of statistical analysis of change in inclination of slopes of the pyramids (3rd 2nd millennia BC) depending on time of their building. The first year of the corresponding pharaoh’s reign has been accepted, as usually it is considered that building of pyramids ones started during either the first or second year of ...

  19. New limits on 2β processes in 40Ca and 46Ca by using low radioactive CaF2(Eu) crystal scintillators

    International Nuclear Information System (INIS)

    Belli, P.; Bernabei, R.; Dai, C.J.

    2001-01-01

    The development of highly radiopure CaF 2 (Eu) crystal scintillators has been performed aiming at a substantial sensitivity enhancement of the 2β decay investigation and of the search for dark matter particles with spin-dependent (SD) interaction. The results of CaF 2 (Eu) background measurements and simulation are presented. New and highly improved T 1/2 limits on the 2β decay of 46 Ca and the double electron capture of 40 Ca are obtained

  20. Experimental evidence of enhanced ferroelectricity in Ca doped BiFeO{sub 3}

    Energy Technology Data Exchange (ETDEWEB)

    Costa, L.V.; Deus, R.C. [Universidade Estadual Paulista, UNESP, Faculdade de Engenharia de Guaratinguetá, Av. Dr. Ariberto Pereira da Cunha, 333, Bairro Portal das Colinas, CEP 12516-410 Guaratinguetá, SP (Brazil); Foschini, C.R.; Longo, E. [Universidade Estadual Paulista, UNESP, Faculdade de Engenharia de Bauru, Dept. de Eng. Mecânica, Av. Eng. Luiz Edmundo C. Coube 14-01, 17033-360 Bauru, SP (Brazil); Cilense, M. [Universidade Estadual Paulista, UNESP, Instituto de Química – Laboratório Interdisciplinar em Cerâmica (LIEC), Rua Professor Francisco Degni s/n, 14800-90 Araraquara, SP (Brazil); Simões, A.Z., E-mail: alezipo@yahoo.com [Universidade Estadual Paulista, UNESP, Faculdade de Engenharia de Guaratinguetá, Av. Dr. Ariberto Pereira da Cunha, 333, Bairro Portal das Colinas, CEP 12516-410 Guaratinguetá, SP (Brazil)

    2014-04-01

    Calcium (Ca)-doped bismuth ferrite (BiFeO{sub 3}) thin films prepared by using the polymeric precursor method (PPM) were characterized by X-ray diffraction (XRD), field emission gun scanning electron microscopy (FEG-SEM), transmission electron microscopy (TEM), polarization and piezoelectric measurements. Structural studies by XRD and TEM reveal the co-existence of distorted rhombohedral and tetragonal phases in the highest doped BiFeO{sub 3} where enhanced ferroelectric and piezoelectric properties are produced by internal strain. Resistive switching is observed in BFO and Ca-doped BFO which are affected by the barrier contact and work function of multiferroic materials and Pt electrodes. A high coercive field in the hysteresis loop is observed for the BiFeO{sub 3} film. Piezoelectric properties are improved in the highest Ca-doped sample due to changes in the crystal structure of BFO for a primitive cubic perovskite lattice with four-fold symmetry and a large tetragonal distortion within the crystal domain. This observation introduces magnetoelectronics at room temperature by combining electronic conduction with electric and magnetic degrees of freedom which are already present in the multiferroic BiFeO{sub 3}. - Highlights: • Ca doped BiFeO{sub 3} thin films were obtained by the polymeric precursor method. • Co-existence of distorted rhombohedral and tetragonal phases are evident. • Enhanced ferroelectric and piezoelectric properties are produced by the internal strain in the Ca doped BiFeO{sub 3} film.

  1. Enhanced Ce{sup 3+} photoluminescence by Li{sup +} co-doping in CaO phosphor and its use in blue-pumped white LEDs

    Energy Technology Data Exchange (ETDEWEB)

    Hao, Zhendong, E-mail: haozd@ciomp.ac.cn; Zhang, Xia; Luo, Yongshi; Zhang, Ligong; Zhao, Haifeng; Zhang, Jiahua, E-mail: zhangjh@ciomp.ac.cn

    2013-08-15

    In this paper, we demonstrate a method to improve the photoluminescence of CaO: Ce{sup 3+} phosphor and delineate its first use in blue-pumped white LEDs. The results show that the yellow emission of Ce{sup 3+} is enhanced by a factor of 1.88 by adding Li{sup +} into CaO host at 474 nm blue light excitation. On analyzing the diffuse reflection spectra and fluorescence decay curves, we reveal that the photoluminescence enhancement is originated from the rise of absorbance to the excitation photons but not from the improvement of the luminescent efficiency. Li{sup +}-improved CaO: Ce{sup 3+} exhibits more red component when it is compared with the commercial Y{sub 3}Al{sub 5}O{sub 12}: Ce{sup 3+} (YAG: Ce{sup 3+}) phosphor, indicating its potential application for high color rendering white LEDs. Thus, a white LED is fabricated by combining blue InGaN LED chip with CaO: Ce{sup 3+}, Li{sup +} phosphor and a warm white light with high color rendering index (R{sub a}) of 80, low correlated color temperature (T{sub c}) of 4524 K, and sufficient luminous efficiency of 50 lm W{sup −1} is obtained. -- Highlights: • The photoluminescence of Ce{sup 3+} in CaO host was enhanced by Li{sup +} co-doping. • A CaO: Ce{sup 3+}, Li{sup +} based white LED was fabricated for the first time. • An efficient warm white light was obtained. • CaO: Ce{sup 3+}, Li{sup +} is expected to be used as a yellow phosphor for blue-pumped white LEDs.

  2. Long-term plasticity in identified hippocampal GABAergic interneurons in the CA1 area in vivo.

    Science.gov (United States)

    Lau, Petrina Yau-Pok; Katona, Linda; Saghy, Peter; Newton, Kathryn; Somogyi, Peter; Lamsa, Karri P

    2017-05-01

    Long-term plasticity is well documented in synapses between glutamatergic principal cells in the cortex both in vitro and in vivo. Long-term potentiation (LTP) and -depression (LTD) have also been reported in glutamatergic connections to hippocampal GABAergic interneurons expressing parvalbumin (PV+) or nitric oxide synthase (NOS+) in brain slices, but plasticity in these cells has not been tested in vivo. We investigated synaptically-evoked suprathreshold excitation of identified hippocampal neurons in the CA1 area of urethane-anaesthetized rats. Neurons were recorded extracellularly with glass microelectrodes, and labelled with neurobiotin for anatomical analyses. Single-shock electrical stimulation of afferents from the contralateral CA1 elicited postsynaptic action potentials with monosynaptic features showing short delay (9.95 ± 0.41 ms) and small jitter in 13 neurons through the commissural pathway. Theta-burst stimulation (TBS) generated LTP of the synaptically-evoked spike probability in pyramidal cells, and in a bistratified cell and two unidentified fast-spiking interneurons. On the contrary, PV+ basket cells and NOS+ ivy cells exhibited either LTD or LTP. An identified axo-axonic cell failed to show long-term change in its response to stimulation. Discharge of the cells did not explain whether LTP or LTD was generated. For the fast-spiking interneurons, as a group, no correlation was found between plasticity and local field potential oscillations (1-3 or 3-6 Hz components) recorded immediately prior to TBS. The results demonstrate activity-induced long-term plasticity in synaptic excitation of hippocampal PV+ and NOS+ interneurons in vivo. Physiological and pathological activity patterns in vivo may generate similar plasticity in these interneurons.

  3. Ventral tegmental area disruption selectively affects CA1/CA2 but not CA3 place fields during a differential reward working memory task.

    Science.gov (United States)

    Martig, Adria K; Mizumori, Sheri J Y

    2011-02-01

    Hippocampus (HPC) receives dopaminergic (DA) projections from the ventral tegmental area (VTA) and substantia nigra. These inputs appear to provide a modulatory signal that influences HPC dependent behaviors and place fields. We examined how efferent projections from VTA to HPC influence spatial working memory and place fields when the reward context changes. CA1 and CA3 process environmental context changes differently and VTA preferentially innervates CA1. Given these anatomical data and electrophysiological evidence that implicate DA in reward processing, we predicted that CA1 place fields would respond more strongly to both VTA disruption and changes in the reward context than CA3 place fields. Rats (N = 9) were implanted with infusion cannula targeting VTA and recording tetrodes aimed at HPC. Then they were tested on a differential reward, win-shift working memory task. One recording session consisted of 5 baseline and 5 manipulation trials during which place cells in CA1/CA2 (N = 167) and CA3 (N = 94) were recorded. Prior to manipulation trials rats were infused with either baclofen or saline and then subjected to control or reward conditions during which the learned locations of large and small reward quantities were reversed. VTA disruption resulted in an increase in errors, and in CA1/CA2 place field reorganization. There were no changes in any measures of CA3 place field stability during VTA disruption. Reward manipulations did not affect performance or place field stability in CA1/CA2 or CA3; however, changes in the reward locations "rescued" performance and place field stability in CA1/CA2 when VTA activity was compromised, perhaps by trigging compensatory mechanisms. These data support the hypothesis that VTA contributes to spatial working memory performance perhaps by maintaining place field stability selectively in CA1/CA2. Copyright © 2009 Wiley-Liss, Inc.

  4. Effect of lures and colors on capture of lady beetles (coleoptera: coccinellidae) in tedders pyramidal traps

    Science.gov (United States)

    Purposeful attraction and/or aggregation of adult Coccinellidae at target sites would be useful for sampling purposes and/or pest suppression. We field-tested 1) lures in yellow and black pyramidal traps and 2) pyramidal traps that had been painted one or two colors (without lures) to determine if ...

  5. Depolarization-dependent sup 45 Ca uptake by synaptosomes of rat cerebral cortex is enhanced by L-triiodothyronine

    Energy Technology Data Exchange (ETDEWEB)

    Mason, G.A.; Walker, C.H.; Prange, A.J. Jr. (Univ. of North Carolina, Chapel Hill (USA))

    1990-08-01

    Depolarization-induced release of neurotransmitters and other secretions from nerve endings is triggered by the rapid entry of Ca++ through voltage-sensitive channels. Calcium entry is thought to occur in two distinct phases or processes: a fast-phase response to an action potential, which initiates release; and a slow phase associated with extended stimulation of the neuron. Thyroid hormones are sequestered by nerve terminals and can produce changes in behaviour and mood. They may therefore be involved in modulating central synaptic transmission. We studied the effects of L-triiodothyronine (T3), L-thyroxine (T4), reverse T3 (rT3) and D-T3 on depolarization-induced uptake of 45Ca by synaptosomes from euthyroid and hypothyroid rats. T3, but not T4, rT3, or D-T3 significantly enhanced depolarization-induced 45Ca uptake at physiologically relevant (1 to 10 nmol/L) concentrations. The stimulatory effect of 10 nmol/L T3 on depolarization-induced uptake after 2 seconds (21%) was greater than after 5 (10%) or 30 (8%) seconds, indicating that T3 enhanced primarily the fast-phase process. There was no effect of T3 or other hormones tested on nondepolarization-induced 45Ca uptake. Preincubation of synaptosomes with T3 prior to depolarization did not enhance the effect of T3; in fact, preincubations of 30 seconds or more resulted in diminished T3 effects. Preincubation of synaptosomes for 15 seconds with D-T3 or the addition of D-T3 and T3 together reduced the effect of T3. We found no difference in the effect of T3 on 45Ca uptake by synaptosomes from euthyroid and hypothyroid rats. These results suggest a novel mechanism of action of thyroid hormones in the brain.

  6. Rapamycin inhibits mTOR/p70S6K activation in CA3 region of the hippocampus of the rat and impairs long term memory.

    Science.gov (United States)

    Lana, D; Di Russo, J; Mello, T; Wenk, G L; Giovannini, M G

    2017-01-01

    The present study was aimed at establishing whether the mTOR pathway and its downstream effector p70S6K in CA3 pyramidal neurons are under the modulation of the cholinergic input to trigger the formation of long term memories, similar to what we demonstrated in CA1 hippocampus. We performed in vivo behavioral experiments using the step down inhibitory avoidance test in adult Wistar rats to evaluate memory formation under different conditions. We examined the effects of rapamycin, an inhibitor of mTORC1 formation, scopolamine, a muscarinic receptor antagonist or mecamylamine, a nicotinic receptor antagonist, on short and long term memory formation and on the functionality of the mTOR pathway. Acquisition was conducted 30min after i.c.v. injection of rapamycin. Recall testing was performed 1h, 4h or 24h after acquisition. We found that (1) mTOR and p70S6K activation in CA3 pyramidal neurons were involved in long term memory formation; (2) rapamycin significantly inhibited mTOR and of p70S6K activation at 4h, and long term memory impairment 24h after acquisition; (3) scopolamine impaired short but not long term memory, with an early increase of mTOR/p70S6K activation at 1h followed by stabilization at longer times; (4) mecamylamine and scopolamine co-administration impaired short term memory at 1h and 4h and reduced the scopolamine-induced increase of mTOR/p70S6K activation at 1h and 4h; (5) mecamylamine and scopolamine treatment did not impair long term memory formation; (6) unexpectedly, rapamycin increased mTORC2 activation in microglial cells. Our results demonstrate that in CA3 pyramidal neurons the mTOR/p70S6K pathway is under the modulation of the cholinergic system and is involved in long-term memory encoding, and are consistent with the hypothesis that the CA3 region of the hippocampus is involved in memory mechanisms based on rapid, one-trial object-place learning and recall. Furthermore, our results are in accordance with previous reports that selective

  7. Exciton binding energy in a pyramidal quantum dot

    Science.gov (United States)

    Anitha, A.; Arulmozhi, M.

    2018-05-01

    The effects of spatially dependent effective mass, non-parabolicity of the conduction band and dielectric screening function on exciton binding energy in a pyramid-shaped quantum dot of GaAs have been investigated by variational method as a function of base width of the pyramid. We have assumed that the pyramid has a square base with area a× a and height of the pyramid H=a/2. The trial wave function of the exciton has been chosen according to the even mirror boundary condition, i.e. the wave function of the exciton at the boundary could be non-zero. The results show that (i) the non-parabolicity of the conduction band affects the light hole (lh) and heavy hole (hh) excitons to be more bound than that with parabolicity of the conduction band, (ii) the dielectric screening function (DSF) affects the lh and hh excitons to be more bound than that without the DSF and (iii) the spatially dependent effective mass (SDEM) affects the lh and hh excitons to be less bound than that without the SDEM. The combined effects of DSF and SDEM on exciton binding energy have also been calculated. The results are compared with those available in the literature.

  8. Pyramid Algorithm Framework for Real-Time Image Effects

    DEFF Research Database (Denmark)

    Sangüesa, Adriá Arbués; Ene, Andreea-Daniela; Jørgensen, Nicolai Krogh

    2016-01-01

    Pyramid methods are useful for certain image processing techniques due to their linear time complexity. Implementing them using compute shaders provides a basis for rendering image effects with reduced impact on performance compared to conventional methods. Although pyramid methods are used...... in the game industry, they are not easily accessible to all developers because many game engines do not include built-in support. We present a framework for a popular game engine that allows users to take advantage of pyramid methods for developing image effects. In order to evaluate the performance...... and to demonstrate the framework, a few image effects were implemented. These effects were compared to built-in effects of the same game engine. The results showed that the built-in image effects performed slightly better. The performance of our framework could potentially be improved through optimisation, mainly...

  9. Gating of hippocampal activity, plasticity, and memory by entorhinal cortex long-range inhibition.

    Science.gov (United States)

    Basu, Jayeeta; Zaremba, Jeffrey D; Cheung, Stephanie K; Hitti, Frederick L; Zemelman, Boris V; Losonczy, Attila; Siegelbaum, Steven A

    2016-01-08

    The cortico-hippocampal circuit is critical for storage of associational memories. Most studies have focused on the role in memory storage of the excitatory projections from entorhinal cortex to hippocampus. However, entorhinal cortex also sends inhibitory projections, whose role in memory storage and cortico-hippocampal activity remains largely unexplored. We found that these long-range inhibitory projections enhance the specificity of contextual and object memory encoding. At the circuit level, these γ-aminobutyric acid (GABA)-releasing projections target hippocampal inhibitory neurons and thus act as a disinhibitory gate that transiently promotes the excitation of hippocampal CA1 pyramidal neurons by suppressing feedforward inhibition. This enhances the ability of CA1 pyramidal neurons to fire synaptically evoked dendritic spikes and to generate a temporally precise form of heterosynaptic plasticity. Long-range inhibition from entorhinal cortex may thus increase the precision of hippocampal-based long-term memory associations by assessing the salience of mnemonormation to the immediate sensory input. Copyright © 2016, American Association for the Advancement of Science.

  10. Effects of inhaled anesthetic isoflurane on long-term potentiation of CA3 pyramidal cell afferents in vivo

    Directory of Open Access Journals (Sweden)

    Ballesteros KA

    2012-11-01

    Full Text Available Kristen A Ballesteros,1 Angela Sikorski,2 James E Orfila,3 Joe L Martinez Jr41Department of Biology, The University of Texas at San Antonio, San Antonio, TX, USA; 2Texas A&M University Texarkana, Texarkana, TX, USA; 3University of Colorado in Denver, Denver, CO, USA; 4University of Illinois in Chicago, Chicago, IL, USAAbstract: Isoflurane is a preferred anesthetic, due to its properties that allow a precise concentration to be delivered continually during in vivo experimentation. The major mechanism of action of isoflurane is modulation of the γ-amino butyric acid (GABAA receptor-chloride channel, mediating inhibitory synaptic transmission. Animal studies have shown that isoflurane does not cause cell death, but it does inhibit cell growth and causes long-term hippocampal learning deficits. As there are no studies characterizing the effects of isoflurane on electrophysiological aspects of long-term potentiation (LTP in the hippocampus, it is important to determine whether isoflurane alters the characteristic responses of hippocampal afferents to cornu ammonis region 3 (CA3. We investigated the effects of isoflurane on adult male rats during in vivo induction of LTP, using the mossy fiber pathway, the lateral perforant pathway, the medial perforant pathway, and the commissural CA3 (cCA3 to CA3, with intracranial administration of Ringer’s solution, naloxone, RS-aminoindan-1, 5-dicarboxylic acid (AIDA, or 3-[(R-2-carboxypiperazin-4-yl]-propo-2-enyl-1-phosphonic acid (CPP. Then, we compared these responses to published electrophysiological data, using sodium pentobarbital as an anesthetic, under similar experimental conditions. Our results showed that LTP was exhibited in animals anesthetized with isoflurane under vehicle conditions. With the exception of AIDA in the lateral perforant pathway, the defining characteristics of the four pathways appeared to remain intact, except for the observation that LTP was markedly reduced in animals

  11. Growth and characterization of CaFe1-xCoxAsF single crystals by CaAs flux method

    Science.gov (United States)

    Ma, Yonghui; Hu, Kangkang; Ji, Qiucheng; Gao, Bo; Zhang, Hui; Mu, Gang; Huang, Fuqiang; Xie, Xiaoming

    2016-10-01

    Millimeter sized single crystals of CaFe1-x Cox AsF were grown using a self-flux method. It is found that high-quality single crystals can be grown from three approaches with different initial raw materials. The chemical compositions and crystal structure were characterized carefully. Compared with the undoped parent phase CaFeAsF, the crystal lattice along the c-axis is suppressed by the Co substitution while that along the a-axis expands slightly. Superconductivity with the critical transition Tc as high as 21 K was confirmed by both the resistivity and magnetic susceptibility measurements in the sample with x=0.118. Moreover, it is found that Tc can be enhanced for about 1 K under the very small hydrostatic pressure of 0.22 GPa, which is more quick than that reported in the polycrystalline samples. Our results are a promotion for the physical investigations of 1111 phase iron-pnictide superconductors.

  12. Localization of peroxisome proliferator-activated receptor alpha (PPARα) and N-acyl phosphatidylethanolamine phospholipase D (NAPE-PLD) in cells expressing the Ca2+-binding proteins calbindin, calretinin, and parvalbumin in the adult rat hippocampus

    Science.gov (United States)

    Rivera, Patricia; Arrabal, Sergio; Vargas, Antonio; Blanco, Eduardo; Serrano, Antonia; Pavón, Francisco J.; Rodríguez de Fonseca, Fernando; Suárez, Juan

    2014-01-01

    The N-acylethanolamines (NAEs), oleoylethanolamide (OEA) and palmithylethanolamide (PEA) are known to be endogenous ligands of PPARα receptors, and their presence requires the activation of a specific phospholipase D (NAPE-PLD) associated with intracellular Ca2+ fluxes. Thus, the identification of a specific population of NAPE-PLD/PPARα-containing neurons that express selective Ca2+-binding proteins (CaBPs) may provide a neuroanatomical basis to better understand the PPARα system in the brain. For this purpose, we used double-label immunofluorescence and confocal laser scanning microscopy for the characterization of the co-existence of NAPE-PLD/PPARα and the CaBPs calbindin D28k, calretinin and parvalbumin in the rat hippocampus. PPARα expression was specifically localized in the cell nucleus and, occasionally, in the cytoplasm of the principal cells (dentate granular and CA pyramidal cells) and some non-principal cells of the hippocampus. PPARα was expressed in the calbindin-containing cells of the granular cell layer of the dentate gyrus (DG) and the SP of CA1. These principal PPARα+/calbindin+ cells were closely surrounded by NAPE-PLD+ fiber varicosities. No pyramidal PPARα+/calbindin+ cells were detected in CA3. Most cells containing parvalbumin expressed both NAPE-PLD and PPARα in the principal layers of the DG and CA1/3. A small number of cells containing PPARα and calretinin was found along the hippocampus. Scattered NAPE-PLD+/calretinin+ cells were specifically detected in CA3. NAPE-PLD+ puncta surrounded the calretinin+ cells localized in the principal cells of the DG and CA1. The identification of the hippocampal subpopulations of NAPE-PLD/PPARα-containing neurons that express selective CaBPs should be considered when analyzing the role of NAEs/PPARα-signaling system in the regulation of hippocampal functions. PMID:24672435

  13. Corticosterone rapidly increases thorns of CA3 neurons via synaptic/extranuclear glucocorticoid receptor in rat hippocampus

    Directory of Open Access Journals (Sweden)

    Miyuki eYoshiya

    2013-11-01

    Full Text Available Modulation of synapses under acute stress is attracting much attention. Exposure to acute stress induces corticosterone (CORT secretion from the adrenal cortex, resulting in rapid increase of CORT levels in plasma and the hippocampus. We tried to test whether rapid CORT effects involve activation of essential kinases as non-genomic processes.We demonstrated rapid effects (~ 1 h of CORT on the density of thorns, by imaging Lucifer Yellow-injected neurons in adult male rat hippocampal slices. Thorns of thorny excrescences of CA3 hippocampal neurons are post-synaptic regions whose presynaptic partners are mossy fiber terminals. The application of CORT at 100, 500 and 1000 nM induced a rapid increase in the density of thorns in the stratum lucidum of CA3 pyramidal neurons. Co-administration of RU486, an antagonist of glucocorticoid receptor (GR, abolished the effect of CORT. Blocking a single kinase, including MAPK, PKA or PKC, suppressed CORT-induced enhancement of thorn-genesis. On the other hand, GSK-3β was not involved in the signaling of thorn-genesis. Blocking AMPA receptors suppressed the CORT effect. Expression of CA3 synaptic/extranuclear GR was demonstrated by immunogold electron microscopic analysis. From these results, stress levels of CORT (100-1000 nM might drive the rapid thorn-genesis via synaptic/extranuclear GR and multiple kinase pathways, although a role of nuclear GRs cannot be completely excluded.

  14. Control theory-based regulation of hippocampal CA1 nonlinear dynamics.

    Science.gov (United States)

    Hsiao, Min-Chi; Song, Dong; Berger, Theodore W

    2008-01-01

    We are developing a biomimetic electronic neural prosthesis to replace regions of the hippocampal brain area that have been damaged by disease or insult. Our previous study has shown that the VLSI implementation of a CA3 nonlinear dynamic model can functionally replace the CA3 subregion of the hippocampal slice. As a result, the propagation of temporal patterns of activity from DG-->VLSI-->CA1 reproduces the activity observed experimentally in the biological DG-->CA3-->CA1 circuit. In this project, we incorporate an open-loop controller to optimize the output (CA1) response. Specifically, we seek to optimize the stimulation signal to CA1 using a predictive dentate gyrus (DG)-CA1 nonlinear model (i.e., DG-CA1 trajectory model) and a CA1 input-output model (i.e., CA1 plant model), such that the ultimate CA1 response (i.e., desired output) can be first predicted by the DG-CA1 trajectory model and then transformed to the desired stimulation through the inversed CA1 plant model. Lastly, the desired CA1 output is evoked by the estimated optimal stimulation. This study will be the first stage of formulating an integrated modeling-control strategy for the hippocampal neural prosthetic system.

  15. Anti-reflection textured structures by wet etching and island lithography for surface-enhanced Raman spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Chao, Bo-Kai [Department of Materials Science and Engineering, National Taiwan University, Taipei 10617, Taiwan (China); Cheng, Hsin-Hung [Department of Marine Engineering, Taipei College of Maritime Technology, Taipei 11174, Taiwan (China); Nien, Li-Wei; Chen, Miin-Jang [Department of Materials Science and Engineering, National Taiwan University, Taipei 10617, Taiwan (China); Nagao, Tadaaki [Center for Materials Nanoarchitectonics, National Institute for Materials Science, Tsukuba, Ibaraki 305-0044 (Japan); Li, Jia-Han [Department of Engineering Science and Ocean Engineering, National Taiwan University, Taipei 10617, Taiwan (China); Hsueh, Chun-Hway, E-mail: hsuehc@ntu.edu.tw [Department of Materials Science and Engineering, National Taiwan University, Taipei 10617, Taiwan (China)

    2015-12-01

    Graphical abstract: - Highlights: • We fabricated textured SERS substrate with a high surface area and low reflectance. • Large surface area of substrate contains more gold nanodroplets to absorb analytes. • Low reflectance of textured SERS substrate enabled multiple reflections of incident laser light. • We obtained strong SERS enhancement from nanopillar-on-pyramid SERS substrate. - Abstract: A high surface area and low reflection textured surface-enhanced Raman scattering (SERS) substrate with plasmonic gold nanodroplets fabricated by wet etching and island lithography was reported in the present study. Specifically, four textured substrates, planar, pyramid, nanopillar, and nanopillar-on-pyramid, were fabricated. The fabricated structures were simulated using the finite-difference time-domain method and the results agreed with the reflection and dark-field scattering measurements. Although the SERS signals varied in different measured regions because of the random nanostructure, the SERS substrates with nanopillar-on-pyramid structure always have the stronger enhancement factor than the SERS substrates with only pyramids or nanopillars. Based on the atomic force microscope and reflection measurements, the nanopillar-on-pyramid structure provided a large surface area and multiple reflections for SERS enhancement, which was about 3 orders of magnitude larger than that of the planar substrate. Our results can be applied to fabricate the inexpensive, large surface area, and high SERS enhancement substrates.

  16. Silencing of dehydrin CaDHN1 diminishes tolerance to multiple abiotic stresses in Capsicum annuum L.

    Science.gov (United States)

    Chen, Ru-gang; Jing, Hua; Guo, Wei-li; Wang, Shu-Bin; Ma, Fang; Pan, Bao-Gui; Gong, Zhen-Hui

    2015-12-01

    We cloned a dehydrins gene CaDHN1 from pepper and the expression of CaDHN1 was markedly upregulated by cold, salt, osmotic stresses and salicylic acid (SA) treatment. Dehydrins (DHNs) are a subfamily of group 2 late embryogenesis-abundant (LEA) proteins that are thought to play an important role in enhancing abiotic stress tolerance in plants. In this study, a DHN EST (Expressed Sequence Tag) was obtained from 6 to 8 true leaves seedlings of pepper cv P70 (Capsicum annuum L.) by our laboratory. However, the DHN gene in pepper was not well characterized. According to this EST sequence, we isolated a DHN gene, designated as CaDHN1, and investigated the response and expression of this gene under various stresses. Our results indicated that CaDHN1 has the DHN-specific and conserved K- and S- domain and encodes 219 amino acids. Phylogenetic analysis showed that CaDHN1 belonged to the SKn subgroup. Tissue expression profile analysis revealed that CaDH N1 was expressed predominantly in fruits and flowers. The expression of CaDHN1 was markedly upregulated in response to cold, salt, osmotic stresses and salicylic acid (SA) treatment, but no significant change by abscisic acid (ABA) and heavy metals treatment. Loss of function of CaDHN1 using the virus-induced gene silencing (VIGS) technique led to decreased tolerance to cold-, salt- and osmotic-induced stresses. Overall, these results suggest that CaDHN1 plays an important role in regulating the abiotic stress resistance in pepper plants.

  17. Transdermal agomelatine microemulsion gel: pyramidal screening, statistical optimization and in vivo bioavailability.

    Science.gov (United States)

    Said, Mayada; Elsayed, Ibrahim; Aboelwafa, Ahmed A; Elshafeey, Ahmed H

    2017-11-01

    Agomelatine is a new antidepressant having very low oral drug bioavailability less than 5% due to being liable to extensive hepatic 1st pass effect. This study aimed to deliver agomelatine by transdermal route through formulation and optimization of microemulsion gel. Pyramidal screening was performed to select the most suitable ingredients combinations and then, the design expert software was utilized to optimize the microemulsion formulations. The independent variables of the employed mixture design were the percentages of capryol 90 as an oily phase (X 1 ), Cremophor RH40 and Transcutol HP in a ratio of (1:2) as surfactant/cosurfactant mixture 'S mix ' (X 2 ) and water (X 3 ). The dependent variables were globule size, optical clarity, cumulative amount permeated after 1 and 24 h, respectively (Q1 and Q 24 ) and enhancement ratio (ER). The optimized formula was composed of 5% oil, 45% S mix and 50% water. The optimized microemulsion formula was converted into carbopol-based gel to improve its retention on the skin. It enhanced the drug permeation through rat skin with an enhancement ratio of 37.30 when compared to the drug hydrogel. The optimum ME gel formula was found to have significantly higher C max , AUC 0-24 h and AUC 0-∞ than that of the reference agomelatine hydrogel and oral solution. This could reveal the prosperity of the optimized microemulsion gel formula to augment the transdermal bioavailability of agomelatine.

  18. Ischemic stroke of the pyramidal decussation causing quadriplegia and anarthria.

    Science.gov (United States)

    Wilkins, Emilia G; Kamel, Hooman; Johnson, Eric C B; Shalev, Sarah M; Josephson, S Andrew

    2012-10-01

    A 52-year-old man with a history of hypertension and previously irradiated head and neck cancer presented with quadriplegia and anarthria sparing the face and sensory functions. Brain magnetic resonance imaging (MRI) demonstrated acute infarction of the pyramidal decussation. We describe the clinical and radiological characteristics of infarction at the pyramidal decussation and review the arterial supply to this region in the lower brainstem. Although rare, infarction of the pyramidal decussation should be considered in the differential diagnosis when patients present with atraumatic pure motor quadriplegia. Copyright © 2012 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  19. Regulation of the voltage-gated Ca2+ channel CaVα2δ-1 subunit expression by the transcription factor Egr-1.

    Science.gov (United States)

    González-Ramírez, Ricardo; Martínez-Hernández, Elizabeth; Sandoval, Alejandro; Gómez-Mora, Kimberly; Felix, Ricardo

    2018-04-23

    It is well known that the Ca V α 2 δ auxiliary subunit regulates the density of high voltage-activated Ca 2+ channels in the plasma membrane and that alterations in their functional expression might have implications in the pathophysiology of diverse human diseases such as neuropathic pain. However, little is known concerning the transcriptional regulation of this protein. We previously characterized the promoter of Ca V α 2 δ, and here we report its regulation by the transcription factor Egr-1. Using the neuroblastoma N1E-115 cells, we found that Egr-1 interacts specifically with its binding site in the promoter, affecting the transcriptional regulation of Ca V α 2 δ. Overexpression and knockdown analysis of Egr-1 showed significant changes in the transcriptional activity of the Ca V α 2 δ promoter. Egr-1 also regulated the expression of Ca V α 2 δ at the level of protein. Also, functional studies showed that Egr-1 knockdown significantly decreases Ca 2+ currents in dorsal root ganglion (DRG) neurons, while overexpression of the transcription factor increased Ca 2+ currents in the F11 cell line, a hybrid of DRG and N18TG2 neuroblastoma cells. Studying the effects of Egr-1 on the transcriptional expression of Ca V α 2 δ could help to understand the regulatory mechanisms of this protein in both health and disease. Copyright © 2018 Elsevier B.V. All rights reserved.

  20. Understanding political radicalization: The two-pyramids model.

    Science.gov (United States)

    McCauley, Clark; Moskalenko, Sophia

    2017-04-01

    This article reviews some of the milestones of thinking about political radicalization, as scholars and security officials struggled after 9/11 to discern the precursors of terrorist violence. Recent criticism of the concept of radicalization has been recognized, leading to a 2-pyramids model that responds to the criticism by separating radicalization of opinion from radicalization of action. Security and research implications of the 2-pyramids model are briefly described, ending with a call for more attention to emotional experience in understanding both radicalization of opinion and radicalization of action. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  1. Layer 5 Pyramidal Neurons’ Dendritic Remodeling and Increased Microglial Density in Primary Motor Cortex in a Murine Model of Facial Paralysis

    Directory of Open Access Journals (Sweden)

    Diana Urrego

    2015-01-01

    Full Text Available This work was aimed at characterizing structural changes in primary motor cortex layer 5 pyramidal neurons and their relationship with microglial density induced by facial nerve lesion using a murine facial paralysis model. Adult transgenic mice, expressing green fluorescent protein in microglia and yellow fluorescent protein in projecting neurons, were submitted to either unilateral section of the facial nerve or sham surgery. Injured animals were sacrificed either 1 or 3weeks after surgery. Two-photon excitation microscopy was then used for evaluating both layer 5 pyramidal neurons and microglia in vibrissal primary motor cortex (vM1. It was found that facial nerve lesion induced long-lasting changes in the dendritic morphology of vM1 layer 5 pyramidal neurons and in their surrounding microglia. Dendritic arborization of the pyramidal cells underwent overall shrinkage. Apical dendrites suffered transient shortening while basal dendrites displayed sustained shortening. Moreover, dendrites suffered transient spine pruning. Significantly higher microglial cell density was found surrounding vM1 layer 5 pyramidal neurons after facial nerve lesion with morphological bias towards the activated phenotype. These results suggest that facial nerve lesions elicit active dendrite remodeling due to pyramidal neuron and microglia interaction, which could be the pathophysiological underpinning of some neuropathic motor sequelae in humans.

  2. Layer 5 Pyramidal Neurons' Dendritic Remodeling and Increased Microglial Density in Primary Motor Cortex in a Murine Model of Facial Paralysis

    Science.gov (United States)

    Urrego, Diana; Troncoso, Julieta; Múnera, Alejandro

    2015-01-01

    This work was aimed at characterizing structural changes in primary motor cortex layer 5 pyramidal neurons and their relationship with microglial density induced by facial nerve lesion using a murine facial paralysis model. Adult transgenic mice, expressing green fluorescent protein in microglia and yellow fluorescent protein in projecting neurons, were submitted to either unilateral section of the facial nerve or sham surgery. Injured animals were sacrificed either 1 or 3weeks after surgery. Two-photon excitation microscopy was then used for evaluating both layer 5 pyramidal neurons and microglia in vibrissal primary motor cortex (vM1). It was found that facial nerve lesion induced long-lasting changes in the dendritic morphology of vM1 layer 5 pyramidal neurons and in their surrounding microglia. Dendritic arborization of the pyramidal cells underwent overall shrinkage. Apical dendrites suffered transient shortening while basal dendrites displayed sustained shortening. Moreover, dendrites suffered transient spine pruning. Significantly higher microglial cell density was found surrounding vM1 layer 5 pyramidal neurons after facial nerve lesion with morphological bias towards the activated phenotype. These results suggest that facial nerve lesions elicit active dendrite remodeling due to pyramidal neuron and microglia interaction, which could be the pathophysiological underpinning of some neuropathic motor sequelae in humans. PMID:26064916

  3. Fabrication of 20.19% Efficient Single-Crystalline Silicon Solar Cell with Inverted Pyramid Microstructure.

    Science.gov (United States)

    Zhang, Chunyang; Chen, Lingzhi; Zhu, Yingjie; Guan, Zisheng

    2018-04-03

    This paper reports inverted pyramid microstructure-based single-crystalline silicon (sc-Si) solar cell with a conversion efficiency up to 20.19% in standard size of 156.75 × 156.75 mm 2 . The inverted pyramid microstructures were fabricated jointly by metal-assisted chemical etching process (MACE) with ultra-low concentration of silver ions and optimized alkaline anisotropic texturing process. And the inverted pyramid sizes were controlled by changing the parameters in both MACE and alkaline anisotropic texturing. Regarding passivation efficiency, the textured sc-Si with normal reflectivity of 9.2% and inverted pyramid size of 1 μm was used to fabricate solar cells. The best batch of solar cells showed a 0.19% higher of conversion efficiency and a 0.22 mA cm -2 improvement in short-circuit current density, and the excellent photoelectric property surpasses that of the same structure solar cell reported before. This technology shows great potential to be an alternative for large-scale production of high efficient sc-Si solar cells in the future.

  4. Nano-fibrin stabilized CaSO4 crystals incorporated injectable chitin composite hydrogel for enhanced angiogenesis & osteogenesis.

    Science.gov (United States)

    Arun Kumar, R; Sivashanmugam, A; Deepthi, S; Bumgardner, Joel D; Nair, Shantikumar V; Jayakumar, R

    2016-04-20

    Calcium sulfate (CaSO4), an excellent biodegradable bone forming agent that is an ideal choice as additive in gels, however, its disadvantage being poor gel rheology and angiogenesis. Here, we have synthesized chitin-CaSO4-nano-fibrin based injectable gel system which shows improved rheology and angiogenic potential. Rheological studies showed that the composite gel was a shear thinning gel with elastic modulus of 15.4±0.275kPa; a 1.67 fold increase over chitin control. SEM and XRD analyses revealed the effect of nano-fibrin (nFibrin) in transforming CaSO4 crystal shape from needle to hexagonal. It also masked the retarding effect of CaSO4 towards in vitro early cell attachment and angiogenesis using rabbit adipose derived mesenchymal stem cells (rASCs) and HUVECs, respectively. rASCs osteogenesis was confirmed by spectrophotometric endpoint assay, which showed 6-fold early increase in alkaline phosphatase levels and immuno-cytochemistry analysis. These in vitro results highlight the potential of injectable chitin-CaSO4-nFibrin gel for osteo-regeneration via enhanced angiogenesis. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Enhanced Energy-Storage Density and High Efficiency of Lead-Free CaTiO3-BiScO3 Linear Dielectric Ceramics.

    Science.gov (United States)

    Luo, Bingcheng; Wang, Xiaohui; Tian, Enke; Song, Hongzhou; Wang, Hongxian; Li, Longtu

    2017-06-14

    A novel lead-free (1 - x)CaTiO 3 -xBiScO 3 linear dielectric ceramic with enhanced energy-storage density was fabricated. With the composition of BiScO 3 increasing, the dielectric constant of (1 - x)CaTiO 3 -xBiScO 3 ceramics first increased and then decreased after the composition x > 0.1, while the dielectric loss decreased first and increased. For the composition x = 0.1, the polarization was increased into 12.36 μC/cm 2 , 4.6 times higher than that of the pure CaTiO 3 . The energy density of 0.9CaTiO 3 -0.1BiScO 3 ceramic was 1.55 J/cm 3 with the energy-storage efficiency of 90.4% at the breakdown strength of 270 kV/cm, and the power density was 1.79 MW/cm 3 . Comparison with other lead-free dielectric ceramics confirmed the superior potential of CaTiO 3 -BiScO 3 ceramics for the design of ceramics capacitors for energy-storage applications. First-principles calculations revealed that Sc subsitution of Ti-site induced the atomic displacement of Ti ions in the whole crystal lattice, and lattice expansion was caused by variation of the bond angles and lenghths. Strong hybridization between O 2p and Ti 3d was observed in both valence band and conduction band; the hybridization between O 2p and Sc 3d at high conduction band was found to enlarge the band gap, and the static dielectric tensors were increased, which was the essential for the enhancement of polarization and dielectric properties.

  6. Overexpression of CaTLP1, a putative transcription factor in chickpea (Cicer arietinum L.), promotes stress tolerance.

    Science.gov (United States)

    Wardhan, Vijay; Jahan, Kishwer; Gupta, Sonika; Chennareddy, Srinivasarao; Datta, Asis; Chakraborty, Subhra; Chakraborty, Niranjan

    2012-07-01

    Dehydration is the most crucial environmental constraint on plant growth and development, and agricultural productivity. To understand the underlying mechanism of stress tolerance, and to identify proteins for improving such important trait, we screened the dehydration-responsive proteome of chickpea and identified a tubby-like protein, referred to as CaTLP1. The CaTLP1 was found to predominantly bind to double-stranded DNA but incapable of transcriptional activation. We investigated the gene structure and organization and demonstrated, for the first time, that CaTLP1 may be involved in osmotic stress response in plants. The transcripts are strongly expressed in vegetative tissues but weakly in reproductive tissues. CaTLP1 is upregulated by dehydration and high salinity, and by treatment with abscisic acid (ABA), suggesting that its stress-responsive function might be associated with ABA-dependent network. Overexpression of CaTLP1 in transgenic tobacco plants conferred dehydration, salinity and oxidative stress tolerance along with improved shoot and root architecture. Molecular genetic analysis showed differential expression of CaTLP1 under normal and stress condition, and its preferential expression in the nucleus might be associated with enhanced stress tolerance. Our work suggests important roles of CaTLP1 in stress response as well as in the regulation of plant development.

  7. Atomistic modeling to investigate the favored composition for metallic glass formation in the Ca-Mg-Ni ternary system.

    Science.gov (United States)

    Zhao, S; Li, J H; An, S M; Li, S N; Liu, B X

    2017-05-17

    A realistic interatomic potential was first constructed for the Ca-Mg-Ni system and then applied to Monte Carlo simulations to predict the favored composition for metallic glass formation in the ternary system. The simulations not only predict a hexagonal composition region, within which the Ca-Mg-Ni metallic glass formation is energetically favored, but also pinpoint an optimized sub-region within which the amorphization driving force, i.e. the energy difference between the solid solution and disordered phase, is larger than that outside. The simulations further reveal that the physical origin of glass formation is the solid solution collapsing when the solute atom exceeds the critical solid solubility. Further structural analysis indicates that the pentagonal bi-pyramids dominate in the optimized sub-region. The large atomic size difference between Ca, Mg and Ni extends the short-range landscape and facilitates the development of a hybridized packing model in the medium-range, and eventually enhancing the glass formation in the system. The predictions are well supported by the experimental observations reported so far, and could be of help for designing the ternary glass formation.

  8. A Medicago truncatula EF-hand family gene, MtCaMP1, is involved in drought and salt stress tolerance.

    Directory of Open Access Journals (Sweden)

    Tian-Zuo Wang

    Full Text Available BACKGROUND: Calcium-binding proteins that contain EF-hand motifs have been reported to play important roles in transduction of signals associated with biotic and abiotic stresses. To functionally characterize genes of EF-hand family in response to abiotic stress, an MtCaMP1 gene belonging to EF-hand family from legume model plant Medicago truncatula was isolated and its function in response to drought and salt stress was investigated by expressing MtCaMP1 in Arabidopsis. METHODOLOGY/PRINCIPAL FINDINGS: Transgenic Arabidopsis seedlings expressing MtCaMP1 exhibited higher survival rate than wild-type seedlings under drought and salt stress, suggesting that expression of MtCaMP1 confers tolerance of Arabidopsis to drought and salt stress. The transgenic plants accumulated greater amounts of Pro due to up-regulation of P5CS1 and down-regulation of ProDH than wild-type plants under drought stress. There was a less accumulation of Na(+ in the transgenic plants than in WT plants due to reduced up-regulation of AtHKT1 and enhanced regulation of AtNHX1 in the transgenic plants compared to WT plants under salt stress. There was a reduced accumulation of H2O2 and malondialdehyde in the transgenic plants than in WT plants under both drought and salt stress. CONCLUSIONS/SIGNIFICANCE: The expression of MtCaMP1 in Arabidopsis enhanced tolerance of the transgenic plants to drought and salt stress by effective osmo-regulation due to greater accumulation of Pro and by minimizing toxic Na(+ accumulation, respectively. The enhanced accumulation of Pro and reduced accumulation of Na(+ under drought and salt stress would protect plants from water default and Na(+ toxicity, and alleviate the associated oxidative stress. These findings demonstrate that MtCaMP1 encodes a stress-responsive EF-hand protein that plays a regulatory role in response of plants to drought and salt stress.

  9. Effects of 1,2,4-Trichlorobenzene and Mercury Ion Stress on Ca2+ Fluxion and Protein Phosphorylation in Rice

    Directory of Open Access Journals (Sweden)

    Cai-lin GE

    2007-12-01

    Full Text Available The effects of 5 mg/L 1,2,4-trichlorobenzene (TCB and 0.1 mmol/L mercury ion (Hg2+ stresses on Ca2+ fluxion and protein phosphorylation in rice seedlings were investigated by isotope exchange kinetics and in vitro phosphorylation assay. The Ca2+ absorption in rice leaves and Ca2+ transportation from roots to leaves were promoted significantly in response to Hg2+ and TCB treatments for 4-48 h. The Ca2+ absorption peaks presented in the leaves when the rice seedlings were exposed to Hg2+ for 8-12 h or to TCB for 12-24 h. Several Ca2+ absorption peaks presented in the roots during rice seedlings being exposed to Hg2+ and TCB, and the first Ca2+ absorption peak was at 8 h after being exposed to Hg2+ and TCB. The result of isotope exchange kinetic analysis confirmed that short-term (8 h Hg2+ and TCB stresses caused Ca2+ channels or pumps located on plasmalemma to open transiently. The phosphorylation assay showed that short-term TCB stress enhanced protein phosphorylation in rice roots (TCB treatment for 4-8 h and leaves (TCB treatment for 4-24 h, and short-term (4-8 h Hg2+ stress also enhanced protein phosphorylation in rice leaves. The enhancement of protein phosphorylation in both roots and leaves corresponded with the first Ca2+ absorption peak, which confirmed that the enhancement of protein phosphorylation caused by TCB or Hg2+ stress might be partly triggered by the increases of cytosolic calcium. TCB treatment over 12 h inhibited protein phosphorylation in rice roots, which might be partly due to that TCB stress suppressed the protein kinase activity. Whereas, Hg2+ treatment inhibited protein phosphorylation in rice roots, and Hg2+ treatment over 12 h inhibited protein phosphorylation in rice leaves. This might be attributed to that not only the protein kinase activity, but also the expressions of phosphorylation proteins were restrained by Hg2+ stress.

  10. The mammalian neocortical pyramidal cell: a new theory on prenatal development

    Directory of Open Access Journals (Sweden)

    Miguel eMarín-Padilla

    2014-01-01

    Full Text Available Mammals’ new cerebral cortex (neocortex and the new type of pyramidal neuron are mammalian innovations that have evolved for operating their increasing motor capabilities using essentially analogous anatomical and neural makeups. The human neocortex starts to develop in the 6-week-old embryo with the establishment of a primordial cortical organization that resembles the primitive cortices of amphibian and reptiles that operated his early motor activities. From the 8th to the 15th week of age, the new pyramidal neurons, of ependymal origin, are progressively incorporated within this primordial cortex forming a cellular plate that divide its components into those above it (neocortex first lamina and those below it (neocortex subplate elements. From the 16th week of age to birth and postnatally, the new pyramidal neurons continue to elongate functionally their apical dendrite by adding synaptic membrane to incorporate the needed sensory information for operating the animal muscular activities. The new pyramidal neuron’ distinguishing feature is the capacity of elongating anatomically and functionally its apical dendrite (its main receptive surface without losing its original attachment to first lamina or the location of its soma retaining its essential nature. The number of pyramidal cell functional strata established in the motor cortex increases and reflects each mammalian species motor capabilities: the hedgehog needs 2 pyramidal cell functional strata to carry out all its motor activities, the mouse three, cat four, primates 5 and humans 6. The presence of six pyramidal cell functional strata distinguish the human motor cortex from that of others primates. Homo sapiens represent a new evolutionary stage that have transformed his primate brain for operating his unique motor capabilities, such as speaking, writing, painting, sculpturing including thinking as a premotor activity.

  11. A muon detector to be installed at the Pyramid of the Sun

    International Nuclear Information System (INIS)

    Alfaro, R.; Belmont M, E.; Cervantes, A.; Grabski, V.; Lopez R, J.M.; Manzanilla, L.; Martinez D, A.; Moreno, M.; Menchaca R, A.

    2003-01-01

    Is the Pyramid of the Sun at Teotihuacan a mausoleum, or just a ceremonial monument? A similar question inspired Luis Alvarez over 30 years ago to carry out his famous muon detection experiment at the Chephren Pyramid, in Giza. A fortunate similarity between this monument and the Pyramid of the Sun is a tunnel, running 8 m below the base and ending close to the symmetry axis, which allows us to emulate Alvarez in a search for possible hidden chambers in one of the largest pyramids in Latin America. Here we elaborate on what is known about this monument, on a description of the proposed detector design, and its expected performance based on simulations. (Author)

  12. Functional roles of the pepper RING finger protein gene, CaRING1, in abscisic acid signaling and dehydration tolerance.

    Science.gov (United States)

    Lim, Chae Woo; Hwang, Byung Kook; Lee, Sung Chul

    2015-09-01

    Plants are constantly exposed to a variety of biotic and abiotic stresses, which include pathogens and conditions of high salinity, low temperature, and drought. Abscisic acid (ABA) is a major plant hormone involved in signal transduction pathways that mediate the defense response of plants to abiotic stress. Previously, we isolated Ring finger protein gene (CaRING1) from pepper (Capsicum annuum), which is associated with resistance to bacterial pathogens, accompanied by hypersensitive cell death. Here, we report a new function of the CaRING1 gene product in the ABA-mediated defense responses of plants to dehydration stress. The expression of the CaRING1 gene was induced in pepper leaves treated with ABA or exposed to dehydration or NaCl. Virus-induced gene silencing of CaRING1 in pepper plants exhibited low degree of ABA-induced stomatal closure and high levels of transpirational water loss in dehydrated leaves. These led to be more vulnerable to dehydration stress in CaRING1-silenced pepper than in the control pepper, accompanied by reduction of ABA-regulated gene expression and low accumulation of ABA and H2O2. In contrast, CaRING1-overexpressing transgenic plants showed enhanced sensitivity to ABA during the seedling growth and establishment. These plants were also more tolerant to dehydration stress than the wild-type plants because of high ABA accumulation, enhanced stomatal closure and increased expression of stress-responsive genes. Together, these results suggest that the CaRING1 acts as positive factor for dehydration tolerance in Arabidopsis by modulating ABA biosynthesis and ABA-mediated stomatal closing and gene expression.

  13. Apo-states of calmodulin and CaBP1 control CaV1 voltage-gated calcium channel function through direct competition for the IQ domain

    Science.gov (United States)

    Findeisen, Felix; Rumpf, Christine; Minor, Daniel L.

    2013-01-01

    In neurons, binding of calmodulin (CaM) or calcium-binding protein 1 (CaBP1) to the CaV1 (L-type) voltage-gated calcium channel IQ domain endows the channel with diametrically opposed properties. CaM causes calcium-dependent inactivation (CDI) and limits calcium entry, whereas CaBP1 blocks CDI and allows sustained calcium influx. Here, we combine isothermal titration calorimetry (ITC) with cell-based functional measurements and mathematical modeling to show that these calcium sensors behave in a competitive manner that is explained quantitatively by their apo-state binding affinities for the IQ domain. This competition can be completely blocked by covalent tethering of CaM to the channel. Further, we show that Ca2+/CaM has a sub-picomolar affinity for the IQ domain that is achieved without drastic alteration of calcium binding properties. The observation that the apo-forms of CaM and CaBP1 compete with each other demonstrates a simple mechanism for direct modulation of CaV1 function and suggests a means by which excitable cells may dynamically tune CaV activity. PMID:23811053

  14. Apo states of calmodulin and CaBP1 control CaV1 voltage-gated calcium channel function through direct competition for the IQ domain.

    Science.gov (United States)

    Findeisen, Felix; Rumpf, Christine H; Minor, Daniel L

    2013-09-09

    In neurons, binding of calmodulin (CaM) or calcium-binding protein 1 (CaBP1) to the CaV1 (L-type) voltage-gated calcium channel IQ domain endows the channel with diametrically opposed properties. CaM causes calcium-dependent inactivation and limits calcium entry, whereas CaBP1 blocks calcium-dependent inactivation (CDI) and allows sustained calcium influx. Here, we combine isothermal titration calorimetry with cell-based functional measurements and mathematical modeling to show that these calcium sensors behave in a competitive manner that is explained quantitatively by their apo-state binding affinities for the IQ domain. This competition can be completely blocked by covalent tethering of CaM to the channel. Further, we show that Ca(2+)/CaM has a sub-picomolar affinity for the IQ domain that is achieved without drastic alteration of calcium-binding properties. The observation that the apo forms of CaM and CaBP1 compete with each other demonstrates a simple mechanism for direct modulation of CaV1 function and suggests a means by which excitable cells may dynamically tune CaV activity. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

  15. Shift of the pyramidal tract during resection of the intraaxial brain tumors estimated by intraoperative diffusion-weighted imaging

    International Nuclear Information System (INIS)

    Ozawa, Norihiko; Muragaki, Yoshihiro; Nakamura, Ryoichi; Iseki, Hiroshi; Hori, Tomokatsu

    2009-01-01

    The present study evaluated the shift of the pyramidal tract during resection of 17 proximal intraaxial brain tumors. In each case intraoperative diffusion-weighted (iDW) magnetic resonance imaging with a motion-probing gradient applied in the anteroposterior direction was performed using a scanner with a 0.3 T vertical magnetic field. The position of the white matter bundles containing the pyramidal tract was estimated on the coronal images before and after resection of the neoplasm, and both quantitative and directional evaluation of its displacement was done. In all cases iDW imaging provided visualization of the structure of interest. The magnitude of the pyramidal tract displacement due to removal of the neoplasm varied from 0.5 to 8.7 mm (mean 4.4±2.5 mm) on the lesion side and from 0 to 3.6 mm (mean 1.3±1.1 mm) on the normal side (p<0.001). Tumor location in regards to the pyramidal tract was significantly associated with the direction of the pyramidal tract displacement (p<0.05). Outward shift occurred in 10 out of 13 cases of the lateral neoplasms, whereas in all 4 superomedial tumors inward shift was marked. In conclusion, the direction of the pyramidal tract displacement during resection of the proximal intraaxial brain tumors is mainly determined by position of the neoplasm, but can be unpredictable in some cases, which necessitates use of subcortical brain mapping and intraoperative imaging, particularly iDW imaging with updated neuronavigation. (author)

  16. Control of CA3 output by feedforward inhibition despite developmental changes in the excitation-inhibition balance.

    Science.gov (United States)

    Torborg, Christine L; Nakashiba, Toshiaki; Tonegawa, Susumu; McBain, Chris J

    2010-11-17

    In somatosensory cortex, the relative balance of excitation and inhibition determines how effectively feedforward inhibition enforces the temporal fidelity of action potentials. Within the CA3 region of the hippocampus, glutamatergic mossy fiber (MF) synapses onto CA3 pyramidal cells (PCs) provide strong monosynaptic excitation that exhibit prominent facilitation during repetitive activity. We demonstrate in the juvenile CA3 that MF-driven polysynaptic IPSCs facilitate to maintain a fixed EPSC-IPSC ratio during short-term plasticity. In contrast, in young adult mice this MF-driven polysynaptic inhibitory input can facilitate or depress in response to short trains of activity. Transgenic mice lacking the feedback inhibitory loop continue to exhibit both facilitating and depressing polysynaptic IPSCs, indicating that this robust inhibition is not caused by the secondary engagement of feedback inhibition. Surprisingly, eliminating MF-driven inhibition onto CA3 pyramidal cells by blockade of GABA(A) receptors did not lead to a loss of temporal precision of the first action potential observed after a stimulus but triggered in many cases a long excitatory plateau potential capable of triggering repetitive action potential firing. These observations indicate that, unlike other regions of the brain, the temporal precision of single MF-driven action potentials is dictated primarily by the kinetics of MF EPSPs, not feedforward inhibition. Instead, feedforward inhibition provides a robust regulation of CA3 PC excitability across development to prevent excessive depolarization by the monosynaptic EPSP and multiple action potential firings.

  17. Distribution and function of HCN channels in the apical dendritic tuft of neocortical pyramidal neurons.

    Science.gov (United States)

    Harnett, Mark T; Magee, Jeffrey C; Williams, Stephen R

    2015-01-21

    The apical tuft is the most remote area of the dendritic tree of neocortical pyramidal neurons. Despite its distal location, the apical dendritic tuft of layer 5 pyramidal neurons receives substantial excitatory synaptic drive and actively processes corticocortical input during behavior. The properties of the voltage-activated ion channels that regulate synaptic integration in tuft dendrites have, however, not been thoroughly investigated. Here, we use electrophysiological and optical approaches to examine the subcellular distribution and function of hyperpolarization-activated cyclic nucleotide-gated nonselective cation (HCN) channels in rat layer 5B pyramidal neurons. Outside-out patch recordings demonstrated that the amplitude and properties of ensemble HCN channel activity were uniform in patches excised from distal apical dendritic trunk and tuft sites. Simultaneous apical dendritic tuft and trunk whole-cell current-clamp recordings revealed that the pharmacological blockade of HCN channels decreased voltage compartmentalization and enhanced the generation and spread of apical dendritic tuft and trunk regenerative activity. Furthermore, multisite two-photon glutamate uncaging demonstrated that HCN channels control the amplitude and duration of synaptically evoked regenerative activity in the distal apical dendritic tuft. In contrast, at proximal apical dendritic trunk and somatic recording sites, the blockade of HCN channels decreased excitability. Dynamic-clamp experiments revealed that these compartment-specific actions of HCN channels were heavily influenced by the local and distributed impact of the high density of HCN channels in the distal apical dendritic arbor. The properties and subcellular distribution pattern of HCN channels are therefore tuned to regulate the interaction between integration compartments in layer 5B pyramidal neurons. Copyright © 2015 the authors 0270-6474/15/351024-14$15.00/0.

  18. STIM1 as a key regulator for Ca2+ homeostasis in skeletal-muscle development and function

    Directory of Open Access Journals (Sweden)

    Kiviluoto Santeri

    2011-04-01

    enhanced Ca2+ influx through Orai1 and/or TRPC channels, leading to Ca2+-dependent apoptosis and muscle degeneration. In addition, human myopathies have been associated with dysfunctional SOCE. Immunodeficient patients harboring loss-of-function Orai1 mutations develop myopathies, while patients suffering from Duchenne muscular dystrophy display alterations in their Ca2+-handling proteins, including STIM proteins. In any case, the molecular determinants responsible for SOCE in human skeletal muscle and for dysregulated SOCE in patients of muscular dystrophy require further examination.

  19. Wooden's pyramid: building a hierarchy of skills for successful communication.

    Science.gov (United States)

    Epner, Daniel E; Baile, Walter F

    2011-01-01

    John Wooden, the legendary college basketball coach, created the "Pyramid of Success", which he constructed from 14 timeless character traits and interpersonal skills that are critical to competitive greatness. Wooden's pyramid is a powerful symbol that he and others have used for several decades as an educational tool to promote leadership and teamwork. This article proposes the "Pyramid of Relational Excellence (PRE)", patterned after Wooden's pyramid, as a mnemonic-based educational symbol for communication skills training. Literature review, personal reflection. The PRE is constructed of four tiers with a total of 12 building blocks, with each successive tier built upon the one beneath it. The building blocks represent fundamental elements that are known to be critical to successful communication. The PRE is process oriented rather than task oriented and focuses exclusively on the face-to-face encounter. It therefore complements established communications curricula, such as the UK communication wheel and others, which are more comprehensive and task oriented. The PRE is constructed of timeless, fundamental principles. It is therefore particularly well suited for training medical students and residents.

  20. Dexamethasone enhances necrosis-like neuronal death in ischemic rat hippocampus involving μ-calpain activation

    DEFF Research Database (Denmark)

    Müller, Georg Johannes; Hasseldam, Henrik; Rasmussen, Rune Skovgaard

    2014-01-01

    - and necrosis-like cell death morphologies in CA1 of rats treated with dexamethasone prior to TFI (DPTI). In addition, apoptosis- (casp-9, casp-3, casp-3-cleaved PARP and cleaved α-spectrin 145/150 and 120kDa) and necrosis-related (calpain-specific casp-9 cleavage, μ-calpain upregulation and cleaved α......Transient forebrain ischemia (TFI) leads to hippocampal CA1 pyramidal cell death which is aggravated by glucocorticoids (GC). It is unknown how GC affect apoptosis and necrosis in cerebral ischemia. We therefore investigated the co-localization of activated caspase-3 (casp-3) with apoptosis......-spectrin 145/150kDa) cell death mechanisms were investigated by Western blot analysis. DPTI expedited CA1 neuronal death from day 4 to day 1 and increased the magnitude of CA1 neuronal death from 66.2% to 91.3% at day 7. Furthermore, DPTI decreased the overall (days 1-7) percentage of dying neurons displaying...

  1. Reassigning the CaH+ 11Σ → 21Σ vibronic transition with CaD+

    Science.gov (United States)

    Condoluci, J.; Janardan, S.; Calvin, A. T.; Rugango, R.; Shu, G.; Sherrill, C. D.; Brown, K. R.

    2017-12-01

    We observe vibronic transitions in CaD+ between the 11Σ and 21Σ electronic states by resonance enhanced multiphoton photodissociation spectroscopy in a Coulomb crystal. The vibronic transitions are compared with previous measurements on CaH+. The result is a revised assignment of the CaH+ vibronic levels and a disagreement with multi-state-complete-active-space second-order perturbation theory theoretical calculations by approximately 700 cm-1. Updated high-level coupled-cluster calculations that include core-valence correlations reduce the disagreement between theory and experiment to 300 cm-1.

  2. PGC-1{alpha} accelerates cytosolic Ca{sup 2+} clearance without disturbing Ca{sup 2+} homeostasis in cardiac myocytes

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Min, E-mail: chenminyx@gmail.com [Institute of Molecular Medicine, State Key Laboratory of Biomembrane and Membrane Biotechnology, Peking University, Beijing 100871 (China); Yunnan Centers for Diseases Prevention and Control, Kunming 650022 (China); Wang, Yanru [Institute of Molecular Medicine, State Key Laboratory of Biomembrane and Membrane Biotechnology, Peking University, Beijing 100871 (China); Qu, Aijuan [Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States)

    2010-06-11

    Energy metabolism and Ca{sup 2+} handling serve critical roles in cardiac physiology and pathophysiology. Peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1{alpha}) is a multi-functional coactivator that is involved in the regulation of cardiac mitochondrial functional capacity and cellular energy metabolism. However, the regulation of PGC-1{alpha} in cardiac Ca{sup 2+} signaling has not been fully elucidated. To address this issue, we combined confocal line-scan imaging with off-line imaging processing to characterize calcium signaling in cultured adult rat ventricular myocytes expressing PGC-1{alpha} via adenoviral transduction. Our data shows that overexpressing PGC-1{alpha} improved myocyte contractility without increasing the amplitude of Ca{sup 2+} transients, suggesting that myofilament sensitivity to Ca{sup 2+} increased. Interestingly, the decay kinetics of global Ca{sup 2+} transients and Ca{sup 2+} waves accelerated in PGC-1{alpha}-expressing cells, but the decay rate of caffeine-elicited Ca{sup 2+} transients showed no significant change. This suggests that sarcoplasmic reticulum (SR) Ca{sup 2+}-ATPase (SERCA2a), but not Na{sup +}/Ca{sup 2+} exchange (NCX) contribute to PGC-1{alpha}-induced cytosolic Ca{sup 2+} clearance. Furthermore, PGC-1{alpha} induced the expression of SERCA2a in cultured cardiac myocytes. Importantly, overexpressing PGC-1{alpha} did not disturb cardiac Ca{sup 2+} homeostasis, because SR Ca{sup 2+} load and the propensity for Ca{sup 2+} waves remained unchanged. These data suggest that PGC-1{alpha} can ameliorate cardiac Ca{sup 2+} cycling and improve cardiac work output in response to physiological stress. Unraveling the PGC-1{alpha}-calcium handing pathway sheds new light on the role of PGC-1{alpha} in the therapy of cardiac diseases.

  3. The azimuth-dependent offset-midpoint traveltime pyramid in 3D HTI media

    KAUST Repository

    Hao, Qi

    2013-09-22

    Analytical representation of offset-midpoint traveltime equation is very important for pre-stack Kirchhoff migration and velocity inversion in anisotropic media. For VTI media, the offset-midpoint traveltime resembles the shape of Cheop\\'s pyramid. In this study, we extend the offset-midpoint traveltime pyramid to the case of 3D HTI media. We employ the stationary phase method to derive the analytical representation of traveltime equation, and then use Shanks transformation to improve the accuracy of horizontal and vertical slownesses. The traveltime pyramid is derived in both the depth- and time-domain. Numerical examples indicate that the azimuthal characteristics of both the traveltime pyramid and the migration isochrones are very obvious in HTI media due to the effect of anisotropy.

  4. Regulation of Blood Pressure by Targeting CaV1.2-Galectin-1 Protein Interaction.

    Science.gov (United States)

    Hu, Zhenyu; Li, Guang; Wang, Jiong-Wei; Chong, Suet Yen; Yu, Dejie; Wang, Xiaoyuan; Soon, Jia Lin; Liang, Mui Cheng; Wong, Yuk Peng; Huang, Na; Colecraft, Henry M; Liao, Ping; Soong, Tuck Wah

    2018-04-12

    Background -L-type Ca V 1.2 channels play crucial roles in regulation of blood pressure. Galectin-1 (Gal-1), has been reported to bind to the I-II loop of Ca V 1.2 channels to reduce their current density. However, the mechanistic understanding for the down-regulation of Ca V 1.2 channels by Gal-1, and whether Gal-1 plays a direct role in blood pressure regulation remain unclear. Methods - In vitro experiments involving co-IP, western blot, patch-clamp recordings, immunohistochemistry and pressure myography were used to evaluate the molecular mechanisms by which Gal-1 down-regulates Ca V 1.2 channel in transfected HEK 293 cells, smooth muscle cells, arteries from Lgasl1 -/- mice, rat and human patients. In vivo experiments involving delivery of Tat-e9c peptide and AAV5-Gal-1 into rats were performed to investigate the effect of targeting Ca V 1.2-Gal-1 interaction on blood pressure monitored by tail cuff or telemetry methods. Results -Our study reveals that Gal-1 is a key regulator for proteasomal degradation of Ca V 1.2 channels. Gal-1 competed allosterically with Ca V β subunit for binding to the I-II loop of Ca V 1.2 channel. This competitive disruption of Ca V β binding led to Ca V 1.2 degradation by exposing the channels to poly-ubiquitination. Notably, we demonstrated that the inverse relationship of reduced Gal-1 and increased Ca V 1.2 protein levels in arteries was associated with hypertension in hypertensive rats and patients, and Gal-1 deficiency induces higher blood pressure in mice due to up-regulated Ca V 1.2 protein level in arteries. To directly regulate blood pressure by targeting the Ca V 1.2-Gal-1 interaction, we administered Tat-e9c, a peptide that competed for binding of Gal-1, by a mini-osmotic pump and this specific disruption of Ca V 1.2-Gal-1 coupling increased smooth muscle Ca V 1.2 currents, induced larger arterial contraction and caused hypertension in rats. In contrasting experiments, over-expression of Gal-1 in smooth muscle by a

  5. The Sphinx and the Pyramids at Giza. Educational Packet.

    Science.gov (United States)

    Gagliano, Sara; Rapport, Wendy

    This packet of materials was created to accompany the exhibit "The Sphinx and the Pyramids: 100 Years of American Archaeology at Giza" at the Semitic Museum of Harvard University. The lessons and teacher's guide focus on the following: (1) "The Mystery of the Secret Tomb" where students take on the role of an archaeologist by…

  6. Intermittent fasting promotes prolonged associative interactions during synaptic tagging/capture by altering the metaplastic properties of the CA1 hippocampal neurons.

    Science.gov (United States)

    Dasgupta, Ananya; Kim, Joonki; Manakkadan, Anoop; Arumugam, Thiruma V; Sajikumar, Sreedharan

    2017-12-19

    Metaplasticity is the inherent property of a neuron or neuronal population to undergo activity-dependent changes in neural function that modulate subsequent synaptic plasticity. Here we studied the effect of intermittent fasting (IF) in governing the interactions of associative plasticity mechanisms in the pyramidal neurons of rat hippocampal area CA1. Late long-term potentiation and its associative mechanisms such as synaptic tagging and capture at an interval of 120 min were evaluated in four groups of animals, AL (Ad libitum), IF12 (daily IF for 12 h), IF16 (daily IF for 16 h) and EOD (every other day IF for 24 h). IF had no visible effect on the early or late plasticity but it manifested a critical role in prolonging the associative interactions between weak and strong synapses at an interval of 120 min in IF16 and EOD animals. However, both IF12 and AL did not show associativity at 120 min. Plasticity genes such as Bdnf and Prkcz, which are well known for their expressions in late plasticity and synaptic tagging and capture, were significantly upregulated in IF16 and EOD in comparison to AL. Specific inhibition of brain derived neurotropic factor (BDNF) prevented the prolonged associativity expressed in EOD. Thus, daily IF for 16 h or more can be considered to enhance the metaplastic properties of synapses by improving their associative interactions that might translate into animprovedmemoryformation. Copyright © 2017. Published by Elsevier Inc.

  7. Graphene oxide-Ag nanoparticles-pyramidal silicon hybrid system for homogeneous, long-term stable and sensitive SERS activity

    Science.gov (United States)

    Guo, Jia; Xu, Shicai; Liu, Xiaoyun; Li, Zhe; Hu, Litao; Li, Zhen; Chen, Peixi; Ma, Yong; Jiang, Shouzhen; Ning, Tingyin

    2017-02-01

    In our work, few layers graphene oxide (GO) were directly synthesized on Ag nanoparticles (AgNPs) by spin-coating method to fabricate a GO-AgNPs hybrid structure on a pyramidal silicon (PSi) substrate for surface-enhanced Raman scattering (SERS). The GO-AgNPs-PSi substrate showed excellent Raman enhancement effect, the minimum detected concentration for Rhodamine 6G (R6G) can reach 10-12 M, which is one order of magnitude lower than the AgNPs-PSi substrate and two order of magnitude lower than the GO-AgNPs-flat-Si substrate. The linear fit calibration curve with error bars is presented and the value of R2 of 612 and 773 cm-1 can reach 0.986 and 0.980, respectively. The excellent linear response between the Raman intensity and R6G concentrations prove that the prepared GO-AgNPs-PSi substrates can serve as good SERS substrate for molecule detection. The maximum deviations of SERS intensities from 20 positions of the GO-AgNPs-PSi substrate are less than 8%, revealing the high homogeneity of the SERS substrate. The excellent homogeneity of the enhanced Raman signals can be attributed to well-separated pyramid arrays of PSi, the uniform morphology of AgNPs and multi-functions of GO layer. Besides, the uniform GO film can effectively protect AgNPs from oxidation and endow the hybrid system a good stability and long lifetime. This GO-AgNPs-PSi substrate may provide a new way toward practical applications for the ultrasensitive and label-free SERS detection in areas of medicine, food safety and biotechnology.

  8. Climbing the Needs Pyramids

    OpenAIRE

    J. C. Lomas

    2013-01-01

    Abraham Maslow’s theory of human adult motivation is often represented by a pyramid image showing two proposals: First, the five needs stages in emergent order of hierarchical ascension and second, a percentage of the adult population suggested to occupy each needs tier. Specifically, Maslow proposed that adults would be motivated to satisfy their unfilled needs until they reached the hierarchy’s apex and achieved self...

  9. Pyramidal-Reflector Solar Heater

    Science.gov (United States)

    1982-01-01

    Motor-driven reflector compensates for seasonal changes in Sun's altitude. System has flat-plate absorbers mounted on north side of attic interior. Skylight window on south-facing roof admits Sunlight into attic, lined with mirrors that reflect light to absorbers. Reflectors are inner surfaces of a pyramid lying on its side with window at its base and absorber plates in a cross-sectional plane near its apex.

  10. Ablation of CaV2.1 Voltage-Gated Ca2+ Channels in Mouse Forebrain Generates Multiple Cognitive Impairments

    Science.gov (United States)

    Mallmann, Robert Theodor; Elgueta, Claudio; Sleman, Faten; Castonguay, Jan; Wilmes, Thomas; van den Maagdenberg, Arn; Klugbauer, Norbert

    2013-01-01

    Voltage-gated CaV2.1 (P/Q-type) Ca2+ channels located at the presynaptic membrane are known to control a multitude of Ca2+-dependent cellular processes such as neurotransmitter release and synaptic plasticity. Our knowledge about their contributions to complex cognitive functions, however, is restricted by the limited adequacy of existing transgenic CaV2.1 mouse models. Global CaV2.1 knock-out mice lacking the α1 subunit Cacna1a gene product exhibit early postnatal lethality which makes them unsuitable to analyse the relevance of CaV2.1 Ca2+ channels for complex behaviour in adult mice. Consequently we established a forebrain specific CaV2.1 knock-out model by crossing mice with a floxed Cacna1a gene with mice expressing Cre-recombinase under the control of the NEX promoter. This novel mouse model enabled us to investigate the contribution of CaV2.1 to complex cognitive functions, particularly learning and memory. Electrophysiological analysis allowed us to test the specificity of our conditional knock-out model and revealed an impaired synaptic transmission at hippocampal glutamatergic synapses. At the behavioural level, the forebrain-specific CaV2.1 knock-out resulted in deficits in spatial learning and reference memory, reduced recognition memory, increased exploratory behaviour and a strong attenuation of circadian rhythmicity. In summary, we present a novel conditional CaV2.1 knock-out model that is most suitable for analysing the in vivo functions of CaV2.1 in the adult murine forebrain. PMID:24205277

  11. MR findings of the pyramidal tract in ALS

    Energy Technology Data Exchange (ETDEWEB)

    Segawa, Fuminori (Toho Univ., Tokyo (Japan). School of Medicine)

    1993-08-01

    MR imaging using the conventional spin each technique along with diffusion weighted imaging and water-fat imaging was performed in 16 patients with amyotrophic lateral sclerosis (ALS), 20 normal subjects, and 113 controls with other neurological disorders. Diffusion weighted images in the patients with ALS and the controls disclosed a high signal band from the subcortical area to the medullary pyramids. The high signal band on the diffusion weighted images corresponded to the pyramidal tract in the anatomical atlas described by Talairach. The T1- and T2-relaxation times, proton density, diffusion coefficient and diffusion anisotropy were measured at the points where high signal bands appeared on the diffusion weighted images. The T2-weighted images revealed high signal areas on the posterior limbs of the internal capsules in all the patients with ALS, 60% of the normal subjects, and 73% of the disease controls. The T1-weighted images disclosed high signal areas on the posterior limbs in 62% of the patients with ALS, but not in any of the normal subjects and the disease controls. The proton weighted images disclosed high signal areas on the posterior limbs in all the patients with ALS and 5% of the disease controls, but not in any of the normal subjects. Analysis of diffusion weighted images revealed no significant difference between the patients with ALS and the normal subjects in diffusion coefficient and diffusion anisotropy on the posterior limbs. Measurement of MR parameters (T1- and T2-relaxation times and proton density) showed that the proton density at the posterior limbs increased in ALS. Water-fat images using the method of Dixon revealed abnormal signals in the water images. These signal abnormalities were more prominent in the internal capsule than in the medullary pyramids. Our findings confirm that there is an increase in water molecules that have normal diffusion coefficient and diffusion anisotropy values in patients with ALS. (author).

  12. Aging effect in CaLaBa{l_brace}Cu{sub 1 - x}Fe{sub x}{r_brace}{sub 3}O{sub 7 - {delta}} with 0 {<=} x {<=} 0.07 studied by Moessbauer spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Bustamante, Angel, E-mail: angelbd1@gmail.com [Universidad Nacional Mayor de San Marcos, Laboratorio de Ceramicos y Nanomateriales, Facultad de Ciencias Fisicas (Peru); Santos Valladares, Luis De Los, E-mail: ld301@cam.ac.uk [University of Cambridge, Cavendish Laboratory (United Kingdom); Flores, Jesus [Universidad Nacional Mayor de San Marcos, Laboratorio de Ceramicos y Nanomateriales, Facultad de Ciencias Fisicas (Peru); Barnes, Crispin H. W. [University of Cambridge, Cavendish Laboratory (United Kingdom); Majima, Yutaka [Tokyo Institute of Technology, Materials and Structures Laboratory (Japan)

    2011-11-15

    In this work, we study the long-term aging effect caused by Fe atoms in the superconductor CaLaBa{l_brace}Cu{sub 1 - x}Fe{sub x}{r_brace}{sub 3}O{sub 7 - {delta}} with 0 {<=} x {<=} 0.07. XRD confirms that this system has a YBCO-like structure. The critical temperature (T{sub c}) is strongly affected by aging and depends on the amount of Fe in the structure. Room temperature Moessbauer spectroscopy reveals the presence of the typical species A, B-B Prime , C and new species E Prime and F. Interestingly; A, which corresponds to the Fe{sup 3 + } atom located in the Cu(1) of the chains with spin S{sub z} = 3/2, shows a drastic reduction which means migration to the species B, B Prime and C. Species B and B Prime correspond to the Fe{sup 3 + } in the Cu(2) site forming planar quasi-octahedral and planar square pyramidal, while the C specie is a square pyramidal with O(5) respectively (spin S{sub z} = 3/2 in all these cases). Aging causes loss of superconductivity in the samples with 5 and 7% of iron content.

  13. Aging effect in CaLaBa{Cu1 − xFex}3O7 − δ with 0 ≤ x ≤ 0.07 studied by Mössbauer spectroscopy

    International Nuclear Information System (INIS)

    Bustamante, Angel; Santos Valladares, Luis De Los; Flores, Jesús; Barnes, Crispin H. W.; Majima, Yutaka

    2011-01-01

    In this work, we study the long-term aging effect caused by Fe atoms in the superconductor CaLaBa{Cu 1 − x Fe x } 3 O 7 − δ with 0 ≤ x ≤ 0.07. XRD confirms that this system has a YBCO-like structure. The critical temperature (T c ) is strongly affected by aging and depends on the amount of Fe in the structure. Room temperature Mössbauer spectroscopy reveals the presence of the typical species A, B–B′, C and new species E′ and F. Interestingly; A, which corresponds to the Fe 3 +  atom located in the Cu(1) of the chains with spin S z = 3/2, shows a drastic reduction which means migration to the species B, B′ and C. Species B and B′ correspond to the Fe 3 +  in the Cu(2) site forming planar quasi-octahedral and planar square pyramidal, while the C specie is a square pyramidal with O(5) respectively (spin S z = 3/2 in all these cases). Aging causes loss of superconductivity in the samples with 5 and 7% of iron content.

  14. Structure of the CaMKIIdelta/calmodulin complex reveals the molecular mechanism of CaMKII kinase activation.

    Directory of Open Access Journals (Sweden)

    Peter Rellos

    2010-07-01

    Full Text Available Long-term potentiation (LTP, a long-lasting enhancement in communication between neurons, is considered to be the major cellular mechanism underlying learning and memory. LTP triggers high-frequency calcium pulses that result in the activation of Calcium/Calmodulin (CaM-dependent kinase II (CaMKII. CaMKII acts as a molecular switch because it remains active for a long time after the return to basal calcium levels, which is a unique property required for CaMKII function. Here we describe the crystal structure of the human CaMKIIdelta/Ca2+/CaM complex, structures of all four human CaMKII catalytic domains in their autoinhibited states, as well as structures of human CaMKII oligomerization domains in their tetradecameric and physiological dodecameric states. All four autoinhibited human CaMKIIs were monomeric in the determined crystal structures but associated weakly in solution. In the CaMKIIdelta/Ca2+/CaM complex, the inhibitory region adopted an extended conformation and interacted with an adjacent catalytic domain positioning T287 into the active site of the interacting protomer. Comparisons with autoinhibited CaMKII structures showed that binding of calmodulin leads to the rearrangement of residues in the active site to a conformation suitable for ATP binding and to the closure of the binding groove for the autoinhibitory helix by helix alphaD. The structural data, together with biophysical interaction studies, reveals the mechanism of CaMKII activation by calmodulin and explains many of the unique regulatory properties of these two essential signaling molecules.This article can also be viewed as an enhanced version in which the text of the article is integrated with interactive 3-D representations and animated transitions. Please note that a web plugin is required to access this enhanced functionality. Instructions for the installation and use of the Web plugin are available in Text S1.

  15. Different patterns of amygdala priming differentially affect dentate gyrus plasticity and corticosterone, but not CA1 plasticity.

    Directory of Open Access Journals (Sweden)

    Rose-Marie eVouimba

    2013-05-01

    Full Text Available Stress-induced activation of the amygdala is involved in the modulation of memory processes in the hippocampus. However, stress effects on amygdala and memory remain complex. The activation of the basolateral amygdala (BLA was found to modulate plasticity in other brain areas, including the hippocampus. We previously demonstrated a differential effect of BLA priming on LTP in the CA1 and the dentate gyrus (DG. While BLA priming suppressed long term potentiation (LTP in CA1, it was found to enhance it in the DG. However, since the amygdala itself is amenable to experience-induced plasticity it is thus conceivable that when activity within the amygdala is modified this will have impact on the way the amygdala modulates activity and plasticity in other brain areas. In the current study we examined the effects of different patterns of BLA activation on the modulation of LTP in the DG and CA1, as well as on serum corticosterone (CORT. In CA1, BLA priming impaired LTP induction as was reported before. In contrast, in the DG, varying BLA stimulation intensity and frequency resulted in differential effects on LTP, ranging from no effect to strong impairment or enhancement. Varying BLA stimulation patterns resulted in also differential alterations in Serum CORT, leading to higher CORT levels being positively correlated with LTP magnitude in DG but not in CA1.The results support the notion of a differential role for the DG in aspects of memory, and add to this view the possibility that DG-associated aspects of memory will be enhanced under more emotional or stressful conditions. It is interesting to think of BLA patterns of activation and the differential levels of circulating CORT as two arms of the emotional and stress response that attempt to synchronize brain activity to best meet the challenge. It is foreseeable to think of abnormal such synchronization under extreme conditions, which would lead to the development of maladaptive behavior.

  16. Searching for possible hidden chambers in the Pyramid of the Sun

    Science.gov (United States)

    Alfaro, R.; Belmont, E.; Grabski, V.; Manzanilla, L.; Martinez-Davalos, A.; Menchaca-Rocha, A.; Moreno, M.; Sandoval, A.

    The Pyramid of the Sun, at Teotihuacan, Mexico, is being searched for possible hidden chambers, using a muon tracking technique inspired in the experiment carried out by Luis Alvarez over 30 years ago at the Chephren Pyramid, in Giza. A fortunate similarity between this monument and the Pyramid of the Sun is a tunnel, running 8 m below the base and ending close to the symmetry axis, which permits the use muon attenuation measurements. A brief account of the project, including planning, detector design, construction and simulations, as well as the current status of the project is presented

  17. The promoter of the pepper pathogen-induced membrane protein gene CaPIMP1 mediates environmental stress responses in plants.

    Science.gov (United States)

    Hong, Jeum Kyu; Hwang, Byung Kook

    2009-01-01

    The promoter of the pepper pathogen-induced membrane protein gene CaPIMP1 was analyzed by an Agrobacterium-mediated transient expression assay in tobacco leaves. Several stress-related cis-acting elements (GT-1, W-box and ABRE) are located within the CaPIMP1 promoter. In tobacco leaf tissues transiently transformed with a CaPIMP1 promoter-beta-glucuronidase (GUS) gene fusion, serially 5'-deleted CaPIMP1 promoters were differentially activated by Pseudomonas syringae pv. tabaci, ethylene, methyl jasmonate, abscisic acid, and nitric oxide. The -1,193 bp region of the CaPIMP1 gene promoter sequence exhibited full promoter activity. The -417- and -593 bp promoter regions were sufficient for GUS gene activation by ethylene and methyl jasmonate treatments, respectively. However, CaPIMP1 promoter sequences longer than -793 bp were required for promoter activation by abscisic acid and sodium nitroprusside treatments. CaPIMP1 expression was activated in pepper leaves by treatment with ethylene, methyl jasmonate, abscisic acid, beta-amino-n-butyric acid, NaCl, mechanical wounding, and low temperature, but not with salicylic acid. Overexpression of CaPIMP1 in Arabidopsis conferred hypersensitivity to mannitol, NaCl, and ABA during seed germination but not during seedling development. In contrast, transgenic plants overexpressing CaPIMP1 exhibited enhanced tolerance to oxidative stress induced by methyl viologen during germination and early seedling stages. These results suggest that CaPIMP1 expression may alter responsiveness to environmental stress, as well as to pathogen infection.

  18. Thyroid hormone activates rat liver adenosine 5,-monophosphate-activated protein kinase: relation to CaMKKb, TAK1 and LKB1 expression and energy status.

    Science.gov (United States)

    Vargas, R; Ortega, Y; Bozo, V; Andrade, M; Minuzzi, G; Cornejo, P; Fernandez, V; Videla, L A

    2013-01-01

    AMP-activated protein kinase (AMPK) is a sensor of energy status supporting cellular energy homeostasis that may represent the metabolic basis for 3,3,,5-triiodo-L-thyronine (T3) liver preconditioning. Functionally transient hyperthyroid state induced by T3 (single dose of 0.1 mg/kg) in fed rats led to upregulation of mRNA expression (RT-PCR) and protein phosphorylation (Western blot) of hepatic AMPK at 8 to 36 h after treatment. AMPK Thr 172 phosphorylation induced by T3 is associated with enhanced mRNA expression of the upstream kinases Ca2+ -calmodulin-dependent protein kinase kinase-beta (CaMKKbeta) and transforming growth-factor-beta-activated kinase-1 (TAK1), with increased protein levels of CaMKKbeta and higher TAK1 phosphorylation, without changes in those of the liver kinase B1 (LKB1) signaling pathway. Liver contents of AMP and ADP were augmented by 291 percent and 44 percent by T3 compared to control values (p less than 0.05), respectively, whereas those of ATP decreased by 64% (p less than 0.05), with no significant changes in the total content of adenine nucleotides (AMP + ADP + ATP) at 24 h after T3 administration. Consequently, hepatic ATP/ADP content ratios exhibited 64 percent diminution (p less than 0.05) and those of AMP/ATP increased by 425 percent (p less than 0.05) in T3-treated rats over controls. It is concluded that in vivoT3 administration triggers liver AMPK upregulation in association with significant enhancements in AMPK mRNA expression, AMPK phosphorylation coupled to CaMKKbeta and TAK1 activation, and in AMP/ATP ratios, which may promote enhanced AMPK activity to support T3-induced energy consuming processes such as those of liver preconditioning.

  19. The Base of the Pyramid

    NARCIS (Netherlands)

    Hutte, E.; Vermeulen, P.A.M.; Vermeulen, P.; Hutte, E.

    2014-01-01

    This chapter provides a brief background to the Base of the Pyramid (BoP) phenomenon. It begins with a discussion on what sets the BoP markets apart from more traditional markets and why companies have not identified them as a business opportunity. The chapter then provides an overview of how

  20. Evaluation of the Green Egyptian Pyramid

    Directory of Open Access Journals (Sweden)

    Mohamed Gamal Ammar

    2012-12-01

    The research concluded to the need of developing the Egyptian pyramid system through studying more global systems, in addition to the need to benefit from the Egyptian experience stock of solutions and environmental treatments in ancient architecture.

  1. Effective lifetime of minority carriers in black silicon nano-textured by cones and pyramids

    DEFF Research Database (Denmark)

    Onyshchenko, V.F.; Karachevtseva, L.A.; Lytvynenko, O.O.

    2017-01-01

    We calculated the dependence of effective lifetime of minority carriers in black silicon nano-textured by cones and pyramids on the diameter of the cone base, the side of the pyramid base, the height of cone and pyramid. The numerical calculation shows that n-type polished plate of single crystal...

  2. Effect of varying durations of pyramid exposure - an indication towards a possibility of overexposure.

    Science.gov (United States)

    Bhat, Surekha; Rao, Guruprasad; Murthy, K Dilip; Bhat, P Gopalakrishna

    2009-10-01

    Miniature replicas modeled after the Great Pyramid of Giza are believed to concentrate geoelectromagnetic energy within their cavities and hence act as antistressors in humans and animals. Although there are not many reports of adverse effects of 'overexposure' in the pyramid, subjects have claimed to feel uneasy after certain duration of staying in the pyramid. The present study was aimed to analyze the effects of prolonged pyramid exposure on plasma cortisol level, markers of oxidative damage and antioxidant defense in erythrocytes of adult female Wistar rats. Rats were divided into three groups, normal controls (NC, n=6) that were maintained under standard laboratory conditions in their home cages, pyramid exposed group-2 (PE-2, n=6) & pyramid exposed group-4 (PE-4, n=6) where the rats were housed under the pyramid for 6 hours/day for 2 weeks and 4 weeks respectively. Plasma cortisol and erythrocyte TBARS levels were significantly lower in both PE-2 and PE-4 rats and erythrocyte GSH levels and GSH-Px activity were significantly higher in them as compared to the NC rats. There was no significant difference in the results for these parameters between the PE-2 and PE-4 rats except for erythrocyte GSH-Px activity which was significantly more in the PE-2 rats than in the PE-4 rats. Although these results don't confirm any adverse effects of prolonged exposure in pyramids, they indicate a possibility of such adverse effects.

  3. GABA(B) receptor modulation of feedforward inhibition through hippocampal neurogliaform cells.

    Science.gov (United States)

    Price, Christopher J; Scott, Ricardo; Rusakov, Dmitri A; Capogna, Marco

    2008-07-02

    Feedforward inhibition of neurons is a fundamental component of information flow control in the brain. We studied the roles played by neurogliaform cells (NGFCs) of stratum lacunosum moleculare of the hippocampus in providing feedforward inhibition to CA1 pyramidal cells. We recorded from synaptically coupled pairs of anatomically identified NGFCs and CA1 pyramidal cells and found that, strikingly, a single presynaptic action potential evoked a biphasic unitary IPSC (uIPSC), consisting of two distinct components mediated by GABA(A) and GABA(B) receptors. A GABA(B) receptor-mediated unitary response has not previously been observed in hippocampal excitatory neurons. The decay of the GABA(A) receptor-mediated response was slow (time constant = 50 ms), and was tightly regulated by presynaptic GABA(B) receptors. Surprisingly, the GABA(B) receptor ligands baclofen and (2S)-3-{[(1S)-1-(3,4-dichlorophenyl)ethyl]amino-2-hydroxypropyl}(phenylmethyl)phosphinic acid (CGP55845), while affecting the NGFC-mediated uIPSCs, had no effect on action potential-evoked presynaptic Ca2+ signals monitored in individual axonal boutons of NGFCs with two-photon microscopy. In contrast, baclofen clearly depressed presynaptic Ca2+ transients in non-NGF interneurons. Changes in extracellular Ca2+ concentration that mimicked the effects of baclofen or CGP55845 on uIPSCs significantly altered presynaptic Ca2+ transients. Electrophysiological data suggest that GABA(B) receptors expressed by NGFCs contribute to the dynamic control of the excitatory input to CA1 pyramidal neurons from the temporoammonic path. The NGFC-CA1 pyramidal cell connection therefore provides a unique and subtle mechanism to shape the integration time domain for signals arriving via a major excitatory input to CA1 pyramidal cells.

  4. CaV 3.1 and CaV 3.3 account for T-type Ca2+ current in GH3 cells

    Directory of Open Access Journals (Sweden)

    M.A. Mudado

    2004-06-01

    Full Text Available T-type Ca2+ channels are important for cell signaling by a variety of cells. We report here the electrophysiological and molecular characteristics of the whole-cell Ca2+ current in GH3 clonal pituitary cells. The current inactivation at 0 mV was described by a single exponential function with a time constant of 18.32 ± 1.87 ms (N = 16. The I-V relationship measured with Ca2+ as a charge carrier was shifted to the left when we applied a conditioning pre-pulse of up to -120 mV, indicating that a low voltage-activated current may be present in GH3 cells. Transient currents were first activated at -50 mV and peaked around -20 mV. The half-maximal voltage activation and the slope factors for the two conditions are -35.02 ± 2.4 and 6.7 ± 0.3 mV (pre-pulse of -120 mV, N = 15, and -27.0 ± 0.97 and 7.5 ± 0.7 mV (pre-pulse of -40 mV, N = 9. The 8-mV shift in the activation mid-point was statistically significant (P < 0.05. The tail currents decayed bi-exponentially suggesting two different T-type Ca2+ channel populations. RT-PCR revealed the presence of a1G (CaV3.1 and a1I (CaV3.3 T-type Ca2+ channel mRNA transcripts.

  5. Ancient Egyptian chronology and the astronomical orientation of pyramids

    Science.gov (United States)

    Spence, Kate

    2000-11-01

    The ancient Egyptian pyramids at Giza have never been accurately dated, although we know that they were built approximately around the middle of the third millennium BC. The chronologies of this period have been reconstructed from surviving lists of kings and the lengths of their reigns, but the lists are rare, seldom complete and contain known inconsistencies and errors. As a result, the existing chronologies for that period (the Old Kingdom) can be considered accurate only to about +/-100 years, a figure that radiocarbon dating cannot at present improve. Here I use trends in the orientation of Old Kingdom pyramids to demonstrate that the Egyptians aligned them to north by using the simultaneous transit of two circumpolar stars. Modelling the precession of these stars yields a date for the start of construction of the Great Pyramid that is accurate to +/-5 yr, thereby providing an anchor for the Old Kingdom chronologies.

  6. Difference in transient ischemia-induced neuronal damage and glucose transporter-1 immunoreactivity in the hippocampus between adult and young gerbils

    Directory of Open Access Journals (Sweden)

    Seung Min Park

    2016-05-01

    Full Text Available Objective(s: The alteration of glucose transporters is closely related with the pathogenesis of brain edema. We compared neuronal damage/death in the hippocampus between adult and young gerbils following transient cerebral ischemia/reperfusion and changes of glucose transporter-1(GLUT-1-immunoreactive microvessels in their ischemic hippocampal CA1 region. Materials and Methods: Transient cerebral ischemia was developed by 5-min occlusion of both common carotid arteries. Neuronal damage was examined by cresyl violet staining, NeuN immunohistochemistry and Fluoro-Jade B histofluorescence staining and changes in GLUT-1 expression was carried out by immunohistochemistry. Results: About 90% of pyramidal neurons only in the adult CA1 region were damaged after ischemia/reperfusion; in the young, about 53 % of pyramidal neurons were damaged from 7 days after ischemia/reperfusion. The density of GLUT-1-immunoreactive microvessels was significantly higher in the young sham-group than that in the adult sham-group. In the ischemia-operated-groups, the density of GLUT-1-immunoreactive microvessels was significantly decreased in the adult and young at 1 and 4 days post-ischemia, respectively, thereafter, the density of GLUT-1-immunoreactive microvessels was gradually increased in both groups after ischemia/reperfusion. Conclusion: CA1 pyramidal neurons of the young gerbil were damaged much later than that in the adult and that GLUT-1-immunoreactive microvessels were significantly decreased later in the young. These data indicate that GLUT-1 might differently contribute to neuronal damage according to age after ischemic insults.

  7. Cannabinoids disrupt memory encoding by functionally isolating hippocampal CA1 from CA3.

    Directory of Open Access Journals (Sweden)

    Roman A Sandler

    2017-07-01

    Full Text Available Much of the research on cannabinoids (CBs has focused on their effects at the molecular and synaptic level. However, the effects of CBs on the dynamics of neural circuits remains poorly understood. This study aims to disentangle the effects of CBs on the functional dynamics of the hippocampal Schaffer collateral synapse by using data-driven nonparametric modeling. Multi-unit activity was recorded from rats doing an working memory task in control sessions and under the influence of exogenously administered tetrahydrocannabinol (THC, the primary CB found in marijuana. It was found that THC left firing rate unaltered and only slightly reduced theta oscillations. Multivariate autoregressive models, estimated from spontaneous spiking activity, were then used to describe the dynamical transformation from CA3 to CA1. They revealed that THC served to functionally isolate CA1 from CA3 by reducing feedforward excitation and theta information flow. The functional isolation was compensated by increased feedback excitation within CA1, thus leading to unaltered firing rates. Finally, both of these effects were shown to be correlated with memory impairments in the working memory task. By elucidating the circuit mechanisms of CBs, these results help close the gap in knowledge between the cellular and behavioral effects of CBs.

  8. Modulators of cytoskeletal reorganization in CA1 hippocampal neurons show increased expression in patients at mid-stage Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Patricia F Kao

    2010-10-01

    Full Text Available During the progression of Alzheimer's disease (AD, hippocampal neurons undergo cytoskeletal reorganization, resulting in degenerative as well as regenerative changes. As neurofibrillary tangles form and dystrophic neurites appear, sprouting neuronal processes with growth cones emerge. Actin and tubulin are indispensable for normal neurite development and regenerative responses to injury and neurodegenerative stimuli. We have previously shown that actin capping protein beta2 subunit, Capzb2, binds tubulin and, in the presence of tau, affects microtubule polymerization necessary for neurite outgrowth and normal growth cone morphology. Accordingly, Capzb2 silencing in hippocampal neurons resulted in short, dystrophic neurites, seen in neurodegenerative diseases including AD. Here we demonstrate the statistically significant increase in the Capzb2 expression in the postmortem hippocampi in persons at mid-stage, Braak and Braak stage (BB III-IV, non-familial AD in comparison to controls. The dynamics of Capzb2 expression in progressive AD stages cannot be attributed to reactive astrocytosis. Moreover, the increased expression of Capzb2 mRNA in CA1 pyramidal neurons in AD BB III-IV is accompanied by an increased mRNA expression of brain derived neurotrophic factor (BDNF receptor tyrosine kinase B (TrkB, mediator of synaptic plasticity in hippocampal neurons. Thus, the up-regulation of Capzb2 and TrkB may reflect cytoskeletal reorganization and/or regenerative response occurring in hippocampal CA1 neurons at a specific stage of AD progression.

  9. Introduction of a pyramid guiding process for general musculoskeletal physical rehabilitation

    Directory of Open Access Journals (Sweden)

    Stark Timothy W

    2006-06-01

    Full Text Available Abstract Successful instruction of a complicated subject as Physical Rehabilitation demands organization. To understand principles and processes of such a field demands a hierarchy of steps to achieve the intended outcome. This paper is intended to be an introduction to a proposed pyramid scheme of general physical rehabilitation principles. The purpose of the pyramid scheme is to allow for a greater understanding for the student and patient. As the respected Food Guide Pyramid accomplishes, the student will further appreciate and apply supported physical rehabilitation principles and the patient will understand that there is a progressive method to their functional healing process.

  10. Distinctive transcriptome alterations of prefrontal pyramidal neurons in schizophrenia and schizoaffective disorder.

    Science.gov (United States)

    Arion, D; Corradi, J P; Tang, S; Datta, D; Boothe, F; He, A; Cacace, A M; Zaczek, R; Albright, C F; Tseng, G; Lewis, D A

    2015-11-01

    Schizophrenia is associated with alterations in working memory that reflect dysfunction of dorsolateral prefrontal cortex (DLPFC) circuitry. Working memory depends on the activity of excitatory pyramidal cells in DLPFC layer 3 and, to a lesser extent, in layer 5. Although many studies have profiled gene expression in DLPFC gray matter in schizophrenia, little is known about cell-type-specific transcript expression in these two populations of pyramidal cells. We hypothesized that interrogating gene expression, specifically in DLPFC layer 3 or 5 pyramidal cells, would reveal new and/or more robust schizophrenia-associated differences that would provide new insights into the nature of pyramidal cell dysfunction in the illness. We also sought to determine the impact of other variables, such as a diagnosis of schizoaffective disorder or medication use at the time of death, on the patterns of gene expression in pyramidal neurons. Individual pyramidal cells in DLPFC layers 3 or 5 were captured by laser microdissection from 36 subjects with schizophrenia or schizoaffective disorder and matched normal comparison subjects. The mRNA from cell collections was subjected to transcriptome profiling by microarray followed by quantitative PCR validation. Expression of genes involved in mitochondrial (MT) or ubiquitin-proteasome system (UPS) functions were markedly downregulated in the patient group (P-values for MT-related and UPS-related pathways were schizoaffective disorder subjects (diagnosis of schizoaffective disorder was the most significant covariate, Pschizoaffective disorder, providing a potential molecular-cellular basis of differences in clinical phenotypes.

  11. Co_3V_2O_8 Hexagonal Pyramid with Tunable Inner Structure as High Performance Anode Materials for Lithium Ion Battery

    International Nuclear Information System (INIS)

    Zhang, Qiang; Pei, Jian; Chen, Gang; Bie, Changfeng; Chen, Dahong; Jiao, Yang; Rao, Jiancun

    2017-01-01

    Co_3V_2O_8 hexagonal pyramid was successfully fabricated via a simple hydrothermal process and subsequent heat treatment. The inner structure of the hexagonal pyramid was further adjusted by controlling the size of Co_7V_4O_1_6(OH)_2(H_2O) precursors. Hierarchical Co_3V_2O_8 hexagonal pyramid with height of 1 μm were orderly constructed from 60–80 nm inter-connected particles, showing numerous interval voids. Benefiting from its unique structure, the as-prepared sample showed higher electrochemical performance as an anode material for lithium-ion batteries than that of another bulk sample with height of 5 μm and adhesive inner structure. When tested at a current density of 500 mA g"−"1, the hierarchical Co_3V_2O_8 hexagonal pyramid exhibited good rate capacity, high cycling stability, and excellent discharge capacity up to 712 mA h g"−"1, making it promising electrode materials for lithium-ion batteries.

  12. Discovery of a big void in Khufu's Pyramid by observation of cosmic-ray muons.

    Science.gov (United States)

    Morishima, Kunihiro; Kuno, Mitsuaki; Nishio, Akira; Kitagawa, Nobuko; Manabe, Yuta; Moto, Masaki; Takasaki, Fumihiko; Fujii, Hirofumi; Satoh, Kotaro; Kodama, Hideyo; Hayashi, Kohei; Odaka, Shigeru; Procureur, Sébastien; Attié, David; Bouteille, Simon; Calvet, Denis; Filosa, Christopher; Magnier, Patrick; Mandjavidze, Irakli; Riallot, Marc; Marini, Benoit; Gable, Pierre; Date, Yoshikatsu; Sugiura, Makiko; Elshayeb, Yasser; Elnady, Tamer; Ezzy, Mustapha; Guerriero, Emmanuel; Steiger, Vincent; Serikoff, Nicolas; Mouret, Jean-Baptiste; Charlès, Bernard; Helal, Hany; Tayoubi, Mehdi

    2017-12-21

    The Great Pyramid, or Khufu's Pyramid, was built on the Giza plateau in Egypt during the fourth dynasty by the pharaoh Khufu (Cheops), who reigned from 2509 bc to 2483 bc. Despite being one of the oldest and largest monuments on Earth, there is no consensus about how it was built. To understand its internal structure better, we imaged the pyramid using muons, which are by-products of cosmic rays that are only partially absorbed by stone. The resulting cosmic-ray muon radiography allows us to visualize the known and any unknown voids in the pyramid in a non-invasive way. Here we report the discovery of a large void (with a cross-section similar to that of the Grand Gallery and a minimum length of 30 metres) situated above the Grand Gallery. This constitutes the first major inner structure found in the Great Pyramid since the nineteenth century. The void, named ScanPyramids' Big Void, was first observed with nuclear emulsion films installed in the Queen's chamber, then confirmed with scintillator hodoscopes set up in the same chamber and finally re-confirmed with gas detectors outside the pyramid. This large void has therefore been detected with high confidence by three different muon detection technologies and three independent analyses. These results constitute a breakthrough for the understanding of the internal structure of Khufu's Pyramid. Although there is currently no information about the intended purpose of this void, these findings show how modern particle physics can shed new light on the world's archaeological heritage.

  13. Transport activity of the sodium bicarbonate cotransporter NBCe1 is enhanced by different isoforms of carbonic anhydrase.

    Directory of Open Access Journals (Sweden)

    Christina Schueler

    Full Text Available Transport metabolons have been discussed between carbonic anhydrase II (CAII and several membrane transporters. We have now studied different CA isoforms, expressed in Xenopus oocytes alone and together with the electrogenic sodium bicarbonate cotransporter 1 (NBCe1, to determine their catalytic activity and their ability to enhance NBCe1 transport activity. pH measurements in intact oocytes indicated similar activity of CAI, CAII and CAIII, while in vitro CAIII had no measurable activity and CAI only 30% of the activity of CAII. All three CA isoforms increased transport activity of NBCe1, as measured by the transport current and the rate of intracellular sodium rise in oocytes. Two CAII mutants, altered in their intramolecular proton pathway, CAII-H64A and CAII-Y7F, showed significant catalytic activity and also enhanced NBCe1 transport activity. The effect of CAI, CAII, and CAII mutants on NBCe1 activity could be reversed by blocking CA activity with ethoxyzolamide (EZA, 10 µM, while the effect of the less EZA-sensitive CAIII was not reversed. Our results indicate that different CA isoforms and mutants, even if they show little enzymatic activity in vitro, may display significant catalytic activity in intact cells, and that the ability of CA to enhance NBCe1 transport appears to depend primarily on its catalytic activity.

  14. Cadmium induces Ca2+ mediated, calpain-1/caspase-3-dependent apoptosis in primary cultured rat proximal tubular cells.

    Science.gov (United States)

    Wang, Hong; Zhai, Nianhui; Chen, Ying; Xu, Haibin; Huang, Kehe

    2017-07-01

    Calcium, as a ubiquitous second messenger, governs a large array of cellular processes and is necessary for cell survival. More recently, it was observed that the cytosolic Ca 2+ concentration ([Ca 2+ ] c ) elevation could induce apoptosis in primary cultured rat proximal tubular (rPT) cells exposed to cadmium (Cd), but the concrete mechanism is still unclear. This study was designed to investigate the signal pathway involved in [Ca 2+ ] c elevation-mediated apoptosis. The results confirmed the elevation of [Ca 2+ ] c by confocal microscopy and enhancement of the apoptosis by Hoechst 33258 staining and flow cytometer when rPT cells were exposed to Cd for 12h. Then we demonstrated that Cd enhanced the protein levels of active calpain-1 and caspase-3 in rPT cells. Pretreatment with a cytosolic Ca 2+ chelator, 1,2-Bis (2-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid acetoxymethyl ester (BAPTA-AM), markedly blocked the up-regulation of active calpain-1 and caspase-3 and inhibited the apoptosis induced by Cd. Further, rPT cells were pretreated with a cell-permeable selective calpain-1 inhibitor, 3-(4-iodophenyl)-2-mercapto-(Z)-2-propenoic acid (PD150606) and caspase-3 inhibitor, N-Acetyl-Asp-Glu-Val-Asp-CHO (Ac-DEVD-CHO), respectively. PD150606 significantly attenuated the up-regulation of active caspase-3 and the apoptosis induced by Cd. As expected, inhibition of active caspase-3 by Ac-DEVD-CHO decreased the apoptosis induced by Cd. Taken together, it could be concluded that [Ca 2+ ] c elevation did act as a pro-apoptotic signal in Cd-induced cytotoxicity of rPT cells, triggered calpain-1 and caspase-3 activation in turn, and induced apoptosis of rPT cells. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Building online genomics applications using BioPyramid.

    Science.gov (United States)

    Stephenson, Liam; Wakeham, Yoshua; Seidenman, Nick; Choi, Jarny

    2018-03-29

    BioPyramid is a python package, which serves as a scaffold for building an online application for the exploration of gene expression data. It is designed for bioinformaticians wishing to quickly share transformed data and interactive analyses with collaborators. Current R-based tools similarly address the need to quickly share "omics"-data in an exploratory format, but these are generally small-scale, single-dataset solutions. Biopyramid is written in python pyramid framework and scalable to address longer-term or more complex projects. It contains a number of components designed to reduce the time and effort in building such an application from scratch, including gene annotation, dataset models and visualisation tools. Freely available at http://github.com/jarny/biopyramid. Implemented in python and javascript. jarnyc@unimelb.edu.au.

  16. The Differences between Multilevel Marketing and the Financial Pyramids or “Pyramid Scheme”

    Directory of Open Access Journals (Sweden)

    Vanessa Braga Santos

    2017-06-01

    Full Text Available This research aims to analyze and understand the difference between the concept of Multilevel Marketing and the Financial Pyramids. The main objective of this work is to clarify the differences between these two business models that are growing worldwide and also present concepts that show the success of professionals in this kind of new business model. Multilevel Marketing shows a sustainable system, a direct selling business that includes recruiting distributors with a profit share and also by recruiting new members. In the Financial Pyramid concept, the problem is that business support is the network itself, and often there are no products to be commercialized, so this model is unsustainable and considered as an illegal business in several countries, including Brazil. Within this approach, a case study was conducted with one of the largest Multilevel Marketing companies in the world, Mary Kay. We conducted a direct interview with one of Mary Kay Independent Sales Directors from the city of Piracicaba, held in October 2016, and collected data surveys from the internet. The markets today are based on moving products, so we concluded that Multilevel Marketing is a great business opportunity to make an extra income by marketing services and products.

  17. Technique Based on Image Pyramid and Bayes Rule for Noise Reduction in Unsupervised Change Detection

    Institute of Scientific and Technical Information of China (English)

    LI Zhi-qiang; HUO hong; FANG Tao; ZHU Ju-lian; GE Wei-li

    2009-01-01

    In this paper, a technique based on image pyramid and Bayes rule for reducing noise effects in unsupervised change detection is proposed. By using Gaussian pyramid to process two multitemporal images respectively, two image pyramids are constructed. The difference pyramid images are obtained by point-by-point subtraction between the same level images of the two image pyramids. By resizing all difference pyramid images to the size of the original multitemporal image and then making product operator among them, a map being similar to the difference image is obtained. The difference image is generated by point-by-point subtraction between the two multitemporal images directly. At last, the Bayes rule is used to distinguish the changed pixels. Both synthetic and real data sets are used to evaluate the performance of the proposed technique. Experimental results show that the map from the proposed technique is more robust to noise than the difference image.

  18. On the dynamic mechanical property and deformation mechanism of as-extruded Mg-Sn-Ca alloys under tension

    International Nuclear Information System (INIS)

    Huang, Qiuyan; Pan, Hucheng; Tang, Aitao; Ren, Yuping; Song, Bo; Qin, Gaowu; Zhang, Mingxing; Pan, Fusheng

    2016-01-01

    To further understand the deformation mechanism of magnesium alloys and expand their applications under dynamic conditions, the newly developed Mg-2Sn-1Ca alloy (TX21) is selected as the representative sample and tested under wide loading rate ranging from quasi-static to dynamic level (10"−"3–500/s). Both ultimate tensile strength and elongation of the as-extruded TX21 alloys increase with strain rate. Although twinning is accompanied due to the enhanced activity at higher strain rate, the preferential activation of dislocations is readily clarified and confirmed as the dominant deformation modes. Active interactions of pyramidal dislocations result in the higher strain hardening ability and could be correlated to the obviously positive strain-rate sensitivity for mechanical properties. Moreover, it is observed that the larger grain size and higher content of solute atoms dissolved in matrix would lead to the more active dislocations and twinning formations. The present results would provide insight into further understanding the deformation mechanism under dynamic rate loading and designing Mg alloy suitable for impact conditions.

  19. On the dynamic mechanical property and deformation mechanism of as-extruded Mg-Sn-Ca alloys under tension

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Qiuyan [National Engineering Research Center for Magnesium Alloys, Chongqing University, Chongqing 400044 (China); Pan, Hucheng [Key Laboratory for Anisotropy and Texture of Materials (Ministry of Education), Northeastern University, Shenyang 110819 (China); Tang, Aitao, E-mail: tat@cqu.edu.cn [National Engineering Research Center for Magnesium Alloys, Chongqing University, Chongqing 400044 (China); Ren, Yuping [Key Laboratory for Anisotropy and Texture of Materials (Ministry of Education), Northeastern University, Shenyang 110819 (China); Song, Bo [Faculty of Materials and Energy, Southwest University, Chongqing 400715 (China); Qin, Gaowu, E-mail: qingw@smm.neu.edu.cn [Key Laboratory for Anisotropy and Texture of Materials (Ministry of Education), Northeastern University, Shenyang 110819 (China); Zhang, Mingxing [School of Mechanical and Mining Engineering, University of Queensland, St Lucia, QLD 4072 (Australia); Pan, Fusheng [National Engineering Research Center for Magnesium Alloys, Chongqing University, Chongqing 400044 (China)

    2016-05-10

    To further understand the deformation mechanism of magnesium alloys and expand their applications under dynamic conditions, the newly developed Mg-2Sn-1Ca alloy (TX21) is selected as the representative sample and tested under wide loading rate ranging from quasi-static to dynamic level (10{sup −3}–500/s). Both ultimate tensile strength and elongation of the as-extruded TX21 alloys increase with strain rate. Although twinning is accompanied due to the enhanced activity at higher strain rate, the preferential activation of dislocations is readily clarified and confirmed as the dominant deformation modes. Active interactions of pyramidal dislocations result in the higher strain hardening ability and could be correlated to the obviously positive strain-rate sensitivity for mechanical properties. Moreover, it is observed that the larger grain size and higher content of solute atoms dissolved in matrix would lead to the more active dislocations and twinning formations. The present results would provide insight into further understanding the deformation mechanism under dynamic rate loading and designing Mg alloy suitable for impact conditions.

  20. P2X7 receptor activation ameliorates CA3 neuronal damage via a tumor necrosis factor-α-mediated pathway in the rat hippocampus following status epilepticus

    Directory of Open Access Journals (Sweden)

    Ryu Hea Jin

    2011-06-01

    Full Text Available Abstract Background The release of tumor necrosis factor-α (TNF-α appears depend on the P2X7 receptor, a purinergic receptor. In the present study, we addressed the question of whether P2X7 receptor-mediated TNF-α regulation is involved in pathogenesis and outcome of status epilepticus (SE. Methods SE was induced by pilocarpine in rats that were intracerebroventricularly infused with saline-, 2',3'-O-(4-benzoylbenzoyl-adenosine 5'-triphosphate (BzATP, adenosine 5'-triphosphate-2',3'-dialdehyde (OxATP, A-438079, or A-740003 prior to SE induction. Thereafter, we performed Fluoro-Jade B staining and immunohistochemical studies for TNF-α and NF-κB subunit phosphorylations. Results Following SE, P2X7 receptor agonist (BzATP infusion increased TNF-α immunoreactivity in dentate granule cells as compared with that in saline-infused animals. In addition, TNF-α immunoreactivity was readily apparent in the mossy fibers, while TNF-α immunoreactivity in CA1-3 pyramidal cells was unaltered. However, P2X7 receptor antagonist (OxATP-, A-438079, and A-740003 infusion reduced SE-induced TNF-α expression in dentate granule cells. In the CA3 region, BzATP infusion attenuated SE-induced neuronal damage, accompanied by enhancement of p65-Ser276 and p65-Ser311 NF-κB subunit phosphorylations. In contrast, OxATP-, A-438079, and A-740003 infusions increased SE-induced neuronal death. Soluble TNF p55 receptor (sTNFp55R, and cotreatment with BzATP and sTNFp55R infusion also increased SE-induced neuronal damage in CA3 region. However, OxATP-, sTNFp55R or BzATP+sTNFp55R infusions could not exacerbate SE-induced neuronal damages in the dentate gyrus and the CA1 region, as compared to BzATP infusion. Conclusions These findings suggest that TNF-α induction by P2X7 receptor activation may ameliorate SE-induced CA3 neuronal damage via enhancing NF-κB p65-Ser276 and p65-Ser311 phosphorylations.

  1. Pyramidal anchor stone from Baga waters of Goa, west coast of India

    Digital Repository Service at National Institute of Oceanography (India)

    Tripati, S.

    . Pyramidal anchor stones have an apex hole which goes up to the round hole, however Goa anchor stone has no such perforation, but, instead has a rectangular cutting on the apex. The anchor stone is compared with Greek pyramidal anchor stones, and probably...

  2. Enhanced dielectric and ferroelectric characteristics in Ca-modified BaTiO3 ceramics

    Directory of Open Access Journals (Sweden)

    Xiao Na Zhu

    2013-08-01

    Full Text Available Synergic modification of BaTiO3 ceramics was investigated by Ca-substitution, and the superior dielectric and ferroelectric properties were determined together with the structure evolution. X-ray diffraction (XRD analysis demonstrated a large solubility limit above x = 0.25 in Ba1−xCaxTiO3 solid solution where the fine grain structure was observed with increasing x. Room temperature dielectric constant as high as 1655 was achieved in the present ceramics together with the significantly reduced dielectric loss of 0.013 (x = 0.20 at 100 kHz, where the Curie temperature kept almost a constant while other two transition temperatures decreased continuously with increasing x. More importantly, the remanent polarization Pr and dielectric strength Eb were significantly enhanced by Ca-substitution, and the best Pr (11.34 μC/cm2 and the highest dielectric strength Eb (75 kV/cm were acquired at x = 0.25. The present ceramics should be very desirable for the applications such as high density energy storage devices.

  3. Ventromedial prefrontal cortex pyramidal cells have a temporal dynamic role in recall and extinction of cocaine-associated memory.

    Science.gov (United States)

    Van den Oever, Michel C; Rotaru, Diana C; Heinsbroek, Jasper A; Gouwenberg, Yvonne; Deisseroth, Karl; Stuber, Garret D; Mansvelder, Huibert D; Smit, August B

    2013-11-13

    In addicts, associative memories related to the rewarding effects of drugs of abuse can evoke powerful craving and drug seeking urges, but effective treatment to suppress these memories is not available. Detailed insight into the neural circuitry that mediates expression of drug-associated memory is therefore of crucial importance. Substantial evidence from rodent models of addictive behavior points to the involvement of the ventromedial prefrontal cortex (vmPFC) in conditioned drug seeking, but specific knowledge of the temporal role of vmPFC pyramidal cells is lacking. To this end, we used an optogenetics approach to probe the involvement of vmPFC pyramidal cells in expression of a recent and remote conditioned cocaine memory. In mice, we expressed Channelrhodopsin-2 (ChR2) or Halorhodopsin (eNpHR3.0) in pyramidal cells of the vmPFC and studied the effect of activation or inhibition of these cells during expression of a cocaine-contextual memory on days 1-2 (recent) and ∼3 weeks (remote) after conditioning. Whereas optical activation of pyramidal cells facilitated extinction of remote memory, without affecting recent memory, inhibition of pyramidal cells acutely impaired recall of recent cocaine memory, without affecting recall of remote memory. In addition, we found that silencing pyramidal cells blocked extinction learning at the remote memory time-point. We provide causal evidence of a critical time-dependent switch in the contribution of vmPFC pyramidal cells to recall and extinction of cocaine-associated memory, indicating that the circuitry that controls expression of cocaine memories reorganizes over time.

  4. Effect of Nd substitution for Ca on crystal structure, optical and magnetic properties of multiferroic Bi0.9Ca0.1FeO3

    International Nuclear Information System (INIS)

    Quan, Chuye; Ma, Yuhui; Han, Yumin; Tang, Xingxing; Lu, Mengjia; Mao, Weiwei; Zhang, Jian; Yang, Jianping; Li, Xing’ao

    2015-01-01

    Highlights: • Crystal structure of doped samples transform to two phase coexistence. • The crystal size decreased to ∼50 nm after doping. • Ultraviolet absorption peak demonstrates apparent blue shift for doped sample. • The ratio of Fe 2+ increased by merging Nd. • Ca, Nd co-doped can promote the ferromagnetism obviously. - Abstract: Pure and co-doped BiFeO 3 (Ca, Nd) nanoparticles with diameter in the range of 50–250 nm were synthesized through a sol–gel method. X-ray diffraction (XRD) and Raman results show that Bi-site co-doped with Ca, Nd could result in a transition of crystal structure (from single phase rhombohedral (R3c) to two phase coexistence). An apparent blue shift can be observed in the co-doped samples along with a decrease of the direct optical band gap. Moreover, the leakage current was decreased due to the introduction of nonvolatile Ca and Nd at Bi 3+ site. Analysis of MPMS-VSM magnetic hysteresis data reveals a further enhancement in magnetism in the Nd doped Bi 0.9 Ca 0.1 FeO 3, which is further explained by XPS characterization

  5. High-pressure synthesis and structural, physical properties of CaIr1-xPtxO3 and CaIr1-xRhxO3

    Science.gov (United States)

    Hirai, S.; Bromiley, G. D.; Klemme, S.; Irifune, T.; Ohfuji, H.; Attfield, P.; Nishiyama, N.

    2010-12-01

    in terms of materials science applications. To our knowledge, this will be the first report on structural, magnetic and charge-transport properties of B-site substituted solid solutions of post-perovskite oxides with 4d/5d transition metals. High-quality polycrystalline samples of CaIr1-xPtxO3 and CaIr1-xRhxO3 have been obtained at high pressures, and structural, magnetic and charge-transport properties of the compounds will be reported. ODF analysis reveals that solutions of CaIrO3, CaPtO3 and CaRhO3 exhibit similar grain growth features to the mother compound, although growth in [0 1 0] plays a more dominant role than the growth in [0 0 1] for the solid solutions. CaIrO3 is a characteristic hard magnet suitable for applications such as magnetic recording, with TN = 108K. A new phase of CaIr1-xPtxO3 synthesized at a high P/T condition has Raman modes which resemble those of CaIrO3 perovskite, suggesting this phase has a perovskite structure.The instability of the perovskite phase of CaIr1-xPtxO3 reveals why the post-perovskite to peovskite phase transition has not been observed for CaPtO3 unlike the case for CaIrO3, CaRhO3 and CaRuO3.

  6. CO2 laser irradiation enhances CaF2 formation and inhibits lesion progression on demineralized dental enamel-in vitro study.

    Science.gov (United States)

    Zancopé, Bruna R; Rodrigues, Lívia P; Parisotto, Thais M; Steiner-Oliveira, Carolina; Rodrigues, Lidiany K A; Nobre-dos-Santos, Marinês

    2016-04-01

    This study evaluated if Carbon dioxide (CO2) (λ 10.6 μm) laser irradiation combined with acidulated phosphate fluoride gel application (APF gel) enhances "CaF2" uptake by demineralized enamel specimens (DES) and inhibits enamel lesion progression. Thus, two studies were conducted and DES were subjected to APF gel combined or not with CO2 laser irradiation (11.3 or 20.0 J/cm(2), 0.4 or 0.7 W) performed before, during, or after APF gel application. In study 1, 165 DES were allocated to 11 groups. Fluoride as "CaF2 like material" formed on enamel was determined in 100 DES (n = 10/group), and the surface morphologies of 50 specimens were evaluated by scanning electron microscopy (SEM) before and after "CaF2" extraction. In study 2, 165 DES (11 groups, n = 15), subjected to the same treatments as in study 1, were further subjected to a pH-cycling model to simulate a high cariogenic challenge. The progression of demineralization in DES was evaluated by cross-sectional microhardness and polarized light microscopy analyses. Laser at 11.3 J/cm(2) applied during APF gel application increased "CaF2" uptake on enamel surface. Laser irradiation and APF gel alone arrested the lesion progression compared with the control (p enamel surface and a synergistic effect was found. However, regarding the inhibition of caries lesion progression, no synergistic effect could be demonstrated. In conclusion, the results have shown that irradiation with specific laser parameters significantly enhanced CaF2 uptake by demineralized enamel and inhibited lesion progression.

  7. Elementary properties of CaV1.3 Ca2+ channels expressed in mouse cochlear inner hair cells

    Science.gov (United States)

    Zampini, Valeria; Johnson, Stuart L; Franz, Christoph; Lawrence, Neil D; Münkner, Stefan; Engel, Jutta; Knipper, Marlies; Magistretti, Jacopo; Masetto, Sergio; Marcotti, Walter

    2010-01-01

    Mammalian cochlear inner hair cells (IHCs) are specialized to process developmental signals during immature stages and sound stimuli in adult animals. These signals are conveyed onto auditory afferent nerve fibres. Neurotransmitter release at IHC ribbon synapses is controlled by L-type CaV1.3 Ca2+ channels, the biophysics of which are still unknown in native mammalian cells. We have investigated the localization and elementary properties of Ca2+ channels in immature mouse IHCs under near-physiological recording conditions. CaV1.3 Ca2+ channels at the cell pre-synaptic site co-localize with about half of the total number of ribbons present in immature IHCs. These channels activated at about −70 mV, showed a relatively short first latency and weak inactivation, which would allow IHCs to generate and accurately encode spontaneous Ca2+ action potential activity characteristic of these immature cells. The CaV1.3 Ca2+ channels showed a very low open probability (about 0.15 at −20 mV: near the peak of an action potential). Comparison of elementary and macroscopic Ca2+ currents indicated that very few Ca2+ channels are associated with each docked vesicle at IHC ribbon synapses. Finally, we found that the open probability of Ca2+ channels, but not their opening time, was voltage dependent. This finding provides a possible correlation between presynaptic Ca2+ channel properties and the characteristic frequency/amplitude of EPSCs in auditory afferent fibres. PMID:19917569

  8. Elementary properties of CaV1.3 Ca(2+) channels expressed in mouse cochlear inner hair cells.

    Science.gov (United States)

    Zampini, Valeria; Johnson, Stuart L; Franz, Christoph; Lawrence, Neil D; Münkner, Stefan; Engel, Jutta; Knipper, Marlies; Magistretti, Jacopo; Masetto, Sergio; Marcotti, Walter

    2010-01-01

    Mammalian cochlear inner hair cells (IHCs) are specialized to process developmental signals during immature stages and sound stimuli in adult animals. These signals are conveyed onto auditory afferent nerve fibres. Neurotransmitter release at IHC ribbon synapses is controlled by L-type Ca(V)1.3 Ca(2+) channels, the biophysics of which are still unknown in native mammalian cells. We have investigated the localization and elementary properties of Ca(2+) channels in immature mouse IHCs under near-physiological recording conditions. Ca(V)1.3 Ca(2+) channels at the cell pre-synaptic site co-localize with about half of the total number of ribbons present in immature IHCs. These channels activated at about 70 mV, showed a relatively short first latency and weak inactivation, which would allow IHCs to generate and accurately encode spontaneous Ca(2+) action potential activity characteristic of these immature cells. The Ca(V)1.3 Ca(2+) channels showed a very low open probability (about 0.15 at 20 mV: near the peak of an action potential). Comparison of elementary and macroscopic Ca(2+) currents indicated that very few Ca(2+) channels are associated with each docked vesicle at IHC ribbon synapses. Finally, we found that the open probability of Ca(2+) channels, but not their opening time, was voltage dependent. This finding provides a possible correlation between presynaptic Ca(2+) channel properties and the characteristic frequency/amplitude of EPSCs in auditory afferent fibres.

  9. CaV1.3 L-type Ca2+ channels modulate depression-like behaviour in mice independent of deaf phenotype.

    Science.gov (United States)

    Busquet, Perrine; Nguyen, Ngoc Khoi; Schmid, Eduard; Tanimoto, Naoyuki; Seeliger, Mathias W; Ben-Yosef, Tamar; Mizuno, Fengxia; Akopian, Abram; Striessnig, Jörg; Singewald, Nicolas

    2010-05-01

    Mounting evidence suggests that voltage-gated L-type Ca2+ channels can modulate affective behaviour. We therefore explored the role of CaV1.3 L-type Ca2+ channels in depression- and anxiety-like behaviours using CaV1.3-deficient mice (CaV1.3-/-). We showed that CaV1.3-/- mice displayed less immobility in the forced swim test as well as in the tail suspension test, indicating an antidepressant-like phenotype. Locomotor activity in the home cage or a novel open-field test was not influenced. In the elevated plus maze (EPM), CaV1.3-/- mice entered the open arms more frequently and spent more time there indicating an anxiolytic-like phenotype which was, however, not supported in the stress-induced hyperthermia test. By performing parallel experiments in Claudin 14 knockout mice (Cldn14-/-), which like CaV1.3-/- mice are congenitally deaf, an influence of deafness on the antidepressant-like phenotype could be ruled out. On the other hand, a similar EPM behaviour indicative of an anxiolytic phenotype was also found in the Cldn14-/- animals. Using electroretinography and visual behavioural tasks we demonstrated that at least in mice, CaV1.3 channels do not significantly contribute to visual function. However, marked morphological changes were revealed in synaptic ribbons in the outer plexiform layer of CaV1.3-/- retinas by immunohistochemistry suggesting a possible role of this channel type in structural plasticity at the ribbon synapse. Taken together, our findings indicate that CaV1.3 L-type Ca2+ channels modulate depression-like behaviour but are not essential for visual function. The findings raise the possibility that selective modulation of CaV1.3 channels could be a promising new therapeutic concept for the treatment of mood disorders.

  10. Gravitational attraction of a vertical pyramid model of flat top-and ...

    Indian Academy of Sciences (India)

    Gravity pyramid model. 1737 contains the final analytical expression (forward problem solution) with relevant mathematical details. The integral evaluations on RHS of equation (3) are undertaken by Wolfram Mathe- matica 9.0.1. Drafting of illustrations were imple- mented through MATLAB 2013b. 3. Results and discussion.

  11. The Effect of Increasing Sn Content on High-Temperature Mechanical Deformation of an Mg-3%Cu-1%Ca Alloy

    Directory of Open Access Journals (Sweden)

    Georgios S.E. Antipas

    2013-11-01

    Full Text Available Chill casting of magnesium alloy samples with secondary alloying elements of Cu, Ca and Sn at % w.t. concentrations in the range 1–5, 0.1–5 and 0.1–3 respectively, gave rise to appreciably enhanced resistance to high-temperature creep, while maintaining good heat conductivity. The latter was considered to be driven by Cu and Mg-Cu intermetallics while it was clear that Sn mediated the high-temperature performance, mainly via networks of Mg2Sn and MgCaSn precipitates along the Mg matrix grain boundaries. It was postulated that Sn formed intermetallics by preferential substitution of Ca atoms and, thus, did not degrade the heat conductivity by retaining Cu. The % w.t. stoichiometry with the optimum combination of heat conductivity and resistance to high-temperature creep was found to be Mg-3Cu-1Ca-0.1Sn.

  12. A pliocene cliff-line around the Giza Pyramids Plateau, Egypt

    OpenAIRE

    Aigner, Thomas

    1982-01-01

    Aigner, T., 1983. A Pliocene cliff-line around the Giza Pyramids Plateau, Egypt. Palaeogeogr., Palaeoclimatol., Palaeoecol., 4 2 : 313—322. Escarpments bordering the Giza Pyramids Plateau represent the cliff-line of a Pliocene transgression up the pre-Nile ("Eonile") Valley. Geomorphologically, a limestone cliff can be distinguished from a slip-block shore associated with a distinct fining-up sequence. Differences in bedrock lithology and in structure (Joint pattern, faults) are morphogen...

  13. Cloning and expression analysis of CaPIP1-1 gene in pepper (Capsicum annuum L.).

    Science.gov (United States)

    Yin, Yan-Xu; Wang, Shu-Bin; Zhang, Huai-Xia; Xiao, Huai-Juan; Jin, Jing-Hao; Ji, Jiao-Jiao; Jing, Hua; Chen, Ru-Gang; Arisha, Mohamed Hamed; Gong, Zhen-Hui

    2015-05-25

    Plant aquaporins are responsible for water transmembrane transport, which play an important role on abiotic and biotic stresses. A novel plasma membrane intrinsic protein of CaPIP1-1 was isolated from the pepper P70 according to transcriptome databases of Phytophthora capsici inoculation and chilling stress library. CaPIP1-1, which is 1155 bp in length with an open reading frame of 861 bp, encoded 286 amino acids. Three introns, exhibited CT/AC splice junctions, were observed in CaPIP1-1. The numbers and location of introns in CaPIP1-1 were the same as observed in tomato and potato. CaPIP1-1 was abundantly expressed in pepper fruit. Increased transcription levels of CaPIP1-1 were found in the different stresses, including chilling stress, salt stress, mannitol stress, salicylic acid, ABA treatment and Phytophthora capsici infection. The expression of CaPIP1-1 was downregulated by 50 μM HgCl2 and 100 μM fluridone. The pepper plants silenced CaPIP1-1 in cv. Qiemen showed growth inhibition and decreased tolerance to salt and mannitol stresses using detached leaf method. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Aberrant Splicing Induced by Dysregulated Rbfox2 Produces Enhanced Function of CaV1.2 Calcium Channel and Vascular Myogenic Tone in Hypertension.

    Science.gov (United States)

    Zhou, Yingying; Fan, Jia; Zhu, Huayuan; Ji, Li; Fan, Wenyong; Kapoor, Isha; Wang, Yue; Wang, Yuan; Zhu, Guoqing; Wang, Juejin

    2017-12-01

    Calcium influx from activated voltage-gated calcium channel Ca V 1.2 in vascular smooth muscle cells is indispensable for maintaining myogenic tone and blood pressure. The function of Ca V 1.2 channel can be optimized by alternative splicing, one of post-transcriptional modification mechanisms. The splicing factor Rbfox2 is known to regulate the Ca V 1.2 pre-mRNA alternative splicing events during neuronal development. However, Rbfox2's roles in modulating the key function of vascular Ca V 1.2 channel and in the pathogenesis of hypertension remain elusive. Here, we report that the proportion of Ca V 1.2 channels with alternative exon 9* is increased by 10.3%, whereas that with alternative exon 33 is decreased by 10.5% in hypertensive arteries. Surprisingly, the expression level of Rbfox2 is increased ≈3-folds, presumably because of the upregulation of a dominant-negative isoform of Rbfox2. In vascular smooth muscle cells, we find that knockdown of Rbfox2 dynamically increases alternative exon 9*, whereas decreases exon 33 inclusion of Ca V 1.2 channels. By patch-clamp studies, we show that diminished Rbfox2-induced alternative splicing shifts the steady-state activation and inactivation curves of vascular Ca V 1.2 calcium channel to hyperpolarization, which makes the window current potential to more negative. Moreover, siRNA-mediated knockdown of Rbfox2 increases the pressure-induced vascular myogenic tone of rat mesenteric artery. Taken together, our data indicate that Rbfox2 modulates the functions of vascular Ca V 1.2 calcium channel by dynamically regulating the expressions of alternative exons 9* and 33, which in turn affects the vascular myogenic tone. Therefore, our work suggests a key role for Rbfox2 in hypertension, which provides a rational basis for designing antihypertensive therapies. © 2017 American Heart Association, Inc.

  15. Local Ca²+ entry via Orai1 regulates plasma membrane recruitment of TRPC1 and controls cytosolic Ca²+ signals required for specific cell functions.

    Directory of Open Access Journals (Sweden)

    Kwong Tai Cheng

    2011-03-01

    Full Text Available Store-operated Ca²+ entry (SOCE has been associated with two types of channels: CRAC channels that require Orai1 and STIM1 and SOC channels that involve TRPC1, Orai1, and STIM1. While TRPC1 significantly contributes to SOCE and SOC channel activity, abrogation of Orai1 function eliminates SOCE and activation of TRPC1. The critical role of Orai1 in activation of TRPC1-SOC channels following Ca²+ store depletion has not yet been established. Herein we report that TRPC1 and Orai1 are components of distinct channels. We show that TRPC1/Orai1/STIM1-dependent I(SOC, activated in response to Ca²+ store depletion, is composed of TRPC1/STIM1-mediated non-selective cation current and Orai1/STIM1-mediated I(CRAC; the latter is detected when TRPC1 function is suppressed by expression of shTRPC1 or a STIM1 mutant that lacks TRPC1 gating, STIM1(⁶⁸⁴EE⁶⁸⁵. In addition to gating TRPC1 and Orai1, STIM1 mediates the recruitment and association of the channels within ER/PM junctional domains, a critical step in TRPC1 activation. Importantly, we show that Ca²+ entry via Orai1 triggers plasma membrane insertion of TRPC1, which is prevented by blocking SOCE with 1 µM Gd³+, removal of extracellular Ca²+, knockdown of Orai1, or expression of dominant negative mutant Orai1 lacking a functional pore, Orai1-E106Q. In cells expressing another pore mutant of Orai1, Orai1-E106D, TRPC1 trafficking is supported in Ca²+-containing, but not Ca²+-free, medium. Consistent with this, I(CRAC is activated in cells pretreated with thapsigargin in Ca²+-free medium while I(SOC is activated in cells pretreated in Ca²+-containing medium. Significantly, TRPC1 function is required for sustained K(Ca activity and contributes to NFκB activation while Orai1 is sufficient for NFAT activation. Together, these findings reveal an as-yet unidentified function for Orai1 that explains the critical requirement of the channel in the activation of TRPC1 following Ca²+ store

  16. Altered thalamocortical rhythmicity and connectivity in mice lacking CaV3.1 T-type Ca2+ channels in unconsciousness

    Science.gov (United States)

    Choi, Soonwook; Yu, Eunah; Lee, Seongwon; Llinás, Rodolfo R.

    2015-01-01

    In unconscious status (e.g., deep sleep and anesthetic unconsciousness) where cognitive functions are not generated there is still a significant level of brain activity present. Indeed, the electrophysiology of the unconscious brain is characterized by well-defined thalamocortical rhythmicity. Here we address the ionic basis for such thalamocortical rhythms during unconsciousness. In particular, we address the role of CaV3.1 T-type Ca2+ channels, which are richly expressed in thalamic neurons. Toward this aim, we examined the electrophysiological and behavioral phenotypes of mice lacking CaV3.1 channels (CaV3.1 knockout) during unconsciousness induced by ketamine or ethanol administration. Our findings indicate that CaV3.1 KO mice displayed attenuated low-frequency oscillations in thalamocortical loops, especially in the 1- to 4-Hz delta band, compared with control mice (CaV3.1 WT). Intriguingly, we also found that CaV3.1 KO mice exhibited augmented high-frequency oscillations during unconsciousness. In a behavioral measure of unconsciousness dynamics, CaV3.1 KO mice took longer to fall into the unconscious state than controls. In addition, such unconscious events had a shorter duration than those of control mice. The thalamocortical interaction level between mediodorsal thalamus and frontal cortex in CaV3.1 KO mice was significantly lower, especially for delta band oscillations, compared with that of CaV3.1 WT mice, during unconsciousness. These results suggest that the CaV3.1 channel is required for the generation of a given set of thalamocortical rhythms during unconsciousness. Further, that thalamocortical resonant neuronal activity supported by this channel is important for the control of vigilance states. PMID:26056284

  17. Long-term potentiation in the CA1 hippocampus induced by NR2A subunit-containing NMDA glutamate receptors is mediated by Ras-GRF2/Erk map kinase signaling.

    Directory of Open Access Journals (Sweden)

    Shan-xue Jin

    Full Text Available BACKGROUND: NMDA-type glutamate receptors (NMDARs are major contributors to long-term potentiation (LTP, a form of synaptic plasticity implicated in the process of learning and memory. These receptors consist of calcium-permeating NR1 and multiple regulatory NR2 subunits. A majority of studies show that both NR2A and NR2B-containing NMDARs can contribute to LTP, but their unique contributions to this form of synaptic plasticity remain poorly understood. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we show that NR2A and NR2B-containing receptors promote LTP differently in the CA1 hippocampus of 1-month old mice, with the NR2A receptors functioning through Ras-GRF2 and its downstream effector, Erk Map kinase, and NR2B receptors functioning independently of these signaling molecules. CONCLUSIONS/SIGNIFICANCE: This study demonstrates that NR2A-, but not NR2B, containing NMDA receptors induce LTP in pyramidal neurons of the CA1 hippocampus from 1 month old mice through Ras-GRF2 and Erk. This difference add new significance to the observation that the relative levels of these NMDAR subtypes is regulated in neurons, such that NR2A-containing receptors become more prominent late in postnatal development, after sensory experience and synaptic activity.

  18. Electrical and magnetic behavior of La0.7Ca0.3MnO3/La0.7Sr0.2Ca0.1MnO3 composites

    International Nuclear Information System (INIS)

    Phong, P.T.; Dai, N.V.; Manh, D.H.; Thanh, T.D.; Khiem, N.V.; Hong, L.V.; Phuc, N.X.

    2010-01-01

    The electrical transport properties and the magnetoresistance of La 0.7 Ca 0.3 MnO 3 /La 0.7 Sr 0.2 Ca 0.1 MnO 3 composites are investigated as a function of sintering temperature. On the basis of an analysis by X-ray powder diffraction and scanning electron microscopy we suggest that raising the sintering temperature enhanced the interfacial reaction and creates interfacial phases at the boundaries of the La 0.7 Ca 0.3 MnO 3 and La 0.7 Sr 0.2 Ca 0.1 MnO 3 . Results also show that in 3 kOe, and at the Curie temperature, the magnetoresistance value of 14% was observed for the composite sintered at 1300 o C. Based on the phenomenological equation for conductivity under a percolation approach, which depends on the phase segregation of ferromagnetic metallic clusters and paramagnetic insulating regions, we fitted the experimental resistivity-temperature data from 50-300 K and find that the activation barrier decreases as temperature is increased.

  19. XAFS study of copper(II) complexes with square planar and square pyramidal coordination geometries

    Science.gov (United States)

    Gaur, A.; Klysubun, W.; Nitin Nair, N.; Shrivastava, B. D.; Prasad, J.; Srivastava, K.

    2016-08-01

    X-ray absorption fine structure of six Cu(II) complexes, Cu2(Clna)4 2H2O (1), Cu2(ac)4 2H2O (2), Cu2(phac)4 (pyz) (3), Cu2(bpy)2(na)2 H2O (ClO4) (4), Cu2(teen)4(OH)2(ClO4)2 (5) and Cu2(tmen)4(OH)2(ClO4)2 (6) (where ac, phac, pyz, bpy, na, teen, tmen = acetate, phenyl acetate, pyrazole, bipyridine, nicotinic acid, tetraethyethylenediamine, tetramethylethylenediamine, respectively), which were supposed to have square pyramidal and square planar coordination geometries have been investigated. The differences observed in the X-ray absorption near edge structure (XANES) features of the standard compounds having four, five and six coordination geometry points towards presence of square planar and square pyramidal geometry around Cu centre in the studied complexes. The presence of intense pre-edge feature in the spectra of four complexes, 1-4, indicates square pyramidal coordination. Another important XANES feature, present in complexes 5 and 6, is prominent shoulder in the rising part of edge whose intensity decreases in the presence of axial ligands and thus indicates four coordination in these complexes. Ab initio calculations were carried out for square planar and square pyramidal Cu centres to observe the variation of 4p density of states in the presence and absence of axial ligands. To determine the number and distance of scattering atoms around Cu centre in the complexes, EXAFS analysis has been done using the paths obtained from Cu(II) oxide model and an axial Cu-O path from model of a square pyramidal complex. The results obtained from EXAFS analysis have been reported which confirmed the inference drawn from XANES features. Thus, it has been shown that these paths from model of a standard compound can be used to determine the structural parameters for complexes having unknown structure.

  20. A dual triangular pyramidal indentation technique based on FEA solutions for Material property evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Minsoo; Hyun, Hong Chul [Sogana Univ., Seoul (Korea, Republic of); Lee, Jin Haeng; Lee, Hyungyil [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2012-01-15

    In this study, we suggest a method for material property evaluation by dual triangular pyramidal indenters using the reverse analysis. First, we demonstrated that load displacement curves of conical and triangular pyramidal indenters are different for the same material. For this reason, an independent research on the triangular pyramidal indenter is needed. From FE indentation analyses on various materials, we then investigated the relationships among material properties, indentation parameters and load displacement curves. From this, we established property evaluation formula using dual triangular pyramidal indenters having two different half included angles. The approach provides the values of elastic modulus, yield strength and strain hardening exponent within an average error of 3% for various materials.

  1. Ablation of Ca(V)2.1 voltage-gated Ca²⁺ channels in mouse forebrain generates multiple cognitive impairments.

    Science.gov (United States)

    Mallmann, Robert Theodor; Elgueta, Claudio; Sleman, Faten; Castonguay, Jan; Wilmes, Thomas; van den Maagdenberg, Arn; Klugbauer, Norbert

    2013-01-01

    Voltage-gated Ca(V)2.1 (P/Q-type) Ca²⁺ channels located at the presynaptic membrane are known to control a multitude of Ca²⁺-dependent cellular processes such as neurotransmitter release and synaptic plasticity. Our knowledge about their contributions to complex cognitive functions, however, is restricted by the limited adequacy of existing transgenic Ca(V)2.1 mouse models. Global Ca(V)2.1 knock-out mice lacking the α1 subunit Cacna1a gene product exhibit early postnatal lethality which makes them unsuitable to analyse the relevance of Ca(V)2.1 Ca²⁺ channels for complex behaviour in adult mice. Consequently we established a forebrain specific Ca(V)2.1 knock-out model by crossing mice with a floxed Cacna1a gene with mice expressing Cre-recombinase under the control of the NEX promoter. This novel mouse model enabled us to investigate the contribution of Ca(V)2.1 to complex cognitive functions, particularly learning and memory. Electrophysiological analysis allowed us to test the specificity of our conditional knock-out model and revealed an impaired synaptic transmission at hippocampal glutamatergic synapses. At the behavioural level, the forebrain-specific Ca(V)2.1 knock-out resulted in deficits in spatial learning and reference memory, reduced recognition memory, increased exploratory behaviour and a strong attenuation of circadian rhythmicity. In summary, we present a novel conditional Ca(V)2.1 knock-out model that is most suitable for analysing the in vivo functions of Ca(V)2.1 in the adult murine forebrain.

  2. Regional cerebral palmitate incorporation following transient bilateral carotid occlusion in awake gerbils

    Energy Technology Data Exchange (ETDEWEB)

    Tone, O.; Miller, J.C.; Bell, J.M.; Rapoport, S.I.

    1987-11-01

    (/sup 14/C)Palmitate was injected intravenously in awake gerbils at various times after 5 minutes of bilateral carotid artery occlusion or a sham operation. Regional rates of incorporation of plasma palmitate into the hippocampus and other regions of the anterior circulation were determined relative to the mean rate of incorporation into regions of the posterior circulation using quantitative autoradiography and a ratio method of analysis. One day after bilateral carotid occlusion, relative palmitate incorporation was elevated significantly by 16% in the CA4 pyramidal cell layer and by 20% in the dentate gyrus of the hippocampus compared with sham-operated gerbils. At 3 days, significant elevations of this magnitude were found in the CA3 and CA4 cell layers, whereas relative incorporation was reduced by 26% in the CA1 pyramidal cell layer. At 7 days, the only significant difference from control was a 15% elevated incorporation in the CA3 pyramidal cell layer. Histologic examination indicated substantial cell death in the CA1 pyramidal layer at 3 days, with extensive glial reaction and phagocytic invasion at 7 days. Our results suggest that the turnover of palmitate-containing lipids is reduced in the CA1 layer of the gerbil hippocampus but that lipid synthesis is stimulated in hippocampal regions (CA3, CA4, dentate gyrus) affected by but recovering from transient bilateral carotid occlusion.

  3. Regional cerebral palmitate incorporation following transient bilateral carotid occlusion in awake gerbils

    International Nuclear Information System (INIS)

    Tone, O.; Miller, J.C.; Bell, J.M.; Rapoport, S.I.

    1987-01-01

    [ 14 C]Palmitate was injected intravenously in awake gerbils at various times after 5 minutes of bilateral carotid artery occlusion or a sham operation. Regional rates of incorporation of plasma palmitate into the hippocampus and other regions of the anterior circulation were determined relative to the mean rate of incorporation into regions of the posterior circulation using quantitative autoradiography and a ratio method of analysis. One day after bilateral carotid occlusion, relative palmitate incorporation was elevated significantly by 16% in the CA4 pyramidal cell layer and by 20% in the dentate gyrus of the hippocampus compared with sham-operated gerbils. At 3 days, significant elevations of this magnitude were found in the CA3 and CA4 cell layers, whereas relative incorporation was reduced by 26% in the CA1 pyramidal cell layer. At 7 days, the only significant difference from control was a 15% elevated incorporation in the CA3 pyramidal cell layer. Histologic examination indicated substantial cell death in the CA1 pyramidal layer at 3 days, with extensive glial reaction and phagocytic invasion at 7 days. Our results suggest that the turnover of palmitate-containing lipids is reduced in the CA1 layer of the gerbil hippocampus but that lipid synthesis is stimulated in hippocampal regions (CA3, CA4, dentate gyrus) affected by but recovering from transient bilateral carotid occlusion

  4. Flat-on ambipolar triphenylamine/C60 nano-stacks formed from the self-organization of a pyramid-sphere-shaped amphiphile.

    Science.gov (United States)

    Liang, Wei-Wei; Huang, Chi-Feng; Wu, Kuan-Yi; Wu, San-Lien; Chang, Shu-Ting; Cheng, Yen-Ju; Wang, Chien-Lung

    2016-04-21

    A giant amphiphile, which is constructed with an amorphous nano-pyramid (triphenylamine, TPA) and a crystalline nano-sphere (C 60 ), was synthesized. Structural characterization indicates that this pyramid-sphere-shaped amphiphile ( TPA-C 60 ) forms a solvent-induced ordered phase, in which the two constituent units self-assemble into alternating stacks of two-dimensional (2D) TPA and C 60 nano-sheets. Due to the complexity of the molecular structure and the amorphous nature of the nano-pyramid, phase formation was driven by intermolecular C 60 -C 60 interactions and the ordered phase could not be reformed from the TPA-C 60 melt. Oriented crystal arrays of TPA-C 60 , which contain flat-on TPA/C 60 nano-stacks, can be obtained via a PDMS-assisted crystallization (PAC) technique. The flat-on dual-channel supramolecular structure of TPA-C 60 delivered ambipolar and balanced charge-transport characteristics with an average μ e of 2.11 × 10 -4 cm 2 V -1 s -1 and μ h of 3.37 × 10 -4 cm 2 V -1 s -1 . The anisotropic charge-transport ability of the pyramid-sphere-shaped amphiphile was further understood based on the lattice structure and the lattice orientation of TPA-C 60 revealed from electron diffraction analyses.

  5. The offset-midpoint traveltime pyramid of P-waves in homogeneous orthorhombic media

    KAUST Repository

    Hao, Qi

    2016-07-18

    The offset-midpoint traveltime pyramid describes the diffraction traveltime of a point diffractor in homogeneous media. We have developed an analytic approximation for the P-wave offset-midpoint traveltime pyramid for homogeneous orthorhombic media. In this approximation, a perturbation method and the Shanks transform were implemented to derive the analytic expressions for the horizontal slowness components of P-waves in orthorhombic media. Numerical examples were shown to analyze the proposed traveltime pyramid formula and determined its accuracy and the application in calculating migration isochrones and reflection traveltime. The proposed offset-midpoint traveltime formula is useful for Kirchhoff prestack time migration and migration velocity analysis for orthorhombic media.

  6. The offset-midpoint traveltime pyramid of P-waves in homogeneous orthorhombic media

    KAUST Repository

    Hao, Qi; Stovas, Alexey; Alkhalifah, Tariq Ali

    2016-01-01

    The offset-midpoint traveltime pyramid describes the diffraction traveltime of a point diffractor in homogeneous media. We have developed an analytic approximation for the P-wave offset-midpoint traveltime pyramid for homogeneous orthorhombic media. In this approximation, a perturbation method and the Shanks transform were implemented to derive the analytic expressions for the horizontal slowness components of P-waves in orthorhombic media. Numerical examples were shown to analyze the proposed traveltime pyramid formula and determined its accuracy and the application in calculating migration isochrones and reflection traveltime. The proposed offset-midpoint traveltime formula is useful for Kirchhoff prestack time migration and migration velocity analysis for orthorhombic media.

  7. Temporal redistribution of inhibition over neuronal subcellular domains underlies state-dependent rhythmic change of excitability in the hippocampus

    Science.gov (United States)

    Somogyi, Peter; Katona, Linda; Klausberger, Thomas; Lasztóczi, Bálint; Viney, Tim J.

    2014-01-01

    The behaviour-contingent rhythmic synchronization of neuronal activity is reported by local field potential oscillations in the theta, gamma and sharp wave-related ripple (SWR) frequency ranges. In the hippocampus, pyramidal cell assemblies representing temporal sequences are coordinated by GABAergic interneurons selectively innervating specific postsynaptic domains, and discharging phase locked to network oscillations. We compare the cellular network dynamics in the CA1 and CA3 areas recorded with or without anaesthesia. All parts of pyramidal cells, except the axon initial segment, receive GABA from multiple interneuron types, each with distinct firing dynamics. The axon initial segment is exclusively innervated by axo-axonic cells, preferentially firing after the peak of the pyramidal layer theta cycle, when pyramidal cells are least active. Axo-axonic cells are inhibited during SWRs, when many pyramidal cells fire synchronously. This dual inverse correlation demonstrates the key inhibitory role of axo-axonic cells. Parvalbumin-expressing basket cells fire phase locked to field gamma activity in both CA1 and CA3, and also strongly increase firing during SWRs, together with dendrite-innervating bistratified cells, phasing pyramidal cell discharge. Subcellular domain-specific GABAergic innervation probably developed for the coordination of multiple glutamatergic inputs on different parts of pyramidal cells through the temporally distinct activity of GABAergic interneurons, which differentially change their firing during different network states. PMID:24366131

  8. Atomic structure of CaF2/MnF2-Si(1 1 1) superlattices from X-ray diffraction

    International Nuclear Information System (INIS)

    Alcock, Simon G.; Nicklin, C.L.; Howes, P.B.; Norris, C.A.; Kyutt, R.N.; Sokolov, N.S.; Yakovlev, N.L.

    2007-01-01

    X-ray reflectivity and non-specular crystal truncation rod scans have been used to determine the three-dimensional atomic structure of the buried CaF 2 -Si(1 1 1) interface and ultrathin films of MnF 2 and CaF 2 within a superlattice. We show that ultrathin films of MnF 2 , below a critical thickness of approximately four monolayers, are crystalline, pseudomorphic, and adopt the fluorite structure of CaF 2 . High temperature deposition of the CaF 2 buffer layer produces a fully reacted, CaF 2 -Si(1 1 1) type-B interface. The mature, 'long' interface is shown to consist of a partially occupied layer of CaF bonded to the Si substrate, followed by a distorted CaF layer. Our atomistic, semi-kinematical scattering method extends the slab reflectivity method by providing in-plane structural information

  9. IP3 stimulates CA++ efflux from fusogenic carrot protoplasts

    International Nuclear Information System (INIS)

    Rincon, M.; Boss, W.F.

    1986-01-01

    Polyphosphoinositide breakdown plays an important role in signal transduction in animal cells (Berridge and Irvine, 1984, Nature, 312:315). Upon stimulation, phospholipase C hydrolyzes phosphatidylinositol 4,5-bisphosphate to inositol 1,4,5-trisphosphate (IP 3 ) and diacylglycerol both of which act as cellular second messengers. IP 3 mobilizes Ca ++ from internal stores, hence the cytosolic free Ca ++ concentration increases and those physiological activities regulated by Ca ++ are stimulated. To test if plant cells also responded to IP 3 , Ca ++ efflux studies were done with fusogenic carrot protoplasts released in EGTA. The protoplasts were preloaded with 45 Ca ++ placed in a Ca ++ -free medium, and efflux determined as 45 Ca ++ loss from the protoplasts. IP 3 (10-20μM) caused enhanced 45 Ca ++ efflux and the response was sustained for at least 15 min. In plants, as in animals, the observed IP 3 -enhanced 45 Ca ++ efflux suggested that IP 3 released Ca ++ from internal stores, and the increased free cytosolic Ca ++ activated Ca ++ pumping mechanisms which restored the Ca ++ concentration in the cytosol to the normal level

  10. The interhemispheric CA1 circuit governs rapid generalisation but not fear memory.

    Science.gov (United States)

    Zhou, Heng; Xiong, Gui-Jing; Jing, Liang; Song, Ning-Ning; Pu, De-Lin; Tang, Xun; He, Xiao-Bing; Xu, Fu-Qiang; Huang, Jing-Fei; Li, Ling-Jiang; Richter-Levin, Gal; Mao, Rong-Rong; Zhou, Qi-Xin; Ding, Yu-Qiang; Xu, Lin

    2017-12-19

    Encoding specificity theory predicts most effective recall by the original conditions at encoding, while generalization endows recall flexibly under circumstances which deviate from the originals. The CA1 regions have been implicated in memory and generalization but whether and which locally separated mechanisms are involved is not clear. We report here that fear memory is quickly formed, but generalization develops gradually over 24 h. Generalization but not fear memory is impaired by inhibiting ipsilateral (ips) or contralateral (con) CA1, and by optogenetic silencing of the ipsCA1 projections onto conCA1. By contrast, in vivo fEPSP recordings reveal that ipsCA1-conCA1 synaptic efficacy is increased with delay over 24 h when generalization is formed but it is unchanged if generalization is disrupted. Direct excitation of ipsCA1-conCA1 synapses using chemogenetic hM3Dq facilitates generalization formation. Thus, rapid generalization is an active process dependent on bilateral CA1 regions, and encoded by gradual synaptic learning in ipsCA1-conCA1 circuit.

  11. Comparing Volumes of Prisms and Pyramids

    Science.gov (United States)

    Vinogradova, Natalya

    2012-01-01

    Students' experience in using formulas for volumes is often limited to substituting numbers into given formulas. An activity presented in this article may help students make connections between the formulas for volumes of prisms and volumes of pyramids. In addition, some interesting facts from number theory arise, demonstrating strong connections…

  12. Protein Kinase Cα and P-Type Ca2+ Channel CaV2.1 in Red Blood Cell Calcium Signalling

    Directory of Open Access Journals (Sweden)

    Lisa Wagner-Britz

    2013-06-01

    Full Text Available Background/Aims: Protein kinase Cα (PKCα is activated by an increase in cytosolic Ca2+ in red blood cells (RBCs. Previous work has suggested that PKCα directly stimulates the CaV2.1 channel, whereas other studies revealed that CaV2.1 is insensitive to activation by PKC. The aim of this study was to resolve this discrepancy. Methods: We performed experiments based on a single cell read-out of the intracellular Ca2+ concentration in terms of Fluo-4 fluorescence intensity and phosphatidylserine exposure to the external membrane leaflet. Measurement modalities included flow cytometry and live cell imaging. Results: Treatment of RBCs with phorbol 12-myristate 13-acetate (PMA led to two distinct populations of cells with an increase in intracellular Ca2+: a weak-responding and a strong-responding population. The EC50 of PMA for the number of cells with Ca2+ elevation was 2.7±1.2 µM; for phosphatidylserine exposure to the external membrane surface, it was 2.8±0.5 µM; and for RBC haemolysis, it was 2.9±0.5 µM. Using pharmacological manipulation with the CaV2.1 inhibitor ω-agatoxin TK and the broad protein kinase C inhibitor Gö6983, we are able to show that there are two independent PMA-activated Ca2+ entry processes: the first is independent of CaV2.1 and directly PKCα-activated, while the second is associated with a likely indirect activation of CaV2.1. Further studies using lysophosphatidic acid (LPA as a stimulation agent have provided additional evidence that PKCα and CaV2.1 are not directly interconnected in a signalling chain. Conclusion: Although we provide evidence for a lack of interaction between PKCα and CaV2.1 in RBCs, further studies are required to decipher the signalling relationship between LPA, PKCα and CaV2.1.

  13. Ablation of Ca(V2.1 voltage-gated Ca²⁺ channels in mouse forebrain generates multiple cognitive impairments.

    Directory of Open Access Journals (Sweden)

    Robert Theodor Mallmann

    Full Text Available Voltage-gated Ca(V2.1 (P/Q-type Ca²⁺ channels located at the presynaptic membrane are known to control a multitude of Ca²⁺-dependent cellular processes such as neurotransmitter release and synaptic plasticity. Our knowledge about their contributions to complex cognitive functions, however, is restricted by the limited adequacy of existing transgenic Ca(V2.1 mouse models. Global Ca(V2.1 knock-out mice lacking the α1 subunit Cacna1a gene product exhibit early postnatal lethality which makes them unsuitable to analyse the relevance of Ca(V2.1 Ca²⁺ channels for complex behaviour in adult mice. Consequently we established a forebrain specific Ca(V2.1 knock-out model by crossing mice with a floxed Cacna1a gene with mice expressing Cre-recombinase under the control of the NEX promoter. This novel mouse model enabled us to investigate the contribution of Ca(V2.1 to complex cognitive functions, particularly learning and memory. Electrophysiological analysis allowed us to test the specificity of our conditional knock-out model and revealed an impaired synaptic transmission at hippocampal glutamatergic synapses. At the behavioural level, the forebrain-specific Ca(V2.1 knock-out resulted in deficits in spatial learning and reference memory, reduced recognition memory, increased exploratory behaviour and a strong attenuation of circadian rhythmicity. In summary, we present a novel conditional Ca(V2.1 knock-out model that is most suitable for analysing the in vivo functions of Ca(V2.1 in the adult murine forebrain.

  14. Photoemission study of Ca-intercalated graphite superconductor CaC6

    International Nuclear Information System (INIS)

    Okazaki, Hiroyuki; Yoshida, Rikiya; Iwai, Keisuke; Noami, Kengo; Muro, Takayuki; Nakamura, Tetsuya; Wakita, Takanori; Muraoka, Yuji; Hirai, Masaaki; Tomioka, Fumiaki; Takano, Yoshihiko; Takenaka, Asami; Toyoda, Masahiro; Oguchi, Tamio; Yokoya, Takayoshi

    2010-01-01

    In this work, we have performed resonant photoemission studies of Ca-intercalated graphite superconductor CaC 6 . Using photon energy of the Ca 2p-3d threshold, the photoemission intensity of the peak at Fermi energy (E F ) is resonantly enhanced. This result provides spectroscopic evidence for the existence of Ca 3d states at E F , and strongly supports that Ca 3d state plays a crucial role for the superconductivity of this material with relatively high T c .

  15. Logical thinking in the pyramidal schema of concepts the logical and mathematical elements

    CERN Document Server

    Geldsetzer, Lutz

    2014-01-01

    This book proposes a new way of formalizing in logic and mathematics - a "pyramidal graph system," devised by the author and based on Porphyrian trees and modern concepts of classification, in both of which pyramids act as the organizing schema.

  16. Mechanism of the Ca2+-induced enhancement of the intrinsic factor VIIa activity

    DEFF Research Database (Denmark)

    Bjelke, Jais R; Olsen, Ole H; Fodje, Michel

    2008-01-01

    between the loop and Lys(161) in the N-terminal tail. In support of the first mechanism, the mutations E296V and D212N resulted in similar, about 2-fold, enhancements of the amidolytic activity. Moreover, mutation of the Lys(161)-interactive residue Asp(217) or Asp(219) to Ala reduced the amidolytic...... activity by 40-50%, whereas the K161A mutation resulted in 80% reduction. Hence one of these Asp residues in the Ca(2+)-binding loop appears to suffice for some residual interaction with Lys(161), whereas the more severe effect upon replacement of Lys(161) is due to abrogation of the interaction with the N......-terminal tail. However, Ca(2+) attenuation of the repulsion between Asp(212) and Glu(296) keeps the activity above that of apoFVIIa. Altogether, our data suggest that repulsion involving Asp(212) in the Ca(2+)-binding loop suppresses FVIIa activity and that optimal activity requires a favorable interaction...

  17. Quantum percolation transition in Eu{sub 1-x}Ca{sub x}B{sub 6}

    Energy Technology Data Exchange (ETDEWEB)

    Glushkov, V.V. [A.M.Prokhorov General Physics Institute of RAS, 38, Vavilov str., Moscow 119991 (Russian Federation); Moscow Institute of Physics and Technology, 9, Institutskii per., Dolgoprudny, Moscow Region 141700 (Russian Federation); Anisimov, M.A. [Moscow Institute of Physics and Technology, 9, Institutskii per., Dolgoprudny, Moscow Region 141700 (Russian Federation); Bogach, A.V.; Demishev, S.V.; Sluchanko, N.E. [A.M.Prokhorov General Physics Institute of RAS, 38, Vavilov str., Moscow 119991 (Russian Federation); Filipov, V.B.; Levchenko, A.V.; Shitsevalova, N.Yu. [Institute for Problems of Materials Science NAS, 3, Krzhyzhanovsky str., Kiev 03680 (Ukraine); Flachbart, K. [Centre of Low Temperature Physics, IEP SAS and IPS FS UPJS, Kosice SK-04001 (Slovakia); Kuznetsov, A.V. [Moscow Engineering Physics Institute, 31, Kashirskoe Shosse, Moscow 115409 (Russian Federation)

    2010-03-15

    The study of transport and magnetic properties performed on Eu{sub 1-x}Ca{sub x}B{sub 6} single crystals with nominal Ca content 0 {<=} x {<=} 0.4 at temperatures 1.8-300 K in magnetic fields up to 80 kOe provides the direct experimental evidence of metal-to-insulator transition (MIT) earlier proposed for the system by V. M. Pereira et al. [Phys. Rev. Lett., 93, 147202 (2004)]. A giant enhancement of magnetoresistance up to the values of ({rho}(0) - {rho}(H))/{rho}(H) {proportional_to} 7 x 10{sup 7}% was detected for x = 0.4 in the wide vicinity of the ferromagnetic insulating state. The field induced crossover from hole-like to electron-like regime of charge transport observed for the first time in the paramagnetic phase of Eu{sub 0.6}Ca{sub 0.4}B{sub 6} is discussed in terms of quantum percolation transition predicted for this low carrier density system within double exchange model. (Abstract Copyright [2010], Wiley Periodicals, Inc.)

  18. Synthesis and luminescence enhancement of CaTiO{sub 3}:Bi{sup 3+} yellow phosphor by codoping Al{sup 3+}/B{sup 3+} ions

    Energy Technology Data Exchange (ETDEWEB)

    Cao, Renping, E-mail: jxcrp@163.com; Fu, Ting; Xu, Haidong; Luo, Wenjie; Peng, Dedong; Chen, Zhiquan; Fu, Jingwei

    2016-07-25

    CaTiO{sub 3}:Bi{sup 3+} and CaTiO{sub 3}:Bi{sup 3+}, Al{sup 3+}/B{sup 3+} phosphors are synthesized by solid-state reaction method in air. With excitation 272 and 320 nm, broad PL band peaking at 555 nm with full width at half maximum ∼200 nm is observed in the range of 400–800 nm due to the {sup 3}P{sub 1,0} → {sup 1}S{sub 0} transitions of Bi{sup 3+} ion. PLE spectrum monitored at 555 nm contains two PLE band peaking at ∼272 and 320 nm within the range 230–420 nm owing to metal-to-metal charge-transfer and {sup 1}S{sub 0} → {sup 3}P{sub 1} transition of Bi{sup 3+} ion, respectively. The optimal Bi{sup 3+} doping concentration in CaTiO{sub 3}:Bi{sup 3+} phosphor is about 0.5 mol%. Luminescence properties of CaTiO{sub 3}:Bi{sup 3+} phosphor may be improved obviously by co-doping Al{sup 3+}/B{sup 3+} ions, and its emission intensity can be enhanced 13–15 times after Al{sup 3+} ion is co-doped. Luminous mechanism of CaTiO{sub 3}:Bi{sup 3+} phosphor is analyzed by energy level diagram of Bi{sup 3+} ion. Decay curve and time-resolved spectra confirm that only a single type of Bi{sup 3+} luminescence center exists in CaTiO{sub 3}:Bi{sup 3+} phosphor. - Graphical abstract: PL spectra of CaTiO{sub 3}:Bi{sup 3+} and CaTiO{sub 3}:Bi{sup 3+}, Al{sup 3+}/B{sup 3+} phosphors and the corresponding pictures under 365 nm UV lamp. - Highlights: • CaTiO{sub 3}:Bi{sup 3+} and CaTiO{sub 3}:Bi{sup 3+}, Al{sup 3+}/B{sup 3+} phosphors are synthesized by solid-state reaction in air. • Broadband emission with FWHM ∼200 nm is observed within the range 400–800 nm. • Luminescence properties of CaTiO{sub 3}:Bi{sup 3+} phosphor can be improved by codoping Al{sup 3+}/B{sup 3+} ions. • PL intensity of CaTiO{sub 3}:Bi{sup 3+} phosphor can be enhanced 13–15 times after Al{sup 3+} ion is codoped.

  19. Computing Homology Group Generators of Images Using Irregular Graph Pyramids

    OpenAIRE

    Peltier , Samuel; Ion , Adrian; Haxhimusa , Yll; Kropatsch , Walter; Damiand , Guillaume

    2007-01-01

    International audience; We introduce a method for computing homology groups and their generators of a 2D image, using a hierarchical structure i.e. irregular graph pyramid. Starting from an image, a hierarchy of the image is built, by two operations that preserve homology of each region. Instead of computing homology generators in the base where the number of entities (cells) is large, we first reduce the number of cells by a graph pyramid. Then homology generators are computed efficiently on...

  20. Voltage-gated ion channels in the axon initial segment of human cortical pyramidal cells and their relationship with chandelier cells.

    Science.gov (United States)

    Inda, Maria Carmen; DeFelipe, Javier; Muñoz, Alberto

    2006-02-21

    The axon initial segment (AIS) of pyramidal cells is a critical region for the generation of action potentials and for the control of pyramidal cell activity. Here we show that Na+ and K+ voltage-gated channels, together with other molecules involved in the localization of ion channels, are distributed asymmetrically in the AIS of pyramidal cells situated in the human temporal neocortex. There is a high density of Na+ channels distributed along the length of the AIS together with the associated proteins spectrin betaIV and ankyrin G. In contrast, Kv1.2 channels are associated with the adhesion molecule Caspr2, and they are mostly localized to the distal region of the AIS. In general, the distal region of the AIS is targeted by the GABAergic axon terminals of chandelier cells, whereas the proximal region is innervated, mostly by other types of GABAergic interneurons. We suggest that this molecular segregation and the consequent regional specialization of the GABAergic input to the AIS of pyramidal cells may have important functional implications for the control of pyramidal cell activity.

  1. Deficits in synaptic function occur at medial perforant path-dentate granule cell synapses prior to Schaffer collateral-CA1 pyramidal cell synapses in the novel TgF344-Alzheimer's Disease Rat Model.

    Science.gov (United States)

    Smith, Lindsey A; McMahon, Lori L

    2018-02-01

    Alzheimer's disease (AD) pathology begins decades prior to onset of clinical symptoms, and the entorhinal cortex and hippocampus are among the first and most extensively impacted brain regions. The TgF344-AD rat model, which more fully recapitulates human AD pathology in an age-dependent manner, is a next generation preclinical rodent model for understanding pathophysiological processes underlying the earliest stages of AD (Cohen et al., 2013). Whether synaptic alterations occur in hippocampus prior to reported learning and memory deficit is not known. Furthermore, it is not known if specific hippocampal synapses are differentially affected by progressing AD pathology, or if synaptic deficits begin to appear at the same age in males and females in this preclinical model. Here, we investigated the time-course of synaptic changes in basal transmission, paired-pulse ratio, as an indirect measure of presynaptic release probability, long-term potentiation (LTP), and dendritic spine density at two hippocampal synapses in male and ovariectomized female TgF344-AD rats and wildtype littermates, prior to reported behavioral deficits. Decreased basal synaptic transmission begins at medial perforant path-dentate granule cell (MPP-DGC) synapses prior to Schaffer-collateral-CA1 (CA3-CA1) synapses, in the absence of a change in paired-pulse ratio (PPR) or dendritic spine density. N-methyl-d-aspartate receptor (NMDAR)-dependent LTP magnitude is unaffected at CA3-CA1 synapses at 6, 9, and 12months of age, but is significantly increased at MPP-DGC synapses in TgF344-AD rats at 6months only. Sex differences were only observed at CA3-CA1 synapses where the decrease in basal transmission occurs at a younger age in males versus females. These are the first studies to define presymptomatic alterations in hippocampal synaptic transmission in the TgF344-AD rat model. The time course of altered synaptic transmission mimics the spread of pathology through hippocampus in human AD and provides

  2. The architectonic encoding of the minor lunar standstills in the horizon of the Giza pyramids.

    Science.gov (United States)

    Hossam, M. K. Aboulfotouh

    The paper is an attempt to show the architectonic method of the ancient Egyptian designers for encoding the horizontal-projections of the moon's declinations during two events of the minor lunar standstills, in the design of the site-plan of the horizon of the Giza pyramids, using the methods of descriptive geometry. It shows that the distance of the eastern side of the second Giza pyramid from the north-south axis of the great pyramid encodes a projection of a lunar declination, when earth's obliquity-angle was ~24.10°. Besides, it shows that the angle of inclination of the causeway of the second Giza pyramid, of ~13.54° south of the cardinal east, encodes the projection of another lunar declination when earth's obliquity-angle reaches ~22.986°. In addition, it shows the encoded coordinate system in the site-plan of the horizon of the Giza pyramids.

  3. Loss of Synapse Repressor MDGA1 Enhances Perisomatic Inhibition, Confers Resistance to Network Excitation, and Impairs Cognitive Function

    Directory of Open Access Journals (Sweden)

    Steven A. Connor

    2017-12-01

    Full Text Available Synaptopathies contributing to neurodevelopmental disorders are linked to mutations in synaptic organizing molecules, including postsynaptic neuroligins, presynaptic neurexins, and MDGAs, which regulate their interaction. The role of MDGA1 in suppressing inhibitory versus excitatory synapses is controversial based on in vitro studies. We show that genetic deletion of MDGA1 in vivo elevates hippocampal CA1 inhibitory, but not excitatory, synapse density and transmission. Furthermore, MDGA1 is selectively expressed by pyramidal neurons and regulates perisomatic, but not distal dendritic, inhibitory synapses. Mdga1−/− hippocampal networks demonstrate muted responses to neural excitation, and Mdga1−/− mice are resistant to induced seizures. Mdga1−/− mice further demonstrate compromised hippocampal long-term potentiation, consistent with observed deficits in spatial and context-dependent learning and memory. These results suggest that mutations in MDGA1 may contribute to cognitive deficits through altered synaptic transmission and plasticity by loss of suppression of inhibitory synapse development in a subcellular domain- and cell-type-selective manner.

  4. Dielectrophoresis-Assisted Raman Spectroscopy of Intravesicular Analytes on Metallic Pyramids.

    Science.gov (United States)

    Barik, Avijit; Cherukulappurath, Sudhir; Wittenberg, Nathan J; Johnson, Timothy W; Oh, Sang-Hyun

    2016-02-02

    Chemical analysis of membrane-bound containers such as secretory vesicles, organelles, and exosomes can provide insights into subcellular biology. These containers are loaded with a range of important biomolecules, which further underscores the need for sensitive and selective analysis methods. Here we present a metallic pyramid array for intravesicular analysis by combining site-selective dielectrophoresis (DEP) and Raman spectroscopy. Sharp pyramidal tips act as a gradient force generator to trap nanoparticles or vesicles from the solution, and the tips are illuminated by a monochromatic light source for concurrent spectroscopic detection of trapped analytes. The parameters suitable for DEP trapping were optimized by fluorescence microscopy, and the Raman spectroscopy setup was characterized by a nanoparticle based model system. Finally, vesicles loaded with 4-mercaptopyridine were concentrated at the tips and their Raman spectra were detected in real time. These pyramidal tips can perform large-area array-based trapping and spectroscopic analysis, opening up possibilities to detect molecules inside cells or cell-derived vesicles.

  5. Increased arterial smooth muscle Ca2+ signaling, vasoconstriction, and myogenic reactivity in Milan hypertensive rats

    Science.gov (United States)

    Linde, Cristina I.; Karashima, Eiji; Raina, Hema; Zulian, Alessandra; Wier, Withrow G.; Hamlyn, John M.; Ferrari, Patrizia; Blaustein, Mordecai P.

    2012-01-01

    The Milan hypertensive strain (MHS) rats are a genetic model of hypertension with adducin gene polymorphisms linked to enhanced renal tubular Na+ reabsorption. Recently we demonstrated that Ca2+ signaling is augmented in freshly isolated mesenteric artery myocytes from MHS rats. This is associated with greatly enhanced expression of Na+/Ca2+ exchanger-1 (NCX1), C-type transient receptor potential (TRPC6) protein, and sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA2) compared with arteries from Milan normotensive strain (MNS) rats. Here, we test the hypothesis that the enhanced Ca2+ signaling in MHS arterial smooth muscle is directly reflected in augmented vasoconstriction [myogenic and phenylephrine (PE)-evoked responses] in isolated mesenteric small arteries. Systolic blood pressure was higher in MHS (145 ± 1 mmHg) than in MNS (112 ± 1 mmHg; P arteries from MHS rats had significantly augmented myogenic tone and reactivity and enhanced constriction to low-dose (1–100 nM) PE. Isolated MHS arterial myocytes exhibited approximately twofold increased peak Ca2+ signals in response to 5 μM PE or ATP in the absence and presence of extracellular Ca2+. These augmented responses are consistent with increased vasoconstrictor-evoked sarcoplasmic reticulum (SR) Ca2+ release and increased Ca2+ entry, respectively. The increased SR Ca2+ release correlates with a doubling of inositol 1,4,5-trisphosphate receptor type 1 and tripling of SERCA2 expression. Pressurized MHS arteries also exhibited a ∼70% increase in 100 nM ouabain-induced vasoconstriction compared with MNS arteries. These functional alterations reveal that, in a genetic model of hypertension linked to renal dysfunction, multiple mechanisms within the arterial myocytes contribute to enhanced Ca2+ signaling and myogenic and vasoconstrictor-induced arterial constriction. MHS rats have elevated plasma levels of endogenous ouabain, which may initiate the protein upregulation and enhanced Ca2+ signaling. These

  6. Disorder effects in the S=1 antiferromagnetic spin ladder CaV{sub 2}O{sub 4}

    Energy Technology Data Exchange (ETDEWEB)

    Guitarra, S.R. [Colegio de Ciencias e Ingeniería, Universidad San Francisco de Quito, Quito (Ecuador); Caneiro, A. [Instituto Balseiro - Centro Atómico Bariloche, 8400 Bariloche (Argentina); Niebieskikwiat, D., E-mail: dniebieskikwiat@usfq.edu.ec [Colegio de Ciencias e Ingeniería, Universidad San Francisco de Quito, Quito (Ecuador)

    2015-10-15

    We study the physical properties of the antiferromagnetic spin ladder CaV{sub 2}O{sub 4} (CVO) and the Y-doped related compound Ca{sub 0.9}Y{sub 0.1}V{sub 2}O{sub 4}. In the latter, X-ray diffraction demonstrates the segregation of a small amount of a vanadium–perovskite impurity phase, leading to the formation of V vacancies within the main CVO-type structure. The 1D character of this calcium–vanadite enhances the influence of the vacancies on the electric and magnetic properties of Ca{sub 0.9}Y{sub 0.1}V{sub 2}O{sub 4}. Electrical transport is characterized by a variable-range hopping mechanism determined by the charging energy of nm-sized segments of V chains delimited by V vacancies, i.e. a Coulomb gap is formed at the Fermi level. These vacancies also locally affect the magnetic correlations, breaking the long-range AFM order observed in CaV{sub 2}O{sub 4} and producing exchange bias when the Y-doped sample is cooled with an applied magnetic field. - Highlights: • We study disorder effects in the quasi-1D antiferromagnetic spin ladder CaV{sub 2}O{sub 4}. • V vacancies in CaV{sub 2}O{sub 4} lead to variable-range hopping electrical transport. • The charging energy of nm-sized V chains determine the transport mechanism exponents. • V vacancies break the long-range AFM order of CaV{sub 2}O{sub 4}. • Local magnetic correlations in the vicinity of the defects produce exchange bias.

  7. Ca and Mg binding induce conformational stability of Calfumirin-1 ...

    Indian Academy of Sciences (India)

    The thermal unfolding curves of wtCAF-1 monitored at neutral pH by CD spectroscopy are reversible and show ... These domains have either structurally dependent or independent Ca2+- ... that behave as a Ca2+ sensor protein, CaBP1 and.

  8. Were Viking Dry-dock methods in the Americas used earlier to Build Pyramids, with Outflow Eroding the Sphinx, and were Stonehenge, the Obelisks, and Moas Similarly Erected?

    Science.gov (United States)

    McLeod, Edward; McLeod, Roger

    2006-03-01

    Chisel-quarried recycled granite in MA is datable by runes to 1069 CE; it could corroborate dating by a LIDAR. Associated sites, possibly used by Vikings to dry-dock their ships, could have exploited lock-like controls, possibly a continued technology. Site-leveling at the Giza Pyramids proves water was used. `Locks' and body-immersion worked for building, moving, erecting, or watering, at sites like Stonehenge, The Hanging Gardens at Babylon, the Moas of Easter Island, or The Pyramids, where the eroding water discharge was deliberately flushed over the Sphinx complex. It enhance the electromagnetically excited blue light signals we can detect, especially at sites frequented by Molocket of ME. Information, as at America's Stonehenge, in NH, and constructions at Acton MA, at Giza or at Rumford ME proves that the Pyramids and Sphinx were engineered and built about 4500 BP.

  9. The Conflict Pyramid: A Holistic Approach to Structuring Conflict Resolution in Schools

    Science.gov (United States)

    Hakvoort, Ilse

    2010-01-01

    This paper examines how the conflict pyramid, originally defined and used by Richard Cohen, can be used as a model to describe the relations between different conflict resolution education programs and activities included in the programs. The central questions posed in the paper are: How can Richard Cohen's conflict pyramid be used as a model for…

  10. Effects of 45Ca on murine skeletal muscle. 1

    International Nuclear Information System (INIS)

    Asotra, K.; Katoch, S.S.; Krishan, K.; Malhotra, R.K.

    1983-01-01

    Adult Swiss albino mice weighing 16+-1 g were injected with 3.7x10 4 Bq and 7.4x10 4 Bq/g body weight of 45 Ca. Mice of both dose groups were autopsied on days 1, 3, 5, 7, 14 and 28 after 45 Ca administration. Diaphragm and gastrocnemius in the 45 Ca-treated and normal mice were analyzed for quantitation of glycogen as well as bioassay of phosphorylase and phosphohexose isomerase activities. Internal irradiation with the two doses of 45 Ca resulted in glycogen accumulation in both the muscles. 45 Ca-treated diaphragm showed greater radioresponse but a slower recovery than gastrocnemius with respect to glycogen accumulation. A decline in the rates of glycogenolysis and glycolysis indicated by decreased phosphorylase and phosphohexose isomerase activities appeared to be responsible for glycogen accumulation in skeletal muscle on account of 45 Ca treatment. (author)

  11. On higher order pyramidal finite elements

    Czech Academy of Sciences Publication Activity Database

    Liu, L.; Davies, K.B.; Křížek, Michal; Guan, L.

    2011-01-01

    Roč. 3, č. 2 (2011), s. 131-140 ISSN 2070-0733 R&D Projects: GA AV ČR(CZ) IAA100190803 Institutional research plan: CEZ:AV0Z10190503 Keywords : pyramidal polynomial basis functions * finite element method * composite elements * three-dimensional mortar elements Subject RIV: BA - General Mathematics Impact factor: 0.750, year: 2011

  12. PPARγ agonists upregulate sphingosine 1-phosphate (S1P) receptor 1 expression, which in turn reduces S1P-induced [Ca(2+)]i increases in renal mesangial cells.

    Science.gov (United States)

    Koch, Alexander; Völzke, Anja; Puff, Bianca; Blankenbach, Kira; Meyer Zu Heringdorf, Dagmar; Huwiler, Andrea; Pfeilschifter, Josef

    2013-11-01

    We previously identified peroxisome proliferator-activated receptor gamma (PPARγ) agonists (thiazolidinediones, TZDs) as modulators of the sphingolipid metabolism in renal mesangial cells. TZDs upregulated sphingosine kinase 1 (SK-1) and increased the formation of intracellular sphingosine 1-phosphate (S1P), which in turn reduced the expression of pro-fibrotic connective tissue growth factor. Since S1P also acts as extracellular ligand at specific S1P receptors (S1PR, S1P1-5), we investigated here the effect of TZDs on S1PR expression in mesangial cells and evaluated the functional consequences by measuring S1P-induced increases in intracellular free Ca(2+) concentration ([Ca(2+)]i). Treatment with two different TZDs, troglitazone and rosiglitazone, enhanced S1P1 mRNA and protein expression in rat mesangial cells, whereas S1P2-5 expression levels were not altered. Upregulation of S1P1 mRNA upon TZD treatment was also detected in human mesangial cells and mouse glomeruli. PPARγ antagonism and promoter studies revealed that the TZD-dependent S1P1 mRNA induction involved a functional PPAR response element in the S1P1 promoter. Pharmacological approaches disclosed that S1P-induced [Ca(2+)]i increases in rat mesangial cells were predominantly mediated by S1P2 and S1P3. Interestingly, the transcriptional upregulation of S1P1 by TZDs resulted in a reduction of S1P-induced [Ca(2+)]i increases, which was reversed by the S1P1/3 antagonist VPC-23019, the protein kinase C (PKC) inhibitor PKC-412, and by S1P1 siRNA. These data suggest that PPARγ-dependent upregulation of S1P1 leads to an inhibition of S1P-induced Ca(2+) signaling in a PKC-dependent manner. Overall, these results reveal that TZDs not only modulate intracellular S1P levels but also regulate S1PR signaling by increasing S1P1 expression in mesangial cells. © 2013.

  13. Estrogen administration modulates hippocampal GABAergic subpopulations in the hippocampus of trimethyltin-treated rats

    Directory of Open Access Journals (Sweden)

    Valentina eCorvino

    2015-11-01

    Full Text Available Given the well-documented involvement of estrogens in the modulation of hippocampal functions in both physiological and pathological conditions, the present study investigates the effects of 17-beta estradiol (E2 administration in the rat model of hippocampal neurodegeneration induced by trimethyltin (TMT administration (8mg/kg, characterized by loss of pyramidal neurons in CA1, CA3/hilus hippocampal subfields associated with astroglial and microglial activation, seizures and cognitive impairment. After TMT/saline treatment, ovariectomized animals received two doses of E2 (0.2 mg/kg i.p. or vehicle, and were sacrificed 48h or 7 days after TMT-treatment. Our results indicate that in TMT-treated animals E2 administration induces the early (48h upregulation of genes involved in neuroprotection and synaptogenesis, namely Bcl2, trkB, Cadherin and cyclin-dependent-kinase-5. Increased expression levels of glutamic acid decarboxylase (gad 67, neuropeptide Y (Npy, parvalbumin , Pgc-1α and Sirtuin 1genes, the latter involved in parvalbumin (PV synthesis, were also evident. Unbiased stereology performed on rats sacrificed 7 days after TMT treatment showed that although E2 does not significantly influence the extent of TMT-induced neuronal death, significantly enhances the TMT-induced modulation of GABAergic interneuron population size in selected hippocampal subfields. In particular, E2 administration causes, in TMT treated rats, a significant increase in the number of GAD67-expressing interneurons in CA1 stratum oriens, CA3 pyramidal layer, hilus and dentate gyrus, accompanied by a parallel increase in NPY-expressing cells, essentially in the same regions, and of PV-positive cells in CA1 pyramidal layer. The present results add information concerning the role of in vivo E2 administration on mechanisms involved in cellular plasticity in the adult brain.

  14. Inhibiting cholesterol degradation induces neuronal sclerosis and epileptic activity in mouse hippocampus

    Science.gov (United States)

    Chali, Farah; Djelti, Fathia; Eugene, Emmanuel; Valderrama, Mario; Marquer, Catherine; Aubourg, Patrick; Duykaerts, Charles; Miles, Richard; Cartier, Nathalie; Navarro, Vincent

    2015-01-01

    Elevations in neuronal cholesterol have been associated with several degenerative diseases. An enhanced excitability and synchronous firing in surviving neurons are among the sequels of neuronal death in these diseases and also in some epileptic syndromes. Here, we attempted to increase neuronal cholesterol levels, using a short hairpin RNA (shRNA) to suppress expression of the enzyme CYP46A1. This protein hydroxylates cholesterol and so facilitates trans-membrane extrusion. A sh-RNA CYP46A1construction coupled to an adeno-associated virus (AAV5) was injected focally and unilaterally into mouse hippocampus. It was selectively expressed first in neurons of the CA3a region. Cytoplasmic and membrane cholesterol increased, neuronal soma volume increased and then decreased before pyramidal cells died. As CA3a pyramidal cells died, inter-ictal EEG events occurred during exploration and non-REM sleep. With time, neuronal death spread to involve pyramidal cells and interneurons of the CA1 region. CA1 neuronal death was correlated with a delayed local expression of phosphorylated tau. Astrocytes were activated throughout the hippocampus and microglial activation was specific to regions of neuronal death. CA1 neuronal death was correlated with distinct aberrant EEG activity. During exploratory behaviour and rapid eye movement sleep, EEG oscillations at 7-10 Hz (theta) could accelerate to 14-21 Hz (beta) waves. They were accompanied by low amplitude, high-frequency oscillations of peak power at ~300Hz and a range of 250-350 Hz. While episodes of EEG acceleration were not correlated with changes in exploratory behaviour, they were followed in some animals by structured seizure-like discharges. These data strengthen links between increased cholesterol, neuronal sclerosis and epileptic behavior PMID:25847620

  15. Static Posturography and Falls According to Pyramidal, Sensory and Cerebellar Functional Systems in People with Multiple Sclerosis

    Science.gov (United States)

    Kalron, Alon; Givon, Uri; Frid, Lior; Dolev, Mark; Achiron, Anat

    2016-01-01

    Balance impairment is common in people with multiple sclerosis (PwMS) and frequently impacts quality of life by decreasing mobility and increasing the risk of falling. However, there are only scarce data examining the contribution of specific neurological functional systems on balance measures in MS. Therefore, the primary aim of our study was to examine the differences in posturography parameters and fall incidence according to the pyramidal, cerebellar and sensory systems functional systems in PwMS. The study included 342 PwMS, 211 women and mean disease duration of 8.2 (S.D = 8.3) years. The study sample was divided into six groups according to the pyramidal, cerebellar and sensory functional system scores, derived from the Expanded Disability Status Scale (EDSS) data. Static postural control parameters were obtained from the Zebris FDM-T Treadmill (zebris® Medical GmbH, Germany). Participants were defined as "fallers" and "non-fallers" based on their fall history. Our findings revealed a trend that PwMS affected solely in the pyramidal system, have reduced stability compared to patients with cerebellar and sensory dysfunctions. Moreover, the addition of sensory impairments to pyramidal dysfunction does not exacerbate postural control. The patients in the pure sensory group demonstrated increased stability compared to each of the three combined groups; pyramidal-cerebellar, pyramidal-sensory and pyramidal-cerebellar-sensory groups. As for fall status, the percentage of fallers in the pure pyramidal, cerebellar and sensory groups were 44.3%, 33.3% and 19.5%, respectively. As for the combined functional system groups, the percentage of fallers in the pyramidal-cerebellar, pyramidal-sensory and pyramidal-cerebellar-sensory groups were 59.7%, 40.7% and 65%, respectively. This study confirms that disorders in neurological functional systems generate different effects on postural control and incidence of falls in the MS population. From a clinical standpoint, the

  16. Static Posturography and Falls According to Pyramidal, Sensory and Cerebellar Functional Systems in People with Multiple Sclerosis.

    Science.gov (United States)

    Kalron, Alon; Givon, Uri; Frid, Lior; Dolev, Mark; Achiron, Anat

    2016-01-01

    Balance impairment is common in people with multiple sclerosis (PwMS) and frequently impacts quality of life by decreasing mobility and increasing the risk of falling. However, there are only scarce data examining the contribution of specific neurological functional systems on balance measures in MS. Therefore, the primary aim of our study was to examine the differences in posturography parameters and fall incidence according to the pyramidal, cerebellar and sensory systems functional systems in PwMS. The study included 342 PwMS, 211 women and mean disease duration of 8.2 (S.D = 8.3) years. The study sample was divided into six groups according to the pyramidal, cerebellar and sensory functional system scores, derived from the Expanded Disability Status Scale (EDSS) data. Static postural control parameters were obtained from the Zebris FDM-T Treadmill (zebris® Medical GmbH, Germany). Participants were defined as "fallers" and "non-fallers" based on their fall history. Our findings revealed a trend that PwMS affected solely in the pyramidal system, have reduced stability compared to patients with cerebellar and sensory dysfunctions. Moreover, the addition of sensory impairments to pyramidal dysfunction does not exacerbate postural control. The patients in the pure sensory group demonstrated increased stability compared to each of the three combined groups; pyramidal-cerebellar, pyramidal-sensory and pyramidal-cerebellar-sensory groups. As for fall status, the percentage of fallers in the pure pyramidal, cerebellar and sensory groups were 44.3%, 33.3% and 19.5%, respectively. As for the combined functional system groups, the percentage of fallers in the pyramidal-cerebellar, pyramidal-sensory and pyramidal-cerebellar-sensory groups were 59.7%, 40.7% and 65%, respectively. This study confirms that disorders in neurological functional systems generate different effects on postural control and incidence of falls in the MS population. From a clinical standpoint, the

  17. The Ca2+ Status of the Endoplasmic Reticulum Is Altered by Induction of Calreticulin Expression in Transgenic Plants1

    Science.gov (United States)

    Persson, Staffan; Wyatt, Sarah E.; Love, John; Thompson, William F.; Robertson, Dominique; Boss, Wendy F.

    2001-01-01

    To investigate the endoplasmic reticulum (ER) Ca2+ stores in plant cells, we generated tobacco (Nicotiana tabacum; NT1) suspension cells and Arabidopsis plants with altered levels of calreticulin (CRT), an ER-localized Ca2+-binding protein. NT1 cells and Arabidopsis plants were transformed with a maize (Zea mays) CRT gene in both sense and antisense orientations under the control of an Arabidopsis heat shock promoter. ER-enriched membrane fractions from NT1 cells were used to examine how altered expression of CRT affects Ca2+ uptake and release. We found that a 2.5-fold increase in CRT led to a 2-fold increase in ATP-dependent 45Ca2+ accumulation in the ER-enriched fraction compared with heat-shocked wild-type controls. Furthermore, after treatment with the Ca2+ ionophore ionomycin, ER microsomes from NT1 cells overproducing CRT showed a 2-fold increase in the amount of 45Ca2+ released, and a 2- to 3-fold increase in the amount of 45Ca2+ retained compared with wild type. These data indicate that altering the production of CRT affects the ER Ca2+ pool. In addition, CRT transgenic Arabidopsis plants were used to determine if altered CRT levels had any physiological effects. We found that the level of CRT in heat shock-induced CRT transgenic plants correlated positively with the retention of chlorophyll when the plants were transferred from Ca2+-containing medium to Ca2+-depleted medium. Together these data are consistent with the hypothesis that increasing CRT in the ER increases the ER Ca2+ stores and thereby enhances the survival of plants grown in low Ca2+ medium. PMID:11457960

  18. Solidification of Bi2Sr2Ca1Cu2Oy and Bi2Sr1.75Ca0.25CuOy

    International Nuclear Information System (INIS)

    Holesinger, T.G.; Miller, D.J.; Viswanathan, H.K.; Chumbley, L.S.

    1993-01-01

    The solidification processes for the compositions Bi 2 Sr 2 CaCu 2 O y (2212) and Bi 2 Sr 1.75 Ca 0.25 CuO y (2201) were determined as a function of oxygen partial pressure. During solidification in argon, the superconducting phases were generally not observed to form for either composition. In both cases, the solidus is lowered to approximately 750 degree C. Solidification of Bi 2 Sr 1.75 Ca 0.25 CuO y in Ar resulted in a divorced eutectic structure of Bi 2 Sr 2-x Ca x O y (22x) and Cu 2 O while solidification of Bi 2 Sr 2 CaCu 2 O y in Ar resulted in a divorced eutectic structure of Bi 2 Sr 3-x Ca x O y (23x) and Cu 2 O. Solidification of Bi 2 Sr 1.75 Ca 0.25 CuO y in O 2 resulted in large grains of 2201 interspersed with small regions containing the eutectic structure of 22x and CuO/Cu 2 O. Solidification of Bi 2 Sr 2 CaCu 2 O y in partial pressures of 1%, 20%, and 100% oxygen resulted in multiphase samples consisting of 2212, 2201, some alkaline-earth cuprates, and both divorced eutectic structures found during solidification in Ar. For both compositions, these latter structures can be attributed to oxygen deficiencies present in the melt regardless of the overpressure of oxygen. These eutectic structures are unstable and convert into the superconducting phases during subsequent anneals in oxygen. The formation process of the 2212 phase during solidification from the melt was determined to proceed through an intermediate state involving the 2201 phase

  19. Sparse aperture differential piston measurements using the pyramid wave-front sensor

    Science.gov (United States)

    Arcidiacono, Carmelo; Chen, Xinyang; Yan, Zhaojun; Zheng, Lixin; Agapito, Guido; Wang, Chaoyan; Zhu, Nenghong; Zhu, Liyun; Cai, Jianqing; Tang, Zhenghong

    2016-07-01

    In this paper we report on the laboratory experiment we settled in the Shanghai Astronomical Observatory (SHAO) to investigate the pyramid wave-front sensor (WFS) ability to measure the differential piston on a sparse aperture. The ultimate goal is to verify the ability of the pyramid WFS work in close loop to perform the phasing of the primary mirrors of a sparse Fizeau imaging telescope. In the experiment we installed on the optical bench we performed various test checking the ability to flat the wave-front using a deformable mirror and to measure the signal of the differential piston on a two pupils setup. These steps represent the background from which we start to perform full close loop operation on multiple apertures. These steps were also useful to characterize the achromatic double pyramids (double prisms) manufactured in the SHAO optical workshop.

  20. Study of heat conductivity, electric conductivity and thermo-emf of BiSrCaCu2Ox and Bi1.82Sr1.73Ca1.73Ca1.25Cu2.2Ox systems

    International Nuclear Information System (INIS)

    Zhukova, T.B.; Parfen'eva, L.S.; Popov, V.V.; Melekh, B.T.; Smirnov, I.A.; Khalmedov, Kh.M.

    1991-01-01

    Phase compositions are determined and temperature dependences are measured of x-heat conductivity, ρ-electric resistance and α-thermo-emf of polycrystal, monophase, highly textured HTSC samples of BiSrCaCu 2 O x and Bi 1.82 Sr 1.73 Ca 1.25 Cu 2.2 O x produced through method of direct induction melting in the air in a cold container. Sample 'aging' after storage in the air and vacuum, leading to decrease in the number of foring phases and increase in the basic phase content as well as to change of x, ρ and α coefficients is identified

  1. Usefulness of MR coronal imaging of the ''pyramidal line''. Predictive value in motor function of stroke patients

    International Nuclear Information System (INIS)

    Satoh, Kenichi; Matsuzaki, Takayuki; Shimazaki, Mitsunori

    1997-01-01

    A coronal image was obtained along a straight line between the front edge of the medulla and the deepest point of the interpeduncular cistern in the midsagittal plane (the ''pyramidal line''). This coronal image along the pyramidal line revealed the pyramidal tract extending from the internal capsule down to the medulla. Using this technique, we studied 25 patients with motor deficit associated with cerebrovascular disease. We predicted the possibility of their recovery in the subacute stage. We were able to predict the recovery in 23 patients (92%). We conclude that a coronal image along the pyramidal line is useful for the understanding of relation between pyramidal tract and lesion and for predicting motor function. (author)

  2. Usefulness of MR coronal imaging of the ``pyramidal line``. Predictive value in motor function of stroke patients

    Energy Technology Data Exchange (ETDEWEB)

    Satoh, Kenichi; Matsuzaki, Takayuki; Shimazaki, Mitsunori [Hakodate Red Cross Hospital, Hokkaido (Japan)

    1997-06-01

    A coronal image was obtained along a straight line between the front edge of the medulla and the deepest point of the interpeduncular cistern in the midsagittal plane (the ``pyramidal line``). This coronal image along the pyramidal line revealed the pyramidal tract extending from the internal capsule down to the medulla. Using this technique, we studied 25 patients with motor deficit associated with cerebrovascular disease. We predicted the possibility of their recovery in the subacute stage. We were able to predict the recovery in 23 patients (92%). We conclude that a coronal image along the pyramidal line is useful for the understanding of relation between pyramidal tract and lesion and for predicting motor function. (author)

  3. 1,25 (OH)2 vitamin D3-induced 45Ca uptake in vascular myocytes cultured from spontaneously hypertensive and normotensive rats

    International Nuclear Information System (INIS)

    Xue, Hong; McCarron, D.A.; Bukoski, R.D.

    1991-01-01

    The effect of 1,25 (OH) 2 vitamin D 3 on basal 45 Ca uptake was examined in vasvular smooth muscle cells cultured from mesenteric arteries of spontaneously hypertensive (SHR) and Wistar Kyoto (WKY) normotensive rats. Basal uptake of 45 Ca was significantly greater in myocytes of WKY than SHR at 5, 10, 30 and 60 min incubation with the isotope. Incubation with 1 ng/ml 1,25 (OH) 2 vitamin D 3 for 48 hr increased basal 45 Ca uptake between 1-10 min in SHR and between 5-10 min in WKY. The dose-response relationship indicated that cells from both strains are equally sensitive to the calciotropic effects of 1,25 (OH) 2 vitamin D 3 with half-maximal stimulation occurring at approximately 0.3-0.4 ng/ml. In cells of both strains maximal stimulation of 45 Ca uptake was achieved only after a 12-24 hr period of incubation with hormone and pretreatment with cycloheximide inhibited 1,24 (OH) 2 vitamin D 3 -enhanced 45 Ca uptake. Although 45 Ca binding by extracellular matrix material was significantly greater in WKY than SHR, 1,25 (OH) 2 vitamin D 3 had no effect on the amount of matrix 45 Ca binding in either strain

  4. Field emission properties of an array of pyramidal structures

    Energy Technology Data Exchange (ETDEWEB)

    De Assis, Thiago A [Departamento de QuImica, Universidad Autonoma de Madrid, Cantoblanco, 28049 Madrid (Spain); Borondo, F [Departamento de QuImica, Instituto Mixto de Ciencias Matematicas CSIC-UAM-UC3M-UCM, Universidad Autonoma de Madrid, Cantoblanco, 28049 Madrid (Spain); De Castilho, C M C; Brito Mota, F [Grupo de Fisica de SuperfIcies e Materiais, Instituto de Fisica, Universidade Federal da Bahia, Campus Universitario da Federacao, 40210-340, Salvador, BA (Brazil); Benito, R M, E-mail: t.albuquerque@uam.e, E-mail: f.borondo@uam.e, E-mail: caio@ufba.b, E-mail: fbmota@ufba.b, E-mail: rosamaria.benito@upm.e [Grupo de Sistemas Complejos, Departamento de Fisica y Mecanica, Escuela Tecnica Superior de Ingenieros Agronomos, Universidad Politecnica de Madrid, Ciudad Universitaria, 28040 Madrid (Spain)

    2009-10-07

    The properties and efficiency of the emission current density produced by a metallic array of pyramidal structures are investigated. The theoretical results obtained by numerical integration of the corresponding Laplace equation using a finite differences scheme offer useful information for the optimization of field emission devices based on cathodes with this geometry. Our study shows that the inter-pyramidal distance strongly affects the current density, and even more important for this issue is the protrusion characteristics of these structures. Another relevant, although less important, parameter determining this density is the anode-cathode distance. The effect of the array characteristics on the maximum local electric field intensity is also discussed.

  5. Construction and evaluation of BSA-CaP nanomaterials with enhanced transgene performance via biocorona-inspired caveolae-mediated endocytosis

    Science.gov (United States)

    Ma, Xi-Xi; Gao, Han; Zhang, Ya-Xuan; Jia, Yi-Yang; Li, Chen; Zhou, Si-Yuan; Zhang, Bang-Le

    2018-02-01

    Non-viral nanovectors have attracted much attention owing to their ability to condense genetic materials and their ease of modification. However, their poor stability, low biocompatibility and gene degradation in endosomes or lysosomes has significantly hampered their application in vivo and in the clinic. In an attempt to overcome these difficulties a series of bovine serum albumin (BSA)-calcium phosphate (CaP) nanoparticles were constructed. The CaP condenses with DNA to form nanocomplexes coated with a biomimetic corona of BSA. Such complexes may retain the inherent endocytosis profile of BSA, with improved biocompatibility. In particular the transgene performance may be enhanced by stimulating the cellular uptake pathway via caveolae-mediated endocytosis. Two methods were employed to construct and optimize the formulation of BSA-CaP nanomaterials. The optimized BSA-CaP-50-M2 nanoparticles prepared by our second method exhibited good stability, negligible cytotoxicity and enhanced transgene performance with long-term expression for 72 h in vivo even with a single dose. Determination of the cellular uptake pathway and Western blot revealed that cellular uptake of the designed BSA-CaP-50-M2 nanoparticles was mainly via caveolae-mediated endocytosis in a non-degradative pathway in which the biomimetic uptake profile of BSA was retained.

  6. Lysosomes shape Ins(1,4,5)P3-evoked Ca2+ signals by selectively sequestering Ca2+ released from the endoplasmic reticulum

    Science.gov (United States)

    López-Sanjurjo, Cristina I.; Tovey, Stephen C.; Prole, David L.; Taylor, Colin W.

    2013-01-01

    Summary Most intracellular Ca2+ signals result from opening of Ca2+ channels in the plasma membrane or endoplasmic reticulum (ER), and they are reversed by active transport across these membranes or by shuttling Ca2+ into mitochondria. Ca2+ channels in lysosomes contribute to endo-lysosomal trafficking and Ca2+ signalling, but the role of lysosomal Ca2+ uptake in Ca2+ signalling is unexplored. Inhibition of lysosomal Ca2+ uptake by dissipating the H+ gradient (using bafilomycin A1), perforating lysosomal membranes (using glycyl-L-phenylalanine 2-naphthylamide) or lysosome fusion (using vacuolin) increased the Ca2+ signals evoked by receptors that stimulate inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] formation. Bafilomycin A1 amplified the Ca2+ signals evoked by photolysis of caged Ins(1,4,5)P3 or by inhibition of ER Ca2+ pumps, and it slowed recovery from them. Ca2+ signals evoked by store-operated Ca2+ entry were unaffected by bafilomycin A1. Video-imaging with total internal reflection fluorescence microscopy revealed that lysosomes were motile and remained intimately associated with the ER. Close association of lysosomes with the ER allows them selectively to accumulate Ca2+ released by Ins(1,4,5)P3 receptors. PMID:23097044

  7. Regulatory Phosphorylation of Bacterial-Type PEP Carboxylase by the Ca2+-Dependent Protein Kinase RcCDPK1 in Developing Castor Oil Seeds1[OPEN

    Science.gov (United States)

    Hill, Allyson T.; Anderson, Erin M.; She, Yi-Min

    2017-01-01

    Phosphoenolpyruvate carboxylase (PEPC) is a tightly controlled cytosolic enzyme situated at a crucial branch point of central plant metabolism. In developing castor oil seeds (Ricinus communis) a novel, allosterically desensitized 910-kD Class-2 PEPC hetero-octameric complex, arises from a tight interaction between 107-kD plant-type PEPC and 118-kD bacterial-type (BTPC) subunits. The native Ca2+-dependent protein kinase (CDPK) responsible for in vivo inhibitory phosphorylation of Class-2 PEPC’s BTPC subunit’s at Ser-451 was highly purified from COS and identified as RcCDPK1 (XP_002526815) by mass spectrometry. Heterologously expressed RcCDPK1 catalyzed Ca2+-dependent, inhibitory phosphorylation of BTPC at Ser-451 while exhibiting: (i) a pair of Ca2+ binding sites with identical dissociation constants of 5.03 μM, (ii) a Ca2+-dependent electrophoretic mobility shift, and (iii) a marked Ca2+-independent hydrophobicity. Pull-down experiments established the Ca2+-dependent interaction of N-terminal GST-tagged RcCDPK1 with BTPC. RcCDPK1-Cherry localized to the cytosol and nucleus of tobacco bright yellow-2 cells, but colocalized with mitochondrial-surface associated BTPC-enhanced yellow fluorescent protein when both fusion proteins were coexpressed. Deletion analyses demonstrated that although its N-terminal variable domain plays an essential role in optimizing Ca2+-dependent RcCDPK1 autophosphorylation and BTPC transphosphorylation activity, it is not critical for in vitro or in vivo target recognition. Arabidopsis (Arabidopsis thaliana) CPK4 and soybean (Glycine max) CDPKβ are RcCDPK1 orthologs that effectively phosphorylated castor BTPC at Ser-451. Overall, the results highlight a potential link between cytosolic Ca2+ signaling and the posttranslational control of respiratory CO2 refixation and anaplerotic photosynthate partitioning in support of storage oil and protein biosynthesis in developing COS. PMID:28363991

  8. Calcium binding properties of calcium dependent protein kinase 1 (CaCDPK1) from Cicer arietinum.

    Science.gov (United States)

    Dixit, Ajay Kumar; Jayabaskaran, Chelliah

    2015-05-01

    Calcium plays a crucial role as a secondary messenger in all aspects of plant growth, development and survival. Calcium dependent protein kinases (CDPKs) are the major calcium decoders, which couple the changes in calcium level to an appropriate physiological response. The mechanism by which calcium regulates CDPK protein is not well understood. In this study, we investigated the interactions of Ca(2+) ions with the CDPK1 isoform of Cicer arietinum (CaCDPK1) using a combination of biophysical tools. CaCDPK1 has four different EF hands as predicted by protein sequence analysis. The fluorescence emission spectrum of CaCDPK1 showed quenching with a 5 nm red shift upon addition of calcium, indicating conformational changes in the tertiary structure. The plot of changes in intensity against calcium concentrations showed a biphasic curve with binding constants of 1.29 μM and 120 μM indicating two kinds of binding sites. Isothermal calorimetric (ITC) titration with CaCl2 also showed a biphasic curve with two binding constants of 0.027 μM and 1.7 μM. Circular dichroism (CD) spectra showed two prominent peaks at 208 and 222 nm indicating that CaCDPK1 is a α-helical rich protein. Calcium binding further increased the α-helical content of CaCDPK1 from 75 to 81%. Addition of calcium to CaCDPK1 also increased fluorescence of 8-anilinonaphthalene-1-sulfonic acid (ANS) indicating exposure of hydrophobic surfaces. Thus, on the whole this study provides evidence for calcium induced conformational changes, exposure of hydrophobic surfaces and heterogeneity of EF hands in CaCDPK1. Copyright © 2015 Elsevier GmbH. All rights reserved.

  9. CD147 reinforces [Ca2+]i oscillations and promotes oncogenic progression in hepatocellular carcinoma.

    Science.gov (United States)

    Tang, Juan; Guo, Yun-Shan; Yu, Xiao-Ling; Huang, Wan; Zheng, Ming; Zhou, Ying-Hui; Nan, Gang; Wang, Jian-Chao; Yang, Hai-Jiao; Yu, Jing-Min; Jiang, Jian-Li; Chen, Zhi-Nan

    2015-10-27

    Oscillations in intracellular Ca2+ concentrations ([Ca2+]i) mediate various cellular function. Although it is known that [Ca2+]i oscillations are susceptible to dysregulation in tumors, the tumor-specific regulators of [Ca2+]i oscillations are poorly characterized. We discovered that CD147 promotes hepatocellular carcinoma (HCC) metastasis and proliferation by enhancing the amplitude and frequency of [Ca2+]i oscillations in HCC cells. CD147 activates two distinct signaling pathways to regulate [Ca2+]i oscillations. By activating FAK-Src-IP3R1 signaling pathway, CD147 promotes Ca2+ release from endoplasmic reticulum (ER) and enhances the amplitude of [Ca2+]i oscillations. Furthermore, CD147 accelerates ER Ca2+refilling and enhances the frequency of [Ca2+]i oscillations through activating CaMKP-PAK1-PP2A-PLB-SERCA signaling pathway. Besides, CD147-promoted ER Ca2+ release and refilling are tightly regulated by changing [Ca2+]i. CD147 may activate IP3R1 channel under low [Ca2+]i conditions and CD147 may activate SERCA pump under high [Ca2+]i conditions. CD147 deletion suppresses HCC tumorigenesis and increases the survival rate of liver-specific CD147 knockout mice by regulating [Ca2+]i oscillations in vivo. Together, these results reveal that CD147 functions as a critical regulator of ER-dependent [Ca2+]i oscillations to promote oncogenic progression in HCC.

  10. Self-assembly of the general membrane-remodeling protein PVAP into sevenfold virus-associated pyramids.

    Science.gov (United States)

    Daum, Bertram; Quax, Tessa E F; Sachse, Martin; Mills, Deryck J; Reimann, Julia; Yildiz, Özkan; Häder, Sabine; Saveanu, Cosmin; Forterre, Patrick; Albers, Sonja-Verena; Kühlbrandt, Werner; Prangishvili, David

    2014-03-11

    Viruses have developed a wide range of strategies to escape from the host cells in which they replicate. For egress some archaeal viruses use a pyramidal structure with sevenfold rotational symmetry. Virus-associated pyramids (VAPs) assemble in the host cell membrane from the virus-encoded protein PVAP and open at the end of the infection cycle. We characterize this unusual supramolecular assembly using a combination of genetic, biochemical, and electron microscopic techniques. By whole-cell electron cryotomography, we monitored morphological changes in virus-infected host cells. Subtomogram averaging reveals the VAP structure. By heterologous expression of PVAP in cells from all three domains of life, we demonstrate that the protein integrates indiscriminately into virtually any biological membrane, where it forms sevenfold pyramids. We identify the protein domains essential for VAP formation in PVAP truncation mutants by their ability to remodel the cell membrane. Self-assembly of PVAP into pyramids requires at least two different, in-plane and out-of-plane, protein interactions. Our findings allow us to propose a model describing how PVAP arranges to form sevenfold pyramids and suggest how this small, robust protein may be used as a general membrane-remodeling system.

  11. Discovery of a big void in Khufu’s Pyramid by observation of cosmic-ray muons

    Science.gov (United States)

    Morishima, Kunihiro; Kuno, Mitsuaki; Nishio, Akira; Kitagawa, Nobuko; Manabe, Yuta; Moto, Masaki; Takasaki, Fumihiko; Fujii, Hirofumi; Satoh, Kotaro; Kodama, Hideyo; Hayashi, Kohei; Odaka, Shigeru; Procureur, Sébastien; Attié, David; Bouteille, Simon; Calvet, Denis; Filosa, Christopher; Magnier, Patrick; Mandjavidze, Irakli; Riallot, Marc; Marini, Benoit; Gable, Pierre; Date, Yoshikatsu; Sugiura, Makiko; Elshayeb, Yasser; Elnady, Tamer; Ezzy, Mustapha; Guerriero, Emmanuel; Steiger, Vincent; Serikoff, Nicolas; Mouret, Jean-Baptiste; Charlès, Bernard; Helal, Hany; Tayoubi, Mehdi

    2017-12-01

    The Great Pyramid, or Khufu’s Pyramid, was built on the Giza plateau in Egypt during the fourth dynasty by the pharaoh Khufu (Cheops), who reigned from 2509 BC to 2483 BC. Despite being one of the oldest and largest monuments on Earth, there is no consensus about how it was built. To understand its internal structure better, we imaged the pyramid using muons, which are by-products of cosmic rays that are only partially absorbed by stone. The resulting cosmic-ray muon radiography allows us to visualize the known and any unknown voids in the pyramid in a non-invasive way. Here we report the discovery of a large void (with a cross-section similar to that of the Grand Gallery and a minimum length of 30 metres) situated above the Grand Gallery. This constitutes the first major inner structure found in the Great Pyramid since the nineteenth century. The void, named ScanPyramids’ Big Void, was first observed with nuclear emulsion films installed in the Queen’s chamber, then confirmed with scintillator hodoscopes set up in the same chamber and finally re-confirmed with gas detectors outside the pyramid. This large void has therefore been detected with high confidence by three different muon detection technologies and three independent analyses. These results constitute a breakthrough for the understanding of the internal structure of Khufu’s Pyramid. Although there is currently no information about the intended purpose of this void, these findings show how modern particle physics can shed new light on the world’s archaeological heritage.

  12. Enhanced structural and optical properties of the polyaniline-calcium tungstate (PANI-CaWO4 nanocomposite for electronics applications

    Science.gov (United States)

    Sabu, N. Aloysius; Francis, Xavier; Anjaly, Jose; Sankararaman, S.; Varghese, Thomas

    2017-06-01

    In this article, we report the synthesis and characterization of polyaniline-calcium tungstate nanocomposite, a novel material for potential applications. The PANI-CaWO4 nanocomposite was prepared by in situ oxidative polymerization of aniline in the presence of CaWO4 nanoparticles dispersed in ethanol. Investigations using X-ray diffraction, Fourier-transformed infrared spectroscopy, UV-visible, photoluminescence and Raman spectroscopy confirmed the formation of the nanocomposite of PANI with CaWO4 nanoparticles. Scanning electron microscopy revealed almost uniform distribution of CaWO4 nanoparticles in the polyaniline matrix. These studies also confirmed electronic structure modification as a result of incorporating CaWO4 nanoparticles in PANI. Composite formation resulted in large decrease in the optical band gap and enhanced photoluminescence. The augmented structural, optical and photoluminescence properties of the PANI-CaWO4 nanocomposite can be used to explore potential applications in micro- and optoelectronics. This is the first report presenting synthesis and characterization of the PANI-CaWO4 nanocomposite.

  13. Nano-pyramid arrays for nano-particle trapping

    NARCIS (Netherlands)

    Sun, Xingwu; Veltkamp, Henk-Willem; Berenschot, Johan W.; Gardeniers, Johannes G.E.; Tas, Niels Roelof

    2016-01-01

    Abstract In this paper we present the drastic miniaturization of nano-wire pyramids fabricated by corner lithography. A particle trapping device was fabricated in a well-defined and symmetrical array. The entrance and exit hole-size can be tuned by adjusting fabrication parameters. We describe here

  14. Foundations of Meta-Pyramids: Languages vs. Metamodels -- Episode II: Story of Thotus the Baboon1

    OpenAIRE

    Favre, Jean-Marie

    2005-01-01

    Despite the recent interest for Model Driven Engineering approaches, the so-called four-layers metamodelling architecture is subject to a lot of debate. The relationship that exists between a model and a metamodel is often called instanceOf, but this terminology, which comes directly from the object oriented technology, is not appropriate for the modelling of similar meta-pyramids in other domains. The goal of this paper is to study which are the foundations of the meta-pyra...

  15. Effects of chronic malnourishment and aging on the ultrastructure of pyramidal cells of the dorsal hippocampus.

    Science.gov (United States)

    Castro-Chavira, Susana Angelica; Aguilar-Vázquez, Azucena Ruth; Martínez-Chávez, Yvonne; Palma, Lourdes; Padilla-Gómez, Euridice; Diaz-Cintra, Sofia

    2016-10-01

    Malnourishment (M) produces permanent alterations during the development of the CNS and might modify the aging process. In pyramidal neurons (PN) of the hippocampus, which are associated with learning and memory performance, few studies have focused on changes at the subcellular level under chronic malnutrition (ChM) in young (Y, 2 months old) and aged (A, 22 months old) rats. The present work evaluated the extent to which ChM disrupts organelles in PN of the dorsal hippocampus CA1 as compared to controls (C). Ultrastructural analysis was performed at 8000×  and 20 000×  magnification: Nucleus eccentricity and somatic, cytoplasmic, and nuclear areas were measured; and in the PN perikaryon, density indices (number of organelles/cytoplasmic area) of Golgi membrane systems (GMS, normal, and swollen), mitochondria (normal and abnormal), and vacuolated organelles (lysosomes, lipofuscin granules, and multivesicular bodies (MVB)) were determined. The density of abnormal mitochondria, swollen GMS, and MVB increased significantly in the AChM group compared to the other groups. The amount of lipofuscin was significantly greater in the AChM than in the YChM groups - a sign of oxidative stress due to malnutrition and aging; however, in Y animals, ChM showed no effect on organelle density or the cytoplasmic area. An increased density of lysosomes as well as nucleus eccentricity was observed in the AC group, which also showed an increase in the cytoplasmic area. Malnutrition produces subcellular alterations in vulnerable hippocampal pyramidal cells, and these alterations may provide an explanation for the previously reported deficient performance of malnourished animals in a spatial memory task in which aging and malnutrition were shown to impede the maintenance of long-term memory.

  16. Identification of expressed genes in cDNA library of hemocytes from the RLO-challenged oyster, Crassostrea ariakensis Gould with special functional implication of three complement-related fragments (CaC1q1, CaC1q2 and CaC3).

    Science.gov (United States)

    Xu, Ting; Xie, Jiasong; Li, Jianming; Luo, Ming; Ye, Shigen; Wu, Xinzhong

    2012-06-01

    A SMARTer™ cDNA library of hemocyte from Rickettsia-like organism (RLO) challenged oyster, Crassostrea ariakensis Gould was constructed. Random clones (400) were selected and single-pass sequenced, resulted in 200 unique sequences containing 96 known genes and 104 unknown genes. The 96 known genes were categorized into 11 groups based on their biological process. Furthermore, we identified and characterized three complement-related fragments (CaC1q1, CaC1q2 and CaC3). Tissue distribution analysis revealed that all of three fragments were ubiquitously expressed in all tissues studied including hemocyte, gills, mantle, digestive glands, gonads and adductor muscle, while the highest level was seen in the hemocyte. Temporal expression profile in the hemocyte monolayers reveled that the mRNA expression levels of three fragments presented huge increase after the RLO incubation at 3 h and 6 h in post-challenge, respectively. And the maximal expression levels at 3 h in post-challenge are about 256, 104 and 64 times higher than the values detected in the control of CaC1q1, CaC1q2 and CaC3, respectively. Copyright © 2012 Elsevier Ltd. All rights reserved.

  17. Enhanced luminescence in Mg{sup 2+} codoped CaTiO{sub 3}:Eu{sup 3+} phosphor prepared by solid state reaction

    Energy Technology Data Exchange (ETDEWEB)

    Vandana, C. Sai; Rudramadevi, B. Hemalatha [Department of Physics, Sri Venkateswara University, Tirupati-517 502 (India)

    2016-05-23

    CaTiO{sub 3} phosphors doped with Eu{sup 3+} and codoped with Mg{sup 2+} were prepared by Solid State Reaction method. The powders were characterized by X-ray diffraction, SEM with EDS, Raman scattering, and photoluminescence spectroscopy. The Crystalline phase and vibrational modes of the phosphors were studied using XRD pattern and Raman Spectrum respectively. The morphological studies of the phosphor samples were carried out using SEM analysis. From PL spectra we have observed two prominent red emission peaks around at 595 nm ({sup 5}D{sub 0}→{sup 7}F{sub 1}), 619 nm ({sup 5}D{sub 0}→{sup 7}F{sub 2}) with the excitation of 399 nm for Eu{sup 3+} doped CaTiO{sub 3} powders. The PL intensity of CaTiO{sub 3}:Eu{sup 3+} phosphor is enhanced significantly on codoping with Mg{sup 2+}. The observed enhanced emissions are due to energy transfer from Mg{sup 2+} to Eu{sup 3+}, which is due to radiative recombination. Eu{sup 3+} doped phosphors are well known to be promising materials for electroluminescent devices, optical amplifiers, and lasers.

  18. Effect of Nd substitution for Ca on crystal structure, optical and magnetic properties of multiferroic Bi{sub 0.9}Ca{sub 0.1}FeO{sub 3}

    Energy Technology Data Exchange (ETDEWEB)

    Quan, Chuye; Ma, Yuhui; Han, Yumin; Tang, Xingxing; Lu, Mengjia [Key Laboratory for Organic Electronics & Information Displays (KLOEID), Synergetic Innovation Center for Organic Electronics and Information Displays (SICOEID), Institute of Advanced Materials - IAM, School of Materials Science and Engineering - SMSE, Nanjing University of Posts and Telecommunications - NUPT, Nanjing 210023 (China); Mao, Weiwei [Key Laboratory for Organic Electronics & Information Displays (KLOEID), Synergetic Innovation Center for Organic Electronics and Information Displays (SICOEID), Institute of Advanced Materials - IAM, School of Materials Science and Engineering - SMSE, Nanjing University of Posts and Telecommunications - NUPT, Nanjing 210023 (China); School of Science, Nanjing University of Posts and Telecommunications (NUPT), Nanjing 210023 (China); Zhang, Jian [Key Laboratory for Organic Electronics & Information Displays (KLOEID), Synergetic Innovation Center for Organic Electronics and Information Displays (SICOEID), Institute of Advanced Materials - IAM, School of Materials Science and Engineering - SMSE, Nanjing University of Posts and Telecommunications - NUPT, Nanjing 210023 (China); Yang, Jianping [School of Science, Nanjing University of Posts and Telecommunications (NUPT), Nanjing 210023 (China); Li, Xing’ao, E-mail: lxahbmy@126.com [Key Laboratory for Organic Electronics & Information Displays (KLOEID), Synergetic Innovation Center for Organic Electronics and Information Displays (SICOEID), Institute of Advanced Materials - IAM, School of Materials Science and Engineering - SMSE, Nanjing University of Posts and Telecommunications - NUPT, Nanjing 210023 (China); and others

    2015-06-25

    Highlights: • Crystal structure of doped samples transform to two phase coexistence. • The crystal size decreased to ∼50 nm after doping. • Ultraviolet absorption peak demonstrates apparent blue shift for doped sample. • The ratio of Fe{sup 2+} increased by merging Nd. • Ca, Nd co-doped can promote the ferromagnetism obviously. - Abstract: Pure and co-doped BiFeO{sub 3} (Ca, Nd) nanoparticles with diameter in the range of 50–250 nm were synthesized through a sol–gel method. X-ray diffraction (XRD) and Raman results show that Bi-site co-doped with Ca, Nd could result in a transition of crystal structure (from single phase rhombohedral (R3c) to two phase coexistence). An apparent blue shift can be observed in the co-doped samples along with a decrease of the direct optical band gap. Moreover, the leakage current was decreased due to the introduction of nonvolatile Ca and Nd at Bi{sup 3+} site. Analysis of MPMS-VSM magnetic hysteresis data reveals a further enhancement in magnetism in the Nd doped Bi{sub 0.9}Ca{sub 0.1}FeO{sub 3,} which is further explained by XPS characterization.

  19. Cholinergic induction of input-specific late-phase LTP via localized Ca2+ release in the visual cortex.

    Science.gov (United States)

    Cho, Kwang-Hyun; Jang, Hyun-Jong; Jo, Yang-Hyeok; Singer, Wolf; Rhie, Duck-Joo

    2012-03-28

    Acetylcholine facilitates long-term potentiation (LTP) and long-term depression (LTD), substrates of learning, memory, and sensory processing, in which acetylcholine also plays a crucial role. Ca(2+) ions serve as a canonical regulator of LTP/LTD but little is known about the effect of acetylcholine on intracellular Ca(2+) dynamics. Here, we investigated dendritic Ca(2+) dynamics evoked by synaptic stimulation and the resulting LTP/LTD in layer 2/3 pyramidal neurons of the rat visual cortex. Under muscarinic stimulation, single-shock electrical stimulation (SES) inducing ∼20 mV EPSP, applied via a glass electrode located ∼10 μm from the basal dendrite, evoked NMDA receptor-dependent fast Ca(2+) transients and the subsequent Ca(2+) release from the inositol 1,4,5-trisphosphate (IP(3))-sensitive stores. These secondary dendritic Ca(2+) transients were highly localized within 10 μm from the center (SD = 5.0 μm). The dendritic release of Ca(2+) was a prerequisite for input-specific muscarinic LTP (LTPm). Without the secondary Ca(2+) release, only muscarinic LTD (LTDm) was induced. D(-)-2-amino-5-phosphopentanoic acid and intracellular heparin blocked LTPm as well as dendritic Ca(2+) release. A single burst consisting of 3 EPSPs with weak stimulus intensities instead of the SES also induced secondary Ca(2+) release and LTPm. LTPm and LTDm were protein synthesis-dependent. Furthermore, LTPm was confined to specific dendritic compartments and not inducible in distal apical dendrites. Thus, cholinergic activation facilitated selectively compartment-specific induction of late-phase LTP through IP(3)-dependent Ca(2+) release.

  20. Enhanced basal contractility but reduced excitation-contraction coupling efficiency and beta-adrenergic reserve of hearts with increased Cav1.2 activity.

    Science.gov (United States)

    Tang, Mingxin; Zhang, Xiaoying; Li, Yingxin; Guan, Yinzheng; Ai, Xiaojie; Szeto, Christopher; Nakayama, Hiroyuki; Zhang, Hongyu; Ge, Shuping; Molkentin, Jeffery D; Houser, Steven R; Chen, Xiongwen

    2010-08-01

    Cardiac remodeling during heart failure development induces a significant increase in the activity of the L-type Ca(2+) channel (Cav1.2). However, the effects of enhanced Cav1.2 activity on myocyte excitation-contraction (E-C) coupling, cardiac contractility, and its regulation by the beta-adrenergic system are not clear. To recapitulate the increased Cav1.2 activity, a double transgenic (DTG) mouse model overexpressing the Cavbeta2a subunit in a cardiac-specific and inducible manner was established. We studied cardiac (in vivo) and myocyte (in vitro) contractility at baseline and upon beta-adrenergic stimulation. E-C coupling efficiency was evaluated in isolated myocytes as well. The following results were found: 1) in DTG myocytes, L-type Ca(2+) current (I(Ca,L)) density, myocyte fractional shortening (FS), peak Ca(2+) transients, and sarcoplasmic reticulum (SR) Ca(2+) content (caffeine-induced Ca(2+) transient peak) were significantly increased (by 100.8%, 48.8%, 49.8%, and 46.8%, respectively); and 2) cardiac contractility evaluated with echocardiography [ejection fraction (EF) and (FS)] and invasive intra-left ventricular pressure (maximum dP/dt and -dP/dt) measurements were significantly greater in DTG mice than in control mice. However, 1) the cardiac contractility (EF, FS, dP/dt, and -dP/dt)-enhancing effect of the beta-adrenergic agonist isoproterenol (2 microg/g body wt ip) was significantly reduced in DTG mice, which could be attributed to the loss of beta-adrenergic stimulation on contraction, Ca(2+) transients, I(Ca,L), and SR Ca(2+) content in DTG myocytes; and 2) E-C couplng efficiency was significantly lower in DTG myocytes. In conclusion, increasing Cav1.2 activity by promoting its high-activity mode enhances cardiac contractility but decreases E-C coupling efficiency and the adrenergic reserve of the heart.

  1. Search for weak M 1 transitions in 48Ca with inelastic proton scattering

    Science.gov (United States)

    Mathy, M.; Birkhan, J.; Matsubara, H.; von Neumann-Cosel, P.; Pietralla, N.; Ponomarev, V. Yu.; Richter, A.; Tamii, A.

    2017-05-01

    Background: The quenching of spin-isospin modes in nuclei is an important field of research in nuclear structure. It has an impact on astrophysical reaction rates and on fundamental processes like neutrinoless double-β decay. Gamow-Teller (GT) and spin-flip M 1 strengths are quenched. Concerning the latter, the Jπ=1+ resonance in the doubly magic nucleus 48Ca, dominated by a single transition, serves as a reference case. Purpose: The aim of the present work is to search for weak M 1 transitions in 48Ca with a high-resolution (p ,p') experiment at 295 MeV and forward angles including 0∘ and a comparison with results from a similar study using backward-angle electron scattering at low momentum transfers in order to estimate their contribution to the total B (M 1 ) strength in 48Ca. Methods: The spin-M 1 cross sections of individual peaks in the spectra are deduced with a multipole decomposition analysis (MDA) and converted to reduced spin-M 1 transition strengths by using the unit cross-section method. For a comparison with electron-scattering results, corresponding reduced B (M 1 ) transition strengths are extracted following the approach outlined in Birkhan et al. [Phys. Rev. C 93, 041302(R) (2016), 10.1103/PhysRevC.93.041302]. Results: In total, 30 peaks containing a M 1 contribution are found in the excitation energy region 7-13 MeV. The resulting B (M 1 ) strength distribution compares well to the electron-scattering results considering different factors limiting the sensitivity in both experiments and the enhanced importance of mechanisms breaking the proportionality of nuclear cross sections and electromagnetic matrix elements for weak transitions as studied here. The total strength of 1.14(7) μN2 deduced assuming a nonquenched isoscalar part of the (p ,p') cross sections agrees with the (e ,e') result of 1.21(13) μN2. A bin-wise analysis above 10 MeV provides an upper limit of 1.51(17) μN2. Conclusions: The present results confirm the previous electron

  2. Hexa-μ-acetato-1:2κ4O,O′;1:2κ2O:O;2:3κ4O,O′;2:3κ2O:O-bis(4,4′-dimethyl-2,2′-bipyridine-1κ2N,N′;3κ2N,N′-2-calcium-1,3-dizinc

    Directory of Open Access Journals (Sweden)

    Md. Alamgir Hossain

    2013-12-01

    Full Text Available In the centrosymmetric trinuclear ZnII...CaII...ZnII title complex, [CaZn2(CH3COO6(C12H12N22], the CaII ion lies on an inversion centre and is octahedrally coordinated by six acetate O atoms. The ZnII ion is coordinated by two N atoms from a bidentate dimethylbipyridine ligand and three O atoms from acetate ligands bridging to the CaII ion, leading to a distorted square-pyramidal coordination sphere. The Zn...Ca distance is 3.4668 (5 Å.

  3. Effect of Ca2+ Ions on Electrical Properties of Ba1-x Ca x Ti0.90Sn0.10O3-0.05Y2O3 Ceramics

    Science.gov (United States)

    Chen, Zhi-hui; Li, Zhi-wei; Ding, Jian-ning; Zhao, Tian-xiang; Qiu, Jian-hua; Zhu, Ke-qian; Xu, Jiu-jun; Zhang, Bing

    2018-03-01

    Ba1-x Ca x Ti0.90Sn0.10O3-0.05Y2O3 (BCTSY) lead-free piezoceramics with x = 0.02 to 0.10 have been fabricated by solid-state sintering method at 1420°C. The effects of Ca2+ ions on the microstructure and electrical properties of the samples were studied. X-ray diffraction analysis showed that all samples possessed pure perovskite structure with Ca2+ ions diffused into the matrix lattice. The rhombohedral phase and tetragonal phase coexisted in the composition range of 0.02 ceramic became more homogeneous with addition of Ca2+ ions, and the average grain size of the samples decreased from 97 μm (x = 0.02) to 18 μm (x = 0.10). Addition of Ca2+ remarkably improved the piezoelectric properties, enhanced the dielectric frequency dispersion, and increased the Curie temperature of the ceramics. The piezoelectric properties of the ceramics were optimized at x = 0.04 with d 33 and K p values of 579 pC/N and 52.7%, respectively.

  4. MIRO-1 Determines Mitochondrial Shape Transition upon GPCR Activation and Ca2+ Stress

    Directory of Open Access Journals (Sweden)

    Neeharika Nemani

    2018-04-01

    Full Text Available Summary: Mitochondria shape cytosolic calcium ([Ca2+]c transients and utilize the mitochondrial Ca2+ ([Ca2+]m in exchange for bioenergetics output. Conversely, dysregulated [Ca2+]c causes [Ca2+]m overload and induces permeability transition pore and cell death. Ablation of MCU-mediated Ca2+ uptake exhibited elevated [Ca2+]c and failed to prevent stress-induced cell death. The mechanisms for these effects remain elusive. Here, we report that mitochondria undergo a cytosolic Ca2+-induced shape change that is distinct from mitochondrial fission and swelling. [Ca2+]c elevation, but not MCU-mediated Ca2+ uptake, appears to be essential for the process we term mitochondrial shape transition (MiST. MiST is mediated by the mitochondrial protein Miro1 through its EF-hand domain 1 in multiple cell types. Moreover, Ca2+-dependent disruption of Miro1/KIF5B/tubulin complex is determined by Miro1 EF1 domain. Functionally, Miro1-dependent MiST is essential for autophagy/mitophagy that is attenuated in Miro1 EF1 mutants. Thus, Miro1 is a cytosolic Ca2+ sensor that decodes metazoan Ca2+ signals as MiST. : Metazoan Ca2+ signal determines mitochondrial shape transition (MiST and cellular quality control. Nemani et al. find that mitochondria undergo shape changes upon Ca2+ stress. MiST is distinct from matrix Ca2+-induced swelling and mitochondrial dynamics. The conserved Ca2+ sensor Miro1 enables MiST and promotes autophagy/mitophagy. Keywords: mitochondrial shape, MiST, calcium, Miro, EF hand, PTP, MCU, mitophagy, autophagy, mitochondrial dynamics

  5. Synergistic pretreatment of waste activated sludge using CaO_2 in combination with microwave irradiation to enhance methane production during anaerobic digestion

    International Nuclear Information System (INIS)

    Wang, Jie; Li, Yongmei

    2016-01-01

    Highlights: • CaO_2/MW pretreatment synergistically enhanced WAS solubilization and CH_4 production. • MW irradiation facilitated more "·OH generation from CaO_2. • The optimal pretreatment condition for methane production was determined. • The growths of both hydrogenotrophic and acetate-utilizing methanogens were promoted. • The dewaterability of WAS was improved considerably by CaO_2/MW treatment. - Abstract: To investigate the effects of combined calcium peroxide (CaO_2) and microwave pretreatment on anaerobic digestion of waste activated sludge, lab-scale experiments were conducted to measure the solubilization, biodegradation, and dewaterability of the waste activated sludge. Additionally, the synergistic effects between CaO_2 and microwave were studied, and the microbial activity and methanogenic archaea community structure were analyzed. Combined pretreatment considerably facilitated the solubilization and subsequent anaerobic digestion of the waste activated sludge. The optimal pretreatment condition was CaO_2 (0.1 g/gVSS)/microwave (480 W, 2 min) for methane production during the subsequent anaerobic digestion process. Under this condition, 80.2% higher CH_4 accumulation yield was achieved after 16 d of anaerobic digestion when compared with the control. The synergistic effects of CaO_2/microwave pretreatment resulted from the different mechanisms of CaO_2 and microwave treatments. Further, microwave irradiation increased "·OH generation from CaO_2 and significantly alleviated the inhibitory effect of CaO_2 on methanogens. The activities of hydrolytic enzymes and acid-forming enzymes in the waste activated sludge were improved after CaO_2 (0.1 g/gVSS)/microwave (480 W, 2 min) pretreatment. Methanogenesis enzyme activity was also higher after CaO_2 treatment (0.1 g/gVSS)/microwave (480 W, 2 min) following a lag period. Illumina MiSeq sequencing analysis indicated that acetate-utilizing methanogen (Methanosaeta sp.) and H_2/CO_2-utilizing

  6. Structure/activity relationship of thapsigargin inhibition on the purified Golgi/secretory pathway Ca2+/Mn2+-transport ATPase (SPCA1a)

    DEFF Research Database (Denmark)

    Chen, Jialin; De Raeymaecker, Joren; Hovgaard, Jannik Brondsted

    2017-01-01

    SPCA1a displays a higher apparent Ca2+ affinity and lower maximal turnover rate than the purified sarco(endo)plasmic reticulum Ca2+ ATPase (SERCA1a). The lipids cholesteryl hemisuccinate, linole-/oleamide and phosphatidyl ethanolamine inhibit, whereas phosphatidic acid and sphingomyelin enhance SPCA1a...... activity. Moreover, SPCA1a is blocked by μM concentrations of commonly used SERCA1a inhibitors thapsigargin (Tg), cyclopiazonic acid (CPA) and 2,5-di-tert-butyl hydroquinone (BHQ). Since tissue-specific targeting of SERCA2b by Tg analogues is considered for prostate cancer therapy, the inhibition of SPCA1a...

  7. Facile synthesis of CNTs/CaIn{sub 2}S{sub 4} composites with enhanced visible-light photocatalytic performance

    Energy Technology Data Exchange (ETDEWEB)

    Xia, Yang; Li, Qin, E-mail: liqin0518@mail.scuec.edu.cn; Wu, Xiaofeng; Lv, Kangle; Tang, Dingguo; Li, Mei, E-mail: limei@mail.scuec.edu.cn

    2017-01-01

    Highlights: • CNTs/CaIn{sub 2}S{sub 4} (CIS) composites were prepared by a microwave hydrothermal method. • CNTs were embedded tightly in the hierarchical marigold-like CIS microspheres. • Intimate contact between CNTs and CIS made interfacial charge transfer available. • The composite exhibited obviously higher photocatalytic activity than bare CIS. • The composite was applicable in both environment remediation and energy conversion. - Abstract: In response to the continuous concerns to environmental contamination and energy crisis, visible-light-driven photocatalysis has attracted broad attention for its potential applications in environment remediation and energy conversion. In this study, visible-light-responsive CNTs/CaIn{sub 2}S{sub 4} (CIS) composite photocatalyst was designed and synthesized by a facile one-step microwave hydrothermal method. The effects of CNTs content on the crystallinity, structure, light absorption, specific surface area and photocatalytic performance of CIS semiconductor were systematically studied. The results demonstrated that the prepared composite with a suitable amount of CNTs exhibited an apparently enhanced photocatalytic activity than bare CIS for both X-3B dye degradation and H{sub 2} production under visible-light irradiation. The optimal content of CNTs was found to be 1 wt%. The corresponding apparent rate constants of photocatalytic degradation and H{sub 2}-production rate are about two times as that of bare CaIn{sub 2}S{sub 4} semiconductor. Comprehensive analysis demonstrated that such enhancement was mainly attributed to the strong coupling interface between CNTs and CIS, which largely improved the separation efficiency of photogenerated charge carriers in space. However, excessive CNTs resulted in a decreased photocatalytic activity due to the shield of active sites and absorbed photons on the surface of CIS photocatalyst. This work could shed new light on the design and synthesis of carbon material

  8. Fabrication of CaFe2O4 nanofibers via electrospinning method with enhanced visible light photocatalytic activity

    Science.gov (United States)

    Wang, Jianmin; Wang, Yunan; Liu, Yinglei; Li, Song; Cao, Feng; Qin, Gaowu

    CaFe2O4 nanofibers with diameters of about 130nm have been fabricated via a facile electrospinning method. The structures, morphologies and optical properties of the obtained CaF2O4 nanofibers have been investigated by X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM) and UV-Visible UV-Vis diffuse reflectance spectrum. The photocatalytic activities of the CaFe2O4 nanofibers are evaluated by the photo-degradation of Methyl orange (MO). The results show that the CaFe2O4 nanofibers (72%) exhibit much higher photocatalytic performance than the CaFe2O4 powders (27%) prepared by conventional method under visible light irradiation. The enhanced photocatalytic performance of CaFe2O4 nanofibers could be attributed to the large surface area, high photogenerated charge carriers density and low charge transfer resistance, as revealed by photoelectrochemical measurement. And fundamentally, it could be attributed to the decreased particle size and the fibrous nanostructure. This work not only provides an efficient way to improve the photocatalytic activity of CaFe2O4, but also provides a new method for preparing materials with nanofibrous structure.

  9. Enhanced orange-red emission by using Mo codoped in Ba2CaWO6: Eu3+, Li+ phosphor under near UV excitation

    International Nuclear Information System (INIS)

    Sun, Xiaoyuan; Hao, Zhendong; Li, Chunjie; He, Xiaoguang; Qi, Haiyan; Yu, Lijun; Luo, Yongshi; Zhang, Jiahua; Gao, Jiwei; Zhong, Ruixia

    2013-01-01

    The orange-red emitting phosphors Ba 2 Ca 0.9 Mo x W 1−x O 6 :Eu 3+ 0.05 , Li + 0.05 (x=0, 0.05, 0.1, 0.15, 0.2, 0.25, 0.5, 0.75, and 1.0) and Ba 2 Ca 1−2y Mo 0.2 W 0.8 O 6 :Eu 3+ y , Li + y (y=0.03, 0.05, 0.07, 0.1, and 0.15) were synthesized. The crystalline structure and photoluminescence properties of these phosphors were described. The strong orange-red emission of Eu 3+ ( 5 D 0 — 7 F 1 transition) at around 593 nm was observed. Addition of Mo strongly enhances the charge transfer band absorption in the near ultraviolet region that corresponds to near ultraviolet white light emitting diode. The dependence of photoluminescence intensities on Eu 3+ concentrations with optimal Mo concentration under 400 nm excitation was studied. The phosphor is considered to be a promising orange-red emitting phosphor for near ultraviolet GaN-based white light emitting diode. - Highlights: ► The samples form solid solutions when Mo is added into Ba 2 CaWO 6 : Eu 3+ , Li + phosphors. ► Addition of Mo in Ba 2 CaWO 6 : Eu 3+ , Li + shifts the PLE spectra maximum from UV region to near UV region. ► In Ba 2 CaMo x W 1−x O 6 :Eu 3+ , Li + , the most efficient concentrations occur at 0.1 and 0.2 for Eu and Mo.

  10. Calculation of M1-excitations in the 42Ca, 44Ca and 54Fe with allowance for the 1p 1h * phonon configurations

    International Nuclear Information System (INIS)

    Kamerdzhiev, S.P.; Tkachev, V.N.

    1988-01-01

    The microscopic model of account of 1p1hx phonon configurations is used to describe M1-excitations in 42 Ca, 44 Ca and 54 Fe 1f 7/2 -shell. The most low-lying and more collectivized electrical phonons are taken into account. The Boron-Mottelson collective model with parameters obtained in the experiment is used to describe them. The calculation results are compared with calculations on other models. A set of all data allows to make the supposition that the deficient part of M1-resonance force in nuclei of 1f 7/2 -shell should be distributed on low-intensive 1 + -levels in the wide range of the nucleon binding energy

  11. From ¡°Double Pyramid¡± Thoughts to Corporate Social Responsibility for Enterprise Employees

    OpenAIRE

    Guiling Wei

    2013-01-01

    The purpose of this paper is to study corporate social responsibility for staffs based on the pyramid of Maslow¡¯s hierarchy of human needs and the pyramid of Carroll¡¯s corporate social responsibility. This research takes advantage of ¡°double pyramid¡± thoughts to discuss some enterprises lack of corporate social responsibility for their employees. Today, we are building of a harmonious society, each enterprise should not only realize the profit maximization, but also to meet the individual...

  12. THE ARCHITECTONIC ENCODING OF THE MINOR LUNAR STANDSTILLS IN THE HORIZON OF THE GIZA PYRAMIDS

    OpenAIRE

    Aboulfotouh, Hossam M. K.

    2014-01-01

    The paper is an attempt to show the architectonic method of the ancient Egyptian designers for encoding the horizontal-projections of the moon’s declinations during two events of the minor lunar standstills, in the design of the site-plan of the horizon of the Giza pyramids, using the methods of descriptive geometry. It shows that the distance of the eastern side of the second Giza pyramid from the north-south axis of the great pyramid encodes a projection of a lunar declination, when earth’s...

  13. Breast cancer 1 (BrCa1 may be behind decreased lipogenesis in adipose tissue from obese subjects.

    Directory of Open Access Journals (Sweden)

    Francisco J Ortega

    Full Text Available CONTEXT: Expression and activity of the main lipogenic enzymes is paradoxically decreased in obesity, but the mechanisms behind these findings are poorly known. Breast Cancer 1 (BrCa1 interacts with acetyl-CoA carboxylase (ACC reducing the rate of fatty acid biosynthesis. In this study, we aimed to evaluate BrCa1 in human adipose tissue according to obesity and insulin resistance, and in vitro cultured adipocytes. RESEARCH DESIGN AND METHODS: BrCa1 gene expression, total and phosphorylated (P- BrCa1, and ACC were analyzed in adipose tissue samples obtained from a total sample of 133 subjects. BrCa1 expression was also evaluated during in vitro differentiation of human adipocytes and 3T3-L1 cells. RESULTS: BrCa1 gene expression was significantly up-regulated in both omental (OM; 1.36-fold, p = 0.002 and subcutaneous (SC; 1.49-fold, p = 0.001 adipose tissue from obese subjects. In parallel with increased BrCa1 mRNA, P-ACC was also up-regulated in SC (p = 0.007 as well as in OM (p = 0.010 fat from obese subjects. Consistent with its role limiting fatty acid biosynthesis, both BrCa1 mRNA (3.5-fold, p<0.0001 and protein (1.2-fold, p = 0.001 were increased in pre-adipocytes, and decreased during in vitro adipogenesis, while P-ACC decreased during differentiation of human adipocytes (p = 0.005 allowing lipid biosynthesis. Interestingly, BrCa1 gene expression in mature adipocytes was restored by inflammatory stimuli (macrophage conditioned medium, whereas lipogenic genes significantly decreased. CONCLUSIONS: The specular findings of BrCa1 and lipogenic enzymes in adipose tissue and adipocytes reported here suggest that BrCa1 might help to control fatty acid biosynthesis in adipocytes and adipose tissue from obese subjects.

  14. Effect of Pyramidal Dome Geometry on the Acoustical Characteristics in A Mosque

    Directory of Open Access Journals (Sweden)

    Dg. H. Kassim

    2014-12-01

    Full Text Available As an important symbol in Islam, a mosque is built with architectural grandeur. Among the characteristics is its high ceiling and it is usually constructed with a typical spherical dome shape. Some mosques, however, are influenced by the local culture and the dome can be of a different shape, such as pyramidal, as found in mosques in Malacca, Malaysia. This paper presents an assessment of the internal acoustical characteristics of a mosque having a pyramidal dome. The study is conducted by means of computer simulation using CATT indoor acoustic software. Reverberation time and clarity are taken to evaluate the intelligibility of speech. The effect of the angle and height of the dome on the acoustical parameters is discussed. It is found that a pyramidal dome with a steeper angle contributes to poor acoustic clarity.

  15. Marker-assisted pyramiding of Thinopyrum-derived leaf rust ...

    Indian Academy of Sciences (India)

    Mona Singh

    2017-12-08

    Dec 8, 2017 ... Abstract. This study was undertaken to pyramid two effective leaf rust resistance genes (Lr19 and Lr24) derived from ... genes such as Lr9, Lr19, Lr26 and Lr28 became ineffective ..... Disease management recommendations.

  16. The cognition-enhancing activity of E1R, a novel positive allosteric modulator of sigma-1 receptors

    Science.gov (United States)

    Zvejniece, L; Vavers, E; Svalbe, B; Vilskersts, R; Domracheva, I; Vorona, M; Veinberg, G; Misane, I; Stonans, I; Kalvinsh, I; Dambrova, M

    2014-01-01

    Background and Purpose Here, we describe the in vitro and in vivo effects of (4R,5S)-2-(5-methyl-2-oxo-4-phenyl-pyrrolidin-1-yl)-acetamide (E1R), a novel positive allosteric modulator of sigma-1 receptors. Experimental Approach E1R was tested for sigma receptor binding activity in a [3H](+)-pentazocine assay, in bradykinin (BK)-induced intracellular Ca2+ concentration ([Ca2+]i) assays and in an electrically stimulated rat vas deferens model. E1R's effects on cognitive function were tested using passive avoidance (PA) and Y-maze tests in mice. A selective sigma-1 receptor antagonist (NE-100), was used to study the involvement of the sigma-1 receptor in the effects of E1R. The open-field test was used to detect the effects of E1R on locomotion. Key Results Pretreatment with E1R enhanced the selective sigma-1 receptor agonist PRE-084's stimulating effect during a model study employing electrically stimulated rat vasa deferentia and an assay measuring the BK-induced [Ca2+]i increase. Pretreatment with E1R facilitated PA retention in a dose-related manner. Furthermore, E1R alleviated the scopolamine-induced cognitive impairment during the PA and Y-maze tests in mice. The in vivo and in vitro effects of E1R were blocked by treatment with the selective sigma-1 receptor antagonist NE-100. E1R did not affect locomotor activity. Conclusion and Implications E1R is a novel 4,5-disubstituted derivative of piracetam that enhances cognition and demonstrates efficacy against scopolamine-induced cholinergic dysfunction in mice. These effects are attributed to its positive modulatory action on the sigma-1 receptor and this activity may be relevant when developing new drugs for treating cognitive symptoms related to neurodegenerative diseases. PMID:24490863

  17. Housing in Pyramid Counteracts Neuroendocrine and Oxidative Stress Caused by Chronic Restraint in Rats

    Directory of Open Access Journals (Sweden)

    M. Surekha Bhat

    2007-01-01

    Full Text Available The space within the great pyramid and its smaller replicas is believed to have an antistress effect. Research has shown that the energy field within the pyramid can protect the hippocampal neurons of mice from stress-induced atrophy and also reduce neuroendocrine stress, oxidative stress and increase antioxidant defence in rats. In this study, we have, for the first time, attempted to study the antistress effects of pyramid exposure on the status of cortisol level, oxidative damage and antioxidant status in rats during chronic restraint stress. Adult female Wistar rats were divided into four groups as follows: normal controls (NC housed in home cage and left in the laboratory; restrained rats (with three subgroups subject to chronic restraint stress by placing in a wire mesh restrainer for 6 h per day for 14 days, the restrained controls (RC having their restrainers kept in the laboratory; restrained pyramid rats (RP being kept in the pyramid; and restrained square box rats (RS in the square box during the period of restraint stress everyday. Erythrocyte malondialdehyde (MDA and plasma cortisol levels were significantly increased and erythrocyte-reduced glutathione (GSH levels, erythrocyte glutathione peroxidase (GSH-Px and superoxide dismutase (SOD activities were significantly decreased in RC and RS rats as compared to NC. However, these parameters were maintained to near normal levels in RP rats which showed significantly decreased erythrocyte MDA and plasma cortisol and significantly increased erythrocyte GSH levels, erythrocyte GSH-Px and SOD activities when compared with RS rats. The results showed that housing in pyramid counteracts neuroendocrine and oxidative stress caused by chronic restraint in rats.

  18. Provisions for the pyramid builders: new evidence from the ancient site of Giza

    Directory of Open Access Journals (Sweden)

    Mary Anne Murray

    2004-08-01

    Full Text Available The great pyramids of Giza are famous emblems of ancient Egyptian civilization, but until recently little was known about where and how the pyramid builders lived. The site of their large settlement has now been found, and excavation is revealing its complex layout and providing evidence of the plants and animals on which the builders depended for their food supply.

  19. Provisions for the pyramid builders: new evidence from the ancient site of Giza

    OpenAIRE

    Mary Anne Murray

    2004-01-01

    The great pyramids of Giza are famous emblems of ancient Egyptian civilization, but until recently little was known about where and how the pyramid builders lived. The site of their large settlement has now been found, and excavation is revealing its complex layout and providing evidence of the plants and animals on which the builders depended for their food supply.

  20. Mutated CaV2.1 channels dysregulate CASK/P2X3 signaling in mouse trigeminal sensory neurons of R192Q Cacna1a knock-in mice.

    Science.gov (United States)

    Gnanasekaran, Aswini; Bele, Tanja; Hullugundi, Swathi; Simonetti, Manuela; Ferrari, Michael D; van den Maagdenberg, Arn M J M; Nistri, Andrea; Fabbretti, Elsa

    2013-12-02

    ATP-gated P2X3 receptors of sensory ganglion neurons are important transducers of pain as they adapt their expression and function in response to acute and chronic nociceptive signals. The present study investigated the role of calcium/calmodulin-dependent serine protein kinase (CASK) in controlling P2X3 receptor expression and function in trigeminal ganglia from Cacna1a R192Q-mutated knock-in (KI) mice, a genetic model for familial hemiplegic migraine type-1. KI ganglion neurons showed more abundant CASK/P2X3 receptor complex at membrane level, a result that likely originated from gain-of-function effects of R192Q-mutated CaV2.1 channels and downstream enhanced CaMKII activity. The selective CaV2.1 channel blocker ω-Agatoxin IVA and the CaMKII inhibitor KN-93 were sufficient to return CASK/P2X3 co-expression to WT levels. After CASK silencing, P2X3 receptor expression was decreased in both WT and KI ganglia, supporting the role of CASK in P2X3 receptor stabilization. This process was functionally observed as reduced P2X3 receptor currents. We propose that, in trigeminal sensory neurons, the CASK/P2X3 complex has a dynamic nature depending on intracellular calcium and related signaling, that are enhanced in a transgenic mouse model of genetic hemiplegic migraine.

  1. Structure and properties of electron-doped Ca1-xSmxMnO3 nanoparticles

    International Nuclear Information System (INIS)

    Sanmathi, C.S.; Retoux, R.; Singh, M.P.; Noudem, J.

    2009-01-01

    In this paper, we report the structural and magnetic properties of electron-doped Ca 1-x Sm x MnO 3 (CSM) nanoparticles. The samarium's composition 'x' was varied from 0 to 0.2 with the special attention up to 0.05. Spherical 60-70 nm polycrystalline CSM nanoparticles were synthesised by chemical co-precipitation technique. Doping of Sm 3+ in antiferromagnetic CaMnO 3 has drastically altered its magnetic behavior due to the formation of ferromagnetic clusters. For example, the CSM powder with x = 0.04 displays about 115 K magnetic Curie temperature and about 0.1 emu/mole saturation magnetization. Physical properties of our nano-CSM powders are also compared with identical bulk-samples. To understand the differences, we invoked the intra-grain and inter-grain magnetic coupling process that facilitates to enhance their ferromagnetic behaviors. Unlike the bulk samples, such magnetic couplings in nanoparticles are favored by the presence of low-level crystal and interfacial defects

  2. Bidirectional Hebbian Plasticity Induced by Low-Frequency Stimulation in Basal Dendrites of Rat Barrel Cortex Layer 5 Pyramidal Neurons.

    Science.gov (United States)

    Díez-García, Andrea; Barros-Zulaica, Natali; Núñez, Ángel; Buño, Washington; Fernández de Sevilla, David

    2017-01-01

    According to Hebb's original hypothesis (Hebb, 1949), synapses are reinforced when presynaptic activity triggers postsynaptic firing, resulting in long-term potentiation (LTP) of synaptic efficacy. Long-term depression (LTD) is a use-dependent decrease in synaptic strength that is thought to be due to synaptic input causing a weak postsynaptic effect. Although the mechanisms that mediate long-term synaptic plasticity have been investigated for at least three decades not all question have as yet been answered. Therefore, we aimed at determining the mechanisms that generate LTP or LTD with the simplest possible protocol. Low-frequency stimulation of basal dendrite inputs in Layer 5 pyramidal neurons of the rat barrel cortex induces LTP. This stimulation triggered an EPSP, an action potential (AP) burst, and a Ca 2+ spike. The same stimulation induced LTD following manipulations that reduced the Ca 2+ spike and Ca 2+ signal or the AP burst. Low-frequency whisker deflections induced similar bidirectional plasticity of action potential evoked responses in anesthetized rats. These results suggest that both in vitro and in vivo similar mechanisms regulate the balance between LTP and LTD. This simple induction form of bidirectional hebbian plasticity could be present in the natural conditions to regulate the detection, flow, and storage of sensorimotor information.

  3. Bidirectional Hebbian Plasticity Induced by Low-Frequency Stimulation in Basal Dendrites of Rat Barrel Cortex Layer 5 Pyramidal Neurons

    Science.gov (United States)

    Díez-García, Andrea; Barros-Zulaica, Natali; Núñez, Ángel; Buño, Washington; Fernández de Sevilla, David

    2017-01-01

    According to Hebb's original hypothesis (Hebb, 1949), synapses are reinforced when presynaptic activity triggers postsynaptic firing, resulting in long-term potentiation (LTP) of synaptic efficacy. Long-term depression (LTD) is a use-dependent decrease in synaptic strength that is thought to be due to synaptic input causing a weak postsynaptic effect. Although the mechanisms that mediate long-term synaptic plasticity have been investigated for at least three decades not all question have as yet been answered. Therefore, we aimed at determining the mechanisms that generate LTP or LTD with the simplest possible protocol. Low-frequency stimulation of basal dendrite inputs in Layer 5 pyramidal neurons of the rat barrel cortex induces LTP. This stimulation triggered an EPSP, an action potential (AP) burst, and a Ca2+ spike. The same stimulation induced LTD following manipulations that reduced the Ca2+ spike and Ca2+ signal or the AP burst. Low-frequency whisker deflections induced similar bidirectional plasticity of action potential evoked responses in anesthetized rats. These results suggest that both in vitro and in vivo similar mechanisms regulate the balance between LTP and LTD. This simple induction form of bidirectional hebbian plasticity could be present in the natural conditions to regulate the detection, flow, and storage of sensorimotor information. PMID:28203145

  4. Neonatal seizures alter NMDA glutamate receptor GluN2A and 3A subunit expression and function in hippocampal CA1 neurons

    Science.gov (United States)

    Zhou, Chengwen; Sun, Hongyu; Klein, Peter M.; Jensen, Frances E.

    2015-01-01

    Neonatal seizures are commonly caused by hypoxic and/or ischemic injury during birth and can lead to long-term epilepsy and cognitive deficits. In a rodent hypoxic seizure (HS) model, we have previously demonstrated a critical role for seizure-induced enhancement of the AMPA subtype of glutamate receptor (GluA) in epileptogenesis and cognitive consequences, in part due to GluA maturational upregulation of expression. Similarly, as the expression and function of the N-Methyl-D-aspartate (NMDA) subtype of glutamate receptor (GluN) is also developmentally controlled, we examined how early life seizures during the critical period of synaptogenesis could modify GluN development and function. In a postnatal day (P)10 rat model of neonatal seizures, we found that seizures could alter GluN2/3 subunit composition of GluNs and physiological function of synaptic GluNs. In hippocampal slices removed from rats within 48–96 h following seizures, the amplitudes of synaptic GluN-mediated evoked excitatory postsynaptic currents (eEPSCs) were elevated in CA1 pyramidal neurons. Moreover, GluN eEPSCs showed a decreased sensitivity to GluN2B selective antagonists and decreased Mg2+ sensitivity at negative holding potentials, indicating a higher proportion of GluN2A and GluN3A subunit function, respectively. These physiological findings were accompanied by a concurrent increase in GluN2A phosphorylation and GluN3A protein. These results suggest that altered GluN function and expression could potentially contribute to future epileptogenesis following neonatal seizures, and may represent potential therapeutic targets for the blockade of future epileptogenesis in the developing brain. PMID:26441533

  5. Homeostatic maintenance in excitability of tree shrew hippocampal CA3 pyramidal neurons after chronic stress

    NARCIS (Netherlands)

    Kole, MHP; Czeh, B; Fuchs, E

    2004-01-01

    The experience of chronic stress induces a reversible regression of hippocampal CA3 apical neuron dendrites. Although such postsynaptic membrane reduction will obviously diminish the possibility of synaptic input, the consequences for the functional membrane properties of these cells are not well

  6. Large conductance Ca2+-activated K+ (BK channel: Activation by Ca2+ and voltage

    Directory of Open Access Journals (Sweden)

    RAMÓN LATORRE

    2006-01-01

    Full Text Available Large conductance Ca2+-activated K+ (BK channels belong to the S4 superfamily of K+ channels that include voltage-dependent K+ (Kv channels characterized by having six (S1-S6 transmembrane domains and a positively charged S4 domain. As Kv channels, BK channels contain a S4 domain, but they have an extra (S0 transmembrane domain that leads to an external NH2-terminus. The BK channel is activated by internal Ca2+, and using chimeric channels and mutagenesis, three distinct Ca2+-dependent regulatory mechanisms with different divalent cation selectivity have been identified in its large COOH-terminus. Two of these putative Ca2+-binding domains activate the BK channel when cytoplasmic Ca2+ reaches micromolar concentrations, and a low Ca2+ affinity mechanism may be involved in the physiological regulation by Mg2+. The presence in the BK channel of multiple Ca2+-binding sites explains the huge Ca2+ concentration range (0.1 μM-100 μM in which the divalent cation influences channel gating. BK channels are also voltage-dependent, and all the experimental evidence points toward the S4 domain as the domain in charge of sensing the voltage. Calcium can open BK channels when all the voltage sensors are in their resting configuration, and voltage is able to activate channels in the complete absence of Ca2+. Therefore, Ca2+ and voltage act independently to enhance channel opening, and this behavior can be explained using a two-tiered allosteric gating mechanism.

  7. Image-guided preoperative prediction of pyramidal tract side effect in deep brain stimulation: proof of concept and application to the pyramidal tract side effect induced by pallidal stimulation

    OpenAIRE

    Baumgarten, Clement; Zhao, Yulong; Sauleau, Paul; Malrain, Cecile; Jannin, Pierre; Haegelen, Claire

    2016-01-01

    Deep brain stimulation of the medial globus pallidus (GPm) is a surgical procedure for treating patients suffering from Parkinson���s disease. Its therapeutic effect may be limited by the presence of pyramidal tract side effect (PTSE). PTSE is a contraction time-locked to the stimulation when the current spreading reaches the motor fibers of the pyramidal tract within the internal capsule. The objective of the study was to propose a preoperative predictive model of PTSE. A machine learning-ba...

  8. Ancient Pyramids Help Students Learn Math Concepts

    Science.gov (United States)

    Smith, Courtney D.; Stump, Amanda M.; Lazaros, Edward J.

    2010-01-01

    This article presents an activity that allows students to use mathematics and critical-thinking skills to emulate processes used by the ancient Egyptians to prepare the site for the Pyramids of Giza. To accomplish this, they use three different methods. First, they create a square using only simple technological tools that were available to the…

  9. SPECT and 123I-Iodolisuride (123-I-ILIS) in extra-pyramidal syndromes. The use of different models of γ-cameras

    International Nuclear Information System (INIS)

    Ribeiro, M.J.; Jannuario, C.; Santos, A.C.; Cunha, L.; Pedroso de Lima, J.J.; Prunier-Levilion, C.; Autret, A.; Guilloteau, D.; Besnard, J.C.; Baulieu, J.L.; Chassat, F.; Bekhechi, D.; Marchand, J.; Mauclaire, L.; Catela, L.

    1999-01-01

    The aim of this work was to evaluate 123 I-ILIS as a radioligand of dopamine receptors in patients with extra-pyramidal diseases by using different cameras in two different centers. 45 patients were included and divided in 2 groups: group I (n=28): idiopathic Parkinson disease, group II (n=17): other extra-pyramidal syndrome. 123 I-ILIS, 1.7 to 2.8 MBq/kg, was injected after informed consent. Imaging was performed with a single head camera, a dual head camera, a triple head camera and a brain dedicated annular detector. The pattern of the transverse slices containing the basal ganglia was classified according to 3 types: type 1: visible basal ganglia and invisible cortex, type 2: invisible basal ganglia and visible cortex, type 3: visible basal ganglia and cortex. Striatal/frontal cortex ratio (S/FC) was calculated from standardized, geometrical ROI's. No patient showed any undesirable effect. All SPECT images were interpretable. In group 1, 45/45 scintigraphic pattern were type 1 or 3, in group II 18/23 scintigraphic patterns were type 2 or 3. S/FC was significantly lower in group II than in group I patients. We conclude that 123 I-ILIS SPECT can be performed with any conventional γ-camera. It provides functional informations about the striatal dopaminergic synapse in patients with extra-pyramidal degenerative disease, and could be useful in the differential diagnosis between Parkinson disease and other extra-pyramidal syndromes. (author)

  10. Rac1-stimulated macropinocytosis enhances Gβγ activation of PI3Kβ.

    Science.gov (United States)

    Erami, Zahra; Khalil, Bassem D; Salloum, Gilbert; Yao, Yanhua; LoPiccolo, Jaclyn; Shymanets, Aliaksei; Nürnberg, Bernd; Bresnick, Anne R; Backer, Jonathan M

    2017-11-16

    Phosphoinositide 3-kinases (PI 3-kinases) are regulated by a diverse range of upstream activators, including receptor tyrosine kinases (RTKs), G-protein-coupled receptors (GPCRs), and small GTPases from the Ras, Rho and Rab families. For the Class IA PI 3-kinase PI3Kβ, two mechanisms for GPCR-mediated regulation have been described: direct binding of Gβγ subunits to the C2-helical domain linker of p110β, and Dock180/Elmo1-mediated activation of Rac1, which binds to the Ras-Binding Domain of p110β. We now show that the integration of these dual pathways is unexpectedly complex. In breast cancer cells, expression of constitutively activated Rac1 (CA-Rac1) along with either GPCR stimulation or expression of Gβγ led to an additive PI3Kβ-dependent activation of Akt. Whereas CA-Rac1-mediated activation of Akt was blocked in cells expressing a mutated PI3Kβ that cannot bind Gβγ, Gβγ and GPCR-mediated activation of Akt was preserved when Rac1 binding to PI3Kβ was blocked. Surprisingly, PI3Kβ-dependent CA-Rac1 signaling to Akt was still seen in cells expressing a mutant p110β that cannot bind Rac1. Instead of directly binding to PI3Kβ, CA-Rac1 acts by enhancing Gβγ coupling to PI3Kβ, as CA-Rac1-mediated Akt activation was blocked by inhibitors of Gβγ. Cells expressing CA-Rac1 exhibited a robust induction of macropinocytosis, and inhibitors of macropinocytosis blocked the activation of Akt by CA-Rac1 or lysophosphatidic acid. Our data suggest that Rac1 can potentiate the activation of PI3Kβ by GPCRs through an indirect mechanism, by driving the formation of macropinosomes that serve as signaling platforms for Gβγ coupling to PI3Kβ. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

  11. The attraction of the pyramids: virtual realization of Hutton's suggestion to improve Maskelyne's 1774 Earth density estimate

    Science.gov (United States)

    Smallwood, John R.

    2018-01-01

    Charles Hutton suggested in 1821 that the pyramids of Egypt be used to site an experiment to measure the deflection of the vertical by a large mass. The suggestion arose as he had estimated the attraction of a Scottish mountain as part of Nevil Maskelyne's (1774) "Schiehallion Experiment", a demonstration of Isaac Newton's law of gravitational attraction and the earliest reasonable quantitative estimate of Earth's mean density. I present a virtual realization of an experiment at the Giza pyramids to investigate how Hutton's concept might have emerged had it been undertaken as he suggested. The attraction of the Great Pyramid would have led to inward north-south deflections of the vertical totalling 1.8 arcsec (0.0005°), and east-west deflections totalling 2.0 arcsec (0.0006°), which although small, would have been within the contemporaneous detectable range, and potentially given, as Hutton wished, a more accurate Earth density measurement than he reported from the Schiehallion experiment.

  12. Involvement of N-methyl-D-aspartate receptor subunits in zinc-mediated modification of CA1 long-term potentiation in the developing hippocampus.

    Science.gov (United States)

    Takeda, Atsushi; Itagaki, Kosuke; Ando, Masaki; Oku, Naoto

    2012-03-01

    Zinc is an endogenous N-methyl-D-aspartate (NMDA) receptor blocker. It is possible that zinc-mediated modification of hippocampal CA1 long-term potentiation (LTP) is linked to the expression of NMDA receptor subunits, which varies with postnatal development. In the present study, the effect of ZnCl(2) and CaEDTA, a membrane-impermeable zinc chelator, on CA1 LTP induction was examined in hippocampal slices from immature (3-week-old) and young (6-week-old) rats. Tetanus (10-100 Hz, 1 sec)-induced CA1 LTP was more greatly enhanced in 3-week-old rats. CA1 LTP was inhibited in the presence of 2-amino-5-phosphonovalerate (APV), an NMDA receptor antagonist, and CaEDTA in 3-week-old rats, as in the case of 6-week-old rats reported previously. In 3-week-old rats, on the other hand, 5 μM ZnCl(2) attenuated NMDA receptor-mediated EPSPs more than in 6-week-old rats and significantly attenuated CA1 LTP. Moreover, 5 μM ZnCl(2) significantly attenuated CA1 LTP in the presence of (2R,4S)-4-(3-phosphonopropyl)-2-piperidinecarboxylic acid (PPPA), an NR2A antagonist, in 3-week-old rats, but not that in the presence of ifenprodil, an NR2B antagonist, suggesting that zinc-mediated attenuation of CA1 LTP is associated with the preferential expression of NR2B subunit in 3-week-old rats. In 6-week-old rats, however, 5 μM ZnCl(2) significantly potentiated CA1 LTP and also CA1 LTP in the presence of PPPA. The present study demonstrates that endogenous zinc may participate in the induction of CA1 LTP. It is likely that the changes in expression of NMDA receptor subunits are involved in the zinc-mediated modification of CA1 LTP in the developing hippocampus. Copyright © 2011 Wiley Periodicals, Inc.

  13. Assessment of the pyramidal tract by diffusion tensor analysis in brain hemorrhage patients for motor function prognosis

    International Nuclear Information System (INIS)

    Kawamo, Michiaki; Abe, Takumi; Izumiyama, Hitoshi

    2008-01-01

    In patients with brain hemorrhage, the entire visualized pyramidal tract was established as an area of interest (ROI). Its Fractional Anisotropy (FA) value was determined by diffusion tensor analysis (DTA), and its relationship to motor function at the onset and three months later was investigated. In 30 patients with brain hemorrhage accompanying paralysis, MRI was performed during the subacute phase (6-14 days after onset). In addition, using a workstation, DTA was performed in order to visualize the pyramidal tract. The FA of the ROI was measured on the affected and unaffected sides, and as previously reported, the ratio of FA in the affected and unaffected sides was calculated. Subsequently, we examined the relationship between the FA ratio and motor function prognosis. Motor function prognosis was assessed based on the sum of the Brunnstrom stage at the onset and three months later. A strong correlation coefficient existed between the FA ratio of the entire pyramidal tract and the sum of the Brunnstrom stage three months after onset (0.74, p<0.001), and prognosis of motor function tended to improve in patients with FA ratios of 0.95 or higher. Patients with mild paralysis were identified in order to ascertain the degree of improvement in paralysis, and a significant correlation between the FA ratio of the entire pyramidal tract and the degree of improvement in the Brunnstrom stage was observed (correlation coefficient 0.77, p<0.001). When compared to putamen hemorrhage, the FA ratio affected the prognosis of paralysis more in thalamic hemorrhage. The results suggest that in patients with an FA ratio of 1.0, the recovery rate of paralysis three months after onset is markedly high. In brain hemorrhage patients, a reduction in the FA ratio of the entire pyramidal tract was correlated with the functional prognosis of motor paralysis, and in thalamic hemorrhage, it may be possible to predict motor function based on FA ratios. Hence, the DTA of the pyramidal tract

  14. Electrical and microstructural properties of CaTiO3-doped K1/2Na1 ...

    Indian Academy of Sciences (India)

    KNN) and CaTiO3- modified K1/2Na1/2NbO3 (CTO-KNN) systems, were investigated. Discs doped with 0 to 0.55% mol of CaTiO3 (CTO) were sintered at 1125°C for 2 h. Although minority phases were found in doped samples, CaTiO3 was not ...

  15. Gadolinium-enhanced turbo FLASH MR imaging of renal perfusion and excretion

    International Nuclear Information System (INIS)

    Watanabe, A.; Teresi, L.M.; Herbst, M.; O'Sullivan, R.M.; Lee, R.; Smith, C.; Renner, J.; Rappaport, A.; Bradley, W.G. Jr.

    1990-01-01

    This paper describes a novel approach to MR imaging of renal perfusion and excretion using gadolinium-enhanced, T1-weighted TURBP, fast low-angle shot (FLASH) imaging. Five normal volunteers and four patients were studied on a 1.5-T imaging system. Time-intensity curves of the appearance of gadolinium in each kidney and the bladder were then generated. In normal volunteers, marked first-pass enhancement of renal cortex followed by renal pyramids and collecting systems could be demonstrated on the first-pass gadolinium images. Delayed images showed hyperintense gadolinium within the bladder

  16. THE MORPHOLOGICAL PYRAMID AND ITS APPLICATIONS TO REMOTE SENSING: MULTIRESOLUTION DATA ANALYSIS AND FEATURES EXTRACTION

    Directory of Open Access Journals (Sweden)

    Laporterie Florence

    2011-05-01

    Full Text Available In remote sensing, sensors are more and more numerous, and their spatial resolution is higher and higher. Thus, the availability of a quick and accurate characterisation of the increasing amount of data is now a quite important issue. This paper deals with an approach combining a pyramidal algorithm and mathematical morphology to study the physiographic characteristics of terrestrial ecosystems. Our pyramidal strategy involves first morphological filters, then extraction at each level of resolution of well-known landscapes features. The approach is applied to a digitised aerial photograph representing an heterogeneous landscape of orchards and forests along the Garonne river (France. This example, simulating very high spatial resolution imagery, highlights the influence of the parameters of the pyramid according to the spatial properties of the studied patterns. It is shown that, the morphological pyramid approach is a promising attempt for multi-level features extraction by modelling geometrical relevant parameters.

  17. Scanning Ultrasound (SUS Causes No Changes to Neuronal Excitability and Prevents Age-Related Reductions in Hippocampal CA1 Dendritic Structure in Wild-Type Mice.

    Directory of Open Access Journals (Sweden)

    Robert John Hatch

    Full Text Available Scanning ultrasound (SUS is a noninvasive approach that has recently been shown to ameliorate histopathological changes and restore memory functions in an Alzheimer's disease mouse model. Although no overt neuronal damage was reported, the short- and long-term effects of SUS on neuronal excitability and dendritic tree morphology had not been investigated. To address this, we performed patch-clamp recordings from hippocampal CA1 pyramidal neurons in wild-type mice 2 and 24 hours after a single SUS treatment, and one week and 3 months after six weekly SUS treatments, including sham treatments as controls. In both treatment regimes, no changes in CA1 neuronal excitability were observed in SUS-treated neurons when compared to sham-treated neurons at any time-point. For the multiple treatment groups, we also determined the dendritic morphology and spine densities of the neurons from which we had recorded. The apical trees of sham-treated neurons were reduced at the 3 month time-point when compared to one week; however, surprisingly, no longitudinal change was detected in the apical dendritic trees of SUS-treated neurons. In contrast, the length and complexity of the basal dendritic trees were not affected by SUS treatment at either time-point. The apical dendritic spine densities were reduced, independent of the treatment group, at 3 months compared to one week. Collectively, these data suggest that ultrasound can be employed to prevent an age-associated loss of dendritic structure without impairing neuronal excitability.

  18. Peroxisome proliferation activation receptor alpha modulation of Ca2+-regulated exocytosis via arachidonic acid in guinea-pig antral mucous cells.

    Science.gov (United States)

    Sawabe, Yukinori; Shimamoto, Chikao; Sakai, Akiko; Kuwabara, Hiroko; Saad, Adel H; Nakano, Takashi; Takitani, Kimitaka; Tamai, Hiroshi; Mori, Hiroshi; Marunaka, Yoshinori; Nakahari, Takashi

    2010-08-01

    Indomethacin (IDM, 10 microm), not aspirin (ASA; 10 microm), enhanced the Ca(2+)-regulated exocytosis stimulated by 1 microm acetylcholine (ACh) in guinea-pig antral mucous cells. Indomethacin inhibits prostaglandin G/H (PGG/H) and 15R-hydroperoxy-eicosatetraenoic acid (15R-HPETE) production from arachidonic acid (AA), while ASA inhibits PGG/H production but accelerates 15R-HPETE production. This suggests that IDM accumulates AA. Arachidonic acid (2 microm) enhanced Ca(2+)-regulated exocytosis in antral mucous cells to a similar extent to IDM. Moreover, a stable analogue of AA, arachidonyltrifluoromethyl ketone (AACOCF(3)), also enhanced Ca(2+)-regulated exocytosis, indicating that AA, not products from AA, enhances Ca(2+)-regulated exocytosis. We hypothesized that AA activates peroxisome proliferation activation receptor alpha (PPARalpha), because AA is a natural ligand for PPARalpha. A PPARalpha agonist (WY14643; 1 microm) enhanced Ca(2+)-regulated exocytosis, and a PPARalpha blocker (MK886; 50 microm) abolished the enhancement of Ca(2+)-regulated exocytosis induced by AA, IDM, AACOCF(3) and WY14643. Western blotting and immunohistochemical examinations demonstrated that PPARalpha exists in antral mucous cells. Moreover, MK886 decreased the frequency of Ca(2+)-regulated exocytosis activated by 1 microm ACh or 2 microm thapsigargin alone by 25-30%. Thus, ACh stimulates AA accumulation via an [Ca(2+)](i) increase, which activates PPARalpha, leading to enhancement of Ca(2+)-regulated exocytosis in antral mucous cells. A novel autocrine mechanism mediated via PPARalpha enhances Ca(2+)-regulated exocytosis in guinea-pig antral mucous cells.

  19. Delayed hippocampal neuronal death in young gerbil following transient global cerebral ischemia is related to higher and longer-term expression of p63 in the ischemic hippocampus

    Directory of Open Access Journals (Sweden)

    Eun Joo Bae

    2015-01-01

    Full Text Available The tumor suppressor p63 is one of p53 family members and plays a vital role as a regulator of neuronal apoptosis in the development of the nervous system. However, the role of p63 in mature neuronal death has not been addressed yet. In this study, we first compared ischemia-induced effects on p63 expression in the hippocampal regions (CA1- 3 between the young and adult gerbils subjected to 5 minutes of transient global cerebral ischemia. Neuronal death in the hippocampal CA1 region of young gerbils was significantly slow compared with that in the adult gerbils after transient global cerebral ischemia. p63 immunoreactivity in the hippocampal CA1 pyramidal neurons in the sham-operated young group was significantly low compared with that in the sham-operated adult group. p63 immunoreactivity was apparently changed in ischemic hippocampal CA1 pyramidal neurons in both ischemia-operated young and adult groups. In the ischemia-operated adult groups, p63 immunoreactivity in the hippocampal CA1 pyramidal neurons was significantly decreased at 4 days post-ischemia; however, p63 immunoreactivity in the ischemia-operated young group was significantly higher than that in the ischemia-operated adult group. At 7 days post-ischemia, p63 immunoreactivity was decreased in the hippocampal CA1 pyramidal neurons in both ischemia-operated young and adult groups. Change patterns of p63 level in the hippocampal CA1 region of adult and young gerbils after ischemic damage were similar to those observed in the immunohistochemical results. These findings indicate that higher and longer-term expression of p63 in the hippocampal CA1 region of the young gerbils after ischemia/reperfusion may be related to more delayed neuronal death compared to that in the adults.

  20. Jonestown in the Shadow of Maslow's Pyramid.

    Science.gov (United States)

    Easley, Edgar M.; Wigglesworth, David C.

    1979-01-01

    Reviews Maslow's hierarchy of needs in the light of the Jonestown tragedy. Maintains that members of the People's Temple felt frustrated in attaining the lower levels in the world of reality, and so moved outside the pyramid in search of the top, self-actualization. In the process, their primary needs were met. Journal availability: see SO 507…

  1. Electrochemical Activity of a La0.9Ca0.1Co1−xFexO3 Catalyst for a Zinc Air Battery Electrode

    Directory of Open Access Journals (Sweden)

    Seungwook Eom

    2015-01-01

    Full Text Available The optimum composition of cathode catalyst has been studied for rechargeable zinc air battery application. La0.9Ca0.1Co1−xFexO3  (x=0–0.4 perovskite powders were prepared using the citrate method. The substitution ratio of Co2+ with Fe3+ cations was controlled in the range of 0–0.4. The optimum substitution ratio of Fe3+ cations was determined by electrochemical measurement of the air cathode composed of the catalyst, polytetrafluoroethylene (PTFE binder, and Vulcan XC-72 carbon. The substitution by Fe enhanced the electrochemical performances of the catalysts. Considering oxygen reduction/evolution reactions and cyclability, we achieved optimum substitution level of x=0.1 in La0.9Ca0.1Co1−xFexO3.

  2. Djedkare’s pyramid complex: Preliminary report of the 2016 season

    Directory of Open Access Journals (Sweden)

    Mohamed Megahed

    2017-12-01

    Full Text Available The article presents the results of the 2016 archaeological season of the Egyptian mission in the pyramid complex of King Djedkare in South Saqqara. The works focused on the western part of the causeway where remains of a drainage was documented, and on the storerooms situated to the south of the entrance passage. During this work, also the north side of the so-called southern massive was cleaned. Besides the funerary temple, also the private cemetery located to the south-east of it started to be documented in this season. A mud brick structure, MS 1, was cleaned; it consisted of six shafts with vaulted burial chambers. Only one of the chambers (in shaft 5 was cased with limestone slabs, which bear a well preserved painted decoration. This burial chamber belonged to Pepyankh Setju and can be dated to the late Sixth Dynasty. Another part of the work in 2016 concentrated inside the pyramid of the king. The consolidation and restoration works were carried out in the burial apartments, concentrating on the missing part of the eastern wall of the antechamber and the core behind it.

  3. Orai1 mediates exacerbated Ca(2+ entry in dystrophic skeletal muscle.

    Directory of Open Access Journals (Sweden)

    Xiaoli Zhao

    Full Text Available There is substantial evidence indicating that disruption of Ca(2+ homeostasis and activation of cytosolic proteases play a key role in the pathogenesis and progression of Duchenne Muscular Dystrophy (DMD. However, the exact nature of the Ca(2+ deregulation and the Ca(2+ signaling pathways that are altered in dystrophic muscles have not yet been resolved. Here we examined the contribution of the store-operated Ca(2+ entry (SOCE for the pathogenesis of DMD. RT-PCR and Western blot found that the expression level of Orai1, the pore-forming unit of SOCE, was significantly elevated in the dystrophic muscles, while parallel increases in SOCE activity and SR Ca(2+ storage were detected in adult mdx muscles using Fura-2 fluorescence measurements. High-efficient shRNA probes against Orai1 were delivered into the flexor digitorum brevis muscle in live mice and knockdown of Orai1 eliminated the differences in SOCE activity and SR Ca(2+ storage between the mdx and wild type muscle fibers. SOCE activity was repressed by intraperitoneal injection of BTP-2, an Orai1 inhibitor, and cytosolic calpain1 activity in single muscle fibers was measured by a membrane-permeable calpain substrate. We found that BTP-2 injection for 2 weeks significantly reduced the cytosolic calpain1 activity in mdx muscle fibers. Additionally, ultrastructural changes were observed by EM as an increase in the number of triad junctions was identified in dystrophic muscles. Compensatory changes in protein levels of SERCA1, TRP and NCX3 appeared in the mdx muscles, suggesting that comprehensive adaptations occur following altered Ca(2+ homeostasis in mdx muscles. Our data indicates that upregulation of the Orai1-mediated SOCE pathway and an overloaded SR Ca(2+ store contributes to the disrupted Ca(2+ homeostasis in mdx muscles and is linked to elevated proteolytic activity, suggesting that targeting Orai1 activity may be a promising therapeutic approach for the prevention and treatment of

  4. Specificity of drug transport mediated by CaMDR1: a major facilitator ...

    Indian Academy of Sciences (India)

    Unknown

    CaMDR1 encodes a major facilitator superfamily (MFS) protein in Candida albicans whose expression has been linked to .... by plaque assay and the integration of CaMDR1 at the ... with recombinant virus, vAcCaMDR1 and cells infected.

  5. Role of Caspase-3 Cleaved IP3R1 on Ca2+ Homeostasis and Developmental Competence of Mouse Oocytes and Eggs

    Science.gov (United States)

    Zhang, Nan; Fissore, Rafael. A.

    2014-01-01

    Apoptosis in most cell types is accompanied by altered Ca2+ homeostasis. During apoptosis, caspase-3 mediated cleavage of the type 1 inositol 1,4,5-trisphosphate receptor (IP3R1) generates a 95-kDa C-terminal fragment (C-IP3R1), which represents the channel domain of the receptor. Aged mouse eggs display abnormal Ca2+ homeostasis and express C-IP3R1, although whether or not C-IP3R1 expression contributes to Ca2+ misregulation or a decrease in developmental competency is unknown. We sought to answer these questions by injecting in mouse oocytes and eggs cRNAs encoding CIP3R1. We found that: 1) expression of C-IP3R1 in eggs lowered the Ca2+ content of the endoplasmic reticulum (ER), although, as C-IP3R1 is quickly degraded at this stage, its expression did not impair pre-implantation embryo development; 2) expression of CIP3R1 in eggs enhanced fragmentation associated with aging; 3) endogenous IP3R1 is required for aging associated apoptosis, as its down-regulation prevented fragmentation, and expression of C-IP3R1 in eggs with downregulated IP3R1 partly restored fragmentation; 4) C-IP3R1 expression in GV oocytes resulted in persistent levels of protein, which abolished the increase in the ER releasable Ca2+ pool that occurs during maturation, undermined the Ca2+ oscillatory ability of matured eggs and their activation potential. Collectively, this study supports a role for IP3R1 and C-IP3R1 in regulating Ca2+ homeostasis and the ER Ca2+ content during oocyte maturation. Nevertheless, the role of C-IP3R1 on Ca2+ homeostasis in aged eggs seems minor, as in MII eggs the majority of endogenous IP3R1 remains intact and C-IP3R1 undergoes rapid turnover. PMID:24692207

  6. Characterization of intrinsic properties of cingulate pyramidal neurons in adult mice after nerve injury

    Directory of Open Access Journals (Sweden)

    Chen Tao

    2009-12-01

    Full Text Available Abstract The anterior cingulate cortex (ACC is important for cognitive and sensory functions including memory and chronic pain. Glutamatergic excitatory synaptic transmission undergo long-term potentiation in ACC pyramidal cells after peripheral injury. Less information is available for the possible long-term changes in neuronal action potentials or intrinsic properties. In the present study, we characterized cingulate pyramidal cells in the layer II/III of the ACC in adult mice. We then examined possible long-term changes in intrinsic properties of the ACC pyramidal cells after peripheral nerve injury. In the control mice, we found that there are three major types of pyramidal cells according to their action potential firing pattern: (i regular spiking (RS cells (24.7%, intrinsic bursting (IB cells (30.9%, and intermediate (IM cells (44.4%. In a state of neuropathic pain, the population distribution (RS: 21.3%; IB: 31.2%; IM: 47.5% and the single action potential properties of these three groups were indistinguishable from those in control mice. However, for repetitive action potentials, IM cells from neuropathic pain animals showed higher initial firing frequency with no change for the properties of RS and IB neurons from neuropathic pain mice. The present results provide the first evidence that, in addition to synaptic potentiation reported previously, peripheral nerve injury produces long-term plastic changes in the action potentials of cingulate pyramidal neurons in a cell type-specific manner.

  7. An essential role for neuregulin-4 in the growth and elaboration of developing neocortical pyramidal dendrites.

    Science.gov (United States)

    Paramo, Blanca; Wyatt, Sean; Davies, Alun M

    2018-04-01

    Neuregulins, with the exception of neuregulin-4 (NRG4), have been shown to be extensively involved in many aspects of neural development and function and are implicated in several neurological disorders, including schizophrenia, depression and bipolar disorder. Here we provide the first evidence that NRG4 has a crucial function in the developing brain. We show that both the apical and basal dendrites of neocortical pyramidal neurons are markedly stunted in Nrg4 -/- neonates in vivo compared with Nrg4 +/+ littermates. Neocortical pyramidal neurons cultured from Nrg4 -/- embryos had significantly shorter and less branched neurites than those cultured from Nrg4 +/+ littermates. Recombinant NRG4 rescued the stunted phenotype of embryonic neocortical pyramidal neurons cultured from Nrg4 -/- mice. The majority of cultured wild type embryonic cortical pyramidal neurons co-expressed NRG4 and its receptor ErbB4. The difference between neocortical pyramidal dendrites of Nrg4 -/- and Nrg4 +/+ mice was less pronounced, though still significant, in juvenile mice. However, by adult stages, the pyramidal dendrite arbors of Nrg4 -/- and Nrg4 +/+ mice were similar, suggesting that compensatory changes in Nrg4 -/- mice occur with age. Our findings show that NRG4 is a major novel regulator of dendritic arborisation in the developing cerebral cortex and suggest that it exerts its effects by an autocrine/paracrine mechanism. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  8. Rate-based modelling and validation of a pilot absorber using MDEA enhanced with carbonic anhydrase (CA)

    DEFF Research Database (Denmark)

    Gaspar, Jozsef; Gladis, Arne; Woodley, John

    2017-01-01

    solvent-regeneration energy demand.The focus of this work is to develop a rate-based model for CO2 absorption using MDEA enhanced with CA and to validate it against pilot-scale absorption experiments. In this work, we compare model predictions to measured temperature and CO2 concentration profiles...

  9. A Comparison of Pyramidal Staff Training and Direct Staff Training in Community-Based Day Programs

    Science.gov (United States)

    Haberlin, Alayna T.; Beauchamp, Ken; Agnew, Judy; O'Brien, Floyd

    2012-01-01

    This study evaluated two methods of training staff who were working with individuals with developmental disabilities: pyramidal training and consultant-led training. In the pyramidal training, supervisors were trained in the principles of applied behavior analysis (ABA) and in delivering feedback. The supervisors then trained their direct-care…

  10. Enhanced piezoelectric properties and excellent thermal stabilities of cobalt-modified Aurivillius-type calcium bismuth titanate (CaBi_4Ti_4O_1_5)

    International Nuclear Information System (INIS)

    Zhao, Tian-Long; Wang, Chun-Ming; Wang, Chun-Lei; Wang, Yi-Ming; Dong, Shuxiang

    2015-01-01

    Highlights: • Cobalt oxide modified CBT-based ceramics were prepared and investigated in detail. • XRPD analysis revealed Co ions enter into B-site of CBT-based ceramics. • CBT-Co4 ceramics show the enhanced d_3_3 of 14 pC/N and T_c of 782 °C. • CBT-Co4 ceramics present the improved high-temperature resistivity. • Thermal depoling behavior indicates CBT-Co4 ceramics exhibit good thermal stability. - Abstract: Bismuth layer-structured ferroelectric (BLSF) calcium bismuth titanate (CaBi_4Ti_4O_1_5, CBT) piezoelectric ceramics with 0.0–1.0 wt.% cobalt oxide (Co_2O_3) have been prepared via a conventional solid-state reaction method. Microstructural morphology and electrical properties of cobalt oxide-modified CBT ceramics were investigated in detail. X-ray powder diffraction (XRPD) analysis revealed that the cobalt oxide-modified CBT ceramics have a pure four-layer Aurivillius-type structure. The piezoelectric properties of CBT ceramics were significantly enhanced by cobalt oxide modifications. The piezoelectric coefficient d_3_3 and Curie temperature T_c of 0.2 wt.% cobalt oxide-modified CBT ceramics (CBT-Co4) are 14 pC/N and 782 °C, respectively. The DC resistivity and thermal depoling behavior at elevated temperature indicated that the CBT-Co4 ceramics exhibit good thermal stability, demonstrating that the CBT-Co4 ceramics are potential materials for high temperature piezoelectric applications.

  11. Enhanced production of nitric oxide in A549 cells through activation of TRPA1 ion channel by cold stress.

    Science.gov (United States)

    Sun, Wenwu; Wang, Zhonghua; Cao, Jianping; Wang, Xu; Han, Yaling; Ma, Zhuang

    2014-08-31

    The respiratory epithelium is exposed to the external environment, and inhalation of cold air is common during the season of winter. In addition, the lung is a major source of nitric oxide (NO). However, the effect of cold stress on the production of NO is still unclear. In the present work, We measured the change of NO in single cell with DACF-DA and the change in cytosolic Ca(2+) concentration ([Ca(2+)]c) in A549 cell. We observed that cold stress (from 20 °C to 5 °C) induced an increase of NO in A549 cell, which was completely abolished by applying an extracellular Ca(2+) free medium. Further experiments showed that cold-sensing transient receptor potential subfamily member 1 (TRPA1) channel agonist (allyl isothiocyanate, AITC) increased the production of NO and the level of [Ca(2+)]c in A549 cell. Additionally, TRPA1 inhibitor, Ruthenium red (RR) and camphor, significantly blocked the enhanced production of NO and the rise of [Ca(2+)]c induced by AITC or cold stimulation, respectively. Taken together, these data indicated that cold-induced TRPA1 activation was responsible for the enhanced production of NO in A549 cell. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. The TAPS Pyramid: Where, Who and How?

    Science.gov (United States)

    Hopwood-Stephens, Isabel

    2018-01-01

    The TAPS pyramid was developed in late 2014 and has been available as a download on the Primary Science Teaching Trust (PSTT) website since August 2015. But where has it gone since then? Who is using it? And how is it being used in schools to change primary science assessment practice? This article attempts to answer these questions with data from…

  13. Sulfolobus turreted icosahedral virus c92 protein responsible for the formation of pyramid-like cellular lysis structures.

    Science.gov (United States)

    Snyder, Jamie C; Brumfield, Susan K; Peng, Nan; She, Qunxin; Young, Mark J

    2011-07-01

    Host cells infected by Sulfolobus turreted icosahedral virus (STIV) have been shown to produce unusual pyramid-like structures on the cell surface. These structures represent a virus-induced lysis mechanism that is present in Archaea and appears to be distinct from the holin/endolysin system described for DNA bacteriophages. This study investigated the STIV gene products required for pyramid formation in its host Sulfolobus solfataricus. Overexpression of STIV open reading frame (ORF) c92 in S. solfataricus alone is sufficient to produce the pyramid-like lysis structures in cells. Gene disruption of c92 within STIV demonstrates that c92 is an essential protein for virus replication. Immunolocalization of c92 shows that the protein is localized to the cellular membranes forming the pyramid-like structures.

  14. Using the Pyramid Approach to Teaching Marketing Research.

    Science.gov (United States)

    Peltier, James W.; Westfall, John; Ainscough, Thomas L.

    2001-01-01

    Underscores the need for teaching marketing research skills at the secondary level and shows how marketing research fits into marketing education. Provides an example of how to use the pyramid approach to research, which involves review of secondary sources, key informant interviews, focus groups, and quantitative research. (Author/JOW)

  15. Enhancement of Low-field Magnetoresistance in Self-Assembled Epitaxial La0.67Ca0.33MnO3:NiO and La0.67Ca0.33MnO3:Co3O4 Composite Films via Polymer-Assisted Deposition.

    Science.gov (United States)

    Zhou, Meng; Li, Yuling; Jeon, Il; Yi, Qinghua; Zhu, Xuebin; Tang, Xianwu; Wang, Haiyan; Fei, Ling; Sun, Yuping; Deng, Shuguang; Matsuo, Yutaka; Luo, Hongmei; Zou, Guifu

    2016-07-06

    Polymer-assisted deposition method has been used to fabricate self-assembled epitaxial La0.67Ca0.33MnO3:NiO and La0.67Ca0.33MnO3:Co3O4 films on LaAlO3 substrates. Compared to pulsed-laser deposition method, polymer-assisted deposition provides a simpler and lower-cost approach to self-assembled composite films with enhanced low-field magnetoresistance effect. After the addition of NiO or Co3O4, triangular NiO and tetrahedral Co3O4 nanoparticles remain on the surface of La0.67Ca0.33MnO3 films. This results in a dramatic increase in resistivity of the films from 0.0061 Ω•cm to 0.59 Ω•cm and 1.07 Ω•cm, and a decrease in metal-insulator transition temperature from 270 K to 180 K and 172 K by the addition of 10%-NiO and 10%-Co3O4, respectively. Accordingly, the maximum absolute magnetoresistance value is improved from -44.6% to -59.1% and -52.7% by the addition of 10%-NiO and 10%-Co3O4, respectively. The enhanced low-field magnetoresistance property is ascribed to the introduced insulating phase at the grain boundaries. The magnetism is found to be more suppressed for the La0.67Ca0.33MnO3:Co3O4 composite films than the La0.67Ca0.33MnO3:NiO films, which can be attributed to the antiferromagnetic properties of the Co3O4 phase. The solution-processed composite films show enhanced low-field magnetoresistance effect which are crucial in practical applications. We expect our polymer-assisted deposited films paving the pathway in the field of hole-doped perovskites with their intrinsic colossal magnetoresistance.

  16. Enhanced performance of solar cells with optimized surface recombination and efficient photon capturing via anisotropic-etching of black silicon

    International Nuclear Information System (INIS)

    Chen, H. Y.; Peng, Y.; Hong, M.; Zhang, Y. B.; Cai, Bin; Zhu, Y. M.; Yuan, G. D.; Zhang, Y.; Liu, Z. Q.; Wang, J. X.; Li, J. M.

    2014-01-01

    We report an enhanced conversion efficiency of femtosecond-laser treated silicon solar cells by surface modification of anisotropic-etching. The etching improves minority carrier lifetime inside modified black silicon area substantially; moreover, after the etching, an inverted pyramids/upright pyramids mixed texture surface is obtained, which shows better photon capturing capability than that of conventional pyramid texture. Combing of these two merits, the reformed solar cells show higher conversion efficiency than that of conventional pyramid textured cells. This work presents a way for fabricating high performance silicon solar cells, which can be easily applied to mass-production

  17. Ketogenic food pyramid for patients with refractory epilepsy: From theory to clinical practice

    OpenAIRE

    PRUDENCIO, Mariana Baldini; LIMA, Patricia de Azevedo; FREITAS, Maria Camila Pruper de; CARTOLANO, Flávia de Conti; MURAKAMI, Daniela Kawamoto; DAMASCENO, Nágila Raquel Teixeira

    2017-01-01

    ABSTRACT Objective: To develop a graphical representation in the form of a food pyramid for a ketogenic diet for dietary treatment in children and adolescents with refractory epilepsy. Methods: The pyramid was constructed based on: the estimation of energy requirements for different age groups, macronutrient distribution, food groups, and the number of servings and respective amounts of food according to the ketogenic diet. Serving sizes were based on the calculation of energy and macronutr...

  18. Long-term fluoxetine treatment induces input-specific LTP and LTD impairment and structural plasticity in the CA1 hippocampal subfield.

    Directory of Open Access Journals (Sweden)

    Francisco J Rubio

    2013-05-01

    Full Text Available Antidepressant drugs are usually administered for long time for the treatment of major depressive disorder. However, they are also prescribed in several additional psychiatric conditions as well as during long term maintenance treatments. Antidepressants induce adaptive changes in several forebrain structures which include modifications at glutamatergic synapses. We recently found that repetitive administration of the selective serotonin reuptake inhibitor fluoxetine to naϊve adult male rats induced an increase of mature, mushroom-type dendritic spines in several forebrain regions. This was associated with an increase of GluA2-containing α-amino-3-hydroxy-5-methylisoxazole-4-propionate receptors (AMPA-Rs in telencephalic postsynaptic densities. To unravel the functional significance of such a synaptic re-arrangement, we focused on glutamate neurotransmission in the hippocampus. We evaluated the effect of four weeks of treatment with 0.7 mg/kg of fluoxetine on long-term potentiation (LTP and long-term depression (LTD in the Schaffer collateral-CA1 synapses and the perforant path-CA1 synapses. Recordings in hippocampal slices revealed profound deficits in LTP and LTD at Schaffer collateral-CA1 synapses associated to increased spine density and enhanced presence of mushroom-type spines, as revealed by Golgi staining. However, the same treatment had neither an effect on spine morphology, nor on LTP and LTD at perforant path-CA1 synapses. Cobalt staining experiments revealed decreased AMPA-R Ca2+ permeability in the stratum radiatum together with increased GluA2-containing, Ca2+-impermeable AMPA-Rs. Therefore, 4 weeks of fluoxetine treatment promoted structural and functional adaptations in CA1 neurons in a pathway-specific manner that were selectively associated with impairment of activity-dependent plasticity at Schaffer collateral-CA1 synapses.

  19. Kinetic properties and adrenergic control of TREK-2-like channels in rat medial prefrontal cortex (mPFC) pyramidal neurons.

    Science.gov (United States)

    Ładno, W; Gawlak, M; Szulczyk, P; Nurowska, E

    2017-06-15

    TREK-2-like channels were identified on the basis of electrophysiological and pharmacological tests performed on freshly isolated and enzymatically/mechanically dispersed pyramidal neurons of the rat medial prefrontal cortex (mPFC). Single-channel currents were recorded in cell-attached configuration and the impact of adrenergic receptors (α 1 , α 2 , β) stimulation on spontaneously appearing TREK-2-like channel activity was tested. The obtained results indicate that noradrenaline decreases the mean open probability of TREK-2-like channel currents by activation of β 1 but not of α 1 - and α 2 -adrenergic receptors. Mean open time and channel conductance were not affected. The system of intracellular signaling pathways depends on the activation of protein kinase A. We also show that adrenergic control of TREK-2-like channel currents by adrenergic receptors was similar in pyramidal neurons isolated from young, adolescent, and adult rats. Immunofluorescent confocal scans of mPFC slices confirmed the presence of the TREK-2 protein, which was abundant in layer V pyramidal neurons. The role of TREK-2-like channel control by adrenergic receptors is discussed. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Sulfolobus Turreted Icosahedral Virus c92 Protein Responsible for the Formation of Pyramid-Like Cellular Lysis Structures

    DEFF Research Database (Denmark)

    Snyder, Jamie C; Brumfield, Susan K; Peng, Nan

    2011-01-01

    Host cells infected by Sulfolobus turreted icosahedral virus (STIV) have been shown to produce unusual pyramid-like structures on the cell surface. These structures represent a virus-induced lysis mechanism that is present in Archaea and appears to be distinct from the holin/endolysin system desc...... disruption of c92 within STIV demonstrates that c92 is an essential protein for virus replication. Immunolocalization of c92 shows that the protein is localized to the cellular membranes forming the pyramid-like structures.......Host cells infected by Sulfolobus turreted icosahedral virus (STIV) have been shown to produce unusual pyramid-like structures on the cell surface. These structures represent a virus-induced lysis mechanism that is present in Archaea and appears to be distinct from the holin/endolysin system...... described for DNA bacteriophages. This study investigated the STIV gene products required for pyramid formation in its host Sulfolobus solfataricus. Overexpression of STIV open reading frame (ORF) c92 in S. solfataricus alone is sufficient to produce the pyramid-like lysis structures in cells. Gene...

  1. The attraction of the pyramids: virtual realization of Hutton's suggestion to improve Maskelyne's 1774 Earth density estimate

    Directory of Open Access Journals (Sweden)

    J. R. Smallwood

    2018-01-01

    Full Text Available Charles Hutton suggested in 1821 that the pyramids of Egypt be used to site an experiment to measure the deflection of the vertical by a large mass. The suggestion arose as he had estimated the attraction of a Scottish mountain as part of Nevil Maskelyne's (1774 "Schiehallion Experiment", a demonstration of Isaac Newton's law of gravitational attraction and the earliest reasonable quantitative estimate of Earth's mean density. I present a virtual realization of an experiment at the Giza pyramids to investigate how Hutton's concept might have emerged had it been undertaken as he suggested. The attraction of the Great Pyramid would have led to inward north–south deflections of the vertical totalling 1.8 arcsec (0.0005°, and east–west deflections totalling 2.0 arcsec (0.0006°, which although small, would have been within the contemporaneous detectable range, and potentially given, as Hutton wished, a more accurate Earth density measurement than he reported from the Schiehallion experiment.

  2. Mood Components in Cocoa and Chocolate: The Mood Pyramid.

    Science.gov (United States)

    Tuenter, Emmy; Foubert, Kenn; Pieters, Luc

    2018-03-14

    Cocoa and chocolate, prepared from cocoa beans that originate from the fruits of the cocoa tree Theobroma cacao , have a long-standing reputation as healthy food, including mood-enhancing effects. In spite of many clinical trials with chocolate, cocoa, or its constituents, the mechanisms of action on mood and cognition remain unclear. More in particular, it is still controversial which constituents may contribute to the psychopharmacological activities, ranging from the major cacao flavanols and methylxanthines to the minor amines, amides, and alkaloids. In this review a critical appraisal is made of recent studies on mood and cognition, with a special emphasis on analytical characterization of the test samples. It is concluded that the mood and cognition-enhancing effects of cocoa and chocolate can be ranked from more general activities associated with flavanols and methylxanthines, to more specific activities related to minor constituents such as salsolinol, with on top the orosensory properties of chocolate. Therefore, the "mood pyramid" of cocoa and chocolate is proposed as a new concept. To understand the role and interactions of the different major and minor constituents of cocoa, it is recommended that all test samples used in future in vitro, in vivo , or human studies should be phytochemically characterized in much more detail than is common practice today. Georg Thieme Verlag KG Stuttgart · New York.

  3. Ca2+ toxicity due to reverse Na+/Ca2+ exchange contributes to degeneration of neurites of DRG neurons induced by a neuropathy-associated Nav1.7 mutation

    Science.gov (United States)

    Estacion, M.; Vohra, B. P. S; Liu, S.; Hoeijmakers, J.; Faber, C. G.; Merkies, I. S. J.; Lauria, G.; Black, J. A.

    2015-01-01

    Gain-of-function missense mutations in voltage-gated sodium channel Nav1.7 have been linked to small-fiber neuropathy, which is characterized by burning pain, dysautonomia and a loss of intraepidermal nerve fibers. However, the mechanistic cascades linking Nav1.7 mutations to axonal degeneration are incompletely understood. The G856D mutation in Nav1.7 produces robust changes in channel biophysical properties, including hyperpolarized activation, depolarized inactivation, and enhanced ramp and persistent currents, which contribute to the hyperexcitability exhibited by neurons containing Nav1.8. We report here that cell bodies and neurites of dorsal root ganglion (DRG) neurons transfected with G856D display increased levels of intracellular Na+ concentration ([Na+]) and intracellular [Ca2+] following stimulation with high [K+] compared with wild-type (WT) Nav1.7-expressing neurons. Blockade of reverse mode of the sodium/calcium exchanger (NCX) or of sodium channels attenuates [Ca2+] transients evoked by high [K+] in G856D-expressing DRG cell bodies and neurites. We also show that treatment of WT or G856D-expressing neurites with high [K+] or 2-deoxyglucose (2-DG) does not elicit degeneration of these neurites, but that high [K+] and 2-DG in combination evokes degeneration of G856D neurites but not WT neurites. Our results also demonstrate that 0 Ca2+ or blockade of reverse mode of NCX protects G856D-expressing neurites from degeneration when exposed to high [K+] and 2-DG. These results point to [Na+] overload in DRG neurons expressing mutant G856D Nav1.7, which triggers reverse mode of NCX and contributes to Ca2+ toxicity, and suggest subtype-specific blockade of Nav1.7 or inhibition of reverse NCX as strategies that might slow or prevent axon degeneration in small-fiber neuropathy. PMID:26156380

  4. The functional genome of CA1 and CA3 neurons under native conditions and in response to ischemia

    Directory of Open Access Journals (Sweden)

    Rossner Moritz

    2007-10-01

    Full Text Available Abstract Background The different physiological repertoire of CA3 and CA1 neurons in the hippocampus, as well as their differing behaviour after noxious stimuli are ultimately based upon differences in the expressed genome. We have compared CA3 and CA1 gene expression in the uninjured brain, and after cerebral ischemia using laser microdissection (LMD, RNA amplification, and array hybridization. Results Profiling in CA1 vs. CA3 under normoxic conditions detected more than 1000 differentially expressed genes that belong to different, physiologically relevant gene ontology groups in both cell types. The comparison of each region under normoxic and ischemic conditions revealed more than 5000 ischemia-regulated genes for each individual cell type. Surprisingly, there was a high co-regulation in both regions. In the ischemic state, only about 100 genes were found to be differentially expressed in CA3 and CA1. The majority of these genes were also different in the native state. A minority of interesting genes (e.g. inhibinbetaA displayed divergent expression preference under native and ischemic conditions with partially opposing directions of regulation in both cell types. Conclusion The differences found in two morphologically very similar cell types situated next to each other in the CNS are large providing a rational basis for physiological differences. Unexpectedly, the genomic response to ischemia is highly similar in these two neuron types, leading to a substantial attenuation of functional genomic differences in these two cell types. Also, the majority of changes that exist in the ischemic state are not generated de novo by the ischemic stimulus, but are preexistant from the genomic repertoire in the native situation. This unexpected influence of a strong noxious stimulus on cell-specific gene expression differences can be explained by the activation of a cell-type independent conserved gene-expression program. Our data generate both novel

  5. Value and significance of tumor markers as CEA, CA125, SCC-Ag, CA199 and CYFRA21-1 in the diagnosis of cervical cancer

    Directory of Open Access Journals (Sweden)

    Xiao-Juan Wang

    2017-09-01

    Full Text Available Objective: To investigate the value and significance of serum CEA, CA125, SCC-Ag, CA199 and CYFRA21-1 in the diagnosis of cervical cancer by comparing the detection of five serum markers. Methods: A total of 108 cases were divided into three groups, including 60 cervical cancerpatients and 20 cervical intraepithelial neoplasiain patients treated in our hospital from September 2015 to September 2016 and 28 healthy women. Radioimmunoassay was used to detect and compare the serum levels of CA125, CA199, CYFRA21-1 and ELISA method was used to detect and compare the serum levels of SCC-Ag, CEA. Results: (1 There was no statistically significant difference in the serum CEA, CA125, SCC-Ag, CA199, CYFRA21-1 levels between CIN group and control group. The serums CEA, CA125, SCC-Ag, CA199, CYFRA21-1 levels of cervical cancer patients were significantly higher than the other two groups. The differences were statistically significant. (2There were statistically significant differences in the serum CEA, CA125, SCC-Ag, CA199, CYFRA21-1 levels between different cervical pathological type groups.The serum CA125, CA199, CEA levels of cervical glandular cancer patients were significantly higher than the other two groups. The differences were statistically significant. The serum SCC-Ag, CYFRA21-1 levels of cervical squamous cancer patients were significantly higher than the other two groups. The differences were statistically significant. Conclusion: The serums CEA, CA125, SCC-Ag, CA199, CYFRA21-1 levels of cervical cancer patients were significantly higher than cervical intraepithelial neoplasiain patients and healthy women. The serum CA125, CA199, CEA levels of cervical glandular cancer patients were significantly higher and the serum SCC-Ag, CYFRA21-1 levels of cervical squamous cancer patients were significantly higher. The five tumor markers can be used in diagnosis of cervical cancer and they are also worthy in distinguishing cervical pathological types.

  6. 3D-Printing of inverted pyramid suspending architecture for pyroelectric infrared detectors with inhibited microphonic effect

    Science.gov (United States)

    Xu, Qing; Zhao, Xiangyong; Li, Xiaobing; Deng, Hao; Yan, Hong; Yang, Linrong; Di, Wenning; Luo, Haosu; Neumann, Norbert

    2016-05-01

    A sensitive chip with ultralow dielectric loss based on Mn doped PMNT (71/29) has been proposed for high-end pyroelectric devices. The dielectric loss at 1 kHz is 0.005%, one order lower than the minimum value reported so far. The detective figure of merit (Fd) is up to 92.6 × 10-5 Pa-1/2 at 1 kHz and 53.5 × 10-5 Pa-1/2 at 10 Hz, respectively. In addition, an inverted pyramid suspending architecture for supporting the sensitive chip has been designed and manufactured by 3D printing technology. The combination of this sensitive chip and the proposed suspending architecture largely enhances the performance of the pyroelectric detectors. The responsivity and specific detectivity are 669,811 V/W and 3.32 × 109 cm Hz1/2/W at 10 Hz, respectively, 1.9 times and 1.5 times higher than those of the highest values in literature. Furthermore, the microphonic effect can be largely inhibited according to the theoretical and experimental analysis. This architecture will have promising applications in high-end and stable pyroelectric infrared detectors.

  7. Setting aside transactions from pyramid schemes as impeachable ...

    African Journals Online (AJOL)

    These schemes, which are often referred to as pyramid or Ponzi schemes, are unsustainable operations and give rise to problems in the law of insolvency. Investors in these schemes are often left empty-handed upon the scheme's eventual collapse and insolvency. Investors who received pay-outs from the scheme find ...

  8. PPARα induced NOS1 phosphorylation via PI3K/Akt in guinea pig antral mucous cells: NO-enhancement in Ca(2+)-regulated exocytosis.

    Science.gov (United States)

    Tanaka, Saori; Hosogi, Shigekuni; Sawabe, Yukinori; Shimamoto, Chikao; Matsumura, Hitoshi; Inui, Toshio; Marunaka, Yoshinori; Nakahari, Takashi

    2016-01-01

    A PPARα (peroxisome proliferation activation receptor α) agonist (GW7647) activates nitric oxide synthase 1 (NOS1) to produce NO leading to cGMP accumulation in antral mucous cells. In this study, we examined how PPARα activates NOS1. The NO production stimulated by GW7647 was suppressed by inhibitors of PI3K (wortmannin) and Akt (AKT 1/2 Kinase Inhibitor, AKT-inh), although it was also suppressed by the inhibitors of PPARα (GW6471) and NOS1 (N-PLA). GW7647 enhanced the ACh (acetylcholine)-stimulated exocytosis (Ca(2+)-regulated exocytosis) mediated via NO, which was abolished by GW6471, N-PLA, wortmannin, and AKT-inh. The Western blotting revealed that GW7647 phosphorylates NOS1 via phosphorylation of PI3K/Akt in antral mucous cells. The immunofluorescence examinations demonstrated that PPARα existing with NOS1 co-localizes with PI3K and Akt in the cytoplasm of antral mucous cells. ACh alone and AACOCF3, an analogue of arachidonic acid (AA), induced the NOS1 phosphorylation via PI3K/Akt to produce NO, which was inhibited by GW6471. Since AA is a natural ligand for PPARα, ACh stimulates PPARα probably via AA. In conclusion, PPARα activates NOS1 via PI3K/Akt phosphorylation to produce NO in antral mucous cells during ACh stimulation.

  9. Thermoelectric properties of Ca1-xYxMnO3 and Ca0.9Y0.1-yFeyMnO3 perovskite compounds

    DEFF Research Database (Denmark)

    Thuy, Nguyen Thi; Minh, Dang Le; Van Nong, Ngo

    2012-01-01

    Polycrystalline Ca1-xYxMnO3 (x = 0.0; 0.1; 0.3; 0.5; 0.7) and Ca0.9Y0.1-yFeyMnO3 (y = 0.00; 0.01; 0.03; 0.05) compounds were prepared by solid-state reaction. X-ray diffraction (XRD) analysis revealed all XRD peaks of all the samples as identical to the orthorhombic structure. The thermoelectric ...

  10. Preferential removal and immobilization of stable and radioactive cesium in contaminated fly ash with nanometallic Ca/CaO methanol suspension

    Energy Technology Data Exchange (ETDEWEB)

    Mallampati, Srinivasa Reddy, E-mail: srireddys@ulsan.ac.kr [Department of Civil and Environmental Engineering, University of Ulsan, Ulsan 680-749 (Korea, Republic of); Mitoma, Yoshiharu, E-mail: mitomay@pu-hiroshima.ac.jp [Department of Environmental Sciences, Faculty of Life and Environmental Sciences, Prefectural University of Hiroshima, 562 Nanatsuka-Cho, Shobara City, Hiroshima 727-0023 (Japan); Okuda, Tetsuji [Environmental Research and Management Center, Hiroshima University, 1-5-3 Kagamiyama, Higashi-Hiroshima, Hiroshima 739-8513 (Japan); Sakita, Shogo [Department of Environmental Sciences, Faculty of Life and Environmental Sciences, Prefectural University of Hiroshima, 562 Nanatsuka-Cho, Shobara City, Hiroshima 727-0023 (Japan); Simion, Cristian [Politehnica University of Bucharest, Department of Organic Chemistry, Bucharest 060042 (Romania)

    2014-08-30

    Graphical abstract: Schematic representation of possible mechanisms determining the Cs extraction and immobilization in fly ash during water, methanol or n-MCaS extraction. - Highlights: • nMCaS suspension for cesium extraction and immobilization in fly ash was developed. • Enhanced cesium immobilization was done by nanometallic Ca/CaO methanol suspension. • By SEM analysis the amount of cesium detectable on soil particle surface decreases. • Leachable cesium concentrations reduced, lower than the standard regulatory limit. • nMCaS unique and a highly potential amendment for the remediation of Cs. - Abstract: In this work, the capability of nanometallic Ca/CaO methanol suspension in removing and/or immobilizing stable ({sup 133}Cs) and radioactive cesium species ({sup 134}Cs and {sup 137}Cs) in contaminated fly ash was investigated. After a first methanol and second water washing yielded only 45% of {sup 133}Cs removal. While, after a first methanol washing, the second solvent with nanometallic Ca/CaO methanol suspension yielded simultaneous enhanced removal and immobilization about 99% of {sup 133}Cs. SEM-EDS analysis revealed that the mass percent of detectable {sup 133}Cs on the fly ash surface recorded a 100% decrease. When real radioactive cesium contaminated fly ash (containing an initial 14,040 Bq kg{sup −1134}Cs and {sup 137}Cs cumulated concentration) obtained from burning wastes from Fukushima were reduced to 3583 Bq kg{sup −1} after treatment with nanometallic Ca/CaO methanol suspension. Elution test conducted on the treated fly ash gave 100 Bq L{sup −1} total {sup 134}Cs and {sup 137}Cs concentrations in eluted solution. Furthermore, both ash content and eluted solution concentrations of {sup 134}Cs and {sup 137}Cs were much lower than the Japanese Ministry of the Environment regulatory limit of 8000 Bq kg{sup −1} and 150 Bq L{sup −1} respectively. The results of this study suggest that the nanometallic Ca/CaO methanol suspension is

  11. Essential role of the NO signaling pathway in the hippocampal CA1 in morphine-associated memory depends on glutaminergic receptors.

    Science.gov (United States)

    Shen, Fang; Wang, Xue-Wei; Ge, Fei-Fei; Li, Yi-Jing; Cui, Cai-Lian

    2016-03-01

    The nitric oxide (NO)/soluble guanylyl cyclase (sGC)/cGMP-dependent protein kinase (PKG) signaling pathway has been reported to play a key role in memory processing. However, little is known about its role in drug-associated reward memory. Here, we report the following. 1) The NO pathway in the CA1 is critical for the retrieval of morphine-associated reward memory. Specifically, the nNOS, sGC and PKG protein levels in the CA1 were increased after the expression of morphine conditioned place preference (CPP). Intra-CA1 injection of an NOS, sGC or PKG inhibitor prevented morphine CPP expression. 2) The involvement of the NO pathway in morphine CPP requires NR2B-containing NMDA receptors (NR2B-NMDARs). NR2B-NMDAR expression was elevated in the CA1 following morphine CPP expression, and intra-CA1 injection of the NR2B-NMDAR antagonist Ro25-6981 not only blocked morphine CPP expression but also inhibited the up-regulation of nNOS, sGC and PKG. Moreover, the Ro25-6981-induced blockade of morphine CPP was abolished by intra-CA1 injection of a NOS substrate or an sGC activator. 3) The NR2B-NMDAR stimulated the NO pathway by up-regulating the phosphorylation of Akt(Ser473). Morphine CPP expression enhanced the pAkt(Ser473) level, which has been corroborated to regulate nNOS activity, and this effect was reversed by intra-CA1 injection of Ro25-6981. 4) GluR1 acted downstream of the NO pathway. The membrane level of GluR1 in the CA1 was increased after morphine CPP expression, and this effect was prevented by pre-injection of a PKG inhibitor into the CA1. Additionally, co-immunoprecipitation revealed an interaction between PKG and GluR1; this result further indicated a role of PKG in regulating GluR1 trafficking. Collectively, the results of our study demonstrated that the activation of the NR2B-NMDAR/NO/sGC/PKG signaling pathway is necessary for the retrieval of morphine-associated reward memory. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Enhanced emission of encaged-OH--free Ca12(1-x)Sr12xAl14O33:0.1%Gd3+ conductive phosphors via tuning the encaged-electron concentration for low-voltage FEDs.

    Science.gov (United States)

    Zhang, Meng; Liu, Yuxue; Yang, Jian; Zhu, Hancheng; Yan, Duanting; Zhang, Xinyang; Liu, Chunguang; Xu, Changshan; Zhang, Hong

    2017-05-24

    Encaged-OH - -free Ca 12(1-x) Sr 12x Al 14 O 33 :0.1%Gd 3+ conductive phosphors were prepared through a melt-solidification process in combination with a subsequent heat treatment. Absorption spectra showed that the maximum encaged-electron concentration was increased to 1.08 × 10 21 cm -3 through optimizing the doping amount of Sr 2+ (x = 0.005). Meanwhile, FTIR and Raman spectra indicated that pure Ca 11.94 Sr 0.06 Al 14 O 33 :0.1%Gd 3+ conductive phosphor without encaged OH - and C 2 2- anions was acquired. For the conductive powders heat-treated in air for different times, the encaged-electron concentrations were tuned from 1.02 × 10 21 to 8.3 × 10 20 cm -3 . ESR, photoluminescence, and luminescence kinetics analyses indicated that the emission at 312 nm mainly originated from Gd 3+ ions surrounded by encaged O 2- anions, while Gd 3+ ions surrounded by encaged electrons had a negative contribution to the UV emission due to the existence of an energy transfer process. Under low-voltage electron-beam excitation (3 kV), enhanced cathodoluminescence (CL) of the conductive phosphors could be achieved by tuning the encaged-electron concentrations. In particular, for the encaged-OH - -free conductive phosphor, the emission intensity of the CL was about one order of magnitude higher than that of the conductive phosphor containing encaged OH - anions. Our results suggested that the encaged-OH - -free conductive phosphors have potential application in low-voltage FEDs.

  13. Road Map to Statewide Implementation of the Pyramid Model. Roadmap to Effective Intervention Practices #6

    Science.gov (United States)

    Dunlap, Glen; Smith, Barbara J.; Fox, Lise; Blase, Karen

    2014-01-01

    This document is a guide--a "Road Map"--for implementing widespread use of the Pyramid Model for Promoting Social Emotional Competence in Infants and Young Children (http://www.challengingbehavior.org/do/pyramid_model. htm). It is a road map of systems change. The Road Map is written for statewide systems change, although it could be…

  14. Short-term repeated corticosterone administration enhances glutamatergic but not GABAergic transmission in the rat motor cortex.

    Science.gov (United States)

    Kula, Joanna; Blasiak, Anna; Czerw, Anna; Tylko, Grzegorz; Sowa, Joanna; Hess, Grzegorz

    2016-04-01

    It has been demonstrated that stress impairs performance of skilled reaching and walking tasks in rats due to the action of glucocorticoids involved in the stress response. Skilled reaching and walking are controlled by the primary motor cortex (M1); however, it is not known whether stress-related impairments in skilled motor tasks are related to functional and/or structural alterations within the M1. We studied the effects of single and repeated injections of corticosterone (twice daily for 7 days) on spontaneous excitatory and inhibitory postsynaptic currents (sEPSCs and sIPSCs) recorded from layer II/III pyramidal neurons in ex vivo slices of the M1, prepared 2 days after the last administration of the hormone. We also measured the density of dendritic spines on pyramidal cells and the protein levels of selected subunits of AMPA, NMDA, and GABAA receptors after repeated corticosterone administration. Repeatedly administered corticosterone induced an increase in the frequency but not in the amplitude of sEPSCs, while a single administration had no effect on the recorded excitatory currents. The frequency and amplitude of sIPSCs as well as the excitability of pyramidal cells were changed neither after single nor after repeated corticosterone administration. Treatment with corticosterone for 7 days did not modify the density of dendritic spines on pyramidal neurons. Corticosterone influenced neither the protein levels of GluA1, GluA2, GluN1, GluN2A, and GluN2B subunits of glutamate receptors nor those of α1, β2, and γ2 subunits of the GABAA receptor. The increase in sEPSCs frequency induced by repeated corticosterone administration faded out within 7 days. These data indicate that prolonged administration of exogenous corticosterone selectively and reversibly enhances glutamatergic, but not GABAergic transmission in the rat motor cortex. Our results suggest that corticosterone treatment results in an enhancement of spontaneous glutamate release from presynaptic

  15. Potentiation of glycine-gated NR1/NR3A NMDA receptors relieves Ca2+-dependent outward rectification

    Directory of Open Access Journals (Sweden)

    Christian Madry

    2010-03-01

    Full Text Available Glycine has diverse functions within the mammalian central nervous system. It inhibits postsynaptic neurons via strychnine-sensitive glycine receptors (GlyRs and enhances neuronal excitation through co-activation of N-methyl-D-aspartate (NMDA receptors. Classical Ca2+-permeable NMDA receptors are composed of glycine-binding NR1 and glutamate-binding NR2 subunits, and hence require both glutamate and glycine for efficient activation. In contrast, recombinant receptors composed of NR1 and the glycine binding NR3A and/or NR3B subunits lack glutamate binding sites and can be activated by glycine alone. Therefore these receptors are also named excitatory glycine receptors. Co-application of antagonists of the NR1 glycine-binding site or of the divalent cation Zn2+ markedly enhances the glycine responses of these receptors. To gain further insight into the properties of these glycine-gated NMDA receptors, we investigated their current-voltage (I-V dependence. Whole-cell current-voltage relations of glycine currents recorded from NR1/NR3B and NR1/NR3A/NR3B expressing oocytes were found to be linear under our recording conditions. In contrast, NR1/NR3A receptors displayed a strong outwardly rectifying I-V relation. Interestingly, the voltage-dependent inward current block was abolished in the presence of NR1 antagonists, Zn2+ or a combination of both. Further analysis revealed that Ca2+ (1.8 mM present in our recording solutions was responsible for the voltage-dependent inhibition of ion flux through NR1/NR3A receptors. Since physiological concentrations of the divalent cation Mg2+ did not affect the I-V dependence, our data suggest that relief of the voltage-dependent Ca2+ block of NR1/NR3A receptors by Zn2+ may be important for the regulation of excitatory glycinergic transmission, according to the Mg2+-block of conventional NR1/NR2 NMDA receptors.

  16. Marker-assisted pyramiding of Thinopyrum-derived leaf rust ...

    Indian Academy of Sciences (India)

    Annual Meetings · Mid Year Meetings · Discussion Meetings · Public Lectures · Lecture Workshops · Refresher Courses · Symposia · Live Streaming. Home; Journals; Journal of Genetics; Volume 96; Issue 6. Marker-assisted pyramiding of Thinopyrum-derived leaf rust resistance genes Lr19 and Lr24 in bread wheat variety ...

  17. Angles of Elevation of the Pyramids of Egypt.

    Science.gov (United States)

    Smith, Arthur F.

    1982-01-01

    The nature and history of the construction of pyramids in Egypt is detailed. It is noted that one can only theorize about why the Egyptians used particular angles of elevation. It is thought, perhaps, that new clues will provide a clear solution to this mystery as additional artifacts and hieroglyphics are discovered. (MP)

  18. Data of evolutionary structure change: 1A5CA-2QUTD [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available ryChain> 2QUT D 2QUTD ence>LLTADDRVNPC...T D 2QUTD ence>INKCPLLKPWA...1A5CA-2QUTD 1A5C 2QUT A D ------LPADVAEELATTAQKLVQAGKGILAADESTQTI...bID> A 1A5CA ence>LFGTK-GLGKFence> 1 1A5C A 1A5CA

  19. LKB1 Regulates Mitochondria-Dependent Presynaptic Calcium Clearance and Neurotransmitter Release Properties at Excitatory Synapses along Cortical Axons.

    Science.gov (United States)

    Kwon, Seok-Kyu; Sando, Richard; Lewis, Tommy L; Hirabayashi, Yusuke; Maximov, Anton; Polleux, Franck

    2016-07-01

    Individual synapses vary significantly in their neurotransmitter release properties, which underlie complex information processing in neural circuits. Presynaptic Ca2+ homeostasis plays a critical role in specifying neurotransmitter release properties, but the mechanisms regulating synapse-specific Ca2+ homeostasis in the mammalian brain are still poorly understood. Using electrophysiology and genetically encoded Ca2+ sensors targeted to the mitochondrial matrix or to presynaptic boutons of cortical pyramidal neurons, we demonstrate that the presence or absence of mitochondria at presynaptic boutons dictates neurotransmitter release properties through Mitochondrial Calcium Uniporter (MCU)-dependent Ca2+ clearance. We demonstrate that the serine/threonine kinase LKB1 regulates MCU expression, mitochondria-dependent Ca2+ clearance, and thereby, presynaptic release properties. Re-establishment of MCU-dependent mitochondrial Ca2+ uptake at glutamatergic synapses rescues the altered neurotransmitter release properties characterizing LKB1-null cortical axons. Our results provide novel insights into the cellular and molecular mechanisms whereby mitochondria control neurotransmitter release properties in a bouton-specific way through presynaptic Ca2+ clearance.

  20. US adolescents and MyPyramid: associations between fast-food consumption and lower likelihood of meeting recommendations.

    Science.gov (United States)

    Sebastian, Rhonda S; Wilkinson Enns, Cecilia; Goldman, Joseph D

    2009-02-01

    To determine whether fast-food consumption is associated with adolescents' food group intakes and likelihood of meeting recommendations outlined in the MyPyramid Food Guidance System. Data from two 24-hour recalls collected in What We Eat in America, National Health and Nutrition Examination Survey 2003-2004 were analyzed. Fast-food consumers were divided into tertiles based on the proportion of 2-day energy intake derived from fast food. Adolescent boys and nonpregnant girls aged 12 to 19 years (n=1,956). All statistical analyses included sample weights to account for the survey design. Regression analyses were used to detect associations between fast-food consumption and both food group intakes and percentages of individuals meeting MyPyramid recommendations, and to predict odds of meeting recommendations by fast-food consumption level. Fast-food consumption was associated negatively with MyPyramid fruit and milk group intakes (boys and girls) and positively with discretionary energy and solid fats (girls only). Negative associations were also found between fast-food consumption and percentages of adolescents meeting recommendations for milk (boys), fruits (girls), and vegetables and discretionary energy (boys and girls). Compared with those consuming no fast food, adolescents in the highest tertile of energy from fast food were less likely to meet recommendations for vegetables (odds ratio [OR]=0.16, 95% confidence interval [CI]: 0.05 to 0.52 for boys; OR=0.18, 95% CI: 0.04 to 0.79 for girls) and discretionary energy (OR=0.41, 95% CI: 0.22 to 0.77 for boys; OR=0.04, 95% CI: 0.01 to 0.24 for girls). No relationships were found between fast-food consumption and grains, meat/beans, and oils. Adolescents' intakes, whether containing fast food or not, need improvement. Fast food is one factor that impacts adolescents' intake of MyPyramid groups and their likelihood of meeting recommendations. Awareness of fast-food's role in discrepancies between adolescent intakes